726 research outputs found

    Domain Walls Motion and Resistivity in a Fully-Frustrated Josephson Array

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    It is identified numerically that the resistivity of a fully-frustrated Josephson-junction array is due to motion of domain walls in vortex lattice rather than to motion of single vortices

    Evaluation of the protein characteristics of four diverse grasses

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    Forage protein characteristics in four grasses were evaluated by the nylon bag method. All of the forages used (Bermudagrass hay, brome hay, forage sorghum hay, and prairie hay) were of relatively low quality, except the Bermudagrass, which was of average quality. The forages differed in the size of different protein fractions and in the rate and extent of protein degradation. Predicted extent of ruminal protein degradation (i.e., ruminal protein availability) was lowest for prairie hay, intermediate for Bermudagrass and forage sorghum hay, and highest for the brome hay

    Parties, promiscuity and politicisation: business-political networks in Poland

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    Research on post-communist political economy has begun to focus on the interface between business and politics. It is widely agreed that informal networks rather than business associations dominate this interface, but there has been very little systematic research in this area. The literature tends to assume that a politicised economy entails business-political networks that are structured by parties. Theoretically, this article distinguishes politicisation from party politicisation and argues that the two are unlikely to be found together in a post-communist context. Empirically, elite survey data and qualitative interviews are used to explore networks of businesspeople and politicians in Poland. Substantial evidence is found against the popular idea that Polish politicians have business clienteles clearly separated from each other according to party loyalties. Instead, it is argued that these politicians and businesspeople are promiscuous. Since there seems to be little that is unusual about the Polish case, this conclusion has theoretical, methodological, substantive and policy implications for other post-communist countries

    Exceptional chemotherapy response in metastatic colorectal cancer associated with hyper-indel-hypermutated cancer genome and comutation of POLD1 and MLH1

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    Purpose A 73-year-old woman with metastatic colon cancer experienced a complete response to chemotherapy with dose-intensified irinotecan that has been durable for 5 years.Wesequenced her tumor and germ line DNA and looked for similar patterns in publicly available genomic data from patients with colorectal cancer. Patients and Methods Tumor DNA was obtained from a biopsy before therapy, and germ line DNA was obtained from blood. Tumor and germline DNA were sequenced using a commercial panel with approximately 250 genes. Whole-genome amplification and exome sequencing were performed for POLE and POLD1. A POLD1 mutation was confirmed by Sanger sequencing. The somatic mutation and clinical annotation data files from the colon (n = 461) and rectal (n = 171) adenocarcinoma data sets were downloaded from The Cancer Genome Atlas data portal and analyzed for patterns of mutations and clinical outcomes in patients withPOLE- and/orPOLD1- mutated tumors. Results The pattern of alterations included APC biallelic inactivation and microsatellite instability high (MSI-H) phenotype, with somatic inactivation of MLH1 and hypermutation (estimated mutation rate > 200 per megabase). The extremely high mutation rate led us to investigate additional mechanisms for hypermutation, including loss of function of POLE. POLE was unaltered, but a related gene not typically associated with somatic mutation in colon cancer, POLD1, had a somatic mutation c.2171G > A[p.Gly724Glu]. Additionally, we noted that the high mutation rate was largely composed of dinucleotide deletions. A similar pattern of hypermutation (dinucleotide deletions, POLD1 mutations, MSI-H) was found in tumors from The Cancer Genome Atlas. Conclusion POLD1 mutation with associated MSI-H and hyper-indel-hypermutated cancer genome characterizes a previously unrecognized variant of colon cancer that was found in this patient with an exceptional response to chemotherapy

    Evidence for softening of first-order transition in 3D by quenched disorder

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    We study by extensive Monte Carlo simulations the effect of random bond dilution on the phase transition of the three-dimensional 4-state Potts model which is known to exhibit a strong first-order transition in the pure case. The phase diagram in the dilution-temperature plane is determined from the peaks of the susceptibility for sufficiently large system sizes. In the strongly disordered regime, numerical evidence for softening to a second-order transition induced by randomness is given. Here a large-scale finite-size scaling analysis, made difficult due to strong crossover effects presumably caused by the percolation fixed point, is performed.Comment: LaTeX file with Revtex, 4 pages, 4 eps figure

    Effects of supplemental degradable intake protein on intake and digestibility of low-quality brome hay

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    The effects of increasing levels of degradable intake and digestion of low-quality brome hay were evaluated using 16 ruminally fistulated beef steers. Trends were evident for small, positive changes in total intake and digestion with increasing level of DIP supplementation. As a result, total digestible to feeding forage to provide .041, .082, and OM intake (TDOMI) increased with DIP supplementation but tended to plateau below the highest supplementation level

    Situationally edited empathy: an effect of socio-economic structure on individual choice

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    Criminological theory still operates with deficient models of the offender as agent, and of social influences on the agent’s decision-making process. This paper takes one ‘emotion’, empathy, which is theoretically of considerable importance in influencing the choices made by agents; particularly those involving criminal or otherwise harmful action. Using a framework not of rational action, but of ‘rationalised action’, the paper considers some of the effects on individual psychology of social, economic, political and cultural structure. It is suggested that the climate-setting effects of these structures promote normative definitions of social situations which allow unempathic, harmful action to be rationalised through the situational editing of empathy. The ‘crime is normal’ argument can therefore be extended to include the recognition that the uncompassionate state of mind of the criminal actor is a reflection of the self-interested values which govern non-criminal action in wider society

    Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays

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    Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care

    Comprehensive molecular characterization of urachal adenocarcinoma reveals commonalities with colorectal cancer, including a hypermutable phenotype

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    Purpose Urachal adenocarcinoma is a rare type of primary bladder adenocarcinoma that comprises less than 1% of all bladder cancers. The low incidence of urachal adenocarcinomas does not allow for an evidence-based approach to therapy. Transcriptome profiling of urachal adenocarcinomas has not been previously reported.Wehypothesized that an in-depth molecular understanding of urachal adenocarcinoma would uncover rational therapeutic strategies. Patients and Methods We performed targeted exon sequencing and global transcriptome profiling of 12 urachal tumors to generate a comprehensive molecular portrait of urachal adenocarcinoma. A single patient with an MSH6 mutation was treated with the anti-programmed death-ligand 1 antibody, atezolizumab. Results Urachal adenocarcinoma closely resembles colorectal cancer at the level of RNA expression, which extends previous observations that urachal tumors harbor genomic alterations that are found in colorectal adenocarcinoma. A subset of tumors was found to have alterations in genes that are associated with microsatellite instability (MSH2 and MSH6) and hypermutation (POLE).Apatient with anMSH6mutation was treated withimmunecheckpoint blockade, which resulted in stable disease. Conclusion Because clinical trials are next to impossible for patients with rare tumors, precision oncology may be an important adjunct for treatment decisions. Our findings demonstrate that urachal adenocarcinomas molecularly resemble colorectal adenocarcinomas at the level ofRNA expression, are the first report, to our knowledge, of MSH2andMSH6mutations in this disease, and support the consideration of immune checkpoint blockade as a rational therapeutic treatment of this exceedingly rare tumor
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