In medium T-matrix for superfluid nuclear matter

We study a generalized ladder resummation in the superfluid phase of the nuclear matter. The approach is based on a conserving generalization of the usual T-matrix approximation including also anomalous self-energies and propagators. The approximation here discussed is a generalization of the usual mean-field BCS approach and of the in medium T-matrix approximation in the normal phase. The numerical results in this work are obtained in the quasi-particle approximation. Properties of the resulting self-energy, superfluid gap and spectral functions are studied.Comment: 38 pages, 19 figures, Introduction rewritten, Refs. adde

Retargeting azithromycin analogues to have dual-modality antimalarial activity

Background: Resistance to front-line antimalarials (artemisinin combination therapies) is spreading, and development of new drug treatment strategies to rapidly kill Plasmodium spp. malaria parasites is urgently needed. Azithromycin is a clinically used macrolide antibiotic proposed as a partner drug for combination therapy in malaria, which has also been tested as monotherapy. However, its slow-killing 'delayed-death' activity against the parasite's apicoplast organelle and suboptimal activity as monotherapy limit its application as a potential malaria treatment. Here, we explore a panel of azithromycin analogues and demonstrate that chemical modifications can be used to greatly improve the speed and potency of antimalarial action. Results: Investigation of 84 azithromycin analogues revealed nanomolar quick-killing potency directed against the very earliest stage of parasite development within red blood cells. Indeed, the best analogue exhibited 1600-fold higher potency than azithromycin with less than 48 hrs treatment in vitro. Analogues were effective against zoonotic Plasmodium knowlesi malaria parasites and against both multi-drug and artemisinin-resistant Plasmodium falciparum lines. Metabolomic profiles of azithromycin analogue-treated parasites suggested activity in the parasite food vacuole and mitochondria were disrupted. Moreover, unlike the food vacuole-targeting drug chloroquine, azithromycin and analogues were active across blood-stage development, including merozoite invasion, suggesting that these macrolides have a multi-factorial mechanism of quick-killing activity. The positioning of functional groups added to azithromycin and its quick-killing analogues altered their activity against bacterial-like ribosomes but had minimal change on 'quick-killing' activity. Apicoplast minus parasites remained susceptible to both azithromycin and its analogues, further demonstrating that quick-killing is independent of apicoplast-targeting, delayed-death activity. Conclusion: We show that azithromycin and analogues can rapidly kill malaria parasite asexual blood stages via a fast action mechanism. Development of azithromycin and analogues as antimalarials offers the possibility of targeting parasites through both a quick-killing and delayed-death mechanism of action in a single, multifactorial chemotype.Amy L. Burns, Brad E. Sleebs, Ghizal Siddiqui, Amanda E. De Paoli, Dovile Anderson, Benjamin Liffner, Richard Harvey, James G. Beeson, Darren J. Creek, Christopher D. Goodman, Geoffrey I. McFadden, and Danny W. Wilso

Atmospheric Heating and Wind Acceleration: Results for Cool Evolved Stars based on Proposed Processes

A chromosphere is a universal attribute of stars of spectral type later than ~F5. Evolved (K and M) giants and supergiants (including the zeta Aurigae binaries) show extended and highly turbulent chromospheres, which develop into slow massive winds. The associated continuous mass loss has a significant impact on stellar evolution, and thence on the chemical evolution of galaxies. Yet despite the fundamental importance of those winds in astrophysics, the question of their origin(s) remains unsolved. What sources heat a chromosphere? What is the role of the chromosphere in the formation of stellar winds? This chapter provides a review of the observational requirements and theoretical approaches for modeling chromospheric heating and the acceleration of winds in single cool, evolved stars and in eclipsing binary stars, including physical models that have recently been proposed. It describes the successes that have been achieved so far by invoking acoustic and MHD waves to provide a physical description of plasma heating and wind acceleration, and discusses the challenges that still remain.Comment: 46 pages, 9 figures, 1 table; modified and unedited manuscript; accepted version to appear in: Giants of Eclipse, eds. E. Griffin and T. Ake (Berlin: Springer

Targeting malaria parasites with novel derivatives of azithromycin

Introduction: The spread of artemisinin resistant Plasmodium falciparum parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a macrolide antibiotic used clinically against malaria, kills parasites via two mechanisms: ‘delayed death’ by inhibiting the bacterium-like ribosomes of the apicoplast, and ‘quick-killing’ that kills rapidly across the entire blood stage development. Methods: Here, 22 azithromycin analogues were explored for delayed death and quick-killing activities against P. falciparum (the most virulent human malaria) and P. knowlesi (a monkey parasite that frequently infects humans). Results: Seventeen analogues showed improved quick-killing against both Plasmodium species, with up to 38 to 20-fold higher potency over azithromycin after less than 48 or 28 hours of treatment for P. falciparum and P. knowlesi, respectively. Quick-killing analogues maintained activity throughout the blood stage lifecycle, including ring stages of P. falciparum parasites (5-fold more selective against P. falciparum than human cells. Isopentenyl pyrophosphate supplemented parasites that lacked an apicoplast were equally sensitive to quick-killing analogues, confirming that the quick killing activity of these drugs was not directed at the apicoplast. Further, activity against the related apicoplast containing parasite Toxoplasma gondii and the gram-positive bacterium Streptococcus pneumoniae did not show improvement over azithromycin, highlighting the specific improvement in antimalarial quick-killing activity. Metabolomic profiling of parasites subjected to the most potent compound showed a build-up of non-haemoglobin derived peptides that was similar to chloroquine, while also exhibiting accumulation of haemoglobin-derived peptides that was absent for chloroquine treatment. Discussion: The azithromycin analogues characterised in this study expand the structural diversity over previously reported quick-killing compounds and provide new starting points to develop azithromycin analogues with quickkilling antimalarial activity.Amy L. Burns, Brad E. Sleebs, Maria Gancheva, Kimberley T. McLean, Ghizal Siddiqui, Henrietta Venter, James G. Beeson, Ryan O, Handley, Darren J. Creek, Shutao Ma, Sonja Frölich, Christopher D. Goodman, Geoffrey I. McFadden, and Danny W. Wilso

Macrophyte abundance in Waquoit Bay : effects of land-derived nitrogen loads on seasonal and multi-year biomass patterns

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Estuaries and Coasts 31 (2008): 532-541, doi:10.1007/s12237-008-9039-6.Anthropogenic inputs of nutrients to coastal waters have rapidly restructured coastal ecosystems. To examine the response of macrophyte communities to land-derived nitrogen loading, we measured macrophyte biomass monthly for six years in three estuaries subject to different nitrogen loads owing to different land uses on the watersheds. The set of estuaries sampled had nitrogen loads over the broad range of 12 to 601 kg N ha-1 y-1. Macrophyte biomass increased as nitrogen loads increased, but the response of individual taxa varied. Specifically, biomass of Cladophora vagabunda and Gracilaria tikvahiae increased significantly as nitrogen loads increased. The biomass of other macroalgal taxa tended to decrease with increasing load, and the relative proportion of these taxa to total macrophyte biomass also decreased. The seagrass, Zostera marina, disappeared from the higher loaded estuaries, but remained abundant in the estuary with the lowest load. Seasonal changes in macroalgal standing stock were also affected by nitrogen load, with larger fluctuations in biomass across the year and higher minimum biomass of macroalgae in the higher loaded estuaries. There were no significant changes in macrophyte biomass over the six years of this study, but there was a slight trend of increasing macroalgal biomass in the latter years. Macroalgal biomass was not related to irradiance or temperature, but Z. marina biomass was highest during the summer months when light and temperatures peak. Irradiance might, however, be a secondary limiting factor controlling macroalgal biomass in the higher loaded estuaries by restricting the depth of the macroalgal canopy. The relationship between the bloom-forming macroalgal species, C. vagabunda and G. tikvahiae, and nitrogen loads suggested a strong connection between development on watersheds and macroalgal blooms and loss of seagrasses. The influence of watershed land uses largely overwhelmed seasonal and inter-annual differences in standing stock of macrophytes in these temperate estuaries.This research was supported by the National Oceanic and Atmospheric Administration (NOAA), Cooperative Institute for Coastal and Estuarine Environmental Technologies (CICEET-UNH#99-304, NOAA NA87OR512), NOAA National Estuarine Research Reserve Graduate Research Fellowship NERRS GRF, #NA77OR0228), and an Environmental Protection Agency (EPA) STAR Fellowship for Graduate Environmental Study (U-915335-01-0) awarded to J. Hauxwell. S. Fox was supported by a NOAA NERRS GRF (#NA03NOS4200132) and an EPA STAR Graduate Research Fellowship. We also thank the Quebec-Labrador Foundation Atlantic Center for the Environment's Sounds Conservancy Program and the Boston University Ablon/Bay Committee for their awarding research funds

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Milagro limits and HAWC sensitivity for the rate-density of evaporating Primordial Black Holes

postprin

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

Search for dark matter produced in association with a hadronically decaying vector boson in pp collisions at sqrt (s) = 13 TeV with the ATLAS detector

A search is presented for dark matter produced in association with a hadronically decaying W or Z boson using 3.2 fb−1 of pp collisions at View the MathML sources=13 TeV recorded by the ATLAS detector at the Large Hadron Collider. Events with a hadronic jet compatible with a W or Z boson and with large missing transverse momentum are analysed. The data are consistent with the Standard Model predictions and are interpreted in terms of both an effective field theory and a simplified model containing dark matter

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe