Can spacetime curvature induced corrections to Lamb shift be observable?

The Lamb shift results from the coupling of an atom to vacuum fluctuations of quantum fields, so corrections are expected to arise when the spacetime is curved since the vacuum fluctuations are modified by the presence of spacetime curvature. Here, we calculate the curvature-induced correction to the Lamb shift outside a spherically symmetric object and demonstrate that this correction can be remarkably significant outside a compact massive astrophysical body. For instance, for a neutron star or a stellar mass black hole, the correction is $\sim$ 25% at a radial distance of $4GM/c^2$, $\sim$ 16% at $10GM/c^2$ and as large as $\sim$ 1.6% even at $100GM/c^2$, where $M$ is the mass of the object, $G$ the Newtonian constant, and $c$ the speed of light. In principle, we can look at the spectra from a distant compact super-massive body to find such corrections. Therefore, our results suggest a possible way of detecting fundamental quantum effects in astronomical observations.Comment: 13 pages, 3 figures, slight title change, clarifications and more discussions added, version to be published in JHE

The Comparative Oncology Trials Consortium: Using Spontaneously Occurring Cancers in Dogs to Inform the Cancer Drug Development Pathway

Chand Khanna and colleagues describe the work of the Comparative Oncology Trials Consortium (COTC), which provides infrastructure and resources to integrate naturally occurring dog cancer models into the development of new human cancer drugs, devices, and imaging techniques

Bacterial microevolution and the Pangenome

The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history

Simultaneous Quantitation of Amino Acid Mixtures using Clustering Agents

A method that uses the abundances of large clusters formed in electrospray ionization to determine the solution-phase molar fractions of amino acids in multi-component mixtures is demonstrated. For solutions containing either four or 10 amino acids, the relative abundances of protonated molecules differed from their solution-phase molar fractions by up to 30-fold and 100-fold, respectively. For the four-component mixtures, the molar fractions determined from the abundances of larger clusters consisting of 19 or more molecules were within 25% of the solution-phase molar fractions, indicating that the abundances and compositions of these clusters reflect the relative concentrations of these amino acids in solution, and that ionization and detection biases are significantly reduced. Lower accuracy was obtained for the 10-component mixtures where values determined from the cluster abundances were typically within a factor of three of their solution molar fractions. The lower accuracy of this method with the more complex mixtures may be due to specific clustering effects owing to the heterogeneity as a result of significantly different physical properties of the components, or it may be the result of lower S/N for the more heterogeneous clusters and not including the low-abundance more highly heterogeneous clusters in this analysis. Although not as accurate as using traditional standards, this clustering method may find applications when suitable standards are not readily available

Genotypic classification of patients with Wolfram syndrome: insights into the natural history of the disease and correlation with phenotype

Purpose: Wolfram syndrome is a degenerative, recessive rare disease with an onset in childhood. It is caused by mutations in WFS1 or CISD2 genes. More than 200 different variations in WFS1 have been described in patients with Wolfram syndrome, which complicates the establishment of clear genotype-phenotype correlation. The purpose of this study was to elucidate the role of WFS1 mutations and update the natural history of the disease. Methods: This study analyzed clinical and genetic data of 412 patients with Wolfram syndrome published in the last 15 years. Results: (i) 15% of published patients do not fulfill the current ­inclusion criterion; (ii) genotypic prevalence differences may exist among countries; (iii) diabetes mellitus and optic atrophy might not be the first two clinical features in some patients; (iv) mutations are nonuniformly distributed in WFS1; (v) age at onset of diabetes mellitus, hearing defects, and diabetes insipidus may depend on the patient"s genotypic class; and (vi) disease progression rate might depend on genotypic class. Conclusion: New genotype-phenotype correlations were established, disease progression rate for the general population and for the genotypic classes has been calculated, and new diagnostic criteria have been proposed. The conclusions raised could be important for patient management and counseling as well as for the development of treatments for Wolfram syndrome

Tracking the evolutionary history of Cortinarius species in section Calochroi, with transoceanic disjunct distributions

<p>Abstract</p> <p>Background</p> <p><it>Cortinarius </it>species in section <it>Calochroi </it>display local, clinal and circumboreal patterns of distribution across the Northern Hemisphere where these ectomycorrhizal fungi occur with host trees throughout their geographical range within a continent, or have disjunct intercontinental distributions, the origins of which are not understood. We inferred evolutionary histories of four species, 1) <it>C</it>. <it>arcuatorum</it>, 2) <it>C. aureofulvus</it>, 3) <it>C</it>. <it>elegantior </it>and 4) <it>C. napus</it>, from populations distributed throughout the Old World, and portions of the New World (Central- and North America) based on genetic variation of 154 haplotype internal transcribed spacer (ITS) sequences from 83 population samples. By describing the population structure of these species across their geographical distribution, we attempt to identify their historical migration and patterns of diversification.</p> <p>Results</p> <p>Models of population structure from nested clade, demographic and coalescent-based analyses revealed genetically differentiated and geographically structured haplotypes in <it>C</it>. <it>arcuatorum </it>and <it>C</it>. <it>elegantior</it>, while <it>C</it>. <it>aureofulvus </it>showed considerably less population structure and <it>C. napus </it>lacked sufficient genetic differentiation to resolve any population structure. Disjunct populations within <it>C</it>. <it>arcuatorum, C. aureofulvus </it>and <it>C</it>. <it>elegantior </it>show little or no morphological differentiation, whereas in <it>C. napus </it>there is a high level of homoplasy and phenotypic plasticity for veil and lamellae colour. The ITS sequences of the type specimens of <it>C. albobrunnoides </it>and <it>C. albobrunnoides </it>var. <it>violaceovelatus </it>were identical to one another and are treated as one species with a wider range of geographic distribution under <it>C. napus</it>.</p> <p>Conclusions</p> <p>Our results indicate that each of the <it>Calochroi </it>species has undergone a relatively independent evolutionary history, hypothesised as follows: 1) a widely distributed ancestral population of <it>C</it>. <it>arcuatorum </it>diverged into distinctive sympatric populations in the New World; 2) two divergent lineages in <it>C</it>. <it>elegantior </it>gave rise to the New World and Old World haplotypes, respectively; and 3) the low levels of genetic divergence within <it>C</it>. <it>aureofulvus </it>and <it>C</it>. <it>napus </it>may be the result of more recent demographic population expansions. The scenario of migration via the Bering Land Bridge provides the most probable explanation for contemporaneous disjunct geographic distributions of these species, but it does not offer an explanation for the low degree of genetic divergence between populations of <it>C. aureofulvus </it>and <it>C. napus</it>. Our findings are mostly consistent with the designation of New World allopatric populations as separate species from the European counterpart species <it>C. arcuatorum </it>and <it>C. elegantior</it>. We propose the synonymy of <it>C. albobrunnoides</it>, <it>C. albobrunnoides </it>var. <it>violaceovelatus </it>and <it>C. subpurpureophyllus </it>var. <it>sulphureovelatus </it>with <it>C. napus</it>. The results also reinforce previous observations that linked <it>C. arcuatorum </it>and <it>C. aureofulvus </it>displaying distributions in parts of North America and Europe. Interpretations of the population structure of these fungi suggest that host tree history has heavily influenced their modern distributions; however, the complex issues related to co-migration of these fungi with their tree hosts remain unclear at this time.</p

Extracellular Hsp72, an endogenous DAMP, is released by virally infected airway epithelial cells and activates neutrophils via Toll-like receptor (TLR)-4

<p>Abstract</p> <p>Background</p> <p>Neutrophils play an important role in the pathophysiology of RSV, though RSV does not appear to directly activate neutrophils in the lower airways. Therefore locally produced cytokines or other molecules released by virally-infected airway epithelial cells are likely responsible for recruiting and activating neutrophils. Heat shock proteins (HSPs) are generally regarded as intracellular proteins acting as molecular chaperones; however, HSP72 can also be released from cells, and the implications of this release are not fully understood.</p> <p>Methods</p> <p>Human bronchial epithelial cells (16HBE14o-) were infected with RSV and Hsp72 levels were measured by Western blot and ELISA. Tracheal aspirates were obtained from critically ill children infected with RSV and analyzed for Hsp72 levels by ELISA. Primary human neutrophils and differentiated HL-60 cells were cultured with Hsp72 and supernatants analyzed for cytokine production. In some cases, cells were pretreated with polymyxin B prior to treatment with Hsp72. IκBα was assessed by Western blot and EMSA's were performed to determine NF-κB activation. HL-60 cells were pretreated with neutralizing antibody against TLR4 prior to Hsp72 treatment. Neutrophils were harvested from the bone marrow of wild type or TLR4-deficient mice prior to treatment with Hsp72.</p> <p>Results</p> <p>Infection of 16HBE14o- with RSV showed an induction of intracellular Hsp72 levels as well as extracellular release of Hsp72. Primary human neutrophils from normal donors and differentiated HL-60 cells treated with increasing concentrations of Hsp72 resulted in increased cytokine (IL-8 and TNFα) production. This effect was independent of the low levels of endotoxin in the Hsp72 preparation. Hsp72 mediated cytokine production via activation of NF-κB translocation and DNA binding. Using bone marrow-derived neutrophils from wild type and TLR4-mutant mice, we showed that Hsp72 directly activates neutrophil-derived cytokine production via the activation of TLR4.</p> <p>Conclusion</p> <p>Collectively these data suggest that extracellular Hsp72 is released from virally infected airway epithelial cells resulting in the recruitment and activation of neutrophils.</p

Improving the teaching skills of residents as tutors/facilitators and addressing the shortage of faculty facilitators for PBL modules

BACKGROUND: Residents play an important role in teaching of medical undergraduate students. Despite their importance in teaching undergraduates they are not involved in any formal training in teaching and leadership skills. We aimed to compare the teaching skills of residents with faculty in facilitating small group Problem Based Learning (PBL) sessions. METHODS: This quasi experimental descriptive comparative research involved 5 postgraduate year 4 residents and five senior faculty members. The study was conducted with all phase III (Final year) students rotating in Gastroenterology. The residents and faculty members received brief training of one month in facilitation and core principles of adult education. Different aspects of teaching skills of residents and faculty were evaluated by students on a questionnaire (graded on Likert Scale from 1 to 10) assessing i) Knowledge Base-content Learning (KBL), ii) PBL, iii) Student Centered Learning (SCL) and iv) Group Skills (GS). RESULTS: There were 33 PBL teaching sessions in which 120 evaluation forms were filled; out of these 53% forms were filled for residents and 47% for faculty group. The faculty showed a statistically greater rating in KBL (faculty 8.37 Vs resident 7.94; p-value 0.02), GS (faculty 8.06 vs. residents 7.68; p-value 0.04). Differences in faculty and resident scores in the PBL and SCL were not significant. The overall score of faculty facilitators, however, was statistically significant for resident facilitators. (p = .05). CONCLUSION: 1) Residents are an effective supplement to faculty members for PBL; 2) Additional facilitators for PBL sessions can be identified in an institution by involvement of residents in teacher training workshop

Left atrial voltage, circulating biomarkers of fibrosis, and atrial fibrillation ablation. A prospective cohort study.

Aims To test the ability of four circulating biomarkers of fibrosis, and of low left atrial voltage, to predict recurrence of atrial fibrillation after catheter ablation. Background Circulating biomarkers potentially may be used to improve patient selection for atrial fibrillation ablation. Low voltage areas in the left atrium predict arrhythmia recurrence when mapped in sinus rhythm. This study tested type III procollagen N terminal peptide (PIIINP), galectin-3 (gal-3), fibroblast growth factor 23 (FGF-23), and type I collagen C terminal telopeptide (ICTP), and whether low voltage areas in the left atrium predicted atrial fibrillation recurrence, irrespective of the rhythm during mapping. Methods 92 atrial fibrillation ablation patients were studied. Biomarker levels in peripheral and intra-cardiac blood were measured with enzyme-linked immunosorbent assay. Low voltage (<0.5mV) was expressed as a proportion of the mapped left atrial surface area. Follow-up was one year. The primary endpoint was recurrence of arrhythmia. The secondary endpoint was a composite of recurrence despite two procedures, or after one procedure if no second procedure was undertaken. Results The biomarkers were not predictive of either endpoint. After multivariate Cox regression analysis, high proportion of low voltage area in the left atrium was found to predict the primary endpoint in sinus rhythm mapping (hazard ratio 4.323, 95% confidence interval 1.337–13.982, p = 0.014) and atrial fibrillation mapping (hazard ratio 5.195, 95% confidence interval 1.032–26.141, p = 0.046). This effect was also apparent for the secondary endpoint. Conclusion The studied biomarkers do not predict arrhythmia recurrence after catheter ablation. Left atrial voltage is an independent predictor of recurrence, whether the left atrium is mapped in atrial fibrillation or sinus rhythm

Theory of disk accretion onto supermassive black holes

Accretion onto supermassive black holes produces both the dramatic phenomena associated with active galactic nuclei and the underwhelming displays seen in the Galactic Center and most other nearby galaxies. I review selected aspects of the current theoretical understanding of black hole accretion, emphasizing the role of magnetohydrodynamic turbulence and gravitational instabilities in driving the actual accretion and the importance of the efficacy of cooling in determining the structure and observational appearance of the accretion flow. Ongoing investigations into the dynamics of the plunging region, the origin of variability in the accretion process, and the evolution of warped, twisted, or eccentric disks are summarized.Comment: Mostly introductory review, to appear in "Supermassive black holes in the distant Universe", ed. A.J. Barger, Kluwer Academic Publishers, in pres