Development of a Humanized HLA-A2.1/DP4 Transgenic Mouse Model and the Use of This Model to Map HLA-DP4-Restricted Epitopes of HBV Envelope Protein

A new homozygous humanized transgenic mouse strain, HLA-A2.1+/+HLA-DP4+/+ hCD4+/+mCD4−/−IAβ−/−β2m−/− (HLA-A2/DP4), was obtained by crossing the previously characterized HLA-A2+/+β2m−/− (A2) mouse and our previously created HLA-DP4+/+ hCD4+/+mCD4−/−IAβ−/− (DP4) mouse. We confirmed that the transgenes (HLA-A2, HLA-DP4, hCD4) inherited from the parental A2 and DP4 mice are functional in the HLA-A2/DP4 mice. After immunizing HLA-A2/DP4 mice with a hepatitis B DNA vaccine, hepatitis B virus-specific antibodies, HLA-A2-restricted and HLA-DP4-restricted responses were observed to be similar to those in naturally infected humans. Therefore, the present study demonstrated that HLA-A2/DP4 transgenic mice can faithfully mimic human cellular responses. Furthermore, we reported four new HLA-DP4-restricted epitopes derived from HBsAg that were identified in both vaccinated HLA-A2/DP4 mice and HLA-DP4-positive human individuals. The HLA-A2/DP4 mouse model is a promising preclinical animal model carrying alleles present to more than a quarter of the human population. This model should facilitate the identification of novel HLA-A2- and HLA-DP4-restricted epitopes and vaccine development as well as the characterization of HLA-DP4-restricted responses against infection in humans

The historical origins of corruption in the developing world: a comparative analysis of East Asia

A new approach has emerged in the literature on corruption in the developing world that breaks with the assumption that corruption is driven by individualistic self-interest and, instead, conceptualizes corruption as an informal system of norms and practices. While this emerging neo-institutionalist approach has done much to further our understanding of corruption in the developing world, one key question has received relatively little attention: how do we explain differences in the institutionalization of corruption between developing countries? The paper here addresses this question through a systematic comparison of seven developing and newly industrialized countries in East Asia. The argument that emerges through this analysis is that historical sequencing mattered: countries in which the "political marketplace" had gone through a process of concentration before universal suffrage was introduced are now marked by less harmful types of corruption than countries where mass voting rights where rolled out in a context of fragmented political marketplaces. The paper concludes by demonstrating that this argument can be generalized to the developing world as a whole

Heat Shock Proteins and Amateur Chaperones in Amyloid-Beta Accumulation and Clearance in Alzheimer’s Disease

The pathologic lesions of Alzheimer’s disease (AD) are characterized by accumulation of protein aggregates consisting of intracellular or extracellular misfolded proteins. The amyloid-β (Aβ) protein accumulates extracellularly in senile plaques and cerebral amyloid angiopathy, whereas the hyperphosphorylated tau protein accumulates intracellularly as neurofibrillary tangles. “Professional chaperones”, such as the heat shock protein family, have a function in the prevention of protein misfolding and subsequent aggregation. “Amateur” chaperones, such as apolipoproteins and heparan sulfate proteoglycans, bind amyloidogenic proteins and may affect their aggregation process. Professional and amateur chaperones not only colocalize with the pathological lesions of AD, but may also be involved in conformational changes of Aβ, and in the clearance of Aβ from the brain via phagocytosis or active transport across the blood–brain barrier. Thus, both professional and amateur chaperones may be involved in the aggregation, accumulation, persistence, and clearance of Aβ and tau and in other Aβ-associated reactions such as inflammation associated with AD lesions, and may, therefore, serve as potential targets for therapeutic intervention

Luminescence quenching by OH groups in highly Er-doped phosphate glasses

Highly (up to 4 mol% Er2O3) Er-doped phosphate bulk glasses have been prepd. by common glass-melting techniques. Afterwards, a heat treatment was performed on the as-melted samples. The photoluminescence lifetime of Er ions for the 4I13/2-4I15/2 transition increases substantially, typically from 3 ms up to 7 ms for a sample doped with 2 mol% Er2O3, due to the heat treatment. The increase of the lifetime is ascribed to a decrease in concn. of hydroxyl groups incorporated in the glass, which is confirmed by IR absorption spectroscopic measurements. The photoluminescence peak intensity also increases because of drying by a factor of 3 to 7 depending on glass compn. Based on elec. dipole-dipole interaction theory, the luminescence concn. quenching mechanism by hydroxyl groups is modelled. The model predicts that more than half of the hydroxyl groups in the glass is coupled to Er ions. The influence of the glass structure and role of Al3+ on the Er3+ luminescence is studied by IR spectroscopy. [on SciFinder (R)

Prelude to Part II

Due to copyright restrictions, the access to the full text of this article is only available via subscription.In Part II, we focus on decentralized stochastic control problems and their applications. In Chapter 8, we present our results on the finite model approximation of multi-agent stochastic control problems (team decision problems). We show that optimal strategies obtained from finite models approximate the optimal cost with arbitrary precision under mild technical assumptions. In particular, we show that quantized team policies are asymptotically optimal. In Chapter 9, the results are applied to Witsenhausen’s counterexample and the Gaussian relay channel problem