A Numerical Study of Brown Dwarf Formation via Encounters of Protostellar Disks

The formation of brown dwarfs (BDs) due to the fragmentation of proto-stellar disks undergoing pairwise encounters was investigated. High resolution allowed the use of realistic initial disk models where both the vertical structure and the local Jeans mass were resolved. The results show that objects with masses ranging from giant planets to low mass stars can form during such encounters from initially stable disks. The parameter space of initial spin-orbit orientations and the azimuthal angles for each disk was explored. An upper limit on the initial Toomre Q value of ~2 was found for fragmentation to occur. Depending on the initial configuration, shocks, tidal-tail structures and mass inflows were responsible for the condensation of disk gas. Retrograde disks were generally more likely to fragment. When the interaction timescale was significantly shorter than the disks' dynamical timescales, the proto-stellar disks tended to be truncated without forming objects. The newly-formed objects had masses ranging from 0.9 to 127 Jupiter masses, with the majority in the BD regime. They often resided in star-BD multiples and in some cases also formed hierarchical orbiting systems. Most of them had large angular momenta and highly flattened, disk-like shapes. The objects had radii ranging from 0.1 to 10 AU. The disk gas was assumed to be locally isothermal, appropriate for the short cooling times in extended proto-stellar disks, but not for condensed objects. An additional case with explicit cooling that reduced to zero for optically thick gas was simulated to test the extremes of cooling effectiveness and it was still possible to form objects in this case. Detailed radiative transfer is expected to lengthen the internal evolution timescale for these objects, but not to alter our basic results.Comment: 18 pages, 12 figures and 2 tables. Accepted for publication in MNRA

Fitting the Elementary Rate Constants of the P-gp Transporter Network in the hMDR1-MDCK Confluent Cell Monolayer Using a Particle Swarm Algorithm

P-glycoprotein, a human multidrug resistance transporter, has been extensively studied due to its importance to human health and disease. In order to understand transport kinetics via P-gp, confluent cell monolayers overexpressing P-gp are widely used. The purpose of this study is to obtain the mass action elementary rate constants for P-gp's transport and to functionally characterize members of P-gp's network, i.e., other transporters that transport P-gp substrates in hMDR1-MDCKII confluent cell monolayers and are essential to the net substrate flux. Transport of a range of concentrations of amprenavir, loperamide, quinidine and digoxin across the confluent monolayer of cells was measured in both directions, apical to basolateral and basolateral to apical. We developed a global optimization algorithm using the Particle Swarm method that can simultaneously fit all datasets to yield accurate and exhaustive fits of these elementary rate constants. The statistical sensitivity of the fitted values was determined by using 24 identical replicate fits, yielding simple averages and standard deviations for all of the kinetic parameters, including the efflux active P-gp surface density. Digoxin required additional basolateral and apical transporters, while loperamide required just a basolateral tranporter. The data were better fit by assuming bidirectional transporters, rather than active importers, suggesting that they are not MRP or active OATP transporters. The P-gp efflux rate constants for quinidine and digoxin were about 3-fold smaller than reported ATP hydrolysis rate constants from P-gp proteoliposomes. This suggests a roughly 3∶1 stoichiometry between ATP hydrolysis and P-gp transport for these two drugs. The fitted values of the elementary rate constants for these P-gp substrates support the hypotheses that the selective pressures on P-gp are to maintain a broad substrate range and to keep xenobiotics out of the cytosol, but not out of the apical membrane

Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model

Controlled Release from Cleavable Polymerized Liposomes upon Redox and pH Stimulation

A gallate derivative with three propargyl groups was coupled to palmitoyl oleoyl phosphoethanolamine (POPE). The resulting anionic lipid was formulated with common lipids such as palmitoyl oleoyl phosphatidyl choline (POPC) to form large unilamellar vesicles (LUVs). Polymerization of the LUVs was accomplished by the Cu(I)-catalyzed click reaction between the propargyl groups and the azide groups in the cross-linker. When the cross-linker contained a disulfide or ketal group, the resulting polymerized liposomes depolymerized and released entrapped contents upon the addition of a reducing thiol or under weakly acidic conditions. The click reaction allowed simultaneous multivalent surface functionalization during cross-linking, making these cleavable polymerized liposomes (CPLs) potentially very useful in the delivery and controlled release of pharmaceutical agents

Repetitive mild traumatic brain injury alters central and peripheral clock gene expression in the adolescent rat

Mild traumatic brain injury (mTBI) or concussion is a common injury worldwide leading to substantial medical costs and a high burden on society. In adolescents, falls and sports related trauma are often the causes of mTBI. Importantly, critical brain growth and development occurs during this sensitive period making the prospect of a brain injury a worrying phenomenon. Upwards of 70% of patients report circadian disruption following these injuries and this has been shown to impede recovery. Therefore, we sought to determine if core circadian clock gene expression was disrupted in rat model of repetitive mTBI (RmTBI). Male and female adolescent rats (n = 129) received sham or RmTBI. The animals were then euthanized at different times throughout the day and night. Tissue from the hypothalamus, cerebellum, hippocampus, liver, and small intestine were evaluated for the expression of per1, per2, cry1, clock, bmal1 and rev-erb-α. We found most clock genes varied across the day/night indicating circadian expression patterns. In the hypothalamus we found RmTBI altered the expression of cry1 and bmal1 in addition to sex differences in per2, cry1, clock, bmal1 and rev-erb- α. In the cerebellum, per1, per2, cry1, clock, bmal1 and rev-erb-α rhythms were all knocked out by RmTBI in addition to sex differences in cry1, clock and bmal1 expression. We also detected a significant decrease in overall expression of all clock genes in males in the middle of the night. In the hippocampus we found that RmTBI changed the rhythm of rev-erb-α expression in addition to sex differences in bmal1 expression. In the liver we detected strong rhythms in all genes examined, however only per2 expression was knocked out by RmTBI, in addition we also detected sex differences in per2 and cry1. We also detected an overall decrease in female clock gene expression in the early night. In the small intestine, RmTBI altered cry1 expression and there were sex differences in rev-erb-α. These results indicate that RmTBI alters core circadian clock gene expression in the central and peripheral nervous system in a time, tissue and sex dependent manner. This may be disrupting important phase relationships between the brain and peripheral nervous system and contributing to post-injury symptomology and also highlights the importance for time and sex dependent assessment of injury outcomes

Comparison of a computer vision system against three-dimensional motion capture for tracking football movements in a stadium environment

Three-dimensional motion capture systems such as Vicon have been used to validate commercial electronic performance and tracking systems. However, three-dimensional motion capture cannot be used for large capture areas such as a full football pitch due to the need for many fragile cameras to be placed around the capture volume and a lack of suitable depth of field of those cameras. There is a need, therefore, for a hybrid testing solution for commercial electronic performance and tracking systems using highly precise three-dimensional motion capture in a small test area and a computer vision system in other areas to test for full-pitch coverage by the commercial systems. This study aimed to establish the validity of VisionKit computer vision system against three-dimensional motion capture in a stadium environment. Ten participants undertook a series of football-specific movement tasks, including a circuit, small-sided games and a 20 m sprint. There was strong agreement between VisionKit and three-dimensional motion capture across each activity undertaken. The root mean square difference for speed was 0.04 m·s−1 and for position was 0.18 m. VisionKit had strong agreement with the criterion three-dimensional motion capture system three-dimensional motion capture for football-related movements tested in stadium environments. VisionKit can thus be used to establish the concurrent validity of other electronic performance and tracking systems in circumstances where three-dimensional motion capture cannot be used