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A 300-member flavonoid dimer library of multidrug resistance-associated protein 1 (MRP1, ABCC1) modulators was rapidly assembled using "click chemistry". Subsequent highthroughput screening has led to the discovery of highly potent (EC 50 ranging from 53 to 298 nM) and safe (selective indexes ranging from >190 to >1887) MRP1 modulators. Some dimers have potency about 6.5-to 36-fold and 64-to 358-fold higher than the well-known MRP1 inhibitors, verapamil, and MK571, respectively. They inhibited DOX efflux and restored intracellular DOX concentration. The most potent modulator, Ac3Az11, was predicted to bind to the bipartite substrate-binding site of MRP1 in a competitive manner. Moreover, it provided sufficient concentration to maintain its plasma level above its in vitro EC 50 (53 nM for DOX) for about 90 min. Overall, we demonstrate that "click chemistry" coupled with high throughput screening is a rapid, reliable, and efficient tool in the discovery of compounds having potent MRP1-modualting activity.

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The Digital Imaging and Communications in Medicine (DICOM) standard is now widely implemented in radiology as the standard for diagnostic imaging. It has also been extended for use in various subspecialties. One of the first extensions was applied to radiation therapy and is known as DICOM-RT. In addition to the protocol used in the DICOM standard, seven DICOM-RT objects-namely, RT Image, RT Structure Set, RT Plan, RT Dose, RT Beams Treatment Record, RT Brachy Treatment Record, and RT Treatment Summary Recordhave been created, each with a well-defined data model. The data models set the standard for integration of radiation therapy information for an electronic patient record and would facilitate the interoperability of different radiation therapy systems, thus making possible the sharing of information from different systems.

The present work describes the syntheses of diverse triazole bridged flavonoid dimers and identifies potent, nontoxic, and highly selective BCRP inhibitors. A homodimer, Ac22­(Az8) 2 , with m-methoxycarbonylbenzyloxy substitution at C-3 of the flavone moieties and a bis-triazole-containing linker (21 atoms between the two flavones) showed low toxicity (IC50 toward L929, 3T3, and HFF-1 > 100 μM), potent BCRP-inhibitory activity (EC50 = 1–2 nM), and high BCRP selectivity (BCRP selectivity over MRP1 and P-gp > 455–909). Ac22­(Az8) 2 inhibits BCRP-ATPase activity, blocks the drug efflux activity of BCRP, elevates the intracellular drug accumulation, and finally restores the drug sensitivity of BCRP-overexpressing cells. It does not down-regulate the surface BCRP protein expression to enhance the drug retention. Therefore, Ac22­(Az8) 2 and similar flavonoid dimers appear to be promising candidates for further development into combination therapy to overcome MDR cancers with BCRP overexpression.

We investigated the acceptability of power variation during a cycling time trial (TT) with simulated uphill and downhill sections. Seven cyclists first completed an 800-kJ self-paced TT on a simulated flat course. An 800-kJ TT course with four sections of uphill/downhill was then modeled. Each section involved 100 kJ of cycling up a simulated gradient of 5 % followed by 100 kJ of riding down a simulated gradient of - 5 %. Participants were required to complete this simulated course using two pacing strategies; (i) at a constant power equivalent to the mean power achieved during the initial TT, and (ii) increasing power by 5 % of mean power when traveling uphill (mean duration of each climb = 714 s) and decreasing power in the downhill sections (mean duration of each descent = 190 s), so that overall mean power was equivalent to that in (i). All participants maintained this variable power strategy during the first half of the TT, but two riders could not adhere to the power variations during the final 400 kJ. Nevertheless, mean +/- SD finish time for the variable power trial (3670 +/- 589 s) was significantly faster than that for the constant power TT (3758 +/- 645 s), the 95 % confidence interval for the percentage improvement being 0.4 to 4.3 %. Heart rate and lactate responses were highest in the initial self-paced TT and did not differ between the subsequent constant and variable power trials. Ratings of perceived exertion were also similar between trials. In our externally-valid TT, we found that some cyclists cannot fully adhere to a pacing strategy involving an approximate +/- 5 % variation in mean power in parallel with gradient variation. Nevertheless, an important time saving can still result even if a variable pacing strategy is only partially adopted during a hilly time trial, so that no additional physiological strain is incurred.

What makes consumers adopt energy-sustainable innovations? Drawing from psychological research on environmental behaviors, we propose a model integrating attitudinal factors, normative factors and self-control to explain the purchase of electric vehicles (EVs) by consumers. Specifically, we utilized structural equation modeling to develop a model to identify relationships between perceived values, green attitudes, normative factors, and self-expressive benefits and purchase intention of EVs. An empirical study was carried out to test the conceptual framework and 11 hypotheses were developed based on literature. The model was tested with survey data from 205 Hong Kong respondents from the automobile community. SEM analyses confirmed that perceived value, trust in EV, responsive efficacy, and willingness to pay had significant and positive influence on purchase intention of EVs. This study offers insights into the development of marketing program for EV in Hong Kong. The findings will help EV manufacturers to facilitate EV purchases. Future research opportunities are discussed.