147 research outputs found

    Rolling of Modulated Tachyon with Gauge Flux and Emergent Fundamental String

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    We investigate real-time tachyon dynamics of unstable D-brane carrying fundamental string charge. We construct the boundary state relevant for rolling of modulated tachyon with gauge fields excited on the world-volume, and study spatial distribution of the fundamental string charge and current as the D-brane decays. We find that, in contrast to homogeneous tachyon rolling, spatial modulation of the tachyon field triggers density wave of strings when electric field is turned on, and of string anti-string pairs when magnetic field is turned on. We show that the energy density and the fundamental string charge density are locked together, and evolve into a localized delta-function array (instead of evolving into a string fluid) until a critical time set by initial condition of rolling tachyon. When the gauge fields approach the critical limit, the fundamental strings produced become BPS-like. We also study the dynamics via effective field theory, and find agreement.Comment: 28 pages, Latex, 7 .eps figures v2: stability discussion update

    <sup>18</sup>F-FDG-PET/CT to Detect Pathological Complete Response After Neoadjuvant Treatment in Patients with Cancer of the Esophagus or Gastroesophageal Junction:Accuracy and Long-Term Implications

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    Purpose : The curative strategy for patients with esophageal cancer without distant metastases consists of esophagectomy with preceding chemo(radio)therapy (CRT). In 10–40% of patients treated with CRT, no viable tumor is detectable in the resection specimen (pathological complete response (pCR)). This study aims to define the clinical outcomes of patients with a pCR and to assess the accuracy of post-CRT FDG-PET/CT in the detection of a pCR. Methods: Four hundred sixty-three patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after CRT between 1994 and 2013 were included. Patients were categorized as pathological complete responders or noncomplete responders. Standardized uptake value (SUV) ratios of 135 post-CRT FDG-PET/CTs were calculated and compared with the pathological findings in the corresponding resection specimens. Results: Of the 463 included patients, 85 (18.4%) patients had a pCR. During follow-up, 25 (29.4%) of these 85 patients developed recurrent disease. Both 5-year disease-free survival (5y-DFS) and 5-year overall survival (5y-OS) were significantly higher in complete responders compared to noncomplete responders (5y-DFS 69.6% vs. 44.2%; P = 0.001 and 5y-OS 66.5% vs. 43.7%; P = 0.001). Not pCR, but only pN0 was identified as an independent predictor of (disease-free) survival. Conclusion: Patients with a pCR have a higher probability of survival compared to noncomplete responders. One third of patients with a pCR do develop recurrent disease, and pCR can therefore not be equated with cure. FDG-PET/CT was inaccurate to predict pCR and therefore cannot be used as a sole diagnostic tool to predict pCR after CRT for esophageal cancer.</p

    Limitations of the isolated GP-STN network

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    An in vitro mouse slice preparation from control and MPTP-treated mice in which functional reciprocal GP-STN connectivity is maintained, does not produce oscillatory bursting or synchronous activity neuronal activity. Pharmacological interventions that produce bursting activity do so without concomitant neuronal synchrony, or a requirement for glutamate or GABA transmission. Pre-treatment with MPTP did not alter this behaviour. Thus, we have no evidence that the functionally connected, but isolated, GP — STN network can act as a pacemaker for synchronous correlated activity in the basal ganglia and must conclude that other inputs such as those from cortex and/or striatum are required

    Cosmology from Rolling Massive Scalar Field on the anti-D3 Brane of de Sitter Vacua

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    We investigate a string-inspired scenario associated with a rolling massive scalar field on D-branes and discuss its cosmological implications. In particular, we discuss cosmological evolution of the massive scalar field on the ant-D3 brane of KKLT vacua. Unlike the case of tachyon field, because of the warp factor of the anti-D3 brane, it is possible to obtain the required level of amplitude of density perturbations. We study the spectra of scalar and tensor perturbations generated during the rolling scalar inflation and show that our scenario satisfies the observational constraint coming from the Cosmic Microwave Background anisotropies and other observational data. We also implement the negative cosmological constant arising from the stabilization of the modulus fields in the KKLT vacua and find that this leads to a successful reheating in which the energy density of the scalar field effectively scales as a pressureless dust. The present dark energy can be also explained in our scenario provided that the potential energy of the massive rolling scalar does not exactly cancel with the amplitude of the negative cosmological constant at the potential minimum.Comment: RevTex4, 15 pages, 5 eps figures, minor clarifications and few references added, final version to appear in PR

    Performance of gastrointestinal pathologists within a national digital review panel for Barrett's oesophagus in the Netherlands: Results of 80 prospective biopsy reviews

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    Aims: The histopathological diagnosis of low-grade dysplasia (LGD) in Barrett's oesophagus (BO) is associated with poor interobserver agreement and guidelines dictate expert review. To facilitate nationwide expert review in the Netherlands, a web-based digital review panel has been set up, which currently consists of eight 'core' pathologists. The aim of this study was to evaluate if other pathologists from the Dutch BO expert centres qualify for the expert panel by assessing their performance in 80 consecutive LGD reviews submitted to the panel. Methods: Pathologists independently assessed digital slides in two phases. Both phases consisted of 40 cases, with a group discussion after phase I. For all cases, a previous consensus diagnosis made by five core pathologists was available, which was used as reference. The following criteria were used: (1) percentage of 'indefinite for dysplasia' diagnoses, (2) percentage agreement with consensus diagnosis and (3) proportion of cases with a consensus diagnosis of dysplasia underdiagnosed as non-dysplastic. Benchmarks were based on scores of the core pathologists. Results: After phase I, 1/7 pathologists met the benchmark scor

    Ultra-High Energy Cosmic Ray Probes of Large Scale Structure and Magnetic Fields

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    We study signatures of a structured universe in the multi-pole moments, auto-correlation function, and cluster statistics of ultra-high energy cosmic rays above 10^19 eV. We compare scenarios where the sources are distributed homogeneously or according to the baryon density distribution obtained from a cosmological large scale structure simulation. The influence of extragalactic magnetic fields is studied by comparing the case of negligible fields with fields expected to be produced along large scale shocks with a maximal strength consistent with observations. We confirm that strongly magnetized observers would predict considerable anisotropy on large scales, which is already in conflict with current data. In the best fit scenario only the sources are strongly magnetized, although deflection can still be considerable, of order 20 degrees up to 10^20 eV, and a pronounced GZK cutoff is predicted. We then discuss signatures for future large scale full-sky detectors such as the Pierre Auger and EUSO projects. Auto-correlations are sensitive to the source density only if magnetic fields do not significantly affect propagation. In contrast, for a weakly magnetized observer, degree scale auto-correlations below a certain level indicate magnetized discrete sources. It may be difficult even for next generation experiments to distinguish between structured and unstructured source distributions.Comment: 17 revtex pages, 29 ps figures, published version with minor changes, see http://link.aps.org/abstract/PRD/v70/e04300

    Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus

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    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P&lt;5&times;10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights

    Parental origin of sequence variants associated with complex diseases

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    To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldEffects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.info:eu-repo/grantAgreement/EC/FP7/21807

    The APEX Large CO Heterodyne Orion Legacy Survey (ALCOHOLS): I. Survey overview

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    Context: The Orion molecular cloud complex harbours the nearest Giant Molecular Clouds (GMCs) and the nearest site of high-mass star formation. Its young star and protostar populations are thoroughly characterized. The region is therefore a prime target for the study of star formation. Aims: Here, we verify the performance of the SuperCAM 64 pixel heterodyne array on the Atacama Pathfinder Experiment (APEX). We give a descriptive overview of a set of wide-field CO(3-2) spectral line cubes obtained towards the Orion GMC complex, aimed at characterizing the dynamics and structure of the extended molecular gas in diverse regions of the clouds, ranging from very active sites of clustered star formation in Orion B to comparatively quiet regions in southern Orion A. In a future publication, we will characterize the full population of protostellar outflows and their feedback over an entire GMC. Methods: We present a 2.7 square degree (130 pc2) mapping survey in the 12CO(3-2) transition, obtained using SuperCAM on APEX at an angular resolution of 1900 (7600 AU or 0.037 pc at a distance of 400 pc), covering the main sites of star formation in the Orion B cloud (L 1622, NGC 2071, NGC 2068, Ori B9, NGC 2024, and NGC 2023), and a large patch in the southern part of the L 1641 cloud in Orion A. Results: We describe CO integrated line emission and line moment maps and position-velocity diagrams for all survey fields and discuss a few subregions in some detail. Evidence for expanding bubbles is seen with lines splitting into double components, often in areas of optical nebulosities, most prominently in the NGC 2024 H ii region, where we argue that the bulk of the molecular gas is in the foreground of the H ii region. High CO(3-2)/CO(1-0) line ratios reveal warm CO along the western edge of the Orion B cloud in the NGC 2023/NGC 2024 region facing the IC 434 H ii region. We see multiple, well separated radial velocity cloud components towards several fields and propose that L 1641-S consists of a sequence of clouds at increasingly larger distances. We find a small, seemingly spherical cloud, which we term ’Cow Nebula’ globule, north of NGC 2071. We confirm that we can trace high velocity line wings out to the ’extremely high velocity’ regime in protostellar molecular outflows for the NGC 2071-IR outflow and the NGC 2024 CO jet, and identify the protostellar dust core FIR4 (rather than FIR5) as the true driving source of the NGC 2024 monopolar outflow
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