Direct Observations of the Ionizing Star in the UC HII Region G29.96-0.02: A Strong Constraint on the Stellar Birth Line for Massive Stars

We have observed the ultracompact HII region G29.96-0.02 in the near infrared J, H, and K bands and in the Br-gamma line. By comparison with radio observations, we determine that the extinction to the nebula is AK = 2.14 with a 3 sigma uncertainty of 0.25. We identify the ionizing star and determine its intrinsic K magnitude. The star does not have an infrared excess and so appears to be no longer accreting. The K magnitude and the bolometric luminosity allow us to place limits on the location of the ionizing star in the HR diagram. The 3 sigma upper limit on the effective temperature of the ionizing star is 42500 K. We favor a luminosity appropriate for star with a mass in excess of about 60 solar masses. The limit on the temperature and luminosity exclude stars on the ZAMS and stars within 10^6 yr of the ZAMS. Since the age of the UC HII region is estimated to be only about 10^5 yr, we suggest that this is direct evidence that the stellar birth line for massive stars at twice solar metallicity must be significantly redder than the ZAMS.Comment: 42 pages; LaTex; 11 Postscript figures; accepted for publication in Ap

Stage-specific fluorescence intensity of GFP and mCherry during sporulation In Bacillus Subtilis

<p>Abstract</p> <p>Background</p> <p>Fluorescent proteins are powerful molecular biology tools that have been used to study the subcellular dynamics of proteins within live cells for well over a decade. Two fluorescent proteins commonly used to enable dual protein labelling are GFP (green) and mCherry (red). Sporulation in the Gram positive bacterium <it>Bacillus subtilis </it>has been studied for many years as a paradigm for understanding the molecular basis for differential gene expression. As sporulation initiates, cells undergo an asymmetric division leading to differential gene expression in the small prespore and large mother cell compartments. Use of two fluorescent protein reporters permits time resolved examination of differential gene expression either in the same compartments or between compartments. Due to the spectral properties of GFP and mCherry, they are considered an ideal combination for co-localisation and co-expression experiments. They can also be used in combination with fluorescent DNA stains such as DAPI to correlate protein localisation patterns with the developmental stage of sporulation which can be linked to well characterised changes in DNA staining patterns.</p> <p>Findings</p> <p>While observing the recruitment of the transcription machinery into the forespore of sporulating <it>Bacillus subtilis</it>, we noticed the occurrence of stage-specific fluorescence intensity differences between GFP and mCherry. During vegetative growth and the initial stages of sporulation, fluorescence from both GFP and mCherry fusions behaved similarly. During stage II-III of sporulation we found that mCherry fluorescence was considerably diminished, whilst GFP signals remained clearly visible. This fluorescence pattern reversed during the final stage of sporulation with strong mCherry and low GFP fluorescence. These trends were observed in reciprocal tagging experiments indicating a direct effect of sporulation on fluorescent protein fluorophores.</p> <p>Conclusions</p> <p>Great care should be taken when interpreting the results of protein localisation and quantitative gene expression patterns using fluorescent proteins in experiments involving intracellular physiological change. We believe changes in the subcellular environment of the sporulating cell leads to conditions that differently alter the spectral properties of GFP and mCherry making an accurate interpretation of expression profiles technically challenging.</p

Coherent dynamics of Bose-Einstein condensates in high-finesse optical cavities

We study the mutual interaction of a Bose-Einstein condensed gas with a single mode of a high-finesse optical cavity. We show how the cavity transmission reflects condensate properties and calculate the self-consistent intra-cavity light field and condensate evolution. Solving the coupled condensate-cavity equations we find that while falling through the cavity, the condensate is adiabatically transfered into the ground state of the periodic optical potential. This allows time dependent non-destructive measurements on Bose-Einstein condensates with intriguing prospects for subsequent controlled manipulation.Comment: 5 pages, 5 figures; revised version: added reference

Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune- System-Mediated Protection and Subsequent Long-Term Adaptive Immunity

The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigendependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8! T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8! T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity

Evaluating Metacognitive Therapy to Improve Treatment of Anxiety and Depression in Cardiovascular Disease: The NIHR Funded PATHWAY Research Programme

BackgroundAnxiety and depression contribute to poorer physical and mental health outcomes in cardiac patients. Psychological treatments are not routinely offered in cardiac care and have mixed and small effects. We conducted a series of studies under the PATHWAY research programme aimed at understanding and improving mental health outcomes for patients undergoing cardiac rehabilitation (CR) through provision of metacognitive therapy (MCT).MethodsPATHWAY was a series of feasibility trials, single-blind, multicenter, randomized controlled trials (RCTs), qualitative, stated preferences for therapy and health economics studies.FindingsPatients felt their psychological needs were not met in CR and their narratives of distress could be parsimoniously explained by the metacognitive model. Patients reported they would prefer therapy over no therapy as part of CR, which included delivery by a cardiac professional. Two feasibility studies demonstrated that RCTs of group-based and self-help MCT were acceptable, could be embedded in CR services, and that RCTs of these interventions were feasible. A definitive RCT of group-MCT within CR (n = 332) demonstrated significantly greater reductions in the severity of anxiety and depression, exceeding CR alone, with gains maintained at 12 month follow-up (SMD HADS total score = 0.52 at 4 months and 0.33 at 12 months). A definitive trial of self-help MCT is ongoing.ConclusionThere is a need to better meet the psychological needs of CR patients. Embedding MCT into CR demonstrated high acceptability and improved efficacy on psychological outcomes. Results support roll-out of MCT in CR with evaluation of national implementation.RegistrationURL: NCT02420431; ISRCTN74643496; NCT03129282.</jats:sec

BET bromodomain proteins regulate enhancer function during adipogenesis

Developmental transitions are guided by master regulatory transcription factors. During adipogenesis, a transcriptional cascade culminates in the expression of PPARγ and C/EBPα, which orchestrate activation of the adipocyte gene expression program. However, the coactivators controlling PPARγ and C/EBPα expression are less well characterized. Here, we show the bromodomain-containing protein, BRD4, regulates transcription of PPARγ and C/EBPα. Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in 3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super-enhancers proximal to genes controlling adipocyte differentiation. Inhibition of the bromodomain and extraterminal domain (BET) family of bromodomain-containing proteins impedes BRD4 occupancy at these de novo enhancers and disrupts transcription of Pparg and Cebpa, thereby blocking adipogenesis. Furthermore, silencing of these BRD4-occupied distal regulatory elements at the Pparg locus by CRISPRi demonstrates a critical role for these enhancers in the control of Pparg gene expression and adipogenesis in 3T3L1s. Together, these data establish BET bromodomain proteins as time- and context-dependent coactivators of the adipocyte cell state transition

Progression of a large syphilis outbreak in rural North Carolina through space and time: Application of a Bayesian Maximum Entropy graphical user interface

In 2001, the primary and secondary syphilis incidence rate in rural Columbus County, North Carolina was the highest in the nation. To understand the development of syphilis outbreaks in rural areas, we developed and used the Bayesian Maximum Entropy Graphical User Interface (BMEGUI) to map syphilis incidence rates from 1999–2004 in seven adjacent counties in North Carolina. Using BMEGUI, incidence rate maps were constructed for two aggregation scales (ZIP code and census tract) with two approaches (Poisson and simple kriging). The BME maps revealed the outbreak was initially localized in Robeson County and possibly connected to more urban endemic cases in adjacent Cumberland County. The outbreak spread to rural Columbus County in a leapfrog pattern with the subsequent development of a visible low incidence spatial corridor linking Roberson County with the rural areas of Columbus County. Though the data are from the early 2000s, they remain pertinent, as the combination of spatial data with the extensive sexual network analyses, particularly in rural areas gives thorough insights which have not been replicated in the past two decades. These observations support an important role for the connection of micropolitan areas with neighboring rural areas in the spread of syphilis. Public health interventions focusing on urban and micropolitan areas may effectively limit syphilis indirectly in nearby rural areas

Determinants of Physical Health Self-Management Behaviours in Adults With Serious Mental Illness:A Systematic Review

Behavioural interventions can support the adoption of healthier lifestyles and improve physical health outcomes, but it is unclear what factors might drive success of such interventions in people with serious mental illness (SMI). We systematically identified and reviewed evidence of the association between determinants of physical health self-management behaviours in adults with SMI. Data about American Association of Diabetes Educator’s Self-Care Behaviours (AADE-7) were mapped against the novel Mechanisms of Action (MoA) framework. Twenty-eight studies were included in the review, reporting evidence on 104 determinant-behaviour links. Beliefs about capabilities and beliefs about consequences were the most important determinants of behaviour, especially for being physically active and healthy eating. There was some evidence that emotion and environmental context and resources played a role in determining reducing risks, being active, and taking medications. We found very limited evidence associated with problem solving, and no study assessed links between MoAs and healthy coping. Although the review predominantly identified evidence about associations from cross-sectional studies that lacked validated and objective measures of self-management behaviours, these findings can facilitate the identification of behaviour change techniques with hypothesised links to determinants to support self-management in people with SMI