282 research outputs found

    Spin Transfer Torques in MnSi at Ultra-low Current Densities

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    Spin manipulation using electric currents is one of the most promising directions in the field of spintronics. We used neutron scattering to observe the influence of an electric current on the magnetic structure in a bulk material. In the skyrmion lattice of MnSi, where the spins form a lattice of magnetic vortices similar to the vortex lattice in type II superconductors, we observe the rotation of the diffraction pattern in response to currents which are over five orders of magnitude smaller than those typically applied in experimental studies on current-driven magnetization dynamics in nanostructures. We attribute our observations to an extremely efficient coupling of inhomogeneous spin currents to topologically stable knots in spin structures

    Skyrmion Lattice in a Chiral Magnet

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    Skyrmions represent topologically stable field configurations with particle-like properties. We used neutron scattering to observe the spontaneous formation of a two-dimensional lattice of skyrmion lines, a type of magnetic vortices, in the chiral itinerant-electron magnet MnSi. The skyrmion lattice stabilizes at the border between paramagnetism and long-range helimagnetic order perpendicular to a small applied magnetic field regardless of the direction of the magnetic field relative to the atomic lattice. Our study experimentally establishes magnetic materials lacking inversion symmetry as an arena for new forms of crystalline order composed of topologically stable spin states

    It's Time for Color Vision Deficiency Friendly Color Maps in the Radar Community

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    Color Vision Deficiency (CVD) is a decreased ability to discern between particular colors. 8% of men and 0.4% of women have some form of CVD. An informal poll of AGU and AMS twitter followers yielded 10% of 70 respondents self identifying as having CVD. When presenting data on a two-dimensional plane it is common to use colors to represent values, the mapping between values and colors is known as a colormap. Colormap choice is personal and is influenced by: (1) Ability to highlight scientifically interesting data. (2) Institutional choices (supervisor insists on a certain colormap). (3) Domain dominance of a particular colormap (common in the radar community). Colormap choice should be influenced by: (1) Ability to highlight scientifically interesting data. (2) Perceptual uniformity (thus not creating artificial structure). (3) Approachability by those with visual impairments (CVD). (4) Ideally, but not always achievable, reproducibility in greyscale

    Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells

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    In patients with bile acid malabsorption, high concentrations of bile acids enter the colon and stimulate Cl− and fluid secretion, thereby causing diarrhoea. However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally present at lower concentrations where its role in regulating transport is unclear. Thus, the current study set out to investigate the effects of physiologically relevant DCA concentrations on colonic epithelial secretory function. Cl− secretion was measured as changes in short-circuit current across voltage-clamped T84 cell monolayers. At high concentrations (0.5–1 mM), DCA acutely stimulated Cl− secretion but this effect was associated with cell injury, as evidenced by decreased transepithelial resistance (TER) and increased lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to lower DCA concentrations (10–200 μM) inhibited responses to Ca2+ and cAMP-dependent secretagogues without altering TER, LDH release, or secretagogue-induced increases in intracellular second messengers. Other bile acids – taurodeoxycholic acid, chenodeoxycholic acid and cholic acid – had similar antisecretory effects. DCA (50 μM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest that, in contrast to its acute prosecretory effects at pathophysiological concentrations, lower, physiologically relevant, levels of DCA chronically down-regulate colonic epithelial secretory function. On the basis of these data, we propose a novel role for bile acids as physiological regulators of colonic secretory capacity

    Artificial intelligence for renal cancer: From imaging to histology and beyond

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    Artificial intelligence (AI) has made considerable progress within the last decade and is the subject of contemporary literature. This trend is driven by improved computational abilities and increasing amounts of complex data that allow for new approaches in analysis and interpretation. Renal cell carcinoma (RCC) has a rising incidence since most tumors are now detected at an earlier stage due to improved imaging. This creates considerable challenges as approximately 10%–17% of kidney tumors are designated as benign in histopathological evaluation; however, certain co-morbid populations (the obese and elderly) have an increased peri-interventional risk. AI offers an alternative solution by helping to optimize precision and guidance for diagnostic and therapeutic decisions. The narrative review introduced basic principles and provide a comprehensive overview of current AI techniques for RCC. Currently, AI applications can be found in any aspect of RCC management including diagnostics, perioperative care, pathology, and follow-up. Most commonly applied models include neural networks, random forest, support vector machines, and regression. However, for implementation in daily practice, health care providers need to develop a basic understanding and establish interdisciplinary collaborations in order to standardize datasets, define meaningful endpoints, and unify interpretation

    Pain management in the neonatal piglet during routine management procedures. Part 2:Grading the quality of evidence and the strength of recommendations

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    Piglets reared in swine production in the USA undergo painful procedures that include castration, tail docking, teeth clipping, and identification with ear notching or tagging. These procedures are usually performed without pain mitigation. The objective of this project was to develop recommendations for pain mitigation in 1- to 28-day-old piglets undergoing these procedures. The National Pork Board funded project to develop recommendations for pain mitigation in piglets. Recommendation development followed a defined multi-step process that included an evidence summary and estimates of the efficacies of interventions. The results of a systematic review of the interventions were reported in a companion paper. This manuscript describes the recommendation development process and the final recommendations. Recommendations were developed for three interventions (CO2/O2 general anesthesia, non-steroidal anti-inflammatory drugs (NSAIDs), and lidocaine) for use during castration. The ability to make strong recommendations was limited by low-quality evidence and strong certainty about variation in stakeholder values and preferences. The panel strongly recommended against the use of a CO2/O2 general anesthesia mixture, weakly recommended for the use of NSAIDs and weakly recommended against the use of lidocaine for pain mitigation during castration of 1- to 28-day-old piglets

    Hepatitis C virus-induced changes in microRNA 107 (miRNA-107) and miRNA-449a modulate CCL2 by targeting the interleukin-6 receptor complex in hepatitis

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    Hepatitis C virus (HCV)-mediated liver diseases are one of the major health issues in the United States and worldwide. HCV infection has been reported to modulate microRNAs (miRNAs) that control various cell surface receptors and gene-regulatory complexes involved in hepatic inflammation and liver diseases. We report here that specific downregulation of miRNA-107 and miRNA-449a following HCV infection in patients with HCV-mediated liver diseases modulates expression of CCL2, an inflammatory chemokine upregulated in patients with chronic liver diseases, by targeting components of the interleukin-6 receptor (IL-6R) complex. Computational analysis for DNA-bound transcription factors in the CCL2 promoter identified adjacent binding sites for CCAAT/CEBPα, spleen focus-forming virus, proviral integration oncogene (SPI1/PU.1), and STAT3. We demonstrate that CEBPα, PU.1, and STAT3 interacted with each other physically to cooperatively bind to the promoter and activate CCL2 expression. Analysis of IL-6R and JAK1 expression in HCV patients by quantitative PCR showed significant upregulation when there was impaired miRNA-107 and miRNA-449a expression, along with upregulation of PU.1 and STAT3, but not CEBPα. miRNA-449a and miRNA-107 target expression of IL-6R and JAK1, respectively, in vitro and also inhibit IL-6 signaling and impair STAT3 activation in human hepatocytes. Taken together, our results demonstrate a novel gene-regulatory mechanism in which HCV-induced changes in miRNAs (miRNA-449a and miRNA-107) regulate CCL2 expression by activation of the IL-6-mediated signaling cascade, which we propose will result in HCV-mediated induction of inflammatory responses and fibrosis. IMPORTANCE Hepatitis C virus (HCV)-induced hepatitis is a major health concern worldwide. HCV infection results in modulation of noncoding microRNAs affecting major cellular pathways, including inflammatory responses. In this study, we have identified a microRNA-regulated pathway for the chemokine CCL2 in HCV-induced hepatitis. Understanding microRNA-mediated transcriptional-regulatory pathways will result in development of noninvasive biomarkers for better disease prediction and development of effective therapeutics

    Study of Transcriptional Effects in Cis at the IFIH1 Locus

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    Background: The Thr allele at the non-synonymous single-nucleotide polymorphism (nsSNP) Thr946Ala in the IFIH1 gene confers risk for Type 1 diabetes (T1D). The SNP is embedded in a 236 kb linkage disequilibrium (LD) block that includes four genes: IFIH1, GCA, FAP and KCNH7. The absence of common nsSNPs in the other genes makes the IFIH1 SNP the strongest functional candidate, but it could be merely a marker of association, due to LD with a variant regulating expression levels of IFIH1 or neighboring genes. Methodology/Principal Findings: We investigated the effect of the T1D-associated variation on mRNA transcript expression of these genes. Heterozygous mRNA from lymphoblastoid cell lines (LCLs), pancreas and thymus was examined by allelic expression imbalance, to detect effects in cis on mRNA expression. Using single-nucleotide primer extension, we found no difference between mRNA transcripts in 9 LCLs, 6 pancreas and 13 thymus samples, suggesting that GCA and FAP are not involved. On the other hand, KCNH7 was not expressed at a detectable level in all tissues examined. Moreover, the association of the Thr946Ala SNP with T1D is not due to modulation of IFIH1 expression in organs involved in the disease, pointing to the IFIH1 nsSNP as the causal variant. Conclusions/Significance: The mechanism of the association of the nsSNP with T1D remains to be determined, but does not involve mRNA modulation. It becomes necessary to study differential function of the IFIH1 protein alleles at Thr946Al
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