Conformation of Tax-response elements in the human T-cell leukemia virus type I promoter

Background: HTLV I Tax is believed to activate viral gene expression by binding bZIP proteins (such as CRIB) and increasing their affinities for proviral THE target sites. Each 21 by THE target site contains an imperfect copy of the intrinsically bent CRE target site (the TRE core) surrounded by highly conserved flanking sequences. These flanking sequences are essential for maximal increases in DNA affinity and transactivation, but they are not, apparently, contacted by protein. Here we employ non-denaturing gel electrophoresis to evaluate TRE conformation in the presence and absence of bZIP proteins, and to explore the role of DNA conformation in viral transactivation.Results: Our results show that the TRE-1 flanking sequences modulate the structure and modestly increase the affinity of a CREB bZIP peptide for the TRE-1 core recognition sequence. These flanking sequences are also essential for a maximal increase in stability of the CREB-DNA complex in the presence of Tax.Conclusions: The CRE-like TRE core and the TRE flanking sequences are both essential for formation of stable CRIB-TRE-1 and Tax-CREB-TRE-1 complexes. These two DNA segments may have co-evolved into a unique structure capable of recognizing Tax and a bZIP protein.     

Folate antagonists. 6. Synthesis and antimalarial effects of fused 2,4-diaminothieno[2,3-d]pyrimidines

2,4-Diamino-5,7-dihydro-6H-thiopyrano[4′,3′:4,5]thieno[2,3-d]pyrirnidine, 2,4-diamino-9H-mdeno[1′,2′:4,5]thieno[2,3-d]pyrimidine, 2,4-diamino-5H-indeno[2′,1′:4,5]thieno[2,3-d]pyrimidine, 9,11-diamino-5,6-dihydronaphtho[1′,2′:4,5]thieno[2,3-d]pyrimidine, 7,9-diamino-5,6-dihydronaphtho[2′,1′:4,5]thieno[2,3-d]pyrimidine, 2,4-diamino-7-benzy]-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine, and various 2,4-diamino-5,6,7,8-tetrahydro-[1]benzothieno[2,3-d]pyrimidines were synthesized by cyclization of the requisite fused 2-aminothio-phenene-3-carbonitriles utilizing chloroformamidine hydrochloride in diglyme. Several compounds exhibited strong inhibitory effects against Streptococcus faecalis (MGH-2), Staphylococcus aureus (UC-76), Streptococcus faecium (ATCC 8043), Lactobacillus casei (ATCC 7469), and Pediococcus cerevisiae (ATCC 8081) in vitro, and three compounds displayed antimalarial activity against Plasmodium berghei in mice and P. falciparum (Uganda I) in vitro.     

Electron-stimulated production of molecular hydrogen at the interfaces of amorphous solid water films on Pt(111)

The electron-stimulated production of molecular hydrogen (D(2), HD, and H(2)) from amorphous solid water (ASW) deposited on Pt(111) is investigated. Experiments with isotopically layered films of H(2)O and D(2)O are used to profile the spatial distribution of the electron-stimulated reactions leading to hydrogen within the water films. The molecular hydrogen yield has two components that have distinct reaction kinetics due to reactions that occur at the ASW/Pt interface and the ASW/vacuum interface, but not in the bulk. However, the molecular hydrogen yield as a function of the ASW film thickness in both pure and isotopically layered films indicates that the energy for the reactions is absorbed in the bulk of the films and electronic excitations migrate to the interfaces where they drive the reactions.     

A QM/MM study on the reaction pathway leading to 2‐Aceto‐2‐hydroxybutyrate in the catalytic cycle of AHAS

The reaction between the intermediate 2‐hydroxyethyl‐thiamin diphosphate (HEThDP^?) and 2‐ketobutyrate, in the third step of the catalytic cycle of acetodydroxy acid synthase, is addressed from a theoretical point of view by means of hybrid quantum/molecular mechanical calculations. The QM region includes one molecule of 2‐ketobutyrate, the HEThDP^? intermediate, and the residues Arg 380 y Glu 139; whereas the MM region includes the rest of the protein. The study includes potential energy surface scans to identify and characterize critical points on it, transition state search and activation barrier calculations. The results show that the reaction occurs via a two‐step mechanism corresponding to the carboligation and proton transfer in the first stage; and the product release in the second step. © 2014 Wiley Periodicals, Inc.     

Far-Red Dibenzo[a,j]Perylene-8,16-Dione Dyes as Fluorescent Enzyme Substrates and Tags for Biomolecules

The synthesis of fluorescent 2,10-derivatives of the title chromophore are described. The substituents contain amino-reactive N-hydroxysuccinimde ester and thiol-reactive iodoacetamide groups for attachment to biomolecules. A phosphate derivative was also prepared as an enzyme substrate.     

Visual Speech Recognition with Lightweight Psychologically Motivated Gabor Features

Extraction of relevant lip features is of continuing interest in the visual speech domain. Using end-to-end feature extraction can produce good results, but at the cost of the results being difficult for humans to comprehend and relate to. We present a new, lightweight feature extraction approach, motivated by human-centric glimpse-based psychological research into facial barcodes, and demonstrate that these simple, easy to extract 3D geometric features (produced using Gabor-based image patches), can successfully be used for speech recognition with LSTM-based machine learning. This approach can successfully extract low dimensionality lip parameters with a minimum of processing. One key difference between using these Gabor-based features and using other features such as traditional DCT, or the current fashion for CNN features is that these are human-centric features that can be visualised and analysed by humans. This means that it is easier to explain and visualise the results. They can also be used for reliable speech recognition, as demonstrated using the Grid corpus. Results for overlapping speakers using our lightweight system gave a recognition rate of over 82%, which compares well to less explainable features in the literature.     

THE CHEMISTRY OF HETEROARYLPHOSPHORUS COMPOUNDS. PART XII.1 THE DIFFERENTIAL-PULSE POLAROGRAPHIC REDUCTION OF HETEROARYL-AND HETEROARYLMETHYLPHOSPHONIUM SALTS

Abstract

The polarographic reduction of series of heteroaryl- and heteroarylmethylphosphonium salts has been studied using a differential pulse polarographic technique, this having a number of advantages over classical dc polarography. For the salts Ar₃P⁺CH₂PhBr^-, the observed order of ease of reduction correlates with the electron-withdrawing ability of the heteroaryl group (i.e. Ar = 2-furyl > 2-thienyl > phenyl > 1-methylpyrrol-2-yl). In contrast, for the salts Ph₃P⁺CH₂ArBr^- (Ar = 2-furyl, 2-thienyl, phenyl, 1-methylpyrrol-2-yl, 3-thienyl and 3-furyl), the ease of reduction correlates best with the order of stability of the forming carbanions as established in earlier studies of the alkaline hydrolysis of these salts.     

Theoretical studies of smectic C liquid crystals confined in a wedge. Stability considerations and Frederiks transitions

Abstract

A general deformation of a smectic C liquid crystal is composed of five different distortions, each of which can be made independently. Here we show that to each of these distortions we can assign a simple vector operator. Use of these five basis operators enables us to write down the elastic free energy density as a quadratic form consisting of nine terms. We also discuss how the nine elastic constants defined by the elastic energy expansion must fulfil certain restrictions in terms of inequalities and a specific tilt angle dependence. Assuming the smectic layers to be incompressible, we examine how certain arrangements of the smectic layers can be stable due to an interplay between the incompressibility condition and the boundary conditions which we impose on the director. One such stable configuration is the wedge, where the smectic layers form parts of concentric cylinders with the common axis coinciding with the centre of the wedge. For such a system we discuss the different director configurations which can be achieved and their stability. We also discuss the possibility of inducing Frederiks transitions for some of these configurations and calculate the corresponding thresholds, thereby demonstrating the design of an experiment which would make it possible to measure those elastic constants which are related to the deformations of the smectic layers, constants which are normally difficult to determine experimentally.