Concurrent Crystallization Mechanism Leading to Low Temperature Percolation of LAGP Glass-Ceramic Electrolyte.

Sintering of ceramic electrolytes (CE) is the most efficient way to obtain a dense, all ceramic solid-state battery with oxide-based materials. However, the high temperature required for this process leads to detrimental reactivity between CE and the active material. Crystalline ceramics are necessary for highly conductive oxide materials.

NMR Study of Lithium Transport in Liquid-Ceramic Hybrid Solid Composite Electrolytes.

Despite their high conductivity, factors such as being fragile enough to face processing issues and interfacial incompatibility with lithium electrodes are some of the main drawbacks hindering the commercialization of inorganic (mainly oxide-based) solid electrolytes for use in all-solid-state lithium batteries. To this end, strategies such as the addition of solid polymer electrolytes have been proposed to improve the electrode-electrolyte interface. Hybrid electrolytes, which are usually composed of ceramic particles dispersed in a polymer, generally have a better affinity with electrodes and higher ionic conductivity than pure inorganic electrolytes.

Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants.

Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice.

MCH-R1 Antagonist GPS18169, a Pseudopeptide, Is a Peripheral Anti-Obesity Agent in Mice.

Melanin-concentrating hormone (MCH) is a 19 amino acid long peptide found in the brain of animals, including fishes, batrachians, and mammals. MCH is implicated in appetite and/or energy homeostasis. Antagonists at its receptor (MCH-R1) could be major tools (or ultimately drugs) to understand the mechanism of MCH action and to fight the obesity syndrome that is a worldwide societal health problem.

S29434, a Quinone Reductase 2 Inhibitor: Main Biochemical and Cellular Characterization.

Quinone reductase 2 (QR2, E.C. 1.

Influence of foot position and vision on dynamic postural strategies during the "grand plié" ballet movement (squatting) in young and adult ballet dancers.

Purpose: To analyse dynamic postural strategies during the "grand plié" in two different foot positions (parallel or turned out), with and without vision, and as a function of age in ballet dancers.

Method: Twenty young dancers (YD) aged from 8 to 16 years, and 20 adult dancers (AD) aged from 17 to 30 years were recruited. Center of pressure (CoP) and ground reaction forces (GRF) were recorded (500 Hz) during the grand plié (lowering, squatting and rising).

Comparison of balance strategies in mountain climbers during real altitude exposure between 1.500m and 3.200m: Effects of age and expertise.

Purpose: The aim of this study was to estimate the effect of altitude (1500m vs. 3200m) on balance strategies, and to determine the influence of age (> or <40 years) and expertise (> or <20days of mountain climbing/year) on postural stability at altitude.

Method: Eighty-nine volunteer mountaineers were tested at 1500m, 3200m immediately after exiting the cable car and at 3200m following the climb and return.

QSAR Modelling of CYP3A4 Inhibition as a Screening Tool in the Context of DrugDrug Interaction Studies.

Drugdrug interaction potential (DDI), especially cytochrome P450 (CYP) 3A4 inhibition potential, is one of the most important parameters to be optimized before preclinical and clinical pharmaceutical development as regard to the number of marketed drug metabolized mainly by this CYP and potentially co-administered with the future drug. The present study aims to develop in silico models for CYP3A4 inhibition prediction to help medicinal chemists during the discovery phase and even before the synthesis of new chemical entities (NCEs), focusing on NCEs devoid of any inhibitory potential toward this CYP. In order to find a relevant relationship between CYP3A4 inhibition and chemical features of the screened compounds, we applied a genetic-algorithm-based QSAR exploratory tool SQS (Stochastic QSAR Sampler) in combination with different description approaches comprising alignment-independent Volsurf descriptors, ISIDA fragments and Topological Fuzzy Pharmacophore Triplets.

[Chemoinformatics and virtual screening of molecules for therapeutic use].

Successful identification of new chemical entities with drug-like properties in pharmaceutical and academic research groups involves an early screen and the use of a large number of public and proprietary chemical libraries. Before applying high-throughput experimental screening approaches, virtual screening strategies have been put in place in order to sort and filter this massive amount of compounds and data available at these very early stages. Chemoinformatic tools have a crucial role in this selection process and enable therapeutic chemists to focus very early on promising candidates.

S32826, a nanomolar inhibitor of autotaxin: discovery, synthesis and applications as a pharmacological tool.

Autotaxin catalyzes the transformation of lyso-phosphatidylcholine in lyso-phosphatidic acid (LPA). LPA is a phospholipid possessing a large panel of activity, in particular as a motility factor or as a growth signal, through its G-protein coupled seven transmembrane receptors. Indirect evidence strongly suggests that autotaxin is the main, if not the only source of circulating LPA.

The use of intraoperative ultrasound by anesthesiologists to facilitate the surgical management of peripheral nerve tumors of the upper extremity.

Background: Traditional uses of ultrasound by anesthesiologists include transesophageal echocardiography, facilitation of vascular access, and guidance of peripheral nerve blocks.

Methods: In this case series, we report a novel application of ultrasound by anesthesiologists to facilitate the operative dissection of upper extremity peripheral nerve tumors.

Results: In four cases, ultrasound was used to intraoperatively locate the tumor, plan the safest surgical approach, and exclude tumor vascularity.

Characterizing novice behavior associated with learning ultrasound-guided peripheral regional anesthesia.

Background And Objectives: Ultrasound-guided regional anesthesia is a rapidly growing field. There exists little information regarding the competencies involved with such a practice. The objective of this exploratory study was to characterize the behavior of novices as they undertook the challenges of learning a new technique.

An abnormal clinical course of an ultrasound-guided supraclavicular brachial plexus block using 0.375% bupivacaine.

We report on the case of a reappearance of a supraclavicular nerve block after the apparent initiation of its resolution in a 21-year-old athlete undergoing repair of a valgus impaction syndrome of his right elbow. The patient's anesthetic management consisted of a supraclavicular nerve block and general anesthesia. The patient was discharged home with an apparent resolving nerve block.

Functional expression of sinusoidal drug transporters in primary human and rat hepatocytes.

Primary hepatocyte cultures are considered as a useful in vitro system for pharmacological/toxicological studies. Although expression of drug-metabolizing enzymes and canalicular drug transporters has been well documented in this cellular model, less information is available about sinusoidal drug transporter activities. This has led us to investigate functional expression of the major sinusoidal transporters in primary human and rat hepatocytes.

Stereospecific synthesis of 5-substituted 2-bisarylthiocyclopentane carboxylic acids as specific matrix metalloproteinase inhibitors.

The synthesis and structure-activity relationship (SAR) studies of a series of cyclopentane carboxylic acid matrix metalloproteinase (MMP) inhibitors are described. Potent and specific MMP-2, -3, -9, -13 inhibitors were obtained by regio- and stereoselective substitutions at positions 2 and 5 on the cyclopentane ring. Compounds 2a and 2e are active in the mouse B16-F10 metastasis model and display very good pharmacokinetic parameters.

Synthesis and pharmacological evaluation of new 1,2-dithiolane based antioxidants.

Molecules containing a dithiolane moiety are widely investigated due to their antioxidant properties. The archetypal representative of this class of compounds is lipoic acid and indeed the lipoic acid-dihydrolipoic acid couple is part of the antioxidant defence system of the cell. In the course of a program aiming to find improved antioxidants effective in vivo, we designed, synthesised and pharmacologically investigated new lipoic acid analogs.

Substituted benzocyloheptenes as potent and selective alpha(v) integrin antagonists.

A novel series of potent and specific alpha(v) integrin antagonists has been obtained by aminoalkyl substitutions on benzocyloheptene acetic acids as a rigid GD bioisostere. The preferred compounds 1-2, 1-3 and 1-8, showed nano- to subnanomolar IC(50) values on alpha(v)beta(3) and alpha(v)beta(5) integrins, with favorable pharmacokinetics.

Solid-phase synthesis of alpha-substituted 3-bisarylthio N-hydroxy propionamides as specific MMP inhibitors.

A novel series of potent and specific MMP-2,3,9,13 inhibitors has been obtained by modulation on solid phase by alpha and aryl substitutions on 3-arylthio-N-hydroxy-propionamides starting from itaconic acid.

Improvement in the selectivity and metabolic stability of the serotonin 5-HT(1A) ligand, S 15535: a series of cis- and trans-2-(arylcycloalkylamine) 1-indanols.

S 15535 (1) displays a distinctive profile of agonist and antagonist (weak partial agonist) activity at pre- and postsynaptic 5-HT(1A) receptors, respectively. It has proven to be active in several models predictive of anxiolytic, antidepressant, and procognitive properties. In an attempt to increase its selectivity and metabolic stability, and guided by the results of human metabolic studies, we prepared a series of cis- and trans-2-(arylcycloalkylamine) 1-indanols.