Bayesian Methods for Exoplanet Science

Exoplanet research is carried out at the limits of the capabilities of current telescopes and instruments. The studied signals are weak, and often embedded in complex systematics from instrumental, telluric, and astrophysical sources. Combining repeated observations of periodic events, simultaneous observations with multiple telescopes, different observation techniques, and existing information from theory and prior research can help to disentangle the systematics from the planetary signals, and offers synergistic advantages over analysing observations separately. Bayesian inference provides a self-consistent statistical framework that addresses both the necessity for complex systematics models, and the need to combine prior information and heterogeneous observations. This chapter offers a brief introduction to Bayesian inference in the context of exoplanet research, with focus on time series analysis, and finishes with an overview of a set of freely available programming libraries.Comment: Invited revie

Effect of topical honey application along with intralesional injection of glucantime in the treatment of cutaneous leishmaniasis

<p>Abstract</p> <p>Background</p> <p>Leishmaniasis is an endemic disease in Iran. Although many treatments have been suggested for this disease, there hasn't been an effective and safe treatment yet. Regarding the healing effect of honey in the chronic ulcers and its reported therapeutic effect in cutaneous leishmaniasis, we performed a study to better evaluate the efficacy of honey in cutaneous leishmaniasis and its final scar.</p> <p>Methods</p> <p>In a prospective clinical trial, 100 patients with confirmed cutaneous leishmaniasis were selected and randomized into 2 groups. Group A were treated with topical honey twice daily along with intralesional injection of glucantime once weekly until complete healing of the ulcer or for maximum of 6 weeks. Group B were treated with intralesional injection of glucantime alone until complete healing of the ulcer or for a maximum of 6 weeks, too. The patients were followed for 4 months. The collected data were analyzed statistically using statistical tests including Chi-square, Mann Whitney and Kaplan – Mayer tests.</p> <p>Results</p> <p>In this study, 45 patients that had cutaneous leishmaniasis were treated with intralesional glucantime alone and 45 patients were treated with topical honey and glucantime . Ten patients left out the study. In the glucantime alone treated group, 32 patients (71.1%) had complete cure whereas in the group treated with both glucantime & topical honey, 23 patients (51.1%) achieved complete cure. This difference was significant statistically (p = 0.04).</p> <p>Conclusion</p> <p>Further studies to better clarify the efficacy of honey in cutaneous leishmaniasis is needed. We suggest that in another study, the efficacy of honey with standardized level of antibacterial activity is evaluated against cutaneous leishmaniasis.</p

The importance of plasma apolipoprotein E concentration in addition to its common polymorphism on inter-individual variation in lipid levels: results from Apo Europe

The ApoEurope group, collaborating centres, and their associated investigators: Portugal: Unidade de Química Clínica, Instituto Nacional de Saúde, Lisboa: Maria do Carmo Martins, Maria Odete Rodrigues, Maria Isabel Albergaria, Maria Liseta AlpendreInterindividual variation in the concentration of plasma lipids which are associated with coronary artery disease (CAD) risk is determined by a combination of genetic and environmental factors. This study investigates the effects of apoE genotype and plasma concentration on cholesterol and triglycerides (TG) levels in subjects from five countries: Finland, France, Northern Ireland, Portugal, and Spain. Age and sex significantly influenced serum cholesterol, TG and apoE concentrations. The age effect differs in males and females. The allele frequencies of the apoE gene, one of the most widely studied CAD susceptibility genes, were determined: the epsilon2 allele frequency and the apoE concentration showed a north-south increasing gradient while the epsilon4 allele frequency showed the reverse. ApoE plays an important role in lipid metabolism. Total cholesterol and TG concentrations were significantly dependent on apoE genotype in both sexes. These differences in lipids between genotypes were more pronounced when plasma apoE concentrations were taken into account

Next generation sequencing analysis of nine Corynebacterium ulcerans isolates reveals zoonotic transmission and a novel putative diphtheria toxin-encoding pathogenicity island

Background: Toxigenic Corynebacterium ulcerans can cause a diphtheria-like illness in humans and have been found in domestic animals, which were suspected to serve as reservoirs for a zoonotic transmission. Additionally, toxigenic C. ulcerans were reported to take over the leading role in causing diphtheria in the last years in many industrialized countries. Methods: To gain deeper insights into the tox gene locus and to understand the transmission pathway in detail, we analyzed nine isolates derived from human patients and their domestic animals applying next generation sequencing and comparative genomics. Results: We provide molecular evidence for zoonotic transmission of C. ulcerans in four cases and demonstrate the superior resolution of next generation sequencing compared to multi-locus sequence typing for epidemiologic research. Additionally, we provide evidence that the virulence of C. ulcerans can change rapidly by acquisition of novel virulence genes. This mechanism is exemplified by an isolate which acquired a prophage not present in the corresponding isolate from the domestic animal. This prophage contains a putative novel virulence factor, which shares high identity with the RhuM virulence factor from Salmonella enterica but which is unknown in Corynebacteria so far. Furthermore, we identified a putative pathogenicity island for C. ulcerans bearing a diphtheria toxin gene. Conclusion: The novel putative diphtheria toxin pathogenicity island could provide a new and alternative pathway for Corynebacteria to acquire a functional diphtheria toxin-encoding gene by horizontal gene transfer, distinct from the previously well characterized phage infection model. The novel transmission pathway might explain the unexpectedly high number of toxigenic C. ulcerans

A comprehensive study on the role of the Yersinia pestis virulence markers in an animal model of pneumonic plague

We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF– strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression

DISPARE: DIScriminative PAttern REfinement for Position Weight Matrices

<p>Abstract</p> <p>Background</p> <p>The accurate determination of transcription factor binding affinities is an important problem in biology and key to understanding the gene regulation process. Position weight matrices are commonly used to represent the binding properties of transcription factor binding sites but suffer from low information content and a large number of false matches in the genome. We describe a novel algorithm for the refinement of position weight matrices representing transcription factor binding sites based on experimental data, including ChIP-chip analyses. We present an iterative weight matrix optimization method that is more accurate in distinguishing true transcription factor binding sites from a negative control set. The initial position weight matrix comes from JASPAR, TRANSFAC or other sources. The main new features are the discriminative nature of the method and matrix width and length optimization.</p> <p>Results</p> <p>The algorithm was applied to the increasing collection of known transcription factor binding sites obtained from ChIP-chip experiments. The results show that our algorithm significantly improves the sensitivity and specificity of matrix models for identifying transcription factor binding sites.</p> <p>Conclusion</p> <p>When the transcription factor is known, it is more appropriate to use a discriminative approach such as the one presented here to derive its transcription factor-DNA binding properties starting with a matrix, as opposed to performing <it>de novo </it>motif discovery. Generating more accurate position weight matrices will ultimately contribute to a better understanding of eukaryotic transcriptional regulation, and could potentially offer a better alternative to <it>ab initio </it>motif discovery.</p

Reduction in Learning Rates Associated with Anterograde Interference Results from Interactions between Different Timescales in Motor Adaptation

Prior experiences can influence future actions. These experiences can not only drive adaptive changes in motor output, but they can also modulate the rate at which these adaptive changes occur. Here we studied anterograde interference in motor adaptation – the ability of a previously learned motor task (Task A) to reduce the rate of subsequently learning a different (and usually opposite) motor task (Task B). We examined the formation of the motor system's capacity for anterograde interference in the adaptive control of human reaching-arm movements by determining the amount of interference after varying durations of exposure to Task A (13, 41, 112, 230, and 369 trials). We found that the amount of anterograde interference observed in the learning of Task B increased with the duration of Task A. However, this increase did not continue indefinitely; instead, the interference reached asymptote after 15–40 trials of Task A. Interestingly, we found that a recently proposed multi-rate model of motor adaptation, composed of two distinct but interacting adaptive processes, predicts several key features of the interference patterns we observed. Specifically, this computational model (without any free parameters) predicts the initial growth and leveling off of anterograde interference that we describe, as well as the asymptotic amount of interference that we observe experimentally (R2 = 0.91). Understanding the mechanisms underlying anterograde interference in motor adaptation may enable the development of improved training and rehabilitation paradigms that mitigate unwanted interference

Effects of Blood Collection Conditions on Ovarian Cancer Serum Markers

Evaluating diagnostic and early detection biomarkers requires comparing serum protein concentrations among biosamples ascertained from subjects with and without cancer. Efforts are generally made to standardize blood processing and storage conditions for cases and controls, but blood sample collection conditions cannot be completely controlled. For example, blood samples from cases are often obtained from persons aware of their diagnoses, and collected after fasting or in surgery, whereas blood samples from some controls may be obtained in different conditions, such as a clinic visit. By measuring the effects of differences in collection conditions on three different markers, we investigated the potential of these effects to bias validation studies.We analyzed serum concentrations of three previously studied putative ovarian cancer serum biomarkers-CA 125, Prolactin and MIF-in healthy women, women with ovarian cancer undergoing gynecologic surgery, women undergoing surgery for benign ovary pathology, and women undergoing surgery with pathologically normal ovaries. For women undergoing surgery, a blood sample was collected either in the clinic 1 to 39 days prior to surgery, or on the day of surgery after anesthesia was administered but prior to the surgical procedure, or both. We found that one marker, prolactin, was dramatically affected by collection conditions, while CA 125 and MIF were unaffected. Prolactin levels were not different between case and control groups after accounting for the conditions of sample collection, suggesting that sample ascertainment could explain some or all of the previously reported results about its potential as a biomarker for ovarian cancer.Biomarker validation studies should use standardized collection conditions, use multiple control groups, and/or collect samples from cases prior to influence of diagnosis whenever feasible to detect and correct for potential biases associated with sample collection