Combinatorial solid-phase synthesis and screening of a diverse tripodal triazacyclophane (TAC)-based synthetic receptor library showing a remarkable selectivity towards a d-Ala-d-Ala containing ligand

A large and diverse library of a TAC-based tripodal synthetic receptor library (6) has been prepared by split-mix synthesis on the solid phase. Each receptor of the 46,656-member TAC-based library (6) is attached to a solid support bead and contains three different dipeptide arms. On-bead screening for binding of a d-Ala-d-Ala containing ligand (7) by the TAC-based library (6) was performed in phosphate buffer (0.2 N, pH=7.0). Remarkable selectivity for particular library members was observed. The best binding members from the screening were manually selected using fluorescence microscopy and subjected to structural analysis by sequencing. The thus determined binding sequences showed a high consensus.     

Evaluation of the effect of silicon on the carbonization process of Colombian semi-anthracites

The environmental impacts associated with the exploitation and transformation of fossil resources aggravate the planet's situation in terms of climate change. Due to this, this paper studies an alternative use of mineral coal as a precursor to obtaining new materials with different properties to the starting coals. The thermal degradation of two Colombian semi-anthracites is analyzed through the thermogravimetry (TG) technique coupled to a Fourier transform infrared spectroscopy (FTIR) equipment from room temperature (25 °C) to 900 °C, at a heating rate of 10 K min^?1 in an inert atmosphere. The catalytic effect of the addition of silicon to these samples before being subjected to a carbonization process is evaluated during this process. The results indicated that the primary reaction occurs in the temperature range between 400 and 680 °C, where the highest mass loss rate was observed. At the end of the heating process, the TG profile of the samples with silicon addition showed losses between 14.33 and 18.82% in mass, these values being slightly higher compared to the starting and demineralized samples. The release of water, light gases such as CO₂, CH₄, and species such as toluene, phenol and formic acid was identified in most of the samples. The presence of silica seems to favor the release of all these species, being more evident in one of the semi-anthracites studied. According to the results obtained, it is proved that the presence of silicon in samples subjected to carbonization processes has a catalytic effect that improves some characteristics of the new materials obtained, thus contributing to the use of carbon to get new materials.

     

A Multi-Objective Approach for Drug Repurposing in Preeclampsia

Preeclampsia is a hypertensive disorder that occurs during pregnancy. It is a complex disease with unknown pathogenesis and the leading cause of fetal and maternal mortality during pregnancy. Using all drugs currently under clinical trial for preeclampsia, we extracted all their possible targets from the DrugBank and ChEMBL databases and labeled them as “targets”. The proteins labeled as “off-targets” were extracted in the same way but while taking all antihypertensive drugs which are inhibitors of ACE and/or angiotensin receptor antagonist as query molecules. Classification models were obtained for each of the 55 total proteins (45 targets and 10 off-targets) using the TPOT pipeline optimization tool. The average accuracy of the models in predicting the external dataset for targets and off-targets was 0.830 and 0.850, respectively. The combinations of models maximizing their virtual screening performance were explored by combining the desirability function and genetic algorithms. The virtual screening performance metrics for the best model were: the Boltzmann-Enhanced Discrimination of ROC (BEDROC)_α=160.9 = 0.258, the Enrichment Factor (EF)_1% = 31.55 and the Area Under the Accumulation Curve (AUAC) = 0.831. The most relevant targets for preeclampsia were: AR, VDR, SLC6A2, NOS3 and CHRM4, while ABCG2, ERBB2, CES1 and REN led to the most relevant off-targets. A virtual screening of the DrugBank database identified estradiol, estriol, vitamins E and D, lynestrenol, mifrepristone, simvastatin, ambroxol, and some antibiotics and antiparasitics as drugs with potential application in the treatment of preeclampsia.     

Complete minimal hypersurfaces in quaternionic hyperbolic space

We construct new examples of embedded, complete minimal hypersurfaces in quaternionic hyperbolic space and also some minimal foliations. We introduce fans and construct analytic deformations of bisectors.     

The corrections for non-ideal behavior of the epithermal neutron spectrum and the restitution of the simplicity in parametric activation analysis

The errors occurred when α, the parameter that accounts for the non-ideal behavior of the epithermal flux, are neglected, have been evaluated for the determination of twenty elements in biological materials, using. gold and sodium comparators, and zirconium to measure the thermal to epithermal flux ratio (f). Sodium allows the determination of 15 elements, and up to 18 elements can be determined in positions relatively well thermalized by the simultaneous use of gold and sodium comparators, in all the cases with errors ≦2%, when α is not considered. Results obtained for reference materials are presented.     

Hiv-1 Specific Reverse Transcriptase Inhibitors: why are Tsao-Nucleosides so Unique?

1. INTRODUCTION

AIDS will still be one of the most important challenges for the Scientific Community in the approaching new century. Since the identification, in 1983-84,^1,2 of human immunodeficiency virus (HIV) as the etiological agent of AIDS, significant progress has been made in the treatment of HIV-infected patients. This has been in part due to the discovery and clinical use of an increasing number of anti-HIV drugs. However, while highly active antiretroviral therapy (HAART)³ approaches have reduced the morbidity and mortality, the intertwined problems of drug induced viral resistance, poor compliance with complex regimens and therapy failure continue. Therefore, there remains a pressing need for the development of new antiviral agents that can be used not only as first line therapeutic candidates, but also in the antiretroviral-experienced patient population.     

Energy and angular momentum of charged rotating black holes

We show that the pseudotensors of Einstein, Tolman, Landau and Lifshitz, Papapetrou, and Weinberg essentially coincide for any Kerr-Schild metric if calculations are carried out in Kerr-Schild Cartesian coordinates. This generalizes a previous result by Gürses and Gürsey that dealt only with the pseudotensors of Einstein and Landau-Lifshitz. We compute exactly the energy and angular momentum distributions for the Kerr-Newman metric in Kerr-Schild Cartesian coordinates and compare the results with those obtained by using different definitions of quasilocal mass, which unlike pseudotensors do not agree for all Kerr-Schild metrics.     

Method for construction of operators in Fock space

It is shown, by providing a general method for the construction that any Fock space linear operator defined on the dense linear manifold spanned by the particle number representation basis can be represented in terms of the annihilation and creation operators. The normal form of the representation is unique.