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1.
《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action. 相似文献
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Carl Ganter 《Magnetic resonance in medicine》2006,55(1):98-107
Spoiled gradient echo sequences can only reach a homogeneous steady state if sufficiently strong crusher gradients are used in combination with RF phase cycling (RF spoiling). However, the signal depends quite sensitively on the chosen phase increment ? and—lacking analytical solutions—numerical simulations must be used to study the transient and steady‐state magnetization. For the steady state an exact analytical solution is derived, which holds for arbitrary sequence and tissue parameters. Besides a considerably improved computation performance, the analytical approach enables a better understanding of the complicated dependence on ?. For short repetition times (TR) the regime of small ? turns out to be particularly interesting: It is shown that the typical ?c, where RF spoiling starts to become effective, is essentially inversely proportional to T2. This tissue dependence implies that contrasts can be considerably larger with partial spoiling (? ≈ ?c) than with conventional RF spoiling (? ? ?c). As an example, the uptake of contrast agents in tissues is investigated. For typical parameters a considerably improved contrast enhancement can be obtained, both theoretically and experimentally. Magn Reson Med, 2006. © 2005 Wiley‐Liss, Inc. 相似文献
4.
Enrico Verrina Barbara Andreetta Sergio Bassi Roberto Bonaudo Domenica A. Caringella Alfonso Castellani Pierluigi Cavalli Alberto Edefonti Giancarlo Lavoratti Luigi Longo Ivana Pela Rosa Penza Francesco Perfumo Virgilio Petrucci Marina Picca Mauro Ragaiolo Stefano Rinaldi Gianfranco Rizzoni Palma Sorino Giusto Viglino Graziella Zacchello Rosanna Gusmano 《Pediatric nephrology (Berlin, Germany)》1992,6(1):78-81
The results of the first 3 year' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986–1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%. 相似文献
5.
本文观察了10名游泳运动员和10名实验室工作人员在递增负荷运动中心功能的变化及其与无氧阈的关系.结果为:(1)游泳队员的无氧阈值明显高于无训练的实验室工作人员;(2)运动中每搏量稳定时的强度与无氧阈强度是密切相关的;(3)运动至无氧阈强度以后,心输出量的增加主要靠心率的增加来维持;(4)无训练者在运动一开始就动用心力储备,增加心率和每搏量,而游泳队员则在运动至40W以后才开始增加心率和每搏量.这些结果表明,无氧阈与心功能具有很密切的关系,可用它来反映心功能的好坏. 相似文献
6.
Summary This technique for reconstruction of the short philtrum requires an understanding of the viscoelastic properties of the skin and how to use these to increase skin dimensions. This is combined with contouring and splinting with a subcutaneous cartilage graft. Three representative cases are presented to illustrate the method to achieve an aesthetically acceptable lip and its long-term follow-up. No complications have been encountered using this over a 15-year period. The technique can be combined with other secondary reconstructive procedures on the lip and palate.
Work completed at: Providence Hospital, 16001 West Nine Mile Road, P.O. Box 2043, Southfield, Michigan 48037, USA 相似文献
7.
The purposes of this study were to apply the linear power versus inverse of time relationship to high-intensity upper-body
exercise and to assess the repeatability of the parameters critical power (CP) and anaerobic working capacity (AWC), using
limits of agreement (Bland and Altman 1986). Sixteen active male subjects (aged 20–34 years), performed two sets of five constant-power
exercises on an adapted cycle ergometer. There were no significant differences between mean estimates of CP [96 (16) W and
95 (17) W] and AWC [7457 (2011) J and 7608 (1684) J] from the first and second sets of bouts. Despite the lack of systematic
bias, there was evidence of large random error. Ratio limits of agreement for time to exhaustion during constant-power exercises
suggested that a repeat measurement might be expected in 95% of cases to be between 0.64 and 1.59 times the original measurement.
The 95% limits of agreement for CP were –15 W to +17 W. The ratio limits of agreement for AWC suggest that in 95% of cases
a repeat measurement might be between 0.57 and 1.67 times the original estimate. The results of this study suggest a poor
repeatability of constant-power upper-body exercises to exhaustion, which may contribute to a poor repeatability of CP and
AWC determined from the linear power versus inverse of time model.
Electronic Publication 相似文献
8.
OBJECTIVE: To examine children's competence while cycling, as demonstrated in mistakes in performance and failure to comply with safety rules. METHODS: Children in three age groups (8, 10, and 12 years) participated in a realistic yet simulated traffic environment. RESULTS: The boys' cycling speed increased steadily with age, while that of the girls increased from 8 to 10 but decreased at age 12. Most children had adequate motor control by age 10, and the youngest compensated for their less developed skills by cycling slowly and braking early at junctions. Serious mistakes, often related to the children's age and gender, consisted of the children failing to stop at signals or stopping too late, especially at short stopping range. CONCLUSIONS: There are considerable individual differences in children's cycling competence that are related to biological factors, such as age and gender, and psychological factors, such as rule compliance and choice of cycling speed. 相似文献
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This study investigated the mechanical changes induced by muscle fatigue caused by repeated sprints and determined whether
a friction-loaded cycle ergometer has any advantages for assessing muscle fatigue. Nine subjects performed 15 sprints, each
of 5 s with a 25-s rest, on a friction-loaded cycle ergometer. The averaged force, power and velocity of each push-off were
calculated. Maximal power decreased by 17.9%, with a concomittent slowing of muscle contraction, but without any change in
the maximal force. These results demonstrated that repeated sprints slow down muscle contraction, leading to a fall in maximal
power without any loss of force. This would suggest that fast twitch fibres are selectively fatigued by repeated sprints.
However, the ergometer used in the present study made it difficult to evaluate the relative influences of contraction velocity
and sprinting time. This was certainly the most important limitation. On the other hand, it showed the advantage of measuring
instantaneous power and total work dissipated in the environment simultaneously. It also permitted a force-velocity relationship
to be obtained from a single sprint and this relationship is known to be closely related to the muscle fibre composition.
Accepted: 5 March 1998 相似文献