Role of T-Cell Polarization and Inflammation and Their Modulation by n-3 Fatty Acids in Gestational Diabetes and Macrosomia

International audienceTh (T helper) cells are differentiated into either Th1 or Th2 phenotype. It is generally considered that Th1 phenotype is proinflammatory, whereas Th2 phenotype exerts anti-inflammatory or protective effects. Gestational diabetes mellitus (GDM) has been associated with a decreased Th1 phenotype, whereas macrosomia is marked with high expression ofTh1 cytokines. Besides, these two pathological situations are marked with high concentrations of inflammatory mediators like tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), known to play a pivotal role in insulin resistance. Dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) may exert a beneficial effect by shifting Th1/Th2 balance to a Th2 phenotype and increasing insulin sensitivity. In this paper, we shed light on the role of T-cell malfunction that leads to an inflammatory and pathophysiological state, related to insulin resistance in GDM and macrosomia. We will also discuss the nutritional management of these pathologies by dietary n-3 polyunsaturated fatty acids (PUFAs)

Rain attenuation prediction model for satellite communications based on the Météo-France ensemble prediction system PEARP

This paper presents an example of the usage of ensemble weather forecasting for the control of satellite-based communication systems. Satellite communication systems become increasingly sensitive to weather conditions as their operating frequency increases to avoid electromagnetic spectrum congestion and enhance their capacity. In the microwave domain, electromagnetic waves that are conveying information are attenuated between the satellite and Earth terminals in the presence of hydrometeors (mostly rain drops and more marginally cloud droplets). To maintain a reasonable level of service availability, even with adverse weather conditions considering the scarcity of amplification power in spacecraft, fade mitigation techniques have been developed. The general idea behind those fade mitigation techniques is to reroute, change the characteristics or reschedule the transmission in the case of too-significant propagation impairments. For some systems, a scheduling on how to use those mechanisms some hours in advance is required, making assumptions on the future weather conditions affecting the link. To this aim the use of weather forecast data to control the attenuation compensation mechanisms seems of particular interest to maximize the performances of the communication links and hence of the associated economic value. A model to forecast the attenuation on the link based on forecasted rainfall amounts from deterministic or ensemble weather forecasting is presented and validated. In a second phase, the model's application to a simplified telecommunication system allows us to demonstrate the valuable contribution of weather forecasting in the system's availability optimization or in the system's throughput optimization. The benefit of using ensemble forecasts rather than deterministic ones is demonstrated as well.</p

Brugada syndrome and fever: genetic and molecular characterization of patients carrying SCN5A mutations.

OBJECTIVE: Brugada syndrome (BrS) is characterized by ventricular tachyarrhythmias leading to sudden cardiac death and is caused, in part, by mutations in the SCN5A gene encoding the sodium channel Na(v)1.5. Fever can trigger or exacerbate the clinical manifestations of BrS. The aim of this work was to characterize the genetic and molecular determinants of fever-dependent BrS. METHODS: Four male patients with typical BrS ST-segment elevation in V1-V3 or ventricular arrhythmias during fever were screened for mutations in the SCN5A gene. Wild-type (WT) and mutant Na(v)1.5 channels were expressed in HEK293 cells. The sodium currents (I(Na)) were analysed using the whole-cell patch clamp technique at various temperatures. Protein expression of WT and mutant channels was studied by Western blot experiments. RESULTS: Two mutations in SCN5A, L325R and R535X, were identified. Expression of the two mutant Na(v)1.5 channels in HEK293 cells revealed in each case a severe loss-of-function. Upon the increase of temperature up to 42 degrees C, we observed a pronounced acceleration of Na(v)1.5 activation and fast inactivation kinetics. Cardiac action potential modelling experiments suggest that in patients with reduced I(Na), fever could prematurely shorten the action potential by virtue of its effect on WT channels. Further experiments revealed that L325R channels are likely misfolded, since their function could be partially rescued by mexiletine or curcumin. In co-expression experiments, L325R channels interfered with the proper function of WT channels, suggesting that a dominant negative phenomenon may underlie BrS triggered by fever. CONCLUSIONS: The genetic background of BrS patients sensitive to fever is heterogeneous. Our experimental data suggest that the clinical manifestations of fever-exacerbated BrS may not be mutation specific

Preliminary results of the project A.I.D.A. (Auto Immunity: Diagnosis Assisted by computer)

In this paper, are presented the preliminary results of the A.I.D.A. (Auto Immunity: Diagnosis Assisted by computer) project which is developed in the frame of the cross-border cooperation Italy-Tunisia. According to the main objectives of this project, a database of interpreted Indirect ImmunoFluorescence (IIF) images on HEp 2 cells is being collected thanks to the contribution of Italian and Tunisian experts involved in routine diagnosis of autoimmune diseases. Through exchanging images and double reporting; a Gold Standard database, containing around 1000 double reported IIF images with different patterns including negative tests, has been settled. This Gold Standard database has been used for optimization of a computing solution (CADComputer Aided Detection) and for assessment of its added value in order to be used along with an immunologist as a second reader in detection of auto antibodies for autoimmune disease diagnosis. From the preliminary results obtained, the CAD appeared more powerful than junior immunologists used as second readers and may significantly improve their efficacy

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Dynamic performance simulation of an aeroderivative gas turbine using the matlab simulink environment

In fossil fuel applications, such as air transportation and power generation systems, gas turbine is the prime mover which governs the aircraft's propulsive and the plant's thermal efficiency, respectively. Therefore, an accurate engine performance simulation has a significant impact on the operation and maintenance of gas turbines as far as reliability and availability considerations are concerned. Current trends in achieving stable engine operation, reliable fault diagnosis and prognosis requirements do motivate the development and implementation of real-time dynamic simulators for gas turbines that are sufficiently complex, highly nonlinear, have high fidelity and include fast response modules. This paper presents a gas turbine performance model for predicting the transient dynamic behavior of an aero derivativ e engine that is suitable for both mechanical drive and power generation applications. The engine model has been developed in the Matlab/Simulink environment and combines both the inter-component volume and the constant mass flow methods. Dynamic equations of the mass momentum and the energy balance are incorporated into the steady state thermodynamic equations. This allows one to represent the engine model by a set of first order differential and algebraic equations. The developed Simulink model in an object oriented environment, can be easily adapted to any kind of gas turbine configuration. The model consists of a number of subsystems for representing the gas turbine's components and the thermodynamic relationships among them. The components are represented by a set of suitable performance maps that are available from the open literature. The engine model has been validated with an established gas turbine performance simulation software. Time responses of the main variables that describe the gas turbine dynamic behavior are also included. The proposed gas turbine model with its dynamic simulation characteristics is a useful tool for development of real-time model-based diagnostics and prognostics technologies. Copyright © 2013 by ASME

Multiple sensor fault diagnosis by evolving data-driven approach

Sensors are indispensable components of modern plants and processes and their reliability is vital to ensure reliable and safe operation of complex systems. In this paper, the problem of design and development of a data-driven Multiple Sensor Fault Detection and Isolation (MSFDI) algorithm for nonlinear processes is investigated. The proposed scheme is based on an evolving multi-Takagi Sugeno framework in which each sensor output is estimated using a model derived from the available input/output measurement data. Our proposed MSFDI algorithm is applied to Continuous-Flow Stirred-Tank Reactor (CFSTR). Simulation results demonstrate and validate the performance capabilities of our proposed MSFDI algorithm.Qatar Foundation (Project: NPRP 09-393-2-145/1/2011).Scopu

A resolver converter based upon a novel open-Loop Technique

The paper presents a novel technique for the determination of the angle from slowly-varying quadrature co-sinusoidal signals produced, for example, by position sensors. In the presented scheme applied to a resolver, the separately generated constant-frequency sine wave used for exciting the resolver together with an additional cosine wave are used as reference against which the amplitudes of the angle-dependent demodulated resolver sine and cosine signals are compared. At the instant equality between respective amplitudes of the signals are detected, two sample and hold circuits sample a voltage proportional to the angle of the shaft of the resolver from a triangular waveform generated from the reference signals. In theory, the sample and hold devices produce identical output voltages proportional to the unknown angle of the transducer. In order to improve the precision of the proposed converter, the two sample and hold circuits outputs are fed into a multiplexer to produce a single output that takes full advantage of the accurate comparison outside the peak regions of the signals. With this method, the validated output is obtained from the accurate comparisons involving the alternating pseudo-linear segments of the trigonometric signals. Another important feature of this converter is its robustness to amplitude fluctuations in the trigonometric reference signals which are used for the excitation of the resolver. A converter based on this technique has been successfully implemented using basic electronic components. Theory of operation, computer simulation and experimental results are given

A New Low Cost Linear Resolver Converter

A new low cost converter topology is proposed for sinusoidal position encoders. The converter enables determination of the angle from the sine and cosine signals of the encoder. When used with resolvers, the implementation of the present scheme takes advantage of the available excitation signal used to operate the device. This trigonometric reference signal is optimally used to generate an analogue signal equivalent to a digital look-up table (LUT). This enables determination of the mechanical angle without using LUT, A/D, and D/A converters. The scheme is optimized in order to achieve highest possible precision. Beside simplicity of its implementation, the proposed converter offers the advantage of robustness to amplitude fluctuation of the transducer excitation signal. The converter was implemented using ordinary low-cost analog components. The theory of operation, computer simulation, and experimental results are given