Periodic force induced stabilization or destabilization of the denatured state of a protein

We have studied the effects of an external sinusoidal force in protein folding kinetics. The externally applied force field acts on the each amino acid residues of polypeptide chains. Our simulation results show that mean protein folding time first increases with driving frequency and then decreases passing through a maximum. With further increase of the driving frequency the mean folding time starts increasing as the noise-induced hoping event (from the denatured state to the native state) begins to experience many oscillations over the mean barrier crossing time period. Thus unlike one-dimensional barrier crossing problems, the external oscillating force field induces both \emph{stabilization or destabilization of the denatured state} of a protein. We have also studied the parametric dependence of the folding dynamics on temperature, viscosity, non-Markovian character of bath in presence of the external field

Interference of stochastic resonances: Splitting of Kramers' rate

We consider the escape of particles located in the middle well of a symmetric triple well potential driven sinusoidally by two forces such that the potential wells roll as in stochastic resonance and the height of the potential barrier oscillates symmetrically about a mean as in resonant activation. It has been shown that depending on their phase difference the application of these two synchronized signals may lead to a splitting of time averaged Kramers' escape rate and a preferential product distribution in a parallel chemical reaction in the steady state

Dipole binding in a cosmic string background due to quantum anomalies

We propose quantum dynamics for the dipole moving in cosmic string background and show that the classical scale symmetry of a particle moving in cosmic string background is still restored even in the presence of dipole moment of the particle. However, we show that the classical scale symmetry is broken due to inequivalent quantization of the the non-relativistic system. The consequence of this quantum anomaly is the formation of bound state in the interval \xi\in(-1,1). The inequivalent quantization is characterized by a 1-parameter family of self-adjoint extension parameter \Sigma. We show that within the interval \xi\in(-1,1), cosmic string with zero radius can bind the dipole and the dipole does not fall into the singularity.Comment: Accepted for publication in Phys. Rev.

Kinetics of self-induced aggregation of Brownian particles: non-Markovian and non-Gaussian features

In this paper we have studied a model for self-induced aggregation in Brownian particle incorporating the non-Markovian and non-Gaussian character of the associated random noise process. In this model the time evolution of each individual is guided by an over-damped Langevin equation of motion with a non-local drift resulting from the local unbalance distributions of the other individuals. Our simulation result shows that colored nose can induce the cluster formation even at large noise strength. Another observation is that critical noise strength grows very rapidly with increase of noise correlation time for Gaussian noise than non Gaussian one. However, at long time limit the cluster number in aggregation process decreases with time following a power law. The exponent in the power law increases remarkable for switching from Markovian to non Markovian noise process

Bim/Bcl-2 balance is critical for maintaining naive and memory T cell homeostasis

We examined the role of the antiapoptotic molecule Bcl-2 in combating the proapoptotic molecule Bim in control of naive and memory T cell homeostasis using Bcl-2−/− mice that were additionally deficient in one or both alleles of Bim. Naive T cells were significantly decreased in Bim+/−Bcl-2−/− mice, but were largely restored in Bim−/−Bcl-2−/− mice. Similarly, a synthetic Bcl-2 inhibitor killed wild-type, but not Bim−/−, T cells. Further, T cells from Bim+/−Bcl-2−/− mice died rapidly ex vivo and were refractory to cytokine-driven survival in vitro. In vivo, naive CD8+ T cells required Bcl-2 to combat Bim to maintain peripheral survival, whereas naive CD4+ T cells did not. In contrast, Bim+/−Bcl-2−/− mice generated relatively normal numbers of memory T cells after lymphocytic choriomeningitis virus infection. Accumulation of memory T cells in Bim+/−Bcl-2−/− mice was likely caused by their increased proliferative renewal because of the lymphopenic environment of the mice. Collectively, these data demonstrate a critical role for a balance between Bim and Bcl-2 in controlling homeostasis of naive and memory T cells

Langevin dynamics with dichotomous noise; direct simulation and applications

We consider the motion of a Brownian particle moving in a potential field and driven by dichotomous noise with exponential correlation. Traditionally, the analytic as well as the numerical treatments of the problem, in general, rely on Fokker-Planck description. We present a method for direct numerical simulation of dichotomous noise to solve the Langevin equation. The method is applied to calculate nonequilibrium fluctuation induced current in a symmetric periodic potential using asymmetric dichotomous noise and compared to Fokker-Planck-Master equation based algorithm for a range of parameter values. Our second application concerns the study of resonant activation over a fluctuating barrier.Comment: Accepted in Journal of Statistical Mechanics: Theory and Experimen

Normal mode analysis for scalar fields in BTZ black hole background

We analyze the possibility of inequivalent boundary conditions for a scalar field propagating in the BTZ black hole space-time. We find that for certain ranges of the black hole parameters, the Klein-Gordon operator admits a one-parameter family of self-adjoint extensions. For this range, the BTZ space-time is not quantum mechanically complete. We suggest a physically motivated method for determining the spectra of the Klein-Gordon operator.Comment: 6 pages, no figure, late

Atom capture by nanotube and scaling anomaly

The existence of bound state of the polarizable neutral atom in the inverse square potential created by the electric field of single walled charged carbon nanotube (SWNT) is shown to be theoretically possible. The consideration of inequivalent boundary conditions due to self-adjoint extensions lead to this nontrivial bound state solution. It is also shown that the scaling anomaly is responsible for the existence of bound state. Binding of the polarizable atoms in the coupling constant interval \eta^2\in[0,1) may be responsible for the smearing of the edge of steps in quantized conductance, which has not been considered so far in literature.Comment: Accepted in Int.J.Theor.Phy

Miniaturized Embryo Array for Automated Trapping, Immobilization and Microperfusion of Zebrafish Embryos

Zebrafish (Danio rerio) has recently emerged as a powerful experimental model in drug discovery and environmental toxicology. Drug discovery screens performed on zebrafish embryos mirror with a high level of accuracy the tests usually performed on mammalian animal models, and fish embryo toxicity assay (FET) is one of the most promising alternative approaches to acute ecotoxicity testing with adult fish. Notwithstanding this, automated in-situ analysis of zebrafish embryos is still deeply in its infancy. This is mostly due to the inherent limitations of conventional techniques and the fact that metazoan organisms are not easily susceptible to laboratory automation. In this work, we describe the development of an innovative miniaturized chip-based device for the in-situ analysis of zebrafish embryos. We present evidence that automatic, hydrodynamic positioning, trapping and long-term immobilization of single embryos inside the microfluidic chips can be combined with time-lapse imaging to provide real-time developmental analysis. Our platform, fabricated using biocompatible polymer molding technology, enables rapid trapping of embryos in low shear stress zones, uniform drug microperfusion and high-resolution imaging without the need of manual embryo handling at various developmental stages. The device provides a highly controllable fluidic microenvironment and post-analysis eleuthero-embryo stage recovery. Throughout the incubation, the position of individual embryos is registered. Importantly, we also for first time show that microfluidic embryo array technology can be effectively used for the analysis of anti-angiogenic compounds using transgenic zebrafish line (fli1a:EGFP). The work provides a new rationale for rapid and automated manipulation and analysis of developing zebrafish embryos at a large scale

CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus

CD47 is a ubiquitous cell surface receptor that directly regulates T cell immunity by interacting with its inhibitory ligand thrombospondin-1 and limits clearance of cells by phagocytes that express its counter-receptor signal-regulatory protein-α. Murine natural killer (NK) cells express higher levels of CD47 than other lymphocytes, but the role of CD47 in regulating NK cell homeostasis and immune function remains unclear. Cd47−/− mice exhibited depletion of NK precursors in bone marrow, consistent with the antiphagocytic function of CD47. In contrast, antisense CD47 knockdown or gene disruption resulted in a dose dependent accumulation of immature and mature NK cells in spleen. Mature Cd47−/− NK cells exhibited increased expression of NK effector and interferon gene signatures and an increased proliferative response to interleukin-15 in vitro. Cd47−/− mice showed no defect in their early response to acute Armstrong lymphocytic choriomeningitis virus (LCMV) infection but were moderately impaired in controlling chronic Clone-13 LCMV infection, which was associated with depletion of splenic NK cells and loss of effector cytokine and interferon response gene expression in Cd47−/− NK cells. Broad CD47-dependent differences in NK activation, survival, and exhaustion pathways were observed in NK cell transcriptional signatures in LCMV infected mice. These data identify CD47 as a cell-intrinsic and systemic regulator of NK cell homeostasis and NK cell function in responding to a viral infection