Helimeric porphyrinoids: Stereostructure and chiral resolution of meso -tetraarylmorpholinochlorins

The synthesis and chiral resolution of free-base and Ni(II) complexes of a number of derivatives of meso-tetraphenylmorpholinochlorins, with and without direct β-carbon-to-o-phenyl linkages to the flanking phenyl groups, is described. The morpholinochlorins, a class of stable chlorin analogues, were synthesized in two to three steps from meso-tetraphenylporphyrin. The conformations and the relative stereostructures of a variety of free-base and Ni(II) complexes of these morpholinochlorins were elucidated by X-ray diffractometry. Steric and stereoelectronic arguments explain the relative stereoarray of the morpholino-substituents, which differ in the free-base and Ni(II) complexes, and in the monoalkoxy, β-carbon-to-o-phenyl linked morpholinochlorins, and the dialkoxy derivatives. The Ni(II) complexes were all found to be severely ruffled whereas the free-base chromophores are more planar. As a result of the helimeric distortion of their porphyrinoid chromophores, the ruffled macrocycles possess a stable inherent element of chirality. Most significantly, resolution of the racemic mixtures was achieved, both by classical methods via diastereomers and by HPLC on a chiral phase. Full CD spectra were recorded and modeled using quantum-chemical computational methods, permitting, for the first time, an assignment of the absolute configurations of the chromophores. The report expands the range of known pyrrole-modified porphyrins. Beyond this, it introduces large chiral porphyrinoid π-systems that exist in the form of two enantiomeric, stereochemically stable helimers that can be resolved. This forms the basis for possible future applications, for example, in molecular-recognition systems or in materials with chiroptic properties. © 2011 American Chemical Society

Treatment of Marburg and Ebola hemorrhagic fevers: A strategy for testing new drugs and vaccines under outbreak conditions.

The filoviruses, Marburg and Ebola, have the dubious distinction of being associated with some of the highest case-fatality rates of any known infectious disease-approaching 90% in many outbreaks. In recent years, laboratory research on the filoviruses has produced treatments and vaccines that are effective in laboratory animals and that could potentially drastically reduce case-fatality rates and curtail outbreaks in humans. However, there are significant challenges in clinical testing of these products and eventual delivery to populations in need. Most cases of filovirus infection are recognized only in the setting of large outbreaks, often in the most remote and resource-poor areas of sub-Saharan Africa, with little infrastructure and few personnel experienced in clinical research. Significant political, legal, and socio-cultural barriers also exist. Here, we review the present research priorities and environment for field study of the filovirus hemorrhagic fevers and outline a strategy for future prospective clinical research on treatment and vaccine prevention

Vesicular Stomatitis Virus-Based Ebola Vaccine Is Well-Tolerated and Protects Immunocompromised Nonhuman Primates

Ebola virus (EBOV) is a significant human pathogen that presents a public health concern as an emerging/re-emerging virus and as a potential biological weapon. Substantial progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against EBOV. Among these prospects, a vaccine based on recombinant vesicular stomatitis virus (VSV) is particularly robust, as it can also confer protection when administered as a postexposure treatment. A concern that has been raised regarding the replication-competent VSV vectors that express EBOV glycoproteins is how these vectors would be tolerated by individuals with altered or compromised immune systems such as patients infected with HIV. This is especially important as all EBOV outbreaks to date have occurred in areas of Central and Western Africa with high HIV incidence rates in the population. In order to address this concern, we evaluated the safety of the recombinant VSV vector expressing the Zaire ebolavirus glycoprotein (VSVΔG/ZEBOVGP) in six rhesus macaques infected with simian-human immunodeficiency virus (SHIV). All six animals showed no evidence of illness associated with the VSVΔG/ZEBOVGP vaccine, suggesting that this vaccine may be safe in immunocompromised populations. While one goal of the study was to evaluate the safety of the candidate vaccine platform, it was also of interest to determine if altered immune status would affect vaccine efficacy. The vaccine protected 4 of 6 SHIV-infected macaques from death following ZEBOV challenge. Evaluation of CD4+ T cells in all animals showed that the animals that succumbed to lethal ZEBOV challenge had the lowest CD4+ counts, suggesting that CD4+ T cells may play a role in mediating protection against ZEBOV

Recombinant Vesicular Stomatitis Virus Vaccine Vectors Expressing Filovirus Glycoproteins Lack Neurovirulence in Nonhuman Primates

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with high mortality in humans and nonhuman primates. Among the most promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses an individual filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). The main concern with all replication-competent vaccines, including the rVSV filovirus GP vectors, is their safety. To address this concern, we performed a neurovirulence study using 21 cynomolgus macaques where the vaccines were administered intrathalamically. Seven animals received a rVSV vector expressing the Zaire ebolavirus (ZEBOV) GP; seven animals received a rVSV vector expressing the Lake Victoria marburgvirus (MARV) GP; three animals received rVSV-wild type (wt) vector, and four animals received vehicle control. Two of three animals given rVSV-wt showed severe neurological symptoms whereas animals receiving vehicle control, rVSV-ZEBOV-GP, or rVSV-MARV-GP did not develop these symptoms. Histological analysis revealed major lesions in neural tissues of all three rVSV-wt animals; however, no significant lesions were observed in any animals from the filovirus vaccine or vehicle control groups. These data strongly suggest that rVSV filovirus GP vaccine vectors lack the neurovirulence properties associated with the rVSV-wt parent vector and support their further development as a vaccine platform for human use

Factors influencing nurses' compliance with Standard Precautions in order to avoid occupational exposure to microorganisms: A focus group study

<p>Abstract</p> <p>Background</p> <p>Nurses may acquire an infection during the provision of nursing care because of occupational exposure to microorganisms. Relevant literature reports that, compliance with Standard Precautions (a set of guidelines that can protect health care professionals from being exposed to microorganisms) is low among nurses. Additionally, high rates of exposure to microorganisms among nurses via several modes (needlesticks, hand contamination with blood, exposure to air-transmitted microorganisms) occur. The aim of the study was to study the factors that influence nurses' compliance with Standard Precaution in order to avoid occupational exposure to pathogens, by employing a qualitative research design.</p> <p>Method</p> <p>A focus group approach was used to explore the issue under study. Four focus groups (N = 30) were organised to elicit nurses' perception of the factors that influence their compliance with Standard Precautions. The Health Belief Model (HBM) was used as the theoretical framework and the data were analysed according to predetermined criteria.</p> <p>Results</p> <p>Following content analysis, factors that influence nurses' compliance emerged. Most factors could be applied to one of the main domains of the HBM: benefits, barriers, severity, susceptibility, cues to action, and self-efficacy.</p> <p>Conclusions</p> <p>Changing current behavior requires knowledge of the factors that may influence nurses' compliance with Standard Precautions. This knowledge will facilitate in the implementation of programs and preventive actions that contribute in avoiding of occupational exposure.</p

Women, sport and new media technologies:Derby grrrls online

Sport has long been viewed as a public ‘good’ — a space for the creation and enactment of the ‘good, healthy citizen’. Yet this public ‘good’ has also been gendered masculine: competitive, public and ‘tough’, with women’s participation historically marginal to men’s. In Australia in recent years, the participation of women and girls has fluctuated, with decline or stagnation in more traditional organised sports (netball, basketball) and growth in other areas, such as roller derby and football. However, women’s sports are still largely invisible in the popular sport media. In this chapter we focus on roller derby as one particular women’s sport that has undergone a global revival, mobilised through ‘new’ youth-oriented media forms. We examine four diverse websites that form part of the ‘social web’ of derby: two official league sites, a blog and a Facebook group. The reinvention of roller derby is intimately connected to the alternative mediated spaces made possible by the social web. Roller derby players and organisers have used online spaces for various ends: to promote the sport community, to make visible the relations of power between those involved, to create and maintain boundaries of inclusion and exclusion within the sport, and to express ‘creative’ aspects of identity. This chapter provides examples of the strategies and tactics used to establish and maintain roller derby as a ‘women’s only’ sport and some of the challenges and possibilities inherent in this highly mediated space.No Full Tex

A low-cost Indoor and Outdoor terrestrial autonomous navigation model

A method for low-cost system design oriented to indoor and outdoor autonomous navigation is illustrated. In order to provide a motivation for the solution presented, a brief discussion of the typical drawbacks of state-of-the-art technologies is reported. Finally, an application of such a method for the design of a navigation system for blindfolded people is show

Determination of optimal doses of glyphosate for controlling weeds at several stages in southwestern Buenos Aires province (Argentina)

Efficient weed management is essential for avoiding competition for water, light, and nutrient resources in semiarid zones. Chemical weed control with glyphosate was evaluated on perennial wall-rocket (Diplotaxis tenuifolia), artichoke thistle (Cynara cardunculus), slender wild oat (Avena barbata), and perennial ryegrass (Lolium perenne). Plants at early, middle and advanced vegetative stages were used in this study. Glyphosate potassium salt was applied at rates of 0.0675 (1/16x), 0.135 (1/8x), 0.27 (1/4x), 0.54 (1/2x), 1.08 (x) and 2.16 (2x) kg acid equivalent (ae) ⋅ ha–1. Glyphosate combined with 2,4-D amine salt was evaluated at rates of 1.08 kg ae ⋅ ha–1 and 0.53 kg active ingredient (ai) ⋅ ha–1, respectively. The volume of the spray was 100 l ⋅ ha–1 with 86 droplets ⋅ cm–2 and a Volume Median Diameter (VMD) of 421.19 μm. In general, all the tested weeds were controlled with a quarter of the label rate. Three sizes of tested plants were controlled in a similar way at the same glyphosate dose rate. Moreover, the addition of 2,4-D to glyphosate did not produce an increase in the control of broadleaf weeds. The results showed that glyphosate was effective in controlling the tested weed species, including low application rates for all the growth stages in the southwestern Buenos Aires province