The method of Gaussian weighted trajectories. V. On the 1GB procedure for polyatomic processes

In recent years, many chemical reactions have been studied by means of the quasi-classical trajectory (QCT) method within the Gaussian binning (GB) procedure. The latter consists in "quantizing" the final vibrational actions in Bohr spirit by putting strong emphasis on the trajectories reaching the products with vibrational actions close to integer values. A major drawback of this procedure is that if N is the number of product vibrational modes, the amount of trajectories necessary to converge the calculations is ~ 10^N larger than with the standard QCT method. Applying it to polyatomic processes is thus problematic. In a recent paper, however, Czako and Bowman propose to quantize the total vibrational energy instead of the vibrational actions [G. Czako and J. M. Bowman, J. Chem. Phys., 131, 244302 (2009)], a procedure called 1GB here. The calculations are then only ~ 10 times more time-consuming than with the standard QCT method, allowing thereby for considerable numerical saving. In this paper, we propose some theoretical arguments supporting the 1GB procedure and check its validity on model test cases as well as the prototype four-atom reaction OH+D_2 -> HOD+D

Knockdown of Malic Enzyme 2 Suppresses Lung Tumor Growth, Induces Differentiation and Impacts PI3K/AKT Signaling

Mitochondrial malic enzyme 2 (ME2) catalyzes the oxidative decarboxylation of malate to yield CO2 and pyruvate, with concomitant reduction of dinucleotide cofactor NAD+ or NADP+. We find that ME2 is highly expressed in many solid tumors. In the A549 non-small cell lung cancer (NSCLC) cell line, ME2 depletion inhibits cell proliferation and induces cell death and differentiation, accompanied by increased reactive oxygen species (ROS) and NADP+/NADPH ratio, a drop in ATP, and increased sensitivity to cisplatin. ME2 knockdown impacts phosphoinositide-dependent protein kinase 1 (PDK1) and phosphatase and tensin homolog (PTEN) expression, leading to AKT inhibition. Depletion of ME2 leads to malate accumulation and pyruvate decrease, and exogenous cell permeable dimethyl-malate (DMM) mimics the ME2 knockdown phenotype. Both ME2 knockdown and DMM treatment reduce A549 cell growth in vivo. Collectively, our data suggest that ME2 is a potential target for cancer therapy

Positron and positronium affinities in the work-formalism Hartree-Fock approximation

Positron binding to anions is investigated within the work formalism proposed by Harbola and Sahni for the halide anions and the systems Li^- through O^- excluding Be^- and N^-. The toal ground-state energies of the anion-positron bound systems are empirically found to be an upper bound to the Hartree-Fock energies. The computed expectation values as well as positron and positronium affinities are in good agreement with their restricted Hartree-Fock counterparts. Binding of a positron to neutral species is also investigated using an iterative method.Comment: 12 pages, to appear in Physical Review

Expression capable library for studies of Neisseria gonorrhoeae, version 1.0

Background The sexually transmitted disease, gonorrhea, is a serious health problem in developed as well as in developing countries, for which treatment continues to be a challenge. The recent completion of the genome sequence of the causative agent, Neisseria gonorrhoeae, opens up an entirely new set of approaches for studying this organism and the diseases it causes. Here, we describe the initial phases of the construction of an expression-capable clone set representing the protein-coding ORFs of the gonococcal genome using a recombination-based cloning system. Results The clone set thus far includes 1672 of the 2250 predicted ORFs of the N. gonorrhoeae genome, of which 1393 (83%) are sequence-validated. Included in this set are 48 of the 61 ORFs of the gonococcal genetic island of strain MS11, not present in the sequenced genome of strain FA1090. L-arabinose-inducible glutathione-S-transferase (GST)-fusions were constructed from random clones and each was shown to express a fusion protein of the predicted size following induction, demonstrating the use of the recombination cloning system. PCR amplicons of each ORF used in the cloning reactions were spotted onto glass slides to produce DNA microarrays representing 2035 genes of the gonococcal genome. Pilot experiments indicate that these arrays are suitable for the analysis of global gene expression in gonococci. Conclusion This archived set of Gateway® entry clones will facilitate high-throughput genomic and proteomic studies of gonococcal genes using a variety of expression and analysis systems. In addition, the DNA arrays produced will allow us to generate gene expression profiles of gonococci grown in a wide variety of conditions. Together, the resources produced in this work will facilitate experiments to dissect the molecular mechanisms of gonococcal pathogenesis on a global scale, and ultimately lead to the determination of the functions of unknown genes in the genome

Gene translocation links insects and crustaceans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62560/1/392667a0.pd

A genomic and evolutionary approach reveals non-genetic drug resistance in malaria

Background: Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. Results: We previously described two mutations in the cytoplasmic prolyl-tRNA synthetase (cPRS) gene that confer resistance to halofuginone. We describe here the evolutionary trajectory of halofuginone resistance of two independent drug resistance selections in Plasmodium falciparum. Using this novel methodology, we discover an unexpected non-genetic drug resistance mechanism that P. falciparum utilizes before genetic modification of the cPRS. P. falciparum first upregulates its proline amino acid homeostasis in response to halofuginone pressure. We show that this non-genetic adaptation to halofuginone is not likely mediated by differential RNA expression and precedes mutation or amplification of the cPRS gene. By tracking the evolution of the two drug resistance selections with whole genome sequencing, we further demonstrate that the cPRS locus accounts for the majority of genetic adaptation to halofuginone in P. falciparum. We further validate that copy-number variations at the cPRS locus also contribute to halofuginone resistance. Conclusions: We provide a three-step model for multi-locus evolution of halofuginone drug resistance in P. falciparum. Informed by genomic approaches, our results provide the first comprehensive view of the evolutionary trajectory malaria parasites take to achieve drug resistance. Our understanding of the multiple genetic and non-genetic mechanisms of drug resistance informs how we will design and pair future anti-malarials for clinical use. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0511-2) contains supplementary material, which is available to authorized users

A cross-national examination of motivation to volunteer: religious context, national value patterns, and nonprofit regimes

Although motivation to volunteer (MTV) is one of the most frequently researched topics in the field of volunteering research, few studies have compared and explained MTV cross-nationally. Using data from the 1990 World Values Surveys, this study examines if and how specific societal characteristics are asso-ciated with self-reported motivations to volunteer, focusing on national religious context, dominant value patterns, and institutional variations in terms of welfare state regimes and characteristics of the nonprofit sector. Across all countries stud-ied, people who volunteered expressed both altruistic and self-oriented motiva-tions, but we observed important cross-national variations in the emphasis put on both motivational dimensions. Besides the influence of individual-level character-istics, we found partial evidence for a contextual understanding of motivation to volunteer. With respect to religion, we expected a beneficial relationship with al-truistic motivations. While such a positive relationship was found at the individual level, the evidence for a religious national context was ambiguous: on the one hand, no relationship was found between extensive religious networks and support for altruistic motivations; on the other, strong religious beliefs among the general population were negatively associated with both altruistic and self-interested MTV. The prevalence of a post-material value pattern did not represent a threat to feelings of altruism, and produced mixed findings concerning self-interested MTV. Finally, welfare states with lower social spending, a large nonprofit sector with little revenue from government, and an active citizenry, in terms of a high rate of volunteering, stimulated the expression of altruistic motivations

Calculation of the positron bound state with the copper atom

A new relativistic method for calculation of positron binding to atoms is presented. The method combines a configuration interaction treatment of the valence electron and the positron with a many-body perturbation theory description of their interaction with the atomic core. We apply this method to positron binding by the copper atom and obtain the binding energy of 170 meV (+ - 10%). To check the accuracy of the method we use a similar approach to calculate the negative copper ion. The calculated electron affinity is 1.218 eV, in good agreement with the experimental value of 1.236 eV. The problem of convergence of positron-atom bound state calculations is investigated, and means to improve it are discussed. The relativistic character of the method and its satisfactory convergence make it a suitable tool for heavier atoms.Comment: 15 pages, 5 figures, RevTe

Photoproduction of K+K− meson pairs on the proton

The exclusive reaction γp→pK+K− was studied in the photon energy range 3.0–3.8  GeV and momentum transfer range 0.6<−t<1.3  GeV2. Data were collected with the CLAS detector at the Thomas Jefferson National Accelerator Facility. In this kinematic range the integrated luminosity was approximately 20  pb−1. The reaction was isolated by detecting the K+ and the proton in CLAS, and reconstructing the K− via the missing-mass technique. Moments of the dikaon decay angular distributions were extracted from the experimental data. Besides the dominant contribution of the ϕ meson in the P wave, evidence for S−P interference was found. The differential production cross sections dσ/dt for individual waves in the mass range of the ϕ resonance were extracted and compared to predictions of a Regge-inspired model. This is the first time the t-dependent cross section of the S-wave contribution to the elastic K+K− photoproduction has been measured

Activation of a Metabolic Gene Regulatory Network Downstream of mTOR Complex 1

Aberrant activation of the mammalian target of rapamycin complex 1 (mTORC1) is a common molecular event in a variety of pathological settings, including genetic tumor syndromes, cancer, and obesity. However, the cell-intrinsic consequences of mTORC1 activation remain poorly defined. Through a combination of unbiased genomic, metabolomic, and bioinformatic approaches, we demonstrate that mTORC1 activation is sufficient to stimulate specific metabolic pathways, including glycolysis, the oxidative arm of the pentose phosphate pathway, and de novo lipid biosynthesis. This is achieved through the activation of a transcriptional program affecting metabolic gene targets of hypoxia-inducible factor (HIF1α) and sterol regulatory element-binding protein (SREBP1 and SREBP2). We find that SREBP1 and 2 promote proliferation downstream of mTORC1, and the activation of these transcription factors is mediated by S6K1. Therefore, in addition to promoting protein synthesis, mTORC1 activates specific bioenergetic and anabolic cellular processes that are likely to contribute to human physiology and disease