Protection against adoptive transfer of autoimmune diabetes mediated through very late antigen-4 integrin

The very late antigen-4 (VLA-4) integrin expressed on the surface of lymphocytes and macrophages can regulate their migration to inflammatory sites as well as control cellular activation. The role of VLA-4 in the establishment of autoimmune diabetes is not easily predicted given the multiplicity of adhesion pathways and their differential use by various cell types. The contribution of VLA-4 to insulin-dependent diabetes mellitus was investigated by administration of VLA-4-specific monoclonal antibodies (MoAb) in an adoptive transfer model of disease in NOD mice. This study shows that VLA-4-specific MoAbs profoundly inhibit the development of diabetes with protection sustained by repeated MoAb exposure. Insulitis was completely inhibited during treatment and progressed to a severe degree once MoAb treatment was suspended, yet approximately 40% of treated recipients failed to become diabetic during 1-2 months post-treatment. Although we cannot rule out depletion of a relatively minor subpopulation of cells by prolonged anti-VLA-4 MoAb exposure, this inhibition of diabetes onset by treatment with MoAbs to VLA-4 supports a dependence on VLA-4 for cellular functions leading to diabetes and demonstrates that a significant disease modifying effect can be mediated by targeting the VLA-4 integrin.     

Can heat pipes solve the problems of drift and vibration of cryoholders?

Drift and vibration are the main factors limiting the resolution that can be attained with liquid-nitrogen (LN₂)-cooled cryoholders. Tests with a Gatan holder show that resolution is usually anisotropic. We propose that the metallic heat-conducting element could be replaced by a heat pipe, because such a device can, in principle, minimize drift. The vibration problem could be combatted by using supercooled cryogens.     

Dielectric integrity of thin thermal oxides on silicon

The role of silicon dioxide layers in microelectronics and the importance of their integrity are undisputable. From passivating coatings and masking layers for diffusion to ultra-thin tunneling films — all the silicon technology could not exist without silicon dioxide. This review deals with some aspects of the integrity of thin silicon dioxide films for VLSI applications. The problems of dielectric strength and wear-out are considered from the point of view of their mechanisms, models, oxide processing dependence, testing, and measuring. A brief presentation of statistical approaches commonly applied to reliability topics is also included.     

Editing function of Escherichia coli cysteinyl-tRNA synthetase: cyclization of cysteine to cysteine thiolactone

A cyclic sulfur compound, identified as cysteine thiolactone by several chemical and enzymatic tests, is formed from cysteine during in vitro tRNA(Cys) aminoacylation catalyzed by Escherichia coli cysteinyl-tRNA synthetase. The mechanism of cysteine thiolactone formation involves enzymatic deacylation of Cys-tRNA(Cys) (k = 0.017 s-1) in which nucleophilic sulfur of the side chain of cysteine in Cys-tRNA(Cys) attacks its carboxyl carbon to yield cysteine thiolactone. Nonenzymatic deacylation of Cys-tRNA(Cys) (k = 0.0006 s-1) yields cysteine, as expected. Inhibition of enzymatic deacylation of Cys-tRNA(Cys) by cysteine and Cys-AMP, but not by ATP, indicates that both synthesis of Cys-tRNA(Cys) and cyclization of cysteine to the thiolactone occur in a single active site of the enzyme. The cyclization of cysteine is mechanistically similar to the editing reactions of methionyl-tRNA synthetase. However, in contrast to methionyl-tRNA synthetase which needs the editing function to reject misactivated homocysteine, cysteinyl-tRNA synthetase is highly selective and is not faced with a problem in rejecting noncognate amino acids. Despite this, the present day cysteinyl-tRNA synthetase, like methionyl-tRNA synthetase, still retains an editing activity toward the cognate product, the charged tRNA. This function may be a remnant of a chemistry used by an ancestral cysteinyl-tRNA synthetase.     

Theoretical analysis of shunting effect in resistance spot welding (RSW) of AA2219

Shunting effect is the loss of electrical current via the secondary circuit provided due to existence of previous nugget in a series of welding spots. This phenomenon is important for products containing intermittent spots. In this study, a theoretical model is developed for shunting effect in resistance spot welding for aluminum alloy 2219. Welding distance together with welding current and time is included in the model to analyze the shunting effect on final nugget quality. Thermal and electrical interactions are considered in the model as well as geometrical aspects of the process. Temperature dependence of material properties, integration through the whole volume of the nugget and heat-affected zone, and assuming a simple cooling mechanism are the most important modifications designated in the proposed theoretical model. Predicted results of nugget diameter are compatible with experimental and finite element analysis results.     

Development of a Management Tool to Support the Beneficial Use of Treated Coal Seam Gas Water for Irrigation in Eastern Australia

An infiltration and salinity transport model (ISTM) based on the HYDRUS modeling platform was developed to support the beneficial use of treated coal seam gas (CSG) water to irrigate perennial forage plots in eastern Australia. The ISTM was used to support the expansion of irrigated areas under the CSG industry’s first specific irrigation beneficial use approval issued by the Queensland environmental regulatory administering authorities in March 2009. To support meeting regulatory requirements for expansion beyond the original irrigation area, forward modelling within the vadose zone was used to evaluate the fate and transport of the irrigation water as it migrates through the shallow soils and unsaturated bedrock toward the saturated zone; simulations beneath three agricultural systems with contrasting infiltration capacities were assessed. The model simulation results were used to guide irrigation activities to maximize water use in the readily available soil water capacity range for these agroecosystems, without detrimental impacts to plant growth or surface water/groundwater and soil resources. In this paper, a practical irrigation and rainfall systems-driven hydrogeochemical conceptual model is presented to identify processes that are likely to govern infiltration from the land surface, root water uptake, and solute transport into, and potentially through, the unsaturated zone. A numerical model is then parameterized to represent the primary processes hypothesized to affect water and salinity movement in the vadose zone. Finally, a series of simulations, conducted to identify the key parameters and processes governing the potential movement of water and salt through the root zone and into the bedrock vadose zone, are discussed. The simulations are used to support continuous improvement in modeling approaches for sustainably managing treated CSG extraction water allocated to irrigation.     

Molecular mapping with functional antibodies localizes critical sites on the human IL receptor common gamma (gamma c) chain

The IL receptor common gamma (gamma c) chain is required for the formation of high affinity cytokine receptor complexes for IL-2, IL-4, IL-7, IL-9, and IL-15, and for signals regulating cell survival, growth, and differentiation. Our current understanding of how gamma c chain associates with multiple ligands and receptor subunits is drawn largely from its structural homology to the human growth hormone (hGH) receptor and known structure of the hGH/hGH receptor complex. These receptors share distinct features in their extracellular portions and are believed to function by a mechanism of ligand-induced association of receptor subunits. Here, we report the first directed mutational analysis of the human gamma c chain by alanine scanning conducted across seven regions likely to contain residues required for intermolecular contact. Functionally distinct, neutralizing anti-gamma c mAbs were employed to define critical residues. One particular mAb, CP.B8, unique in its ability to inhibit IL-2-, IL-4-, IL-7-, and IL-15-induced proliferation and high affinity cytokine binding of normal T cells as an intact mAb and as a Fab fragment, localized critical residues to four noncontinuous stretches, namely residues in loops AB and EF of domain 1, in the interdomain segment, and in loop FG of domain 2. Notably, these residues form a contiguous patch on the gamma c chain surface in a three-dimensional structural model. These results provide functional evidence for the location of contact points on gamma c chain required for its association with multiple ligands.     

Effect of minority carrier injection on lateral current in MIS tunnel structures

In this work it is shown that the MIS structure with an ultra-thin $\text{(20}\text{A}\text{?}\text{< x}{}_{\mathrm{i}}\text{< 40}\text{A}\text{?}\text{)}$ oxide is distinguished by a unique mechanism of lateral conduction. The flow of the lateral current between the two metal electrodes formed on the surface of an ultra-thin silicon dioxide is found to take place through the silicon substrate and the two non-equilibrium MIS tunnel diodes formed by the metal electrodes, the ultra-thin oxide, and the silicon. One of these diodes is forward biased and the other reverse biased. It is shown that the main limitation to the lateral current comes from the reverse biased diode. A structure is proposed in which such a lateral current can be efficiently controlled by the injection of minority carriers from the gate of an appropriately formed, conventional MIS tunnel diode into the depletion region of the reverse biased diode, so limiting the lateral current. Various physical phenomena related to this effect are studied and discussed.The MIS lateral tunnel structure considered in this work was fabricated in order to investigate the influence of minority carrier injection on the lateral conduction in MIS tunnel devices. However, the ideas proposed in this work can be developed into useful device structures.     

Interface optimization for poly silicon/tungsten gates

Novel dual work function (DWF) based transistors featuring low gate resistances are presented. The process discussed enables extremely fast array timings easily and is thus key to fulfilling the performance requirements for high performance DRAM chips. The key enabler of the advanced gate integration scheme and its properties is the understanding of tuning the interface contact resistance. The objective of this work was to systematically investigate the role of the interface between poly-Si and metal of DRAM gate structures focused on electrical data. Contact resistance values, speed and elemental analysis information summarize the main findings of the gate development and furthermore the stable control of the very thin film stack in high volume production.     

Metabolism of homocysteine thiolactone in human cell cultures. Possible mechanism for pathological consequences of elevated homocysteine levels

Editing of the non-protein amino acid homocysteine, a frequent type of error-correcting process in amino acid selection for protein synthesis by an aminoacyl-tRNA synthetase, results in formation of a cyclic thioester, homocysteine thiolactone. Here it is shown that human cells in which homocysteine metabolism is deregulated by a mutation in the cystathionine beta-synthase gene and/or by an antifolate drug, aminopterin (which prevents remethylation of homocysteine to methionine by methionine synthase), produce more homocysteine thiolactone, in addition to homocysteine, than unaffected cells. The thiolactone is incorporated into cellular and extracellular proteins, in addition to being secreted and hydrolyzed to homocysteine. Experiments with model proteins and amino acids suggest that the mechanism of incorporation involves acylation of side chain amino groups of lysine residues by the activated carboxyl group of the thiolactone. The metabolic conversion of homocysteine to homocysteine thiolactone and the reactivity of the thiolactone toward proteins may explain pathological consequences of elevated levels of homocysteine such as observed in vascular disease.