Development of a fully automated rapid irradiated sample transport system for neutron activation analysis

textThe need for trace, minor and main element analysis becomes more prevalent each year with an every expanding variety of applications. Neutron Activation Analysis (NAA) is an attractive non-destructive analysis tool that can be utilized on small samples regardless of what physical state the material is in. The analysis process however, typically requires researchers to physically handle a radioactive sample in order to transport the sample to detection systems for data gathering. The purpose of this project was to design a Fully Automated Rapid Irradiated Sample Transit (FARIST) system that could deliver samples into a reactor core and then transfer them to a detector for analysis with zero human interaction. The system would be designed to hold up to 30 samples prior to analysis with the irradiation, decay, and counting times programmed in initially so that once analysis was initiated, no user interaction was required for the next 29 samples. The last requirement of the system was that it supports cyclic NAA. This work discusses the science and history behind NAA as well as the design, construction, installation, and testing of the new FARIST system.Mechanical Engineerin

Hospital infectious waste disposal system design

Call number: LD2668 .R4 IE 1989 C67Master of ScienceIndustrial and Manufacturing Systems Engineerin

The identification of native grasses by their vegetative characters

Call number: LD2668 .T4 1930 C6

The Use of Contingent Valuation Methodology in Natural Resource Damage Assessments: Legal Fact and Economic Fiction.

The creation of comprehensive statutory schemes for protection of the environment has required the legal system to focus on the definition problems associated with environmental goods and with the physical, tmeporal, and aesthetic considerations related to such goods. Clearly, the events of the twentieth century have taught us that individual physical components of the natural environment, such as streams, forests, wildlife, and biota, do not exist in isolation. Instead, these components are part of the interrelated environmental systems that may, in turn, impact other environmental systems. Likewise, damage to one or more of the components of a system can result in a loss to humans of these environmental goods or the Uses provided by the system

Contingent Valuation Methodology in the Natural Resource Damage Regulatory Process: Choice Theory and the Embedding Phenomenon

In their most recent article on the use of Contingent Valuation Methodology ( CVM ) in the natural resource damages assessment ( NRDA ) process, the authors take issue with the CVM components of the National Oceanic and Atmospheric Administration\u27s ( NOAA ) proposed NRDA rules. In particular, the authors argue that NOAA\u27s proposed NRDA process does not comport with basic tenets of choice theory and that the CVM safeguards created by NOAA are not adequate to address the inherent, and perhaps irreconcilable, flaws in CVM assessments. To illustrate their arguments, the authors examine and criticize NOAA\u27s treatment and general disregard of the embedding phenomenon. The author\u27s argue that the existence of the embedding phenomenon in CVM valuations demonstrates the inappropriateness of CVM as a regulatory tool in the NRDA process

Interleukin-10 disrupts liver repair in acetaminophen-induced acute liver failure

IntroductionSystemic levels of the anti-inflammatory cytokine interleukin 10 (IL-10) are highest in acetaminophen (APAP)-induced acute liver failure (ALF) patients with the poorest prognosis. The mechanistic basis for this counterintuitive finding is not known, as induction of IL-10 is hypothesized to temper the pathological effects of immune cell activation. Aberrant production of IL-10 after severe liver injury could conceivably interfere with the beneficial, pro-reparative actions of immune cells, such as monocytes.MethodsTo test this possibility, we determined whether IL-10 levels are dysregulated in mice with APAP-induced ALF and further evaluated whether aberrant production of IL-10 prevents monocyte recruitment and/or the resolution of necrotic lesions by these cells.ResultsOur studies demonstrate that in mice challenged with 300 mg/kg acetaminophen (APAP), a hepatotoxic dose of APAP that fails to produce ALF (i.e., APAP-induced acute liver injury; AALI), Ly6Chi monocytes were recruited to the liver and infiltrated the necrotic lesions by 48 hours coincident with the clearance of dead cell debris. At 72 hours, IL-10 was upregulated, culminating in the resolution of hepatic inflammation. By contrast, in mice treated with 600 mg/kg APAP, a dose that produces clinical features of ALF (i.e., APAP-induced ALF; AALF), IL-10 levels were markedly elevated by 24 hours. Early induction of IL-10 was associated with a reduction in the hepatic numbers of Ly6Chi monocytes resulting in the persistence of dead cell debris. Inhibition of IL-10 in AALF mice, beginning at 24 hours after APAP treatment, increased the hepatic numbers of monocytes which coincided with a reduction in the necrotic area. Moreover, pharmacologic elevation of systemic IL-10 levels in AALI mice reduced hepatic myeloid cell numbers and increased the area of necrosis.DiscussionCollectively, these results indicate that during ALF, aberrant production of IL-10 disrupts the hepatic recruitment of monocytes, which prevents the clearance of dead cell debris. These are the first studies to document a mechanistic basis for the link between high IL-10 levels and poor outcome in patients with ALF

ALS-FTLD associated mutations of SQSTM1 impact on Keap1-Nrf2 signalling

The transcription factor Nrf2 and its repressor protein Keap1 play key roles in the regulation of antioxidant stress responses and both Keap1-Nrf2 signalling and oxidative stress have been implicated in the pathogenesis of the ALS-FTLD spectrum of neurodegenerative disorders. The Keap1-binding partner and autophagy receptor SQSTM1/p62 has also recently been linked genetically to ALS-FTLD, with some missense mutations identified in patients mapping within or close to its Keap1-interacting region (KIR, residues 347–352) of SQSTM1/p62. Here we report the effects on protein function of four different disease associated mutations of SQSTM1/p62 which affect the KIR region. Only mutations mapping precisely to the KIR (P348L and G351 A) were associated with a loss of Keap1 binding in co-immunoprecipitations comparable to wild-type SQSTM1/p62. These selective effects on Keap1 recognition were entirely rational based on protein structural models. Consistent with impaired Keap1 binding, the P348L and G351A KIR mutants showed reduced ability to activate Nrf2 signalling compared to wild-type SQSTM1/p62 in antioxidant response element (ARE)-luciferase reporter assays. The results suggest that SQSTM1 mutations within the KIR of SQSTM1/p62 contribute to aetiology of some cases of ALS-FTLD through a mechanism involving aberrant expression or regulation of oxidative response genes

A tetraoxane-based antimalarial drug candidate that overcomes PfK13-C580Y dependent artemisinin resistance.

K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P. falciparum and P. vivax in vitro, is efficacious against P. falciparum in in vivo rodent models, produces parasite reduction ratios equivalent to dihydroartemisinin and has pharmacokinetic and pharmacodynamic characteristics compatible with a single-dose cure. In vitro studies with transgenic parasites expressing variant forms of K13 show no cross-resistance with the C580Y mutation, the primary variant observed in Southeast Asia. E209 is a superior next generation endoperoxide with combined pharmacokinetic and pharmacodynamic features that overcome the liabilities of artemisinin derivatives