Egr-2 and PD-1 Are Required for Induction and Maintenance of T Cell Anergy: A Dissertation

The prevalence of diabetes is approaching epidemic proportions worldwide. There is currently no cure for type 1 diabetes, and successful treatment requires constant monitoring of blood sugars and use of exogenous insulin to prevent hyperglycemia. Diabetes will be curable when pancreatic β-islet cells can be transplanted into diabetes patients without requiring long-term immunosuppression. This will require learning more about the induction of functional tolerance, a state that maintains the competence of the immune system to most antigens but protects graft-specific antigens from immune rejection, permitting transplantation. One known mechanism of peripheral tolerance is T cell anergy, a phenotype of hypo-reponsiveness in CD4+ T cells. The focus of this thesis is a description of factors shown to be specific to the induction and maintenance of T cell anergy, whose loss reverses the anergic phenotype, restoring the ability of the cells to proliferate in response to antigen. The first of these is Egr-2, a zinc-finger transcription factor, whose presence is required for the induction of anergy induced in T cell clones by TCR stimulation in the absence of costimulation. Egr-2 is shown to be important to anergy induction but not anergy maintenance. In contrast, a negative costimulation receptor, PD-1, is shown to be necessary for the maintenance of anergy. It is possible that learning more about the genetic factors that orchestrate T cell anergy will prove useful in the development of tolerance-based protocols for organ and tissue transplantation without the use of long-term immunosuppression

Space shuttle main engine fault detection using neural networks

A method for on-line Space Shuttle Main Engine (SSME) anomaly detection and fault typing using a feedback neural network is described. The method involves the computation of features representing time-variance of SSME sensor parameters, using historical test case data. The network is trained, using backpropagation, to recognize a set of fault cases. The network is then able to diagnose new fault cases correctly. An essential element of the training technique is the inclusion of randomly generated data along with the real data, in order to span the entire input space of potential non-nominal data

Mems device with large out-of-plane actuation and low-resistance interconnect and methods of use

Source: United States Patent and Trademark Office, www.uspto.gov”The present application is directed to a MEMS device. The MEMS device includes a substrate having a first end and a second end extending along a longitudinal axis, the Substrate including an electrostatic actuator. The device also includes a movable plate having a first end and a second end. The device also includes a thermal actuator having a first end coupled to the first end of the substrate and a second end coupled to the first end of the plate. The actuator moves the plate in relation to the substrate. Further, the device includes a power source electrically coupled to the thermal actuator and the Substrate. The application is also directed to a method for operating a MEMS device

Soil-nailed and the Tie-back Wall Construction Using Hollow Nails

Excavation support is commonly provided using soil-nailed walls or tie-hack walls. This paper describes two case histories where nails and anchors where installed using a hollow reinforcing bar and a disposable drill bit. A lean grout was pumped through the reinforcing bar as it was driven into the ground. This process created a reinforced grout column with a diameter of about 150 mm. This procedure reduced the time of installation and resulted in cost savings of about 25% in comparison with conventional procedures. The procedure was used successfully to install nails in sandy gravels and silty sands. It was also used successfully to install tic-back anchors and the measured horizontal and vertical movements behind the wall were well within acceptable limits. Pull-out tests indicated that the ultimate pull-out resistance of the nails/anchors was between 58.3 to 65.6 kN/m (4 to 4.5 kips/ft) in the gravelly sands and 49.6 kN/m to 56.8 kN/m (3.4 to 3.9 kips/ft) in the silly sand (30%) tines. The soil-nail approach was not found to be practical where thick sequences of clean sands were encountered due to surface raveling and caving

Design of a Bioreactor to Cyclically Strain Tissue Engineered Blood Vessels

Cyclic mechanical loading improves strength and extracellular matrix (ECM) synthesis in tissue engineered blood vessels (TEBV). The goal of this project was to design a device to impart cyclic circumferential stretch on cell-derived TEBV rings cultured on flexible silicone tubing. Our device cyclically displaces water (75 uL volume) to inflate tubing at a frequency of 1 Hz. During static inflation tests, the tubing diameter increased by 10+/-1.6%. TEBV rings were loaded onto silicone tubing and subjected to mechanical conditioning for 3-7 days. Our device conditioned samples in an incubator at 10% distension at a frequency of 1 Hz. Static and conditioned tissues remained viable and uncontaminated and exhibited high cell densities and increased thicknesses from 3 to 7 days

An Economic Appraisal of Reuse Concepts in Regional Water Supply Planning

Using a conceptual model of a water supply firm, the necessary conditions for production and market efficiency are derived when renovated wastewater is considered as a potential water resource. The nature and extent of the supply augmentation due to recycled reuse is demonstrated using classical optimization techniques. Three stages of short-run supply corresponding to no recycling, partial recycled reuse and complete recycling of all reclaimable water are identified through appropriate Lagrangian Multipliers as well as graphical techniques. A mathematical programming model is structured to determine the optimal water resource allocation and pricing policy for Salt Lake County. By maximizing the sum of consumer and producer surplus (the difference between total willingness-to-pay and total cost) economically efficient equilibria are derived. The feasibility of recycled reuse for municipal purposes is examined in a planning context. The impact of higher water quality discharge standards on the attractiveness of water recycling option is studies. To ensure social acceptability of renovated wastewater for culinary purposes, blending restrictions are imposed, which stipulate that the amount of water for reuse be less than a fixed percentage of the water from other sources. The effect of such a constraint on the prices and water allocation are delineated. The hydrologic uncertainty in water supply is treated using stochastic programming techniques. Application of the concepts of single and joint change-constrained programming are illustrated. The resulting changes in pricing and allocation policies are discussed

Iowa\u27s 1975 Waterfowl Bag Check Program

A waterfowl bag check program was initiated in 1975 to estimate duck harvest, hunting pressure, hunter success and species composition of the harvest on 24 waterfowl areas. Sample design was such that it was easily repeatable and would permit detection of changes in harvest parameters. Analysis of management practices in light of these changes would then be possible. Estimated harvest for the 24 areas was 32,591 birds while estimated hunter trips totaled 46,131. Big Marsh, Eagle Lake, Otter Creek Marsh, Hawkeye Wildlife Area, Rush Lake (Palo Alto County), Riverton Wildlife Area, Green Island, New Albin Access, and Sweet Marsh accounted for 84.8% of the harvest and 81.4% of hunter trips. Harvest and hunting pressure was highest on weekends with the greatest intensity occurring on season openings. Species composition of checks showed the mallard (Anas platyrhynchos) was number one in the bag (28.6%) followed by blue-winged teal (Anas discors, 22.7%), green-winged teal (Anas carolinensis, 21.2%) and wood ducks (Aix sponsa, 14.1 %). The importance of each species in the bag varied greatly between areas

Glucocorticoid-Induced TNFR-Related Protein Stimulation Reverses Cardiac Allograft Acceptance Induced by CD40-CD40L Blockade

CD40-CD40L blockade has potent immunosuppressive effects in cardiac allograft rejection but is less effective in the presence of inflammatory signals. To better understand the factors that mediate CD40-CD40L blockade-resistant rejection, we studied the effects of stimulation through glucocorticoid-induced TNFR-related protein (GITR), a costimulatory protein expressed by regulatory and effector T cells. Stimulation of CD40−/− or wild-type recipient mice treated with anti-CD40L mAb (WT+anti-CD40L) and with agonistic anti-GITR mAb resulted in cardiac allograft rejection. GITR stimulation did not induce rejection once long-term graft acceptance was established. In vitro, GITR stimulation increased proliferation of effector T cells and decreased regulatory T cell () differentiation in both treatment groups. GITR-stimulated CD40−/− recipients rejected their allografts more rapidly compared to GITR-stimulated WT+anti-CD40L recipients, and this rejection, characterized by a robust Th2 response and significant eosinophilic infiltrate, could be mediated by CD4+ T cells alone. In contrast, both CD4+ and CD8+ T cells were required to induce rejection in GITR-stimulated WT+anti-CD40L-treated recipients, and the pathology of rejection was less severe. Hence, early GITR stimulation could initiate graft rejection despite CD40 deficiency or anti-CD40L mAb treatment, though the recipient response was dependent on the mechanism of CD40-CD40L disruption

BLASTPLOT: a PERL module to plot next generation sequencing NCBI-BLAST results

BACKGROUND: The development of Next Generation Sequencing (NGS) during the last decade has created an unprecedented amount of sequencing data, as well as the ability to rapidly sequence specimens of interest. Read-based BLAST analysis of NGS data is a common procedure especially in the case of metagenomic samples. However, coverage is usually not enough to allow for de novo assembly. This type of read-based analysis often creates the question of how the reads that align to the same sequence are distributed. The same question applies to preparation of primers or probes for microarray experiments. Although there are several packages that allow the visualization of DNA segments in relation to a reference, in most cases they require the visualization of one reference at a time and the capture of screen shots for each segment. Such a procedure could be tedious and time consuming. The field is in need of a solution that automates the capture of coverage plots for all the segments of interest. RESULTS: We have created BLASTPLOT, a PERL module to quickly plot the BLAST results from short sequences (primers, probes, reads) against reference targets. CONCLUSIONS: BLASTPLOT is a simple to use PERL module that allows the generation of PNG graphs for all the reference sequences associated with a BLAST result set