Université d'Orléans

Good bacteria help fight cancer Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32

Abstract With the description of more and more complex one‐ and two‐dimensional NMR experiments comes the need to develop methods to make a comprehensive interpretation of the various different experiments that can be carried out on the same sample or series of related samples. We present some examples of modelling one‐ and two‐dimensional solid‐state NMR spectra of I = ½ spin and quadrupolar nuclei, using laboratory‐developed software that is made available to the NMR community. Copyright © 2001 John Wiley & Sons, Ltd.

LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.

The ‘4 per mille Soils for Food Security and Climate’ was launched at the COP21 with an aspiration to increase global soil organic matter stocks by 4 per 1000 (or 0.4 %) per year as a compensation for the global emissions of greenhouse gases by anthropogenic sources. This paper surveyed the soil organic carbon (SOC) stock estimates and sequestration potentials from 20 regions in the world (New Zealand, Chile, South Africa, Australia, Tanzania, Indonesia, Kenya, Nigeria, India, China Taiwan, South Korea, China Mainland, United States of America, France, Canada, Belgium, England & Wales, Ireland, Scotland, and Russia). We asked whether the 4 per mille initiative is feasible for the region. The outcomes highlight region specific efforts and scopes for soil carbon sequestration. Reported soil C sequestration rates globally show that under best management practices, 4 per mille or even higher sequestration rates can be accomplished. High C sequestration rates (up to 10 per mille) can be achieved for soils with low initial SOC stock (topsoil less than 30 t C ha− 1), and at the first twenty years after implementation of best management practices. In addition, areas which have reached equilibrium will not be able to further increase their sequestration. We found that most studies on SOC sequestration only consider topsoil (up to 0.3 m depth), as it is considered to be most affected by management techniques. The 4 per mille number was based on a blanket calculation of the whole global soil profile C stock, however the potential to increase SOC is mostly on managed agricultural lands. If we consider 4 per mille in the top 1m of global agricultural soils, SOC sequestration is between 2-3 Gt C year− 1, which effectively offset 20–35% of global anthropogenic greenhouse gas emissions. As a strategy for climate change mitigation, soil carbon sequestration buys time over the next ten to twenty years while other effective sequestration and low carbon technologies become viable. The challenge for cropping farmers is to find disruptive technologies that will further improve soil condition and deliver increased soil carbon. Progress in 4 per mille requires collaboration and communication between scientists, farmers, policy makers, and marketeers.

BACKGROUND: Virtual screening methods start to be well established as effective approaches to identify hits, candidates and leads for drug discovery research. Among those, structure based virtual screening (SBVS) approaches aim at docking collections of small compounds in the target structure to identify potent compounds. For SBVS, the identification of candidate pockets in protein structures is a key feature, and the recent years have seen increasing interest in developing methods for pocket and cavity detection on protein surfaces. RESULTS: Fpocket is an open source pocket detection package based on Voronoi tessellation and alpha spheres built on top of the publicly available package Qhull. The modular source code is organised around a central library of functions, a basis for three main programs: (i) Fpocket, to perform pocket identification, (ii) Tpocket, to organise pocket detection benchmarking on a set of known protein-ligand complexes, and (iii) Dpocket, to collect pocket descriptor values on a set of proteins. Fpocket is written in the C programming language, which makes it a platform well suited for the scientific community willing to develop new scoring functions and extract various pocket descriptors on a large scale level. Fpocket 1.0, relying on a simple scoring function, is able to detect 94% and 92% of the pockets within the best three ranked pockets from the holo and apo proteins respectively, outperforming the standards of the field, while being faster. CONCLUSION: Fpocket provides a rapid, open source and stable basis for further developments related to protein pocket detection, efficient pocket descriptor extraction, or drugablity prediction purposes. Fpocket is freely available under the GNU GPL license at http://fpocket.sourceforge.net.

We present the third Fermi Large Area Telescope (LAT) source catalog (3FGL) of sources in the 100 MeV-300 GeV range. Based on the first 4 yr of science data from the Fermi Gamma-ray Space Telescope mission, it is the deepest yet in this energy range. Relative to the Second Fermi LAT catalog, the 3FGL catalog incorporates twice as much data, as well as a number of analysis improvements, including improved calibrations at the event reconstruction level, an updated model for Galactic diffuse -ray emission, a refined procedure for source detection, and improved methods for associating LAT sources with potential counterparts at other wavelengths. The 3FGL catalog includes 3033 sources above 4 significance, with source location regions, spectral properties, and monthly light curves for each. Of these, 78 are flagged as potentially being due to imperfections in the model for Galactic diffuse emission. Twenty-five sources are modeled explicitly as spatially extended, and overall 238 sources are considered as identified based on angular extent or correlated variability (periodic or otherwise) observed at other wavelengths. For 1010 sources we have not found plausible counterparts at other wavelengths. More than 1100 of the identified or associated sources are active galaxies of the blazar class; several other classes of non-blazar active galaxies are also represented in the 3FGL. Pulsars represent the largest Galactic source class. From source counts of Galactic sources we estimate that the contribution of unresolved sources to the Galactic diffuse emission is 3% at 1 GeV.

Abstract Metasedimentary rocks generally contain carbonaceous material (CM) deriving from the evolution of organic matter originally present in the host sedimentary rock. During metamorphic processes, this organic matter is progressively transformed into graphite s.s. and the degree of organisation of CM is known as a reliable indicator of metamorphic grade. In this study, the degree of organisation of CM was systematically characterised by Raman microspectroscopy across several Mesozoic and Cenozoic reference metamorphic belts. This degree of organisation, including within‐sample heterogeneity, was quantified by the relative area of the defect band (R2 ratio). The results from the Schistes Lustrés (Western Alps) and Sanbagawa (Japan) cross‐sections show that (1) even through simple visual inspection, changes in the CM Raman spectrum appear sensitive to variations of metamorphic grade, (2) there is an excellent agreement between the R2 values calculated for the two sections when considering samples with an equivalent metamorphic grade, and (3) the evolution of the R2 ratio with metamorphic grade is controlled by temperature ( T ). Along the Tinos cross‐section (Greece), which is characterised by a strong gradient of greenschist facies overprint on eclogite facies rocks, the R2 ratio is nearly constant. Consequently, the degree of organisation of CM is not affected by the retrogression and records peak metamorphic conditions. More generally, analysis of 54 samples representative of high‐temperature, low‐pressure to high‐pressure, low‐temperature metamorphic gradients shows that there is a linear correlation between the R2 ratio and the peak temperature [ T (°C) = −445 R2 + 641], whatever the metamorphic gradient and, probably, the organic precursor. The Raman spectrum of CM can therefore be used as a geothermometer of the maximum temperature conditions reached during regional metamorphism. Temperature can be estimated to ± 50 °C in the range 330–650 °C. A few technical indications are given for optimal application.

<p>Ammonia, a molecule that is gaining more interest as a fueling vector, has been considered as a candidate to power transport, produce energy, and support heating applications for decades. However, the particular characteristics of the molecule always made it a chemical with low, if any, benefit once compared to conventional fossil fuels. Still, the current need to decarbonize our economy makes the search of new methods crucial to use chemicals, such as ammonia, that can be produced and employed without incurring in the emission of carbon oxides. Therefore, current efforts in this field are leading scientists, industries, and governments to seriously invest efforts in the development of holistic solutions capable of making ammonia a viable fuel for the transition toward a clean future. On that basis, this review has approached the subject gathering inputs from scientists actively working on the topic. The review starts from the importance of ammonia as an energy vector, moving through all of the steps in the production, distribution, utilization, safety, legal considerations, and economic aspects of the use of such a molecule to support the future energy mix. Fundamentals of combustion and practical cases for the recovery of energy of ammonia are also addressed, thus providing a complete view of what potentially could become a vector of crucial importance to the mitigation of carbon emissions. Different from other works, this review seeks to provide a holistic perspective of ammonia as a chemical that presents benefits and constraints for storing energy from sustainable sources. State-of-the-art knowledge provided by academics actively engaged with the topic at various fronts also enables a clear vision of the progress in each of the branches of ammonia as an energy carrier. Further, the fundamental boundaries of the use of the molecule are expanded to real technical issues for all potential technologies capable of using it for energy purposes, legal barriers that will be faced to achieve its deployment, safety and environmental considerations that impose a critical aspect for acceptance and wellbeing, and economic implications for the use of ammonia across all aspects approached for the production and implementation of this chemical as a fueling source. Herein, this work sets the principles, research, practicalities, and future views of a transition toward a future where ammonia will be a major energy player. </p>

Abstract This paper presents a synthetic view of the geodynamic evolution of the Zagros orogen within the frame of the Arabia–Eurasia collision. The Zagros orogen and the Iranian plateau preserve a record of the long-standing convergence history between Eurasia and Arabia across the Neo-Tethys, from subduction/obduction processes to present-day collision (from ~ 150 to 0 Ma). We herein combine the results obtained on several geodynamic issues, namely the location of the oceanic suture zone, the age of oceanic closure and collision, the magmatic and geochemical evolution of the Eurasian upper plate during convergence (as testified by the successive Sanandaj–Sirjan, Kermanshah and Urumieh–Dokhtar magmatic arcs), the P–T–t history of the few Zagros blueschists, the convergence characteristics across the Neo-Tethys (kinematic velocities, tomographic constraints, subduction zones and obduction processes), together with a survey of recent results gathered by others. We provide lithospheric-scale reconstructions of the Zagros orogen from ~ 150 to 0 Ma across two SW–NE transects. The evolution of the Zagros orogen is also compared to those of the nearby Turkish and Himalayan orogens. In our geotectonic scenario for the Zagros convergence, we outline three main periods/regimes: (1) the Mid to Late Cretaceous (115–85 Ma) corresponds to a distinctive period of perturbation of subduction processes and interplate mechanical coupling marked by blueschist exhumation and upper-plate fragmentation, (2) the Paleocene–Eocene (60–40 Ma) witnesses slab break-off, major shifts in arc magmatism and distributed extension within the upper plate, and (3) from the Oligocene onwards (~ 30–0 Ma), collision develops with a progressive SW migration of deformation and topographic build-up (Sanandaj–Sirjan Zone: 20–15 Ma, High Zagros: ~12–8 Ma; Simply Folded Belt: 5–0 Ma) and with partial slab tear at depths (~10 Ma to present). Our reconstructions underline the key role played by subduction throughout the whole convergence history. We finally stress that such a long-lasting subduction system with changing boundary conditions also makes the Zagros orogen an ideal natural laboratory for subduction processes.

<p>Journal of Physics D: Applied Physics published the first Plasma Roadmap in 2012 consisting of the individual perspectives of 16 leading experts in the various sub-fields of low temperature plasma science and technology. The 2017 Plasma Roadmap is the first update of a planned series of periodic updates of the Plasma Roadmap. The continuously growing interdisciplinary nature of the low temperature plasma field and its equally broad range of applications are making it increasingly difficult to identify major challenges that encompass all of the many sub-fields and applications. This intellectual diversity is ultimately a strength of the field. The current state of the art for the 19 sub-fields addressed in this roadmap demonstrates the enviable track record of the low temperature plasma field in the development of plasmas as an enabling technology for a vast range of technologies that underpin our modern society. At the same time, the many important scientific and technological challenges shared in this roadmap show that the path forward is not only scientifically rich but has the potential to make wide and far reaching contributions to many societal challenges.</p>

We present the new catalog of principal galaxies (PGC2003). It constitutes the framework of the HYPERLEDA database that supersedes the LEDA one, with more data and more capabilities. The catalog is still restricted to confirmed galaxies, i.e. about one million galaxies, brighter than ≈18 B-mag. In order to provide the best possible identification for each galaxy we give: accurate coordinates (typical accuracy better than 2 arcsec), diameter, axis ratio and position angle. Diameters and axis ratios have been homogenized to the RC2 system at the limiting surface brightness of , using a new method, the EPIDEMIC method. In order to provide the best designation for each galaxy, we collected the names from 50 catalogues. The compatibility of the spelling is tested against NED and SIMBAD, and, as far as possible we used a spelling compatible with both. For some cases, where no consensus exists between NED, SIMBAD and LEDA, we propose some changes that could make the spelling of names fully compatible. The full catalog is distributed through the CDS and can be extracted from HYPERLEDA.

NASA’s Solar Probe Plus (SPP) mission will make the first in situ measurements of the solar corona and the birthplace of the solar wind. The FIELDS instrument suite on SPP will make direct measurements of electric and magnetic fields, the properties of in situ plasma waves, electron density and temperature profiles, and interplanetary radio emissions, amongst other things. Here, we describe the scientific objectives targeted by the SPP/FIELDS instrument, the instrument design itself, and the instrument concept of operations and planned data products.

This paper considers the psychological impact of past unemployment. Using 11 waves of German panel data, we show that life satisfaction is lower not only for the current unemployed (relative to the employed), but also for those with higher levels of past unemployment. However, the negative wellbeing effect of current unemployment is weaker for those who have been unemployed more often in the past. The panel data also reveal some evidence that those suffering greater falls in wellbeing on entering unemployment are less likely to remain unemployed one year later. Together, these findings offer a psychological explanation of persistent unemployment.

To gain a better understanding of the global application of soil erosion prediction models, we comprehensively reviewed relevant peer-reviewed research literature on soil-erosion modelling published between 1994 and 2017. We aimed to identify (i) the processes and models most frequently addressed in the literature, (ii) the regions within which models are primarily applied, (iii) the regions which remain unaddressed and why, and (iv) how frequently studies are conducted to validate/evaluate model outcomes relative to measured data. To perform this task, we combined the collective knowledge of 67 soil-erosion scientists from 25 countries. The resulting database, named 'Global Applications of Soil Erosion Modelling Tracker (GASEMT)', includes 3030 individual modelling records from 126 countries, encompassing all continents (except Antarctica). Out of the 8471 articles identified as potentially relevant, we reviewed 1697 appropriate articles and systematically evaluated and transferred 42 relevant attributes into the database. This GASEMT database provides comprehensive insights into the state-of-the-art of soil- erosion models and model applications worldwide. This database intends to support the upcoming country-based United Nations global soil-erosion assessment in addition to helping to inform soil erosion research priorities by building a foundation for future targeted, in-depth analyses. GASEMT is an open-source database available to the entire user-community to develop research, rectify errors, and make future expansions.

In their late stages of evolution, peraluminous granitic melts exsolve large amounts of fluids which can modify the chemical composition of granitic whole-rock samples. The niobium/tantalum (Nb/Ta) ratio is expected to decrease during the magmatic differentiation of granitic melts, but the behavior of both elements at the magmatic-hydrothermal transition remains unclear. Using a compilation of whole-rock geochemical data available in the literature, we demonstrate that fractional crystallization alone is not sufficient to explain the distribution of Nb-Ta in most peraluminous granites. However, we notice that most of the granitic samples displaying evidence of interactions with fluids have Nb/Ta < 5. We propose that the decrease of the Nb/Ta ratio in evolved melts is the consequence of both fractional crystallization and sub-solidus hydrothermal alteration. We suggest that the Nb/Ta value of ~5 fingerprints the magmatic-hydrothermal transition in peraluminous granites. Furthermore, a Nb/Ta ratio of ~5 appears to be a good marker to discriminate mineralized from barren peraluminous granites.

The LOFAR Two-metre Sky Survey (LoTSS) is a deep 120-168 MHz imaging survey that will eventually cover the entire northern sky. Each of the 3170 pointings will be observed for 8 h, which, at most declinations, is sufficient to produce 5 resolution images with a sensitivity of 100 Jy/beam and accomplish the main scientific aims of the survey, which are to explore the formation and evolution of massive black holes, galaxies, clusters of galaxies and large-scale structure. Owing to the compact core and long baselines of LOFAR, the images provide excellent sensitivity to both highly extended and compact emission. For legacy value, the data are archived at high spectral and time resolution to facilitate subarcsecond imaging and spectral line studies. In this paper we provide an overview of the LoTSS. We outline the survey strategy, the observational status, the current calibration techniques, a preliminary data release, and the anticipated scientific impact. The preliminary images that we have released were created using a fully automated but direction-independent calibration strategy and are significantly more sensitive than those produced by any existing large-area low-frequency survey. In excess of 44 000 sources are detected in the images that have a resolution of 25 , typical noise levels of less than 0.5 mJy/beam, and cover an area of over 350 square degrees in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45 00 00 to 57 00 00 ).

Abstract Plasma catalysis is gaining increasing interest for various gas conversion applications, such as CO 2 conversion into value-added chemicals and fuels, CH 4 activation into hydrogen, higher hydrocarbons or oxygenates, and NH 3 synthesis. Other applications are already more established, such as for air pollution control, e.g. volatile organic compound remediation, particulate matter and NO x removal. In addition, plasma is also very promising for catalyst synthesis and treatment. Plasma catalysis clearly has benefits over ‘conventional’ catalysis, as outlined in the Introduction. However, a better insight into the underlying physical and chemical processes is crucial. This can be obtained by experiments applying diagnostics, studying both the chemical processes at the catalyst surface and the physicochemical mechanisms of plasma-catalyst interactions, as well as by computer modeling. The key challenge is to design cost-effective, highly active and stable catalysts tailored to the plasma environment. Therefore, insight from thermal catalysis as well as electro- and photocatalysis is crucial. All these aspects are covered in this Roadmap paper, written by specialists in their field, presenting the state-of-the-art, the current and future challenges, as well as the advances in science and technology needed to meet these challenges.

Abstract This paper presents a theoretical growth model which explicitly takes into account technological interdependence among economies and examines the impact of spillover effects. Technological interdependence is assumed to operate through spatial externalities. The magnitude of the physical capital externalities at steady state, which is not usually identified in the literature, is estimated using a spatial econometric specification. Spatial externalities are found to be significant. This spatially augmented Solow model yields a conditional convergence equation which is characterized by parameter heterogeneity. A locally linear spatial autoregressive specification is then estimated providing a convergence speed estimate for each country of the sample. Copyright © 2007 John Wiley & Sons, Ltd.

Non-thermal plasma (NTP) is generated by ionizing neutral gas molecules/atoms leading to a highly reactive gas at ambient temperature containing excited molecules, reactive species and generating transient electric fields. Given its potential to interact with tissue or cells without a significant temperature increase, NTP appears as a promising approach for the treatment of various diseases including cancer. The aim of our study was to evaluate the interest of NTP both in vitro and in vivo. To this end, we evaluated the antitumor activity of NTP in vitro on two human cancer cell lines (glioblastoma U87MG and colorectal carcinoma HCT-116). Our data showed that NTP generated a large amount of reactive oxygen species (ROS), leading to the formation of DNA damages. This resulted in a multiphase cell cycle arrest and a subsequent apoptosis induction. In addition, in vivo experiments on U87MG bearing mice showed that NTP induced a reduction of bioluminescence and tumor volume as compared to nontreated mice. An induction of apoptosis was also observed together with an accumulation of cells in S phase of the cell cycle suggesting an arrest of tumor proliferation. In conclusion, we demonstrated here that the potential of NTP to generate ROS renders this strategy particularly promising in the context of tumor treatment.

The influence of physicochemical properties, including lipophilicity, H-bonding capacity and molecular size and shape descriptors on brain uptake has been investigated using a selection of marketed CNS and CNS-inactive drugs. It is demonstrated that the polar surface area of a drug can be used as a suitable descriptor for the drugs' H-bonding potential. A combination of a H-bonding and a molecular size descriptor, i.e., the major components of lipophilicity and permeability, avoiding knowledge of distribution coefficients, is proposed to estimate brain penetration potential of new drug candidates. Previously reported experimental surface activity data appear to be strongly correlated to molecular size of the drug compounds. Present analysis offers a modern basis for property-based design and targeting of CNS drugs.