Extension of the MIRS computer package for the modeling of molecular spectra : from effective to full ab initio ro-vibrational hamiltonians in irreducible tensor form

The MIRS software for the modeling of ro-vibrational spectra of polyatomic molecules was considerably extended and improved. The original version (Nikitin, et al. JQSRT, 2003, pp. 239--249) was especially designed for separate or simultaneous treatments of complex band systems of polyatomic molecules. It was set up in the frame of effective polyad models by using algorithms based on advanced group theory algebra to take full account of symmetry properties. It has been successfully used for predictions and data fitting (positions and intensities) of numerous spectra of symmetric and spherical top molecules within the vibration extrapolation scheme. The new version offers more advanced possibilities for spectra calculations and modeling by getting rid of several previous limitations particularly for the size of polyads and the number of tensors involved. It allows dealing with overlapping polyads and includes more efficient and faster algorithms for the calculation of coefficients related to molecular symmetry properties (6C, 9C and 12C symbols for C_{3v}, T_{d}, and O_{h} point groups) and for better convergence of least-square-fit iterations as well. The new version is not limited to polyad effective models. It also allows direct predictions using full ab initio ro-vibrational normal mode hamiltonians converted into the irreducible tensor form. Illustrative examples on CH_{3} D, CH_{4}, CH_{3} Cl, CH_{3} F and PH_{3} are reported reflecting the present status of data available. It is written in C++ for standard PC computer operating under Windows. The full package including on-line documentation and recent data are freely available at [http://www.iao.ru/mirs/mirs.htm] or [http://xeon.univ-reims.fr/Mirs/||http://xeon.univ-reims.fr/Mirs/] or [http://icb.u-bourgogne.fr/OMR/SMA/SHTDS/MIRS.html].Comment: Journal of Quantitative Spectroscopy and Radiative Transfer (2012) xxx-xx

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

Chemical kinetics in an atmospheric pressure helium plasma containing humidity

Atmospheric pressure plasmas are sources of biologically active oxygen and nitrogen species, which makes them potentially suitable for the use as biomedical devices. Here, experiments and simulations are combined to investigate the formation of the key reactive oxygen species, atomic oxygen (O) and hydroxyl radicals (OH), in a radio-frequency driven atmospheric pressure plasma jet operated in humidified helium. Vacuum ultra-violet high-resolution Fourier-transform absorption spectroscopy and ultra-violet broad-band absorption spectroscopy are used to measure absolute densities of O and OH. These densities increase with increasing H 2 O content in the feed gas, and approach saturation values at higher admixtures on the order of 3 × 10 14 cm −3 for OH and 3 × 10 13 cm −3 for O. Experimental results are used to benchmark densities obtained from zero-dimensional plasma chemical kinetics simulations, which reveal the dominant formation pathways. At low humidity content, O is formed from OH + by proton transfer to H 2 O, which also initiates the formation of large cluster ions. At higher humidity content, O is created by reactions between OH radicals, and lost by recombination with OH. OH is produced mainly from H 2 O + by proton transfer to H 2 O and by electron impact dissociation of H 2 O. It is lost by reactions with other OH molecules to form either H 2 O + O or H 2 O 2 . Formation pathways change as a function of humidity content and position in the plasma channel. The understanding of the chemical kinetics of O and OH gained in this work will help in the development of plasma tailoring strategies to optimise their densities in applications

Independent and combined effects of improved water, sanitation, and hygiene, and improved complementary feeding, on child stunting and anaemia in rural Zimbabwe: a cluster-randomised trial.

BACKGROUND: Child stunting reduces survival and impairs neurodevelopment. We tested the independent and combined effects of improved water, sanitation, and hygiene (WASH), and improved infant and young child feeding (IYCF) on stunting and anaemia in in Zimbabwe. METHODS: We did a cluster-randomised, community-based, 2 × 2 factorial trial in two rural districts in Zimbabwe. Clusters were defined as the catchment area of between one and four village health workers employed by the Zimbabwe Ministry of Health and Child Care. Women were eligible for inclusion if they permanently lived in clusters and were confirmed pregnant. Clusters were randomly assigned (1:1:1:1) to standard of care (52 clusters), IYCF (20 g of a small-quantity lipid-based nutrient supplement per day from age 6 to 18 months plus complementary feeding counselling; 53 clusters), WASH (construction of a ventilated improved pit latrine, provision of two handwashing stations, liquid soap, chlorine, and play space plus hygiene counselling; 53 clusters), or IYCF plus WASH (53 clusters). A constrained randomisation technique was used to achieve balance across the groups for 14 variables related to geography, demography, water access, and community-level sanitation coverage. Masking of participants and fieldworkers was not possible. The primary outcomes were infant length-for-age Z score and haemoglobin concentrations at 18 months of age among children born to mothers who were HIV negative during pregnancy. These outcomes were analysed in the intention-to-treat population. We estimated the effects of the interventions by comparing the two IYCF groups with the two non-IYCF groups and the two WASH groups with the two non-WASH groups, except for outcomes that had an important statistical interaction between the interventions. This trial is registered with ClinicalTrials.gov, number NCT01824940. FINDINGS: Between Nov 22, 2012, and March 27, 2015, 5280 pregnant women were enrolled from 211 clusters. 3686 children born to HIV-negative mothers were assessed at age 18 months (884 in the standard of care group from 52 clusters, 893 in the IYCF group from 53 clusters, 918 in the WASH group from 53 clusters, and 991 in the IYCF plus WASH group from 51 clusters). In the IYCF intervention groups, the mean length-for-age Z score was 0·16 (95% CI 0·08-0·23) higher and the mean haemoglobin concentration was 2·03 g/L (1·28-2·79) higher than those in the non-IYCF intervention groups. The IYCF intervention reduced the number of stunted children from 620 (35%) of 1792 to 514 (27%) of 1879, and the number of children with anaemia from 245 (13·9%) of 1759 to 193 (10·5%) of 1845. The WASH intervention had no effect on either primary outcome. Neither intervention reduced the prevalence of diarrhoea at 12 or 18 months. No trial-related serious adverse events, and only three trial-related adverse events, were reported. INTERPRETATION: Household-level elementary WASH interventions implemented in rural areas in low-income countries are unlikely to reduce stunting or anaemia and might not reduce diarrhoea. Implementation of these WASH interventions in combination with IYCF interventions is unlikely to reduce stunting or anaemia more than implementation of IYCF alone. FUNDING: Bill & Melinda Gates Foundation, UK Department for International Development, Wellcome Trust, Swiss Development Cooperation, UNICEF, and US National Institutes of Health.The SHINE trial is funded by the Bill & Melinda Gates Foundation (OPP1021542 and OPP113707); UK Department for International Development; Wellcome Trust, UK (093768/Z/10/Z, 108065/Z/15/Z and 203905/Z/16/Z); Swiss Agency for Development and Cooperation; US National Institutes of Health (2R01HD060338-06); and UNICEF (PCA-2017-0002)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Multi-resolution investigations of the methane IR spectrum. At the borderline between modelling state of the art and astrophysical needs

International audienceRemote sensing of the atmosphere of astrophysical objects relies essentially on molecular spectroscopy. Astrophysical investigations generally need both complete and accurate spectroscopic databases. Despite continuous efforts in experimental and theoretical spectroscopic investigations, the lack of data in specific spectral regions of interest is one of the principal limitation of the presently available spectroscopic databases. Extrapolations to relevant experimental conditions like high temperature is also a major issue for astrophysical applications. Among other molecules, methane is present in the atmosphere of many astrophysical objects. The modeling of its absorption coefficient in the near infrared and/or at high temperature remains a challenge mainly because of the intrinsic complexity of its ro-vibrational spectrum. Global effective models, introduced very early, were successfully applied to provide a unified description of the successive lower polyads of the molecule. Unfortunaltely, the extremely large density of levels in highly excited polyads make it very difficult (if not to say impossible) to envisage line by line modeling above say 10 000 cm-1. In fact, the present state of the art of high-resolution modeling is limited approximately to the spectral region below around 5 000 cm-1 (see [1] and references therein). It is very likely that high-resolution line by line modeling up to 10 000 cm-1 will take several years. The talk will be focused on multi-resolution approaches especially designed for astrophysical applications for which the completeness and the reliability of spectroscopic data is at least as important as the resolution itself. The interest of low resolution investigations based on low order expansions of global effective polyad hamiltonians and transition moment operators will be discussed. By fitting observed data including band profils or ab initio results such models may provide usefull information in situations where a gap exists between astrophysical needs and the present state of the art of spectroscopic modeling. Illustrations will be presented about high temperature methane : (i) improved partition sum calculation of methane at high temperature [2]; (ii) advanced statistical error analysis of multi-resolution absorption predictions involving hot band systems arising from highly excited states [3]. References 1. S. Albert, et al., Chem. Phys. 356, 131-146 (2009) 2. C. Wenger, J.P. Champion, V. Boudon, J.Q.S.R.T.. 109, 2697-2706 (2008), http://hal.archives-ouvertes.fr/hal-00277904/fr/ 3. C. Wenger, J.P. Champion, in preparation

Multi-resolution error analysis of predicted absorption coefficients. Method and computer implementation. Application to the IR spectrum of methane at high temperature.

A general method for the estimation of the confidence interval of molecular absorption coefficients is presented. It combines statistical numerical experiments with analytical calculations. The method uses line parameter predictions (position and intensity) with known estimated uncertainties. The propagation of errors from line parameters to absorption coefficients or cross-sections are analyzed in detail as a function of the resolution. This work is especially intended to provide expert information for applications requiring theoretical predictions for which the present state of the art of line by line high-resolution modeling is not accurate enough to meet the experimental precision. As an illustration, it is applied to predict the absorption coefficient of methane at high temperature involving simultaneously well known lower energy levels (cold bands) and higher energy levels with much lower precisions (hot bands). Potential extensions to applications for atmospheric remote sensing of astrophysical objects are discussed

Simulation de spectres à haute température : une approche statistique du compromis résolution / précision

International audienceMalgré les progrès continus enregistrés dans le domaine de la spectroscopie moléculaire, théorique et expérimentale, les banques de données spectroscopiques disponibles présentent des lacunes importantes, notamment pour l'interprétation des observations des environnements astrophysiques à haute température. Ce constat s'applique en particulier à la molécule de méthane présente dans les atmosphères de nombreux objets astrophysiques. La modélisation du coefficient d'absorption du méthane dans le proche infrarouge et/ou à haute température continue à défier les théoriciens du fait de la complexité intrinsèque de son spectre rovibrationnel. De fait, les analyses à haute résolution concernent les basses énergies et les efforts actuels portent sur la région allant jusqu'à environ 6000 cm-1 [1]. Des travaux théoriques récents seront présentés proposant des outils à destination des applications astrophysiques pour lesquelles l'exhaustivité et la fiabilité des données spectroscopiques est primordiale [2-3]. Ces travaux exploitent les modèles d'hamiltoniens effectifs globaux selon une approche multi-résolution incluant le calcul statistique. Il s'agit en fait d'intégrer dans les simulations de spectre des informations sur les niveaux très excités et sur la précision estimée de telles informations. Dans chaque contexte, le meilleur compromis « résolution / précision » est recherché, avec un souci de rigueur dans l'estimation même de la précision des données. Deux applications seront abordées : le calcul de la fonction de partition du méthane à haute température et la détermination de la bande de confiance du coefficient d'absorption du méthane à haute température en fonction de la résolution. Références [1] S. Albert, S. Bauerecker, V. Boudon, L. R. Brown, J. P. Champion, M. Loete, A. Nikitin, M. Quack, Global analysis of the high resolution infrared spectrum of methane 12CH4 in the region from 0 to 4800 cm-1, Chemical Physics 356 (1-3) (2009) 131-146. doi:10.1016/j.chemphys.2008.10.019. Et papier en préparation. [2] C. Wenger, J. P. Champion, V. Boudon, The partition sum of methane at high temperature, Journal of Quantitative Spectroscopy and Radiative Transfer 109 (16) (2008) 2697-2706. doi:10.1016/j.jqsrt.2008.06.006. http://icb.u-bourgogne.fr/JSP/TIPS.jsp http://hal.archives-ouvertes.fr/hal-00277904/fr/ [3] C. Wenger, J. P. Champion, Multi-Resolution error analysis of predicted absorption coefficients. Method and application to the infrared spectrum of methane at high temperature http://hal.archives-ouvertes.fr/hal-00473611/fr