The Super-Kamiokande detector Fukuda, S.; Hayakawa, T.; Ichihara, E. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
04/2003, Letnik:
501, Številka:
2
Journal Article
Recenzirano
Super-Kamiokande is the world's largest water Cherenkov detector, with net mass 50,000 tons. During the period April, 1996 to July, 2001, Super-Kamiokande I collected 1678 live-days of data, ...observing neutrinos from the Sun, Earth's atmosphere, and the K2K long-baseline neutrino beam with high efficiency. These data provided crucial information for our current understanding of neutrino oscillations, as well as setting stringent limits on nucleon decay. In this paper, we describe the detector in detail, including its site, configuration, data acquisition equipment, online and offline software, and calibration systems which were used during Super-Kamiokande I.
Because of its low cost, high tensile strength, fatigue resistance, and wear resistance, austempered ductile iron (ADI) has been utilized in a wide variety of mechanical applications. However, in ...opposition to the versatility of the above-mentioned mechanical properties, the shortcomings of ADI are its surface hardness (Hv: 396) and corrosion resistance. And, because its relatively low austempering temperature falls in the range of Ms–450
°C (Ms: the martensite start temperature), ADI cannot be case hardened using traditional high temperature heat treatment. This study explored the effects of TiN and TiAlN coatings on ADI, with respect to surface hardness and corrosion resistance. The process employed for coating TiN/TiAlN onto ADI involved variable target current low temperature cathodic arc deposition (CAD). The coating characteristics and corrosion resistance of TiN/TiAlN-coated ADI were analyzed for further understanding of the feasibility of the low temperature CAD coating process. The analysis showed that TiN and TiAlN films could successfully be coated onto ADI through CAD technology without altering the unique microstructure of ADI. Utilizing a variety of target currents in the coating process yielded an acceptable level of adhesion while raising the surface hardness of ADI by a factor of 2–4 (Hv: 396 versus 1356–1910). It was observed that as target current increased, the surface roughness of the specimens also increased. TiN/TiAlN-coated ADI specimens exhibited higher corrosion resistance than uncoated ones when both were immersed in separate solutions of both 3.5
wt% NaCl and 10
vol.% HCl. Conclusively, the application of TiN and TiAlN films to ADI through the coating process of low temperature CAD is a viable surface modification for ADI applications that require increased surface hardness and corrosion resistance.
Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through ...arsenic-contaminated air and food. Here we report the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China. Coal in this region has undergone mineralization and thus produces high concentrations of arsenic. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such overexposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.
Metastable oligomeric and protofibrillar forms of amyloidogenic proteins have been implicated as on-pathway assembly intermediates in amyloid formation and as the major toxic species in a number of ...amyloid diseases including Alzheimer's disease. We describe here a chemical biology approach to structural analysis of Aβ protofibrils. Library screening yielded several molecules that stimulate Aβ aggregation. One of these compounds, calmidazolium chloride (CLC), rapidly and efficiently converts Aβ(1-40) monomers into clusters of protofibrils. As monitored by electron microscopy, these protofibrils persist for days when incubated in PBS at 37°C, with a slow transition to fibrillar structures apparent only after several weeks. Like normal protofibrils, the CLC-Aβ aggregates exhibit a low thioflavin T response. Like Aβ fibrils, the clustered protofibrils bind the anti-amyloid Ab WO1. The CLC-Aβ aggregates exhibit the same protection from hydrogen-deuterium exchange as do protofibrils isolated from a spontaneous Aβ fibril formation reaction: ≈12 of the 39 Aβ(1-40) backbone amide protons are protected from exchange in the protofibril, compared with approximately twice that number in amyloid fibrils. Scanning proline mutagenesis analysis shows that the Aβ molecule in these protofibrillar assemblies exhibits the same flexible N and C termini as do mature amyloid fibrils. The major difference in Aβ conformation between fibrils and protofibrils is added structural definition in the 22-29 segment in the fibril. Besides aiding structural analysis, compounds capable of facilitating oligomer and protofibril formation might have therapeutic potential, if they act to sequester Aβ in a form and/or location that cannot engage the toxic pathway.
Clostridium difficile toxin A increases paracellular permeability in colonic epithelial T84 cells by mechanisms involving RhoA glucosylation and actin depolymerization. However, we previously ...observed that toxin A-mediated decline in transepithelial electrical resistance preceded changes in cell morphology and tight junction ultrastructure (Hecht, G., Pothoulakis, C., LaMont, J. T., and Madara, J. L. (1988) J. Clin. Invest. 82, 1516-1524). Recent studies also showed that C. difficile toxins induce early cellular responses, including activation of mitogen-activated protein kinases, generation of reactive oxygen metabolites, and calcium influx. The aim of this study was to investigate whether toxin A-induced early cellular responses contribute to the permeability changes. We found that toxin A stimulated the activities of membrane and cytosolic protein kinase Calpha (PKCalpha) and cytosolic PKCbeta. A specific PKCalpha/beta antagonist (myristoylated PKCalpha/beta peptide) blocked toxin A-mediated RhoA glucosylation. Furthermore, decreased transepithelial electrical resistance and increased translocation of ZO-1 from tight junction occurred within 2-3 h of toxin A exposure and were also inhibited by PKCalpha/beta antagonist. During this time period, toxin exposure did not induce translocation of ZO-2, dephosphorylation or translocation of occludin, or cell rounding. Our data indicate that PKC signaling regulates toxin A-mediated paracellular permeability changes and ZO-1 translocation.
The effects of ethanol (EEP) and water (WSD) extracts of propolis collected from north China on blood glucose, blood lipid and free radicals in rats with diabetes mellitus were studied. The results ...show that EEP and WSD led to decreased levels of blood glucose (FBG), fructosamine (FRU), malonaldehyde (MDA), nitric oxide (NO), nitric oxide synthetase (NOS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) in serum of fasting rats; and to increased serum levels of high-density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD). This suggests that propolis can control blood glucose and modulate the metabolism of glucose and blood lipid, leading to decreased outputs of lipid peroxidation and scavenge the free radicals in rats with diabetes mellitus.
Understanding the Earth's climate system and how it might be changing is a preeminent scientific challenge. Global climate models are used to simulate past, present, and future climates, and ...experiments are executed continuously on an array of distributed supercomputers. The resulting data archive, spread over several sites, currently contains upwards of 100 TB of simulation data and is growing rapidly. Looking toward mid-decade and beyond, we must anticipate and prepare for distributed climate research data holdings of many petabytes. The Earth System Grid (ESG) is a collaborative interdisciplinary project aimed at addressing the challenge of enabling management, discovery, access, and analysis of these critically important datasets in a distributed and heterogeneous computational environment. The problem is fundamentally a Grid problem. Building upon the Globus toolkit and a variety of other technologies, ESG is developing an environment that addresses authentication, authorization for data access, large-scale data transport and management, services and abstractions for high-performance remote data access, mechanisms for scalable data replication, cataloging with rich semantic and syntactic information, data discovery, distributed monitoring, and Web-based portals for using the system.
To examine the effect of common excipients such as sugars (sorbitol versus sucrose) on bioequivalence between pharmaceutical formulations, using ranitidine and metoprolol as model drugs.
Two ...single-dose, replicated, crossover studies were first conducted in healthy volunteers (N=20 each) to compare the effect of 5 Gm of sorbitol and sucrose on bioequivalence of 150 mg ranitidine or 50 mg metoprolol in aqueous solution, followed by a single-dose, nonreplicated, crossover study (N=24) to determine the threshold of sorbitol effect on bioequivalence of 150 mg ranitidine in solution.
Ranitidine Cmax and AUC0-infinity were decreased by approximately 50% and 45%, respectively, in the presence of sorbitol versus sucrose. Similarly, sorbitol reduced metoprolol Cmax by 23% but had no significant effect on AUC0-infinity. An appreciable subject-by-formulation interaction was found for ranitidine Cmax and AUC0-infinity, as well as metoprolol Cmax. Sorbitol decreased the systemic exposure of ranitidine in a dose-dependent manner and affected bioequivalence at a level of 1.25 Gm or greater.
As exemplified by sorbitol, some common excipients have unexpected effect on bioavailability/bioequivalence, depending on the pharmacokinetic characteristics of the drug, as well as the type and amount of the excipient present in the formulation. More research is warranted to examine other 'common' excipients that may have unintended influence on bioavailability/bioequivalence.
We aimed to investigate the expression of EGFR and the autophagy-related markers Beclin1 and LC3 in cervical cancer.
Beclin1, LC3, and EGFR expression were analyzed in 80 samples of cervical squamous ...cell carcinoma (SCC), 40 samples of high-grade cervical intraepithelial neoplasia (CIN), and 40 samples of normal cervical tissues by immunohistochemistry. The protein expression rates were analyzed with χ (2) and Fisher's exact tests. Differences in overall survival (OS) were determined using the Kaplan-Meier method and log-rank tests.
Cervical cancer, high-grade CIN, and normal cervical epithelial cells expressed Beclin1 in 26.2%, 77.5%, and 82.5% of patients, respectively, and expressed LC3 in 28.8%, 70.0%, and 75.0% of patients, respectively. There was a significant difference between cervical SCC and high-grade CIN or normal cervical epithelial cells (P=0.000). Cervical cancer cells, high-grade CIN cells, and normal cervical epithelial cells expressed EGFR in 68.8%, 62.5%, and 12.5% of patients, respectively. There was a significant difference between cervical SCC or high-grade CIN and normal cervical epithelial cells (P=0.000). No significant association between Beclin1 or LC3 or EGFR expression and various clinicopathological parameters was observed in cervical SCC. There was no significant correlation between Beclin1, LC3, EGFR expression, and 5-year OS rates of cervical SCC patients. Beclin1- or LC3-negativity with EGFR-positivity in cervical SCC was associated with a higher Federation International of Gynecology and Obstetrics (FIGO) stage (P=0.011 and P=0.013, respectively) and pelvic lymph node metastasis (P=0.036 and P=0.092, respectively). The 5-year OS rates did not significantly differ between Beclin1- or LC3-positive and -negative patients with positive EGFR.
Autophagy was downregulated and EGFR was upregulated in cervical SCC. Autophagy downregulation combined with EGFR upregulation promotes the progression of cervical SCC.
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