172 research outputs found

    A Spatio-Temporal Data Imputation Model for Supporting Analytics at the Edge

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    Current applications developed for the Internet of Things (IoT) usually involve the processing of collected data for delivering analytics and support efficient decision making. The basis for any processing mechanism is data analysis, usually having as an outcome responses in various analytics queries defined by end users or applications. However, as already noted in the respective literature, data analysis cannot be efficient when missing values are present. The research community has already proposed various missing data imputation methods paying more attention of the statistical aspect of the problem. In this paper, we study the problem and propose a method that combines machine learning and a consensus scheme. We focus on the clustering of the IoT devices assuming they observe the same phenomenon and report the collected data to the edge infrastructure. Through a sliding window approach, we try to detect IoT nodes that report similar contextual values to edge nodes and base on them to deliver the replacement value for missing data. We provide the description of our model together with results retrieved by an extensive set of simulations on top of real data. Our aim is to reveal the potentials of the proposed scheme and place it in the respective literature

    Equity in development and access to health services in the Wild Coast of South Africa: the community view through four linked cross-sectional studies between 1997 and 2007

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    <p>Abstract</p> <p>Background</p> <p>After election in 1994, the South African government implemented national and regional programmes, such as the Wild Coast Spatial Development Initiative (SDI), to provoke economic growth and to decrease inequities. CIET measured development in the Wild Coast region across four linked cross-sectional surveys (1997-2007). The 2007 survey was an opportunity to look at inequities since the original 1997 baseline, and how such inequities affect access to health care.</p> <p>Methods</p> <p>The 2000, 2004 and 2007 follow-up surveys revisited the communities of the 1997 baseline. Household-level multivariate analysis looked at development indicators and access to health in the context of inequities such as household crowding, access to protected sources of water, house roof construction, main food item purchased, and perception of community empowerment. Individual multivariate models accounted for age, sex, education and income earning opportunities.</p> <p>Results</p> <p>Overall access to protected sources of water increased since the baseline (from 20% in 1997 to 50% in 2007), yet households made of mud and grass, and households who bought basics as their main food item were still less likely to have protected sources of water. The most vulnerable, such as those with less education and less water and food security, were also less likely to have worked for wages leaving them with little chance of improving their standard of living (less education OR 0.59, 95%CI 0.37-0.94; less water security OR 0.67, 95%CI 0.48-0.93; less food security OR 0.43, 95%CI 0.29-0.64). People with less income were more likely to visit government services (among men OR 0.28, 95%CI 0.13-0.59; among women OR 0.33, 95%CI 0.20-0.54), reporting decision factors of cost and distance; users of private clinics sought out better service and medication. Lower food security and poorer house construction was also associated with women visiting government rather than private health services. Women with some formal education were nearly eight times more likely than women with no education to access health services for prevention rather than curative reasons (OR 7.65, 95%CI 4.10-14.25).</p> <p>Conclusion</p> <p>While there have been some improvements, the Wild Coast region still falls well below provincial and national standards in key areas such as access to clean water and employment despite years of government-led investment. Inequities remain prominent, particularly around access to health services.</p

    Potential of Host Markers Produced by Infection Phase-Dependent Antigen-Stimulated Cells for the Diagnosis of Tuberculosis in a Highly Endemic Area

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    CITATION: Chegou, N. N. et al. 2012. Potential of host markers produced by infection phase-dependent antigen-stimulated cells for the diagnosis of tuberculosis in a highly endemic area. PLoS ONE, 7(6): e38501, doi:10.1371/journal.pone.0038501.The original publication is available at http://journals.plos.org/plosoneBackground: Recent interferon gamma (IFN-Ξ³)-based studies have identified novel Mycobacterium tuberculosis (M.tb) infection phase-dependent antigens as diagnostic candidates. In this study, the levels of 11 host markers other than IFN-Ξ³, were evaluated in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens, for the diagnosis of TB disease. Methodology and Principal Findings: Five M.tb infection phase-dependent antigens, comprising of three DosR-regulon-encoded proteins (Rv2032, Rv0081, Rv1737c), and two resucitation promoting factors (Rv0867c and Rv2389c), were evaluated in a case-control study with 15 pulmonary TB patients and 15 household contacts that were recruited from a high TB incidence setting in Cape Town, South Africa. After a 7-day whole blood culture, supernatants were harvested and the levels of the host markers evaluated using the Luminex platform. Multiple antigen-specific host markers were identified with promising diagnostic potential. Rv0081-specific levels of IL-12(p40), IP-10, IL-10 and TNF-Ξ± were the most promising diagnostic candidates, each ascertaining TB disease with an accuracy of 100%, 95% confidence interval for the area under the receiver operating characteristics plots, (1.0 to 1.0). Conclusions: Multiple cytokines other than IFN-Ξ³ in whole blood culture supernatants after stimulation with M.tb infection phase-dependent antigens show promise as diagnostic markers for active TB. These preliminary findings should be verified in well-designed diagnostic studies employing short-term culture assays. Β© 2012 Chegou et al.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0038501Publisher's versio

    The Promoter of Rv0560c Is Induced by Salicylate and Structurally-Related Compounds in Mycobacterium tuberculosis

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    Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a major global health threat. During infection, bacteria are believed to encounter adverse conditions such as iron depletion. Mycobacteria synthesize iron-sequestering mycobactins, which are essential for survival in the host, via the intermediate salicylate. Salicylate is a ubiquitous compound which is known to induce a mild antibiotic resistance phenotype. In M. tuberculosis salicylate highly induces the expression of Rv0560c, a putative methyltransferase. We identified and characterized the promoter and regulatory elements of Rv0560c. PRv0560c activity was highly inducible by salicylate in a dose-dependent manner. The induction kinetics of PRv0560c were slow, taking several days to reach maximal activity, which was sustained over several weeks. Promoter activity could also be induced by compounds structurally related to salicylate, such as aspirin or para-aminosalicylic acid, but not by benzoate, indicating that induction is specific to a structural motif. The βˆ’10 and βˆ’35 promoter elements were identified and residues involved in regulation of promoter activity were identified in close proximity to an inverted repeat spanning the βˆ’35 promoter element. We conclude that Rv0560c expression is controlled by a yet unknown repressor via a highly-inducible promoter

    Appropriate DevR (DosR)-Mediated Signaling Determines Transcriptional Response, Hypoxic Viability and Virulence of Mycobacterium tuberculosis

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    Background: The DevR(DosR) regulon is implicated in hypoxic adaptation and virulence of Mycobacterium tuberculosis. The present study was designed to decipher the impact of perturbation in DevR-mediated signaling on these properties. Methodology/Principal Findings: M. tb complemented (Comp) strains expressing different levels of DevR were constructed in Mut1 * background (expressing DevR N-terminal domain in fusion with AphI (DevRN-Kan) and in Mut2DdevR background (deletion mutant). They were compared for their hypoxia adaptation and virulence properties. Diverse phenotypes were noted; basal level expression (,5.362.3 mM) when induced to levels equivalent to WT levels (,25.869.3 mM) was associated with robust DevR regulon induction and hypoxic adaptation (Comp 9 * and 10*), whereas low-level expression (detectable at transcript level) as in Comp 11 * and Comp15 was associated with an adaptation defect. Intermediate-level expression (,3.361.2 mM) partially restored hypoxic adaptation functions in Comp2, but not in Comp1 * bacteria that coexpressed DevRN-Kan. Comp * strains in Mut1 * background also exhibited diverse virulence phenotypes; high/very low-level DevR expression was associated with virulence whereas intermediate-level expression was associated with low virulence. Transcription profiling and gene expression analysis revealed up-regulation of the phosphate starvation response (PSR) in Mut1 * and Comp11 * bacteria, but not in WT/Mut2DdevR/other Comp strains, indicating a plasticity in expression pathways that is determined by the magnitude of signaling perturbation through DevRN-Kan

    Fumarate Reductase Activity Maintains an Energized Membrane in Anaerobic Mycobacterium tuberculosis

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    Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and central metabolism. We have developed a chemostat model of M. tuberculosis where growth rate was a function of dissolved oxygen concentration to analyze metabolic adaptation to hypoxia. A drop in dissolved oxygen concentration from 50 mmHg to 0.42 mmHg led to a 2.3 fold decrease in intracellular ATP levels with an almost 70-fold increase in the ratio of NADH/NAD+. This suggests that re-oxidation of this co-factor becomes limiting in the absence of a terminal electron acceptor. Upon oxygen limitation genes involved in the reverse TCA cycle were upregulated and this upregulation was associated with a significant accumulation of succinate in the extracellular milieu. We confirmed that this succinate was produced by a reversal of the TCA cycle towards the non-oxidative direction with net CO2 incorporation by analysis of the isotopomers of secreted succinate after feeding stable isotope (13C) labeled precursors. This showed that the resulting succinate retained both carbons lost during oxidative operation of the TCA cycle. Metabolomic analyses of all glycolytic and TCA cycle intermediates from 13C-glucose fed cells under aerobic and anaerobic conditions showed a clear reversal of isotope labeling patterns accompanying the switch from normoxic to anoxic conditions. M. tuberculosis encodes three potential succinate-producing enzymes including a canonical fumarate reductase which was highly upregulated under hypoxia. Knockout of frd, however, failed to reduce succinate accumulation and gene expression studies revealed a compensatory upregulation of two homologous enzymes. These major realignments of central metabolism are consistent with a model of oxygen-induced stasis in which an energized membrane is maintained by coupling the reductive branch of the TCA cycle to succinate secretion. This fermentative process may offer unique targets for the treatment of latent tuberculosis

    Potential of novel Mycobacterium tuberculosis infection phase-dependent antigens in the diagnosis of TB disease in a high burden setting

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    <p>Abstract</p> <p>Background</p> <p>Confirming tuberculosis (TB) disease in suspects in resource limited settings is challenging and calls for the development of more suitable diagnostic tools. Different <it>Mycobacterium tuberculosis (M.tb) </it>infection phase-dependent antigens may be differentially recognized in infected and diseased individuals and therefore useful as diagnostic tools for differentiating between <it>M.tb </it>infection states. In this study, we assessed the diagnostic potential of 118 different <it>M.tb </it>infection phase-dependent antigens in TB patients and household contacts (HHCs) in a high-burden setting.</p> <p>Methods</p> <p>Antigens were evaluated using the 7-day whole blood culture technique in 23 pulmonary TB patients and in 19 to 21 HHCs (total n = 101), who were recruited from a high-TB incidence community in Cape Town, South Africa. Interferon-gamma (IFN-Ξ³) levels in culture supernatants were determined by ELISA.</p> <p>Results</p> <p>Eight classical TB vaccine candidate antigens, 51 DosR regulon encoded antigens, 23 TB reactivation antigens, 5 TB resuscitation promoting factors (rpfs), 6 starvation and 24 other stress response-associated TB antigens were evaluated in the study. The most promising antigens for ascertaining active TB were the rpfs (Rv0867c, Rv2389c, Rv2450c, Rv1009 and Rv1884c), with Areas under the receiver operating characteristics curves (AUCs) between 0.72 and 0.80. A combination of <it>M.tb </it>specific ESAT-6/CFP-10 fusion protein, Rv2624c and Rv0867c accurately predicted 73% of the TB patients and 80% of the non-TB cases after cross validation.</p> <p>Conclusions</p> <p>IFN-Ξ³ responses to TB rpfs show promise as TB diagnostic candidates and should be evaluated further for discrimination between <it>M.tb </it>infection states.</p
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