666 research outputs found

    The global field of multi-family offices: An institutionalist perspective

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    We apply the notion of the organisational field to internationally operating multi-family offices. These organisations specialise on the preservation of enterprising and geographically dispersed families’ fortunes. They provide their services across generations and countries. Based on secondary data of Bloomberg’s Top 50 Family Offices, we show that they constitute a global organisational field that comprises two clusters of homogeneity. Clients may decide between two different configurations of activities, depending on their preferences regarding asset management, resource management, family management, and service architecture. The findings also reveal that multi-family offices make relatively similar value propositions all over the world. The distinctiveness of the clusters within the field is not driven by the embeddedness of the multi-family offices in different national environments or their various degrees of international experience. Rather, it is weakly affected by two out of four possible value propositions, namely the exclusiveness and the transparency of services

    Transitory electrochemical masking for precision jet processing techniques

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    Electrochemical jet processing techniques provide an efficient method for large area surface structuring and micro-milling, where the metallurgy of the near-surface is assured and not adversely affected by thermal loading. Here, doped electrolytes are specifically developed for jet techniques to exploit the Gaussian energy distribution as found in energy beam processes. This allows up to 26% reduction in dissolution kerf and enhancements of the defined precision metric of up to 284% when compared to standard electrolytes. This is achieved through the filtering of low energy at discrete points within the energy distribution curve. Two fundamental mechanisms of current filtering and refresh rate are proposed and investigated in order to underpin the performance enhancements found using this methodology. This study aims to demonstrate that a step change in process fidelity and flexibility can be achieved through optimisation of the electrochemistry specific to jet processes

    The impact of training and working conditions on junior doctors' intention to leave clinical practice

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    Background: The shortage of physicians is an evolving problem throughout the world. In this study we aimed to identify to what extent junior doctors' training and working conditions determine their intention to leave clinical practice after residency training. Methods: A prospective cohort study was conducted in 557 junior doctors undergoing residency training in German hospitals. Self-reported specialty training conditions, working conditions and intention to leave clinical practice were measured over three time points. Scales covering training conditions were assessed by structured residency training, professional support, and dealing with lack of knowledge; working conditions were evaluated by work overload, job autonomy and social support, based on the Demand-Control-Support model. Multivariate ordinal logistic regression analyses with random intercept for longitudinal data were applied to determine the odds ratio of having a higher level of intention to leave clinical practice. Results: In the models that considered training and working conditions separately to predict intention to leave clinical practice we found significant baseline effects and change effects. After modelling training and working conditions simultaneously, we found evidence that the change effect of job autonomy (OR 0.77, p = .005) was associated with intention to leave clinical practice, whereas for the training conditions, only the baseline effects of structured residency training (OR 0.74, p = .017) and dealing with lack of knowledge (OR 0.74, p = .026) predicted intention to leave clinical practice. Conclusions: Junior doctors undergoing specialty training experience high workload in hospital practice and intense requirements in terms of specialty training. Our study indicates that simultaneously improving working conditions over time and establishing a high standard of specialty training conditions may prevent junior doctors from considering leaving clinical practice after residency training

    Psychosocial working conditions and the risk of depression and anxiety disorders in the Danish workforce

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    <p>Abstract</p> <p>Background</p> <p>To examine the risk of depressive and anxiety disorders according to psychosocial working conditions in a large population-based sample.</p> <p>Methods</p> <p>Job Exposure Matrix was applied to assess psychosocial working conditions in a population-based nested case-control study of 14,166 psychiatric patients, diagnosed with depressive or anxiety disorders during 1995–1998 selected from The Danish Psychiatric Central Research Register, compared with 58,060 controls drawn from Statistics Denmark's Integrated Database for Labour Market Research.</p> <p>Results</p> <p>Low job control was associated with an increased risk of anxiety disorders in men (IRR 1.40, 95% CI 1.24–1.58).</p> <p>In women an elevated risk of depression was related to high emotional demands (IRR 1.39, 95%CI 1.22–1.58) and to working with people (IRR 1.15, 95% CI 1.01–1.30). In both sexes high demands were associated with a decreased risk of anxiety disorders. There was a weak association between job strain and anxiety disorders in men (IRR 1.13, 95%, CI 1.02–1.25)</p> <p>Conclusion</p> <p>Psychosocial work exposures related to the risk of depressive and anxiety disorders differ as between the sexes. The pattern of risks is inconsistent. The results give rise to rethinking both study designs and possible causal links between work exposures and mental health.</p

    Current challenges in software solutions for mass spectrometry-based quantitative proteomics

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    This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

    Defending the genome from the enemy within:mechanisms of retrotransposon suppression in the mouse germline

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    The viability of any species requires that the genome is kept stable as it is transmitted from generation to generation by the germ cells. One of the challenges to transgenerational genome stability is the potential mutagenic activity of transposable genetic elements, particularly retrotransposons. There are many different types of retrotransposon in mammalian genomes, and these target different points in germline development to amplify and integrate into new genomic locations. Germ cells, and their pluripotent developmental precursors, have evolved a variety of genome defence mechanisms that suppress retrotransposon activity and maintain genome stability across the generations. Here, we review recent advances in understanding how retrotransposon activity is suppressed in the mammalian germline, how genes involved in germline genome defence mechanisms are regulated, and the consequences of mutating these genome defence genes for the developing germline

    Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres

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    Long interspersed element-1 (LINE-1 or L1) elements are abundant, non-long-terminal-repeat (non-LTR) retrotransposons that comprise 17% of human DNA(1). The average human genome contains similar to 80-100 retrotransposition- competent L1s (ref. 2), and they mobilize by a process that uses both the L1 endonuclease and reverse transcriptase, termed target-site primed reverse transcription(3-5). We have previously reported an efficient, endonuclease-independent L1 retrotransposition pathway (ENi) in certain Chinese hamster ovary (CHO) cell lines that are defective in the non-homologous end-joining (NHEJ) pathway of DNA double-strand-break repair(6). Here we have characterized ENi retrotransposition events generated in V3 CHO cells, which are deficient in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and have both dysfunctional telomeres and an NHEJ defect. Notably, similar to 30% of ENi retrotransposition events insert in an orientation-specific manner adjacent to a perfect telomere repeat (5'-TTAGGG-3'). Similar insertions were not detected among ENi retrotransposition events generated in controls or in XR-1 CHO cells deficient for XRCC4, an NHEJ factor that is required for DNA ligation but has no known function in telomere maintenance. Furthermore, transient expression of a dominant-negative allele of human TRF2 ( also called TERF2) in XRCC4-deficient XR-1 cells, which disrupts telomere capping, enables telomere-associated ENi retrotransposition events. These data indicate that L1s containing a disabled endonuclease can use dysfunctional telomeres as an integration substrate. The findings highlight similarities between the mechanism of ENi retrotransposition and the action of telomerase, because both processes can use a 3' OH for priming reverse transcription at either internal DNA lesions or chromosome ends(7,8). Thus, we propose that ENi retrotransposition is an ancestral mechanism of RNA-mediated DNA repair associated with non-LTR retrotransposons that may have been used before the acquisition of an endonuclease domain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62964/1/nature05560.pd

    Deep-Inelastic Inclusive ep Scattering at Low x and a Determination of alpha_s

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    A precise measurement of the inclusive deep-inelastic e^+p scattering cross section is reported in the kinematic range 1.5<= Q^2 <=150 GeV^2 and 3*10^(-5)<= x <=0.2. The data were recorded with the H1 detector at HERA in 1996 and 1997, and correspond to an integrated luminosity of 20 pb^(-1). The double differential cross section, from which the proton structure function F_2(x,Q^2) and the longitudinal structure function F_L(x,Q^2) are extracted, is measured with typically 1% statistical and 3% systematic uncertainties. The measured partial derivative (dF_2(x,Q^2)/dln Q^2)_x is observed to rise continuously towards small x for fixed Q^2. The cross section data are combined with published H1 measurements at high Q^2 for a next-to-leading order DGLAP QCD analysis.The H1 data determine the gluon momentum distribution in the range 3*10^(-4)<= x <=0.1 to within an experimental accuracy of about 3% for Q^2 =20 GeV^2. A fit of the H1 measurements and the mu p data of the BCDMS collaboration allows the strong coupling constant alpha_s and the gluon distribution to be simultaneously determined. A value of alpha _s(M_Z^2)=0.1150+-0.0017 (exp) +0.0009-0.0005 (model) is obtained in NLO, with an additional theoretical uncertainty of about +-0.005, mainly due to the uncertainty of the renormalisation scale.Comment: 68 pages, 24 figures and 18 table

    Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats

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    Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel. © 2009 Goldstein et al
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