605 research outputs found

    Being Focused: When the Purpose of Inference Matters for Model Selection

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    In contrast to conventional model selection criteria, the Focused Information Criterion (FIC) allows for purpose-specific choice of models. This accommodates the idea that one kind of model might be highly appropriate for inferences on a particular parameter, but not for another. Ever since its development, the FIC has been increasingly applied in the realm of statistics, but this concept appears to be virtually unknown in the economic literature. Using a classical example and data for 35 U.S. industry sectors (1960-2005), this paper provides for an illustration of the FIC and a demonstration of its usefulness in empirical applications

    Lipid and protein content profiling of isolated native autophagic vesicles

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    Autophagy is responsible for clearance of an extensive portfolio of cargoes, which are sequestered into vesicles, called autophagosomes, and are delivered to lysosomes for degradation. The pathway is highly dynamic and responsive to several stress conditions. However, the phospholipid composition and protein contents of human autophagosomes under changing autophagy rates are elusive so far. Here, we introduce an antibody-based FACS-mediated approach for the isolation of native autophagic vesicles and ensured the quality of the preparations. Employing quantitative lipidomics, we analyze phospholipids present within human autophagic vesicles purified upon basal autophagy, starvation, and proteasome inhibition. Importantly, besides phosphoglycerides, we identify sphingomyelin within autophagic vesicles and show that the phospholipid composition is unaffected by the different conditions. Employing quantitative proteomics, we obtain cargo profiles of autophagic vesicles isolated upon the different treatment paradigms. Interestingly, starvation shows only subtle effects, while proteasome inhibition results in the enhanced presence of ubiquitin-proteasome pathway factors within autophagic vesicles. Thus, here we present a powerful method for the isolation of native autophagic vesicles, which enabled profound phospholipid and cargo analyses

    Effects of fibre content and textile structure on dynamic-mechanical and shape-memory properties of ELO/flax biocomposites

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    Biocomposites were prepared using epoxidized linseed oil (ELO) and flax fibre reinforcements in different assemblies. ELO was cured by two different anhydrides to check how its thermomechanical properties can be influenced. As reinforcements nonwoven mat, twill weave and quasi-unidirectional textile fabrics with two different yarn finenesses were used. Their reinforcing effect was determined in dynamic mechanical analysis (DMA) in flexure. DMA served also to determine the glass transition temperature (Tg). Shape memory properties were derived from quasiunconstrained flexural tests performed near to the Tg of the ELO and its biocomposites. Flax reinforcement reduced the Tg that was attributed to off-stoichiometry owing to chemical reaction between the hydroxyl groups of flax and anhydride hardener. The shape memory parameters were moderate or low. They were affected by both textile content and type

    Registration of ‘LCS Compass’ Wheat

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    ‘LCS Compass’ (Reg. No. CV-1149, PI 675458), a hard red winter (HRW) wheat (Triticum aestivum L.), was developed and tested as VA10HRW-13 and co-released by the Virginia Agricultural Experiment Station and Limagrain Cereal Seeds, LLC, in 2015. LCS Compass was derived from the cross ‘Vision 20’ /‘Stanof’ using a modified bulk breeding method. LCS Compass is a widely adapted, high-yielding, awned, semidwarf (Rht1) HRW wheat with early to medium maturity and resistance or moderate resistance to diseases prevalent in the mid-Atlantic and Great Plains regions of the United States. In the 2013 Uniform Bread Wheat Trial conducted over 18 locations in eastern states, LCS Compass produced an average grain yield of 4609 kg ha−1 that was similar to ‘Vision 30’ (4697 kg ha−1). In the northern Great Plains, the average grain yield of LCS Compass (4015 kg ha−1) over 44 locations in 2013 was similar to ‘Jerry’ (4013 kg ha−1). In the South Dakota crop zone 3 variety test, LCS Compass had a 3-yr (2015–2017) yield average of 5575 kg ha−1 and was one of highest-yielding cultivars among the 19 cultivars tested over the 3-yr period. LCS Compass has good end-use quality in both the eastern and Great Plains regions of the United States

    Investigating the causal role of MRE11A p.E506* in breast and ovarian cancer

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    The nuclease MRE11A is often included in genetic test panels for hereditary breast and ovarian cancer (HBOC) due to its BRCA1-related molecular function in the DNA repair pathway. However, whether MRE11A is a true predisposition gene for HBOC is still questionable. We determined to investigate this notion by dissecting the molecular genetics of the c.1516G > T;p.E506* truncating MRE11A variant, that we pinpointed in two unrelated French-Canadian (FC) HBOC patients. We performed a case-control study for the variant in ~ 2500 breast, ovarian, and endometrial cancer patients from the founder FC population of Quebec. Furthermore, we looked for the presence of second somatic alterations in the MRE11A gene in the tumors of the carriers. In summary, these investigations suggested that the identified variant is not associated with an increased risk of developing breast or ovarian cancer. We finally performed a systematic review for all the previously reported MRE11A variants in breast and ovarian cancer. We found that MRE11A germline variants annotated as pathogenic on ClinVar often lacked evidence for such classification, hence misleading the clinical management for affected patients. In summary, our report suggests the lack of clinical utility of MRE11A testing in HBOC, at least in the White/Caucasian populations

    3D printing of twisting and rotational bistable structures with tuning elements

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    Three-dimensional (3D) printing is ideal for the fabrication of various customized 3D components with fine details and material-design complexities. However, most components fabricated so far have been static structures with fixed shapes and functions. Here we introduce bistability to 3D printing to realize highly-controlled, reconfigurable structures. Particularly, we demonstrate 3D printing of twisting and rotational bistable structures. To this end, we have introduced special joints to construct twisting and rotational structures without post-assembly. Bistability produces a well-defined energy diagram, which is important for precise motion control and reconfigurable structures. Therefore, these bistable structures can be useful for simplified motion control in actuators or for mechanical switches. Moreover, we demonstrate tunable bistable components exploiting shape memory polymers. We can readjust the bistability-energy diagram (barrier height, slope, displacement, symmetry) after printing and achieve tunable bistability. This tunability can significantly increase the use of bistable structures in various 3D-printed components

    Ginkgo biloba for the treatment of vitilgo vulgaris: an open label pilot clinical trial

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    <p>Abstract</p> <p>Background</p> <p>Vitiligo is a common hypopigmentation disorder with significant psychological impact if occurring before adulthood. A pilot clinical trial to determine the feasibility of an RCT was conducted and is reported here.</p> <p>Methods</p> <p>12 participants 12 to 35 years old were recruited to a prospective open-label pilot trial and treated with 60 mg of standardized <it>G. biloba </it>two times per day for 12 weeks. The criteria for feasibility included successful recruitment, 75% or greater retention, effectiveness and lack of serious adverse reactions. Effectiveness was assessed using the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF), which are validated outcome measures evaluating the area and intensity of depigmentation of vitiligo lesions. Other outcomes included photographs and adverse reactions. Safety was assessed by serum coagulation factors (platelets, PTT, INR) at baseline and week 12.</p> <p>Results</p> <p>After 2 months of recruitment, the eligible upper age limit was raised from 18 to 35 years of age in order to facilitate recruitment of the required sample size. Eleven participants completed the trial with 85% or greater adherence to the protocol. The total VASI score improved by 0.5 (P = 0.021) from 5.0 to 4.5, range of scale 0 (no depigmentation) to 100 (completely depigmented). The progression of vitiligo stopped in all participants; the total VASI indicated an average repigmentation of vitiligo lesions of 15%. VETF total vitiligo lesion area decreased 0.4% (P = 0.102) from 5.9 to 5.6 from baseline to week 12. VETF staging score improved by 0.7 (P = 0.101) from 6.6 to 5.8, and the VETF spreading score improved by 3.9 (P < 0.001)) from 2.7 to -1.2. There were no statistically significant changes in platelet count, PTT, or INR.</p> <p>Conclusions</p> <p>The criteria for feasibility were met after increasing the maximum age limit of the successful recruitment criterion; participant retention, safety and effectiveness criteria were also met. Ingestion of 60 mg of <it>Ginkgo biloba </it>BID was associated with a significant improvement in total VASI vitiligo measures and VETF spread, and a trend towards improvement on VETF measures of vitiligo lesion area and staging. Larger, randomized double-blind clinical studies are warranted and appear feasible.</p> <p>Trial Registration</p> <p>Clinical trials.gov registration number <a href="http://www.clinicaltrials.gov/ct2/show/NCT00907062">NCT00907062</a></p

    Microsatellite based genetic diversity and population structure of the endangered Spanish Guadarrama goat breed

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    <p>Abstract</p> <p>Background</p> <p>Assessing genetic biodiversity and population structure of minor breeds through the information provided by neutral molecular markers, allows determination of their extinction risk and to design strategies for their management and conservation. Analysis of microsatellite loci is known to be highly informative in the reconstruction of the historical processes underlying the evolution and differentiation of animal populations. Guadarrama goat is a threatened Spanish breed which actual census (2008) consists of 3057 females and 203 males distributed in 22 populations more or less isolated. The aim of this work is to study the genetic status of this breed through the analysis of molecular data from 10 microsatellites typed in historic and actual live animals.</p> <p>Results</p> <p>The mean expected heterozygosity across loci within populations ranged from 0.62 to 0.77. Genetic differentiation measures were moderate, with a mean F<sub>ST </sub>of 0.074, G<sub>ST </sub>of 0.081 and R<sub>ST </sub>of 0.085. Percentages of variation among and within populations were 7.5 and 92.5, respectively. Bayesian clustering analyses pointed out a population subdivision in 16 clusters, however, no correlation between geographical distances and genetic differences was found. Management factors such as the limited exchange of animals between farmers (estimated gene flow Nm = 3.08) mostly due to sanitary and social constraints could be the major causes affecting Guadarrama goat population subdivision.</p> <p>Conclusion</p> <p>Genetic diversity measures revealed a good status of biodiversity in the Guadarrama goat breed. Since diseases are the first cause affecting the census in this breed, population subdivision would be an advantage for its conservation. However, to maintain private alleles present at low frequencies in such small populations minimizing the inbreeding rate, it would necessitate some mating designs of animals carrying such alleles among populations. The systematic use of molecular markers will facilitate the comprehensive management of these populations, which in combination with the actual breeding program to increase milk yield, will constitute a good strategy to preserve the breed.</p
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