The stereochemistry of the Nozaki-Hiyama-Kishi reaction and the construction of 10-membered lactones. the enantioselective total synthesis of (-)-decarestrictine D.

The use of the intramolecular Nozaki-Hiyama-Kishi reaction to construct 10-membered lactones is described. The influence of the nature of the protecting groups at C4 and C5 on the stereochemistry of the newly formed stereogenic center at C7 was investigated. The utility of this methodology has been demonstrated in the stereoselective total synthesis of (-)-decarestrictine D from 1,3-propanediol and polyhydroxybutyrate (PHB) in 13 steps and 6.3% overall yield.12337338

Does owning a pet protect older people against loneliness?

This article has been made available through the Brunel Open Access Publishing Fund.Pet ownership is thought to make a positive contribution to health, health behaviours and the general well-being of older people. More specifically pet ownership is often proposed as a solution to the problem of loneliness in later life and specific 'pet based' interventions have been developed to combat loneliness. However the evidence to support this relationship is slim and it is assumed that pet ownership is a protection against loneliness rather than a response to loneliness. The aim of this paper is to examine the association between pet ownership and loneliness by exploring if pet ownership is a response to, or protection against, loneliness using Waves 0-5 from the English Longitudinal Study of Ageing (ELSA)

Visualizing landscapes of the superconducting gap in heterogeneous superconductor thin films: geometric influences on proximity effects

The proximity effect is a central feature of superconducting junctions as it underlies many important applications in devices and can be exploited in the design of new systems with novel quantum functionality. Recently, exotic proximity effects have been observed in various systems, such as superconductor-metallic nanowires and graphene-superconductor structures. However, it is still not clear how superconducting order propagates spatially in a heterogeneous superconductor system. Here we report intriguing influences of junction geometry on the proximity effect for a 2D heterogeneous superconductor system comprised of 2D superconducting islands on top of a surface metal. Depending on the local geometry, the superconducting gap induced in the surface metal region can either be confined to the boundary of the superconductor, in which the gap decays within a short distance (~ 15 nm), or can be observed nearly uniformly over a distance of many coherence lengths due to non-local proximity effects.Comment: 17 pages, 4 figure

Lower cerebrospinal fluid/plasma fibroblast growth factor 21 (FGF21) ratios and placental FGF21 production in gestational diabetes

Objectives: Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants. Design: CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m2) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m2)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA. Results: Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05). Conclusions: The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points

Reconsidering the Barefoot Doctor Programme

This paper examines the widely acclaimed Barefoot Doctor campaign in China. The Barefoot Doctor Campaign has come to symbolize the success of Chinese health care to the extent that it has become a model for WHO public health strategy. Yet little has been done to understand how or whether it worked on the ground and what difficulties and contradictions emerged in its implementation. Using previously unexplored party archives as well as newly collected oral interviews, this paper moves away from a narrow focus on party politics and policy formulation by examining the reality of health care at the local level and the challenges faced by local authorities and individuals as the campaigns evolved

First insights into the phylogenetic diversity of Mycobacterium tuberculosis in Nepal

BACKGROUND: Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. METHODS AND FINDINGS: We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42-4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43-5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. CONCLUSIONS: We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian reg

Total Hadronic Cross Section Data and the Froissart-Martin Bound

The energy dependence of the total hadronic cross section at high energies is investigated with focus on the recent experimental result by the TOTEM Collaboration at 7 TeV and the Froissart-Martin bound. On the basis of a class of analytical parametrization with the exponent $\gamma$ in the leading logarithm contribution as a free parameter, different variants of fits to $pp$ and $\bar{p}p$ total cross section data above 5 GeV are developed. Two ensembles are considered, the first comprising data up to 1.8 TeV, the second also including the data collected at 7 TeV. We shown that in all fit variants applied to the first ensemble the exponent is statistically consistent with $\gamma$ = 2. Applied to the second ensemble, however, the same variants yield $\gamma$'s above 2, a result already obtained in two other analysis, by U. Amaldi \textit{et al}. and by the UA4/2 Collaboration. As recently discussed by Ya. I. Azimov, this faster-than-squared-logarithm rise does not necessarily violate unitarity. Our results suggest that the energy dependence of the hadronic total cross section at high energies still constitute an open problem.Comment: 20 pages, 10 figures, introduction extended and general references added to match editorial style, to appear in the Brazilian Journal of Physic

A Variant of TNFR2-Fc Fusion Protein Exhibits Improved Efficacy in Treating Experimental Rheumatoid Arthritis

Etanercept, a TNF receptor 2-Fc fusion protein, is currently being used for the treatment of rheumatoid arthritis (RA). However, 25% to 38% of patients show no response which is suspected to be partially due to insufficient affinity of this protein to TNFα. By using computational protein design, we found that residue W89 and E92 of TNFR2 were critical for ligand binding. Among several mutants tested, W89Y/E92N displayed 1.49-fold higher neutralizing activity to TNFα, as compared to that of Etanercept. Surface plasmon resonance (SPR) based binding assay revealed that the equilibrium dissociation constant of W89Y/E92N to TNFα was 3.65-fold higher than that of Etanercept. In a rat model of collagen-induced arthritis (CIA), W89Y/E92N showed a significantly better ability than Etanercept in reducing paw swelling and improvement of arthritic joint histopathologically. These data demonstrate that W89Y/E92N is potentially a better candidate with improved efficacy in treating RA and other autoimmune diseases

Concurrent Outbreak of Norovirus Genotype I and Enterotoxigenic Escherichia coli on a U.S. Navy Ship following a Visit to Lima, Peru

An outbreak of norovirus (NoV) genotype I and Enterotoxigenic Escherichia coli (ETEC) occurred among US Navy Ship personnel following a visit to Lima, Peru, in June 2008. Visiting a specific area in Lima was significantly associated with illness. While ETEC and NoV are commonly recognized as causative agents of outbreaks, co-circulation of both pathogens has been rarely observed in shipboard outbreaks