Variation in Ancillary Testing among Pediatric Asthma Patients Seen in Emergency Departments

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72605/1/j.aem.2007.01.016.pd

The legacies of coercion and the challenges of contingency: Mozambican unions in difficult times

Although insecure work may be found everywhere, the general lack of secure work in emerging economies is a particularly striking feature of the contemporary condition, undermining the continued viability of the labour movement in such countries. Yet, this topic is rarely tackled directly in African studies or business history journals. The two key questions addressed in this paper are, first, to what extent does the labour movement’s past define their present and future, and second, what are the challenges and opportunities affecting their ability to mobilise workers, influence government and effectively tackle employment security? This article details how in Mozambique, unions’ ability to mobilise has been affected by: the post-colonial, post-conflict and post-socialist historical context; the resulting legacies of regional and racial discrimination; international imperatives for liberalisation and privatisation; challenging relationships with the country’s African neighbours; and high levels of informal sector work. In order to remain viable, key imperatives include: effectively influencing national government, engaging internationally and working with organisations representing informal sector workers

Clinical significance of HIV-1 coreceptor usage

The identification of phenotypically distinct HIV-1 variants with different prevalence during the progression of the disease has been one of the earliest discoveries in HIV-1 biology, but its relevance to AIDS pathogenesis remains only partially understood. The physiological basis for the phenotypic variability of HIV-1 was elucidated with the discovery of distinct coreceptors employed by the virus to infect susceptible cells. The role of the viral phenotype in the variable clinical course and treatment outcome of HIV-1 infection has been extensively investigated over the past two decades. In this review, we summarize the major findings on the clinical significance of the HIV-1 coreceptor usage

Adoption of an “Open” Envelope Conformation Facilitating CD4 Binding and Structural Remodeling Precedes Coreceptor Switch in R5 SHIV-Infected Macaques

A change in coreceptor preference from CCR5 to CXCR4 towards the end stage disease in some HIV-1 infected individuals has been well documented, but the reasons and mechanisms for this tropism switch remain elusive. It has been suggested that envelope structural constraints in accommodating amino acid changes required for CXCR4 usage is an obstacle to tropism switch, limiting the rate and pathways available for HIV-1 coreceptor switching. The present study was initiated in two R5 SHIVSF162P3N-infected rapid progressor macaques with coreceptor switch to test the hypothesis that an early step in the evolution of tropism switch is the adoption of a less constrained and more “open” envelope conformation for better CD4 usage, allowing greater structural flexibility to accommodate further mutational changes that confer CXCR4 utilization. We show that, prior to the time of coreceptor switch, R5 viruses in both macaques evolved to become increasingly sCD4-sensitive, suggestive of enhanced exposure of the CD4 binding site and an “open” envelope conformation, and this correlated with better gp120 binding to CD4 and with more efficient infection of CD4low cells such as primary macrophages. Moreover, significant changes in neutralization sensitivity to agents and antibodies directed against functional domains of gp120 and gp41 were seen for R5 viruses close to the time of X4 emergence, consistent with global changes in envelope configuration and structural plasticity. These observations in a simian model of R5-to-X4 evolution provide a mechanistic basis for the HIV-1 coreceptor switch

Rapid metal‐free macromolecular coupling via In Situ nitrile oxide‐activated alkene cycloaddition

Nitrile oxide 1,3 dipolar cycloaddition is a simple and powerful coupling methodology. However, the self-dimerization of nitrile oxides has prevented the widespread use of this strategy for macromolecular coupling. By combining an in situ nitrile oxide generation with a highly reactive activated dipolarophile, we have overcome these obstacles and present a metal-free macromolecular coupling strategy for the modular synthesis of several ABA triblock copolymers. Nitrile oxides were generated in situ from chloroxime terminated poly(dimethylsiloxane) B-blocks and coupled with several distinct hydrophilic (poly(2-methyloxazoline) and poly(ethylene glycol)), and poly(N-isopropylacrylamide) or hydrophobic (poly(L-lactide) A-blocks terminated in activated dipolarophiles in a rapid fashion with high yield. This methodology overcomes many drawbacks of previously reported metal-free methods due to its rapid kinetics, versatility, scalability, and ease of introduction of necessary functionality. Nitrile oxide cycloaddition should find use as an attractive macromolecular coupling strategy for the synthesis of biocompatible polymeric nanostructures

Tailored Polymeric Membranes for Mycobacterium Smegmatis Porin A (MspA) Based Biosensors.

Nanopores based on protein channels inserted into lipid membranes have paved the way towards a wide-range of inexpensive biosensors, especially for DNA sequencing. A key obstacle in using these biological ion channels as nanodevices is the poor stability of lipid bilayer membranes. Amphiphilic block copolymer membranes have emerged as a robust alternative to lipid membranes. While previous efforts have shown feasibility, we demonstrate for the first time the effect of polymer composition on MspA protein functionality. We show that membrane-protein interaction depends on the hydrophobic-hydrophilic ratio (f-ratio) of the block copolymer. These effects are particularly pronounced in asymmetric protein pores like MspA compared to the cylindrical α-Hemolysin pore. A key effect of membrane-protein interaction is the increased 1/fα noise. After first showing increases in 1/fα behaviour arise from increased substate activity, the noise power spectral density S(f) was used as a qualitative tool for understanding protein-membrane interactions in polymer membranes. Polymer compositions with f-ratios close to lipid membranes caused noise behaviour not observed in lipid membranes. However, by modifying the f-ratio using a modular synthetic approach, we were able to design a block copolymer exhibiting noise properties similar to a lipid membrane, albeit with better stability. Thus, by careful optimization, block copolymer membranes can emerge as a robust alternative for protein-pore based nano-biosensors