Small-Molecule Inhibition of the uPAR ⋅ uPA Interaction by Conformational Selection

The urokinase receptor (uPAR) is a cell surface receptor that binds to the serine protease urokinase-type plasminogen activator (uPA) with high affinity. This interaction is beneficial for extravascular fibrin clearance, but it has also been associated with a broad range of pathological conditions including cancer, atherosclerosis, and kidney disease. Here, starting with a small molecule that we previously discovered by virtual screening and cheminformatics analysis, we design and synthesize several derivatives that were tested for binding and inhibition of the uPAR ⋅ uPA interaction. To confirm the binding site and establish a binding mode of the compounds, we carried out biophysical studies using uPAR mutants, among them uPAR^H47C−N259C, a mutant previously developed to mimic the structure of uPA-bound uPAR. Remarkably, a substantial increase in potency is observed for inhibition of uPAR^H47C−N259C binding to uPA compared to wild-type uPAR, consistent with our use of the structure of uPAR in its uPA-bound state to design small-molecule uPAR ⋅ uPA antagonists. Combined with the biophysical studies, molecular docking followed by extensive explicit-solvent molecular dynamics simulations and MM-GBSA free energy calculations yielded the most favorable binding pose of the compound. Collectively, these results suggest that potent inhibition of uPAR binding to uPA with small molecules will likely only be achieved by developing small molecules that exhibit high-affinity to solution apo structures of uPAR, rather than uPA-bound structures of the receptor.     

Performance of RSS Based Cooperative Localization in Millimeter Wave Wireless Sensor Networks

Wireless Personal Communications - Localization in wireless sensor networks (WSNs) is a necessity as there is a vital need to have location information combined with the measured quantities. The...     

Accelerating video encoding using cluster computing

The great advance and variety of multimedia applications such as video streaming, TV broadcasting, and video conferencing stimulated research to enhance video encoding, where a video is reduced in size and possibly transformed to numerous formats for portability. This paper is concerned with solving the problem of the huge processing time taken by the serial video encoding approaches by proposing a hybrid-parallel video encoding technique to speed up the process. In this work, the Joint Scalable Video Model (JSVM 9.19.14) is chosen as the basic serial video encoding algorithm for building different parallel video encoding architectures. The proposed technique exploits the triple-step nature of JSVM and intelligently determines the best task organization to achieve speedup and increase the efficiency on a cluster computing platform. Moreover, a dynamic load sharing scheme is proposed to redistribute load among different machines for additional parallelism. The remarkable feature of our approach is that, both the granularity of load partitioning among the cluster machines and all the associated overheads are considered. The experimental results are applied on a compact library of 160 mp4 encoded videos and two other bench mark datasets. The results proves a significant improvement in performance in comparison to the sequential version; which ranges from 64.2% to 95.3%, for a cluster with a number of machines ranging from 2 to 20 respectively.

     

Appraisal of Agriglass in Promoting Maize Production Under Abiotic Stress Conditions

An agriglass composition containing different oxides acts as a slow release for macro and micro nutrients and was chosen to improve maize yield under most important abiotic stresses which affecting agriculture development; salinity and drought. A field experiment was performed in salt affected soil (EC =?7.5 dSm^??1) by using different water deficit rates (I1 = 100, I2 = 85 and I3 = 70% of maize water requirements). Irrigation levels were located in main plots. Every main-plot divided into six sub-plots contained glassy fertilizer treatments [F1 = 55 kg fed^?1 with 1/2 mm diameter of agriglass (fed. =?4200 m²), F2 = 55 kg fed^?1 with 1 mm diameter, F3 = 80 kg fed^?1 with 1/2 mm diameter, F4 = 80 kg fed^?1 with 1 mm diameter, F5 = Recommendations of Ministry of Agriculture and F6 = control]. The experimental results demonstrated that, ears, straw, grains and biological yields increased with increasing both water and agriglass rates. Application of agriglass as a slow release fertilizer improved yield more than mineral fertilizer. Some growth parameters, water use efficiency (IWUE), macronutrients concentration and their relations were included. Other studies on residual effect of agriglass and the annual application rates to withstand salinity and drought stress by strategic crops are required.     

Analyzing the Variability in Low-Flow Projections under GCM CMIP5 Scenarios

Water Resources Management - The present study considered the impacts of global climate model (GCM) selection in the Couple Model Intercomparison Phase 5 (CMIP5) scenarios on the low-flow...     

Fabricating Janus membranes via physicochemical selective chemical vapor deposition

Membranes with asymmetric wettability-Janus membranes-have recently received considerable attention for a variety of critical applications. Here, we report on a simple approach to introduce asymmetric wettability into hydrophilic porous domains. Our approach is based on the physicochemical-selective deposition of polytetrafluoroethylene (PTFE) on hydrophilic polymeric substrates. To achieve selective deposition of PTFE, we inhibit the polymerization reaction within the porous domain. We prefill the substrates with glycerol, containing a known amount of free radical inhibitor, and utilize initiated chemical vapor deposition (iCVD) for the polymerization of PTFE. We show that the glycerol/inhibitor mixture hinders the deposition of PTFE within the membrane pores. As a result, the surface of the substrates remains open and porous. The fabricated Janus membranes show stable wetting-resistant properties, evaluated through sessile drop contact angle measurements and direct contact membrane distillation (DCMD).     

1,2,3-Triazolium-based poly(acrylate ionic liquid)s

Nitroxide-mediated radical polymerization of a tailor-made acrylate carrying a 1,2,3-triazole group with an undecanoyl spacer affords a well-defined (M_n = 7860 g mol⁻¹ and D = 1.39) neutral polyacrylate precursor. A series of 1,2,3-triazolium-based poly(ionic liquid)s (TPILs) is then obtained by straightforward quaternization of the 1,2,3-triazole groups with methyl iodide and subsequent anion metathesis reactions. Among the prepared materials, TPIL with bis(trifluoromethane)sulfonimide anion exhibits low glass transition temperature (T_g = −40 °C), high thermal stability (T_d10 = 325 °C) and anhydrous ionic conductivity of 4 × 10⁻⁶ S cm⁻¹ at 30 °C, as measured by differential scanning calorimetry, thermogravimetric analysis and broadband dielectric spectroscopy, respectively.     

Thermally stable antimicrobial PVC/maleimido phenyl urea composites

Four novel antimicro bial maleimido phenyl urea derivatives were synthesized from N-[4-(chlorocarbonyl) phenyl] maleimide with phenyl urea derivatives (p-methyl, o-chloro and p-carboxy). They were characterized by FTIR, ¹H-NMR, mass spectra, elemental analyses and antimicrobial activities. These derivatives were investigated as thermal stabilizers for rigid poly(vinyl chloride) at 180 °C in air by measuring the rate of dehydrochlorination and the extent of discoloration. The results reveal the greater stabilizing efficiency of the investigated derivatives as shown by their longer thermal stability periods (Ts) and lower dehydrochlorination rates in relation to dibasic lead carbonate, cadmium-barium-zinc stearate and n-octyltin mercaptide industrial stabilizers. The stabilizing efficiency increases with the introduction of electron donating substituent groups in the aromatic ring of the stabilizer molecules. Moreover, the investigated stabilizers impart better color stability for the degraded samples as compared with the reference stabilizers.     

Titanate Anodes for Sodium Ion Batteries

For reasons of cost and supply security issues, there is growing interest in the development of rechargeable sodium ion batteries, particularly for large-scale grid storage applications. Like the much better known and technologically important lithium ion analogs, the devices operate by shuttling alkali metal cations between two host materials, which undergo insertion processes at different electrochemical potentials. A particular challenge for the sodium systems is identification of a suitable anode material due to the fact that sodium does not intercalate into graphite. Although several alternatives, including disordered carbons and alloys are being investigated, the most promising options at present lie with titanates, not in the least because of attractive characteristics such as low toxicity, ease of synthesis, wide availability, and low cost. A large variety of sodium titanate compounds can be prepared, many of which have tunnel or layered structures that can readily undergo reversible reductive intercalation reactions. A brief overview of the physical, structural, and electrochemical characteristics of several of the most promising materials for sodium-ion battery applications is given in this paper, and a comparison is made between the sodium and the lithium insertion behaviors. For some of these compounds, insertion of sodium occurs at unusually low potentials, a feature that has important implications for the design of high-energy sodium-ion systems.