Homological algebra for Schwartz algebras of reductive p-adic groups

Let G be a reductive group over a non-Archimedean local field. Then the canonical functor from the derived category of smooth tempered representations of G to the derived category of all smooth representations of G is fully faithful. Here we consider representations on bornological vector spaces. As a consequence, if V and W are two tempered irreducible representations and if V or W is square-integrable, then Ext_G^n(V,W) vanishes for all n>0. We use this to prove in full generality a formula for the formal dimension of square-integrable representations due to Schneider and Stuhler.Comment: 34 pages, version 2 contains, in addition, a discussion about formal dimensions from the point of view of Schwartz algebras and von Neumann algebra

Soluble Adenylyl Cyclase Is Localized to Cilia and Contributes to Ciliary Beat Frequency Regulation via Production of cAMP

Ciliated airway epithelial cells are subject to sustained changes in intracellular CO2/HCO3− during exacerbations of airway diseases, but the role of CO2/HCO3−-sensitive soluble adenylyl cyclase (sAC) in ciliary beat regulation is unknown. We now show not only sAC expression in human airway epithelia (by RT-PCR, Western blotting, and immunofluorescence) but also its specific localization to the axoneme (Western blotting and immunofluorescence). Real time estimations of [cAMP] changes in ciliated cells, using FRET between fluorescently tagged PKA subunits (expressed under the foxj1 promoter solely in ciliated cells), revealed CO2/HCO3−-mediated cAMP production. This cAMP production was specifically blocked by sAC inhibitors but not by transmembrane adenylyl cyclase (tmAC) inhibitors. In addition, this cAMP production stimulated ciliary beat frequency (CBF) independently of intracellular pH because PKA and sAC inhibitors were uniquely able to block CO2/HCO3−-mediated changes in CBF (while tmAC inhibitors had no effect). Thus, sAC is localized to motile airway cilia and it contributes to the regulation of human airway CBF. In addition, CO2/HCO3− increases indeed reversibly stimulate intracellular cAMP production by sAC in intact cells

Alarming rates of virological failure and HIV-1 drug resistance amongst adolescents living with perinatal HIV in both urban and rural settings: evidence from the EDCTP READY-study in Cameroon

Objectives: Adolescents living with perinatal HIV infection (ALPHI) experience persistently high mortality rates, particularly in resource-limited settings. It is therefore clinically important for us to understand the therapeutic response, acquired HIV drug resistance (HIVDR) and associated factors among ALPHI, according to geographical location. Methods: A study was conducted among consenting ALPHI in two urban and two rural health facilities in the Centre Region of Cameroon. World Health Organization (WHO) clinical staging, self-reported adherence, HIVDR early warning indicators (EWIs), immunological status (CD4 count) and plasma viral load (VL) were assessed. For those experiencing virological failure (VF, VL ≥ 1000 copies/mL), HIVDR testing was performed and interpreted using the Stanford HIV Drug Resistance Database v.8.9-1. Results: Of the 270 participants, most were on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens (61.7% urban vs. 82.2% rural), and about one-third were poorly adherent (30.1% vs. 35.1%). Clinical failure rates (WHO-stage III/IV) in both settings were < 15%. In urban settings, the immunological failure (IF) rate (CD4  < 250 cells/μL) was 15.8%, statistically associated with late adolescence, female gender and poor adherence. The VF rate was 34.2%, statistically associated with poor adherence and NNRTI-based antiretroviral therapy. In the rural context, the IF rate was 26.9% and the VF rate was 52.7%, both statistically associated with advanced clinical stages. HIVDR rate was over 90% in both settings. EWIs were delayed drug pick-up, drug stock-outs and suboptimal viral suppression. Conclusions: Poor adherence, late adolescent age, female gender and advanced clinical staging worsen IF. The VF rate is high and consistent with the presence of HIVDR in both settings, driven by poor adherence, NNRTI-based regimen and advanced clinical staging

Investigating the Role of Islet Cytoarchitecture in Its Oscillation Using a New β-Cell Cluster Model

The oscillatory insulin release is fundamental to normal glycemic control. The basis of the oscillation is the intercellular coupling and bursting synchronization of β cells in each islet. The functional role of islet β cell mass organization with respect to its oscillatory bursting is not well understood. This is of special interest in view of the recent finding of islet cytoarchitectural differences between human and animal models. In this study we developed a new hexagonal closest packing (HCP) cell cluster model. The model captures more accurately the real islet cell organization than the simple cubic packing (SCP) cluster that is conventionally used. Using our new model we investigated the functional characteristics of β-cell clusters, including the fraction of cells able to burst fb, the synchronization index λ of the bursting β cells, the bursting period Tb, the plateau fraction pf, and the amplitude of intracellular calcium oscillation [Ca]. We determined their dependence on cluster architectural parameters including number of cells nβ, number of inter-β cell couplings of each β cell nc, and the coupling strength gc. We found that at low values of nβ, nc and gc, the oscillation regularity improves with their increasing values. This functional gain plateaus around their physiological values in real islets, at nβ∼100, nc∼6 and gc∼200 pS. In addition, normal β-cell clusters are robust against significant perturbation to their architecture, including the presence of non-β cells or dead β cells. In clusters with nβ>∼100, coordinated β-cell bursting can be maintained at up to 70% of β-cell loss, which is consistent with laboratory and clinical findings of islets. Our results suggest that the bursting characteristics of a β-cell cluster depend quantitatively on its architecture in a non-linear fashion. These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd