Recent advances in end-to-end continuous-flow synthesis are rapidly expanding the capabilities of automated customized syntheses of small-molecule pharmacophores, resulting in considerable industrial ...and societal impacts; however, many hurdles persist that limit the number of sequential steps that can be achieved in such systems, including solvent and reagent incompatibility between individual steps, cumulated by-product formation, risk of clogging and mismatch of timescales between steps in a processing chain. To address these limitations, herein we report a strategy that merges solid-phase synthesis and continuous-flow operation, enabling push-button automated multistep syntheses of active pharmaceutical ingredients. We demonstrate our platform with a six-step synthesis of prexasertib in 65% isolated yield after 32 h of continuous execution. As there are no interactions between individual synthetic steps in the sequence, the established chemical recipe file was directly adopted or slightly modified for the synthesis of twenty-three prexasertib derivatives, enabling both automated early and late-stage diversification.
•Effects of some geometrical parameters of a LTDSE have been studied by using CFD.•These parameters have little effect on compression ratio yet are influential on engine performance.•They affects ...engine power by the margins up to 32% and efficiency up to 13%.•The results are useful for guiding the design of new LTDSEs.
This study conducts a parametric investigation on a γ-type low temperature differential Stirling engine (LTDSE) using CFD. The effects on engine performance posed by four geometrical parameters namely phase angle between power piston and displacer, gap width between displacer and displacer cylinder, length of displacer, and length of power piston linkage bar, are systematically examined. One crucial advantage of using CFD is that temperature and velocity vector fields in engine space can be obtained, allowing important physical processes to be studied in great detail. Then the physical mechanisms through which a parameter affects engine performance can be identified. It is found that all four parameters are quite influential on engine performance despite that they are of little effect on the magnitude of engine’s compression ratio. Within the ranges of parameters examined here, they affect engine performance by margins up to 32% on indicated power and 13% on efficiency. The results highlight the importance of every geometrical parameter on overall engine performance, and the information concluded in this study is very useful for the design of a new LTDSE.
The slow-releasing hydrogen sulfide (H₂S) donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS) but ...did not affect survival of normal human lung fibroblasts (IMR90, WI-38) as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS) was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122) lacking sulfur and thence not able to release H₂S was inactive. Similar results were obtained using a clonogenic assay. Incubation of GYY4137 (400 µM) in culture medium led to the generation of low (<20 µM) concentrations of H₂S sustained over 7 days. In contrast, incubation of NaHS (400 µM) in the same way led to much higher (up to 400 µM) concentrations of H₂S which persisted for only 1 hour. Mechanistic studies revealed that GYY4137 (400 µM) incubated for 5 days with MCF-7 but not IMR90 cells caused the generation of cleaved PARP and cleaved caspase 9, indicative of a pro-apoptotic effect. GYY4137 (but not ZYJ1122) also caused partial G₂/M arrest of these cells. Mice xenograft studies using HL-60 and MV4-11 cells showed that GYY4137 (100-300 mg/kg/day for 14 days) significantly reduced tumor growth. We conclude that GYY4137 exhibits anti-cancer activity by releasing H₂S over a period of days. We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H₂S donors should be investigated further as potential anti-cancer agents.
•An in-house CFD code has been developed to simulate a β-type Stirling engine.•Temperature distribution is highly non-uniform across the engine volume.•Impingement is the major heat transfer ...mechanism in the engine.•The motions of displace and power piston are also important for heat transfer.
A compressible CFD code has been developed to study the heat transfer characteristics of a β-type Stirling engine with a very simple design and geometry. The results include temperature contours, velocity vectors, and distributions of local heat flux along solid boundaries at several important time steps as well as variations of average temperatures, integrated rates of heat input, heat output, and engine power. It is found that impingement is the major heat transfer mechanism in the expansion and compression chamber, and the temperature distribution is highly non-uniform across the engine at any given moment. The results, especially the rates of heat transfer, are quite different from those obtained by a second-order model. The variations of heat transfer rates are much more complicated than the simple variations returned by the second-order model. This study sheds light into the complex heat transfer mechanism inside the Stirling engine and is very helpful to the understanding of the fundamental process of the engine cycle.
•A parametric study on a low-temperature-differential Stirling engine has been conducted by using CFD.•The effects of three geometric and two operational parameters on engine performance have been ...investigated.•It is found that each parameter produces different effects except power piston stroke and power piston radius.•The results are useful for guiding the design of new low-temperature-differential Stirling engines.
An in-house CFD code has been applied to a low-temperature-differential (LTD) γ-type Stirling engine to understand the effects posed by several geometrical and operational parameters on engine performance. The results include variations of pressure, temperature, and heat transfer rates within an engine cycle as well as variations of engine’s power and efficiency versus these parameters. It is found that power piston stroke and radius influence engine performance very similarly, and power and efficiency both increase as these two parameters increase. In fact, the effects of the two parameters can be assimilated into those by the parameter of compression ratio. The stroke of displacer is observed to affect strongly on heat input but weakly on power, thus causing the efficiency to decrease as it increases. As expected, both power and efficiency increase as temperature difference between the hot and cold ends increases. Lastly, engine speed is observed to pose strong positive effects on power but exert weak effects on efficiency. This study reveals the effects produced by several important parameters on engine performance, and such information is very useful for the design of new LTD Stirling engines.
This study proposes a biosyngas-fueled power system, which is a fusion between a micro-thermophotovoltaic (micro-TPV) system and a Stirling engine. The combustor in the micro-TPV is a coaxial tube ...made of platinum. Biosyngas was simulated using different compositions of H2 and CO mixture. The H2/CO/air mixture was delivered to the inner channel of the micro-TPV combustor, while the CH4/air mixture was delivered to the outer channel. This study realized a micro-CHP system with a combustion-driven TPV cell array, and a Stirling engine-driven power generation system. This micro-CHP system harvests energy generated through thermal radiation from the reactor's surface as well as thermal energy from hot flue gas. The results indicate that the overall efficiency of the biosyngas-fueled micro-CHP system was strongly dependent on fuel composition, fuel/air ratio, and flowrate mixture. Thus, Taguchi method was employed to find optimal operative conditions; the highest efficiency was achieved under a biosyngas composition of 80% CO and 20% H2, with a flow velocity of 6 ms−1, and an equivalence ratio of 1.2, and its corresponding overall efficiency reached 43%, incorporating 0.84 W electricity output by TPV cell array, 3.25 W electricity output by Striling engine-driven power generation system, and 325.5 W of water energy gained.
•Biosyngas-fueled micro-CHP system features good fuel adaptability and reliability.•The catalytic reactivity of micro TPV combustor extends system maneuverability.•Taguchi method was employed to optimize the overall efficiency of Micro-CHP.•Three optimal indicators were proposed and implemented in the Taguchi method.•The overall efficiency of the micro-CHP system with optimal conditions reached 43%.
Currently, alternative fuels, derived from biomass and urban maximize the overall power output, have been increasingly attracting more attention in the industrial and residential sectors. ...Micro-combined heat and power (CHP) systems with high energy efficiency have been developed, particularly for the use in remote and rural areas. This study used a micro-CHP system, with a combustion-driven thermophotovoltaic (TPV) cell array and a Stirling engine-driven power system, within which methane and bio-syngas fuels were deployed strategically. This micro-CHP system harvests energy generated through thermal radiation from the reactor surface and harvests thermal energy from hot flue gas. Eventually, the micro-CHP prototype was proven that all energies are converted to electricity, and hot water can be simultaneously supplied. High incandescent surface and high-temperature flue gas of platinum reactor provide the thermal sources for TPV cell array and Stirling engine. The overall efficiency of the micro-CHP system was 35.0% for 50%H2+50%CO, and the generated power included 2.7, 3.5, and 272.1 W from the Stirling engine-driven power system, GaSb TPV cell array, and hot water supply system, respectively. The systematic performance of the micro-CHP system, the combustion features, radiation efficiency, fuel conversion rate, total electricity output, and corresponding overall efficiencies were examined thoroughly.
•Micro-combined heat and power (CHP) system fueled with biosyngas was developed.•The micro-CHP system comprises the PV array and Stirling engine power system.•The platinum combustor mitigates fuel variability and flame instability.•The overall efficiencies of the micro-CHP are assessed under various conditions.
US Renal Data System 2010 Annual Data Report Collins, Allan J., MD; Foley, Robert N., MB; Herzog, Charles, MD ...
American journal of kidney diseases,
01/2011, Volume:
57, Issue:
1
Journal Article
In this study, an inverse algorithm based on the conjugate gradient method and the discrepancy principle is applied to estimate the unknown space- and time-dependent heat flux of the disc in a disc ...brake system from the knowledge of temperature measurements taken within the disc. In the direct problem, the specific heat and thermal conductivity are functions of temperature; hence this is a nonlinear inverse problem. The temperature data obtained from the direct problem are used to simulate the temperature measurements, and the effect of the errors in these measurements upon the precision of the estimated results is also considered. Results show that an excellent estimation on the space- and time-dependent heat flux can be obtained for the test cases considered in this study. The current methodology can be also applied to the prediction of heat flux in the pads, and then the heat partition coefficient between the disc and the pad in a brake system can be calculated.
► We use conjugate gradient inverse method to determine the unknown space- and time-dependent heat flux into the disc during a braking process. ► Temperature-dependent specific heat and thermal conductivity of the disc are used. ► The temperature measurement location should be put as close to the friction interface as possible. ► Results show that the space- and time-dependent heat flux can be estimated accurately even involving measurement errors.
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