1,685 research outputs found

    On the universality of the Discrete Nonlinear Schroedinger Equation

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    We address the universal applicability of the discrete nonlinear Schroedinger equation. By employing an original but general top-down/bottom-up procedure based on symmetry analysis to the case of optical lattices, we derive the most widely applicable and the simplest possible model, revealing that the discrete nonlinear Schroedinger equation is ``universally'' fit to describe light propagation even in discrete tensorial nonlinear systems and in the presence of nonparaxial and vectorial effects.Comment: 6 Pages, to appear in Phys. Rev.

    Resolving new ultrastructural features of cytokinetic abscission with soft X ray cryo tomography

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    Mammalian cytokinetic abscission is mediated by the ESCRT membrane fission machinery. While much has been clarified on the topology and kinetics of abscission through high resolution microscopy, key questions regarding the mechanism of abscission remain open. Here we apply cryogenic soft X ray tomography to elucidate new ultrastructural details in the intercellular membrane bridge connecting cells undergoing abscission. In particular, we resolve defined ring like structures inside the midbody dark zone that have been inaccessible to EM, and identify membrane extrusions at the abscission sites. In cells at late stages of abscission we resolve a complex array of helical spirals, extending the structural information obtained by EM. Our results highlight the advantages of soft X ray tomography and emphasize the importance of using complementary approaches for characterizing cellular structures. Notably, by providing new structural data from intact cells we present a realistic view on the topology of abscission and suggest new mechanistic models for ESCRT mediated abscissio

    The structural basis for Z α1-antitrypsin polymerization in the liver

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    The serpinopathies are among a diverse set of conformational diseases that involve the aberrant self-association of proteins into ordered aggregates. α1-Antitrypsin deficiency is the archetypal serpinopathy and results from the formation and deposition of mutant forms of α1-antitrypsin as “polymer” chains in liver tissue. No detailed structural analysis has been performed of this material. Moreover, there is little information on the relevance of well-studied artificially induced polymers to these disease-associated molecules. We have isolated polymers from the liver tissue of Z α1-antitrypsin homozygotes (E342K) who have undergone transplantation, labeled them using a Fab fragment, and performed single-particle analysis of negative-stain electron micrographs. The data show structural equivalence between heat-induced and ex vivo polymers and that the intersubunit linkage is best explained by a carboxyl-terminal domain swap between molecules of α1-antitrypsin

    The natural history of primary sclerosing cholangitis in 781 children. A multicenter, international collaboration

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    There are limited data on the natural history of primary sclerosing cholangitis (PSC) in children. We aimed to describe the disease characteristics and long-term outcomes of pediatric PSC. We retrospectively collected all pediatric PSC cases from 36 participating institutions and conducted a survival analysis from the date of PSC diagnosis to dates of diagnosis of portal hypertensive or biliary complications, cholangiocarcinoma, liver transplantation, or death. We analyzed patients grouped by disease phenotype and laboratory studies at diagnosis to identify objective predictors of long-term outcome. We identified 781 patients, median age 12 years, with 4,277 person-years of follow-up; 33% with autoimmune hepatitis, 76% with inflammatory bowel disease, and 13% with small duct PSC. Portal hypertensive and biliary complications developed in 38% and 25%, respectively, after 10 years of disease. Once these complications developed, median survival with native liver was 2.8 and 3.5 years, respectively. Cholangiocarcinoma occurred in 1%. Overall event-free survival was 70% at 5 years and 53% at 10 years. Patient groups with the most elevated total bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis had the worst outcomes. In multivariate analysis PSC-inflammatory bowel disease and small duct phenotypes were associated with favorable prognosis (hazard ratios 0.6, 95% confidence interval 0.5-0.9, and 0.7, 95% confidence interval 0.5-0.96, respectively). Age, gender, and autoimmune hepatitis overlap did not impact long-term outcome. CONCLUSION: PSC has a chronic, progressive course in children, and nearly half of patients develop an adverse liver outcome after 10 years of disease; elevations in bilirubin, gamma-glutamyltransferase, and aspartate aminotransferase-to-platelet ratio index at diagnosis can identify patients at highest risk; small duct PSC and PSC-inflammatory bowel disease are more favorable disease phenotypes

    Constructing identity through symbols by groups demanding self-determination: Bosnian Serbs and Iraqi Kurds

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    This contribution revisits the question over which much ink has been spilled in the study of national self-determination; who are the people? More specifically, the authors ask how national identity in self-determination claims is constructed. Drawing on observations from two case studies, they submit that cultural/ethnic definitions of national identity continue to underwrite self-determination claims. The authors argue that these practices have been central to the process of defining and reproducing the group identity on behalf of which the claim to political autonomy is made. The use of symbols and practices referring to territorially bound distinct nations with different linguistic and cultural features compared with other groups inhabiting the state reinforces the assertiveness of self-determination claims. Despite their differences, Bosnian Serbs and Iraqi Kurds typically follow similar trajectories in their use of ethnic, cultural and territorial symbols to reinstate the validity of their demands

    Guiding Neutral Atoms

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    We demonstrate the guiding of neutral atoms by the magnetic fields due to microfabricated current-carrying wires on a chip. Atoms are guided along a magnetic field minimum parallel to and above the current-carrying wires. Two waveguide configurations are demonstrated: one using two wires with an external magnetic field, and a second using four wires without an external field. These waveguide geometries can be extended to integrated atom optics circuits, including beamsplitters.Comment: 11 pages, 4 figure

    Molecular mechanisms of extracellular adenine nucleotides-mediated inhibition of human Cd4+ T lymphocytes activation

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    We have previously reported that ATPγS, a slowly hydrolyzed analog of ATP, inhibits the activation of human CD4+ T lymphocytes by anti-CD3 and anti-CD28 mAb. In this report we have partially characterized the signaling mechanisms involved in this immunosuppressive effect. ATPγS had no inhibitory effect on CD4+ T-cell activation induced by PMA and anti-CD28, indicating that it acts proximally to the TCR. It had no effect on the calcium rise induced by CD3/CD28 stimulation, but inhibited the phosphorylation of three kinases, ERK2, p38 MAPK and PKB, that play a key role in the activation of T cells. The receptor involved in these actions remains unidentified
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