Quantitative Proteomic Approach Reveals Altered Metabolic Pathways in Response to the Inhibition of Lysine Deacetylases in A549 Cells under Normoxia and Hypoxia

Growing evidence is showing that acetylation plays an essential role in cancer, but studies on the impact of KDAC inhibition (KDACi) on the metabolic profile are still in their infancy. Here, we analyzed, by using an iTRAQ-based quantitative proteomics approach, the changes in the proteome of KRAS-mutated non-small cell lung cancer (NSCLC) A549 cells in response to trichostatin-A (TSA) and nicotinamide (NAM) under normoxia and hypoxia. Part of this response was further validated by molecular and biochemical analyses and correlated with the proliferation rates, apoptotic cell death, and activation of ROS scavenging mechanisms in opposition to the ROS production. Despite the differences among the KDAC inhibitors, up-regulation of glycolysis, TCA cycle, oxidative phosphorylation and fatty acid synthesis emerged as a common metabolic response underlying KDACi. We also observed that some of the KDACi effects at metabolic levels are enhanced under hypoxia. Furthermore, we used a drug repositioning machine learning approach to list candidate metabolic therapeutic agents for KRAS mutated NSCLC. Together, these results allow us to better understand the metabolic regulations underlying KDACi in NSCLC, taking into account the microenvironment of tumors related to hypoxia, and bring new insights for the future rational design of new therapies.     

Slip and Twinning in Polycrystalline Alumina (α-Al2O3) Deformed under Hydrostatic Pressure between 600° and 1000°C

The microstructure of polycrystalline alumina deformed under hydrostatic pressure and at low temperature is investigated by transmission electron microscopy. Deformation occurs mainly by prism plane slip and rhombohedral twinning. Introduction of hydrogen leads to a significant decrease in the yield stress. In large grain size alumina deformed with hydrogen, accommodation of twinning involves dislocation reactions in the twin boundary and in the grains rather than by cracking. Prism plane dislocations decompose into basal dislocations by cross slip probably due to a decrease of Peierls stress for basal slip in the presence of hydrogen.     

Residual Stress Evolution in Repair Welds

Abstract: The aim of this paper is to study the influence of the repair procedure on the evolution of residual stress distribution in butt welds. C-Mn steel coupon plates of 11 mm thickness were prepared, subjected to stress relief heat treatment and welded with two beads, using the gas metal arc welding process. After the deposition of two weld beads, two successive repair welds were made on the middle length of the second bead. Longitudinal and transverse residual stresses were measured in the vicinity of the weld, after deposition of the two weld beads and after each repair weld. Residual stress evaluation was conducted using an X-ray diffraction method. The repair welds caused a decrease in magnitude of the initial longitudinal residual welding stresses, and an increase of the transverse residual stress magnitude, in tension at points within the repair length, and in compression at points outside the repair length.     

L'IPAH, version canadienne-fran?aise de l'échelle de Levenson mesurant le lieu de contr?le tridimensionnel.

Assessed the reliability and validity of the French-Canadian version of H. Levenson's (1973) internality, powerful others, and chance locus of control scales. Data from 2 studies of 294 middle-class adults show that the French-Canadian version of the scales was comparable to that of the original version. The importance of utilizing the appropriate statistical models of analysis to benefit from the multidimensional model of locus of control is emphasized. (English abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

évaluation du livre intitulé manuel de gérontologie sociale 2.

Reviews the book, Manuel de gérontologie sociiale 2 by Jean Carette (1992). The Handbook of Social Gerontology 2 constitutes a practical complement of volume 1 which related to the social aspects of ageing and the retirement. Volume 2 relates mainly to the social intervention whose objective is to support the action and the collective mobilization individuals and associations of retirements. Using a 30-year experiment with groups of retirees, either in preparation of retirement, or in the collective action, the author approaches a new ground in gerontology. He proposes a new approach--social gerontology, (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Telechelic polydimethylsiloxanes with terminal acetylenic groups prepared by phase-transfer catalysis

Telechelic, hydroxyalkyl terminated polydimethylsiloxanes were obtained under mild conditions via hydrosilylation of allyl alcohol or ethylene glycol monoallyl ether by oligomeric αω-hydride terminated polydimethylsiloxanes, with the use of a platinum catalyst. They were subsequently modified in a phase transfer catalyzed reaction by propargyl bromide, to give telechelic polysiloxanes terminated by acetylenic groups. The synthetic pathway is described and the characterization of the obtained products is presented.     

Structure discovery in medical databases: a conceptual clustering approach

Clustering is an important data analysis tool for discovering structure in data sets. Although research on conceptual clustering has produced algorithms showing significant advantages over earlier numerical ones, existing methods still present some limitations regarding applicability to biomedical domains. In this paper we describe ADAGIO, a conceptual clustering algorithm combining a low-cost preordering process with a breadth-first incremental control strategy that incorporates merging and splitting operators. Experimental evaluation indicated that the algorithm achieves a good balance between structure discovery performance and computational efficiency, and demonstrated the comparative effectiveness of its missing information handling process. ADAGIO is able to handle qualitative, quantitative and mixed-type data. An application example to a cancer domain is given, where the algorithm was able to suggest interesting epidemiological interpretations.     

Motion synthesis and editing for the generation of new sign language content

Machine Translation - Existing work on the animation of signing avatars often relies on pure procedural techniques or on the playback of Motion Capture (MoCap) data. While the first solution...     

Differential Effects of STCH and Stress-Inducible Hsp70 on the Stability and Maturation of NKCC2

Mutations in the Na-K-2Cl co-transporter NKCC2 lead to type I Bartter syndrome, a life-threatening kidney disease. We previously showed that export from the ER constitutes the limiting step in NKCC2 maturation and cell surface expression. Yet, the molecular mechanisms involved in this process remain obscure. Here, we report the identification of chaperone stress 70 protein (STCH) and the stress-inducible heat shock protein 70 (Hsp70), as two novel binding partners of the ER-resident form of NKCC2. STCH knock-down increased total NKCC2 expression whereas Hsp70 knock-down or its inhibition by YM-01 had the opposite effect. Accordingly, overexpressing of STCH and Hsp70 exerted opposite actions on total protein abundance of NKCC2 and its folding mutants. Cycloheximide chase assay showed that in cells over-expressing STCH, NKCC2 stability and maturation are heavily impaired. In contrast to STCH, Hsp70 co-expression increased NKCC2 maturation. Interestingly, treatment by protein degradation inhibitors revealed that in addition to the proteasome, the ER associated degradation (ERAD) of NKCC2 mediated by STCH, involves also the ER-to-lysosome-associated degradation pathway. In summary, our data are consistent with STCH and Hsp70 having differential and antagonistic effects with regard to NKCC2 biogenesis. These findings may have an impact on our understanding and potential treatment of diseases related to aberrant NKCC2 trafficking and expression.     

Feature extraction of the first difference of EMG time series for EMG pattern recognition

This paper demonstrates the utility of a differencing technique to transform surface EMG signals measured during both static and dynamic contractions such that they become more stationary. The technique was evaluated by three stationarity tests consisting of the variation of two statistical properties, i.e., mean and standard deviation, and the reverse arrangements test. As a result of the proposed technique, the first difference of EMG time series became more stationary compared to the original measured signal. Based on this finding, the performance of time-domain features extracted from raw and transformed EMG was investigated via an EMG classification problem (i.e., eight dynamic motions and four EMG channels) on data from 18 subjects. The results show that the classification accuracies of all features extracted from the transformed signals were higher than features extracted from the original signals for six different classifiers including quadratic discriminant analysis. On average, the proposed differencing technique improved classification accuracies by 2–8%.