New vibrational assignments for the nu1 to nu17 vibrational modes of aziridine and first analysis of the high resolution infrared spectrum of aziridine between 720 cm-1 and 1050 cm-1

International audienceFourier transform spectra of aziridine (C2H4NH) were recorded at high resolution (0.002 or 0.003 cm-1) in the 600-1750 and 1750-4000 cm-1 regions, using a Bruker IFS125HR spectrometer, located at the LISA facility in Creteil. In parallel, the harmonic force field of aziridine was evaluated analytically at the optimized geometry with second-order Møller-Plesset perturbation theory (MP2) together with the correlation-consistent polarized valence triple zeta basis sets cc-pVTZ. These ab initio predictions were used to perform consistent vibrational assignments for the nu1 to nu17 fundamental bands of aziridine observed in the infrared spectra recorded during this study. Finally, a first detailed rotational assignment was performed for two B-type bands located at 772.3571 cm-1 (nu10, CH2 rock) and 997.1592 cm-1 (nu8, NH bend) and for an A-type band located at 904.0429 cm-1 nu17 , ring deform). We noticed that the nu10 band is weakly perturbed, presumably because the v10 = 1 rotational levels are coupled with those of the v18 = 1 dark band located around 817 cm-1 through B-type and C-type Coriolis resonances

Hardware division by small integer constants

International audienceThis article studies the design of custom circuits for division by a small positive constant. Such circuits can be useful to specific FPGA and ASIC applications. The first problem studied is the Euclidean division of an unsigned integer by a constant, computing a quotient and a remainder. Several new solutions are proposed and compared against the state of the art. As the proposed solutions use small look-up tables, they match well the hardware resources of an FPGA. The article then studies whether the division by the product of two constants is better implemented as two successive dividers or as one atomic divider. It also considers the case when only a quotient or only a remainder are needed. Finally, it addresses the correct rounding of the division of a floating-point number by a small integer constant. All these solutions, and the previous state of the art, are compared in terms of timing, area, and area-timing product. In general, the relevance domains of the various techniques are very different on FPGA and on ASIC

13C—methyl formate : observations of a sample of high mass starforming regions including Orion—KL and spectroscopic characterization

We have surveyed a sample of massive star-forming regions located over a range of distances from the Galactic centre for methyl formate, HCOOCH3, and its isotopologues H13COOCH3 and HCOO13CH3. The observations were carried out with the APEX telescope in the frequency range 283.4-287.4 GHz. Based on the APEX observations, we report tentative detections of the 13C-methyl formate isotopologue HCOO13CH3 towards the following four massive star-forming regions: Sgr B2(N-LMH), NGC 6334 IRS 1, W51 e2 and G19.61-0.23. In addition, we have used the 1 mm ALMA science verification observations of Orion-KL and confirm the detection of the 13C-methyl formate species in Orion-KL and image its spatial distribution. Our analysis shows that the 12C/13C isotope ratio in methyl formate toward Orion-KL Compact Ridge and Hot Core-SW components (68.4±10.1 and 71.4±7.8, respectively) are, for both the 13C-methyl formate isotopologues, commensurate with the average 12C/13C ratio of CO derived toward Orion-KL. Likewise, regarding the other sources, our results are consistent with the 12C/13C in CO. We also report the spectroscopic characterization, which includes a complete partition function, of the complex H13COOCH3 and HCOO13CH3 species. New spectroscopic data for both isotopomers H13COOCH3 and HCOO13CH3, presented in this study, has made it possible to measure this fundamentally important isotope ratio in a large organic molecule for the first time.This work was supported by the National Science Foundation under grant 1008800. We are grateful to the Ministerio de Economia y Competitividad of Spain for the financial support through grant No. FIS2011-28738-C02-02 and to the French Government through grant No. ANR-08-BLAN-0054 and the French PCMI (Programme National de Physique Chimie du Milieu Interstellaire). This paper makes use of the following ALMA data: ADS/JAO. ALMA#2011.0.00009.SV.ALMAis a partnership of ESO (representing its member states), NSF (USA), and NINS (Japan), together with NRC (Canada) and NSC and ASIAA (Taiwan), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO, and NAOJ. C.F. thanks Dahbia Talbi, Eric Herbst, and Anthony Remijan for enlightening discussions. Finally, we thank the anonymous referee for helpful comments

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

Survival of the Fittest: Positive Selection of CD4+ T Cells Expressing a Membrane-Bound Fusion Inhibitor Following HIV-1 Infection

Although a variety of genetic strategies have been developed to inhibit HIV replication, few direct comparisons of the efficacy of these inhibitors have been carried out. Moreover, most studies have not examined whether genetic inhibitors are able to induce a survival advantage that results in an expansion of genetically-modified cells following HIV infection. We evaluated the efficacy of three leading genetic strategies to inhibit HIV replication: 1) an HIV-1 tat/rev-specific small hairpin (sh) RNA; 2) an RNA antisense gene specific for the HIV-1 envelope; and 3) a viral entry inhibitor, maC46. In stably transduced cell lines selected such that >95% of cells expressed the genetic inhibitor, the RNA antisense envelope and viral entry inhibitor maC46 provided the strongest inhibition of HIV-1 replication. However, when mixed populations of transduced and untransduced cells were challenged with HIV-1, the maC46 fusion inhibitor resulted in highly efficient positive selection of transduced cells, an effect that was evident even in mixed populations containing as few as 1% maC46-expressing cells. The selective advantage of the maC46 fusion inhibitor was also observed in HIV-1-infected cultures of primary T lymphocytes as well as in HIV-1-infected humanized mice. These results demonstrate robust inhibition of HIV replication with the fusion inhibitor maC46 and the antisense Env inhibitor, and importantly, a survival advantage of cells expressing the maC46 fusion inhibitor both in vitro and in vivo. Evaluation of the ability of genetic inhibitors of HIV-1 replication to confer a survival advantage on genetically-modified cells provides unique information not provided by standard techniques that may be important in the in vivo efficacy of these genes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Une présentation condensée des règles de sélection en spectroscopie micro-onde

Les auteurs proposent une nouvelle présentation graphique simple et concise des règles de sélection régissant le spectre de rotation pure d’une toupie rigide asymétrique et en soulignent l’intérêt en décrivant quelques applications

Semiexperimental Equilibrium Structure For Cis,trans-1,4-difluorobutadiene By The Mixed Estimation Method

The available experimental rotational constants of cis,trans-1,4-difluorobutadiene do not permit a determination of a complete structure. However, this problem, rather frequent in finding structures, may be solved by the mixed estimation method. The experimental ground state rotational constants are corrected for the rovibrational contribution calculated from an ab initio force field. These semiexperimental data are supplemented by structural parameters from ab initio calculations and a weighted least-squares fit allows us to obtain a reasonable structure. The accuracy of the fitted parameters is checked by optimizing a structure at the coupled cluster level. A good agreement is found between the two methods, validating our procedure