Selective Withdrawal Research Articles

Numerical investigation of selective withdrawal in a pancreatic cell islet encapsulation apparatus

The development of an efficient microencapsulation apparatus is a major challenge for islet transplantation. To that end, the flow generated by selective withdrawal in an apparatus for micro-encapsulation of pancreatic islets is studied through CFD simulations. Each islet enters individually a chamber containing a twolayer system in which is encapsulated by selective withdrawal. Optimal encapsulation occurs, when the perturbed interface is kept stable and transition to viscous entrainment is prevented. Simulations were validated with experimental data. Contrary to previous studies that simplify the problem by approximating the tubes as a doublet of a point mass source and sink, the model presented here employs a detailed geometry. Numerical results shed light on the dependence of the shape of the interface on flow, geometry and physical parameters. These observations can contribute to the design of encapsulation apparatuses considering polydispersity in size and the different shape of the islets.

Sustainable Management of Reservoir Water Quality and Quantity Through Reservoir Operational Strategy and Watershed Control Strategies

Water quality impairment is a serious health concern for reservoirs; two strategies were used to control reservoir outflow quality: (1) control of reservoir inflows with implementation of structural best management practices (BMPs) at the watershed, and (2) management of reservoir outflows by reservoir operational strategy. To assess the effectiveness of two strategies on reservoir water quality, an extension of the Sustainability Index (SI) for water quality was defined. Additionally, a quantity-based SI for supplying of downstream water demands was defined. So il and water assessment tool was linked to a reservoir simulation model (CE-QUAL-W2), and coupled with multi-objective particle swarm optimization algorithm. The proposed model was applied in four different scenarios on Alavian reservoir and its watershed, in Iran, during a 6-year time horizon. Four BMPs, named detention ponds, filter strips, parallel terraces, and grade stabilization structures, were used. The results indicated that application of the proposed approach provides the best set of solutions for decision makers to manage outflow quality and quantity. Whenever the watershed management strategy is not possible/practical, the reservoir operational strategy in selective withdrawal scheme would improve reservoir outflow quality by up to 77%. On the other hand, when the reservoir downstream water demand satisfaction is necessary, the watershed management strategy, or selective withdrawal scheme would be improved when the reservoir outflow dissolved oxygen concentration SI by up to 30 and 52%, respectively. Among the applied BMPs, filter strip had more effect on reducing nutrient loads and it was the most chosen BMP.

Abstract 1337: MEK1:MAPK1/2 targeting attenuates pro-survival autophagy and enhances antiestrogen-induced apoptosis in breast cancer cells via a cathepsin L-dependent mechanism

Abstract Antiestrogen resistance is still a major clinical challenge preventing the eradication of estrogen receptor positive (ER+) breast cancer. A major goal of our laboratory is to identify targeted therapies that can be combined with antiestrogen treatment to block the emergence of antiestrogen resistant breast cancer. Toward this goal, we previously determined that the catabolic process of autophagy facilitates the emergence of antiestrogen resistance (Sammadar et al., Molecular Cancer Ther. 9, 2008) and identified cathepsin L as a key lysosomal protease required for antiestrogen induced pro-survival autophagy ER+ MCF-7cells (Periyasamy-Thandavan et al., Autophagy. 6:19-35, 2010). Thus, we hypothesize that blocking cathepsin L expression / activity is one approach to targeting pro-survival autophagy during antiestrogen treatment of breast cancer. In support of this hypothesis, we now show that antiestrogen resistant TR5 cells show increased levels of active cathepsin L compared to the levels in the parent antiestrogen sensitive MCF-7 cells. The upregulation of cathepsin L expression is consistent with the fact that TR5 cells utilized autophagy to survive long-term 4-hydroxytamoxifen (4-OHT) selection. Withdrawal of 4-OHT selection during TR5 passage does not lead to a reduction in cathepsin L levels, suggesting that the increased expression of cathepsin L is a stable genetic or epigenetic alteration. Elevated expression of active (phosphorylated) MAPK1/2 is also present in TR5 cells and targeting MEK1/MAPK1/2 with the selective inhibitor U0126 consistently reduced the levels of active cathepsin L. We further established a key role for MEK1/MAPK1/2 in the regulation of cathepsin L in the parent MCF-7 cells by performing cathepsin L activity assays. Cells treated with 4-OHT showed increased cathepsin L activity compared to E2-treated control cells; whereas, cathepsin L activity in cells treated with 4-OHT + UO126 was significantly reduced compared to the levels in 4-OHT-treated cells. This reduction in cathepsin L by U0126-mediated blockade of MEK1/MAPK1/2 correlated directly to “impaired” autophagic flux and increased BimEL-dependent apoptosis in the antiestrogen-treated cell populations and was mediated, at least in part, via transcriptional regulation of cathepsin L as determined by quantitative PCR. Further, MEK1/MAPK1/2 up-regulation of cathepsin L is selective, as cathepsin B activity is not reduced by MEK1 targeting. These studies provide evidence that the targeting MEK1/MAPK1/2 in combination with antiestrogen treatment has the potential to reduce cathepsin-L mediated pro-survival autophagy in ER+ breast cancer. Citation Format: Annie Liu, Carol Joseph, Jesse Wayson, Timothy Summers, Haifeng Cai, Patricia V. Schoenlein. MEK1:MAPK1/2 targeting attenuates pro-survival autophagy and enhances antiestrogen-induced apoptosis in breast cancer cells via a cathepsin L-dependent mechanism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1337.

Dealing with reservoir eutrophication in a trans-boundary river

Article 21 of the United Nation 1997 Convention is related to the protection of water resource quality in non-navigable border rivers. Based on this article, the countries located in the border catchment are prohibited from the actions which contaminate the water sources and jeopardize the health of residents. Further, upon the request of one of the beneficiaries, a common standard, integrated monitoring program and planning to reduce non-point and point pollution sources should be developed. In spite of this law, experience has shown that the management of pollution sources, especially non-point resources in border basins, would be very complicated and time-consuming. Selective withdrawal and discharge of contaminated water from lower level of the dam are regarded as one of the effective ways to optimize the eutrophication condition of dam reservoirs in downstream of border basins. The present study aimed to develop an optimization model to improve reservoir water quality and protect water quality of downstream. This method was employed in Dousti dam located on the river of Harirud. Salma dam construction and agricultural development in Afghanistan strengthen the eutrophication condition of the Dousti dam reservoir. The results showed that reservoir conditions in the status quo were Mesotrophic, which convert to the acute conditions of Eutrophic due to the upstream development. In the case of discharging a percentage of downstream need from the reservoir bottom outlet, based on the results of the optimization model, about 30% of the dissolved oxygen is improved.

Assessment of Selective Withdrawal and Inflow Control on the Hydrodynamics and Water Quality of Ilam Reservoir.

The hydrodynamics and water quality of Ilam reservoir, consisting of three main inlet branches and two outlets, was simulated with the CE-QUAL-W2 model. After calibrating and verifying the numerical model, effects of various management scenarios (selective withdrawal, controlling water inflow, and their combinations) were investigated on thermal stratification and water quality. The total reduction of nutrient loads derived from the Chaviz and Ema rivers decreased the total phosphorus concentration. The chlorophyll a concentration of this scenario increased less than in other scenarios. Variation of the withdrawal elevation from the surface to the bottom significantly facilitated the heat conduction of the water column, therefore, the thermal and dissolved oxygen stratification was weakened. The best management scenario was a combination of water withdrawal from the bottom and surface and total reduction of nutrient loads derived from Chaviz and Ema rivers because of improving eutrophication, thermal, and dissolved oxygen stratification in Ilam reservoir.

A New Device used in Selective Withdrawal from Reservoirs and its Effectiveness Verified in Computational Fluid Dynamics

Water intake with fixed height limits the application of selective withdrawal technology in a certain degree. This study proposes a technological idea to install baffles on water intake. Through the rotation of upper and lower baffle, poor water layer can be blocked. A Computational Fluid Dynamics (CFD) model for the upper baffle on water intake is constructed. The results show that the baffle installed on the upper part of orifice can reduce the withdrawal layer thickness and flow on the upper part of orifice centre. Thereby, the withdrawal flow on lower part can be indirectly increased. While, baffle length and inclining angle are the important factors to influence the withdrawal layer thickness and flow distribution. Therefore, the adjusting range of selective withdrawal can be economically enhanced by installing baffles on water intake.

Selective withdrawal from an intake channel connected to a reservoir

This paper investigates selective withdrawal from an intake channel connected to a two-layer stratified reservoir using a line sink located at the downstream end of the intake channel. Such a withdrawal scenario is commonly observed at intake channels, skimming operations, and pump intake bays. This study formulates mathematical expressions for such a withdrawal scenario in order to extend our knowledge and to develop a mathematically simpler method in the case where a solution already exists. An expression to compute the incipient Froude number was developed considering the effect of a boundary. Expressions were developed to obtain discharge ratios for the scenarios when the line sink is located at the channel bottom and far away from the channel bottom. When the interface is located below the channel bottom and only at the reservoir, the intake channel itself behaves as a rectangular orifice, and an expression to compute the incipient Froude number for such a case was developed. The mathematical results were compared to the results obtained from a computational fluid dynamics solver and other relevant published studies.

Experimental and numerical study on the thrust of a water-retaining curtain

Abstract A water-retaining curtain (WRC) has become a useful facility in selective withdrawal and sedimentation control, but the force analysis of a curved curtain is still lacking. Based on flume experimental tests and numerical simulations, this paper analyzes the variation laws of pressure difference and thrust of WRC. The results show that under the uniform inflow condition, the distribution of pressure difference on the WRC is relatively even, and the maximum value is located at the upper part of the curtain. When arc length–height ratio increases, the location of maximum pressure difference gets lower. In addition, the variation law of thrust of WRC conforms to the classical resistance equation. The drag coefficient is found to fit a power function of the water-retaining ratio, a second-degree polynomial function of arc length–height ratio, and linear function of inclination ratio. The results also yield a simplified forecasting formula of thrust of WRC which is proposed and verified using flume simulations and a real reservoir model test. The newly developed formula systematically considers the water-retaining height, arc length and inclination degree, providing a rapid and accurate algorithm to predict the thrust, and lays a theoretical foundation for practical application.

Оптимальное позиционирование источников выбросов загрязнений в задачах промышленной экологии

The problem related to the conflict between sources group’s excessive emissions and region’s pollution standards has been considered. It is possible to resolve the conflict by emissions sources efficiencies restrictions or reduction of pollution standards. Both actions lead to economic losses. It has been proposed to ease the conflict by the optimal sources allocation, in comparison with the initial one. The sources’ efficiencies and the region’s standards have been preserved during optimization. The sources emissions were modeling by parabolic functions, thus was solving the geometric problem of optimizing the coordinates for allocation of paraboloids with constant volumes. Different sources coordinates usually lead to a multiextremal function of pollution excess over the region's standards. The optimization problem is reduced to excess function control. The sources coordinates are becoming the control parameter. The numerical integral of the excess function has been defined as optimization criterion. Assuming a unimodal relationship between the criterion and the parameter, the Nelder-Mead procedure has been chosen as an algorithm for multidimensional nonlinear optimization. The optimization criterion’s convinced convergence to zero has been established due to a change on the sources coordinates’ iterations. Numerical experiments have been carried out, in which a high level of conflict (pollution function’s multiple excesses over the standards) has been set by the initial parameters. The region has been divided into 6 regulatory zones with non-standard flexible boundaries. The excess function was generating by 24 sources with different emissions efficiencies. A series of iterations has been performed, at which the conflict level was reduced to 1.32% due to the sources displacement. Such a decrease has required a selective withdrawal of 18 sources out of the region. This withdrawal does not exclude further trans-boundary pollutions emissions into the controlled area. The problems of trans-boundary pollutions transfer have been discussed. Iterations results have been shown in 2D-3D graphics. Having at disposal detailed iterations tapes, including their visualization, a designer is free to choose different input data of the model and to achieve the required conflict level. The presentation of optimization results in numerical and graphical formats is a convenient tool for designing of areas with complex infrastructure.

Modeling the effect of temperature-control curtain on the thermal structure in a deep stratified reservoir

Temperature-control curtain (TCC) is an effective facility of selective withdrawal. Previous research has estimated the influence of TCC on the outflow temperature, but its effect on the thermal structure of a reservoir area is unknown, which is crucial to the reservoir ecology. For this purpose, taking the Sanbanxi Reservoir as a case study, a 2-D hydrodynamic and temperature model covering the whole reservoir was built and calibrated to simulate the flow and temperature fields under different TCC scenarios, and the change rules of thermal stability and outflow temperature are obtained. When the water-retaining proportion (Pr) of bottom-TCC increases, the temperature difference between inflow and outflow monotonously decreases, while the thermal stability first increases and later decreases. The maximum thermal stability exists at Pr = 62.5%; it goes against water quality improvement and should be avoided in practice. A bottom-TCC with Pr > 80% is practical for deep reservoirs such as Sanbanxi Reservoir to decrease the temperature difference between inflow and outflow without the increase of thermal stability. In terms of top-TCC, as Pr increases, the temperature difference between inflow and outflow monotonously increases and thermal stability decreases. The top-TCCs are recommended when a smaller thermal stability is more preferentially considered than outflow temperature, or a cool outflow in the summer is required for downstream coldwater fishes. In addition, the TCC cannot decrease or increase the outflow temperature all of the time throughout the whole year, and it primarily changes the phase and variation range of the outflow temperature. This study quantitatively estimates the potential effect of TCCs on the thermal structure and water environment management and provides a theoretical basis for the application of TCC.

Effects of reservoir operation and climate change on thermal stratification of a canyon-shaped reservoir, in northwest China

Abstract Thermal stratification has a significant impact on water quality and ecological characteristics. Reservoir operation and climate change have an effect on the thermal regime. The Jinpen Reservoir is a large canyon-shaped reservoir located in Shaanxi Province with a strong thermal stratification, which resulted in an anaerobic condition in the hypolimnion. We used a hydrodynamic module based on MIKE 3 to simulate the thermal structure of the Jinpen Reservoir and study the relationship between the thermal regime, reservoir operation and climate change. Based on the daily hydrological and climatic data from 2004 to 2013, we made 13 hypothetical simulated conditions that included extreme change of inflow volume, water level, air temperature, radiation, inflow water temperature and selective withdrawal to explore the effect of different factors on the thermal regime. The results showed that the period of thermal stratification, water column stability and surface water temperature were influenced by these factors. With the increase of air temperature, the simulation results indicated a stronger thermal stratification and a higher surface water temperature, which could cause water safety problems. Deep withdrawal could decrease water column stability and prompt water column mixing early, which could be used by reservoir managers to optimize the reservoir operation.

Modeling of Turbidity Variation in Two Reservoirs Connected by a Water Transfer Tunnel in South Korea

The Andong and Imha reservoirs in South Korea are connected by a water transfer tunnel. The turbidity of the Imha reservoir is much higher than that of the Andong reservoir. Thus, it is necessary to examine the movement of turbidity between the two reservoirs via the water transfer tunnel. The aim of this study was to investigate the effect of the water transfer tunnel on the turbidity behavior of the two connecting reservoirs and to further understand the effect of reservoir turbidity distribution as a function of the selective withdrawal depth. This study applied the CE-QUAL-W2, a water quality and 2-dimensional hydrodynamic model, for simulating the hydrodynamic processes of the two reservoirs. Results indicate that, in the Andong reservoir, the turbidity of the released water with the water transfer tunnel was similar to that without the tunnel. However, in the Imha reservoir, the turbidity of the released water with the water transfer tunnel was lower than that without the tunnel. This can be attributed to the higher capacity of the Andong reservoir, which has double the storage of the Imha reservoir. Withdrawal turbidity in the Imha reservoir was investigated using the water transfer tunnel. This study applied three withdrawal selections as elevation (EL.) 141.0 m, 146.5 m, and 152.0 m. The highest withdrawal turbidity resulted in EL. 141.0 m, which indicates that the high turbidity current is located at a vertical depth of about 20–30 m because of the density difference. These results will be helpful for understanding the release and selective withdrawal turbidity behaviors for a water transfer tunnel between two reservoirs.

Strategies to engage older adults with behavioral and psychological symptoms of dementia in exercise: A multiple case study

Alzheimer’s disease (AD) affects 5.2 million Americans in 2016 and this number will increase to 14.7 million by 2050. Unfortunately, AD cannot yet be prevented, slowed, or cured. Aerobic exercise is potentially therapeutic for Alzheimer’s disease (AD) as it favorably affects brain structure and function. A critical determinant in testing its effectiveness is optimal adherence to the exercise prescription. AD symptoms, particularly behavioral and psychological symptoms of dementia (BPSD), however, make exercise delivery and adherence challenging. The purpose of this paper is to discuss the strategies used for managing BPSD during exercise using a multiple case study design. Three cases with BPSD that met the eligibility criteria were selected from the FIT-AD Trial. The FIT-AD Trial is an ongoing randomized controlled trial that tests the effects of a 6-month moderate intensity aerobic exercise on cognition and hippocampal volume in community-dwelling persons with AD. The cases included: a 77-year-old woman with mild AD, a 79-year-old woman with mild AD, and a 69-year-old man with moderate AD. The participants exhibited anxiety, repetitive questioning, irritability, hostility, extreme distractedness, resistance to instruction, and hoarding during exercise. The symptoms were effectively addressed using person-centered strategies such as routine schedules, reassurance, timely communications, distraction, small rewards, rephrasing, immediate answers, selective withdrawal from conversations that were hostile, step by step instructions, building on rapport and relationship with staff, and affirmation. They achieved 83.3%–100% attendance and 52.8%–81.7% session adherence, respectively. In conclusion, individualized strategies for BPSD are necessary to ensure optimal exercise adherence.

Meta-Model Assisted 2D Hydrodynamic and Thermal Simulation Model (CE-QUAL-W2) in Deriving Optimal Reservoir Operational Strategy in Selective Withdrawal Scheme

Reconciling simultaneous water quantity and quality aspects in drawing optimal reservoir operational strategy involves extensive computational burdens. Surrogate based optimization techniques (SBOTs) are common approaches to overcome computational bottlenecks of numerical hydrodynamic simulation models coupling evolutionary algorithm in simulation-optimization approaches. In this study, the reservoir high resolution CE-QUAL-W2 model is replaced by the lower resolution CE-QUAL-W2 and/or static ANN to speed up the optimization process. These surrogate models could consider the complex relationships to emulate the main dynamics of HR CE-QUAL-W2 model due to various reservoir operational strategies. The performance of various SBOTs, based on adaptive and sequential surrogate models coupled with particle swarm optimization algorithm, are evaluated in deriving optimal reservoir operational strategies. Then adaptive surrogate model, as the more efficient and accurate one, is applied to derive long term optimal reservoir operational strategy in the selective withdrawal scheme. The results show application of the proposed approach could enhance downstream water temperature, water demand satisfactions, and hydropower peak energy generation compared with the standard operation policy (SOP) in Karkheh reservoir during 15-year-time horizon.

Formation of aerobic granules for the treatment of real and low-strength municipal wastewater using a sequencing batch reactor operated at constant volume

This study aimed at evaluating the formation of aerobic granular sludge (AGS) for the treatment of real and low-strength municipal wastewater using a column sequencing batch reactor (SBR) operated in fill-draw mode (constant volume). The focus was on understanding how the wastewater upflow velocity (VWW) applied during the anaerobic feeding influenced the sludge properties and in turn the substrate conversion. Two different strategies were tested: (1) washing-out the flocs by imposing high wastewater upflow velocities (between 5.9 and 16 m h−1) during the anaerobic feeding (Approach #1) and (2) selective utilization of organic carbon during the anaerobic feeding (1 m h−1) combined with a selective sludge withdrawal (Approach #2). A column SBR of 190 L was operated in constant volume during 1500 days and fed with real and low-strength municipal wastewater. The formation of AGS with SVI30 of around 80 mL gTSS−1 was observed either at very low (1 m h−1) or at high VWW (16 m h−1). At 16 m h−1 the AGS was mainly composed of large and round granules (d > 0.63 mm) with a fluffy surface, while at 1 m h−1 the sludge was dominated by small granules (0.25 < d < 0.63 mm). The AGS contained a significant fraction of flocs during the whole operational period. A considerable and continuous washout of biomass occurred at VWW higher than 5.9 m h−1 (Approach #1) due to the lower settling velocity of the AGS fed with municipal wastewater. The low sludge retention observed at VWW higher than 5.9 m h−1 deteriorated the substrate conversion and in turn the effluent quality. High solid concentrations (and thus solid retention time) were maintained during Approach #2 (VWW of 1 m h−1), which resulted in an excellent effluent quality. The study demonstrated that the formation of AGS is possible during the treatment of real and low-strength municipal wastewater in a SBR operated at constant volume. Low wastewater upflow velocities should be applied during the anaerobic feeding phase in order to ensure enough biomass retention and efficient substrate removal.

Gravity currents in a linearly stratified ambient fluid created by lock release and influx in semi-circular and rectangular channels

We present an experimental investigation, supported by a theoretical model, of the motion of lock-release, constant inflow, and time varying inflow gravity currents (GCs) into a linearly stratified ambient fluid at large Reynolds number. The aim is the experimental validation of a simple model able to predict the slumping phase front speed and the asymptotic self-similar front speed for rectangular and circular cross section channels. The first investigated system is of Boussinesq type with the dense current (salt water dyed with aniline) released in a circular channel of 19 cm diameter and 400 cm long (605 cm in the inflow experiments), half-filled of linearly stratified ambient fluid (salt water with varying salt concentration). The second system has the same components but with a channel of rectangular cross section of 14 cm width, 11 cm ambient fluid depth, and 504 cm length. The density stratification of the ambient fluid was obtained with a computer controlled set of pumps and of mixing tanks. For the experiments with inflow, a multi-pipes drainage system was set at the opposite end with respect to the inflow section, computer controlled to avoid the selective withdrawal. The numerous experiments (28 for circular cross section, lock release; 26 for circular and 14 for rectangular cross section, constant inflow (fluid volume ∝tα, with α = 1); 6 for circular cross section, linearly increasing inflow (α = 2)), with several combination of the stratification parameter (0 &amp;lt; S &amp;lt; 1) confirm the theory within ≈30% (≈40% for a single series of experiments), which is considered a good result in view of the various underlying simplifications and approximations. The results on the front speed of the GCs are discussed in the presence of the internal waves, which have a celerity given by a theoretical and experimentally tested model for the rectangular but not for the circular cross section. The theoretical analysis of internal waves in circular cross sections has been extended and experimentally validated.

Optimal Selective Withdrawal Rules Using a Coupled Data Mining Model and Genetic Algorithm

AbstractThis work presents a methodology for extracting optimal operational rules for selective reservoir water withdrawal by considering fixed levels of reservoir water outlets for thermal control. The outlet water temperature of the Karkheh reservoir, Iran, is simulated with the CE-QUAL-W2 model. A data-mining model (the LIBSVM model) is applied as a surrogate model of the CE-QUAL-W2 model and coupled with a genetic algorithm (GA), resulting in the LIBSVM-GA algorithm. The selective withdrawal approach considered four fixed reservoir outlets, located at 120, 140, 163, and 181 m above sea level, to account for reservoir thermal stratification. This paper’s methods are evaluated with nonselective and selective withdrawal operations through different scenarios in which single outlet, fixed withdrawal proportions, fixed monthly variable proportions, continually variable (10-day) proportions using total monthly LIBSVM input data, and continually variable (10-day) proportions using separated monthly LIBSVM in...

Optimal control of reservoir release temperature through selective withdrawal intake at hydropower dam

This study is motivated by the need to understand the temperature dynamics and warm-water temperature withdrawal. This study also recognizes the need for an environmental assessment of the proposed temperature control schemes at New Fengman Dam. An unsteady three-dimensional (3D) non-hydrostatic model is used in the present study to predict the hydrodynamics and thermal dynamics in the forebay and intakes of the New Fengman Dam. The numerical model is validated using hydrodynamic data collected from a 1:120 entire physical model and 1:30 local model in the present paper. The numerical and experimental results indicate that the Stop Log Gate has no effect on warm-water withdrawal. After dam reconstruction, the reservoir release temperatures can be increased from 4.0 °C to 6.0 °C to improve the habitat of native fishes. The cancellation of the Stop Log Gate program is recommended; the old dam meets the performance objectives for temperature increase.

Short-Term Estrogen Withdrawal Increases Adiposity in Healthy Men.

T deprivation increases risk of insulin resistance in men, but whether this risk is independent of changes in body composition is unknown. Further, the metabolic roles of T and its metabolite estradiol have not been clearly defined in men. This study sought to establish the effects of selective sex steroid withdrawal on insulin sensitivity in healthy men. This was a double-blinded, placebo-controlled, randomized trial at an academic medical center of 56 healthy men, 19-55 years of age. Subjects received the GnRH antagonist acyline plus one of the following: placebo gel (Castrate), 1.25 g testosterone gel (Low T/E), 5 g testosterone gel (Normal T/E), or 5 g testosterone gel with letrozole (Normal T/Low E) daily for 4 weeks. Body composition and glucose tolerance were assessed at baseline and end of treatment. Insulin sensitivity was quantified by the Matsuda index. Predicted circulating sex steroid concentrations were achieved in all treatment groups. The time-by-group interaction for Matsuda index did not achieve significance in overall repeated measures ANOVA (baseline vs week 4; P = .16). A significant time-by-group interaction was observed for fat mass (P = .003), with changes in fat mass attributable predominantly to estrogen exposure in linear regression analysis (P = .016). A time-by-group interaction also was observed for lean mass (P = .03) and influenced by androgen exposure (P = .003). Short-term sex steroid withdrawal in healthy men causes adverse changes in body composition. These findings support the role of estradiol as a determinant of adiposity in men.

Selective withdrawal optimization in river-reservoir systems; trade-offs between maximum allowable receiving waste load and water quality criteria enhancement.

In this paper, a new systematic approach is designed to maximize the demand coverage and receiving waste load by river-reservoir systems while enhancing water quality criteria. The approach intends to control the reservoir eutrophication while developing a trade-off between the maximum receiving load and shortage on demand coverage. To simulate the system, a hybrid process-based and data-driven model is tailored. Initially, the two-dimensional hydrodynamics and water quality simulation model (CE-QUAL-W2) is linked with an effective single and/or multiple optimization algorithms (PSO) to evaluate the proposed scenarios. To increase the computational efficiencies, the simulation model is substituted with a surrogate model (ANN) in an adaptive-dynamically refined routine. The proposed method is illustrated by a case study in Iran, namely, Karkheh River Reservoir, for 180-monthly periods. The results showed the applicability of the methodology especially to solve high-dimensional multi-period complex water resource optimization problems. Also, the results demonstrated that eutrophication could be reduced under the optimal inflow phosphate control and reservoir operation, regulating the total phosphorous concentration in the reservoir.