Techno-economic optimization of a scaled-up solar concentrator combined with CSPonD thermal energy storage

A molten salt direct absorption receiver, CSPonD, used to simultaneously collect and store thermal energy is being tested by Masdar Institute and MIT in Abu Dhabi, UAE. Whilst a research-scale prototype has been combined with a beam-down tower in Abu Dhabi, the original design coupled the receiver with a hillside heliostat field. With respect to a conventional power-tower setup, a hillside solar field presents the advantages of eliminating tower costs, heat tracing equipment, and high-pressure pumps. This analysis considers the industrial viability of the CSPonD concept by modeling a 10 MWe up-scaled version of a molten salt direct absorption receiver combined with a hillside heliostat field. Five different slope angles are initially simulated to determine the optimum choice using a combination of lowest LCOE and highest IRR, and sensitivity analyses are carried out based on thermal energy storage duration, power output, and feed-in tariff price. Finally, multi-objective optimization is undertaken to determine a Pareto front representing optimum cases. The study indicates that a 40° slope and a combination of 14 h thermal energy storage with a 40-50 MW[subscript e] power output provide the best techno-economic results. By selecting one simulated result and using a feed-in tariff of 0.25 $/kWh, a competitive IRR of 15.01 % can be achieved

Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects.

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3-month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug-free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β-guanidinopropionic acid, MitoQ, and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), but none of these led to a change in survival in either sex

Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects.

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3-month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug-free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β-guanidinopropionic acid, MitoQ, and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), but none of these led to a change in survival in either sex

Techno-economic analysis of concentrated solar power plants in terms of levelized cost of electricity

Levelized Cost of Electricity (LCOE) is an important metric which provides one way to compare the economic competitiveness of different electricity generation systems, calculated simply by dividing lifetime costs by lifetime production. Hidden behind the simplicity of this formula are various assumptions which may significantly alter results. Different LCOE studies exist in the literature, although their assumptions are rarely explicitly stated. This analysis gives all formulas and assumptions which allow for inter-study comparisons. The results of this analysis indicate that CSP LCOE is reducing markedly over time and that given the right location and market conditions, the SunShot 6¢/kWh 2020 target can be reached. Increased industrial cooperation is needed to advance the CSP market and continue to drive down LCOE. The results also indicate that there exist a country and technology level learning effect, either when installing an existing CSP technology in a new country or when using a new technology in an existing CSP country, which seems to impact market progress.MIT & Masdar Institute Cooperative Program (Grant FR2014-000002

A Phase Ib Study of Sotrastaurin, a PKC Inhibitor, and Alpelisib, a PI3Kα Inhibitor, in Patients with Metastatic Uveal Melanoma

Uveal melanoma (UM) is a rare subset of melanoma characterized by the presence of early initiating GNAQ/11 mutations, with downstream activation of the PKC, MAPK, and PI3Kα pathways. Activity has been observed with the PKC inhibitors sotrastaurin (AEB071) and darovasertib (IDE196) in patients with UM. Inhibition of the PI3K pathway enhances PKC inhibition in in vivo models. We therefore conducted a phase Ib study of sotrastaurin in combination with the PI3Kα inhibitor alpelisib to identify a tolerable regimen that may enhance the activity of PKC inhibition alone. Patients with metastatic uveal melanoma (n = 24) or GNAQ/11 mutant cutaneous melanoma (n = 1) were enrolled on escalating dose levels of sotrastaurin (100–400 mg BID) and alpelisib (200–350 mg QD). The primary objective was to identify the maximum tolerated dose (MTD) of these agents when administered in combination. Treatment-related adverse events (AE) occurred in 86% (any grade) and 29% (Grade 3). No Grade 4–5-related AEs occurred. Dose Level 4 (sotrastaurin 200 mg BID and alpelisib 350 mg QD) was identified as the maximum tolerated dose. Pharmacokinetic analysis demonstrated increasing concentration levels with increasing doses of sotrastaurin and alpelisib, without evidence of interaction between agents. Pharmacodynamic assessment of pMARCKS and pAKT protein expression with drug exposure suggested modest target inhibition that did not correlate with clinical response. No objective responses were observed, and median progression-free survival was 8 weeks (range, 3–51 weeks). Although a tolerable dose of sotrastaurin and alpelisib was identified with pharmacodynamic evidence of target inhibition and without evidence of a corresponding immunosuppressive effect, limited clinical activity was observed

Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3‐month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug‐free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β‐guanidinopropionic acid, MitoQ, and 17‐dimethylaminoethylamino‐17‐demethoxygeldanamycin (17‐DMAG), but none of these led to a change in survival in either sex.Intermittent (1 month on/1 month off) or a limited 3‐month exposure to rapamycin, beginning at 20 months, was as effective as continuous exposure in increasing survival in males. In females, only intermittent exposure increased survival but the increase was not as great as continuous exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163548/2/acel13269.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163548/1/acel13269_am.pd

Rapamycin‐mediated mouse lifespan extension: Late‐life dosage regimes with sex‐specific effects

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3‐month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug‐free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β‐guanidinopropionic acid, MitoQ, and 17‐dimethylaminoethylamino‐17‐demethoxygeldanamycin (17‐DMAG), but none of these led to a change in survival in either sex.Intermittent (1 month on/1 month off) or a limited 3‐month exposure to rapamycin, beginning at 20 months, was as effective as continuous exposure in increasing survival in males. In females, only intermittent exposure increased survival but the increase was not as great as continuous exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163548/2/acel13269.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163548/1/acel13269_am.pd

Rapamycin-mediated mouse lifespan extension: Late-life dosage regimes with sex-specific effects.

To see if variations in timing of rapamycin (Rapa), administered to middle aged mice starting at 20 months, would lead to different survival outcomes, we compared three dosing regimens. Initiation of Rapa at 42 ppm increased survival significantly in both male and female mice. Exposure to Rapa for a 3-month period led to significant longevity benefit in males only. Protocols in which each month of Rapa treatment was followed by a month without Rapa exposure were also effective in both sexes, though this approach was less effective than continuous exposure in female mice. Interpretation of these results is made more complicated by unanticipated variation in patterns of weight gain, prior to the initiation of the Rapa treatment, presumably due to the use of drug-free food from two different suppliers. The experimental design included tests of four other drugs, minocycline, β-guanidinopropionic acid, MitoQ, and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), but none of these led to a change in survival in either sex