Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library

The muscle weakness in myasthenia gravis (MG) is caused by heterogeneous high-affinity IgG autoantibodies to the nicotinic acetylcholine receptor (AChR), a complex ion channel glycoprotein. These antibodies are clearly responsible for reducing AChR numbers at the neuromuscular junction in myasthenia; however, the origins, diversity, specificity and pathogenicity of individual antibodies have not yet been established. We have cloned and characterized four different AChR-specific Fab from an MG patient's thymus by screening an IgG1/kappa gene combinatorial lambda phage library with soluble human AChR labeled with [125I] alpha-bungarotoxin. Unlike most previously cloned human antibodies, all four Fab immunoprecipitated soluble human muscle AChR. Two Fab strongly inhibited binding of mAb to the main immunogenic region on the alpha subunits and one Fab bound to an epitope on the fetal-specific gamma subunit. In sensitivity and fine specificity, these Fab resembled the anti-AChR antibodies found in many MG patients, including the donor. The closest germline counterparts for their heavy chains were in VH families 1, 3 and 4; however, there were many differences consistent with an antigen-driven response of diverse B cell clones. The combinatorial approach holds promise for further analysis of human autoantibodies.     

Cholesterol transport and uptake in miniature swine fed vegetable and animal fats and proteis. 1. Plasma lipoproteins and LDL clearance

In a 2×2 factorial arrangement, miniature pigs were fed four diets containing vegetable protein/fat (soybean) and animal protein (egg white)/fat (beef tallow) to demonstrate the effects of protein and fat source on total plasma cholesterol, lipoprotein distribution, low density lipoprotein (LDL) composition, and plasma clearance of LDL-cholesterol and protein. Beef tallow consumption resulted in greater plasma cholesterol concentration, decreased LDL-cholesterol concentration, and a lower LDL-cholesterol to LDL-protein ratio than did consumption of soybean oil. High density lipoprotein (HDL)-cholesterol concentration was increased by beef tallow consumption. Cholesterol percentage by weight in LDL was significantly greater in pigs consuming soybean oil than those consuming beef tallow. Percentages by weight of protein, triglyceride and phospholipid in LDL were not significantly different in any group. Dietary protein source had no significant effect on total plasma cholesterol concentration, lipoprotein concentration or LDL composition. Egg white consumption decreased fractional catabolic rate and irreversible loss of LDL-cholesterol and LDL-protein when compared with consumption of soy protein. Dietary fat source had no consistent effect on LDL clearance from plasma. Dietary fat and protein seemed to influence lipoprotein metabolism by different mechanisms. Fat source altered lipoprotein concentration and LDL composition, whereas protein source affected the removal rate of LDL from plasma. Data taken from a dissertation submitted to Iowa State University by L. S. Walsh Hentges as partial fulfillment of the requirements for the Ph.D. degree. A preliminary paper, was presented at the meeting of the American Oil Chemists' Society in Dallas, Texas, May, 1984.     

Chemical Stability of the Fiber Coating Matrix Interface in Silicon-Based Ceramic Matrix Composites

Carbon and boron nitride are used as fiber coatings in silicon-based composites. In order to assess the long-term stability of these materials, reactions of carbon/Si₃N₄ and BN/SiC were studied at high temperatures with Knudsen effusion, coupon tests, and by microstructural examination. In the carbon/Si₃N₄ system, carbon reacted with Si₃N₄ to form gaseous N₂ and SiC. The formation of SiC limited further reaction by physically separating the carbon and Si₃N₄. Consequently, the development of high p (N₂) at the interface, predicted from thermochemical calculations, did not occur, thus limiting the potential deleterious effects of the reaction on the composite. Strong indications of a reaction between BN and SiC were shown by TEM and SIMS analysis of the BN/SiC interface. In long-term exposures, this reaction can lead to a depletion of a BN coating and/or an unfavorable change of the interfacial properties, limiting the beneficial effects of the coating.     

Ractions of SiC with H2/H2O/Ar Mixtures at 1300°C

The reactions of a sintered α-SiC with 5% H₂/H₂O/Ar at 1300°C were studied. Thermomchemical modeling indicates that three reaction regions are expected, depending on the initial water vapor or equivalently oxygen content of the gas stream. A high oxygen content ( P (O₂) > 10⁻²² atm) leads to a SiO₂ formation. This generally forms as a protective film and limits consumption of the SiC (passive oxidation). An intermediate oxygen content (10⁻²² atm > P (O₂) > 10⁻²⁶ atm) leads to SiO and CO formation. These gaseous products can lead to rapid consumption of the SiC (active oxidation). Thermogravimetric studies in this intermediate region gave reaction rates which appear to be controlled by H₂O gas-phase transport to the sample and reacted microstructures showed extensive grain-boundary attack in this region. Finally, a very low oxygen content ( P (O₂) < 10⁻²⁶ atm) is thermochemically predicted to lead to selective removal of carbon and formation of free silicon. Experimentally low weight losses and iron silicides are observed in this region. The iron silicides are attributed to reaction of free silicon and iron impurities in the system.     

What localizes beneath: A metric multisensor localization and mapping system for autonomous underground mining vehicles

Robustly and accurately localizing vehicles in underground mines is particularly challenging due to the unavailability of GPS, variable and often poor lighting conditions, visual aliasing in long tunnels, and airborne dust and water. In this paper, we present a novel, infrastructure‐less, multisensor localization method for robust autonomous operation within underground mines. The proposed method integrates with existing mine site commissioning and operation procedures and includes both an offline map‐building process and an online localization algorithm. The approach combines the strengths of visual‐based place recognition, LIDAR‐based localization, and odometry in a particle filter fusion process. We provide an extensive experimental validation using new large data sets acquired in two operational Australian underground hard‐rock mines (including a 600m‐deep multilevel mine with approximately 33 km of mapping data and 7 km of vehicle localization) by actual mining vehicles during production operations. We demonstrate a significant increase in localization accuracy over prior state‐of‐the‐art SLAM research systems and real‐time operation, with processing times in the order of 10 Hz. We present results showing a mean error of 0.68 m from the Queensland Mine data set and 1.32 m from the New South Wales Mine data set and at least 86% reduction in error compared with prior state of the art. We also analyze the impact of the particle filter parameters with respect to localization accuracy. Together this study represents a new approach to positioning systems for currently deployed autonomous vehicles within underground mine environments.     

Compatibility of inconel 617R alloy with LIF-MGF2-kf thermal energy storage salts and vacuum at high temperature

Thermal energy storage capsules made of Inconel 617 alloy were filled with high- purity LiF- MgF2- KF salts and thermally cycled at 983 ± 100 K in vacuum for up to 5 years. The containment life performance characteristics with fluoride salts and in vacuum were examined. Metallographic study indicated that the inside surfaces of the post- test containers had a corrosion damage of 100 um in depth after 5 years of thermal cycling. The outer surface showed a vaporization damage of 120 μm after the same period. After 5 years of thermal cycling, the aluminum concentration at the capsule interior surface was reduced to 0.424 wt% from a nominal concentration of 1.34 wt% and chromium was reduced to 18.7 wt% from a nominal concentration of 21.8 wt%. A more significant depletion of aluminum and chromium was observed at the outer surfaces. Atomic absorption spectroscopy (AAS) and differential thermal analysis (DTA) were used to reveal the alloying element dissolution and the changes in melting temperature and heat of fusion of fluoride salts during thermal cycling. A modified diffusion equation for a one-dimensional semi-infinite bar was applied to the depletion of aluminum on the interior surfaces of the containers. Good agreement was obtained between the analysis and the measured concentration profiles. Inconel 617 is a registered trademark of the Inco Alloys International, Inc.     

Sodium sulfate: Deposition and dissolution of silica

The hot-corrosion process for SiO₂-protected materials involves deposition of Na₂SO₄ and dissolution of the protective SiO₂ scale. Dew points for Na ₂SO₄ deposition are calculated as a function of pressure, sodium content, and sulfur content. Expected dissolution regimes for SiO₂ are calculated as a function of Na₂SO₄ basicity, hence generated by fuels with 0.5% and 0.05% S. Controlled-condition burner-rig tests on quartz verify some of these predicted dissolution regimes. However, the basicity of Na₂SO₄ is not always a simple function of (Na₂O) show that carbon creates basic conditions in Na₂SO₄, which explains the extensive corrosion of SiO₂-protected materials containing carbon, such as SiC.     

SiO(g) formation from SiC in mixed oxidizing-reducing gases

The formation of SiO(g) from SiC by either active oxidation or an oxidation-reduction process is discussed. The Wagner criterion for the transition from active to passive oxidation is generalized for any oxidant. Kinetic modeling of both active oxidation and oxidation-reduction is described.Symbols - - MW _SiC/MW _Si - _CO CO(g) boundary layer thickness - _ox gaseous-oxidant, boundary layer thickness - stoichiometric factor from Eqs. (2)–(4), # of CO produced/# of oxidant (on oxygen atom basis) - gas viscosity - concentration of diffusing gas species in boundary layer - concentration of major gas species in boundary layer - _oxide density of SiO₂ - D diffusion coefficient of diffusing species in gas-boundary layer - D _CO diffusion coefficient of CO(g) - D _ox gas diffusion coefficient of oxidant - J flux, rate of weight loss limited by diffusion in gas-boundary layer - J _CO flux of CO(g) - J _ox flux of gaseous oxidant - K _g linear oxide growth constant, weight/(length² time) - k _g linear oxide growth constant, length/time - k _l linear volatilization constant for SiO₂,k _lo+k _ls, weight/(length² time) - k _lo linear volatilization constant for oxygen from SiO₂, weight/(length² time) - k _ls linear volatilization constant for silicon from SiO₂, weight/(length² time) - k _l linear volatilization constant for SiO₂, length/time - k _p parabolic oxide growth constant, weight²/(length⁴ time) - k _p parabolic oxide growth constant, length²/time - L sample length parallel to gas flow direction - (M/A)₁ specific weight change due to oxygen gain and associated carbon loss in paralinear oxidation - (M/A)_1L limiting value of weight change due to oxygen gain and associated carbon loss in paralinear oxidation - (M/A)₂ specific weight change due to silicon loss and associated carbon loss in paralinear oxidation - MW _C molecular weight of carbon - molecular weight of O₂ - MW _Si molecular weight of silicon - MW _SiC molecular weight of silicon carbide - molecular weight of silica - n number of oxygen atoms per oxidant molecule - P _CO ^eq eqiilibrium CO(g) pressure - P _CO ^g CO(g) pressure outside of boundary layer - P _CO ⁱ CO(g) pressure at SiC-gas interface - P _ox ^g oxidant gas pressure outside of boundary layer - P _ox ⁱ oxidant gas pressure at SiC-gas interface - R gas constant - t time - T absolute temperature - v linear gas velocity - x oxide thickness - x _L limiting oxide thickness achieved in paralinear oxidation - x _t oxide thickness at which transition from linear to parabolic growth occurs     

Successful engraftment of T-cell-depleted haploidentical "three-loci" incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum

Patients who undergo transplantation with haploidentical "three-loci" mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells from HLA-haploidentical "three-loci" incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E-rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.     

Long latency postural reflexes are under supraspinal dopaminergic control

Scaling of posturally stabilizing long latency (LL) reflexes in tibialis anterior muscles induced by "toe-up" rotational perturbations is abnormal in standing patients with Parkinson's disease. To investigate the contribution of dopaminergic pathways to abnormal scaling, we studied LL reflexes in 22 patients with selective hypodopaminergic syndromes: 10 psychiatric patients taking chronic neuroleptic medication (7 with mild parkinsonism), 8 patients with young-onset Parkinson's disease, and 4 patients with MPTP-induced parkinsonism. Results were compared with those of 10 healthy controls. Stimuli consisted of (a) 10 serial (predictable) perturbations of 4 degrees amplitude, (b) 10 serial (predictable) perturbations of 10 degrees amplitude, and (c) 20 randomly mixed (unpredictable) perturbations of either 4 or 10 degrees amplitude. In normal subjects, LL reflex amplitudes were adapted to match predictable variations in stimulus size, whereas under unpredictable conditions a "default" response emerged that anticipated the 10 degrees perturbation. LL reflex scaling under predictable conditions was intact in patients with neuroleptic-induced parkinsonism and young-onset Parkinson's disease, but the large default LL response under unpredictable conditions was absent. In patients with MPTP-induced parkinsonism, LL reflex scaling was absent during both predictable and unpredictable conditions. We conclude that abnormal scaling of posturally stabilizing LL reflexes is related to decreased supraspinal dopaminergic influence.