Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP's). MARK4 is known for its major role ...in tau phosphorylation via phosphorylating Ser
residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer's disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson's disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of -6.9 kcal/mol forming interactions with binding pocket's critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC
= 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 10
M
. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.
Organic Rankine cycles (ORC) have unique properties that are well suited to solar power generation. In this work design and performance calculations are performed using
MatLab/SimuLink computational ...environment. The cycle consists of thermal solar collectors (Flat Plate Solar Collector (FPC), or Parabolic Trough Collector (PTC), or Compound Parabolic Concentrator (CPC)) for heat input, expansion turbine for work output, condenser unit for heat rejection, pump unit, and Reverse Osmosis (RO) unit. Reverse osmosis unit specifications used in this work is based on Sharm El-Shiekh RO desalination plant. Different working fluids such as: butane, isobutane, propane, R134a, R152a, R245ca, and R245fa are examined for FPC. R113, R123, hexane, and pentane are investigated for CPC. Dodecane, nonane, octane, and toluene are allocated for PTC. The proposed process units are modeled and show a good validity with literatures. Exergy and cost analysis are performed for saturation and superheated operating conditions. Exergy efficiency, total exergy destruction, thermal efficiency, and specific capital cost are evaluated for direct vapor generation (DVG) process. Toluene and Water achieved minimum results for total solar collector area, specific total cost and the rate of exergy destruction.
Solar power assisted different techniques of MED-VC (multi effect distillation-vapor compression) processes is thermo-economically analyzed and evaluated. In this work, two techniques of solar power ...cycles are considered to power on MED-PF-TVC, MVC (multi effect distillation thermal and mechanical vapor compressions). In the first technique, the developed solar thermal power is directly transmitted from the solar collector field via boiler heat exchanger unit toward the steam ejector of the MED-PF-TVC process. In the second technique, the electrical power generated from the SORC (Solar Organic Rankine Cycle) is used to power on the vapor compressor of the MED-PF-MVC process. The comparison is implemented according to the operation of PTC (parabolic trough collector) with Toluene organic oil and Water working fluids (2nd technique). Therminol-VP1 HTO (Heat Transfer Oil) is considered across the solar field and water is considered for boiler heat exchanger (1st technique). A case study is performed according to 4545 m
3/day of distillate product. As a result, reducing the value of compression ratio with increasing the evaporator’s numbers would reduce the specific power consumption, solar field area, and thermo-economic costs. Also it is clear that the operation of steam ejector would increase the gain ratio instead of increasing the evaporator’s numbers.
► Different configurations of MED-VC desalination process are compared however, Parallel feed configuration is dominant. ► Combining solar organic cycle with such configuration is required to overcome the water shortage problem. ► The combination is evaluated based on exergy and thermo-economic analysis by using SDS (solar desalination system) software package. ► Increasing number of effects is connected with decreasing the compression ratio and top steam temperature. These parameters may reduce the product cost. It is found that solar thermal technique with MED-TVC is reliable and low in costs.
Solar energy with different configurations of multi-effect distillation process is thermo-economically evaluated. In this work, two different combined solar cycles with different configurations of ...multi effect distillation (MED) processes are considered. In the first technique, the solar energy is directly utilized from the solar collector field via evaporator heat exchanger to the first effect of the MED process. This technique produces only potable water. In the second technique, the exhausted energy from the organic Rankine cycle (ORC) turbine is used in the first effect of the MED process. The second technique produces power electricity and desalted water. The comparison is implemented according to the operation of Parabolic Trough Collector (PTC) with toluene organic oil and water working fluids. Therminol-VP1 Heat Transfer Oil (HTO) is considered for indirect vapor generation operation across the solar field and evaporator heat exchanger. The comparisons are manipulated according to 100
m
3/day of distillate product as a case study. As a result, only desalination technique is considered more attractive than desalination and power technique due to higher gain ratio and lower solar field area needed. Parallel feed configuration is dominated against the forward feed with feed heater configuration while increasing the number of effects to more than 12 effects.
► Different configurations of MED desalination process are compared. ► Parallel feed configuration could be dominant while increasing the number of effects. ► Combining solar organic cycle with such configuration is required. ► The combination is evaluated based on exergy and thermo-economic analyses. ► Stand alone technique harvests lower solar field area and higher gain ratio.
The maximum power tracking problem and efficient energy utilization of a stand-alone photovoltaic array (PVA) feeding voltage controlled linear and nonlinear loads is studied. A novel and simple ...on-line fuzzy logic-based dynamic search, detection and tracking controller is developed to ensure maximum power point (MPP) operation under excursions in solar insolation, ambient temperature and electric load variations. A computer simulation model of the PVA renewable utilization scheme including the effects of temperature and solar irradiation changes was developed and fully simulated. The load voltage is controlled by a DC chopper and kept constant at the required rated voltage. A permanent magnet DC motor (PMDC) driving a fan-type load was connected in parallel to an RL passive load. A speed control scheme is also used for the PMDC motor drive so that the drive can be operated at specified speeds. Different controllers have been employed in the unified PVA scheme to control three separate loads at MPP tracking condition namely voltage at load bus and speed of the PMDC motor. The main objective of the paper is to present a novel enhanced, cost-effective MPP detector (MPPD) and dynamic MPP tracking (MPPT) controller for a hybrid mix of electric loads.
Objectives
To assess the long‐term functional outcomes after pyeloplasty in solitary kidney (SK) models and to define factors affecting postoperative renal function recoverability in adults.
Patients ...and Methods
We retrospectively evaluated all adult patients who underwent pyeloplasty for pelvi‐ureteric junction obstruction (PUJO) in SK. Long‐term renal function was assessed by diuretic scintigraphy and morphological changes were also determined, e.g. renal parenchymal volume (RPV) and parenchymal thickness (PT). We considered a >20% increase in glomerular filtration rate (GFR) as improvement, >20% decrease as deterioration, and changes within 20% as stationary renal function. Univariate and multivariate analysis for factors affecting renal function recoverability, including the Acute Kidney Injury Network (AKIN) Staging System postoperatively, were performed.
Results
The study included 62 patients with a mean (SD) age of 29 (10.5) years. At a median of 48 months, the mean (SD) GFR increased from 41.3 (17) to 48.5 (20.1) mL/min (P < 0.001), with a significant increase in RPV and PT (P = 0.02 and P = 0.001, respectively). Follow‐up renal function was static, improved and decreased in 39 (63.4%), 17 (27%) and six (9.6%) patients, respectively. Functional success was achieved in 90.4%. Patient’s age ≥39 years, PT ≤0.75 cm and higher early postoperative AKIN staging were predictors associated with a 4.8‐, 3.2‐ and 2.7‐fold deterioration in renal function.
Conclusion
Pyeloplasty in SK preserved renal function in 90.4% of the present patients. Pyeloplasty in SK when associated with older age, decreased PT preoperatively, and early higher AKIN staging postoperatively was associated with poor renal function recoverability.
