The interaction of ICAM-1 with LFA-1: intercellular signaling and implication in type I diabetes

T lymphocytes are cells that play an essential role in both the regulation and activation of an immune response. The T cells role is two-fold: they migrate to an inflammatory site by interacting with endothelial cells lining the blood vessels and upon reaching the site of inflammation, interact with antigen presenting cells to facilitate clearance of the invading microorganism. The cell surface molecules ICAM-1 and LFA-1 play a large role in the function of T lymphocytes. These proteins act as counter-receptors that mediate both migration and activation. Proper regulation of T cell activation requires two costimulatory signals, one from the T cell receptor (TCR)-CD3 complex and the second from a surface molecule on an antigen presenting cell (APC). The first signal is characterized by the TCR-CD3 complex binding cognate antigen as it is being presented on a major histocompatibility complex (MHC) molecule. The second signal involves binding of a costimulatory molecule on the surface of a T cell, usually CD28, with a counter receptor present on the surface of an APC. ICAM-1, the focus of the present work, is located on the surface of T cells and functions in adhesion and extravasation of the cell during inflammation. Our lab and others have previously published that ICAM-1 can also act as a costimulatory molecule capable of delivering the second signal for T cell activation independent of the more traditional second signal, CD28. In the present work, we elucidated the components of the signaling complex formed after stimulation through ICAM-1. The proteins identified thus far include mitogen- activated protein kinase (MAPK), CD45, LFA-1, LAT, Gads, the Src tyrosine kinase family proteins Lck and Fyn, and the ZAP-70/CD3ζ complex. Since the ICAM-1/LFA-1 interaction is essential for proper T cell function, blocking the interaction could be a useful means of regulating improper immune response thus treating the diseases associated with its dysfunction. Previous studies in our lab using peptides derived from ICAM-1 and LFA-1 have proven beneficial in treating several autoimmune diseases. Here we sought to test a shorter course of peptide therapy and evaluated the treatment in a model for type I diabetes. The peptides not only delayed the onset of diabetes in the treated animals, but also drastically reduced the amount of infiltration seen within the islets of the pancreas. In addition to the diabetes study using the native peptides, we also used computational approaches to develop an alternative set of peptides with an increased affinity for ICAM-1 and LFA-1 and assessed their effect on T cell activation and function. We found that both peptides were able to inhibit MDHC-induced T cell adhesion in a clumping assay indicating specificity for both ICAM-1 and LFA-1. We also found that stimulating with anti-CD3 in the presence of each peptide caused a marked increase in proliferation of human T cells. This result suggests that the redesigned peptides are capable of acting as a costimulatory signal themselves

Provide thermogravimetric analysis data to performance assessment

Recent experimental testing has investigated the effect of a deposited mixed salt on the corrosion of carbon steel in high relative humidity air. This result is compared with previous studies where pure sodium chloride was deposited. There are aspects of the degradation process which are significantly different when the different salts are deposited. With deposited sodium chloride, corrosion occurs almost immediately after introduction of 80% RH air. With deposited mixed salts, there is an initial inhibition of corrosion in 80% RH air. After the initial inhibition period, corrosion occurs at localized regions of the specimen. At longer times, the specimen suffers extensive corrosion. A very porous and non-adherent corrosion product forms and readily spalls. The initial inhibition of the corrosion with the deposited mixed salt is most likely due to the bicarbonate component. Bicarbonate is a known inhibitor of general corrosion of carbon steel [Thomas, 1994] and a promoter of localized corrosion at moderate alkalinity when chloride ions are present [Marsh, 1985]. The results of this testing indicate that the bicarbonate component of thin water layers can initially inhibit corrosion of the carbon steel. With time, however, inhibition is lost. A mechanism for this loss of inhibition is suggested. It is plausible that moderately alkaline bicarbonate aqueous solutions could develop on the surface of a waste package due to Yucca Mountain water contacting the waste packages. Aqueous conditions might develop where carbon steel is susceptible to localized corrosion [Dunn, 1998]. The initial test results presented here suggest that the inhibition of general corrosion, and hence, the promotion of localized corrosion of carbon steel by thin aqueous bicarbonate-chloride layers may not be sustainable. Additional testing is underway to further understand the effects of thin aqueous solution chemistry on carbon steel corrosion

Formulation and make-up of simulate dilute water, low ionic content aqueous solution

This procedure describes the formulation and make-up of Simulated Dilute Water (SOW), a low-ionic-content water to be used for Activity E-20-50, Long-Term Corrosion Studies. This water has an ionic content which is nominally a factor of ten higher than that of representative waters at or near Yucca Mountain. Representative waters were chosen as J-13 well water [Harrar, 1990] and perched water at Yucca Mountain [Glassley, 1996]. J-13 well water is obtained from ground water that is in contact with the Topopah Spring tuff, which is the repository horizon rock. The perched water is located in the Topopah Spring tuff, but below the repository horizon and above the water table. A nominal times ten higher ionic content was chosen to simulate the effect of ionic concentrating due to elevated temperature water flowing through fractures where salts and minerals have been deposited due to evaporation and boiling

Formulation and make-up of simulated acidic concentrated water (SAW), high ionic content aqueous solution

This procedure describes the formulation and make-up of Simulated Acidified Water (SAW), a high-ionic-content water to be used for Activity E-20-50 ''Long-Term Corrosion Studies.'' Acidic solutions at the repository may result as a consequence of microbial activity. In formulating the ionic composition of the SAW, it was attempted to simulate the acidification of high ionic content water contacting a waste package. Therefore, the composition of this water is based on the acidification of the Simulated Concentrated Water (SCW), which is described in TIP-CM-07. The pH of the solution will be controlled at a nominal value of 2

Anticipatory eye movements stabilize gaze during self‐generated head movements

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87072/1/j.1749-6632.2011.06165.x.pd

Thermogravimetric analysis studies

Independent of thermal loading scenarios, the waste packages at the proposed repository at Yucca Mountain, Nevada will be exposed to environmental conditions of temperatures below 100 C with a range of possible relative humidities. Under high relative humidities, the formation of thin water films on the metal surfaces will occur. Previous work at ambient conditions has shown that on susceptible metals, the water-film-covered metal has an enhanced corrosion rate relative to the dry oxidation of the metal. The transition relative humidity where oxidation changes from dry oxidation to aqueous electrochemical corrosion is called the critical relative humidity. Determination of this transition is important in estimating the performance of the candidate materials (especially corrosion allowance materials), because of the marked increase in degradation rate above the critical relative humidity, typically 10-10{sup 2} times This activity is concerned with short term measurements of corrosion and oxidation rates using a high sensitivity microbalance. The experimental work will determine the critical humidity level for candidate metals under a variety of conditions. From the literature, the critical humidity level typically are around 70% relative humidity, but this level is affected by the metal, gas composition, temperature, and the presence of contaminants on the surface, particularly contaminants that are deliquescent. A series of experiments will bracket a range of humidity, temperature, metal alloy, and surface condition

The Reflector

Incorporates etymology, history, art, drawing, and reflective writing to support medical students in the integration of the science and humanity of anatomy. A comprehensive and holistic understanding of human anatomy is foundational to the care of patients. The Reflector is an innovative and interdisciplinary approach to the learning of human anatomy; it incorporates etymology, history, art, drawing, and reflective writing to integrate the learning of anatomical structures with the nonanatomical curriculum of the anatomy lab, thus establishing the foundation for a biopsychosocial approach to medicine. To develop visual skills, this work features drawings that illustrate the original inspirations for anatomical terminology while also providing the space to artistically reimagine these structures. Together, these activities enhance the comprehension and retention of anatomical information for application in medical sciences. The Reflector employs thought-provoking questions that emphasize humanity in anatomy, in order to prompt consideration of the anatomical structures beyond basic science. Reflecting on the experiences of anatomical dissections, specifically in relation to development of habits of mind necessary for patient- and family-centered care, continually connects students to the purpose of their studies - to become a knowledgeable, compassionate, self-aware, reflective, and skilled member of a healing profession. Edited by a medical student with a Master's of Science degree in Medical Humanities; an anatomical science faculty member dedicated to the holistically educated medical provider; an expert in visual learning and self-reflection; and a bioethicist, The Reflector is a valuable resource for all who want to understand the human in human anatomy

The effect of water vapor on the corrosion of carbon steel at 65{degree}C

AISI 1020 carbon steel was exposed to air at various relative humidities at 65{degrees}C. A ``critical relative humidity`` (CRH) of 75--85% was determined. The CRH is the transitional relative humidity where oxidation/corrosion changes from dry oxidation to aqueous film electrochemical corrosion. Short term testing suggests that aqueous film electrochemical corrosion results in the formation of an inner oxide of Fe{sub 3}O{sub 4}, and an outer oxide of a powdery Fe{sub 2}O{sub 3} and/or Fe{sub 2}O{sub 3}{center_dot}xH{sub 2}O

Representation of Neck Velocity and Neck–Vestibular Interactions in Pursuit Neurons in the Simian Frontal Eye Fields

The smooth pursuit system must interact with the vestibular system to maintain the accuracy of eye movements in space (i.e., gaze-movement) during head movement. Normally, the head moves on the stationary trunk. Vestibular signals cannot distinguish whether the head or whole body is moving. Neck proprioceptive inputs provide information about head movements relative to the trunk. Previous studies have shown that the majority of pursuit neurons in the frontal eye fields (FEF) carry visual information about target velocity, vestibular information about whole-body movements, and signal eye- or gaze-velocity. However, it is unknown whether FEF neurons carry neck proprioceptive signals. By passive trunk-on-head rotation, we tested neck inputs to FEF pursuit neurons in 2 monkeys. The majority of FEF pursuit neurons tested that had horizontal preferred directions (87%) responded to horizontal trunk-on-head rotation. The modulation consisted predominantly of velocity components. Discharge modulation during pursuit and trunk-on-head rotation added linearly. During passive head-on-trunk rotation, modulation to vestibular and neck inputs also added linearly in most neurons, although in half of gaze-velocity neurons neck responses were strongly influenced by the context of neck rotation. Our results suggest that neck inputs could contribute to representing eye- and gaze-velocity FEF signals in trunk coordinates