SPLIT-STEP FORWARD MILSTEIN METHOD FOR STOCHASTIC DIFFERENTIAL EQUATIONS

In this paper, we consider the problem of computing numerical solutions for stochastic differential equations (SDEs) of Ito form. A fully explicit method, the split-step forward Milstein (SSFM) method, is constructed for solving SDEs. It is proved that the SSFM method is convergent with strong order gamma = 1 in the mean-square sense. The analysis of stability shows that the mean-square stability properties of the method proposed in this paper are an improvement on the mean-square stability properties of the Milstein method and three stage Milstein methods.

Zero-Sum Risk-Sensitive Stochastic Differential Games

We study zero-sum risk-sensitive stochastic differential games on the infinite horizon with discounted and ergodic payoff criteria. Under certain assumptions, we establish the existence of values and saddle-point equilibria. We obtain our results by studying the corresponding Hamilton-Jacobi-Isaacs equations. Finally, we show that the value of the ergodic payoff criterion is a constant multiple of the maximal eigenvalue of the generators of the associated nonlinear semigroups.

Existence of Value in Stochastic Differential Games of Mixed Type

In this article, we address stochastic differential games of mixed type with both control and stopping times. Under standard assumptions, we show that the value of the game can be characterized as the unique viscosity solution of corresponding Hamilton-Jacobi-Isaacs (HJI) variational inequalities.

Equal channel angular pressing processing routes and associated structure modification: a differential scanning calorimetry and X-ray line profile analysis

The effectiveness of different routes of equal channel angular pressing (A, B-c, and C) is studied for commercially pure copper. The stored energy and the activation energy of recrystallization for the deformed samples were quantified using differential scanning calorimetry and X-ray diffraction line profile analysis. Results of the study revealed that the dislocation density and the stored energy are higher in the case of route B-c deformed sample. The activation energy for recrystallization is lower for route B-c. (C) 2012 International Centre for Diffraction Data doi:10.1017/S0885715612000310]

Differential Activities of the Two Closely Related Withanolides, Withaferin A and Withanone: Bioinformatics and Experimental Evidences

Background and Purpose: Withanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects. Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar withanolides isolated from Withania somnifera, also known as Ashwagandha in Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely related purified phytochemicals, Wi-A and Wi-N, showed differential activity in normal and cancer human cells in vitro and in vivo. We had earlier identified several genes involved in cytotoxicity of i-Extract in human cancer cells by loss-of-function assays using either siRNA or randomized ribozyme library. Methodology/Principal Findings: In the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails.

Differential modulation of intracellular survival of cytosolic and vacuolar pathogens by curcumin

Curcumin, a principal component of turmeric, acts as an immunomodulator regulating the host defenses in response to a diseased condition. The role of curcumin in controlling certain infectious diseases is highly controversial. It is known to alleviate symptoms of Helicobacter pylori infection and exacerbate that of Leishmania infection. We have evaluated the role of curcumin in modulating the fate of various intracellular bacterial pathogens. We show that pretreatment of macrophages with curcumin attenuates the infections caused by Shigella flexneri (clinical isolates) and Listeria monocytogenes and aggravates those caused by Salmonella enterica serovar Typhi CT18 (a clinical isolate), Salmonella enterica serovar Typhimurium, Staphylococcus aureus, and Yersinia enterocolitica. Thus, the antimicrobial nature of curcumin is not a general phenomenon. It modulated the intracellular survival of cytosolic (S. flexneri and L. monocytogenes) and vacuolar (Salmonella spp., Y. enterocolitica, and S. aureus) bacteria in distinct ways. Through colocalization experiments, we demonstrated that curcumin prevented the active phagosomal escape of cytosolic pathogens and enhanced the active inhibition of lysosomal fusion by vacuolar pathogens. A chloroquine resistance assay confirmed that curcumin retarded the escape of the cytosolic pathogens, thus reducing their inter- and intracellular spread. We have demonstrated that the membrane-stabilizing activity of curcumin is crucial for its differential effect on the virulence of the bacteria.

Differential reflectance modulation sensing with diffractive microstructures

We present a method for differential ratiometric measurement of reflectance change due to molecular adsorption using a diffractive microstructure fabricated on a reflectance contrast enhancing substrate for bulk refractometry and surface molecular binding detection applications. The differential method suppresses signal fluctuations due to thermal or concentration gradients in the sample flow cell by more than 40x and enables the real-time measurement of molecular interactions on the surface with a noise floor of about 70 pm. (V)C 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4766190]

Low-pass filters and differential tympanal tuning in a paleotropical bushcricket with an unusually low frequency call

Low-frequency sounds are advantageous for long-range acoustic signal transmission, but for small animals they constitute a challenge for signal detection and localization. The efficient detection of sound in insects is enhanced by mechanical resonance either in the tracheal or tympanal system before subsequent neuronal amplification. Making small structures resonant at low sound frequencies poses challenges for insects and has not been adequately studied. Similarly, detecting the direction of long-wavelength sound using interaural signal amplitude and/or phase differences is difficult for small animals. Pseudophylline bushcrickets predominantly call at high, often ultrasonic frequencies, but a few paleotropical species use lower frequencies. We investigated the mechanical frequency tuning of the tympana of one such species, Onomarchus uninotatus, a large bushcricket that produces a narrow bandwidth call at an unusually low carrier frequency of 3.2. kHz. Onomarchus uninotatus, like most bushcrickets, has two large tympanal membranes on each fore-tibia. We found that both these membranes vibrate like hinged flaps anchored at the dorsal wall and do not show higher modes of vibration in the frequency range investigated (1.5-20. kHz). The anterior tympanal membrane acts as a low-pass filter, attenuating sounds at frequencies above 3.5. kHz, in contrast to the high-pass filter characteristic of other bushcricket tympana. Responses to higher frequencies are partitioned to the posterior tympanal membrane, which shows maximal sensitivity at several broad frequency ranges, peaking at 3.1, 7.4 and 14.4. kHz. This partitioning between the two tympanal membranes constitutes an unusual feature of peripheral auditory processing in insects. The complex tracheal shape of O. uninotatus also deviates from the known tube or horn shapes associated with simple band-pass or high-pass amplification of tracheal input to the tympana. Interestingly, while the anterior tympanal membrane shows directional sensitivity at conspecific call frequencies, the posterior tympanal membrane is not directional at conspecific frequencies and instead shows directionality at higher frequencies.

Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-gamma and IL-17 production in blood from TB plus patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras

Background: A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Methods: Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-gamma and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). Results: M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-gamma production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. Conclusions: The pattern of immune target recognition is different in regard to IFN-gamma and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.

Negative differential resistance and effect of defects and deformations in MoS2 armchair nanoribbon metal-oxide-semiconductor field effect transistor

In this work, we present a study on the negative differential resistance (NDR) behavior and the impact of various deformations (like ripple, twist, wrap) and defects like vacancies and edge roughness on the electronic properties of short-channel MoS2 armchair nanoribbon MOSFETs. The effect of deformation (3 degrees-7 degrees twist or wrap and 0.3-0.7 angstrom ripple amplitude) and defects on a 10 nm MoS2 ANR FET is evaluated by the density functional tight binding theory and the non-equilibrium Green's function approach. We study the channel density of states, transmission spectra, and the I-D-V-D characteristics of such devices under the varying conditions, with focus on the NDR behavior. Our results show significant change in the NDR peak to valley ratio and the NDR window with such minor intrinsic deformations, especially with the ripple. (C) 2013 AIP Publishing LLC.

Differential Action of Glycoprotein Hormones: Significance in Cancer Progression

Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

Differential evolution based 3-D guidance law for a realistic interceptor model

This paper presents a novel, soft computing based solution to a complex optimal control or dynamic optimization problem that requires the solution to be available in real-time. The complexities in this problem of optimal guidance of interceptors launched with high initial heading errors include the more involved physics of a three dimensional missile-target engagement, and those posed by the assumption of a realistic dynamic model such as time-varying missile speed, thrust, drag and mass, besides gravity, and upper bound on the lateral acceleration. The classic, pure proportional navigation law is augmented with a polynomial function of the heading error, and the values of the coefficients of the polynomial are determined using differential evolution (DE). The performance of the proposed DE enhanced guidance law is compared against the existing conventional laws in the literature, on the criteria of time and energy optimality, peak lateral acceleration demanded, terminal speed and robustness to unanticipated target maneuvers, to illustrate the superiority of the proposed law. (C) 2013 Elsevier B. V. All rights reserved.

Common-Mode and Differential-Mode Active Damping for PWM Rectifiers

Modern pulse-width-modulated (PWM) rectifiers use LC L filters that can be applied in both the common mode and differential mode to obtain high-performance filtering. Interaction between the passive L and C components in the filter leads to resonance oscillations. These oscillations need to be damped either by the passive damping or active damping. The passive damping increases power loss and can reduce the effectiveness of the filter. Methods of active damping, using control strategy, are lossless while maintaining the effectiveness of the filters. In this paper, an active damping strategy is proposed to damp the oscillations in both line-to-line and line-to-ground. An approach based on pole placement by the state feedback is used to actively damp both the differential-and common-mode filter oscillations. Analytical expressions for the state-feedback controller gains are derived for both continuous and discrete-time model of the filter. Tradeoff in selection of the active damping gain on the lower order power converter harmonics is analyzed using a weighted admittance function. Experimental results on a 10-kVA laboratory prototype PWM rectifier are presented. The results validate the effectiveness of the active damping method, and the tradeoff in the settings of the damping gain.

Molecular Basis for the Differential Quinolone Susceptibility of Mycobacterial DNA Gyrase

DNA gyrase is a type II topoisomerase that catalyzes the introduction of negative supercoils in the genomes of eubacteria. Fluoroquinolones (FQs), successful as drugs clinically, target the enzyme to trap the gyrase-DNA complex, leading to the accumulation of double-strand breaks in the genome. Mycobacteria are less susceptible to commonly used FQs. However, an 8-methoxy-substituted FQ, moxifloxacin (MFX), is a potent antimycobacterial, and a higher susceptibility of mycobacterial gyrase to MFX has been demonstrated. Although several models explain the mechanism of FQ action and gyrase-DNA-FQ interaction, the basis for the differential susceptibility of mycobacterial gyrase to various FQs is not understood. We have addressed the basis of the differential susceptibility of the gyrase and revisited the mode of action of FQs. We demonstrate that FQs bind both Escherichia coli and Mycobacterium tuberculosis gyrases in the absence of DNA and that the addition of DNA enhances the drug binding. The FQs bind primarily to the GyrA subunit of mycobacterial gyrase, while in E. coli holoenzyme is the target. The binding of MFX to GyrA of M. tuberculosis correlates with its effectiveness as a better inhibitor of the enzyme and its efficacy in cell killing.