Conflicts of interest in translational research

Translational research requires a team approach to scientific inquiry and product development. Translational research teams consist of basic and clinical scientists who can be members of both academic and industrial communities. The conception, pre-clinical testing, and clinical evaluation of a diagnostic or therapeutic approach demands an intense interaction between investigators with diverse backgrounds. As the barriers between industry and academia are removed, issues of potential conflict of interest become more complex. Translational researchers must become aware of the situations which constitute conflict of interest and understand how such conflicts can impact their research programs. Finally, the translational research community must participate in the dialogue ongoing in the public and private sectors and help shape the rules that will govern conflicts that arise during the evolution of their research programs

Transcranial magnetic stimulation to the occipital place area biases gaze during scene viewing

We can understand viewed scenes and extract task-relevant information within a few hundred milliseconds. This process is generally supported by three cortical regions that show selectivity for scene images: parahippocampal place area (PPA), medial place area (MPA) and occipital place area (OPA). Prior studies have focused on the visual information each region is responsive to, usually within the context of recognition or navigation. Here, we move beyond these tasks to investigate gaze allocation during scene viewing. Eye movements rely on a scene’s visual representation to direct saccades, and thus foveal vision. In particular, we focus on the contribution of OPA, which is i) located in occipito-parietal cortex, likely feeding information into parts of the dorsal pathway critical for eye movements, and ii) contains strong retinotopic representations of the contralateral visual field. Participants viewed scene images for 1034 ms while their eye movements were recorded. On half of the trials, a 500 ms train of five transcranial magnetic stimulation (TMS) pulses was applied to the participant’s cortex, starting at scene onset. TMS was applied to the right hemisphere over either OPA or the occipital face area (OFA), which also exhibits a contralateral visual field bias but shows selectivity for face stimuli. Participants generally made an overall left-to-right, top-to-bottom pattern of eye movements across all conditions. When TMS was applied to OPA, there was an increased saccade latency for eye movements toward the contralateral relative to the ipsilateral visual field after the final TMS pulse (400ms). Additionally, TMS to the OPA biased fixation positions away from the contralateral side of the scene compared to the control condition, while the OFA group showed no such effect. There was no effect on horizontal saccade amplitudes. These combined results suggest that OPA might serve to represent local scene information that can then be utilized by visuomotor control networks to guide gaze allocation in natural scenes

Following microscopic motion in a two dimensional glass-forming binary fluid

The dynamics of a binary mixture of large and small discs are studied at temperatures approaching the glass transition using an analysis based on the topology of the Voronoi polygon surrounding each atom. At higher temperatures we find that dynamics is dominated by fluid-like motion that involves particles entering and exiting the nearest-neighbour shells of nearby particles. As the temperature is lowered, the rate of topological moves decreases and motion becomes localised to regions of mixed pentagons and heptagons. In addition we find that in the low temperature state particles may translate significant distances without undergoing changes in their nearest neig hbour shell. These results have implications for dynamical heterogeneities in glass forming liquids.Comment: 12 pages, 7 figure

Categorisation and Detection of Dark Matter Candidates from String/M-theory Hidden Sectors

We study well-motivated dark matter candidates arising from weakly-coupled hidden sectors in compactified string/$M$-theory. Imposing generic top-down constraints greatly restricts allowed candidates. By considering the possible mechanisms for achieving the correct dark matter relic density, we compile categories of viable dark matter candidates and annihilation mediators. We consider the case where supersymmetry breaking occurs via moduli stabilisation and is gravitationally mediated to the visible and other hidden sectors, without assuming sequestering of the sector in which supersymmetry is broken. We find that in this case, weakly-coupled hidden sectors only allow for fermionic dark matter. Additionally, most of the mechanisms for obtaining the full relic density only allow for a gauge boson mediator, such as a dark $Z'$. Given these considerations, we study the potential for discovering or constraining the allowed parameter space given current and future direct detection experiments, and direct production at the LHC. We also present a model of a hidden sector which would contain a satisfactory dark matter candidate.Comment: 29 pages, 10 figure

Lipid-free Antigen B subunits from echinococcus granulosus: oligomerization, ligand binding, and membrane interaction properties

Background: The hydatid disease parasite Echinococcus granulosus has a restricted lipid metabolism, and needs to harvest essential lipids from the host. Antigen B (EgAgB), an abundant lipoprotein of the larval stage (hydatid cyst), is thought to be important in lipid storage and transport. It contains a wide variety of lipid classes, from highly hydrophobic compounds to phospholipids. Its protein component belongs to the cestode-specific Hydrophobic Ligand Binding Protein family, which includes five 8-kDa isoforms encoded by a multigene family (EgAgB1-EgAgB5). How lipid and protein components are assembled into EgAgB particles remains unknown. EgAgB apolipoproteins self-associate into large oligomers, but the functional contribution of lipids to oligomerization is uncertain. Furthermore, binding of fatty acids to some EgAgB subunits has been reported, but their ability to bind other lipids and transfer them to acceptor membranes has not been studied.<p></p> Methodology/Principal Findings: Lipid-free EgAgB subunits obtained by reverse-phase HPLC were used to analyse their oligomerization, ligand binding and membrane interaction properties. Size exclusion chromatography and cross-linking experiments showed that EgAgB8/2 and EgAgB8/3 can self-associate, suggesting that lipids are not required for oligomerization. Furthermore, using fluorescent probes, both subunits were found to bind fatty acids, but not cholesterol analogues. Analysis of fatty acid transfer to phospholipid vesicles demonstrated that EgAgB8/2 and EgAgB8/3 are potentially capable of transferring fatty acids to membranes, and that the efficiency of transfer is dependent on the surface charge of the vesicles.<p></p> Conclusions/Significance: We show that EgAgB apolipoproteins can oligomerize in the absence of lipids, and can bind and transfer fatty acids to phospholipid membranes. Since imported fatty acids are essential for Echinococcus granulosus, these findings provide a mechanism whereby EgAgB could engage in lipid acquisition and/or transport between parasite tissues. These results may therefore indicate vulnerabilities open to targeting by new types of drugs for hydatidosis therapy.<p></p&gt

Very High Mach Number Electrostatic Shocks in Collisionless Plasmas

The kinetic theory of collisionless electrostatic shocks resulting from the collision of plasma slabs with different temperatures and densities is presented. The theoretical results are confirmed by self-consistent particle-in-cell simulations, revealing the formation and stable propagation of electrostatic shocks with very high Mach numbers ($M \gg 10$), well above the predictions of the classical theories for electrostatic shocks.Comment: 6 pages, submitted to Phys. Rev. Let

Quantum and classical surface acoustic wave induced magnetoresistance oscillations in a 2D electron gas

We study theoretically the geometrical and temporal commensurability oscillations induced in the resistivity of 2D electrons in a perpendicular magnetic field by surface acoustic waves (SAWs). We show that there is a positive anisotropic dynamical classical contribution and an isotropic non-equilibrium quantum contribution to the resistivity. We describe how the commensurability oscillations modulate the resonances in the SAW-induced resistivity at multiples of the cyclotron frequency. We study the effects of both short-range and long-range disorder on the resistivity corrections for both the classical and quantum non-equilibrium cases. We predict that the quantum correction will give rise to zero-resistance states with associated geometrical commensurability oscillations at large SAW amplitude for sufficiently large inelastic scattering times. These zero resistance states are qualitatively similar to those observed under microwave illumination, and their nature depends crucially on whether the disorder is short- or long-range. Finally, we discuss the implications of our results for current and future experiments on two dimensional electron gases.Comment: 16 pages, 8 figure