Browsing by Author "Kumar, A"

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    Genetic signatures in the envelope glycoproteins of HIV-1 that associate with broadly neutralizing antibodies.
    (PLoS Comput Biol, 2010-10-07) Gnanakaran, S; Daniels, MG; Bhattacharya, T; Lapedes, AS; Sethi, A; Li, M; Tang, H; Greene, K; Gao, H; Haynes, BF; Cohen, MS; Shaw, GM; Seaman, MS; Kumar, A; Gao, F; Montefiori, DC; Korber, B
    A steady increase in knowledge of the molecular and antigenic structure of the gp120 and gp41 HIV-1 envelope glycoproteins (Env) is yielding important new insights for vaccine design, but it has been difficult to translate this information to an immunogen that elicits broadly neutralizing antibodies. To help bridge this gap, we used phylogenetically corrected statistical methods to identify amino acid signature patterns in Envs derived from people who have made potently neutralizing antibodies, with the hypothesis that these Envs may share common features that would be useful for incorporation in a vaccine immunogen. Before attempting this, essentially as a control, we explored the utility of our computational methods for defining signatures of complex neutralization phenotypes by analyzing Env sequences from 251 clonal viruses that were differentially sensitive to neutralization by the well-characterized gp120-specific monoclonal antibody, b12. We identified ten b12-neutralization signatures, including seven either in the b12-binding surface of gp120 or in the V2 region of gp120 that have been previously shown to impact b12 sensitivity. A simple algorithm based on the b12 signature pattern was predictive of b12 sensitivity/resistance in an additional blinded panel of 57 viruses. Upon obtaining these reassuring outcomes, we went on to apply these same computational methods to define signature patterns in Env from HIV-1 infected individuals who had potent, broadly neutralizing responses. We analyzed a checkerboard-style neutralization dataset with sera from 69 HIV-1-infected individuals tested against a panel of 25 different Envs. Distinct clusters of sera with high and low neutralization potencies were identified. Six signature positions in Env sequences obtained from the 69 samples were found to be strongly associated with either the high or low potency responses. Five sites were in the CD4-induced coreceptor binding site of gp120, suggesting an important role for this region in the elicitation of broadly neutralizing antibody responses against HIV-1.
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    Intensification of summer rainfall variability in the southeastern United States during recent decades
    (Journal of Hydrometeorology, 2010-08-01) Wang; H; Fu, R; Kumar, A; Li, W
    The variability of summer precipitation in the southeastern United States is examined in this study using 60-yr (1948-2007) rainfall data. The Southeast summer rainfalls exhibited higher interannual variability with more intense summer droughts and anomalous wetness in the recent 30 years (1978-2007) than in the prior 30 years (1948-77). Such intensification of summer rainfall variability was consistent with a decrease of light (0.1-1 mm day-1) and medium (1-10 mm day-1) rainfall events during extremely dry summers and an increase of heavy (.10 mm day-1) rainfall events in extremely wet summers. Changes in rainfall variability were also accompanied by a southward shift of the region of maximum zonal wind variability at the jet stream level in the latter period. The covariability between the Southeast summer precipitation and sea surface temperatures (SSTs) is also analyzed using the singular value decomposition (SVD) method. It is shown that the increase of Southeast summer precipitation variability is primarily associated with a higher SST variability across the equatorial Atlantic and also SST warming in the Atlantic. © 2010 American Meteorological Society.
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    Viewing the Role of Alternate Care Service Pathways in the Emergency Care System through a Causal Loop Diagram Lens
    (Systems) Kumar, A; Liu, Z; Ansah, JP; Ng, YY; Leong, BSH; Matchar, DB; Ong, MEH; Siddiqui, FJ
    Globally, Emergency Care Systems (ECS) are a critical resource that needs to be used judiciously as demand can easily exceed supply capacity. Sub-optimal ECS use contributes to Emergency Department (ED) crowding; this adversely affects ECS as well as system-wide service performance. Alternate Care Service Pathways (ACSPs) are innovations intended to mitigate ED crowding by re-routing less-urgent cases to sites of care other than the ED. As in other countries, policymakers in Singapore need to respond to increasing ED utilization and are evaluating the introduction of ACSPs. However, developing ACSPs is costly, entails tinkering with established critical services, and runs the risk of unintended adverse consequences. Through a Causal Loop Diagram (CLD) developed in four stages, we present a view of the current Singapore ECS and the intended role of ACSPs in relieving its stress. This exercise suggests that to be successful ACSPs must change the prevailing mental model of the ED as a “one-stop shop” but should focus on integrating with primary care. The discussions stimulated by the development, critiquing, and revision of the CLD highlighted the importance of accounting for the reservations of stakeholders for changes. The CLD has enhanced shared understanding and will be used to guide quantitative simulation modeling to promote informed policy.