Engagement of T cell receptor triggers its recruitment to low-density detergent-insoluble membrane domains

T-cell receptors (TCRs) upon binding to peptide-MHC ligands transduce signals in T lymphocytes. Tyrosine phosphorylations in the cytoplasmic domains of the CD3 (gammadeltaepsilon) and zeta subunits of the TCR complex by Src family kinases initiate the signaling cascades via docking and activation of ZAP-70 kinase and other signaling components. We examined the role of the low-density detergent-insoluble membranes (DIMs) in TCR signaling. Using mouse thymocytes as a model, we characterized the structural organization of DIMs in detail. We then demonstrated that TCR engagement triggered an immediate increase in the amount of TCR/CD3 present in DIMs, which directly involves the engaged receptor complexes. TCR/CD3 recruitment is accompanied by the accumulation of a series of prominent tyrosine-phosphorylated substrates and by an increase of the Lck activity in DIMs. Upon TCR stimulation, the DIM-associated receptor complexes are highly enriched in the hyperphosphorylated p23 zeta chains, contain most of the TCR/CD3-associated, phosphorylation-activated ZAP-70 kinases and seem to integrate into higher order, multiple tyrosine-phosphorylated substrate-containing protein complexes. The TCR/CD3 recruitment was found to depend on the activity of Src family kinases. We thus provide the first demonstration of recuitment of TCR/CD3 to DIMs upon receptor stimulation and propose it as a mechanism whereby TCR engagement is coupled to downstream signaling cascades.     

Studies of elemental distributions within discrete coal macerals: Use of secondary ion mass spectrometry and X-ray photoelectron spectroscopy

Secondary ion mass spectrometry has been used to measure qualitatively the distributions of many trace and minor elements within some well-characterized coal macerals: vitrinite, fusinite and exinite. Complementary information was obtained by using X-ray photoelectron spectroscopy. Within the vitrinite specimens studied, a widely-dispersed largely inorganic aluminosilicate phase was identified, which contained a number of other trace elements. By contrast, within the organic-rich phase of this macerai, titanium was detected in a very even distribution; this suggests that some titanium may be bonded in an organic complex. The fusinite was shown to contain elevated concentrations of calcium, magnesium and fluorine, dispersed over a large portion of the maceral. The high fluorine content could be identified as an organo-fluoro compound using XPS. Exinite was found to contain lower concentrations of most elements, compared to other macerals. The organic composition of this maceral was significantly different from that of surrounding macerals; this could be seen from the enhanced emission of the C₂H₂-secondary ion and images of this ion thus clearly outlined the position of such macerals.     

Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial

PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.     

Experimental study and modelling of the thermoelastic behaviour of composite fuel in reactors - emphasis on spinel based composites.

Among the different ways studied to transmute minor actinides (MA), the heterogeneous mode is preferred, where high contents of MAs are put in selected reactor locations. An inert matrix fuel (IMF) with MA compound particles is commonly considered. Its specificities are such that its behaviour under irradiation cannot be predicted directly by standard fuel codes. In the reactor, the IMF thermomechanical behaviour may be calculated following several principles, taking into account all the microstructures considered. Thermal modelling has been tested by an experimental irradiation, called THERMHET (THERMal behaviour of HETerogeneous fuel), where three different IMF were studied.     

Experimental investigation and numerical simulation of liquid supported stretch blow molding

An innovative production process for PET bottles ad containers is analyzed in this article. Liquid Bi‐Orientation (LBO) is a liquid supported stretch blow molding (SBM), which combines the separate blowing and filling phases of conventional SBM. The process modification is mainly characterized by forming the bottle using the desired liquid product instead of pressurized air. Consequently, possible improvements evolve regarding production cycle time, energy consumption and machine footprint. To make use of these capabilities, comprehensive process understanding is required, which can be increased using numerical simulation methods. Therefore, in this article, an LBO process model is set‐up and experimentally evaluated. The model explicitly considers the fluid‐structure interaction between liquid and PET, which significantly influences the PET forming behavior. The key simulation parameters namely the strong rate and temperature dependency of PET and a realistic process parameter determination are also included. The model is evaluated using two different methods to show the reliability of the process prediction. POLYM. ENG. SCI., 55:933–944, 2015. © 2014 Society of Plastics Engineers     

Aquifex aeolicus membrane hydrogenase for hydrogen biooxidation: Role of lipids and physiological partners in enzyme stability and activity

Hydrogenase I from the hyperthermophilic bacterium Aquifex aeolicus is a good candidate for biotechnological devices thanks to its ability to oxidize hydrogen at high temperature, even in the presence of oxygen and CO. In order to enhance the enzyme stability and the catalytic efficiency, we investigated the hydrogen oxidation process with hydrogenase I embedded in a physiological-like environment. Hydrogenase I partners in the metabolic chain, namely membrane quinone and cytochrome b, were purified and fully characterized. The complex hydrogenase I–cytochrome b was inserted into liposomes. Surface Plasmon Resonance revealed that quinone took part in the stabilization of the complex. By use of molecular modelization and electrochemistry analysis, enzyme stability has been demonstrated to be stronger and enzymatic efficiency to be five times higher when hydrogenase is embedded into the liposomes. This result raises the possibility of using hydrogenases as biocatalysts in fuel cells.     

Effects of gabapentin on the different components of peripheral and central neuropathic pain syndromes: a pilot study

Anticonvulsants are widely used in the treatment of neuropathic pain, and are assumed to act preferentially on lancinating, shooting pain. In the present study, the effects of gabapentin, a novel anticonvulsant, were evaluated systematically on both spontaneous and evoked pain in 18 patients with peripheral nerve injuries or central lesions. Gabapentin was administered orally in gradually increasing doses up to a maximum of 2,400 mg/day. Evaluations of spontaneous ongoing and paroxysmal pain, allodynia and hyperalgesia were performed at the beginning of the study ('baseline') and 6 weeks after the steady-state dose had been reached. Quantitative sensory tests were used to measure detection and pain thresholds to mechanical and thermal stimuli and the responses to suprathreshold stimuli. Gabapentin induced a moderate and statistically significant relief of ongoing spontaneous pain and was particularly effective in reducing paroxysmal pain. A striking finding was the significant effect on brush-induced and cold allodynia. In contrast, no effects were observed on detection and pain thresholds to static mechanical and hot stimuli. Side effects were generally minor and did not interfere with everyday activities. The present study suggests that gabapentin has preferential antihyperalgesic and/or antiallodynic effects, and is equally effective in pain due to peripheral nerve injuries and central lesions.     

New polymer electrolytes based on ether sulfate anions for lithium polymer batteries: Part I. Multifunctional ionomers: Conductivity and electrochemical stability

New lithium conducting ionomers based on commercial polyethers were synthesized by chemical modification in order to incorporate not only the anionic function on the polymer backbone but also polar aprotic and (or) protic groups improving both the salt dissociation and the anion-solvating ability of the multifunctional copolymers. The choice of environmentally friendly rather than perfluorinated anionic functions did not appear to compromise for the ionic conductivity. Lastly, the preliminary results on the use of an electrochemically stable and relatively cheap additive sparteine appear promising and could be generalized to a variety of polymer electrolytes for lithium batteries.     

A wind turbine blade profile analysis code based on the singularities method

The aerodynamic characteristics of wind turbines are closely related to the geometry of their blade profiles. The innovation and the technological development of wind turbine blade profiles can be centred on two tendencies. The first is to improve the shape of the existing airfoils and the second is to design new shapes of airfoils in order to get some more ambitious aerodynamic characteristics and enhanced performance.The aim of this paper is to develop an accurate airfoil analysis lower order code, based on the singularities method, for wind turbine applications. The 2D incompressible potential flow model has been used. In the implementation of the singularities method, source–vortex distributions over the airfoil contour are used to compute the flow characteristics. The accuracy and the validity of the results have been tested using experimental data obtained from Wind Turbine Airfoil Catalogue “Risø National Laboratory, Roskilde, Denmark, August 2001” and have shown considerable agreement.