11^{11}B NMR study of pure and lightly carbon doped MgB2_2 superconductors

We report a $^{11}$B NMR line shape and spin-lattice relaxation rate ($1/(T_1T)$) study of pure and lightly carbon doped MgB$_{2-x}$C$_{x}$ for $x=0$, 0.02, and 0.04, in the vortex state and in magnetic field of 23.5 kOe. We show that while pure MgB$_2$ exhibits the magnetic field distribution from superposition of the normal and the Abrikosov state, slight replacement of boron with carbon unveils the magnetic field distribution of the pure Abrikosov state. This indicates a considerable increase of $H_{c2}^c$ with carbon doping with respect to pure MgB$_2$. The spin-lattice relaxation rate $1/(T_1T)$ demonstrates clearly the presence of a coherence peak right below $T_c$ in pure MgB$_2$, followed by a typical BCS decrease on cooling. However, at temperatures lower than $\approx 10$K strong deviation from the BCS behavior is observed, probably from residual contribution of the vortex dynamics. In the carbon doped systems both the coherence peak and the BCS temperature dependence of $1/(T_1T)$ weaken, an effect attributed to the gradual shrinking of the $\sigma$ hole cylinders of the Fermi surface with electron doping.Comment: 8 pages, 6 figures, submitted to Phys. Rev.

Spatio-temporal drivers of soil and ecosystem carbon fluxes at field scale in an upland grassland in Germany

Ecosystem carbon (C) fluxes in terrestrial ecosystems are affected by varying environmental conditions (e.g. soil heterogeneity and the weather) and land management. However, the interactions between soil respiration (Rs) and net ecosystem exchange (NEE) and their spatio-temporal dependence on environmental conditions and land management at field scale is not well understood. We performed repeated C flux measurement at 21 sites during the 2013 growing season in a temperate upland grassland in Germany, which was fertilized and cut three times according to the agricultural practice typical of the region. Repeated measurements included determination of NEE, Rs, leaf area index (LAI), meteorological conditions as well as physical and chemical soil properties. Temporal variability of Rs was controlled by air temperature, while LAI influenced the temporal variability of NEE. The three grass cuts reduced LAI and affected NEE markedly. More than 50% of NEE variability was explained by defoliation at field scale. Additionally, soil heterogeneity affected NEE, but to a lower extent (>30%), while Rs remained unaffected. We conclude that grassland management (i.e. repeated defoliation) and soil heterogeneity affects the spatio-temporal variability of NEE at field scale

High-throughput, parallelized and automated protein purification for therapeutic antibody development

Abstract Antibody therapeutic development often involves significant demands for purified protein samples, from initial assessments of numerous constructs from early stage screening campaigns through to lead identification and then for process development and pilot scale runs. Efforts to reduce timelines and cost per sample are common to both platform purification and for process development. In the earliest stages, high-throughput purification platforms that utilize liquid handlers or other small volume approaches can be suitable, as the quantity requirements for assays are minimal. However, as the number of candidate molecules diminishes, the scope of assays can quickly expand and include a variety of cell-based and in vivo experiments which can require tens or hundreds of milligrams of products of defined purity and with low endotoxin levels. Purification of these samples in a high-throughput, parallelized manner represents a significant challenge with relatively few available off-the-shelf solutions. Process development requirements are also amendable to high-throughput purification strategies combined with statistical approaches in order to optimize the design space and narrow initial process operation parameters suitable for a given purification unit operation. While less often utilized, non-chromatographic purification methods may also be amenable to automation and parallelization at the initial stages of purification development

Psychosocial interventions for supporting women to stop smoking in pregnancy

Background: Tobacco smoking remains one of the few preventable factors associated with complications in pregnancy, and has serious long-term implications for women and babies. Smoking in pregnancy is decreasing in high-income countries, but is strongly associated with poverty and is increasing in low- to middle-income countries. Objectives: To assess the effects of smoking cessation interventions during pregnancy on smoking behaviour and perinatal health outcomes. Search methods: In this sixth update, we searched the Cochrane Pregnancy and Childbirth Group's Trials Register (13 November 2015), checked reference lists of retrieved studies and contacted trial authors. Selection criteria: Randomised controlled trials, cluster-randomised trials, and quasi-randomised controlled trials of psychosocial smoking cessation interventions during pregnancy. Data collection and analysis: Two review authors independently assessed trials for inclusion and trial quality, and extracted data. Direct comparisons were conducted in RevMan, with meta-regression conducted in STATA 14. Main results: The overall quality of evidence was moderate to high, with reductions in confidence due to imprecision and heterogeneity for some outcomes. One hundred and two trials with 120 intervention arms (studies) were included, with 88 trials (involving over 28,000 women) providing data on smoking abstinence in late pregnancy. Interventions were categorised as counselling, health education, feedback, incentives, social support, exercise and dissemination. In separate comparisons, there is high-quality evidence that counselling increased smoking cessation in late pregnancy compared with usual care (30 studies; average risk ratio (RR) 1.44, 95% confidence interval (CI) 1.19 to 1.73) and less intensive interventions (18 studies; average RR 1.25, 95% CI 1.07 to 1.47). There was uncertainty whether counselling increased the chance of smoking cessation when provided as one component of a broader maternal health intervention or comparing one type of counselling with another. In studies comparing counselling and usual care (largest comparison), it was unclear whether interventions prevented smoking relapse among women who had stopped smoking spontaneously in early pregnancy. However, a clear effect was seen in smoking abstinence at zero to five months postpartum (11 studies; average RR 1.59, 95% CI 1.26 to 2.01) and 12 to 17 months (two studies, average RR 2.20, 95% CI 1.23 to 3.96), with a borderline effect at six to 11 months (six studies; average RR 1.33, 95% CI 1.00 to 1.77). In other comparisons, the effect was unclear for most secondary outcomes, but sample sizes were small. Evidence suggests a borderline effect of health education compared with usual care (five studies; average RR 1.59, 95% CI 0.99 to 2.55), but the quality was downgraded to moderate as the effect was unclear when compared with less intensive interventions (four studies; average RR 1.20, 95% CI 0.85 to 1.70), alternative interventions (one study; RR 1.88, 95% CI 0.19 to 18.60), or when smoking cessation health education was provided as one component of a broader maternal health intervention. There was evidence feedback increased smoking cessation when compared with usual care and provided in conjunction with other strategies, such as counselling (average RR 4.39, 95% CI 1.89 to 10.21), but the confidence in the quality of evidence was downgraded to moderate as this was based on only two studies and the effect was uncertain when feedback was compared to less intensive interventions (three studies; average RR 1.29, 95% CI 0.75 to 2.20). High-quality evidence suggests incentive-based interventions are effective when compared with an alternative (non-contingent incentive) intervention (four studies; RR 2.36, 95% CI 1.36 to 4.09). However pooled effects were not calculable for comparisons with usual care or less intensive interventions (substantial heterogeneity, I2 = 93%). High-quality evidence suggests the effect is unclear in social support interventions provided by peers (six studies; average RR 1.42, 95% CI 0.98 to 2.07), in a single trial of support provided by partners, or when social support for smoking cessation was provided as part of a broader intervention to improve maternal health. The effect was unclear in single interventions of exercise compared to usual care (RR 1.20, 95% CI 0.72 to 2.01) and dissemination of counselling (RR 1.63, 95% CI 0.62 to 4.32). Importantly, high-quality evidence from pooled results demonstrated that women who received psychosocial interventions had a 17% reduction in infants born with low birthweight, a significantly higher mean birthweight (mean difference (MD) 55.60 g, 95% CI 29.82 to 81.38 g higher) and a 22% reduction in neonatal intensive care admissions. However the difference in preterm births and stillbirths was unclear. There did not appear to be adverse psychological effects from the interventions. The intensity of support women received in both the intervention and comparison groups has increased over time, with higher-intensity interventions more likely to have higher-intensity comparisons, potentially explaining why no clear differences were seen with increasing intervention intensity in meta-regression analyses. Among meta-regression analyses: studies classified as having 'unclear' implementation and unequal baseline characteristics were less effective than other studies. There was no clear difference between trials implemented by researchers (efficacy studies), and those implemented by routine pregnancy staff (effectiveness studies), however there was uncertainty in the effectiveness of counselling in four dissemination trials where the focus on the intervention was at an organisational level. The pooled effects were similar in interventions provided for women classified as having predominantly low socio-economic status, compared to other women. The effect was significant in interventions among women from ethnic minority groups; however not among indigenous women. There were similar effect sizes in trials with biochemically validated smoking abstinence and those with self-reported abstinence. It was unclear whether incorporating use of self-help manuals or telephone support increased the effectiveness of interventions. Authors' conclusions: Psychosocial interventions to support women to stop smoking in pregnancy can increase the proportion of women who stop smoking in late pregnancy and the proportion of infants born low birthweight. Counselling, feedback and incentives appear to be effective, however the characteristics and context of the interventions should be carefully considered. The effect of health education and social support is less clear. New trials have been published during the preparation of this review and will be included in the next update

Computational prediction of CRISPR-impaired non-coding regulatory regions

Genome-wide CRISPR screens are becoming more widespread and allow the simultaneous interrogation of thousands of genomic regions. Although recent progress has been made in the analysis of CRISPR screens, it is still an open problem how to interpret CRISPR mutations in non-coding regions of the genome. Most of the tools concentrate on the interpretation of mutations introduced in gene coding regions. We introduce a computational pipeline that uses epigenomic information about regulatory elements for the interpretation of CRISPR mutations in non-coding regions. We illustrate our approach on the analysis of a genome-wide CRISPR screen in hTERT-RPE-1 cells and reveal novel regulatory elements that mediate chemoresistance against doxorubicin in these cells. We infer links to established and to novel chemoresistance genes. Our approach is general and can be applied on any cell type and with different CRISPR enzymes