153 research outputs found

    Seismic performance of mid-rise code-conforming X-braced steel frames

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    Prolixity and complexities inherent in the nonlinear dynamic analysis (NDA) impel engineers to lean towards nonlinear static analysis (NSA) in practice. This paper partly explores differences and similarities in responses obtained from these two simulation techniques. The scope of the study is narrowed down to ubiquitous regular code-conforming mid-rise steel X-braced frames. Different common lateral load patterns are coupled with NSA to study their interactive effects on responses. The modal nonlinear static analysis is also carried out, where deemed necessary. NDA using three different earthquake records are conducted as well, to validate NSA results. Results of nonlinear analyses are undertaken to compare provisions of seismic rehabilitation code with those of seismic design codes. Base shear, story drift, lateral displacement profile obtained for each model are independently thoroughly discussed. Eventually, some suggestions to improve design code requirements are accordingly provided, as applicable

    Seismic performance of mid-rise code-conforming X-braced steel frames

    Get PDF
    Prolixity and complexities inherent in the nonlinear dynamic analysis (NDA) impel engineers to lean towards nonlinear static analysis (NSA) in practice. This paper partly explores differences and similarities in responses obtained from these two simulation techniques. The scope of the study is narrowed down to ubiquitous regular code-conforming mid-rise steel X-braced frames. Different common lateral load patterns are coupled with NSA to study their interactive effects on responses. The modal nonlinear static analysis is also carried out, where deemed necessary. NDA using three different earthquake records are conducted as well, to validate NSA results. Results of nonlinear analyses are undertaken to compare provisions of seismic rehabilitation code with those of seismic design codes. Base shear, story drift, lateral displacement profile obtained for each model are independently thoroughly discussed. Eventually, some suggestions to improve design code requirements are accordingly provided, as applicable

    Human genetic variation, relationships of peoples of sub- Saharan Africa and implications for healthcare

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    Sub-Saharan Africa is thought to have the most genetic variation of any continent and to be the place of origin of anatomically modern human. Nevertheless it is the subject of relatively few studies of human genetic variation. This thesis contributes to redressing this imbalance. Sex-specific genetic systems (non-recombining portion of the Y chromosome (NRY) and mitochondrial DNA (mtDNA)) along with functional nuclear loci were characterised in multiple sub-Saharan African populations with large sample sizes to infer relationships of peoples and identify implications for healthcare. This thesis contains four projects which addressed questions in genetic anthropology, human evolution and pharmacogenetics utilising human genetic variation. In chapter 2, NRY analysis shows that a hypothesised paternal Yombe (Congo) ancestry of Palenque (Colombia), based on linguistic and historical evidence, is consistent with genetic data. Chapter 3, based on NRY data, demonstrates that a) multiple waves of migration occurred southwards during the expansion of Bantu-speaking peoples (EBSP), b) the eastern route displayed more recent migrations than the western route and c) the absence of substantial east to west NRY gene flow in sub-Saharan Africa over the past millennium. Chapter 4 suggests an eastern route out of Africa for the CASP12 truncated variant is more likely than a western route. (The stop-codon mutation was also dated to around 120,000 YBP). Chapter 5 demonstrates that a potentially functional CYP1A2 variant which has not been reported outside Africa is present at considerable frequencies in sub-Saharan African population groups and that exons associated with active sites in CYP1A genes are well conserved

    Group-based pharmacogenetic prediction: is it feasible and do current NHS England ethnic classifications provide appropriate data?

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    Inter-individual variation of drug metabolising enzymes (DMEs) leads to variable efficacy of many drugs and even adverse drug responses. Consequently, it would be desirable to test variants of many DMEs before drug treatment. Inter-ethnic differences in frequency mean that the choice of SNPs to test may vary across population groups. Here we examine the utility of testing representative groups as a way of assessing what variants might be tested. We show that publicly available population information is potentially useful for determining loci for pre-treatment genetic testing, and for determining the most prevalent risk haplotypes in defined groups. However, we also show that the NHS England classifications have limitations for grouping for these purposes, in particular for people of African descent. We conclude: (1) genotyping of hospital patients and people from the hospital catchment area confers no advantage over using samples from appropriate existing ethnic group collections or publicly available data, (2) given the current NHS England Black African grouping, a decision as to whether to test, would have to apply to all patients of recent Black African ancestry to cover reported risk alleles and (3) the current scarcity of available genome and drug effect data from Africans is a problem for both testing and treatment decisions

    Fly fauna of livestock’ s of Marvdasht County of Fars Province in the South of Iran

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    Flies damage the livestock industry in many ways, including damages, physical disturbances, the transmissions of pathogens and the emergence of problems for livestock like Myiasis. In this research, the fauna of flies of Marvdasht County was investigating, which is one of the central counties of Fars province in southern Iran. In this study, a total of 20 species of flies from 6 families and 15 genera have been identified and reported. The species collected are as follows: Muscidae: Musca domestica Linnaeus, 1758, Musca autumnalis* De Geer, 1776, Stomoxys calci-trans** Linnaeus, 1758, Haematobia irritans** Linnaeus, 1758 Fanniidae: Fannia canicularis* Linnaeus, 1761 Calliphoridae: Calliphora vomitoria* Linnaeus, 1758, Chrysomya albiceps* Wiedemann, 1819, Lu-cilia caesar* Linnaeus, 1758, Lucilia sericata* Meigen, 1826, Lucilia cuprina* Wiedemann, 1830 Sarcophagidae: Sarcophaga africa* Wiedemann, 1824, Sarcophaga aegyptica* Salem, 1935, Wohl-fahrtia magnifica** Schiner, 1862 Syrphidae: Eristalis tenax* Linnaeus, 1758, Syritta pipiens* Linnaeus, 1758, Eupeodes nuba* Wiedemann, 1830, Syrphus vitripennis** Meigen, 1822, Scaeva albomaculata* Macquart, 1842 Species identified with * for the first time in the county and the species marked with ** are reported for the first time from the Fars province

    Palenque de San Basilio in Colombia: genetic data support an oral history of a paternal ancestry in Congo

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    The Palenque, a black community in rural Colombia, have an oral history of fugitive African slaves founding a free village near Cartagena in the seventeenth century. Recently, linguists have identified some 200 words in regular use that originate in a Kikongo language, with Yombe, mainly spoken in the Congo region, being the most likely source. The non-recombining portion of the Y chromosome (NRY) and mitochondrial DNA were analysed to establish whether there was greater similarity between present-day members of the Palenque and Yombe than between the Palenque and 42 other African groups (for all individuals,n= 2799) from which forced slaves might have been taken. NRY data are consistent with the linguistic evidence that Yombe is the most likely group from which the original male settlers of Palenque came. Mitochondrial DNA data suggested substantial maternal sub-Saharan African ancestry and a strong founder effect but did not associate Palenque with any particular African group. In addition, based on cultural data including inhabitants' claims of linguistic differences, it has been hypothesized that the two districts of the village (Abajo and Arriba) have different origins, with Arriba founded by men originating in Congo and Abajo by those born in Colombia. Although significant genetic structuring distinguished the two from each other, no supporting evidence for this hypothesis was found

    Can We Assume the Gene Expression Profile as a Proxy for Signaling Network Activity?

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    Studying relationships among gene products by expression profile analysis is a common approach in systems biology. Many studies have generalized the outcomes to the different levels of central dogma information flow and assumed a correlation of transcript and protein expression levels. However, the relation between the various types of interaction (i.e., activation and inhibition) of gene products to their expression profiles has not been widely studied. In fact, looking for any perturbation according to differentially expressed genes is the common approach, while analyzing the effects of altered expression on the activity of signaling pathways is often ignored. In this study, we examine whether significant changes in gene expression necessarily lead to dysregulated signaling pathways. Using four commonly used and comprehensive databases, we extracted all relevant gene expression data and all relationships among directly linked gene pairs. We aimed to evaluate the ratio of coherency or sign consistency between the expression level as well as the causal relationships among the gene pairs. Through a comparison with random unconnected gene pairs, we illustrate that the signaling network is incoherent, and inconsistent with the recorded expression profile. Finally, we demonstrate that, to infer perturbed signaling pathways, we need to consider the type of relationships in addition to gene-product expression data, especially at the transcript level. We assert that identifying enriched biological processes via differentially expressed genes is limited when attempting to infer dysregulated pathways.Peer reviewe

    Contrasting exome constancy and regulatory region variation in the gene encoding CYP3A4: an examination of the extent and potential implications.

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    OBJECTIVE: CYP3A4 expression varies up to 100-fold among individuals, and, to date, genetic causes remain elusive. As a major drug-metabolizing enzyme, elucidation of such genetic causes would increase the potential for introducing personalized dose adjustment of therapies involving CYP3A4 drug substrates. The foetal CYP3A isoform, CYP3A7, is reported to be expressed in ∼10% of European adults and may thus contribute towards the metabolism of endogenous substances and CYP3A drug substrates. However, little is known about the distribution of the variant expressed in the adult. METHODS: We resequenced the exons, flanking introns, regulatory elements and 3'UTR of CYP3A4 in five Ethiopian populations and incorporated data from the 1000 Genomes Project. Using bioinformatic analysis, we assessed likely consequences of observed CYP3A4 genomic variation. We also conducted the first extensive geographic survey of alleles associated with adult expression of CYP3A7 - that is, CYP3A7*1B and CYP3A7*1C. RESULTS AND CONCLUSION: Ethiopia contained 60 CYP3A4 variants (26 novel) and more variants (>1%) than all non-African populations combined. No nonsynonymous mutation was found in the homozygous form or at more than 2.8% in any population. Seventy-nine per cent of haplotypes contained 3'UTR and/or regulatory region variation with striking pairwise population differentiation, highlighting the potential for interethnic variation in CYP3A4 expression. Conversely, coding region variation showed that significant interethnic variation is unlikely at the protein level. CYP3A7*1C was found at up to 17.5% in North African populations and in significant linkage disequilibrium with CYP3A5*3, indicating that adult expression of the foetal isoform is likely to be accompanied by reduced or null expression of CYP3A5
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