Policy Gradients for CVaR-Constrained MDPs

We study a risk-constrained version of the stochastic shortest path (SSP) problem, where the risk measure considered is Conditional Value-at-Risk (CVaR). We propose two algorithms that obtain a locally risk-optimal policy by employing four tools: stochastic approximation, mini batches, policy gradients and importance sampling. Both the algorithms incorporate a CVaR estimation procedure, along the lines of Bardou et al. [2009], which in turn is based on Rockafellar-Uryasev's representation for CVaR and utilize the likelihood ratio principle for estimating the gradient of the sum of one cost function (objective of the SSP) and the gradient of the CVaR of the sum of another cost function (in the constraint of SSP). The algorithms differ in the manner in which they approximate the CVaR estimates/necessary gradients - the first algorithm uses stochastic approximation, while the second employ mini-batches in the spirit of Monte Carlo methods. We establish asymptotic convergence of both the algorithms. Further, since estimating CVaR is related to rare-event simulation, we incorporate an importance sampling based variance reduction scheme into our proposed algorithms

Gas channel rerouting in a primordial enzyme: Structural insights of the carbon-monoxide dehydrogenase/acetyl-CoA synthase complex from the acetogen Clostridium autoethanogenum

Clostridium autoethanogenum, the bacterial model for biological conversion of waste gases into biofuels, grows under extreme carbon-monoxide (CO) concentrations. The strictly anaerobic bacterium derives its entire cellular energy and carbon from this poisonous gas, therefore requiring efficient molecular machineries for CO-conversion. Here, we structurally and biochemically characterized the key enzyme of the CO-converting metabolism: the CO-dehydrogenase/Acetyl-CoA synthase (CODH/ACS). We obtained crystal structures of natively isolated complexes from fructose-grown and CO-grown C. autoethanogenum cultures. Both contain the same isoforms and if the overall structure adopts the classic alpha(2)beta(2) architecture, comparable to the model enzyme from Moorella thermoacetica, the ACS binds a different position on the CODH core. The structural characterization of a proteolyzed complex and the conservation of the binding interface in close homologs rejected the possibility of a crystallization artefact. Therefore, the internal CO-channeling system, critical to transfer CO generated at the C-cluster to the ACS active site, drastically differs in the complex from C. autoethanogenum. The 1.9-angstrom structure of the CODH alone provides an accurate picture of the new CO-routes, leading to the ACS core and reaching the surface. Increased gas accessibility would allow the simultaneous CO-oxidation and acetyl-CoA production. Biochemical experiments showed higher flexibility of the ACS subunit from C. autoethanogenum compared to M. thermoacetica, albeit monitoring similar CO-oxidation and formation rates. These results show a reshuffling of internal CO-tunnels during evolution of these Firmicutes, putatively leading to a bidirectional complex that ensure a high flux of CO-conversion toward energy conservation, acting as the main cellular powerplant

A Structural View of Alkyl-Coenzyme M Reductases, the First Step of Alkane Anaerobic Oxidation Catalyzed by Archaea

Microbial anaerobic oxidation of alkanes intrigues the scientific community by way of its impact on the global carbon cycle, and its biotechnological applications. Archaea are proposed to degrade short- and long-chain alkanes to CO2 by reversing methanogenesis, a theoretically reversible process. The pathway would start with alkane activation, an endergonic step catalyzed by methyl-coenzyme M reductase (MCR) homologues that would generate alkyl-thiols carried by coenzyme M. While the methane-generating MCR found in methanogens has been well characterized, the enzymatic activity of the putative alkane-fixing counterparts has not been validated so far. Such an absence of biochemical investigations contrasts with the current explosion of metagenomics data, which draws new potential alkane-oxidizing pathways in various archaeal phyla. Therefore, validating the physiological function of these putative alkane-fixing machines and investigating how their structures, catalytic mechanisms, and cofactors vary depending on the targeted alkane have become urgent needs. The first structural insights into the methane- and ethane-capturing MCRs highlighted unsuspected differences and proposed some explanations for their substrate specificity. This Perspective reviews the current physiological, biochemical, and structural knowledge of alkyl-CoM reductases and offers fresh ideas about the expected mechanistic and chemical differences among members of this broad family. We conclude with the challenges of the investigation of these particular enzymes, which might one day generate biofuels for our modern society

ORIGAMIX, a CdTe-based spectro-imager development for nuclear applications

The Astrophysics Division of CEA Saclay has a long history in the development of CdTe based pixelated detection planes for X and gamma-ray astronomy, with time-resolved imaging and spectrometric capabilities. The last generation, named Caliste HD, is an all-in-one modular instrument that fulfills requirements for space applications. Its full-custom front-end electronics is designed to work over a large energy range from 2 keV to 1 MeV with excellent spectroscopic performances, in particular between 10 and 100 keV (0.56 keV FWHM and 0.67 keV FWHM at 13.9 and 59.5 keV). In the frame of the ORIGAMIX project, a consortium based on research laboratories and industrials has been settled in order to develop a new generation of gamma camera. The aim is to develop a system based on the Caliste architecture for post-accidental interventions or homeland security, but integrating new properties (advanced spectrometry, hybrid working mode) and suitable for industry. A first prototype was designed and tested to acquire feedback for further developments. In this study, we particularly focused on spectrometric performances with high energies and high fluxes. Therefore, our device was exposed to energies up to 700 keV (133Ba, 137Cs) and we measured the evolution of energy resolution (0.96 keV at 80 keV, 2.18 keV at 356 keV, 3.33 keV at 662 keV). Detection efficiency decreases after 150 keV, as Compton effect becomes dominant. However, CALISTE is also designed to handle multiple events, enabling Compton scattering reconstruction, which can drastically improve detection efficiencies and dynamic range for higher energies up to 1408 keV (22Na, 60Co, 152Eu) within a 1-mm thick detector. In particular, such spectrometric performances obtained with 152Eu and 60Co were never measured before with this kind of detector.Comment: Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. Available online 9 January 2015, ISSN 0168-9002 (http://www.sciencedirect.com/science/article/pii/S0168900215000133). Keywords: CdTe; X-ray; Gamma-ray; Spectrometry; Charge-sharing; Astrophysics Instrumentation; Nuclear Instrumentation; Gamma-ray camera

CO2-Fixation Strategies in Energy Extremophiles: What Can We Learn From Acetogens?

Domestication of CO2-fixation became a worldwide priority enhanced by the will to convert this greenhouse gas into fuels and valuable chemicals. Because of its high stability, CO2-activation/fixation represents a true challenge for chemists. Autotrophic microbial communities, however, perform these reactions under standard temperature and pressure. Recent discoveries shine light on autotrophic acetogenic bacteria and hydrogenotrophic methanogens, as these anaerobes use a particularly efficient CO2-capture system to fulfill their carbon and energy needs. While other autotrophs assimilate CO2 via carboxylation followed by a reduction, acetogens and methanogens do the opposite. They first generate formate and CO by CO2-reduction, which are subsequently fixed to funnel the carbon toward their central metabolism. Yet their CO2-reduction pathways, with acetate or methane as end-products, constrain them to thrive at the "thermodynamic limits of Life". Despite this energy restriction acetogens and methanogens are growing at unexpected fast rates. To overcome the thermodynamic barrier of CO2-reduction they apply different ingenious chemical tricks such as the use of flavin-based electron-bifurcation or coupled reactions. This mini-review summarizes the current knowledge gathered on the CO2-fixation strategies among acetogens. While extensive biochemical characterization of the acetogenic formate-generating machineries has been done, there is no structural data available. Based on their shared mechanistic similarities, we apply the structural information obtained from hydrogenotrophic methanogens to highlight common features, as well as the specific differences of their CO2-fixation systems. We discuss the consequences of their CO2-reduction strategies on the evolution of Life, their wide distribution and their impact in biotechnological applications

Effect of Hydrodynamic Force on Microcantilever Vibrations: Applications to Liquid-Phase Chemical Sensing

At the microscale, cantilever vibrations depend not only on the microstructure’s properties and geometry but also on the properties of the surrounding medium. In fact, when a microcantilever vibrates in a fluid, the fluid offers resistance to the motion of the beam. The study of the influence of the hydrodynamic force on the microcantilever’s vibrational spectrum can be used to either (1) optimize the use of microcantilevers for chemical detection in liquid media or (2) extract the mechanical properties of the fluid. The classical method for application (1) in gas is to operate the microcantilever in the dynamic transverse bending mode for chemical detection. However, the performance of microcantilevers excited in this standard out-of-plane dynamic mode drastically decreases in viscous liquid media. When immersed in liquids, in order to limit the decrease of both the resonant frequency and the quality factor, and improve sensitivity in sensing applications, alternative vibration modes that primarily shear the fluid (rather than involving motion normal to the fluid/beam interface) have been studied and tested: these include in-plane vibration modes (lateral bending mode and elongation mode). For application (2), the classical method to measure the rheological properties of fluids is to use a rheometer. However, such systems require sampling (no in-situ measurements) and a relatively large sample volume (a few milliliters). Moreover, the frequency range is limited to low frequencies (less than 200Hz). To overcome the limitations of this classical method, an alternative method based on the use of silicon microcantilevers is presented. The method, which is based on the use of analytical equations for the hydrodynamic force, permits the measurement of the complex shear modulus of viscoelastic fluids over a wide frequency range

Structural Rearrangements of a Dodecameric Ketol-Acid Reductoisomerase Isolated from a Marine Thermophilic Methanogen

Ketol-acid reductoisomerase (KARI) orchestrates the biosynthesis of branched-chain amino acids, an elementary reaction in prototrophic organisms as well as a valuable process in biotechnology. Bacterial KARIs belonging to class I organise as dimers or dodecamers and were intensively studied to understand their remarkable specificity towards NADH or NADPH, but also to develop antibiotics. Here, we present the first structural study on a KARI natively isolated from a methanogenic archaea. The dodecameric structure of 0.44-MDa was obtained in two different conformations, an open and close state refined to a resolution of 2.2-Å and 2.1-Å, respectively. These structures illustrate the conformational movement required for substrate and coenzyme binding. While the close state presents the complete NADP bound in front of a partially occupied Mg2+-site, the Mg2+-free open state contains a tartrate at the nicotinamide location and a bound NADP with the adenine-nicotinamide protruding out of the active site. Structural comparisons show a very high conservation of the active site environment and detailed analyses point towards few specific residues required for the dodecamerisation. These residues are not conserved in other dodecameric KARIs that stabilise their trimeric interface differently, suggesting that dodecamerisation, the cellular role of which is still unknown, might have occurred several times in the evolution of KARIs

Visual Field Analysis: A reliable method to score left and right eye use using automated tracking

Brain and behavioural asymmetries have been documented in various taxa. Many of these asymmetries involve preferential left and right eye use. However, measuring eye use through manual frame-by-frame analyses from video recordings is laborious and may lead to biases. Recent progress in technology has allowed the development of accurate tracking techniques for measuring animal behaviour. Amongst these techniques, DeepLabCut, a Python-based tracking toolbox using transfer learning with deep neural networks, offers the possibility to track different body parts with unprecedented accuracy. Exploiting the potentialities of DeepLabCut, we developed Visual Field Analysis, an additional open-source application for extracting eye use data. To our knowledge, this is the first application that can automatically quantify left–right preferences in eye use. Here we test the performance of our application in measuring preferential eye use in young domestic chicks. The comparison with manual scoring methods revealed a near perfect correlation in the measures of eye use obtained by Visual Field Analysis. With our application, eye use can be analysed reliably, objectively and at a fine scale in different experimental paradigms

Neobisium yozgati n. sp., and N. anaisae n. sp. (Neobisiidae, Pseudoscorpiones), from Turkey and Macedonia (FYROM), respectively

Two new species of endemic and relict cave-dwellers of genus Neobisium Chamberlin, have been described from Turkey and Macedonia (FYROM), respectively. From its phenetically close congener, N. granulatum Beier, N. yozgati n. sp. (from Yozgat, Turkey) is distinguished in many important respects. In addition, N. anaisae n. sp. (from a cave in Krapa, FYROM) differs from its closest forms (N. korabense Ćurčić, N. ohridanum Hadži, and N. vladimirpantici Ćurčić) by many morphological characters and form of different body parts. Both species are illustrated, diagnosed, and thoroughly described. They both represent endemic and relict forms

New polymer coating to visualize surgical mesh by MRI

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