Analysis of stellar spectra with 3D and NLTE models

Models of radiation transport in stellar atmospheres are the hinge of modern astrophysics. Our knowledge of stars, stellar populations, and galaxies is only as good as the theoretical models, which are used for the interpretation of their observed spectra, photometric magnitudes, and spectral energy distributions. I describe recent advances in the field of stellar atmosphere modelling for late-type stars. Various aspects of radiation transport with 1D hydrostatic, LTE, NLTE, and 3D radiative-hydrodynamical models are briefly reviewed.Comment: 21 pages, accepted for publication as a chapter in "Determination of Atmospheric Parameters of B, A, F and G Type Stars", Springer (2014), eds. E. Niemczura, B. Smalley, W. Pyc

Glycolysis and Fatty Acid Oxidation Inhibition Improves Survival in Glioblastoma

Glioblastoma (GBM) is the most aggressive adult glioma with a median survival of 14 months. While standard treatments (safe maximal resection, radiation, and temozolomide chemotherapy) have increased the median survival in favorable O(6)-methylguanine-DNA methyltransferase (MGMT)-methylated GBM (~21 months), a large proportion of patients experience a highly debilitating and rapidly fatal disease. This study examined GBM cellular energetic pathways and blockade using repurposed drugs: the glycolytic inhibitor, namely dicholoroacetate (DCA), and the partial fatty acid oxidation (FAO) inhibitor, namely ranolazine (Rano). Gene expression data show that GBM subtypes have similar glucose and FAO pathways, and GBM tumors have significant upregulation of enzymes in both pathways, compared to normal brain tissue (p < 0.01). DCA and the DCA/Rano combination showed reduced colony-forming activity of GBM and increased oxidative stress, DNA damage, autophagy, and apoptosis in vitro. In the orthotopic Gl261 and CT2A syngeneic murine models of GBM, DCA, Rano, and DCA/Rano increased median survival and induced focal tumor necrosis and hemorrhage. In conclusion, dual targeting of glycolytic and FAO metabolic pathways provides a viable treatment that warrants further investigation concurrently or as an adjuvant to standard chemoradiation for GBM

Combined Tevatron upper limit on gg->H->W+W- and constraints on the Higgs boson mass in fourth-generation fermion models

Report number: FERMILAB-PUB-10-125-EWe combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg->H->W+W- in p=pbar collisions at the Fermilab Tevatron Collider at sqrt{s}=1.96 TeV. With 4.8 fb-1 of integrated luminosity analyzed at CDF and 5.4 fb-1 at D0, the 95% Confidence Level upper limit on \sigma(gg->H) x B(H->W+W-) is 1.75 pb at m_H=120 GeV, 0.38 pb at m_H=165 GeV, and 0.83 pb at m_H=200 GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% Confidence Level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.We combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg→H→W+W- in pp̅ collisions at the Fermilab Tevatron Collider at √s=1.96  TeV. With 4.8  fb-1 of integrated luminosity analyzed at CDF and 5.4  fb-1 at D0, the 95% confidence level upper limit on σ(gg→H)×B(H→W+W-) is 1.75 pb at mH=120  GeV, 0.38 pb at mH=165  GeV, and 0.83 pb at mH=200  GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% confidence level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.Peer reviewe

Songlines for Parkinson’s: The Process of Co-Developing a New Music-and-Movement Group-Based Intervention to Improve Mood and Movement for Parkinson’s

Data availability statement: Due to issues of anonymity (e.g., with the video recordings) we are only able to make parts of the data available, which we will do on request.Supplementary Material is available online at: https://journals.sagepub.com/doi/10.1177/16094069251335453#supplementary-materials .Participatory research promotes inclusive practice and enables stakeholder expertise to be recognized as a valuable contribution throughout the research cycle. However, there is little guidance regarding how to disseminate these qualitative processes, and the methodological insights gained. Based on preliminary research, we had developed a session framework for a new intervention using music to improve motor and non-motor symptoms for people with Parkinson’s. Our next step was to work in a trans- and interdisciplinary way to further explore concepts (e.g., imagery) and to co-develop content (e.g., musical exercises). Through a synthesis of materials including video footage, worksheets, field notes, transcriptions of interviews and feedback forms derived though workshops and interviews with people with Parkinson’s, a range of practitioners and healthcare professionals, and researchers in the UK (in English) and in Switzerland (in German and Italian), we developed a draft protocol for a 12-week course. This was then optimized through a final round of feedback with the stakeholders. We gained direct methodological insights throughout these processes, including some that led to changes in protocol (addition of two new sections), and the revision (rhythmic exercises) and removal (e.g., singing and syncopation) of some planned content. We also changed our use of language. Indirect insights included the need for cultural and contextual sensitivity, and a new understanding of the bidirectional nature of impact. A new group-based music and movement course, Songlines for Parkinson’s, has been co-developed for and with people with Parkinson’s. The methodological insights gained have not only shaped the protocol but also provided lessons that could be useful for planning and guidance in future participatory projects involving the Parkinson’s community and extended to other groups.In addition to the resources provided by the institutions, individuals and companies as described in the affiliations, this project was made possible by grants awarded to the first author from Parkinson Schweiz and the Swiss National Science Foundation (Project Grant 100001C_204/290)

Ancient Antimicrobial Peptides Kill Antibiotic-Resistant Pathogens: Australian Mammals Provide New Options

Background: To overcome the increasing resistance of pathogens to existing antibiotics the 10× 20 Initiative declared the urgent need for a global commitment to develop 10 new antimicrobial drugs by the year 2020. Naturally occurring animal antibiotics are an obvious place to start. The recently sequenced genomes of mammals that are divergent from human and mouse, including the tammar wallaby and the platypus, provide an opportunity to discover novel antimicrobials. Marsupials and monotremes are ideal potential sources of new antimicrobials because they give birth to underdeveloped immunologically naïve young that develop outside the sterile confines of a uterus in harsh pathogen-laden environments. While their adaptive immune system develops innate immune factors produced either by the mother or by the young must play a key role in protecting the immune-compromised young. In this study we focus on the cathelicidins, a key family of antimicrobial peptide genes. Principal Finding: We identified 14 cathelicidin genes in the tammar wallaby genome and 8 in the platypus genome. The tammar genes were expressed in the mammary gland during early lactation before the adaptive immune system of the young develops, as well as in the skin of the pouch young. Both platypus and tammar peptides were effective in killing a broad range of bacterial pathogens. One potent peptide, expressed in the early stages of tammar lactation, effectively killed multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii. Conclusions and Significance: Marsupial and monotreme young are protected by antimicrobial peptides that are potent, broad spectrum and salt resistant. The genomes of our distant relatives may hold the key for the development of novel drugs to combat multidrug-resistant pathogens

A simulation model approach to analysis of the business case for eliminating health care disparities

<p>Abstract</p> <p>Background</p> <p>Purchasers can play an important role in eliminating racial and ethnic disparities in health care. A need exists to develop a compelling "business case" from the employer perspective to put, and keep, the issue of racial/ethnic disparities in health care on the quality improvement agenda for health plans and providers.</p> <p>Methods</p> <p>To illustrate a method for calculating an employer business case for disparity reduction and to compare the business case in two clinical areas, we conducted analyses of the direct (medical care costs paid by employers) and indirect (absenteeism, productivity) effects of eliminating known racial/ethnic disparities in mammography screening and appropriate medication use for patients with asthma. We used Markov simulation models to estimate the consequences, for defined populations of African-American employees or health plan members, of a 10% increase in HEDIS mammography rates or a 10% increase in appropriate medication use among either adults or children/adolescents with asthma.</p> <p>Results</p> <p>The savings per employed African-American woman aged 50-65 associated with a 10% increase in HEDIS mammography rate, from direct medical expenses and indirect costs (absenteeism, productivity) combined, was $50. The findings for asthma were more favorable from an employer point of view at approximately$1,660 per person if raising medication adherence rates in African-American employees or dependents by 10%.</p> <p>Conclusions</p> <p>For the employer business case, both clinical scenarios modeled showed positive results. There is a greater potential financial gain related to eliminating a disparity in asthma medications than there is for eliminating a disparity in mammography rates.</p

Integration of P2Y receptor-activated signal transduction pathways in G protein-dependent signalling networks

The role of nucleotides in intracellular energy provision and nucleic acid synthesis has been known for a long time. In the past decade, evidence has been presented that, in addition to these functions, nucleotides are also autocrine and paracrine messenger molecules that initiate and regulate a large number of biological processes. The actions of extracellular nucleotides are mediated by ionotropic P2X and metabotropic P2Y receptors, while hydrolysis by ecto-enzymes modulates the initial signal. An increasing number of studies have been performed to obtain information on the signal transduction pathways activated by nucleotide receptors. The development of specific and stable purinergic receptor agonists and antagonists with therapeutical potential largely contributed to the identification of receptors responsible for nucleotide-activated pathways. This article reviews the signal transduction pathways activated by P2Y receptors, the involved second messenger systems, GTPases and protein kinases, as well as recent findings concerning P2Y receptor signalling in C6 glioma cells. Besides vertical signal transduction, lateral cross-talks with pathways activated by other G protein-coupled receptors and growth factor receptors are discussed

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe