An improved algorithm for optimal load shedding in power systems

A blackout is usually the result of load increasing beyond the transmission capacity of the power system. A collapsing system enters a contingency state before the blackout. This contingency state is characterized by a decline in the bus voltage magnitudes. To avoid blackouts, power systems may start shedding load when a contingency state occurs called under voltage load shedding (UVLS). The success of a UVLS scheme in arresting the contingency state depends on shedding the optimum amount of load at the optimum time and location. This paper proposes a hybrid algorithm based on genetic algorithms (GA) and particle swarm optimization (PSO). The proposed algorithm can be used to find the optimal amount of load shed for systems under stress (overloaded) in smart grids. The proposed algorithm uses the fast voltage stability index (FVSI) to determine the weak buses in the system and then calculates the optimal amount of load shed to recover a collapsing system. The performance analysis shows that the proposed algorithm can improve the voltage profile by 0.022 per units with up to 75% less load shedding and a convergence time that is 53% faster than GA

Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis

Malaria and cryptosporidiosis, caused by apicomplexan parasites, remain major drivers of global child mortality. New drugs for the treatment of malaria and cryptosporidiosis, in particular, are of high priority; however, there are few chemically validated targets. The natural product cladosporin is active against blood- and liver-stage; Plasmodium falciparum; and; Cryptosporidium parvum; in cell-culture studies. Target deconvolution in; P. falciparum; has shown that cladosporin inhibits lysyl-tRNA synthetase (; Pf; KRS1). Here, we report the identification of a series of selective inhibitors of apicomplexan KRSs. Following a biochemical screen, a small-molecule hit was identified and then optimized by using a structure-based approach, supported by structures of both; Pf; KRS1 and; C. parvum; KRS (; Cp; KRS). In vivo proof of concept was established in an SCID mouse model of malaria, after oral administration (ED; 90; = 1.5 mg/kg, once a day for 4 d). Furthermore, we successfully identified an opportunity for pathogen hopping based on the structural homology between; Pf; KRS1 and; Cp; KRS. This series of compounds inhibit; Cp; KRS and; C. parvum; and; Cryptosporidium hominis; in culture, and our lead compound shows oral efficacy in two cryptosporidiosis mouse models. X-ray crystallography and molecular dynamics simulations have provided a model to rationalize the selectivity of our compounds for; Pf; KRS1 and; Cp; KRS vs. (human); Hs; KRS. Our work validates apicomplexan KRSs as promising targets for the development of drugs for malaria and cryptosporidiosis

A 2–40 GHz Probe Station Based Setup for On-Wafer Antenna Measurements

A probe station based setup for on-wafer antenna measurements is presented The setup allows for measurement of return loss and radiation patterns of an on-wafer antenna-henceforth referred to as the antenna under test (AUT), radiating at broadside and fed through a coplanar waveguide (CPW). It eliminates the need for wafer dicing and custom-built test fixtures with coaxial connectors or waveguide flanges by contacting the AUT with a coplanar microwave probe. In addition, the AUT is probed exactly where it will be connected to a transceiver IC later on, obviating de-embedding of the measured data. Sources of measurement errors are related to calibration, insufficient dynamic range, misalignment, forward scattering from nearby objects, and vibrations. The performance of the setup is demonstrated from 2 to 40 GHz through measurement of an on-wafer electrically small slot antenna (lambda(0)/35 x lambda(0)/35,3.5 x 3.5 mm(2)) radiating at 2.45 GHz and an aperture coupled microstrip antenna (2.4 X 1.7 mm(2)) radiating at 38 GHz.11612sciescopu

Targeting Prolyl-tRNA Synthetase to Accelerate Drug Discovery against Malaria, Leishmaniasis, Toxoplasmosis, Cryptosporidiosis, and Coccidiosis.

Developing anti-parasitic lead compounds that act on key vulnerabilities are necessary for new anti-infectives. Malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis and coccidiosis together kill >500,000 humans annually. Their causative parasites Plasmodium, Leishmania, Toxoplasma, Cryptosporidium and Eimeria display high conservation in many housekeeping genes, suggesting that these parasites can be attacked by targeting invariant essential proteins. Here, we describe selective and potent inhibition of prolyl-tRNA synthetases (PRSs) from the above parasites using a series of quinazolinone-scaffold compounds. Our PRS-drug co-crystal structures reveal remarkable active site plasticity that accommodates diversely substituted compounds, an enzymatic feature that can be leveraged for refining drug-like properties of quinazolinones on a per parasite basis. A compound we termed In-5 exhibited a unique double conformation, enhanced drug-like properties, and cleared malaria in mice. It thus represents a new lead for optimization. Collectively, our data offer insights into the structure-guided optimization of quinazolinone-based compounds for drug development against multiple human eukaryotic pathogens

Pharmacokinetic properties of CFZ.

<p>(A) Plasma concentration of CFZ or BKI-1294 in mice dosed with 20 mg/kg compound. CFZ was formulated in either corn oil (black) or MC-Tween (gray); BKI-1294 was formulated in 7% Tween 80, 3% ethanol, and 90% water (white). Data shown are mean ± SEM (n = 3). (B) Unchanged CFZ or BKI-1294 recovered in the feces of mice dosed in (A). Recovery was measured each day for three days. Data shown are mean ± SEM (n = 3).</p