Distribution system reconfiguration (DSR) is a multi-objective, nonlinear problem. This paper introduces a new, fast, nondominated sorting genetic algorithm (FNSGA) for the purpose of solving the DSR ...problem in normal operation by satisfying all objectives simultaneously with a relatively small number of generations and relatively short computation time. The objectives of the problem are to minimize real power losses and improve the voltage profile and load balancing index with minimum switching operations. Instead of generating several ranks from the nondominated set of solutions, this algorithm deals with only one rank; then the most suitable solution is chosen according to the operator's wishes. If there is no preference and all objectives have the same degree of importance, the best solution is determined by simply considering the sum of the normalized objective values. Also, a guided mutation operation is applied instead of a random one to speed up convergence. Radial system topology is satisfied using graph theory by formulating the branch-bus incidence matrix (BBIM) and checking the rank of each topology. To test the algorithm, it was applied to two widely studied test systems and a real one. The results show the efficiency of this algorithm as compared to other methods in terms of achieving all the goals simultaneously with reasonable population and generation sizes and without using a mutation rate, which is usually problem-dependent.
Background. Serious non-AIDS events cause substantial disease and death despite human immunodeficiency virus (HIV) suppression with antiretroviral therapy (ART). Biomarkers of inflammation, ...coagulation cascade activation, and fibrosis predict these end-organ events. We aimed to determine whether ART initiation during acute HIV infection would attenuate changes in these biomarker levels. Methods. Plasma samples were obtained from participants starting ART during acute or chronic HIV infection and from HIV-uninfected participants from Bangkok, Thailand. Biomarkers of inflammation (C-reactive protein CRP, interleukin 6, soluble interleukin 6 receptor sIL-6R, soluble gp130, tumor necrosis factor TNF), enterocyte turnover (intestinal fatty acid binding protein I-FABP), lipopolysaccharide-induced monocyte activation (soluble CD14 sCD14), coagulation cascade activation D-dimer, and fibrosis (hyaluronic acid HA) were measured at baseline and through 96 weeks of ART. Results. CRP, TNF, sIL-6R, I-FABP, sCD14, D-dimer, and HA levels were elevated in acute HIV infection. Early ART was associated with increased I-FABP levels but normalization of TNF, sIL-6R, and D-dimer levels. CRP, sCD14, and HA levels decreased during ART but remained elevated compared with HIV-uninfected participants. Higher sCD14, CRP, and D-dimer levels were associated with higher peripheral blood mononuclear cell and gut integrated HIV DNA levels. Decreases in sCD14 and CRP levels were correlated with increases in CD4 T-cell counts. Conclusions. ART initiated in early acute HIV infection was associated with normalization of the coagulation cascade and several systemic inflammatory biomarkers, but the acute-phase response, enterocyte turnover, monocyte activation, and fibrosis biomarkers remained elevated. Additional interventions to attenuate inflammation may be needed to optimize clinical outcomes in persons with HIV infection.
This paper proposes a new interleaved non-isolated high step-up dc-dc converter for interfacing renewable energy applications. The proposed converter achieves a very high step-up voltage gain by ...using two coupled inductors and a voltage multiplier cell. This topology utilizes the interleaved boost converter in the input side, and the input current is shared with low ripple. Moreover, a voltage multiplier cell with the secondary windings of the coupled inductors is employed in the output side to achieve the interleaved energy storage. The voltage stress on the semiconductor switches and the passive components is significantly reduced and lower than the output voltage. The aforementioned converter can be operated without an extreme duty cycle or a high turns ratio. The reverse recovery problem of the diodes is mitigated, and the leakage energy is recycled. Furthermore, by implementing low-voltage-rated MOSFETs with a small ON-resistance, the conduction losses can be reduced, and the efficiency can be improved. The topology is fed by a single input voltage, and the mathematical expression is methodically explored. The operation principle of the proposed converter and the comparison between the proposed converter with other topologies are discussed. The design, parameters selection, and experimental results are thoroughly introduced. A 32 to 800 V-dc is verified and simulated by using PLECS. Consequently, a 400 W hardware prototype is verified to validate the theory and the design.
The RV144 clinical trial of a prime/boost immunizing regimen using recombinant canary pox (ALVAC-HIV) and two gp120 proteins (AIDSVAX B and E) was previously shown to have a 31.2% efficacy rate. ...Plasma specimens from vaccine and placebo recipients were used in an extensive set of assays to identify correlates of HIV-1 infection risk. Of six primary variables that were studied, only one displayed a significant inverse correlation with risk of infection: the antibody (Ab) response to a fusion protein containing the V1 and V2 regions of gp120 (gp70-V1V2). This finding prompted a thorough examination of the results generated with the complete panel of 13 assays measuring various V2 Abs in the stored plasma used in the initial pilot studies and those used in the subsequent case-control study. The studies revealed that the ALVAC-HIV/AIDSVAX vaccine induced V2-specific Abs that cross-react with multiple HIV-1 subgroups and recognize both conformational and linear epitopes. The conformational epitope was present on gp70-V1V2, while the predominant linear V2 epitope mapped to residues 165-178, immediately N-terminal to the putative α4β7 binding motif in the mid-loop region of V2. Odds ratios (ORs) were calculated to compare the risk of infection with data from 12 V2 assays, and in 11 of these, the ORs were ≤1, reaching statistical significance for two of the variables: Ab responses to gp70-V1V2 and to overlapping V2 linear peptides. It remains to be determined whether anti-V2 Ab responses were directly responsible for the reduced infection rate in RV144 and whether anti-V2 Abs will prove to be important with other candidate HIV vaccines that show efficacy, however, the results support continued dissection of Ab responses to the V2 region which may illuminate mechanisms of protection from HIV-1 infection and may facilitate the development of an effective HIV-1 vaccine.
In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 ...infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection.
ClinicalTrials.gov NCT00223080.
Progress in HIV vaccine development Hsu, Denise C.; O'Connell, Robert J.
Human vaccines & immunotherapeutics,
05/2017, Letnik:
13, Številka:
5
Journal Article
Recenzirano
Odprti dostop
An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of ...functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials. The induction of bnAb using mimics of the natural Env trimer or B-cell lineage vaccine design is still in pre-clinical phase. An attempt at optimization of protective functional antibodies will be assessed next with the efficacy trial (HVTN702) about to start. With on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb, the prospects for a preventive HIV vaccine have never been more promising.
Advances in flow cytometry and other single-cell technologies have enabled high-dimensional, high-throughput measurements of individual cells as well as the interrogation of cell population ...heterogeneity. However, in many instances, computational tools to analyze the wealth of data generated by these technologies are lacking. Here, we present a computational framework for unbiased combinatorial polyfunctionality analysis of antigen-specific T-cell subsets (COMPASS). COMPASS uses a Bayesian hierarchical framework to model all observed cell subsets and select those most likely to have antigen-specific responses. Cell-subset responses are quantified by posterior probabilities, and human subject-level responses are quantified by two summary statistics that describe the quality of an individual's polyfunctional response and can be correlated directly with clinical outcome. Using three clinical data sets of cytokine production, we demonstrate how COMPASS improves characterization of antigen-specific T cells and reveals cellular 'correlates of protection/immunity' in the RV144 HIV vaccine efficacy trial that are missed by other methods. COMPASS is available as open-source software.
An important approach to stopping the AIDS epidemic is the development of a vaccine that elicits antibodies that block virus capture, the initial interactions of HIV-1 with the target cells, and ...replication. We utilized a previously developed qRT-PCR-based assay to examine the effects of broadly neutralizing antibodies (bNAbs), plasma from vaccine trials, and monoclonal antibodies (mAbs) on virus capture and replication. A panel of bNAbs inhibited primary HIV-1 replication in PBMCs but not virus capture. Plasma from RV144 and RV305 trial vaccinees demonstrated inhibition of virus capture with the HIV-1 subtype prevalent in Thailand. Several RV305 derived V2-specific mAbs inhibited virus replication. One of these RV305 derived V2-specific mAbs inhibited both virus capture and replication, demonstrating that it is possible to elicit antibodies by vaccination that inhibit virus capture and replication. Induction of a combination of such antibodies may be the key to protection from HIV-1 acquisition.
•RV144 and RV305 vaccinee plasma inhibited primary HIV-1 capture by PBMCs.•One of the RV305 elicited mAb inhibited both virus capture and replication.•Vaccination can induce antibodies that inhibit HIV-1 capture and replication.
Team-based learning (TBL) is a form of student-centered active learning in which students independently study new conceptual material before it is treated in the classroom, and then subsequently ...spend considerable classroom time working in groups on increasingly challenging problems and applications based on that new material. TBL provides students with opportunities to not only learn course content better than in the traditional lecture-based setting, but also to develop various transferable professional skills, such as self-directed independent learning, problem solving, and interpersonal team skills. Because of these potential benefits, TBL was adapted as the principal teaching and learning strategy in a two-course sophomore-level electric circuit theory sequence, where it has been used since 2010. This paper describes beneficial changes that have evolved in the implementation of TBL in the circuit theory sequence. Those changes have been based, in part, on student evaluations of the strategy, which are described. Finally, instruments used to assess student learning in the TBL-taught courses are also described. They provide evaluation information that suggests the described revised version of TBL is an effective way to facilitate learning of both technical content and several professional skills in the sophomore-level electric circuit theory sequence.
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