A Long-Period Totally Eclipsing Binary Star at the Turnoff of the Open Cluster NGC 6819 Discovered with Kepler

We present the discovery of the totally eclipsing long-period (P = 771.8 d) binary system WOCS 23009 in the old open cluster NGC 6819 that contains both an evolved star near central hydrogen exhaustion and a low-mass (0.45 Msun) star. This system was previously known to be a single-lined spectroscopic binary, but the discovery of an eclipse near apastron using data from the Kepler space telescope makes it clear that the system has an inclination that is very close to 90 degrees. Although the secondary star has not been identified in spectra, the mass of the primary star can be constrained using other eclipsing binaries in the cluster. The combination of total eclipses and a mass constraint for the primary star allows us to determine a reliable mass for the secondary star and radii for both stars, and to constrain the cluster age. Unlike well-measured stars of similar mass in field binaries, the low-mass secondary is not significantly inflated in radius compared to model predictions. The primary star characteristics, in combination with cluster photometry and masses from other cluster binaries, indicates a best age of 2.62+/-0.25 Gyr, although stellar model physics may introduce systematic uncertainties at the ~10% level. We find preliminary evidence that the asteroseismic predictions for red giant masses in this cluster are systematically too high by as much as 8%.Comment: 38 pages,11 figures, accepted for Ap

Darboux Transformations for Supersymmetric Korteweg - de Vries Equations

\hspace{.2in}We consider the Darboux type transformations for the spectral problems of supersymmetric KdV systems. The supersymmetric analogies of Darboux and Darboux-Levi transformations are established for the spectral problems of Manin-Radul-Mathieu sKdV and Manin-Radul sKdV. Several B\"acklund transformations are derived for the MRM sKdV and MR sKdV systems.Comment: Latex, 8 pages AS-ITP-94-4

Validation of a new automatic smoking machine to study the effects of cigarette smoke in newborn lambs

The aim of this study was to describe the characteristics and validate the use of a new, custom-built automatic smoking machine (ASM), primarily designed to study the effects of an environmental tobacco smoke surrogate (ETS surrogate) exposure in animals of various sizes, including large animals. The equipment includes a programmable ASM coupled to a vented whole body chamber, where animals can be exposed to both mainstream and sidestream smoke. The user-friendly interface allows for full programming of puff volume (1-60 mL), time interval between two puffs (1-60 s) and between two cigarettes (1-60 min). Eight newborn lambs were exposed to either 10 (4 lambs, C10 group) or 20 (4 lambs, C20 group) cigarettes, 8 h per day for 15 days. Four additional control, lambs were exposed to air (C0 group). Weight gain was identical in all three groups of lambs. Urinary cotinine/creatinine ratio increased with the number of cigarettes smoked (C0: 11 ± 7 ng/mg; C10: 961 ± 539 ng/mg; C20: 1821 ± 312 ng/mg), with levels in the C10 and C20 groups in keeping with values published in infants exposed to ETS. Overall, results show that our new ASM is especially well suited for ETS surrogate exposure in non-restrained, non-anaesthetized large animals such as sheep

The melanoma-specific graded prognostic assessment does not adequately discriminate prognosis in a modern population with brain metastases from malignant melanoma

The melanoma-specific graded prognostic assessment (msGPA) assigns patients with brain metastases from malignant melanoma to 1 of 4 prognostic groups. It was largely derived using clinical data from patients treated in the era that preceded the development of newer therapies such as BRAF, MEK and immune checkpoint inhibitors. Therefore, its current relevance to patients diagnosed with brain metastases from malignant melanoma is unclear. This study is an external validation of the msGPA in two temporally distinct British populations.Performance of the msGPA was assessed in Cohort I (1997-2008, n=231) and Cohort II (2008-2013, n=162) using Kaplan-Meier methods and Harrell's c-index of concordance. Cox regression was used to explore additional factors that may have prognostic relevance.The msGPA does not perform well as a prognostic score outside of the derivation cohort, with suboptimal statistical calibration and discrimination, particularly in those patients with an intermediate prognosis. Extra-cerebral metastases, leptomeningeal disease, age and potential use of novel targeted agents after brain metastases are diagnosed, should be incorporated into future prognostic models.An improved prognostic score is required to underpin high-quality randomised controlled trials in an area with a wide disparity in clinical care

A method for the reconstruction of unknown non-monotonic growth functions in the chemostat

We propose an adaptive control law that allows one to identify unstable steady states of the open-loop system in the single-species chemostat model without the knowledge of the growth function. We then show how one can use this control law to trace out (reconstruct) the whole graph of the growth function. The process of tracing out the graph can be performed either continuously or step-wise. We present and compare both approaches. Even in the case of two species in competition, which is not directly accessible with our approach due to lack of controllability, feedback control improves identifiability of the non-dominant growth rate.Comment: expansion of ideas from proceedings paper (17 pages, 8 figures), proceedings paper is version v

Performance of the 2007 WHO Algorithm to diagnose Smear-negative Pulmonary Tuberculosis in a HIV prevalent setting

The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Genome-wide linkage analysis of 972 bipolar pedigrees using single-nucleotide polymorphisms.

Because of the high costs associated with ascertainment of families, most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. Although microsatellite markers spaced every 10 cM typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carried out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 single-nucleotide polymorphisms. Of the ~1100 families, 972 were informative for further analyses, and mean information content was 0.86 after pruning for linkage disequilibrium. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with bipolar II disorder (BPII) and 702 subjects with recurrent major depression. Three affection status models (ASMs) were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus recurrent major depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (non-parametric pairs LOD 3.4 for rs1046943 at 119 cM) and 9q21 (non-parametric pairs logarithm of odds (LOD) 3.4 for rs722642 at 78 cM) using only BPI and schizoaffective (SA), BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis, we observed 59 parametric LODs of 2 or greater, many of which are likely to be close to maximum possible scores. Although some linkage findings may be false positives, the results could help prioritize the search for rare variants using whole exome or genome sequencing

Population genetics of trypanosoma brucei rhodesiense: clonality and diversity within and between foci

African trypanosomes are unusual among pathogenic protozoa in that they can undergo their complete morphological life cycle in the tsetse fly vector with mating as a non-obligatory part of this development. Trypanosoma brucei rhodesiense, which infects humans and livestock in East and Southern Africa, has classically been described as a host-range variant of the non-human infective Trypanosoma brucei that occurs as stable clonal lineages. We have examined T. b. rhodesiense populations from East (Uganda) and Southern (Malawi) Africa using a panel of microsatellite markers, incorporating both spatial and temporal analyses. Our data demonstrate that Ugandan T. b. rhodesiense existed as clonal populations, with a small number of highly related genotypes and substantial linkage disequilibrium between pairs of loci. However, these populations were not stable as the dominant genotypes changed and the genetic diversity also reduced over time. Thus these populations do not conform to one of the criteria for strict clonality, namely stability of predominant genotypes over time, and our results show that, in a period in the mid 1990s, the previously predominant genotypes were not detected but were replaced by a novel clonal population with limited genetic relationship to the original population present between 1970 and 1990. In contrast, the Malawi T. b. rhodesiense population demonstrated significantly greater diversity and evidence for frequent genetic exchange. Therefore, the population genetics of T. b. rhodesiense is more complex than previously described. This has important implications for the spread of the single copy T. b. rhodesiense gene that allows human infectivity, and therefore the epidemiology of the human disease, as well as suggesting that these parasites represent an important organism to study the influence of optional recombination upon population genetic dynamics