Scalable Cold-Atom Quantum Simulator for Two-Dimensional QED.

We propose a scalable analog quantum simulator for quantum electrodynamics in two spatial dimensions. The setup for the U(1) lattice gauge field theory employs interspecies spin-changing collisions in an ultracold atomic mixture trapped in an optical lattice. We engineer spatial plaquette terms for magnetic fields, thus solving a major obstacle toward experimental realizations of realistic gauge theories in higher dimensions. We apply our approach to the pure gauge theory of compact QED and discuss how the phenomenon of confinement of electric charges can be described by the quantum simulator.

Acute outcome of chronic total occlusion (CTO) recanalizsation in the elderly.

OBJECTIVES: Percutaneous coronary intervention (PCI) of total chronic total occlusion (CTO) still remains a major challenge in interventional cardiology. There is only insignificant knowledge reported in the literature about age differences in CTO recanalization. We analyzed in this study the issue of the impact of age on procedural characteristics, complications and short-term outcome. METHODS: Between 2012-2016 we included 440 patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied. The retrograde approach was used only after failed antegrade intervention. Continuous data are presented as the mean ± standard deviation; categorical data are presented as numbers and percentages unless otherwise specified. We used Twosamplet- t-test with equal variance to test the significant differences of the variables between the two cohorts. RESULTS: Procedural success proved independently of age. There was no significant interaction between age and procedural success (p=0.5). Complication rates were low in both groups (2.7% vs. 4%; p=0,4) with no difference in statistical significance. CONCLUSIONS: Our study suggests that in an aging society patients with severe coronary artery disease and chronical total occlusions an interventional therapy should be used more intensively. It can be performed safe and feasible.

Gender-based acute outcome in percutaneous coronary intervention of chronic total coronary occlusion.

BACKGROUND: Percutaneous coronary intervention (PCI) of total chronic coronary occlusion (CTO) still remains a major challenge. Insignificant data are reported in the literature about gender differences in CTO-PCI in the era of new drug-eluting stents. In this study we analysed the impact of gender on procedural characteristics, complications and acute results. METHODS: Between 2010-2015 we included 780 consecutive patients. They underwent PCI for at least one CTO. Antegrade and retrograde CTO techniques were applied. RESULTS: Patients undergoing CTO-PCI were mainly men (84%). Male patients were younger (66.9 years ±10.6 vs. 61.1 years ±10.4; p < 0.001), more often smokers, but less frequently had a history of coronary artery disease (24.4% vs. 32.7%; p = 0.085) compared with female patients. Female patients more often had diabetes mellitus (29.6% vs. 26.7%; p = 0.55) and hypertension (82.7% vs. 80.7%; p = 0.55). There were no differences with respect to the amount of contrast fluid, fluoroscopy time and examination time as well as to the length of the stent or the number of the stents. The stent diameter was slightly smaller in women, which was not surprising because the lumen calibre tends to be smaller in women than in men (3.0 mm (2.5-3) vs. 3.0 mm (3-3.5); p < 0.001). The success rates were 81.0% in women and 80.1% in men. There was no significant interaction between gender and procedural success and complication rates. CONCLUSIONS: Our retrospective study suggests that women and men have a comparable success rate at a low complication rate after recanalisation of CTO.

Seroprevalence of campylobacteriosis and relevant post-infectious sequelae.

Post-infectious sequelea such as Guillain Barré syndrome (GBS), reactive arthritis (RA), and inflammatory bowel disease (IBD) may arise as a consequence of acute Campylobacter-enteritis (AE). However, reliable seroprevalence data of Campylobacter-associated sequelae has not been established. The objectives of this study were, first, to identify the most specific and sensitive test antigen in an optimized ELISA assay for diagnosing a previous Campylobacter-infection and, second, to compare the prevalence of anti-Campylobacter antibodies in cohorts of healthy blood donors (BD), AE, GBS, RA, and IBD patients with antibodies against known GBS, RA and IBD triggering pathogens. Optimized ELISAs of single and combined Campylobacter-proteins OMP18 and P39 as antigens were prepared and sera from AE, GBS, RA and IBD patients and BD were tested for Campylobcter-specific IgA and IgG antibodies. The results were compared with MIKROGEN™-recomLine Campylobacter IgA/IgG and whole cell lysate-immunoblot. Antibodies specific for Helicobacter pylori, Mycoplasma pneumoniae, Yersinia enterocolitica, and Borrelia afzelii were tested with commercial immunoblots. ROC plot analysis revealed AUC maxima in the combination of OMP18 and P39 for IgA and in the P39-antigen for IgG. As a result, 34-49 % GBS cases, 44-62 % RA cases and 23-40 % IBD cases were associated with Campylobacter-infection. These data show that Campylobcater-seropositivity in these patient groups is significantly higher than other triggering pathogens suggesting that it plays an important role in development of GBS and RA, and supports the hypothesis that recurrent acute campylobacteriosis triggers IBD.

Neuroenhancement among Swiss students--a comparison of users and non-users.

INTRODUCTION: This survey aims to contribute to the current discussion about neuroenhancement by comparing cognitive enhancer(s) (CE) users with CE non-users with a focus on their characteristics and attitudes. METHODS: An online survey was sent out to all undergraduate and graduate students of the University of Zürich who allow such e-mails (n=8642), accompanied by advertisement for the survey in lectures. 1765 students completed the survey, which was about healthy people's use of Ritalin, Adderall and/or Modasomil to increase concentration and/or alertness. A complementary paper-and-pencil survey (n=97 students, response rate: 95.1%) was also carried out in order to compare data. RESULTS: Non-therapeutic CE users (6.2%) were more often male, considered religion to be of less importance and had more experience with drugs. CE had been taken for study purposes by 4.7% of all students. CE users had tried Ritalin most often, which about half of them received from friends and colleagues. The CE users had more reasons for and fewer concerns about taking CE than non-users. The most common reasons for both groups were "the effects of learning quicker" and "for finishing more work in less time". The most common concerns for both groups were "the worries about possible side effects" and "the goal of CE to achieve more", and "an unnatural interference of such products with our bodies" (CE-users) or "the gut feeling of not using such products" (CE non-users). DISCUSSION: The comparison of CE users with CE non-users reveals insights about their attitudes, which will add to the understanding of why students take or could imagine taking such products.

Prevalence of antibodies against influenza A and B viruses in children in Germany, 2008 to 2010.

The prevalence of influenza A and B virus-specific IgG was determined in sera taken between 2008 and 2010 from 1,665 children aged 0-17 years and 400 blood donors in Germany. ELISA on the basis of whole virus antigens was applied. Nearly all children aged nine years and older had antibodies against influenza A. In contrast, 40% of children aged 0-4 years did not have any influenza A virus-specific IgG antibodies. Eightysix percent of 0-6 year-olds, 47% of 7-12 year-olds and 20% of 13-17 year-olds were serologically naïve to influenza B viruses. By the age of 18 years, influenza B seroprevalence reached approximately 90%. There were obvious regional differences in the seroprevalence of influenza B in Germany. In conclusion, seroprevalences of influenza A and influenza B increase gradually during childhood. The majority of children older than eight years have basal immunity to influenza A, while comparable immunity against influenza B is only acquired at the age of 18 years. Children aged 0-6 years, showing an overall seroprevalence of 67% for influenza A and of 14% for influenza B, are especially at risk for primary infections during influenza B seasons.

Systematic mapping of icosahedral short-range order in a melt-spun Zr36Cu64 metallic glass.

By analyzing the angular correlations in scanning electron nanodiffraction patterns from a melt-spun Zr(36)Cu(64) glass, the dominant local order was identified as icosahedral clusters. Mapping the extent of this icosahedral short-range order demonstrates that the medium-range order in this material is consistent with a face-sharing or interpenetrating configuration. These conclusions support results from atomistic modeling and a structural basis for the glass formability of this system.

Long-term follow-up in patients with indeterminate Barrett esophagus.

BACKGROUND: Barrett esophagus (BE) is a major risk factor for adenocarcinoma of the distal esophagus. Reliable detection of BE during upper endoscopy is therefore mandatory. According to most guidelines, diagnosis of BE requires both endoscopy and histology for confirmation. However, since adenocarcinomas were also described in patients with indeterminate BE, i.e. endoscopic visible columnar metaplasia but no histological confirmation of goblet cells or vice versa, debate has risen on the risk of malignancy and the need for endoscopic surveillance in such patients. PATIENTS AND METHODS: The study was aimed to assess long-term follow-up data on 209 patients with indeterminate BE (on histopathology or endoscopy) initially examined between 1999 and 2000. Patients or referring physicians were contacted concerning the most recent endoscopic and histopathological results. RESULTS: Follow-up data could be assessed in 149/209 patients (65.1%) after a mean follow-up period of 9.4 years (SD ±2.4 years). Neoplasia was not reported for any patient. The previous endoscopic-histopathological diagnoses could be confirmed in 3 patients only. In the group with endoscopic diagnosis of BE but no histopathological confirmation, BE was described histopathologically in 1 patient during follow-up. CONCLUSION: Persistence of indeterminate BE is poor during long-term follow up. The risk of cancer appears to be negligible. Hence, surveillance of these patients appears equivocal.

Influenza vaccination is associated with reduced severity of community-acquired pneumonia.

Pneumonia is an important cause of influenza-associated morbidity and mortality. Influenza vaccination has been shown to reduce morbidity and mortality during influenza seasons. Protection from severe pneumonia may contribute to the beneficial effect of influenza vaccination. Therefore, we investigated the impact of prior influenza vaccination on disease severity and mortality in patients with community-acquired pneumonia (CAP). Analysis from an observational, multicentre cohort study initiated by the German competence network for CAP was performed. Patients were analysed separately as an influenza season and off-season cohort. Associations between vaccination status and outcome parameters were evaluated by multivariate analyses. In the season cohort (2,368 patients) CAP in vaccinated patients was significantly less severe according to most analysed parameters (CURB index ≥ 1: OR 0.76, 95% CI 0.60-0.98; procalcitonin ≥ 2.0 ng·mL(-1): OR 0.53, 95% CI 0.35-0.81; procalcitonin ≥ 0.5 ng·mL(-1): OR 0.71, 95% CI 0.51-0.99) and these patients showed a significantly better overall survival within the 6-month follow-up period (HR 0.63, 95% CI 0.45-0.89). Within the off-season cohort (2,632 patients) there was no significant influence of vaccination status on CAP severity or disease outcome. In conclusion, prior influenza vaccination was associated with less severe clinical course and improved overall long-term survival in patients with CAP during influenza seasons.

Achieving large uniform tensile ductility in nanocrystalline metals.

Synchrotron x-ray diffraction and high-resolution electron microscopy revealed the origin of different strain hardening behaviors (and dissimilar tensile ductility) in nanocrystalline Ni and nanocrystalline Co. Planar defect accumulations and texture evolution were observed in Co but not in Ni, suggesting that interfacial defects are an effective passage to promote strain hardening in truly nanograins. Twinning becomes less significant in Co when grain sizes reduce to below ~15 nm. This study offers insights into achieving excellent mechanical properties in nanocrystalline materials.

Activation of the DNA replication checkpoint through RNA synthesis by primase.

When DNA replication is inhibited during the synthesis (S) phase of the cell cycle, a signaling pathway (checkpoint) is activated that serves to prevent mitosis from initiating before completion of replication. This replication checkpoint acts by down-regulating the activity of the mitotic inducer cdc2-cyclin B. Here, we report the relation between chromatin structure and induction of the replication checkpoint. Chromatin was competent to initiate a checkpoint response only after the DNA was unwound and DNA polymerase alpha had been loaded. Checkpoint induction did not require new DNA synthesis on the unwound template strand but did require RNA primer synthesis by primase. These findings identify the RNA portion of the primer as an important component of the signal that activates the replication checkpoint.

Seroprevalence of influenza A and B in German infants and adolescents.

The objective of this study was to provide seroepidemiological information on influenza A and B antibodies in children and adolescents. Viral immunoglobulin G antibodies were determined retrospectively using enzyme-linked immunosorbent assays in a group of 1,111 children and adolescents. Sera (809) from healthy adult blood donors served as controls. In children, the prevalence of antibodies against influenza A was 82.0% and against influenza B 9.6%, whereas in adults the prevalence of antibodies against influenza A was calculated as 99.4% and against influenza B 56.7%. After decline of maternal antibodies during the first year of life, there was an increase of prevalence of influenza A antibodies up to 100% by the age of 12 years. In contrast, only 1-2% of children up to 9 years had influenza B antibodies increasing to 25% by the age of 18 years and to 70% among adults aged 30 years. Children aged 0-6 years had significantly lower concentrations and >12-15-year-old adolescents had significantly higher concentrations of antibodies against influenza A than adults. For all age groups of children and adolescents, significantly lower antibody concentrations against influenza B were measured in comparison to the blood donor control group. In conclusion, the annual influenza vaccination in children and adolescents may improve considerably the protection against influenza virus infection occurring during epidemics.

Observation of η-Al41Sm5 reveals motif-aware structural evolution in Al-Sm alloys.

Using an effective genetic algorithm, we uncover the structure of a metastable Al41Sm5 phase that supplements its family sharing similar short-range orders. The phase evolves upon heating an amorphous Al-9.7 at.% Sm ribbon, produced by melt-spinning. The dynamical phase selection is discussed with respect to the structural connections between the short-range packing motifs in the amorphous precursor and those observed in the selected phases. The phase elucidated here is one of several newly discovered large-unit-cell phases found to form during devitrification from the glass in this binary system, further illustrating the power and efficiency of our approach, the important role of structural hierarchy in phase selection, and the richness of the metastable phase landscape accessible from the glassy structure.

JunB is a gatekeeper for B-lymphoid leukemia.

Loss of JunB has been observed in human leukemia and lymphoma, but it remains unknown, whether this loss is relevant to disease progression. Here, we investigated the consequences of JunB deficiency using Abelson-induced B-lymphoid leukemia as a model system. Mice deficient in JunB expression succumbed to Abelson-induced leukemia with increased incidence and significantly reduced latency. Similarly, bcr/abl p185-transformed JunB-deficient (junB(Delta/Delta)) cells induced leukemia in RAG2(-/-) mice displaying a more malignant phenotype. These observations indicated that cell intrinsic effects within the junB(Delta/Delta) tumor cells accounted for the accelerated leukemia development. Indeed, explantated bcr/abl p185 transformed junB(Delta/Delta) cells proliferated faster than the control cells. The proliferative advantage emerged slowly after the initial transformation process and was associated with increased expression levels of the cell cycle kinase cdk6 and with decreased levels of the cell cycle inhibitor p16(INK4a). These alterations were due to irreversible reprogramming of the cell, because - once established - accelerated disease induced by junB(Delta/Delta) cells was not reverted by re-introducing JunB. Consistent with this observation, we found that the p16 promoter was methylated. Thus, JunB functions as a gatekeeper during tumor evolution. In its absence, transformed leukemic cells acquire an enhanced proliferative capacity, which presages a more malignant disease.

An investigation into the use of CMOS active pixel technology in image-guided radiotherapy.

The increased intelligence, read-out speed, radiation hardness and potential large size of CMOS active pixel sensors (APS) gives them a potential advantage over systems currently used for verification of complex treatments such as IMRT and the tracking of moving tumours. The aim of this work is to investigate the feasibility of using an APS-based system to image the megavoltage treatment beam produced by a linear accelerator (Linac), and to demonstrate the logic which may ultimately be incorporated into future sensor and FPGA design to evaluate treatment and track motion. A CMOS APS was developed by the MI(3) consortium and incorporated into a megavoltage imaging system using the standard lens and mirror configuration employed in camera-based EPIDs. The ability to resolve anatomical structure was evaluated using an Alderson RANDO head phantom, resolution evaluated using a quality control (QC3) phantom and contrast using an in-house developed phantom. A complex intensity-modulated radiotherapy (IMRT) treatment was imaged and two algorithms were used to determine the field-area and delivered dose, and the position of multi-leaf collimator (MLC) leaves off-line. Results were compared with prediction from the prescription and found to agree within a single image frame time for dose delivery and 0.02-0.03 cm for the position of collimator leaves. Such a system therefore shows potential as the basis for an on-line verification system capable of treatment verification and monitoring patient motion.

True adenomas of the cardia: a case series of 3 patients.

BACKGROUND/AIM: True adenomas of the cardia appear to be extremely rare lesions. There are no data on the natural history and histopathological background of these lesions. We report 3 patients with true adenomas of the cardia. METHODS AND RESULTS: Three patients with polypoid masses at the cardia below the Z-line were submitted to a tertiary referral center for further diagnosis and therapy. In 2 of the 3 cases Barrett's esophagus with low-grade intraepithelial neoplasia was assumed on the basis of histopathological examination of biopsy specimens taken from the surface of the lesions. Polypectomy was performed in all 3 cases. In 2 of the 3 cases the final histopathological diagnosis of low-grade adenoma of the cardia could only be established after complete removal of the polypoid masses. CONCLUSIONS: Adenomas of the cardia can be mistaken for dysplasia arising from Barrett's esophagus, if the diagnosis is based on endoscopic biopsies only. It is, therefore, reasonable to completely remove any suspicious lesions by endoscopy not only for therapeutic but also for diagnostic reasons.

Feline glucose-6-phosphate dehydrogenase cellular mosaicism. Application to the study of retrovirus-induced pure red cell aplasia.

Neoplasms result from the uncontrolled proliferation of abnormal or transformed cells. The early stages of this process are difficult to study because of the lack of sensitive and specific markers of clonal evolution in an experimental system. We have developed a cat model using cellular mosaicism for glucose-6-phosphate dehydrogenase (G-6-PD). Our findings confirm that the structural locus for feline G-6-PD is on the X-chromosome and demonstrate that it is randomly inactivated in somatic cells. Heterozygous cats have balanced ratios of G-6-PD enzyme types in peripheral blood cells and hematopoietic progenitors that remain stable over time. In our initial studies, we used the model to analyze the events surrounding marrow failure experimentally induced by selected strains of feline leukemia virus (FeLV). Two G-6-PD heterozygous cats, one F1 male hybrid and one domestic cat were infected with FeLV (C or KT) and developed pure red cell aplasia (PRCA). Colonies arising from the more mature erythroid colony-forming cell were not detected in marrow culture of anemic animals although erythroid bursts persisted, suggesting that the differentiation of early erythroid progenitors (BFU-E) was inhibited in vivo. The ratio of G-6-PD types in hematopoietic progenitors and peripheral blood cells from the heterozygous cats did not change when the animals developed PRCA. Thus, the anemia did not result from the clonal expansion of a transformed myeloid stem cell. With this experimental approach, one may prospectively assess clonal evolution and cellular interactions in other FeLV-induced diseases.

Multiple Mycobacterium antigens induce interferon-gamma production from sarcoidosis peripheral blood mononuclear cells.

Studies of sarcoidosis immunology have noted oligoclonal T cell populations, suggesting cell-mediated immunity that is antigen-specific. Sarcoidosis immunology and pathology are most similar to mycobacterial infections. Mycobacterium tuberculosis infection in mice and humans reflects T helper 1 (Th1) immune responses to multiple cell wall and secreted antigens. We investigated if the oligoclonal immune response in individual sarcoidosis subjects could be elicited by multiple secreted mycobacterial antigens by performing ex vivo enzyme-linked immunospot assay (ELISPOT) on peripheral blood mononuclear cells (PBMC) from 30 sarcoidosis, 26 purified protein derivative negative (PPD-) control and 10 latent tuberculosis subjects (PPD+) to assess Th1 responses to mycobacterial superoxide dismutase A (sodA), catalase-peroxidase (katG) and early secreted antigenic target protein (ESAT-6). A significant difference was noted among the sarcoidosis and PPD- control subjects to ESAT-6 [12 of 30 versus one of 26 (P = 0.0014)], katG [nine of 30 versus none of 26 (P = 0.002)] and sodA [12 of 30 versus none of 26 (P = 0.002)]. There was no significant difference between sarcoidosis and PPD+ subjects. Twelve sarcoidosis subjects recognized two or more mycobacterial proteins, as well as multiple distinct epitopes within individual proteins. One sarcoidosis subject on whom we collected bronchoalveolar lavage (BAL) fluid and PBMC had no recognition of mycobacterial antigens using PBMC, but BAL fluid demonstrated strong Th1 immune responses to ESAT-6 and katG. Individual sarcoidosis subjects recognized not only multiple mycobacterial proteins, but multiple distinct peptides within a specific protein, thus demonstrating that multiple mycobacterial epitopes elicit the Th1 immune response observed. Immune responses by sarcoidosis T cells to mycobacterial proteins may have an important role in sarcoidosis pathogenesis.

Cell cycle-dependent regulation of human DNA polymerase alpha-primase activity by phosphorylation.

DNA polymerase alpha-primase is known to be phosphorylated in human and yeast cells in a cell cycle-dependent manner on the p180 and p68 subunits. Here we show that phosphorylation of purified human DNA polymerase alpha-primase by purified cyclin A/cdk2 in vitro reduced its ability to initiate simian virus 40 (SV40) DNA replication in vitro, while phosphorylation by cyclin E/cdk2 stimulated its initiation activity. Tryptic phosphopeptide mapping revealed a family of p68 peptides that was modified well by cyclin A/cdk2 and poorly by cyclin E/cdk2. The p180 phosphopeptides were identical with both kinases. By mass spectrometry, the p68 peptide family was identified as residues 141 to 160. Cyclin A/cdk2- and cyclin A/cdc2-modified p68 also displayed a phosphorylation-dependent shift to slower electrophoretic mobility. Mutation of the four putative phosphorylation sites within p68 peptide residues 141 to 160 prevented its phosphorylation by cyclin A/cdk2 and the inhibition of replication activity. Phosphopeptide maps of the p68 subunit of DNA polymerase alpha-primase from human cells, synchronized and labeled in G1/S and in G2, revealed a cyclin E/cdk2-like pattern in G1/S and a cyclin A/cdk2-like pattern in G2. The slower-electrophoretic-mobility form of p68 was absent in human cells in G1/S and appeared as the cells entered G2/M. Consistent with this, the ability of DNA polymerase alpha-primase isolated from synchronized human cells to initiate SV40 replication was maximal in G1/S, decreased as the cells completed S phase, and reached a minimum in G2/M. These results suggest that the replication activity of DNA polymerase alpha-primase in human cells is regulated by phosphorylation in a cell cycle-dependent manner.