Radial velocity measurements of B stars in the Scorpius-Centaurus association

We derive single-epoch radial velocities for a sample of 56 B-type stars members of the subgroups Upper Scorpius, Upper Centaurus Lupus and Lower Centaurus Crux of the nearby Sco-Cen OB association. The radial velocity measurements were obtained by means of high-resolution echelle spectra via analysis of individual lines. The internal accuracy obtained in the measurements is estimated to be typically 2-3 km/s, but depends on the projected rotational velocity of the target. Radial velocity measurements taken for 2-3 epochs for the targets HD120307, HD142990 and HD139365 are variable and confirm that they are spectroscopic binaries, as previously identified in the literature. Spectral lines from two stellar components are resolved in the observed spectra of target stars HD133242, HD133955 and HD143018, identifying them as spectroscopic binaries.Comment: accepted for publication in A&

PIKES Analysis Reveals Response to Degraders and Key Regulatory Mechanisms of the CRL4 Network

Co-opting Cullin4 RING ubiquitin ligases (CRL4s) to inducibly degrade pathogenic proteins is emerging as a promising therapeutic strategy. Despite intense efforts to rationally design degrader molecules that co-opt CRL4s, much about the organization and regulation of these ligases remains elusive. Here, we establish protein interaction kinetics and estimation of stoichiometries (PIKES) analysis, a systematic proteomic profiling platform that integrates cellular engineering, affinity purification, chemical stabilization, and quantitative mass spectrometry to investigate the dynamics of interchangeable multiprotein complexes. Using PIKES, we show that ligase assemblies of Cullin4 with individual substrate receptors differ in abundance by up to 200-fold and that Cand1/2 act as substrate receptor exchange factors. Furthermore, degrader molecules can induce the assembly of their cognate CRL4, and higher expression of the associated substrate receptor enhances degrader potency. Beyond the CRL4 network, we show how PIKES can reveal systems level biochemistry for cellular protein networks important to drug development

The Efficiency of Globular Cluster Formation

(Abridged): The total populations of globular cluster systems (GCSs) are discussed in terms of their connection to the efficiency of globular cluster formation---the mass fraction of star-forming gas that was able to form bound stellar clusters rather than isolated stars or unbound associations---in galaxy halos. Observed variations in GCS specific frequencies (S_N=N_gc/L_gal), both as a function of galactocentric radius in individual systems and globally between entire galaxies, are reviewed in this light. It is argued that trends in S_N do not reflect any real variation in the underlying efficiency of cluster formation; rather, they result from ignoring the hot gas in many large ellipticals. This claim is checked and confirmed in each of M87, M49, and NGC 1399, for which existing data are combined to show that the volume density profile of globular clusters, rho_cl, is directly proportional to the sum of (rho_gas+rho_stars) at large radii. The constant of proportionality is the same in each case: epsilon=0.0026 +/- 0.0005 in the mean. This is identified with the globular cluster formation efficiency. The implication that epsilon might have had a universal value is supported by data on the GCSs of 97 early-type galaxies, on the GCS of the Milky Way, and on the ongoing formation of open clusters. These results have specific implications for some issues in GCS and galaxy formation, and they should serve as a strong constraint on more general theories of star and cluster formation.Comment: 36 pages with 11 figures; accepted for publication in The Astronomical Journa

Evaluating the impact and cost-effectiveness of chlamydia management strategies in Hong Kong:A modeling study

OBJECTIVES: To illustrate the epidemiologic and cost-effectiveness impact of shifting the focus from population-based screening toward a targeted management approach for genital chlamydia infection. DESIGN: Modeling study, implementing an individual-based, stochastic, dynamic network model. SETTING: Hong Kong. POPULATION: A hypothetical sample network of 10,000 people with a partnership distribution based on Hong Kong's sexually active population of reproductive age (age 18–49 years). INTERVENTIONS: In this study, we present several scenarios with different implementations of universal vs. targeted screening (based on partner numbers). We also explored the impact of (1) screening only, (2) screening plus expedited partner therapy, and (3) screening plus partner testing. PRIMARY OUTCOME MEASURES: Change of chlamydia prevalence before and after implementing the different strategies. The cost-effectiveness analysis reports total direct cost from a health provider perspective, the QALYs gained, and incremental cost-effectiveness ratios (ICER). RESULTS: In comparing the effects of universal screening only and targeted screening of the high-risk population, the mean prevalence during the 10th year of intervention was 2.75 ± 0.30% and 2.35 ± 0.21%, respectively (compared with 3.24 ± 0.30% and 3.35 ± 0.21% before the interventions, respectively). The addition of contact tracing to the latter targeted screening scenario reduces the mean prevalence during the 10th year of intervention to 1.48 ± 0.13% (compared with 3.31 ± 0.33% at baseline) in the best-case of testing before treatment and maximal contact-tracing effectiveness (40%). Overall, the most effective scenarios were those for which interventions focused on the high-risk population defined by the number of partners, with contact tracing included. The ICER for targeted screening with contact tracing at 20% and 40% efficiency was $4,634 and$7,219 per QALY gained, respectively (10-year time horizon). Expedited partner therapy did not significantly impact overall chlamydia prevalence and caused overtreatment. CONCLUSIONS: Our study suggests that targeted screening with strengthened contact tracing efforts is the most cost-effective strategy to reduce the prevalence of chlamydia in Hong Kong

Genetic predisposition score predicts the increases of knee strength and muscle mass after one-year exercise in healthy elderly

This study aims to identify a genetic predisposition score from a set of candidate gene variants that predicts the response to a one-year exercise intervention. 200 participants (aged 60–83 years) were randomly assigned to a fitness (FIT), whole-body vibration (WBV) and control group. Participants in the exercise (FIT and WBV) groups performed a one-year intervention program. Whole-body skeletal muscle mass (SMM) and isometric knee extension strength (PTIM60) were measured before and after the intervention. A set of 170 muscle-related single nucleotide polymorphisms (SNPs) were genotyped. Stepwise regression analysis was applied to select significantly contributing SNPs for baseline and relative change parameters. A data-driven genetic predisposition score (GPS) was calculated by adding up predisposing alleles for each of the phenotypes. GPS was calculated based on 4 to 8 SNPs which were significantly related to the corresponding phenotypes. These SNPs belong to genes that are involved in myoblast differentiation, muscle and bone growth, myofiber contraction, cytokines and DNA methylation. GPS was related to baseline PTIM60and relative changes of SMM and PTIM60in the exercise groups, explaining the variance of the corresponding parameter by 3.2%, 14% and 27%, respectively. Adding one increasing allele in the GPS increased baseline PTIM60by 4.73 Nm, and exercise-induced relative changes of SMM and PTIM60by 1.78% and 3.86% respectively. The identified genetic predisposition scores were positively related to baseline knee extension strength and muscle adaptations to exercise in healthy elderly. These findings provide supportive genetic explanations for high and low responders in exercise-induced muscle adaptations

Reasoning deficits among illicit drug users are associated with aspects of cannabis use

Background. Deficits in deductive reasoning have been observed among ecstasy/polydrug users. The present study seeks to investigate dose-related effects of specific drugs and whether these vary with the cognitive demands of the task. Methods. One hundred and five participants (mean age 21.33, S.D. 3.14; 77 females, 28 males) attempted to generate solutions for eight one-model syllogisms and one syllogism for which there was no valid conclusion (NVC). All of the one model syllogisms generated at least one valid conclusion and six generated two valid conclusions. In these six cases one of the conclusions was classified as common and the other as non-common. Results. The number of valid common inferences was negatively associated with aspects of short term cannabis use and with measures of IQ. The outcomes observed were more than simple post intoxication effects since cannabis use in the 10 days immediately before testing was unrelated to reasoning performance. Following adjustment for multiple comparisons, the number of non-common valid inferences was not significantly associated with any of the drug use measures. Conclusions. Recent cannabis use appears to impair the processes associated with generating valid common inferences while not affecting the production of non-common inferences. It is possible, therefore, that the two types of inference may recruit different executive resources which may differ in their susceptibility to cannabis-related effects

Is the metabolic cost of walking higher in people with diabetes?

People with diabetes walk slower and display biomechanical gait alterations compared with controls, but it remains unknown whether the metabolic cost of walking (CoW) is elevated. The aim of this study was to investigate the CoW and the lower limb concentric joint work as a major determinant of the CoW, in patients with diabetes and diabetic peripheral neuropathy (DPN). Thirty-one nondiabetic controls (Ctrl), 22 diabetic patients without peripheral neuropathy (DM), and 14 patients with moderate/severe DPN underwent gait analysis using a motion analysis system and force plates and treadmill walking using a gas analyzer to measure oxygen uptake. The CoW was significantly higher particularly in the DPN group compared with controls and also in the DM group (at selected speeds only) compared with controls, across a range of matched walking speeds. Despite the higher CoW in patients with diabetes, concentric lower limb joint work was significantly lower in DM and DPN groups compared with controls. The higher CoW is likely due to energetic inefficiencies associated with diabetes and DPN reflecting physiological and biomechanical characteristics. The lower concentric joint work in patients with diabetes might be a consequence of kinematic gait alterations and may represent a natural strategy aimed at minimizing the CoW