561 research outputs found
Band structure and atomic sum rules for x-ray dichroism
Corrections to the atomic orbital sum rule for circular magnetic x-ray
dichroism in solids are derived using orthonormal LMTOs as a single-particle
basis for electron band states.Comment: 7 pages, no figure
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Imputing gene expression from optimally reduced probe sets
Measuring complete gene expression profiles for a large number of experiments is costly. We propose an approach in which a small subset of probes is selected based on a preliminary set of full expression profiles. In subsequent experiments, only the subset is measured, and the missing values are imputed. We develop several algorithms to simultaneously select probes and impute missing values, and demonstrate that these probe selection for imputation (PSI) algorithms can successfully reconstruct missing gene expression values in a wide variety of applications, as evaluated using multiple metrics of biological importance. We analyze the performance of PSI methods under varying conditions, provide guidelines for choosing the optimal method based on the experimental setting, and indicate how to estimate imputation accuracy. Finally, we apply our approach to a large-scale study of immune system variation
An Inverse Method for Cracks Characterization from Ultrasonic Bscan Images
Concern has been expressed about the capabilities of performing non destructive evaluation (NDE) of flaws located near to the outer surface in nuclear pressurized water reactor (PWR) vessels. The ultrasonic examination of PWR is accomplished from the inside with ultrasonic focused transducers working in the pulse echo mode. By recording the echoes as a function of time, the Ascan representation may be obtained. Many ultrasonic flaw detectors used for NDE are based on the simple Ascan concept involving measuring a time interval called “time of flight”. By combining the Ascan concept with synchronized transducer scanning, one can produce Bscan images that are two dimensional descriptions of the flaw interaction with the ultrasonic field
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Neonatal Tolerance Revisited: A Perinatal Window for Aire Control of Autoimmunity
There has long been conceptual and experimental support for, but also challenges to, the notion that the initial period of the immune system's development is particularly important for the establishment of tolerance to self. The display of self-antigens by thymic epithelial cells is key to inducing tolerance in the T lymphocyte compartment, a process enhanced by the Aire transcription factor. Using a doxycycline-regulated transgene to target Aire expression to the thymic epithelium, complementing the Aire knockout in a temporally controlled manner, we find that Aire is essential in the perinatal period to prevent the multiorgan autoimmunity that is typical of Aire deficiency. Surprisingly, Aire could be shut down soon thereafter and remain off for long periods, with few deleterious consequences. The lymphopenic state present in neonates was a factor in this dichotomy because inducing lymphopenia during Aire turnoff in adults recreated the disease, which, conversely, could be ameliorated by supplementing neonates with adult lymphocytes. In short, Aire expression during the perinatal period is both necessary and sufficient to induce long-lasting tolerance and avoid autoimmunity. Aire-controlled mechanisms of central tolerance are largely dispensable in the adult, as a previously tolerized T cell pool can buffer newly generated autoreactive T cells that might emerge
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Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging
All juvenile NOD mice exhibit insulitis, but there is substantial variation in their progression to diabetes. We demonstrate that a patient-validated magnetic-resonance-imaging (MRI) strategy to non-invasively visualize local effects of pancreatic-islet inflammation can predict diabetes onset in NOD mice. MRI signals acquired during a narrow early time-window allowed pre-sorting into disease-progressors and -nonprogressors and an estimate of time-to-diabetes. We exploited this capability to identify novel elements correlated with disease protection, including CRIg (complement receptor of the immunoglobulin superfamily), which marked a subset of macrophages associated with diabetes resistance. Administration of CRIg-Fc depressed MRI signals and diabetes incidence. In addition to identifying regulators of disease progression, this study shows that diabetes is set at an early age in NOD mice
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Thymic negative selection is functional in NOD mice
Based on analyses of multiple TCR transgenic (tg) models, the emergence of pathogenic T cells in diabetes-prone NOD mice has been ascribed to a failure to censure autoreactive clones in the thymus. In contrast, using isolated and preselected thymocytes, we show that nonobese diabetic (NOD) genetic variation impairs neither clonal deletion nor downstream transcriptional programs. However, we find that NOD genetic variation influences αβ/γδ-lineage decisions promoted by early expression of tg αβ-TCRs at the double-negative (DN) stage. In B6 and other genetic backgrounds, tg αβ-TCRs behave like γδ-TCRs and commit a large fraction of DNs toward the γδ-lineage, thereby decreasing the size of the double-positive (DP) pool, which is efficiently positively and negatively selected. In NOD DNs, αβ-TCR signalosomes instead behave like pre-TCRs, resulting in high numbers of DPs competing for limited selection niches, and poor positive and negative selection. Once niche effects are neutralized in mixed bone marrow chimeras, positive and negative selection are equally efficient on B6 and NOD backgrounds. Biochemical analysis revealed a selective defect in the activation of Erk1/2 downstream of NOD αβ-TCR signalosomes. Therefore, NOD genetic variation influences αβ/γδ-lineage decisions when the αβ-TCR heterodimer is prematurely expressed, but not the process of negative selection
A refined stable restriction theorem for vector bundles on quadric threefolds
Let E be a stable rank 2 vector bundle on a smooth quadric threefold Q in the
projective 4-space P. We show that the hyperplanes H in P for which the
restriction of E to the hyperplane section of Q by H is not stable form, in
general, a closed subset of codimension at least 2 of the dual projective
4-space, and we explicitly describe the bundles E which do not enjoy this
property. This refines a restriction theorem of Ein and Sols [Nagoya Math. J.
96, 11-22 (1984)] in the same way the main result of Coanda [J. reine angew.
Math. 428, 97-110 (1992)] refines the restriction theorem of Barth [Math. Ann.
226, 125-150 (1977)].Comment: Ann. Mat. Pura Appl. 201
Phase transition curves for mesoscopic superconducting samples
We compute the phase transition curves for mesoscopic superconductors.
Special emphasis is given to the limiting shape of the curve when the magnetic
flux is large. We derive an asymptotic formula for the ground state of the
Schr\"odinger equation in the presence of large applied flux. The expansion is
shown to be sensitive to the smoothness of the domain. The theoretical results
are compared to recent experiments.Comment: 8 pages, 1 figur
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PPARγ is a Major Driver of the Accumulation and Phenotype of Adipose-Tissue Cells
Obesity and type-2 diabetes have increased markedly over the past few decades, in parallel. One of the major links between these two disorders is chronic, low-grade inflammation. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues, leading to metabolic abnormalities such as insulin resistance, type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance, little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T cells was recently implicated in control of the inflammatory state of adipose tissue and, thereby, insulin sensitivity. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ, the ‘master regulator’ of adipocyte differentiation, as a crucial molecular orchestrator of VAT cell accumulation, phenotype and function. Unexpectedly, PPAR-γ expression by VAT cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs, and provide proof-of-principle that discrete populations of cells with unique functions can be precisely targeted to therapeutic ends
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Circulating C3 is Necessary and Sufficient for Induction of Autoantibody-Mediated Arthritis in a Mouse Model
Objective. For the inflammation characteristic of rheumatoid arthritis, the relative contribution of mediators produced locally in the synovium versus those circulating systemically is unknown. Complement factor C3 is made in rheumatoid synovium and has been proposed to be a crucial driver of inflammation. The aim of this study was to test, in a mouse model of rheumatoid arthritis, whether C3 synthesized within the synovium is important in promoting inflammation. Methods. Radiation bone marrow chimeras between normal and C3−/− mice were constructed in order to generate animals that expressed or lacked expression of C3 only in hematopoietic cells. Parabiotic mice were made by surgically linking C3−/− mice to irradiated wild-type mice to obtain animals having C3 only in the circulation. Arthritis was induced by injection of serum from arthritic K/BxN mice.Results In bone marrow chimeras, synthesis of C3 by radioresistant cells was necessary and sufficient to confer susceptibility to serum-transferred arthritis. Parabionts having C3 only in the circulation remained sensitive to arthritis induction, and the cartilage of these arthritic mice contained deposits of C3. Conclusion. In a mouse model in which the alternative pathway of complement activation is critical to the induction of arthritis by autoantibodies, circulating C3 was necessary and sufficient for arthritis induction.Stem Cell and Regenerative Biolog
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