A novel single-particle technique to measure emittance has been developed and used to characterise seventeen different muon beams for the Muon Ionisation Cooling Experiment (MICE). The muon beams, ...whose mean momenta vary from 171 to 281 MeV/c, have emittances of approximately 1.2-2.3 π mm-rad horizontally and 0.6-1.0 π mm-rad vertically, a horizontal dispersion of 90-190 mm and momentum spreads of about 25 MeV/c. There is reasonable agreement between the measured parameters of the beams and the results of simulations. The beams are found to meet the requirements of MICE.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A series of 3-substituted 2,2'-dithiobis(1H-indoles) were synthesized and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal growth factor receptor (EGFR) and ...the nonreceptor pp60v-src tyrosine kinase, to extend the available structure-activity relationships for this series. The majority of the compounds were prepared either by reaction of 2-chloro-1-methylindole-3-carbonyl chloride with amines, followed by thiomethylation, demethylation, and oxidative dimerization, or by reaction of isocyanates with the anion of 1-methyl-2-indolinethione followed by dimerization. Overall, inhibitory activity is retained by analogues having a wide variety of side chains. A series of 3-carboxamide analogues had moderate to good activity against isolated EGFR (IC50s 1-20 microM), with monoalkyl substitution of the carboxamide being optimal. Polar side chains were generally less effective than lipophilic ones, with benzyl being particularly effective. However, N,N-disubstitution was the most effective pattern for inhibition of pp60v-src. A variety of substituted N-phenylcarboxamides had lower activity against EGFR than the parent derivative, and a N-thienylcarboxamide also had low activity. A series of 3-ketones, including methyl, phenyl, and furyl derivatives, showed moderate activity against the pp60v-src kinase, but were less effective against EGFR. The mechanism of inhibition of both kinases by these drugs was shown to be noncompetitive with respect to both ATP and peptide substrate. Selected compounds inhibited the growth of Swiss 3T3 cells with IC50s in the low micromolar range and inhibited bFGF-mediated intracellular tyrosine phosphorylation in the same cell line. Thiol inhibits the effects of the compounds, suggesting that one possible mechanism of inhibition is thiol-disulfide exchange with thiol-containing residues in the catalytic sites. Crystal structures of two representative compounds show a folded, V-shaped structure, with the disulfide bridge exposed, consistent with this hypothesis.
A series of indole-substituted 2,2'-dithiobis(1-methyl-N-phenyl-1H-indole-3-carboxamides) were prepared and evaluated for their ability to inhibit the tyrosine kinase activity of both the epidermal ...growth factor receptor (EGFR) and the nonreceptor pp60v-src tyrosine kinase. The compounds were synthesized by conversion of appropriate 1-methyloxindoles to 1-methyl-2-indolinethiones with P2S5 followed by subsequent reaction with NaH and phenyl isocyanate and oxidative dimerization of the resulting 2,3-dihydro-N-phenyl-2-thioxo-1H-indole-3-carboxamides. The parent compound and many of the substituted analogues were moderately potent inhibitors of both kinase enzymes, but no clear relationships were seen between substitution on the indole ring and inhibitory activity. While 4-substituted compounds were generally inactive, 5-substituted derivatives with electron-withdrawing groups showed inhibitory activity. However, none of the substituted compounds showed significantly better activity than the unsubstituted parent compound. There was generally a good correlation between activity against the EGFR and pp60v-src kinases, but several compounds did show some specificity (> 20-fold) of inhibition; 5-Cl and 5-Br derivatives preferentially inhibited pp60v-src, while the 5-CF3 compound preferentially inhibited EGFR. Selected compounds from the series were found to inhibit the growth of Swiss 3T3 fibroblasts with IC50S in the range 2-25 microM, the most active being 4-substituted derivatives. The compounds inhibited bFGF-mediated protein tyrosine phosphorylation in intact cells more effectively than EGFR- or PDGF-mediated phosphorylation.
To facilitate collaborative research efforts between multi-investigator teams using DNA microarrays, we identified sources of error and data variability between laboratories and across microarray ...platforms, and methods to accommodate this variability. RNA expression data were generated in seven laboratories, which compared two standard RNA samples using 12 microarray platforms. At least two standard microarray types (one spotted, one commercial) were used by all laboratories. Reproducibility for most platforms within any laboratory was typically good, but reproducibility between platforms and across laboratories was generally poor. Reproducibility between laboratories increased markedly when standardized protocols were implemented for RNA labeling, hybridization, microarray processing, data acquisition and data normalization. Reproducibility was highest when analysis was based on biological themes defined by enriched Gene Ontology (GO) categories. These findings indicate that microarray results can be comparable across multiple laboratories, especially when a common platform and set of procedures are used.
A point source outbreak of haemorrhagic colitis due to Escherichia coli O 157. H7 producing verocytotoxin (VT), took place following a christening party in Birmingham in June 1987. Twenty-six people ...were affected, six were admitted to hospital and one developed haemolytic uraemic syndrome: there were no deaths. VT + E. coli O 157. H7 was isolated from 13 (57%) of 23 faecal specimens from affected people and from 3 (9%) of 33 specimens from asymptomatic people. Free VT was detected in the faeces of one further asymptomatic person. Illness was associated with eating turkey-roll sandwiches (P < 0·001) suggesting that cold meats might be an important source of infection.
A point source outbreak of haemorrhagic colitis due to Escherichia coli O 157.H7 producing verocytotoxin (VT), took place following a christening party in Birmingham in June 1987. Twenty-six people ...were affected, six were admitted to hospital and one developed haemolytic uraemic syndrome: there were no deaths. VT + E. coli O 157.H7 was isolated from 13 (57%) of 23 faecal specimens from affected people and from 3 (9%) of 33 specimens from asymptomatic people. Free VT was detected in the faeces of one further asymptomatic person. Illness was associated with eating turkey-roll sandwiches (P < 0·001) suggesting that cold meats might be an important source of infection.
Reviews of Books McInerney, Jeremy; Burton, Paul J.; Gruen, Erich S. ...
International history review,
09/2003, Letnik:
25, Številka:
3
Journal Article
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