Robustness of a bisimulation-type faster-than preorder

TACS is an extension of CCS where upper time bounds for delays can be specified. Luettgen and Vogler defined three variants of bismulation-type faster-than relations and showed that they all three lead to the same preorder, demonstrating the robustness of their approach. In the present paper, the operational semantics of TACS is extended; it is shown that two of the variants still give the same preorder as before, underlining robustness. An explanation is given why this result fails for the third variant. It is also shown that another variant, which mixes old and new operational semantics, can lead to smaller relations that prove the same preorder.Comment: Express Worksho

A FAST AND SENSITIVE SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF HYDRAZINE IN ATAZANAVIR SULFATE DRUG SUBSTANCE

Objective: To develop a fast and sensitive UV spectrophotometric method for the quantitative estimation of Hydrazine in Atazanavir Sulfate drug substances and validate as per ICH guidelines. Methods: The method was based upon the observation, that a characteristic colour results upon addition of a solution of p-Dimethylaminobenzaldehyde in ethyl alcohol and hydrochloric acid to hydrazine and estimated at absorbance maximum  458 nm in Atazanavir drug substance. Results: The developed method resulted in Hydrazine exhibiting linearity in the range 0.2 to 2.7 µg/g. The Intraday and interday precision is exemplified by relative standard deviation of 0.959 % and 0.947%. Percentage Mean recovery was found to be in the range of 97â€101%, during accuracy studies. The limit of detection (LOD) and limit of quantitiation (LOQ) were found to be 0.2 µg/g and 0.6 µg/g respectively. Conclusion: The present work was aimed to develop a visible spectrophotometric method, which is simple, sensitive, accurate and cost effective to evaluate the quality of the bulk and pharmaceutical formulations

Thermo-fluidic Transport Process in a Novel M-shaped Cavity Packed with Non-Darcian Porous Medium and Hybrid Nanofluid: Application of Artificial Neural Network (ANN)

In this work, an attempt has been made to explore numerically the thermo-fluidic transport process in a novel M-shaped enclosure filled with permeable material along with Al2O3-Cu hybrid nanoparticles suspended in water under the influence of a horizontal magnetizing field. To exercise the influence of geometric parameters, a classical trapezoidal cavity is modified with an inverted triangle at the top to construct an M-shaped cavity. The cavity is heated isothermally from the bottom and cooled from the top, whereas the inclined sidewalls are insulated. The role of geometric parameters on the thermal performance is scrutinized thoroughly by changing the sidewall inclination, number, and height of the top inverted triangular undulation under similar boundary conditions. The governing equations transformed into dimensionless form are solved by using a computing code written in the finite volume approach. The analysis is conducted by considering a wide range of parametric influences like sidewall angles (γ), number (n), and height (δ) of the top triangular undulations, modified Rayleigh number (Ram), Darcy number (Da), Hartmann number (Ha), and hybrid nanoparticle concentrations (φ). Furthermore, the artificial neural network (ANN) technique is implemented and tested to predict the overall thermal behavior of the novel cavity to predict new cases. The results revealed that the design of sidewall inclination (γ) is an important parameter for modulating the thermo-flow physics. The M-shaped cavity (compared to trapezoidal) reveals either a rise or drop in the fluid circulation strength depending upon the magnitude of δ, but the heat transfer rate always increases due to an increase in the cooling length. The heat transfer increment is ∼61.01% as δ increases. Single undulation with higher depth is the optimum choice for achieving improved heat transfer (which may go up to ∼355.75% for δ = 0.5 and γ  = 45°). A decrease in Da or Ha causes a drop in the flow strength, which consequently leads to a drop in the heat transfer rate. Furthermore, the concepts of ANN will help researchers predict the behavior for such complicated cavity shapes with a multiphysics approach. This will save efforts as well as computing time for exploring the thermal behavior of any range of a dataset

Structure of Cryptosporidium IMP de­hydrogenase bound to an inhibitor with in vivo antiparasitic activity

Inosine 50-monophosphate dehydrogenase (IMPDH) is a promising target for the treatment of Cryptosporidium infections. Here, the structure of C. parvum IMPDH (CpIMPDH) in complex with inosine 50-monophosphate (IMP) and P131, an inhibitor with in vivo anticryptosporidial activity, is reported. P131 contains two aromatic groups, one of which interacts with the hypoxanthine ring of IMP, while the second interacts with the aromatic ring of a tyrosine in the adjacent subunit. In addition, the amine and NO2 moieties bind in hydrated cavities, forming water-mediated hydrogen bonds to the protein. The design of compounds to replace these water molecules is a new strategy for the further optimization of C. parvum inhibitors for both antiparasitic and antibacterial applications

Selective and potent urea inhibitors of Cryptosporidium parvum inosine 5’-monophosphate dehydrogenase

Cryptosporidium parvum and related species are zoonotic intracellular parasites of the intestine. Cryptosporidium is a leading cause of diarrhea in small children around the world. Infection can cause severe pathology in children and immunocompromised patients. This waterborne parasite is resistant to common methods of water treatment and therefore a prominent threat to drinking and recreation water even in countries with strong water safety systems. The drugs currently used to combat these organisms are ineffective. Genomic analysis revealed that the parasite relies solely on inosine-5?-monophosphate dehydrogenase (IMPDH) for the biosynthesis of guanine nucleotides. Herein, we report a selective urea-based inhibitor of C. parvum IMPDH (CpIMPDH) identified by high-throughput screening. We performed a SAR study of these inhibitors with some analogues exhibiting high potency (IC50 1000-fold versus human IMPDH type 2 and good stability in mouse liver microsomes. A subset of inhibitors also displayed potent antiparasitic activity in a Toxoplasma gondii model

The Structural Basis of Cryptosporidium-Specific IMP Dehydrogenase Inhibitor Selectivity

Cryptosporidium parvum is a potential biowarfare agent, an important AIDS pathogen, and a major cause of diarrhea and malnutrition. No vaccines or effective drug treatment exist to combat Cryptosporidium infection. This parasite relies on inosine 5?-monophosphate dehydrogenase (IMPDH) to obtain guanine nucleotides, and inhibition of this enzyme blocks parasite proliferation. Here, we report the first crystal structures of CpIMPDH. These structures reveal the structural basis of inhibitor selectivity and suggest a strategy for further optimization. Using this information, we have synthesized low-nanomolar inhibitors that display 103 selectivity for the parasite enzyme over human IMPDH2

Searches for neutrinoless double beta decay

Neutrinoless double beta decay is a lepton number violating process whose observation would also establish that neutrinos are their own anti-particles. There are many experimental efforts with a variety of techniques. Some (EXO, Kamland-Zen, GERDA phase I and CANDLES) started take data in 2011 and EXO has reported the first measurement of the half life for the double beta decay with two neutrinos of $^{136}$Xe. The sensitivities of the different proposals are reviewed.Comment: 8 pages, prepared for TAUP 201