Density Functional Theory calculation on many-cores hybrid CPU-GPU architectures

The implementation of a full electronic structure calculation code on a hybrid parallel architecture with Graphic Processing Units (GPU) is presented. The code which is on the basis of our implementation is a GNU-GPL code based on Daubechies wavelets. It shows very good performances, systematic convergence properties and an excellent efficiency on parallel computers. Our GPU-based acceleration fully preserves all these properties. In particular, the code is able to run on many cores which may or may not have a GPU associated. It is thus able to run on parallel and massive parallel hybrid environment, also with a non-homogeneous ratio CPU/GPU. With double precision calculations, we may achieve considerable speedup, between a factor of 20 for some operations and a factor of 6 for the whole DFT code.Comment: 14 pages, 8 figure

Universal quantum interfaces

To observe or control a quantum system, one must interact with it via an interface. This letter exhibits simple universal quantum interfaces--quantum input/output ports consisting of a single two-state system or quantum bit that interacts with the system to be observed or controlled. It is shown that under very general conditions the ability to observe and control the quantum bit on its own implies the ability to observe and control the system itself. The interface can also be used as a quantum communication channel, and multiple quantum systems can be connected by interfaces to become an efficient universal quantum computer. Experimental realizations are proposed, and implications for controllability, observability, and quantum information processing are explored.Comment: 4 pages, 3 figures, RevTe

Modular cell-based platform for high throughput identification of compounds that inhibit a viral interferon antagonist of choice

The work was supported by the Medical Research Council, U.K. (University of St Andrews Doctoral Training Grant to AV and CSA), Deutsche Forschungsgemeinschaft (PA 815/2-1) to CP, Tenovus Scotland (T15/38) to MN and Wellcome Trust to CP, MN (ISSF) and RER (101788/Z/13/Z)Viral interferon (IFN) antagonists are a diverse class of viral proteins that counteract the host IFN response, which is important for controlling viral infections. Viral IFN antagonists are often multifunctional proteins that perform vital roles in virus replication beyond IFN antagonism. The critical importance of viral IFN antagonists is highlighted by the fact that almost all viruses encode one of these proteins. Inhibition of viral IFN antagonists has the potential to exert pleiotropic antiviral effects and thus this important protein class represents a diverse plethora of novel therapeutic targets. To exploit this, we have successfully developed and executed a novel modular cell-based platform that facilitates the safe and rapid screening for inhibitors of a viral IFN antagonist of choice. The platform is based on two reporter cell-lines that provide a simple method to detect activation of IFN induction or signaling via an eGFP gene placed under the control of the IFNβ or an ISRE-containing promoter, respectively. Expression of a target IFN antagonist in the appropriate reporter cell-line will block the IFN response and hence eGFP expression. We hypothesized that addition of a compound that inhibits IFN antagonist function will release the block imposed on the IFN response and hence restore eGFP expression, providing a measurable parameter for high throughput screening (HTS). We demonstrate assay proof-of-concept by (i) exploiting hepatitis C virus (HCV) protease inhibitors to inhibit NS3-4A's capacity to block IFN induction and (ii) successfully executing two HTS targeting viral IFN antagonists that block IFN signaling; NS2 and IE1 from human respiratory syncytial virus (RSV) and cytomegalovirus (CMV) respectively, two clinically important viruses for which vaccine development has thus far been unsuccessful and new antivirals are required. Both screens performed robustly and Z′ Factor scores of >0.6 were achieved. We identified (i) four hit compounds that specifically inhibit RSV NS2's ability to block IFN signaling by mediating STAT2 degradation and exhibit modest antiviral activity and (ii) two hit compounds that interfere with IE1 transcription and significantly impair CMV replication. Overall, we demonstrate assay proof-of-concept as we target viral IFN antagonists from unrelated viruses and demonstrate its suitability for HTS.Publisher PDFPeer reviewe

Acetylsalicylic acid as an adjuvant therapy for schizophrenia

BACKGROUND: Findings from both epidemiological and basic research point to the possibility that NSAIDS impede the deterioration in schizophrenia. METHODS: To study the efficacy of acetylsalicylic acid we will perform a randomized placebo controlled double-blind add-on trial of 80 inpatients and outpatients with schizophrenia, schizophreniform or schizoaffective disorder. Patients will be 1:1 randomized to either 3 months 1000 mg acetylsalicylic acid per day or 3 months placebo, in addition to their regular antipsychotic treatment. All patients will receive pantoprazole treatment for gastroprotection. The outcomes of this study are 3-month change in psychotic and negative symptom severity, cognitive function, and several immunological parameters. This trial may (1) yield a new (adjuvant) therapy for schizophrenia and (2) add to the knowledge on the pathogenesis of this major psychiatric disorder

The Complete Genome of Propionibacterium freudenreichii CIRM-BIA1T, a Hardy Actinobacterium with Food and Probiotic Applications

Background: Propionibacterium freudenreichii is essential as a ripening culture in Swiss-type cheeses and is also considered for its probiotic use [1]. This species exhibits slow growth, low nutritional requirements, and hardiness in many habitats. It belongs to the taxonomic group of dairy propionibacteria, in contrast to the cutaneous species P. acnes. The genome of the type strain, P. freudenreichii subsp. shermanii CIRM-BIA1 (CIP 103027T), was sequenced with an 11-fold coverage. Methodology/Principal Findings: The circular chromosome of 2.7 Mb of the CIRM-BIA1 strain has a GC-content of 67% and contains 22 different insertion sequences (3.5% of the genome in base pairs). Using a proteomic approach, 490 of the 2439 predicted proteins were confirmed. The annotation revealed the genetic basis for the hardiness of P. freudenreichii, as the bacterium possesses a complete enzymatic arsenal for de novo biosynthesis of aminoacids and vitamins (except panthotenate and biotin) as well as sequences involved in metabolism of various carbon sources, immunity against phages, duplicated chaperone genes and, interestingly, genes involved in the management of polyphosphate, glycogen and trehalose storage. The complete biosynthesis pathway for a bifidogenic compound is described, as well as a high number of surface proteins involved in interactions with the host and present in other probiotic bacteria. By comparative genomics, no pathogenicity factors found in P. acnes or in other pathogenic microbial species were identified in P. freudenreichii, which is consistent with the Generally Recognized As Safe and Qualified Presumption of Safety status of P. freudenreichii. Various pathways for formation of cheese flavor compounds were identified: the Wood-Werkman cycle for propionic acid formation, amino acid degradation pathways resulting in the formation of volatile branched chain fatty acids, and esterases involved in the formation of free fatty acids and esters. Conclusions/Significance: With the exception of its ability to degrade lactose, P. freudenreichii seems poorly adapted to dairy niches. This genome annotation opens up new prospects for the understanding of the P. freudenreichii probiotic activity

Lipid Nanocapsules Loaded with Rhenium-188 Reduce Tumor Progression in a Rat Hepatocellular Carcinoma Model

International audienceBACKGROUND: Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC(188)Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC(188)Re-SSS in a chemically induced hepatocellular carcinoma rat model. METHODOLOGY/PRINCIPAL FINDINGS: Animals were treated with an injection of LNC(188)Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n = 12; 120 MBq, n = 11) were compared with sham (n = 12), blank LNC (n = 7) and (188)Re-perrhenate (n = 4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC(188)Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC(188)Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. CONCLUSIONS/SIGNIFICANCE: Overall, these results demonstrate that internal radiation with LNC(188)Re-SSS is a promising new strategy for hepatocellular carcinoma treatment

Diffusion-Driven Looping Provides a Consistent Framework for Chromatin Organization

Chromatin folding inside the interphase nucleus of eukaryotic cells is done on multiple scales of length and time. Despite recent progress in understanding the folding motifs of chromatin, the higher-order structure still remains elusive. Various experimental studies reveal a tight connection between genome folding and function. Chromosomes fold into a confined subspace of the nucleus and form distinct territories. Chromatin looping seems to play a dominant role both in transcriptional regulation as well as in chromatin organization and has been assumed to be mediated by long-range interactions in many polymer models. However, it remains a crucial question which mechanisms are necessary to make two chromatin regions become co-located, i.e. have them in spatial proximity. We demonstrate that the formation of loops can be accomplished solely on the basis of diffusional motion. The probabilistic nature of temporary contacts mimics the effects of proteins, e.g. transcription factors, in the solvent. We establish testable quantitative predictions by deriving scale-independent measures for comparison to experimental data. In this Dynamic Loop (DL) model, the co-localization probability of distant elements is strongly increased compared to linear non-looping chains. The model correctly describes folding into a confined space as well as the experimentally observed cell-to-cell variation. Most importantly, at biological densities, model chromosomes occupy distinct territories showing less inter-chromosomal contacts than linear chains. Thus, dynamic diffusion-based looping, i.e. gene co-localization, provides a consistent framework for chromatin organization in eukaryotic interphase nuclei

PoPMuSiC 2.1: a web server for the estimation of protein stability changes upon mutation and sequence optimality

ABSTRACT:Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Novel Anti-Metastatic Action of Cidofovir Mediated by Inhibition of E6/E7, CXCR4 and Rho/ROCK Signaling in HPV+ Tumor Cells

Cervical cancer is frequently associated with HPV infection. The expression of E6 and E7 HPV oncoproteins is a key factor in its carcinogenicity and might also influence its virulence, including metastatic conversion. The cellular mechanisms involved in metastatic spread remain elusive, but pro-adhesive receptors and their ligands, such as SDF-1α and CXCR4 are implicated. In the present study, we assessed the possible relationship between SDF-1α/CXCR4 signaling, E6/E7 status and the metastatic process. We found that SDF-1α stimulated the invasion of E6/E7-positive cancer cell lines (HeLa and TC-1) in Matrigel though CXCR4 and subsequent Rho/ROCK activation. In pulmonary metastatic foci generated by TC-1 cells IV injection a high proportion of cells expressed membrane-associated CXCR4. In both cases models (in vitro and in vivo) cell adhesion and invasion was abrogated by CXCR4 immunological blockade supporting a contribution of SDF-1α/CXCR4 to the metastatic process. E6 and E7 silencing using stable knock-down and the approved anti-viral agent, Cidofovir decreased CXCR4 gene expression as well as both, constitutive and SDF-1α-induced cell invasion. In addition, Cidofovir inhibited lung metastasis (both adhesion and invasion) supporting contribution of E6 and E7 oncoproteins to the metastatic process. Finally, potential signals activated downstream SDF-1α/CXCR4 and involved in lung homing of E6/E7-expressing tumor cells were investigated. The contribution of the Rho/ROCK pathway was suggested by the inhibitory effect triggered by Cidofovir and further confirmed using Y-27632 (a small molecule ROCK inhibitor). These data suggest a novel and highly translatable therapeutic approach to cervix cancer, by inhibition of adhesion and invasion of circulating HPV-positive tumor cells, using Cidofovir and/or ROCK inhibition

Developmental Stability: A Major Role for Cyclin G in Drosophila melanogaster

Morphological consistency in metazoans is remarkable given the pervasive occurrence of genetic variation, environmental effects, and developmental noise. Developmental stability, the ability to reduce developmental noise, is a fundamental property of multicellular organisms, yet its genetic bases remains elusive. Imperfect bilateral symmetry, or fluctuating asymmetry, is commonly used to estimate developmental stability. We observed that Drosophila melanogaster overexpressing Cyclin G (CycG) exhibit wing asymmetry clearly detectable by sight. Quantification of wing size and shape using geometric morphometrics reveals that this asymmetry is a genuine—but extreme—fluctuating asymmetry. Overexpression of CycG indeed leads to a 40-fold increase of wing fluctuating asymmetry, which is an unprecedented effect, for any organ and in any animal model, either in wild populations or mutants. This asymmetry effect is not restricted to wings, since femur length is affected as well. Inactivating CycG by RNAi also induces fluctuating asymmetry but to a lesser extent. Investigating the cellular bases of the phenotypic effects of CycG deregulation, we found that misregulation of cell size is predominant in asymmetric flies. In particular, the tight negative correlation between cell size and cell number observed in wild-type flies is impaired when CycG is upregulated. Our results highlight the role of CycG in the control of developmental stability in D. melanogaster. Furthermore, they show that wing developmental stability is normally ensured via compensatory processes between cell growth and cell proliferation. We discuss the possible role of CycG as a hub in a genetic network that controls developmental stability