2,318 research outputs found

    Local abstraction refinement for probabilistic timed programs

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    We consider models of programs that incorporate probability, dense real-time and data. We present a new abstraction refinement method for computing minimum and maximum reachability probabilities for such models. Our approach uses strictly local refinement steps to reduce both the size of abstractions generated and the complexity of operations needed, in comparison to previous approaches of this kind. We implement the techniques and evaluate them on a selection of large case studies, including some infinite-state probabilistic real-time models, demonstrating improvements over existing tools in several cases

    Investigation on the durability of man-made vitreous fibers in rat lungs.

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    Two types of sized stonewool with median lengths of 6.7 and 10.1 microns and median diameters of 0.63 and 0.85 microns, and crocidolite with fibers of median length of 4.8 microns and median diameter of 0.18 microns were instilled intratracheally into female Wistar rats. A single dose of 2 mg in 0.3 ml saline was used for the stonewool samples and 0.1 mg in 0.3 ml saline for crocidolite. The evenness of distribution of fibers in the lung was checked by scanning electron microscopy (SEM). Five animals per group were sacrificed after 2 days, 1, 3, 6, and 12 months. After low-temperature ashing of the lungs about 200 fibers per animal were analyzed by SEM for length and diameter. The number and mass of fibers in the total lung were calculated. For the stonewool samples the decrease in the number of fibers in the lung ash followed approximately first order kinetics resulting in half-times of 90 and 120 days. The analysis of fiber number and diameter of different length fractions was used to estimate the contribution of three processes of fiber elimination: transport by macrophages for short fibers, breakage of fibers, and dissolution of fibers. (The process of transport by macrophages was found fastest for fibers with length < 2.5 microns). For the elimination of critical fibers with length > 5 microns, the breakage and dissolution were the most important processes. The breakage of fibers was predominant for one of the stonewool samples. The preferential type of the mechanism of fiber elimination is dependent on chemical composition and size distribution

    An integrated study of earth resources in the State of California using remote sensing techniques

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    The author has identified the following significant results. The supply, demand, and impact relationships of California's water resources as exemplified by the Feather River project and other aspects of the California Water Plan are discussed

    DIRECT AIR BLAST EXPOSURE EFFECTS IN ANIMALS, OPERATION UPSHOT-KNOTHOLE, PROJECT 4.2

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    Project 4.2 was designed to study direct (primary) air blast injury, in animals, from an atomic weapon in the range of 20 to 50 psi under circumstances affording protection against missiles, thermal and ionizing radiation and to estimate the probable direct air blast hazard in man. The pressure levels at which atomic weapons direct air blast injuries occur will determine, to a large extent, the number of blast casualties likely to be encountered. It is probable that fatal overpressures are not reached until well within the range at which indirect (secondary) blast, thermal and ionizing radiation are practically certain to prove fatal. Only in special situations affording partial protection from other injuries are blast injuries likely to be of practical importance. Two animal species of widely different body weights (700 rats and 56 dogs) were exposed, together with air pressure recorders, in aluminum cylinders, covered by sandbags and dirt but open at both ends, at seven stations distributed within the intended overpressure range of 20 to 50 psi of Shot 10« About 200 rats were likewise exposed in Shot 9. Unfortunately, the destructive effect of the air blast of Shot 10 was much greater than anticipated. Many of the exposure cylinders were displaced and their contents destroyed. Only a partial recovery of the animals was possible due to the excessive radioactive contamination which greatly limited the time in the area. Most of the animals were dead upon recovery. Those living were in a state of severe shock. Autopsy findings showed remarkably few traumatic lesions and lung hemorrhages in spite of the rough treatment and high overpressure to which they were subjected. The rats recovered from Shot 9 were exposed to a recorded pressure of 18 to 2k psi. The autopsy findings showed moderate lung hemorrhage in most of the animals undoubtedly due to direct air blast injury. The findings were typical of those seen following exposure to air blast from HE or in the shock tube. The agreement between the estimated pressures and the recorded pressures in the containers were good in some instances but not in others. Discounting the initial pressure rise, it was thought that the records represent the pressure changes in the exposure containers. The individual records exhibited rather wide variations in recorded pressures indicating a complex pressure field. The attempt to compare levels of direct air blast in small and large animals, and thereby to extrapolate to man, was not accomplished due to the lack of statistically reliable data on the dogs. The lapse of time between the death of the dogs and autopsy reduced the interpretable findings below the level required for statistical significance. Laboratory studies are planned to evaluate the relative importance of the several blast wave parameters in the production of injury, Recommendations for future field test studies will depend upon the outcome of this laboratory work

    The expression levels of three raft-associated molecules in cultivated vascular cells are dependent on culture conditions

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    Relaying a signal across the plasma membrane requires functional connections between the partner molecules. Membrane microdomains or lipid rafts provide an environment in which such specific interactions can take place. The integrity of these sites is often taken for granted when signalling pathways are investigated in cell culture. However, it is well known that smooth muscle and endothelial cells undergo cytoskeletal rearrangements during monolayer culturing. Likewise affected - and with potentially important consequences for signalling events - is the organization of the plasma membrane. The expression levels of three raft markers were massively upregulated, and raft-associated 5′-nucleotidase activity increased in conventional monolayer cultures as compared with a spheroidal coculture model, shown to promote the differentiation of endothelial cells. Our data point to a shift of raft components in monolayer cultures and demonstrate potential advantages of the spheroid coculture system for investigation of raft-mediated signalling events in endothelial cell

    Circulating calcitonin and carcinoembryonic antigen m-RNA detected by RT-PCR as tumour markers in medullary thyroid carcinoma

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    Detection of local relapse or metastasis in medullary thyroid carcinoma (MTC) continue to pose a major diagnostic challenge. Besides established diagnostic studies such as serum calcitonin (CT) and carcinoembryonic antigen (CEA), molecular detection of circulating tumour cells may be an additional diagnostic tool for the early detection of disease recurrence. We performed reverse transcription-polymerase chain reaction (RT-PCR) on blood samples from patients diagnosed with MTC disease using primers specific for CT and CEA, respectively. CT mRNA was not detectable in peripheral blood of all patients with MTC (n = 11) and all controls (n = 32). CEA mRNA was significantly more often detected patients with MTC (72.7%) than in controls (34.4%; p = 0.038; Fisher exact test). With an example of a patient with MTC and massive tumour mass in the neck we demonstrate the failure of detection of CT mRNA over a period of 6 months, whereas CEA mRNA could be detected in peripheral blood of this patient. As a consequence, CT mRNA detected by RT-PCR in the peripheral blood can not be recommended as a tumour marker in MTC. However, the use of carcinoembryonic mRNA may provide a significant improvement in diagnosis of recurrent disease in MTC. © 2001 Cancer Research Campaign   http://www.bjcancer.co

    Molar volume of solid isotopic helium mixtures

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    Solid isotopic helium mixtures have been studied by path-integral Monte Carlo simulations in the isothermal-isobaric ensemble. This method allowed us to study the molar volume as a function of temperature, pressure, and isotopic composition. At 25 K and 0.2 GPa, the relative difference between molar volumes of isotopically-pure crystals of 3He and 4He is found to be about 3%. This difference decreases under pressure, and for 12 GPa it is smaller than 1%. For isotopically-mixed crystals, a linear relation between lattice parameters and concentrations of helium isotopes is found, in agreement with Vegard's law. The virtual crystal approximation, valid for isotopic mixtures of heavier atoms, does not give reliable results for solid solutions of helium isotopes.Comment: 7 pages, 5 figure

    The catalytically inactive tyrosine phosphatase HD-PTP/PTPN23 is a novel regulator of SMN complex localization

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    The survival motor neuron (SMN) complex fulfils essential functions in the assembly of snRNPs, which are key components in the splicing of pre-mRNAs. Little is known about the regulation of SMN complex activity by posttranslational modification despite its complicated phosphorylation pattern. Several phosphatases had been implicated in the regulation of SMN, including the nuclear phosphatases PPM1G and PP1γ. Here we systematically screened all human phosphatase gene products for a regulatory role in the SMN complex. We used the accumulation of SMN in Cajal bodies of intact proliferating cells, which actively assemble snRNPs, as a readout for unperturbed SMN complex function. Knockdown of 29 protein phosphatases interfered with SMN accumulation in Cajal bodies, suggesting impaired SMN complex function, among those the catalytically inactive, non–receptor-type tyrosine phosphatase PTPN23/HD-PTP. Knockdown of PTPN23 also led to changes in the phosphorylation pattern of SMN without affecting the assembly of the SMN complex. We further show interaction between SMN and PTPN23 and document that PTPN23, like SMN, shuttles between nucleus and cytoplasm. Our data provide the first comprehensive screen for SMN complex regulators and establish a novel regulatory function of PTPN23 in maintaining a highly phosphorylated state of SMN, which is important for its proper function in snRNP assembly
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