Finsler geometry modeling of reverse piezoelectric effect in PVDF

We apply the Finsler geometry (FG) modeling technique to study the electric field-induced strain in ferroelectric polymers. Polyvinylidene difluoride (PVDF) has a negative longitudinal piezoelectric coefficient, which is unusual in ferroelectrics, and therefore the shape changes in this material are hard to predict. We find that the results of Monte Carlo simulations for the FG model are in good agreement with experimental strain-electric field curves of PVDF-based polymers in both longitudinal and transverse directions. This implies that FG modeling is suitable for reproducing the reverse piezoelectric effect in PVDF

A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Modelling study of dimerization in mammalian defensins

BACKGROUND: Defensins are antimicrobial peptides of innate immunity functioning by non-specific binding to anionic phospholipids in bacterial membranes. Their cationicity, amphipathicity and ability to oligomerize are considered key factors for their action. Based on structural information on human β-defensin 2, we examine homologous defensins from various mammalian species for conserved functional physico-chemical characteristics. RESULTS: Based on homology greater than 40%, structural models of 8 homologs of HBD-2 were constructed. A conserved pattern of electrostatics and dynamics was observed across 6 of the examined defensins; models backed by energetics suggest that the defensins in these 6 organisms are characterized by dimerization-linked enhanced functional potentials. In contrast, dimerization is not energetically favoured in the sheep, goat and mouse defensins, suggesting that they function efficiently as monomers. CONCLUSION: β-defensin 2 from some mammals may work as monomers while those in others, including humans, work as oligomers. This could potentially be used to design human defensins that may be effective at lower concentrations and hence have therapeutic benefits

Post-Training Dephosphorylation of eEF-2 Promotes Protein Synthesis for Memory Consolidation

Memory consolidation, which converts acquired information into long-term storage, is new protein synthesis-dependent. As protein synthesis is a dynamic process that is under the control of multiple translational mechanisms, however, it is still elusive how these mechanisms are recruited in response to learning for memory consolidation. Here we found that eukaryotic elongation factor-2 (eEF-2) was dramatically dephosphorylated within 0.5–2 hr in the hippocampus and amygdala of mice following training in a fear-conditioning test, whereas genome-wide microarrays did not reveal any significant change in the expression level of the mRNAs for translational machineries or their related molecules. Moreover, blockade of NMDA receptors with MK-801 immediately following the training significantly impeded both the post-training eEF-2 dephosphorylation and memory retention. Notably, with an elegant sophisticated transgenic strategy, we demonstrated that hippocampus-specific overexpression of eEF-2 kinase, a kinase that specifically phosphorylates and hence inactivates eEF-2, significantly inhibited protein synthesis in the hippocampus, and this effects was more robust during an “ongoing” protein synthesis process. As a result, late phase long-term potentiation (L-LTP) in the hippocampus and long-term hippocampus-dependent memory in the mice were significantly impaired, whereas short-term memory and long-term hippocampus-independent memory remained intact. These results reveal a novel translational underpinning for protein synthesis pertinent to memory consolidation in the mammalian brain

Overview of the Proton-coupled MCT (SLC16A) Family of Transporters: Characterization, Function and Role in the Transport of the Drug of Abuse γ-Hydroxybutyric Acid

The transport of monocarboxylates, such as lactate and pyruvate, is mediated by the SLC16A family of proton-linked membrane transport proteins known as monocarboxylate transporters (MCTs). Fourteen MCT-related genes have been identified in mammals and of these seven MCTs have been functionally characterized. Despite their sequence homology, only MCT1–4 have been demonstrated to be proton-dependent transporters of monocarboxylic acids. MCT6, MCT8 and MCT10 have been demonstrated to transport diuretics, thyroid hormones and aromatic amino acids, respectively. MCT1–4 vary in their regulation, tissue distribution and substrate/inhibitor specificity with MCT1 being the most extensively characterized isoform. Emerging evidence suggests that in addition to endogenous substrates, MCTs are involved in the transport of pharmaceutical agents, including γ-hydroxybuytrate (GHB), 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors (statins), salicylic acid, and bumetanide. MCTs are expressed in a wide range of tissues including the liver, intestine, kidney and brain, and as such they have the potential to impact a number of processes contributing to the disposition of xenobiotic substrates. GHB has been extensively studied as a pharmaceutical substrate of MCTs; the renal clearance of GHB is dose-dependent with saturation of MCT-mediated reabsorption at high doses. Concomitant administration of GHB and l-lactate to rats results in an approximately two-fold increase in GHB renal clearance suggesting that inhibition of MCT1-mediated reabsorption of GHB may be an effective strategy for increasing renal and total GHB elimination in overdose situations. Further studies are required to more clearly define the role of MCTs on drug disposition and the potential for MCT-mediated detoxification strategies in GHB overdose

Neodymium(III) Complexes with Bulky ansa-Bis(cyclopentadienyl) Ligands: Synthesis and Use in Olefin Oligomerization

The trivalent neodymium complexes [rac-{Me2Si(η5-2-SiMe3-4-t-Bu-C5H2)2}Nd(μ-Cl)2Li(THF)2] (rac-3), [rac-{Me2Si(η5-2,4-(SiMe3)2C5H2)2}Nd(μ-Cl)2Li(THF)2] (rac-5), and [{Me2Si(η5-2,4-(SiMe3)2C5H2)(η5-3,4-(SiMe3)2C5H2)}Nd(μ-Cl)2Li(THF)2] (C1-6) have been prepared and their structures investigated by NMR and X-ray crystallography. These new chlorolanthanocenes, when combined in situ with a dialkylmagnesium cocatalyst, initiate the polymerization of ethylene and 1-octene to yield di(oligoalkyl)magnesium species, which can be finally hydrolyzed to oligomers. Bulky bridged complexes rac-3, rac-5, and C1-6 gave significantly more active catalysts for 1-octene oligomerization (Mn = 400−1300, Mw/Mn = 1.11−1.65) than systems based on nonbridged complexes [(η5-C5Me5)2Nd(μ-Cl)2Li(Et2O)2] (1) and [(η5-1,3-(SiMe3)2C5H3)2Nd(μ-Cl)2Li(THF)2] (7). Ethylene oligomerization (Mn = 400−5000) was best achieved with complexes 1 and rac-3, as important catalyst decay occurred with bridged bis(trimethylsilyl) systems rac-5 and C1-6

Incorporation of plasticizers in sugarcane-based poly(3-hydroxybutyrate)(PHB): Changes in microstructure and properties through ageing and annealing

cited By 10International audiencePoly(3-hydroxybutyrate)(PHB), a natural polymer produced by bacteria via crop-based manufacturing, presents interesting characteristics like thermoplastic behaviour and biodegradability. However, its peculiar fine lamellar structure is highly susceptible to an intrinsic ageing phenomenon that contributes to a remarkable brittleness and low toughness. It has been shown that an annealing treatment can be used to increase toughness and avoid ageing for some PHB-based materials. The incorporation of plasticizers can be another alternative to increase toughness in brittle polymers. In this work, three industrial plasticizers, tri(ethylene glycol) bis(2-ethylhexanoate)(TEG-EH), triethyl citrate (TEC) and tributyl citrate (TBC), were incorporated in PHB via melt-mixing and the effect of these additives through ageing and after annealing was investigated. TEC and TBC were also added to a reactive blend of PHB/PEMGMA. All the compositions studied had 10. wt% of plasticizer. Samples were characterized by differential scanning calorimetry, small angle X-ray scattering, scanning electron microscopy, tensile and impact testing and dynamic mechanical analysis. The compositions with plasticizers presented poor mechanical performance even though they were less affected by ageing. Annealing the samples deteriorated even further their mechanical properties due to plasticizer migration out of the interlamellar amorphous regions. © 2015 Elsevier B.V

Interactive extraction of linear structures from LiDAR raw data for archaeomorphological structure prospection

International audienceAnewdetectionandvisualizationtooltoinspectrawLiDARdataforarchaeological prospection is introduced in this paper. It allowsthe supervised extraction oflinear structures (ridge or hollow)from the 3D ground points, for on-line detailed analysis of their crossand longitudinal profiles. Using raw data provides a richer information than an interpolated digital terrain model. In particular, theextraction process ismade aware ofpoint repartition irregularities caused by dense canopies in forested environments. The tool isbased on a recent curvilinear structure extraction framework withfast execution time, that ensures a good interaction. Additionalperformance is achieved through the detection of the local terrain trend around the structure, that allows finer characterizations ofthe extracted structure. The suitability to several application purposes has been evaluated by archaeologists through real contextexperiments. The tool was first applied to the survey of a well-known medieval wall and to the identification of its less preservedparts, that are still undisclosed in the forested landscape. Then it was used in the scope of a prospective work about man impactson its environment to detect and analyze old holloways andto get a betterunderstanding of their local sunkness or the cause oftheir local deviations. Potential and limits of the tools are discussed. Open source and executable codes are left available for moreextensive exploitation and possible integration into GIS softwares

Effect of nanoclay addition on physical, chemical, optical and biological properties of experimental dental resin composites

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