Length of Dialysis Session Is More Important Than Large Kt/V in Hemodialysis

Long, slow hemodialysis (3 × 8 hours/week) has been used without significant modification in Tassin, France, for 30 years with excellent morbidity and mortality rates. A long dialysis session easily provides high Kt/V_urea and allows for good control of nutrition and correction of anemia with a limited need for erythropoietin (EPO). Control of serum phosphate and potassium is usually achieved with low-dose medication. The good survival achieved by long hemodialysis sessions is essentially due to lower cardiovascular morbidity and mortality than in short dialysis sessions. This, in turn, is mainly explained by good blood pressure (BP) control without the need for antihypertensive medication. Normotension in this setting is due to the gentle but powerful ultrafiltration provided by the long sessions, associated with a low salt diet and moderate interdialytic weight gains. These allow for adequate control of extracellular volume (dry weight) in most patients without important intradialytic morbidity. Therefore, increasing the length of the dialysis session seems to be the best way of achieving satisfactory long-term clinical results.     

Unraveling Membrane Perturbations Caused by the Bacterial Riboregulator Hfq

Hfq is a pleiotropic regulator that mediates several aspects of bacterial RNA metabolism. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, usually via its interaction with small regulatory RNAs. Previously, we showed that the Hfq C-terminal region forms an amyloid-like structure and that these fibrils interact with membranes. The immediate consequence of this interaction is a disruption of the membrane, but the effect on Hfq structure was unknown. To investigate details of the mechanism of interaction, the present work uses different in vitro biophysical approaches. We show that the Hfq C-terminal region influences membrane integrity and, conversely, that the membrane specifically affects the amyloid assembly. The reported effect of this bacterial master regulator on membrane integrity is discussed in light of the possible consequence on small regulatory RNA-based regulation.     

Next-Generation Grade and Survival Expression Biomarkers of Human Gliomas Based on Algorithmically Reconstructed Molecular Pathways

In gliomas, expression of certain marker genes is strongly associated with survival and tumor type and often exceeds histological assessments. Using a human interactome model, we algorithmically reconstructed 7494 new-type molecular pathways that are centered each on an individual protein. Each single-gene expression and gene-centric pathway activation was tested as a survival and tumor grade biomarker in gliomas and their diagnostic subgroups (IDH mutant or wild type, IDH mutant with 1p/19q co-deletion, MGMT promoter methylated or unmethylated), including the three major molecular subtypes of glioblastoma (proneural, mesenchymal, classical). We used three datasets from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas, which in total include 527 glioblastoma and 1097 low grade glioma profiles. We identified 2724 such gene and 2418 pathway survival biomarkers out of total 17,717 genes and 7494 pathways analyzed. We then assessed tumor grade and molecular subtype biomarkers and with the threshold of AUC > 0.7 identified 1322/982 gene biomarkers and 472/537 pathway biomarkers. This suggests roughly two times greater efficacy of the reconstructed pathway approach compared to gene biomarkers. Thus, we conclude that activation levels of algorithmically reconstructed gene-centric pathways are a potent class of new-generation diagnostic and prognostic biomarkers for gliomas.     

Solving the electricity production planning problem by a column generation based heuristic

This paper presents a heuristic method based on column generation for the EDF (Electricité De France) long-term electricity production planning problem proposed as subject of the ROADEF/EURO 2010 Challenge. This is to our knowledge the first-ranked method among those methods based on mathematical programming, and was ranked fourth overall. The problem consists in determining a production plan over the whole time horizon for each thermal power plant of the French electricity company, and for nuclear plants, a schedule of plant outages which are necessary for refueling and maintenance operations. The average cost of the overall outage and production planning, computed over a set of demand scenarios, is to be minimized. The method proceeds in two stages. In the first stage, dates for outages are fixed once for all for each nuclear plant. Data are aggregated with a single average scenario and reduced time steps, and a set-partitioning reformulation of this aggregated problem is solved for fixing outage dates with a heuristic based on column generation. The pricing problem associated with each nuclear plant is a shortest path problem in an appropriately constructed graph. In the second stage, the reload level is determined at each date of an outage, considering now all scenarios. Finally, the production quantities between two outages are optimized for each plant and each scenario by solving independent linear programming problems.     

Multi-heuristic scheduling: three approaches to tune compromises

Most of the available industrial schedulers are based on a simulation approach using dispatching rules. These rules are often dedicated to the satisfaction of a single performance criterion, and are used whatever the characteristics of the workshop or of the set of jobs. An approach which allows one to bring in compromises between rules is set out in this paper. These compromises can be parametered in accordance with the objectives of the workshop and the characteristics of the jobs in order to introduce some reactivity in the decision system. Three ways to set up the parameters are compared: experimental design, fuzzy expert system and neural network. The method allowing one to define compromises can be implemented on each scheduler that uses a simulation approach. Tests have been made with an industrial scheduler called SIPAPLUS, the results of which are developed in this paper.     

Back and forth between continuous and discrete for the working computer scientist

This paper gives a perfect, ideal, discretization of continuous notions. This is a very convenient frame to treat continuous problems or theories with the help of a computer. This is illustrated by the conversion of algorithms using real numbers into algorithms using integers only and the founding of discrete geometry.     

Twelve-Nitrogen-Atom Cyclic Structure Stabilized by 3d-Element Atoms: Quantum Chemical Modeling

Using various versions of density functional theory (DFT), DFT M06/TZVP, DFT B3PW91/TZVP, DFT OPBE/TZVP, and, partially, the MP2 method, the possibility of the existence of 3d-element (M) compounds with nitrogen having unusual M: nitrogen ratio 1:12, unknown for these elements at the present, was shown. Structural parameter data were presented. It was shown that all MN4 groupings have tetragonal-pyramidal structure. It was noted that the bond lengths formed by nitrogen atoms and an M atom were equal to each other only in the case of M = Ti, V, Cr and Co, whereas for other Ms, they were slightly different; moreover, the bond angles formed by nitrogen atoms and an M atom were equal to 90.0°, or practically did not differ from this value. Thermodynamic parameters, NBO analysis data and HOMO/LUMO images for this compound were also presented. Good agreement between the calculated data obtained using the above three quantum chemical methods was also noted.     

Membrane Targeting and GTPase Activity of Rab7 Are Required for Its Ubiquitination by RNF167

Rab7 is a GTPase that controls late endosome and lysosome trafficking. Recent studies have demonstrated that Rab7 is ubiquitinated, a post-translational modification mediated by an enzymatic cascade. To date, only one ubiquitin E3 ligase and one deubiquitinase have been identified in regulating Rab7 ubiquitination. Here, we report that RNF167, a transmembrane endolysosomal ubiquitin ligase, can ubiquitinate Rab7. Using immunoprecipitation and in vitro ubiquitination assays, we demonstrate that Rab7 is a direct substrate of RNF167. Subcellular fractionation indicates that RNF167 activity maintains Rab7′s membrane localization. Epifluorescence microscopy in HeLa cells shows that Rab7-positive vesicles are larger under conditions enabling Rab7 ubiquitination by RNF167. Characterization of its ubiquitination reveals that Rab7 must be in its GTP-bound active form for membrane anchoring and, thus, accessible for RNF167-mediated ubiquitin attachment. Cellular distribution analyses of lysosome marker Lamp1 show that vesicle positioning is independent of Rab7 and RNF167 expression and that Rab7 endosomal localization is not affected by RNF167 knockdown. However, both Rab7 and RNF167 depletion affect each other’s lysosomal localization. Finally, this study demonstrates that the RNF167-mediated ubiquitination of Rab7 GTPase is impaired by variants of Charcot–Marie–Tooth Type 2B disease. This study identified RNF167 as a new ubiquitin ligase for Rab7 while expanding our knowledge of the mechanisms underlying the ubiquitination of Rab7.     

Pure Chitosan Biomedical Textile Fibers from Mixtures of Low- and High-Molecular Weight Bidisperse Polymer Solutions: Processing and Understanding of Microstructure–Mechanical Properties’ Relationship

Natural polymers, as extracted from biomass, may exhibit large macromolecular polydispersity. We investigated the impact of low molar mass chitosan (LMW, DP_w~115) on the properties of chitosan fibers obtained by wet spinning of chitosan solutions with bimodal distributions of molar masses. The fiber crystallinity index (CrI) was assessed by synchrotron X-ray diffraction and the mechanical properties were obtained by uniaxial tensile tests. The LMW chitosan showed to slightly increase the crystallinity index in films which were initially processed from the bimodal molar mass chitosan solutions, as a result of increased molecular mobility and possible crystal nucleating effects. Nevertheless, the CrI remained almost constant or slightly decreased in stretched fibers at increasing content of LMW chitosan in the bidisperse chitosan collodion. The ultimate mechanical properties of fibers were altered by the addition of LMW chitosan as a result of a decrease of entanglement density and chain orientation in the solid state. An increase of crystallinity might not be expected from LMW chitosan with a still relatively high degree of polymerization (DPw ≥ 115). Instead, different nucleation agents—either smaller molecules or nanoparticles—should be used to improve the mechanical properties of chitosan fibers for textile applications.     

On the applicability of the Heliosat-2 method to assess surface solar irradiance in the Intertropical Convergence Zone,French Guiana

Measurements of daily means of surface solar irradiance made at four ground stations in French Guiana are compared to estimates from the HelioClim-3 database produced by the Heliosat-2 method applied to Meteosat satellite images. The bias ranges from 12 W m^?2 (6% of the mean of measurements) to 23 W m^?2 (12%), depending on the stations. The root mean square difference ranges between 23 W m^?2 (11%) and 35 W m^?2 (18%). The correlation coefficient (r) is close to 0.9. Better results are observed during the rainy season than during the dry season. Uncertainties are mainly due to the presence of clouds, large viewing angles of the Meteosat satellite, and limitations of the atmospheric transmittance model under the tropical atmospheric conditions. It is concluded that the Heliosat-2 method provides new knowledge about solar radiation in French Guiana.