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Potentially repurposable drugs for schizophrenia identified from its interactome
No full textWe previously presented the protein-protein interaction network of schizophrenia associated genes, and from it, the drug-protein interactome which showed the drugs that target any of the proteins in the interactome. Here, we studied these drugs further to identify whether any of them may potentially be repurposable for schizophrenia. In schizophrenia, gene expression has been described as a measurable aspect of the disease reflecting the action of risk genes. We studied each of the drugs from the interactome using the BaseSpace Correlation Engine, and shortlisted those that had a negative correlation with differential gene expression of schizophrenia. This analysis resulted in 12 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for schizophrenia (disorder versus normal). Some of these drugs were already being tested for their clinical activity in schizophrenia and other neuropsychiatric disorders. Several proteins in the protein interactome of the targets of several of these drugs were associated with various neuropsychiatric disorders. The network of genes with opposite drug-induced versus schizophrenia-associated expression profiles were significantly enriched in pathways relevant to schizophrenia etiology and GWAS genes associated with traits or diseases that had a pathophysiological overlap with schizophrenia. Drugs that targeted the same genes as the shortlisted drugs, have also demonstrated clinical activity in schizophrenia and other related disorders. This integrated computational analysis will help translate insights from the schizophrenia drug-protein interactome to clinical research - an important step, especially in the field of psychiatric drug development which faces a high failure rate
Generation of strain-induced pseudo-magnetic field in a doped type-II Weyl semimetal
No full textIn Weyl semimetals, there is an intriguing possibility of realizing a pseudo-magnetic field in the presence of small strain due to certain special cases of static deformations. This pseudo-magnetic field can be large enough to form quantized Landau levels and thus become observable in Weyl semimetals. In this paper we experimentally show the emergence of a pseudo-magnetic field (similar to 3 T) by scanning tunneling spectroscopy on the doped Weyl semimetal Re-MoTe2, where distinct Landau-level oscillations in the tunneling conductance are clearly resolved. The crystal lattice is intrinsically strained where large area scanning tunneling microscopy imaging of the surface reveals differently strained domains where atomic scale deformations exist forming topographic ripples with varying periodicity in the real space. The effect of the pseudo-magnetic field is clearly resolved in areas under maximum strain
A conformal gauge theory of solids: Insights into a class of electromechanical and magnetomechanical phenomena
No full textA gauge theory of solids with conformal symmetry is formulated to model various electromechanical and magnetomechanical coupling phenomena. If the pulled back metric of the current configuration (the right Cauchy-Green tensor) is scaled with a constant, the volumetric part of the Lagrange density changes while the isochoric part remains invariant. However, upon a position dependent scaling, the isochoric part also loses invariance. In order to restore the invariance of the isochoric part, a 1-form compensating field is introduced and the notion of a gauge covariant derivative is utilized to minimally replace the Lagrangian. In view of obvious similarities with the Weyl geometry, the Weyl condition is imposed through the Lagrangian and a minimal coupling is employed so the 1-form could evolve. On deriving the Euler-Lagrange equations based on Hamilton's principle, we observe a close similarity with the governing equations for flexoelectricity under isochoric deformation if the exact part of 1-form is interpreted as the electric field and the anti exact part as the polarization vector. Next, we model piezoelectricity and electrostriction phenomena by contracting the Weyl condition in various ways. Applying the Hodge decomposition theorem on the 1-form which leads to the curl of a pseudo-vector field and a vector field, we also model magnetomechanical phenomena. Identifying the pseudo-vector field with magnetic potential and the vector part with magnetization, flexomagnetism, piezomagnetism and magnetostriction phenomena under isochoric deformation are also modeled. Finally, we consider an analytical solution of the equations for piezoelectricity and propose a flexoelectric plate model to illustrate on the insightful information that the present approach potentially provides
Thermodynamic properties of PrRhO3 and phase diagrams of the system Pr-Rh-O
No full textA solid-state electrochemical cell with yttria-stabilized zirconia (YSZ) as the electrolyte is used to measure accurately thermodynamic properties of PrRhO3 in the range of temperature from 875 to 1325 K. The standard Gibbs energy of formation of PrRhO3 with orthorhombically distorted perovskite structure from its binary oxides beta-Rh2O3 and hexagonal Pr2O3 is given by, Delta Gf mml:mfenced close=) open=(oxomml:mfenced close=) open=(separators=+/- 50mml:mfenced close='')'' open=''(separators=Jmol-1=-67813+5.299mml:mfenced close=) open=''(Separators=T/K. Invoking the Newmann-Kopp rule, the standard enthalpy of formation from elements and standard entropy of PrRhO3 at 298.15 K are evaluated: Delta Hfo=-1175.53mml:mfenced close=)open=(separators=+/- 3.26kJmol-1 and So=108.89mml:mfenced close=)open=''('' separators=+/- 0.1.3J mol-1K-1. Phase relations in the system Pr-Rh-O at 1200 K are computed from thermodynamic data. Calorimetric data on enthalpy of formation of two intermetallic compounds are combined with the semi-empirical model of Miedema and phase diagram to estimate Gibbs energy of formation for the intermetallics and liquid alloys. An isothermal section of ternary phase diagram, an oxygen potential-composition diagram in 2-D and a 3-D chemical potential diagram for the system Pr-Rh-O at 1200 K are presented. In addition, temperature-composition diagrams at different oxygen pressures are developed. The diagrams provide a road map for design and optimization of processing routes for catalysts based on Rh
Multi-Length Scale Characterization of Microstructure Evolution and Its Consequence on Mechanical Properties in Dissimilar Friction Stir Welding of Titanium to Aluminum
No full textIn dissimilar friction stir welding (FSW), the weld nugget is composed of two elements, which are mechanically mixed. This microstructure helps enhance the mechanical properties when they are homogeneously mixed, and the particles are sub-micron in size. Therefore, it is important to understand the mechanism of the particle formation and their distribution for engineering the mechanical properties of the weld. In the present investigation, dissimilar FSW between commercial purity Al and Ti has been carried out. The weld nugget consisted of distributed Ti particles in an Al matrix. The distribution of the Ti particles in the weld nugget was characterized using X-ray micro-computed tomography (XCT). Microstructural evolution in Ti and Al was examined using a scanning electron microscope (SEM) equipped with an energy dispersive spectrometer (EDS), X-ray diffraction and electron back-scattered diffraction (EBSD). Hardness and tensile tests were carried out to determine the integrity of the welds. The XCT result shows that the weld nugget contains Ti particles of variable size. The finer particles of Ti are distributed homogeneously in the weld nugget, unlike large particles. The deformation mechanisms and microstructural evolution of the Ti interface and Al matrix are investigated using EBSD. It is observed that the microstructure of both Ti and Al is substantially refined. However, for a given grain in Al, the boundary is of mixed character, namely low- and high-angle boundaries. Hardness data of the weld indicate large variation within the nugget region. The tensile test sample revealed that the failure of the sample occurs on the Al side of the weld. The fractograph indicates ductile and brittle modes of fracture with a bimodal distribution of dimples at the surface. Lack of twining and fine grains (40 to 5 mu m) at the Ti interface indicates high-temperature deformation. Deformation of Ti at low temperature and high strain rate is caused by adiabatic shear banding (ASB). In these shear bands, a high level of grain refinement is observed and is a path for easy crack propagation. It is proposed that the ASB-controlled deformation of Ti leads to a recrystallized microstructure at the interface and fragmentation of Ti. These Ti particles undergo further fragmentation to form smaller particles. On the other hand, microstructural evolution in Al is gradual because of the high stacking fault energy, which leads to continuous dynamic recrystallization (CDRX) through the dynamic recovery (DRV) mechanism. The mechanical properties of the weld depend on the characteristics of particles in the Al matrix. Proper control of the fragmentation and distribution of Ti particles and interface property can lead to superior mechanical properties of the weld
Reentrant Efficiency of Phototaxis in Chlamydomonas reinhardtii Cells
No full textPhototaxis is one of the most fundamental stimulus-response behaviors in biology wherein motile microorganisms sense light gradients to swim toward the light source. Apart from single-cell survival and growth, it plays a major role at the global scale of aquatic ecosystems and bioreactors. We study phototaxis of single-celled algae Chlamydomonas reinhardtii as a function of cell number density and light stimulus using high spatiotemporal video microscopy. Surprisingly, the phototactic efficiency has a minimum at a well-defined number density, for a given light gradient, above which the phototaxis behavior of a collection of cells can even exceed the performance obtainable from single isolated cells. We show that the origin of enhancement of performance above the critical concentration lies in the slowing down of the cells, which enables them to sense light more effectively. We also show that this steady-state phenomenology is well captured by modeling the phototactic response as a density-dependent torque acting on an active Brownian particle
Chaos bound in Bershadsky-Polyakov theory
No full textWe consider two dimensional conformal field theory (CFT) with large central charge c in an excited state obtained by the insertion of an operator Phi with large dimension Delta(Phi) similar to O (c) at spatial infinities in the thermal state. We argue that correlation functions of light operators in such a state can be viewed as thermal correlators with a rescaled effective temperature. The effective temperature controls the growth of out-of-time order (OTO) correlators and results in a violation of the universal upper bound on the associated Lyapunov exponent when Delta(Phi) < 0 and the CFT is nonunitary. We present a specific realization of this situation in the holographic Chern-Simons formulation of a CFT with W-3((2)) symmetry also known as the Bershadsky-Polyakov algebra. We examine the precise correspondence between the semiclassical (large-c) representations of this algebra and the Chern-Simons formulation, and infer that the holographic CFT possesses a discretuum of degenerate ground states with negative conformal dimension Delta(Phi) = -c/8. Using the Wilson line prescription to compute entanglement entropy and OTO correlators in the holographic CFT undergoing a local quench, we find the Lyapunov exponent lambda(L) = 4 pi/beta, violating the universal chaos bound
Sensory and decisional components of endogenous attention are dissociable
No full textEndogenous cueing of attention enhances sensory processing of the attended stimulus (perceptual sensitivity) and prioritizes information from the attended location for guiding behavioral decisions (spatial choice bias). Here, we test whether sensitivity and bias effects of endogenous spatial attention are under the control of common or distinct mechanisms. Human observers performed a multialternative visuospatial attention task with probabilistic spatial cues. Observers' behavioral choices were analyzed with a recently developed multidimensional signal detection model (the m-ADC model). The model effectively decoupled the effects of spatial cueing on sensitivity from those on spatial bias and revealed striking dissociations between them. Sensitivity was highest at the cued location and not significantly different among uncued locations, suggesting a spotlight-like allocation of sensory resources at the cued location. On the other hand, bias varied systematically with cue validity, suggesting a graded allocation of decisional priority across locations. Cueing-induced modulations of sensitivity and bias were uncorrelated within and across subjects. Bias, but not sensitivity, correlated with key metrics of prioritized decision-making, including reaction times and decision optimality indices. In addition, we developed a novel metric, differential risk curvature, for distinguishing bias effects of attention from those of signal expectation. Differential risk curvature correlated selectively with m-ADC model estimates of bias but not with estimates of sensitivity. Our results reveal dissociable effects of endogenous attention on perceptual sensitivity and choice bias in a multialternative choice task and motivate the search for the distinct neural correlates of each. NEW & NOTEWORTHY Attention is often studied as a unitary phenomenon. Yet, attention can both enhance the perception of important stimuli (sensitivity) and prioritize such stimuli for decision-making (bias). Employing a multialternative spatial attention task with probabilistic cueing, we show that attention affects sensitivity and bias through dissociable mechanisms. Specifically, the effects on sensitivity alone match the notion of an attentional ``spotlight.'' Our behavioral model enables quantifying component processes of attention, and identifying their respective neural correlates
Organic Bidirectional Phototransistors Based on Diketopyrrolopyrrole and Fullerene
No full textIt is shown that simple bilayer devices consisting of the diketopyrrolopyrrole (DPP) monomer Ph-TDPP-Ph as donor and C-60 as acceptor feature J-V-characteristics of a bidirectional organic phototransistor where illumination intensity plays the role of the gate voltage as compared to a conventional field-effect transistor. The output current may therefore be controlled both electrically and optically. The underlying mechanism is based on the good charge transport in Ph-TDPP-Ph and C-60, the intrinsic dissociation properties of C-60, and the presence of an injection barrier for holes. In addition to this, it is demonstrated that the observed behavior of the DPP/C-60 system allows the realization of basic logic elements like NOT-, AND-, and OR-Gates, which may provide the basis for advanced analog and digital applications
Effect of dimensionality on the vortex dynamics in a type-II superconductor
No full textWe explore the effects of sample dimensionality on vortex pinning in a type-II, low-T-C, s-wave superconductor, NbN, in the presence of a perpendicular magnetic field, H. We find significant differences in the phase diagrams in the magnetic field-temperature plane between three-dimensional (3D) and 2D NbN films. The differences are most striking close to the normal-superconductor phase transition. We establish that these variances have their origin in the differing pinning properties in two different dimensions. We obtain the pinning strength quantitatively in both the dimensions from two independent transport measurements performed in two different regimes of vortex motion: (i) thermally assisted flux-flow regime and (ii) flux flow regime. Both the measurements consistently show that both the pinning potential and the zero-field free-energy barrier to depinning in the 3D superconductor are at least an order of magnitude stronger than that in the 2D superconductor. Further, we probed the dynamics of pinning in both 2D and 3D superconductor through voltage fluctuation spectroscopy. We find that the mechanism of vortex pinning-depinning is qualitatively similar for the 3D and 2D superconductors. The voltage-fluctuations arising from vortex motion are found to be correlated only in the 2D superconductor. We establish this to be due to the presence of long-range phase fluctuations near the Berezinskii-Kosterlitz-Thouless-type superconducting transition in 2D superconductors