Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies.

BACKGROUND: Previous clinical efficacy trials failed to support the continued development of recombinant gp120 (rgp120) as a candidate HIV vaccine. However, the recent RV144 HIV vaccine trial in Thailand showed that a prime/boost immunization strategy involving priming with canarypox vCP1521 followed by boosting with rgp120 could provide significant, although modest, protection from HIV infection. Based on these results, there is renewed interest in the development of rgp120 based antigens for follow up vaccine trials, where this immunization approach can be applied to other cohorts at high risk for HIV infection. Of particular interest are cohorts in Africa, India, and China that are infected with clade C viruses. METHODOLOGY/PRINCIPAL FINDINGS: A panel of 10 clade C rgp120 envelope proteins was expressed in 293 cells, purified by immunoaffinity chromatography, and used to immunize guinea pigs. The resulting sera were collected and analyzed in checkerboard experiments for rgp120 binding, V3 peptide binding, and CD4 blocking activity. Virus neutralization studies were carried out with two different assays and two different panels of clade C viruses. A high degree of cross reactivity against clade C and clade B viruses and viral proteins was observed. Most, but not all of the immunogens tested elicited antibodies that neutralized tier 1 clade B viruses, and some sera neutralized multiple clade C viruses. Immunization with rgp120 from the CN97001 strain of HIV appeared to elicit higher cross neutralizing antibody titers than the other antigens tested. CONCLUSIONS/SIGNIFICANCE: While all of the clade C antigens tested were immunogenic, some were more effective than others in eliciting virus neutralizing antibodies. Neutralization titers did not correlate with rgp120 binding, V3 peptide binding, or CD4 blocking activity. CN97001 rgp120 elicited the highest level of neutralizing antibodies, and should be considered for further HIV vaccine development studies.

The Emergence of Access Controls in Small-Scale Fishing Commons: A Comparative Analysis of Individual Licenses and Common Property-Rights in Two Mexican Communities

Addressing global fisheries overexploitation requires better understanding of how small-scale fishing communities in developing countries limit access to fishing grounds. We analyze the performance of a system based on individual licenses and a common property-rights regime in their ability to generate incentives for self-governance and conservation of fishery resources. Using a qualitative before-after-control-impact approach, we compare two neighbouring fishing communities in the Gulf of California, Mexico. Both were initially governed by the same permit system, are situated in the same ecosystem, use similar harvesting technology, and have overharvested similar species. One community changed to a common property-right regime, enabling the emergence of access controls and avoiding overexploitation of benthic resources, while the other community, still relies on the permit system. We discuss the roles played by power, institutions, socio-historic, and biophysical factors to develop access controls. © 2012 The Author(s).

Comparative analyses of seven algorithms for copy number variant identification from single nucleotide polymorphism arrays.

Determination of copy number variants (CNVs) inferred in genome wide single nucleotide polymorphism arrays has shown increasing utility in genetic variant disease associations. Several CNV detection methods are available, but differences in CNV call thresholds and characteristics exist. We evaluated the relative performance of seven methods: circular binary segmentation, CNVFinder, cnvPartition, gain and loss of DNA, Nexus algorithms, PennCNV and QuantiSNP. Tested data included real and simulated Illumina HumHap 550 data from the Singapore cohort study of the risk factors for Myopia (SCORM) and simulated data from Affymetrix 6.0 and platform-independent distributions. The normalized singleton ratio (NSR) is proposed as a metric for parameter optimization before enacting full analysis. We used 10 SCORM samples for optimizing parameter settings for each method and then evaluated method performance at optimal parameters using 100 SCORM samples. The statistical power, false positive rates, and receiver operating characteristic (ROC) curve residuals were evaluated by simulation studies. Optimal parameters, as determined by NSR and ROC curve residuals, were consistent across datasets. QuantiSNP outperformed other methods based on ROC curve residuals over most datasets. Nexus Rank and SNPRank have low specificity and high power. Nexus Rank calls oversized CNVs. PennCNV detects one of the fewest numbers of CNVs.

Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in Botswana.

Cryptococcus neoformans var. grubii (Cng) is the most common cause of fungal meningitis, and its prevalence is highest in sub-Saharan Africa. Patients become infected by inhaling airborne spores or desiccated yeast cells from the environment, where the fungus thrives in avian droppings, trees and soil. To investigate the prevalence and population structure of Cng in southern Africa, we analysed isolates from 77 environmental samples and 64 patients. We detected significant genetic diversity among isolates and strong evidence of geographic structure at the local level. High proportions of isolates with the rare MATa allele were observed in both clinical and environmental isolates; however, the mating-type alleles were unevenly distributed among different subpopulations. Nearly equal proportions of the MATa and MATα mating types were observed among all clinical isolates and in one environmental subpopulation from the eastern part of Botswana. As previously reported, there was evidence of both clonality and recombination in different geographic areas. These results provide a foundation for subsequent genomewide association studies to identify genes and genotypes linked to pathogenicity in humans.

Restorative Justice and Political Forgiveness: A Comparative Study of Truth and Reconciliation Commissions

This research project involves a comparative, cross-national study of truth and reconciliation commissions (TRCs) in countries around the world that have used these extra-judicial institutions to pursue justice and promote national reconciliation during periods of democratic transition or following a civil conflict marked by intense violence and severe human rights abuses. An important objective of truth and reconciliation commissions involves instituting measures to address serious human rights abuses that have occurred as a result of discrimination, ethnocentrism and racism. In recent years, rather than solely utilizing traditional methods of conflict resolution and criminal prosecution, transitional governments have established truth and reconciliation commissions as part of efforts to foster psychological, social and political healing.

The primary objective of this research project is to determine why there has been a proliferation of truth and reconciliation commissions around the world in recent decades, and assess whether the perceived effectiveness of these commissions is real and substantial. In this work, using a multi-method approach that involves quantitative and qualitative analysis, I consider the institutional design and structural composition of truth and reconciliation commissions, as well as the roles that these commissions play in the democratic transformation of nations with a history of civil conflict and human rights violations.

In addition to a focus on institutional design of truth and reconciliation commissions, I use a group identity framework that is grounded in social identity theory to examine the historical background and sociopolitical context in which truth commissions have been adopted in countries around the world. This group identity framework serves as an invaluable lens through which questions related to truth and reconciliation commissions and other transitional justice mechanisms can be explored. I also present a unique theoretical framework, the reconciliatory democratization paradigm, that is especially useful for examining the complex interactions between the various political elements that directly affect the processes of democratic consolidation and reconciliation in countries in which truth and reconciliation commissions have been established. Finally, I tackle the question of whether successor regimes that institute truth and reconciliation commissions can effectively address the human rights violations that occurred in the past, and prevent the recurrence of these abuses.

A Comparative Review of Computational Methods as Applied to Gold(I) Complexes and Mechanisms

In the last two decades, the field of homogeneous gold catalysis has been

extremely active, growing at a rapid pace. Another rapidly-growing field—that of

computational chemistry—has often been applied to the investigation of various gold-

catalyzed reaction mechanisms. Unfortunately, a number of recent mechanistic studies

have utilized computational methods that have been shown to be inappropriate and

inaccurate in their description of gold chemistry. This work presents an overview of

available computational methods with a focus on the approximations and limitations

inherent in each, and offers a review of experimentally-characterized gold(I) complexes

and proposed mechanisms as compared with their computationally-modeled

counterparts. No aim is made to identify a “recommended” computational method for

investigations of gold catalysis; rather, discrepancies between experimentally and

computationally obtained values are highlighted, and the systematic errors between

different computational methods are discussed.