1,878 research outputs found

    Oxidation chemistry of d^0 organometallic complexes

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    Electron-transfer processes can play an important role in organometallic chemistry. Herein, we demonstrate that even d^0 organometallic complexes exhibit a rich redox chemistry and present electrochemical, kinetics, and stereochemical studies that establish a general outer-sphere oxidation process for d^0 group 4 metallocene complexes. This oxidation chemistry closely parallels the reported LMCT photochemistry of these complexes

    The Labour Government, the Treasury and the £6 pay policy of July 1975

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    The 1974-79 Labour Government was elected in a climate of opinion that was fiercely opposed to government intervention in the wage determination process, and was committed to the principles of free collective bargaining in its manifestoes. However, by December 1974 the Treasury was advocating a formal incomes policy, and by July 1975 the government had introduced a £6 flat rate pay norm. With reference to archival sources, the paper demonstrates that TUC and Labour Party opposition to incomes policy was reconciled with the Treasury's advocacy by limiting the Bank of England‟s intervention in the foreign exchange market when sterling came under pressure. This both helped to achieve the Treasury's objective of improving the competitiveness of British industry, and acted as a catalyst for the introduction of incomes policy because the slide could be attributed to a lack of market confidence in British counter-inflation policy

    HIF-2α downregulation in the absence of functional VHL is not sufficient for renal cell differentiation

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    <p>Abstract</p> <p>Background</p> <p>Mutational inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene has been linked to hereditary as well as sporadic clear cell renal carcinomas. The product of the VHL gene, pVHL, acts to target hypoxia-inducible factor alpha (HIF-α) subunits for ubiquitination and subsequent degradation. Using an RNA interference approach to lower levels of HIF-2α in two different renal cell lines that lack functional pVHL, we have tested the contribution of HIF-2α toward cellular pVHL activities.</p> <p>Results</p> <p>Knockdown of HIF-2α resulted in cell cycle arrest of renal cells that were grown on collagen I, indicating that this pVHL function is dependent on HIF-2α regulation. However, cellular morphological changes and downregulation of integrins α5 and β1, which were seen upon pVHL replacement, were not faithfully phenocopied by HIF-2α reduction. Moreover, fibronectin deposition and expression of renal cell differentiation markers were observed in cells containing replaced pVHL, but not in HIF-2α knockdown cells, indicating that these pVHL functions may occur independently of HIF-2α downregulation.</p> <p>Conclusion</p> <p>These results indicate that HIF-2α regulation is not sufficient for pVHL-induced renal cell differentiation. We hypothesize that in addition to HIF-2α dysregulation, abrogation of additional pVHL functions is required for the initiation of renal carcinogenesis.</p

    Long term study of the seismic environment at LIGO

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    The LIGO experiment aims to detect and study gravitational waves using ground based laser interferometry. A critical factor to the performance of the interferometers, and a major consideration in the design of possible future upgrades, is isolation of the interferometer optics from seismic noise. We present the results of a detailed program of measurements of the seismic environment surrounding the LIGO interferometers. We describe the experimental configuration used to collect the data, which was acquired over a 613 day period. The measurements focused on the frequency range 0.1-10 Hz, in which the secondary microseismic peak and noise due to human activity in the vicinity of the detectors was found to be particularly critical to interferometer performance. We compare the statistical distribution of the data sets from the two interferometer sites, construct amplitude spectral densities of seismic noise amplitude fluctuations with periods of up to 3 months, and analyze the data for any long term trends in the amplitude of seismic noise in this critical frequency range.Comment: To be published in Classical and Quantum Gravity. 24 pages, 15 figure

    Fetal baboon sex-specific outcomes in adipocyte differentiation at 0.9 gestation in response to moderate maternal nutrient reduction

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    Objective:To investigate in vitro adipocyte differentiation in baboon fetuses in response to reduced maternal nutrition.Design:Cross-sectional comparison of adipocyte differentiation in normally grown fetuses and fetuses of pregnant baboons fed 70% of the control global diet from 30 days of pregnancy to term.Subjects:The subjects comprised control (CTR) fetuses (five female and five male) of mothers fed ad libitum and fetuses of mothers fed 70% of the global diet consumed by CTR (maternal nutrient reduction (MNR), five female and five male fetuses). The expression of genes/proteins involved in adipogenesis (PPARγ, FABP4 and adiponectin) and brown adipose tissue development (UCP1, TBX15 and COXIV) were determined in in vitro-differentiated stromal-vascular cultures from subcutaneous abdominal, subcutaneous femoral and omental adipose tissue depots. Adipocyte number per area (mm 2) was determined histologically to assist in the evaluation of adipocyte size.Results:Maternal suboptimal nutrition suppressed growth of male but not female fetuses and led to adipocyte hypertrophy accompanied by increased markers of white- and, particularly, brown-type adipogenesis in male but not female fetuses.Conclusion:Adipose tissue responses to fetal nonhuman primate undernutrition are sexually dimorphic. While female fetuses adapt adequately, the male ones enhance pathways involved in white and brown adipose tissue development but are unable to compensate for a delayed development of adipose tissue associated with intrauterine growth restriction. These differences need to be considered when assessing developmental programming of adiposity in response to suboptimal maternal nutrition. © 2014 Macmillan Publishers Limited

    Effects of mesenchymal stromal cells versus serum on tendon healing in a controlled experimental trial in an equine model

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    Abstract Background Mesenchymal stromal cells (MSC) have shown promising results in the treatment of tendinopathy in equine medicine, making this therapeutic approach seem favorable for translation to human medicine. Having demonstrated that MSC engraft within the tendon lesions after local injection in an equine model, we hypothesized that they would improve tendon healing superior to serum injection alone. Methods Quadrilateral tendon lesions were induced in six horses by mechanical tissue disruption combined with collagenase application 3 weeks before treatment. Adipose-derived MSC suspended in serum or serum alone were then injected intralesionally. Clinical examinations, ultrasound and magnetic resonance imaging were performed over 24 weeks. Tendon biopsies for histological assessment were taken from the hindlimbs 3 weeks after treatment. Horses were sacrificed after 24 weeks and forelimb tendons were subjected to macroscopic and histological examination as well as analysis of musculoskeletal marker expression. Results Tendons injected with MSC showed a transient increase in inflammation and lesion size, as indicated by clinical and imaging parameters between week 3 and 6 (p < 0.05). Thereafter, symptoms decreased in both groups and, except that in MSC-treated tendons, mean lesion signal intensity as seen in T2w magnetic resonance imaging and cellularity as seen in the histology (p < 0.05) were lower, no major differences could be found at week 24. Conclusions These data suggest that MSC have influenced the inflammatory reaction in a way not described in tendinopathy studies before. However, at the endpoint of the current study, 24 weeks after treatment, no distinct improvement was observed in MSC-treated tendons compared to the serum-injected controls. Future studies are necessary to elucidate whether and under which conditions MSC are beneficial for tendon healing before translation into human medicine

    Comparison of Fecal Collection Methods for Microbiome and Metabolomics Studies

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    Background: Integrated microbiome and metabolomics analyses hold the potential to reveal interactions between host and microbiota in relation to disease risks. However, there are few studies evaluating how field methods influence fecal microbiome characterization and metabolomics profiling.Methods: Five fecal collection methods [immediate freezing at −20°C without preservative, OMNIgene GUT, 95% ethanol, RNAlater, and Flinders Technology Associates (FTA) cards] were used to collect 40 fecal samples from eight healthy volunteers. We performed gut microbiota 16S rRNA sequencing, untargeted metabolomics profiling, and targeted metabolomics focusing on short chained fatty acids (SCFAs). Metrics included α-diversity and β-diversity as well as distributions of predominant phyla. To evaluate the concordance with the “gold standard” immediate freezing, the intraclass correlation coefficients (ICCs) for alternate fecal collection systems were calculated. Correlations between SCFAs and gut microbiota were also examined.Results: The FTA cards had the highest ICCs compared to the immediate freezing method for α-diversity indices (ICCs = 0.96, 0.96, 0.76 for Shannon index, Simpson's Index, Chao-1 Index, respectively), followed by OMNIgene GUT, RNAlater, and 95% ethanol. High ICCs (all &gt;0.88) were observed for all methods for the β-diversity metric. For untargeted metabolomics, in comparison to immediate freezing which detected 621 metabolites at ≥75% detectability level, 95% ethanol showed the largest overlapping set of metabolites (n = 430; 69.2%), followed by FTA cards (n = 330; 53.1%) and OMNIgene GUT (n = 213; 34.3%). Both OMNIgene GUT (ICCs = 0.82, 0.93, 0.64) and FTA cards (ICCs = 0.87, 0.85, 0.54) had acceptable ICCs for the top three predominant SCFAs (butyric acid, propionic acid and acetic acid). Nominally significant correlations between bacterial genera and SCFAs (P &lt; 0.05) were observed in fecal samples collected by different methods. Of note, a high correlation between the genus Blautia (known butyrate producer) and butyric acid was observed for both immediate freezing (r = 0.83) and FTA cards (r = 0.74).Conclusions: Four alternative fecal collection methods are generally comparable with immediate freezing, but there are differences in certain measures of the gut microbiome and fecal metabolome across methods. Choice of method depends on the research interests, simplicity of fecal collection procedures and ease of transportation to the lab, especially for large epidemiological studies
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