ICT Usage for Learning in Tottori prefecture - The Proposal and Vision by ICT Usage in Schools Promotion group -

departmental bulletin pape

Observation of the DsJ(2317) and DsJ(2457) in B Decays

journal articl

SUPERPARACOMPACT TYPE PROPERTIES

application/pdfIn this paper we continue the study of superparacompact and weakly superparacompact spaces. Several new characterizations of superparacompact spaces are given. We also define two new covering properties which we show to be different from the above properties. The question of invariance and inverse invariance under various maps of these four covering properties is analysed. Finally we give a Tamano type theorem with respect to CO-normality.departmental bulletin pape

Rearrangements Encountered in the Attempted Syntheses of Pyridoazepinone Carboxylic Acids

Attempts to synthesize pyridoazepinone carboxylic acids such as 33 by standard methodologies resulted exclusively in unusual and unexpected rearrangement products. Seven-membered ring formation was attempted by ring expansion of a six-membered ring and by aldol ring closure. In each case, the major product resulted from rearrangement of the starting material without detection of the desired product. Ultimately, an isomeric pyridoazepinone ethyl ester was prepared; however, attempted saponification resulted in another unusual rearrangement

Effect of 6S RNA on the transcription from σ and σ-specific promoters on linear DNA fragments

<p><b>Copyright information:</b></p><p>Taken from "Studies on the function of the riboregulator 6S RNA from : RNA polymerase binding, inhibition of transcription and synthesis of RNA-directed transcripts"</p><p></p><p>Nucleic Acids Research 2007;35(6):1885-1896.</p><p>Published online 1 Mar 2007</p><p>PMCID:PMC1874619.</p><p>© 2007 The Author(s)</p> Products from transcription reactions were separated on denaturing polyacrylamide gels and visualized by autoradiography. Reactions with the or P1 promoters are shown on the left or right side, respectively. The different holoenzymes employed (E70, E38) are indicated above the lanes. For each system the amount of 6S RNA present in the reaction was varied (lanes 1, 6, 11, 16: 0 nM, lane 2, 7, 12, 17: 10 nM, lane 3, 8, 13, 18: 50 nM, lane 4, 9, 14, 19: 100 nM, lane 5, 10, 15, 20: 250 nM). A 260 bp radiolabelled DNA fragment, indicated at the margin, was included as internal standard for quantification. The positions of the run-off transcripts for the (∼124 nt) and P1 (64 nt) promoters are marked. An arrow denotes a product that consistently arises when 6S RNA is incubated with RNA polymerase, even in the absence of any template DNA

片麻痺患者における下肢装具と下肢筋力の関係 : 脚伸展トルクを指標とした検討

journal articl

Novel Antibacterial Class: A Series of Tetracyclic Derivatives

We describe the synthesis and antibacterial activity of a series of tetracyclic naphthyridones. The members of this series act primarily via inhibition of bacterial translation and belong to the class of novel ribosome inhibitors (NRIs). In this paper we explore the structure−activity relationships (SAR) of these compounds to measure their ability both to inhibit bacterial translation and also to inhibit the growth of bacterial cells in culture. The most active of these compounds inhibit Streptococcus pneumoniae translation at concentrations of <5 μM and have minimum inhibitory concentrations (MICs) of <8 μg/mL against clinically relevant strains of bacteria

Discovery of Potent Inhibitors of Dihydroneopterin Aldolase Using CrystaLEAD High-Throughput X-ray Crystallographic Screening and Structure-Directed Lead Optimization

Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) have been discovered using CrystaLEAD X-ray crystallographic high-throughput screening followed by structure-directed optimization. Screening of a 10 000 compound random library provided several low affinity leads and their corresponding X-ray crystal structures bound to the enzyme. The presence of a common structural feature in each of the leads suggested a strategy for the construction of a directed library of approximately 1000 compounds that were screened for inhibitory activity in a traditional enzyme assay. Several lead compounds with IC50 values of about 1 μM against DHNA were identified, and crystal structures of their enzyme-bound complexes were obtained by cocrystallization. Structure-directed optimization of one of the leads thus identified afforded potent inhibitors with submicromolar IC50 values

Inhibitors of Hepatitis C Virus Polymerase: Synthesis and Biological Characterization of Unsymmetrical Dialkyl-Hydroxynaphthalenoyl-benzothiadiazines

The hepatitis C virus (HCV) NS5B polymerase is essential for viral replication and has been a prime target for drug discovery research. Our efforts directed toward the discovery of HCV polymerase inhibitors resulted in the identification of unsymmetrical dialkyl-hydroxynaphthalenoyl-benzothiadiazines 2 and 3. The most active compound displayed activity in genotypes 1a and 1b polymerase and replicon cell culture inhibition assays at subnanomolar and low nanomolar concentrations, respectively. It also displayed an excellent pharmacokinetic profile in rats, with a plasma elimination half-life after intravenous dosing of 4.5 h, oral bioavailability of 77%, and a peak liver concentration of 21.8 μg/mL

Highlights of the Structure–Activity Relationships of Benzimidazole Linked Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor Pibrentasvir (ABT-530)

Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component of these treatments is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the component NS5A inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1–6. In particular, these first generation NS5A inhibitors tend to select for viral drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as a key component of Viekira Pak for the treatment of patients with HCV genotype 1 infection. Since the launch of next generation HCV treatments, functional cure for genotype 1–6 HCV infections has been achieved, as well as shortened treatment duration across a wider spectrum of genotypes. In this paper, we show how we have modified the anchor, linker, and end-cap architecture of our NS5A inhibitor design template to discover a next generation NS5A inhibitor pibrentasvir (ABT-530), which exhibits potent inhibition of the replication of wild-type genotype 1–6 HCV replicons, as well as improved activity against replicon variants demonstrating resistance against first generation NS5A inhibitors