A generalized finite-difference time-domain quantum method for the N-body interacting Hamiltonian

The Quantum Finite-Difference Time-Domain (FDTD-Q) method is a numerical method for solving the time evolution of the Schrödinger equation. It can be applied to systems of interacting particles, allowing for realistic simulations of quantum mechanics of various experimental systems. One of the drawbacks of the method is that divergences in the numerical evolution occur rather easily in the presence of interactions, which necessitates a large number of evolution steps or imaginary time evolution. We present a generalized (GFDTD-Q) method for solving the time-dependent Schrödinger equation including interactions between the particles. The new scheme provides a more relaxed condition for stability when the finite difference approximations for spatial derivatives are employed, as compared with the original FDTD-Q scheme. We demonstrate our scheme by simulating the time evolution of a two-particle interaction Hamiltonian. Our results show that the generalized method allows for stable time evolutions, in contrast to the original FDTD-Q scheme which produces a divergent solution.     

Increased Vulnerability to Stress Following Opiate Exposures: Behavioral and Autonomic Correlates.

The authors used rats to study the impact of a history of opiate exposures on behavioral and autonomic responses to restraint stress. Brief restraint (30 min) provoked tachycardia and a pressor response, anxiety (as indexed by social interaction), grooming, and reduced exploration. The pressor response was reduced at 1 day, but not 7 days, after last opiate exposure; tachycardia was unaffected (Experiment 1). Stress-induced anxiety was potentiated 1 and 7 days after last opiate exposure (Experiment 2), and this potentiation was a function of dose (Experiment 3) and duration (Experiment 4) of opiate exposure. The results show that a history of opiate exposures alters vulnerability to stress and has implications for understanding coping, anxiety, and emotionality in former opiate users. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Informational Turn in Philosophy1

This paper traces the application of information theory to philosophical problems of mind and meaning from the earliest days of the creation of the mathematical theory of communication. The use of information theory to understand purposive behavior, learning, pattern recognition, and more marked the beginning of the naturalization of mind and meaning. From the inception of information theory, Wiener, Turing, and others began trying to show how to make a mind from informational and computational materials. Over the last 50 years, many philosophers saw different aspects of the naturalization of the mind, though few saw at once all of the pieces of the puzzle that we now know. Starting with Norbert Wiener himself, philosophers and information theorists used concepts from information theory to understand cognition. This paper provides a window on the historical sequence of contributions made to the overall project of naturalizing the mind by philosophers from Shannon, Wiener, and MacKay, to Dennett, Sayre, Dretske, Fodor, and Perry, among others. At some time between 1928 and 1948, American engineers and mathematicians began to talk about `Theory of Information' and `Information Theory,' understanding by these terms approximately and vaguely a theory for which Hartley's `amount of information' is a basic concept. I have been unable to find out when and by whom these names were first used. Hartley himself does not use them nor does he employ the term `Theory of Transmission of Information,' from which the two other shorter terms presumably were derived. It seems that Norbert Wiener and Claude Shannon were using them in the Mid-Forties.(Yehoshua Bar-Hillel, 1955)     

Full-body interface pressure testing as a method for performance evaluation of clinical support surfaces

A method for evaluating the performance of clinical support surfaces is required by designers in their efforts to produce better clinical support surfaces that will reduce the incidence of pressure ulcers. In this study, a Pressure Index (P_index) is defined which is derived from an analytical equation used to evaluate the average interface pressure, the peak pressure, the magnitude of the peak pressure, and the number of peak pressures on the entire body. The type of subjects needed to represent a population of users as well as the head of bed elevations necessary to simulate clinical applications were integrated with the P_index to create a single-value mean pressure index which can be used to evaluate any type of surface. To determine the accuracy and repeatability of the mean pressure index, three surfaces (a standard hospital innerspring, a replacement foam mattress, and a low-airloss surface) were tested and evaluated using this method. The low airloss performed the best and the standard innerspring clearly performed the worst (p < 0.0001). The method appeared to accurately and reproducibly predict the relative performance of the three surfaces in reducing pressure.     

CtpB Facilitates Mycobacterium tuberculosis Growth in Copper-Limited Niches

Copper is required for aerobic respiration by Mycobacterium tuberculosis and its human host, but this essential element is toxic in abundance. Copper nutritional immunity refers to host processes that modulate levels of free copper to alternately starve and intoxicate invading microbes. Bacteria engulfed by macrophages are initially contained within copper-limited phagosomes, which fuse with ATP7A vesicles that pump in toxic levels of copper. In this report, we examine how CtpB, a P-type ATPase in M. tuberculosis, aids in response to nutritional immunity. In vitro, the induced expression of ctpB in copper-replete medium inhibited mycobacterial growth, while deletion of the gene impaired growth only in copper-starved medium and within copper-limited host cells, suggesting a role for CtpB in copper acquisition or export to the copper-dependent respiration supercomplex. Unexpectedly, the absence of ctpB resulted in hypervirulence in the DBA/2 mouse infection model. As ctpB null strains exhibit diminished growth only in copper-starved conditions, reduced copper transport may have enabled the mutant to acquire a “Goldilocks” amount of the metal during transit through copper-intoxicating environments within this model system. This work reveals CtpB as a component of the M. tuberculosis toolkit to counter host nutritional immunity and underscores the importance of elucidating copper-uptake mechanisms in pathogenic mycobacteria.     

Targeting CD10 on B-Cell Leukemia Using the Universal CAR T-Cell Platform (UniCAR)

Chimeric antigen receptor (CAR)-expressing T-cells are without a doubt a breakthrough therapy for hematological malignancies. Despite their success, clinical experience has revealed several challenges, which include relapse after targeting single antigens such as CD19 in the case of B-cell acute lymphoblastic leukemia (B-ALL), and the occurrence of side effects that could be severe in some cases. Therefore, it became clear that improved safety approaches, and targeting multiple antigens, should be considered to further improve CAR T-cell therapy for B-ALL. In this paper, we address both issues by investigating the use of CD10 as a therapeutic target for B-ALL with our switchable UniCAR system. The UniCAR platform is a modular platform that depends on the presence of two elements to function. These include UniCAR T-cells and the target modules (TMs), which cross-link the T-cells to their respective targets on tumor cells. The TMs function as keys that control the switchability of UniCAR T-cells. Here, we demonstrate that UniCAR T-cells, armed with anti-CD10 TM, can efficiently kill B-ALL cell lines, as well as patient-derived B-ALL blasts, thereby highlighting the exciting possibility for using CD10 as an emerging therapeutic target for B-cell malignancies.     

Analysis for an Effective Operation of a General Automaton: Recursive Methods Applied to a Graph Model

In [1], we first identified a component of a general system and treated it as a general automaton. That work concluded with a graph model for a general automaton. The natural extension presented here is the development and application of recursive methods for determining properties of these graphs that reflect the effective operation of the automaton.     

Rat behavior in go/no-go and two-alternative choice odor discrimination: Differences and similarities.

To elucidate the cognitive structures of animals, neuroscientists use several behavioral tasks. Therefore, it is imperative to have a firm understanding of each task's behavioral parameters in order to parse out possible task effects. We compare two operant discrimination tasks (Go/No-Go: GNG; Two-Alternative Choice: TAC) that are commonly used in olfactory research. Past research has suggested that solving the two tasks requires divergent cognitive strategies. One hypothesis is that the two tasks differ in how an animal optimizes reward rate by means of a speed–accuracy trade-off (SAT). If this is true, then changing tasks could give researchers an additional tool to understand animal cognition. However, no study has systematically analyzed the two tasks in parallel using odor stimuli. Using standardized training protocols, we test GNG and TAC in parallel. Our protocols allow us to isolate the stimulus sampling period from a general reaction time period. We find that the two tasks do not differ with regard to the stimulus sampling period and conclude that the two tasks do not differ in the amount of time it takes an animal to perform a discrimination. Instead, tasks differ in the time it takes to make an overt behavioral response, with GNG showing shorter periods than TAC. We also find no evidence of rats using either task-specific or intertrial interval-dependent SAT schema in order to optimize reward rate. We show that similarities between dependent variables, with the possible exception of response delay, appear to be under experimenter control. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Rational Optimization of Dihydropyrimidinone-Quinoline Hybrids as Plasmodium falciparum Glutathione Reductase Inhibitors

A series of dihydropyrimidinone-based antimalarial compounds were designed and synthesised based on the previously identified amide-based quinoline hybrids which showed good resistance reversal ability against the resistant strain of Plasmodium falciparum. The aromatic ring on the dihydropyrimidinone of the original hits was exchanged for a methyl group to bring the molecular weights below 500 Da and also determine the effect of the aromatic ring count on the resistance reversal ability of the hybrids. Apart from the previously used amide bond, the hybrid linker was also extended to the triazole linker. Although the triazole linker is synthetically easier to access, the use of an amide linker seems to have an activity advantage. The synthesised compounds in addition to the previously identified hits were subjected to molecular docking particularly targeting the orthosteric site of Plasmodium falciparum glutathione reductase (PfGR) protein. The ligand with the best binding interaction was rationally optimised to increase its suitability as a competitive inhibitor against the cofactor of the PfGR. Two of the optimised ligands showed better binding affinities than the cofactor while one of the two ligands displayed hydrophobically packed correlated hydrogen-bond which is very important in maintaining the ligand stability within the protein. In silico ADME predictions of the synthesised compounds indicate that these compounds possess good pharmacokinetic properties.