Showing papers by "University of Lorraine published in 2012"

Guidelines and good clinical practice recommendations for contrast enhanced ultrasound (CEUS) in the liver - Update 2012

Abstract: Initially, a set of guidelines for the use of ultrasound contrast agents was published in 2004 dealing only with liver applications. A second edition of the guidelines in 2008 reflected changes in the available contrast agents and updated the guidelines for the liver, as well as implementing some non-liver applications. Time has moved on, and the need for international guidelines on the use of CEUS in the liver has become apparent. The present document describes the third iteration of recommendations for the hepatic use of contrast enhanced ultrasound (CEUS) using contrast specific imaging techniques. This joint WFUMB-EFSUMB initiative has implicated experts from major leading ultrasound societies worldwide. These liver CEUS guidelines are simultaneously published in the official journals of both organizing federations (i.e., Ultrasound in Medicine and Biology for WFUMB and Ultraschall in der Medizin/European Journal of Ultrasound for EFSUMB). These guidelines and recommendations provide general advice on the use of all currently clinically available ultrasound contrast agents (UCA). They are intended to create standard protocols for the use and administration of UCA in liver applications on an international basis and improve the management of patients worldwide.

Miscanthus: a fast-growing crop for biofuels and chemicals production

Abstract: Miscanthus represents a key candidate energy crop for use in biomass-to-liquid fuel-conversion processes and biorefineries to produce a range of liquid fuels and chemicals; it has recently attracted considerable attention. Its yield, elemental composition, carbohydrate and lignin content and composition are of high importance to be reviewed for future biofuel production and development. Starting from Miscanthus, various pre-treatment technologies have recently been developed in the literature to break down the lignin structure, disrupt the crystalline structure of cellulose, and enhance its enzyme digestibility. These technologies included chemical, physicochemical, and biological pre-treatments. Due to its significantly lower concentrations of moisture and ash, Miscanthus also represents a key candidate crop for use in biomass-to-liquid conversion processes to produce a range of liquid fuels and chemicals by thermochemical conversion. The goal of this paper is to review the current status of the technology for biofuel production from this crop within a biorefinery context.

Cell membrane electroporation- Part 1: The phenomenon

Abstract: Each biological cell, trillions of which build our bodies, is enveloped by its plasma membrane. Composed largely of a bilayer (double layer) of lipids just two molecules thick (about 5 nm), and behaving partly as a liquid and partly as a gel, the cell plasma membrane nonetheless separates and protects the cell from its surrounding environment very reliably and stably. Embedded within the lipid bilayer, also quite stably, are a number of different proteins, some of which act as channels and pumps, providing a pathway for transporting specific molecules across the membrane. Without these proteins, the membrane would be a largely impenetrable barrier. Electrically, the cell plasma membrane can be viewed as a thin insulating sheet surrounded on both sides by aqueous electrolyte solutions. When exposed to a sufficiently strong electric field, the membrane will undergo electrical breakdown, which renders it permeable to molecules that are otherwise unable to cross it. The process of rendering the membrane permeable is called membrane electroporation. Unlike solid insulators, in which an electrical breakdown generally causes permanent structural change, the membrane, with its lipids behaving as a two-dimensional liquid, can spontaneously return to its prebreakdown state. If the exposure is sufficiently short and the membrane recovery sufficiently rapid for the cell to remain viable, electroporation is termed reversible; otherwise, it is termed irreversible. Since its discovery [1]���[3], electroporation has steadily gained ground as a useful tool in various areas of medicine and biotechnology. Today, reversible electroporation is an established method for introducing chemotherapeutic drugs into tumor cells (electrochemotherapy) [4]. It also offers great promise as a technique for gene therapy without the risks caused by viral vectors (DNA electrotransfer) [5]. In clinical medicine, irreversible electroporation is being investigated as a method for tissue ablation (nonthermal electroablation) [6], whereas in biotechnology, it is useful for extraction of biomolecules [7] and for microbial deactivation, particularly in food preservation [8]. This article, the first in a series of three focusing on electroporation, describes the phenomenon at the molecular level of the lipid bilayer, and then proceeds to the cellular level, explaining how exposure of a cell as a whole to an external electric field results in an inducement of voltage on its plasma membrane, its electroporation, and transport thorough the electroporated membrane. The second article will review the most important and promising applications of electroporation, and the third article will focus on the hardware for electroporation (pulse generators and electrodes) and on the need for standards, safety, and certification.

Human coronaviruses: insights into environmental resistance and its influence on the development of new antiseptic strategies.

Abstract: The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.

Nomenclature of the hydrotalcite supergroup: natural layered double hydroxides

Abstract: Layered double hydroxide (LDH) compounds are characterized by structures in which layers with a brucite-like structure carry a net positive charge, usually due to the partial substitution of trivalent octahedrally coordinated cations for divalent cations, giving a general layer formula [(M 1–x 2+ M 3+ x )(OH)2] x+. This positive charge is balanced by anions which are intercalated between the layers. Intercalated molecular water typically provides hydrogen bonding between the brucite layers. In addition to synthetic compounds, some of which have significant industrial applications, more than 40 mineral species conform to this description. Hydrotalcite, Mg6Al2(OH)16[CO3]·4H2O, as the longest-known example, is the archetype of this supergroup of minerals. We review the history, chemistry, crystal structure, polytypic variation and status of all hydrotalcite-supergroup species reported to date. The dominant divalent cations, M 2+, that have been reported in hydrotalcite supergroup minerals are Mg, Ca, Mn, Fe, Ni, Cu and Zn; the dominant trivalent cations, M 3+, are Al, Mn, Fe, Co and Ni. The most common intercalated anions are (CO3)2–, (SO4)2– and Cl–; and OH–, S2– and [Sb(OH)6]– have also been reported. Some species contain intercalated cationic or neutral complexes such as [Na(H2O)6]+ or [MgSO4]0. We define eight groups within the supergroup on the basis of a combination of criteria. These are (1) the hydrotalcite group, with M 2+:M 3+ = 3:1 (layer spacing ∼7.8 A); (2) the quintinite group, with M 2+:M 3+ = 2:1 (layer spacing ∼7.8 A); (3) the fougerite group, with M 2+ = Fe2+, M 3+ = Fe3+ in a range of ratios, and with O2– replacing OH– in the brucite module to maintain charge balance (layer spacing ∼7.8 A); (4) the woodwardite group, with variable M 2+:M 3+ and interlayer [SO4]2 –, leading to an expanded layer spacing of ∼8.9 A; (5) the cualstibite group, with interlayer [Sb(OH)6]– and a layer spacing of ∼9.7 A; (6) the glaucocerinite group, with interlayer [SO4]2– as in the woodwardite group, and with additional interlayer H2O molecules that further expand the layer spacing to ∼11 A; (7) the wermlandite group, with a layer spacing of ∼11 A, in which cationic complexes occur with anions between the brucite-like layers; and (8) the hydrocalumite group, with M 2+ = Ca2+ and M 3+ = Al, which contains brucite-like layers in which the Ca:Al ratio is 2:1 and the large cation, Ca2+, is coordinated to a seventh ligand of 'interlayer' water. The principal mineral status changes are as follows. (1) The names manasseite, sjogrenite and barbertonite are discredited; these minerals are the 2H polytypes of hydrotalcite, pyroaurite and stichtite, respectively. Cyanophyllite is discredited as it is the 1M polytype of cualstibite. (2) The mineral formerly described as fougerite has been found to be an intimate intergrowth of two phases with distinct Fe2+:Fe3+ ratios. The phase with Fe2+:Fe3+ = 2:1 retains the name fougerite; that with Fe2+:Fe3+ = 1:2 is defined as the new species trebeurdenite. (3) The new minerals omsite (IMA2012-025), Ni2Fe3+(OH)6[Sb(OH)6], and mossbauerite (IMA2012-049), Fe3+6O4(OH)8[CO3]·3H2O, which are both in the hydrotalcite supergroup are included in the discussion. (4) Jamborite, carrboydite, zincaluminite, motukoreaite, natroglaucocerinite, brugnatellite and muskoxite are identified as questionable species which need further investigation in order to verify their structure and composition. (5) The ranges of compositions currently ascribed to motukoreaite and muskoxite may each represent more than one species. The same applies to the approved species hydrowoodwardite and hydrocalumite. (6) Several unnamed minerals have been reported which are likely to represent additional species within the supergroup. This report has been approved by the Commission on New Minerals, Nomenclature and Classification (CNMNC) of the International Mineralogical Association, voting proposal 12-B. We also propose a compact notation for identifying synthetic LDH phases, for use by chemists as a preferred alternative to the current widespread misuse of mineral names.

Large Signal Stability Analysis Tools in DC Power Systems With Constant Power Loads and Variable Power Loads—A Review

Abstract: Electric motor drives and power electronic converters have become increasingly common in advanced power systems. Passive LC filters are used in these systems to reduce the power ripples. These filters are usually poorly damped for reducing the losses as well as the size/weight and the cost of the system. This leads to instability phenomena if the load power exceeds a power limit depending on the filter parameters. The purpose of this paper is to present tools allowing large signal stability analysis of a dc power system. These tools allow estimation of the domain of attraction of the system operating point. It will be shown that this large signal stability analysis gives useful hints on the design of the system to optimize the stability criteria for constant and variable power loads. The impact of the load dynamics on stability is also studied. An electric drive connected to a dc power supply through a poorly damped LC filter is used as a case study. The simulations and the experimentations confirm the analytical results.

Improved dielectric properties of nanocomposites based on poly(vinylidene fluoride) and poly(vinyl alcohol)-functionalized graphene.

Abstract: In this work, two series of nanocomposites of poly(vinylidene fluoride) (PVDF) incorporated with reduced graphene oxide (rGO) and poly(vinyl alcohol)-modified rGO (rGO-PVA) were fabricated using solution-cast method and their dielectric properties were carefully characterized. Infrared spectroscopy and atom force microscope analysis indicated that PVA chains were successfully grafted onto graphene through ester linkage. The PVA functionalization of graphene surface can not only prevent the agglomeration of original rGO but also enhance the interaction between PVDF and rGO-PVA. Strong hydrogen bonds and charge transfer effect between rGO-PVA and PVDF were determined by infrared and Raman spectroscopies. The dielectric properties of rGO-PVA/PVDF and rGO/PVDF nanocomposites were investigated in a frequency range from 10² Hz to 10⁷ Hz. Both composite systems exhibited an insulator-to-conductor percolating transition as the increase of the filler content. The percolation thresholds were estimated to be 2.24 vol % for rGO-PVA/PVDF composites and 0.61 vol % for rGO/PVDF composites, respectively. Near the percolation threshold, the dielectric permittivity of the nanocomposites was significantly promoted, which can be well explained by interfacial polarization effect and microcapacitor model. Compared to rGO/PVDF composites, higher dielectric constant and lower loss factor were simultaneously achieved in rGO-PVA/PVDF nanocomposites at a frequency range lower than 1 × 10³ Hz. This work provides a potential design strategy based on graphene interface engineering, which would lead to higher-performance flexible dielectric materials.

A chemical model for the atmosphere of hot Jupiters

Abstract: Our purpose is to release a chemical network, and the associated rate coefficients, developed for the temperature and pressure range relevant to hot Jupiters atmospheres. Using this network, we study the vertical atmospheric composition of the two hot Jupiters (HD209458b, HD189733b) with a model that includes photolyses and vertical mixing and we produce synthetic spectra. The chemical scheme is derived from applied combustion models that have been methodically validated over a range of temperatures and pressures typical of the atmospheric layers influencing the observations of hot Jupiters. We compare the predictions obtained from this scheme with equilibrium calculations, with different schemes available in the literature that contain N-bearing species and with previously published photochemical models. Compared to other chemical schemes that were not subjected to the same systematic validation, we find significant differences whenever non-equilibrium processes take place. The deviations from the equilibrium, and thus the sensitivity to the network, are more important for HD189733b, as we assume a cooler atmosphere than for HD209458b. We found that the abundances of NH3 and HCN can vary by two orders of magnitude depending on the network, demonstrating the importance of comprehensive experimental validation. A spectral feature of NH3 at 10.5$\mu$m is sensitive to these abundance variations and thus to the chemical scheme. Due to the influence of the kinetics, we recommend the use of a validated scheme to model the chemistry of exoplanet atmospheres. Our network is robust for temperatures within 300-2500K and pressures from 10mbar up to a few hundreds of bars, for species made of C,H,O,N. It is validated for species up to 2 carbon atoms and for the main nitrogen species.

Adding Virtualization Capabilities to the Grid’5000 Testbed

Abstract: Almost ten years after its premises, the Grid’5000 testbed has become one of the most complete testbed for designing or evaluating large-scale distributed systems. Initially dedicated to the study of High Performance Computing, the infrastructure has evolved to address wider concerns related to Desktop Computing, the Internet of Services and more recently the Cloud Computing paradigm. This paper present recent improvements of the Grid’5000 software and services stack to support large-scale experiments using virtualization technologies as building blocks. Such contributions include the deployment of customized software environments, the reservation of dedicated network domain and the possibility to isolate them from the others, and the automation of experiments with a REST API. We illustrate the interest of these contributions by describing three different use-cases of large-scale experiments on the Grid’5000 testbed. The first one leverages virtual machines to conduct larger experiments spread over 4000 peers. The second one describes the deployment of 10000 KVM instances over 4 Grid’5000 sites. Finally, the last use case introduces a one-click deployment tool to easily deploy major IaaS solutions. The conclusion highlights some important challenges of Grid’5000 related to the use of OpenFlow and to the management of applications dealing with tremendous amount of data.

Compared performance of high-sensitivity cameras dedicated to myocardial perfusion SPECT: a comprehensive analysis of phantom and human images.

Abstract: Differences in the performance of cadmium-zinc-telluride (CZT) cameras or collimation systems that have recently been commercialized for myocardial SPECT remain unclear. In the present study, the performance of 3 of these systems was compared by a comprehensive analysis of phantom and human SPECT images. Methods: We evaluated the Discovery NM 530c and DSPECT CZT cameras, as well as the Symbia Anger camera equipped with an astigmatic (IQ⋅SPECT) or parallel-hole (conventional SPECT) collimator. Physical performance was compared on reconstructed SPECT images from a phantom and from comparable groups of healthy subjects. Results: Classifications were as follows, in order of performance. For count sensitivity on cardiac phantom images (counts⋅s−1⋅MBq−1), DSPECT had a sensitivity of 850; Discovery NM 530c, 460; IQ⋅SPECT, 390; and conventional SPECT, 130. This classification was similar to that of myocardial counts normalized to injected activities from human images (respective mean values, in counts⋅s−1⋅MBq−1: 11.4 ± 2.6, 5.6 ± 1.4, 2.7 ± 0.7, and 0.6 ± 0.1). For central spatial resolution: Discovery NM 530c was 6.7 mm; DSPECT, 8.6 mm; IQ⋅SPECT, 15.0 mm; and conventional SPECT, 15.3 mm, also in accordance with the analysis of the sharpness of myocardial contours on human images (in cm−1: 1.02 ± 0.17, 0.92 ± 0.11, 0.64 ± 0.12, and 0.65 ± 0.06, respectively). For contrast-to-noise ratio on the phantom: Discovery NM 530c had a ratio of 4.6; DSPECT, 4.1; IQ⋅SPECT, 3.9; and conventional SPECT, 3.5, similar to ratios documented on human images (5.2 ± 1.0, 4.5 ± 0.5, 3.9 ± 0.6, and 3.4 ± 0.3, respectively). Conclusion: The performance of CZT cameras is dramatically higher than that of Anger cameras, even for human SPECT images. However, CZT cameras differ in that spatial resolution and contrast-to-noise ratio are better with the Discovery NM 530c, whereas count sensitivity is markedly higher with the DSPECT.

Eplerenone in patients with systolic heart failure and mild symptoms: analysis of repeat hospitalizations.

Abstract: BACKGROUND: Eplerenone is known to reduce time to first hospitalization for heart failure or cardiovascular death in patients with heart failure and mild symptoms. In chronic diseases such as heart failure, characterized by repeat hospitalizations, analyzing all heart failure hospitalizations, not just the first, should give a more complete picture of treatment benefits. METHODS AND RESULTS: The Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure (EMPHASIS-HF) trial compared eplerenone with placebo in 2737 patients with mild heart failure, followed for a median 2.08 years (interquartile range, 1.08-3.10 years). Data were collected on all hospitalizations, with a focus on those due to heart failure. Heart failure hospitalization rates in the eplerenone and placebo groups were 10.70 and 16.99 per 100 patient-years, respectively. Allowing for skewness in the frequency of hospitalizations by using the negative binomial generalized linear model, the rate ratio (eplerenone versus placebo) was 0.53 (95% confidence interval, 0.42-0.66; P<0.0001). A plot of cumulative hospitalization rates over time revealed that most of the reduced risk on eplerenone occurred in the first year of follow-up. Several baseline variables strongly predicted the risk of hospitalization. More complex statistical methods, adjusting for mortality (as informative censoring), made a negligible difference in these findings. CONCLUSIONS: Eplerenone markedly reduces the risk of heart failure hospitalizations in patients with heart failure and mild symptoms to a greater extent than is captured by only studying the time to first hospitalization. Future clinical trials in heart failure would gain from incorporating repeat hospitalizations into their primary evaluation of treatment effects. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00232180.

Pulse-labelling trees to study carbon allocation dynamics: a review of methods, current knowledge and future prospects

Abstract: Pulse-labelling of trees with stable or radioactive carbon (C) isotopes offers the unique opportunity to trace the fate of labelled CO(2) into the tree and its release to the soil and the atmosphere. Thus, pulse-labelling enables the quantification of C partitioning in forests and the assessment of the role of partitioning in tree growth, resource acquisition and C sequestration. However, this is associated with challenges as regards the choice of a tracer, the methods of tracing labelled C in tree and soil compartments and the quantitative analysis of C dynamics. Based on data from 47 studies, the rate of transfer differs between broadleaved and coniferous species and decreases as temperature and soil water content decrease. Labelled C is rapidly transferred belowground-within a few days or less-and this transfer is slowed down by drought. Half-lives of labelled C in phloem sap (transfer pool) and in mature leaves (source organs) are short, while those of sink organs (growing tissues, seasonal storage) are longer. (13)C measurements in respiratory efflux at high temporal resolution provide the best estimate of the mean residence times of C in respiratory substrate pools, and the best basis for compartmental modelling. Seasonal C dynamics and allocation patterns indicate that sink strength variations are important drivers for C fluxes. We propose a conceptual model for temperate and boreal trees, which considers the use of recently assimilated C versus stored C. We recommend best practices for designing and analysing pulse-labelling experiments, and identify several topics which we consider of prime importance for future research on C allocation in trees: (i) whole-tree C source-sink relations, (ii) C allocation to secondary metabolism, (iii) responses to environmental change, (iv) effects of seasonality versus phenology in and across biomes, and (v) carbon-nitrogen interactions. Substantial progress is expected from emerging technologies, but the largest challenge remains to carry out in situ whole-tree labelling experiments on mature trees to improve our understanding of the environmental and physiological controls on C allocation.

Properties- and applications of quasicrystals and complex metallic alloys

Abstract: This article aims at an account of what is known about the potential for applications of quasicrystals and related compounds, the so-called family of Complex Metallic Alloys (CMAs‡). Attention is focused at aluminium-based CMAs, which comprise a large number of crystalline compounds and quasicrystals made of aluminium alloyed with transition metals (like Fe or Cu) or normal metals like Mg. Depending on composition, the structural complexity varies from a few atoms per unit cell up to thousands of atoms. Quasicrystals appear then as CMAs of ultimate complexity and exhibit a lattice that shows no periodicity anymore in the usual 3-dimensional space. Properties change dramatically with lattice complexity and turn the metal-type behaviour of simple Al-based crystals into a far more complex behaviour, with a fingerprint of semi-conductors that may be exploited in various applications, potential or realised. An account of the ones known to the author is given in the light of the relevant properties, namely light absorption, reduced adhesion and friction, heat insulation, reinforcement of composites for mechanical devices, and few more exotic ones. The role played by the search for applications of quasicrystals in the development of the field is briefly addressed in the concluding section.

The impact of temperature on the inactivation of enteric viruses in food and water: a review

Abstract: Summary Temperature is considered as the major factor determining virus inactivation in the environment. Food industries, therefore, widely apply temperature as virus inactivating parameter. This review encompasses an overview of viral inactivation and virus genome degradation data from published literature as well as a statistical analysis and the development of empirical formulae to predict virus inactivation. A total of 658 data (time to obtain a first log10 reduction) were collected from 76 published studies with 563 data on virus infectivity and 95 data on genome degradation. Linear model fitting was applied to analyse the effects of temperature, virus species, detection method (cell culture or molecular methods), matrix (simple or complex) and temperature category (<50 and ≥50°C). As expected, virus inactivation was found to be faster at temperatures ≥50°C than at temperatures <50°C, but there was also a significant temperature–matrix effect. Virus inactivation appeared to occur faster in complex than in simple matrices. In general, bacteriophages PRD1 and PhiX174 appeared to be highly persistent whatever the matrix or the temperature, which makes them useful indicators for virus inactivation studies. The virus genome was shown to be more resistant than infectious virus. Simple empirical formulas were developed that can be used to predict virus inactivation and genome degradation for untested temperatures, time points or even virus strains.

Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans

Abstract: Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10(-11)) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10(-8)). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10(-8)) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10(-8)) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.

Flatness-Based Trajectory Planning/Replanning for a Quadrotor Unmanned Aerial Vehicle

Abstract: A flatness-based flight trajectory planning/replanning strategy is proposed for a quadrotor unmanned aerial vehicle (UAV). In the nominal situation (fault-free case), the objective is to drive the system from an initial position to a final one without hitting the actuator constraints while minimizing the total time of the mission or minimizing the total energy spent. When actuator faults occur, fault-tolerant control (FTC) is combined with trajectory replanning to change the reference trajectory in function of the remaining resources in the system. The approach employs differential flatness to express the control inputs to be applied in the function of the desired trajectories and formulates the trajectory planning/replanning problem as a constrained optimization problem.

Rootstock control of scion transpiration and its acclimation to water deficit are controlled by different genes.

Abstract: The stomatal control of transpiration is one of the major strategies by which plants cope with water stress. Here, we investigated the genetic architecture of the rootstock control of scion transpiration-related traits over a period of 3 yr. The rootstocks studied were full sibs from a controlled interspecific cross (Vitis vinifera cv. Cabernet Sauvignon x Vitis riparia cv. Gloire de Montpellier), onto which we grafted a single scion genotype. After 10 d without stress, the water supply was progressively limited over a period of 10 d, and a stable water deficit was then applied for 15 d. Transpiration rate was estimated daily and a mathematical curve was fitted to its response to water deficit intensity. We also determined delta C-13 values in leaves, transpiration efficiency and water extraction capacity. These traits were then analysed in a multienvironment (year and water status) quantitative trait locus (QTL) analysis. Quantitative trait loci, independent of year and water status, were detected for each trait. One genomic region was specifically implicated in the acclimation of scion transpiration induced by the rootstock. The QTLs identified colocalized with genes involved in water deficit responses, such as those relating to ABA and hydraulic regulation. Scion transpiration rate and its acclimation to water deficit are thus controlled genetically by the rootstock, through different genetic architectures.

Molecular Dynamics Simulations of Lipid Membrane Electroporation

Abstract: The permeability of cell membranes can be transiently increased following the application of external electric fields. Theoretical approaches such as molecular modeling provide a significant insight into the processes affecting, at the molecular level, the integrity of lipid cell membranes when these are subject to voltage gradients under similar conditions as those used in experiments. This article reports on the progress made so far using such simulations to model membrane—lipid bilayer—electroporation. We first describe the methods devised to perform in silico experiments of membranes subject to nanosecond, megavolt-per-meter pulsed electric fields and of membranes subject to charge imbalance, mimicking therefore the application of low-voltage, long-duration pulses. We show then that, at the molecular level, the two types of pulses produce similar effects: provided the TM voltage these pulses create are higher than a certain threshold, hydrophilic pores stabilized by the membrane lipid headgroups form within the nanosecond time scale across the lipid core. Similarly, when the pulses are switched off, the pores collapse (close) within similar time scales. It is shown that for similar TM voltages applied, both methods induce similar electric field distributions within the membrane core. The cascade of events following the application of the pulses, and taking place at the membrane, is a direct consequence of such an electric field distribution.

Mineralocorticoid receptor antagonists for heart failure with reduced ejection fraction: integrating evidence into clinical practice

Abstract: Mineralocorticoid receptor antagonists (MRAs) improve survival and reduce morbidity in patients with heart failure, reduced ejection fraction (HF–REF), and mild-to-severe symptoms, and in patients with left ventricular systolic dysfunction and heart failure after acute myocardial infarction. These clinical benefits are observed in addition to those of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and beta-blockers. The morbidity and mortality benefits of MRAs may be mediated by several proposed actions, including antifibrotic mechanisms that slow heart failure progression, prevent or reverse cardiac remodelling, or reduce arrhythmogenesis. Both eplerenone and spironolactone have demonstrated survival benefits in individual clinical trials. Pharmacologic differences exist between the drugs, which may be relevant for therapeutic decision making in individual patients. Although serious hyperkalaemia events were reported in the major MRA clinical trials, these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up. When used appropriately, MRAs significantly improve outcomes across the spectrum of patients with HF–REF.

Daclatasvir for previously untreated chronic hepatitis C genotype-1 infection: a randomised, parallel-group, double-blind, placebo-controlled, dose-finding, phase 2a trial.

Abstract: Summary Background Several direct-acting antivirals for chronic hepatitis C virus (HCV) infection are available, but they are limited by tolerability and dosing schedules. Once-daily daclatasvir, a potent NS5A replication complex inhibitor, was generally well tolerated in phase 1 studies. We assessed daclatasvir in combination with pegylated interferon (peginterferon) and ribavirin for chronic HCV. Methods In this double-blind, parallel-group, dose-finding, phase 2a study, treatment-naive patients with HCV genotype-1 infection (without cirrhosis) from 14 centres in the USA and France were randomly assigned (1:1:1:1) to receive peginterferon alfa-2a (180 μg per week) and ribavirin (1000–1200 mg daily) plus placebo or 3 mg, 10 mg, or 60 mg of daclatasvir taken once daily, for 48 weeks. The primary efficacy endpoint was undetectable HCV RNA at 4 weeks and 12 weeks after start of treatment (extended rapid virological response, eRVR). Analysis was of all participants who received one dose of study drug. We used descriptive analyses to compare results. This study is registered with ClinicalTrials.gov, number NCT00874770. Findings 48 patients were randomly assigned (12 per group); all received at least one dose of study drug. 15 patients discontinued treatment before week 48. Five of 12 patients (42%, 80% CI 22–64%) who received 3 mg daclatasvir achieved eRVR, compared with ten of 12 (83%, 61–96%) who received 10 mg daclatasvir, nine of 12 (75%, 53–90%) who received 60 mg daclatasvir, and one of 12 (8%, 1–29%) who received placebo. Adverse events and discontinuations as a result of adverse events occurred with similar frequency across groups. Interpretation Daclatasvir seems to be a potent NS5A replication complex inhibitor that increases the antiviral potency of peginterferon and ribavirin. Our findings support the further development of regimens containing 60 mg daclatasvir for the treatment of chronic genotype-1 HCV infection. Funding Bristol-Myers Squibb.