Synthesis and evaluation of human phosphodiesterases (PDE) 5 inhibitor analogs as trypanosomal PDE inhibitors. 2. Tadalafil analogs

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Bioorganic & Medicinal Chemistry Letters 22 (2012): 2582-2584, doi:10.1016/j.bmcl.2012.01.118.In this report we describe our ongoing target repurposing efforts focused on discovery of inhibitors of the essential trypanosomal phosphodiesterase TbrPDEB1. This enzyme has been implicated in virulence of Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). We outline the synthesis and biological evaluation of analogs of tadalafil, a human PDE5 inhibitor currently utilized for treatment of erectile dysfunction, and report that these analogs are weak inhibitors of TbrPDEB1.This work was supported by the National Institutes of Health (R01AI082577), Boston University and Northeastern University

Peranan Badan Kepegawaian Daerah dalam Pelaksanaan Mutasi Pegawai Negeri Sipil di Kabupaten Kepulauan Talaud

This research is to know the role of the Agency in the implementation of regionalstaffing mutation civil servant in talaud Islands Regency. Talaud Islands Regency Area Staffing Agencyhas an important role in improving the performance of civil servants and is responsible for theimplementation of mutation and mutational effects on the welfare of civil servants. One example is not aseffective as the role of the Agency in the implementation of Regional Staffing i.e., mutation mutation civilservant in the Regency Talaud rated still tend to have political interests as a cornerstone of itsimplementation which we know as the seniority system and spoil system we know together not because ofhis objective based on seniority and family. So the performance of the Agency's Staffing Area in particularin the implementation of the mutation is still not qualified because its implementation is not based on theground of a mutation that we are familiar with the term meryt system or mutations that uses up therunway that is scientific, objective, and outcomes achievement it works.This research uses Qualitative Research Methods by using techniques of data analysis throughinterviews to 10 Informants, observation and document additional instrument-assisted search formguidelines interview with using techniques of data analysis, data presentation, data reduction, andwithdrawal of the conclusion.Based on the research results through data analysis, and performance measurement indicators.The following is the measurement indicators: productivity (effectiveness and efficiency), quality of service,Responsiveness, Accountability, corporate responsibility. Talaud Islands Regency BKD in itsimplementation is still not good, let alone in carrying out duties, functions, and his authority insurveillance, designation, the rules of the mutation. the performance of human resources Staffing Agencyin Areas still not in optimize thoroughly. It was evident from the coordination between subordinates andsuperiors are still unfavourable, liability is still very closed, in addition to Staffing The Agency also doesnot answer the needs of society in General.Referring to the conclusions above, shall recommend in a good cooperation between, civilservants, with Staffing Agencies, Staffing Agencies and Regional Areas and local governments mustfacilitate the work of civil servants by holding trainings – training

Structure and Magnetism of well-defined cobalt nanoparticles embedded in a niobium matrix

Our recent studies on Co-clusters embedded in various matrices reveal that the co-deposition technique (simultaneous deposition of two beams : one for the pre-formed clusters and one for the matrix atoms) is a powerful tool to prepare magnetic nanostructures with any couple of materials even though they are miscible. We study, both sharply related, structure and magnetism of the Co/Nb system. Because such a heterogeneous system needs to be described at different scales, we used microscopic and macroscopic techniques but also local selective absorption ones. We conclude that our clusters are 3 nm diameter f.c.c truncated octahedrons with a pure cobalt core and a solid solution between Co and Nb located at the interface which could be responsible for the magnetically inactive monolayers we found. The use of a very diluted Co/Nb film, further lithographed, would allow us to achieve a pattern of microsquid devices in view to study the magnetic dynamics of a single-Co cluster.Comment: 7 TeX pages, 9 Postscript figures, detailed heading adde

Temperature dependence and mechanisms for vortex pinning by periodic arrays of Ni dots in Nb films

Pinning interactions between superconducting vortices in Nb and magnetic Ni dots were studied as a function of current and temperature to clarify the nature of pinning mechanisms. A strong current dependence is found for a square array of dots, with a temperature dependent optimum current for the observation of periodic pinning, that decreases with temperature as (1-T/Tc)3/2. This same temperature dependence is found for the critical current at the first matching field with a rectangular array of dots. The analysis of these results allows to narrow the possible pinning mechanisms to a combination of two: the interaction between the vortex and the magnetic moment of the dot and the proximity effect. Moreover, for the rectangular dot array, the temperature dependence of the crossover between the low field regime with a rectangular vortex lattice to the high field regime with a square configuration has been studied. It is found that the crossover field increases with decreasing temperature. This dependence indicates a change in the balance between elastic and pinning energies, associated with dynamical effects of the vortex lattice in the high field range.Comment: 12 text pages (revtex), 6 figures (1st jpeg, 2nd-6th postscript) accepted in Physical Review

Assessment of selected Saudi and Yemeni plants for mosquitocidal activities against the yellow fever mosquito Aedes aegypti

© 2019 by the authors. Marine organisms are recognized as a source of compounds with interesting biological activities. Vibrio neocaledonicus has been reported on for its high effectiveness against corrosion in metals but it has been little studied for its chemical and biological activities. In this study, four compounds were isolated from V. neocaledonicus: indole (1); 1H-indole-3-carboxaldehyde (2); 4-hydroxybenzaldehyde (3) and Cyclo (-Pro-Tyr) (4); using a bioassay-guided method, since in a previous study it was found that the ethyl acetate extract was active on the enzymes acetylcholinesterase (AChE), alpha-glucosidase (AG) and xanthine oxidase (XO). The inhibitory activities of the three compounds against AChE, AG and XO was also evaluated. In addition, the enzymatic inhibitory activity of indole to the toxins from the venom of Bothrops asper was tested. Results showed that indole exhibited strong inhibitory activity to AG (IC50 = 18.65 ± 1.1 µM), to AChE, and XO (51.3% and 44.3% at 50 µg/mL, respectively). 1H-indole-3-carboxaldehyde displayed strong activity to XO (IC50 = 13.36 ± 0.39 µM). 4-hydroxybenzaldehyde showed moderate activity to XO (50.75% at 50 µg/mL) and weak activity to AChE (25.7% at 50 µg/mL). Furthermore, indole showed a significant in vitro inhibition to the coagulant effect induced by 1.0 µg of venom. The findings were supported by molecular docking. This is the first comprehensive report on the chemistry of V. neocaledonicus and the bioactivity of its metabolites

Dirac electrons in graphene-based quantum wires and quantum dots

In this paper we analyse the electronic properties of Dirac electrons in finite-size ribbons and in circular and hexagonal quantum dots made of graphene.Comment: Contribution for J. Phys.: Cond. Mat. special issue on graphene physic

Periprosthetic osteolysis due to metastatic renal cell carcinoma: a case report

Failure of total hip arthroplasty through septic or aseptic loosening, periprosthetic fracture, or recurrent dislocation is well recognized and understood. We present an unusual cause of failure of total hip replacement which occurred on a 79 year old gentleman: that of prosthetic loosening secondary to malignant infiltration around components. Our aim is to highlight the fact that malignant infiltration should be considered as part of the differential diagnosis in aseptic and septic loosening of prosthetic implants

Excitons in a Photosynthetic Light-Harvesting System: A Combined Molecular Dynamics/Quantum Chemistry and Polaron Model Study

The dynamics of pigment-pigment and pigment-protein interactions in light-harvesting complexes is studied with a novel approach which combines molecular dynamics (MD) simulations with quantum chemistry (QC) calculations. The MD simulations of an LH-II complex, solvated and embedded in a lipid bilayer at physiological conditions (with total system size of 87,055 atoms) revealed a pathway of a water molecule into the B800 binding site, as well as increased dimerization within the B850 BChl ring, as compared to the dimerization found for the crystal structure. The fluctuations of pigment (B850 BChl) excitation energies, as a function of time, were determined via ab initio QC calculations based on the geometries that emerged from the MD simulations. From the results of these calculations we constructed a time-dependent Hamiltonian of the B850 exciton system from which we determined the linear absorption spectrum. Finally, a polaron model is introduced to describe quantum mechanically both the excitonic and vibrational (phonon) degrees of freedom. The exciton-phonon coupling that enters into the polaron model, and the corresponding phonon spectral function are derived from the MD/QC simulations. It is demonstrated that, in the framework of the polaron model, the absorption spectrum of the B850 excitons can be calculated from the autocorrelation function of the excitation energies of individual BChls, which is readily available from the combined MD/QC simulations. The obtained result is in good agreement with the experimentally measured absorption spectrum.Comment: REVTeX3.1, 23 pages, 13 (EPS) figures included. A high quality PDF file of the paper is available at http://www.ks.uiuc.edu/Publications/Papers/PDF/DAMJ2001/DAMJ2001.pd