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    Strong violation of critical phenomena universality: Wang-Landau study of the two-dimensional Blume-Capel model under bond randomness

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    We study the pure and random-bond versions of the square lattice ferromagnetic Blume-Capel model, in both the first-order and second-order phase transition regimes of the pure model. Phase transition temperatures, thermal and magnetic critical exponents are determined for lattice sizes in the range L=20-100 via a sophisticated two-stage numerical strategy of entropic sampling in dominant energy subspaces, using mainly the Wang-Landau algorithm. The second-order phase transition, emerging under random bonds from the second-order regime of the pure model, has the same values of critical exponents as the two-dimensional Ising universality class, with the effect of the bond disorder on the specific heat being well described by double-logarithmic corrections, our findings thus supporting the marginal irrelevance of quenched bond randomness. On the other hand, the second-order transition, emerging under bond randomness from the first-order regime of the pure model, has a distinctive universality class with nu=1.30(6) and beta/nu=0.128(5). These results amount to a strong violation of universality principle of critical phenomena, since these two second-order transitions, with different sets of critical exponents, are between the same ferromagnetic and paramagnetic phases. Furthermore, the latter of these two sets of results supports an extensive but weak universality, since it has the same magnetic critical exponent (but a different thermal critical exponent) as a wide variety of two-dimensional systems with and without quenched disorder. In the conversion by bond randomness of the first-order transition of the pure system to second order, we detect, by introducing and evaluating connectivity spin densities, a microsegregation that also explains the increase we find in the phase transition temperature under bond randomness

    Quantum-mechanically induced asymmetry in the phase diagrams of spin-glass systems

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    The spin-1/2 quantum Heisenberg spin-glass system is studied in all spatial dimensions d by renormalization-group theory. Strongly asymmetric phase diagrams in temperature and antiferromagnetic bond probability p are obtained in dimensions d >= 3. The asymmetry at high temperatures approaching the pure ferromagnetic and antiferromagnetic systems disappears as d is increased. However, the asymmetry at low but finite temperatures remains in all dimensions, with the antiferromagnetic phase receding from the ferromagnetic phase. A finite-temperature second-order phase boundary directly between the ferromagnetic and antiferromagnetic phases occurs in d >= 6, resulting in a new multicritical point. In d=3, 4, 5, a paramagnetic phase reaching zero temperature intervenes asymmetrically between the ferromagnetic and reentrant antiferromagnetic phases. There is no spin-glass phase in any dimension

    Entropy transfer between residue pairs and allostery in proteins: quantifying allosteric communication in ubiquitin

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    It has recently been proposed by Gunasakaran et al. that allostery may be an intrinsic property of all proteins. Here, we develop a computational method that can determine and quantify allosteric activity in any given protein. Based on Schreiber's transfer entropy formulation, our approach leads to an information transfer landscape for the protein that shows the presence of entropy sinks and sources and explains how pairs of residues communicate with each other using entropy transfer. The model can identify the residues that drive the fluctuations of others. We apply the model to Ubiquitin, whose allosteric activity has not been emphasized until recently, and show that there are indeed systematic pathways of entropy and information transfer between residues that correlate well with the activities of the protein. We use 600 nanosecond molecular dynamics trajectories for Ubiquitin and its complex with human polymerase iota and evaluate entropy transfer between all pairs of residues of Ubiquitin and quantify the binding susceptibility changes upon complex formation. We explain the complex formation propensities of Ubiquitin in terms of entropy transfer. Important residues taking part in allosteric communication in Ubiquitin predicted by our approach are in agreement with results of NMR relaxation dispersion experiments. Finally, we show that time delayed correlation of fluctuations of two interacting residues possesses an intrinsic causality that tells which residue controls the interaction and which one is controlled. Our work shows that time delayed correlations, entropy transfer and causality are the required new concepts for explaining allosteric communication in protein

    Haptic manipulation of microspheres using optical tweezers under the guidance of artificial force fields

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    Using optical tweezers (OT) and a haptic device, microspheres having diameters ranging from 3 to 4 mu m (floating in a fluid solution) are manipulated in order to form patterns of coupled optical microresonators by assembling the spheres via chemical binding. For this purpose, biotin-coated microspheres trapped by a laser beam are steered and chemically attached to an immobilized streptavi d in -coated sphere (i.e., the anchor sphere) one by one using an xyz piezo scanner controlled by a haptic device. The positions of all spheres in the scene are detected using a CCD camera and a collision-free path for each manipulated sphere is generated using the potential field approach. The forces acting on the manipulated particle due to the viscosity of the fluid and the artificial potential field are scaled and displayed to the user through the haptic device for better guidance and control during steering. In addition, a virtual fixture is implemented such that the desired angle of approach and strength are achieved during the binding phase. Our experimental studies in virtual and real environments with eight human subjects show that haptic feedback significantly improves the user performance by reducing the task completion time, the number of undesired collisions during steering, and the positional errors during binding. To our knowledge, this is the first time that a haptic device is coupled with OTs to guide the user during an optical manipulation task involving steering and assembly of microspheres to construct a coupled microresonator

    MerR and ChrR mediate blue light induced photo-oxidative stress response at the transcriptional level in Vibrio cholerae

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    Blue light (BL) is a major environmental factor that affects the physiology, behavior, and infectivity of bacteria as it contributes to the generation of reactive oxygen species (ROS) while increasing photo-oxidative stress in cells. However, precise photo-oxidative response mechanism in non-phototrophic bacteria is yet to be elucidated. In this study, we investigated the effect of BL in Vibrio cholerae by using genetics and transcriptome profiling. Genome-wide analysis revealed that transcription of 6.3% of V. cholerae genes were regulated by BL. We further showed that BL enhances ROS production, which is generated through the oxidative phosphorylation. To understand signaling mechanisms, we generated several knockouts and analyzed their transcriptome under BL exposure. Studies with a double-knockout confirm an anti-sigma factor (ChrR) and putative metalloregulatory-like protein (MerR) are responsible for the genome-wide regulation to BL response in V. cholerae. Collectively, these results demonstrate that MerR-like proteins, in addition to ChrR, are required for V. cholerae to mount an appropriate response against photo-oxidative stress induced by BL. Outside its natural host, V. cholerae can survive for extended periods in natural aquatic environments. Therefore, the regulation of light response for V. cholerae may be a critical cellular process for its survival in these environments

    Temperature dependence of the threshold electric field in a hot electron VCSEL

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    The operation of the Hot Electron Light Emitting and Lasing in Semiconductor Heterostructure - Vertical Cavity Surface Emitting Laser (HELLISH-VCSEL) devices is based on hot carrier transport parallel to the layers of Ga1-xAlxAs p-n junction. It is therefore a field - effect device and the light emission from the device is independent of the polarity of the applied voltage. In this study, we present the temperature dependence of the operational characteristics of the device. Experimental studies comprising of the measurements of the IN characteristics, electroluminescence, reflectivity, and temperature dependent light-applied electric field (L-F) characteristics are conducted to find the optimum operating temperature of the device

    A conserved tetraspanin subfamily promotes Notch signaling in Caenorhabditis elegans and in human cells

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    The cytosolic domain of Notch is a membrane-tethered transcription factor. Ligand binding ultimately leads to γ-secretase cleavage within the transmembrane domain, allowing the intracellular domain to translocate to the nucleus and activate target gene transcription. Constitutive Notch signaling has been associated with human cancers such as T cell acute lymphoblastic leukemia (T-ALL). As tetraspanins have been implicated in many different signaling processes, we assessed their potential contribution to Notch signaling. We used a genetic assay in Caenorhabditis elegans to identify TSP-12 as a positive factor for Notch activity in several cellular contexts. Then, using a cell culture system, we showed that two human TSP-12 orthologs, TSPAN33 and TSPAN5, promote Notch activity and are likely to act at the γ-secretase cleavage step. We also acquired evidence for functional redundancy among tetraspanins in both C. elegans and human cells. Selective inhibition of tetraspanins may constitute an anti-NOTCH therapeutic approach to reduce γ-secretase activity

    Silicon microspheres for optoelectronic applications

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    Having high quality factors, optical microsphere resonators are shown to be ideal circuit elements for wavelength division multiplexing. Silicon, as a common semiconductor and thus being a building block in the integrated circuits, also is a very important material with its optical properties. We have experimentally observed the shifts in resonance wavelengths of an electrically driven silicon microsphere of 500 microns in radius, in the near-IR. We have used a DFB laser at 1475nm, and applied voltages ranging from 0V to 9V to the microsphere and observed the respected shifts in the resonance wavelengths around 0.005 nm to 0.050 nm, and respective shifts in the refractive index are 10(-5) to 10(-4)

    A new method to determine reflex latency induced by high rate stimulation of the nervous system

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    High rate stimulations of the neuromuscular system, such as continuous whole body vibration, tonic vibration reflex and high frequency electrical stimulation, are used in the physiological research with an increasing interest. In these studies, the neuronal circuitries underlying the reflex responses remain unclear due to the problem of determining the exact reflex latencies. We present a novel 'cumulated average method" to determine the reflex latency during high rate stimulation of the nervous system which was proven to be significantly more accurate than the classical method. The classical method, cumulant density analysis, reveals the relationship between the two synchronously recorded signals as a function of the lag between the signals. The comparison of new method with the classical technique and their relative accuracy was tested using a computer simulation. In the simulated signals the EMG response latency was constructed to be exactly 40 ms. The new method accurately indicated the value of the simulated reflex latency (40 ms). However, the classical method showed that the lag time between the simulated triggers and the simulated signals was 49 ms. Simulation results illustrated that the cumulated average method is a reliable and more accurate method compared with the classical method. We therefore suggest that the new cumulated average method is able to determine the high rate stimulation induced reflex latencies more accurately than the classical method

    Nanometer-scale siRNA carriers incorporating peptidomimetic oligomers: physical characterization and biological activity

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    Synthetic short interfering RNA (siRNA) oligonucleotides can trigger the RNA interference pathway and lead to selective gene silencing. Despite considerable enthusiasm and investment, formidable challenges remain that may deter translating this breakthrough discovery into clinical applications. In particular, the development of efficient, nontoxic, nonimmunogenic methods for delivering siRNA in vivo has proven to be exceptionally challenging. Thorough analysis of the relationship between the structure and function of siRNA carrier systems, both in isolation and in complex with RNA, will facilitate the design of efficient nonviral siRNA delivery vehicles. In this study, we explore the relationship between the physicochemical characteristics and the biological activity of "lipitoid" compounds as potent siRNA delivery vehicles. Lipitoids are cationic peptidomimetic oligomers incorporating a peptoid and a phospholipid moiety. Lipitoids can associate with siRNA oligonucleotides and self-assemble into spherical lipitoid-based nanoparticles (LNPs), with dimensions that are dependent upon the medium and the stoichiometric ratio between the cationic monomers of the lipitoid and anionic siRNA oligonucleotides. The morphology, gene silencing efficiency, and cytotoxicity of the siRNA-loaded LNPs are similarly sensitive to the stoichiometry of the complexes. The medium in which the LNPs are formed affects the assembled cargo particles' characteristics such as particle size, transfection efficiency, and stability. Formation of the LNPs in the biological, serum-free medium OptiMEM resulted in LNPs an order of magnitude larger than LNPs formed in water, and were twice as efficient in siRNA transfection compared to LNPs formed in water. Inhibitor studies were conducted to elucidate the efficiency of lysosomal escape and the uptake mechanism of the siRNA-loaded LNPs. Our results suggest that these lipitoid-based, siRNA-loaded spherical LNPs are internalized through a lipid raft-dependent and dynaminmediated pathway, circumventing endosomal and lysosomal encapsulation. The lipitoid-siRNA nanospheres proved to be suitable platforms for investigating the critical parameters determining the efficiency of transfection agents, revealing the necessity for conducting characterization studies in biological media. The investigation of the LNP internalization pathway points to an alternative uptake route that bypasses the lysosome, explaining the surprisingly high efficiency of LNPs and suggesting that the uptake mechanism should be probed rather than assumed for the next generation of rationally designed -transfection agents

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