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&

The shape of the initial cluster mass function: what it tells us about the local star formation efficiency

We explore how the expulsion of gas from star-cluster forming cloud-cores due to supernova explosions affects the shape of the initial cluster mass function, that is, the mass function of star clusters when effects of gas expulsion are over. We demonstrate that if the radii of cluster-forming gas cores are roughly constant over the core mass range, as supported by observations, then more massive cores undergo slower gas expulsion. Therefore, for a given star formation efficiency, more massive cores retain a larger fraction of stars after gas expulsion. The initial cluster mass function may thus differ from the core mass function substantially, with the final shape depending on the star formation efficiency. A mass-independent star formation efficiency of about 20 per cent turns a power-law core mass function into a bell-shaped initial cluster mass function, while mass-independent efficiencies of order 40 per cent preserve the shape of the core mass function.Comment: accepted in Ap

Variations in Stellar Clustering with Environment: Dispersed Star Formation and the Origin of Faint Fuzzies

The observed increase in star formation efficiency with average cloud density, from several percent in whole giant molecular clouds to ~30 or more in cluster-forming cores, can be understood as the result of hierarchical cloud structure if there is a characteristic density as which individual stars become well defined. Also in this case, the efficiency of star formation increases with the dispersion of the density probability distribution function (pdf). Models with log-normal pdf's illustrate these effects. The difference between star formation in bound clusters and star formation in loose groupings is attributed to a difference in cloud pressure, with higher pressures forming more tightly bound clusters. This correlation accounts for the observed increase in clustering fraction with star formation rate and with the observation of Scaled OB Associations in low pressure environments. ``Faint fuzzie'' star clusters, which are bound but have low densities, can form in regions with high Mach numbers and low background tidal forces. The proposal by Burkert, Brodie & Larsen (2005) that faint fuzzies form at large radii in galactic collisional rings, satisfies these constraints.Comment: 14 pages, 2 figures, ApJ, 672, January 10th 200

Repositioning the Catalytic Triad Aspartic Acid of Haloalkane Dehalogenase: Effects on Stability, Kinetics, and Structure

Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an alkyl-enzyme intermediate. The covalent intermediate, which is formed by nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is activated by His289. The role of Asp260, which is the third member of the catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to asparagine resulted in a catalytically inactive D260N mutant, which demonstrates that the triad acid Asp260 is essential for dehalogenase activity. Furthermore, Asp260 has an important structural role, since the D260N enzyme accumulated mainly in inclusion bodies during expression, and neither substrate nor product could bind in the active-site cavity. Activity for brominated substrates was restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre-steady-state kinetic analysis of the D260N+N148E double mutant showed that the decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon-bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster and via a different pathway than in the wild-type enzyme. Molecular modeling of the mutant showed that Glu148 indeed could take over the interaction with His289 and that there was a change in charge distribution in the tunnel region that connects the active site with the solvent. On the basis of primary structure similarity between DhlA and other α/β-hydrolase fold dehalogenases, we propose that a conserved acidic residue at the equivalent position of Asn148 in DhlA is the third catalytic triad residue in the latter enzymes.

Three-dimensional Structure of L-2-Haloacid Dehalogenase from Xanthobacter autotrophicus GJ10 Complexed with the Substrate-analogue Formate

The L-2-haloacid dehalogenase from the 1,2-dichloroethane degrading bacterium Xanthobacter autotrophicus GJ10 catalyzes the hydrolytic dehalogenation of small L-2-haloalkanoic acids to yield the corresponding D-2-hydroxyalkanoic acids. Its crystal structure was solved by the method of multiple isomorphous replacement with incorporation of anomalous scattering information and solvent flattening, and was refined at 1.95-Å resolution to an R factor of 21.3%. The three-dimensional structure is similar to that of the homologous L-2-haloacid dehalogenase from Pseudomonas sp. YL (1), but the X. autotrophicus enzyme has an extra dimerization domain, an active site cavity that is completely shielded from the solvent, and a different orientation of several catalytically important amino acid residues. Moreover, under the conditions used, a formate ion is bound in the active site. The position of this substrate-analogue provides valuable information on the reaction mechanism and explains the limited substrate specificity of the Xanthobacter L-2-haloacid dehalogenase.

Effects of aging and dual tasking on step adjustments to perturbations in visually cued walking

Making step adjustments is an essential component of walking. However, the ability to make step adjustments may be compromised when the walker's attentional capacity is limited. This study compared the effects of aging and dual tasking on step adjustments in response to stepping-target perturbations during visually cued treadmill walking. Fifteen older adults (69.4 ± 5.0 years; mean ± SD) and fifteen young adults (25.4 ± 3.0 years) walked at a speed of 3 km/h on a treadmill. Both groups performed visually cued step adjustments in response to unpredictable shifts of projected stepping targets in forward (FW), backward (BW) or sideward (SW) directions, at different levels of task difficulty [which increased as the available response distance (ARD) decreased], and with and without dual tasking (auditory Stroop task). In both groups, step adjustments were smaller than required. For FW and BW shifts, older adults undershot more under dual-task conditions. For these shifts, ARD affected the age groups differentially. For SW shifts, larger errors were found for older adults, dual tasking and the most difficult ARD. Stroop task performance did not differ between groups in all conditions. Older adults have more difficulty than young adults to make corrective step adjustments while walking, especially under dual-tasking conditions. Furthermore, they seemed to prioritize the cognitive task over the step adjustment task, a strategy that may pose aging populations at a greater fall risk. For comparable task difficulty, the older adults performed considerably worse than the young adults, indicating a decreased ability to adjust steps under time pressure

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

Dynamic Neuromuscular Control of the Lower Limbs in Response to Unexpected Single-Planar versus Multi-Planar Support Perturbations in Young, Active Adults.

PURPOSE: An anterior cruciate ligament (ACL) injury involves a multi-planar injury mechanism. Nevertheless, unexpected multi-planar perturbations have not been used to screen athletes in the context of ACL injury prevention yet could reveal those more at risk. The objective of this study was to compare neuromuscular responses to multi-planar (MPP) and single-planar perturbations (SPP) during a stepping-down task. These results might serve as a basis for future implementation of external perturbations in ACL injury screening programs. METHODS: Thirteen young adults performed a single leg stepping-down task in eight conditions (four MPP and four SPP with a specified amplitude and velocity). The amplitudes of vastus lateralis (VL), vastus medialis (VM), hamstrings lateralis (HL), hamstrings medialis (HM) EMG activity, medio-lateral and anterior-posterior centre of mass (COM) displacements, the peak knee flexion and abduction angles were compared between conditions using an one-way ANOVA. Number of stepping responses were monitored during all conditions. RESULTS: Significantly greater muscle activity levels were found in response to the more challenging MPP and SPP compared to the less challenging conditions (p < 0.05). No differences in neuromuscular activity were found between the MPP conditions and their equivalents in the SPP. Eighteen stepping responses were monitored in the SPP versus nine in the MPP indicating that the overall neuromuscular control was even more challenged during the SPP which was supported by greater COM displacements in the SPP. CONCLUSION: The more intense MPP and SPP evoked different neuromuscular responses resulting in greater muscle activity levels compared to small perturbations. Based on the results of COM displacements and based on the amount of stepping responses, dynamic neuromuscular control of the knee joint appeared less challenged during the MPP. Therefore, future work should investigate extensively if other neuromuscular differences (i.e. co-activation patterns and kinetics) exist between MPP and SPP. In addition, future work should examine the influence on the neuromuscular control of the magnitude of the perturbations and the magnitude of stepping height and stepping distance

Computational Controversy

Climate change, vaccination, abortion, Trump: Many topics are surrounded by fierce controversies. The nature of such heated debates and their elements have been studied extensively in the social science literature. More recently, various computational approaches to controversy analysis have appeared, using new data sources such as Wikipedia, which help us now better understand these phenomena. However, compared to what social sciences have discovered about such debates, the existing computational approaches mostly focus on just a few of the many important aspects around the concept of controversies. In order to link the two strands, we provide and evaluate here a controversy model that is both, rooted in the findings of the social science literature and at the same time strongly linked to computational methods. We show how this model can lead to computational controversy analytics that have full coverage over all the crucial aspects that make up a controversy.Comment: In Proceedings of the 9th International Conference on Social Informatics (SocInfo) 201

Development of CliniPup, a Serious Game Aimed at Reducing Perioperative Anxiety and Pain in Children: Mixed Methods Study

Background: Increasing numbers of children undergo ambulatory surgery each year and a significant proportion experiences substantial preoperative anxiety and postoperative pain. The management of perioperative anxiety and pain remains challenging in children and is inadequate, which negatively impacts physical, psychosocial, and economic outcomes. Existing non-pharmacological interventions are costly, time consuming, vary in availability, and lack benefits. Therefore, there is a need for an evidence-based, accessible, non-pharmacological intervention as an adjunct to existing pharmacological alternatives to reduce perioperative anxiety and pain in children undergoing ambulatory surgery. Technology-enabled interventions have been proposed as a method to address the unmet need in this setting. In particular, serious games for health (SGHs) hold unique potential to change health beliefs and behaviors in children. Objective: The objective of this research was to describe the rationale, scientific evidence, design aspects, and features of CliniPup, an SGH aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. Methods: The SERES framework for SGH development was used to create the SGH, CliniPup. In particular, a mixed-methods approach was applied that consisted of a structured literature review supplemented with ethnographic research, such as expert interviews and a time-motion exercise. The resulting scientific evidence base was leveraged to ensure that the resulting SGH was relevant, realistic, and theory-driven. A participatory design approach was applied wherein clinical experts qualitatively reviewed several versions of the SGH and an iterative creative process was used to integrate the applicable feedback. Results: CliniPup, an SGH, was developed to incorporate (1) scientific evidence base from a structured literature review, (2) realistic content collected during ethnographic research such as expert interviews, (3) explicit pedagogical objectives from scientific literature, and (4) game mechanics and user interface design that address key aspects of the evidence. Conclusions: This report details the systematic development of CliniPup, an SGH aimed at reducing perioperative anxiety and pain in children undergoing ambulatory surgery. Clinical experts validated CliniPup’s underlying scientific evidence base and design foundations, suggesting that it was well designed for preliminary evaluation in the target population. An evaluation plan is proposed and briefly described