Searching for the most powerful thermonuclear X-ray bursts with the Neil Gehrels Swift Observatory

We searched for thermonuclear X-ray bursts from Galactic neutron stars in all event mode data of the Neil Gehrels Swift Observatory collected until March 31, 2018. In particular, we are interested in the intermediate-duration bursts (shell flashes fueled by thick helium piles) with the ill-understood phenomenon of strong flux fluctuations. Nine such bursts have been discussed in the literature to date. Swift is particularly suitable for finding additional examples. We find and list a total of 134 X-ray bursts; 44 are detected with BAT only, 41 with XRT only, and 49 with both. Twenty-eight bursts involve automatic slews. We find 12 intermediate-duration bursts, all detected in observations involving automatic slews. Five show remarkably long Eddington-limited phases in excess of 200 s. Five show fluctuations during the decay phase; four of which are first discussed in the present study. We discuss the general properties of the fluctuations, considering also 7 literature cases. In general two types of fluctuations are observed: fast ones, with a typical timescale of 1 s and up and downward fluctuations of up to 70%, and slow ones, with a typical timescale of 1 min and only downward fluctuations of up to 90%. The latter look like partial eclipses because the burst decay remains visible in the residual emission. We revisit the interpretation of this phenomenon in the context of the new data set and find that it has not changed fundamentally despite the expanded data set. It is thought to be due to a disturbance of the accretion disk by outflowing matter and photons, causing obscuration and reflection due to Thompson scattering in an orbiting highly ionized cloud or structure above or below the disk. We discuss in detail the most pronounced burster SAX J1712.6-3739. One of the bursts from this source is unusual in that it lasts longer than 5600 s, but does not appear to be a superburst.Comment: Accepted for publication in Astronomy & Astrophysics, 29 pages, 12 figures. Version 2 has 3 bursts from IGR J17480-2446 re-identified to 2 from Swift J174805.3-244637 and 1 from EXO 1745-24

Maternal smoking during pregnancy and appetite control in offspring

Aims: Intrauterine exposure to tobacco smoke products has been associated with long-term neurobehavioral effects. Modified appetite control might explain the recently observed association between maternal smoking during pregnancy and obesity in offspring. Methods: Some 10,557 British adults aged 42 years born between 3-9 March 1958 were followed up in a birth cohort study (NCDS). The main outcome measure was self-reported poor appetite at age 42 years and main exposure was maternal smoking during pregnancy. Results: The proportion of offspring with poor appetite increased with maternal smoking during pregnancy: nonsmoking 4.5%; (4.0% - 5.0%), medium smoking 5.6%; (4.5 % - 6.8 %), variable smoking 6.8 %; (4.9 % - 9.1 %) and heavy smoking 7.7 %; (6.3 % - 9.4 %). The unadjusted odds ratios for maternal smoking during pregnancy (ever/never) and poor appetite is 1.49 (1.25 - 1.77) and after adjustment for BMI at 42 years and other potential confounding factors it is 1.22 (1.07 - 1.48). Conclusions: Offspring of mothers who smoked during pregnancy were more likely to report a poor appetite independent of a number of potential confounding factors. Although not in the expected direction, the results suggest maternal smoking during pregnancy may influence appetite perception through a developmental influence or through confounding by social factors

Assessment of varicella vaccine effectiveness in Germany: a time-series approach

A multivariate time-series regression model was developed in order to describe the 2005-2008 age-specific time-course of varicella sentinel surveillance data following the introduction of a varicella childhood vaccination programme in Germany. This ecological approach allows the assessment of vaccine effectiveness under field conditions by relating vaccine coverage in cohorts of 24-month-old children to the mean number of cases per reporting unit in the sentinel network. For the 1-2 years age group, which is directly affected by the vaccination programme, a one-dose vaccine effectiveness of 83·2% (95% CI 80·2-85·7) was estimated which corresponds to previous approaches assessing varicella vaccine effectiveness in the field in the US

Impact of 10-and 13-valent pneumococcal conjugate vaccines on incidence of invasive pneumococcal disease in children aged under 16 years in Germany, 2009 to 2012

We assessed the impact of 10-valent and 13-valent pneumococcal vaccines (PCV10 and PCV13), which were introduced in Germany in 2009, on the incidence of meningitis and non-meningitis invasive pneumococcal disease (IPD) in children aged under 16 years in a population previously vaccinated with a sevenvalent vaccine (PCV7). Surveillance of IPD (isolation of Streptococcus pneumonia from a normally sterile body site) is based on data from two independent reporting sources: hospitals and laboratories. IPD incidence was estimated by capture-recapture analysis. Incidence rate ratios (IRRs) were calculated for 2009 and 2012, thus comparing pre-and post-PCV10 and PCV13 data. IPD incidence caused by serotypes included in PCV13 decreased in all age and diagnosis groups. A rise in non-vaccine serotype incidence was seen only in children aged under two years. The overall impact varied by age group and infection site: for meningitis IPD in children aged under 2, 2-4 and 5-15 years, incidence changed by 3% (95% CI: -31 to 52), -60% (95% CI: -81 to -17) and -9% (95% CI: -46 to 53), respectively. A more pronounced incidence reduction was observed for non-meningitis IPD: -30% (95% CI: -46 to -7), -39% (95% CI: -54 to -20) and -83% (95% CI: -89 to -73) in children aged under 2, 2-4 and 5-15 years, respectively. A higher tropism of the additional serotypes for non-meningitis IPD may be a potential explanation. The heterogeneous findings emphasise the need for rigorous surveillance

Vinylphosphonites for staudinger-induced chemoselective peptide cyclization and functionalization

In this paper, we introduce vinylphosphonites for chemoselective Staudinger-phosphonite reactions (SPhR) with azides to form vinylphosphonamidates for the subsequent modification of cysteine residues in peptides and proteins. An electron-rich alkene is turned into an electron-deficient vinylphosphonamidate, thereby inducing electrophilic reactivity for a following thiol addition. We show that by varying the phosphonamidate ester substituent we can fine-tune the reactivity of the thiol addition and even control the functional properties of the final conjugate. Furthermore, we observed a drastic increase in thiol addition efficiency when the SPhR is carried out in the presence of a thiol substrate in a one-pot reaction. Hence, we utilize vinylphosphonites for the chemoselective intramolecular cyclization of peptides carrying an azide-containing amino acid and a cysteine in high yields. Our concept was demonstrated for the stapling of a cell-permeable peptidic inhibitor for protein–protein interaction (PPI) between BCL9 and beta-catenin, which is known to create a transcription factor complex playing a role in embryonic development and cancer origin, and for macrocyclization of cell-penetrating peptides (CPPs) to enhance the cellular uptake of proteins

Identification of a novel benzimidazole pyrazolone scaffold that inhibits KDM4 lysine demethylases and reduces proliferation of prostate cancer cells

Human lysine demethylase (KDM) enzymes (KDM1-7) constitute an emerging class of therapeutic targets, with activities that support growth and development of metastatic disease. By interacting with and co-activating the androgen receptor, the KDM4 subfamily (KDM4A-E) promotes aggressive phenotypes of prostate cancer (PCa). Knockdown of KDM4 expression or inhibition of KDM4 enzyme activity reduces the proliferation of PCa cell lines and highlights inhibition of lysine demethylation as a possible therapeutic method for PCa treatment. To address this possibility, we screened the ChemBioNet small molecule library for inhibitors of the human KDM4E isoform and identified several compounds with IC50 values in the low micromolar range. Two hits, validated as active by an orthogonal enzyme-linked immunosorbent assay, displayed moderate selectivity toward the KDM4 subfamily and exhibited antiproliferative effects in cellular models of PCa. These compounds were further characterized by their ability to maintain the transcriptionally silent histone H3 tri-methyl K9 epigenetic mark at subcytotoxic concentrations. Taken together, these efforts identify and validate a hydroxyquinoline scaffold and a novel benzimidazole pyrazolone scaffold as tractable for entry into hit-to-lead chemical optimization campaigns

Latent class analysis of diagnostic tests for adenovirus, Bordetella pertussis and influenza virus infections in German adults with longer lasting coughs

Laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. While the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus A and B infections is unclear. A sentinel study into the population-based incidence of longer lasting coughs in adults was done in Rostock (former East Germany) and Krefeld (former West Germany). A total of 971 outpatients who consulted general practitioners or internists were included. Inclusion criteria were coughing for 51 week and no chronic respiratory diseases. We evaluated the performance of polymerase chain reaction (PCR) as well as IgG and IgA serology, applying a latent class model for diagnosing infections with adenovirus, B. pertussis, and influenza virus A and B. The adult outpatients first sought medical attention when they had been coughing for a median of 3 weeks. In this situation, direct detection of infectious agents by PCR had a low sensitivity. Modelling showed that additional serological tests equally improved sensitivity and specificity for diagnosis for adenovirus, B. pertussis and influenza virus A and B infections. The combination of serology and PCR may improve the overall performance of diagnostic tests for B. pertussis and also for adenovirus, and influenza virus A and B infections