342 research outputs found

    Ebolavirus is evolving but not changing: No evidence for functional change in EBOV from 1976 to the 2014 outbreak

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    The 2014 epidemic of Ebola virus disease (EVD) has had a devastating impact in West Africa. Sequencing of ebolavirus (EBOV) from infected individuals has revealed extensive genetic variation, leading to speculation that the virus may be adapting to humans, accounting for the scale of the 2014 outbreak. We computationally analyze the variation associated with all EVD outbreaks, and find none of the amino acid replacements lead to identifiable functional changes. These changes have minimal effect on protein structure, being neither stabilizing nor destabilizing, are not found in regions of the proteins associated with known functions and tend to cluster in poorly constrained regions of proteins, specifically intrinsically disordered regions. We find no evidence that the difference between the current and previous outbreaks is due to evolutionary changes associated with transmission to humans. Instead, epidemiological factors are likely to be responsible for the unprecedented spread of EVD

    Adaptive HIV-1 evolutionary trajectories are constrained by protein stability

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    Despite the use of combination antiretroviral drugs for the treatment of HIV-1 infection, the emergence of drug resistance remains a problem. Resistance may be conferred either by a single mutation or a concerted set of mutations. The involvement of multiple mutations can arise due to interactions between sites in the amino acid sequence as a consequence of the need to maintain protein structure. To better understand the nature of such epistatic interactions, we reconstructed the ancestral sequences of HIV-1's Pol protein, and traced the evolutionary trajectories leading to mutations associated with drug resistance. Using contemporary and ancestral sequences we modelled the effects of mutations (i.e. amino acid replacements) on protein structure to understand the functional effects of residue changes. Although the majority of resistance-associated sequences tend to destabilise the protein structure, we find there is a general tendency for protein stability to decrease across HIV-1's evolutionary history. That a similar pattern is observed in the non-drug resistance lineages indicates that non-resistant mutations, for example, associated with escape from the immune response, also impacts on protein stability. Maintenance of optimal protein structure therefore represents a major constraining factor to the evolution of HIV-1

    Significance of Coriolis Force on Eyring-Powell Flow Over A Rotating Non-uniform Surface

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    Coriolis force plays significant roles in natural phenomena such as atmospheric dynamics, weather patterns, etc. Meanwhile, to circumvent the unreliability of Newtonian law for flows involving varying speed, Eyring-Powell fluid equations are used in computational fluid dynamics. This paper unravels the significance of Coriolis force on Eyring-Powell fluid over the rotating upper horizontal surface of a paraboloid of revolution. Relevant body forces are included in the Navier-Stokes equations to model the flow of non-Newtonian Eyring-Powell fluid under the influence of Coriolis force. Using similarity transformation, the governing equations are nondimensionalized, thereby transforming the nonlinear partial differential equations to a system of boundary value nonlinear ordinary differential equations. The shooting technique is adopted to convert the boundary value problem to an initial value problem, which is in turn solved using the Runge-Kutta-Gill Scheme. At low Coriolis force, temperature profiles increase as Eyring-Powell parameter increases, whereas at high Coriolis force, temperature profiles decrease with increasing Eyring-Powell parameter

    Best distribution and plotting positions of daily maximum flood estimation at Ona River in Ogun-Oshun river basin, Nigeria

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    The paper discusses how Normal, Lognormal, and log-Pearson type 3 distributions were investigated as distributions for modelling at-site annual maximum flood flows using the Hazen, Weibull, and California plotting positions at Ogun-Oshun river basin in Nigeria.  All the probability distributions when matched with Weibull plotting position gave similar values near the center of the distribution but varied considerably in the tails.  The Weibull plotting position when matched with Normal, Log-normal and Log Pearson Type III probability distributions gave the highest coefficient of determinations of 0.967, 0.987, and 0.986 respectively.  Hazen plotting position gave minimal errors with the RMSE of 6.988, 6.390, and 6.011 for Normal, Log-normal, and Log-Pearson Type III probability distributions respectively.  This implies that, predicting statistically using Hazen plotting position, the central tendency of predicted values to deviate from observed flows will be minimal for the period under consideration.  Minimum absolute differences of 2.3516 and 0.5763 at 25- and 50-year return periods were obtained under the Log-Pearson Type III distribution when matched with Weibull plotting position, while an absolute difference of 0.2338 at 100-year return period was obtained under the Log-Pearson Type III distribution when matched with California plotting position.  Comparing the probability distributions, Log-Pearson Type III distribution with the least absolute differences for all the plotting positions is the best distribution among the three for Ona River under Ogun-osun river basin study location

    Proximate and Phytochemical Analyses of Solanum aethiopicum L. and Solanum macrocarpon L. Fruits

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    Chemical analyses were carried out to determine the nutritional and phytochemical constituents of fruits of two indigenous Africa eggplants, S. aethiopicum L. and S. macrocarpon L. Proximate analysis of fresh fruits of S. aethiopicum L. (per 100 g) showed: 89.27 ± 0.12 g moisture, 2.24 ± 0.03 g protein, 0.52 ± 0.04 g fat, 0.87 ± 0.03 g ash, 2.96 ± 0.08 g crude fiber, 4.14 ± 0.11 g carbohydrate and 498.47 ± 2.14 mg calcium, 1.98 ± 0.10 mg magnesium and 1.02 ± 0.02 mg iron. Fresh fruits of S. macrocarpon L. contained (per 100 g): 92.50 ± 0.14 g moisture, 1.33 ± 0.05 g protein, 0.17 ± 0.01 g fat, 0.47 ± 0.02 g ash, 1.11 ± 0.03 g crude fiber, 4.42 ± 0.12 g carbohydrate, 101.56 ± 1.21 mg calcium, 1.01 ± 0.08 mg magnesium and 0.70 ± 0.01 mg iron. There was a significant presence of alkaloids, saponins, flavonoids, tannins and ascorbic acid in both fruits; terpenoids was found in trace amount. Steroids were present in S. aethiopicum L. and absent in S. macrocarpon L. These phytochemicals are of therapeutic importance; their presence in S. aethiopicum and S. macrocarpon fruits indicate the beneficial effects of the plants. Solanum aethiopicum L. contained higher levels of the beneficial agents than S. macrocarpon L. The two indigenous eggplants are not only nutritionally and therapeutically valuable, but also have the potential of providing precursors for the synthesis of useful drugs

    Facial Image Verification and Quality Assessment System -FaceIVQA

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    Although several techniques have been proposed for predicting biometric system performance using quality values, many of the research works were based on no-reference assessment technique using a single quality attribute measured directly from the data. These techniques have proved to be inappropriate for facial verification scenarios and inefficient because no single quality attribute can sufficient measure the quality of a facial image. In this research work, a facial image verification and quality assessment framework (FaceIVQA) was developed. Different algorithms and methods were implemented in FaceIVQA to extract the faceness, pose, illumination, contrast and similarity quality attributes using an objective full-reference image quality assessment approach. Structured image verification experiments were conducted on the surveillance camera (SCface) database to collect individual quality scores and algorithm matching scores from FaceIVQA using three recognition algorithms namely principal component analysis (PCA), linear discriminant analysis (LDA) and a commercial recognition SDK. FaceIVQA produced accurate and consistent facial image assessment data. The Result shows that it accurately assigns quality scores to probe image samples. The resulting quality score can be assigned to images captured for enrolment or recognition and can be used as an input to quality-driven biometric fusion systems.DOI:http://dx.doi.org/10.11591/ijece.v3i6.503

    DNA polymerase B deficiency is linked to aggressive breast cancer: a comprehensive analysis of gene copy number, mRNA and protein expression in multiple cohorts

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    Short arm of chromosome 8 is a hot spot for chromosomal breaks, losses and amplifications in breast cancer. Although such genetic changes may have phenotypic consequences, the identity of candidate gene(s) remains to be clearly defined. Pol β gene is localized to chromosome 8p12 - p11 and encodes a key DNA base excision repair protein. Pol β may be a tumour suppressor and involved in breast cancer pathogenesis. We conducted the first and the largest study to comprehensively evaluate pol β in breast cancer. We investigated pol β gene copy number changes in two cohorts (n=128 & n=1952), pol β mRNA expression in two cohorts (n=249 & n=1952) and pol β protein expression in two cohorts (n=1406 & n=252). Artificial neural network analysis for pol β interacting genes was performed in 249 tumours. For mechanistic insights, pol β gene copy number changes, mRNA and protein levels were investigated together in 1 28 tumours and validated in 1952 tumours. Low pol β mRNA expression as well as low pol β protein expression was associated high grade, lymph node positivity, pleomorphism, triple negative, basal - like phenotypes and poor survival (ps<0.001). In oestrogen receptor (ER) positive sub - group that received tamoxifen, low pol β protein remains associated with aggressive phenotype and poor survival (ps<0.001). Artificial neural network analysis revealed ER as a top pol β interacting gene. Mechanistically, there was strong positive correlation between pol β gene copy number changes and pol β mRNA expression (p<0.0000001) and between pol β mRNA and pol β protein expression (p<0.0000001). This is the first study to provide evidence that pol β deficiency is linked to aggressive breast cancer and may have prognostic and predictive significance in patients

    Sulfoxide Synthase versus Cysteine Dioxygenase Reactivity in a Nonheme Iron Enzyme

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    The sulfoxide synthase EgtB represents a unique family of nonheme iron enzymes that catalyze the formation of a C-S bond between N-α-trimethyl histidine and γ-glutamyl cysteine, which is the key step in the biosynthesis of ergothioneine, an important amino acid related to aging. A controversy has arisen regarding its catalytic mechanism related to the function of the active-site Tyr377 residue. The biosynthesis of ergothioneine in EgtB shows structural similarities to cysteine dioxygenase which transfers two oxygen atoms to the thiolate group of cysteine. The question, therefore, is how do EgtB enzymes catalyze the C-S bond-formation reaction, while also preventing a dioxygenation of its cysteinate substrate? In this work we present a quantum mechanics/molecular mechanics study into the mechanism of sulfoxide synthase enzymes as compared to cysteine dioxygenase enzymes and present pathways for both reaction channels in EgtB. We show that EgtB contains a conserved tyrosine residue that reacts via proton-coupled electron transfer with the iron(III)-superoxo species and creates an iron(III)-hydroperoxo intermediate, thereby preventing the possible thiolate dioxygenation side reaction. The nucleophilic C-S bond-formation step happens subsequently concomitant to relay of the proton of the iron(II)-hydroperoxo back to Tyr377. This is the rate-determining step in the reaction cycle and is followed by hydrogen-atom transfer from the CE1-H group of trimethyl histidine substrate to iron(II)-superoxo. In the final step, a quick and almost barrierless sulfoxidation leads to the sulfoxide product complexes. The work highlights a unique machinery and active-site setup of the enzyme that drives the sulfoxide synthase reaction

    The multidisciplinary management of type 2 and gestational diabetes in pregnancy

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    The UK is experiencing a dramatic increase in the prevalence of type 2 diabetes mellitus (T2D). Consequently, there is a corresponding increase in diabetes in pregnancy, with 87.5% of pregnancies in the UK complicated by diabetes due to gestational diabetes mellitus (GDM), and 27% of those with pre-existing diabetes having T2D (National Centre for Health and Clinical Excellence (NICE), 2008a). Although the risks to mother and baby are similar to type 1 diabetes (T1D), the approach and management often differ. Women with GDM and T2D are more likely to be older, multiparous and live in deprived areas. Certain ethnic groups are more prone to GDM and T2D, and there is a strong association between being overweight or obese and diabetes. Women who develop GDM in pregnancy also have an increased risk of T2D in later life (Diabetes UK, 2011a). Some surveys, such as the Confidential Enquiry into Maternal and Child Health (CEMACH, 2007a) have shown that women with T2D often receive suboptimum care prior to conception and in early pregnancy. This paper presents an overview of the multidisciplinary management of T2D and GDM in pregnancy and identifies areas where care may be lacking for these women

    Bacterial vaginosis: Prevalence and associated risk factors among non-pregnant women of reproductive age attending a Nigerian tertiary hospital

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    Aim: To determine the prevalence and risk factors associated with bacterial vaginosis (BV) among non-pregnant women of reproductive age group.Methods: A cross-sectional study among non-pregnant asymptomatic women aged 19 to 45 years, attending the gynaecological clinic at University of Ilorin Teaching Hospital, Ilorin, Nigeria. Participants were counselled and an informed consent was obtained. This was followed by vaginal swabs for microscopy, culture and sensitivity. Diagnosis of BV was by Nugent’s criteria. Data analysis was by Statistical Package for Social Sciences (SPSS) version 20.0. Chi-square and Yates corrected chi-square were calculated, and p value &lt;0.05 was significant.Results: Among the 212 participants, prevalence of BV was 40.1%; it was common among women aged 25-34 years (50; 58.8%), the married (77; 90.6%) and those with tertiary education (39; 45.9%). The risk factors for BV were common among women with laboratory evidence of the infection, however statistically significant risk factors were the use of intrauterine device (OR 1.61, 95%CI 0.543-4.759; p0.020) and previous voluntary termination of pregnancy (OR 1.04, 95%CI 0.600-1.808; p0.047).Conclusion: There was high prevalence of bacterial vaginosis in the study population. Universal screening and treatment of cases may assist in lowering the associated morbidity
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