WorldWideScience

Sample records for reverse genetics approaches

  1. Reverse Genetic Approaches in Zebrafish

    Institute of Scientific and Technical Information of China (English)

    Peng Huang; Zuoyan Zhu; Shuo Lin; Bo Zhang

    2012-01-01

    Zebrafish (Danio rerio) is a well-established vertebrate animal model.A comprehensive collection of reverse genetics tools has been developed for studying gene function in this useful organism.Morpholino is the most widely used reagent to knock down target gene expression post-transcriptionally.For a long time,targeted genome modification has been heavily relied on large-scale traditional forward genetic screens,such as ENU (N-ethyl-N-nitrosourea) mutagenesis derived TILLING (Targeting Induced Local Lesions IN Genomes)strategy and pseudo-typed retrovirus mediated insertional mutagenesis.Recently,engineered endonucleases,including ZFNs (zinc finger nucleases) and TALENs (transcription activator-like effector nucleases),provide new and efficient strategies to directly generate sitespecific indel mutations by inducing double strand breaks in target genes.Here we summarize the major reverse genetic approaches for loss-of-function studies used and emerging in zebrafish,including strategies based on genome-wide mutagenesis and methods for sitespecific gene targeting.Future directions and expectations will also be discussed.

  2. Reverse Genetics Approaches to Control Arenavirus.

    Science.gov (United States)

    Martínez-Sobrido, Luis; Cheng, Benson Yee Hin; de la Torre, Juan Carlos

    2016-01-01

    Several arenavirus cause hemorrhagic fever disease in humans and pose a significant public health problem in their endemic regions. To date, no licensed vaccines are available to combat human arenavirus infections, and anti-arenaviral drug therapy is limited to an off-label use of ribavirin that is only partially effective. The development of arenavirus reverse genetics approaches provides investigators with a novel and powerful approach for the investigation of the arenavirus molecular and cell biology. The use of cell-based minigenome systems has allowed examining the cis- and trans-acting factors involved in arenavirus replication and transcription and the identification of novel anti-arenaviral drug targets without requiring the use of live forms of arenaviruses. Likewise, it is now feasible to rescue infectious arenaviruses entirely from cloned cDNAs containing predetermined mutations in their genomes to investigate virus-host interactions and mechanisms of pathogenesis, as well as to facilitate screens to identify anti-arenaviral drugs and development of novel live-attenuated arenavirus vaccines. Recently, reverse genetics have also allowed the generation of tri-segmented arenaviruses expressing foreign genes, facilitating virus detection and opening the possibility of implementing live-attenuated arenavirus-based vaccine vector approaches. Likewise, the development of single-cycle infectious, reporter-expressing, arenaviruses has provided a new experimental method to study some aspects of the biology of highly pathogenic arenaviruses without the requirement of high-security biocontainment required to study HF-causing arenaviruses. In this chapter we summarize the current knowledge on arenavirus reverse genetics and the implementation of plasmid-based reverse genetics techniques for the development of arenavirus vaccines and vaccine vectors.

  3. Reverse genetics approaches to combat pathogenic arenaviruses.

    Science.gov (United States)

    de la Torre, Juan C

    2008-12-01

    Several arenaviruses cause hemorrhagic fever (HF) in humans, and evidence indicates that the worldwide-distributed prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a neglected human pathogen of clinical significance. Moreover, arenaviruses pose a biodefense threat. No licensed anti-arenavirus vaccines are available, and current anti-arenavirus therapy is limited to the use of ribavirin, which is only partially effective and is associated with anemia and other side effects. Therefore, it is important to develop effective vaccines and better antiviral drugs to combat the dual threats of naturally occurring and intentionally introduced arenavirus infections. The development of arenavirus reverse genetic systems is allowing investigators to conduct a detailed molecular characterization of the viral cis-acting signals and trans-acting factors that control each of the steps of the arenavirus life cycle, including RNA synthesis, packaging and budding. Knowledge derived from these studies is uncovering potential novel targets for therapeutic intervention, as well as facilitating the establishment of assays to identify and characterize candidate antiviral drugs capable of interfering with specific steps of the virus life cycle. Likewise, the ability to generate predetermined specific mutations within the arenavirus genome and analyze their phenotypic expression would significantly contribute to the elucidation of arenavirus-host interactions, including the basis of their ability to cause severe HF. This, in turn, could lead to the development of novel, potent and safe arenavirus vaccines.

  4. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Aitor Nogales

    2016-12-01

    Full Text Available Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines.

  5. Reverse Genetics Approaches for the Development of Influenza Vaccines

    Science.gov (United States)

    Nogales, Aitor; Martínez-Sobrido, Luis

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influenza virus allows for the reassortment between two or more viruses within a co-infected cell, and this characteristic has also been harnessed in the laboratory to generate reassortant viruses for their use as either inactivated or live-attenuated influenza vaccines. With the implementation of plasmid-based reverse genetics techniques, it is now possible to engineer recombinant influenza viruses entirely from full-length complementary DNA copies of the viral genome by transfection of susceptible cells. These reverse genetics systems have provided investigators with novel and powerful approaches to answer important questions about the biology of influenza viruses, including the function of viral proteins, their interaction with cellular host factors and the mechanisms of influenza virus transmission and pathogenesis. In addition, reverse genetics techniques have allowed the generation of recombinant influenza viruses, providing a powerful technology to develop both inactivated and live-attenuated influenza vaccines. In this review, we will summarize the current knowledge of state-of-the-art, plasmid-based, influenza reverse genetics approaches and their implementation to provide rapid, convenient, safe and more effective influenza inactivated or live-attenuated vaccines. PMID:28025504

  6. A reverse genetics approach to study feline infectious peritonitis.

    Science.gov (United States)

    Tekes, Gergely; Spies, Danica; Bank-Wolf, Barbara; Thiel, Volker; Thiel, Heinz-Jürgen

    2012-06-01

    Feline infectious peritonitis (FIP) is a lethal immunopathological disease caused by feline coronaviruses (FCoVs). Here, we describe a reverse genetics approach to study FIP by assessing the pathogenicity of recombinant type I and type II and chimeric type I/type II FCoVs. All recombinant FCoVs established productive infection in cats, and recombinant type II FCoV (strain 79-1146) induced FIP. Virus sequence analyses from FIP-diseased cats revealed that the 3c gene stop codon of strain 79-1146 has changed to restore a full-length open reading frame (ORF).

  7. Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

    Science.gov (United States)

    Traglia, Michela; Tsang, Kathryn; Bearden, Carrie E.; Rauen, Katherine A.

    2017-01-01

    Although gene-gene interaction, or epistasis, plays a large role in complex traits in model organisms, genome-wide by genome-wide searches for two-way interaction have limited power in human studies. We thus used knowledge of a biological pathway in order to identify a contribution of epistasis to autism spectrum disorders (ASDs) in humans, a reverse-pathway genetic approach. Based on previous observation of increased ASD symptoms in Mendelian disorders of the Ras/MAPK pathway (RASopathies), we showed that common SNPs in RASopathy genes show enrichment for association signal in GWAS (P = 0.02). We then screened genome-wide for interactors with RASopathy gene SNPs and showed strong enrichment in ASD-affected individuals (P < 2.2 x 10−16), with a number of pairwise interactions meeting genome-wide criteria for significance. Finally, we utilized quantitative measures of ASD symptoms in RASopathy-affected individuals to perform modifier mapping via GWAS. One top region overlapped between these independent approaches, and we showed dysregulation of a gene in this region, GPR141, in a RASopathy neural cell line. We thus used orthogonal approaches to provide strong evidence for a contribution of epistasis to ASDs, confirm a role for the Ras/MAPK pathway in idiopathic ASDs, and to identify a convergent candidate gene that may interact with the Ras/MAPK pathway. PMID:28076348

  8. Search for genetic virulence markers in viral haemorrhagic septicaemia virus (VHSV) using a reverse genetics approach

    DEFF Research Database (Denmark)

    Stegmann, Anders; Biacchesi, S.; Bremont, M.

    2011-01-01

    VHSV is a negative strand RNA virus causing serious disease in farmed rainbow trout. Although VHSV has been eradicated by stamping out procedures in several fresh water bodies, recently including all streams in Denmark, the wildlife marine reservoir still represents a threat against rainbow trout...... farming. Particularly in Scandinavia, outbreaks of VHS in sea reared rainbow trout have demonstrated that although marine variants of VHSV are considered to be avirulent to rainbow trout, the virus is potentially able to adapt to this host and cause disease. Limited knowledge about the genetic background...

  9. Marburg Virus Reverse Genetics Systems.

    Science.gov (United States)

    Schmidt, Kristina Maria; Mühlberger, Elke

    2016-06-22

    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.

  10. Marburg Virus Reverse Genetics Systems

    Directory of Open Access Journals (Sweden)

    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.

  11. Establishing RNA interference as a reverse-genetic approach for gene functional analysis in protoplasts.

    Science.gov (United States)

    Zhai, Zhiyang; Sooksa-nguan, Thanwalee; Vatamaniuk, Olena K

    2009-02-01

    Double-stranded (ds)RNA interference (RNAi) is widely used for functional analysis of plant genes and is achieved via generating stable transformants expressing dsRNA in planta. This study demonstrated that RNAi can also be utilized to examine gene functions in protoplasts. Because protoplasts are nongrowing cells, effective RNAi-triggered gene silencing depends not only on a depletion of gene transcripts but also on turnover rates of corresponding polypeptides. Herein, we tested if transient RNAi in protoplasts would result in the depletion of a targeted polypeptide and, because protoplasts have a limited life span, if functional assays of RNAi knockout genes would be feasible in protoplasts. We showed that protoplasts transfection with an in vitro-synthesized dsRNA against Arabidopsis (Arabidopsis thaliana) beta-glutamylcysteine synthase (ECS1), a key enzyme in the synthesis of glutathione, resulted in a 95% depletion of ECS1 transcript, a 72% decrease of ECS1 polypeptide, and a 60% drop in glutathione content. These results were comparable with those obtained upon analysis of Arabidopsis seedlings bearing the cad2-1 mutant allele of ECS1. We also improved the procedure for RNAi inactivation of several genes simultaneously. Finally, because we isolated protoplasts from tissues of 14-d-old seedlings instead of 1-month-old mature plants, the described procedure is rapid (as it only takes 20 d from seed planting to functional studies), suitable for analyzing multiple genes in parallel, and independent of cloning dsRNAs into plant expression vectors. Therefore, RNAi in protoplasts complements existing genetic tools, as it allows rapid, cost- and space-efficient initial screening and selection of genes for subsequent in planta studies.

  12. Reverse genetics in ecological research.

    Directory of Open Access Journals (Sweden)

    Jens Schwachtje

    Full Text Available By precisely manipulating the expression of individual genetic elements thought to be important for ecological performance, reverse genetics has the potential to revolutionize plant ecology. However, untested concerns about possible side-effects of the transformation technique, caused by Agrobacterium infection and tissue culture, on plant performance have stymied research by requiring onerous sample sizes. We compare 5 independently transformed Nicotiana attenuata lines harboring empty vector control (EVC T-DNA lacking silencing information with isogenic wild types (WT, and measured a battery of ecologically relevant traits, known to be important in plant-herbivore interactions: phytohormones, secondary metabolites, growth and fitness parameters under stringent competitive conditions, and transcriptional regulation with microarrays. As a positive control, we included a line silenced in trypsin proteinase inhibitor gene (TPI expression, a potent anti-herbivore defense known to exact fitness costs in its expression, in the analysis. The experiment was conducted twice, with 10 and 20 biological replicates per genotype. For all parameters, we detected no difference between any EVC and WT lines, but could readily detect a fitness benefit of silencing TPI production. A statistical power analyses revealed that the minimum sample sizes required for detecting significant fitness differences between EVC and WT was 2-3 orders of magnitude larger than the 10 replicates required to detect a fitness effect of TPI silencing. We conclude that possible side-effects of transformation are far too low to obfuscate the study of ecologically relevant phenotypes.

  13. Reverse genetics: Its origins and prospects

    Energy Technology Data Exchange (ETDEWEB)

    Berg, P. (Stanford Univ., CA (United States))

    1991-04-01

    The nucleotide sequence of a gene and its flanking segments alone will not tell us how its expression is regulated during development and differentiation, or in response to environmental changes. To comprehend the physiological significance of the molecular details requires biological analysis. Recombinant DNA techniques provide a powerful experimental approach. A strategy termed reverse genetics' utilizes the analysis of the activities of mutant and normal genes and experimentally constructed mutants to explore the relationship between gene structure and function thereby helping elucidate the relationship between genotype and phenotype.

  14. Arenavirus reverse genetics for vaccine development.

    Science.gov (United States)

    Ortiz-Riaño, Emilio; Cheng, Benson Yee Hin; Carlos de la Torre, Juan; Martínez-Sobrido, Luis

    2013-06-01

    Arenaviruses are important human pathogens with no Food and Drug Administration (FDA)-licensed vaccines available and current antiviral therapy being limited to an off-label use of the nucleoside analogue ribavirin of limited prophylactic efficacy. The development of reverse genetics systems represented a major breakthrough in arenavirus research. However, rescue of recombinant arenaviruses using current reverse genetics systems has been restricted to rodent cells. In this study, we describe the rescue of recombinant arenaviruses from human 293T cells and Vero cells, an FDA-approved line for vaccine development. We also describe the generation of novel vectors that mediate synthesis of both negative-sense genome RNA and positive-sense mRNA species of lymphocytic choriomeningitis virus (LCMV) directed by the human RNA polymerases I and II, respectively, within the same plasmid. This approach reduces by half the number of vectors required for arenavirus rescue, which could facilitate virus rescue in cell lines approved for human vaccine production but that cannot be transfected at high efficiencies. We have shown the feasibility of this approach by rescuing both the Old World prototypic arenavirus LCMV and the live-attenuated vaccine Candid#1 strain of the New World arenavirus Junín. Moreover, we show the feasibility of using these novel strategies for efficient rescue of recombinant tri-segmented both LCMV and Candid#1.

  15. Reversing hypoxic cell chemoresistance in vitro using genetic and small molecule approaches targeting hypoxia inducible factor-1.

    Science.gov (United States)

    Brown, Louisa M; Cowen, Rachel L; Debray, Camille; Eustace, Amanda; Erler, Janine T; Sheppard, Freda C D; Parker, Catriona A; Stratford, Ian J; Williams, Kaye J

    2006-02-01

    The resistance of hypoxic cells to conventional chemotherapy is well documented. Using both adenovirus-mediated gene delivery and small molecules targeting hypoxia-inducible factor-1 (HIF-1), we evaluated the impact of HIF-1 inhibition on the sensitivity of hypoxic tumor cells to etoposide. The genetic therapy exploited a truncated HIF-1alpha protein that acts as a dominant-negative HIF-1alpha (HIF-1alpha-no-TAD). Its functionality was validated in six human tumor cell lines using HIF-1 reporter assays. An EGFP-fused protein demonstrated that the dominant-negative HIF-1alpha was nucleus-localized and constitutively expressed irrespective of oxygen tension. The small molecules studied were quinocarmycin monocitrate (KW2152), its analog 7-cyanoquinocarcinol (DX-52-1), and topotecan. DX-52-1 and topotecan have been previously established as HIF-1 inhibitors. HT1080 and HCT116 cells were treated with either AdHIF-1alpha-no-TAD or nontoxic concentrations (0.1 microM; TAD (multiplicity of infection 50) ablated the anoxic resistance in both cell lines (IC(50) values: HT1080, 0.7 +/- 0.04 microM; HCT116, 3 +/- 1 microM). HIF-1alpha-no-TAD expression inhibited HIF-1-mediated down-regulation of the proapoptotic protein Bid under anoxia. These data support the potential development of HIF-1 targeted approaches in combination with chemotherapy, where hypoxic cell resistance contributes to treatment failure.

  16. Reverse genetics of Newcastle disease virus

    Science.gov (United States)

    Reverse genetics allows the generation of recombinant viruses or vectors used in functional studies, vaccine development, and gene therapy. This technique allows genetic manipulation and cloning of viral genomes, mutation through site-directed mutagenesis, and gene insertion or deletion, among othe...

  17. Reversing hypoxic cell chemoresistance in vitro using genetic and small molecule approaches targeting hypoxia inducible factor-1

    DEFF Research Database (Denmark)

    Brown, Louisa M; Cowen, Rachel L; Debray, Camille;

    2006-01-01

    . The genetic therapy exploited a truncated HIF-1alpha protein that acts as a dominant-negative HIF-1alpha (HIF-1alpha-no-TAD). Its functionality was validated in six human tumor cell lines using HIF-1 reporter assays. An EGFP-fused protein demonstrated that the dominant-negative HIF-1alpha was nucleus......HIF-1alpha-no-TAD or nontoxic concentrations (0.1 microM; ... higher than those in air for HT1080 (2.2 +/- 0.3 versus 0.7 +/- 0.2 microM) and HCT116 (9 +/- 4 versus 3 +/- 2 microM) cells. KW2152 and DX-52-1 significantly reduced the anoxic etoposide IC(50) in HT1080 cells, whereas only KW2152 yielded sensitization in HCT116 cells. In contrast, AdHIF-1alpha-no-TAD...

  18. Identification of genes necessary for wild-type levels of seed phytic acid in Arabidopsis thaliana using a reverse genetics approach.

    Science.gov (United States)

    Kim, Sang-Ic; Tai, Thomas H

    2011-08-01

    The majority of phosphorus (P) in seeds is found in phytic acid (InsP(6)) which accumulates as the mixed salt phytate. InsP(6) is generally considered to be an anti-nutrient and the development of low phytic acid (lpa) seed crops is of significant interest. We have employed a reverse genetics approach to examine the impact of disrupting genes involved in inositol phosphate metabolism on Arabidopsis seed InsP(6) levels. Our analysis revealed that knockout mutations in three genes (AtITPK1, AtITPK4, and AtMIK/At5g58730) reduced seed InsP(6) in addition to knockouts of four previously reported genes (AtIPK1, AtIPK2β, AtMRP5, and At5g60760). Seeds of these lpa mutants also exhibited reduced germination under various stress conditions. The greatest reduction in InsP(6) (>70%) was observed in atmrp5 seeds which were also among the least sensitive to the stresses examined. Expression analysis of the lpa genes revealed three distinct patterns in developing siliques consistent with their presumed roles. Disruption of each lpa gene resulted in changes in the expression in some of the other lpa genes indicating that transcription of lpa genes is modulated by other constituents of InsP(6) metabolism. While all the lpa genes represent possible targets for genetic engineering of low phytate seed crops, mutations in AtMRP5, AtMIK, and At5g60760 may be most successful for conventional approaches such as mutation breeding.

  19. Tackling feline infectious peritonitis via reverse genetics.

    Science.gov (United States)

    Thiel, Volker; Thiel, Heinz-Jürgen; Tekes, Gergely

    2014-01-01

    Feline infectious peritonitis (FIP) is caused by feline coronaviruses (FCoVs) and represents one of the most important lethal infectious diseases of cats. To date, there is no efficacious prevention and treatment, and our limited knowledge on FIP pathogenesis is mainly based on analysis of experiments with field isolates. In a recent study, we reported a promising approach to study FIP pathogenesis using reverse genetics. We generated a set of recombinant FCoVs and investigated their pathogenicity in vivo. The set included the type I FCoV strain Black, a type I FCoV strain Black with restored accessory gene 7b, two chimeric type I/type II FCoVs and the highly pathogenic type II FCoV strain 79-1146. All recombinant FCoVs and the reference strain isolates were found to establish productive infections in cats. While none of the type I FCoVs and chimeric FCoVs induced FIP, the recombinant type II FCoV strain 79-1146 was as pathogenic as the parental isolate. Interestingly, an intact ORF 3c was confirmed to be restored in all viruses (re)isolated from FIP-diseased animals.

  20. Transgenesis and reverse genetics of mosquito innate immunity.

    Science.gov (United States)

    Shin, Sang Woon; Kokoza, Vladimir A; Raikhel, Alexander S

    2003-11-01

    In recent years, mosquito molecular biology has been a scene of astounding achievements, namely the development of genetic transformation, characterization of inducible tissue-specific promoters, and acquirement of mosquito genome sequences. However, the lack of a complete genetic tool box for mosquitoes remains a serious obstacle in our ability to study essential mosquito-specific mechanisms. Unlike Drosophila, very few null mutations for mosquito genes exist. The development of reverse-genetic analyses based on RNAi and transgenic techniques will help to compensate for these deficiencies and aid in identification of critical genes in important regulatory pathways. The study of mosquito innate immunity is one example and described here. In this study, we combine mosquito transgenesis with reverse genetics. The advantage of transgenesis is the ability to establish genetically stable, dominant-negative and overexpression phenotypes. Using the blood-meal-activated vitellogenin gene (Vg) promoter, we have generated transgenic mosquitoes with blood-meal-activated, overexpressed antimicrobial peptides, Defensin A and Cecropin A. Moreover, we have recently generated a transgenic dominant-negative Relish mosquito strain, which after taking a blood meal, becomes immune-deficient to infection by Gram-negative bacteria. The latter accomplishment has opened the door to a reverse-genetic approach in mosquitoes based on transgenesis.

  1. Manipulations in Maternal Environment Reverse Periodontitis in Genetically Predisposed Rats

    OpenAIRE

    Sluyter, Frans; Breivik, Torbjørn; Cools, Alexander

    2002-01-01

    The predisposition to develop periodontitis is partly genetically determined in humans as well as in animals. Here we demonstrate, however, that early manipulations in the maternal environment of an animal (rat) model of periodontitis can fully reverse the genetic predisposition to develop periodontitis at adult age.

  2. Reversible circuit synthesis by genetic programming using dynamic gate libraries

    Science.gov (United States)

    Abubakar, Mustapha Y.; Jung, Low Tang; Zakaria, Nordin; Younes, Ahmed; Abdel-Aty, Abdel-Haleem

    2017-06-01

    We have defined a new method for automatic construction of reversible logic circuits by using the genetic programming approach. The choice of the gate library is 100% dynamic. The algorithm is capable of accepting all possible combinations of the following gate types: NOT TOFFOLI, NOT PERES, NOT CNOT TOFFOLI, NOT CNOT SWAP FREDKIN, NOT CNOT TOFFOLI SWAP FREDKIN, NOT CNOT PERES, NOT CNOT SWAP FREDKIN PERES, NOT CNOT TOFFOLI PERES and NOT CNOT TOFFOLI SWAP FREDKIN PERES. Our method produced near optimum circuits in some cases when a particular subset of gate types was used in the library. Meanwhile, in some cases, optimal circuits were produced due to the heuristic nature of the algorithm. We compared the outcomes of our method with several existing synthesis methods, and it was shown that our algorithm performed relatively well compared to the previous synthesis methods in terms of the output efficiency of the algorithm and execution time as well.

  3. Pragmatic approaches to genetic screening.

    NARCIS (Netherlands)

    Mallia, P.; Have, H.A.M.J. ten

    2005-01-01

    Pragmatic approaches to genetic testing are discussed and appraised. Whilst there are various schools of pragmatism, the Deweyan approach seems to be the most appreciated in bioethics as it allows a historical approach indebted to Hegel. This in turn allows the pragmatist to specify and balance prin

  4. Genetic program based data mining to reverse engineer digital logic

    Science.gov (United States)

    Smith, James F., III; Nguyen, Thanh Vu H.

    2006-04-01

    A data mining based procedure for automated reverse engineering and defect discovery has been developed. The data mining algorithm for reverse engineering uses a genetic program (GP) as a data mining function. A genetic program is an algorithm based on the theory of evolution that automatically evolves populations of computer programs or mathematical expressions, eventually selecting one that is optimal in the sense it maximizes a measure of effectiveness, referred to as a fitness function. The system to be reverse engineered is typically a sensor. Design documents for the sensor are not available and conditions prevent the sensor from being taken apart. The sensor is used to create a database of input signals and output measurements. Rules about the likely design properties of the sensor are collected from experts. The rules are used to create a fitness function for the genetic program. Genetic program based data mining is then conducted. This procedure incorporates not only the experts' rules into the fitness function, but also the information in the database. The information extracted through this process is the internal design specifications of the sensor. Uncertainty related to the input-output database and the expert based rule set can significantly alter the reverse engineering results. Significant experimental and theoretical results related to GP based data mining for reverse engineering will be provided. Methods of quantifying uncertainty and its effects will be presented. Finally methods for reducing the uncertainty will be examined.

  5. Reverse genetics mediated recovery of infectious murine norovirus.

    Science.gov (United States)

    Arias, Armando; Ureña, Luis; Thorne, Lucy; Yunus, Muhammad A; Goodfellow, Ian

    2012-06-24

    efficiency of viral recovery by conventional reverse genetics approaches. Here we report two different strategies based on the generation of murine norovirus-1 (referred to as MNV herewith) transcripts capped at the 5' end. One of the methods involves both in vitro synthesis and capping of viral RNA, whereas the second approach entails the transcription of MNV cDNA in cells expressing T7 RNA polymerase. The availability of these reverse genetics systems for the study of MNV and a small animal model has provided an unprecedented ability to dissect the role of viral sequences in replication and pathogenesis (15-17).

  6. TILLING is an effective reverse genetics technique for Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Zetka Monique C

    2006-10-01

    Full Text Available Abstract Background TILLING (Targeting Induced Local Lesions in Genomes is a reverse genetic technique based on the use of a mismatch-specific enzyme that identifies mutations in a target gene through heteroduplex analysis. We tested this technique in Caenorhabditis elegans, a model organism in which genomics tools have been well developed, but limitations in reverse genetics have restricted the number of heritable mutations that have been identified. Results To determine whether TILLING represents an effective reverse genetic strategy for C. elegans we generated an EMS-mutagenised population of approximately 1500 individuals and screened for mutations in 10 genes. A total of 71 mutations were identified by TILLING, providing multiple mutant alleles for every gene tested. Some of the mutations identified are predicted to be silent, either because they are in non-coding DNA or because they affect the third bp of a codon which does not change the amino acid encoded by that codon. However, 59% of the mutations identified are missense alleles resulting in a change in one of the amino acids in the protein product of the gene, and 3% are putative null alleles which are predicted to eliminate gene function. We compared the types of mutation identified by TILLING with those previously reported from forward EMS screens and found that 96% of TILLING mutations were G/C-to-A/T transitions, a rate significantly higher than that found in forward genetic screens where transversions and deletions were also observed. The mutation rate we achieved was 1/293 kb, which is comparable to the mutation rate observed for TILLING in other organisms. Conclusion We conclude that TILLING is an effective and cost-efficient reverse genetics tool in C. elegans. It complements other reverse genetic techniques in this organism, can provide an allelic series of mutations for any locus and does not appear to have any bias in terms of gene size or location. For eight of the 10

  7. A genetic engineering approach to genetic algorithms.

    Science.gov (United States)

    Gero, J S; Kazakov, V

    2001-01-01

    We present an extension to the standard genetic algorithm (GA), which is based on concepts of genetic engineering. The motivation is to discover useful and harmful genetic materials and then execute an evolutionary process in such a way that the population becomes increasingly composed of useful genetic material and increasingly free of the harmful genetic material. Compared to the standard GA, it provides some computational advantages as well as a tool for automatic generation of hierarchical genetic representations specifically tailored to suit certain classes of problems.

  8. An insightful approach for understanding solvatochromic reversal

    Science.gov (United States)

    Manzoni, Vinicius; Coutinho, Kaline; Canuto, Sylvio

    2016-07-01

    Several studies have shown that organic dyes may show solvatochromic reversal with respect to the solvent polarity. This controversial non-monotonic behavior is still not well understood. This has been analyzed here using the merocyanine of Brooker as the working example. Associating a continuous variable to model the solvent polarity a solvatochromic reversal is obtained with a single solute without aggregation. This reversal is in excellent agreement with the experimental results and is shown to be the outcome of a competition between structural change and intramolecular charge transfer.

  9. Genetic Synthesis of New Reversible/Quantum Ternary Comparator

    Directory of Open Access Journals (Sweden)

    DEIBUK, V.

    2015-08-01

    Full Text Available Methods of quantum/reversible logic synthesis are based on the use of the binary nature of quantum computing. However, multiple-valued logic is a promising choice for future quantum computer technology due to a number of advantages over binary circuits. In this paper we have developed a synthesis of ternary reversible circuits based on Muthukrishnan-Stroud gates using a genetic algorithm. The method of coding chromosome is presented, and well-grounded choice of algorithm parameters allowed obtaining better circuit schemes of one- and n-qutrit ternary comparators compared with other methods. These parameters are quantum cost of received reversible devices, delay time and number of constant input (ancilla lines. Proposed implementation of the genetic algorithm has led to reducing of the device delay time and the number of ancilla qutrits to 1 and 2n-1 for one- and n-qutrits full comparators, respectively. For designing of n-qutrit comparator we have introduced a complementary device which compares output functions of 1-qutrit comparators.

  10. Implementation of Genetic Algorithm in Network Modelling of Multi-level Reverse Logistics for Single Product

    Directory of Open Access Journals (Sweden)

    Siva Prasad Darla

    2014-08-01

    Full Text Available In this study, a multi level reverse logistics network is developed for a single product. Reverse logistics is a logistic activity beginning from intake of products returned by customers to selling of remanufactured or new products in market; so, it is considered that reverse flow of used products is from various sources like customers, dealers, retailers, manufacturers, etc., to remanufacturer and followed by transportation to secondary market. Due to uncertainties, any traditional supply chain approach to identify potential manufacturing facilities in this situation cannot be employed. Hence, Genetic Algorithm (GA is used for optimization and minimization of various costs involved in reverse logistics process. A sample numerical data is considered to test performance of the proposed model.

  11. An Approach to Simplify Reversible Logic Circuits

    Directory of Open Access Journals (Sweden)

    Pabitra Roy

    2012-09-01

    Full Text Available Energy loss is one of the major problems in traditional irreversible circuits. For every bit of information loss kTln2 joules of heat is lost. In order to reduce the energy loss the concept of reversible logic circuits are introduced. Here we have described an algorithm for simplifying the reversible logic circuit and hence reduction of circuit cost and energy. The algorithm considers sub_circuit with respect to their number of lines and contiguous gates. The resulting sub_circuits are re-synthesized with smaller equivalent implementation. The process continues until circuit cost reaches good enough for Application or until a given computation budget has been exhausted. The circuit is constructed by NOT, CNOT and Toffoli gates only. By applying the algorithm and using the equivalent implementation we will get significant reduction of circuit cost and hence energy.

  12. [Applications of reverse genetics in studying classical swine fever virus].

    Science.gov (United States)

    Liu, Dafei; Sun, Yuan; Qiu, Huaji

    2009-10-01

    Classical swine fever (CSF), caused by classical swine fever virus (CSFV), has been epidemic or endemic in many countries, and causes great economical losses to pig industry worldwide. Attenuated vaccines (such as C-strain) have played an important role in the control of CSF. Recently some new phenomena appear, such as atypical and persistent infections of CSF, immunization failure and so on. Meanwhile, eradication programs have been implemented in many countries, restricting the widespread applications of attenuated vaccines. Thus, currently the priority is to strengthen the research in pathogenesis and transmission mechanisms, as well as to develop marker vaccines. Recently, the applications of reverse genetics technology open up a new way for research of structure and function of CSFV proteins and development of novel vaccines against CSF. This review focuses on the progress of applications of reverse genetics in the functional analysis and marker vaccine development of CSFV, and also discusses the problems confronted now and prospective aspects in the study of CSFV.

  13. Deciphering the biology of porcine epidemic diarrhea virus in the era of reverse genetics.

    Science.gov (United States)

    Teeravechyan, Samaporn; Frantz, Phanramphoei Namprachan; Wongthida, Phonphimon; Chailangkarn, Thanathom; Jaru-Ampornpan, Peera; Koonpaew, Surapong; Jongkaewwattana, Anan

    2016-12-02

    Emergence of the porcine epidemic diarrhea virus (PEDV) as a global threat to the swine industry underlies the urgent need for deeper understanding of this virus. To date, we have yet to identify functions for all the major gene products, much less grasp their implications for the viral life cycle and pathogenic mechanisms. A major reason is the lack of genetic tools for studying PEDV. In this review, we discuss the reverse genetics approaches that have been successfully used to engineer infectious clones of PEDV as well as other potential and complementary methods that have yet to be applied to PEDV. The importance of proper cell culture for successful PEDV propagation and maintenance of disease phenotype are addressed in our survey of permissive cell lines. We also highlight areas of particular relevance to PEDV pathogenesis and disease that have benefited from reverse genetics studies and pressing questions that await resolution by such studies. In particular, we examine the spike protein as a determinant of viral tropism, entry and virulence, ORF3 and its association with cell culture adaptation, and the nucleocapsid protein and its potential role in modulating PEDV pathogenicity. Finally, we conclude with an exploration of how reverse genetics can help mitigate the global impact of PEDV by addressing the challenges of vaccine development. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Cost Efficient Design Approach for Reversible Programmable Logic Arrays

    Directory of Open Access Journals (Sweden)

    Md. RiazurRahman

    2016-06-01

    Full Text Available Reversible programmable logicarrays (PLA are at the heart of designing of efficient low power computers. This paper presents anefficient approach to design Reversible PLAs that maximizes the usability of garbage outputs and also reduces the number of ancilla inputs generated. The designfor proposed essentialcomponents and the architecture of reversible grid network for designing AND and EX-OR planes are also presented. Several algorithms have been proposed and presented to describe the programming interfaces in context of Reversible PLAs construction. Lastly, recent result on the trade-off between cost factors of standard benchmarkcircuits shows that the proposed design clearly outperforms the existing ones in terms various cost factors.

  15. Reverse engineering gene networks: Integrating genetic perturbations with dynamical modeling

    Science.gov (United States)

    Tegnér, Jesper; Yeung, M. K. Stephen; Hasty, Jeff; Collins, James J.

    2003-01-01

    While the fundamental building blocks of biology are being tabulated by the various genome projects, microarray technology is setting the stage for the task of deducing the connectivity of large-scale gene networks. We show how the perturbation of carefully chosen genes in a microarray experiment can be used in conjunction with a reverse engineering algorithm to reveal the architecture of an underlying gene regulatory network. Our iterative scheme identifies the network topology by analyzing the steady-state changes in gene expression resulting from the systematic perturbation of a particular node in the network. We highlight the validity of our reverse engineering approach through the successful deduction of the topology of a linear in numero gene network and a recently reported model for the segmentation polarity network in Drosophila melanogaster. Our method may prove useful in identifying and validating specific drug targets and in deconvolving the effects of chemical compounds. PMID:12730377

  16. Reverse genetics through random mutagenesis in Histoplasma capsulatum

    Directory of Open Access Journals (Sweden)

    Rappleye Chad A

    2009-11-01

    Full Text Available Abstract Background The dimorphic fungal pathogen Histoplasma capsulatum causes respiratory and systemic disease in humans and other mammals. Progress in understanding the mechanisms underlying the biology and the pathogenesis of Histoplasma has been hindered by a shortage of methodologies for mutating a gene of interest. Results We describe a reverse genetics process that combines the random mutagenesis of Agrobacterium-mediated transformation with screening techniques to identify targeted gene disruptions in a collection of insertion mutants. Isolation of the desired mutant is accomplished by arraying individual clones from a pool and employing a PCR-addressing method. Application of this procedure facilitated the isolation of a cbp1 mutant in a North American type 2 strain, a Histoplasma strain recalcitrant to gene knock-outs through homologous recombination. Optimization of cryopreservation conditions allows pools of mutants to be banked for later analysis and recovery of targeted mutants. Conclusion This methodology improves our ability to isolate mutants in targeted genes, thereby facilitating the molecular genetic analysis of Histoplasma biology. The procedures described are widely applicable to many fungal systems and will be of particular interest to those for which homologous recombination techniques are inefficient or do not currently exist.

  17. Optimization Approaches for Designing Quantum Reversible Arithmetic Logic Unit

    Science.gov (United States)

    Haghparast, Majid; Bolhassani, Ali

    2016-03-01

    Reversible logic is emerging as a promising alternative for applications in low-power design and quantum computation in recent years due to its ability to reduce power dissipation, which is an important research area in low power VLSI and ULSI designs. Many important contributions have been made in the literatures towards the reversible implementations of arithmetic and logical structures; however, there have not been many efforts directed towards efficient approaches for designing reversible Arithmetic Logic Unit (ALU). In this study, three efficient approaches are presented and their implementations in the design of reversible ALUs are demonstrated. Three new designs of reversible one-digit arithmetic logic unit for quantum arithmetic has been presented in this article. This paper provides explicit construction of reversible ALU effecting basic arithmetic operations with respect to the minimization of cost metrics. The architectures of the designs have been proposed in which each block is realized using elementary quantum logic gates. Then, reversible implementations of the proposed designs are analyzed and evaluated. The results demonstrate that the proposed designs are cost-effective compared with the existing counterparts. All the scales are in the NANO-metric area.

  18. Deciphering the genic basis of yeast fitness variation by simultaneous forward and reverse genetics.

    Science.gov (United States)

    Maclean, Calum J; Metzger, Brian P H; Yang, Jian-Rong; Ho, Wei-Chin; Moyers, Bryan; Zhang, Jianzhi

    2017-05-04

    The budding yeast Saccharomyces cerevisiae is the best studied eukaryote in molecular and cell biology, but its utility for understanding the genetic basis of phenotypic variation in natural populations is limited by inefficient association mapping due to strong and complex population structure. To overcome this challenge, we generated genome sequences for 85 strains and performed a comprehensive population genomic survey of a total of 190 diverse strains. We identified considerable variation in population structure among chromosomes and identified 181 genes that are absent from the reference genome. Many of these non-reference genes are expressed and we functionally confirmed that two of these genes confer increased resistance to antifungals. Next, we simultaneously measured the growth rates of over 4500 laboratory strains, each of which lacks a nonessential gene, and 81 natural strains across multiple environments using unique DNA barcode present in each strain. By combining the genome-wide reverse genetic information gained from the gene deletion strains with a genome-wide association analysis from the natural strains, we identified genomic regions associated with fitness variation in natural populations. To experimentally validate a subset of these associations, we used reciprocal hemizygosity tests, finding that while the combined forward and reverse genetic approaches can identify a single causal gene, the phenotypic consequences of natural genetic variation often follow a complicated pattern. The resources and approach provided outline an efficient and reliable route to association mapping in yeast and significantly enhance its value as a model for understanding the genetic mechanisms underlying phenotypic variation and evolution in natural populations. © The Author 2017. 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.

  19. A genetic algorithm for dynamic parameters reverse deduction of integrated anchorage system

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In the analysis of the system of anchoring bar and wall rock in small strain and longitudinal vibration dynamic response, the influence of the cement grouting as well as the rock layer on the anchor bar can be evaluated as the two kinds of parameters: the dynamic stiffness and the damp, which are the vital reference of the anchorage quality. Based on the analytic solution to the dynamic equation of the integrated anchor bar, the new approach which combines genetic algorithm and the toolbox of Matlab is applied to solve the problem of multi-parameters reverse deduction for integrated anchorage system in dynamic testing. Using the traits of the self-organizing, self-adapting and the fast convergence speed of the genetic algorithm, the optimum of all possible solutions to dynamic parameters is obtained by calculating the project instances. Examples show that the method presented in this paper is effective and reliable.

  20. Planning in Reverse: A Viable Approach to Organizational Leadership

    Science.gov (United States)

    Ballantyne, Scott; Berret, Beth; Wells, Mary Ellen

    2011-01-01

    Planning in Reverse is an innovative concept designed to make organizations more successful by altering the perspective utilized in the strategy process. What is needed for organizations to thrive in this new environment of change and uncertainty is a short-term approach for long-term viability. In this book, tools and concepts regarding Planning…

  1. Reverse Pharmacognosy and Reverse Pharmacology; Two Closely Related Approaches for Drug Discovery Development.

    Science.gov (United States)

    Saeidnia, Soodabeh; Gohari, Ahmad R; Manayi, Azadeh

    Pharmacognosy is a science, which study natural products as a source of new drug leads and effective drug development. Rational and economic search for novel lead structures could maximize the speed of drug discovery by using powerful high technology methods. Reverse pharmacognosy, a complementary to pharmacognosy, couples the high throughput screening (HTS), virtual screening and databases along with the knowledge of traditional medicines. These strategies lead to identification of numerous in vitro active and selective hits enhancing the speed of drug discovery from natural sources. Besides, reverse pharmacology is a target base drug discovery approach; in the first step, a hypothesis is made that the alteration of specific protein activity will produce beneficial curative effects. Both, reverse pharmacognosy and reverse pharmacology take advantages of high technology methods to accomplish their particular purposes. Moreover, reverse pharmacognosy effectively utilize traditional medicines and natural products as promising sources to provide new drug leads as well as promote the rational use of them by using valuable information like protein structure databases and chemical libraries which prepare pharmacological profile of traditional medicine, plant extract or natural compounds.

  2. A Multi-Stage Reverse Logistics Network Problem by Using Hybrid Priority-Based Genetic Algorithm

    Science.gov (United States)

    Lee, Jeong-Eun; Gen, Mitsuo; Rhee, Kyong-Gu

    Today remanufacturing problem is one of the most important problems regarding to the environmental aspects of the recovery of used products and materials. Therefore, the reverse logistics is gaining become power and great potential for winning consumers in a more competitive context in the future. This paper considers the multi-stage reverse Logistics Network Problem (m-rLNP) while minimizing the total cost, which involves reverse logistics shipping cost and fixed cost of opening the disassembly centers and processing centers. In this study, we first formulate the m-rLNP model as a three-stage logistics network model. Following for solving this problem, we propose a Genetic Algorithm pri (GA) with priority-based encoding method consisting of two stages, and introduce a new crossover operator called Weight Mapping Crossover (WMX). Additionally also a heuristic approach is applied in the 3rd stage to ship of materials from processing center to manufacturer. Finally numerical experiments with various scales of the m-rLNP models demonstrate the effectiveness and efficiency of our approach by comparing with the recent researches.

  3. Enlarged transacromial superior approach with reverse shoulder arthroplasty for fractures

    Directory of Open Access Journals (Sweden)

    Alexandre Poignard

    2013-10-01

    Full Text Available The authors describe a step-by-step technique for reverse total shoulder arthroplasty using arthrotomy via the enlarged transacromial superior approach. This technique seems ideal for reinsertion of the tuberosities and to ensure adequate postoperative tensional balance of the infraspinatus and the subscapularis, which is critical for the rotator cuffs to function properly and to achieve optimal arthroplasty stability. Reviewing these different steps helps understanding each rotator cuff individual component's contribution to achieve optimal arthroplasty stability and external rotation with a reverse shoulder arthroplasty.

  4. Addition of exogenous polypeptides on the mammalian reovirus outer capsid using reverse genetics.

    Science.gov (United States)

    Brochu-Lafontaine, Virginie; Lemay, Guy

    2012-02-01

    Addition of exogenous peptide sequences on viral capsids is a powerful approach to study the process of viral infection or to retarget viruses toward defined cell types. Until recently, it was not possible to manipulate the genome of mammalian reovirus and this was an obstacle to the addition of exogenous sequence tags onto the capsid of a replicating virus. This obstacle has now been overcome by the availability of the plasmid-based reverse genetics system. In the present study, reverse genetics was used to introduce different exogenous peptides, up to 40 amino acids long, at the carboxyl-terminal end of the σ1 outer capsid protein. The tagged viruses obtained were infectious, produce plaques of similar size, and could be easily propagated at high titers. However, attempts to introduce a 750 nucleotides-long sequence failed, even when it was added after the stop codon, suggesting a possible size limitation at the nucleic acid level. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. [Incest--forensic genetic approach].

    Science.gov (United States)

    Raczek, Ewa

    2012-01-01

    The paper presents intimate relationships between biologically and legally close relatives, complicated in the social, culture and religion perspective. (art. 201 of the Penal Code), but it chiefly addresses problems associated with giving opinion on the fatherhood towards the incestuous child. The report calls for a broader interest in this issue from expert witnesses in forensic genetics, as well as encourages them to publish examples taken from their own professional experience that may unquestionably be helpful to other practitioners in this field and above all will lead to extending educational methods related to widely understood DNA analysis in giving an opinion on arguable fatherhood.

  6. Educational Approach of Refactoring in Facilitating Reverse Engineering

    Directory of Open Access Journals (Sweden)

    Mazni Omar

    2010-05-01

    Full Text Available Refactoring improves software codes and design. This activity often neglected by software developers because they need time to decide tactically where and when to refactor codes. Although the concepts theoretically instilled in the developer’s mind, this activity is not easy to apply and visualize. This situation became more problematic when deals with inexperienced developers. Therefore, there is a need to develop an educational approach to comprehend refactoring activity.This activity was applied through reverse engineering tasks. Thesoftware engineering (SE teams were required to apply reverseengineering activity in order to check the consistency betweencodes and design. The teams were encouraged to apply Model-View-Controller (MVC pattern architecture in order to facilitatethe activities. Findings revealed that Extreme Programming (XPteams managed to complete reverse engineering tasks earlierthan Formal teams. This study found that the approach is important to increase understanding of refactoring activities in reverse engineering process. This approach will be furthered applied for others SE teams to gain more insight and perceptions towards improving SE course.

  7. A Predictive Approach to Network Reverse-Engineering

    Science.gov (United States)

    Wiggins, Chris

    2005-03-01

    A central challenge of systems biology is the ``reverse engineering" of transcriptional networks: inferring which genes exert regulatory control over which other genes. Attempting such inference at the genomic scale has only recently become feasible, via data-intensive biological innovations such as DNA microrrays (``DNA chips") and the sequencing of whole genomes. In this talk we present a predictive approach to network reverse-engineering, in which we integrate DNA chip data and sequence data to build a model of the transcriptional network of the yeast S. cerevisiae capable of predicting the response of genes in unseen experiments. The technique can also be used to extract ``motifs,'' sequence elements which act as binding sites for regulatory proteins. We validate by a number of approaches and present comparison of theoretical prediction vs. experimental data, along with biological interpretations of the resulting model. En route, we will illustrate some basic notions in statistical learning theory (fitting vs. over-fitting; cross- validation; assessing statistical significance), highlighting ways in which physicists can make a unique contribution in data- driven approaches to reverse engineering.

  8. Quantum Genetics in terms of Quantum Reversible Automata and Quantum Computation of Genetic Codes and Reverse Transcription

    CERN Document Server

    Baianu,I C

    2004-01-01

    The concepts of quantum automata and quantum computation are studied in the context of quantum genetics and genetic networks with nonlinear dynamics. In previous publications (Baianu,1971a, b) the formal concept of quantum automaton and quantum computation, respectively, were introduced and their possible implications for genetic processes and metabolic activities in living cells and organisms were considered. This was followed by a report on quantum and abstract, symbolic computation based on the theory of categories, functors and natural transformations (Baianu,1971b; 1977; 1987; 2004; Baianu et al, 2004). The notions of topological semigroup, quantum automaton, or quantum computer, were then suggested with a view to their potential applications to the analogous simulation of biological systems, and especially genetic activities and nonlinear dynamics in genetic networks. Further, detailed studies of nonlinear dynamics in genetic networks were carried out in categories of n-valued, Lukasiewicz Logic Algebra...

  9. The calculus a genetic approach

    CERN Document Server

    Toeplitz, Otto

    2007-01-01

    When first published posthumously in 1963, this book presented a radically different approach to the teaching of calculus.  In sharp contrast to the methods of his time, Otto Toeplitz did not teach calculus as a static system of techniques and facts to be memorized. Instead, he drew on his knowledge of the history of mathematics and presented calculus as an organic evolution of ideas beginning with the discoveries of Greek scholars, such as Archimedes, Pythagoras, and Euclid, and developing through the centuries in the work of Kepler, Galileo, Fermat, Newton, and Leibniz. Through this unique a

  10. Genetic Algorithm Approaches for Actuator Placement

    Science.gov (United States)

    Crossley, William A.

    2000-01-01

    This research investigated genetic algorithm approaches for smart actuator placement to provide aircraft maneuverability without requiring hinged flaps or other control surfaces. The effort supported goals of the Multidisciplinary Design Optimization focus efforts in NASA's Aircraft au program. This work helped to properly identify various aspects of the genetic algorithm operators and parameters that allow for placement of discrete control actuators/effectors. An improved problem definition, including better definition of the objective function and constraints, resulted from this research effort. The work conducted for this research used a geometrically simple wing model; however, an increasing number of potential actuator placement locations were incorporated to illustrate the ability of the GA to determine promising actuator placement arrangements. This effort's major result is a useful genetic algorithm-based approach to assist in the discrete actuator/effector placement problem.

  11. Development of a novel single step reverse genetics system for feline calicivirus.

    Science.gov (United States)

    Oka, Tomoichiro; Takagi, Hirotaka; Tohya, Yukinobu

    2014-10-01

    The reverse genetics system is a useful tool to generate infectious virus. Feline calicivirus (FCV), a member of the genus Vesivirus in the family Caliciviridae, has a positive sense, single-stranded RNA genome. Two reverse genetics systems have been established for FCV; however, these methods need multi-steps to produce progeny infectious virus. In this study, a novel plasmid-based single step reverse genetics system for FCV has been developed. The plasmid carries FCV F4 strain genomic sequence with an introduced silent mutation. In addition, at the 5'- and 3'-end, a human elongation factor-1α promoter and a cis-acting hepatitis delta virus ribozyme following poly-A, were added, respectively. When the plasmid was transfected into Crandell-Rees feline kidney cells, progeny FCV was generated. The reverse genetics system-derived FCV (rFCV) showed similar growth kinetics and antigenic characteristics and had identical genomic terminals to those of the original FCV F4 strain. The presence of the introduced silent mutation in the rFCV genomic cDNA supported that the progeny virus was originated from the plasmid. This novel FCV reverse genetics system is simple and can be used to evaluate the functions of the viral genome, proteins, and phenotypic characterization of FCV strains in the future. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. genomic and transcriptomic approaches towards the genetic ...

    African Journals Online (AJOL)

    USER

    to the complex nature of these stresses, and the genotype x environment interaction (GxE). .... collection (Azam-Ali et al., 2001); (vi) biological .... Integrative platform to study gene function and gene evolution in legumes ..... a powerful dissection of the genetic control of ... complemented by a new approach called genomic.

  13. Directed genetic modification of African horse sickness virus by reverse genetics

    Directory of Open Access Journals (Sweden)

    Elaine Vermaak

    2015-07-01

    Full Text Available African horse sickness virus (AHSV, a member of the Orbivirus genus in the family Reoviridae, is an arthropod-transmitted pathogen that causes a devastating disease in horses with a mortality rate greater than 90%. Fundamental research on AHSV and the development of safe, efficacious vaccines could benefit greatly from an uncomplicated genetic modification method to generate recombinant AHSV. We demonstrate that infectious AHSV can be recovered by transfection of permissive mammalian cells with transcripts derived in vitro from purified AHSV core particles. These findings were expanded to establish a genetic modification system for AHSV that is based on transfection of the cells with a mixture of purified core transcripts and a synthetic T7 transcript. This approach was applied successfully to recover a directed cross-serotype reassortant AHSV and to introduce a marker sequence into the viral genome. The ability to manipulate the AHSV genome and engineer specific mutants will increase understanding of AHSV replication and pathogenicity, as well as provide a tool for generating designer vaccine strains.

  14. [Progress in establishment and application of feline calicivirus reverse genetics operating system].

    Science.gov (United States)

    Zhao, Yanli; Dong, Hongwei; Chen, Xiaoqing; Gao, Chao; Liu, Qiuyan; Yang, Songtao; Hu, Guixue

    2015-01-01

    Feline calicivirus (FCV) is an important and highly prevalent pathogen of cats that causes feline respiratory disease. The reverse genetic systems for FCV have been established in national and international laboratories since 1995. This technique has been used widely in FCV basic research and good progress has consequently been made to determine the relationship between viral genome structures and the function of their proteins, the expression of foreign proteins, virus-host interactions, and viral pathogenic mechanisms. In this article,we review the state of progress with regards to the establishment and application of the FCV reverse genetic operating system,which will provide a useful reference tool for future related research.

  15. Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast

    Science.gov (United States)

    Oud, Bart; Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

    2012-01-01

    Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages. PMID:22152095

  16. Genome-wide analytical approaches for reverse metabolic engineering of industrially relevant phenotypes in yeast.

    Science.gov (United States)

    Oud, Bart; van Maris, Antonius J A; Daran, Jean-Marc; Pronk, Jack T

    2012-03-01

    Successful reverse engineering of mutants that have been obtained by nontargeted strain improvement has long presented a major challenge in yeast biotechnology. This paper reviews the use of genome-wide approaches for analysis of Saccharomyces cerevisiae strains originating from evolutionary engineering or random mutagenesis. On the basis of an evaluation of the strengths and weaknesses of different methods, we conclude that for the initial identification of relevant genetic changes, whole genome sequencing is superior to other analytical techniques, such as transcriptome, metabolome, proteome, or array-based genome analysis. Key advantages of this technique over gene expression analysis include the independency of genome sequences on experimental context and the possibility to directly and precisely reproduce the identified changes in naive strains. The predictive value of genome-wide analysis of strains with industrially relevant characteristics can be further improved by classical genetics or simultaneous analysis of strains derived from parallel, independent strain improvement lineages.

  17. New Approaches to Establish Genetic Causality

    Science.gov (United States)

    McNally, Elizabeth M.; George, Alfred L.

    2015-01-01

    Cardiovascular medicine has evolved rapidly in the era of genomics with many diseases having primary genetic origins becoming the subject of intense investigation. The resulting avalanche of information on the molecular causes of these disorders has prompted a revolution in our understanding of disease mechanisms and provided new avenues for diagnoses. At the heart of this revolution is the need to correctly classify genetic variants discovered during the course of research or reported from clinical genetic testing. This review will address current concepts related to establishing the cause and effect relationship between genomic variants and heart diseases. A survey of general approaches used for functional annotation of variants will also be presented. PMID:25864169

  18. Genetic Algorithm Approaches to Prebiobiotic Chemistry Modeling

    Science.gov (United States)

    Lohn, Jason; Colombano, Silvano

    1997-01-01

    We model an artificial chemistry comprised of interacting polymers by specifying two initial conditions: a distribution of polymers and a fixed set of reversible catalytic reactions. A genetic algorithm is used to find a set of reactions that exhibit a desired dynamical behavior. Such a technique is useful because it allows an investigator to determine whether a specific pattern of dynamics can be produced, and if it can, the reaction network found can be then analyzed. We present our results in the context of studying simplified chemical dynamics in theorized protocells - hypothesized precursors of the first living organisms. Our results show that given a small sample of plausible protocell reaction dynamics, catalytic reaction sets can be found. We present cases where this is not possible and also analyze the evolved reaction sets.

  19. Genetic Network Inference: From Co-Expression Clustering to Reverse Engineering

    Science.gov (United States)

    Dhaeseleer, Patrik; Liang, Shoudan; Somogyi, Roland

    2000-01-01

    Advances in molecular biological, analytical, and computational technologies are enabling us to systematically investigate the complex molecular processes underlying biological systems. In particular, using high-throughput gene expression assays, we are able to measure the output of the gene regulatory network. We aim here to review datamining and modeling approaches for conceptualizing and unraveling the functional relationships implicit in these datasets. Clustering of co-expression profiles allows us to infer shared regulatory inputs and functional pathways. We discuss various aspects of clustering, ranging from distance measures to clustering algorithms and multiple-duster memberships. More advanced analysis aims to infer causal connections between genes directly, i.e., who is regulating whom and how. We discuss several approaches to the problem of reverse engineering of genetic networks, from discrete Boolean networks, to continuous linear and non-linear models. We conclude that the combination of predictive modeling with systematic experimental verification will be required to gain a deeper insight into living organisms, therapeutic targeting, and bioengineering.

  20. Reverse genetics in Chlamydomonas: a platform for isolating insertional mutants

    OpenAIRE

    de Montaigu Amaury; Magneschi Leonardo; Catalanotti Claudia; Yang Wenqiang; Mus Florence; Pootakham Wirulda; Gonzalez-Ballester David; Higuera Jose J; Prior Matthew; Galván Aurora; Fernandez Emilio; Grossman Arthur R

    2011-01-01

    Abstract A method was developed to identify insertional mutants of Chlamydomonas reinhardtii disrupted for selected target genes. The approach relies on the generation of thousands of transformants followed by PCR-based screenings that allow for identification of strains harboring the introduced marker gene within specific genes of interest. Our results highlight the strengths and limitations of two independent screens that differed in the nature of the marker DNA used (PCR-amplified fragment...

  1. Reverse convex problems: an approach based on optimality conditions

    Directory of Open Access Journals (Sweden)

    Ider Tseveendorj

    2006-01-01

    Full Text Available We present some results concerning reverse convex problems. Global optimality conditions for the problems with a nonsmooth reverse convex constraint are established and convergence of an algorithm in the case of linear program with an additional quadratic reverse convex constraint is studied.

  2. Reverse convex problems: an approach based on optimality conditions

    OpenAIRE

    Ider Tseveendorj

    2006-01-01

    We present some results concerning reverse convex problems. Global optimality conditions for the problems with a nonsmooth reverse convex constraint are established and convergence of an algorithm in the case of linear program with an additional quadratic reverse convex constraint is studied.

  3. Forward and reverse genetics: The LORE1 retrotransposon insertion mutants

    DEFF Research Database (Denmark)

    Fukai, Eigo; Malolepszy, Anna; Sandal, Niels Nørgaard

    2014-01-01

    The endogenous Lotus retrotransposon 1 (LORE1) transposes in the germ line of Lotus japonicus plants that carry an active element. This feature of LORE1 has been exploited for generation of a large non-transgenic insertion mutant population, where insertions have been annotated using next......-generation sequencing approaches. The LORE1 mutant lines are freely available and can be ordered online. Endogenous retrotransposons are also active in many other plant species. Based on the methods developed for LORE1 mutagenesis, it should be simple to establish similar systems in other species, once an appropriate...

  4. Reverse genetics in Chlamydomonas: a platform for isolating insertional mutants

    Directory of Open Access Journals (Sweden)

    de Montaigu Amaury

    2011-07-01

    Full Text Available Abstract A method was developed to identify insertional mutants of Chlamydomonas reinhardtii disrupted for selected target genes. The approach relies on the generation of thousands of transformants followed by PCR-based screenings that allow for identification of strains harboring the introduced marker gene within specific genes of interest. Our results highlight the strengths and limitations of two independent screens that differed in the nature of the marker DNA used (PCR-amplified fragment containing the plasmid-free marker versus entire linearized plasmid with the marker and in the strategies used to maintain and store transformants.

  5. Master equation approach to reversible and conservative discrete systems.

    Science.gov (United States)

    Urbina, Felipe; Rica, Sergio

    2016-12-01

    A master equation approach is applied to a reversible and conservative cellular automaton model (Q2R). The Q2R model is a dynamical variation of the Ising model for ferromagnetism that possesses quite a rich and complex dynamics. The configuration space is composed of a huge number of cycles with exponentially long periods. Following Nicolis and Nicolis [G. Nicolis and C. Nicolis, Phys. Rev. A 38, 427 (1988)0556-279110.1103/PhysRevA.38.427], a coarse-graining approach is applied to the time series of the total magnetization, leading to a master equation that governs the macroscopic irreversible dynamics of the Q2R automata. The methodology is replicated for various lattice sizes. In the case of small systems, we show that the master equation leads to a tractable probability transfer matrix of moderate size, which provides a master equation for a coarse-grained probability distribution. The method is validated and some explicit examples are discussed.

  6. Master equation approach to reversible and conservative discrete systems

    Science.gov (United States)

    Urbina, Felipe; Rica, Sergio

    2016-12-01

    A master equation approach is applied to a reversible and conservative cellular automaton model (Q2R). The Q2R model is a dynamical variation of the Ising model for ferromagnetism that possesses quite a rich and complex dynamics. The configuration space is composed of a huge number of cycles with exponentially long periods. Following Nicolis and Nicolis [G. Nicolis and C. Nicolis, Phys. Rev. A 38, 427 (1988), 10.1103/PhysRevA.38.427], a coarse-graining approach is applied to the time series of the total magnetization, leading to a master equation that governs the macroscopic irreversible dynamics of the Q2R automata. The methodology is replicated for various lattice sizes. In the case of small systems, we show that the master equation leads to a tractable probability transfer matrix of moderate size, which provides a master equation for a coarse-grained probability distribution. The method is validated and some explicit examples are discussed.

  7. Reversible Circuit Synthesis Using a Cycle-Based Approach

    CERN Document Server

    Saeedi, Mehdi; Sedighi, Mehdi; Sasanian, Zahra

    2010-01-01

    Reversible logic has applications in various research areas including signal processing, cryptography and quantum computation. In this paper, direct NCT-based synthesis of a given $k$-cycle in a cycle-based synthesis scenario is examined. To this end, a set of seven building blocks is proposed that reveals the potential of direct synthesis of a given permutation to reduce both quantum cost and average runtime. To synthesize a given large cycle, we propose a decomposition algorithm to extract the suggested building blocks from the input specification. Then, a synthesis method is introduced which uses the building blocks and the decomposition algorithm. Finally, a hybrid synthesis framework is suggested which uses the proposed cycle-based synthesis method in conjunction with one of the recent NCT-based synthesis approaches which is based on Reed-Muller (RM) spectra. The time complexity and the effectiveness of the proposed synthesis approach are analyzed in detail. Our analyses show that the proposed hybrid fra...

  8. Optimization Approaches for Designing a Novel 4-Bit Reversible Comparator

    Science.gov (United States)

    Zhou, Ri-gui; Zhang, Man-qun; Wu, Qian; Li, Yan-cheng

    2013-02-01

    Reversible logic is a new rapidly developed research field in recent years, which has been receiving much attention for calculating with minimizing the energy consumption. This paper constructs a 4×4 new reversible gate called ZRQ gate to build quantum adder and subtraction. Meanwhile, a novel 1-bit reversible comparator by using the proposed ZRQC module on the basis of ZRQ gate is proposed as the minimum number of reversible gates and quantum costs. In addition, this paper presents a novel 4-bit reversible comparator based on the 1-bit reversible comparator. One of the vital important for optimizing reversible logic is to design reversible logic circuits with the minimum number of parameters. The proposed reversible comparators in this paper can obtain superiority in terms of the number of reversible gates, input constants, garbage outputs, unit delays and quantum costs compared with the existed circuits. Finally, MATLAB simulation software is used to test and verify the correctness of the proposed 4-bit reversible comparator.

  9. Pharmacological or genetic inactivation of the serotonin transporter improves reversal learning in mice.

    Science.gov (United States)

    Brigman, Jonathan L; Mathur, Poonam; Harvey-White, Judith; Izquierdo, Alicia; Saksida, Lisa M; Bussey, Timothy J; Fox, Stephanie; Deneris, Evan; Murphy, Dennis L; Holmes, Andrew

    2010-08-01

    Growing evidence supports a major contribution of cortical serotonin (5-hydroxytryptamine, 5-HT) to the modulation of cognitive flexibility and the cognitive inflexibility evident in neuropsychiatric disorders. The precise role of 5-HT and the influence of 5-HT gene variation in mediating this process is not fully understood. Using a touch screen-based operant system, we assessed reversal of a pairwise visual discrimination as an assay for cognitive flexibility. Effects of constitutive genetic or pharmacological inactivation of the 5-HT transporter (5-HTT) on reversal were examined by testing 5-HTT null mice and chronic fluoxetine-treated C57BL/6J mice, respectively. Effects of constitutive genetic loss or acute pharmacological depletion of 5-HT were assessed by testing Pet-1 null mice and para-chlorophenylalanine (PCPA)-treated C57BL/6J mice, respectively. Fluoxetine-treated C57BL/6J mice made fewer errors than controls during the early phase of reversal when perseverative behavior is relatively high. 5-HTT null mice made fewer errors than controls in completing the reversal task. However, reversal in Pet-1 null and PCPA-treated C57BL/6J mice was not different from controls. These data further support an important role for 5-HT in modulating reversal learning and provide novel evidence that inactivating the 5-HTT improves this process. These findings could have important implications for understanding and treating cognitive inflexibility in neuropsychiatric disease.

  10. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Odir A. Dellagostin

    2017-01-01

    Full Text Available Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.

  11. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Science.gov (United States)

    Dellagostin, Odir A.; Grassmann, André A.; Rizzi, Caroline; Schuch, Rodrigo A.; Jorge, Sérgio; Oliveira, Thais L.; McBride, Alan J. A.; Hartwig, Daiane D.

    2017-01-01

    Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins) are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV) has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis. PMID:28098813

  12. Reverse genetics of SARS-related coronavirus using vaccinia virus-based recombination.

    Directory of Open Access Journals (Sweden)

    Sjoerd H E van den Worm

    Full Text Available Severe acute respiratory syndrome (SARS is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV. Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs. In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E. Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs.

  13. Reverse Genetics of SARS-Related Coronavirus Using Vaccinia Virus-Based Recombination

    Science.gov (United States)

    Zevenhoven, Jessika C.; Weber, Friedemann; Züst, Roland; Kuri, Thomas; Dijkman, Ronald; Chang, Guohui; Siddell, Stuart G.; Snijder, Eric J.; Thiel, Volker; Davidson, Andrew D.

    2012-01-01

    Severe acute respiratory syndrome (SARS) is a zoonotic disease caused by SARS-related coronavirus (SARS-CoV) that emerged in 2002 to become a global health concern. Although the original outbreak was controlled by classical public health measures, there is a real risk that another SARS-CoV could re-emerge from its natural reservoir, either in its original form or as a more virulent or pathogenic strain; in which case, the virus would be difficult to control in the absence of any effective antiviral drugs or vaccines. Using the well-studied SARS-CoV isolate HKU-39849, we developed a vaccinia virus-based SARS-CoV reverse genetic system that is both robust and biosafe. The SARS-CoV genome was cloned in separate vaccinia virus vectors, (vSARS-CoV-5prime and vSARS-CoV-3prime) as two cDNAs that were subsequently ligated to create a genome-length SARS-CoV cDNA template for in vitro transcription of SARS-CoV infectious RNA transcripts. Transfection of the RNA transcripts into permissive cells led to the recovery of infectious virus (recSARS-CoV). Characterization of the plaques produced by recSARS-CoV showed that they were similar in size to the parental SARS-CoV isolate HKU-39849 but smaller than the SARS-CoV isolate Frankfurt-1. Comparative analysis of replication kinetics showed that the kinetics of recSARS-CoV replication are similar to those of SARS-CoV Frankfurt-1, although the titers of virus released into the culture supernatant are approximately 10-fold less. The reverse genetic system was finally used to generate a recSARS-CoV reporter virus expressing Renilla luciferase in order to facilitate the analysis of SARS-CoV gene expression in human dendritic cells (hDCs). In parallel, a Renilla luciferase gene was also inserted into the genome of human coronavirus 229E (HCoV-229E). Using this approach, we demonstrate that, in contrast to HCoV-229E, SARS-CoV is not able to mediate efficient heterologous gene expression in hDCs. PMID:22412934

  14. Reverse logistics network design: a holistic life cycle approach

    National Research Council Canada - National Science Library

    Daaboul, Joanna; Le Duigou, Julien; Penciuc, Diana; Eynard, Benoît

    2014-01-01

    .... This article addresses the issue of designing the reverse logistics network assuring the needed volume of recycled aluminum for the production of L-shaped front lower control arms for personal cars. It details the developed method and demonstrator for designing a reverse logistics network based on a life cycle assessment.

  15. Application of reverse genetics for producing attenuated vaccine strains against highly pathogenic avian influenza viruses.

    Science.gov (United States)

    Uchida, Yuko; Takemae, Nobuhiro; Saito, Takehiko

    2014-08-01

    In this study, reverse genetics was applied to produce vaccine candidate strains against highly pathogenic avian influenza viruses (HPAIVs) of the H5N1 subtype. The H5 subtype vaccine strains were generated by a reverse genetics method in a biosafety level 2 facility. The strain contained the HA gene from the H5N1 subtype HPAIV attenuated by genetic modification at the cleavage site, the NA gene derived from the H5N1 subtype HPAI or the H5N3 subtype of avian influenza virus and internal genes from A/Puerto Rico/8/34. Vaccination with an inactivated recombinant virus with oil-emulsion completely protected chickens from a homologous viral challenge with a 640 HAU or 3,200 HAU/vaccination dose. Vaccination with a higher dose of antigen, 3,200 HAU, was effective at increasing survival and efficiently reduced viral shedding even when challenged by a virus of a different HA clade. The feasibility of differentiation of infected from vaccinated animals (DIVA) was demonstrated against a challenge with H5N1 HPAIVs when the recombinant H5N3 subtype viruses were used as the antigens of the vaccine. Our study demonstrated that the use of reverse genetics would be an option to promptly produce an inactivated vaccine with better matching of antigenicity to a circulating strain.

  16. Reverse Genetics Approaches for the Development of Influenza Vaccines

    OpenAIRE

    Aitor Nogales; Luis Martínez-Sobrido

    2016-01-01

    Influenza viruses cause annual seasonal epidemics and occasional pandemics of human respiratory disease. Influenza virus infections represent a serious public health and economic problem, which are most effectively prevented through vaccination. However, influenza viruses undergo continual antigenic variation, which requires either the annual reformulation of seasonal influenza vaccines or the rapid generation of vaccines against potential pandemic virus strains. The segmented nature of influ...

  17. Immunotherapy: A promising approach to reverse sepsis-induced immunosuppression.

    Science.gov (United States)

    Patil, Naeem K; Bohannon, Julia K; Sherwood, Edward R

    2016-09-01

    Sepsis is defined as life-threatening organ dysfunction caused by dysregulated host responses to infection (Third International Consensus definition for Sepsis and septic shock). Despite decades of research, sepsis remains the leading cause of death in intensive care units. More than 40 clinical trials, most of which have targeted the sepsis-associated pro-inflammatory response, have failed. Thus, antibiotics and fluid resuscitation remain the mainstays of supportive care and there is intense need to discover and develop novel, targeted therapies to treat sepsis. Both pre-clinical and clinical studies over the past decade demonstrate unequivocally that sepsis not only causes hyper-inflammation, but also leads to simultaneous adaptive immune system dysfunction and impaired antimicrobial immunity. Evidences for immunosuppression include immune cell depletion (T cells most affected), compromised T cell effector functions, T cell exhaustion, impaired antigen presentation, increased susceptibility to opportunistic nosocomial infections, dysregulated cytokine secretion, and reactivation of latent viruses. Therefore, targeting immunosuppression provides a logical approach to treat protracted sepsis. Numerous pre-clinical studies using immunomodulatory agents such as interleukin-7, anti-programmed cell death 1 antibody (anti-PD-1), anti-programmed cell death 1 ligand antibody (anti-PD-L1), and others have demonstrated reversal of T cell dysfunction and improved survival. Therefore, identifying immunosuppressed patients with the help of specific biomarkers and administering specific immunomodulators holds significant potential for sepsis therapy in the future. This review focusses on T cell dysfunction during sepsis and discusses the potential immunotherapeutic agents to boost T cell function during sepsis and improve host resistance to infection.

  18. Copy-choice recombination by reverse transcriptases: Reshuffling of genetic markers mediated by RNA chaperones

    Science.gov (United States)

    Negroni, Matteo; Buc, Henri

    2000-01-01

    Copy-choice recombination efficiently reshuffles genetic markers in retroviruses. In vivo, the folding of the genomic RNA is controlled by the nucleocapsid protein (NC). We show that binding of NC onto the acceptor RNA molecule is sufficient to enhance recombination, providing evidence for a mechanism where the structure of the acceptor template determines the template switch. NC as well as another RNA chaperone (StpA) converts recombination into a widespread process no longer restricted to rare hot spots, an effect maximized when both the NC and the reverse transcriptase come from HIV-1. These data suggest that RNA chaperones confer a higher genetic flexibility to retroviruses. PMID:10829081

  19. 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.

  20. A novel mating approach for genetic algorithms.

    Science.gov (United States)

    Galán, Severino F; Mengshoel, Ole J; Pinter, Rafael

    2013-01-01

    Genetic algorithms typically use crossover, which relies on mating a set of selected parents. As part of crossover, random mating is often carried out. A novel approach to parent mating is presented in this work. Our novel approach can be applied in combination with a traditional similarity-based criterion to measure distance between individuals or with a fitness-based criterion. We introduce a parameter called the mating index that allows different mating strategies to be developed within a uniform framework: an exploitative strategy called best-first, an explorative strategy called best-last, and an adaptive strategy called self-adaptive. Self-adaptive mating is defined in the context of the novel algorithm, and aims to achieve a balance between exploitation and exploration in a domain-independent manner. The present work formally defines the novel mating approach, analyzes its behavior, and conducts an extensive experimental study to quantitatively determine its benefits. In the domain of real function optimization, the experiments show that, as the degree of multimodality of the function at hand grows, increasing the mating index improves performance. In the case of the self-adaptive mating strategy, the experiments give strong results for several case studies.

  1. Forward and Reverse Process Models for the Squeeze Casting Process Using Neural Network Based Approaches

    Directory of Open Access Journals (Sweden)

    Manjunath Patel Gowdru Chandrashekarappa

    2014-01-01

    Full Text Available The present research work is focussed to develop an intelligent system to establish the input-output relationship utilizing forward and reverse mappings of artificial neural networks. Forward mapping aims at predicting the density and secondary dendrite arm spacing (SDAS from the known set of squeeze cast process parameters such as time delay, pressure duration, squeezes pressure, pouring temperature, and die temperature. An attempt is also made to meet the industrial requirements of developing the reverse model to predict the recommended squeeze cast parameters for the desired density and SDAS. Two different neural network based approaches have been proposed to carry out the said task, namely, back propagation neural network (BPNN and genetic algorithm neural network (GA-NN. The batch mode of training is employed for both supervised learning networks and requires huge training data. The requirement of huge training data is generated artificially at random using regression equation derived through real experiments carried out earlier by the same authors. The performances of BPNN and GA-NN models are compared among themselves with those of regression for ten test cases. The results show that both models are capable of making better predictions and the models can be effectively used in shop floor in selection of most influential parameters for the desired outputs.

  2. Reverse breeding: a novel breeding approach based on engineered meiosis

    NARCIS (Netherlands)

    Dirks, R.; Dun, van K.P.M.; Snoo, de B.; Berg, van den M.; Lelivelt, C.L.C.; Voermans, W.; Woudenberg, L.; Wit, de J.P.C.; Reinink, K.; Schut, J.W.; Jong, de J.H.S.G.M.; Wijnker, T.G.

    2009-01-01

    Reverse breeding (RB) is a novel plant breeding technique designed to directly produce parental lines for any heterozygous plant, one of the most sought after goals in plant breeding. RB generates perfectly complementing homozygous parental lines through engineered meiosis. The method is based on re

  3. An Integrated Approach to Crop Genetic Improvement

    Institute of Scientific and Technical Information of China (English)

    Martin A. J. Parry; Malcolm J. Hawkesford

    2012-01-01

    The balance between the supply and demand of the major food crops is fragile,fueling concerns for long-term global food security.The rising population,increasing wealth and a proliferation of nonfood uses (e.g.bioenergy) has led to growing demands on agriculture,while increased production is limited by greater urbanization,and the degradation of land.Furthermore,global climate change with increasing temperatures and lower,more erratic rainfall is projected to decrease agricultural yields.There is a predicted need to increase food production by at least 70% by 2050 and therefore an urgent need to develop novel and integrated approaches,incorporating high-throughput phenotyping that will both increase production per unit area and simultaneously improve the resource use efficiency of crops.Yield potential,yield stability,nutrient and water use are all complex multigenic traits and while there is genetic variability,their complexity makes such traits difficult to breed for directly.Nevertheless molecular plant breeding has the potential to deliver substantial improvements,once the component traits and the genes underlying these traits have been identified.In addition,interactions between the individual traits must also be taken into account,a demand that is difficult to fulfill with traditional screening approaches.Identified traits will be incorporated into new cultivars using conventional or biotechnological tools.In order to better understand the relationship between genotype,component traits,and environment over time,a multidisciplinary approach must be adopted to both understand the underlying processes and identify candidate genes,QTLs and traits that can be used to develop improved crops.

  4. Expanding the Lotus japonicus reverse genetics toolbox – Development of LORE1 retrotransposon mutagenesis and artificial miRNA-mediated silencing

    DEFF Research Database (Denmark)

    Urbanski, Dorian Fabian

    2011-01-01

    Currently, the most common approach to studying Lotus japonicus (Lotus) genes is forward genetics in which a gene responsible for the studied phenotype is identified through map-based cloning. In reverse genetics, the activity of a gene of interest is modified to discover its mutant phenotype......-generation sequencing. Automatic assignment of insertions to individuals within the pools was done using an in-house developed bioinformatics pipeline. Analysis of the 8935 novel LORE1 insertions obtained in this study showed LORE1 to be an efficient mutagen with strong exon-specific insertional preference....... The protocols developed in the current project are now the cornerstone of a new LORE1 reverse genetics resource characterized by efficient mutant line generation and accurate mutation annotation. In parallel, artificial microRNAs (amiRNAs) were designed based on both Arabidopsis and Lotus backbones...

  5. Fuzzy Inspired Hybrid Genetic Approach to Optimize Travelling Salesman Problem

    Directory of Open Access Journals (Sweden)

    Bindu

    2012-06-01

    Full Text Available One of the category of algorithm Problems are basically exponential problems. These problems are basically exponential problems and take time to find the solution. In the present work we are optimising one of the common NP complete problem called Travelling Salesman Problem. In our work we have defined a genetic approach by combining fuzzy approach along with genetics. In this work we have implemented the modified DPX crossover to improve genetic approach. The work is implemented in MATLAB environment and obtained results shows the define approach has optimized the existing genetic algorithm results

  6. Genetic Approaches to Develop Salt Tolerant Germplasm

    KAUST Repository

    Tester, Mark A.

    2015-08-19

    Forty percent of the world\\'s food is produced under irrigation, and this is directly threatened by over-exploitation and changes in the global environment. One way to address this threat is to develop systems for increasing our ability to use lower quality water, in particular saline water. Low cost partial desalination of brackish water, use of saline water for cooling and increases in the salinity tolerance of crops can all contribute to the development of this new agricultural system. In this talk, the focus will be on the use of forward genetic approaches for discovery of genes related to salinity tolerance in barley and tomatoes. Rather than studying salinity tolerance as a trait in itself, we dissect salinity tolerance into a series of components that are hypothesised to contribute to overall salinity tolerance (following the paradigm of Munns & Tester, 2008). For example, one significant component of tolerance of most crop plants to moderate soil salinity is due to the ability to maintain low concentrations of Na+ in the leaves, and much analysis of this aspect has been done (e.g. Roy et al., 2013, 2014). A major site for the control of shoot Na+ accumulation is at the plasma membrane of the mature stele of the root. Alleles of HKT, a major gene underlying this transport process have been characterized and, in work led by Dr Rana Munns (CSIRO), have now been introgressed into commercial durum wheat and led to significantly increased yields in saline field conditions (Munns et al., 2012). The genotyping of mapping populations is now highly efficient. However, the ability to quantitatively phenotype these populations is now commonly limiting forward progress in plant science. The increasing power of digital imaging and computational technologies offers the opportunity to relieve this phenotyping bottleneck. The Plant Accelerator is a 4500m2 growth facility that provides non-destructive phenotyping of large populations of plants (http

  7. Design of a Ternary Reversible/Quantum Adder using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Vitaly G. Deibuk

    2015-08-01

    Full Text Available —Typical methods of quantum/reversible synthesis are based on using the binary character of quantum computing. However, multi-valued logic is a promising choice for future computer technologies, given a set of advantages when comparing to binary circuits. In this work, we have developed a genetic algorithm-based synthesis of ternary reversible circuits using Muthukrishnan-Stroud gates. The method for chromosomes coding that we present, as well as a judicious choice of algorithm parameters, allowed obtaining circuits for half-adder and full adder which are better than other published methods in terms of cost, delay times and amount of input ancillary bits. A structure of the circuits is analyzed in details, based on their decomposition.

  8. Genetic approaches to the molecular/neuronal mechanisms underlying learning and memory in the mouse.

    Science.gov (United States)

    Nakajima, Akira; Tang, Ya-Ping

    2005-09-01

    Learning and memory is an essential component of human intelligence. To understand its underlying molecular and neuronal mechanisms is currently an extensive focus in the field of cognitive neuroscience. We have employed advanced mouse genetic approaches to analyze the molecular and neuronal bases for learning and memory, and our results showed that brain region-specific genetic manipulations (including transgenic and knockout), inducible/reversible knockout, genetic/chemical kinase inactivation, and neuronal-based genetic approach are very powerful tools for studying the involvements of various molecules or neuronal substrates in the processes of learning and memory. Studies using these techniques may eventually lead to the understanding of how new information is acquired and how learned information is memorized in the brain.

  9. Dosage Effects of Fadrozole on Growth and Development of Sex-Reversed Genetic Female Chickens

    Institute of Scientific and Technical Information of China (English)

    YANG Xiu-rong; JIANG He-sheng; ZHENG Jiang-xia; QU Lu-jiang; CHEN Si-rui; LI Jun-ying; XU Gui-yun; YANG Ning

    2013-01-01

    Fadrozole, an aromatase inhibitor, can masculinize genetic female chickens and high-dose decreases the hatchability. Therefore, it is important to study the growth and development of sex-reversed females after hatch. Chick embryos from a population of CAU3 egg-type were treated with different concentrations of Fadrozole prior to the sexual differentiation at E3.0 (st18). At hatch, the phenotypic sex and genetic sex were identified by vent sexing and genetic diagnosis with CHD1, respectively. Body weight and shank length of sex reversal were tested at 8 and 20 wk, respectively. Testicular development, oviduct and ovarian degeneration were observed and serum concentration of estradiol and testosterone were tested with radioimmunoassay (RIA) at 30 wk. The results showed that body weight and shank length of sex-reversed females were not significantly different between low-dose groups (0.1, 0.3, and 0.5 mg for F1, F2, and F3, respectively) and high-dose groups (1.0 and 1.3 mg for F4 and F5, respectively) (P>0.05). Left and right testes or ovotestes in F2, F3, F4, and F5 groups were heavier than that of in F1 group (P<0.05). While the gonad weight of treatment groups were less than that in male control (P<0.05), oviduct weight in F2, F3, F4, and F5 groups were significant differences compared with female control and F1 group (P<0.05). Egg number from onset of laying egg to 30 wk in F4 and F5 groups were less than in female control, F1 and F2 groups (P<0.05). Serum testosterone level in F5 group was significant higher compared with female control, F1, F2, F3, and F4 groups (P<0.05), but significant lower compared with male control (P<0.05). While concentration of serum estradiol in F5 group was significant lower compared with female control, F1, F2, and F4 groups (P<0.05). In conclusion, the concentration of Fadrozole do not affect postnatal growth of sex-reversed female chicken and the degree of sex-reversed females elevate with the increase of Fadrozole concentration at

  10. Dual selection mechanisms drive efficient single-gene reverse genetics for rotavirus

    OpenAIRE

    Trask, Shane D.; Taraporewala, Zenobia F.; Boehme, Karl W.; Dermody, Terence S.; Patton, John T.

    2010-01-01

    Current methods for engineering the segmented double-stranded RNA genome of rotavirus (RV) are limited by inefficient recovery of the recombinant virus. In an effort to expand the utility of RV reverse genetics, we developed a method to recover recombinant viruses in which independent selection strategies are used to engineer single-gene replacements. We coupled a mutant SA11 RV encoding a temperature-sensitive (ts) defect in the NSP2 protein with RNAi-mediated degradation of NSP2 mRNAs to is...

  11. An in vitro recombination-based reverse genetic system for rapid mutagenesis of structural genes of the Japanese encephalitis virus

    Institute of Scientific and Technical Information of China (English)

    Ruikun; Du; Manli; Wang; Zhihong; Hu; Hualin; Wang; Fei; Deng

    2015-01-01

    Japanese encephalitis virus(JEV) is one of the most common pathogens of severe viral encephalitis, which is a severe threat to human health. Despite instability of the JEV genome in bacteria, many strategies have been developed to establish molecular clone systems of JEV, providing convenient tools for studying the virus life cycle and virus–host interactions. In this study, we adapted an In-Fusion enzyme-based in vitro recombination method to construct a reverse genetic system of JEV, thereby providing a rapid approach to introduce mutations into the structural genes. A truncated genome without the structural genes was constructed as the backbone, and the complementary segment containing the structural genes was recombined in vitro, which was then transfected directly into virus-permissive cells. The progeny of the infectious virus was successfully detected in the supernatant of the transfected cells, and showed an identical phenotype to its parental virus. To provide a proof-of-principle, the 12 conserved cysteine residues in the envelope(E) protein of JEV were respectively mutated using this approach, and all mutations resulted in a complete failure to generate infectious virus. However, a leucine-tophenylanine mutation at amino acid 107 of the E protein did not interfere with the production of the infectious virus. These results suggested that all 12 cysteines in the E protein are essential for the JEV life cycle. In summary, a novel reverse genetic system of JEV was established for rapidly introducing mutations into structural genes, which will serve as a useful tool for functional studies.

  12. Some new approaches to the study of the Earth's magnetic field reversals

    Directory of Open Access Journals (Sweden)

    G. Consolini

    2003-06-01

    Full Text Available Paleomagnetic studies clearly show that the polarity of the magnetic fi eld has been subject to reversals. It is generally assumed that polarity intervals are exponentially distributed. Here, the geomagnetic polarity reversal record, for the past 166 Ma, is analysed and a new approach to the study of the reversals is presented. In detail, the occurrence of 1/f-noise in the Power Spectral Density (PSD, relative to geomagnetic fi eld reversals, the existence of a Zipf's law behaviour for the cumulative distribution of polarity intervals, and the occurrence of punctuated equilibrium, as shown by a sort of Devil's staircase for the reversal time series, are investigated. Our results give a preliminary picture of the dynamical state of the geomagnetic dynamo suggesting that the geodynamo works in a marginally stable out-of-equilibrium confi guration, and that polarity reversals are equivalent to a sort of phase transition between two metastable states.

  13. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Science.gov (United States)

    DiTommaso, Tia; Jones, Lynelle K; Cottle, Denny L; Gerdin, Anna-Karin; Vancollie, Valerie E; Watt, Fiona M; Ramirez-Solis, Ramiro; Bradley, Allan; Steel, Karen P; Sundberg, John P; White, Jacqueline K; Smyth, Ian M

    2014-10-01

    The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP). A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1), while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1). The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  14. Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse.

    Directory of Open Access Journals (Sweden)

    Tia DiTommaso

    2014-10-01

    Full Text Available The skin is a highly regenerative organ which plays critical roles in protecting the body and sensing its environment. Consequently, morbidity and mortality associated with skin defects represent a significant health issue. To identify genes important in skin development and homeostasis, we have applied a high throughput, multi-parameter phenotype screen to the conditional targeted mutant mice generated by the Wellcome Trust Sanger Institute's Mouse Genetics Project (Sanger-MGP. A total of 562 different mouse lines were subjected to a variety of tests assessing cutaneous expression, macroscopic clinical disease, histological change, hair follicle cycling, and aberrant marker expression. Cutaneous lesions were associated with mutations in 23 different genes. Many of these were not previously associated with skin disease in the organ (Mysm1, Vangl1, Trpc4ap, Nom1, Sparc, Farp2, and Prkab1, while others were ascribed new cutaneous functions on the basis of the screening approach (Krt76, Lrig1, Myo5a, Nsun2, and Nf1. The integration of these skin specific screening protocols into the Sanger-MGP primary phenotyping pipelines marks the largest reported reverse genetic screen undertaken in any organ and defines approaches to maximise the productivity of future projects of this nature, while flagging genes for further characterisation.

  15. Optimal Reverse Carpooling Over Wireless Networks - A Distributed Optimization Approach

    CERN Document Server

    ParandehGheibi, Ali; Effros, Michelle; Medard, Muriel

    2010-01-01

    We focus on a particular form of network coding, reverse carpooling, in a wireless network where the potentially coded transmitted messages are to be decoded immediately upon reception. The network is fixed and known, and the system performance is measured in terms of the number of wireless broadcasts required to meet multiple unicast demands. Motivated by the structure of the coding scheme, we formulate the problem as a linear program by introducing a flow variable for each triple of connected nodes. This allows us to have a formulation polynomial in the number of nodes. Using dual decomposition and projected subgradient method, we present a decentralized algorithm to obtain optimal routing schemes in presence of coding opportunities. We show that the primal sub-problem can be expressed as a shortest path problem on an \\emph{edge-graph}, and the proposed algorithm requires each node to exchange information only with its neighbors.

  16. A 'reverse network engineering' framework to develop tourism using a lifestyle approach

    NARCIS (Netherlands)

    Kamann, DJF; Strijker, D; Sijtsma, FJ

    1998-01-01

    This paper uses the network approach in the design of policies for regional development focusing on tourism in rural and peripheral areas. The methodology applied - 'reverse network engineering' - is a combination of a top-down and a bottom-up approach, The top-down approach starts with the demand s

  17. Transcription, reverse transcription, and analysis of RNA containing artificial genetic components.

    Science.gov (United States)

    Leal, Nicole A; Kim, Hyo-Joong; Hoshika, Shuichi; Kim, Myong-Jung; Carrigan, Matthew A; Benner, Steven A

    2015-04-17

    Expanding the synthetic biology of artificially expanded genetic information systems (AEGIS) requires tools to make and analyze RNA molecules having added nucleotide "letters". We report here the development of T7 RNA polymerase and reverse transcriptase to catalyze transcription and reverse transcription of xNA (DNA or RNA) having two complementary AEGIS nucleobases, 6-amino-5-nitropyridin-2-one (trivially, Z) and 2-aminoimidazo[1,2a]-1,3,5-triazin-4(8H)-one (trivially, P). We also report MALDI mass spectrometry and HPLC-based analyses for oligomeric GACUZP six-letter RNA and the use of ribonuclease (RNase) A and T1 RNase as enzymatic tools for the sequence-specific degradation of GACUZP RNA. We then applied these tools to analyze the GACUZP and GACTZP products of polymerases and reverse transcriptases (respectively) made from DNA and RNA templates. In addition to advancing this 6-letter AEGIS toward the biosynthesis of proteins containing additional amino acids, these experiments provided new insights into the biophysics of DNA.

  18. Reversibility of hepatocyte nuclear modifications in mice fed on genetically modified soybean

    Directory of Open Access Journals (Sweden)

    M Malatesta

    2009-06-01

    Full Text Available In the literature, the reports on the effects of a genetically modified (GM diet are scanty and heterogeneous; in particular, no direct evidence has so far been reported that GM food may affect human or animal health. Hepatocytes represent a suitable model for monitoring the effects of a GM diet, the liver potentially being a primary target. In a previous study, we demonstrated that some modifications occur in hepatocyte nuclei of mice fed on GM soybean. In order to elucidate whether such modifications can be reversed, in the present study, 3 months old mice fed on GM soybean since their weaning were submitted to a diet containing wild type soybean only, for one month. In parallel, to investigate the influence of GM soybean on adult individuals, mice fed on wild type soybean were changed to a GM diet, for the same time. Using immunoelectron microscopy, we demonstrated that a one-month diet reversion can influence some nuclear features in adult mice, restoring typical characteristics of controls in GM-fed animals, and inducing in control mice modifications similar to those observed in animals fed on GM soybean from weaning. This suggests that the modifications related to GM soybean are potentially reversible, but also that some modifications are inducible in adult organisms in a short time.

  19. Solidified reverse micellar solutions (SRMS): A novel approach for ...

    African Journals Online (AJOL)

    ... approach for controlling drug release from various lipids based drug delivery systems. ... Its formulation methods, characterisation and delivery systems were ... solutions (SRMS), lipids, wide angle X-ray diffraction analysis (WAXD), small ...

  20. Whole genome approaches to quantitative genetics.

    Science.gov (United States)

    Visscher, Peter M

    2009-06-01

    Apart from parent-offspring pairs and clones, relative pairs vary in the proportion of the genome that they share identical by descent. In the past, quantitative geneticists have used the expected value of sharing genes by descent to estimate genetic parameters and predict breeding values. With the possibility to genotype individuals for many markers across the genome it is now possible to empirically estimate the actual relationship between relatives. We review some of the theory underlying the variation in genetic identity, show applications to estimating genetic variance for height in humans and discuss other applications.

  1. A NEW REVERSE ENGINEERING APPROACH TO CONVERT FORM FILL FORMAT DOCUMENT INTO UML CLASS DIAGRAM

    Directory of Open Access Journals (Sweden)

    Mohammad I. Muhairat

    2014-12-01

    Full Text Available This paper propose a new reverse engineering approach to convert a form fill format document into a set of related tables that can be used to generate the entity relationship diagram. A relationship between the set of tables is generated. In addition, the entity relationship diagram will be converted into a UML class diagram. However, this approach will be very helpful for researchers and practitioners in Software Engineering field, since most of the reverse engineering approaches are based on source code. This approach is tested by using several word form fill format documents and the results show a high accuracy rates comparing with the forward engineering.

  2. Reverse genetics of measles virus and resulting multivalent recombinant vaccines: applications of recombinant measles viruses.

    Science.gov (United States)

    Billeter, M A; Naim, H Y; Udem, S A

    2009-01-01

    An overview is given on the development of technologies to allow reverse genetics of RNA viruses, i.e., the rescue of viruses from cDNA, with emphasis on nonsegmented negative-strand RNA viruses (Mononegavirales), as exemplified for measles virus (MV). Primarily, these technologies allowed site-directed mutagenesis, enabling important insights into a variety of aspects of the biology of these viruses. Concomitantly, foreign coding sequences were inserted to (a) allow localization of virus replication in vivo through marker gene expression, (b) develop candidate multivalent vaccines against measles and other pathogens, and (c) create candidate oncolytic viruses. The vector use of these viruses was experimentally encouraged by the pronounced genetic stability of the recombinants unexpected for RNA viruses, and by the high load of insertable genetic material, in excess of 6 kb. The known assets, such as the small genome size of the vector in comparison to DNA viruses proposed as vectors, the extensive clinical experience of attenuated MV as vaccine with a proven record of high safety and efficacy, and the low production cost per vaccination dose are thus favorably complemented.

  3. Simulation Approach for Timing Analysis of Genetic Logic Circuits.

    Science.gov (United States)

    Baig, Hasan; Madsen, Jan

    2017-02-01

    Constructing genetic logic circuits is an application of synthetic biology in which parts of the DNA of a living cell are engineered to perform a dedicated Boolean function triggered by an appropriate concentration of certain proteins or by different genetic components. These logic circuits work in a manner similar to electronic logic circuits, but they are much more stochastic and hence much harder to characterize. In this article, we introduce an approach to analyze the threshold value and timing of genetic logic circuits. We show how this approach can be used to analyze the timing behavior of single and cascaded genetic logic circuits. We further analyze the timing sensitivity of circuits by varying the degradation rates and concentrations. Our approach can be used not only to characterize the timing behavior but also to analyze the timing constraints of cascaded genetic logic circuits, a capability that we believe will be important for design automation in synthetic biology.

  4. Cellular and genetic approaches to myocardial regeneration

    NARCIS (Netherlands)

    Tuyn, John van

    2008-01-01

    Injection of (stem) cells into the damaged heart has a positive effect on cardiac function. In this thesis two strategies for improving myocardial regeneration over classical cell therapy were investigated. The first is to induce cardiomyogenic differentiation by genetically engineering cells to ex

  5. Neuroimaging genetic approaches to Posttraumatic Stress Disorder.

    Science.gov (United States)

    Lebois, Lauren A M; Wolff, Jonathan D; Ressler, Kerry J

    2016-10-01

    Neuroimaging genetic studies that associate genetic and epigenetic variation with neural activity or structure provide an opportunity to link genes to psychiatric disorders, often before psychopathology is discernable in behavior. Here we review neuroimaging genetics studies with participants who have Posttraumatic Stress Disorder (PTSD). Results show that genes related to the physiological stress response (e.g., glucocorticoid receptor and activity, neuroendocrine release), learning and memory (e.g., plasticity), mood, and pain perception are tied to neural intermediate phenotypes associated with PTSD. These genes are associated with and sometimes predict neural structure and function in areas involved in attention, executive function, memory, decision-making, emotion regulation, salience of potential threats, and pain perception. Evidence suggests these risk polymorphisms and neural intermediate phenotypes are vulnerabilities toward developing PTSD in the aftermath of trauma, or vulnerabilities toward particular symptoms once PTSD has developed. Work distinguishing between the re-experiencing and dissociative sub-types of PTSD, and examining other PTSD symptom clusters in addition to the re-experiencing and hyperarousal symptoms, will further clarify neurobiological mechanisms and inconsistent findings. Furthermore, an exciting possibility is that genetic associations with PTSD may eventually be understood through differential intermediate phenotypes of neural circuit structure and function, possibly underlying the different symptom clusters seen within PTSD. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Construction and identification of reverse genetics system of Dengue type 2 virus isolated in China

    Institute of Scientific and Technical Information of China (English)

    ZHU Wuyang; CHEN Shuiping; QIN Chenggeng; YU Man; JIANG Tao; DENG Yongqiang; QIN Ede

    2006-01-01

    To construct infectious full-length cDNA clone of dengue virus type 2 isolated in China (DEN2-43), according to the published nucleotide sequence of the virus strain, the approximately 11 kb full-length cDNAs of DEN2-43 were amplified by long RT-PCR and fusion PCR. Full-length cDNA clones were constructed by inserting the full-length cDNA into a low copy vector pWSK29, from which rescued virus D212 was acquired by transcription in vitro and electroporation. The full-length cDNA clone pD212 was infectious, and rescued virus acquired in C6/36 cells was indistinguishable from DEN2-43 virus in biological properties including suckling mice neurovirulence. The reverse genetics system helps elucidate the mechanism of pathogenesis of dengue virus and develop novel vaccine against dengue.

  7. Development of a reverse genetics system to generate recombinant Marburg virus derived from a bat isolate.

    Science.gov (United States)

    Albariño, César G; Uebelhoer, Luke S; Vincent, Joel P; Khristova, Marina L; Chakrabarti, Ayan K; McElroy, Anita; Nichol, Stuart T; Towner, Jonathan S

    2013-11-01

    Recent investigations have shown the Egyptian fruit bat (Rousettus aegyptiacus) to be a natural reservoir for marburgviruses. To better understand the life cycle of these viruses in the natural host, a new reverse genetics system was developed for the reliable rescue of a Marburg virus (MARV) originally isolated directly from a R. aegyptiacus bat (371Bat). To develop this system, the exact terminal sequences were first determined by 5' and 3' RACE, followed by the cloning of viral proteins NP, VP35, VP30 and L into expression plasmids. Novel conditions were then developed to efficiently replicate virus mini-genomes followed by the construction of full-length genomic clones from which recombinant wild type and GFP-containing MARVs were rescued. Surprisingly, when these recombinant MARVs were propagated in primary human macrophages, a dramatic difference was found in their ability to grow and to elicit anti-viral cytokine responses.

  8. 1 Hierarchical Approaches to the Analysis of Genetic Diversity in ...

    African Journals Online (AJOL)

    2015-04-14

    Apr 14, 2015 ... Keywords: Genetic diversity, Hierarchical approach, Plant, Clustering,. Descriptive ... utilization) or by clustering (based on a phonetic analysis of individual ...... Improvement of Food Crop Preservatives for the next Millennium.

  9. Reversibly switchable photoacoustic tomography using a genetically encoded near-infrared phytochrome

    Science.gov (United States)

    Yao, Junjie; Kaberniuk, Andrii A.; Li, Lei; Shcherbakova, Daria M.; Zhang, Ruiying; Wang, Lidai; Li, Guo; Verkhusha, Vladislav V.; Wang, Lihong V.

    2016-03-01

    Optical imaging of genetically encoded probes has revolutionized biomedical studies by providing valuable information about targeted biological processes. Here, we report a novel imaging technique, termed reversibly switchable photoacoustic tomography (RS-PAT), which exhibits large penetration depth, high detection sensitivity, and super-resolution. RS-PAT combines advanced photoacoustic imaging techniques with, for the first time, a nonfluorescent photoswitchable bacterial phytochrome. This bacterial phytochrome is the most near-infrared shifted genetically encoded probe reported so far. Moreover, this bacterial phytochrome is reversibly photoconvertible between its far-red and near-infrared light absorption states. Taking maximum advantage of the powerful imaging capability of PAT and the unique photochemical properties of the phytochrome, RS-PAT has broken through both the optical diffusion limit for deep-tissue imaging and the optical diffraction limit for super-resolution photoacoustic microscopy. Specifically, with RS-PAT we have achieved an unprecedented detection sensitivity of ~2 μM, or as few as ~20 tumor cells, at a centimeter depth. Such high sensitivity is fully demonstrated in our study by monitoring tumor growth and metastasis at whole-body level with ~100 μm resolution. Moreover, our microscopic implementation of RS-PAT is capable of imaging mammalian cells with a sub-diffraction lateral resolution of ~140 nm and axial resolution of ~400 nm, which are respectively ~2-fold and ~75-fold finer than those of our conventional photoacoustic microscopy. Overall, RS-PAT is a new and promising imaging technology for studying biological processes at different length scales.

  10. Stego-audio Using Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    V. Santhi

    2014-06-01

    Full Text Available With the rapid development of digital multimedia applications, the secure data transmission becomes the main issue in data communication system. So the multimedia data hiding techniques have been developed to ensure the secured data transfer. Steganography is an art of hiding a secret message within an image/audio/video file in such a way that the secret message cannot be perceived by hacker/intruder. In this study, we use RSA encryption algorithm to encrypt the message and Genetic Algorithm (GA to encode the message in the audio file. This study presents a method to access the negative audio bytes and includes the negative audio bytes in the message encoding and position embedding process. This increases the capacity of encoding message in the audio file. The use of GA operators in Genetic Algorithm reduces the noise distortions.

  11. Genetic & epigenetic approach to human obesity

    Directory of Open Access Journals (Sweden)

    K Rajender Rao

    2014-01-01

    Full Text Available Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D, cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12 th u0 pdate of Human Obesity Gene Map there are 253 quantity trait loci (QTL for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  12. Genetic & epigenetic approach to human obesity.

    Science.gov (United States)

    Rao, K Rajender; Lal, Nirupama; Giridharan, N V

    2014-11-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed.

  13. Genetic & epigenetic approach to human obesity

    Science.gov (United States)

    Rao, K. Rajender; Lal, Nirupama; Giridharan, N.V.

    2014-01-01

    Obesity is an important clinical and public health challenge, epitomized by excess adipose tissue accumulation resulting from an imbalance in energy intake and energy expenditure. It is a forerunner for a variety of other diseases such as type-2-diabetes (T2D), cardiovascular diseases, some types of cancer, stroke, hyperlipidaemia and can be fatal leading to premature death. Obesity is highly heritable and arises from the interplay of multiple genes and environmental factors. Recent advancements in Genome-wide association studies (GWAS) have shown important steps towards identifying genetic risks and identification of genetic markers for lifestyle diseases, especially for a metabolic disorder like obesity. According to the 12th Update of Human Obesity Gene Map there are 253 quantity trait loci (QTL) for obesity related phenotypes from 61 genome wide scan studies. Contribution of genetic propensity of individual ethnic and racial variations in obesity is an active area of research. Further, understanding its complexity as to how these variations could influence ones susceptibility to become or remain obese will lead us to a greater understanding of how obesity occurs and hopefully, how to prevent and treat this condition. In this review, various strategies adapted for such an analysis based on the recent advances in genome wide and functional variations in human obesity are discussed. PMID:25579139

  14. Engaging nurses in genetics: the strategic approach of the NHS National Genetics Education and Development Centre.

    Science.gov (United States)

    Kirk, Maggie; Tonkin, Emma; Burke, Sarah

    2008-04-01

    The UK government announced the establishment of an NHS National Genetics Education and Development Centre in its Genetics White Paper. The Centre aims to lead and coordinate developments to enhance genetics literacy of health professionals. The nursing program takes a strategic approach based on Ajzen's Theory of Planned Behavior, using the UK nursing genetics competences as the platform for development. The program team uses innovative approaches to raise awareness of the relevance of genetics, working collaboratively with policy stakeholders, as key agents of change in promoting competence. Providing practical help in preparing learning and teaching resources lends further encouragement. Evaluation of the program is dependent on gathering baseline data, and the program has been informed by an education needs analysis. The challenges faced are substantial and necessitate international collaboration where expertise and resources can be shared to produce a global system of influence to facilitate the engagement of non-genetic nurses.

  15. Mammalian Reverse Genetics without Crossing Reveals Nr3a as a Short-Sleeper Gene.

    Science.gov (United States)

    Sunagawa, Genshiro A; Sumiyama, Kenta; Ukai-Tadenuma, Maki; Perrin, Dimitri; Fujishima, Hiroshi; Ukai, Hideki; Nishimura, Osamu; Shi, Shoi; Ohno, Rei-ichiro; Narumi, Ryohei; Shimizu, Yoshihiro; Tone, Daisuke; Ode, Koji L; Kuraku, Shigehiro; Ueda, Hiroki R

    2016-01-26

    The identification of molecular networks at the system level in mammals is accelerated by next-generation mammalian genetics without crossing, which requires both the efficient production of whole-body biallelic knockout (KO) mice in a single generation and high-performance phenotype analyses. Here, we show that the triple targeting of a single gene using the CRISPR/Cas9 system achieves almost perfect KO efficiency (96%-100%). In addition, we developed a respiration-based fully automated non-invasive sleep phenotyping system, the Snappy Sleep Stager (SSS), for high-performance (95.3% accuracy) sleep/wake staging. Using the triple-target CRISPR and SSS in tandem, we reliably obtained sleep/wake phenotypes, even in double-KO mice. By using this system to comprehensively analyze all of the N-methyl-D-aspartate (NMDA) receptor family members, we found Nr3a as a short-sleeper gene, which is verified by an independent set of triple-target CRISPR. These results demonstrate the application of mammalian reverse genetics without crossing to organism-level systems biology in sleep research.

  16. Reverse Genetics of Escherichia coli Glycerol Kinase Allosteric Regulation and Glucose Control of Glycerol Utilization In Vivo

    OpenAIRE

    Holtman, C. Kay; Pawlyk, Aaron C.; Meadow, Norman D.; Pettigrew, Donald W.

    2001-01-01

    Reverse genetics is used to evaluate the roles in vivo of allosteric regulation of Escherichia coli glycerol kinase by the glucose-specific phosphocarrier of the phosphoenolpyruvate:glycose phosphotransferase system, IIAGlc (formerly known as IIIglc), and by fructose 1,6-bisphosphate. Roles have been postulated for these allosteric effectors in glucose control of both glycerol utilization and expression of the glpK gene. Genetics methods based on homologous recombination are used to place glp...

  17. Cognitive Radio — Genetic Algorithm Approach

    Science.gov (United States)

    Reddy, Y. B.

    2005-03-01

    Cognitive Radio (CR) is relatively a new technology, which intelligently detects a particular segment of the radio spectrum currently in use and selects unused spectrum quickly without interfering the transmission of authorized users. Cognitive Radios can learn about current use of spectrum in their operating area, make intelligent decisions, and react to immediate changes in the use of spectrum by other authorized users. The goal of CR technology is to relieve radio spectrum overcrowding, which actually translates to a lack of access to full radio spectrum utilization. Due to this adaptive behavior, the CR can easily avoid the interference of signals in a crowded radio frequency spectrum. In this research, we discuss the possible application of genetic algorithms (GA) to create a CR that can respond intelligently in changing and unanticipated circumstances and in the presence of hostile jammers and interferers. Genetic algorithms are problem solving techniques based on evolution and natural selection. GA models adapt Charles Darwin's evolutionary theory for analysis of data and interchanging design elements in hundreds of thousands of different combinations. Only the best-performing combinations are permitted to survive, and those combinations "reproduce" further, progressively yielding better and better results.

  18. Efficient Approaches for Designing Fault Tolerant Reversible Carry Look-Ahead and Carry-Skip Adders

    CERN Document Server

    Islam, Md Saiful; begum, Zerina; Hafiz, Mohd Zulfiquar

    2010-01-01

    Combinational or Classical logic circuits dissipate heat for every bit of information that is lost. Information is lost when the input vector cannot be recovered from its corresponding output vector. Reversible logic circuit implements only the functions having one-to-one mapping between its input and output vectors and therefore naturally takes care of heating. Reversible logic design becomes one of the promising research directions in low power dissipating circuit design in the past few years and has found its application in low power CMOS design, digital signal processing and nanotechnology. This paper presents the efficient approaches for designing fault tolerant reversible fast adders that implement carry look-ahead and carry-skip logic. The proposed high speed reversible adders include MIG gates for the realization of its basic building block. The MIG gate is universal and parity preserving. It allows any fault that affects no more than a single signal readily detectable at the circuit's primary outputs...

  19. Maximizing lifetime of wireless sensor networks using genetic approach

    DEFF Research Database (Denmark)

    Wagh, Sanjeev; Prasad, Ramjee

    2014-01-01

    the cluster head intelligently using auction data of node i.e. its local battery power, topology strength and external battery support. The network lifetime is the centre focus of the research paper which explores intelligently selection of cluster head using auction based approach. The multi......-objective parameters are considered to solve the problem using genetic algorithm of evolutionary approach....

  20. Simulation Approach for Timing Analysis of Genetic Logic Circuits

    DEFF Research Database (Denmark)

    Baig, Hasan; Madsen, Jan

    2017-01-01

    in a manner similar to electronic logic circuits, but they are much more stochastic and hence much harder to characterize. In this article, we introduce an approach to analyze the threshold value and timing of genetic logic circuits. We show how this approach can be used to analyze the timing behavior...

  1. Cellular biosensing: chemical and genetic approaches.

    Science.gov (United States)

    Haruyama, Tetsuya

    2006-05-24

    Biosensors have been developed to determine the concentration of specific compounds in situ. They are already widely employed as a practical technology in the clinical and healthcare fields. Recently, another concept of biosensing has been receiving attention: biosensing for the evaluation of molecular potency. The development of this novel concept has been supported by the development of related technologies, as such as molecular design, molecular biology (genetic engineering) and cellular/tissular engineering. This review is addresses this new concept of biosensing and its application to the evaluation of the potency of chemicals in biological systems, in the field of cellular/tissular engineering. Cellular biosensing may provide information on both pharmaceutical and chemical safety, and on drug efficacy in vitro as a screening tool.

  2. Suitability of PER.C6 cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics

    NARCIS (Netherlands)

    Koudstaal, W.; Hartgroves, L.; Havenga, M.; Legastelois, I.; Ophorst, C.; Siewerts, M.; Zuijdgeest, D.; Vogels, R.; Custers, J.; Boer-Luijtze, E. de; Leeuw, O. de; Cornelissen, L.; Goudsmit, J.; Barclay, W.

    2009-01-01

    Reverse genetics, the generation of influenza viruses from cDNA, presents a rapid method for creating vaccine strains. The technique necessitates the use of cultured cells. Due to technical and regulatory requirements, the choice of cell lines for production of human influenza vaccines is limited. P

  3. Suitability of PER.C6 cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics

    NARCIS (Netherlands)

    Koudstaal, W.; Hartgroves, L.; Havenga, M.; Legastelois, I.; Ophorst, C.; Siewerts, M.; Zuijdgeest, D.; Vogels, R.; Custers, J.; Boer-Luijtze, E. de; Leeuw, O. de; Cornelissen, L.; Goudsmit, J.; Barclay, W.

    2009-01-01

    Reverse genetics, the generation of influenza viruses from cDNA, presents a rapid method for creating vaccine strains. The technique necessitates the use of cultured cells. Due to technical and regulatory requirements, the choice of cell lines for production of human influenza vaccines is limited. P

  4. Reversal of phenotypes in MECP2 duplication mice using genetic rescue or antisense oligonucleotides.

    Science.gov (United States)

    Sztainberg, Yehezkel; Chen, Hong-mei; Swann, John W; Hao, Shuang; Tang, Bin; Wu, Zhenyu; Tang, Jianrong; Wan, Ying-Wooi; Liu, Zhandong; Rigo, Frank; Zoghbi, Huda Y

    2015-12-03

    Copy number variations have been frequently associated with developmental delay, intellectual disability and autism spectrum disorders. MECP2 duplication syndrome is one of the most common genomic rearrangements in males and is characterized by autism, intellectual disability, motor dysfunction, anxiety, epilepsy, recurrent respiratory tract infections and early death. The broad range of deficits caused by methyl-CpG-binding protein 2 (MeCP2) overexpression poses a daunting challenge to traditional biochemical-pathway-based therapeutic approaches. Accordingly, we sought strategies that directly target MeCP2 and are amenable to translation into clinical therapy. The first question that we addressed was whether the neurological dysfunction is reversible after symptoms set in. Reversal of phenotypes in adult symptomatic mice has been demonstrated in some models of monogenic loss-of-function neurological disorders, including loss of MeCP2 in Rett syndrome, indicating that, at least in some cases, the neuroanatomy may remain sufficiently intact so that correction of the molecular dysfunction underlying these disorders can restore healthy physiology. Given the absence of neurodegeneration in MECP2 duplication syndrome, we propose that restoration of normal MeCP2 levels in MECP2 duplication adult mice would rescue their phenotype. By generating and characterizing a conditional Mecp2-overexpressing mouse model, here we show that correction of MeCP2 levels largely reverses the behavioural, molecular and electrophysiological deficits. We also reduced MeCP2 using an antisense oligonucleotide strategy, which has greater translational potential. Antisense oligonucleotides are small, modified nucleic acids that can selectively hybridize with messenger RNA transcribed from a target gene and silence it, and have been successfully used to correct deficits in different mouse models. We find that antisense oligonucleotide treatment induces a broad phenotypic rescue in adult

  5. A reverse taxonomic approach to assess macrofaunal distribution patterns in abyssal Pacific polymetallic nodule fields.

    Directory of Open Access Journals (Sweden)

    Annika Janssen

    Full Text Available Heightened interest in the exploitation of deep seafloor minerals is raising questions on the consequences for the resident fauna. Assessing species ranges and determination of processes underlying current species distributions are prerequisites to conservation planning and predicting faunal responses to changing environmental conditions. The abyssal central Pacific nodule belt, located between the Clarion and Clipperton Fracture Zones (CCZ, is an area prospected for mining of polymetallic nodules. We examined variations in genetic diversity and broad-scale connectivity of isopods and polychaetes across the CCZ. Faunal assemblages were studied from two mining claims (the eastern German and French license areas located 1300 km apart and influenced by different productivity regimes. Using a reverse taxonomy approach based on DNA barcoding, we tested to what extent distance and large-scale changes in environmental parameters lead to differentiation in two macrofaunal taxa exhibiting different functions and life-history patterns. A fragment of the mitochondrial gene Cytochrome Oxidase Subunit 1 (COI was analyzed. At a 97% threshold the molecular operational taxonomic units (MOTUs corresponded well to morphological species. Molecular analyses indicated high local and regional diversity mostly because of large numbers of singletons in the samples. Consequently, variation in composition of genotypic clusters between sites was exceedingly large partly due to paucity of deep-sea sampling and faunal patchiness. A higher proportion of wide-ranging species in polychaetes was contrasted with mostly restricted distributions in isopods. Remarkably, several cryptic lineages appeared to be sympatric and occurred in taxa with putatively good dispersal abilities, whereas some brooding lineages revealed broad distributions across the CCZ. Geographic distance could explain variation in faunal connectivity between regions and sites to some extent, while assumed

  6. Development and application of a positive-negative selectable marker system for use in reverse genetics in Plasmodium.

    Science.gov (United States)

    Braks, Joanna A M; Franke-Fayard, Blandine; Kroeze, Hans; Janse, Chris J; Waters, Andrew P

    2006-03-14

    A limitation of transfection of malaria parasites is the availability of only a low number of positive selectable markers for selection of transformed mutants. This is exacerbated for the rodent parasite Plasmodium berghei as selection of mutants is performed in vivo in laboratory rodents. We here report the development and application of a negative selection system based upon transgenic expression of a bifunctional protein (yFCU) combining yeast cytosine deaminase and uridyl phosphoribosyl transferase (UPRT) activity in P.berghei followed by in vivo selection with the prodrug 5-fluorocytosine (5-FC). The combination of yfcu and a positive selectable marker was used to first achieve positive selection of mutant parasites with a disrupted gene in a conventional manner. Thereafter through negative selection using 5-FC, mutants were selected where the disrupted gene had been restored to its original configuration as a result of the excision of the selectable markers from the genome through homologous recombination. This procedure was carried out for a Plasmodium gene (p48/45) encoding a protein involved in fertilization, the function of which had been previously implied through gene disruption alone. Such reversible recombination can therefore be employed for both the rapid analysis of the phenotype by targeted disruption of a gene and further associate phenotype and function by genotype restoration through the use of a single plasmid and a single positive selectable marker. Furthermore the negative selection system may also be adapted to facilitate other procedures such as 'Hit and Run' and 'vector recycling' which in principle will allow unlimited manipulation of a single parasite clone. This is the first demonstration of the general use of yFCU in combination with a positive selectable marker in reverse genetics approaches and it should be possible to adapt its use to many other biological systems.

  7. Genetic Programming Approach for Predicting Surface Subsidence Induced by Mining

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The surface subsidence induced by mining is a complex problem, which is related with many complex and uncertain factors.Genetic programming (GP) has a good ability to deal with complex and nonlinear problems, therefore genetic programming approach is proposed to predict mining induced surface subsidence in this article.First genetic programming technique is introduced, second, surface subsidence genetic programming model is set up by selecting its main affective factors and training relating to practical engineering data, and finally, predictions are made by the testing of data, whose results show that the relative error is approximately less than 10%, which can meet the engineering needs, and therefore, this proposed approach is valid and applicable in predicting mining induced surface subsidence.The model offers a novel method to predict surface subsidence in mining.

  8. Integrating Genetic Algorithm, Tabu Search Approach for Job Shop Scheduling

    CERN Document Server

    Thamilselvan, R

    2009-01-01

    This paper presents a new algorithm based on integrating Genetic Algorithms and Tabu Search methods to solve the Job Shop Scheduling problem. The idea of the proposed algorithm is derived from Genetic Algorithms. Most of the scheduling problems require either exponential time or space to generate an optimal answer. Job Shop scheduling (JSS) is the general scheduling problem and it is a NP-complete problem, but it is difficult to find the optimal solution. This paper applies Genetic Algorithms and Tabu Search for Job Shop Scheduling problem and compares the results obtained by each. With the implementation of our approach the JSS problems reaches optimal solution and minimize the makespan.

  9. Multiple comparisons in genetic association studies: a hierarchical modeling approach.

    Science.gov (United States)

    Yi, Nengjun; Xu, Shizhong; Lou, Xiang-Yang; Mallick, Himel

    2014-02-01

    Multiple comparisons or multiple testing has been viewed as a thorny issue in genetic association studies aiming to detect disease-associated genetic variants from a large number of genotyped variants. We alleviate the problem of multiple comparisons by proposing a hierarchical modeling approach that is fundamentally different from the existing methods. The proposed hierarchical models simultaneously fit as many variables as possible and shrink unimportant effects towards zero. Thus, the hierarchical models yield more efficient estimates of parameters than the traditional methods that analyze genetic variants separately, and also coherently address the multiple comparisons problem due to largely reducing the effective number of genetic effects and the number of statistically "significant" effects. We develop a method for computing the effective number of genetic effects in hierarchical generalized linear models, and propose a new adjustment for multiple comparisons, the hierarchical Bonferroni correction, based on the effective number of genetic effects. Our approach not only increases the power to detect disease-associated variants but also controls the Type I error. We illustrate and evaluate our method with real and simulated data sets from genetic association studies. The method has been implemented in our freely available R package BhGLM (http://www.ssg.uab.edu/bhglm/).

  10. A Reverse Genetics Platform That Spans the Zika Virus Family Tree

    Science.gov (United States)

    Widman, Douglas G.; Young, Ellen; Yount, Boyd L.; Plante, Kenneth S.; Gallichotte, Emily N.; Carbaugh, Derek L.; Plante, Jessica; Swanstrom, Jesica; Heise, Mark T.; Lazear, Helen M.

    2017-01-01

    ABSTRACT Zika virus (ZIKV), a mosquito-borne flavivirus discovered in 1947, has only recently caused large outbreaks and emerged as a significant human pathogen. In 2015, ZIKV was detected in Brazil, and the resulting epidemic has spread throughout the Western Hemisphere. Severe complications from ZIKV infection include neurological disorders such as Guillain-Barré syndrome in adults and a variety of fetal abnormalities, including microcephaly, blindness, placental insufficiency, and fetal demise. There is an urgent need for tools and reagents to study the pathogenesis of epidemic ZIKV and for testing vaccines and antivirals. Using a reverse genetics platform, we generated six ZIKV infectious clones and derivative viruses representing diverse temporal and geographic origins. These include three versions of MR766, the prototype 1947 strain (with and without a glycosylation site in the envelope protein), and H/PF/2013, a 2013 human isolate from French Polynesia representative of the virus introduced to Brazil. In the course of synthesizing a clone of a circulating Brazilian strain, phylogenetic studies identified two distinct ZIKV clades in Brazil. We reconstructed viable clones of strains SPH2015 and BeH819015, representing ancestral members of each clade. We assessed recombinant virus replication, binding to monoclonal antibodies, and virulence in mice. This panel of molecular clones and recombinant virus isolates will enable targeted studies of viral determinants of pathogenesis, adaptation, and evolution, as well as the rational attenuation of contemporary outbreak strains to facilitate the design of vaccines and therapeutics. PMID:28270583

  11. Partial and full PCR-based reverse genetics strategy for influenza viruses.

    Directory of Open Access Journals (Sweden)

    Hongjun Chen

    Full Text Available Since 1999, plasmid-based reverse genetics (RG systems have revolutionized the way influenza viruses are studied. However, it is not unusual to encounter cloning difficulties for one or more influenza genes while attempting to recover virus de novo. To overcome some of these shortcomings we sought to develop partial or full plasmid-free RG systems. The influenza gene of choice is assembled into a RG competent unit by virtue of overlapping PCR reactions containing a cDNA copy of the viral gene segment under the control of RNA polymerase I promoter (pol1 and termination (t1 signals - herein referred to as Flu PCR amplicons. Transfection of tissue culture cells with either HA or NA Flu PCR amplicons and 7 plasmids encoding the remaining influenza RG units, resulted in efficient virus rescue. Likewise, transfections including both HA and NA Flu PCR amplicons and 6 RG plasmids also resulted in efficient virus rescue. In addition, influenza viruses were recovered from a full set of Flu PCR amplicons without the use of plasmids.

  12. Reveal, A General Reverse Engineering Algorithm for Inference of Genetic Network Architectures

    Science.gov (United States)

    Liang, Shoudan; Fuhrman, Stefanie; Somogyi, Roland

    1998-01-01

    Given the immanent gene expression mapping covering whole genomes during development, health and disease, we seek computational methods to maximize functional inference from such large data sets. Is it possible, in principle, to completely infer a complex regulatory network architecture from input/output patterns of its variables? We investigated this possibility using binary models of genetic networks. Trajectories, or state transition tables of Boolean nets, resemble time series of gene expression. By systematically analyzing the mutual information between input states and output states, one is able to infer the sets of input elements controlling each element or gene in the network. This process is unequivocal and exact for complete state transition tables. We implemented this REVerse Engineering ALgorithm (REVEAL) in a C program, and found the problem to be tractable within the conditions tested so far. For n = 50 (elements) and k = 3 (inputs per element), the analysis of incomplete state transition tables (100 state transition pairs out of a possible 10(exp 15)) reliably produced the original rule and wiring sets. While this study is limited to synchronous Boolean networks, the algorithm is generalizable to include multi-state models, essentially allowing direct application to realistic biological data sets. The ability to adequately solve the inverse problem may enable in-depth analysis of complex dynamic systems in biology and other fields.

  13. Combining Telomerase Reverse Transcriptase Genetic Variant rs2736100 with Epidemiologic Factors in the Prediction of Lung Cancer Susceptibility.

    Science.gov (United States)

    Wang, Xu; Ma, Kewei; Chi, Lumei; Cui, Jiuwei; Jin, Lina; Hu, Ji-Fan; Li, Wei

    2016-01-01

    Genetic variants from a considerable number of susceptibility loci have been identified in association with cancer risk, but their interaction with epidemiologic factors in lung cancer remains to be defined. We sought to establish a forecasting model for identifying individuals with high-risk of lung cancer by combing gene single-nucleotide polymorphisms with epidemiologic factors. Genotyping and clinical data from 500 lung cancer cases and 500 controls were used for developing the logistic regression model. We found that lung cancer was associated with telomerase reverse transcriptase (TERT) rs2736100 single-nucleotide polymorphism. The TERT rs2736100 model was still significantly associated with lung cancer risk when combined with environmental and lifestyle factors, including lower education, lower BMI, COPD history, heavy cigarettes smoking, heavy cooking emission, and dietary factors (over-consumption of meat and deficiency in fish/shrimp, vegetables, dairy products, and soybean products). These data suggest that combining TERT SNP and epidemiologic factors may be a useful approach to discriminate high and low-risk individuals for lung cancer.

  14. High-throughput, luciferase-based reverse genetics systems for identifying inhibitors of Marburg and Ebola viruses.

    Science.gov (United States)

    Uebelhoer, Luke S; Albariño, César G; McMullan, Laura K; Chakrabarti, Ayan K; Vincent, Joel P; Nichol, Stuart T; Towner, Jonathan S

    2014-06-01

    Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, represent a significant challenge to global public health. Currently, no licensed therapies exist to treat filovirus infections, which cause up to 90% mortality in human cases. To facilitate development of antivirals against these viruses, we established two distinct screening platforms based on MARV and EBOV reverse genetics systems that express secreted Gaussia luciferase (gLuc). The first platform is a mini-genome replicon to screen viral replication inhibitors using gLuc quantification in a BSL-2 setting. The second platform is complementary to the first and expresses gLuc as a reporter gene product encoded in recombinant infectious MARV and EBOV, thereby allowing for rapid quantification of viral growth during treatment with antiviral compounds. We characterized these viruses by comparing luciferase activity to virus production, and validated luciferase activity as an authentic real-time measure of viral growth. As proof of concept, we adapt both mini-genome and infectious virus platforms to high-throughput formats, and demonstrate efficacy of several antiviral compounds. We anticipate that both approaches will prove highly useful in the development of anti-filovirus therapies, as well as in basic research on the filovirus life cycle.

  15. Transient aerodynamic forces on a fighter model during simulated approach and landing with thrust reversers

    Science.gov (United States)

    Humphreys, A. P.; Paulson, J. W., Jr.; Kemmerly, G. T.

    1988-01-01

    Previous wind tunnel tests of fighter configurations have shown that thrust reverser jets can induce large, unsteady aerodynamic forces and moments during operation in ground proximity. This is a concern for STOL configurations using partial reversing to spoil the thrust while keeping the engine output near military (MIL) power during landing approach. A novel test technique to simulate approach and landing was developed under a cooperative Northrop/NASA/USAF program. The NASA LaRC Vortex Research Facility was used for the experiments in which a 7-percent F-18 model was moved horizontally at speeds of up to 100 feet per second over a ramp simulating an aircraft to ground rate of closure similar to a no-flare STOL approach and landing. This paper presents an analysis of data showing the effect of reverser jet orientation and jet dynamic pressure ratio on the transient forces for different angles of attack, and flap and horizontal tail deflection. It was found, for reverser jets acting parallel to the plane of symmetry, that the jets interacted strongly with the ground, starting approximately half a span above the ground board. Unsteady rolling moment transients, large enough to cause the probable upset of an aircraft, and strong normal force and pitching moment transients were measured. For jets directed 40 degrees outboard, the transients were similar to the jet-off case, implying only minor interaction.

  16. A multiobjective approach to the genetic code adaptability problem.

    Science.gov (United States)

    de Oliveira, Lariza Laura; de Oliveira, Paulo S L; Tinós, Renato

    2015-02-19

    The organization of the canonical code has intrigued researches since it was first described. If we consider all codes mapping the 64 codes into 20 amino acids and one stop codon, there are more than 1.51×10(84) possible genetic codes. The main question related to the organization of the genetic code is why exactly the canonical code was selected among this huge number of possible genetic codes. Many researchers argue that the organization of the canonical code is a product of natural selection and that the code's robustness against mutations would support this hypothesis. In order to investigate the natural selection hypothesis, some researches employ optimization algorithms to identify regions of the genetic code space where best codes, according to a given evaluation function, can be found (engineering approach). The optimization process uses only one objective to evaluate the codes, generally based on the robustness for an amino acid property. Only one objective is also employed in the statistical approach for the comparison of the canonical code with random codes. We propose a multiobjective approach where two or more objectives are considered simultaneously to evaluate the genetic codes. In order to test our hypothesis that the multiobjective approach is useful for the analysis of the genetic code adaptability, we implemented a multiobjective optimization algorithm where two objectives are simultaneously optimized. Using as objectives the robustness against mutation with the amino acids properties polar requirement (objective 1) and robustness with respect to hydropathy index or molecular volume (objective 2), we found solutions closer to the canonical genetic code in terms of robustness, when compared with the results using only one objective reported by other authors. Using more objectives, more optimal solutions are obtained and, as a consequence, more information can be used to investigate the adaptability of the genetic code. The multiobjective approach

  17. Efficient generation of recombinant influenza A viruses employing a new approach to overcome the genetic instability of HA segments.

    Directory of Open Access Journals (Sweden)

    Ahmed Mostafa

    Full Text Available Influenza A viruses (IAVs are the most relevant and continual source of severe infectious respiratory complications in humans and different animal species, especially poultry. Therefore, an efficient vaccination that elicits protective and neutralizing antibodies against the viral hemagglutinin (HA and neuraminidase (NA is an important strategy to counter annual epidemics or occasional pandemics. With the help of plasmid-based reverse genetics technology, it is possible that IAV vaccine strains (IVVS are rapidly generated. However, the genetic instability of some cloned HA-cDNAs after transformation into competent bacteria represents a major obstacle. Herein, we report efficient cloning strategies of different genetically volatile HA segments (H5- and H9-subtypes employing either a newly constructed vector for reverse genetics (pMKPccdB or by the use of the Escherichia coli strain HB101. Both approaches represent improved and generalizable strategies to establish functional reverse genetics systems preventing genetic changes to the cloned (HA segments of IAV facilitating more efficient rescue of recombinant IAV for basic research and vaccine development.

  18. Population Genetic Diversity in the Australian 'Seascape': A Bioregion Approach.

    Directory of Open Access Journals (Sweden)

    Lisa C Pope

    Full Text Available Genetic diversity within species may promote resilience to environmental change, yet little is known about how such variation is distributed at broad geographic scales. Here we develop a novel Bayesian methodology to analyse multi-species genetic diversity data in order to identify regions of high or low genetic diversity. We apply this method to co-distributed taxa from Australian marine waters. We extracted published summary statistics of population genetic diversity from 118 studies of 101 species and > 1000 populations from the Australian marine economic zone. We analysed these data using two approaches: a linear mixed model for standardised data, and a mixed beta-regression for unstandardised data, within a Bayesian framework. Our beta-regression approach performed better than models using standardised data, based on posterior predictive tests. The best model included region (Integrated Marine and Coastal Regionalisation of Australia (IMCRA bioregions, latitude and latitude squared. Removing region as an explanatory variable greatly reduced model performance (delta DIC 23.4. Several bioregions were identified as possessing notably high genetic diversity. Genetic diversity increased towards the equator with a 'hump' in diversity across the range studied (-9.4 to -43.7°S. Our results suggest that factors correlated with both region and latitude play a role in shaping intra-specific genetic diversity, and that bioregion can be a useful management unit for intra-specific as well as species biodiversity. Our novel statistical model should prove useful for future analyses of within species genetic diversity at broad taxonomic and geographic scales.

  19. Genetic and genomic approaches to understanding macrophage identity and function.

    Science.gov (United States)

    Glass, Christopher K

    2015-04-01

    A major goal of our laboratory is to understand the molecular mechanisms that underlie the development and functions of diverse macrophage phenotypes in health and disease. Recent studies using genetic and genomic approaches suggest a relatively simple model of collaborative and hierarchical interactions between lineage-determining and signal-dependent transcription factors that enable selection and activation of transcriptional enhancers that specify macrophage identity and function. In addition, we have found that it is possible to use natural genetic variation as a powerful tool for advancing our understanding of how the macrophage deciphers the information encoded by the genome to attain specific phenotypes in a context-dependent manner. Here, I will describe our recent efforts to extend genetic and genomic approaches to investigate the roles of distinct tissue environments in determining the phenotypes of different resident populations of macrophages.

  20. Review: domestic animal forensic genetics - biological evidence, genetic markers, analytical approaches and challenges.

    Science.gov (United States)

    Kanthaswamy, S

    2015-10-01

    This review highlights the importance of domestic animal genetic evidence sources, genetic testing, markers and analytical approaches as well as the challenges this field is facing in view of the de facto 'gold standard' human DNA identification. Because of the genetic similarity between humans and domestic animals, genetic analysis of domestic animal hair, saliva, urine, blood and other biological material has generated vital investigative leads that have been admitted into a variety of court proceedings, including criminal and civil litigation. Information on validated short tandem repeat, single nucleotide polymorphism and mitochondrial DNA markers and public access to genetic databases for forensic DNA analysis is becoming readily available. Although the fundamental aspects of animal forensic genetic testing may be reliable and acceptable, animal forensic testing still lacks the standardized testing protocols that human genetic profiling requires, probably because of the absence of monetary support from government agencies and the difficulty in promoting cooperation among competing laboratories. Moreover, there is a lack in consensus about how to best present the results and expert opinion to comply with court standards and bear judicial scrutiny. This has been the single most persistent challenge ever since the earliest use of domestic animal forensic genetic testing in a criminal case in the mid-1990s. Crime laboratory accreditation ensures that genetic test results have the courts' confidence. Because accreditation requires significant commitments of effort, time and resources, the vast majority of animal forensic genetic laboratories are not accredited nor are their analysts certified forensic examiners. The relevance of domestic animal forensic genetics in the criminal justice system is undeniable. However, further improvements are needed in a wide range of supporting resources, including standardized quality assurance and control protocols for sample

  1. Understanding the Science-Learning Environment: A Genetically Sensitive Approach

    Science.gov (United States)

    Haworth, Claire M. A.; Davis, Oliver S. P.; Hanscombe, Ken B.; Kovas, Yulia; Dale, Philip S.; Plomin, Robert

    2013-01-01

    Previous studies have shown that environmental influences on school science performance increase in importance from primary to secondary school. Here we assess for the first time the relationship between the science-learning environment and science performance using a genetically sensitive approach to investigate the aetiology of this link. 3000…

  2. PERFORMA IKAN NILA (Oreochromis niloticus HASIL SEX REVERSAL, GENETICALLY MALE DAN YY PADA FASE PENDEDERAN PERTAMA

    Directory of Open Access Journals (Sweden)

    Odang Carman

    2016-11-01

    Full Text Available Penelitian ini dilakukan untuk mengkaji performa ikan nila hasil sex reversal (SRV, genetically male tilapia (GMT, dan YY pada fase pendederan pertama di akuarium. Benih ikan dipelihara selama 22 hari, dari umur 6 hari hingga 28 hari. Parameter yang diamati meliputi tingkat sintasan, persentase ikan jantan, laju pertumbuhan, dan biomassa. Hasil penelitian menunjukkan bahwa tingkat sintasan tidak berbeda (P>0,05 antar ketiga kelompok ikan dan kontrol (KN, berkisar antara 85,30%--86,20%. Persentase ikan jantan antara SRV (94,5% ± 1,32% vs. GMT (93,8% ± 1,25% dan GMT vs. YY (90,2% ± 1,83% tidak berbeda (P>0,05, sedangkan antara SRV lebih tinggi daripada YY (P0.05, ranged from 85.30%-86.20%. Percentage of male fish between SRV (94.5% ± 1.32% versus GMT (93.8% ± 1.25% and GMT versus YY (90.2% ± 1.83% were also similar (P>0.05, while SRV is higher than YY (P<0.05. Percentage of male fish in the three fish groups was higher than that of control (56.9% ± 3.62%. Growth of YY fish and GMT were higher compared to SRV and control fish (KN. The mean weight of YY fish at the end of the experiment reached 476 mg, GMT fish 447 mg, SRV fish 379 mg and control 342 mg. Biomass of YY, GMT and SRV fish were respectively higher by 41.3%, 32.9%, and 10.3% compared to control. With high performance and technical consideration in farm, GMT fish can be a potential alternative to be cultured in fish farm in order to increase aquaculture production of nile tilapia.

  3. The limitations of the reverse-engineering approach to cognitive modeling.

    Science.gov (United States)

    Rueckl, Jay G

    2012-10-01

    Frost's critique reveals the limitations of the reverse-engineering approach to cognitive modeling--the style of psychological explanation in which a stipulated internal organization (in the form of a computational mechanism) explains a relatively narrow set of phenomena. An alternative is to view organization as both the explanation for some phenomena and a phenomenon to be explained. This move poses new and interesting theoretical challenges for theories of word reading.

  4. WONOEP appraisal: new genetic approaches to study epilepsy

    Science.gov (United States)

    Rossignol, Elsa; Kobow, Katja; Simonato, Michele; Loeb, Jeffrey A.; Grisar, Thierry; Gilby, Krista L.; Vinet, Jonathan; Kadam, Shilpa D.; Becker, Albert J.

    2014-01-01

    Objective New genetic investigation techniques, including next-generation sequencing, epigenetic profiling, cell lineage mapping, targeted genetic manipulation of specific neuronal cell types, stem cell reprogramming and optogenetic manipulations within epileptic networks are progressively unravelling the mysteries of epileptogenesis and ictogenesis. These techniques have opened new avenues to discover the molecular basis of epileptogenesis and to study the physiological impacts of mutations in epilepsy-associated genes on a multilayer level, from cells to circuits. Methods This manuscript reviews recently published applications of these new genetic technologies in the study of epilepsy, as well as work presented by the authors at the genetic session of the XII Workshop on the Neurobiology of Epilepsy in Quebec, Canada. Results Next-generation sequencing is providing investigators with an unbiased means to assess the molecular causes of sporadic forms of epilepsy and have revealed the complexity and genetic heterogeneity of sporadic epilepsy disorders. To assess the functional impact of mutations in these newly identified genes on specific neuronal cell-types during brain development, new modeling strategies in animals, including conditional genetics in mice and in utero knockdown approaches, are enabling functional validation with exquisite cell-type and temporal specificity. In addition, optogenetics, using cell-type specific Cre recombinase driver lines, is enabling investigators to dissect networks involved in epilepsy. Genetically-encoded cell-type labeling is also providing new means to assess the role of the non-neuronal components of epileptic networks such as glial cells. Furthermore, beyond its role in revealing coding variants involved in epileptogenesis, next-generation sequencing can be used to assess the epigenetic modifications that lead to sustained network hyperexcitability in epilepsy, including methylation changes in gene promoters and non

  5. Malformations of cortical development: genetic mechanisms and diagnostic approach

    Science.gov (United States)

    2017-01-01

    Malformations of cortical development are rare congenital anomalies of the cerebral cortex, wherein patients present with intractable epilepsy and various degrees of developmental delay. Cases show a spectrum of anomalous cortical formations with diverse anatomic and morphological abnormalities, a variety of genetic causes, and different clinical presentations. Brain magnetic resonance imaging has been of great help in determining the exact morphologies of cortical malformations. The hypothetical mechanisms of malformation include interruptions during the formation of cerebral cortex in the form of viral infection, genetic causes, and vascular events. Recent remarkable developments in genetic analysis methods have improved our understanding of these pathological mechanisms. The present review will discuss normal cortical development, the current proposed malformation classifications, and the diagnostic approach for malformations of cortical development. PMID:28203254

  6. Network medicine approaches to the genetics of complex diseases.

    Science.gov (United States)

    Silverman, Edwin K; Loscalzo, Joseph

    2012-08-01

    Complex diseases are caused by perturbations of biological networks. Genetic analysis approaches focused on individual genetic determinants are unlikely to characterize the network architecture of complex diseases comprehensively. Network medicine, which applies systems biology and network science to complex molecular networks underlying human disease, focuses on identifying the interacting genes and proteins which lead to disease pathogenesis. The long biological path between a genetic risk variant and development of a complex disease involves a range of biochemical intermediates, including coding and non-coding RNA, proteins, and metabolites. Transcriptomics, proteomics, metabolomics, and other -omics technologies have the potential to provide insights into complex disease pathogenesis, especially if they are applied within a network biology framework. Most previous efforts to relate genetics to -omics data have focused on a single -omics platform; the next generation of complex disease genetics studies will require integration of multiple types of -omics data sets in a network context. Network medicine may also provide insight into complex disease heterogeneity, serve as the basis for new disease classifications that reflect underlying disease pathogenesis, and guide rational therapeutic and preventive strategies.

  7. Chemical genetics approaches for selective intervention in epigenetics.

    Science.gov (United States)

    Runcie, Andrew C; Chan, Kwok-Ho; Zengerle, Michael; Ciulli, Alessio

    2016-08-01

    Chemical genetics is the use of biologically active small molecules (chemical probes) to investigate the functions of gene products, through the modulation of protein activity. Recent years have seen significant progress in the application of chemical genetics to study epigenetics, following the development of new chemical probes, a growing appreciation of the role of epigenetics in disease and a recognition of the need and utility of high-quality, cell-active chemical probes. In this review, we single out the bromodomain reader domains as a prime example of both the success, and challenges facing chemical genetics. The difficulty in generating single-target selectivity has long been a thorn in the side of chemical genetics, however, recent developments in advanced forms of chemical genetics promise to bypass this, and other, limitations. The 'bump-and-hole' approach has now been used to probe - for the first time - the BET bromodomain subfamily with single-target selectivity and may be applicable to other epigenetic domains. Meanwhile, PROTAC compounds have been shown to be significantly more efficacious than standard domain inhibitors, and have the potential to enhance target selectivity.

  8. A genetic approach to understanding asthma and lung function development

    DEFF Research Database (Denmark)

    Kreiner-Møller, Eskil

    2014-01-01

    Asthma is a common heritable disease of the airways with recurrent episodes of symptoms and reversible airflow obstruction that has increased dramatically in prevalence. The disease is highly heterogeneous with varying age at onset and clinical presentation and most likely represents several...... different subtypes of disease associated with distinct clinical features, divergent underlying molecular mechanisms, and individual treatment responses. Information obtained from genetic studies may be an important way of understanding underlying disease subtypes. Genome wide association studies (GWAS) have......, related traits and objective measures in order to disentangle the underlying pathophysiological disease mechanisms for the subtypes of disease. Several genes and loci have been found to be associated with adult lung function in GWAS, but it is currently unknown at what time in life these genes exert...

  9. OPTIMIZING LOCALIZATION ROUTE USING PARTICLE SWARM-A GENETIC APPROACH

    Directory of Open Access Journals (Sweden)

    L. Lakshmanan

    2014-01-01

    Full Text Available One of the most key problems in wireless sensor networks is finding optimal algorithms for sending packets from source node to destination node. Several algorithms exist in literature, since some are in vital role other may not. Since WSN focus on low power consumption during packet transmission and receiving, finally we adopt by merging swarm particle based algorithm with genetic approach. Initially we order the nodes based on their energy criterion and then focusing towards node path; this can be done using Proactive route algorithm for finding optimal path between Source-Destination (S-D nodes. Fast processing and pre traversal can be done using selective flooding approach and results are in genetic. We have improved our results with high accuracy and optimality in rendering routes.

  10. MIMO Modeling Approach for a Small Photovoltaic Reverse Osmosis Desalination System

    Directory of Open Access Journals (Sweden)

    A.B Chaaben

    2011-01-01

    Full Text Available The most widely used desalination processes are based on membrane separation via reverse osmosis (RO which has become an important process for desalting seawater and cleaning brackish water. The use of these processes requires an efficient control system. Consequently, it is necessary to establish a dynamic model of the system with experimental validation. This paper deals with a new modelling approach of a small photovoltaic reverse osmosis (PV-RO desalination unit. The proposed model considers the unit as a Multi Input Multi Output (MIMO process. The relations between the output variables and the input variables are given by the use of empirical transfer matrix. A state model of the unit is also given. Some experimental results are presented to validate the proposed model. As result, the obtained unit model can be easily used for a process control loop implementation in order to assure an optimum operating condition and to reduce the water product cost.

  11. Post-partum hemorrhage complicated by reverse-Takotsubo cardiogenic shock; a novel therapeutic approach.

    Science.gov (United States)

    Papanikolaou, John; Makris, Demosthenes; Tsolaki, Vasiliki; Spathoulas, Konstantinos; Zakynthinos, Epaminondas

    2017-06-01

    Takotsubo Cardiomyopathy (TTC) is a type of transient, yet severe left ventricular systolic dysfunction, rarely complicating extreme emotional stress ("primary" TTC) or critical medical/surgical illness ("secondary" TTC forms). Although usually reversible, TTC may result in cardiogenic shock with dismal prognosis. "Secondary" TTC forms are particularly in danger for this complication, bearing significantly worse short and long-term prognosis. Herein, we report a rare case of a life-threatening "secondary" TTC in a patient with post-cesarean section severe hemorrhage, and we point out that early co-administration of esmolol and levosimendan might be an effective and safe therapeutic approach in "reversing" TTC-induced cardiogenic shock, especially when invasive therapeutic strategies are practically unfeasible. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A Neural Network Approach on Reverse Engineering Surface Reasoning in the Manufacturing Field

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper applied the neural network technology to surfacereasoning in reverse engineering and established the neural network computation model. One of the main advantages of reasoning solid surface using neural network is that no knowledge about surface is needed, and the limited measured points on the surface will do sufficiently. This paper listed the related reasoning cases, including the elementary analytical surfaces and freeform surfaces, discussed the various issues occurring during reasoning process and proved the feasibility and efficiency of this approach from theory and practical computing cases. The results show that a neural network is an excellent aided analysis means for surface reasoning in reversing engineering and possesses practical use for the surface that is complex, incomplete and partially worn-out or damaged.

  13. An approach for protein to be completely reversible to thermal denaturation even at autoclave temperatures.

    Science.gov (United States)

    Iwakura, M; Nakamura, D; Takenawa, T; Mitsuishi, Y

    2001-08-01

    Reversibility of protein denaturation is a prerequisite for all applications that depend on reliable enzyme catalysis, particularly, for using steam to sterilize enzyme reactors or enzyme sensor tips, and for developing protein-based devices that perform on-off switching of the protein function such as enzymatic activity, ligand binding and so on. In this study, we have successfully constructed an immobilized protein that retains full enzymatic activity even after thermal treatments as high as 120 degrees C. The key for the complete reversibility was the development of a new reaction that allowed a protein to be covalently attached to a surface through its C-terminus and the protein engineering approach that was used to make the protein compatible with the new attachment chemistry.

  14. A genetic algorithm approach to routine gamma spectra analysis

    Energy Technology Data Exchange (ETDEWEB)

    Carlevaro, C M [Instituto de FIsica de LIquidos y Sistemas Biologicos, Calle 59 No 789, B1900BTE La Plata (Argentina); Wilkinson, M V [Autoridad Regulatoria Nuclear, Avda. del Libertador 8250, C1429BNP Buenos Aires (Argentina); Barrios, L A [Autoridad Regulatoria Nuclear, Avda. del Libertador 8250, C1429BNP Buenos Aires (Argentina)

    2008-01-15

    In this work we present an alternative method for performing routine gamma spectra analysis based on genetic algorithm techniques. The main idea is to search for patterns of single nuclide spectra obtained by simulation in a sample spectrum targeted for analysis. We show how this approach is applied to the analysis of simulated and real target spectra, and also to the study of interference resolution.

  15. A Hypomethylated population of Brassica rapa for forward and reverse Epi-genetics

    Directory of Open Access Journals (Sweden)

    Amoah Stephen

    2012-10-01

    decreased oil content, as well as decreased erucic acid and corresponding increases in linoleic and/or palmitic acid. Each 5-AzaC-treated line represents a unique combination of hypomethylated epialleles. Conclusions The approach and populations developed are available for forward and reverse screening of epiallelic variation and subsequent functional and inheritance studies. The generation of stochastically hypomethylated populations has utility in epiallele discovery for a wide range of crop plants, and has considerable potential as an intervention strategy for crop improvement.

  16. DNA enrichment approaches to identify unauthorized genetically modified organisms (GMOs).

    Science.gov (United States)

    Arulandhu, Alfred J; van Dijk, Jeroen P; Dobnik, David; Holst-Jensen, Arne; Shi, Jianxin; Zel, Jana; Kok, Esther J

    2016-07-01

    With the increased global production of different genetically modified (GM) plant varieties, chances increase that unauthorized GM organisms (UGMOs) may enter the food chain. At the same time, the detection of UGMOs is a challenging task because of the limited sequence information that will generally be available. PCR-based methods are available to detect and quantify known UGMOs in specific cases. If this approach is not feasible, DNA enrichment of the unknown adjacent sequences of known GMO elements is one way to detect the presence of UGMOs in a food or feed product. These enrichment approaches are also known as chromosome walking or gene walking (GW). In recent years, enrichment approaches have been coupled with next generation sequencing (NGS) analysis and implemented in, amongst others, the medical and microbiological fields. The present review will provide an overview of these approaches and an evaluation of their applicability in the identification of UGMOs in complex food or feed samples.

  17. Inappropriate Use of the Quasi-Reversible Electrode Kinetic Model in Simulation-Experiment Comparisons of Voltammetric Processes That Approach the Reversible Limit

    KAUST Repository

    Simonov, Alexandr N.

    2014-08-19

    Many electrode processes that approach the "reversible" (infinitely fast) limit under voltammetric conditions have been inappropriately analyzed by comparison of experimental data and theory derived from the "quasi-reversible" model. Simulations based on "reversible" and "quasi-reversible" models have been fitted to an extensive series of a.c. voltammetric experiments undertaken at macrodisk glassy carbon (GC) electrodes for oxidation of ferrocene (Fc0/+) in CH3CN (0.10 M (n-Bu)4NPF6) and reduction of [Ru(NH 3)6]3+ and [Fe(CN)6]3- in 1 M KCl aqueous electrolyte. The confidence with which parameters such as standard formal potential (E0), heterogeneous electron transfer rate constant at E0 (k0), charge transfer coefficient (α), uncompensated resistance (Ru), and double layer capacitance (CDL) can be reported using the "quasi- reversible" model has been assessed using bootstrapping and parameter sweep (contour plot) techniques. Underparameterization, such as that which occurs when modeling CDL with a potential independent value, results in a less than optimal level of experiment-theory agreement. Overparameterization may improve the agreement but easily results in generation of physically meaningful but incorrect values of the recovered parameters, as is the case with the very fast Fc0/+ and [Ru(NH3)6]3+/2+ processes. In summary, for fast electrode kinetics approaching the "reversible" limit, it is recommended that the "reversible" model be used for theory-experiment comparisons with only E0, R u, and CDL being quantified and a lower limit of k 0 being reported; e.g., k0 ≥ 9 cm s-1 for the Fc0/+ process. © 2014 American Chemical Society.

  18. Neural network approach for modification and fitting of digitized data in reverse engineering

    Institute of Scientific and Technical Information of China (English)

    JU Hua(鞠华); WANG Wen(王文); XIE Jin (谢金); CHEN Zi-chen(陈子辰)

    2004-01-01

    Reverse engineering in the manufacturing field is a process in which the digitized data are obtained from an existing object model or a part of it, and then the CAD model is reconstructed. This paper presents an RBF neural network approach to modify and fit the digitized data. The centers for the RBF are selected by using the orthogonal least squares learning algorithm. A mathematically known surface is used for generating a number of samples for training the networks. The trained networks then generated a number of new points which were compared with the calculating points from the equations. Moreover, a series of practice digitizing curves are used to test the approach. The results showed that this approach is effective in modifying and fitting digitized data and generating data points to reconstruct the surface model.

  19. Neural network approach for modification and fitting of digitized data in reverse engineering~

    Institute of Scientific and Technical Information of China (English)

    鞠华; 王文; 谢金; 陈子辰

    2004-01-01

    Reverse engineering in the manufacturing field is a process in which the digitized data are obtained from an existing object model or a part of it, and then the CAD model is reconstructed. This paper presents an RBF neural network approach to modify and fit the digitized data. The centers for the RBF are selected by using the orthogonal least squares learning algorithm. A mathematically known surface is used for generating a number of samples for training the networks. The trained networks then generated a number of new points which were compared with the calculating points from the equations. Moreover, a series of practice digitizing curves are used to test the approach. The results showed that this approach is effective in modifying and fitting digitized data and generating data points to reconstruct the surface model.

  20. A HYBRID GENETIC ALGORITHM-NEURAL NETWORK APPROACH FOR PRICING CORES AND REMANUFACTURED CORES

    Directory of Open Access Journals (Sweden)

    M. Seidi

    2012-01-01

    Full Text Available

    ENGLISH ABSTRACT:Sustainability has become a major issue in most economies, causing many leading companies to focus on product recovery and reverse logistics. Remanufacturing is an industrial process that makes used products reusable. One of the important aspects in both reverse logistics and remanufacturing is the pricing of returned and remanufactured products (called cores. In this paper, we focus on pricing the cores and remanufactured cores. First we present a mathematical model for this purpose. Since this model does not satisfy our requirements, we propose a simulation optimisation approach. This approach consists of a hybrid genetic algorithm based on a neural network employed as the fitness function. We use automata learning theory to obtain the learning rate required for training the neural network. Numerical results demonstrate that the optimal value of the acquisition price of cores and price of remanufactured cores is obtained by this approach.

    AFRIKAANSE OPSOMMING: Volhoubaarheid het ‘n belangrike saak geword in die meeste ekonomieë, wat verskeie maatskappye genoop het om produkherwinning en omgekeerde logistiek te onder oë te neem. Hervervaardiging is ‘n industriële proses wat gebruikte produkte weer bruikbaar maak. Een van die belangrike aspekte in beide omgekeerde logistiek en hervervaardiging is die prysbepaling van herwinne en hervervaardigde produkte. Hierdie artikel fokus op die prysbepalingsaspekte by wyse van ‘n wiskundige model.

  1. Evaluation of a reverse-hybridization StripAssay for the detection of genetic polymorphisms leading to acenocoumarol sensitivity.

    Science.gov (United States)

    Gialeraki, Argyri; Markatos, Christos; Grouzi, Elisabeth; Merkouri, Efrosyni; Travlou, Anthi; Politou, Marianna

    2010-04-01

    Acenocoumarol is mainly catabolized by CYP2C9 isoform of cytochrome P450 (CYP) liver complex and exerts its anticoagulant effect through the inhibition of Vitamin K Epoxide Reductase (VKOR). The most important genetic polymorphisms which lead to an impaired enzymatic activity and therefore predispose to acenocoumarol sensitivity, are considered to be CYP2C9*2 (Arg144Cys), CYP2C9*3 (Ile359Leu) and VKORC1-1639G>A, respectively. In this study we compared the results of the PGXThrombo StripAssay kit (ViennaLab Diagnostics,Vienna, Austria) with direct DNA sequencing and in house Restriction Fragment Length Polymorphisms (RFLP) for the detection of the aforementioned Single Nucleotide Polymorphisms (SNPs). The reverse hybridization StripAssay was found to be equally effective with RFLP and direct DNA sequencing for the detection of CYP2C9*2 and CYP2C9*3 polymorphisms, respectively. The comparison of the RFLP reference method with the reverse hybridization StripAssay for the detection of VKORC1-1639 G>A polymorphism showed that the reverse hybridization StripAsssay might misclassify some A/A homozygotes as heterozygotes. Optimization of the hybridization procedures may eliminate the extra low signal band observed in some samples at the reverse hybridization StripAssay and improve its diagnostic value.

  2. [Current methods in genetic analysis : an approach for genetics-based preventive medicine].

    Science.gov (United States)

    Klein, Hans-Georg; Rost, Imma

    2015-02-01

    Modern genetic analysis methods such as DNA arrays (gene chips) or high-throughput DNA sequencing of the next generation (Next Generation Sequencing, NGS) have once again accelerated the pace of innovation that has been powered by genome research over the past 10 years of the "post-genomic era". The present paper introduces array and NGS methods as two important innovation driving methods and provides examples for their application in large-scale scientific projects. However, a broad application of these very powerful technologies for genetic screening for the purpose of disease prevention is currently not yet in sight. The complexity of the interaction of genes, gene products and the environment has so far exceeded all expectations, suggesting that reliable statements about the medical relevance of common genetic variants can presently only be made in a few areas such as pharmacogenetics and oncology. We also discuss ethical issues raised by genetic population screening. The aim of this paper is to provide a brief outline of the development of methods in molecular genetics to the now dominant modern technologies and present their applications in research, in the diagnosis of rare diseases, and in terms of screening approaches.

  3. Impact of genomics approaches on plant genetics and physiology.

    Science.gov (United States)

    Tabata, Satoshi

    2002-08-01

    Comprehensive analysis of genetic information in higher plants is under way for several plants of biological and agronomical importance. Among them, Arabidopsis thaliana, a member of Brassica family, and Oryza sativa(rice) have been chosen as model plants most suitable for genome analysis. Sequencing of the genome of A. thaliana was completed in December 2000, and rice genome sequencing is in progress. The accumulated genome sequences, together with the hundreds of thousands of ESTs from several tens of plant species, have drastically changed the strategy of plant genetics. By utilizing the information on the genome and gene structures, comprehensive approaches for genome-wide functional analysis of the genes, including transcriptome analysis using microarray systems and a comprehensive analysis of a large number of insertion mutant lines, have been widely adopted. As a consequence, a large quantity of information on both the structure and function of genes in these model plants has been accumulated. However, other plant species may have their own characteristics and advantages to study individual phenomena. Application of knowledge from the model plants to other plant species and vice versa through the common language, namely the genome information, should facilitate understanding of the genetic systems underlying a variety of biological phenomena. Introduction of this common language may not be very simple, especially in the case of complex pathways such as a process of cell-covering formation. Nevertheless, it should be emphasized that genomics approaches are the most promising way to understand these processes.

  4. An Airborne Conflict Resolution Approach Using a Genetic Algorithm

    Science.gov (United States)

    Mondoloni, Stephane; Conway, Sheila

    2001-01-01

    An airborne conflict resolution approach is presented that is capable of providing flight plans forecast to be conflict-free with both area and traffic hazards. This approach is capable of meeting constraints on the flight plan such as required times of arrival (RTA) at a fix. The conflict resolution algorithm is based upon a genetic algorithm, and can thus seek conflict-free flight plans meeting broader flight planning objectives such as minimum time, fuel or total cost. The method has been applied to conflicts occurring 6 to 25 minutes in the future in climb, cruise and descent phases of flight. The conflict resolution approach separates the detection, trajectory generation and flight rules function from the resolution algorithm. The method is capable of supporting pilot-constructed resolutions, cooperative and non-cooperative maneuvers, and also providing conflict resolution on trajectories forecast by an onboard FMC.

  5. Genetic Evolutionary Approach for Cutting Forces Prediction in Hard Milling

    Science.gov (United States)

    Taylan, Fatih; Kayacan, Cengiz

    2011-11-01

    Hard milling is a very common used machining procedure in the last years. Therefore the prediction of cutting forces is important. The paper deals with this prediction using genetic evolutionary programming (GEP) approach to set mathematical expression for out cutting forces. In this study, face milling was performed using DIN1.2842 (90MnCrV8) cold work tool steel, with a hardness of 61 HRC. Experimental parameters were selected using stability measurements and simulations. In the hard milling experiments, cutting force data in a total of three axes were collected. Feed direction (Fx) and tangential direction (Fy) cutting forces generated using genetic evolutionary programming were modelled. Cutting speed and feed rate values were treated as inputs in the models, and average cutting force values as output. Mathematical expressions were created to predict average Fxand Fy forces that can be generated in hard material milling.

  6. Prediction of S-shaped characteristics in reversible pump-turbines using different numerical approaches

    Science.gov (United States)

    Lenarcic, M.; Bauer, Ch.; Giese, M.; Jung, A.

    2016-11-01

    The prediction of characteristics and flow phenomena in reversible pump-turbines becomes increasingly important, since operations under off-design conditions are required to respond to frequency fluctuations within the electrical grid as fast as possible. Fulfilling the requirements of a stable and reliable operation under continuously expanding operating ranges challenges the hydraulic design and requires ambitious developments. Beyond that, precise estimations of occurring flow phenomena combined with a detailed understanding of their causes and mechanisms are essential. This study aims at predicting the S-shaped characteristics of two reversible pump-turbines by using different numerical approaches. Therefore, measurements at a constant wicket-gate opening of Δγ = 10° were done. Based on these experimental data, unsteady flow simulations are performed under steady and transient operating conditions respectively: Starting from the best efficiency point in generating mode, through the runaway, along the S-curve, down to operation in reverse pump mode. The hydraulic machines are spatially discretized in model size with a near-wall refinement of y + mean ≤ 5 and y + mean ≥ 30. The application of two different solvers discloses deviations in underlying methods. The turbulence modeling is basically executed by the k-ω-SST and the standard k-ɛ model. Focusing on higher order numerics, the Explicit Algebraic Reynolds Stress Model (EARSM) is selected in the commercial code and extended with an approach for curvature correction (EARSM- CC). In the open-source software, the four-equation v2-f model assumes the role of higher order numerics. The temporal discretization errors are observed using three different time-step sizes. As a supplement, experimental data obtained from the HydroDyna pump-turbine are used as additional validation, providing integral quantities and local pressure distributions at an operating point set on the S-curve. To sum this work up, a

  7. Neural Network Control of CSTR for Reversible Reaction Using Reverence Model Approach

    Directory of Open Access Journals (Sweden)

    Duncan ALOKO

    2007-01-01

    Full Text Available In this work, non-linear control of CSTR for reversible reaction is carried out using Neural Network as design tool. The Model Reverence approach in used to design ANN controller. The idea is to have a control system that will be able to achieve improvement in the level of conversion and to be able to track set point change and reject load disturbance. We use PID control scheme as benchmark to study the performance of the controller. The comparison shows that ANN controller out perform PID in the extreme range of non-linearity.This paper represents a preliminary effort to design a simplified neutral network control scheme for a class of non-linear process. Future works will involve further investigation of the effectiveness of thin approach for the real industrial chemical process

  8. Adiabatic magnetocaloric temperature change in polycrystalline gadolinium – A new approach highlighting reversibility

    Directory of Open Access Journals (Sweden)

    Mohammadreza Ghahremani

    2012-09-01

    Full Text Available The adiabatic temperature change (ΔT during the magnetization and demagnetization processes of bulk gadolinium is directly measured for several applied magnetic fields in the temperature range 285 K to 305 K. During the magnetization process, ΔT measurements display the same maximum for each applied field when plotted against the initial temperature (Ti. However, during the demagnetization process, the maximum ΔT varies for each applied field. This discrepancy between the magnetization and demagnetization measurements appears inconsistent with the reversibility of the magnetocaloric effect. A new approach is undertaken to highlight the reversibility of the magnetocaloric effect by plotting ΔT against the average temperature change (Tavg instead of Ti. The value of Tavg which corresponds to the maximum ΔT is found to increase linearly with the applied magnetic field, consistently for both the magnetization and demagnetization measurements. Solving the linear-fitting equations of these measurements gives a new, and more precise, Curie temperature measurement. This new approach confirmed that the relationship between the maximum adiabatic temperature change (ΔTpeak and the applied magnetic field is perfectly linear.

  9. Generation of an Avian-Mammalian Rotavirus Reassortant by Using a Helper Virus-Dependent Reverse Genetics System.

    Science.gov (United States)

    Johne, Reimar; Reetz, Jochen; Kaufer, Benedikt B; Trojnar, Eva

    2015-11-18

    The genetic diversity of rotavirus A (RVA) strains is facilitated in part by genetic reassortment. Although this process of genome segment exchange has been reported frequently among mammalian RVAs, it remained unknown if mammalian RVAs also could package genome segments from avian RVA strains. We generated a simian RVA strain SA11 reassortant containing the VP4 gene of chicken RVA strain 02V0002G3. To achieve this, we transfected BSR5/T7 cells with a T7 polymerase-driven VP4-encoding plasmid, infected the cells with a temperature-sensitive SA11 VP4 mutant, and selected the recombinant virus by increasing the temperature. The reassortant virus could be stably passaged and exhibited cytopathic effects in MA-104 cells, but it replicated less efficiently than both parental viruses. Our results show that avian and mammalian rotaviruses can exchange genome segments, resulting in replication-competent reassortants with new genomic and antigenic features. This study shows that rotaviruses of mammals can package genome segments from rotaviruses of birds. The genetic diversity of rotaviruses could be broadened by this process, which might be important for their antigenic variability. The reverse genetics system applied in the study could be useful for targeted generation and subsequent characterization of distinct rotavirus reassortant strains. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  10. An analytical approach to the implementation of genetically modified crops

    DEFF Research Database (Denmark)

    Borch, K.; Rasmussen, B.

    2000-01-01

    Public scepticism towards genetically modified (GM) crops is increasing. To address this, the risks and benefits of GM crops must be examined across scientific disciplines, and be discussed with the authorities, the agricultural industry and the consumers. In a feasibility study we have...... systematically analysed the challenges of the development and marketing of GM crops in Europe. A life-cycle inventory was used together with established technology foresight techniques in an interdisciplinary and empirical framework. The approach taken in this study established a dialogue between stakeholders...... and provided a framework for discussions about the future direction of GM crops....

  11. [Mendelian randomisation - a genetic approach to an epidemiological method].

    Science.gov (United States)

    Stensrud, Mats Julius

    2016-06-01

    BACKGROUND Genetic information is becoming more easily available, and rapid progress is being made in developing methods of illuminating issues of interest. Mendelian randomisation makes it possible to study causes of disease using observational data. The name refers to the random distribution of gene variants in meiosis. The methodology makes use of genes that influence a risk factor for a disease, without influencing the disease itself. In this review article I explain the principles behind Mendelian randomisation and present the areas of application for this methodology.MATERIAL AND METHOD Methodology articles describing Mendelian randomisation were reviewed. The articles were found through a search in PubMed with the combination «mendelian randomization» OR «mendelian randomisation», and a search in McMaster Plus with the combination «mendelian randomization». A total of 15 methodology articles were read in full text. Methodology articles were supplemented by clinical studies found in the PubMed search.RESULTS In contrast to traditional observational studies, Mendelian randomisation studies are not affected by two important sources of error: conventional confounding variables and reverse causation. Mendelian randomisation is therefore a promising tool for studying causality. Mendelian randomisation studies have already provided valuable knowledge on the risk factors for a wide range of diseases. It is nevertheless important to be aware of the limitations of the methodology. As a result of the rapid developments in genetics research, Mendelian randomisation will probably be widely used in future years.INTERPRETATION If Mendelian randomisation studies are conducted correctly, they may help to reveal both modifiable and non-modifiable causes of disease.

  12. 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.

  13. Discovering Fuzzy Censored Classification Rules (Fccrs: A Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Renu Bala

    2012-08-01

    Full Text Available Classification Rules (CRs are often discovered in the form of ‘If-Then’ Production Rules (PRs. PRs, beinghigh level symbolic rules, are comprehensible and easy to implement. However, they are not capable ofdealing with cognitive uncertainties like vagueness and ambiguity imperative to real word decision makingsituations. Fuzzy Classification Rules (FCRs based on fuzzy logic provide a framework for a flexiblehuman like reasoning involving linguistic variables. Moreover, a classification system consisting of simple‘If-Then’ rules is not competent in handling exceptional circumstances. In this paper, we propose aGenetic Algorithm approach to discover Fuzzy Censored Classification Rules (FCCRs. A FCCR is aFuzzy Classification Rule (FCRs augmented with censors. Here, censors are exceptional conditions inwhich the behaviour of a rule gets modified. The proposed algorithm works in two phases. In the firstphase, the Genetic Algorithm discovers Fuzzy Classification Rules. Subsequently, these FuzzyClassification Rules are mutated to produce FCCRs in the second phase. The appropriate encodingscheme, fitness function and genetic operators are designed for the discovery of FCCRs. The proposedapproach for discovering FCCRs is then illustrated on a synthetic dataset.

  14. Controlling Risk Exposure in Periodic Environments: A Genetic Algorithm Approach

    CERN Document Server

    Navarro, Emeterio

    2007-01-01

    In this paper, we compare the performance of different agent's investment strategies in an investment scenario with periodic returns and different types and levels of noise. We consider an investment model, where an agent decides the percentage of budget to risk at each time step. Afterwards, agent's investment is evaluated in the market via a return on investment (RoI), which we assume is a stochastic process with unknown periodicities and different levels of noise. To control the risk exposure, we investigate approaches based on: technical analysis (Moving Least Squares, MLS), and evolutionary computation (Genetic Algorithms, GA). In our comparison, we also consider two reference strategies for zero-knowledge and complete-knowledge behaviors, respectively. In our approach, the performance of a strategy corresponds to the average budget that can be obtained with this strategy over a certain number of time steps. To this end, we perform some computer experiments, where for each strategy the budget obtained af...

  15. Current and upcoming approaches to exploit the reversibility of epigenetic mutations in breast cancer.

    Science.gov (United States)

    Falahi, Fahimeh; van Kruchten, Michel; Martinet, Nadine; Hospers, Geke A P; Rots, Marianne G

    2014-07-29

    DNA methylation and histone modifications are important epigenetic modifications associated with gene (dys)regulation. The epigenetic modifications are balanced by epigenetic enzymes, so-called writers and erasers, such as DNA (de)methylases and histone (de)acetylases. Aberrant epigenetic alterations have been associated with various diseases, including breast cancer. Since aberrant epigenetic modifications are potentially reversible, they might represent targets for breast cancer therapy. Indeed, several drugs have been designed to inhibit epigenetic enzymes (epi-drugs), thereby reversing epigenetic modifications. US Food and Drug Administration approval has been obtained for some epi-drugs for hematological malignancies. However, these drugs have had very modest anti-tumor efficacy in phase I and II clinical trials in breast cancer patients as monotherapy. Therefore, current clinical trials focus on the combination of epi-drugs with other therapies to enhance or restore the sensitivity to such therapies. This approach has yielded some promising results in early phase II trials. The disadvantage of epi-drugs, however, is genome-wide effects, which may cause unwanted upregulation of, for example, pro-metastatic genes. Development of gene-targeted epigenetic modifications (epigenetic editing) in breast cancer can provide a novel approach to prevent such unwanted events. In this context, identification of crucial epigenetic modifications regulating key genes in breast cancer is of critical importance. In this review, we first describe aberrant DNA methylation and histone modifications as two important classes of epigenetic mutations in breast cancer. Then we focus on the preclinical and clinical epigenetic-based therapies currently being explored for breast cancer. Finally, we describe epigenetic editing as a promising new approach for possible applications towards more targeted breast cancer treatment.

  16. Passive optical coherence elastography using a time-reversal approach (Conference Presentation)

    Science.gov (United States)

    Nguyen, Thu-Mai; Zorgani, Ali; Fink, Mathias; Catheline, Stefan; Boccara, A. Claude

    2017-02-01

    Background and motivation - Conventional Optical Coherence Elastography (OCE) methods consist in launching controlled shear waves in tissues, and measuring their propagation speed using an ultrafast imaging system. However, the use of external shear sources limits transfer to clinical practice, especially for ophthalmic applications. Here, we propose a totally passive OCE method for ocular tissues based on time-reversal of the natural vibrations. Methods - Experiments were first conducted on a tissue-mimicking phantom containing a stiff inclusion. Pulsatile motions were reproduced by stimulating the phantom surface with two piezoelectric actuators excited asynchronously at low frequencies (50-500 Hz). The resulting random displacements were tracked at 190 frames/sec using spectral-domain optical coherence tomography (SD-OCT), with a 10x5µm² resolution over a 3x2mm² field-of-view (lateral x depth). The shear wavefield was numerically refocused (i.e. time-reversed) at each pixel using noise-correlation algorithms. The focal spot size yields the shear wavelength. Results were validated by comparison with shear wave speed measurements obtained from conventional active OCE. In vivo tests were then conducted on anesthetized rats. Results - The stiff inclusion of the phantom was delineated on the wavelength map with a wavelength ratio between the inclusion and the background (1.6) consistent with the speed ratio (1.7). This validates the wavelength measurements. In vivo, natural shear waves were detected in the eye and wavelength maps of the anterior segment showed a clear elastic contrast between the cornea, the sclera and the iris. Conclusion - We validated the time-reversal approach for passive elastography using SD-OCT imaging at low frame-rate. This method could accelerate the clinical transfer of ocular elastography.

  17. A genetic algorithm approach to recognition and data mining

    Energy Technology Data Exchange (ETDEWEB)

    Punch, W.F.; Goodman, E.D.; Min, Pei [Michigan State Univ., East Lansing, MI (United States)] [and others

    1996-12-31

    We review here our use of genetic algorithm (GA) and genetic programming (GP) techniques to perform {open_quotes}data mining,{close_quotes} the discovery of particular/important data within large datasets, by finding optimal data classifications using known examples. Our first experiments concentrated on the use of a K-nearest neighbor algorithm in combination with a GA. The GA selected weights for each feature so as to optimize knn classification based on a linear combination of features. This combined GA-knn approach was successfully applied to both generated and real-world data. We later extended this work by substituting a GP for the GA. The GP-knn could not only optimize data classification via linear combinations of features but also determine functional relationships among the features. This allowed for improved performance and new information on important relationships among features. We review the effectiveness of the overall approach on examples from biology and compare the effectiveness of the GA and GP.

  18. Two effective approaches to reduce data storage in reverse time migration

    Science.gov (United States)

    Sun, Weijia; Fu, Li-Yun

    2013-07-01

    Prestack reverse time migration (RTM) requires extensive data storage since it computes wavefields in forward time and accesses wavefields in reverse order. We first review several successful schemes that have been proposed to reduce data storage, but require more computational redundancies. We propose two effective strategies to reduce data storage during RTM. The first strategy is based on the Nyquist sampling theorem, which involves no extra computational cost. The fact is that the time sampling intervals required by numerical algorithms or given by field records is generally several times smaller than that satisfied by the Nyquist sampling theorem. Therefore, we can correlate the source wavefields with the receiver wavefields at the Nyquist time step, which helps decrease storage of time history. The second strategy is based on a lossless compression algorithm, which is widely used in computer science and information theory. The compression approach reduces storage significantly at a little computational cost. Numerical examples show that the two proposed strategies are effective and efficient.

  19. Distortion correction in EPI using an extended PSF method with a reversed phase gradient approach.

    Directory of Open Access Journals (Sweden)

    Myung-Ho In

    Full Text Available In echo-planar imaging (EPI, such as commonly used for functional MRI (fMRI and diffusion-tensor imaging (DTI, compressed distortion is a more difficult challenge than local stretching as spatial information can be lost in strongly compressed areas. In addition, the effects are more severe at ultra-high field (UHF such as 7T due to increased field inhomogeneity. To resolve this problem, two EPIs with opposite phase-encoding (PE polarity were acquired and combined after distortion correction. For distortion correction, a point spread function (PSF mapping method was chosen due to its high correction accuracy and extended to perform distortion correction of both EPIs with opposite PE polarity thus reducing the PSF reference scan time. Because the amount of spatial information differs between the opposite PE datasets, the method was further extended to incorporate a weighted combination of the two distortion-corrected images to maximize the spatial information content of a final corrected image. The correction accuracy of the proposed method was evaluated in distortion-corrected data using both forward and reverse phase-encoded PSF reference data and compared with the reversed gradient approaches suggested previously. Further we demonstrate that the extended PSF method with an improved weighted combination can recover local distortions and spatial information loss and be applied successfully not only to spin-echo EPI, but also to gradient-echo EPIs acquired with both PE directions to perform geometrically accurate image reconstruction.

  20. Rat reverse genetics : generation and characterization of chemically induced rat mutants

    NARCIS (Netherlands)

    van Boxtel, R.

    2010-01-01

    The use of animal models has been crucial for studying the function of genetic elements in the human genome. Embryonic stem (ES) cell-based homologous recombination (HR) has proven a very efficient technique for gene manipulation. However, this technique is not (yet) available for all model organism

  1. Metalloproteomics: forward and reverse approaches in metalloprotein structural and functional characterization.

    Science.gov (United States)

    Shi, Wuxian; Chance, Mark R

    2011-02-01

    About one-third of all proteins are associated with a metal. Metalloproteomics is defined as the structural and functional characterization of metalloproteins on a genome-wide scale. The methodologies utilized in metalloproteomics, including both forward (bottom-up) and reverse (top-down) technologies, to provide information on the identity, quantity, and function of metalloproteins are discussed. Important techniques frequently employed in metalloproteomics include classical proteomic tools such as mass spectrometry and 2D gels, immobilized-metal affinity chromatography, bioinformatic sequence analysis and homology modeling, X-ray absorption spectroscopy and other synchrotron radiation based tools. Combinative applications of these techniques provide a powerful approach to understand the function of metalloproteins.

  2. RNA polymerase I-driven reverse genetics system for enterovirus 71 and its implications for vaccine production

    Directory of Open Access Journals (Sweden)

    Meng Tao

    2012-10-01

    Full Text Available Abstract Background Enterovirus 71 (EV71 is a virus that causes from mild hand, foot and mouth disease (HFMD to severe neurological complications and deaths in infants and young children. Effective antiviral agents and vaccines against EV71 are not available. However, Vero cell-based chemically inactivated EV71 vaccines could be developed soon based on the success of inactivated polio vaccine. Like poliovirus, EV71 has a positive single-stranded RNA genome of about 7400 nucleotides which contains a single open reading frame (ORF flanked by conserved and untranslated regions at both the 5′ and 3′ ends. Results The universal amplification of the full length genome of EV71 regardless of its genetic diversity, and the subsequent construction of a human RNA polymerase I-driven reverse genetics (RG system to produce pure virus stocks in Vero cell within 10 days were described. The rescued viruses were characterized by DNA sequencing, cytopathic effect (CPE and indirect fluorescent assay (IFA in comparison with the wild-type viruses. Moreover, the rescued viruses grew to high titers and retained the same immunogenicity as the wild-type viruses. Conclusion We have established a simplified method to rescue RG EV71 virus from diverse clinical isolates with detailed genetic information and to prepare virus stocks in only 10 days. This method could accelerate EV71 vaccine development.

  3. Identifying genetic risk variants for coronary heart disease in familial hypercholesterolemia: an extreme genetics approach

    Science.gov (United States)

    Versmissen, Jorie; Oosterveer, Daniëlla M; Yazdanpanah, Mojgan; Dehghan, Abbas; Hólm, Hilma; Erdman, Jeanette; Aulchenko, Yurii S; Thorleifsson, Gudmar; Schunkert, Heribert; Huijgen, Roeland; Vongpromek, Ranitha; Uitterlinden, André G; Defesche, Joep C; van Duijn, Cornelia M; Mulder, Monique; Dadd, Tony; Karlsson, Hróbjartur D; Ordovas, Jose; Kindt, Iris; Jarman, Amelia; Hofman, Albert; van Vark-van der Zee, Leonie; Blommesteijn-Touw, Adriana C; Kwekkeboom, Jaap; Liem, Anho H; van der Ouderaa, Frans J; Calandra, Sebastiano; Bertolini, Stefano; Averna, Maurizio; Langslet, Gisle; Ose, Leiv; Ros, Emilio; Almagro, Fátima; de Leeuw, Peter W; Civeira, Fernando; Masana, Luis; Pintó, Xavier; Simoons, Maarten L; Schinkel, Arend FL; Green, Martin R; Zwinderman, Aeilko H; Johnson, Keith J; Schaefer, Arne; Neil, Andrew; Witteman, Jacqueline CM; Humphries, Steve E; Kastelein, John JP; Sijbrands, Eric JG

    2015-01-01

    Mutations in the low-density lipoprotein receptor (LDLR) gene cause familial hypercholesterolemia (FH), a disorder characterized by coronary heart disease (CHD) at young age. We aimed to apply an extreme sampling method to enhance the statistical power to identify novel genetic risk variants for CHD in individuals with FH. We selected cases and controls with an extreme contrast in CHD risk from 17 000 FH patients from the Netherlands, whose functional LDLR mutation was unequivocally established. The genome-wide association (GWA) study was performed on 249 very young FH cases with CHD and 217 old FH controls without CHD (above 65 years for males and 70 years of age for females) using the Illumina HumanHap550K chip. In the next stage, two independent samples (one from the Netherlands and one from Italy, Norway, Spain, and the United Kingdom) of FH patients were used as replication samples. In the initial GWA analysis, we identified 29 independent single nucleotide polymorphisms (SNPs) with suggestive associations with premature CHD (P<1 × 10−4). We examined the association of these SNPs with CHD risk in the replication samples. After Bonferroni correction, none of the SNPs either replicated or reached genome-wide significance after combining the discovery and replication samples. Therefore, we conclude that the genetics of CHD risk in FH is complex and even applying an ‘extreme genetics' approach we did not identify new genetic risk variants. Most likely, this method is not as effective in leveraging effect size as anticipated, and may, therefore, not lead to significant gains in statistical power. PMID:24916650

  4. Genetic Approach for the Fast Discovery of Phenazine Producing Bacteria

    Directory of Open Access Journals (Sweden)

    Johannes F. Imhoff

    2011-05-01

    Full Text Available A fast and efficient approach was established to identify bacteria possessing the potential to biosynthesize phenazines, which are of special interest regarding their antimicrobial activities. Sequences of phzE genes, which are part of the phenazine biosynthetic pathway, were used to design one universal primer system and to analyze the ability of bacteria to produce phenazine. Diverse bacteria from different marine habitats and belonging to six major phylogenetic lines were investigated. Bacteria exhibiting phzE gene fragments affiliated to Firmicutes, Alpha- and Gammaproteobacteria, and Actinobacteria. Thus, these are the first primers for amplifying gene fragments from Firmicutes and Alphaproteobacteria. The genetic potential for phenazine production was shown for four type strains belonging to the genera Streptomyces and Pseudomonas as well as for 13 environmental isolates from marine habitats. For the first time, the genetic ability of phenazine biosynthesis was verified by analyzing the metabolite pattern of all PCR-positive strains via HPLC-UV/MS. Phenazine production was demonstrated for the type strains known to produce endophenazines, 2-hydroxy-phenazine, phenazine-1-carboxylic acid, phenazine-1,6-dicarboxylic acid, and chlororaphin as well as for members of marine Actinobacteria. Interestingly, a number of unidentified phenazines possibly represent new phenazine structures.

  5. Estimating Sampling Selection Bias in Human Genetics: A Phenomenological Approach

    Science.gov (United States)

    Risso, Davide; Taglioli, Luca; De Iasio, Sergio; Gueresi, Paola; Alfani, Guido; Nelli, Sergio; Rossi, Paolo; Paoli, Giorgio; Tofanelli, Sergio

    2015-01-01

    This research is the first empirical attempt to calculate the various components of the hidden bias associated with the sampling strategies routinely-used in human genetics, with special reference to surname-based strategies. We reconstructed surname distributions of 26 Italian communities with different demographic features across the last six centuries (years 1447–2001). The degree of overlapping between "reference founding core" distributions and the distributions obtained from sampling the present day communities by probabilistic and selective methods was quantified under different conditions and models. When taking into account only one individual per surname (low kinship model), the average discrepancy was 59.5%, with a peak of 84% by random sampling. When multiple individuals per surname were considered (high kinship model), the discrepancy decreased by 8–30% at the cost of a larger variance. Criteria aimed at maximizing locally-spread patrilineages and long-term residency appeared to be affected by recent gene flows much more than expected. Selection of the more frequent family names following low kinship criteria proved to be a suitable approach only for historically stable communities. In any other case true random sampling, despite its high variance, did not return more biased estimates than other selective methods. Our results indicate that the sampling of individuals bearing historically documented surnames (founders' method) should be applied, especially when studying the male-specific genome, to prevent an over-stratification of ancient and recent genetic components that heavily biases inferences and statistics. PMID:26452043

  6. A Full Bayesian Approach for Boolean Genetic Network Inference

    Science.gov (United States)

    Han, Shengtong; Wong, Raymond K. W.; Lee, Thomas C. M.; Shen, Linghao; Li, Shuo-Yen R.; Fan, Xiaodan

    2014-01-01

    Boolean networks are a simple but efficient model for describing gene regulatory systems. A number of algorithms have been proposed to infer Boolean networks. However, these methods do not take full consideration of the effects of noise and model uncertainty. In this paper, we propose a full Bayesian approach to infer Boolean genetic networks. Markov chain Monte Carlo algorithms are used to obtain the posterior samples of both the network structure and the related parameters. In addition to regular link addition and removal moves, which can guarantee the irreducibility of the Markov chain for traversing the whole network space, carefully constructed mixture proposals are used to improve the Markov chain Monte Carlo convergence. Both simulations and a real application on cell-cycle data show that our method is more powerful than existing methods for the inference of both the topology and logic relations of the Boolean network from observed data. PMID:25551820

  7. A full bayesian approach for boolean genetic network inference.

    Directory of Open Access Journals (Sweden)

    Shengtong Han

    Full Text Available Boolean networks are a simple but efficient model for describing gene regulatory systems. A number of algorithms have been proposed to infer Boolean networks. However, these methods do not take full consideration of the effects of noise and model uncertainty. In this paper, we propose a full Bayesian approach to infer Boolean genetic networks. Markov chain Monte Carlo algorithms are used to obtain the posterior samples of both the network structure and the related parameters. In addition to regular link addition and removal moves, which can guarantee the irreducibility of the Markov chain for traversing the whole network space, carefully constructed mixture proposals are used to improve the Markov chain Monte Carlo convergence. Both simulations and a real application on cell-cycle data show that our method is more powerful than existing methods for the inference of both the topology and logic relations of the Boolean network from observed data.

  8. Human Metabolic Enzymes Deficiency: A Genetic Mutation Based Approach

    Science.gov (United States)

    Chaturvedi, Swati; Singh, Ashok K.; Maity, Siddhartha; Sarkar, Srimanta

    2016-01-01

    One of the extreme challenges in biology is to ameliorate the understanding of the mechanisms which emphasize metabolic enzyme deficiency (MED) and how these pretend to have influence on human health. However, it has been manifested that MED could be either inherited as inborn error of metabolism (IEM) or acquired, which carries a high risk of interrupted biochemical reactions. Enzyme deficiency results in accumulation of toxic compounds that may disrupt normal organ functions and cause failure in producing crucial biological compounds and other intermediates. The MED related disorders cover widespread clinical presentations and can involve almost any organ system. To sum up the causal factors of almost all the MED-associated disorders, we decided to embark on a less traveled but nonetheless relevant direction, by focusing our attention on associated gene family products, regulation of their expression, genetic mutation, and mutation types. In addition, the review also outlines the clinical presentations as well as diagnostic and therapeutic approaches. PMID:27051561

  9. A genetic epidemiology approach to cyber-security.

    Science.gov (United States)

    Gil, Santiago; Kott, Alexander; Barabási, Albert-László

    2014-07-16

    While much attention has been paid to the vulnerability of computer networks to node and link failure, there is limited systematic understanding of the factors that determine the likelihood that a node (computer) is compromised. We therefore collect threat log data in a university network to study the patterns of threat activity for individual hosts. We relate this information to the properties of each host as observed through network-wide scans, establishing associations between the network services a host is running and the kinds of threats to which it is susceptible. We propose a methodology to associate services to threats inspired by the tools used in genetics to identify statistical associations between mutations and diseases. The proposed approach allows us to determine probabilities of infection directly from observation, offering an automated high-throughput strategy to develop comprehensive metrics for cyber-security.

  10. Reverse genetics in the tide pool: knock-down of target gene expression via RNA interference in the copepod Tigriopus californicus.

    Science.gov (United States)

    Barreto, Felipe S; Schoville, Sean D; Burton, Ronald S

    2015-07-01

    Reverse genetic tools are essential for characterizing phenotypes of novel genes and testing functional hypotheses generated from next-generation sequencing studies. RNA interference (RNAi) has been a widely used technique for describing or quantifying physiological, developmental or behavioural roles of target genes by suppressing their expression. The marine intertidal copepod Tigriopus californicus has become an emerging model for evolutionary and physiological studies, but this species is not amenable to most genetic manipulation approaches. As crustaceans are susceptible to RNAi-mediated gene knock-down, we developed a simple method for delivery of gene-specific double-stranded RNA that results in significant suppression of target gene transcription levels. The protocol was examined on five genes of interest, and for each, at least 50% knock-down in expression was achieved. While knock-down levels did not reach 100% in any trial, a well-controlled experiment with one heat-shock gene showed unambiguously that such partial gene suppression may cause dramatic changes in phenotype. Copepods with suppressed expression of heat-shock protein beta 1 (hspb1) exhibited dramatically decreased tolerance to high temperatures, validating the importance of this gene during thermal stress, as proposed by a previous study. The application of this RNAi protocol in T. californicus will be invaluable for examining the role of genes putatively involved in reproductive isolation, mitochondrial function and local adaptation.

  11. A novel genetic programming approach for epileptic seizure detection.

    Science.gov (United States)

    Bhardwaj, Arpit; Tiwari, Aruna; Krishna, Ramesh; Varma, Vishaal

    2016-02-01

    The human brain is a delicate mix of neurons (brain cells), electrical impulses and chemicals, known as neurotransmitters. Any damage has the potential to disrupt the workings of the brain and cause seizures. These epileptic seizures are the manifestations of epilepsy. The electroencephalograph (EEG) signals register average neuronal activity from the cerebral cortex and label changes in activity over large areas. A detailed analysis of these electroencephalograph (EEG) signals provides valuable insights into the mechanisms instigating epileptic disorders. Moreover, the detection of interictal spikes and epileptic seizures in an EEG signal plays an important role in the diagnosis of epilepsy. Automatic seizure detection methods are required, as these epileptic seizures are volatile and unpredictable. This paper deals with an automated detection of epileptic seizures in EEG signals using empirical mode decomposition (EMD) for feature extraction and proposes a novel genetic programming (GP) approach for classifying the EEG signals. Improvements in the standard GP approach are made using a Constructive Genetic Programming (CGP) in which constructive crossover and constructive subtree mutation operators are introduced. A hill climbing search is integrated in crossover and mutation operators to remove the destructive nature of these operators. A new concept of selecting the Globally Prime offspring is also presented to select the best fitness offspring generated during crossover. To decrease the time complexity of GP, a new dynamic fitness value computation (DFVC) is employed to increase the computational speed. We conducted five different sets of experiments to evaluate the performance of the proposed model in the classification of different mixtures of normal, interictal and ictal signals, and the accuracies achieved are outstandingly high. The experimental results are compared with the existing methods on same datasets, and these results affirm the potential use of

  12. Reverse Genetic Analysis of Transcription FactorOsHox9, a Member of Homeobox Family, in Rice

    Institute of Scientific and Technical Information of China (English)

    AI Li-ping; SHEN Ao; GAO Zhi-chao; LI Zheng-long; SUN Qiong-lin; LI Ying-ying; LUAN Wei-jiang

    2014-01-01

    Homeobox transcription factors participate in the growth and development of plants by regulating cell differentiation, morphogenesis and environmental signal response. To reveal the functions of these transcription factors in rice, we constructed the RNAi vectors ofOsHox9, a member of homeobox family, and analyzed the function ofOsHox9 using reverse genetics. The plant height and tillering number of RNAi transgenic plants decreased compared with those of wild-type plants. Reverse transcription-polymerase chain reaction analysis showed thatOsHox9 expression reduced in the transgenic plants with phenotypic variance, whereas that in the transgenic plants without phenotypic variance was similar to that in the wild-type plants. This result suggests that the phenotypes of the transgenic plants were caused by RNAi effects. The tissue-specificity ofOsHox9 expression indicated that it was expressed in different organs, with high expression in stem apical meristem and young panicles. Subcelular location ofOsHox9 demonstrated that it was localized on the cell membrane.

  13. 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

  14. 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 facto

  15. 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 facto

  16. Bayesian approaches to reverse engineer cellular systems: a simulation study on nonlinear Gaussian networks

    Directory of Open Access Journals (Sweden)

    Ramoni Marco F

    2007-05-01

    Full Text Available Abstract Background Reverse engineering cellular networks is currently one of the most challenging problems in systems biology. Dynamic Bayesian networks (DBNs seem to be particularly suitable for inferring relationships between cellular variables from the analysis of time series measurements of mRNA or protein concentrations. As evaluating inference results on a real dataset is controversial, the use of simulated data has been proposed. However, DBN approaches that use continuous variables, thus avoiding the information loss associated with discretization, have not yet been extensively assessed, and most of the proposed approaches have dealt with linear Gaussian models. Results We propose a generalization of dynamic Gaussian networks to accommodate nonlinear dependencies between variables. As a benchmark dataset to test the new approach, we used data from a mathematical model of cell cycle control in budding yeast that realistically reproduces the complexity of a cellular system. We evaluated the ability of the networks to describe the dynamics of cellular systems and their precision in reconstructing the true underlying causal relationships between variables. We also tested the robustness of the results by analyzing the effect of noise on the data, and the impact of a different sampling time. Conclusion The results confirmed that DBNs with Gaussian models can be effectively exploited for a first level analysis of data from complex cellular systems. The inferred models are parsimonious and have a satisfying goodness of fit. Furthermore, the networks not only offer a phenomenological description of the dynamics of cellular systems, but are also able to suggest hypotheses concerning the causal interactions between variables. The proposed nonlinear generalization of Gaussian models yielded models characterized by a slightly lower goodness of fit than the linear model, but a better ability to recover the true underlying connections between

  17. Genetic Modification of the Penicillin G Acylase Surface To Improve Its Reversible Immobilization on Ionic Exchangers▿

    Science.gov (United States)

    Montes, Tamara; Grazú, Valeria; López-Gallego, Fernando; Hermoso, Juan A.; García, Jose L.; Manso, Isabel; Galán, Beatriz; González, Ramón; Fernández-Lafuente, Roberto; Guisán, José M.

    2007-01-01

    A new mutant of the industrial enzyme penicillin G acylase (PGA) from Escherichia coli has been designed to improve its reversible immobilization on anionic exchangers (DEAE- or polyethyleneimine [PEI]-coated agarose) by assembling eight new glutamic residues distributed homogeneously through the enzyme surface via site-directed mutagenesis. The mutant PGA is produced and processed in vivo as is the native enzyme. Moreover, it has a similar specific activity to and shows the same pH activity profile as native PGA; however, its isoelectric point decreased from 6.4 to 4.3. Although the new enzyme is adsorbed on both supports, the adsorption was even stronger when supports were coated with PEI, allowing us to improve the enzyme stability in organic cosolvents. The use of restrictive conditions during the enzyme adsorption on anionic exchangers (pH 5 and high ionic strength) permitted us to still further increase the strength of adsorption and the enzyme stability in the presence of organic solvents, suggesting that these conditions allow the penetration of the enzyme inside the polymeric beds, thus becoming fully covered with the polymer. After the enzyme inactivation, it can be desorbed to reuse the support. The possibility to improve the immobilization properties on an enzyme by site-directed mutagenesis of its surface opens a promising new scenario for enzyme engineering. PMID:17098917

  18. High-density lipoproteincholesterol, reverse cholesterol transport, and cardiovascular risk: a tale of genetics?

    Directory of Open Access Journals (Sweden)

    Giovanni Cimmino

    2013-10-01

    Full Text Available Cholesterol deposition plays a central role in atherogenesis. The accumulation of lipid material is the result of an imbalance between the influx and efflux of cholesterol within the arterial wall. High levels of plasma low-density lipoprotein-cholesterol are considered the major mechanism responsible for the influx and accumulation of cholesterol in the arterial wall, while high-density lipoprotein (HDL- cholesterol seems responsible for its efflux. The mechanism by which cholesterol is removed from extra-hepatic organs and delivered to the liver for its catabolism and excretion is called reverse cholesterol transport (RCT. Epidemiological evidence has associated high levels of HDL-cholesterol/ApoA-I with protection against atherosclerotic disease, but the ultimate mechanism(s responsible for the beneficial effect is not well established. HDLs are synthesized by the liver and small intestine and released to the circulation as a lipid-poor HDL (nascent HDL, mostly formed by ApoA-I and phospholipids. Through their metabolic maturation, HDLs interact with the ABCA1 receptor in the macrophage surface increasing their lipid content by taking phospholipids and cholesterol from macrophages becoming mature HDL. The cholesterol of the HDLs is transported to the liver, via the scavenger receptor class B, type I, for further metabolization and excretion to the intestines in the form of bile acids and cholesterol, completing the process of RCT. It is clear that an inherited mutation or acquired abnormality in any of the key players in RCT mat affect the atherosclerotic process.

  19. Genetics in psychosomatic medicine : research designs and statistical approaches

    NARCIS (Netherlands)

    McCaffery, Jeanne M.; Snieder, Harold; Dong, Yanbin; de Geus, Eco

    2007-01-01

    It has become increasingly clear that genetic factors influence many of the behaviors and disease endpoints of interest to psychosomatic medicine researchers. There has been increasing interest in incorporating genetic variation markers into psychosomatic research. In this Statistical Corner article

  20. The reversal of diabetes in rat model using mouse insulin producing cells - a combination approach of tissue engineering and macroencapsulation.

    Science.gov (United States)

    Muthyala, Sudhakar; Raj, V R Rana; Mohanty, Mira; Mohanan, P V; Nair, Prabha D

    2011-05-01

    Type 1 diabetes is a chronic disorder resulting from the autoimmune destruction of insulin-producing cells, a leading cause of morbidity and mortality all over the world. In this study a tissue engineering approach was compared with a macroencapsulation approach to reverse type 1 diabetes in a rat model, using mouse pancreatic progenitor cell (PPC)-derived islet-like clusters and mouse islets. For the tissue engineering approach the cells were cultured on gelatin scaffolds cross-linked with EDC in the presence of polyvinylpyrrolidone in vitro (GPE scaffolds), while for the macroencapsulation approach the cells were encapsulated in polyurethane-polyvinylpyrrolidone semi-interpenetrating networks. In the combination approach the cells cultured on GPE scaffolds were further encapsulated in a polyurethane-polyvinylpyrrolidone capsule. Real time PCR studies and the glucose challenge assay have shown that cells on GPE scaffolds could express and secrete insulin and glucagon in vitro. However, under in vivo conditions the animals treated by the tissue engineering approach died within 15-20 days and showed no reversal of their diabetes, due to infiltration of immune cells such as CD4 and CD8 cells and macrophages. In the macroencapsulation approach the animals showed euglycemia within 25 days, which was maintained for further 20 days, but after that the animals died. Interestingly, in the combination approach the animals showed reversal of hyperglycemia, and remained euglycemic for up to 3 months. The time needed to achieve initial euglycemia was different with different cell types, i.e. the combination approach with mouse islets achieved euglycemia within 15 days, whereas with PPC-derived islet-like clusters euglycemia was achieved within 25 days. This study confirmed that a combination of tissue engineering and macroencapsulation with mouse islets could reverse diabetes and maintain euglycemia in an experimental diabetes rat model for 90 days.

  1. Cadaveric validation of a finite element modeling approach for studying scapular notching in reverse shoulder arthroplasty.

    Science.gov (United States)

    Permeswaran, Vijay N; Goetz, Jessica E; Rudert, M James; Hettrich, Carolyn M; Anderson, Donald D

    2016-09-06

    Cadaveric experiments were undertaken to validate a finite element (FE) modeling approach for studying impingement-related scapular notching in reverse shoulder arthroplasty (RSA). The specific focus of the validation was contact at the site of impingement between the humeral polyethylene component and the inferior aspect of the scapula during an adduction motion. Lateralization of the RSA center of rotation was varied because it has been advocated clinically to reduce impingement and presumably decrease the risk of scapular notching. Tekscan sensors were utilized to directly measure contact stress at the impingement site, and FE was used to compute contact stresses. Favorable agreement was seen between physically measured and FE-computed impingement site location (within one sensing element of the Tekscan sensor) and contact loads (mean absolute difference of 14.9%). Contact stresses and contact areas were difficult to compare directly due to the disparate spatial resolutions of the Tekscan sensor and the FE model. FE-computed contact at the impingement site was highly focal, with a total contact area comparable to the area of an individual Tekscan sensing element. The good agreement between the physically measured and FE-computed contact data (i.e., contact load and location) support the use of FE modeling as a tool for computationally testing the efficacy of changing various surgical variables associated with RSA.

  2. Reverse breech extraction versus the standard approach of pushing the impacted fetal head up through the vagina in caesarean section for obstructed labour: A randomised controlled trial.

    Science.gov (United States)

    Nooh, Ahmed Mohamed; Abdeldayem, Hussein Mohammed; Ben-Affan, Othman

    2017-01-31

    The objective of this study was to assess effectiveness and safety of the reverse breech extraction approach in Caesarean section for obstructed labour, and compare it with the standard approach of pushing the fetal head up through the vagina. This randomised controlled trial included 192 women. In 96, the baby was delivered by the 'reverse breech extraction approach', and in the remaining 96, by the 'standard approach'. Extension of uterine incision occurred in 18 participants (18.8%) in the reverse breech extraction approach group, and 46 (47.9%) in the standard approach group (p = .0003). Two women (2.1%) in the reverse breech extraction approach group needed blood transfusion and 11 (11.5%) in the standard approach group (p = .012). Pyrexia developed in 3 participants (3.1%) in the reverse breech extraction approach group, and 19 (19.8%) in the standard approach group (p = .0006). Wound infection occurred in 2 women (2.1%) in the reverse breech extraction approach group, and 12 (12.5%) in the standard approach group (p = .007). Apgar score extraction approach group, and 21 (21.9%) in the standard approach group (p = .015). In conclusion, reverse breech extraction in Caesarean section for obstructed labour is an effective and safe alternative to the standard approach of pushing the fetal head up through the vagina.

  3. Genetic braid optimization: A heuristic approach to compute quasiparticle braids

    Science.gov (United States)

    McDonald, Ross B.; Katzgraber, Helmut G.

    2013-02-01

    In topologically protected quantum computation, quantum gates can be carried out by adiabatically braiding two-dimensional quasiparticles, reminiscent of entangled world lines. Bonesteel [Phys. Rev. Lett.10.1103/PhysRevLett.95.140503 95, 140503 (2005)], as well as Leijnse and Flensberg [Phys. Rev. B10.1103/PhysRevB.86.104511 86, 104511 (2012)], recently provided schemes for computing quantum gates from quasiparticle braids. Mathematically, the problem of executing a gate becomes that of finding a product of the generators (matrices) in that set that approximates the gate best, up to an error. To date, efficient methods to compute these gates only strive to optimize for accuracy. We explore the possibility of using a generic approach applicable to a variety of braiding problems based on evolutionary (genetic) algorithms. The method efficiently finds optimal braids while allowing the user to optimize for the relative utilities of accuracy and/or length. Furthermore, when optimizing for error only, the method can quickly produce efficient braids.

  4. Genetic programming approach to evaluate complexity of texture images

    Science.gov (United States)

    Ciocca, Gianluigi; Corchs, Silvia; Gasparini, Francesca

    2016-11-01

    We adopt genetic programming (GP) to define a measure that can predict complexity perception of texture images. We perform psychophysical experiments on three different datasets to collect data on the perceived complexity. The subjective data are used for training, validation, and test of the proposed measure. These data are also used to evaluate several possible candidate measures of texture complexity related to both low level and high level image features. We select four of them (namely roughness, number of regions, chroma variance, and memorability) to be combined in a GP framework. This approach allows a nonlinear combination of the measures and could give hints on how the related image features interact in complexity perception. The proposed complexity measure M exhibits Pearson correlation coefficients of 0.890 on the training set, 0.728 on the validation set, and 0.724 on the test set. M outperforms each of all the single measures considered. From the statistical analysis of different GP candidate solutions, we found that the roughness measure evaluated on the gray level image is the most dominant one, followed by the memorability, the number of regions, and finally the chroma variance.

  5. An unbiased systems genetics approach to mapping genetic loci modulating susceptibility to severe streptococcal sepsis.

    Directory of Open Access Journals (Sweden)

    Nourtan F Abdeltawab

    2008-04-01

    Full Text Available Striking individual differences in severity of group A streptococcal (GAS sepsis have been noted, even among patients infected with the same bacterial strain. We had provided evidence that HLA class II allelic variation contributes significantly to differences in systemic disease severity by modulating host responses to streptococcal superantigens. Inasmuch as the bacteria produce additional virulence factors that participate in the pathogenesis of this complex disease, we sought to identify additional gene networks modulating GAS sepsis. Accordingly, we applied a systems genetics approach using a panel of advanced recombinant inbred mice. By analyzing disease phenotypes in the context of mice genotypes we identified a highly significant quantitative trait locus (QTL on Chromosome 2 between 22 and 34 Mb that strongly predicts disease severity, accounting for 25%-30% of variance. This QTL harbors several polymorphic genes known to regulate immune responses to bacterial infections. We evaluated candidate genes within this QTL using multiple parameters that included linkage, gene ontology, variation in gene expression, cocitation networks, and biological relevance, and identified interleukin1 alpha and prostaglandin E synthases pathways as key networks involved in modulating GAS sepsis severity. The association of GAS sepsis with multiple pathways underscores the complexity of traits modulating GAS sepsis and provides a powerful approach for analyzing interactive traits affecting outcomes of other infectious diseases.

  6. Forward Genetic Approaches for Elucidation of Novel Regulators of Lyme Arthritis Severity

    Directory of Open Access Journals (Sweden)

    Kenneth K.C. Bramwell

    2014-06-01

    Full Text Available Patients experiencing natural infection with Borrelia burgdorferi display a spectrum of associated symptoms and severity, strongly implicating the impact of genetically determined host factors in the pathogenesis of Lyme disease. Herein, we provide a summary of the host genetic factors that have been demonstrated to influence the severity and chronicity of Lyme arthritis symptoms, and a review of the resources available, current progress, and added value of a forward genetic approach for identification of novel genetic regulators.

  7. Representing genetic variation as continuous surfaces: An approach for identifying spatial dependency in landscape genetic studies

    Science.gov (United States)

    Melanie A. Murphy; Jeffrey S. Evans; Samuel A. Cushman; Andrew Storfer

    2008-01-01

    Landscape genetics, an emerging field integrating landscape ecology and population genetics, has great potential to influence our understanding of habitat connectivity and distribution of organisms. Whereas typical population genetics studies summarize gene flow as pairwise measures between sampling localities, landscape characteristics that influence population...

  8. The Genetic Blues: Understanding Genetic Principles Using a Practical Approach and a Historical Perspective.

    Science.gov (United States)

    Mysliwiec, Tami H.

    2003-01-01

    Incorporates history and genetics to explain how genetic traits are passed on to the next generation by focusing on methemoglobinemia, a rare genetic disease, and discusses how oxygen is carried by hemoglobin. Includes individual pedigree analysis and class pedigree analysis. (YDS)

  9. An Indexed, Mapped Mutant Library Enables Reverse Genetics Studies of Biological Processes in Chlamydomonas reinhardtii.

    Science.gov (United States)

    Li, Xiaobo; Zhang, Ru; Patena, Weronika; Gang, Spencer S; Blum, Sean R; Ivanova, Nina; Yue, Rebecca; Robertson, Jacob M; Lefebvre, Paul A; Fitz-Gibbon, Sorel T; Grossman, Arthur R; Jonikas, Martin C

    2016-02-01

    The green alga Chlamydomonas reinhardtii is a leading unicellular model for dissecting biological processes in photosynthetic eukaryotes. However, its usefulness has been limited by difficulties in obtaining mutants in specific genes of interest. To allow generation of large numbers of mapped mutants, we developed high-throughput methods that (1) enable easy maintenance of tens of thousands of Chlamydomonas strains by propagation on agar media and by cryogenic storage, (2) identify mutagenic insertion sites and physical coordinates in these collections, and (3) validate the insertion sites in pools of mutants by obtaining >500 bp of flanking genomic sequences. We used these approaches to construct a stably maintained library of 1935 mapped mutants, representing disruptions in 1562 genes. We further characterized randomly selected mutants and found that 33 out of 44 insertion sites (75%) could be confirmed by PCR, and 17 out of 23 mutants (74%) contained a single insertion. To demonstrate the power of this library for elucidating biological processes, we analyzed the lipid content of mutants disrupted in genes encoding proteins of the algal lipid droplet proteome. This study revealed a central role of the long-chain acyl-CoA synthetase LCS2 in the production of triacylglycerol from de novo-synthesized fatty acids.

  10. Information-theoretic approach to quantum error correction and reversible measurement

    CERN Document Server

    Nielsen, M A; Schumacher, B; Barnum, H N; Caves, Carlton M.; Schumacher, Benjamin; Barnum, Howard

    1997-01-01

    Quantum operations provide a general description of the state changes allowed by quantum mechanics. The reversal of quantum operations is important for quantum error-correcting codes, teleportation, and reversing quantum measurements. We derive information-theoretic conditions and equivalent algebraic conditions that are necessary and sufficient for a general quantum operation to be reversible. We analyze the thermodynamic cost of error correction and show that error correction can be regarded as a kind of ``Maxwell demon,'' for which there is an entropy cost associated with information obtained from measurements performed during error correction. A prescription for thermodynamically efficient error correction is given.

  11. A multi-objective fuzzy mathematical approach for sustainable reverse supply chain configuration

    Directory of Open Access Journals (Sweden)

    Jyoti D. Darbari

    2017-01-01

    Full Text Available Background: Designing and implementation of reverse logistics (RL network which meets the sustainability targets have been a matter of emerging concern for the electronics companies in India.Objectives: The present study developed a two-phase model for configuration of sustainable RL network design for an Indian manufacturing company to manage its end-of-life and endof-use electronic products. The notable feature of the model was the evaluation of facilities under financial, environmental and social considerations and integration of the facility selection decisions with the network design.Method: In the first phase, an integrated Analytical Hierarchical Process Complex Proportional Assessment methodology was used for the evaluation of the alternative locations in terms of their degree of utility, which in turn was based on the three dimensions of sustainability. In the second phase, the RL network was configured as a bi-objective programming problem, and fuzzy optimisation approach was utilised for obtaining a properly efficient solution to the problem.Results: The compromised solution attained by the proposed fuzzy model demonstrated that the cost differential for choosing recovery facilities with better environmental and social performance was not significant; therefore, Indian manufacturers must not compromise on the sustainability aspects for facility location decisions.Conclusion: The results reaffirmed that the bi-objective fuzzy decision-making model can serve as a decision tool for the Indian manufacturers in designing a sustainable RL network. The multi-objective optimisation model captured a reasonable trade-off between the fuzzy goals of minimising the cost of the RL network and maximising the sustainable performance of the facilities chosen.

  12. A novel approach to antibiofilm susceptibility testing using a thermo-reversible matrix.

    Science.gov (United States)

    Taylor, B J; Marsh, L L; Nosworthy, J O; Williams, D W

    2016-02-01

    Biofilm microorganisms are known to have a much higher tolerance to antimicrobials compared to their planktonic equivalents. Therefore, traditional antimicrobial susceptibility testing may not extrapolate to clinical treatment of infections of biofilm origin, and as a result, there is a need to not only develop antimicrobials with antibiofilm activity, but also suitable in vitro testing methods for their evaluation. In this study, we report on a novel method of antibiofilm testing using a thermo-reversible matrix (poloxamer 407), coupled with live/dead staining of bacteria cultured from the matrix. Pseudomonas aeruginosa (NCIMB 8626) was cultured in medium containing poloxamer 407 at 37°C for 24 hours to generate biofilms. The preparation was cooled to liquefy the poloxamer and allow recovery of the biofilm cells, which were then stained with SYTO9 to determine viability following exposure to four antimicrobials: polyhexanide, octenadine dihydrochloride, povidone-iodine and silver carbonate. Over an 8-minute time period, fluorescence levels were spectrophotometrically measured and compared with bacterial controls, cultured in the absence of poloxamer and without antimicrobial. Untreated cells showed no reduction in viability over this period. Importantly, planktonic cells were more susceptible to test agents compared with those of a 'biofilm' phenotype cultured in poloxamer. Antibiofilm activity was evident for all of the test agents, with highest relative activity seen with octenadine dihydrochloride. In summary, a novel and relatively rapid approach to screen compounds for antibiofilm activity has been described. The method uses standard laboratory equipment and can be readily adapted to test a wide range of microorganisms and other antibiofilm compounds. This research was, in part, supported by Advanced Medical Solutions in the form of a Knowledge Transfer Project. Mr J. Nosworthy was employed by Advanced Medical Solutions. There are no other conflicts of

  13. Genetic testing in congenital heart disease:A clinical approach

    Institute of Scientific and Technical Information of China (English)

    Marie A Chaix; Gregor Andelfinger; Paul Khairy

    2016-01-01

    Congenital heart disease(CHD) is the most common type of birth defect. Traditionally, a polygenic model defined by the interaction of multiple genes and environmental factors was hypothesized to account for different forms of CHD. It is now understood that the contribution of genetics to CHD extends beyond a single unified paradigm. For example, monogenic models and chromosomal abnormalities have been associated with various syndromic and non-syndromic forms of CHD. In such instances, genetic investigation and testing may potentially play an important role in clinical care. A family tree with a detailed phenotypic description serves as the initial screening tool to identify potentially inherited defects and to guide further genetic investigation. The selection of a genetic test is contingent upon the particular diagnostic hypothesis generated by clinical examination. Genetic investigation in CHD may carry the potential to improve prognosis by yielding valuable information with regards to personalized medical care, confidence in the clinical diagnosis, and/or targeted patient followup. Moreover, genetic assessment may serve as a tool to predict recurrence risk, define the pattern of inheritance within a family, and evaluate the need for further family screening. In some circumstances, prenatal or preimplantation genetic screening could identify fetuses or embryos at high risk for CHD. Although genetics may appear to constitute a highly specialized sector of cardiology, basic knowledge regarding inheritance patterns, recurrence risks, and available screening and diagnostic tools, including their strengths and limitations, could assist the treating physician in providing sound counsel.

  14. REVERSE DESIGN APPROACH FOR MECHANISM TRAJECTORY BASED ON CODE-CHAINS MATCHING

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shuyou; YI Guodong; XU Xiaofeng

    2007-01-01

    Aiming at the problem of reverse-design of mechanism, a method based on the matching of trajectory code-chains is presented. The motion trajectory of mechanism is described with code-chain,which is normalized to simplify the operation of geometric transformation. The geometric transformation formulas of scale, mirror and rotation for trajectory code-chain are defined, and the reverse design for mechanism trajectory is realized through the analysis and solution of similarity matching between the desired trajectory and the predefined trajectory. The algorithm program and prototype system of reverse design for mechanism trajectory are developed. Application samples show that the method can break the restriction of trajectory patterns in matching, meet the demand of partial matching, and overcome the influence of geometric transformation of trajectory on the reverse design for mechanism.

  15. Reversible logic gates based on enzyme-biocatalyzed reactions and realized in flow cells: a modular approach.

    Science.gov (United States)

    Fratto, Brian E; Katz, Evgeny

    2015-05-18

    Reversible logic gates, such as the double Feynman gate, Toffoli gate and Peres gate, with 3-input/3-output channels are realized using reactions biocatalyzed with enzymes and performed in flow systems. The flow devices are constructed using a modular approach, where each flow cell is modified with one enzyme that biocatalyzes one chemical reaction. The multi-step processes mimicking the reversible logic gates are organized by combining the biocatalytic cells in different networks. This work emphasizes logical but not physical reversibility of the constructed systems. Their advantages and disadvantages are discussed and potential use in biosensing systems, rather than in computing devices, is suggested. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. CONTEMPORARY APPROACH TO DIAGNOSIS OF GENETIC CAUSES OF INTELLECTUAL DISABILITY

    Directory of Open Access Journals (Sweden)

    Ana PETERLIN

    2016-09-01

    Full Text Available Intellectual disability is a lifelong debilitating developmental disorder with important genetic contribution, which remains challenging to investigate due to high clinical and genetic variability. Finding the etiologic diagnosis of ID, however comes with great benefits for patients and their families, therefore establishing a genetic diagnostic pathway with right combination and succession of diagnostic tools is crucial for both prevention and appropriate treatment and/or rehabilitation of patients with ID. New diagnostic tools in genetics such as array comparative genomic hybridization (aCGH and next-generation sequencing (NGS have much higher detection rate for genetic aberrations responsible for ID and have enormous potential to shorten the path to diagnosis, as early diagnosis is a cornerstone for medical and non-medical management of persons suffering from ID.

  17. Roles of interferon-gamma and its target genes in schizophrenia: Proteomics-based reverse genetics from mouse to human.

    Science.gov (United States)

    Kim, Hak-Jae; Eom, Chi-Yong; Kwon, Joseph; Joo, Jaesoon; Lee, Sujeong; Nah, Seong-Su; Kim, Il-Chul; Jang, Ik-Soon; Chung, Young-Ho; Kim, Seung Il; Chung, Joo-Ho; Choi, Jong-Soon

    2012-06-01

    A decreased production of interferon gamma (IFNG) has been observed in acute schizophrenia. In order to explore the possible relationship between IFNG and schizophrenia, we attempted to analyze the differentially expressed proteins in the brains of interferon-gamma knockout (Ifng-KO) mice. Five upregulated and five downregulated proteins were identified with 2D gels and MALDI-TOF/TOF MS analyses in Ifng-KO mouse brain. Of the identified proteins, we focused on creatine kinase brain (CKB) and triose phosphate isomerase 1 (TPI1). Consistent with the proteomic data, reverse transcriptase-mediated PCR, immunoblotting, and immunohistochemistry analyses confirmed that the levels of gene expressions of Ckb and Tpi1 were downregulated and upregulated, respectively. When we analyzed the genetic polymorphisms of the single nucleotide polymorphisms (SNPs) of their human orthologous genes in a Korean population, the promoter SNPs of CKB and TPI1 were weakly associated with schizophrenia. In addition, IFNG polymorphisms were associated with schizophrenia. These results suggest that IFNG and proteins affected by IFNG may play a role in the pathogenesis of schizophrenia.

  18. Reversal of autoimmune diabetes by restoration of antigen-specific tolerance using genetically modified Lactococcus lactis in mice.

    Science.gov (United States)

    Takiishi, Tatiana; Korf, Hannelie; Van Belle, Tom L; Robert, Sofie; Grieco, Fabio A; Caluwaerts, Silvia; Galleri, Letizia; Spagnuolo, Isabella; Steidler, Lothar; Van Huynegem, Karolien; Demetter, Pieter; Wasserfall, Clive; Atkinson, Mark A; Dotta, Francesco; Rottiers, Pieter; Gysemans, Conny; Mathieu, Chantal

    2012-05-01

    Current interventions for arresting autoimmune diabetes have yet to strike the balance between sufficient efficacy, minimal side effects, and lack of generalized immunosuppression. Introduction of antigen via the gut represents an appealing method for induction of antigen-specific tolerance. Here, we developed a strategy for tolerance restoration using mucosal delivery in mice of biologically contained Lactococcus lactis genetically modified to secrete the whole proinsulin autoantigen along with the immunomodulatory cytokine IL-10. We show that combination therapy with low-dose systemic anti-CD3 stably reverted diabetes in NOD mice and increased frequencies of local Tregs, which not only accumulated in the pancreatic islets, but also suppressed immune response in an autoantigen-specific way. Cured mice remained responsive to disease-unrelated antigens, which argues against excessive immunosuppression. Application of this therapeutic tool achieved gut mucosal delivery of a diabetes-relevant autoantigen and a biologically active immunomodulatory cytokine, IL-10, and, when combined with a low dose of systemic anti-CD3, was well tolerated and induced autoantigen-specific long-term tolerance, allowing reversal of established autoimmune diabetes. Therefore, we believe this method could be an effective treatment strategy for type 1 diabetes in humans.

  19. [A novel approach to techniques in genetic testing for cancer].

    Science.gov (United States)

    Kato, Jun-ichi

    2014-04-01

    In molecular targeted drug therapy, genetic screening is carried out to identify the existence of target genes that are specifically expressed in cancer cells. Conventional methods for detecting the mutation of genes in cancer cells through the use of purified DNA is time consuming, especially in the case of the enzymatic treatment of pathological specimens, and it is difficult to finish all these protocols on the same day. Also, depending on the condition of the patients, it may be difficult to perform surgery or biopsy, and pathological specimens are not always obtainable. Thus, sometimes genetic screening using purified DNA and the enzymatic treatment of pathological specimens cannot be performed. We have successfully solved these problems using i-densy, a genetic analysis device, and two different methods of genetic testing for cancer. The first is a method which, without extracting DNA, uses simply pretreated pathological specimens for genetic screening. Using deparaffinized specimens that have only been heat-treated for a short period of time, we were able to obtain the exact same results as if we had extracted DNA. The second is the highly specific genetic screening technique, the MBP-QP method. Using this method, we were able to confirm the detection of genetic mutation from the DNA of blood plasma. It is now possible to screen for the mutation of genes in cancer cells using just a blood sample from patients without using tissue or cells, which also has little burden on the patient.

  20. The strains recommended for use in the bacterial reverse mutation test (OECD guideline 471) can be certified as non-genetically modified organisms.

    Science.gov (United States)

    Sugiyama, Kei-Ichi; Yamada, Masami; Awogi, Takumi; Hakura, Atsushi

    2016-01-01

    The bacterial reverse mutation test, commonly called Ames test, is used worldwide. In Japan, the genetically modified organisms (GMOs) are regulated under the Cartagena Domestic Law, and organisms obtained by self-cloning and/or natural occurrence would be exempted from the law case by case. The strains of Salmonella typhimurium and Escherichia coli recommended for use in the bacterial reverse mutation test (OECD guideline 471), have been considered as non-GMOs because they can be constructed by self-cloning or naturally occurring bacterial strains, or do not disturb the biological diversity. The present article explains the reasons why these tester strains should be classified as non-GMOs.

  1. Investigating an Ethical Approach to Genetically Modified Crops in ...

    African Journals Online (AJOL)

    4carolinebell@gmail.com

    Genetically modified (GM) crops gained attention in southern Africa in the ... cited in Webster, 1999:414) states that political institutions find themselves .... means that risks are socially invisible and must clearly be brought to consciousness, ...

  2. Mobile transporter path planning using a genetic algorithm approach

    Science.gov (United States)

    Baffes, Paul; Wang, Lui

    1988-01-01

    The use of an optimization technique known as a genetic algorithm for solving the mobile transporter path planning problem is investigated. The mobile transporter is a traveling robotic vehicle proposed for the Space Station which must be able to reach any point of the structure autonomously. Specific elements of the genetic algorithm are explored in both a theoretical and experimental sense. Recent developments in genetic algorithm theory are shown to be particularly effective in a path planning problem domain, though problem areas can be cited which require more research. However, trajectory planning problems are common in space systems and the genetic algorithm provides an attractive alternative to the classical techniques used to solve these problems.

  3. Congenital hydrocephalus in clinical practice : A genetic diagnostic approach

    NARCIS (Netherlands)

    Verhagen, J. M. A.; Schrander-Stumpel, C. T. R. M.; Krapels, P. C.; de Die-Smulders, C. E. M.; van Lint, F. H. M.; Willekes, C.; Weber, J. W.; Gavilanes, A. W. D.; Macville, M. V. E.; Stegmann, A. P. A.; Engelen, J. J. M.; Bakker, J.; Vos, Y. J.; Frints, S. G. M.

    2011-01-01

    Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of

  4. Integrating demographic and genetic approaches in plant conservation

    NARCIS (Netherlands)

    Oostermeijer, J.G.B.; Luijten, S.H.; den Nijs, J.C.M.

    2003-01-01

    We summarize the problems that populations of formerly common plants may encounter when habitat fragmentation isolates them and reduces population size. Genetic erosion, inbreeding depression, Allee-effects on reproductive success, catastrophes and environmental stochasticity are illustrated with st

  5. Potential International Approaches to Ownership/Control of Human Genetic Resources.

    Science.gov (United States)

    Rhodes, Catherine

    2016-09-01

    In its governance activities for genetic resources, the international community has adopted various approaches to their ownership, including: free access; common heritage of mankind; intellectual property rights; and state sovereign rights. They have also created systems which combine elements of these approaches. While governance of plant and animal genetic resources is well-established internationally, there has not yet been a clear approach selected for human genetic resources. Based on assessment of the goals which international governance of human genetic resources ought to serve, and the implications for how they will be accessed and utilised, it is argued that common heritage of mankind will be the most appropriate approach to adopt to their ownership/control. It does this with the aim of stimulating discussion in this area and providing a starting point for deeper consideration of how a common heritage of mankind, or similar, regime for human genetic resources would function and be implemented.

  6. Introduction to Focus Issue: Quantitative Approaches to Genetic Networks

    Science.gov (United States)

    Albert, Réka; Collins, James J.; Glass, Leon

    2013-06-01

    All cells of living organisms contain similar genetic instructions encoded in the organism's DNA. In any particular cell, the control of the expression of each different gene is regulated, in part, by binding of molecular complexes to specific regions of the DNA. The molecular complexes are composed of protein molecules, called transcription factors, combined with various other molecules such as hormones and drugs. Since transcription factors are coded by genes, cellular function is partially determined by genetic networks. Recent research is making large strides to understand both the structure and the function of these networks. Further, the emerging discipline of synthetic biology is engineering novel gene circuits with specific dynamic properties to advance both basic science and potential practical applications. Although there is not yet a universally accepted mathematical framework for studying the properties of genetic networks, the strong analogies between the activation and inhibition of gene expression and electric circuits suggest frameworks based on logical switching circuits. This focus issue provides a selection of papers reflecting current research directions in the quantitative analysis of genetic networks. The work extends from molecular models for the binding of proteins, to realistic detailed models of cellular metabolism. Between these extremes are simplified models in which genetic dynamics are modeled using classical methods of systems engineering, Boolean switching networks, differential equations that are continuous analogues of Boolean switching networks, and differential equations in which control is based on power law functions. The mathematical techniques are applied to study: (i) naturally occurring gene networks in living organisms including: cyanobacteria, Mycoplasma genitalium, fruit flies, immune cells in mammals; (ii) synthetic gene circuits in Escherichia coli and yeast; and (iii) electronic circuits modeling genetic networks

  7. Genetic programming-based approach to elucidate biochemical interaction networks from data.

    Science.gov (United States)

    Kandpal, Manoj; Kalyan, Chakravarthy Mynampati; Samavedham, Lakshminarayanan

    2013-02-01

    Biochemical systems are characterised by cyclic/reversible reciprocal actions, non-linear interactions and a mixed relationship structures (linear and non-linear; static and dynamic). Deciphering the architecture of such systems using measured data to provide quantitative information regarding the nature of relationships that exist between the measured variables is a challenging proposition. Causality detection is one of the methodologies that are applied to elucidate biochemical networks from such data. Autoregressive-based modelling approach such as granger causality, partial directed coherence, directed transfer function and canonical variate analysis have been applied on different systems for deciphering such interactions, but with limited success. In this study, the authors propose a genetic programming-based causality detection (GPCD) methodology which blends evolutionary computation-based procedures along with parameter estimation methods to derive a mathematical model of the system. Application of the GPCD methodology on five data sets that contained the different challenges mentioned above indicated that GPCD performs better than the other methods in uncovering the exact structure with less false positives. On a glycolysis data set, GPCD was able to fill the 'interaction gaps' which were missed by other methods.

  8. Combining Single (Mixed) Metric Approach and Genetic Algorithm for QoS Routing Problem

    Institute of Scientific and Technical Information of China (English)

    胡世余; 谢剑英

    2004-01-01

    A hybrid algorithm for the delay constrained least cost path problem is proposed through combination of single (mixed) metric approach and genetic algorithm. Compared with the known genetic algorithm for the same problem, the new algorithm adopts integral coding scheme and new genetic operator, which reduces the search space and improves the efficiency of genetic operation. Meanwhile, the single (mixed) approach accelerates the convergence speed. Simulation results indicate that the proposed algorithm can find near-optimal even optimal solutions within moderate numbers of generations.

  9. Mild desalination demo pilot: New normalization approach to effectively evaluate electrodialysis reversal technology

    Directory of Open Access Journals (Sweden)

    Roel Bisselink

    2016-06-01

    Full Text Available Key performance indicators for characterization of nanofiltration performance are well developed, similar key performance indicators for electrodialysis reversal are however underdeveloped. Under the E4Water project Dow Benelux BV and Evides Industriewater BV operate a pilot facility to compare both technologies for their application to mildly desalinate a variety of brackish water streams. Normalized pressure drop, normalized current efficiency and normalized membrane resistance proved to be a useful tool to interpret process performance and to initiate a cleaning procedure if required. The availability of these normalized key performance indicators enables optimization and process monitoring and control of electrodialysis reversal independent of the continuously changing conditions of the feed water.

  10. A time reversal transmission approach for multi-user UWB communications

    DEFF Research Database (Denmark)

    Nguyen, Tuan Hung; Kovacs Z., Istvan; Eggers, Patrick

    2005-01-01

    In this paper we propose and evaluate the performance of the time reversal technique in impulse radio UWB communications. The evaluation was based on measured channel impulse responses in the UWB frequency band of 3 to 5 GHz of a 4x1 MISO system with both vertical and horizontal polarization...... at the receiver. The results show that there is a great potential in combining time reversal and UWB technique with respect to both reducing the receiver complexity and improving the system performance. Simultaneous communication is illustrated with 5 users with a BER of less than $10^{-3}$ at an average SNR...

  11. Bioethical – Theological and Legal approach in genetic testing of adult persons

    Directory of Open Access Journals (Sweden)

    George Katsimigas

    2012-07-01

    Full Text Available Thorough genetic testing gives possibility's diagnosis of genetic diseases or identity individuals, who genetic predisposed for disease outbreak Aims: To present/identify the ethical and religious issues, which arise from the application of genetic testing in humans. Furthermore, the principles from the European and Greek legislation regarding genetic testing will be discussed. Materials & Methods: A literature review based on both review and research literature, conducted during the period of (1993-2010, derived from MEDLINE, SCOPUS and ΙΑΤΡΟΤΕΚ databases using as key words: Bioethics, genetic testing, bioethics, access, genetic information, orthodox ethics, Legislation. Results: Genetic testing for disease prevention is of primary importance. The main ethical concerns however, are related to the dissemination/ disclosure and use of this information from insurance companies, healthcare authorities, scientists, forensic departments/services and employers. Similarly, the orthodox religion accepts the use of genetic testing for the prevention and treatment of diseases as long as there is no break of confidentiality. Finally, considering the legal issues, it is apparent that genetic information is regarded as personal information and as such it is protected from the national (Greek and international law. Conclusions: It is necessary to ensure that the public authorities protect the rights of their citizens regarding genetic testing and all insurance companies, employers, schools etc. should not be allowed to have access to genetic information. Such an approach will ensure that social discrimination, obstructions or other inequalities between people on the basis of genetic information is avoided.

  12. A novel reverse-genetic approach (SIMF) identifies Mutator insertions in new Myb genes.

    Science.gov (United States)

    Rabinowicz, P D; Grotewold, E

    2000-11-01

    We have developed a new strategy designated SIMF (Systematic Insertional Mutagenesis of Families), to identify DNA insertions in many members of a gene family simultaneously. This method requires only a short amino acid sequence conserved in all members of the family to make a degenerate oligonucleotide, and a sequence from the end of the DNA insertion. The SIMF strategy was successfully applied to the large maize R2R3 Myb family of regulatory genes, and Mutator insertions in several novel Myb genes were identified. Application of this technique to identify insertions in other large gene families could significantly decrease the effort involved in screening at the same time for insertions in all members of groups of genes that share a limited sequence identity.

  13. Susceptibility of Arabidopsis to the downy mildew pathogen Hyaloperonospora parasitica : A reverse genetics approach

    NARCIS (Netherlands)

    de Jong, H.M.

    2008-01-01

    The research described in this thesis was performed to gain insight into disease susceptibility in the model system Arabidopsis thaliana – Hyaloperonospora parasitica. The aim was to identify host genes that support the infection process. For this, global expression profiling using DNA microarrays w

  14. TARGET (Translational Approaches for the Reversal, Genetic Evaluation and Treatment) of Lung Cancer

    Science.gov (United States)

    2005-09-01

    Sigma DMlol; 1:1,000), HDJ-2, acetylated h~ stone 3 (Cell Signalms, Beverly, MA; 1:1,000), actin, and HDAC6 (Cell Signaling; 1: 1,000). Cell...and tonsils were used as positive staining controls and were also stained with the primary antibody omit- ted to confirm staining specificity. Normal

  15. A propensity score approach to correction for bias due to population stratification using genetic and non-genetic factors.

    Science.gov (United States)

    Zhao, Huaqing; Rebbeck, Timothy R; Mitra, Nandita

    2009-12-01

    Confounding due to population stratification (PS) arises when differences in both allele and disease frequencies exist in a population of mixed racial/ethnic subpopulations. Genomic control, structured association, principal components analysis (PCA), and multidimensional scaling (MDS) approaches have been proposed to address this bias using genetic markers. However, confounding due to PS can also be due to non-genetic factors. Propensity scores are widely used to address confounding in observational studies but have not been adapted to deal with PS in genetic association studies. We propose a genomic propensity score (GPS) approach to correct for bias due to PS that considers both genetic and non-genetic factors. We compare the GPS method with PCA and MDS using simulation studies. Our results show that GPS can adequately adjust and consistently correct for bias due to PS. Under no/mild, moderate, and severe PS, GPS yielded estimated with bias close to 0 (mean=-0.0044, standard error=0.0087). Under moderate or severe PS, the GPS method consistently outperforms the PCA method in terms of bias, coverage probability (CP), and type I error. Under moderate PS, the GPS method consistently outperforms the MDS method in terms of CP. PCA maintains relatively high power compared to both MDS and GPS methods under the simulated situations. GPS and MDS are comparable in terms of statistical properties such as bias, type I error, and power. The GPS method provides a novel and robust tool for obtaining less-biased estimates of genetic associations that can consider both genetic and non-genetic factors.

  16. Going Backward : A Flexible Geometric Approach to Reverse Transformation from Coarse Grained to Atomistic Models

    NARCIS (Netherlands)

    Wassenaar, Tsjerk A.; Pluhackova, Kristyna; Böckmann, Rainer A.; Marrink, Siewert J.; Tieleman, D. Peter

    2014-01-01

    The conversion of coarse-grained to atomistic models is an important step in obtaining insight about atomistic scale processes from coarse-grained simulations. For this process, called backmapping or reverse transformation, several tools are available, but these commonly require libraries of molecul

  17. Mild desalination demopilot : New normalization approach to effectively evaluate electrodialysis reversal technology

    NARCIS (Netherlands)

    Bisselink, R.; Schepper, W. de; Trampé, J.; Broek, W. van den; Pinel, P.; Krutko, A.; Groot, N.

    2016-01-01

    Key performance indicators for characterization of nanofiltration performance are well developed, similar key performance indicators for electrodialysis reversal are however underdeveloped. Under the E4Water project Dow Benelux BV and Evides Industriewater BV operate a pilot facility to compare both

  18. A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex.

    NARCIS (Netherlands)

    Boer, H.D. de; Egmond, J. van; Driessen, J.J.; Booij, L.H.D.J.

    2010-01-01

    A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs

  19. A genetic algorithm approach in interface and surface structure optimization

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Jian [Iowa State Univ., Ames, IA (United States)

    2010-01-01

    The thesis is divided into two parts. In the first part a global optimization method is developed for the interface and surface structures optimization. Two prototype systems are chosen to be studied. One is Si[001] symmetric tilted grain boundaries and the other is Ag/Au induced Si(111) surface. It is found that Genetic Algorithm is very efficient in finding lowest energy structures in both cases. Not only existing structures in the experiments can be reproduced, but also many new structures can be predicted using Genetic Algorithm. Thus it is shown that Genetic Algorithm is a extremely powerful tool for the material structures predictions. The second part of the thesis is devoted to the explanation of an experimental observation of thermal radiation from three-dimensional tungsten photonic crystal structures. The experimental results seems astounding and confusing, yet the theoretical models in the paper revealed the physics insight behind the phenomena and can well reproduced the experimental results.

  20. [Molecular genetic bases of adaptation processes and approaches to their analysis].

    Science.gov (United States)

    Salmenkova, E A

    2013-01-01

    Great interest in studying the molecular genetic bases of the adaptation processes is explained by their importance in understanding evolutionary changes, in the development ofintraspecific and interspecific genetic diversity, and in the creation of approaches and programs for maintaining and restoring the population. The article examines the sources and conditions for generating adaptive genetic variability and contribution of neutral and adaptive genetic variability to the population structure of the species; methods for identifying the adaptive genetic variability on the genome level are also described. Considerable attention is paid to the potential of new technologies of genome analysis, including next-generation sequencing and some accompanying methods. In conclusion, the important role of the joint use of genomics and proteomics approaches in understanding the molecular genetic bases of adaptation is emphasized.

  1. Horizontal symmetry in the algebraic approach of genetic code

    CERN Document Server

    Godina-Nava, J J

    2013-01-01

    Using concepts of physics of elementary particles concerning the breaking of symmetry and grannd unified theory we propose to study with the algebraic approximation the degeneracy finded in the genetic code with the incorporation of a horizontal symmetry used in gauge theories to fit the contents of the multiplets of the genetic code. It is used the algebraic approch of Hornos et. al. \\cite{main,PRL71,PRE,MPLB}. We propose an example for the incorporation of horizontal symmetry to study mixtures of elements of the multiplets.

  2. Horizontal symmetry in the algebraic approach of genetic code

    OpenAIRE

    Godina-Nava, J. J.

    2013-01-01

    Using concepts of physics of elementary particles concerning the breaking of symmetry and grannd unified theory we propose to study with the algebraic approximation the degeneracy finded in the genetic code with the incorporation of a horizontal symmetry used in gauge theories to fit the contents of the multiplets of the genetic code. It is used the algebraic approch of Hornos et. al. \\cite{main,PRL71,PRE,MPLB}. We propose an example for the incorporation of horizontal symmetry to study mixtu...

  3. Investigation of laundering and dispersion approaches for silica and calcium phosphosilicate composite nanoparticles synthesized in reverse micelles

    Science.gov (United States)

    Tabakovic, Amra

    Nanotechnology, the science and engineering of materials at the nanoscale, is a booming research area with numerous applications in electronic, cosmetic, automotive and sporting goods industries, as well as in biomedicine. Composite nanoparticles (NPs) are of special interest since the use of two or more materials in NP design imparts multifunctionality on the final NP constructs. This is especially relevant for applications in areas of human healthcare, where the use of dye or drug doped composite NPs is expected to improve the diagnosis and treatment of cancer and other serious illnesses. Since the physicochemical properties of NP suspensions dictate the success of these systems in biomedical applications, especially drug delivery of chemotherapeutics, synthetic routes which offer precise control of NP properties, especially particle diameter and colloidal stability, are utilized to form a variety of composite NPs. Formation of NPs in reverse, or water-in-oil, micelles is one such synthetic approach. However, while the use of reverse micelles to form composite NPs offers precise control over NP size and shape, the post-synthesis laundering and dispersion of synthesized NP suspensions can still be a challenge. Reverse micelle synthetic approaches require the use of surfactants and low dielectric constant solvents, like hexane and cyclohexane, as the oil phase, which can compromise the biocompatibility and colloidal stability of the final composite NP suspensions. Therefore, appropriate dispersants and solvents must be used during laundering and dispersion to remove surfactant and ensure stability of synthesized NPs. In the work presented in this dissertation, two laundering and dispersion approaches, including packed column high performance liquid chromatography (HPLC) and centrifugation (sedimentation and redispersion), are investigated for silver core silica (Ag-SiO2) and calcium phosphosilicate (Caw(HxPO4)y(Si(OH)zOa) b · cH2O, CPS) composite NP suspensions

  4. A "Reverse-Schur" Approach to Optimization With Linear PDE Constraints: Application to Biomolecule Analysis and Design.

    Science.gov (United States)

    Bardhan, Jaydeep P; Altman, Michael D; Tidor, B; White, Jacob K

    2009-01-01

    We present a partial-differential-equation (PDE)-constrained approach for optimizing a molecule's electrostatic interactions with a target molecule. The approach, which we call reverse-Schur co-optimization, can be more than two orders of magnitude faster than the traditional approach to electrostatic optimization. The efficiency of the co-optimization approach may enhance the value of electrostatic optimization for ligand-design efforts-in such projects, it is often desirable to screen many candidate ligands for their viability, and the optimization of electrostatic interactions can improve ligand binding affinity and specificity. The theoretical basis for electrostatic optimization derives from linear-response theory, most commonly continuum models, and simple assumptions about molecular binding processes. Although the theory has been used successfully to study a wide variety of molecular binding events, its implications have not yet been fully explored, in part due to the computational expense associated with the optimization. The co-optimization algorithm achieves improved performance by solving the optimization and electrostatic simulation problems simultaneously, and is applicable to both unconstrained and constrained optimization problems. Reverse-Schur co-optimization resembles other well-known techniques for solving optimization problems with PDE constraints. Model problems as well as realistic examples validate the reverse-Schur method, and demonstrate that our technique and alternative PDE-constrained methods scale very favorably compared to the standard approach. Regularization, which ordinarily requires an explicit representation of the objective function, can be included using an approximate Hessian calculated using the new BIBEE/P (boundary-integral-based electrostatics estimation by preconditioning) method.

  5. DNA enrichment approaches to identify unauthorized genetically modified organisms (GMOs)

    NARCIS (Netherlands)

    Arulandhu, Alfred J.; Dijk, van Jeroen P.; Dobnik, David; Holst-Jensen, Arne; Shi, Jianxin; Zel, Jana; Kok, Esther J.

    2016-01-01

    With the increased global production of different genetically modified (GM) plant varieties, chances increase that unauthorized GM organisms (UGMOs) may enter the food chain. At the same time, the detection of UGMOs is a challenging task because of the limited sequence information that will gener

  6. Congenital hydrocephalus in clinical practice : A genetic diagnostic approach

    NARCIS (Netherlands)

    Verhagen, J. M. A.; Schrander-Stumpel, C. T. R. M.; Krapels, P. C.; de Die-Smulders, C. E. M.; van Lint, F. H. M.; Willekes, C.; Weber, J. W.; Gavilanes, A. W. D.; Macville, M. V. E.; Stegmann, A. P. A.; Engelen, J. J. M.; Bakker, J.; Vos, Y. J.; Frints, S. G. M.

    2011-01-01

    Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of Cli

  7. The characterization of goat genetic diversity : Towards a genomic approach

    NARCIS (Netherlands)

    Ajmone-Marsan, P.; Colli, L.; Han, J. L.; Achilli, A.; Lancioni, H.; Joost, S.; Crepaldi, P.; Pilla, F.; Stella, A.; Taberlet, P.; Boettcher, P.; Negrini, R.; Lenstra, J. A.

    2014-01-01

    The investigation of genetic diversity at molecular level has been proposed as a valuable complement and sometimes proxy to phenotypic diversity of local breeds and is presently considered as one of the FAO priorities for breed characterization. By recommending a set of selected molecular markers fo

  8. The characterization of goat genetic diversity : Towards a genomic approach

    NARCIS (Netherlands)

    Ajmone-Marsan, P.; Colli, L.; Han, J. L.; Achilli, A.; Lancioni, H.; Joost, S.; Crepaldi, P.; Pilla, F.; Stella, A.; Taberlet, P.; Boettcher, P.; Negrini, R.; Lenstra, J. A.|info:eu-repo/dai/nl/067852335

    2014-01-01

    The investigation of genetic diversity at molecular level has been proposed as a valuable complement and sometimes proxy to phenotypic diversity of local breeds and is presently considered as one of the FAO priorities for breed characterization. By recommending a set of selected molecular markers

  9. A Fuzzy Genetic Algorithm Approach to an Adaptive Information Retrieval Agent.

    Science.gov (United States)

    Martin-Bautista, Maria J.; Vila, Maria-Amparo; Larsen, Henrik Legind

    1999-01-01

    Presents an approach to a Genetic Information Retrieval Agent Filter (GIRAF) that filters and ranks documents retrieved from the Internet according to users' preferences by using a Genetic Algorithm and fuzzy set theory to handle the imprecision of users' preferences and users' evaluation of the retrieved documents. (Author/LRW)

  10. Food Control and a Citizen Science Approach for Improving Teaching of Genetics in Universities

    Science.gov (United States)

    Borrell, Y. J.; Muñoz-Colmenero, A. M.; Dopico, E.; Miralles, L.; Garcia-Vazquez, E.

    2016-01-01

    A Citizen Science approach was implemented in the laboratory practices of Genetics at the University of Oviedo, related with the engaging topic of Food Control. Real samples of food products consumed by students at home ("students as samplers") were employed as teaching material in three different courses of Genetics during the academic…

  11. Studies on Genetic Features of Sex Reversal inCynoglossus semilaevis%半滑舌鳎性逆转的遗传特性研究

    Institute of Scientific and Technical Information of China (English)

    宋超; 蒋丽; 王景伟; 李晓芳; 李耕; 张晓慧; 王书; 刘哲; 李恒德

    2015-01-01

    半滑舌鳎雌雄个体生长差异悬殊,由于性逆转而造成的其群体中雌性比例过低大大制约了养殖效率。性逆转是鱼类及两栖类生物性别决定事件中有趣的生物学问题,其发生的遗传机制鲜有研究。在该研究中,分别利用雄鱼和伪雄鱼组建10个半同胞家系,对这10个半同胞家系中的子代雌雄比进行研究,结果发现,2个伪雄鱼的家系,其后代个体中遗传雌性鱼全部逆转为生理雄鱼;在另外8个雄鱼家系中其性逆转比呈连续分布,表现为典型的数量性状特征;半滑舌鳎性逆转的遗传力较低,仅为0.058。以上结果表明,伪雄鱼作为父本的遗传可能为完全的父本效应遗传,性逆转由于其较低的遗传力不适合于做家系选育而适合于做家系内的选育或结合分子标记的遗传评估,以提高雌性比的遗传进展,半滑舌鳎逆转比的数量遗传特征说明其性别决定是多基因作用的结果。%The remarkable individual size differences of half-smooth tongue(Cynoglossus semilavi.)between female and male fishes exist. However, the lower ratio of female in cultured populations arise from sex reversal of the females leads to lower production efficiency. In sex-determination of some fishes and amphibians, sex reversal is interesting biology question and its molecular genetic mechanisms are rarely explored. In this study, 10 half-sib families are set up by utilizing two types of male parents:genetically males and pseudo males which are genetically females. The results showed that the females were all reversed into physiologically male fishes in two families with pseudo male parent. In the other 8 families with normal male parent, the ratio of sex reversal in individual populations presents continuous distribution, which fits for features of QTLs(Quantitative Trait Loci)typically;the heredity of sex reversal is lower, only 0.058. All of these results showed that, the

  12. Using a Formal Approach for Reverse Engineering and Design Recovery to Support Software Reuse

    Science.gov (United States)

    Gannod, Gerald C.

    2002-01-01

    This document describes 3rd year accomplishments and summarizes overall project accomplishments. Included as attachments are all published papers from year three. Note that the budget for this project was discontinued after year two, but that a residual budget from year two allowed minimal continuance into year three. Accomplishments include initial investigations into log-file based reverse engineering, service-based software reuse, and a source to XML generator.

  13. Microcirculation Approach in HELLP Syndrome Complicated by Posterior Reversible Encephalopathy Syndrome and Massive Hepatic Infarction

    OpenAIRE

    Stephanno Gomes Pereira Sarmento; Eduardo Feliz Martins Santana; Felipe Favorette Campanharo; Edward Araujo Júnior; Flavia Ribeiro Machado; Nelson Sass; Antonio Fernandes Moron

    2014-01-01

    HELLP syndrome is a complication of severe forms of preeclampsia and occurs mainly in the third trimester of pregnancy. In extreme cases, it may evolve unfavorably and substantially increase maternal mortality. We present the case of an 18-year-old pregnant woman who was admitted to our emergency service in her 31st week, presenting with headache, visual disturbances, and epigastralgia, with progression to a severe condition of HELLP syndrome followed by posterior reversible encephalopathy sy...

  14. A molecular-genetic approach to studying source-sink interactions in Arabidopsis thalian. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Gibson, S. I.

    2000-06-01

    This is a final report describing the results of the research funded by the DOE Energy Biosciences Program grant entitled ''A Molecular-Genetic Approach to Studying Source-Sink Interactions in Arabidiopsis thaliana''.

  15. A systems genetics approach provides a bridge from discovered genetic variants to biological pathways in rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Hirofumi Nakaoka

    Full Text Available Genome-wide association studies (GWAS have yielded novel genetic loci underlying common diseases. We propose a systems genetics approach to utilize these discoveries for better understanding of the genetic architecture of rheumatoid arthritis (RA. Current evidence of genetic associations with RA was sought through PubMed and the NHGRI GWAS catalog. The associations of 15 single nucleotide polymorphisms and HLA-DRB1 alleles were confirmed in 1,287 cases and 1,500 controls of Japanese subjects. Among these, HLA-DRB1 alleles and eight SNPs showed significant associations and all but one of the variants had the same direction of effect as identified in the previous studies, indicating that the genetic risk factors underlying RA are shared across populations. By receiver operating characteristic curve analysis, the area under the curve (AUC for the genetic risk score based on the selected variants was 68.4%. For seropositive RA patients only, the AUC improved to 70.9%, indicating good but suboptimal predictive ability. A simulation study shows that more than 200 additional loci with similar effect size as recent GWAS findings or 20 rare variants with intermediate effects are needed to achieve AUC = 80.0%. We performed the random walk with restart (RWR algorithm to prioritize genes for future mapping studies. The performance of the algorithm was confirmed by leave-one-out cross-validation. The RWR algorithm pointed to ZAP70 in the first rank, in which mutation causes RA-like autoimmune arthritis in mice. By applying the hierarchical clustering method to a subnetwork comprising RA-associated genes and top-ranked genes by the RWR, we found three functional modules relevant to RA etiology: "leukocyte activation and differentiation", "pattern-recognition receptor signaling pathway", and "chemokines and their receptors".These results suggest that the systems genetics approach is useful to find directions of future mapping strategies to illuminate

  16. The Approach Towards Equilibrium in a Reversible Ising Dynamics Model: An Information-Theoretic Analysis Based on an Exact Solution

    Science.gov (United States)

    Lindgren, Kristian; Olbrich, Eckehard

    2017-08-01

    We study the approach towards equilibrium in a dynamic Ising model, the Q2R cellular automaton, with microscopic reversibility and conserved energy for an infinite one-dimensional system. Starting from a low-entropy state with positive magnetisation, we investigate how the system approaches equilibrium characteristics given by statistical mechanics. We show that the magnetisation converges to zero exponentially. The reversibility of the dynamics implies that the entropy density of the microstates is conserved in the time evolution. Still, it appears as if equilibrium, with a higher entropy density is approached. In order to understand this process, we solve the dynamics by formally proving how the information-theoretic characteristics of the microstates develop over time. With this approach we can show that an estimate of the entropy density based on finite length statistics within microstates converges to the equilibrium entropy density. The process behind this apparent entropy increase is a dissipation of correlation information over increasing distances. It is shown that the average information-theoretic correlation length increases linearly in time, being equivalent to a corresponding increase in excess entropy.

  17. Energy Efficient Routing in Wireless Sensor Networks: A Genetic Approach

    CERN Document Server

    Chakraborty, Ayon; Naskar, Mrinal Kanti

    2011-01-01

    The key parameters that need to be addressed while designing protocols for sensor networks are its energy awareness and computational feasibility in resource constrained sensor nodes. Variation in the distances of nodes from the Base Station and differences in inter-nodal distances are primary factors causing unequal energy dissipation among the nodes. Thus energy difference among the nodes increases with time resulting in degraded network performance. The LEACH and PEGASIS schemes which provided elegant solutions to the problem suffer due to randomization of cluster heads and greedy chain formation respectively. In this paper, we propose a Genetic algorithm inspired ROUting Protocol (GROUP) which shows enhanced performance in terms of energy efficiency and network lifetime over other schemes. GROUP increases the network performance by ensuring a sub-optimal energy dissipation of the individual nodes despite their random deployment. It employs modern heuristics like Genetic Algorithms along with Simulated Ann...

  18. Genetic Approach to Elucidation of Sasang Constitutional Medicine

    OpenAIRE

    Bu-Yeo Kim; Seongwon Cha; Hee-Jeong Jin; Sangkyun Jeong

    2009-01-01

    Sasang Constitutional Medicine (SCM) offers a medical principle that classifies humans into four constitution groups and guides their treatment with constitution-matched medical assistance. The principle of this traditional medicine, although requires significant scientific support, appears to suggest a genetic influence on constitution type. The relative frequency of constitution types in a population, for instance, has remained relatively constant since Jema Lee first described them from hi...

  19. Hierarchical Genetic Algorithm Approach to Determine Pulse Sequences in NMR

    CERN Document Server

    Ajoy, Ashok

    2009-01-01

    We develop a new class of genetic algorithm that computationally determines efficient pulse sequences to implement a quantum gate U in a three-qubit system. The method is shown to be quite general, and the same algorithm can be used to derive efficient sequences for a variety of target matrices. We demonstrate this by implementing the inversion-on-equality gate efficiently when the spin-spin coupling constants $J_{12}=J_{23}=J$ and $J_{13}=0$. We also propose new pulse sequences to implement the Parity gate and Fanout gate, which are about 50% more efficient than the previous best efforts. Moreover, these sequences are shown to require significantly less RF power for their implementation. The proposed algorithm introduces several new features in the conventional genetic algorithm framework. We use matrices instead of linear chains, and the columns of these matrices have a well defined hierarchy. The algorithm is a genetic algorithm coupled to a fast local optimizer, and is hence a hybrid GA. It shows fast con...

  20. Food control and a citizen science approach for improving teaching of Genetics in universities.

    Science.gov (United States)

    Borrell, Y J; Muñoz-Colmenero, A M; Dopico, E; Miralles, L; Garcia-Vazquez, E

    2016-09-10

    A Citizen Science approach was implemented in the laboratory practices of Genetics at the University of Oviedo, related with the engaging topic of Food Control. Real samples of food products consumed by students at home (students as samplers) were employed as teaching material in three different courses of Genetics during the academic year 2014-2015: Experimental Methods in Food Production (MBTA) (Master level), and Applied Molecular Biology (BMA) and Conservation Genetics and Breeding (COMGE) (Bachelor/Degree level). Molecular genetics based on PCR amplification of DNA markers was employed for species identification of 22 seafood products in COMGE and MBTA, and for detection of genetically modified (GM) maize from nine products in BMA. In total six seafood products incorrectly labeled (27%), and two undeclared GM maize (22%) were found. A post-Laboratory survey was applied for assessing the efficacy of the approach for improving motivation in the Laboratory Practices of Genetics. Results confirmed that students that worked on their own samples from local markets were significantly more motivated and better evaluated their Genetic laboratory practices than control students (χ(2)  = 12.11 p = 0.033). Our results suggest that citizen science approaches could not be only useful for improving teaching of Genetics in universities but also to incorporate students and citizens as active agents in food control. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):450-462, 2016.

  1. Price Reversal Pattern of ARV Drugs: A Transaction-Cost Approach Digression

    Directory of Open Access Journals (Sweden)

    Frank LORNE

    2015-05-01

    Full Text Available A price reversal pattern of ARV drugs was noted across lower and middle income countries in that the lower-income countries have higher prices relative to higher-income countries based on a 2008-2009 Summary Report by World Health Organization. The transaction costs affecting AVR drug pricing can be broadly classified into two kinds: One between the final users and the opinion/knowledge experts, and the other between the opinion/knowledge experts and the manufacturers. Economist’s version of price discrimination needs to be modified by including transaction costs. Transaction costs also point to institution creditability factors that will affect NGO procurement.

  2. Reverse paintings on glass-A new approach for dating and localization

    Energy Technology Data Exchange (ETDEWEB)

    Conejos Sanchez, Inma [Universitaet Mainz, Institut fuer Kernchemie, D 55099 Mainz (Germany); Hampel, Gabriele [Universitaet Mainz, Institut fuer Kernchemie, D 55099 Mainz (Germany)], E-mail: Gabriele.Hampel@uni-mainz.de; Zauner, Stefan [Universitaet Mainz, Institut fuer Kernchemie, D 55099 Mainz (Germany); Riederer, Josef [Rathgen-Forschungslabor, Schloss-Str. 1a, D 14069 Berlin (Germany)], E-mail: jriederer@t-online.de

    2009-12-15

    Samples from 20 reverse paintings on glass from different regions have been analyzed by NAA with the aim to deduce the place and date of their origin. A separation of earlier and later paintings was due to different concentrations of K and Na, because a sodium-containing flux came into use after 1870. Since in southern Germany quartz sand, and in the eastern area quartz rock had been used for glass manufacture, specific impurities could be used to distinguish southern from eastern glasses.

  3. A quantitative, high-throughput reverse genetic screen reveals novel connections between Pre-mRNA splicing and 5' and 3' end transcript determinants.

    Directory of Open Access Journals (Sweden)

    Laura-Oana Albulescu

    Full Text Available Here we present the development and implementation of a genome-wide reverse genetic screen in the budding yeast, Saccharomyces cerevisiae, that couples high-throughput strain growth, robotic RNA isolation and cDNA synthesis, and quantitative PCR to allow for a robust determination of the level of nearly any cellular RNA in the background of ~5,500 different mutants. As an initial test of this approach, we sought to identify the full complement of factors that impact pre-mRNA splicing. Increasing lines of evidence suggest a relationship between pre-mRNA splicing and other cellular pathways including chromatin remodeling, transcription, and 3' end processing, yet in many cases the specific proteins responsible for functionally connecting these pathways remain unclear. Moreover, it is unclear whether all pathways that are coupled to splicing have been identified. As expected, our approach sensitively detects pre-mRNA accumulation in the vast majority of strains containing mutations in known splicing factors. Remarkably, however, several additional candidates were found to cause increases in pre-mRNA levels similar to that seen for canonical splicing mutants, none of which had previously been implicated in the splicing pathway. Instead, several of these factors have been previously implicated to play roles in chromatin remodeling, 3' end processing, and other novel categories. Further analysis of these factors using splicing-sensitive microarrays confirms that deletion of Bdf1, a factor that links transcription initiation and chromatin remodeling, leads to a global splicing defect, providing evidence for a novel connection between pre-mRNA splicing and this component of the SWR1 complex. By contrast, mutations in 3' end processing factors such as Cft2 and Yth1 also result in pre-mRNA splicing defects, although only for a subset of transcripts, suggesting that spliceosome assembly in S. cerevisiae may more closely resemble mammalian models of exon

  4. The practice of genetic counselling: a Ccmparative approach to understanding genetic counselling in China

    NARCIS (Netherlands)

    Suli, S.

    2009-01-01

    This article provides an empirical account of the application of genetic counselling in China based on interviews, clinical observation and literature research during a field study from September 2008 to February 2009, carried out mainly in China and partly in Hong Kong and the United Kingdom.

  5. The practice of genetic counselling: a Ccmparative approach to understanding genetic counselling in China

    NARCIS (Netherlands)

    Suli, S.

    2009-01-01

    This article provides an empirical account of the application of genetic counselling in China based on interviews, clinical observation and literature research during a field study from September 2008 to February 2009, carried out mainly in China and partly in Hong Kong and the United Kingdom. Makin

  6. Invasion success in Cogongrass (Imperata cylindrica): A population genetic approach exploring genetic diversity and historical introductions

    Science.gov (United States)

    Rima D. Lucardi; Lisa E. Wallace; Gary N. Ervin

    2014-01-01

    Propagule pressure significantly contributes to and limits the potential success of a biological invasion, especially during transport, introduction, and establishment. Events such as multiple introductions of foreign parent material and gene flow among them can increase genetic diversity in founding populations, often leading to greater invasion success. We applied...

  7. Linkage intensity learning approach with genetic algorithm for causality diagram

    Institute of Scientific and Technical Information of China (English)

    WANG Cheng-liang; CHEN Juan-juan

    2007-01-01

    The causality diagram theory, which adopts graphical expression of knowledge and direct intensity of causality, overcomes some shortages in belief network and has evolved into a mixed causality diagram methodology for discrete and continuous variable. But to give linkage intensity of causality diagram is difficult, particularly in many working conditions in which sampling data are limited or noisy. The classic learning algorithm is hard to be adopted. We used genetic algorithm to learn linkage intensity from limited data. The simulation results demonstrate that this algorithm is more suitable than the classic algorithm in the condition of sample shortage such as space shuttle's fault diagnoisis.

  8. A Genetic-Algorithms-Based Approach for Programming Linear and Quadratic Optimization Problems with Uncertainty

    Directory of Open Access Journals (Sweden)

    Weihua Jin

    2013-01-01

    Full Text Available This paper proposes a genetic-algorithms-based approach as an all-purpose problem-solving method for operation programming problems under uncertainty. The proposed method was applied for management of a municipal solid waste treatment system. Compared to the traditional interactive binary analysis, this approach has fewer limitations and is able to reduce the complexity in solving the inexact linear programming problems and inexact quadratic programming problems. The implementation of this approach was performed using the Genetic Algorithm Solver of MATLAB (trademark of MathWorks. The paper explains the genetic-algorithms-based method and presents details on the computation procedures for each type of inexact operation programming problems. A comparison of the results generated by the proposed method based on genetic algorithms with those produced by the traditional interactive binary analysis method is also presented.

  9. Reversal Learning Task in Children with Autism Spectrum Disorder: A Robot-Based Approach.

    Science.gov (United States)

    Costescu, Cristina A; Vanderborght, Bram; David, Daniel O

    2015-11-01

    Children with autism spectrum disorder (ASD) engage in highly perseverative and inflexible behaviours. Technological tools, such as robots, received increased attention as social reinforces and/or assisting tools for improving the performance of children with ASD. The aim of our study is to investigate the role of the robotic toy Keepon in a cognitive flexibility task performed by children with ASD and typically developing (TD) children. The number of participants included in this study is 81 children: 40 TD children and 41 children with ASD. Each participant had to go through two conditions: robot interaction and human interaction in which they had performed the reversal learning task. Our primary outcomes are the number of errors from acquisition phase and from reversal phase of the task; as secondary outcomes we have measured attentional engagement and positive affect. The results of this study showed that children with ASD are more engaged in the task and they seem to enjoy more the task when interacting with the robot compared with the interaction with the adult. On the other hand their cognitive flexibility performance is, in general, similar in the robot and the human conditions with the exception of the learning phase where the robot can interfere with the performance. Implication for future research and practice are discussed.

  10. Propolis reverses acetaminophen induced acute hepatorenal alterations: a biochemical and histopathological approach.

    Science.gov (United States)

    Nirala, Satendra Kumar; Bhadauria, Monika

    2008-04-01

    The present study has been conducted to evaluate the curative effect of propolis extract, a honey bee-hive product, against acetaminophen (APAP) induced oxidative stress and dysfunction in liver and kidney. Animals were challenged with APAP (2 g/kg, p.o.) followed by treatment of propolis extract (100 and 200 mg/kg, p.o.) once only after 24 h. Release of transaminases, alkaline phosphatase, lactate dehydrogenase, and serum bilirubin were increased, whereas hemoglobin and blood sugar were decreased after APAP administration. Antioxidant status in both the liver and kidney tissues were estimated by determining the glutathione, malondialdehyde content and activities of the CYP enzymes, which showed significant alterations after APAP intoxication. In addition, activities of adenosine triphosphatase, acid phosphatase, alkaline phosphatase, and major cell contents (total protein, glycogen and cholesterol) were also altered due to APAP poisoning. Propolis extract successfully reversed the alterations of these biochemical variables at higher dose. Improvements in hepatorenal histoarchitecture were also consistent with biochemical observations. The results indicated that ethanolic extract of propolis has ability to reverse APAP-induced hepatorenal biochemical and histopathological alterations probably by increasing the antioxidative defense activities due to various phenolic compounds present in it.

  11. Reverse screening approach to identify potential anti-cancer targets of dipyridamole

    Science.gov (United States)

    Ge, Shu-Min; Zhan, Dong-Ling; Zhang, Shu-Hua; Song, Li-Qiang; Han, Wei-Wei

    2016-01-01

    Dipyridamole (DIP) inhibits thrombus formation when given chronically, and causes vasodilation over a short time. To date, DIP can increase the anticancer drugs (5-fluorouracil, methotrexate, piperidine, vincristine) concentration in cancer cells and hence enhance the efficacy of treatment cancer. The inhibition of DIP may result in increased 5-fluorouracil efficacy and diminish the drug side effects. But the actual molecular targets remain unknown. In this study, reverse protein-ligands docking, and quantum mechanics were used to search for the potential molecular targets of DIP. The quantum mechanics calculation was performed by using Gaussian 03 program package. Reverse pharmacophore mapping was used to search for potential molecular target candidates for a given small molecule. The docking study was used for exploring the potential anti-cancer targets of dipyridamole. The two predicted binders with the statistically significant prediction are dihydropyrimidine dehydrogenase (DPD) (PDB Id: 1GTE) and human spindle checkpoint kinase Bub1 (PDB Id: 3E7E). Structure analysis suggests that electrostatic interaction and hydrogen bonding play an important role in their binding process. The strong functional linkage of DIP and 5FU supports our prediction. In conclusion, these results generate a tractable set of anticancer proteins. The exploration of polypharmacology will provide us new opportunities in treating systematic diseases, such as the cancers. The results would generate a tractable set of anticancer target proteins for future experimental validations. PMID:28077994

  12. Classical mechanics approach applied to analysis of genetic oscillators.

    Science.gov (United States)

    Vasylchenkova, Anastasiia; Mraz, Miha; Zimic, Nikolaj; Moskon, Miha

    2016-04-05

    Biological oscillators present a fundamental part of several regulatory mechanisms that control the response of various biological systems. Several analytical approaches for their analysis have been reported recently. They are, however, limited to only specific oscillator topologies and/or to giving only qualitative answers, i.e., is the dynamics of an oscillator given the parameter space oscillatory or not. Here we present a general analytical approach that can be applied to the analysis of biological oscillators. It relies on the projection of biological systems to classical mechanics systems. The approach is able to provide us with relatively accurate results in the meaning of type of behaviour system reflects (i.e. oscillatory or not) and periods of potential oscillations without the necessity to conduct expensive numerical simulations. We demonstrate and verify the proposed approach on three different implementations of amplified negative feedback oscillator.

  13. Ion pair-reversed phase HPLC approach facilitates subcloning of PCR products and screening of recombinant colonies.

    Science.gov (United States)

    Shaw-Bruha, C M; Lamb, K A

    2000-04-01

    The isolation of a single DNA molecule for cloning is technically difficult, and the subsequent screening of colonies for recombinant DNA clones is time consuming. Ion pair-reversed phase HPLC (IP-RP-HPLC) analysis of nucleic acids improves the resolution and isolation of PCR products to be cloned. We demonstrate that PCR products analyzed and collected using the IP-RP-HPLC approach (WAVE DNA Fragment Analysis System) can be cloned directly into a plasmid vector. In addition, we demonstrate that when IP-RP-HPLC analysis is extended to the colony screening process, the time required for these procedures is reduced.

  14. Introduction: integrating genetic and cultural evolutionary approaches to language.

    Science.gov (United States)

    Mesoudi, Alex; McElligott, Alan G; Adger, David

    2011-04-01

    The papers in this special issue of Human Biology address recent research in the field of language evolution, both the genetic evolution of the language faculty and the cultural evolution of specific languages. While both of these areas have received increasing interest in recent years, there is also a need to integrate these somewhat separate efforts and explore the relevant gene-culture coevolutionary interactions. Here we summarize the individual contributions, set them in the context of the wider literature, and identify outstanding future research questions. The first set of papers concerns the comparative study of nonhuman communication in primates and birds from both a behavioral and neurobiological perspective, revealing evidence for several common language-related traits in various nonhuman species and providing clues as to the evolutionary origin and function of the human language faculty. The second set of papers discusses the consequences of viewing language as a culturally evolving system in its own right, including claims that this removes the need for strong genetic biases for language acquisition, and that phylogenetic evolutionary methods can be used to reconstruct language histories. We conclude by highlighting outstanding areas for future research, including identifying the precise selection pressures that gave rise to the language faculty in ancestral hominin species, and determining the strength, domain specificity, and origin of the cultural transmission biases that shape languages as they pass along successive generations of language learners.

  15. Chemical Genetics Approach to Engineer Kinesins with Sensitivity towards a Small-Molecule Inhibitor of Eg5.

    Science.gov (United States)

    Möckel, Martin M; Hund, Corinna; Mayer, Thomas U

    2016-11-03

    Due to their fast and often reversible mode of action, small molecules are ideally suited to dissect biological processes. Yet, the validity of small-molecule studies is intimately tied to the specificity of the applied compounds, thus imposing a great challenge to screens for novel inhibitors. Here, we applied a chemical-genetics approach to render kinesin motor proteins sensitive to inhibition by the well-characterized small molecule S-Trityl-l-cysteine (STLC). STLC specifically inhibits the kinesin Eg5 through binding to a known allosteric site within the motor domain. Transfer of this allosteric binding site into the motor domain of the human kinesins Kif3A and Kif4A sensitizes them towards STLC. Single-molecule microscopy analyses confirmed that STLC inhibits the movement of chimeric but not wild-type Kif4A along microtubules. Thus, our proof-of-concept study revealed that this chemical-genetic approach provides a powerful strategy to specifically inhibit kinesins in vitro for which small-molecule inhibitors are not yet available. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. AGROBACTERIUM-MEDIATED GENETIC TRANSFORMATION OF SORGHUM USING TISSUE CULTURE-BASED AND POLLEN-MEDIATED APPROACHES

    OpenAIRE

    Elkonin L.A.; O.N. Nosova; J.V. Italianskaya

    2012-01-01

    Genetic transformation is a powerful tool for genetic improvement of arable crops. Genetic engineering approaches are especially important for modification of starch and protein contents, vitamin and micronutrient concentration, improvement of nutritive value of protein fractions, and increase tolerance to environmental stresses. Application of transgenic technologies for genetic improvement of sorghum, a highly productive heat tolerant and drought resistant crop, is extremely important since...

  17. The Sociopolitical Importance of Genetic, Phenomenological Approaches to Science Teaching and Learning

    Science.gov (United States)

    Bazzul, Jesse

    2015-01-01

    This article discusses Wolff-Michael Roth's theoretical framework for a phenomenological, genetic approach to science teaching and learning based on the work of Edmund Husserl. This approach advocates the inclusion of student lifeworlds in science education and underlines the importance of thinking about subjectivity in both science and science…

  18. A Genetic Algorithms-based Approach for Optimized Self-protection in a Pervasive Service Middleware

    DEFF Research Database (Denmark)

    Zhang, Weishan; Ingstrup, Mads; Hansen, Klaus Marius

    2009-01-01

    the constraints of heterogeneous devices and networks. In this paper, we present a Genetic Algorithms-based approach for obtaining optimized security configurations at run time, supported by a set of security OWL ontologies and an event-driven framework. This approach has been realized as a prototype for self...

  19. The Sociopolitical Importance of Genetic, Phenomenological Approaches to Science Teaching and Learning

    Science.gov (United States)

    Bazzul, Jesse

    2015-01-01

    This article discusses Wolff-Michael Roth's theoretical framework for a phenomenological, genetic approach to science teaching and learning based on the work of Edmund Husserl. This approach advocates the inclusion of student lifeworlds in science education and underlines the importance of thinking about subjectivity in both science and science…

  20. An approach for in vitro genetic networks assembly

    Science.gov (United States)

    Noireaux, Vincent; Bar-Ziv, Roy; Libchaber, Albert

    2004-03-01

    A cell-free expression extract has been used to assemble genetic circuits in vitro. The extract, which does not contained endogenous DNA and RNA, is used as a battery to carry out transcription and translation of genes inserted into plasmids. We engineered transcriptional activation and repression cascades, in which the protein product of each stage is the input required to drive or block the following stage. Although we can find regions of linear response for single stages, cascading to subsequent stages requires working in non-linear regimes. Substantial time delays and dramatic decreases in output production are incurred with each additional stage, due to a bottleneck at the translation machinery. Faster turnover of RNA message can relieve competition between genes and stabilize output against variations in input and parameters.

  1. Data Mining Using Neural–Genetic Approach: A Review

    Directory of Open Access Journals (Sweden)

    Parvez Rahi

    2014-04-01

    Full Text Available In the advance age of technology, there is an increasing availability of digital documents in various languages in various fields. Data mining is gaining popularity in field of knowledge discovery. Data mining is the knowledge discovery process by which we can analyze the large amounts of data from various data repositories and summarizing it into information useful to us. Due to its importance of extracting information/ knowledge from the large data repositories, data mining has become an essential part of human life in various fields. Data mining has a very wide area of applications, and these applications have enriched the human life in various fields including scientific, medical, business, education etc. Here in this paper we will discuss the emphasis of Neural Network and Genetic Algorithm in the field of data mining.

  2. Graphical approach to evaluate genetic estimates of calf survival.

    Science.gov (United States)

    Schlesser, H N; Shanks, R D; Berger, P J; Healey, M H

    2009-05-01

    Genetic variation and resemblance among relatives are fundamentals of quantitative genetics. Our purpose was to identify bulls with a bimodal pattern of inheritance in the quest for new discoveries about the inheritance of calf survival. A bimodal pattern of inheritance for calf survival was identified in sons of Holstein bulls. A bimodal pattern of inheritance indicates 2 groups of sons resulting from an allele effect, a grandsire effect, or some other common factor. Different combinations (AA, Aa, aa) of 2 alleles at a locus cause varying phenotypes to be expressed. Bulls that are heterozygous for loci affecting reproductive performance may have a bimodal pattern of inheritance if the difference in effect of the 2 alleles is large. If the bimodal pattern is caused by an allele effect, then molecular markers can be identified for use in marker-assisted selection breeding programs. Data on predicted transmitting ability for perinatal survival for the first parity of 8,678 sons of 599 sires were collected from 1984 through 1997 from the National Association of Animal Breeders calving ease database, which included 7 Midwestern states. Sixteen bulls were identified with a potential bimodal pattern of inheritance because they had 2 distinct groups of sons. The 2 groups of sons were separated by calculating the coefficient of variation for each possible combination of sons; the combination that gave the smallest coefficient of variation difference between the 2 groups was considered the correct distribution of the sons into those groups. Bulls with a bimodal distribution were analyzed to determine the distribution of the grandsons among the maternal grandsires (MGS) of the 2 groups of the bimodal distribution. The bimodal distribution may be a result of heterozygous sires or MGS that are homozygous for low or high survival. If the bimodal distribution is caused by a MGS effect, then marker-assisted selection can still be used by evaluating the MGS instead of the sires.

  3. Genetic Approaches to Appearance and Ancestry : Improving Forensic DNA Analysis

    NARCIS (Netherlands)

    L.C. Chaitanya (Lakshmi)

    2016-01-01

    textabstractTraditionally, routine forensic casework is based on comparative grounds. DNA profiles obtained from crime-scenes are compared with those of potential suspects or DNA profiles deposited in forensic DNA databases. The principal limitation of such comparative approach is that trace donors

  4. Molecular Genetic Approaches to Human Diseases Involving Mental Retardation.

    Science.gov (United States)

    Latt, Samuel A.; And Others

    1984-01-01

    Recombinant DNA techniques provide new approaches to the diagnosis and analysis of inherited human diseases associated with mental retardation, such as Lesch-Nyhan syndrome, phenylketonauria, the Fragile X syndrome, Down syndrome, and those associated with deletions or duplications of subchromosomal regions. (Author/CL)

  5. Genetic and metabolomic approaches for coronary heart disease risk prediction

    NARCIS (Netherlands)

    Vaarhorst, Anika Antoinette Maria

    2014-01-01

    The prediction of coronary heart disease (CHD) risk is currently based on traditional risk factors (TRFs) like age, sex, lipid levels, blood pressure. Here we investigated, using the CAREMA cohort, whether this prediction can potentially be improved by applying a metabolomics approach and by includi

  6. A systematic multitechnique approach for detection and characterization of reversible self-association during formulation development of therapeutic antibodies.

    Science.gov (United States)

    Esfandiary, Reza; Hayes, David B; Parupudi, Arun; Casas-Finet, Jose; Bai, Shufeng; Samra, Hardeep S; Shah, Ambarish U; Sathish, Hasige A

    2013-09-01

    In addition to controlling typical instabilities such as physical and chemical degradations, understanding monoclonal antibodies' (mAbs) solution behavior is a key step in designing and developing process and formulation controls during their development. Reversible self-association (RSA), a unique solution property in which native, reversible oligomeric species are formed as a result of the noncovalent intermolecular interactions has been recognized as a developability risk with the potential to negatively impact manufacturing, storage stability, and delivery of mAbs. Therefore, its identification, characterization, and mitigation are key requirements during formulation development. Considering the large number of available analytical methods, choice of the employed technique is an important contributing factor for successful investigation of RSA. Herein, a multitechnique (dynamic light scattering, multiangle static light scattering, and analytical ultracentrifugation) approach is employed to comprehensively characterize the self-association of a model immunoglobulin G1 molecule. Studies herein discuss an effective approach for detection and characterization of RSA during biopharmaceutical development based on the capabilities of each technique, their complementarity, and more importantly their suitability for the stage of development in which RSA is investigated. Copyright © 2013 Wiley Periodicals, Inc.

  7. The underlying mechanisms of genetic innovation and speciation in the family Corynebacteriaceae: A phylogenomics approach.

    Science.gov (United States)

    Zhi, Xiao-Yang; Jiang, Zhao; Yang, Ling-Ling; Huang, Ying

    2017-02-01

    The pangenome of a bacterial species population is formed by genetic reduction and genetic expansion over the long course of evolution. Gene loss is a pervasive source of genetic reduction, and (exogenous and endogenous) gene gain is the main driver of genetic expansion. To understand the genetic innovation and speciation of the family Corynebacteriaceae, which cause a wide range of serious infections in humans and animals, we analyzed the pangenome of this family, and reconstructed its phylogeny using a phylogenomics approach. Genetic variations have occurred throughout the whole evolutionary history of the Corynebacteriaceae. Gene loss has been the primary force causing genetic changes, not only in terms of the number of protein families affected, but also because of its continuity on the time series. The variation in metabolism caused by these genetic changes mainly occurred for membrane transporters, two-component systems, and metabolism related to amino acids and carbohydrates. Interestingly, horizontal gene transfer (HGT) not only caused changes related to pathogenicity, but also triggered the acquisition of antimicrobial resistance. The Darwinian theory of evolution did not adequately explain the effects of dispersive HGT and/or gene loss in the evolution of the Corynebacteriaceae. These findings provide new insight into the evolution and speciation of Corynebacteriaceae and advance our understanding of the genetic innovation in microbial populations.

  8. A large health system's approach to utilization of the genetic counselor CPT® 96040 code.

    Science.gov (United States)

    Gustafson, Shanna L; Pfeiffer, Gail; Eng, Charis

    2011-12-01

    : In 2007, CPT® code 96040 was approved for genetic counseling services provided by nonphysician providers. Because of professional recognition and licensure limitations, experiences in direct billing by genetic counselors for these services are limited. A minority of genetics clinics report using this code because of limitations, including perceived denial of the code and confusion regarding compliant use of this code. We present results of our approach to 96040 billing for genetic counseling services under a supervising physicians National Provider ID number in a strategy for integration of genetics services within nongenetics specialty departments of a large academic medical center. : The 96040 billing encounters were tracked for a 14-month period and analyzed for reimbursement by private payers. Association of denial by diagnosis code or specialty of genetics service was statistically analyzed. Descriptive data regarding appointment availability are also summarized. : Of 350 encounters January 2008 to February 2009, 289 (82%) were billed to private payers. Of these, 62.6% received some level of reimbursement. No association was seen for denial when analyzed by the diagnosis code or by genetics focus. Through this model, genetics appointment availability minimally doubled. : Using 96040 allowed for expanding access to genetics services, increased appointment availability, and was successful in obtaining reimbursement for more than half of encounters billed.

  9. Empirical valence bond models for reactive potential energy surfaces: a parallel multilevel genetic program approach.

    Science.gov (United States)

    Bellucci, Michael A; Coker, David F

    2011-07-28

    We describe a new method for constructing empirical valence bond potential energy surfaces using a parallel multilevel genetic program (PMLGP). Genetic programs can be used to perform an efficient search through function space and parameter space to find the best functions and sets of parameters that fit energies obtained by ab initio electronic structure calculations. Building on the traditional genetic program approach, the PMLGP utilizes a hierarchy of genetic programming on two different levels. The lower level genetic programs are used to optimize coevolving populations in parallel while the higher level genetic program (HLGP) is used to optimize the genetic operator probabilities of the lower level genetic programs. The HLGP allows the algorithm to dynamically learn the mutation or combination of mutations that most effectively increase the fitness of the populations, causing a significant increase in the algorithm's accuracy and efficiency. The algorithm's accuracy and efficiency is tested against a standard parallel genetic program with a variety of one-dimensional test cases. Subsequently, the PMLGP is utilized to obtain an accurate empirical valence bond model for proton transfer in 3-hydroxy-gamma-pyrone in gas phase and protic solvent.

  10. A Domain-Independent Window Approach to Multiclass Object Detection Using Genetic Programming

    Directory of Open Access Journals (Sweden)

    Mengjie Zhang

    2003-07-01

    Full Text Available This paper describes a domain-independent approach to the use of genetic programming for object detection problems in which the locations of small objects of multiple classes in large images must be found. The evolved program is scanned over the large images to locate the objects of interest. The paper develops three terminal sets based on domain-independent pixel statistics and considers two different function sets. The fitness function is based on the detection rate and the false alarm rate. We have tested the method on three object detection problems of increasing difficulty. This work not only extends genetic programming to multiclass-object detection problems, but also shows how to use a single evolved genetic program for both object classification and localisation. The object classification map developed in this approach can be used as a general classification strategy in genetic programming for multiple-class classification problems.

  11. A Detailed look of Audio Steganography Techniques using LSB and Genetic Algorithm Approach

    OpenAIRE

    Gunjan Nehru; Puja Dhar

    2012-01-01

    This paper is the study of various techniques of audio steganography using different algorithmis like genetic algorithm approach and LSB approach. We have tried some approaches that helps in audio steganography. As we know it is the art and science of writing hidden messages in such a way that no one, apart from the sender and intended recipient, suspects the existence of the message, a form of security through obscurity. In steganography, the message used to hide secret message is called hos...

  12. A Genetic Algorithms Based Approach for Group Multicast Routing

    Directory of Open Access Journals (Sweden)

    Luca Sanna Randaccio

    2006-08-01

    Full Text Available Whereas multicast transmission in one-to-many communications allows the operator to drastically save network resources, it also makes the routing of the traffic flows more complex then in unicast transmissions. A huge amount of possible trees have to be considered and analyzed to find the appropriate routing paths. To address this problem, we propose the use of the genetic algorithms (GA, which considerably reduce the number of solutions to be evaluated. A heuristic procedure is first used to discern a set of possible trees for each multicast session in isolation. Then, the GA are applied to find the appropriate combination of the trees to comply with the bandwidth needs of the group of multicast sessions simultaneously. The goodness of each solution is assessed by means of an expression that weights both network bandwidth allocation and one-way delay. The resulting cost function is guided by few parameters that can be easily tuned during traffic engineering operations; an appropriate setting of these parameters allows the operator to configure the desired balance between network resource utilization and provided quality of service. Simulations have been performed to compare the proposed algorithm with alternative solutions in terms of bandwidth utilization and transmission delay.

  13. Hybrid genetic algorithm approach for selective harmonic control

    Energy Technology Data Exchange (ETDEWEB)

    Dahidah, Mohamed S.A. [Faculty of Engineering, Multimedia University, 63100, Jalan Multimedia-Cyberjaya, Selangor (Malaysia); Agelidis, Vassilios G. [School of Electrical and Information Engineering, The University of Sydney, NSW (Australia); Rao, Machavaram V. [Faculty of Engineering and Technology, Multimedia University, 75450, Jalan Ayer Keroh Lama-Melaka (Malaysia)

    2008-02-15

    The paper presents an optimal solution for a selective harmonic elimination pulse width modulated (SHE-PWM) technique suitable for a high power inverter used in constant frequency utility applications. The main challenge of solving the associated non-linear equations, which are transcendental in nature and, therefore, have multiple solutions, is the convergence, and therefore, an initial point selected considerably close to the exact solution is required. The paper discusses an efficient hybrid real coded genetic algorithm (HRCGA) that reduces significantly the computational burden, resulting in fast convergence. An objective function describing a measure of the effectiveness of eliminating selected orders of harmonics while controlling the fundamental, namely a weighted total harmonic distortion (WTHD) is derived, and a comparison of different operating points is reported. It is observed that the method was able to find the optimal solution for a modulation index that is higher than unity. The theoretical considerations reported in this paper are verified through simulation and experimentally on a low power laboratory prototype. (author)

  14. Structural modification of polysaccharides: A biochemical-genetic approach

    Science.gov (United States)

    Kern, Roger G.; Petersen, Gene R.

    1991-01-01

    Polysaccharides have a wide range of industrial and biomedical applications. An industry trend is underway towards the increased use of bacteria to produce polysaccharides. Long term goals of this work are the adaptation and enhancement of saccharide properties for electronic and optic applications. In this report we illustrate the application of enzyme-bearing bacteriophage on strains of the enteric bacterium Klebsiella pneumoniae, which produces a polysaccharide with the relatively rare rheological property of drag-reduction. This has resulted in the production of new polysaccharides with enhanced rheological properties. Our laboratory is developing techniques for processing and structurally modifying bacterial polysaccharides and oligosaccharides which comprise their basic polymeric repeat units. Our research has focused on bacteriophage which produce specific polysaccharide degrading enzymes. This has lead to the development of enzymes generated by bacteriophage as tools for polysaccharide modification and purification. These enzymes were used to efficiently convert the native material to uniform-sized high molecular weight polymers, or alternatively into high-purity oligosaccharides. Enzyme-bearing bacteriophage also serve as genetic selection tools for bacteria that produce new families of polysaccharides with modified structures.

  15. Diagnostic/genetic sreening - approach for genetic diagnoses and prevention of cleft lip and/or palate.

    Science.gov (United States)

    Natsume, Nagato; Kato, Tomoki; Hayakawa, Toko; Imura, Hideto

    2013-01-01

    The treatment, research and volunteer work for cleft lip and/or palate (CL/P) has been led for over 30 years by our team. Within this period, more than 4,000 cases of CL/P were treated and at the same time, and approximately 400 papers were published as the first or partner researcher in Nature Genetics, New England Journal of Medicine and others. In addition, with $20 million that was donated from companies and laypeople, and the grant from the Japanese government, CL/P centres in many countries and in Japan, the oral and craniofacial congenital anomaly gene bank in our CL/P centre was established by our leadership. In the bank there are genes from approximately more than 8,000 cases. The genes were mapped with Professor Jeffery Murray of Iowa University in the United States, the findings about genetic syndromes such as Van der Woude Syndrome and basal cell nevus syndrome were applied in clinical settings. The genetic counselling section that specialises in the oral and maxillofacial field was established by our effort for the first time in Japan. In this review, our clinical experience and approach for genetic diagnoses and prevention of cleft lip and/or palate will be discussed.

  16. A Data-Driven Approach to Reverse Engineering Customer Engagement Models: Towards Functional Constructs

    Science.gov (United States)

    de Vries, Natalie Jane; Carlson, Jamie; Moscato, Pablo

    2014-01-01

    Online consumer behavior in general and online customer engagement with brands in particular, has become a major focus of research activity fuelled by the exponential increase of interactive functions of the internet and social media platforms and applications. Current research in this area is mostly hypothesis-driven and much debate about the concept of Customer Engagement and its related constructs remains existent in the literature. In this paper, we aim to propose a novel methodology for reverse engineering a consumer behavior model for online customer engagement, based on a computational and data-driven perspective. This methodology could be generalized and prove useful for future research in the fields of consumer behaviors using questionnaire data or studies investigating other types of human behaviors. The method we propose contains five main stages; symbolic regression analysis, graph building, community detection, evaluation of results and finally, investigation of directed cycles and common feedback loops. The ‘communities’ of questionnaire items that emerge from our community detection method form possible ‘functional constructs’ inferred from data rather than assumed from literature and theory. Our results show consistent partitioning of questionnaire items into such ‘functional constructs’ suggesting the method proposed here could be adopted as a new data-driven way of human behavior modeling. PMID:25036766

  17. Efavirenz a nonnucleoside reverse transcriptase inhibitor of first-generation: Approaches based on its medicinal chemistry.

    Science.gov (United States)

    Bastos, Mônica M; Costa, Carolina C P; Bezerra, Talitha C; da Silva, Fernando de C; Boechat, Núbia

    2016-01-27

    Acquired immunodeficiency syndrome (AIDS) is a disease caused by human immunodeficiency virus (HIV) that affects individuals on all continents. In 1987, the antiretroviral therapy began increasing survival rates and improving the quality of life for patients. Efavirenz (EFV) is a drug widely used in the treatment of HIV-AIDS since 1998. Belonging to a class of nonnucleoside reverse transcriptase inhibitors (NNRTI), it directly blocks the action of the enzyme and consequently the multiplication of the virus. Although EFV has provided excellent results in reducing viral load, cases of resistance associated with adverse effects have led to the search to find new analogs of this drug. Although many researchers are involved in this quest, curiously there is still no clinical substitute for EFV. To develop a second-generation version of EFV, it is essential understand the structure-activity relationships of the derivative compounds. Thus, the aims of the present review are to compare EFV and its derivatives using medicinal chemistry and to describe the main synthetic routes.

  18. A data-driven approach to reverse engineering customer engagement models: towards functional constructs.

    Directory of Open Access Journals (Sweden)

    Natalie Jane de Vries

    Full Text Available Online consumer behavior in general and online customer engagement with brands in particular, has become a major focus of research activity fuelled by the exponential increase of interactive functions of the internet and social media platforms and applications. Current research in this area is mostly hypothesis-driven and much debate about the concept of Customer Engagement and its related constructs remains existent in the literature. In this paper, we aim to propose a novel methodology for reverse engineering a consumer behavior model for online customer engagement, based on a computational and data-driven perspective. This methodology could be generalized and prove useful for future research in the fields of consumer behaviors using questionnaire data or studies investigating other types of human behaviors. The method we propose contains five main stages; symbolic regression analysis, graph building, community detection, evaluation of results and finally, investigation of directed cycles and common feedback loops. The 'communities' of questionnaire items that emerge from our community detection method form possible 'functional constructs' inferred from data rather than assumed from literature and theory. Our results show consistent partitioning of questionnaire items into such 'functional constructs' suggesting the method proposed here could be adopted as a new data-driven way of human behavior modeling.

  19. A data-driven approach to reverse engineering customer engagement models: towards functional constructs.

    Science.gov (United States)

    de Vries, Natalie Jane; Carlson, Jamie; Moscato, Pablo

    2014-01-01

    Online consumer behavior in general and online customer engagement with brands in particular, has become a major focus of research activity fuelled by the exponential increase of interactive functions of the internet and social media platforms and applications. Current research in this area is mostly hypothesis-driven and much debate about the concept of Customer Engagement and its related constructs remains existent in the literature. In this paper, we aim to propose a novel methodology for reverse engineering a consumer behavior model for online customer engagement, based on a computational and data-driven perspective. This methodology could be generalized and prove useful for future research in the fields of consumer behaviors using questionnaire data or studies investigating other types of human behaviors. The method we propose contains five main stages; symbolic regression analysis, graph building, community detection, evaluation of results and finally, investigation of directed cycles and common feedback loops. The 'communities' of questionnaire items that emerge from our community detection method form possible 'functional constructs' inferred from data rather than assumed from literature and theory. Our results show consistent partitioning of questionnaire items into such 'functional constructs' suggesting the method proposed here could be adopted as a new data-driven way of human behavior modeling.

  20. Reversability of arctic sea ice retreat - A conceptual multi-scale modeling approach

    Science.gov (United States)

    Mueller-Stoffels, Marc

    The ice-albedo feedback has been identified as an important factor in the decay of the Arctic sea ice cover in a warming climate. Mechanisms of transition from perennial ice cover to seasonal ice cover are discussed in the literature; the existence of a tipping point is disputed. A newly developed regular network model for energy exchange and phase transition of an ice covered ocean mixed layer is introduced. The existence of bistability, a key ingredient for irreversibility, on local and regional scales is explored. It is shown in a spatially confined model that the asymptotic behavior and the existence of a parameter region of bistability strongly depend on the albedo parametrization. The spatial dynamics of sea ice retreat are studied for a high resolution latitudinal model of the ocean mixed layer. This regional model suggests that sea ice retreat is reversible. It is shown that laterally driven melt of thick multi-year sea ice, and thus, ice-albedo feedback, is an important mechanism in the transition from perennial to seasonal ice cover at the pole. Results are used to interpret observed changes in the recent ice extent and ice volume record. It is shown that the effectiveness of ice-albedo feedback strongly depends on the existence of lateral heat transfer mechanisms in the ocean.

  1. Reverse electrowetting -- a new approach to high-power harvesting of mechanical energy

    Science.gov (United States)

    Krupenkin, Tom; Taylor, J. Ashley; Manakasettharn, Supone

    2012-02-01

    Over the last decade electrical batteries have emerged as a critical bottleneck in portable electronics development. High-power mechanical energy harvesting can potentially provide a valuable alternative to the use of batteries, but until now, its adoption has been hampered by the lack of an efficient mechanical-to-electrical energy conversion technology. In this talk a novel mechanical-to-electrical energy conversion method is discussed. The method is based on reverse electrowetting (REWOD) -- a novel microfluidic phenomenon. Electrical energy generation is achieved through the interaction of arrays of moving microscopic liquid droplets with novel nanometer-thick multilayer dielectric films. Advantages of this process include the production of high power densities, up to 1 KW sq. m; the ability to directly utilize a very broad range of mechanical forces and displacements; and the ability to directly output a broad range of currents and voltages, from several volts to tens of volts. We hope that the REWOD-based energy harvesting can provide a novel technology platform for a broad range of new electronic products and enable reduction of cost, pollution, and other problems associated with the wide-spread battery use.

  2. [Approach to depressogenic genes from genetic analyses of animal models].

    Science.gov (United States)

    Yoshikawa, Takeo

    2004-01-01

    Human depression or mood disorder is defined as a complex disease, making positional cloning of susceptibility genes a formidable task. We have undertaken genetic analyses of three different animal models for depression, comparing our results with advanced database resources. We first performed quantitative trait loci (QTL) analysis on two mouse models of "despair", namely, the forced swim test (FST) and tail suspension test (TST), and detected multiple chromosomal loci that control immobility time in these tests. Since one QTL detected on mouse chromosome 11 harbors the GABA A receptor subunit genes, we tested these genes for association in human mood disorder patients. We obtained significant associations of the alpha 1 and alpha 6 subunit genes with the disease, particularly in females. This result was striking, because we had previously detected an epistatic interaction between mouse chromosomes 11 and X that regulates immobility time in these animals. Next, we performed genome-wide expression analyses using a rat model of depression, learned helplessness (LH). We found that in the frontal cortex of LH rats, a disease implicated region, the LIM kinase 1 gene (Limk 1) showed greatest alteration, in this case down-regulation. By combining data from the QTL analysis of FST/TST and DNA microarray analysis of mouse frontal cortex, we identified adenylyl cyclase-associated CAP protein 1 (Cap 1) as another candidate gene for depression susceptibility. Both Limk 1 and Cap 1 are key players in the modulation of actin G-F conversion. In summary, our current study using animal models suggests disturbances of GABAergic neurotransmission and actin turnover as potential pathophysiologies for mood disorder.

  3. A genetic programming approach to oral cancer prognosis

    Directory of Open Access Journals (Sweden)

    Mei Sze Tan

    2016-09-01

    Full Text Available Background The potential of genetic programming (GP on various fields has been attained in recent years. In bio-medical field, many researches in GP are focused on the recognition of cancerous cells and also on gene expression profiling data. In this research, the aim is to study the performance of GP on the survival prediction of a small sample size of oral cancer prognosis dataset, which is the first study in the field of oral cancer prognosis. Method GP is applied on an oral cancer dataset that contains 31 cases collected from the Malaysia Oral Cancer Database and Tissue Bank System (MOCDTBS. The feature subsets that is automatically selected through GP were noted and the influences of this subset on the results of GP were recorded. In addition, a comparison between the GP performance and that of the Support Vector Machine (SVM and logistic regression (LR are also done in order to verify the predictive capabilities of the GP. Result The result shows that GP performed the best (average accuracy of 83.87% and average AUROC of 0.8341 when the features selected are smoking, drinking, chewing, histological differentiation of SCC, and oncogene p63. In addition, based on the comparison results, we found that the GP outperformed the SVM and LR in oral cancer prognosis. Discussion Some of the features in the dataset are found to be statistically co-related. This is because the accuracy of the GP prediction drops when one of the feature in the best feature subset is excluded. Thus, GP provides an automatic feature selection function, which chooses features that are highly correlated to the prognosis of oral cancer. This makes GP an ideal prediction model for cancer clinical and genomic data that can be used to aid physicians in their decision making stage of diagnosis or prognosis.

  4. Genetics

    Science.gov (United States)

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  5. Genetic algorithm based image binarization approach and its quantitative evaluation via pooling

    Science.gov (United States)

    Hu, Huijun; Liu, Ya; Liu, Maofu

    2015-12-01

    The binarized image is very critical to image visual feature extraction, especially shape feature, and the image binarization approaches have been attracted more attentions in the past decades. In this paper, the genetic algorithm is applied to optimizing the binarization threshold of the strip steel defect image. In order to evaluate our genetic algorithm based image binarization approach in terms of quantity, we propose the novel pooling based evaluation metric, motivated by information retrieval community, to avoid the lack of ground-truth binary image. Experimental results show that our genetic algorithm based binarization approach is effective and efficiency in the strip steel defect images and our quantitative evaluation metric on image binarization via pooling is also feasible and practical.

  6. [Modern evolutional developmental biology: mechanical and molecular genetic or phenotypic approaches?].

    Science.gov (United States)

    Vorob'eva, É I

    2010-01-01

    Heightened interest in the evolutionary problems of developmental biology in the 1980s was due to the success of molecular genetics and disappointment in the synthetic theory of evolution, where the chapters of embryology and developmental biology seem to have been left out. Modern evo-devo, which turned out to be antipodean to the methodology of the synthetic theory of evolution, propagandized in the development of evolutionary problems only the mechanical and molecular genetic approach to the evolution of ontogenesis, based on cellular and intercellular interactions. The phonotypical approach to the evaluation of evolutionary occurrences in ontogenesis, which aids in the joining of the genetic and epigenetic levels of research, the theory of natural selection, the nomogenetic conception, and the problem of the wholeness of the organism in onto- and phylogenesis may be against this. The phenotypic approach to ontogenesis is methodologically the most perspective for evolutionary developmental biology.

  7. High-power-density approaches to magnetic fusion energy: Problems and promise of compact reversed-field pinch reactors (CRFPR)

    Science.gov (United States)

    Hagenson, Randy L.; Krakowski, Robert A.; Dreicer, Harry

    1983-03-01

    If the costing assumptions upon which the positive assessment of conventional large superconducting fusion reactors are based proves overly optimistic, approaches that promise considerably increased system power density and reduced mass utilization will be required. These more compact reactor embodiments generally must operate with reduced shield thickness and resistive magnets. Because of the unique magnetic topology associated with the Reversed-Field Pinch (RFP), the compact reactor embodiment for this approach is particularly attractive from the viewpoint of low-field resistive coils operating with ohmic losses that can be made small relative to the fusion power. The RFP, therefore, is used as one example of a high-power-density (HPD) approach to magnetic fusion energy. A comprehensive system model is described and applied to select a unique, cost-optimized design point that will be used for a subsequent conceptual engineering design of the compact RFP Reactor (CRFPR). This cost-optimized CRFPR design serves as an example of a HPD fusion reactor that would operate with system power densities and mass utilizations that are comparable to fission power plants, these measures of system performance being an order of magnitude more favorable than the conventional approaches to magnetic fusion energy (MFE).

  8. The reverse cholesterol transport pathway improves understanding of genetic networks for fat deposition and muscle growth in beef cattle

    Science.gov (United States)

    In the present study, thirteen genes involved in the reverse cholesterol transport (RCT) pathway were investigated for their associations with three fat depositions, eight fatty acid compositions and two growth-related phenotypes in a Wagyu x Limousin reference population, including 6 F1 bulls, 113 ...

  9. Reversing the Approach to Null Subjects: A Perspective from Language Acquisition.

    Science.gov (United States)

    Duguine, Maia

    2017-01-01

    This paper proposes a new model for null subjects, and focuses on its implications for language development. The literature on pro-drop generally considers that not allowing null subjects is, informally speaking, the "default" option in natural languages, and appeals to particular morphosyntactic mechanisms in order to account for those languages in which the subject can be omitted. Shifting the perspective, the inverse approach postulates that pro-drop is (almost) a default grammatical setting, and that non-pro-drop results from the intervention of independent factors that block pro-drop in the derivation. The paper explores the consequences of the inverse approach in the domain of language acquisition, arguing that this model allows to account for a number of properties of child languages. It opens an avenue of research worth exploring, one that could give new solutions to old problems.

  10. The pharmacological approach to reverse portal hypertention and hepatic schistosomal fibrosis in Egypt, control experimental study.

    Science.gov (United States)

    Helmy, Ahmed Hazem I; Abdel-Hady, Afaf Ahmed; el-Shanawany, Faten; Hammam, Olfat; Abdel-Hady, Ahmed

    2005-12-01

    Schistosoma mansoni is the most prevalent cause of liver fibrosis in Egypt. It is characterized by hepatocyte damage, inflammation and chronic parasite egg-induced granuloma formation leading to fibrosis. Its management, particularly fibrosis, has focused primarily on treating and preventing the complications of portal hypertension. Unfortunately, there is no therapy that has been proved to prevent progressive hepatic fibrosis which is associated with a significant morbidity and mortality due to granulomatous hypersensitivity to parasite eggs. However, recent developments in understanding hepatic fibrogenesis confirm that recovery from advanced fibrosis is possible. There is a considerable imperative to develop anti-fibrotic strategies that are applicable to liver fibrosis. It was noted that a marked increase in the amount of different interstitial collagens types are associated with the development of fibrotic liver diseases. Meanwhile, it has been suggested that as long as the relative portions of liver collagen are still within the normal limits, the fibrosis may still be reversible. If it exceeds the normal limits fibrogenesis will proceed to its end stage, even if the etiological agent is removed. Collagen type IV and procollagen type III are two of the most accurate fibrosis markers which allow reliable non-invasive diagnosis. The T lymphocytes and the immuno-regulatory cytokines may be important in the host response to S. mansoni granuloma formation and fibrosis. Chronic parasite egg-induced granuloma formation can lead to fibrosis, which is immunologically characterized by the dominant Th2 response. Corticosteroids and prostaglandins interfere with both efferent and afferent mechanisms of immune function. These data indicate that this adjuvant therapy can be a candidate for therapeutic intervention in hepatic fibrosis through induction of a balance between Th1 and Th2 cells response as will be documented by the fibrosis markers. One hundred S. mansoni

  11. Reverse genetics vaccine seeds for influenza: Proof of concept in the source of PB1 as a determinant factor in virus growth and antigen yield.

    Science.gov (United States)

    Gíria, Marta; Santos, Luís; Louro, João; Rebelo de Andrade, Helena

    2016-09-01

    Growth deficits of reverse genetics vaccine seeds have compromised effective immunization. The impairment has been attributed to sub-optimal protein interactions. Some level of dependence may exist between PB1 and antigenic glycoproteins, however, further research is necessary to clarify the extent to which it can be used in favor of seed production. Our objective was to establish proof of concept on the phenotypic outcome of PB1 source in the PR8: A(H1N1)pdm09 reassortants. Reassortants were generated with the gene constellation of the classical 6:2 PR8: HA, NApdm09 seed prototype and the 5:3 reassortant PR8: HA, NA, PB1pdm09. Viral growth and antigen yield were evaluated 12-60h post-infection. The 5:3 reassortant presented statistically significant growth and antigen yield improvements when compared to the 6:2. We believe these findings to be of promising value to vaccine research towards an improvement of reverse genetic seeds, an overall more cost-effective vaccine manufacture and timely delivery. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Constructing Competitive Reverse Transcription Polymerize Chain Reaction Inter-Reference of PC mRNA by Intron Approach

    Institute of Scientific and Technical Information of China (English)

    XU Chuang; XIA Cheng; LIU Guo-wen; WANG Zhe; JIANG Yu-fu; ZHANG Nai-sheng; FU Shi-xin

    2004-01-01

    Inter-reference ofcompetitive reverse transcription polymerase chain reaction(RT-PCR)was constructed by intron method to detect the change of PC mRNA level in the pathway of carbohydrate metabolism.The experiment based on the principle that 81bp intron sequence was deleted in PC mRNA compared with PC DNA sequence.The 466bp competitive DNA template recombinant plasmid of PC mRNAwas successfully built by a pair of primer and was cloned once,PC DNA and PC mRNA could be inter-referred each other.The intron approach used in the experiment has broken through the traditional method of constructing competitive template.

  13. First order reversal curves and intrinsic parameter determination for magnetic materials; limitations of hysteron-based approaches in correlated systems

    Science.gov (United States)

    Ruta, Sergiu; Hovorka, Ondrej; Huang, Pin-Wei; Wang, Kangkang; Ju, Ganping; Chantrell, Roy

    2017-03-01

    The generic problem of extracting information on intrinsic particle properties from the whole class of interacting magnetic fine particle systems is a long standing and difficult inverse problem. As an example, the Switching Field Distribution (SFD) is an important quantity in the characterization of magnetic systems, and its determination in many technological applications, such as recording media, is especially challenging. Techniques such as the first order reversal curve (FORC) methods, were developed to extract the SFD from macroscopic measurements. However, all methods rely on separating the contributions to the measurements of the intrinsic SFD and the extrinsic effects of magnetostatic and exchange interactions. We investigate the underlying physics of the FORC method by applying it to the output predictions of a kinetic Monte-Carlo model with known input parameters. We show that the FORC method is valid only in cases of weak spatial correlation of the magnetisation and suggest a more general approach.

  14. Loco-regional cancer drug therapy: present approaches and rapidly reversible hydrophobization (RRH) of therapeutic agents as the future direction.

    Science.gov (United States)

    Budker, Vladimir G; Monahan, Sean D; Subbotin, Vladimir M

    2014-12-01

    Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction.

  15. First order reversal curves and intrinsic parameter determination for magnetic materials; limitations of hysteron-based approaches in correlated systems

    Science.gov (United States)

    Ruta, Sergiu; Hovorka, Ondrej; Huang, Pin-Wei; Wang, Kangkang; Ju, Ganping; Chantrell, Roy

    2017-01-01

    The generic problem of extracting information on intrinsic particle properties from the whole class of interacting magnetic fine particle systems is a long standing and difficult inverse problem. As an example, the Switching Field Distribution (SFD) is an important quantity in the characterization of magnetic systems, and its determination in many technological applications, such as recording media, is especially challenging. Techniques such as the first order reversal curve (FORC) methods, were developed to extract the SFD from macroscopic measurements. However, all methods rely on separating the contributions to the measurements of the intrinsic SFD and the extrinsic effects of magnetostatic and exchange interactions. We investigate the underlying physics of the FORC method by applying it to the output predictions of a kinetic Monte-Carlo model with known input parameters. We show that the FORC method is valid only in cases of weak spatial correlation of the magnetisation and suggest a more general approach. PMID:28338056

  16. Genetic and Modeling Approaches Reveal Distinct Components of Impulsive Behavior.

    Science.gov (United States)

    Nautiyal, Katherine M; Wall, Melanie M; Wang, Shuai; Magalong, Valerie M; Ahmari, Susanne E; Balsam, Peter D; Blanco, Carlos; Hen, René

    2017-01-18

    Impulsivity is an endophenotype found in many psychiatric disorders including substance use disorders, pathological gambling, and attention deficit hyperactivity disorder. Two behavioral features often considered in impulsive behavior are behavioral inhibition (impulsive action) and delayed gratification (impulsive choice). However, the extent to which these behavioral constructs represent distinct facets of behavior with discrete biological bases is unclear. To test the hypothesis that impulsive action and impulsive choice represent statistically independent behavioral constructs in mice, we collected behavioral measures of impulsivity in a single cohort of mice using well-validated operant behavioral paradigms. Mice with manipulation of serotonin 1B receptor (5-HT1BR) expression were included as a model of disordered impulsivity. A factor analysis was used to characterize correlations between the measures of impulsivity and to identify covariates. Using two approaches, we dissociated impulsive action from impulsive choice. First, the absence of 5-HT1BRs caused increased impulsive action, but not impulsive choice. Second, based on an exploratory factor analysis, a two-factor model described the data well, with measures of impulsive action and choice separating into two independent factors. A multiple-indicator multiple-causes analysis showed that 5-HT1BR expression and sex were significant covariates of impulsivity. Males displayed increased impulsivity in both dimensions, whereas 5-HT1BR expression was a predictor of increased impulsive action only. These data support the conclusion that impulsive action and impulsive choice are distinct behavioral phenotypes with dissociable biological influences that can be modeled in mice. Our work may help inform better classification, diagnosis, and treatment of psychiatric disorders, which present with disordered impulsivity.Neuropsychopharmacology advance online publication, 18 January 2017; doi:10.1038/npp.2016.277.

  17. Improving the accuracy of density-functional theory calculation: the genetic algorithm and neural network approach.

    Science.gov (United States)

    Li, Hui; Shi, LiLi; Zhang, Min; Su, Zhongmin; Wang, XiuJun; Hu, LiHong; Chen, GuanHua

    2007-04-14

    The combination of genetic algorithm and neural network approach (GANN) has been developed to improve the calculation accuracy of density functional theory. As a demonstration, this combined quantum mechanical calculation and GANN correction approach has been applied to evaluate the optical absorption energies of 150 organic molecules. The neural network approach reduces the root-mean-square (rms) deviation of the calculated absorption energies of 150 organic molecules from 0.47 to 0.22 eV for the TDDFTB3LYP6-31G(d) calculation, and the newly developed GANN correction approach reduces the rms deviation to 0.16 eV.

  18. Non-Genetic Engineering Approaches for Isolating and Generating Novel Yeasts for Industrial Applications

    Science.gov (United States)

    Chambers, P. J.; Bellon, J. R.; Schmidt, S. A.; Varela, C.; Pretorius, I. S.

    Generating novel yeast strains for industrial applications should be quite straightforward; after all, research into the genetics, biochemistry and physiology of Baker's Yeast, Saccharomyces cerevisiae, has paved the way for many advances in the modern biological sciences. We probably know more about this humble eukaryote than any other, and it is the most tractable of organisms for manipulation using modern genetic engineering approaches. In many countries, however, there are restrictions on the use of genetically-modified organisms (GMOs), particularly in foods and beverages, and the level of consumer acceptance of GMOs is, at best, variable. Thus, many researchers working with industrial yeasts use genetic engineering techniques primarily as research tools, and strain development continues to rely on non-GM technologies. This chapter explores the non-GM tools and strategies available to such researchers.

  19. Solving an aggregate production planning problem by using multi-objective genetic algorithm (MOGA approach

    Directory of Open Access Journals (Sweden)

    Ripon Kumar Chakrabortty

    2013-01-01

    Full Text Available In hierarchical production planning system, Aggregate Production Planning (APP falls between the broad decisions of long-range planning and the highly specific and detailed short-range planning decisions. This study develops an interactive Multi-Objective Genetic Algorithm (MOGA approach for solving the multi-product, multi-period aggregate production planning (APP with forecasted demand, related operating costs, and capacity. The proposed approach attempts to minimize total costs with reference to inventory levels, labor levels, overtime, subcontracting and backordering levels, and labor, machine and warehouse capacity. Here several genetic algorithm parameters are considered for solving NP-hard problem (APP problem and their relative comparisons are focused to choose the most auspicious combination for solving multiple objective problems. An industrial case demonstrates the feasibility of applying the proposed approach to real APP decision problems. Consequently, the proposed MOGA approach yields an efficient APP compromise solution for large-scale problems.

  20. Anomalous electric birefringence behavior of sonicated DNA fragments as observed in reversing-pulse transients and steady-state sign reversal: a multicomponent approach.

    Science.gov (United States)

    Yamaoka, Kiwamu

    2007-04-15

    Anomalous electric birefringence signals of a sonicated and column-fractionated medium-size calf thymus DNA sample (bp=570) in Na(+) solutions were measured at 7 degrees C. The reversing-pulse electric birefringence (RPEB) signal pattern was theoretically calculated in the low electric field region for two axially symmetric models coexisting in equilibrium in solution. The RPEB theory is based on the electric dipole moment due to ion-fluctuation along the longitudinal direction and the electric polarizability anisotropy (Deltaalpha'), together with various electric and optical parameters assigned to the models. An analytical method was developed for the steady-state birefringence of the two-component system in a wide range of electric fields. The NaDNA samples exhibit complex RPEB patterns mixed with negative- and positive-going profiles. An experimental RPEB signal of NaDNA at an absorbance (A(260)) of 8 was fitted to theoretical curve at weak electric fields. The anomalous RPEB signal was attributed to the component 2, which shows a dip in the buildup and another in the reverse processes with a positive sign and a larger relaxation time. For the component 1, a normal DNA profile with negative sign is associated with a narrow dip in the reverse and a faster relaxation time in the decay signal. The field-strength dependence of observed steady-state birefringence delta(infinity) could be fitted for NaDNA at A(260)=8 by the SUSID orientation function with saturated ionic and electronic moments. An apparent positive maximum and the sign reversal in delta(infinity) at weak electric fields is an interplay between the positive component 2 with positive optical factor Deltag and negative Deltaalpha' and the negative component 1 with negative Deltag and positive Deltaalpha'. Possible conformation of two DNA components involved in solution was estimated.

  1. Genetic and Molecular Approaches to Study Neuronal Migration in the Developing Cerebral Cortex.

    Science.gov (United States)

    Dudok, Jacobus J; Leonards, Pim E G; Wijnholds, Jan

    2017-05-05

    The migration of neuronal cells in the developing cerebral cortex is essential for proper development of the brain and brain networks. Disturbances in this process, due to genetic abnormalities or exogenous factors, leads to aberrant brain formation, brain network formation, and brain function. In the last decade, there has been extensive research in the field of neuronal migration. In this review, we describe different methods and approaches to assess and study neuronal migration in the developing cerebral cortex. First, we discuss several genetic methods, techniques and genetic models that have been used to study neuronal migration in the developing cortex. Second, we describe several molecular approaches to study aberrant neuronal migration in the cortex which can be used to elucidate the underlying mechanisms of neuronal migration. Finally, we describe model systems to investigate and assess the potential toxicity effect of prenatal exposure to environmental chemicals on proper brain formation and neuronal migration.

  2. On Generating Optimal Signal Probabilities for Random Tests: A Genetic Approach

    Directory of Open Access Journals (Sweden)

    M. Srinivas

    1996-01-01

    Full Text Available Genetic Algorithms are robust search and optimization techniques. A Genetic Algorithm based approach for determining the optimal input distributions for generating random test vectors is proposed in the paper. A cost function based on the COP testability measure for determining the efficacy of the input distributions is discussed. A brief overview of Genetic Algorithms (GAs and the specific details of our implementation are described. Experimental results based on ISCAS-85 benchmark circuits are presented. The performance of our GAbased approach is compared with previous results. While the GA generates more efficient input distributions than the previous methods which are based on gradient descent search, the overheads of the GA in computing the input distributions are larger.

  3. Approaches for the Identification of Genetic Modifiers of Nutrient Dependent Phenotypes: Examples from Folate

    OpenAIRE

    MacFarlane, Amanda J.; Ian eZinck

    2014-01-01

    By combining the sciences of nutrition, bioinformatics, genomics, population genetics, and epidemiology, nutrigenomics is improving our understanding of how diet and nutrient intake can interact with or modify gene expression and disease risk. In this review, we explore various approaches to examine gene–nutrient interactions and the modifying role of nutrient consumption, as they relate to nutrient status and disease risk in human populations. Two common approaches include the use of SNPs in...

  4. A Genetic Algorithm Approach for Group Formation in Collaborative Learning Considering Multiple Student Characteristics

    Science.gov (United States)

    Moreno, Julian; Ovalle, Demetrio A.; Vicari, Rosa M.

    2012-01-01

    Considering that group formation is one of the key processes in collaborative learning, the aim of this paper is to propose a method based on a genetic algorithm approach for achieving inter-homogeneous and intra-heterogeneous groups. The main feature of such a method is that it allows for the consideration of as many student characteristics as…

  5. Integrating Genetic, Psychopharmacological and Neuroimaging Studies: A Converging Methods Approach to Understanding the Neurobiology of ADHD

    Science.gov (United States)

    Durston, Sarah; Konrad, Kerstin

    2007-01-01

    This paper aims to illustrate how combining multiple approaches can inform us about the neurobiology of ADHD. Converging evidence from genetic, psychopharmacological and functional neuroimaging studies has implicated dopaminergic fronto-striatal circuitry in ADHD. However, while the observation of converging evidence from multiple vantage points…

  6. A Genetic Algorithm Approach for Group Formation in Collaborative Learning Considering Multiple Student Characteristics

    Science.gov (United States)

    Moreno, Julian; Ovalle, Demetrio A.; Vicari, Rosa M.

    2012-01-01

    Considering that group formation is one of the key processes in collaborative learning, the aim of this paper is to propose a method based on a genetic algorithm approach for achieving inter-homogeneous and intra-heterogeneous groups. The main feature of such a method is that it allows for the consideration of as many student characteristics as…

  7. Application of a single-objective, hybrid genetic algorithm approach to pharmacokinetic model building.

    Science.gov (United States)

    Sherer, Eric A; Sale, Mark E; Pollock, Bruce G; Belani, Chandra P; Egorin, Merrill J; Ivy, Percy S; Lieberman, Jeffrey A; Manuck, Stephen B; Marder, Stephen R; Muldoon, Matthew F; Scher, Howard I; Solit, David B; Bies, Robert R

    2012-08-01

    A limitation in traditional stepwise population pharmacokinetic model building is the difficulty in handling interactions between model components. To address this issue, a method was previously introduced which couples NONMEM parameter estimation and model fitness evaluation to a single-objective, hybrid genetic algorithm for global optimization of the model structure. In this study, the generalizability of this approach for pharmacokinetic model building is evaluated by comparing (1) correct and spurious covariate relationships in a simulated dataset resulting from automated stepwise covariate modeling, Lasso methods, and single-objective hybrid genetic algorithm approaches to covariate identification and (2) information criteria values, model structures, convergence, and model parameter values resulting from manual stepwise versus single-objective, hybrid genetic algorithm approaches to model building for seven compounds. Both manual stepwise and single-objective, hybrid genetic algorithm approaches to model building were applied, blinded to the results of the other approach, for selection of the compartment structure as well as inclusion and model form of inter-individual and inter-occasion variability, residual error, and covariates from a common set of model options. For the simulated dataset, stepwise covariate modeling identified three of four true covariates and two spurious covariates; Lasso identified two of four true and 0 spurious covariates; and the single-objective, hybrid genetic algorithm identified three of four true covariates and one spurious covariate. For the clinical datasets, the Akaike information criterion was a median of 22.3 points lower (range of 470.5 point decrease to 0.1 point decrease) for the best single-objective hybrid genetic-algorithm candidate model versus the final manual stepwise model: the Akaike information criterion was lower by greater than 10 points for four compounds and differed by less than 10 points for three

  8. Physiological fidelity or model parsimony? The relative performance of reverse-toxicokinetic modeling approaches.

    Science.gov (United States)

    Rowland, Michael A; Perkins, Edward J; Mayo, Michael L

    2017-03-11

    Physiologically-based toxicokinetic (PBTK) models are often developed to facilitate in vitro to in vivo extrapolation (IVIVE) using a top-down, compartmental approach, favoring architectural simplicity over physiological fidelity despite the lack of general guidelines relating model design to dynamical predictions. Here we explore the impact of design choice (high vs. low fidelity) on chemical distribution throughout an animal's organ system. We contrast transient dynamics and steady states of three previously proposed PBTK models of varying complexity in response to chemical exposure. The steady states for each model were determined analytically to predict exposure conditions from tissue measurements. Steady state whole-body concentrations differ between models, despite identical environmental conditions, which originates from varying levels of physiological fidelity captured by the models. These differences affect the relative predictive accuracy of the inverted models used in exposure reconstruction to link effects-based exposure data with whole-organism response thresholds obtained from in vitro assay measurements. Our results demonstrate how disregarding physiological fideltiy in favor of simpler models affects the internal dynamics and steady state estimates for chemical accumulation within tissues, which, in turn, poses significant challenges for the exposure reconstruction efforts that underlie many IVIVE methods. Developing standardized systems-level models for ecological organisms would not only ensure predictive consistency among future modeling studies, but also ensure pragmatic extrapolation of in vivo effects from in vitro data or modeling exposure-response relationships.

  9. Epigenetic-genetic chromosome dosage approach for fetal trisomy 21 detection using an autosomal genetic reference marker.

    Directory of Open Access Journals (Sweden)

    Yu K Tong

    Full Text Available BACKGROUND: The putative promoter of the holocarboxylase synthetase (HLCS gene on chromosome 21 is hypermethylated in placental tissues and could be detected as a fetal-specific DNA marker in maternal plasma. Detection of fetal trisomy 21 (T21 has been demonstrated by an epigenetic-genetic chromosome dosage approach where the amount of hypermethylated HLCS in maternal plasma is normalized using a fetal genetic marker on the Y chromosome as a chromosome dosage reference marker. We explore if this method can be applied on both male and female fetuses with the use of a paternally-inherited fetal single nucleotide polymorphism (SNP allele on a reference chromosome for chromosome dosage normalization. METHODOLOGY: We quantified hypermethylated HLCS molecules using methylation-sensitive restriction endonuclease digestion followed by real-time or digital PCR analyses. For chromosome dosage analysis, we compared the amount of digestion-resistant HLCS to that of a SNP allele (rs6636, a C/G SNP that the fetus has inherited from the father but absent in the pregnant mother. PRINCIPAL FINDINGS: Using a fetal-specific SNP allele on a reference chromosome, we analyzed 20 euploid and nine T21 placental tissue samples. All samples with the fetal-specific C allele were correctly classified. One sample from each of the euploid and T21 groups were misclassified when the fetal-specific G allele was used as the reference marker. We then analyzed 33 euploid and 14 T21 maternal plasma samples. All but one sample from each of the euploid and T21 groups were correctly classified using the fetal-specific C allele, while correct classification was achieved for all samples using the fetal-specific G allele as the reference marker. CONCLUSIONS: As a proof-of-concept study, we have demonstrated that the epigenetic-genetic chromosome dosage approach can be applied to the prenatal diagnosis of trisomy 21 for both male and female fetuses.

  10. Reverse and conventional chemical ecology approaches for the development of oviposition attractants for Culex mosquitoes.

    Directory of Open Access Journals (Sweden)

    Walter S Leal

    Full Text Available Synthetic mosquito oviposition attractants are sorely needed for surveillance and control programs for Culex species, which are major vectors of pathogens causing various human diseases, including filariasis, encephalitis, and West Nile encephalomyelitis. We employed novel and conventional chemical ecology approaches to identify potential attractants, which were demonstrated in field tests to be effective for monitoring populations of Cx. p. quinquefasciatus in human dwellings. Immunohistochemistry studies showed that an odorant-binding protein from this species, CquiOBP1, is expressed in trichoid sensilla on the antennae, including short, sharp-tipped trichoid sensilla type, which house an olfactory receptor neuron sensitive to a previously identified mosquito oviposition pheromone (MOP, 6-acetoxy-5-hexadecanolide. CquiOBP1 exists in monomeric and dimeric forms. Monomeric CquiOBP1 bound MOP in a pH-dependent manner, with a change in secondary structure apparently related to the loss of binding at low pH. The pheromone antipode showed higher affinity than the natural stereoisomer. By using both CquiOBP1 as a molecular target in binding assays and gas chromatography-electroantennographic detection (GC-EAD, we identified nonanal, trimethylamine (TMA, and skatole as test compounds. Extensive field evaluations in Recife, Brazil, a region with high populations of Cx. p. quinquefasciatus, showed that a combination of TMA (0.9 microg/l and nonanal (0.15 ng/microl is equivalent in attraction to the currently used infusion-based lure, and superior in that the offensive smell of infusions was eliminated in the newly developed synthetic mixture.

  11. Developing Novel Therapeutic Approaches in Small Cell Lung Carcinoma Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells

    Science.gov (United States)

    2015-10-01

    Using Genetically Engineered Mouse Models and Human Circulating Tumor Cells PRINCIPAL INVESTIGATOR: Jeffrey Engelman MD PhD CONTRACTING...SUBTITLE Developiing Novel Therapeutic Approaches in Small Cell Lung 5a. CONTRACT NUMBER Carcinoma Using Genetically Engineered Mouse Models and 5b...biomarkers. 15. SUBJECT TERMS Small cell lung cancer (SCLC), Genetically engineered mouse model (GEMM), BH3 mimetic, TORC inhibitor, Apoptosis

  12. The Arabidopsis Plant Intracellular Ras-group LRR (PIRL Family and the Value of Reverse Genetic Analysis for Identifying Genes that Function in Gametophyte Development

    Directory of Open Access Journals (Sweden)

    Nancy R. Forsthoefel

    2013-08-01

    Full Text Available Arabidopsis thaliana has proven a powerful system for developmental genetics, but identification of gametophytic genes with developmental mutants can be complicated by factors such as gametophyte-lethality, functional redundancy, or poor penetrance. These issues are exemplified by the Plant Intracellular Ras-group LRR (PIRL genes, a family of nine genes encoding a class of leucine-rich repeat proteins structurally related to animal and fungal LRR proteins involved in developmental signaling. Previous analysis of T-DNA insertion mutants showed that two of these genes, PIRL1 and PIRL9, have an essential function in pollen formation but are functionally redundant. Here, we present evidence implicating three more PIRLs in gametophyte development. Scanning electron microscopy revealed that disruption of either PIRL2 or PIRL3 results in a low frequency of pollen morphological abnormalities. In addition, molecular analysis of putative pirl6 insertion mutants indicated that knockout alleles of this gene are not represented in current Arabidopsis mutant populations, suggesting gametophyte lethality may hinder mutant recovery. Consistent with this, available microarray and RNA-seq data have documented strongest PIRL6 expression in developing pollen. Taken together, these results now implicate five PIRLs in gametophyte development. Systematic reverse genetic analysis of this novel LRR family has therefore identified gametophytically active genes that otherwise would likely be missed by forward genetic screens.

  13. Understanding the complex etiologies of developmental disorders: behavioral and molecular genetic approaches.

    Science.gov (United States)

    Willcutt, Erik G; Pennington, Bruce F; Duncan, Laramie; Smith, Shelley D; Keenan, Janice M; Wadsworth, Sally; Defries, John C; Olson, Richard K

    2010-09-01

    This article has 2 primary goals. First, a brief tutorial on behavioral and molecular genetic methods is provided for readers without extensive training in these areas. To illustrate the application of these approaches to developmental disorders, etiologically informative studies of reading disability (RD), math disability (MD), and attention-deficit hyperactivity disorder (ADHD) are then reviewed. Implications of the results for these specific disorders and for developmental disabilities as a whole are discussed, and novel directions for future research are highlighted. Previous family and twin studies of RD, MD, and ADHD are reviewed systematically, and the extensive molecular genetic literatures on each disorder are summarized. To illustrate 4 novel extensions of these etiologically informative approaches, new data are presented from the Colorado Learning Disabilities Research Center, an ongoing twin study of the etiology of RD, ADHD, MD, and related disorders. RD, MD, and ADHD are familial and heritable, and co-occur more frequently than expected by chance. Molecular genetic studies suggest that all 3 disorders have complex etiologies, with multiple genetic and environmental risk factors each contributing to overall risk for each disorder. Neuropsychological analyses indicate that the 3 disorders are each associated with multiple neuropsychological weaknesses, and initial evidence suggests that comorbidity between the 3 disorders is due to common genetic risk factors that lead to slow processing speed.

  14. 口蹄疫病毒反向遗传技术研究进展%Advance in Reverse Genetics Technology of Foot-and-mouth Disease Virus

    Institute of Scientific and Technical Information of China (English)

    任方; 易忠; 郭会玲; 魏玉荣; 马文戈; 黄炯

    2014-01-01

    Foot-and-mouth disease(FMD)is an infectious disease caused by foot-and-mouth disease virus (FMDV).Office International Des Epizooties (OIE)has listed foot-and-mouth disease as the first disease of the most important animal epidemic diseases.If FMD breaks out,it shall seriously affect the develop-ment of animal husbandry,and the national economy.But now,we still have the blind spot for the foot-and-mouth disease virus's understanding.There are many insufficiencies for the foot-and-mouth disease vaccine.The rapid development of viral reverse genetics technology has provided one new and effective technical method for the research of the foot-and-mouth disease virus structure and the research of the new vaccine and biological preparations.This article reviewed the domestic and foreign research of FMDV mo-lecular pathogenic mechanism and the new FMD vaccine preparation by reverse genetics technology,at last prospected the new trend of foot-and-mouth disease virus reverse genetics.%口蹄疫(FMD)是由口蹄疫病毒(FMDV)引起的一种高度接触性传染病,被世界动物卫生组织(OIE)列为必须报告的传染病之首,其暴发会严重影响畜牧业发展、人民生活以及国民经济。但目前对口蹄疫病毒的了解仍存在盲区,口蹄疫疫苗还有许多不足。病毒反向遗传学技术的飞速发展为口蹄疫病毒结构的深入研究与新型疫苗及其生物制品的研制提供了一种新的高效的技术方法。论文就国内外运用反向遗传学技术对口蹄疫病毒分子致病机理研究及利用反向遗传学操作技术研制新型 FMD 疫苗进行综述,并且展望口蹄疫病毒反向遗传学研究新动向。

  15. A cellular genetics approach identifies gene-drug interactions and pinpoints drug toxicity pathway nodes

    Directory of Open Access Journals (Sweden)

    Oscar Takeo Suzuki

    2014-08-01

    Full Text Available New approaches to toxicity testing have incorporated high-throughput screening across a broad-range of in vitro assays to identify potential key events in response to chemical or drug treatment. To date, these approaches have primarily utilized repurposed drug discovery assays. In this study, we describe an approach that combines in vitro screening with genetic approaches for the experimental identification of genes and pathways involved in chemical or drug toxicity. Primary embryonic fibroblasts isolated from 32 genetically-characterized inbred mouse strains were treated in concentration-response format with 65 compounds, including pharmaceutical drugs, environmental chemicals, and compounds with known modes-of-action. Integrated cellular responses were measured at 24 and 72 hours using high-content imaging and included cell loss, membrane permeability, mitochondrial function, and apoptosis. Genetic association analysis of cross-strain differences in the cellular responses resulted in a collection of candidate loci potentially underlying the variable strain response to each chemical. As a demonstration of the approach, one candidate gene involved in rotenone sensitivity, Cybb, was experimentally validated in vitro and in vivo. Pathway analysis on the combined list of candidate loci across all chemicals identified a number of over-connected nodes that may serve as core regulatory points in toxicity pathways.

  16. A fuzzy genetic approach for network reconfiguration to enhance voltage stability in radial distribution systems

    Energy Technology Data Exchange (ETDEWEB)

    Sahoo, N.C. [Faculty of Engineering and Technology, Multimedia University, Jalan Ayer Keroh Lama, Bukit Beruang, 75450 Melaka (Malaysia); Prasad, K. [Faculty of Information Science and Technology, Multimedia University, Jalan Ayer Keroh Lama, Bukit Beruang, 75450 Melaka (Malaysia)

    2006-11-15

    This paper presents a fuzzy genetic approach for reconfiguration of radial distribution systems (RDS) so as to maximize the voltage stability of the network for a specific set of loads. The network reconfiguration involves a mechanism for selection of the best set of branches to be opened, one from each loop, such that the reconfigured RDS possesses desired performance characteristics. This discrete solution space is better handled by the proposed scheme, which maximizes a suitable optimizing function (computed using two different approaches). In the first approach, this function is chosen as the average of a voltage stability index of all the buses in the RDS, while in the second approach, the complete RDS is reduced to a two bus equivalent system and the optimizing function is the voltage stability index of this reduced two bus system. The fuzzy genetic algorithm uses a suitable coding and decoding scheme for maintaining the radial nature of the network at every stage of genetic evolution, and it also uses a fuzzy rule based mutation controller for efficient search of the solution space. This method, tested on 69 bus and 33 bus RDSs, shows promising results for the both approaches. It is also observed that the network losses are reduced when the voltage stability is enhanced by the network reconfiguration. (author)

  17. Arbitrariness is not enough: towards a functional approach to the genetic code.

    Science.gov (United States)

    Lacková, Ľudmila; Matlach, Vladimír; Faltýnek, Dan

    2017-05-09

    Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.

  18. [Recent progress in gene mapping through high-throughput sequencing technology and forward genetic approaches].

    Science.gov (United States)

    Lu, Cairui; Zou, Changsong; Song, Guoli

    2015-08-01

    Traditional gene mapping using forward genetic approaches is conducted primarily through construction of a genetic linkage map, the process of which is tedious and time-consuming, and often results in low accuracy of mapping and large mapping intervals. With the rapid development of high-throughput sequencing technology and decreasing cost of sequencing, a variety of simple and quick methods of gene mapping through sequencing have been developed, including direct sequencing of the mutant genome, sequencing of selective mutant DNA pooling, genetic map construction through sequencing of individuals in population, as well as sequencing of transcriptome and partial genome. These methods can be used to identify mutations at the nucleotide level and has been applied in complex genetic background. Recent reports have shown that sequencing mapping could be even done without the reference of genome sequence, hybridization, and genetic linkage information, which made it possible to perform forward genetic study in many non-model species. In this review, we summarized these new technologies and their application in gene mapping.

  19. Genetics of schizophrenia and smoking: an approach to studying their comorbidity based on epidemiological findings

    Science.gov (United States)

    de Leon, Jose; Diaz, Francisco J.

    2012-01-01

    The association between schizophrenia and tobacco smoking has been described in more than 1,000 articles, many with inadequate methodology. The studies on this association can focus on: (1) current smoking, ever smoking or smoking cessation; (2) non-psychiatric controls or controls with severe mental illness (e.g., bipolar disorder); and (3) higher smoking frequency or greater usage in smokers. The association with the most potential for genetic studies is that between ever daily smoking and schizophrenia; it may reflect a shared genetic vulnerability. To reduce the number of false-positive genes, we propose a three-stage approach derived from epidemiological knowledge. In the first stage, only genetic variations associated with ever daily smoking that are simultaneously significant within the non-psychiatric controls, the bipolar disorder controls and the schizophrenia cases will be selected. Only those genetic variations that are simultaneously significant in the three hypothesis tests will be tested in the second stage, where the prevalence of the genes must be significantly higher in schizophrenia than in bipolar disorder, and significantly higher in bipolar disorder than in controls. The genes simultaneously significant in the second stage will be included in a third stage where the gene variations must be significantly more frequent in schizophrenia patients who did not start smoking daily until their 20s (late start) versus those who had an early start. Any genetic approach to psychiatric disorders may fail if attention is not given to comorbidity and epidemiological studies that suggest which comorbidities are likely to be explained by genetics and which are not. Our approach, which examines the results of epidemiological studies on comorbidities and then looks for genes that simultaneously satisfy epidemiologically suggested sets of hypotheses, may also apply to the study of other major illnesses. PMID:22190153

  20. Gene Prioritization for Imaging Genetics Studies Using Gene Ontology and a Stratified False Discovery Rate Approach.

    Science.gov (United States)

    Patel, Sejal; Park, Min Tae M; Chakravarty, M Mallar; Knight, Jo

    2016-01-01

    Imaging genetics is an emerging field in which the association between genes and neuroimaging-based quantitative phenotypes are used to explore the functional role of genes in neuroanatomy and neurophysiology in the context of healthy function and neuropsychiatric disorders. The main obstacle for researchers in the field is the high dimensionality of the data in both the imaging phenotypes and the genetic variants commonly typed. In this article, we develop a novel method that utilizes Gene Ontology, an online database, to select and prioritize certain genes, employing a stratified false discovery rate (sFDR) approach to investigate their associations with imaging phenotypes. sFDR has the potential to increase power in genome wide association studies (GWAS), and is quickly gaining traction as a method for multiple testing correction. Our novel approach addresses both the pressing need in genetic research to move beyond candidate gene studies, while not being overburdened with a loss of power due to multiple testing. As an example of our methodology, we perform a GWAS of hippocampal volume using both the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA2) and the Alzheimer's Disease Neuroimaging Initiative datasets. The analysis of ENIGMA2 data yielded a set of SNPs with sFDR values between 10 and 20%. Our approach demonstrates a potential method to prioritize genes based on biological systems impaired in a disease.

  1. A Genetic Algorithm and Fuzzy Logic Approach for Video Shot Boundary Detection

    Directory of Open Access Journals (Sweden)

    Dalton Meitei Thounaojam

    2016-01-01

    Full Text Available This paper proposed a shot boundary detection approach using Genetic Algorithm and Fuzzy Logic. In this, the membership functions of the fuzzy system are calculated using Genetic Algorithm by taking preobserved actual values for shot boundaries. The classification of the types of shot transitions is done by the fuzzy system. Experimental results show that the accuracy of the shot boundary detection increases with the increase in iterations or generations of the GA optimization process. The proposed system is compared to latest techniques and yields better result in terms of F1score parameter.

  2. A Genetic Algorithm and Fuzzy Logic Approach for Video Shot Boundary Detection.

    Science.gov (United States)

    Thounaojam, Dalton Meitei; Khelchandra, Thongam; Manglem Singh, Kh; Roy, Sudipta

    2016-01-01

    This paper proposed a shot boundary detection approach using Genetic Algorithm and Fuzzy Logic. In this, the membership functions of the fuzzy system are calculated using Genetic Algorithm by taking preobserved actual values for shot boundaries. The classification of the types of shot transitions is done by the fuzzy system. Experimental results show that the accuracy of the shot boundary detection increases with the increase in iterations or generations of the GA optimization process. The proposed system is compared to latest techniques and yields better result in terms of F1score parameter.

  3. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  4. Expanding the Lotus japonicus reverse genetics toolbox – Development of LORE1 retrotransposon mutagenesis and artificial miRNA-mediated silencing

    DEFF Research Database (Denmark)

    Urbanski, Dorian Fabian

    2011-01-01

    retrotransposon 1 (LORE1) for generating a virtually unlimited supply of insertion mutants simply by cultivating progeny from a single founder line. Novel insertions were then systematically annotated by combining an accurate and efficient amplification protocol with two-dimensional pooling and next......-generation sequencing. Automatic assignment of insertions to individuals within the pools was done using an in-house developed bioinformatics pipeline. Analysis of the 8935 novel LORE1 insertions obtained in this study showed LORE1 to be an efficient mutagen with strong exon-specific insertional preference....... The protocols developed in the current project are now the cornerstone of a new LORE1 reverse genetics resource characterized by efficient mutant line generation and accurate mutation annotation. In parallel, artificial microRNAs (amiRNAs) were designed based on both Arabidopsis and Lotus backbones...

  5. Lassa virus nucleoprotein mutants generated by reverse genetics induce a robust type I interferon response in human dendritic cells and macrophages.

    Science.gov (United States)

    Carnec, Xavier; Baize, Sylvain; Reynard, Stéphanie; Diancourt, Laure; Caro, Valérie; Tordo, Noel; Bouloy, Michèle

    2011-11-01

    Lassa virus (LASV; Arenaviridae) is responsible for severe hemorrhagic fevers in Africa. LASV nucleoprotein (NP) plays important roles in regulating viral transcription and replication and in inhibiting type I interferon (IFN) production. The NP C-terminal domain contains a 3'-to-5' exonuclease activity involved in suppressing IFN induction. We have established a murine polymerase (Pol) I reverse genetics system for LASV, showing that residues D389 and G392 of NP were critical for LASV viability, while the D389A/G392A and D389T/392A double mutants were severely altered in the ability to suppress IFN in macrophages and dendritic cells. Assessing their attenuation in vivo may open new perspectives in vaccinology.

  6. Implementing reverse genetics in Rosaceae: analysis of T-DNA flanking sequences of insertional mutant lines in the diploid strawberry, Fragaria vesca.

    Science.gov (United States)

    Oosumi, Teruko; Ruiz-Rojas, Juan Jairo; Veilleux, Richard E; Dickerman, Allan; Shulaev, Vladimir

    2010-09-01

    Reverse genetics is used for functional genomics research in model plants. To establish a model system for the systematic reverse genetics research in the Rosaceae family, we analyzed genomic DNA flanking the T-DNA insertions in 191 transgenic plants of the diploid strawberry, Fragaria vesca. One hundred and seventy-six T-DNA flanking sequences were amplified from the right border (RB) and 37 from the left border (LB) by thermal asymmetric interlaced PCR. Analysis of the T-DNA nick positions revealed that T-DNA was most frequently nicked at the cleavage sites. Analysis of 11 T-DNA integration sites indicated that T-DNA was integrated into the F. vesca genome by illegitimate recombination, as reported in other model plants: Arabidopsis, rice and tobacco. First, deletion of DNA was found at T-DNA integration target sites in all transgenic plants tested. Second, microsimilarities of a few base pairs between the left and/or right ends of the T-DNA and genomic sites were found in all transgenic plants tested. Finally, filler DNA was identified in four break-points. Out of 191 transgenic plants, T-DNA flanking sequences of 79 plants (41%) showed significant similarity to genes, elements or proteins of other plant species and 67 (35%) of the sequences are still unknown strawberry gene fragments. T-DNA flanking sequences of 126 plants (66%) showed homology to plant ESTs. This is the first report of T-DNA integration in a sizeable population of a rosaceous species. We have shown in this paper that T-DNA integration in strawberry is not random but directed by sequence microsimilarities in the host genome.

  7. A nearest neighbour approach by genetic distance to the assignment of individual trees to geographic origin.

    Science.gov (United States)

    Degen, Bernd; Blanc-Jolivet, Céline; Stierand, Katrin; Gillet, Elizabeth

    2017-03-01

    During the past decade, the use of DNA for forensic applications has been extensively implemented for plant and animal species, as well as in humans. Tracing back the geographical origin of an individual usually requires genetic assignment analysis. These approaches are based on reference samples that are grouped into populations or other aggregates and intend to identify the most likely group of origin. Often this grouping does not have a biological but rather a historical or political justification, such as "country of origin". In this paper, we present a new nearest neighbour approach to individual assignment or classification within a given but potentially imperfect grouping of reference samples. This method, which is based on the genetic distance between individuals, functions better in many cases than commonly used methods. We demonstrate the operation of our assignment method using two data sets. One set is simulated for a large number of trees distributed in a 120km by 120km landscape with individual genotypes at 150 SNPs, and the other set comprises experimental data of 1221 individuals of the African tropical tree species Entandrophragma cylindricum (Sapelli) genotyped at 61 SNPs. Judging by the level of correct self-assignment, our approach outperformed the commonly used frequency and Bayesian approaches by 15% for the simulated data set and by 5-7% for the Sapelli data set. Our new approach is less sensitive to overlapping sources of genetic differentiation, such as genetic differences among closely-related species, phylogeographic lineages and isolation by distance, and thus operates better even for suboptimal grouping of individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. An Approach To Design A Controlled Multi-logic Function Generator By Using COG Reversible Logic Gates

    National Research Council Canada - National Science Library

    Shefali Mamataj; Biswajit Das

    2016-01-01

    .... Reversible Logic is gaining significant consideration as the potential logic design style for implementation in modern nanotechnology and quantum computing with minimal impact on physical entropy...

  9. Landscape genetic approaches to guide native plant restoration in the Mojave Desert.

    Science.gov (United States)

    Shryock, Daniel F; Havrilla, Caroline A; DeFalco, Lesley A; Esque, Todd C; Custer, Nathan A; Wood, Troy E

    2017-03-01

    Restoring dryland ecosystems is a global challenge due to synergistic drivers of disturbance coupled with unpredictable environmental conditions. Dryland plant species have evolved complex life-history strategies to cope with fluctuating resources and climatic extremes. Although rarely quantified, local adaptation is likely widespread among these species and potentially influences restoration outcomes. The common practice of reintroducing propagules to restore dryland ecosystems, often across large spatial scales, compels evaluation of adaptive divergence within these species. Such evaluations are critical to understanding the consequences of large-scale manipulation of gene flow and to predicting success of restoration efforts. However, genetic information for species of interest can be difficult and expensive to obtain through traditional common garden experiments. Recent advances in landscape genetics offer marker-based approaches for identifying environmental drivers of adaptive genetic variability in non-model species, but tools are still needed to link these approaches with practical aspects of ecological restoration. Here, we combine spatially explicit landscape genetics models with flexible visualization tools to demonstrate how cost-effective evaluations of adaptive genetic divergence can facilitate implementation of different seed sourcing strategies in ecological restoration. We apply these methods to Amplified Fragment Length Polymorphism (AFLP) markers genotyped in two Mojave Desert shrub species of high restoration importance: the long-lived, wind-pollinated gymnosperm Ephedra nevadensis, and the short-lived, insect-pollinated angiosperm Sphaeralcea ambigua. Mean annual temperature was identified as an important driver of adaptive genetic divergence for both species. Ephedra showed stronger adaptive divergence with respect to precipitation variability, while temperature variability and precipitation averages explained a larger fraction of adaptive

  10. Landscape genetic approaches to guide native plant restoration in the Mojave Desert

    Science.gov (United States)

    Shryock, Daniel F.; Havrilla, Caroline A.; DeFalco, Lesley; Esque, Todd; Custer, Nathan; Wood, Troy E.

    2016-01-01

    Restoring dryland ecosystems is a global challenge due to synergistic drivers of disturbance coupled with unpredictable environmental conditions. Dryland plant species have evolved complex life-history strategies to cope with fluctuating resources and climatic extremes. Although rarely quantified, local adaptation is likely widespread among these species and potentially influences restoration outcomes. The common practice of reintroducing propagules to restore dryland ecosystems, often across large spatial scales, compels evaluation of adaptive divergence within these species. Such evaluations are critical to understanding the consequences of large-scale manipulation of gene flow and to predicting success of restoration efforts. However, genetic information for species of interest can be difficult and expensive to obtain through traditional common garden experiments. Recent advances in landscape genetics offer marker-based approaches for identifying environmental drivers of adaptive genetic variability in non-model species, but tools are still needed to link these approaches with practical aspects of ecological restoration. Here, we combine spatially-explicit landscape genetics models with flexible visualization tools to demonstrate how cost-effective evaluations of adaptive genetic divergence can facilitate implementation of different seed sourcing strategies in ecological restoration. We apply these methods to Amplified Fragment Length Polymorphism (AFLP) markers genotyped in two Mojave Desert shrub species of high restoration importance: the long-lived, wind-pollinated gymnosperm Ephedra nevadensis, and the short-lived, insect-pollinated angiosperm Sphaeralcea ambigua. Mean annual temperature was identified as an important driver of adaptive genetic divergence for both species. Ephedra showed stronger adaptive divergence with respect to precipitation variability, while temperature variability and precipitation averages explained a larger fraction of adaptive

  11. Assessing the Dietary Bioavailability of Metals Associated with Natural Particles: Extending the Use of the Reverse Labeling Approach to Zinc.

    Science.gov (United States)

    Croteau, Marie-Noële; Cain, Daniel J; Fuller, Christopher C

    2017-02-22

    We extend the use of a novel tracing technique to quantify the bioavailability of zinc (Zn) associated with natural particles using snails enriched with a less common Zn stable isotope. Lymnaea stagnalis is a model species that has relatively fast Zn uptake rates from the dissolved phase, enabling their rapid enrichment in (67)Zn during the initial phase of labeling. Isotopically enriched snails were subsequently exposed to algae mixed with increasing amounts of metal-rich particles collected from two acid mine drainage impacted rivers. Zinc bioavailability from the natural particles was inferred from calculations of (66)Zn assimilation into the snail's soft tissues. Zinc assimilation efficiency (AE) varied from 28% for the Animas River particles to 45% for the Snake River particles, indicating that particle-bound, or sorbed Zn, was bioavailable from acid mine drainage wastes. The relative binding strength of Zn sorption to the natural particles was inversely related to Zn bioavailability; a finding that would not have been possible without using the reverse labeling approach. Differences in the chemical composition of the particles suggest that their geochemical properties may influence the extent of Zn bioavailability.

  12. Assessing the dietary bioavailability of metals associated with natural particles: Extending the use of the reverse labeling approach to zinc

    Science.gov (United States)

    Croteau, Marie-Noele; Cain, Daniel J.; Fuller, Christopher C.

    2017-01-01

    We extend the use of a novel tracing technique to quantify the bioavailability of zinc (Zn) associated with natural particles using snails enriched with a less common Zn stable isotope. Lymnaea stagnalis is a model species that has relatively fast Zn uptake rates from the dissolved phase, enabling their rapid enrichment in 67Zn during the initial phase of labeling. Isotopically enriched snails were subsequently exposed to algae mixed with increasing amounts of metal-rich particles collected from two acid mine drainage impacted rivers. Zinc bioavailability from the natural particles was inferred from calculations of 66Zn assimilation into the snail’s soft tissues. Zinc assimilation efficiency (AE) varied from 28% for the Animas River particles to 45% for the Snake River particles, indicating that particle-bound, or sorbed Zn, was bioavailable from acid mine drainage wastes. The relative binding strength of Zn sorption to the natural particles was inversely related to Zn bioavailability; a finding that would not have been possible without using the reverse labeling approach. Differences in the chemical composition of the particles suggest that their geochemical properties may influence the extent of Zn bioavailability.

  13. 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.

  14. A pooling-based approach to mapping genetic variants associated with DNA methylation.

    Science.gov (United States)

    Kaplow, Irene M; MacIsaac, Julia L; Mah, Sarah M; McEwen, Lisa M; Kobor, Michael S; Fraser, Hunter B

    2015-06-01

    DNA methylation is an epigenetic modification that plays a key role in gene regulation. Previous studies have investigated its genetic basis by mapping genetic variants that are associated with DNA methylation at specific sites, but these have been limited to microarrays that cover map of DNA methylation. Compared to methods that do not account for ASM, our approach increases statistical power to detect associations while sharply reducing cost, effort, and experimental variability. As a proof of concept, we generated deep sequencing data from a pool of 60 human cell lines; we evaluated almost twice as many CpGs as the largest microarray studies and identified more than 2000 genetic variants associated with DNA methylation. We found that these variants are highly enriched for associations with chromatin accessibility and CTCF binding but are less likely to be associated with traits indirectly linked to DNA, such as gene expression and disease phenotypes. In summary, our approach allows genome-wide mapping of genetic variants associated with DNA methylation in any tissue of any species, without the need for individual-level genotype or methylation data.

  15. GPA-MDS: A Visualization Approach to Investigate Genetic Architecture among Phenotypes Using GWAS Results.

    Science.gov (United States)

    Wei, Wei; Ramos, Paula S; Hunt, Kelly J; Wolf, Bethany J; Hardiman, Gary; Chung, Dongjun

    2016-01-01

    Genome-wide association studies (GWAS) have identified tens of thousands of genetic variants associated with hundreds of phenotypes and diseases, which have provided clinical and medical benefits to patients with novel biomarkers and therapeutic targets. Recently, there has been accumulating evidence suggesting that different complex traits share a common risk basis, namely, pleiotropy. Previously, a statistical method, namely, GPA (Genetic analysis incorporating Pleiotropy and Annotation), was developed to improve identification of risk variants and to investigate pleiotropic structure through a joint analysis of multiple GWAS datasets. While GPA provides a statistically rigorous framework to evaluate pleiotropy between phenotypes, it is still not trivial to investigate genetic relationships among a large number of phenotypes using the GPA framework. In order to address this challenge, in this paper, we propose a novel approach, GPA-MDS, to visualize genetic relationships among phenotypes using the GPA algorithm and multidimensional scaling (MDS). This tool will help researchers to investigate common etiology among diseases, which can potentially lead to development of common treatments across diseases. We evaluate the proposed GPA-MDS framework using a simulation study and apply it to jointly analyze GWAS datasets examining 18 unique phenotypes, which helps reveal the shared genetic architecture of these phenotypes.

  16. New Genetic Approaches to AD: Lessons from APOE-TOMM40 Phylogenetics.

    Science.gov (United States)

    Lutz, Michael W; Crenshaw, Donna; Welsh-Bohmer, Kathleen A; Burns, Daniel K; Roses, Allen D

    2016-05-01

    Clinical trials for Alzheimer's disease are now focusing on the earliest stages of the disease with the goal of delaying dementia onset. There is great utility in using genetic variants to identify individuals at high age-dependent risk when the goal is to begin treatment before the development of any cognitive symptoms. Genetic variants identified through large-scale genome-wide association studies have not substantially improved the accuracy provided by APOE genotype to identify people at high risk of late-onset Alzheimer's disease (LOAD). We describe novel approaches, focused on molecular phylogenetics, to finding genetic variants that predict age at LOAD onset with sufficient accuracy and precision to be useful. We highlight the discovery of a polymorphism in TOMM40 that, in addition to APOE, may improve risk prediction and review how TOMM40 genetic variants may impact the develop of LOAD independently from APOE. The analysis methods described in this review may be useful for other genetically complex human diseases.

  17. Genetic parameters for carcass traits and body weight using a Bayesian approach in the Canchim cattle.

    Science.gov (United States)

    Meirelles, S L C; Mokry, F B; Espasandín, A C; Dias, M A D; Baena, M M; de A Regitano, L C

    2016-06-10

    Correlation between genetic parameters and factors such as backfat thickness (BFT), rib eye area (REA), and body weight (BW) were estimated for Canchim beef cattle raised in natural pastures of Brazil. Data from 1648 animals were analyzed using multi-trait (BFT, REA, and BW) animal models by the Bayesian approach. This model included the effects of contemporary group, age, and individual heterozygosity as covariates. In addition, direct additive genetic and random residual effects were also analyzed. Heritability estimated for BFT (0.16), REA (0.50), and BW (0.44) indicated their potential for genetic improvements and response to selection processes. Furthermore, genetic correlations between BW and the remaining traits were high (P > 0.50), suggesting that selection for BW could improve REA and BFT. On the other hand, genetic correlation between BFT and REA was low (P = 0.39 ± 0.17), and included considerable variations, suggesting that these traits can be jointly included as selection criteria without influencing each other. We found that REA and BFT responded to the selection processes, as measured by ultrasound. Therefore, selection for yearling weight results in changes in REA and BFT.

  18. Identifying human disease genes: advances in molecular genetics and computational approaches.

    Science.gov (United States)

    Bakhtiar, S M; Ali, A; Baig, S M; Barh, D; Miyoshi, A; Azevedo, V

    2014-07-04

    The human genome project is one of the significant achievements that have provided detailed insight into our genetic legacy. During the last two decades, biomedical investigations have gathered a considerable body of evidence by detecting more than 2000 disease genes. Despite the imperative advances in the genetic understanding of various diseases, the pathogenesis of many others remains obscure. With recent advances, the laborious methodologies used to identify DNA variations are replaced by direct sequencing of genomic DNA to detect genetic changes. The ability to perform such studies depends equally on the development of high-throughput and economical genotyping methods. Currently, basically for every disease whose origen is still unknown, genetic approaches are available which could be pedigree-dependent or -independent with the capacity to elucidate fundamental disease mechanisms. Computer algorithms and programs for linkage analysis have formed the foundation for many disease gene detection projects, similarly databases of clinical findings have been widely used to support diagnostic decisions in dysmorphology and general human disease. For every disease type, genome sequence variations, particularly single nucleotide polymorphisms are mapped by comparing the genetic makeup of case and control groups. Methods that predict the effects of polymorphisms on protein stability are useful for the identification of possible disease associations, whereas structural effects can be assessed using methods to predict stability changes in proteins using sequence and/or structural information.

  19. Infant development in family context: Call for a genetically informed approach

    Directory of Open Access Journals (Sweden)

    Stephanie H. Parade

    2012-09-01

    Full Text Available We call for a genetically informed approach in the examination of infant social and emotional development in family context. We recommend that scholars conceptualize family functioning as occurring on three unique levels: the parent-child dyad, the inter-parental dyad, and whole family functioning. Although advances in the area of understanding genetic variation in infants as a potential moderator of the influence of parent-child dyadic functioning have been made over the past decade, it is time to widen this inquiry to consider genetic variation in infants as a potential moderator of the influence of inter-parental dyadic and whole family functioning as well. A critical review of the literature also calls for additional examination of genetic variation in infants as a moderator of positive contextual influences, the integration of unique temperament variables with studies of infant genotype, consideration of the role of the gene-environment correlation, and epigenetic effects. Furthermore, we call for the application of genetically-informed research methods to these questions. Expanding knowledge in this area has the potential to refine treatment and prevention efforts aimed at promoting infant social and emotional development.

  20. 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

    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 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...

  1. The introduction history of invasive garden ants in Europe: integrating genetic, chemical and behavioural approaches

    DEFF Research Database (Denmark)

    Ugelvig, Line; Drijfhout, Falko; Kronauer, Daniel;

    2008-01-01

    BACKGROUND: The invasive garden ant, Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14...... populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We evaluate the relative informative power of the three methodological approaches and estimate both the number...... of independent introduction events from a yet unknown native range somewhere in the Black Sea area, and the invasive potential of the existing introduced populations. RESULTS: Three clusters of genetically similar populations were detected, and all but one population had a similar chemical profile. Aggression...

  2. Discovering Pair-Wise Genetic Interactions: An Information Theory-Based Approach

    Science.gov (United States)

    Ignac, Tomasz M.; Skupin, Alexander; Sakhanenko, Nikita A.; Galas, David J.

    2014-01-01

    Phenotypic variation, including that which underlies health and disease in humans, results in part from multiple interactions among both genetic variation and environmental factors. While diseases or phenotypes caused by single gene variants can be identified by established association methods and family-based approaches, complex phenotypic traits resulting from multi-gene interactions remain very difficult to characterize. Here we describe a new method based on information theory, and demonstrate how it improves on previous approaches to identifying genetic interactions, including both synthetic and modifier kinds of interactions. We apply our measure, called interaction distance, to previously analyzed data sets of yeast sporulation efficiency, lipid related mouse data and several human disease models to characterize the method. We show how the interaction distance can reveal novel gene interaction candidates in experimental and simulated data sets, and outperforms other measures in several circumstances. The method also allows us to optimize case/control sample composition for clinical studies. PMID:24670935

  3. Reverse genetics generation of chimeric infectious Junin/Lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and G2 cytoplasmic domains.

    Science.gov (United States)

    Albariño, César G; Bird, Brian H; Chakrabarti, Ayan K; Dodd, Kimberly A; White, David M; Bergeron, Eric; Shrivastava-Ranjan, Punya; Nichol, Stuart T

    2011-01-01

    The Arenaviridae are a diverse and globally distributed collection of viruses that are maintained primarily by rodent reservoirs. Junin virus (JUNV) and Lassa virus (LASV) can both cause significant outbreaks of severe and often fatal human disease throughout their respective areas of endemicity. In an effort to improve upon the existing live attenuated JUNV Candid1 vaccine, we generated a genetically homogenous stock of this virus from cDNA copies of the virus S and L segments by using a reverse genetics system. Further, these cDNAs were used in combination with LASV cDNAs to successfully generate two recombinant Candid1 JUNV/LASV chimeric viruses (via envelope glycoprotein [GPC] exchange). It was found that while the GPC extravirion domains were readily exchangeable, homologous stable signal peptide (SSP) and G2 transmembrane and cytoplasmic tail domains were essential for correct GPC maturation and production of infectious chimeric viruses. The switching of the JUNV and LASV G1/G2 ectodomains within the Candid1 vaccine background did not alter the attenuated phenotype of the vaccine strain in a lethal mouse model. These recombinant chimeric viruses shed light on the fundamental requirements of arenavirus GPC maturation and may serve as a strategy for the development of bivalent JUNV and LASV vaccine candidates.

  4. Development and characterization of a reverse genetic system for studying dengue virus serotype 3 strain variation and neutralization.

    Directory of Open Access Journals (Sweden)

    William B Messer

    Full Text Available Dengue viruses (DENV are enveloped single-stranded positive-sense RNA viruses transmitted by Aedes spp. mosquitoes. There are four genetically distinct serotypes designated DENV-1 through DENV-4, each further subdivided into distinct genotypes. The dengue scientific community has long contended that infection with one serotype confers lifelong protection against subsequent infection with the same serotype, irrespective of virus genotype. However this hypothesis is under increased scrutiny and the role of DENV genotypic variation in protection from repeated infection is less certain. As dengue vaccine trials move increasingly into field-testing, there is an urgent need to develop tools to better define the role of genotypic variation in DENV infection and immunity. To better understand genotypic variation in DENV-3 neutralization and protection, we designed and constructed a panel of isogenic, recombinant DENV-3 infectious clones, each expressing an envelope glycoprotein from a different DENV-3 genotype; Philippines 1982 (genotype I, Thailand 1995 (genotype II, Sri Lanka 1989 and Cuba 2002 (genotype III and Puerto Rico 1977 (genotype IV. We used the panel to explore how natural envelope variation influences DENV-polyclonal serum interactions. When the recombinant viruses were tested in neutralization assays using immune sera from primary DENV infections, neutralization titers varied by as much as ∼19-fold, depending on the expressed envelope glycoprotein. The observed variability in neutralization titers suggests that relatively few residue changes in the E glycoprotein may have significant effects on DENV specific humoral immunity and influence antibody mediated protection or disease enhancement in the setting of both natural infection and vaccination. These genotypic differences are also likely to be important in temporal and spatial microevolution of DENV-3 in the background of heterotypic neutralization. The recombinant and synthetic tools

  5. Genetic engineering of industrial Saccharomyces cerevisiae strains using a selection/counter-selection approach.

    Science.gov (United States)

    Kutyna, Dariusz R; Cordente, Antonio G; Varela, Cristian

    2014-01-01

    Gene modification of laboratory yeast strains is currently a very straightforward task thanks to the availability of the entire yeast genome sequence and the high frequency with which yeast can incorporate exogenous DNA into its genome. Unfortunately, laboratory strains do not perform well in industrial settings, indicating the need for strategies to modify industrial strains to enable strain development for industrial applications. Here we describe approaches we have used to genetically modify industrial strains used in winemaking.

  6. An integrated approach to structural design of buildings using genetic algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Rafiq, M.Y.; Mathews, J.D. [Univ. of Plymouth (United Kingdom)

    1996-12-31

    This paper presents an evolutionary approach to the integration of design activities, in the area of structural design of buildings, using Genetic Algorithms (GA). Integration process is viewed in two contexts: (i) Integration across the design activities within a particular discipline, and (ii) Integration across of the disciplines involved in the design. Particular advantages of the integration of design activities during the conceptual stage of the design process are highlighted.

  7. The introduction history of invasive garden ants in Europe: Integrating genetic, chemical and behavioural approaches

    OpenAIRE

    Boomsma Jacobus J; Kronauer Daniel JC; Drijfhout Falko P; Ugelvig Line V; Pedersen Jes S; Cremer Sylvia

    2008-01-01

    Abstract Background The invasive garden ant, Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14 populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We eva...

  8. A chemical genetics approach for specific differentiation of stem cells to somatic cells: a new promising therapeutical approach.

    Science.gov (United States)

    Sachinidis, Agapios; Sotiriadou, Isaia; Seelig, Bianca; Berkessel, Albrecht; Hescheler, Jürgen

    2008-01-01

    Cell replacement therapy of severe degenerative diseases such as diabetes, myocardial infarction and Parkinson's disease through transplantation of somatic cells generated from embryonic stem (ES) cells is currently receiving considerable attention for the therapeutic applications. ES cells harvested from the inner cell mass (ICM) of the early embryo, can proliferate indefinitely in vitro while retaining the ability to differentiate into all somatic cells thereby providing an unlimited renewable source of somatic cells. In this context, identifying soluble factors, in particular chemically synthesized small molecules, and signal cascades involved in specific differentiation processes toward a defined tissue specific cell type are crucial for optimizing the generation of somatic cells in vitro for therapeutic approaches. However, experimental models are required allowing rapid and "easy-to-handle" parallel screening of chemical libraries to achieve this goal. Recently, the forward chemical genetic screening strategy has been postulated to screen small molecules in cellular systems for a specific desired phenotypic effect. The current review is focused on the progress of ES cell research in the context of the chemical genetics to identify small molecules promoting specific differentiation of ES cells to desired cell phenotype. Chemical genetics in the context of the cell ES-based cell replacement therapy remains a challenge for the near future for several scientific fields including chemistry, molecular biology, medicinal physics and robotic technologies.

  9. Kernel Approach for Modeling Interaction Effects in Genetic Association Studies of Complex Quantitative Traits.

    Science.gov (United States)

    Broadaway, K Alaine; Duncan, Richard; Conneely, Karen N; Almli, Lynn M; Bradley, Bekh; Ressler, Kerry J; Epstein, Michael P

    2015-07-01

    The etiology of complex traits likely involves the effects of genetic and environmental factors, along with complicated interaction effects between them. Consequently, there has been interest in applying genetic association tests of complex traits that account for potential modification of the genetic effect in the presence of an environmental factor. One can perform such an analysis using a joint test of gene and gene-environment interaction. An optimal joint test would be one that remains powerful under a variety of models ranging from those of strong gene-environment interaction effect to those of little or no gene-environment interaction effect. To fill this demand, we have extended a kernel machine based approach for association mapping of multiple SNPs to consider joint tests of gene and gene-environment interaction. The kernel-based approach for joint testing is promising, because it incorporates linkage disequilibrium information from multiple SNPs simultaneously in analysis and permits flexible modeling of interaction effects. Using simulated data, we show that our kernel machine approach typically outperforms the traditional joint test under strong gene-environment interaction models and further outperforms the traditional main-effect association test under models of weak or no gene-environment interaction effects. We illustrate our test using genome-wide association data from the Grady Trauma Project, a cohort of highly traumatized, at-risk individuals, which has previously been investigated for interaction effects. © 2015 WILEY PERIODICALS, INC.

  10. The introduction history of invasive garden ants in Europe: Integrating genetic, chemical and behavioural approaches

    Directory of Open Access Journals (Sweden)

    Boomsma Jacobus J

    2008-02-01

    Full Text Available Abstract Background The invasive garden ant, Lasius neglectus, is the most recently detected pest ant and the first known invasive ant able to become established and thrive in the temperate regions of Eurasia. In this study, we aim to reconstruct the invasion history of this ant in Europe analysing 14 populations with three complementary approaches: genetic microsatellite analysis, chemical analysis of cuticular hydrocarbon profiles and behavioural observations of aggression behaviour. We evaluate the relative informative power of the three methodological approaches and estimate both the number of independent introduction events from a yet unknown native range somewhere in the Black Sea area, and the invasive potential of the existing introduced populations. Results Three clusters of genetically similar populations were detected, and all but one population had a similar chemical profile. Aggression between populations could be predicted from their genetic and chemical distance, and two major clusters of non-aggressive groups of populations were found. However, populations of L. neglectus did not separate into clear supercolonial associations, as is typical for other invasive ants. Conclusion The three methodological approaches gave consistent and complementary results. All joint evidence supports the inference that the 14 introduced populations of L. neglectus in Europe likely arose from only very few independent introductions from the native range, and that new infestations were typically started through introductions from other invasive populations. This indicates that existing introduced populations have a very high invasive potential when the ants are inadvertently spread by human transport.

  11. Approaches for the identification of genetic modifiers of nutrient dependent phenotypes: Examples from folate

    Directory of Open Access Journals (Sweden)

    Amanda J. Macfarlane

    2014-07-01

    Full Text Available By combining the sciences of nutrition, bioinformatics, genomics, population genetics and epidemiology, nutrigenomics is improving our understanding of how diet and nutrient intake can interact with or modify gene expression and disease risk. In this review, we explore various approaches to examine gene-nutrient interactions and the modifying role of nutrient consumption, as they relate to nutrient status and disease risk in human populations. Two common approaches include the use of SNPs in candidate genes to identify their association with nutritional status or disease outcomes, or genome wide association studies to identify genetic polymorphisms associated with a given phenotype. Here, we examine the results of various gene-nutrient interaction studies, the association of genetic polymorphisms with disease expression and the identification of nutritional factors that modify gene-dependent disease phenotypes. We have focussed on specific examples from investigations of the interactions of folate and B-vitamin consumption and polymorphisms in the genes of B vitamin dependent enzymes and their association with disease risk, followed by an examination of the strengths and limitations of the methods employed. We also present suggestions for future studies, including an approach from an on-going large scale study, to examine the interaction of nutrient intake and genotypic variation and their impact on nutritional status.

  12. Developmental psychopathology in an era of molecular genetics and neuroimaging: A developmental neurogenetics approach.

    Science.gov (United States)

    Hyde, Luke W

    2015-05-01

    The emerging field of neurogenetics seeks to model the complex pathways from gene to brain to behavior. This field has focused on imaging genetics techniques that examine how variability in common genetic polymorphisms predict differences in brain structure and function. These studies are informed by other complimentary techniques (e.g., animal models and multimodal imaging) and have recently begun to incorporate the environment through examination of Imaging Gene × Environment interactions. Though neurogenetics has the potential to inform our understanding of the development of psychopathology, there has been little integration between principles of neurogenetics and developmental psychopathology. The paper describes a neurogenetics and Imaging Gene × Environment approach and how these approaches have been usefully applied to the study of psychopathology. Six tenets of developmental psychopathology (the structure of phenotypes, the importance of exploring mechanisms, the conditional nature of risk, the complexity of multilevel pathways, the role of development, and the importance of who is studied) are identified, and how these principles can further neurogenetics applications to understanding the development of psychopathology is discussed. A major issue of this piece is how neurogenetics and current imaging and molecular genetics approaches can be incorporated into developmental psychopathology perspectives with a goal of providing models for better understanding pathways from among genes, environments, the brain, and behavior.

  13. Pharmacologically regulated induction of silent mutations (PRISM): combined pharmacological and genetic approaches for learning and memory.

    Science.gov (United States)

    Frankland, Paul W; Ohno, Masuo; Takahashi, Eiki; Chen, Adele R; Costa, Rui M; Kushner, Steven A; Silva, Alcino J

    2003-04-01

    Mouse transgenic and knock-out approaches have made fundamental contributions to our understanding of the molecular and cellular bases of learning and memory. These approaches have successfully identified a large number of molecules with either a central or modulatory role in learning and memory. However, there are limitations associated with first-generation mutant mice, which include, for example, the lack of temporal control over the mutation. Recent technical developments have started to address some of these shortcomings. Here, the authors review a newly developed inducible approach that takes advantage of synergistic interactions between subthreshold genetic and pharmacological manipulations. This approach is easily set up and can be used to study the functional interactions between molecules in signaling pathways.

  14. A linear programming approach for estimating the structure of a sparse linear genetic network from transcript profiling data

    Directory of Open Access Journals (Sweden)

    Chandra Nagasuma R

    2009-02-01

    Full Text Available Abstract Background A genetic network can be represented as a directed graph in which a node corresponds to a gene and a directed edge specifies the direction of influence of one gene on another. The reconstruction of such networks from transcript profiling data remains an important yet challenging endeavor. A transcript profile specifies the abundances of many genes in a biological sample of interest. Prevailing strategies for learning the structure of a genetic network from high-dimensional transcript profiling data assume sparsity and linearity. Many methods consider relatively small directed graphs, inferring graphs with up to a few hundred nodes. This work examines large undirected graphs representations of genetic networks, graphs with many thousands of nodes where an undirected edge between two nodes does not indicate the direction of influence, and the problem of estimating the structure of such a sparse linear genetic network (SLGN from transcript profiling data. Results The structure learning task is cast as a sparse linear regression problem which is then posed as a LASSO (l1-constrained fitting problem and solved finally by formulating a Linear Program (LP. A bound on the Generalization Error of this approach is given in terms of the Leave-One-Out Error. The accuracy and utility of LP-SLGNs is assessed quantitatively and qualitatively using simulated and real data. The Dialogue for Reverse Engineering Assessments and Methods (DREAM initiative provides gold standard data sets and evaluation metrics that enable and facilitate the comparison of algorithms for deducing the structure of networks. The structures of LP-SLGNs estimated from the INSILICO1, INSILICO2 and INSILICO3 simulated DREAM2 data sets are comparable to those proposed by the first and/or second ranked teams in the DREAM2 competition. The structures of LP-SLGNs estimated from two published Saccharomyces cerevisae cell cycle transcript profiling data sets capture known

  15. [Genetics and epigenetics. Explanatory approaches for (gender-specific) mechanisms of disease development].

    Science.gov (United States)

    Zerres, K; Eggermann, T

    2014-09-01

    Whereas the central role of DNA as the carrier of genetic information has long been well known, the impact of epigenetic mechanisms as mediators between genes and environment is now becoming increasingly clear. Epigenetics helps explain the partially reversible interplay between gene function and environment and even permits observation of the transgenerational transmission of epigenetic modifications. Of special interest are gender-specific mechanisms of gene regulation which, among others, offer an explanation for gender differences in human diseases. Since the study of epigenetic mechanisms and their impact on the etiology of common diseases is in its infancy, it is too early to draw general conclusions from the current state of knowledge. Moreover, completely new strategies are needed to research these effects. In addition to molecular findings, definitions of specific phenotypes are required, including biographic data of affected individuals and their ancestors. Epigenetics needs to be viewed in the context of the theory of evolution, classical genetics, and environmental research. Its aim is not to substitute the knowledge in these disciplines, but rather to provide a key to link their findings, thereby opening up new possibilities in terms of interpretation and understanding of gender differences in medicine. If these epigenetic mechanisms are better understood, particularly in terms of specific diseases, it is conceivable that these disorders could be influenced and treated in a more targeted manner in the future.

  16. An ICA with reference approach in identification of genetic variation and associated brain networks

    Directory of Open Access Journals (Sweden)

    Jingyu eLiu

    2012-02-01

    Full Text Available To address the statistical challenges associated with genome-wide association studies, we present an independent component analysis (ICA with reference approach to target a specific genetic variation and associated brain networks. First, a small set of single nucleotide polymorphisms (SNPs are empirically chosen to reflect a feature of interest and these SNPs are used as a reference when applying ICA to a full genomic SNP array. After extracting the genetic component maximally representing the characteristics of the reference, we test its association with brain networks in functional magnetic resonance imaging (fMRI data. The method was evaluated on both real and simulated datasets. Simulation demonstrates that ICA with reference can extract a specific genetic factor, even when the variance accounted for by such a factor is so small that a regular ICA fails. Our real data application from 48 schizophrenia patients and 40 healthy controls include 300K SNPs and fMRI images in an auditory oddball task. Using SNPs with allelic frequency difference in two groups as a reference, we extracted a genetic component that maximally differentiates patients from controls (p<4×10-17, and discovered a brain functional network that was significantly associated with this genetic component (p<1×10-4. The regions in the functional network mainly locate in the thalamus, anterior and posterior cingulate gyri. The contributing SNPs in the genetic factor mainly fall into two clusters centered at chromosome 7q21 and chromosome 5q35. The findings from the schizophrenia application are in concordance with previous knowledge about brain regions and gene function. All together, the results suggest that the ICA with reference can be particularly useful to explore the whole genome to find a specific factor of interest and further study its effect on brain.

  17. Comparative genetic approaches to the evolution of human brain and behavior.

    Science.gov (United States)

    Vallender, Eric J

    2011-01-01

    With advances in genomic technologies, the amount of genetic data available to scientists today is vast. Genomes are now available or planned for 14 different primate species and complete resequencing of numerous human individuals from numerous populations is underway. Moreover, high-throughput deep sequencing is quickly making whole genome efforts within the reach of single laboratories allowing for unprecedented studies. Comparative genetic approaches to the identification of the underlying basis of human brain, behavior, and cognitive ability are moving to the forefront. Two approaches predominate: inter-species divergence comparisons and intra-species polymorphism studies. These methodological differences are useful for different time scales of evolution and necessarily focus on different evolutionary events in the history of primate and hominin evolution. Inter-species divergence is more useful in studying large scale primate, or hominoid, evolution whereas intra-species polymorphism can be more illuminating of recent hominin evolution. These differences in methodological utility also extend to studies of differing genetic substrates; current divergence studies focus primarily on protein evolution whereas polymorphism studies are substrate ambivalent. Some of the issues inherent in these studies can be ameliorated by current sequencing capabilities whereas others remain intractable. New avenues are also being opened that allow for the incorporation of novel substrates and approaches. In the post-genomic era, the study of human evolution, specifically as it relates to the brain, is becoming more complete focusing increasingly on the totality of the system and better conceptualizing the entirety of the genetic changes that have lead to the human phenotype today.

  18. Sociability impairments in Genetic Absence Epilepsy Rats from Strasbourg: Reversal by the T-type calcium channel antagonist Z944.

    Science.gov (United States)

    Henbid, Mark T; Marks, Wendie N; Collins, Madeline J; Cain, Stuart M; Snutch, Terrance P; Howland, John G

    2017-10-01

    Childhood absence epilepsy (CAE) is associated with interictal co-morbid symptoms including abnormalities in social behaviour. Genetic Absence Epilepsy Rats from Strasbourg (GAERS) is a model of CAE that exhibits physiological and behavioural alterations characteristic of the human disorder. However, it is unknown if GAERS display the social deficits often observed in CAE. Sociability in rodents is thought to be mediated by neural circuits densely populated with T-type calcium channels and GAERS contain a missense mutation in the Cav3.2 T-type calcium channel gene. Thus, the objective of this study was to examine the effects of the clinical stage pan-T-type calcium channel blocker, Z944, on sociability behaviour in male and female GAERS and non-epileptic control (NEC) animals. Female GAERS showed reduced sociability in a three-chamber sociability task whereas male GAERS, male NECs, and female NECs all showed a preference for the chamber containing a stranger rat. In drug trials, pre-treatment with 5mg/kg of Z944 normalized sociability in female GAERS. In contrast, female NECs showed impaired sociability following Z944 treatment. Dose-dependent decreases in locomotor activity were noted following Z944 treatment in both strains. Treatment with 10mg/kg of Z944 altered exploration such that only 8 of the 16 rats tested explored both sides of the testing chamber. In those that explored the chamber, significant preference for the stranger rat was observed in GAERS but not NECs. Overall, the data suggest that T-type calcium channels are critical in regulating sociability in both GAERS and NEC animals. Future research should focus on T-type calcium channels in the treatment of sociability deficits observed in disorders such as CAE. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Endometriosis: A New Cellular and Molecular Genetic Approach for understanding the pathogenesis and evolutivity

    Directory of Open Access Journals (Sweden)

    Jean eBouquet De Joliniere

    2014-05-01

    Full Text Available ABSTRACT. Endometriosis is a benign disease with high prevalence in women of reproductive age estimated between 10 and 15% and is associated with considerable morbidity. Its etiology and pathogenesis are controversial but it is believed to involve multiple genetic, environmental, immunological, angiogenic and endocrine processes. Altered expressions of growth factors, cytokines, adhesion molecules, matrix metalloproteinases, and enzymes for estrogen synthesis and metabolism have been frequently observed in this condition. The possibility of genetic basis of endometriosis is demonstrated in studies of familial disease, in which the incidence of endometriosis is higher for first-degree relatives of probands as compared to controls. This review describes mainly the cellular, cytochemical, cytogenetic and molecular genetic features of endometriotic lesions and cultured endometriotic cells. In attempts to identify candidate gene (s involved in the pathogenesis of endometriosis, a tissue-based approaches including conventional cytogenetics (RHG-banding, loss of heterozygosity (LOH and Comparative Genomic Hybridization (CGH were employed. In addition to the karyotipic anomalies, consistent chromosome instability was confirmed by CGH and Fluorescence in Situ Hybridization (FISH. The nature and significance of the molecular genetic aberrations in relation to the locations and function of oncogenes and tumor supressor genes will be discussed. At last, a possible pathogenic role of embryonic duct remnants was observed in 7 female foetal reproductive tract in endometriosis and may induce a discussion about the begining of ovarian tumors and malignant proliferations

  20. Gene networks associated with conditional fear in mice identified using a systems genetics approach

    Directory of Open Access Journals (Sweden)

    Eskin Eleazar

    2011-03-01

    Full Text Available Abstract Background Our understanding of the genetic basis of learning and memory remains shrouded in mystery. To explore the genetic networks governing the biology of conditional fear, we used a systems genetics approach to analyze a hybrid mouse diversity panel (HMDP with high mapping resolution. Results A total of 27 behavioral quantitative trait loci were mapped with a false discovery rate of 5%. By integrating fear phenotypes, transcript profiling data from hippocampus and striatum and also genotype information, two gene co-expression networks correlated with context-dependent immobility were identified. We prioritized the key markers and genes in these pathways using intramodular connectivity measures and structural equation modeling. Highly connected genes in the context fear modules included Psmd6, Ube2a and Usp33, suggesting an important role for ubiquitination in learning and memory. In addition, we surveyed the architecture of brain transcript regulation and demonstrated preservation of gene co-expression modules in hippocampus and striatum, while also highlighting important differences. Rps15a, Kif3a, Stard7, 6330503K22RIK, and Plvap were among the individual genes whose transcript abundance were strongly associated with fear phenotypes. Conclusion Application of our multi-faceted mapping strategy permits an increasingly detailed characterization of the genetic networks underlying behavior.

  1. Multiplicity of experimental approaches to therapy for genetic muscle diseases and necessity for population screening.

    Science.gov (United States)

    Laing, Nigel G

    2008-01-01

    Currently a multiplicity of experimental approaches to therapy for genetic muscle diseases is being investigated. These include replacement of the missing gene, manipulation of the gene message, repair of the mutation, upregulation of an alternative gene and pharmacological interventions targeting a number of systems. A number of these approaches are in current clinical trials. There is considerable anticipation that perhaps more than one of the approaches will finally prove of clinical benefit, but there are many voices of caution. No matter which approaches might ultimately prove effective, there is a consensus that for most benefit to the patients it will be necessary to start treatment as early as possible. A consensus is also developing that the only way to do this is to implement population-based newborn screening to identify affected children shortly after birth. Population-based newborn screening is currently practised in very few places in the world and it brings with it implications for prevention rather than cure of genetic muscle diseases.

  2. Evaluating barriers for reverse logistics implementation under a multiple stakeholders' perspective analysis using grey decision making approach

    DEFF Research Database (Denmark)

    Bouzon, Marina; Govindan, Kannan; Rodriguez, Carlos Manuel Taboada

    2017-01-01

    In the past few decades, an interest in reverse logistics has attracted the attention of industries and also has become a subject of interest for researchers. However, while reverse logistics is becoming a mandatory element of the supply chain in developed countries particularly due to legislation...... issues, the subject is still in a state of infancy in emerging economies such as Brazil. In these connections, impediments to reverse logistics implementation must be considered and analyzed, as well as the many different perspectives from the key stakeholders for their development. The objective...... of this research is to evaluate the interrelationship among reverse logistics barriers from the perspectives of the most important stakeholders in the Brazilian context. For this purpose, a Multi-Criteria Decision Making tool named grey-based Decision Making Trial and Evaluation Laboratory (grey-DEMATEL) was used...

  3. An Approach To Design A Controlled Multi-logic Function Generator By Using COG Reversible Logic Gates

    Directory of Open Access Journals (Sweden)

    Shefali Mamataj

    2016-07-01

    Full Text Available In today‟s world everyday a new technology which is faster, smaller and more complex than its predecessor is being developed. Reversible computation is a research area characterized by having only computational models that is both forward and backward deterministic. Reversible Logic is gaining significant consideration as the potential logic design style for implementation in modern nanotechnology and quantum computing with minimal impact on physical entropy. It has become very popular over the last few years since reversible logic circuits dramatically reduce energy loss. It consumes less power by recovering bit loss from its unique input-output mapping. This paper represents the implementation of conventional Boolean functions for basic digital gate by using COG reversible gate. This paper also represents a multi logic function generator circuit for generating multiple logical function simultaneously using COG gates. And also represents a controlled multi logic function generator circuit for generating any specified output in a controlled way.

  4. A reverse genetics system for the Great Lakes strain of viral hemorrhagic septicemia virus: the NV gene is required for pathogenicity

    Science.gov (United States)

    Ammayappan, Arun; Kurath, Gael; Thompson, Tarin M.; Vakharia, Vikram N.

    2011-01-01

    Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus in the family of Rhabdoviridae, causes a highly contagious disease of fresh and saltwater fish worldwide. Recently, a novel genotype of VHSV, designated IVb, has invaded the Great Lakes in North America, causing large-scale epidemics in wild fish. An efficient reverse genetics system was developed to generate a recombinant VHSV of genotype IVb from cloned cDNA. The recombinant VHSV (rVHSV) was comparable to the parental wild-type strain both in vitro and in vivo, causing high mortality in yellow perch (Perca flavescens). A modified recombinant VHSV was generated in which the NV gene was substituted with an enhanced green fluorescent protein gene (rVHSV-ΔNV-EGFP), and another recombinant was made by inserting the EGFP gene into the full-length viral clone between the P and M genes (rVHSV-EGFP). The in vitro replication kinetics of rVHSV-EGFP was similar to rVHSV; however, the rVHSV-ΔNV-EGFP grew 2 logs lower. In yellow perch challenges, wtVHSV and rVHSV induced 82-100% cumulative per cent mortality (CPM), respectively, whereas rVHSV-EGFP produced 62% CPM and rVHSV-ΔNV-EGFP caused only 15% CPM. No reversion of mutation was detected in the recovered viruses and the recombinant viruses stably maintained the foreign gene after several passages. These results indicate that the NV gene of VHSV is not essential for viral replication in vitro and in vivo, but it plays an important role in viral replication efficiency and pathogenicity. This system will facilitate studies of VHSV replication, virulence, and production of viral vectored vaccines.

  5. A Detailed look of Audio Steganography Techniques using LSB and Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Gunjan Nehru

    2012-01-01

    Full Text Available This paper is the study of various techniques of audio steganography using different algorithmis like genetic algorithm approach and LSB approach. We have tried some approaches that helps in audio steganography. As we know it is the art and science of writing hidden messages in such a way that no one, apart from the sender and intended recipient, suspects the existence of the message, a form of security through obscurity. In steganography, the message used to hide secret message is called host message or cover message. Once the contents of the host message or cover message are modified, the resultant message is known as stego message. In other words, stego message is combination of host message and secret message. Audio steganography requires a text or audio secret message to be embedded within a cover audio message. Due to availability of redundancy, the cover audio message before steganography, stego message after steganography remains same. for information hiding.

  6. Evaluation of a non-targeted "Omic"' approach in the safety assessment of genetically modified plants

    DEFF Research Database (Denmark)

    Metzdorff, Stine Broeng; Kok, E. J.; Knuthsen, Pia;

    2006-01-01

    Genetically modified plants must be approved before release in the European Union, and the approval is generally based upon a comparison of various characteristics between the transgenic plant and a conventional counterpart. As a case study, focusing on safety assessment of genetically modified...... plants, we here report the development and characterisation of six independently transformed Arabidopsis thaliana lines modified in the flavonoid biosynthesis. Analyses of integration events and comparative analysis for characterisation of the intended effects were performed by PCR, quantitative Real......, no unintended effects were identified. However, we found that the majority of genes showing differential expression were identified as stress-related genes and that environmental conditions had a large impact on the expression of several genes, proteins, and metabolites. We suggest that the microarray approach...

  7. Branch-pipe-routing approach for ships using improved genetic algorithm

    Science.gov (United States)

    Sui, Haiteng; Niu, Wentie

    2016-09-01

    Branch-pipe routing plays fundamental and critical roles in ship-pipe design. The branch-pipe-routing problem is a complex combinatorial optimization problem and is thus difficult to solve when depending only on human experts. A modified genetic-algorithm-based approach is proposed in this paper to solve this problem. The simplified layout space is first divided into threedimensional (3D) grids to build its mathematical model. Branch pipes in layout space are regarded as a combination of several two-point pipes, and the pipe route between two connection points is generated using an improved maze algorithm. The coding of branch pipes is then defined, and the genetic operators are devised, especially the complete crossover strategy that greatly accelerates the convergence speed. Finally, simulation tests demonstrate the performance of proposed method.

  8. A genetic approach for the identification of exosporium assembly determinants of Bacillus anthracis

    Science.gov (United States)

    Spreng, Krista A.; Thompson, Brian M.; Stewart, George C.

    2013-01-01

    The exosporium is the outermost layer of spores of the zoonotic pathogen Bacillus anthracis. The composition of the exosporium and its functions are only partly understood. Because this outer spore layer is refractive to traditional biochemical analysis, a genetic approach is needed in order to define the proteins which comprise this important spore layer and its assembly pathway. We have created a novel genetic screening system for the identification and isolation of mutants with defects in exosporium assembly during B. anthracis spore maturation. The system is based on the targeting sequence of the BclA exosporium nap layer glycoprotein and a fluorescent reporter. By utilizing this screening system and gene inactivation with Tn916, several novel putative exosporium-associated determinants were identified. A sampling of the mutants obtained was further characterized, confirming their exosporium defect and validating the utility of this screen to identify novel spore determinants in the genome of this pathogen. PMID:23411372

  9. The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery

    Science.gov (United States)

    Grados, Marco A.

    2010-01-01

    Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

  10. At risk, or not at risk: Epidemiological approaches for assessing psychiatric (genetic) risk factors in the general population

    NARCIS (Netherlands)

    Breetvelt, E.J.

    2013-01-01

    This thesis “At risk, or not at risk” describes several approaches - cross-sectional, prospective, phenotype mining and forward genetics - for assessing psychiatric (genetic) risk factors in a general population study. The aims were 1) to investigate how routine and follow-up data from populationbas

  11. The Genetics of Obsessive-Compulsive Disorder and Tourette Syndrome: An Epidemiological and Pathway-Based Approach for Gene Discovery

    Science.gov (United States)

    Grados, Marco A.

    2010-01-01

    Objective: To provide a contemporary perspective on genetic discovery methods applied to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). Method: A review of research trends in genetics research in OCD and TS is conducted, with emphasis on novel approaches. Results: Genome-wide association studies (GWAS) are now in progress in OCD…

  12. Reversible Statistics

    DEFF Research Database (Denmark)

    Tryggestad, Kjell

    2004-01-01

    The study aims is to describe how the inclusion and exclusion of materials and calculative devices construct the boundaries and distinctions between statistical facts and artifacts in economics. My methodological approach is inspired by John Graunt's (1667) Political arithmetic and more recent work...... within constructivism and the field of Science and Technology Studies (STS). The result of this approach is here termed reversible statistics, reconstructing the findings of a statistical study within economics in three different ways. It is argued that all three accounts are quite normal, albeit...... in different ways. The presence and absence of diverse materials, both natural and political, is what distinguishes them from each other. Arguments are presented for a more symmetric relation between the scientific statistical text and the reader. I will argue that a more symmetric relation can be achieved...

  13. Enhancement of lipid production using biochemical, genetic and transcription factor engineering approaches.

    Science.gov (United States)

    Courchesne, Noémie Manuelle Dorval; Parisien, Albert; Wang, Bei; Lan, Christopher Q

    2009-04-20

    This paper compares three possible strategies for enhanced lipid overproduction in microalgae: the biochemical engineering (BE) approaches, the genetic engineering (GE) approaches, and the transcription factor engineering (TFE) approaches. The BE strategy relies on creating a physiological stress such as nutrient-starvation or high salinity to channel metabolic fluxes to lipid accumulation. The GE strategy exploits our understanding to the lipid metabolic pathway, especially the rate-limiting enzymes, to create a channelling of metabolites to lipid biosynthesis by overexpressing one or more key enzymes in recombinant microalgal strains. The TFE strategy is an emerging technology aiming at enhancing the production of a particular metabolite by means of overexpressing TFs regulating the metabolic pathways involved in the accumulation of target metabolites. Currently, BE approaches are the most established in microalgal lipid production. The TFE is a very promising strategy because it may avoid the inhibitive effects of the BE approaches and the limitation of "secondary bottlenecks" as commonly observed in the GE approaches. However, it is still a novel concept to be investigated systematically.

  14. A genetic algorithms approach for altering the membership functions in fuzzy logic controllers

    Science.gov (United States)

    Shehadeh, Hana; Lea, Robert N.

    1992-01-01

    Through previous work, a fuzzy control system was developed to perform translational and rotational control of a space vehicle. This problem was then re-examined to determine the effectiveness of genetic algorithms on fine tuning the controller. This paper explains the problems associated with the design of this fuzzy controller and offers a technique for tuning fuzzy logic controllers. A fuzzy logic controller is a rule-based system that uses fuzzy linguistic variables to model human rule-of-thumb approaches to control actions within a given system. This 'fuzzy expert system' features rules that direct the decision process and membership functions that convert the linguistic variables into the precise numeric values used for system control. Defining the fuzzy membership functions is the most time consuming aspect of the controller design. One single change in the membership functions could significantly alter the performance of the controller. This membership function definition can be accomplished by using a trial and error technique to alter the membership functions creating a highly tuned controller. This approach can be time consuming and requires a great deal of knowledge from human experts. In order to shorten development time, an iterative procedure for altering the membership functions to create a tuned set that used a minimal amount of fuel for velocity vector approach and station-keep maneuvers was developed. Genetic algorithms, search techniques used for optimization, were utilized to solve this problem.

  15. Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle.

    Science.gov (United States)

    Li, Wanbo; Sartelet, Arnaud; Tamma, Nico; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2016-02-01

    In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large-scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild-type allele at the co-dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named 'cool gray'. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed.

  16. A Genetic Algorithm-based Antenna Selection Approach for Large-but-Finite MIMO Networks

    KAUST Repository

    Makki, Behrooz

    2016-12-29

    We study the performance of antenna selectionbased multiple-input-multiple-output (MIMO) networks with large but finite number of transmit antennas and receivers. Considering the continuous and bursty communication scenarios with different users’ data request probabilities, we develop an efficient antenna selection scheme using genetic algorithms (GA). As demonstrated, the proposed algorithm is generic in the sense that it can be used in the cases with different objective functions, precoding methods, levels of available channel state information and channel models. Our results show that the proposed GAbased algorithm reaches (almost) the same throughput as the exhaustive search-based optimal approach, with substantially less implementation complexity.

  17. An Approach to Assembly Sequence Plannning Based on Hierarchical Strategy and Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    Niu Xinwen; Ding Han; Xiong Youlun

    2001-01-01

    Using group and subassembly cluster methods, the hierarchical structure of a product is.generated automatically, which largely reduces the complexity of planning. Based on genetic algofithn the optimal of assembly sequence of each stracture level can be obtained by sequence-bysequence search. As a result, a better assembly sequence of the product can be generated by combining the assembly sequences of all hierarchical structures, which provides more parallelism and flexibility for assembly operations. An industrial example is solved by this new approach.

  18. Genetic algorithm-fuzzy based dynamic motion planning approach for a mobile robot

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Presents the mobile robots dynamic motion planning problem with a task to find an obstacle-free route that requires minimum travel time from the start point to the destination point in a changing environment, due to the obstacle's moving. An Genetic Algorithm fuzzy(GA-Fuzzy)based optimal approach proposed to find any obstacle-free path and the GA used to select the optimal one, points ont that using this learned knowledge off line, a mobile robot can navigate to its goal point when it faces new scenario on-line. Concludes with the opti mal rule base given and the simulation results showing its effectiveness.

  19. Reverse Logistics

    OpenAIRE

    Kulikova, Olga

    2016-01-01

    This thesis was focused on the analysis of the concept of reverse logistics and actual reverse processes which are implemented in mining industry and finding solutions for the optimization of reverse logistics in this sphere. The objective of this paper was the assessment of the development of reverse logistics in mining industry on the example of potash production. The theoretical part was based on reverse logistics and mining waste related literature and provided foundations for further...

  20. 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...

  1. Approach to the genetics of alcoholism: a review based on pathophysiology.

    Science.gov (United States)

    Köhnke, Michael D

    2008-01-01

    Alcohol dependence is a common disorder with a heterogenous etiology. The results of family, twin and adoption studies on alcoholism are reviewed. These studies have revealed a heritability of alcoholism of over 50%. After evaluating the results, it was epidemiologically stated that alcoholism is heterogenous complex disorder with a multiple genetic background. Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcoholism. Strategies for gene identification are introduced to the reader, including family-based and association studies. The susceptibility genes that are in the focus of this article have been chosen because they are known to encode for underlying mechanisms that are linked to the pathophysiology of alcoholism or that are important for the pharmacotherapeutic approaches in the treatment of alcohol dependence. Postulated candidate genes of the metabolism of alcohol and of the involved neurotransmitter systems are introduced. Genetic studies on alcoholism examining the metabolism of alcohol and the dopaminergic, GABAergic, glutamatergic, opioid, cholinergic and serotonergic neurotransmitter systems as well as the neuropeptide Y are presented. The results are critically discussed followed by a discussion of possible consequences.

  2. New Approaches for Crop Genetic Adaptation to the Abiotic Stresses Predicted with Climate Change

    Directory of Open Access Journals (Sweden)

    Robert Redden

    2013-05-01

    Full Text Available Extreme climatic variation is predicted with climate change this century. In many cropping regions, the crop environment will tend to be warmer with more irregular rainfall and spikes in stress levels will be more severe. The challenge is not only to raise agricultural production for an expanding population, but to achieve this under more adverse environmental conditions. It is now possible to systematically explore the genetic variation in historic local landraces by using GPS locators and world climate maps to describe the natural selection for local adaptation, and to identify candidate germplasm for tolerances to extreme stresses. The physiological and biochemical components of these expressions can be genomically investigated with candidate gene approaches and next generation sequencing. Wild relatives of crops have largely untapped genetic variation for abiotic and biotic stress tolerances, and could greatly expand the available domesticated gene pools to assist crops to survive in the predicted extremes of climate change, a survivalomics strategy. Genomic strategies can assist in the introgression of these valuable traits into the domesticated crop gene pools, where they can be better evaluated for crop improvement. The challenge is to increase agricultural productivity despite climate change. This calls for the integration of many disciplines from eco-geographical analyses of genetic resources to new advances in genomics, agronomy and farm management, underpinned by an understanding of how crop adaptation to climate is affected by genotype × environment interaction.

  3. Developing approaches for linear mixed modeling in landscape genetics through landscape-directed dispersal simulations

    Science.gov (United States)

    Row, Jeffrey R.; Knick, Steven T.; Oyler-McCance, Sara J.; Lougheed, Stephen C.; Fedy, Bradley C.

    2017-01-01

    Dispersal can impact population dynamics and geographic variation, and thus, genetic approaches that can establish which landscape factors influence population connectivity have ecological and evolutionary importance. Mixed models that account for the error structure of pairwise datasets are increasingly used to compare models relating genetic differentiation to pairwise measures of landscape resistance. A model selection framework based on information criteria metrics or explained variance may help disentangle the ecological and landscape factors influencing genetic structure, yet there are currently no consensus for the best protocols. Here, we develop landscape-directed simulations and test a series of replicates that emulate independent empirical datasets of two species with different life history characteristics (greater sage-grouse; eastern foxsnake). We determined that in our simulated scenarios, AIC and BIC were the best model selection indices and that marginal R2 values were biased toward more complex models. The model coefficients for landscape variables generally reflected the underlying dispersal model with confidence intervals that did not overlap with zero across the entire model set. When we controlled for geographic distance, variables not in the underlying dispersal models (i.e., nontrue) typically overlapped zero. Our study helps establish methods for using linear mixed models to identify the features underlying patterns of dispersal across a variety of landscapes.

  4. Developing approaches for linear mixed modeling in landscape genetics through landscape-directed dispersal simulations.

    Science.gov (United States)

    Row, Jeffrey R; Knick, Steven T; Oyler-McCance, Sara J; Lougheed, Stephen C; Fedy, Bradley C

    2017-06-01

    Dispersal can impact population dynamics and geographic variation, and thus, genetic approaches that can establish which landscape factors influence population connectivity have ecological and evolutionary importance. Mixed models that account for the error structure of pairwise datasets are increasingly used to compare models relating genetic differentiation to pairwise measures of landscape resistance. A model selection framework based on information criteria metrics or explained variance may help disentangle the ecological and landscape factors influencing genetic structure, yet there are currently no consensus for the best protocols. Here, we develop landscape-directed simulations and test a series of replicates that emulate independent empirical datasets of two species with different life history characteristics (greater sage-grouse; eastern foxsnake). We determined that in our simulated scenarios, AIC and BIC were the best model selection indices and that marginal R(2) values were biased toward more complex models. The model coefficients for landscape variables generally reflected the underlying dispersal model with confidence intervals that did not overlap with zero across the entire model set. When we controlled for geographic distance, variables not in the underlying dispersal models (i.e., nontrue) typically overlapped zero. Our study helps establish methods for using linear mixed models to identify the features underlying patterns of dispersal across a variety of landscapes.

  5. Thermal genetic adaptation in the water flea Daphnia and its impact: an evolving metacommunity approach.

    Science.gov (United States)

    De Meester, Luc; Van Doorslaer, Wendy; Geerts, Aurora; Orsini, Luisa; Stoks, Robby

    2011-11-01

    Genetic adaptation to temperature change can impact responses of populations and communities to global warming. Here we integrate previously published results on experimental evolution trials with follow-up experiments involving the water flea Daphnia as a model system. Our research shows (1) the capacity of natural populations of this species to genetically adapt to changes in temperature in a time span of months to years, (2) the context-dependence of these genetic changes, emphasizing the role of ecology and community composition on evolutionary responses to climatic change, and (3) the impact of micro-evolutionary changes on immigration success of preadapted genotypes. Our study involves (1) experimental evolution trials in the absence and presence of the community of competitors, predators, and parasites, (2) life-table and competition experiments to assess the fitness consequences of micro-evolution, and (3) competition experiments with putative immigrant genotypes. We use these observations as building blocks of an evolving metacommunity to understand biological responses to climatic change. This approach integrates both local and regional responses at both the population and community levels. Finally, we provide an outline of current gaps in knowledge and suggest fruitful avenues for future research. © The Author 2011. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved.

  6. The theological and legal approach of prenatal and preimplantation genetic control

    Directory of Open Access Journals (Sweden)

    George Katsimigas

    2012-04-01

    Full Text Available Aim: The investigation of the theological and legal questions derived from the application of prenatal and preimplantation genetic control on human embryos. Moreover, the review of the European and Greek legislation with regard to the prenatal and preimplantation control. Material and Method: A literature review based on both review and research literature, conducted during the period of 1984-2009, derived from MEDLINE, SCOPUS and ΙΑΤΡΟΤΕΚ databases using as key words Prenatal diagnosis , Bioethics, Orthodox ethics, preimplantation genetic diagnosis, Legislation. Results: The orthodox theology adopts a negative view for the abortion of fetus, which it is considered murder in any stage of growth. The legal approach brought two basic questions a the securing of consent from the examined individual and b the constitutional protection of fetus' life. Conclusions: The orthodox theology, through their teaching places the moral criteria for facing the moral questions derived from the application of prenatal and preimplantation genetic control on human embryos. Also, the Greek citizens need to be informed for all the diagnostic examinations on embryos that should be provided by all public health organizations.

  7. Genetic engineering represents a safe approach for innovations improving nutritional contents of major food crops

    Directory of Open Access Journals (Sweden)

    Werner Arber

    2017-05-01

    Full Text Available About 70 years ago early microbial genetic research revealed that inherited phenotypic traits become determined by DNA filaments composed of 4 different nucleotides that are linearly arranged. In the meantime we know that genes, the determinants of specific life functions, are genomic segments of an average size of about 1000 nucleotides, i.e. a very small part of a genome. Fundamental insights into the structures and functions of selected genes can be reached by sorting out the relevant short DNA segment, splicing this fragment into a natural gene vector such as a viral genome or a fertility plasmid. This allows the researchers to transfer the genetic hybrid into an appropriate host cell in order to produce many copies that can then serve for functional and structural analysis. This research approach became efficient in the 1970s. On the request of involved researchers, safety guidelines became proposed 1975 at the Asilomar Conference on Recombinant DNA (Berg, Baltimore, Brenner, Roblin, & Singer, 1975, then generally introduced and still largely followed nowadays. Carefully carried out genetic engineering by horizontally transferring a selected and functionally well known DNA segment into the genome of another organism has in many published biosafety investigations never shown any unexpected harmful effect. We will present below selected examples of research contributions enabling innovations for the benefit of human life conditions.

  8. A genetic algorithm-based approach to flexible flow-line scheduling with variable lot sizes.

    Science.gov (United States)

    Lee, I; Sikora, R; Shaw, M J

    1997-01-01

    Genetic algorithms (GAs) have been used widely for such combinatorial optimization problems as the traveling salesman problem (TSP), the quadratic assignment problem (QAP), and job shop scheduling. In all of these problems there is usually a well defined representation which GA's use to solve the problem. We present a novel approach for solving two related problems-lot sizing and sequencing-concurrently using GAs. The essence of our approach lies in the concept of using a unified representation for the information about both the lot sizes and the sequence and enabling GAs to evolve the chromosome by replacing primitive genes with good building blocks. In addition, a simulated annealing procedure is incorporated to further improve the performance. We evaluate the performance of applying the above approach to flexible flow line scheduling with variable lot sizes for an actual manufacturing facility, comparing it to such alternative approaches as pair wise exchange improvement, tabu search, and simulated annealing procedures. The results show the efficacy of this approach for flexible flow line scheduling.

  9. Tracing Technological Development Trajectories: A Genetic Knowledge Persistence-Based Main Path Approach.

    Science.gov (United States)

    Park, Hyunseok; Magee, Christopher L

    2017-01-01

    The aim of this paper is to propose a new method to identify main paths in a technological domain using patent citations. Previous approaches for using main path analysis have greatly improved our understanding of actual technological trajectories but nonetheless have some limitations. They have high potential to miss some dominant patents from the identified main paths; nonetheless, the high network complexity of their main paths makes qualitative tracing of trajectories problematic. The proposed method searches backward and forward paths from the high-persistence patents which are identified based on a standard genetic knowledge persistence algorithm. We tested the new method by applying it to the desalination and the solar photovoltaic domains and compared the results to output from the same domains using a prior method. The empirical results show that the proposed method can dramatically reduce network complexity without missing any dominantly important patents. The main paths identified by our approach for two test cases are almost 10x less complex than the main paths identified by the existing approach. The proposed approach identifies all dominantly important patents on the main paths, but the main paths identified by the existing approach miss about 20% of dominantly important patents.

  10. Introduction to reversible computing

    CERN Document Server

    Perumalla, Kalyan S

    2013-01-01

    Few books comprehensively cover the software and programming aspects of reversible computing. Filling this gap, Introduction to Reversible Computing offers an expanded view of the field that includes the traditional energy-motivated hardware viewpoint as well as the emerging application-motivated software approach. Collecting scattered knowledge into one coherent account, the book provides a compendium of both classical and recently developed results on reversible computing. It explores up-and-coming theories, techniques, and tools for the application of rever

  11. Synthetic biology approaches in cancer immunotherapy, genetic network engineering, and genome editing.

    Science.gov (United States)

    Chakravarti, Deboki; Cho, Jang Hwan; Weinberg, Benjamin H; Wong, Nicole M; Wong, Wilson W

    2016-04-18

    Investigations into cells and their contents have provided evolving insight into the emergence of complex biological behaviors. Capitalizing on this knowledge, synthetic biology seeks to manipulate the cellular machinery towards novel purposes, extending discoveries from basic science to new applications. While these developments have demonstrated the potential of building with biological parts, the complexity of cells can pose numerous challenges. In this review, we will highlight the broad and vital role that the synthetic biology approach has played in applying fundamental biological discoveries in receptors, genetic circuits, and genome-editing systems towards translation in the fields of immunotherapy, biosensors, disease models and gene therapy. These examples are evidence of the strength of synthetic approaches, while also illustrating considerations that must be addressed when developing systems around living cells.

  12. An Approach to Derive Parametric L-System Using Genetic Algorithm

    Science.gov (United States)

    Farooq, Humera; Zakaria, M. Nordin; Hassan, Mohd. Fadzil; Sulaiman, Suziah

    In computer graphics, L-System is widely used to model artificial plants structures and fractals. The Genetic Algorithm (GA) is the most popular form of Evolutionary Algorithms. This paper examines a method for automatic plant modeling which is based on an integration of GA and Parametric L-System using appropriate fitness function. The approach is specifically based on the implementation of two layered GA to derive the rewriting rules of Parametric L-System. The higher level of GA deals with the evolution of symbols and lower level deals with the evolution of numerical parameters. Initial results derived from the approach are very promising, which shows that complicated branching structures can be easily derived by the multilayered architecture of GA.

  13. A Parallel Approach To Optimum Actuator Selection With a Genetic Algorithm

    Science.gov (United States)

    Rogers, James L.

    2000-01-01

    Recent discoveries in smart technologies have created a variety of aerodynamic actuators which have great potential to enable entirely new approaches to aerospace vehicle flight control. For a revolutionary concept such as a seamless aircraft with no moving control surfaces, there is a large set of candidate locations for placing actuators, resulting in a substantially larger number of combinations to examine in order to find an optimum placement satisfying the mission requirements. The placement of actuators on a wing determines the control effectiveness of the airplane. One approach to placement Maximizes the moments about the pitch, roll, and yaw axes, while minimizing the coupling. Genetic algorithms have been instrumental in achieving good solutions to discrete optimization problems, such as the actuator placement problem. As a proof of concept, a genetic has been developed to find the minimum number of actuators required to provide uncoupled pitch, roll, and yaw control for a simplified, untapered, unswept wing model. To find the optimum placement by searching all possible combinations would require 1,100 hours. Formulating the problem and as a multi-objective problem and modifying it to take advantage of the parallel processing capabilities of a multi-processor computer, reduces the optimization time to 22 hours.

  14. Intrusion detection: a novel approach that combines boosting genetic fuzzy classifier and data mining techniques

    Science.gov (United States)

    Ozyer, Tansel; Alhajj, Reda; Barker, Ken

    2005-03-01

    This paper proposes an intelligent intrusion detection system (IDS) which is an integrated approach that employs fuzziness and two of the well-known data mining techniques: namely classification and association rule mining. By using these two techniques, we adopted the idea of using an iterative rule learning that extracts out rules from the data set. Our final intention is to predict different behaviors in networked computers. To achieve this, we propose to use a fuzzy rule based genetic classifier. Our approach has two main stages. First, fuzzy association rule mining is applied and a large number of candidate rules are generated for each class. Then the rules pass through pre-screening mechanism in order to reduce the fuzzy rule search space. Candidate rules obtained after pre-screening are used in genetic fuzzy classifier to generate rules for the specified classes. Classes are defined as Normal, PRB-probe, DOS-denial of service, U2R-user to root and R2L- remote to local. Second, an iterative rule learning mechanism is employed for each class to find its fuzzy rules required to classify data each time a fuzzy rule is extracted and included in the system. A Boosting mechanism evaluates the weight of each data item in order to help the rule extraction mechanism focus more on data having relatively higher weight. Finally, extracted fuzzy rules having the corresponding weight values are aggregated on class basis to find the vote of each class label for each data item.

  15. Process planning optimization on turning machine tool using a hybrid genetic algorithm with local search approach

    Directory of Open Access Journals (Sweden)

    Yuliang Su

    2015-04-01

    Full Text Available A turning machine tool is a kind of new type of machine tool that is equipped with more than one spindle and turret. The distinctive simultaneous and parallel processing abilities of turning machine tool increase the complexity of process planning. The operations would not only be sequenced and satisfy precedence constraints, but also should be scheduled with multiple objectives such as minimizing machining cost, maximizing utilization of turning machine tool, and so on. To solve this problem, a hybrid genetic algorithm was proposed to generate optimal process plans based on a mixed 0-1 integer programming model. An operation precedence graph is used to represent precedence constraints and help generate a feasible initial population of hybrid genetic algorithm. Encoding strategy based on data structure was developed to represent process plans digitally in order to form the solution space. In addition, a local search approach for optimizing the assignments of available turrets would be added to incorporate scheduling with process planning. A real-world case is used to prove that the proposed approach could avoid infeasible solutions and effectively generate a global optimal process plan.

  16. A Novel Approach for Discovery Quantitative Fuzzy Multi-Level Association Rules Mining Using Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Saad M. Darwish

    2016-10-01

    Full Text Available Quantitative multilevel association rules mining is a central field to realize motivating associations among data components with multiple levels abstractions. The problem of expanding procedures to handle quantitative data has been attracting the attention of many researchers. The algorithms regularly discretize the attribute fields into sharp intervals, and then implement uncomplicated algorithms established for Boolean attributes. Fuzzy association rules mining approaches are intended to defeat such shortcomings based on the fuzzy set theory. Furthermore, most of the current algorithms in the direction of this topic are based on very tiring search methods to govern the ideal support and confidence thresholds that agonize from risky computational cost in searching association rules. To accelerate quantitative multilevel association rules searching and escape the extreme computation, in this paper, we propose a new genetic-based method with significant innovation to determine threshold values for frequent item sets. In this approach, a sophisticated coding method is settled, and the qualified confidence is employed as the fitness function. With the genetic algorithm, a comprehensive search can be achieved and system automation is applied, because our model does not need the user-specified threshold of minimum support. Experiment results indicate that the recommended algorithm can powerfully generate non-redundant fuzzy multilevel association rules.

  17. The Displacement of Base Station in Mobile Communication with Genetic Approach

    Directory of Open Access Journals (Sweden)

    Kim Nam

    2008-01-01

    Full Text Available Abstract This paper addresses the displacement of a base station with optimization approach. A genetic algorithm is used as optimization approach. A new representation that describes base station placement, transmitted power with real numbers, and new genetic operators is proposed and introduced. In addition, this new representation can describe the number of base stations. For the positioning of the base station, both coverage and economy efficiency factors were considered. Using the weighted objective function, it is possible to specify the location of the base station, the cell coverage, and its economy efficiency. The economy efficiency indicates a reduction in the number of base stations for cost effectiveness. To test the proposed algorithm, the proposed algorithm was applied to homogeneous traffic environment. Following this, the proposed algorithm was applied to an inhomogeneous traffic density environment in order to test it in actual conditions. The simulation results show that the algorithm enables the finding of a near optimal solution of base station placement, and it determines the efficient number of base stations. Moreover, it can offer a proper solution by adjusting the weighted objective function.

  18. The Displacement of Base Station in Mobile Communication with Genetic Approach

    Directory of Open Access Journals (Sweden)

    Nam Kim

    2008-05-01

    Full Text Available This paper addresses the displacement of a base station with optimization approach. A genetic algorithm is used as optimization approach. A new representation that describes base station placement, transmitted power with real numbers, and new genetic operators is proposed and introduced. In addition, this new representation can describe the number of base stations. For the positioning of the base station, both coverage and economy efficiency factors were considered. Using the weighted objective function, it is possible to specify the location of the base station, the cell coverage, and its economy efficiency. The economy efficiency indicates a reduction in the number of base stations for cost effectiveness. To test the proposed algorithm, the proposed algorithm was applied to homogeneous traffic environment. Following this, the proposed algorithm was applied to an inhomogeneous traffic density environment in order to test it in actual conditions. The simulation results show that the algorithm enables the finding of a near optimal solution of base station placement, and it determines the efficient number of base stations. Moreover, it can offer a proper solution by adjusting the weighted objective function.

  19. A New Spectral Shape-Based Record Selection Approach Using Np and Genetic Algorithms

    Directory of Open Access Journals (Sweden)

    Edén Bojórquez

    2013-01-01

    Full Text Available With the aim to improve code-based real records selection criteria, an approach inspired in a parameter proxy of spectral shape, named Np, is analyzed. The procedure is based on several objectives aimed to minimize the record-to-record variability of the ground motions selected for seismic structural assessment. In order to select the best ground motion set of records to be used as an input for nonlinear dynamic analysis, an optimization approach is applied using genetic algorithms focuse on finding the set of records more compatible with a target spectrum and target Np values. The results of the new Np-based approach suggest that the real accelerograms obtained with this procedure, reduce the scatter of the response spectra as compared with the traditional approach; furthermore, the mean spectrum of the set of records is very similar to the target seismic design spectrum in the range of interest periods, and at the same time, similar Np values are obtained for the selected records and the target spectrum.

  20. Examining the family-centred approach to genetic testing and counselling among UK Pakistanis: a community perspective.

    Science.gov (United States)

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Benson, J; Morton, R; Modell, B

    2013-01-01

    WHO advice suggests a family-centred approach for managing the elevated risk of recessively inherited disorders in consanguineous communities, whilst emerging policy recommends community engagement as an integral component of genetic service development. This paper explores the feasibility of the family-centred approach in the UK Pakistani origin community. The study took place within a context of debate in the media, professional and lay circles about cousin marriage causing disability in children. Using qualitative methods, a total of six single-sex focus group discussions (n = 50) were conducted in three UK cities with a high settlement of people of Pakistani origin. Tape-recorded transcripts were analysed using framework analysis. Kinship networks within Pakistani origin communities are being sustained and marriage between close blood relatives continues to take place alongside other marriage options. Study participants were critical of what was perceived as a prevalent notion that cousin marriage causes disability in children. They were willing to discuss cousin marriage and disability, share genetic information and engage with genetic issues. A desire for accurate information and a public informed about genetic issues was articulated whilst ineffective communication of genetic risk information undermined professionals in their support role. This study suggests a community that is embracing change, one in which kinship networks are still active and genetic information exchange is taking place. At the community level, these are conditions supportive of the family-centred approach to genetic testing and counselling.

  1. Pre-emptive resource-constrained multimode project scheduling using genetic algorithm: A dynamic forward approach

    Directory of Open Access Journals (Sweden)

    Aidin Delgoshaei

    2016-09-01

    Full Text Available Purpose: The issue resource over-allocating is a big concern for project engineers in the process of scheduling project activities. Resource over-allocating drawback is frequently seen after scheduling of a project in practice which causes a schedule to be useless. Modifying an over-allocated schedule is very complicated and needs a lot of efforts and time. In this paper, a new and fast tracking method is proposed to schedule large scale projects which can help project engineers to schedule the project rapidly and with more confidence. Design/methodology/approach: In this article, a forward approach for maximizing net present value (NPV in multi-mode resource constrained project scheduling problem while assuming discounted positive cash flows (MRCPSP-DCF is proposed. The progress payment method is used and all resources are considered as pre-emptible. The proposed approach maximizes NPV using unscheduled resources through resource calendar in forward mode. For this purpose, a Genetic Algorithm is applied to solve. Findings: The findings show that the proposed method is an effective way to maximize NPV in MRCPSP-DCF problems while activity splitting is allowed. The proposed algorithm is very fast and can schedule experimental cases with 1000 variables and 100 resources in few seconds. The results are then compared with branch and bound method and simulated annealing algorithm and it is found the proposed genetic algorithm can provide results with better quality. Then algorithm is then applied for scheduling a hospital in practice. Originality/value: The method can be used alone or as a macro in Microsoft Office Project® Software to schedule MRCPSP-DCF problems or to modify resource over-allocated activities after scheduling a project. This can help project engineers to schedule project activities rapidly with more accuracy in practice.

  2. On reversible, endoreversible, and irreversible heat device cycles versus the Carnot cycle: a pedagogical approach to account for losses

    Science.gov (United States)

    Gonzalez-Ayala, J.; Angulo-Brown, F.; Calvo Hernández, A.; Velasco, S.

    2016-07-01

    In this work we analyze the deviations of reversible cycles (for both heat engines and refrigerators) from the corresponding Carnot cycle operating between the same extreme temperatures, and deviations of irreversible cycles from their corresponding reversible realization while putting emphasis on the corresponding losses. The endoreversible models fit in the proposed framework. Two suitable loss factors, which do not need the explicit calculation of entropy variations, are introduced. The behavior of these factors and their interplay allow for a clear and pedagogical visualization of where external and internal irreversibilities are located, and their intensities in terms of the main variables describing the cycle. The analysis could be used as a starting point for more advanced studies on modeling and optimization of real devices and installations.

  3. Experimental pathways towards developing a rotavirus reverse genetics system: synthetic full length rotavirus ssRNAs are neither infectious nor translated in permissive cells.

    Directory of Open Access Journals (Sweden)

    James E Richards

    Full Text Available At present the ability to create rationally engineered mutant rotaviruses is limited because of the lack of a tractable helper virus-free reverse genetics system. Using the cell culture adapted bovine RV RF strain (G6P6 [1], we have attempted to recover infectious RV by co-transfecting in vitro transcribed ssRNAs which are identical in sequence to the positive sense strand of each of the 11 dsRNA genomic segments of the RF strain. The RNAs were produced either from cDNAs cloned by a target sequence-independent procedure, or from purified double layered RV particles (DLPs. We have validated their translational function by in vitro synthesis of (35S-labelled proteins in rabbit reticulocyte lysates; all 11 proteins encoded by the RV genome were expressed. Transfection experiments with DLP- or cDNA-derived ssRNAs suggested that the RNAs do not act independently as mRNAs for protein synthesis, once delivered into various mammalian cell lines, and exhibit cytotoxicity. Transfected RNAs were not infectious since a viral cytopathic effect was not observed after infection of MA104 cells with lysates from transfected cells. By contrast, an engineered mRNA encoding eGFP was expressed when transfected under identical conditions into the same cell lines. Co-expression of plasmids encoding NSP2 and NSP5 using a fowlpox T7 polymerase recombinant virus revealed viroplasm-like structure formation, but this did not enable the translation of transfected RV ssRNAs. Attempts to recover RV from ssRNAs transcribed intracellularly from transfected cDNAs were also unsuccessful and suggested that these RNAs were also not translated, in contrast to successful translation from a transfected cDNA encoding an eGFP mRNA.

  4. Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine.

    Science.gov (United States)

    Jimenez-Guardeño, Jose M; Regla-Nava, Jose A; Nieto-Torres, Jose L; DeDiego, Marta L; Castaño-Rodriguez, Carlos; Fernandez-Delgado, Raul; Perlman, Stanley; Enjuanes, Luis

    2015-10-01

    A SARS-CoV lacking the full-length E gene (SARS-CoV-∆E) was attenuated and an effective vaccine. Here, we show that this mutant virus regained fitness after serial passages in cell culture or in vivo, resulting in the partial duplication of the membrane gene or in the insertion of a new sequence in gene 8a, respectively. The chimeric proteins generated in cell culture increased virus fitness in vitro but remained attenuated in mice. In contrast, during SARS-CoV-∆E passage in mice, the virus incorporated a mutated variant of 8a protein, resulting in reversion to a virulent phenotype. When the full-length E protein was deleted or its PDZ-binding motif (PBM) was mutated, the revertant viruses either incorporated a novel chimeric protein with a PBM or restored the sequence of the PBM on the E protein, respectively. Similarly, after passage in mice, SARS-CoV-∆E protein 8a mutated, to now encode a PBM, and also regained virulence. These data indicated that the virus requires a PBM on a transmembrane protein to compensate for removal of this motif from the E protein. To increase the genetic stability of the vaccine candidate, we introduced small attenuating deletions in E gene that did not affect the endogenous PBM, preventing the incorporation of novel chimeric proteins in the virus genome. In addition, to increase vaccine biosafety, we introduced additional attenuating mutations into the nsp1 protein. Deletions in the carboxy-terminal region of nsp1 protein led to higher host interferon responses and virus attenuation. Recombinant viruses including attenuating mutations in E and nsp1 genes maintained their attenuation after passage in vitro and in vivo. Further, these viruses fully protected mice against challenge with the lethal parental virus, and are therefore safe and stable vaccine candidates for protection against SARS-CoV.

  5. Convenient and efficient approach to the permanent or reversible conjugation of RNA and DNA sequences with functional groups.

    Science.gov (United States)

    Cieślak, Jacek; Ausín, Cristina; Grajkowski, Andrzej; Beaucage, Serge L

    2012-09-01

    The conversion of 3',5'-disilylated 2'-O-(methylthiomethyl)ribonucleosides to 2'-O-(phthalimidooxymethyl)ribonucleosides is achieved in yields of 66% to 94%. Desilylation and dephtalimidation of these ribonucleosides by treatment with NH(4)F in MeOH produce 2'-O-aminooxymethylated ribonucleosides, which are efficient in producing stable and yet reversible 2'-conjugates upon reaction with 1-pyrenecarboxaldehyde. Exposure of 2'-pyrenylated ribonucleosides to 0.5 M tetra-n-butylammonium fluoride (TBAF) in THF or DMSO results in the cleavage of their iminoether functions to give the native ribonucleosides along with an innocuous nitrile side product. Conversely, the reaction of 2'-O-(aminooxymethyl)uridine with 5-cholesten-3-one leads to a permanent uridine 2'-conjugate, which is left unreacted when treated with TBAF. The versatility and uniqueness of 2'-O-(aminooxymethyl)ribonucleosides is demonstrated by the single or double incorporation of a reversible pyrenylated uridine 2'-conjugate into an RNA sequence. Furthermore, the conjugation of 2'-O-(aminooxymethyl)ribonucleosides with various aldehydes, including those generated from their acetals, is also presented. The preparation of 5'-O-(aminooxymethyl)thymidine is also achieved, albeit in modest yields, from the conversion of 5'-O-methylthiomethyl-3'-O-(levulinyl)thymidine to 5'-O-phthalimidooxymethyl-3'-O-(levuliny)lthymidine followed by hydrazinolysis of both 5'-phthalimido and 3'-levulinyl groups. Pyrenylation of the 5'-O-(aminooxymethyl)deoxyribonucleoside also provides a reversible 5'-conjugate that is sensitive to TBAF, thereby further demonstrating the usefulness of 5'-O-(aminooxymethyl)deoxyribonucleosides for permanent or reversible modification of DNA sequences. Curr. Protoc. Nucleic Acid Chem. 50:4.52.1-4.52.36. © 2012 by John Wiley & Sons, Inc.

  6. Establishment of Vero cell RNA polymerase I-driven reverse genetics for Influenza A virus and its application for pandemic (H1N1) 2009 influenza virus vaccine production.

    Science.gov (United States)

    Song, Min-Suk; Baek, Yun Hee; Pascua, Philippe Noriel Q; Kwon, Hyeok-Il; Park, Su-Jin; Kim, Eun-Ha; Lim, Gyo-Jin; Choi, Young-Ki

    2013-06-01

    The constant threat of newly emerging influenza viruses with pandemic potential requires the need for prompt vaccine production. Here, we utilized the Vero cell polymerase I (PolI) promoter, rather than the commonly used human PolI promoter, in an established reverse-genetics system to rescue viable influenza viruses in Vero cells, an approved cell line for human vaccine production. The Vero PolI promoter was more efficient in Vero cells and demonstrated enhanced transcription levels and virus rescue rates commensurate with that of the human RNA PolI promoter in 293T cells. These results appeared to be associated with more efficient generation of A(H1N1)pdm09- and H5N1-derived vaccine seed viruses in Vero cells, whilst the rescue rates in 293T cells were comparable. Our study provides an alternative means for improving vaccine preparation by using a novel reverse-genetics system for generating influenza A viruses.

  7. Efficient Reverse Genetics Reveals Genetic Determinants of Budding and Fusogenic Differences between Nipah and Hendra Viruses and Enables Real-Time Monitoring of Viral Spread in Small Animal Models of Henipavirus Infection

    Science.gov (United States)

    Yun, Tatyana; Park, Arnold; Hill, Terence E.; Pernet, Olivier; Beaty, Shannon M.; Juelich, Terry L.; Smith, Jennifer K.; Zhang, Lihong; Wang, Yao E.; Vigant, Frederic; Gao, Junling; Wu, Ping

    2014-01-01

    ABSTRACT Nipah virus (NiV) and Hendra virus (HeV) are closely related henipaviruses of the Paramyxovirinae. Spillover from their fruit bat reservoirs can cause severe disease in humans and livestock. Despite their high sequence similarity, NiV and HeV exhibit apparent differences in receptor and tissue tropism, envelope-mediated fusogenicity, replicative fitness, and other pathophysiologic manifestations. To investigate the molecular basis for these differences, we first established a highly efficient reverse genetics system that increased rescue titers by ≥3 log units, which offset the difficulty of generating multiple recombinants under constraining biosafety level 4 (BSL-4) conditions. We then replaced, singly and in combination, the matrix (M), fusion (F), and attachment glycoprotein (G) genes in mCherry-expressing recombinant NiV (rNiV) with their HeV counterparts. These chimeric but isogenic rNiVs replicated well in primary human endothelial and neuronal cells, indicating efficient heterotypic complementation. The determinants of budding efficiency, fusogenicity, and replicative fitness were dissociable: HeV-M budded more efficiently than NiV-M, accounting for the higher replicative titers of HeV-M-bearing chimeras at early times, while the enhanced fusogenicity of NiV-G-bearing chimeras did not correlate with increased replicative fitness. Furthermore, to facilitate spatiotemporal studies on henipavirus pathogenesis, we generated a firefly luciferase-expressing NiV and monitored virus replication and spread in infected interferon alpha/beta receptor knockout mice via bioluminescence imaging. While intraperitoneal inoculation resulted in neuroinvasion following systemic spread and replication in the respiratory tract, intranasal inoculation resulted in confined spread to regions corresponding to olfactory bulbs and salivary glands before subsequent neuroinvasion. This optimized henipavirus reverse genetics system will facilitate future investigations into

  8. Parallel tagged next-generation sequencing on pooled samples - a new approach for population genetics in ecology and conservation.

    Science.gov (United States)

    Zavodna, Monika; Grueber, Catherine E; Gemmell, Neil J

    2013-01-01

    Next-generation sequencing (NGS) on pooled samples has already been broadly applied in human medical diagnostics and plant and animal breeding. However, thus far it has been only sparingly employed in ecology and conservation, where it may serve as a useful diagnostic tool for rapid assessment of species genetic diversity and structure at the population level. Here we undertake a comprehensive evaluation of the accuracy, practicality and limitations of parallel tagged amplicon NGS on pooled population samples for estimating species population diversity and structure. We obtained 16S and Cyt b data from 20 populations of Leiopelma hochstetteri, a frog species of conservation concern in New Zealand, using two approaches - parallel tagged NGS on pooled population samples and individual Sanger sequenced samples. Data from each approach were then used to estimate two standard population genetic parameters, nucleotide diversity (π) and population differentiation (FST), that enable population genetic inference in a species conservation context. We found a positive correlation between our two approaches for population genetic estimates, showing that the pooled population NGS approach is a reliable, rapid and appropriate method for population genetic inference in an ecological and conservation context. Our experimental design also allowed us to identify both the strengths and weaknesses of the pooled population NGS approach and outline some guidelines and suggestions that might be considered when planning future projects.

  9. Quantitative genetics approaches to study evolutionary processes in ecotoxicology; a perspective from research on the evolution of resistance.

    Science.gov (United States)

    Klerks, Paul L; Xie, Lingtian; Levinton, Jeffrey S

    2011-05-01

    Quantitative genetic approaches are often used to study evolutionary processes in ecotoxicology. This paper focuses on the evolution of resistance to environmental contaminants-an important evolutionary process in ecotoxicology. Three approaches are commonly employed to study the evolution of resistance: (1) Assessing whether a contaminant-exposed population has an increased resistance relative to a control population, using either spatial or temporal comparisons. (2) Estimating a population's heritability of resistance. (3) Investigating responses in a laboratory selection experiment. All three approaches provide valuable information on the potential for contaminants to affect a population's evolutionary trajectory via natural selection. However, all three approaches have inherent limitations, including difficulty in separating the various genetic and environmental variance components, responses being dependent on specific population and testing conditions, and inability to fully capture natural conditions in the laboratory. In order to maximize insights into the long-term consequences of adaptation, it is important to not just look at resistance itself, but also at the fitness consequences and at correlated responses in characteristics other than resistance. The rapid development of molecular genetics has yielded alternatives to the "black box" approach of quantitative genetics, but the presence of different limitations and strengths in the two fields means that they should be viewed as complementary rather than exchangeable. Quantitative genetics is benefiting from the incorporation of molecular tools and remains an important field for studying evolutionary toxicology.

  10. Reverse Genetics for Fusogenic Bat-Borne Orthoreovirus Associated with Acute Respiratory Tract Infections in Humans: Role of Outer Capsid Protein σC in Viral Replication and Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Takahiro Kawagishi

    2016-02-01

    Full Text Available Nelson Bay orthoreoviruses (NBVs are members of the fusogenic orthoreoviruses and possess 10-segmented double-stranded RNA genomes. NBV was first isolated from a fruit bat in Australia more than 40 years ago, but it was not associated with any disease. However, several NBV strains have been recently identified as causative agents for respiratory tract infections in humans. Isolation of these pathogenic bat reoviruses from patients suggests that NBVs have evolved to propagate in humans in the form of zoonosis. To date, no strategy has been developed to rescue infectious viruses from cloned cDNA for any member of the fusogenic orthoreoviruses. In this study, we report the development of a plasmid-based reverse genetics system free of helper viruses and independent of any selection for NBV isolated from humans with acute respiratory infection. cDNAs corresponding to each of the 10 full-length RNA gene segments of NBV were cotransfected into culture cells expressing T7 RNA polymerase, and viable NBV was isolated using a plaque assay. The growth kinetics and cell-to-cell fusion activity of recombinant strains, rescued using the reverse genetics system, were indistinguishable from those of native strains. We used the reverse genetics system to generate viruses deficient in the cell attachment protein σC to define the biological function of this protein in the viral life cycle. Our results with σC-deficient viruses demonstrated that σC is dispensable for cell attachment in several cell lines, including murine fibroblast L929 cells but not in human lung epithelial A549 cells, and plays a critical role in viral pathogenesis. We also used the system to rescue a virus that expresses a yellow fluorescent protein. The reverse genetics system developed in this study can be applied to study the propagation and pathogenesis of pathogenic NBVs and in the generation of recombinant NBVs for future vaccines and therapeutics.

  11. Gene editing and genetic engineering approaches for advanced probiotics: A Review.

    Science.gov (United States)

    Yadav, Ruby; Kumar, Vishal; Baweja, Mehak; Shukla, Pratyoosh

    2017-01-10

    The applications of probiotics are significant and thus resulted in need of genome analysis of probiotic strains. Various omics methods and systems biology approaches enables us to understand and optimize the metabolic processes. These techniques have increased the researcher's attention towards gut microbiome and provided a new source for the revelation of uncharacterized biosynthetic pathways which enables novel metabolic engineering approaches. In recent years, the broad and quantitative analysis of modified strains relies on systems biology tools such as in silico design which are commonly used methods for improving strain performance. The genetic manipulation of probiotic microorganisms is crucial for defining their role in intestinal microbiota and exploring their beneficial properties. This review describes an overview of gene editing and system biology approaches, highlighting the advent of omics methods which allows the study of new routes for studying probiotic bacteria. We have also summarized gene editing tools like TALEN, ZFNs and CRISPR-Cas that edits or cleave the specific target DNA. Furthermore, in this review an overview of proposed design of advanced customized probiotic is also hypothesized to improvise the probiotics.

  12. Pharmaceutical proteins in plants. A strategic genetic engineering approach for the production of tuberculosis antigens.

    Science.gov (United States)

    Frutos, Roger; Denise, Hubert; Vivares, Christian; Neuhaus, Jean-Marc; Vitale, Sandro; Pedrazzini, Emmanuela; Ma, Julian; Dix, Phil; Gray, John; Pezzotti, Mario; Conrad, Udo; Robinson, David

    2008-12-01

    Tuberculosis (TB) is a re-emerging disease that is considered a major human health priority as well as an important disease of livestock. TB is also a zoonosis, and Mycobacterium tuberculosis and M. bovis, the human and bovine causative agents, respectively, are very closely related. Protection against TB is essentially achieved through vaccination with the Bacille Calmetle-Guerin (BCG) strain of M. bovis. Protection is, however, incomplete, and novel improved vaccines are currently under investigation. Production of protective antigens in transgenic plants, or "pharming," is a promising emerging approach, and a zoonosis-like TB is a good model for investigating the potential of this approach. Pharma-Planta, a European Commission-funded project and consortium, was set up to address this topic, within which a component is aimed at assessing the production efficacy and stability of the TB antigens in different compartments of the plant cell. This article is meant to introduce this promising approach for veterinary medicine by describing the ongoing project and its specific genetic engineering strategy.

  13. A Modified Genetic Algorithm for Product Family Optimization with Platform Specified by Information Theoretical Approach

    Institute of Scientific and Technical Information of China (English)

    CHEN Chun-bao; WANG Li-ya

    2008-01-01

    Many existing product family design methods assume a given platform, However, it is not an in-tuitive task to select the platform and unique variable within a product family. Meanwhile, most approachesare single-platform methods, in which design variables are either shared across all product variants or not atall. While in multiple-platform design, platform variables can have special value with regard to a subset ofproduct variants within the product family, and offer opportunities for superior overall design. An informationtheoretical approach incorporating fuzzy clustering and Shannon's entropy was proposed for platform variablesselection in multiple-platform product family. A 2-level chromosome genetic algorithm (2LCGA) was proposedand developed for optimizing the corresponding product family in a single stage, simultaneously determiningthe optimal settings for the product platform and unique variables. The single-stage approach can yield im-provements in the overall performance of the product family compared with two-stage approaches, in which thefirst stage involves determining the best settings for the platform and values of unique variables are found foreach product in the second stage. An example of design of a family of universal motors was used to verify theproposed method.

  14. Current Status of Pharmaceutical and Genetic Therapeutic Approaches to Treat DMD

    Science.gov (United States)

    Pichavant, Christophe; Aartsma-Rus, Annemieke; Clemens, Paula R; Davies, Kay E; Dickson, George; Takeda, Shin'ichi; Wilton, Steve D; Wolff, Jon A; Wooddell, Christine I; Xiao, Xiao; Tremblay, Jacques P

    2011-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disease affecting about one in every 3,500 boys. This X-linked pathology is due to the absence of dystrophin in muscle fibers. This lack of dystrophin leads to the progressive muscle degeneration that is often responsible for the death of the DMD patients during the third decade of their life. There are currently no curative treatments for this disease but different therapeutic approaches are being studied. Gene therapy consists of introducing a transgene coding for full-length or a truncated version of dystrophin complementary DNA (cDNA) in muscles, whereas pharmaceutical therapy includes the use of chemical/biochemical substances to restore dystrophin expression or alleviate the DMD phenotype. Over the past years, many potential drugs were explored. This led to several clinical trials for gentamicin and ataluren (PTC124) allowing stop codon read-through. An alternative approach is to induce the expression of an internally deleted, partially functional dystrophin protein through exon skipping. The vectors and the methods used in gene therapy have been continually improving in order to obtain greater encapsidation capacity and better transduction efficiency. The most promising experimental approaches using pharmaceutical and gene therapies are reviewed in this article. PMID:21468001

  15. An Interval-Valued Approach to Business Process Simulation Based on Genetic Algorithms and the BPMN

    Directory of Open Access Journals (Sweden)

    Mario G.C.A. Cimino

    2014-05-01

    Full Text Available Simulating organizational processes characterized by interacting human activities, resources, business rules and constraints, is a challenging task, because of the inherent uncertainty, inaccuracy, variability and dynamicity. With regard to this problem, currently available business process simulation (BPS methods and tools are unable to efficiently capture the process behavior along its lifecycle. In this paper, a novel approach of BPS is presented. To build and manage simulation models according to the proposed approach, a simulation system is designed, developed and tested on pilot scenarios, as well as on real-world processes. The proposed approach exploits interval-valued data to represent model parameters, in place of conventional single-valued or probability-valued parameters. Indeed, an interval-valued parameter is comprehensive; it is the easiest to understand and express and the simplest to process, among multi-valued representations. In order to compute the interval-valued output of the system, a genetic algorithm is used. The resulting process model allows forming mappings at different levels of detail and, therefore, at different model resolutions. The system has been developed as an extension of a publicly available simulation engine, based on the Business Process Model and Notation (BPMN standard.

  16. Unambiguous molecular detections with multiple genetic approach for the complicated chromosome 22q11 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Lin Lung-Huang

    2009-02-01

    Full Text Available Abstract Background Chromosome 22q11 deletion syndrome (22q11DS causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions. Methods We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH, quantitative real-time polymerase chain reaction (qPCR and multiplex ligation-dependent probe amplification (MLPA. Results Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p Conclusion Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.

  17. DYNAMIC RELOCATION OF PLANT/WAREHOUSE FACILITIES:A FAST COMPACT GENETIC ALGORITHM APPROACH

    Institute of Scientific and Technical Information of China (English)

    Li Shugang; Wu Zhiming; Pang Xiaohong

    2004-01-01

    The problem of dynamic relocation and phase-out of combined manufacturing plant and warehousing facilities in the supply chain are concerned.A multiple time/multiple objective model is proposed to maximize total profit during the time horizon, minimize total access time from the plant/warehouse facilities to its suppliers and customers and maximize aggregated local incentives during the time horizon.The relocation problem keeps the feature of NP-hard and with the traditional method the optimal result cannot be got easily.So a compact genetic algorithm (CGA) is introduced to solve the problem.In order to accelerate the convergence speed of the CGA, the least square approach is introduced and a fast compact genetic algorithm (fCGA) is proposed.Finally, simulation results with the fCGA are compared with the CGA and classical integer programming (IP).The results show that the fCGA proposed is of high efficiency for Pareto optimality problem.

  18. A bayesian approach to inferring the genetic population structure of sugarcane accessions from INTA (Argentina

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    Mariana Inés Pocovi

    2015-06-01

    Full Text Available Understanding the population structure and genetic diversity in sugarcane (Saccharum officinarum L. accessions from INTA germplasm bank (Argentina will be of great importance for germplasm collection and breeding improvement as it will identify diverse parental combinations to create segregating progenies with maximum genetic variability for further selection. A Bayesian approach, ordination methods (PCoA, Principal Coordinate Analysis and clustering analysis (UPGMA, Unweighted Pair Group Method with Arithmetic Mean were applied to this purpose. Sixty three INTA sugarcane hybrids were genotyped for 107 Simple Sequence Repeat (SSR and 136 Amplified Fragment Length Polymorphism (AFLP loci. Given the low probability values found with AFLP for individual assignment (4.7%, microsatellites seemed to perform better (54% for STRUCTURE analysis that revealed the germplasm to exist in five optimum groups with partly corresponding to their origin. However clusters shown high degree of admixture, F ST values confirmed the existence of differences among groups. Dissimilarity coefficients ranged from 0.079 to 0.651. PCoA separated sugarcane in groups that did not agree with those identified by STRUCTURE. The clustering including all genotypes neither showed resemblance to populations find by STRUCTURE, but clustering performed considering only individuals displaying a proportional membership > 0.6 in their primary population obtained with STRUCTURE showed close similarities. The Bayesian method indubitably brought more information on cultivar origins than classical PCoA and hierarchical clustering method.

  19. Molecular approach to genetic and epigenetic pathogenesisof early-onset colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Colorectal cancer (CRC) is the third most frequent cancertype and the incidence of this disease is increasinggradually per year in individuals younger than 50 yearsold. The current knowledge is that early-onset CRC(EOCRC) cases are heterogeneous population thatincludes both hereditary and sporadic forms of theCRC. Although EOCRC cases have some distinguishingclinical and pathological features than elder age CRC,the molecular mechanism underlying the EOCRC ispoorly clarified. Given the significance of CRC in theworld of medicine, the present review will focus on therecent knowledge in the molecular basis of genetic andepigenetic mechanism of the hereditary forms of EOCRC,which includes Lynch syndrome, Familial CRC type X,Familial adenomatous polyposis, MutYH-associatedpolyposis, Juvenile polyposis syndrome, Peutz-JeghersSyndrome and sporadic forms of EOCRC. Recent findingsabout molecular genetics and epigenetic basis of EOCRCgave rise to new alternative therapy protocols. Althoughexact diagnosis of these cases still remains complicated,the present review paves way for better predictions andcontributes to more accurate diagnostic and therapeuticstrategies into clinical approach.

  20. Genetic approaches for studying myiasis-causing flies: molecular markers and mitochondrial genomics.

    Science.gov (United States)

    de Azeredo-Espin, Ana Maria Lima; Lessinger, Ana Cláudia

    2006-01-01

    "Myiasis-causing flies" is a generic term that includes species from numerous dipteran families, mainly Calliphoridae and Oestridae, of which blowflies, screwworm flies and botflies are among the most important. This group of flies is characterized by the ability of their larvae to develop in animal flesh. When the host is a live vertebrate, such parasitism by dipterous larvae is known as primary myiasis. Myiasis-causing flies can be classified as saprophagous (free-living species), facultative or obligate parasites. Many of these flies are of great medical and veterinary importance in Brazil because of their role as key livestock insect-pests and vectors of pathogens, in addition to being considered important legal evidence in forensic entomology. The characterization of myiasis-causing flies using molecular markers to study mtDNA (by RFLP) and nuclear DNA (by RAPD and microsatellite) has been used to identify the evolutionary mechanisms responsible for specific patterns of genetic variability. These approaches have been successfully used to analyze the population structures of the New World screwworm fly Cochliomyia hominivorax and the botfly Dermatobia hominis. In this review, various aspects of the organization, evolution and potential applications of the mitochondrial genome of myiasis-causing flies in Brazil, and the analysis of nuclear markers in genetic studies of populations, are discussed.

  1. Reproductive outcome of male carriers of chromosomal abnormalities: multidisciplinary approach for genetic counseling and its implications.

    Science.gov (United States)

    Guo, K M; Wu, B; Wang, H B; Tian, R H

    2016-12-02

    Chromosomal abnormality is the most common genetic cause of infertility. Infertility, as a psychological problem, has received an increasing amount of attention. Psychological interventions have been shown to have beneficial effects on infertile patients with chromosomal abnormalities. The present study explored reproductive outcome of male carriers of chromosomal abnormalities, who accepted genetic counseling and psychological support. Cytogenetic analysis was performed using cultured peripheral blood lymphocytes and G-banding. The detection rate of chromosomal abnormalities was 10.3% in pre-pregnancy counseled males, with polymorphisms being most common, followed by 47,XXY and balanced translocation. Follow-up of 170 carriers with normozoospermia, after 3 years, showed that 94.7% of the cases resulted in live births. In the carriers of polymorphisms, balanced translocation, inv(9), Robertsonian translocation, inversion, and 47,XYY, live birth rates were 96.8, 85.7, 100, 83.3, 75, and 100%, respectively. Follow-up of 54 carriers with oligozoospermia or azoospermia, after 3 years, showed that 14.8% of the cases resulted in live births. In the carriers of 47,XXY with severe oligozoospermia or azoospermia, 80 or 5.9% of the cases resulted in live births, respectively. Therefore, timely psychological support would be beneficial and multidisciplinary approach should be preferentially considered for the management of individuals with chromosomal abnormalities.

  2. Pollen Sterility—A Promising Approach to Gene Confinement and Breeding for Genetically Modified Bioenergy Crops

    Directory of Open Access Journals (Sweden)

    Albert P. Kausch

    2012-10-01

    Full Text Available Advanced genetic and biotechnology tools will be required to realize the full potential of food and bioenergy crops. Given current regulatory concerns, many transgenic traits might never be deregulated for commercial release without a robust gene confinement strategy in place. The potential for transgene flow from genetically modified (GM crops is widely known. Pollen-mediated transfer is a major component of gene flow in flowering plants and therefore a potential avenue for the escape of transgenes from GM crops. One approach for preventing and/or mitigating transgene flow is the production of trait linked pollen sterility. To evaluate the feasibility of generating pollen sterility lines for gene confinement and breeding purposes we tested the utility of a promoter (Zm13Pro from a maize pollen-specific gene (Zm13 for driving expression of the reporter gene GUS and the cytotoxic gene barnase in transgenic rice (Oryza sativa ssp. Japonica cv. Nipponbare as a monocot proxy for bioenergy grasses. This study demonstrates that the Zm13 promoter can drive pollen-specific expression in stably transformed rice and may be useful for gametophytic transgene confinement and breeding strategies by pollen sterility in food and bioenergy crops.

  3. Pediatric Cancer Genetics Research and an Evolving Preventive Ethics Approach for Return of Results after Death of the Subject.

    Science.gov (United States)

    Scollon, Sarah; Bergstrom, Katie; McCullough, Laurence B; McGuire, Amy L; Gutierrez, Stephanie; Kerstein, Robin; Parsons, D Williams; Plon, Sharon E

    2015-01-01

    The return of genetic research results after death in the pediatric setting comes with unique complexities. Researchers must determine which results and through which processes results are returned. This paper discusses the experience over 15 years in pediatric cancer genetics research of returning research results after the death of a child and proposes a preventive ethics approach to protocol development in order to improve the quality of return of results in pediatric genomic settings.

  4. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance

    OpenAIRE

    Manning, Alisa K; Hivert, Marie-France; Scott, Robert A.; Grimsby, Jonna L; Bouatia-Naji, Nabila; Chen, Han; Rybin, Denis; Liu, Ching-Ti; Bielak, Lawrence F; Prokopenko, Inga; Amin, Najaf; Barnes, Daniel; Cadby, Gemma; Hottenga, Jouke-Jan; Ingelsson, Erik

    2012-01-01

    Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associat...

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

    DEFF Research Database (Denmark)

    Zhao, Menghua

    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...... of a grid-connected wind farm; 2) the second one is the optimization of electrical system for offshore wind farms (OES-OWF). The capacity of a grid connected wind farm is limited by the transfer capability of the grid system, where the thermal limit of the transmission lines, the voltage stability......, 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...

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

    DEFF Research Database (Denmark)

    Zhao, Menghua

    , 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...... 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......). This platform is based on a knowledge database, and composed of several functional modules such as cost calculation, reliability evaluation, losses calculation, AC-DC integrated load flow algorithm etc. All these modules are based on a spreadsheet database which provides an interface for users to input...

  7. Nonlinear Electrical Circuit Oscillator Control Based on Backstepping Method: A Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Mahsa Khoeiniha

    2012-01-01

    Full Text Available This paper investigated study of dynamics of nonlinear electrical circuit by means of modern nonlinear techniques and the control of a class of chaotic system by using backstepping method based on Lyapunov function. The behavior of such nonlinear system when they are under the influence of external sinusoidal disturbances with unknown amplitudes has been considered. The objective is to analyze the performance of this system at different amplitudes of disturbances. We illustrate the proposed approach for controlling duffing oscillator problem to stabilize this system at the equilibrium point. Also Genetic Algorithm method (GA for computing the parameters of controller has been used. GA can be successfully applied to achieve a better controller. Simulation results have shown the effectiveness of the proposed method.

  8. An Evolutionary Approach to Drug-Design Using a Novel Neighbourhood Based Genetic Algorithm

    CERN Document Server

    Ghosh, Arnab; Chowdhury, Arkabandhu; Konar, Amit

    2012-01-01

    The present work provides a new approach to evolve ligand structures which represent possible drug to be docked to the active site of the target protein. The structure is represented as a tree where each non-empty node represents a functional group. It is assumed that the active site configuration of the target protein is known with position of the essential residues. In this paper the interaction energy of the ligands with the protein target is minimized. Moreover, the size of the tree is difficult to obtain and it will be different for different active sites. To overcome the difficulty, a variable tree size configuration is used for designing ligands. The optimization is done using a novel Neighbourhood Based Genetic Algorithm (NBGA) which uses dynamic neighbourhood topology. To get variable tree size, a variable-length version of the above algorithm is devised. To judge the merit of the algorithm, it is initially applied on the well known Travelling Salesman Problem (TSP).

  9. Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.

    Science.gov (United States)

    Hoban, Megan D; Orkin, Stuart H; Bauer, Daniel E

    2016-02-18

    Effective medical management for sickle cell disease (SCD) remains elusive. As a prevalent and severe monogenic disorder, SCD has been long considered a logical candidate for gene therapy. Significant progress has been made in moving toward this goal. These efforts have provided substantial insight into the natural regulation of the globin genes and illuminated challenges for genetic manipulation of the hematopoietic system. The initial γ-retroviral vectors, next-generation lentiviral vectors, and novel genome engineering and gene regulation approaches each share the goal of preventing erythrocyte sickling. After years of preclinical studies, several clinical trials for SCD gene therapies are now open. This review focuses on progress made toward achieving gene therapy, the current state of the field, consideration of factors that may determine clinical success, and prospects for future development.

  10. NOVEL APPROACH FOR ROBOT PATH PLANNING BASED ON NUMERICAL ARTIFICIAL POTENTIAL FIELD AND GENETIC ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    WANG Weizhong; ZHAO Jie; GAO Yongsheng; CAI Hegao

    2006-01-01

    A novel approach for collision-free path planning of a multiple degree-of-freedom (DOF)articulated robot in a complex environment is proposed. Firstly, based on visual neighbor point (VNP), a numerical artificial potential field is constructed in Cartesian space, which provides the heuristic information, effective distance to the goal and the motion direction for the motion of the robot joints. Secondly, a genetic algorithm, combined with the heuristic rules, is used in joint space to determine a series of contiguous configurations piecewise fiom initial configuration until the goal configuration is attained. A simulation shows that the method can not only handle issues on path planning of the articulated robots in environment with complex obstacles, but also improve the efficiency and quality of path planning.

  11. A NAÏVE APPROACH TO SPEED UP PORTFOLIO OPTIMIZATION PROBLEM USING A MULTIOBJECTIVE GENETIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    Baixauli-Soler, J. Samuel

    2012-05-01

    Full Text Available Genetic algorithms (GAs are appropriate when investors have the objective of obtaining mean‑variance (VaR efficient frontier as minimising VaR leads to non‑convex and non‑differential risk‑return optimisation problems. However GAs are a time‑consuming optimisation technique. In this paper, we propose to use a naïve approach consisting of using samples split by quartile of risk to obtain complete efficient frontiers in a reasonable computation time. Our results show that using reduced problems which only consider a quartile of the assets allow us to explore the efficient frontier for a large range of risk values. In particular, the third quartile allows us to obtain efficient frontiers from the 1.8% to 2.5% level of VaR quickly, while that of the first quartile of assets is from 1% to 1.3% level of VaR.

  12. [A general approach to the structural shape optimization using genetic algorithms and geometric design elements].

    Science.gov (United States)

    Annicchiarico, W

    2001-01-01

    Structural optimization is an engineering field which deal with the improvement of existing solutions or even more find new solutions that are better than the previous ones under some selected criterion. Shape optimization is a research area in this field and it is involved in developing new methodologies to find better structural design based on the shape as resistant element, as for example solutions with the less stress concentration zones and made with the minimum amount of material. The goal of this doctoral dissertation is to present and discuss a general structural shape optimization methodology able to optimize several structural systems or mechanical devices. The approach presented herein is based on global search optimization tools such as Genetic Algorithms and geometric design elements by means of beta-splines curves and surfaces representation. Finally the great versatility of the developed tool is presented and discussed with an application example.

  13. An Adaptive Agent-Based Model of Homing Pigeons: A Genetic Algorithm Approach

    Directory of Open Access Journals (Sweden)

    Francis Oloo

    2017-01-01

    Full Text Available Conventionally, agent-based modelling approaches start from a conceptual model capturing the theoretical understanding of the systems of interest. Simulation outcomes are then used “at the end” to validate the conceptual understanding. In today’s data rich era, there are suggestions that models should be data-driven. Data-driven workflows are common in mathematical models. However, their application to agent-based models is still in its infancy. Integration of real-time sensor data into modelling workflows opens up the possibility of comparing simulations against real data during the model run. Calibration and validation procedures thus become automated processes that are iteratively executed during the simulation. We hypothesize that incorporation of real-time sensor data into agent-based models improves the predictive ability of such models. In particular, that such integration results in increasingly well calibrated model parameters and rule sets. In this contribution, we explore this question by implementing a flocking model that evolves in real-time. Specifically, we use genetic algorithms approach to simulate representative parameters to describe flight routes of homing pigeons. The navigation parameters of pigeons are simulated and dynamically evaluated against emulated GPS sensor data streams and optimised based on the fitness of candidate parameters. As a result, the model was able to accurately simulate the relative-turn angles and step-distance of homing pigeons. Further, the optimised parameters could replicate loops, which are common patterns in flight tracks of homing pigeons. Finally, the use of genetic algorithms in this study allowed for a simultaneous data-driven optimization and sensitivity analysis.

  14. A statistical approach to quantification of genetically modified organisms (GMO) using frequency distributions.

    Science.gov (United States)

    Gerdes, Lars; Busch, Ulrich; Pecoraro, Sven

    2014-12-14

    According to Regulation (EU) No 619/2011, trace amounts of non-authorised genetically modified organisms (GMO) in feed are tolerated within the EU if certain prerequisites are met. Tolerable traces must not exceed the so-called 'minimum required performance limit' (MRPL), which was defined according to the mentioned regulation to correspond to 0.1% mass fraction per ingredient. Therefore, not yet authorised GMO (and some GMO whose approvals have expired) have to be quantified at very low level following the qualitative detection in genomic DNA extracted from feed samples. As the results of quantitative analysis can imply severe legal and financial consequences for producers or distributors of feed, the quantification results need to be utterly reliable. We developed a statistical approach to investigate the experimental measurement variability within one 96-well PCR plate. This approach visualises the frequency distribution as zygosity-corrected relative content of genetically modified material resulting from different combinations of transgene and reference gene Cq values. One application of it is the simulation of the consequences of varying parameters on measurement results. Parameters could be for example replicate numbers or baseline and threshold settings, measurement results could be for example median (class) and relative standard deviation (RSD). All calculations can be done using the built-in functions of Excel without any need for programming. The developed Excel spreadsheets are available (see section 'Availability of supporting data' for details). In most cases, the combination of four PCR replicates for each of the two DNA isolations already resulted in a relative standard deviation of 15% or less. The aims of the study are scientifically based suggestions for minimisation of uncertainty of measurement especially in -but not limited to- the field of GMO quantification at low concentration levels. Four PCR replicates for each of the two DNA isolations

  15. A bioorganometallic approach for rapid electrochemical analysis of human immunodeficiency virus type-1 reverse transcriptase in serum

    Energy Technology Data Exchange (ETDEWEB)

    Labib, Mahmoud; Shipman, Patrick O.; Martic, Sanela [Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, ON, N6A 5B7 (Canada); Kraatz, Heinz-Bernhard, E-mail: hkraatz@uwo.ca [Department of Chemistry, University of Western Ontario, 1151 Richmond Street, London, ON, N6A 5B7 (Canada)

    2011-05-30

    Highlights: > Two-dimensional electrochemical assay of HIV-1 reverse transcriptase in serum is presented. > XPS and ToF-SIMS confirmed binding of synthetic ferrocene-lipoic acid to gold. > Dynamic range was 100-500 pg mL{sup -1} with an LOD of 50 pg mL{sup -1}. > The biosensor allows sensitive and selective detection of reverse transcriptase in 20 s. - Abstract: Determination of low-abundance human immunodeficiency virus (HIV) enzymes is essential for early detection of the viral infection. Designed for the rapid detection of the virus in human serum, a rapid and ultrasensitive electrochemical assay for HIV-1 reverse transcriptase (HIV-1 RT) is presented in this article. The assay format is based on the formation of a self-assembled monolayer (SAM) of a synthesized ferrocene (Fc)-labeled lipoic acid onto a gold electrode. X-ray photoelectron spectroscopy (XPS) and Time-of-Flight secondary ion mass spectrometry (ToF-SIMS) were employed to confirm the binding of the Fc-labeled lipoic acid to the gold via the Au-S bond. A short RT-specific peptide, VEAIIRILQQLLFIH, was covalently attached to the Fc-labeled lipoic acid. Square wave voltammetry (SWV) offered a two-dimensional measurement of RT based on the anodic shift and reduction of current density of the Fc redox signal upon binding of RT to its specific peptide. This allowed a linear quantification of the target RT in the range of 100-500 pg mL{sup -1}, equivalent to 85.5-427.4 fM, with a detection limit of 50 pg mL{sup -1} (42.7 fM). The developed biosensor is inexpensive, easy to prepare and operate, and allows a highly selective detection of RT in 20 s.

  16. On the Predictability of Risk Box Approach by Genetic Programming Method for Bankruptcy Prediction

    Directory of Open Access Journals (Sweden)

    Alireza Bahiraie

    2009-01-01

    Full Text Available Problem statement: Theoretical based data representation is an important tool for model selection and interpretations in bankruptcy analysis since the numerical representation are much less transparent. Some methodological problems concerning financial ratios such as non-proportionality, non-asymetricity, non-scalicity are solved in this study and we presented a complementary technique for empirical analysis of financial ratios and bankruptcy risk. Approach: This study presented new geometric technique for empirical analysis of bankruptcy risk using financial ratios. Within this framework, we proposed the use of a new ratio representation which named Risk Box measure (RB. We demonstrated the application of this geometric approach for variable representation, data visualization and financial ratios at different stages of corporate bankruptcy prediction models based on financial balance sheet ratios. These stages were the selection of variables (predictors, accuracy of each estimation model and the representation of each model for transformed and common ratios. Results: We provided evidence of extent to which changes in values of this index were associated with changes in each axis values and how this may alter our economic interpretation of changes in the patterns and direction of risk components. Results of Genetic Programming (GP models were compared as different classification models and results showed the classifiers outperform by modified ratios. Conclusion/Recommendations: In this study, a new dimension to risk measurement and data representation with the advent of the Share Risk method (SR was proposed. Genetic programming method is substantially superior to the traditional methods such as MDA or Logistic method. It was strongly suggested the use of SR methodology for ratio analysis, which provided a conceptual and complimentary methodological solution to many problems associated with the use of ratios. Respectively, GP will provide

  17. Planning additional drilling campaign using two-space genetic algorithm: A game theoretical approach

    Science.gov (United States)

    Kumral, Mustafa; Ozer, Umit

    2013-03-01

    Grade and tonnage are the most important technical uncertainties in mining ventures because of the use of estimations/simulations, which are mostly generated from drill data. Open pit mines are planned and designed on the basis of the blocks representing the entire orebody. Each block has different estimation/simulation variance reflecting uncertainty to some extent. The estimation/simulation realizations are submitted to mine production scheduling process. However, the use of a block model with varying estimation/simulation variances will lead to serious risk in the scheduling. In the medium of multiple simulations, the dispersion variances of blocks can be thought to regard technical uncertainties. However, the dispersion variance cannot handle uncertainty associated with varying estimation/simulation variances of blocks. This paper proposes an approach that generates the configuration of the best additional drilling campaign to generate more homogenous estimation/simulation variances of blocks. In other words, the objective is to find the best drilling configuration in such a way as to minimize grade uncertainty under budget constraint. Uncertainty measure of the optimization process in this paper is interpolation variance, which considers data locations and grades. The problem is expressed as a minmax problem, which focuses on finding the best worst-case performance i.e., minimizing interpolation variance of the block generating maximum interpolation variance. Since the optimization model requires computing the interpolation variances of blocks being simulated/estimated in each iteration, the problem cannot be solved by standard optimization tools. This motivates to use two-space genetic algorithm (GA) approach to solve the problem. The technique has two spaces: feasible drill hole configuration with minimization of interpolation variance and drill hole simulations with maximization of interpolation variance. Two-space interacts to find a minmax solution

  18. A genetic algorithm approach for assessing soil liquefaction potential based on reliability method

    Indian Academy of Sciences (India)

    M H Bagheripour; I Shooshpasha; M Afzalirad

    2012-02-01

    Deterministic approaches are unable to account for the variations in soil’s strength properties, earthquake loads, as well as source of errors in evaluations of liquefaction potential in sandy soils which make them questionable against other reliability concepts. Furthermore, deterministic approaches are incapable of precisely relating the probability of liquefaction and the factor of safety (FS). Therefore, the use of probabilistic approaches and especially, reliability analysis is considered since a complementary solution is needed to reach better engineering decisions. In this study, Advanced First-Order Second-Moment (AFOSM) technique associated with genetic algorithm (GA) and its corresponding sophisticated optimization techniques have been used to calculate the reliability index and the probability of liquefaction. The use of GA provides a reliable mechanism suitable for computer programming and fast convergence. A new relation is developed here, by which the liquefaction potential can be directly calculated based on the estimated probability of liquefaction (), cyclic stress ratio (CSR) and normalized standard penetration test (SPT) blow counts while containing a mean error of less than 10% from the observational data. The validity of the proposed concept is examined through comparison of the results obtained by the new relation and those predicted by other investigators. A further advantage of the proposed relation is that it relates and FS and hence it provides possibility of decision making based on the liquefaction risk and the use of deterministic approaches. This could be beneficial to geotechnical engineers who use the common methods of FS for evaluation of liquefaction. As an application, the city of Babolsar which is located on the southern coasts of Caspian Sea is investigated for liquefaction potential. The investigation is based primarily on in situ tests in which the results of SPT are analysed.

  19. An In Silico Identification of Common Putative Vaccine Candidates against Treponema pallidum: A Reverse Vaccinology and Subtractive Genomics Based Approach

    Science.gov (United States)

    Kumar Jaiswal, Arun; Tiwari, Sandeep; Jamal, Syed Babar; Barh, Debmalya; Azevedo, Vasco; Soares, Siomar C.

    2017-01-01

    Sexually transmitted infections (STIs) are caused by a wide variety of bacteria, viruses, and parasites that are transmitted from one person to another primarily by vaginal, anal, or oral sexual contact. Syphilis is a serious disease caused by a sexually transmitted infection. Syphilis is caused by the bacterium Treponema pallidum subspecies pallidum. Treponema pallidum (T. pallidum) is a motile, gram-negative spirochete, which can be transmitted both sexually and from mother to child, and can invade virtually any organ or structure in the human body. The current worldwide prevalence of syphilis emphasizes the need for continued preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine targets and putative drugs against syphilis disease using reverse vaccinology and subtractive genomics. We compared 13 strains of T. pallidum using T. pallidum Nichols as the reference genome. Using an in silicoapproach, four pathogenic islands were detected in the genome of T. pallidum Nichols. We identified 15 putative antigenic proteins and sixdrug targets through reverse vaccinology and subtractive genomics, respectively, which can be used as candidate therapeutic targets in the future. PMID:28216574

  20. A Genetic Predictive Model for Canine Hip Dysplasia: Integration of Genome Wide Association Study (GWAS) and Candidate Gene Approaches

    Science.gov (United States)

    Bartolomé, Nerea; Segarra, Sergi; Artieda, Marta; Francino, Olga; Sánchez, Elisenda; Szczypiorska, Magdalena; Casellas, Joaquim; Tejedor, Diego; Cerdeira, Joaquín; Martínez, Antonio; Velasco, Alfonso; Sánchez, Armand

    2015-01-01

    Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors’ opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds. PMID:25874693

  1. A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS and candidate gene approaches.

    Directory of Open Access Journals (Sweden)

    Nerea Bartolomé

    Full Text Available Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B and case (D/E. C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85 and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

  2. A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS) and candidate gene approaches.

    Science.gov (United States)

    Bartolomé, Nerea; Segarra, Sergi; Artieda, Marta; Francino, Olga; Sánchez, Elisenda; Szczypiorska, Magdalena; Casellas, Joaquim; Tejedor, Diego; Cerdeira, Joaquín; Martínez, Antonio; Velasco, Alfonso; Sánchez, Armand

    2015-01-01

    Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.

  3. A population genetics-phylogenetics approach to inferring natural selection in coding sequences.

    Directory of Open Access Journals (Sweden)

    Daniel J Wilson

    2011-12-01

    Full Text Available Through an analysis of polymorphism within and divergence between species, we can hope to learn about the distribution of selective effects of mutations in the genome, changes in the fitness landscape that occur over time, and the location of sites involved in key adaptations that distinguish modern-day species. We introduce a novel method for the analysis of variation in selection pressures within and between species, spatially along the genome and temporally between lineages. We model codon evolution explicitly using a joint population genetics-phylogenetics approach that we developed for the construction of multiallelic models with mutation, selection, and drift. Our approach has the advantage of performing direct inference on coding sequences, inferring ancestral states probabilistically, utilizing allele frequency information, and generalizing to multiple species. We use a Bayesian sliding window model for intragenic variation in selection coefficients that efficiently combines information across sites and captures spatial clustering within the genome. To demonstrate the utility of the method, we infer selective pressures acting in Drosophila melanogaster and D. simulans from polymorphism and divergence data for 100 X-linked coding regions.

  4. Image Retrieval Approach Based on Intuitive Fuzzy Set Combined with Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-yin; XU Wei-hua; HU Chang-zhen

    2009-01-01

    Aiming at shortcomings of traditional image retrieval systems,a new image retrieval approach based on color features of image combining intuitive fuzzy theory with genetic algorithm is proposed.Each image is segmented into a constant number of sub-images in vertical direction.Color features are extracted from every sub-image to get chromosome coding.It is considered that fuzzy membership and intuitive fuzzy hesitancy degree of every pixel's color in image are associated to all the color histogram bins.Certain feature,fuzzy feature and intuitive fuzzy feature of colors in an image,are used together to describe the content of image.Efficient combinations of sub-image are selected according to operation of selecting,crossing and variation.Retrieval resuits are obtained from image matching based on these color feature combinations of sub-images.Tests show that this approach can improve the accuracy of image retrieval in the case of not decreasing the speed of image retrieval.Its mean precision is above 80%.

  5. Evaluation of a LASSO regression approach on the unrelated samples of Genetic Analysis Workshop 17.

    Science.gov (United States)

    Guo, Wei; Elston, Robert C; Zhu, Xiaofeng

    2011-11-29

    The Genetic Analysis Workshop 17 data we used comprise 697 unrelated individuals genotyped at 24,487 single-nucleotide polymorphisms (SNPs) from a mini-exome scan, using real sequence data for 3,205 genes annotated by the 1000 Genomes Project and simulated phenotypes. We studied 200 sets of simulated phenotypes of trait Q2. An important feature of this data set is that most SNPs are rare, with 87% of the SNPs having a minor allele frequency less than 0.05. For rare SNP detection, in this study we performed a least absolute shrinkage and selection operator (LASSO) regression and F tests at the gene level and calculated the generalized degrees of freedom to avoid any selection bias. For comparison, we also carried out linear regression and the collapsing method, which sums the rare SNPs, modified for a quantitative trait and with two different allele frequency thresholds. The aim of this paper is to evaluate these four approaches in this mini-exome data and compare their performance in terms of power and false positive rates. In most situations the LASSO approach is more powerful than linear regression and collapsing methods. We also note the difficulty in determining the optimal threshold for the collapsing method and the significant role that linkage disequilibrium plays in detecting rare causal SNPs. If a rare causal SNP is in strong linkage disequilibrium with a common marker in the same gene, power will be much improved.

  6. Assuring the safety of genetically modified (GM) foods: the importance of an holistic, integrative approach.

    Science.gov (United States)

    Cockburn, Andrew

    2002-09-11

    Genes change continuously by natural mutation and recombination enabling man to select and breed crops having the most desirable traits such as yield or flavour. Genetic modification (GM) is a recent development which allows specific genes to be identified, isolated, copied and inserted into other plants with a high level of specificity. The food safety considerations for GM crops are basically the same as those arising from conventionally bred crops, very few of which have been subject to any testing yet are generally regarded as being safe to eat. In contrast a rigorous safety testing paradigm has been developed for GM crops, which utilises a systematic, stepwise and holistic approach. The resultant science based process, focuses on a classical evaluation of the toxic potential of the introduced novel trait and the wholesomeness of the transformed crop. In addition, detailed consideration is given to the history and safe use of the parent crop as well as that of the gene donor. The overall safety evaluation is conducted under the concept known as substantial equivalence which is enshrined in all international crop biotechnology guidelines. This provides the framework for a comparative approach to identify the similarities and differences between the GM product and its comparator which has a known history of safe use. By building a detailed profile on each step in the transformation process, from parent to new crop, and by thoroughly evaluating the significance from a safety perspective, of any differences that may be detected, a very comprehensive matrix of information is constructed which enables the conclusion as to whether the GM crop, derived food or feed is as safe as its traditional counterpart. Using this approach in the evaluation of more than 50 GM crops which have been approved worldwide, the conclusion has been that foods and feeds derived from genetically modified crops are as safe and nutritious as those derived from traditional crops. The lack of

  7. NEATTILL: A simplified procedure for nucleic acid extraction from arrayed tissue for TILLING and other high-throughput reverse genetic applications

    Directory of Open Access Journals (Sweden)

    Mohan Vijee

    2010-01-01

    Full Text Available Abstract Background TILLING (Targeting Induced Local Lesions in Genomes is a reverse genetics procedure for identifying point mutations in selected gene(s amplified from a mutagenized population using high-throughput detection platforms such as slab gel electrophoresis, capillary electrophoresis or dHPLC. One essential pre-requisite for TILLING is genomic DNA isolation from a large population for PCR amplification of selected target genes. It also requires multiplexing of genomic DNA isolated from different individuals (pooling in typically 8-fold pools, for mutation scanning, and to minimize the number of PCR amplifications, which is a strenuous and long-drawn-out work. We describe here a simplified procedure of multiplexing, NEATTILL (Nucleic acid Extraction from Arrayed Tissue for TILLING, which is rapid and equally efficient in assisting mutation detection. Results The NEATTILL procedure was evaluated for the tomato TILLING platform and was found to be simpler and more efficient than previously available methods. The procedure consisted of pooling tissue samples, instead of nucleic acid, from individual plants in 96-well plates, followed by DNA isolation from the arrayed samples by a novel protocol. The three variants of the NEATTILL procedure (vast, in-depth and intermediate can be applied across various genomes depending upon the population size of the TILLING platform. The 2-D pooling ensures the precise confirmation of the coordinates of the positive mutant line while scanning complementary plates. Choice of tissue for arraying and nucleic acid isolation is discussed in detail with reference to tomato. Conclusion NEATTILL is a convenient procedure that can be applied to all organisms, the genomes of which have been mutagenized and are being scanned for multiple alleles of various genes by TILLING for understanding gene-to-phenotype relationships. It is a time-saving, less labour intensive and reasonably cost-effective method. Tissue

  8. Utility of a multiplex reverse transcriptasepolymerase chain reaction assay (HemaVision in the evaluation of genetic abnormalities in Korean children with acute leukemia: a single institution study

    Directory of Open Access Journals (Sweden)

    Hye-Jin kim

    2013-06-01

    Full Text Available &lt;b&gt;Purpose:&lt;/b&gt; In children with acute leukemia, bone marrow genetic abnormalities (GA have prognostic significance, and may be the basis for minimal residual disease monitoring. Since April 2007, we have used a multiplex reverse transcriptase-polymerase chain reaction tool (HemaVision to detect of GA. &lt;b&gt;Methods:&lt;/b&gt; In this study, we reviewed the results of HemaVision screening in 270 children with acute leukemia, newly diagnosed at The Catholic University of Korea from April 2007 to December 2011, and compared the results with those of fluorescence in situ hybridization (FISH, and G-band karyotyping. &lt;b&gt;Results:&lt;/b&gt; Among the 270 children (153 males, 117 females, 187 acute lymphoblastic leukemia and 74 acute myeloid leukemia patients were identified. Overall, GA was detected in 230 patients (85.2%. HemaVision, FISH, and G-band karyotyping identified GA in 125 (46.3%, 126 (46.7%, and 215 patients (79.6%, respectively. TEL-AML1 (20.9%, 39/187 and AML1-ETO (27%, 20/74 were the most common GA in ALL and AML, respectively. Overall sensitivity of HemaVision was 98.4%, with false-negative results in 2 instances: 1 each for TEL-AML1 and MLL-AF4 . An aggregate of diseasesspecific FISH showed 100% sensitivity in detection of GA covered by HemaVision for actual probes utilized. G-band karyotype revealed GA other than those covered by HemaVison screening in 133 patients (49.3%. Except for hyperdiplody and hypodiploidy, recurrent GA as defined by the World Health Organizationthat were not screened by HemaVision, were absent in the karyotype. &lt;b&gt;Conclusion:&lt;/b&gt; HemaVision, supported by an aggregate of FISH tests for important translocations, may allow for accurate diagnosis of GA in Korean children with acute leukemia.

  9. A candidate gene approach identifies an IL33 genetic variant as a novel genetic risk factor for GCA.

    Directory of Open Access Journals (Sweden)

    Ana Márquez

    Full Text Available Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition.A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays.A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P(MH = 0.041, OR = 0.88, CI 95% 0.78-0.99 and recessive (P(MH = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80 models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis.Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA.

  10. Reverse Engineering of RFID devices

    OpenAIRE

    Bokslag, Wouter

    2015-01-01

    This paper discusses the relevance and potential impact of both RFID and reverse engineering of RFID technology, followed by a discussion of common protocols and internals of RFID technology. The focus of the paper is on providing an overview of the different approaches to reverse engineering RFID technology and possible countermeasures that could limit the potential of such reverse engineering attempts.

  11. Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

    NARCIS (Netherlands)

    B. Giardine (Belinda); J. Borg (Joseph); D.R. Higgs (Douglas); K.R. Peterson (Kenneth R.); J.N.J. Philipsen (Sjaak); D. Maglott (Donna); B.K. Singleton (Belinda K.); D.J. Anstee (David J.); A.N. Basak (Nazli); B.H. Clark (Bruce); F.C. Costa (Flavia C.); P. Faustino (Paula); H. Fedosyuk (Halyna); A.E. Felice (Alex); A. Francina (Alain); R. Galanello (Renzo); M.V.E. Gallivan (Monica V. E.); M. Georgitsi (Marianthi); R.J. Gibbons (Richard J.); P.C. Giordano (Piero Carlo); C.L. Harteveld (Cornelis); J.D. Hoyer (James D.); M. Jarvis (Martin); P. Joly (Philippe); E. Kanavakis (Emmanuel); P. Kollia (Panagoula); S. Menzel (Stephan); W.G. Miller (William); K. Moradkhani (Kamran); J. Old (John); A. Papachatzpoulou (Adamantia); M.N. Papadakis (Manoussos); P. Papadopoulos (Petros); S. Pavlovic (Sonja); L. Perseu (Lucia); M. Radmilovic (Milena); C. Riemer (Cathy); S. Satta (Stefania); I.A. Schrijver (Ingrid); M. Stojiljkovic (Maja); S.L. Thein; J. Traeger-Synodinos (Joanne); R. Tully (Ray); T. Wada (Takahito); J.S. Waye (John); C. Wiemann (Claudia); B. Zukic (Branka); D.H.K. Chui (David H. K.); H. Wajcman (Henri); R. Hardison (Ross); G.P. Patrinos (George)

    2011-01-01

    textabstractWe developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public

  12. Enhancing the Capability of N-Dimension Self-Organizing Petrinet using Neuro-Genetic Approach

    Directory of Open Access Journals (Sweden)

    Manuj Darbari

    2011-05-01

    Full Text Available The paper highlight intelligent Urban Traffic control using Neuro-Genetic Petrinet. The combination of genetic algorithm provides dynamic change of weight for faster learning and converging of Neuro-Petrinet.

  13. Applying new genetic approaches to improve quality of population assessment of green and loggerhead turtles

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — As the NOAA-Fisheries? National Sea Turtle Genetics Lab, the SWFSC Marine Turtle Genetics Program has the lead responsibility for generating, analyzing and...

  14. Expanding the Spectrum of Genes Involved in Huntington Disease Using a Combined Clinical and Genetic Approach.

    Science.gov (United States)

    Mariani, Louise-Laure; Tesson, Christelle; Charles, Perrine; Cazeneuve, Cécile; Hahn, Valérie; Youssov, Katia; Freeman, Leorah; Grabli, David; Roze, Emmanuel; Noël, Sandrine; Peuvion, Jean-Noel; Bachoud-Levi, Anne-Catherine; Brice, Alexis; Stevanin, Giovanni; Durr, Alexandra

    2016-09-01

    iron accumulation. We identified mutations in genes associated with neurodegeneration, including CACNA1A (n = 2), VPS13A (n = 1), UBQLN2 (n = 1), and VCP (n = 1). Huntington disease phenocopies without CAG repeat expansions in HTT are not rare, occurring in 12.4% (28 of 226) herein, and should be considered in genetic counseling. We used next-generation sequencing combined with clinical data and disease evolution to explore multiple etiologies simultaneously. Our combined clinical and genetic exploration of 28 HD phenocopies identified the underlying cause in 35.7% (10 of 28). In conclusion, the etiologies of HD phenocopies are heterogeneous, and clinical evolution should be taken into account when searching for a genetic cause. The panel of candidate genes to be examined is larger than expected but can be guided by specific imaging and clinical features. Other neurodegenerative diseases with late onset in which variant segregation cannot be verified could be productively explored with the combined approach illustrated herein.

  15. Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach.

    Science.gov (United States)

    Han, Sangjo; Lee, Minho; Chang, Hyeshik; Nam, Miyoung; Park, Han-Oh; Kwak, Youn-Sig; Ha, Hye-Jeong; Kim, Dongsup; Hwang, Sung-Ook; Hoe, Kwang-Lae; Kim, Dong-Uk

    2013-07-12

    Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defect measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at http://pombe.kaist.ac.kr/compendium. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Reductions in genetic diversity of Schistosoma mansoni populations under chemotherapeutic pressure: the effect of sampling approach and parasite population definition.

    Science.gov (United States)

    French, Michael D; Churcher, Thomas S; Basáñez, María-Gloria; Norton, Alice J; Lwambo, Nicholas J S; Webster, Joanne P

    2013-11-01

    Detecting potential changes in genetic diversity in schistosome populations following chemotherapy with praziquantel (PZQ) is crucial if we are to fully understand the impact of such chemotherapy with respect to the potential emergence of resistance and/or other evolutionary outcomes of interventions. Doing so by implementing effective, and cost-efficient sampling protocols will help to optimise time and financial resources, particularly relevant to a disease such as schistosomiasis currently reliant on a single available drug. Here we explore the effect on measures of parasite genetic diversity of applying various field sampling approaches, both in terms of the number of (human) hosts sampled and the number of transmission stages (miracidia) sampled per host for a Schistosoma mansoni population in Tanzania pre- and post-treatment with PZQ. In addition, we explore population structuring within and between hosts by comparing the estimates of genetic diversity obtained assuming a 'component population' approach with those using an 'infrapopulation' approach. We found that increasing the number of hosts sampled, rather than the number of miracidia per host, gives more robust estimates of genetic diversity. We also found statistically significant population structuring (using Wright's F-statistics) and significant differences in the measures of genetic diversity depending on the parasite population definition. The relative advantages, disadvantages and, hence, subsequent reliability of these metrics for parasites with complex life-cycles are discussed, both for the specific epidemiological and ecological scenario under study here and for their future application to other areas and schistosome species.

  17. A general approach for combining diverse rare variant association tests provides improved robustness across a wider range of genetic architectures.

    Science.gov (United States)

    Greco, Brian; Hainline, Allison; Arbet, Jaron; Grinde, Kelsey; Benitez, Alejandra; Tintle, Nathan

    2016-05-01

    The widespread availability of genome sequencing data made possible by way of next-generation technologies has yielded a flood of different gene-based rare variant association tests. Most of these tests have been published because they have superior power for particular genetic architectures. However, for applied researchers it is challenging to know which test to choose in practice when little is known a priori about genetic architecture. Recently, tests have been proposed which combine two particular individual tests (one burden and one variance components) to minimize power loss while improving robustness to a wider range of genetic architectures. In our analysis we propose an expansion of these approaches, yielding a general method that works for combining any number of individual tests. We demonstrate that running multiple different tests on the same data set and using a Bonferroni correction for multiple testing is never better than combining tests using our general method. We also find that using a test statistic that is highly robust to the inclusion of non-causal variants (joint-infinity) together with a previously published combined test (sequence kernel adaptive test-optimal) provides improved robustness to a wide range of genetic architectures and should be considered for use in practice. Software for this approach is supplied. We support the increased use of combined tests in practice - as well as further exploration of novel combined testing approaches using the general framework provided here - to maximize robustness of rare variant testing strategies against a wide range of genetic architectures.

  18. Bioinformatics' approaches to detect genetic variation in whole genome sequencing data

    NARCIS (Netherlands)

    Kerstens, H.H.D.

    2010-01-01

    Current genetic marker repositories are not sufficient or even are completely lacking for most farm animals. However, genetic markers are essential for the development of a research tool facilitating discovery of genetic factors that contribute to resistance to disease and the overall welfare and pe

  19. Construction of the first compendium of chemical-genetic profiles in the fission yeast Schizosaccharomyces pombe and comparative compendium approach

    Energy Technology Data Exchange (ETDEWEB)

    Han, Sangjo [Bioinformatics Lab, Healthcare Group, SK Telecom, 9-1, Sunae-dong, Pundang-gu, Sungnam-si, Kyunggi-do 463-784 (Korea, Republic of); Lee, Minho [Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Chang, Hyeshik [Department of Biological Science, Seoul National University, 599 Gwanakro, Gwanak-gu, Seoul 151-747 (Korea, Republic of); Nam, Miyoung [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764 (Korea, Republic of); Park, Han-Oh [Bioneer Corp., 8-11 Munpyeongseo-ro, Daedeok-gu, Daejeon 306-220 (Korea, Republic of); Kwak, Youn-Sig [Department of Applied Biology, Gyeongsang National University, 501 Jinju-daero, Jinju, Gyeongnam 660-701 (Korea, Republic of); Ha, Hye-jeong [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-Gu, Daejeon 305-806 (Korea, Republic of); Kim, Dongsup [Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701 (Korea, Republic of); Hwang, Sung-Ook [Department of Obstetrics and Gynecology, Inha University Hospital, 7-206 Sinheung-dong, Jung-gu, Incheon 400-711 (Korea, Republic of); Hoe, Kwang-Lae [Department of New Drug Discovery and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764 (Korea, Republic of); Kim, Dong-Uk [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Yuseong-Gu, Daejeon 305-806 (Korea, Republic of)

    2013-07-12

    Highlights: •The first compendium of chemical-genetic profiles form fission yeast was generated. •The first HTS of drug mode-of-action in fission yeast was performed. •The first comparative chemical genetic analysis between two yeasts was conducted. -- Abstract: Genome-wide chemical genetic profiles in Saccharomyces cerevisiae since the budding yeast deletion library construction have been successfully used to reveal unknown mode-of-actions of drugs. Here, we introduce comparative approach to infer drug target proteins more accurately using two compendiums of chemical-genetic profiles from the budding yeast S. cerevisiae and the fission yeast Schizosaccharomyces pombe. For the first time, we established DNA-chip based growth defect measurement of genome-wide deletion strains of S. pombe, and then applied 47 drugs to the pooled heterozygous deletion strains to generate chemical-genetic profiles in S. pombe. In our approach, putative drug targets were inferred from strains hypersensitive to given drugs by analyzing S. pombe and S. cerevisiae compendiums. Notably, many evidences in the literature revealed that the inferred target genes of fungicide and bactericide identified by such comparative approach are in fact the direct targets. Furthermore, by filtering out the genes with no essentiality, the multi-drug sensitivity genes, and the genes with less eukaryotic conservation, we created a set of drug target gene candidates that are expected to be directly affected by a given drug in human cells. Our study demonstrated that it is highly beneficial to construct the multiple compendiums of chemical genetic profiles using many different species. The fission yeast chemical-genetic compendium is available at (http://pombe.kaist.ac.kr/compendium)

  20. Next Gen Pop Gen: implementing a high-throughput approach to population genetics in boarfish (Capros aper).

    Science.gov (United States)

    Farrell, Edward D; Carlsson, Jeanette E L; Carlsson, Jens

    2016-12-01

    The recently developed approach for microsatellite genotyping by sequencing (GBS) using individual combinatorial barcoding was further improved and used to assess the genetic population structure of boarfish (Capros aper) across the species' range. Microsatellite loci were developed de novo and genotyped by next-generation sequencing. Genetic analyses of the samples indicated that boarfish can be subdivided into at least seven biological units (populations) across the species' range. Furthermore, the recent apparent increase in abundance in the northeast Atlantic is better explained by demographic changes within this area than by influx from southern or insular populations. This study clearly shows that the microsatellite GBS approach is a generic, cost-effective, rapid and powerful method suitable for full-scale population genetic studies-a crucial element for assessment, sustainable management and conservation of valuable biological resources.

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

    Science.gov (United States)

    Kogelman, Lisette J A; Zhernakova, Daria V; Westra, Harm-Jan; Cirera, Susanna; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja N

    2015-10-20

    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 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. 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 expression analysis was performed using the Obesity Index as a continuous variable in a linear model. eQTL mapping was then performed to integrate 60 K porcine SNP chip data with the RNA sequencing data. Results were restricted based on genome-wide significant single nucleotide polymorphisms, detected differentially expressed genes, and previously detected co-expressed gene modules. Further data integration was performed by detecting co-expression patterns among eQTLs and integration with protein data. Differential expression analysis of RNA sequencing data revealed 458 differentially expressed genes. The eQTL mapping resulted in 987 cis-eQTLs and 73 trans-eQTLs (false discovery rate genes and disease-associated single nucleotide polymorphisms to detect obesity-related genes and pathways. Building a co-expression network using eQTLs resulted in the detection of a module strongly associated with lipid pathways. Furthermore, we detected several obesity candidate genes, for example, ENPP1, CTSL, and ABHD12B. To our knowledge, this is the first study to perform an integrated genomics and

  2. A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA

    Science.gov (United States)

    Márquez, Ana; Solans, Roser; Hernández-Rodríguez, José; Cid, Maria C.; Castañeda, Santos; Ramentol, Marc; Rodriguez-Rodriguez, Luis; Narváez, Javier; Blanco, Ricardo; Ortego-Centeno, Norberto; Palm, Øyvind; Diamantopoulos, Andreas P.; Braun, Niko; Moosig, Frank; Witte, Torsten; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A.; Vaglio, Augusto; Salvarani, Carlo; González-Gay, Miguel A.; Martín, Javier

    2014-01-01

    Introduction Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. Methods A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immune-related diseases, were genotyped using predesigned TaqMan assays. Results A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (PMH = 0.041, OR = 0.88, CI 95% 0.78–0.99) and recessive (PMH = 3.40E-03, OR = 0.53, CI 95% 0.35–0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis. Conclusions Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA. PMID:25409453

  3. Reversal of renal dysfunction by targeted administration of VEGF into the stenotic kidney: a novel potential therapeutic approach.

    Science.gov (United States)

    Chade, Alejandro R; Kelsen, Silvia

    2012-05-15

    Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo studies were repeated, and then renal MV density was quantified by 3D micro-CT, and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2, Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS compared with normal controls. Remarkably, administration of VEGF at 6 wk normalized RBF (from 393.6 ± 50.3 to 607.0 ± 45.33 ml/min, P < 0.05 vs. RAS) and GFR (from 43.4 ± 3.4 to 66.6 ± 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk, accompanied by increased angiogenic signaling, augmented renal MV density, and attenuated renal scarring. This study shows promising therapeutic effects of a targeted renal intervention, using an established clinically relevant large-animal model of chronic RAS. It also implies that disruption of renal MV integrity and function plays a pivotal role in the progression of renal injury in the stenotic kidney. Furthermore, it shows a high level of plasticity of renal microvessels to a single-dose VEGF-targeted intervention after established renal injury, supporting promising renoprotective effects of a novel potential therapeutic intervention to

  4. Reverse logistics

    NARCIS (Netherlands)

    M.P. de Brito (Marisa); S.D.P. Flapper; R. Dekker (Rommert)

    2002-01-01

    textabstractThis paper gives an overview of scientific literature that describes and discusses cases of reverse logistics activities in practice. Over sixty case studies are considered. Based on these studies we are able to indicate critical factors for the practice of reverse logistics. In addi

  5. A Reverse Numerical Approach to Determine Elastic-plastic Properties of Multi-layer Material Systems with Flat Cylindrical Indenters

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In the present study, the indentation testing with a flat cylindrical indenter on typical multi-layer material systems was simulated successfully by finite element method. The emphasis was put on the methods of extracting the yield stresses and strain-hardening modulus of upper and middle-layers of three-layer material systems from the indentation testing. The slope of the indentation depth to the applied indentation stress curve was found to have a turning point, which can be used to determine the yield stress of the upper-layer. Then, a different method was also presented to determine the yield stress of the middle-layer. This method was based on a set of assumed applied indentation stresses which were to be intersected by the experimental results in order to meet the requirement of having the experimental indentation depth. At last, a reverse numerical algorithm was explored to determine the yield stresses of upper and middle-layers simultaneously by using the indentation testing with two different size indenters. This method assumed two ranges of yield stresses to simulate the indentation behavior. The experimental depth behavior was used to intersect the simulated indentation behavior. And the intersection corresponded to the values of yield stresses of upper and middle-layers. This method was also used further to determine the strain-hardening modulus of upper and middle-layers simultaneously.

  6. RT-Bst: an integrated approach for reverse transcription and enrichment of cDNA from viral RNA.

    Science.gov (United States)

    Kabir, M S; Clements, M O; Kimmitt, P T

    2015-01-01

    The synthesis of cDNA from RNA is challenging due to the inefficiency of reverse transcription (RT). In order to address this, an RT-Bst method was developed for sequential RT of RNA and Bst DNA polymerase amplification for enrichment of cDNA in a single-tube reaction. Using genomic RNA from bacteriophage MS2, the yield of cDNA produced by RT alone and RT-Bst were compared by analysis of polymerase chain reaction (PCR)-amplified products. A superior performance was observed when amplifying MS2 cDNA with random primers following RT-Bst compared to RT alone, indicating greater quantities of cDNA were present after RT-Bst. RT-Bst was also compared with RT alone for their relative ability to produce sufficient cDNA to amplify eight target regions spanning the respiratory syncytial virus (RSV) genome. Six out of eight targets were amplified consistently by PCR subsequent to RT-Bst amplification, whereas only three out of eight targets could be amplified after RT alone. The RSV sequences were selectively amplified using RSV-specific primers from a mixed template containing an excess of MS2 RNA without amplifying MS2 sequences. This suggests that RT-Bst can be used to amplify RNA sequences non-specifically using random primers and specifically using sequence-specific primers, and enhances the yield of cDNA when compared to RT alone.

  7. Adaptive Pairing Reversible Watermarking.

    Science.gov (United States)

    Dragoi, Ioan-Catalin; Coltuc, Dinu

    2016-05-01

    This letter revisits the pairwise reversible watermarking scheme of Ou et al., 2013. An adaptive pixel pairing that considers only pixels with similar prediction errors is introduced. This adaptive approach provides an increased number of pixel pairs where both pixels are embedded and decreases the number of shifted pixels. The adaptive pairwise reversible watermarking outperforms the state-of-the-art low embedding bit-rate schemes proposed so far.

  8. A Bayesian approach to analyse genetic variation within RNA viral populations.

    Directory of Open Access Journals (Sweden)

    Trevelyan J McKinley

    2011-03-01

    Full Text Available The development of modern and affordable sequencing technologies has allowed the study of viral populations to an unprecedented depth. This is of particular interest for the study of within-host RNA viral populations, where variation due to error-prone polymerases can lead to immune escape, antiviral resistance and adaptation to new host species. Methods to sequence RNA virus genomes include reverse transcription (RT and polymerase chain reaction (PCR. RT-PCR is a molecular biology technique widely used to amplify DNA from an RNA template. The method itself relies on the in vitro synthesis of copy DNA from RNA followed by multiple cycles of DNA amplification. However, this method introduces artefactual errors that can act as confounding factors when the sequence data are analysed. Although there are a growing number of published studies exploring the intra- and inter-host evolutionary dynamics of RNA viruses, the complexity of the methods used to generate sequences makes it difficult to produce probabilistic statements about the likely sources of observed sequence variants. This complexity is further compounded as both the depth of sequencing and the length of the genome segment of interest increase. Here we develop a bayesian method to characterise and differentiate between likely structures for the background viral population. This approach can then be used to identify nucleotide sites that show evidence of change in the within-host viral population structure, either over time or relative to a reference sequence (e.g. an inoculum or another source of infection, or both, without having to build complex evolutionary models. Identification of these sites can help to inform the design of more focussed experiments using molecular biology tools, such as site-directed mutagenesis, to assess the function of specific amino acids. We illustrate the method by applying to datasets from experimental transmission of equine influenza, and a pre

  9. Biosafety risk assessment approaches for insect-resistant genetically modified crops

    Directory of Open Access Journals (Sweden)

    Inaam Ullah

    2017-02-01

    Full Text Available Background: Environmental risk assessment (ERA is imperative for commercial release of insect resistant, genetically modified crops (IR-GMCs.An insect specific, spider venom peptideω-HXTX-Hv1a (Hvt was successfully expressed in cotton plants. The cotton plants producing Hvt protein have demonstrated resistance against economically important insect pest species. The study was performed to assess the effects of Hvt producing cotton plants on Honey bees (Apis mellifera. Methods: Three approaches were used to evaluate the effects of Hvt protein on adults of honeybees; whole plant assays in flight cages, in vitro assays with pollen of Hvt-cotton, and assays with elevated levels of purified Hvt protein. Pollens of Bt cotton or purified Bt proteins were used as control. Results: The field experiments did not yield any meaningful data due to high rate of mortality in all treatments including the control. However, the laboratory experiments provided conclusive results in which Hvt, purified or in pollens, did not affect the survival or longevity of the bees compared to the control. During the course of study we were able to compare the quality, effectiveness and economics of different experiments. Conclusions: We conclude that Hvt either purified or produced in cotton plants do not affect the survival or longevity of honey bees. We are also of the view that starting at laboratory level assays not only gives meaningful data but also saves a lot of time and money that can be spent on other important questions regarding safety of a particular transgenic crop. Hence, a purpose-based, tiered approach could be the best choice for pre-release ERA of IR-GMCs.

  10. Research progress on the reverse genetics of PRRSV%猪繁殖与呼吸综合征病毒反向遗传技术的研究进展

    Institute of Scientific and Technical Information of China (English)

    邓雨修; 王东东; 潘永飞; 周庆丰; 苏润环; 李春梅

    2012-01-01

    反向遗传操作技术可以在DNA水平上对RNA病毒基因组进行各种修饰或改造,然后通过拯救病毒的表型变化来判断这些基因操作的效果,从而可以对病毒基因组的表达调控机制、病毒致病的分子机理等进行研究。本文就反向遗传操作技术在PRRSV基因功能结构研究以及新型疫苗开发等研究中的应用进行了综述。%Reverse genetics can run a variety of modifying and transforming at DNA level for RNA virus genome, and then these genetic manipulation effect is judged by phenotype change of rescued virus. So it can be used to research the expression and regulation mechanism of virus genome and molecular mechanism of virus pathogenicity. This review mainly focused on the progress of applications of reverse genetics in the genome functional analysis and new type of vaccine development of PRRSV.

  11. Feature Selection and Classification of Electroencephalographic Signals: An Artificial Neural Network and Genetic Algorithm Based Approach.

    Science.gov (United States)

    Erguzel, Turker Tekin; Ozekes, Serhat; Tan, Oguz; Gultekin, Selahattin

    2015-10-01

    Feature selection is an important step in many pattern recognition systems aiming to overcome the so-called curse of dimensionality. In this study, an optimized classification method was tested in 147 patients with major depressive disorder (MDD) treated with repetitive transcranial magnetic stimulation (rTMS). The performance of the combination of a genetic algorithm (GA) and a back-propagation (BP) neural network (BPNN) was evaluated using 6-channel pre-rTMS electroencephalographic (EEG) patterns of theta and delta frequency bands. The GA was first used to eliminate the redundant and less discriminant features to maximize classification performance. The BPNN was then applied to test the performance of the feature subset. Finally, classification performance using the subset was evaluated using 6-fold cross-validation. Although the slow bands of the frontal electrodes are widely used to collect EEG data for patients with MDD and provide quite satisfactory classification results, the outcomes of the proposed approach indicate noticeably increased overall accuracy of 89.12% and an area under the receiver operating characteristic (ROC) curve (AUC) of 0.904 using the reduced feature set.

  12. Molecular genetic approach to human meningioma: loss of genes on chromosome 22

    Energy Technology Data Exchange (ETDEWEB)

    Seizinger, B.R.; De La Monte, S.; Atkins, L.; Gusella, J.F.; Martuza, R.L.

    1987-08-01

    A molecular genetic approach employing polymorphic DNA markers has been used to investigate the role of chromosomal aberrations in meningioma, one of the most common tumors of the human nervous system. Comparison of the alleles detected by DNA markers in tumor DNA versus DNA from normal tissue revealed chromosomal alterations present in primary surgical specimens. In agreement with cytogenetic studies of cultured meningiomas, the most frequent alteration detected was loss of heterozygosity on chromosome 22. Forty of 51 patients were constitutionally heterozygous for at least one chromosome 22 DNA marker. Seventeen of the 40 constitutionally heterozygotic patients (43%) displayed hemizygosity for the corresponding marker in their meningioma tumor tissues. Loss of heterozygosity was also detected at a significantly lower frequency for markers on several other autosomes. In view of the striking association between acoustic neuroma and meningioma in bilateral acoustic neurofibromatosis and the discovery that acoustic neuromas display specific loss of genes on chromosome 22, the authors propose that a common mechanism involving chromosome 22 is operative in the development of both tumor types. Fine-structure mapping to reveal partial deletions in meningiomas may provide the means to clone and characterize a gene (or genes) of importance for tumorigenesis in this and possibly other clinically associated tumors of the human nervous system.

  13. Evaluating the impact of a fluoropolymer plant on a river macrobenthic community by a combined chemical, ecological and genetic approach.

    Science.gov (United States)

    Rusconi, Marianna; Marziali, Laura; Stefani, Fabrizio; Valsecchi, Sara; Bettinetti, Roberta; Mazzoni, Michela; Rosignoli, Federica; Polesello, Stefano

    2015-12-15

    Effect-based monitoring is a recommended approach suggested in European Guidelines to assess the response of ecosystem affected by a pollution source, considering the effects at community, population, individual but also at suborganism level. A combined chemical, ecological and genetic approach was applied in order to assess the impact of a fluoropolymer plant on the macrobenthic community of the Northern Italian river Bormida (Piedmont region). The macrobenthic community living downstream of the industrial discharge was chronically exposed to a mixture of perfluoroalkyl substances (PFAS), with perfluorooctanoic acid as the main compound, at concentrations up to several μgL(-1). Ecological assessment proved that the downstream community was not substantially different from that living upstream of the pollution source. The impact on community is not quantifiable with the traditional monitoring methods used for ecological classification under European regulation because macrobenthic communities showed only slight differences in their structure. In order to highlight effects on genetic variability of the native population, a subcellular analysis by using the AFLP (Amplified Fragment Length Polymorphism) genetic technique was applied to genotype of individuals of a selected species (Hydropsyche modesta, Trichoptera) collected in the two sampling sites. Percentage of variation between the two populations was 6.8%, a threshold compatible with a genetic drift induced in the downstream population. The genetic study carried out in field identified a significant divergence between exposed and non-exposed populations, but at present it is not possible to associate this divergence to a specific effect induced by PFAS.

  14. Uma abordagem bayesiana para o mapeamento de QTLS utilizando o método MCMC com saltos reversíveis A bayesian approach to map QTLs using reversible jump MCMC

    Directory of Open Access Journals (Sweden)

    Joseane Padilha da Silva

    2009-08-01

    Full Text Available A utilização de metodologias bayesianas tem se tornado frequente nas aplicações em Genética, em particular em mapeamento de QTLs usando marcadores moleculares. Mapear um QTL significa identificar sua localização ao longo do genoma, estimar seus efeitos genéticos: aditivo, dominância, epistasia, etc. A abordagem bayesiana permite combinar a verossimilhança dos dados fenotípicos com distribuições a priori atribuídas a todas as quantidades desconhecidas no modelo (número, localização no genoma e efeitos genéticos dos QTLs de forma a fornecer distribuições a posteriori a respeito dessas quantidades. Métodos de mapeamento bayesiano podem incorporar a incerteza relativa ao número desconhecido de QTLs na análise; essa incerteza, no entanto, resulta em complicações na obtenção da amostra da distribuição conjunta a posteriori, uma vez que a dimensão do espaço do modelo pode variar. O método MCMC com Saltos Reversíveis (MCMC-SR, proposto por Green (1995, é uma excelente ferramenta para explorar a distribuição conjunta a posteriori nesse contexto. Neste trabalho, explora-se o método MCMC-SR, utilizando dados artificiais gerados no software WinQTLCart, atribuindo-se diferentes prioris para o número de QTLs.The use of Bayesian methodology in genetic applications has grown increasingly popular, in particular in the analysis of quantitative trait loci (QTL for studies using molecular markers. In such analyses the objectives are mapping QTLs, estimating their locations in the genome and their genotypic effects (additive, dominance, and epistatic. The Bayesian approach proceeds by setting up a likelihood function for the phenotype and assigning prior distributions to all unknown quantities in the model (number, chromosome, locus, and genetic effects of QTL. These induce a posterior distribution of the unknown quantities that contains all of the available information for inference of the genetic architecture of the trait

  15. Progress in the study of producing reversible male sterile line by genetic engineering%基因工程培育可恢复的植物雄性不育系的研究进展

    Institute of Scientific and Technical Information of China (English)

    王玉锋; 黄霁月; 杨金水

    2011-01-01

    植物雄性不育是植物杂种优势利用的资源,具有重要的生产利用价值.植物雄性不育可从自然突变,人工诱变和远缘杂交中发现,现在可通过细胞工程和基因工程等方法来创造.文章综述了利用基因工程方法制备雄性不育品系及其相应的育性恢复策略,分为"单组分策略"和"双组分策略".其中利用"单组分策略"制备的不育植株是条件型雄性不育(可逆转的雄性不育),它能在特定的条件下实现雄性可育与不育的转换,实践中可直接作为两用系(不育系和保持系)用于两系法杂交制种;"双组分策略"是利用基因互作和亲本杂交直接培育雄性不育系,或利用基因互作原理分别研制不育系和恢复系,用于三系法生产杂交种.文章分析了"单组分策略"和"双组分策略"的基因工程方法培育雄性不育系及其相应育性恢复策略优缺点,对以上两种技术路线在实际应用中的现状作了分析和展望.%Plant male sterility is a kind of resource of heterosis, which has important value in production.It may be derived from natural mutations, artificial mutations, distant hybridizations.and now through cell engineering and genetic engineering.This paper reviews the progress of strategies in production of plant male sterile lines and their corresponding fertile lines via genetic engineering approach.All strategies can be grouped into "single component strategy" and"two-component strategy"."Single component strategy" produces conditional (reversible) male sterile line, whose fercility can be switched under given condition.Conditional male sterile line has two roles, which are CMS and maintainer line for breeding in practice; "two-component strategy" takes advantage of gene interaction and parental hybridization to generate male sterile line.Otherwise, it develops sterile line and restorer line respectively for three-line hybrid system for seed production through gene interaction.This paper

  16. Minding the Genes: a Multidisciplinary Approach towards Genetic Assessment of Cardiovascular Disease.

    Science.gov (United States)

    Rhodes, Ashley; Rosman, Lindsey; Cahill, John; Ingles, Jodie; Murray, Brittney; Tichnell, Crystal; James, Cynthia A; Sears, Samuel F

    2017-04-01

    Genetic assessment for inherited cardiovascular disease (CVD) is increasingly available, due in part to rapid innovations in genetic sequencing technologies. While genetic testing is aimed at reducing uncertainty, it also produces awareness of potential medical conditions and can leave patients feeling uncertain about their risk, especially if there are ambiguous results. This uncertainty can produce psychological distress for patients and their families undergoing the assessment process. Additionally, patients may experience psychological distress related to living with inherited CVD. In order to more effectively manage the psychosocial challenges related to genetic assessment for CVD, a multidisciplinary model expanded to include psychologists and other allied health professionals is outlined. A case study is provided to illustrate how psychological distress can manifest in a patient living with inherited CVD, as well as proposed psychological management of this patient. Finally, a guide for genetic counselors is provided to aid in identifying and managing common psychological reactions to genetic assessment for CVD.

  17. Responding to the implications of the genetics revolution for the education and training of doctors: a medical humanities approach.

    Science.gov (United States)

    Kirklin, Deborah

    2003-02-01

    Rapid advances in the field of genetics continue to present medical educators with significant challenges. Whilst there is undoubtedly a pressing need to educate doctors about genetic disorders, research and therapies, there is a parallel need to provide a context for all of these. An interdisciplinary, arts and humanities based approach, responding to this need, is described. This teaching has been successfully delivered both as optional and core undergraduate teaching, and as part of continuing professional development. THE HUMAN PERSPECTIVE: STORIES NOT HISTORIES: Understanding of the patient's perspective can be significantly improved by drawing on both written and oral stories of illness. THE HISTORICAL PERSPECTIVE: LEARNING FROM THE PATIENT: Experiential learning provides insights into the social history of developments in genetics, thereby placing the current concern and debate about the new genetics in context. THE ROLE OF THE MEDIA: THE POWER TO PERSUADE: Critical reading skills can be developed and the power of the popular press to influence the reader acknowledged by analysing and employing the skills of the journalist when reporting developments in biotechnology. LEARNER ASSESSMENT AND EVALUATION: Assessment, both formative and summative, demonstrates sophisticated insights and perspectives into the lived experience of genetic illness. Learner evaluation of the teaching is high. Medical humanities offers a powerful way to convey an understanding of how genetic disorders impact on the lives of patients and families, and to set this against the background of a history rich in the uses, and abuses, of knowledge of heredity.

  18. 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.

  19. Evolutionary approaches for the reverse-engineering of gene regulatory networks: A study on a biologically realistic dataset

    Directory of Open Access Journals (Sweden)

    Gidrol Xavier

    2008-02-01

    Full Text Available Abstract Background Inferring gene regulatory networks from data requires the development of algorithms devoted to structure extraction. When only static data are available, gene interactions may be modelled by a Bayesian Network (BN that represents the presence of direct interactions from regulators to regulees by conditional probability distributions. We used enhanced evolutionary algorithms to stochastically evolve a set of candidate BN structures and found the model that best fits data without prior knowledge. Results We proposed various evolutionary strategies suitable for the task and tested our choices using simulated data drawn from a given bio-realistic network of 35 nodes, the so-called insulin network, which has been used in the literature for benchmarking. We assessed the inferred models against this reference to obtain statistical performance results. We then compared performances of evolutionary algorithms using two kinds of recombination operators that operate at different scales in the graphs. We introduced a niching strategy that reinforces diversity through the population and avoided trapping of the algorithm in one local minimum in the early steps of learning. We show the limited effect of the mutation operator when niching is applied. Finally, we compared our best evolutionary approach with various well known learning algorithms (MCMC, K2, greedy search, TPDA, MMHC devoted to BN structure learning. Conclusion We studied the behaviour of an evolutionary approach enhanced by niching for the learning of gene regulatory networks with BN. We show that this approach outperforms classical structure learning methods in elucidating the original model. These results were obtained for the learning of a bio-realistic network and, more importantly, on various small datasets. This is a suitable approach for learning transcriptional regulatory networks from real datasets without prior knowledge.

  20. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci

    OpenAIRE

    Shen, Changbing; Gao, Jing; Sheng, Yujun; Dou, Jinfa; Zhou, Fusheng; Zheng, Xiaodong; Ko, Randy; Tang, Xianfa; Zhu, Caihong; Yin, Xianyong; Sun, Liangdan; Cui, Yong; Zhang, Xuejun

    2016-01-01

    Vitiligo is an autoimmune disease with a strong genetic component, characterized by areas of depigmented skin resulting from loss of epidermal melanocytes. Genetic factors are known to play key roles in vitiligo through discoveries in association studies and family studies. Previously, vitiligo susceptibility genes were mainly revealed through linkage analysis and candidate gene studies. Recently, our understanding of the genetic basis of vitiligo has been rapidly advancing through genome-wid...