Daze fasteners

A daze fastener system for connecting two or more structural elements wherein the structural elements and fastener parts have substantially different coefficient of thermal expansion physical property characteristics is employed in this invention. By providing frusto-conical abutting surfaces between the structural elements and fastener parts any differences in thermal expansion/contraction between the parts is translated to sliding motion and avoids deleterious thermal stresses in the connection. An essential feature for isotropic homogeneous material connections is that at least two sets of mating surfaces are required wherein each set of mating surfaces has line element extensions that pass through a common point

Pharmacodynamic Modelling of Biomarker Data in Oncology

The development of pharmacodynamic (PD) biomarkers in oncology has implications for design of clinical protocols from preclinical data and for predicting clinical outcomes from early clinical data. Two classes of biomarkers have received particular attention. Phosphoproteins in biopsy samples are markers of inhibition of signalling pathways, target sites for many novel agents. Biomarkers of apoptosis in plasma can measure tumour cell killing by drugs in phase I clinical trials. The predictive power of PD biomarkers is enhanced by data modelling. With pharmacokinetic models, PD models form PK/PD models that predict the time course both of drug concentration and drug effects. If biomarkers of drug toxicity are also measured, the models can predict drug selectivity as well as efficacy. PK/PD models, in conjunction with disease models, make possible virtual clinical trials, in which multiple trial designs are assessed in silico, so the optimal trial design can be selected for experimental evaluation

What can systems pharmacology contribute to drug development? Disease modelling as a predictive tool

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Oral History Interview: Robert C. Jackson

This interview is one of a series conducted concerning West Virginia business history. Robert C. Jackson was Assistant Vice-President of the Bank of Milton. He discusses: his personal background and education; his family and his wife (Marie Jackson); his employment history; Katherine Winthra (who was the first woman to be named to Board of Directors in the Bank of Milton); the banking business in general (including examples from the Bank of Milton); as well as loans and mortgages.https://mds.marshall.edu/oral_history/1279/thumbnail.jp

Deep ocean disposal of sewage sludge off Orange County, California: a research plan

Even though the discharge of sludge into the ocean via an outfall is not now permitted, this research plan has been prepared to show what could be learned with a full scale experimental sludge discharge of 150 dry tons/day by the County Sanitation Districts of Orange County into deep water (over 1000 feet). To provide a wide range of inputs and evaluation, a broad-based Research Planning Committee was established to advise the Environmental Quality Laboratory on the overall content and details of the research plan. Two meetings were held at EQL on: March 4-5, 1982: The entire Committee July 19-20, 1982: A working subgroup of the Committee The entire Committee is listed in Appendix B, with footnotes to indicate meeting attendance. Those unable to come to a meeting were asked to comment on the drafts by mail or telephone. We gratefully acknowledge the members of the Research Planning Committee for their generous help in formulating the research tasks and reviewing report drafts

Cryogenic Insulation System

This invention relates to reusable, low density, high temperature cryogenic foam insulation systems and the process for their manufacture. A pacing technology for liquid hydrogen fueled, high speed aircraft is the development of a fully reusable, flight weight cryogenic insulation system for propellant tank structures. In the invention cryogenic foam insulation is adhesively bonded to the outer wall of the fuel tank structure. The cryogenic insulation consists of square sheets fabricated from an array of abutting square blocks. Each block consists of a sheet of glass cloth adhesively bonded between two layers of polymethacrylimide foam. Each block is wrapped in a vapor impermeable membrane, such as Kapton(R) aluminum Kapton(R), to provide a vapor barrier. Very beneficial results can be obtained by employing the present invention in conjunction with fibrous insulation and an outer aeroshell, a hot fuselage structure with an internal thermal protection system

Noncooperatively Optimized Tolerance: Decentralized Strategic Optimization in Complex Systems

We introduce noncooperatively optimized tolerance (NOT), a generalization of highly optimized tolerance (HOT) that involves strategic (game theoretic) interactions between parties in a complex system. We illustrate our model in the forest fire (percolation) framework. As the number of players increases, our model retains features of HOT, such as robustness, high yield combined with high density, and self-dissimilar landscapes, but also develops features of self-organized criticality (SOC) when the number of players is large enough. For example, the forest landscape becomes increasingly homogeneous and protection from adverse events (lightning strikes) becomes less closely correlated with the spatial distribution of these events. While HOT is a special case of our model, the resemblance to SOC is only partial; for example, the distribution of cascades, while becoming increasingly heavy-tailed as the number of players increases, also deviates more significantly from a power law in this regime. Surprisingly, the system retains considerable robustness even as it becomes fractured, due in part to emergent cooperation between neighboring players. At the same time, increasing homogeneity promotes resilience against changes in the lightning distribution, giving rise to intermediate regimes where the system is robust to a particular distribution of adverse events, yet not very fragile to changes

Modelling c-Abl Signalling in Activated Neutrophils: The Anti-inflammatory Effect of Seliciclib

When mammalian tissues are infected by bacteria or fungi, inflammatory cytokines are released that cause circulating neutrophils to invade the infected tissue. The cytosolic tyrosine kinase, c-Abl, in these tissue neutrophils is activated by TNFα. c-Abl then phosphorylates STAT transcription factors, which results in production of the antiapoptotic protein Mcl-1. The normally short-lived tissue neutrophils are then unable to enter apoptosis. c-Abl also causes release of reactive oxygen species (ROS) from the mitochondria of the activated neutrophils. These ROS, and ROS generated by NADPH oxidase, are bactericidal agents of the innate immune system. In some inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), the invading neutrophils become permanently activated, and the resulting ROS overproduction causes severe tissue damage. The cyclin-dependent kinase inhibitor, seliciclib, blocks transcription through inhibition of cdk9. This results in a relatively rapid decline of antiapoptotic Mcl-1 transcripts in activated neutrophils, an increase in neutrophil apoptosis, and less ROS leakage and oxidative damage. We present here a model of neutrophil kinetics that simulates the principal pathways of c-Abl signalling and use it to explore possible treatment options for inflammatory lung disease

Assessment of alternative strategies for sludge disposal into deep ocean basins off Southern California

The general framework of engineering alternatives for regional ocean sludge disposal is well described in a report by Raksit, and will not be repeated here. The various ocean disposal alternatives are less costly than all land-disposal and incineration/pyrolysis systems studied. Even though ocean sludge disposal is currently contrary to both state and federal regulations, it is hoped that this study will advance our scientific and engineering knowledge of the behavior and effects of sludge discharge in deep water, in case the regulatory policy is reexamined in the future. With this report we hope we have demonstrated the potential and difficulties of some new modeling techniques for predicting the effects of sludge discharge in the ocean. In the future. we believe it will be possible to formulate policy of ocean sludge discharges with much better case-by-case predictions of impacts for comparison with other alternatives (such as land disposal). not only for the Los Angeles/Orange County areas, but for all coastal urban areas