322 research outputs found

    Participatory approaches for the development and use of information and communication technologies (ICTs) for rural farmers

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    Abstract: One of the prime ingredients for rural development in developing countries is information access. Although the Information and Communication Technology (ICT) revolution in these countries has gained momentum, most of the farming communities still have no access to value added information. The agricultural researcher and the farming community need to enhance their knowledge by increased ‘farmer participation’ in research. This paper makes a strong case for the use of participatory approaches involving farming community for development and adoption of ICT in the agricultural sector. It acknowledges that farmers are knowledgeable and encourages researchers to work with farmers and development workers for agricultural improvements. This paper discusses how digital ICT developed by means of participatory learning and action research can spur development and eradicate poverty by providing services to farmers in rural areas. It also highlights how participatory approaches can empower collective groups of farmers and help to put decision-making in the hands of the farmers. Although no single ICT will be satisfactory for farmers, the use of a wide range of ICTs in agriculture can improve the livelihood of the farmers in rural areas and help in their socio-economic growth. The paper focuses on various participatory approaches such as participatory communication and participatory learning for effective use of ICTs in agricultural domain. It highlights how participatory approaches can assist in ‘participatory information and communication technology development’ for rural farming community

    A model-based approach to System of Systems risk management

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    The failure of many System of Systems (SoS) enterprises can be attributed to the inappropriate application of traditional Systems Engineering (SE) processes within the SoS domain, because of the mistaken belief that a SoS can be regarded as a single large, or complex, system. SoS Engineering (SoSE) is a sub-discipline of SE; Risk Management and Modelling and Simulation (M&S) are key areas within SoSE, both of which also lie within the traditional SE domain. Risk Management of SoS requires a different approach to that currently taken for individual systems; if risk is managed for each component system then it cannot be assumed that the aggregated affect will be to mitigate risk at the SoS level. A literature review was undertaken examining three themes: (1) SoS Engineering (SoSE), (2) M&S and (3) Risk. Theme 1 of the literature provided insight into the activities comprising SoSE and its difference from traditional SE with risk management identified as a key activity. The second theme discussed the application of M&S to SoS, providing an output, which supported the identification of appropriate techniques and concluding that, the inherent complexity of a SoS required the use of M&S in order to support SoSE activities. Current risk management approaches were reviewed in theme 3 as well as the management of SoS risk. Although some specific examples of the management of SoS risk were found, no mature, general approach was identified, indicating a gap in current knowledge. However, it was noted most of these examples were underpinned by M&S approaches. It was therefore concluded a general approach SoS risk management utilising M&S methods would be of benefit. In order to fill the gap identified in current knowledge, this research proposed a new model based approach to Risk Management where risk identification was supported by a framework, which combined SoS system of interest dimensions with holistic risk types, where the resulting risks and contributing factors are captured in a causal network. Analysis of the causal network using a model technique selection tool, developed as part of this research, allowed the causal network to be simplified through the replacement of groups of elements within the network by appropriate supporting models. The Bayesian Belief Network (BBN) was identified as a suitable method to represent SoS risk. Supporting models run in Monte Carlo Simulations allowed data to be generated from which the risk BBNs could learn, thereby providing a more quantitative approach to SoS risk management. A method was developed which provided context to the BBN risk output through comparison with worst and best-case risk probabilities. The model based approach to Risk Management was applied to two very different case studies: Close Air Support mission planning and the Wheat Supply Chain, UK National Food Security risks, demonstrating its effectiveness and adaptability. The research established that the SoS SoI is essential for effective SoS risk identification and analysis of risk transfer, effective SoS modelling requires a range of techniques where suitability is determined by the problem context, the responsibility for SoS Risk Management is related to the overall SoS classification and the model based approach to SoS risk management was effective for both application case studies

    The Development, Validation and Implementation of a Broad-Based ADME Genotyping Assay into Research and Clinical Trials

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    Afin d’adresser la variabilitĂ© interindividuelle observĂ©e dans la rĂ©ponse pharmacocinĂ©tique Ă  de nombreux mĂ©dicaments, nous avons crĂ©Ă© un panel de gĂ©notypage personnalisĂ©e en utilisant des mĂ©thodes de conception et d’élaboration d’essais uniques. Celles-ci ont pour but premier de capturer les variations gĂ©nĂ©tiques prĂ©sentent dans les gĂšnes clĂ©s impliquĂ©s dans les processus d'absorption, de distribution, de mĂ©tabolisme et d’excrĂ©tion (ADME) de nombreux agents thĂ©rapeutiques. Bien que ces gĂšnes et voies de signalement sont impliquĂ©s dans plusieurs mĂ©canismes pharmacocinĂ©tiques qui sont bien connues, il y a eu jusqu’à prĂ©sent peu d'efforts envers l’évaluation simultanĂ©e d’un grand nombre de ces gĂšnes moyennant un seul outil expĂ©rimental. La recherche pharmacogĂ©nomique peut ĂȘtre rĂ©alisĂ©e en utilisant deux approches: 1) les marqueurs fonctionnels peuvent ĂȘtre utilisĂ©s pour prĂ©sĂ©lectionner ou stratifier les populations de patients en se basant sur des Ă©tats mĂ©taboliques connus; 2) les marqueurs Tag peuvent ĂȘtre utilisĂ©s pour dĂ©couvrir de nouvelles corrĂ©lations gĂ©notype-phĂ©notype. PrĂ©sentement, il existe un besoin pour un outil de recherche qui englobe un grand nombre de gĂšnes ADME et variantes et dont le contenu est applicable Ă  ces deux modĂšles d'Ă©tude. Dans le cadre de cette thĂšse, nous avons dĂ©veloppĂ© un panel d’essais de gĂ©notypage de 3,000 marqueurs gĂ©nĂ©tiques ADME qui peuvent satisfaire ce besoin. Dans le cadre de ce projet, les gĂšnes et marqueurs associĂ©s avec la famille ADME ont Ă©tĂ© sĂ©lectionnĂ©s en collaboration avec plusieurs groupes du milieu universitaire et de l'industrie pharmaceutique. Pendant trois phases de dĂ©veloppement de cet essai de gĂ©notypage, le taux de conversion pour 3,000 marqueurs a Ă©tĂ© amĂ©liorĂ© de 83% Ă  97,4% grĂące Ă  l'incorporation de nouvelles stratĂ©gies ayant pour but de surmonter les zones d'interfĂ©rence gĂ©nomiques comprenant entre autres les rĂ©gions homologues et les polymorphismes sous-jacent les rĂ©gions d’intĂ©rĂȘt. La prĂ©cision du panel de gĂ©notypage a Ă©tĂ© validĂ©e par l’évaluation de plus de 200 Ă©chantillons pour lesquelles les gĂ©notypes sont connus pour lesquels nous avons obtenu une concordance > 98%. De plus, une comparaison croisĂ©e entre nos donnĂ©es provenant de cet essai et des donnĂ©es obtenues par diffĂ©rentes plateformes technologiques dĂ©jĂ  disponibles sur le marchĂ© a rĂ©vĂ©lĂ© une concordance globale de > 99,5%. L'efficacitĂ© de notre stratĂ©gie de conception ont Ă©tĂ© dĂ©montrĂ©es par l'utilisation rĂ©ussie de cet essai dans le cadre de plusieurs projets de recherche oĂč plus de 1,000 Ă©chantillons ont Ă©tĂ© testĂ©s. Nous avons entre autre Ă©valuĂ© avec succĂšs 150 Ă©chantillons hĂ©patiques qui ont Ă©tĂ© largement caractĂ©risĂ©s pour plusieurs phĂ©notypes. Dans ces Ă©chantillons, nous avons pu valider 13 gĂšnes ADME avec cis-eQTL prĂ©cĂ©demment rapportĂ©s et de dĂ©couvrir et de 13 autres gĂšnes ADME avec cis eQTLs qui n'avaient pas Ă©tĂ© observĂ©s en utilisant des mĂ©thodes standard. Enfin, Ă  l'appui de ce travail, un outil logiciel a Ă©tĂ© dĂ©veloppĂ©, Opitimus Primer, pour aider pour aider au dĂ©veloppement du test. Le logiciel a Ă©galement Ă©tĂ© utilisĂ© pour aider Ă  l'enrichissement de cibles gĂ©nomiques pour d'expĂ©riences sĂ©quençage. Le contenu ainsi que la conception, l’optimisation et la validation de notre panel le distingue largement de l’ensemble des essais commerciaux couramment disponibles sur le marchĂ© qui comprennent soit des marqueurs fonctionnels pour seulement un petit nombre de gĂšnes, ou alors n’offre pas une couverture adĂ©quate pour les gĂšnes connus d’ADME. Nous pouvons ainsi conclure que l’essai que nous avons dĂ©veloppĂ© est et continuera certainement d’ĂȘtre un outil d’une grande utilitĂ© pour les futures Ă©tudes et essais cliniques dans le domaine de la pharmacocinĂ©tique, qui bĂ©nĂ©ficieraient de l'Ă©valuation d'une longue liste complĂšte de gĂšnes d’ADME.In order to better assess the inter-individual variability observed in a patient’s pharmacokinetic response to many medications, we have created a custom genotyping panel that uses unique assay designs to analyze variation present in key genes involved in the absorption, distribution, metabolism and excretion (ADME) of many therapeutic agents. These genes and pathways involved in most pharmacokinetic mechanisms are well known. However, as yet, there has been little effort to develop tools that can interrogate a large number of variations in most known drug metabolizing genes simultaneously within a single experimental tool. Pharmacogenomic research has historically been conducted using two approaches: targeted studies that screen a small number of specific functional markers to identify known metabolic status phenotypes, and genome-wide studies that identify novel genetic correlations with drug response phenotypes. Thus, a gap currently exists for a targeted ADME research tool that can evaluate a large number of key ADME genes and variants in a format that can be applicable to both types of study designs. As part of this thesis, we have developed a 3000 SNP broad based ADME genotyping panel that can address this need. Genes and markers for the genotyping panel were selected in collaboration with many groups from both academia and the pharmaceutical industry in an effort to capture all pertinent genes and metabolic pathways that have been implicated in drug metabolism. The final assay design was composed of over 3000 markers in 181 genes. Over three phases of iterative development, the assay conversion rate for the 3000 markers was improved from 83.0% to 97.4% through the incorporation of novel design strategies to overcome areas of genomic interference such as regions of homology and underlying polymorphisms. Accuracy of the assay was validated by screening more than 200 samples of known genotype with a concordance of 99%. Additionally, data from the assay has also been compared to data from different technological platforms and has an overall concordance of 99.5%. The effectiveness of the design strategy was demonstrated in the successful utilization of the assay in the screening of over 1000 samples which identified several novel pharmacogenetic associations between ADME variations and adverse drug reactions in children. Another goal of this thesis was to demonstrate what added benefit/utility the 3000 SNP ADME panel would have when compared to currently available genotyping assays. Using 150 extensively investigated liver samples, the broad based assay was not only able to detect and validate 13 previously reported cis eQTLs in ADME genes but further identified an additional 13 novel ADME cis eQTLs that had never been observed before, doubling the number previously identified using standard methods on the same samples. Finally, in support of this work, a number of bioinformatic tools had to be developed to help expedite this research. These tools have been further refined and are currently being used to assist with enrichment of genomic targets for next generation sequencing experiments. In conclusion, this work has led to a better understanding of ADME genetics and the nuances of assaying ADME genes. The content and designs of the developed assay sets it apart from currently available commercial assays that contain only functional markers in a small number of genes or do not have adequate coverage across ADME genes. The assay has the ability to play a significant role in pharmacogenomic studies to identify known and novel pharmacogenomic biomarkers. These will lead to improved biomarkers that will help better stratify pharmaceutical clinical trial populations or assist physicians to select better, more personalized, efficacious and safer therapies for their patients

    Identification of compounds with anti-human cytomegalovirus activity that inhibit production of IE2 proteins

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    Using a high throughput screening methodology we surveyed a collection of largely uncharacterized validated or suspected kinase inhibitors for anti-human cytomegalovirus (HCMV) activity. From this screen we identified three structurally related 5-aminopyrazine compounds (XMD7-1, -2 and -27) that inhibited HCMV replication in virus yield reduction assays at low micromolar concentrations. Kinase selectivity assays indicated that each compound was a kinase inhibitor capable of inhibiting a range of cellular protein kinases. Western blotting and RNA sequencing demonstrated that treatment of infected cells with XMD7 compounds resulted in a defect in the production of the major HCMV transcriptional transactivator IE2 proteins (IE2-86, IE2-60 and IE2-40) and an overall reduction in transcription from the viral genome. However, production of certain viral proteins was not compromised by treatment with XMD7 compounds. Thus, these novel anti-HCMV compounds likely inhibited transcription from the viral genome and suppressed production of a subset of viral proteins by inhibiting IE2 protein production

    Cassini nightside observations of the oscillatory motion of Saturn's northern auroral oval

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    In recent years we have benefitted greatly from the first in-orbit multi-wavelength images of Saturn's polar atmosphere from the Cassini spacecraft. Specifically, images obtained from the Cassini UltraViolet Imaging Spectrograph (UVIS) provide an excellent view of the planet's auroral emissions, which in turn give an account of the large-scale magnetosphere-ionosphere coupling and dynamics within the system. However, obtaining near-simultaneous views of the auroral regions with in situ measurements of magnetic field and plasma populations at high latitudes is more difficult to routinely achieve. Here we present an unusual case, during Revolution 99 in January 2009, where UVIS observes the entire northern UV auroral oval during a 2 h interval while Cassini traverses the magnetic flux tubes connecting to the auroral regions near 21 LT, sampling the related magnetic field, particle, and radio and plasma wave signatures. The motion of the auroral oval evident from the UVIS images requires a careful interpretation of the associated latitudinally “oscillating” magnetic field and auroral field-aligned current signatures, whereas previous interpretations have assumed a static current system. Concurrent observations of the auroral hiss (typically generated in regions of downward directed field-aligned current) support this revised interpretation of an oscillating current system. The nature of the motion of the auroral oval evident in the UVIS image sequence, and the simultaneous measured motion of the field-aligned currents (and related plasma boundary) in this interval, is shown to be related to the northern hemisphere magnetosphere oscillation phase. This is in agreement with previous observations of the auroral oval oscillatory motion

    First-principles extrapolation method for accurate CO adsorption energies on metal surfaces

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    We show that a simple first-principles correction based on the difference between the singlet-triplet CO excitation energy values obtained by DFT and high-level quantum chemistry methods yields accurate CO adsorption properties on a variety of metal surfaces. We demonstrate a linear relationship between the CO adsorption energy and the CO singlet-triplet splitting, similar to the linear dependence of CO adsorption energy on the energy of the CO 2π\pi* orbital found recently {[Kresse {\em et al.}, Physical Review B {\bf 68}, 073401 (2003)]}. Converged DFT calculations underestimate the CO singlet-triplet excitation energy ΔES−T\Delta E_{\rm S-T}, whereas coupled-cluster and CI calculations reproduce the experimental ΔES−T\Delta E_{\rm S-T}. The dependence of EchemE_{\rm chem} on ΔES−T\Delta E_{\rm S-T} is used to extrapolate EchemE_{\rm chem} for the top, bridge and hollow sites for the (100) and (111) surfaces of Pt, Rh, Pd and Cu to the values that correspond to the coupled-cluster and CI ΔES−T\Delta E_{\rm S-T} value. The correction reproduces experimental adsorption site preference for all cases and obtains EchemE_{\rm chem} in excellent agreement with experimental results.Comment: Table sent as table1.eps. 3 figure

    Origin of strange metallic phase in cuprate superconductors

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    The origin of strange metallic phase is shown to exist due to these two conditions---(i) the electrons are strongly interacting such that there are no band and Mott-Hubbard gaps, and (ii) the electronic energy levels are crossed in such a way that there is an electronic energy gap between two energy levels associated to two different wave functions. The theory is also exploited to explain (i) the upward- and downward-shifts in the TT-linear resistivity curves, and (ii) the spectral weight transfer observed in the soft X-ray absorption spectroscopic measurements of the La-Sr-Cu-O Mott insulator.Comment: To be published in J. Supercond. Nov. Mag

    Damming the genomic data flood using a comprehensive analysis and storage data structure

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    Data generation, driven by rapid advances in genomic technologies, is fast outpacing our analysis capabilities. Faced with this flood of data, more hardware and software resources are added to accommodate data sets whose structure has not specifically been designed for analysis. This leads to unnecessarily lengthy processing times and excessive data handling and storage costs. Current efforts to address this have centered on developing new indexing schemas and analysis algorithms, whereas the root of the problem lies in the format of the data itself. We have developed a new data structure for storing and analyzing genotype and phenotype data. By leveraging data normalization techniques, database management system capabilities and the use of a novel multi-table, multidimensional database structure we have eliminated the following: (i) unnecessarily large data set size due to high levels of redundancy, (ii) sequential access to these data sets and (iii) common bottlenecks in analysis times. The resulting novel data structure horizontally divides the data to circumvent traditional problems associated with the use of databases for very large genomic data sets. The resulting data set required 86% less disk space and performed analytical calculations 6248 times faster compared to a standard approach without any loss of information

    Nustar and Chandra Insight into the Nature of the 3-40 Kev Nuclear Emission in Ngc 253

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    We present results from three nearly simultaneous Nuclear Spectroscopic Telescope Array (NuSTAR) and Chandra monitoring observations between 2012 September 2 and 2012 November 16 of the local star-forming galaxy NGC 253. The 3-40 kiloelectron volt intensity of the inner approximately 20 arcsec (approximately 400 parsec) nuclear region, as measured by NuSTAR, varied by a factor of approximately 2 across the three monitoring observations. The Chandra data reveal that the nuclear region contains three bright X-ray sources, including a luminous (L (sub 2-10 kiloelectron volt) approximately few 10 (exp 39) erg per s) point source located approximately 1 arcsec from the dynamical center of the galaxy (within the sigma 3 positional uncertainty of the dynamical center); this source drives the overall variability of the nuclear region at energies greater than or approximately equal to 3 kiloelectron volts. We make use of the variability to measure the spectra of this single hard X-ray source when it was in bright states. The spectra are well described by an absorbed (power-law model spectral fit value, N(sub H), approximately equal to 1.6 x 10 (exp 23) per square centimeter) broken power-law model with spectral slopes and break energies that are typical of ultraluminous X-ray sources (ULXs), but not active galactic nuclei (AGNs). A previous Chandra observation in 2003 showed a hard X-ray point source of similar luminosity to the 2012 source that was also near the dynamical center (Phi is approximately equal to 0.4 arcsec); however, this source was offset from the 2012 source position by approximately 1 arcsec. We show that the probability of the 2003 and 2012 hard X-ray sources being unrelated is much greater than 99.99% based on the Chandra spatial localizations. Interestingly, the Chandra spectrum of the 2003 source (3-8 kiloelectron volts) is shallower in slope than that of the 2012 hard X-ray source. Its proximity to the dynamical center and harder Chandra spectrum indicate that the 2003 source is a better AGN candidate than any of the sources detected in our 2012 campaign; however, we were unable to rule out a ULX nature for this source. Future NuSTAR and Chandra monitoring would be well equipped to break the degeneracy between the AGN and ULX nature of the 2003 source, if again caught in a high state
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