Launcher attitude control: discrete-time robust design and gain-scheduling

In this paper, a robust multi-objective design for the control of a launcher during atmospheric flight is investigated. This approach is based on the Cross Standard Form formulation which allows to incorporate the various specifications of the launcher problem in a streamlined manner. An important feature of this approach is that a non-conventional LQG/LTR approach, required to satisfy time-domain specifications, can be embedded into a more general standard problem in order to account for frequency-domain robustness constraints. The specific form of this standard problem is also very interesting for gain scheduling

Use of Penicillium bilaiae to improve phosphorus bioavailability of thermally treated sewage sludge:A potential novel type biofertiliser

This study explored the potential of different phosphorus (P)-rich sewage sludge biochars and ashes to be colonised and be used as a P sources for the phosphate-solubilising fungus, Penicilliurn bilaiae. P. bilaiae was inoculated on five different biochars and ashes supplemented with nutrient solution. Fungal colonisation, pH and water-extractable P (WEP) in the materials were determined after incubation.P. bilaiae colonised at similar rates on all materials tested, but colonisation was affected by glucose level, pH and total N content in the material. A pH decline, accompanied by an increase in WEP concentration, was observed in three materials. The amount of soluble P was significantly greater at the high glucose level and showed the largest relative increase in incineration ash (> 100-fold after 10 days). The results show a potential to use P-solubilising microorganisms to solubilise P from thermally converted sewage sludge, but the approach has to be further investigated regarding its effects in a soil/plant system

Rapid obtention of stable, bioluminescent tumor cell lines using a tCD2-luciferase chimeric construct

<p>Abstract</p> <p>Background</p> <p>Bioluminescent tumor cell lines are experimental tools of major importance for cancer investigation, especially imaging of tumors in xenografted animals. Stable expression of exogenous luciferase in tumor cells combined to systemic injection of luciferin provides an excellent signal/background ratio for external optical imaging. Therefore, there is a need to rationalize and speed up the production of luciferase-positive tumor cell lines representative of multiple tumor phenotypes. For this aim we have designed a fusion gene linking the luciferase 2 protein to the c-terminus of a truncated form of the rat CD2 protein (<it>tCD2-luc2</it>). To allow simultaneous assessment of the wild-type luciferase 2 in a context of tCD2 co-expression, we have made a bicistronic construct for concomitant but separate expression of these two proteins (<it>luc2-IRES-tCD2</it>). Both the mono- and bi-cistronic constructs were transduced in lymphoid and epithelial cells using lentiviral vectors.</p> <p>Results</p> <p>The tCD2-luc2 chimera behaves as a type I membrane protein with surface presentation of CD2 epitopes. One of these epitopes reacts with the OX34, a widely spread, high affinity monoclonal antibody. Stably transfected cells are sorted by flow cytometry on the basis of OX34 staining. <it>In vitro</it> and, moreover, in xenografted tumors, the tCD2-luc2 chimera retains a substantial and stable luciferase activity, although not as high as the wild-type luciferase expressed from the <it>luc2-IRES-tCD2</it> construct. Expression of the tCD2-luc2 chimera does not harm cell and tumor growth.</p> <p>Conclusion</p> <p>Lentiviral transduction of the chimeric <it>tCD2-luc2 </it>fusion gene allows selection of cell clones with stable luciferase expression in less than seven days without antibiotic selection. We believe that it will be helpful to increase the number of tumor cell lines available for <it>in vivo </it>imaging and assessment of novel therapeutic modalities. On a longer term, the tCD2-luc2 chimera has the potential to be expressed from multi-cassette vectors in combination with various inserts of interest.</p

A detailed VM profiler for the Cog VM

International audienceCode profiling enables a user to know where in an application or function the execution time is spent. The Pharo ecosystem offers several code profilers. However, most of the publicly available profilers (MessageTally, Spy, GadgetPro-filer) largely ignore the activity carried out by the virtual machine , thus incurring inaccuracy in the gathered information and missing important information, such as the Just-in-time compiler activity. This paper describes the motivations and the latest improvements carried out in VMProfiler, a code execution pro-filer hooked into the virtual machine, that performs its analysis by monitoring the virtual machine execution. These improvements address some limitations related to assessing the activity of native functions (resulting from a Just-in-time compiler operation): as of now, VMProfiler provides more detailed profiling reports, showing for native code functions in which bytecode range the execution time is spent

Computational protein design to accelerate the conception of fine-tuned biocatalysts

The remarkable properties of enzymes (high catalytic efficiency, regio- and stereo-selectivity) have been recognized and largely exploited in biocatalysis. Accordingly, enzyme-driven processes should play an increasing role in the next decades, potentially substituting chemical processes and contributing to the raise of bioeconomy. However, to foresee a viable future to biocatalysis, advances in R&D are required to accelerate the delivery of fine-tuned enzymes displaying high chemical specificity on non-cognate substrates, high efficiency and better stability in reaction conditions. To this end, structure-based Computational Protein Design (CPD) is a promising strategy to fully rationalize and speed-up the conception of new enzymes while reducing associated human and financial costs. By combining physico-chemical models governing relations between protein amino-acid composition and their 3D structure with optimization algorithms, CPD seeks to identify sequences that fold into a given 3D-scaffold and possess the targeted biochemical properties. Starting from a huge search space, the protein sequence-conformation space, this in silico pre-screening aims to considerably narrow down the number of mutants tested at experimental level while substantially increasing the chances of reaching the desired enzyme. While CPD is still a very young and rapidly evolving field, success stories of computationally designed proteins highlight future prospects of this field. Nonetheless, despite landmark achievements, the success rate of the current computational approaches remains low, and designed enzymes are often way less efficient than their natural counterparts. Therefore, several limitations of the CPD still need to be addressed to improve its efficiency, predictability and reliability. Herein, we present our methodological advances in the CPD field that enabled overcoming technological bottlenecks and hence propose innovative CPD methods to explore large sequence-conformation spaces while providing more accuracy and robustness than classical approaches. Our CPD methods speed-up search across vast sequence-conformation spaces by several orders of magnitude, find the minimum energy enzyme design and generate exhaustive lists of near-optimal sequences, defining small mutant libraries. These new methods, in rupture with classical approaches are based on efficient algorithms issued from recent research in artificial intelligence. The performance and accuracy of our computer-aided enzyme design methods have been evaluated and validated on various types of protein design problems. This work was partially funded by INRA/Région Midi-Pyrénées, IDEX Toulouse, Agreenskills and the French National Research Agency (PROTICAD, ANR-12-MONU-0015-03)

Hepatitis C Virus Infection: Molecular Pathways to Steatosis, Insulin Resistance and Oxidative Stress

The persistent infection with hepatitis C virus is a major cause of chronic liver disease worldwide. However, the morbidity associated with hepatitis C virus widely varies and depends on several host-related cofactors, such as age, gender, alcohol consumption, body weight, and co-infections. The objective of this review is to discuss three of these cofactors: steatosis, insulin resistance and oxidative stress. Although all may occur independently of HCV, a direct role of HCV infection in their pathogenesis has been reported. This review summarizes the current understanding and potential molecular pathways by which HCV contributes to their development

Differential retention of transposable element-derived sequences in outcrossing Arabidopsis genomes

International audienceBackground: Transposable elements (TEs) are genomic parasites with major impacts on host genome architecture and host adaptation. A proper evaluation of their evolutionary significance has been hampered by the paucity of short scale phylogenetic comparisons between closely related species. Here, we characterized the dynamics of TE accumulation at the micro-evolutionary scale by comparing two closely related plant species, Arabidopsis lyrata and A. halleri. Results: Joint genome annotation in these two outcrossing species confirmed that both contain two distinct populations of TEs with either 'recent' or 'old' insertion histories. Identification of rare segregating insertions suggests that diverse TE families contribute to the ongoing dynamics of TE accumulation in the two species. Orthologous TE fragments (i.e. those that have been maintained in both species), tend to be located closer to genes than those that are retained in one species only. Compared to non-orthologous TE insertions, those that are orthologous tend to produce fewer short interfering RNAs, are less heavily methylated when found within or adjacent to genes and these tend to have lower expression levels. These findings suggest that long-term retention of TE insertions reflects their frequent acquisition of adaptive roles and/or the deleterious effects of removing nearly neutral TE insertions when they are close to genes. Conclusion: Our results indicate a rapid evolutionary dynamics of the TE landscape in these two outcrossing species, with an important input of a diverse set of new insertions with variable propensity to resist deletion