Constraints on intragroup stellar mass from hostless Type Ia supernova

We probe the diffuse stellar mass in a sample of 1401 low redshift galaxy groups (10E13 - 10E14 Msun/h) by examining the rate of hostless Type Ia supernova (SNe Ia) within the groups. We correlate the sample of confirmed SNe Ia from the SDSS supernova survey with the positions of our galaxy groups, as well as with the resolved galaxies within them. We find that 19 of the 59 SNe Ia within the group sample have no detectable host galaxy, with another three ambiguous instances. This gives a robust upper limit that a maximum of 2.69% +1.58%/-1.34% of the group's total mass arises from diffuse stars in the intragroup medium. After correcting for a contribution from "prompt" SNe occurring within galaxies, and including a contribution from those which arise in dwarf galaxies below our photometric limit, we find that only 1.32% +0.78%/-0.70% of the group's total mass is likely in the form of diffuse stellar mass. Combining this result with the galaxy stellar mass functions of Yang et al., we find that 47% +16%/-15% of the stellar mass in our groups is in the form of diffuse light, so that stars make up a fraction 0.028 +0.011/-0.010 of the total group mass. Galaxy groups appear to be very efficient in disrupting stellar mass into a diffuse component; however, stars still make up a small fraction of the group mass, comparable to that seen in rich clusters. This remains a challenge to galaxy formation models.Comment: 5 pages, MNRAS Letters, in pres

Development of a Broadly Protective, Self-Adjuvanting Subunit Vaccine to Prevent Infections by Pseudomonas aeruginosa

Infections caused by the opportunistic pathogen Pseudomonas aeruginosa can be difficult to treat due to innate and acquired antibiotic resistance and this is exacerbated by the emergence of multi-drug resistant strains. Unfortunately, no licensed vaccine yet exists to prevent Pseudomonas infections. Here we describe a novel subunit vaccine that targets the P. aeruginosa type III secretion system (T3SS). This vaccine is based on the novel antigen PaF (Pa Fusion), a fusion of the T3SS needle tip protein, PcrV, and the first of two translocator proteins, PopB. Additionally, PaF is made self-adjuvanting by the N-terminal fusion of the A1 subunit of the mucosal adjuvant double-mutant heat-labile enterotoxin (dmLT). Here we show that this triple fusion, designated L-PaF, can activate dendritic cells in vitro and elicits strong IgG and IgA titers in mice when administered intranasally. This self-adjuvanting vaccine expedites the clearance of P. aeruginosa from the lungs of challenged mice while stimulating host expression of IL-17A, which may be important for generating a protective immune response in humans. L-PaF’s protective capacity was recapitulated in a rat pneumonia model, further supporting the efficacy of this novel fusion vaccine

Highly Stable and Conductive Microcapsules for Enhancement of Joule Heating Performance

Nanocarbons show great promise for establishing the next generation of Joule heating systems, but suffer from the limited maximum temperature due to precociously convective heat dissipation from electrothermal system to surrounding environment. Here we introduce a strategy to eliminate such convective heat transfer by inserting highly stable and conductive microcapsules into the electrothermal structures. The microcapsule is composed of encapsulated long-chain alkanes and graphene oxide/carbon nanotube hybrids as core and shell material, respectively. Multiform carbon nanotubes in the microspheres stabilize the capsule shell to resist volume-change-induced rupture during repeated heating/cooling process, and meanwhile enhance the thermal conductance of encapsulated alkanes which facilitates an expeditious heat exchange. The resulting microcapsules can be homogeneously incorporated in the nanocarbon-based electrothermal structures. At a dopant of 5%, the working temperature can be enhanced by 30% even at a low voltage and moderate temperature, which indicates a great value in daily household applications. Therefore, the stable and conductive microcapsule may serve as a versatile and valuable dopant for varieties of heat generation systems

Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

Characterising the application of the “progressive overload” principle of exercise training within cardiac rehabilitation: A United Kingdom-based community programme

Background: Recent concerns have cast doubt over the effectiveness of cardiac rehabilitation [CR] programmes for improving cardiorespiratory fitness [CRF] in patients with a history of cardiac disease in the United Kingdom [UK]. We aimed to characterise the weekly progression of exercise training dose over an 8-week Phase III CR programme as we felt this may be partly responsible for the lack of improvement in CRF reported in previous studies. Design: Observational study. Methods: We evaluated a community-based Phase III CR programme in the UK. During each training session, patients wore an Apple Watch and the weekly progression of exercise training dose/load was quantified. The analysis was based on 332 individual training sessions. Exercise intensity [% heart rate reserve] during the cardiovascular [CV] exercise training component [%HRR-CV], CV training duration; estimated changes in cardiorespiratory fitness [change in estimated metabolic equivalents (METs)]; session rating of perceived exertion [sRPE], sRPE training load [sRPE-TL], and exercise training impulse [TRIMP] were evaluated. Results: Thirty cardiac patients [83% male; age [SD] 67.0 [10.0] years; body mass index [SD] 28.3 [4.6] kg∙m-2] were recruited to an 8-week programme [16 sessions in total]. Bayesian repeated-measures ANOVA indicated anecdotal evidence for the alternative hypothesis for changes in %HRR-CV (BF10 = 0.61), sRPE (BF10 = 1.1), and change in estimated METs (BF10 = 1.2) during CR. Conversely, Bayesian repeated-measures ANOVA showed extreme evidence for changes in CV training duration (BF10 = 2.438e+26), TRIMP (BF10 = 71436), and sRPE-TL (BF10 = 779570). Conclusion: The key exercise training principle of progressive overload was only partially applied. Increases observed in exercise dose were due to increases in the duration of CV training, rather than combined with increases in exercise intensity [%HRR-CV and sRPE]. Accordingly, allied health professionals must ensure that exercise intensity is more consistently progressed to optimise the exercise stimulus and improvements in CRF and patient outcomes

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression

Impact of the TLR4 agonist BECC438 on a novel vaccine formulation against Shigella spp.

Shigellosis (bacillary dysentery) is a severe gastrointestinal infection with a global incidence of 90 million cases annually. Despite the severity of this disease, there is currently no licensed vaccine against shigellosis. Shigella’s primary virulence factor is its type III secretion system (T3SS), which is a specialized nanomachine used to manipulate host cells. A fusion of T3SS injectisome needle tip protein IpaD and translocator protein IpaB, termed DBF, when admixed with the mucosal adjuvant double-mutant labile toxin (dmLT) from enterotoxigenic E. coli was protective using a murine pulmonary model. To facilitate the production of this platform, a recombinant protein that consisted of LTA-1, the active moiety of dmLT, and DBF were genetically fused, resulting in L-DBF, which showed improved protection against Shigella challenge. To extrapolate this protection from mice to humans, we modified the formulation to provide for a multivalent presentation with the addition of an adjuvant approved for use in human vaccines. Here, we show that L-DBF formulated (admix) with a newly developed TLR4 agonist called BECC438 (a detoxified lipid A analog identified as Bacterial Enzymatic Combinatorial Chemistry candidate #438), formulated as an oil-in-water emulsion, has a very high protective efficacy at low antigen doses against lethal Shigella challenge in our mouse model. Optimal protection was observed when this formulation was introduced at a mucosal site (intranasally). When the formulation was then evaluated for the immune response it elicits, protection appeared to correlate with high IFN-γ and IL-17 secretion from mucosal site lymphocytes

Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival

Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5′-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma