HIV Replication Enhances Production of Free Fatty Acids, Low Density Lipoproteins and Many Key Proteins Involved in Lipid Metabolism: A Proteomics Study

BACKGROUND: HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. RESULTS: Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. CONCLUSIONS: We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid-related disorders. The target proteins could then be used for future studies in the development of inhibitors for preventing lipid-metabolic anomalies. This is the first direct evidence that HIV-modulates production of proteins that are significantly involved in disrupting the normal lipid-metabolic pathways

Incorporating radiomics into clinical trials: expert consensus on considerations for data-driven compared to biologically-driven quantitative biomarkers

Existing Quantitative Imaging Biomarkers (QIBs) are associated with known biological tissue characteristics and follow a well-understood path of technical, biological and clinical validation before incorporation into clinical trials. In radiomics, novel data-driven processes extract numerous visually imperceptible statistical features from the imaging data with no a priori assumptions on their correlation with biological processes. The selection of relevant features (radiomic signature) and incorporation into clinical trials therefore requires additional considerations to ensure meaningful imaging endpoints. Also, the number of radiomic features tested means that power calculations would result in sample sizes impossible to achieve within clinical trials. This article examines how the process of standardising and validating data-driven imaging biomarkers differs from those based on biological associations. Radiomic signatures are best developed initially on datasets that represent diversity of acquisition protocols as well as diversity of disease and of normal findings, rather than within clinical trials with standardised and optimised protocols as this would risk the selection of radiomic features being linked to the imaging process rather than the pathology. Normalisation through discretisation and feature harmonisation are essential pre-processing steps. Biological correlation may be performed after the technical and clinical validity of a radiomic signature is established, but is not mandatory. Feature selection may be part of discovery within a radiomics-specific trial or represent exploratory endpoints within an established trial; a previously validated radiomic signature may even be used as a primary/secondary endpoint, particularly if associations are demonstrated with specific biological processes and pathways being targeted within clinical trials

Dexterous Undersea Interventions with Far Distance Onshore Supervision: the DexROV Project

open25siThe operation of a ROV requires significant off-shore dedicated manpower to handle and operate the robotic platform. In order to reduce the burden of operations, DexROV proposes to work out more cost effective and time efficient ROV operations, where manned support is in a large extent delocalized onshore (i.e. from a ROV control center), possibly at a large distance from the actual operations, relying on satellite communications. The proposed scheme makes provision for advanced dexterous manipulation capabilities, exploiting human expertise from a remote location when deemed useful. The outcomes of the project will be integrated and evaluated in a series of tests and evaluation campaigns, culminating with a realistic deep sea (1,300 meters) trial. After one year, the project specified the system architecture of the system and carried out preliminary technological trade-offs for the subsystems.openGancet, Jeremi; Weiss, Peter; Antonelli, Gianluca; Pfingsthorn, Max Folkert; Calinon, Sylvain; Turetta, Alessio; Walen, Cees; Urbina, Diego; Govindaraj, Shashank; Letier, Pierre; Martinez, Xavier; Salini, Joseph; Chemisky, Bertrand; Indiveri, Giovanni; Casalino, Giuseppe; Di Lillo, Paolo; Simetti, Enrico; De Palma, Daniel; Birk, Andreas; Fromm, Tobias; Mueller, Christian; Tanwani, Ajay; Havoutis, Ioannis; Caffaz, Andrea; Guilpain, LisaGancet, Jeremi; Weiss, Peter; Antonelli, Gianluca; Pfingsthorn, Max Folkert; Calinon, Sylvain; Turetta, Alessio; Walen, Cees; Urbina, Diego; Govindaraj, Shashank; Letier, Pierre; Martinez, Xavier; Salini, Joseph; Chemisky, Bertrand; Indiveri, Giovanni; Casalino, Giuseppe; Di Lillo, Paolo; Simetti, Enrico; De Palma, Daniel; Birk, Andreas; Fromm, Tobias; Mueller, Christian; Tanwani, Ajay; Havoutis, Ioannis; Caffaz, Andrea; Guilpain, Lis

Stabilization of Linear Hyperbolic Systems of Balance Laws with Measurement Errors

International audienceThis chapter considers the feedback stabilization of partial differential equations described by linear balance laws when the measurements are subjected to disturbances. Compared to our previous work on robust stabilization of linear hyper-bolic systems, the presence of source terms in the system description complicates the analysis. We first consider the case of static controllers, and provide conditions on system data and feedback gain which result in stability of the closed-loop system, and robustness with respect to measurement errors. Motivated by the applications where it is of interest to bound the maximum norm of the state trajectory, we also study feedback stabilization with dynamic controllers. Conditions in terms of matrix inequalities are proposed which lead to robust stability of the closed-loop system in the presence of measurement errors in the feedback. As an application, we study the problem of quantized control, where the quantization error plays the role of disturbance in the measurements. The simulations for an academic example are reported as an illustration of our theoretical results

Economic assessment of single-walled carbon nanotube processes

The carbon nanotube market is steadily growing and projected to reach $1.9 billion by 2010. This study examines the economics of manufacturing single-walled carbon nanotubes (SWNT) using process-based cost models developed for arc, CVD, and HiPco processes. Using assumed input parameters, manufacturing costs are calculated for 1 g SWNT for arc, CVD, and HiPco, totaling$1,906, $1,706, and$485, respectively. For each SWNT process, the synthesis and filtration steps showed the highest costs, with direct labor as a primary cost driver. Reductions in production costs are calculated for increased working hours per day and for increased synthesis reaction yield (SRY) in each process. The process-based cost models offer a means for exploring opportunities for cost reductions, and provide a structured system for comparisons among alternative SWNT manufacturing processes. Further, the models can be used to comprehensively evaluate additional scenarios on the economics of environmental, health, and safety best manufacturing practices