Roles for transforming growth factor-alpha in gastric physiology and pathophysiology.

Transforming growth factor alpha (TGF alpha) is a 5.6 kd single-chain polypeptide that acts through binding to the epidermal growth factor receptor (EGFR). TGF alpha is produced in a wide range of normal as well as embryonic and neoplastic cells and tissues. TGF alpha and EGFR, but not EGF, are expressed in normal gastric mucosa. We have identified the following biological roles for TGF alpha in the stomach, using a variety of primate and rodent models: inhibition of acid secretion; stimulation of mucous cell growth; protection against ethanol- and aspirin-induced injury. This last effect is associated with a time- and dose-dependent increase in levels of insoluble gastric mucin. Based on these known biological actions of TGF alpha, we have examined TGF alpha production in Ménétrier's disease, a disorder characterized by foveolar hyperplasia, hypochlorhydria, and increased gastric mucin content. In four patients with Ménétrier's disease, there was enhanced TGF alpha immunostaining throughout the gastric mucosa. Furthermore, metallothionein (MT)-TGF alpha transgenic mice which overproduce TGF alpha in the stomach exhibit histopathological and biochemical features characteristic of and consistent with the diagnosis of Ménétrier's disease. Thus locally produced TGF alpha may mediate a number of biological processes in the stomach, and its altered production may participate in the pathogenesis of selected pathological states

Evidence of Counter-Streaming Ions near the Inner Pole of the HERMeS Hall Thruster

NASA is continuing the development of a 12.5-kW Hall thruster system to support a phased exploration concept to expand human presence to cis-lunar space and eventually to Mars. The development team is transitioning knowledge gained from the testing of the government-built Technology Development Unit (TDU) to the contractor-built Engineering Test Unit (ETU). A new laser-induced fluorescence diagnostic was developed to obtain data for validating the Hall thruster models and for comparing the behavior of the ETU and TDU. Analysis of TDU LIF data obtained during initial deployment of the diagnostics revealed evidence of two streams of ions moving in opposite directions near the inner front pole. These two streams of ions were found to intersect the downstream surface of the front pole at large oblique angles. This data points to a possible explanation for why the erosion rate of polished pole covers were observed to decrease over the course of several hundred hours of thruster operation

Topology of amorphous tetrahedral semiconductors on intermediate lengthscales

Using the recently-proposed ``activation-relaxation technique'' for optimizing complex structures, we develop a structural model appropriate to a-GaAs which is almost free of odd-membered rings, i.e., wrong bonds, and possesses an almost perfect coordination of four. The model is found to be superior to structures obtained from much more computer-intensive tight-binding or quantum molecular-dynamics simulations. For the elemental system a-Si, where wrong bonds do not exist, the cost in elastic energy for removing odd-membered rings is such that the traditional continuous-random network is appropriate. Our study thus provides, for the first time, direct information on the nature of intermediate-range topology in amorphous tetrahedral semiconductors.Comment: 4 pages, Latex and 2 postscript figure

Structural, electronic, and dynamical properties of amorphous gallium arsenide: a comparison between two topological models

We present a detailed study of the effect of local chemical ordering on the structural, electronic, and dynamical properties of amorphous gallium arsenide. Using the recently-proposed ``activation-relaxation technique'' and empirical potentials, we have constructed two 216-atom tetrahedral continuous random networks with different topological properties, which were further relaxed using tight-binding molecular dynamics. The first network corresponds to the traditional, amorphous, Polk-type, network, randomly decorated with Ga and As atoms. The second is an amorphous structure with a minimum of wrong (homopolar) bonds, and therefore a minimum of odd-membered atomic rings, and thus corresponds to the Connell-Temkin model. By comparing the structural, electronic, and dynamical properties of these two models, we show that the Connell-Temkin network is energetically favored over Polk, but that most properties are little affected by the differences in topology. We conclude that most indirect experimental evidence for the presence (or absence) of wrong bonds is much weaker than previously believed and that only direct structural measurements, i.e., of such quantities as partial radial distribution functions, can provide quantitative information on these defects in a-GaAs.Comment: 10 pages, 7 ps figures with eps

200-GeV ISA with room temperature magnets

A conceptual design study of 200-GeV proton intersecting storage accclerators with room temperature magnets is presented. The key to this study was thc desire to keep the electric power consumptiom to an acceptable level (40 MW). The design has been optimized by choosing small-gap (4 cm) aluminum coil dipoles operating at about 15 kG. The luminosity of this machine is limited to about 10/sup 32/ cm-/sup -2/ sec/sup -1/ by transverse space-charg e effects. An order of magnitude higher luminositics can be obtained by adding a booster of modest cost. A novel vacuum system using distributed Ti-sublimation pumps results in considerable savings. A cost comparison with a high-luminosity superconducting machine is given. (auth

Fast DNA translocation through a solid-state nanopore

We report translocation experiments on double-strand DNA through a silicon oxide nanopore. Samples containing DNA fragments with seven different lengths between 2000 to 96000 basepairs have been electrophoretically driven through a 10 nm pore. We find a power-law scaling of the translocation time versus length, with an exponent of 1.26 $\pm$ 0.07. This behavior is qualitatively different from the linear behavior observed in similar experiments performed with protein pores. We address the observed nonlinear scaling in a theoretical model that describes experiments where hydrodynamic drag on the section of the polymer outside the pore is the dominant force counteracting the driving. We show that this is the case in our experiments and derive a power-law scaling with an exponent of 1.18, in excellent agreement with our data.Comment: 5 pages, 2 figures. Submitted to PR

Linear-Accelerator Program

Contains reports on one research project

The contribution of open extremity fractures to infection in multiply injured patients

We sought to determine whether a contaminated open fracture was a reliable component for calculating the Outcome Predictive Score in patients with multiple injuries. We studied 41 patients whose primary source of contamination was open extremity fractures. Only one of the 41 patients developed osteomyelitis. The rate of infection from an open fracture is minimal in the multiply injured patient. Inclusion of patients with open fractures in studies that assess the likelihood of infection and the value of anti-infective agents incorrectly identified patients for clinical trials and results in an overestimation of survival based on the Outcome Predictive Score. These findings suggest that open fractures should be excluded as an entry criterion in future clinical trials.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/31658/1/0000592.pd

Thoracic Aortic Calcium Versus Coronary Artery Calcium for the Prediction of Coronary Heart Disease and Cardiovascular Disease Events

ObjectivesThis study compared the ability of coronary artery calcium (CAC) and thoracic aortic calcium (TAC) to predict coronary heart disease (CHD) and cardiovascular disease (CVD) events.BackgroundCoronary artery calcium has been shown to strongly predict CHD and CVD events, but it is unknown whether TAC, also measured within a single cardiac computed tomography (CT) scan, is of further value in predicting events.MethodsA total of 2,303 asymptomatic adults (mean age 55.7 years, 38% female) with CT scans were followed up for 4.4 years for CHD (myocardial infarction, cardiac death, or late revascularizations) and CVD (CHD plus stroke). Cox regression, adjusted for Framingham risk score (FRS), examined the relation of Agatston CAC and TAC categories, and log-transformed CAC and TAC with the incidence of CHD and CVD events and receiver-operator characteristic (ROC) curves tested whether TAC improved prediction of events over CAC and FRS.ResultsA total of 53% of subjects had Agatston CAC scores of 0; 8% 1 to 9; 19% 10 to 99; 12% 100 to 399; and 8% ≥400. For TAC, proportions were 69%, 5%, 12%, 8%, and 7%, respectively; 41 subjects (1.8%) experienced CHD and 47 (2.0%) CVD events. The FRS-adjusted hazard ratios (HR) across increasing CAC groups (relative to <10) ranged from 3.7 (p = 0.04) to 19.6 (p < 0.001) for CHD and from 2.8 (p = 0.07) to 13.1 (p < 0.001) for CVD events; only TAC scores of 100 to 399 predicted CHD and CVD (HR: 3.0, p = 0.008, and HR: 2.3, p = 0.04, respectively); these risks were attenuated after accounting for CAC. Findings were consistent when using log-transformed CAC and TAC Agatston and volume scores. The ROC curve analyses showed CAC predicted CHD and CVD events over FRS alone (p < 0.01); however, TAC did not further add to predicting events over FRS or CAC.ConclusionsThis study found that CAC, but not TAC, is strongly related to CHD and CVD events. Moreover, TAC does not further improve event prediction over CAC

Modern Electronic Techniques Applied to Physics and Engineering

Contains reports on two research projects