Heterotic-Type II duality in the hypermultiplet sector

We revisit the duality between heterotic string theory compactified on K3 x T^2 and type IIA compactified on a Calabi-Yau threefold X in the hypermultiplet sector. We derive an explicit map between the field variables of the respective moduli spaces at the level of the classical effective actions. We determine the parametrization of the K3 moduli space consistent with the Ferrara-Sabharwal form. From the expression of the holomorphic prepotential we are led to conjecture that both X and its mirror must be K3 fibrations in order for the type IIA theory to have an heterotic dual. We then focus on the region of the moduli space where the metric is expressed in terms of a prepotential on both sides of the duality. Applying the duality we derive the heterotic hypermultiplet metric for a gauge bundle which is reduced to 24 point-like instantons. This result is confirmed by using the duality between the heterotic theory on T^3 and M-theory on K3. We finally study the hyper-Kaehler metric on the moduli space of an SU(2) bundle on K3.Comment: 27 pages; references added, typos correcte

Neutrophil-Mediated Experimental Metastasis Is Enhanced by VEGFR Inhibition in a Zebrafish Xenograft Model

Inhibition of VEGF signalling effectively suppresses localized tumour growth but accelerates tumour invasiveness and micrometastasis by unknown mechanisms. To study the dynamic and reciprocal interactions between tumour cells and their microenvironment during these processes, we established a xenograft model by injecting tumour cells into the blood circulation of transparent zebrafish embryos. This reproducibly results in rapid simultaneous formation of a localized tumour and experimental micrometastasis, allowing time-resolved imaging of both processes at single-cell resolution within 1 week. The tumour vasculature was initiated de novo by remodelling of primitive endothelial cells into a functional network. Roles of myeloid cells in critical tumourigenesis steps such as vascularization and invasion were revealed by genetic and pharmaceutical approaches. We discovered that the physiological migration of neutrophils controlled tumour invasion by conditioning the collagen matrix and forming the metastatic niche, as detected by two-photon confocal microscopy and second harmonic generation. Administration of VEGFR inhibitors blocked tumour vascularization and a localized tumour growth but enhanced migration of neutrophils, which in turn promoted tumour invasion and formation of micrometastasis. This demonstrates the in vivo cooperation between VEGF signalling and myeloid cells in metastasis and provides a new mechanism underlying the recent findings that VEGFR targeting can promote tumour invasiveness

Wall-Crossing from Boltzmann Black Hole Halos

A key question in the study of N=2 supersymmetric string or field theories is to understand the decay of BPS bound states across walls of marginal stability in the space of parameters or vacua. By representing the potentially unstable bound states as multi-centered black hole solutions in N=2 supergravity, we provide two fully general and explicit formulae for the change in the (refined) index across the wall. The first, "Higgs branch" formula relies on Reineke's results for invariants of quivers without oriented loops, specialized to the Abelian case. The second, "Coulomb branch" formula results from evaluating the symplectic volume of the classical phase space of multi-centered solutions by localization. We provide extensive evidence that these new formulae agree with each other and with the mathematical results of Kontsevich and Soibelman (KS) and Joyce and Song (JS). The main physical insight behind our results is that the Bose-Fermi statistics of individual black holes participating in the bound state can be traded for Maxwell-Boltzmann statistics, provided the (integer) index \Omega(\gamma) of the internal degrees of freedom carried by each black hole is replaced by an effective (rational) index \bar\Omega(\gamma)= \sum_{m|\gamma} \Omega(\gamma/m)/m^2. A similar map also exists for the refined index. This observation provides a physical rationale for the appearance of the rational Donaldson-Thomas invariant \bar\Omega(\gamma) in the works of KS and JS. The simplicity of the wall crossing formula for rational invariants allows us to generalize the "semi-primitive wall-crossing formula" to arbitrary decays of the type \gamma\to M\gamma_1+N\gamma_2 with M=2,3.Comment: 71 pages, 1 figure; v3: changed normalisation of symplectic form 3.22, corrected 3.35, other cosmetic change

Gorenstein homological algebra and universal coefficient theorems

We study criteria for a ring—or more generally, for a small category—to be Gorenstein and for a module over it to be of finite projective dimension. The goal is to unify the universal coefficient theorems found in the literature and to develop machinery for proving new ones. Among the universal coefficient theorems covered by our methods we find, besides all the classic examples, several exotic examples arising from the KK-theory of C*-algebras and also Neeman’s Brown–Adams representability theorem for compactly generated categories

Predictors of high-cost hospitalization in the treatment of acute coronary syndrome in Asia: findings from EPICOR Asia.

BACKGROUND: The EPICOR Asia (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) study (NCT01361386) was an observational study of patients hospitalized for acute coronary syndromes (ACS) enrolled in 218 hospitals in eight countries/regions in Asia. This study examined costs, length of stay and the predictors of high costs during an ACS hospitalization. METHODS AND RESULTS: Data for patients hospitalized for an ACS (n = 12,922) were collected on demographics, medical history, event characteristics, socioeconomic and insurance status at discharge. Patients were followed up at 6 weeks' post-hospitalization for an ACS event to assess associated treatment costs from a health sector perspective. Primary outcome was the incurring of costs in the highest quintile by country and index event diagnosis, and identification of associated predictors. Cost data were available for 10,819 patients. Mean length of stay was 10.1 days. The highest-cost countries were China, Singapore, and South Korea. Significant predictors of high-cost care were age, male sex, income, country, prior disease history, hospitalization in 3 months before index event, no dependency before index event, having an invasive procedure, hospital type and length of stay. CONCLUSIONS: Substantial variability exists in healthcare costs for hospitalized ACS patients across Asia. Of concern is the observation that the highest costs were reported in China, given the rapidly increasing numbers of procedures in recent years. TRIAL REGISTRATION: NCT01361386

Kroppenstedtia pulmonis sp. nov. and Kroppenstedtia sanguinis sp. nov., isolated from human patients

Three human clinical strains (W9323T, X0209T and X0394) isolated from lung biopsy, blood and cerebral spinal fluid, respectively, were characterized using a polyphasic taxonomic approach. Comparative analysis of the 16S rRNA gene sequences showed the three strains belonged to two novel branches within the genus Kroppenstedtia: 16S rRNA gene sequence analysis of W9323T showed closest sequence similarity to Kroppenstedtia eburnea JFMB-ATE T (95.3 %), Kroppenstedtia guangzhouensis GD02T (94.7 %) and strain X0209T (94.6 %); sequence analysis of strain X0209T showed closest sequence similarity to K. eburnea JFMB-ATE T (96.4 %) and K. guangzhouensis GD02T (96.0 %). Strains X0209T and X0394 were 99.9 % similar to each other by 16S rRNA gene sequence analysis. The DNA-DNA relatedness was 94.6 %, confirming that X0209T and X0394 belong to the same species. Chemotaxonomic data for strains W9323T and X0209T were consistent with those described for the genus Kroppenstedtia: whole-cell peptidoglycan contained LLdiaminopimelic acid; the major cellular fatty acids were iso-C15 and anteiso-C15; and the major menaquinone was MK-7. Different endospore morphology and carbon utilization profiles of strains W9323T and X0209T supported by phylogenetic analysis enabled us to conclude that the strains represent two new species within the genus Kroppenstedtia, for which the names Kroppenstedtia pulmonis sp. nov. (type strain W9323T =DSM 45752 T) and Kroppenstedtia sanguinis sp. nov. (type strain X0209T =DSM 45749T=CCUG 38657 T) are proposed

Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer

In the last decade, optimized treatment for non-small cell lung cancer had lead to improved prognosis, but the overall survival is still very short. To further understand the molecular basis of the disease we have to identify biomarkers related to survival. Here we present the development of an online tool suitable for the real-time meta-analysis of published lung cancer microarray datasets to identify biomarkers related to survival. We searched the caBIG, GEO and TCGA repositories to identify samples with published gene expression data and survival information. Univariate and multivariate Cox regression analysis, Kaplan-Meier survival plot with hazard ratio and logrank P value are calculated and plotted in R. The complete analysis tool can be accessed online at: www.kmplot.com/lung. All together 1,715 samples of ten independent datasets were integrated into the system. As a demonstration, we used the tool to validate 21 previously published survival associated biomarkers. Of these, survival was best predicted by CDK1 (p<1E-16), CD24 (p<1E-16) and CADM1 (p = 7E-12) in adenocarcinomas and by CCNE1 (p = 2.3E-09) and VEGF (p = 3.3E-10) in all NSCLC patients. Additional genes significantly correlated to survival include RAD51, CDKN2A, OPN, EZH2, ANXA3, ADAM28 and ERCC1. In summary, we established an integrated database and an online tool capable of uni- and multivariate analysis for in silico validation of new biomarker candidates in non-small cell lung cancer

Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia

Involvement of global genome repair, transcription coupled repair, and chromatin remodeling in UV DNA damage response changes during development

Nucleotide Excision Repair (NER), which removes a variety of helix-distorting lesions from DNA, is initiated by two distinct DNA damage-sensing mechanisms. Transcription Coupled Repair (TCR) removes damage from the active strand of transcribed genes and depends on the SWI/SNF family protein CSB. Global Genome Repair (GGR) removes damage present elsewhere in the genome and depends on damage recognition by the XPC/RAD23/Centrin2 complex. Currently, it is not well understood to what extent both pathways contribute to genome maintenance and cell survival in a developing organism exposed to UV light. Here, we show that eukaryotic NER, initiated by two distinct subpathways, is well conserved in the nematode Caenorhabditis elegans. In C. elegans, involvement of TCR and GGR in the UV-induced DNA damage response changes during development. In germ cells and early embryos, we find that GGR is the major pathway contributing to normal development and survival after UV irradiation, whereas in later developmental stages TCR is predominantly engaged. Furthermore, we identify four ISWI/Cohesin and four SWI/SNF family chromatin remodeling factors that are implicated in the UV damage response in a developmental stage dependent manner. These in vivo studies strongly suggest that involvement of different repair pathways and chromatin remodeling proteins in UV-induced DNA repair depends on developmental stage of cells