Given a passage classify if the passage has a definite objective/aim/goal or not. Output '1' if the passage has a defininte objective/aim/goal and output '0' if the passage does not have a definite objective/aim/goal.

del(17p), del(11q), and associated p53 dysfunction predict for short survival and chemoresistance in B-cell chronic lymphocytic leukemia (CLL). DNA-dependent protein kinase (DNA-PK) is activated by DNA damage and mediates DNA double-strand break repair. We hypothesized that inhibiting DNA-PK would sensitize CLL cells to drug-induced DNA damage and that this approach could increase the therapeutic index of agents used to treat CLL.', 'Fifty-four CLL cases were characterized for poor prognosis markers [del(17p), del(11q), CD38, and ZAP-70]. In selected cases, DNA-PK catalytic subunit (DNA-PKcs) expression and activity and p53 function were also measured. Ex vivo viability assays established sensitivity to fludarabine and chlorambucil and also tested the ability of a novel DNA-PK inhibitor (NU7441) to sensitize CLL cells to these drugs. The effects of NU7441 on fludarabine-induced DNA damage repair were also assessed (Comet assays and detection of gammaH2AX).', 'DNA-PKcs levels correlated with DNA-PK activity and varied 50-fold between cases but were consistently higher in del(17p) (P = 0.01) and del(11q) cases. NU7441 sensitized CLL cells to chlorambucil and fludarabine, including cases with del(17p), del(11q), p53 dysfunction, or high levels of DNA-PKcs. NU7441 increased fludarabine-induced double-strand breaks and abrogated drug-induced autophosphorylation of DNA-PKcs at Ser2056. High DNA-PK levels predicted for reduced treatment-free interval.
1

Hydrocortisone therapy is based on a dosing regimen derived from estimates of cortisol secretion, but little is known of how the dose should be distributed throughout the 24 h. We have used deconvolution analysis of 24-h serum cortisol profiles to determine 24-h cortisol secretion and distribution to inform hydrocortisone dosing schedules in young children and older adults.', 'Twenty four hour serum cortisol profiles from 80 adults (41 men, aged 60-74 years) and 29 children (24 boys, aged 5-9 years) were subject to deconvolution analysis using an 80-min half-life to ascertain total cortisol secretion and distribution throughout the 24-h period.', 'Mean daily cortisol secretion was similar between adults (6.3 mg/m(2) body surface area/day, range 5.1-9.3) and children (8.0 mg/m(2) body surface area/day, range 5.3-12.0). Peak serum cortisol concentration was higher in children compared with adults, whereas nadir serum cortisol concentrations were similar. Timing of the peak serum cortisol concentration was similar (07.05-07.25), whereas that of the nadir concentration occurred later in adults (midnight) compared with children (22.48) (P = 0.003). Children had the highest percentage of cortisol secretion between 06.00 and 12.00 (38.4%), whereas in adults this took place between midnight and 06.00 (45.2%).
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The objective of this study was to describe a pattern of recovery and histological nerve cell loss in Sprague-Dawley rats exposed to severe brain ischemia and to compare it to that of Wistar rats.', 'Ether- and ketamine-anesthetized Sprague-Dawley rats were exposed to 3, 5, 6 and 10 min of normothermic severe brain ischemia (4 groups) induced by hypotension and neck compression. In group No. 5, the brain temperature was rapidly lowered, after 10 min of ischemia, to 30 degrees C during 45-50 min of recirculation. Wistar rats (group No. 6) served as controls (10-min normothermic ischemia).', 'In Sprague-Dawley (S-D) rats, post-ischemic audiogenic seizures (PAS) increased with the duration of ischemia and reached 86% (6/7 rats), after 10 min of ischemia. Mortality rate was high (50% = 7/14 rats). No seizure activity was observed after 10 min of ischemia in 6 Wistar (W) rats, and all survived. In the S-D rats, 10 min of ischemia produced histopathological damage in all brain regions examined, except in the thalamus. Damage was less severe in the W rats. Post-ischemic hypothermia ameliorated hippocampal and cortical nerve cell damage, but had no effect on the incidence of PAS activity and mortality. In W rats, hippocampal nerve cell loss was much less severe than in the S-D rats and cortical damage was not observed.
1