scholarly journals Synthesis and anti-HBV activity of carbocyclic nucleoside hybrids with salient features of entecavir and aristeromycin

2020 ◽  
Vol 11 (5) ◽  
pp. 597-601
Author(s):  
Ramakrishnamraju Samunuri ◽  
Masaaki Toyama ◽  
Renuka Sivasankar Pallaka ◽  
Seshubabu Neeladri ◽  
Ashok Kumar Jha ◽  
...  
Keyword(s):  
Lead Candidate ◽  
Salient Features ◽  
Carbocyclic Nucleoside

A new carbocyclic nucleoside with the salient features of entecavir and aristeromycin identified as the anti-HBV lead candidate.

Metastable Defects in the Amorphous Silicon-Germanium Alloys

2003 ◽  
Vol 762 ◽  
Author(s):  
J. David Cohen
Keyword(s):  
Amorphous Silicon ◽  
Silicon Germanium ◽  
Dangling Bonds ◽  
Annealing Behavior ◽  
Fundamental Properties ◽  
Silicon Materials ◽  
Salient Features ◽  
The Individual ◽  
Amorphous Silicon Germanium ◽  
Silicon Germanium Alloys

AbstractThis paper first briefly reviews a few of the early studies that established some of the salient features of light-induced degradation in a-Si,Ge:H. In particular, I discuss the fact that both Si and Ge metastable dangling bonds are involved. I then review some of the recent studies carried out by members of my laboratory concerning the details of degradation in the low Ge fraction alloys utilizing the modulated photocurrent method to monitor the individual changes in the Si and Ge deep defects. By relating the metastable creation and annealing behavior of these two types of defects, new insights into the fundamental properties of metastable defects have been obtained for amorphous silicon materials in general. I will conclude with a brief discussion of the microscopic mechanisms that may be responsible.

scholarly journals 1592U89, a novel carbocyclic nucleoside analog with potent, selective anti-human immunodeficiency virus activity.

1997 ◽  
Vol 41 (5) ◽  
pp. 1082-1093 ◽  
Author(s):  
S M Daluge ◽  
S S Good ◽  
M B Faletto ◽  
W H Miller ◽  
M H St Clair ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Oral Bioavailability ◽  
Human Peripheral Blood ◽  
Cross Resistance ◽  
Immunodeficiency Virus ◽  
Carbocyclic Nucleoside ◽  
Hiv 1 ◽  
In Cells

1592U89, (-)-(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclo pentene-1-methanol, is a carbocyclic nucleoside with a unique biological profile giving potent, selective anti-human immunodeficiency virus (HIV) activity. 1592U89 was selected after evaluation of a wide variety of analogs containing a cyclopentene substitution for the 2'-deoxyriboside of natural deoxynucleosides, optimizing in vitro anti-HIV potency, oral bioavailability, and central nervous system (CNS) penetration. 1592U89 was equivalent in potency to 3'-azido-3'-deoxythymidine (AZT) in human peripheral blood lymphocyte (PBL) cultures against clinical isolates of HIV type 1 (HIV-1) from antiretroviral drug-naive patients (average 50% inhibitory concentration [IC50], 0.26 microM for 1592U89 and 0.23 microM for AZT). 1592U89 showed minimal cross-resistance (approximately twofold) with AZT and other approved HIV reverse transcriptase (RT) inhibitors. 1592U89 was synergistic in combination with AZT, the nonnucleoside RT inhibitor nevirapine, and the protease inhibitor 141W94 in MT4 cells against HIV-1 (IIIB). 1592U89 was anabolized intracellularly to its 5'-monophosphate in CD4+ CEM cells and in PBLs, but the di- and triphosphates of 1592U89 were not detected. The only triphosphate found in cells incubated with 1592U89 was that of the guanine analog (-)-carbovir (CBV). However, the in vivo pharmacokinetic, distribution, and toxicological profiles of 1592U89 were distinct from and improved over those of CBV, probably because CBV itself was not appreciably formed from 1592U89 in cells or animals (<2%). The 5'-triphosphate of CBV was a potent, selective inhibitor of HIV-1 RT, with Ki values for DNA polymerases (alpha, beta, gamma, and epsilon which were 90-, 2,900-, 1,200-, and 1,900-fold greater, respectively, than for RT (Ki, 21 nM). 1592U89 was relatively nontoxic to human bone marrow progenitors erythroid burst-forming unit and granulocyte-macrophage CFU (IC50s, 110 microM) and human leukemic and liver tumor cell lines. 1592U89 had excellent oral bioavailability (105% in the rat) and penetrated the CNS (rat brain and monkey cerebrospinal fluid) as well as AZT. Having demonstrated an excellent preclinical profile, 1592U89 has progressed to clinical evaluation in HIV-infected patients.

scholarly journals Super-Cationic Peptide Dendrimers—Synthesis and Evaluation as Antimicrobial Agents

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 695
Author(s):  
Estelle J. Ramchuran ◽  
Isabel Pérez-Guillén ◽  
Linda A. Bester ◽  
René Khan ◽  
Fernando Albericio ◽  
...  
Keyword(s):  
Antibacterial Agent ◽  
Antimicrobial Agents ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Cationic Peptide ◽  
Public Health Concern ◽  
Gram Negative ◽  
Peptide Dendrimers ◽  
Microbial Infections ◽  
Lead Candidate

Microbial infections are a major public health concern. Antimicrobial peptides (AMPs) have been demonstrated to be a plausible alternative to the current arsenal of drugs that has become inefficient due to multidrug resistance. Herein we describe a new AMP family, namely the super-cationic peptide dendrimers (SCPDs). Although all members of the series exert some antibacterial activity, we propose that special attention should be given to (KLK)2KLLKLL-NH2 (G1KLK-L2KL2), which shows selectivity for Gram-negative bacteria and virtually no cytotoxicity in HepG2 and HEK293. These results reinforce the validity of the SCPD family as a valuable class of AMP and support G1KLK-L2KL2 as a strong lead candidate for the future development of an antibacterial agent against Gram-negative bacteria.

scholarly journals The Conversion Gradient at HIS4 of Saccharomyces cerevisiae. II. A Role for Mismatch Repair Directed by Biased Resolution of the Recombinational Intermediate

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 573-583 ◽  
Author(s):  
Henriette M Foss ◽  
Kenneth J Hillers ◽  
Franklin W Stahl
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Synthesis ◽  
Mismatch Repair ◽  
Strand Break ◽  
Double Strand Break ◽  
Double Strand Break Repair ◽  
Holliday Junction ◽  
Crossing Over ◽  
Gradient Type ◽  
Salient Features

AbstractSalient features of recombination at ARG4 of Saccharomyces provoke a variation of the double-strand-break repair (DSBR) model that has the following features: (1) Holliday junction cutting is biased in favor of strands upon which DNA synthesis occurred during formation of the joint molecule (this bias ensures that cutting both junctions of the joint-molecule intermediate arising during DSBR usually leads to crossing over); (2) cutting only one junction gives noncrossovers; and (3) repair of mismatches that are semirefractory to mismatch repair and/or far from the DSB site is directed primarily by junction resolution. The bias in junction resolution favors restoration of 4:4 segregation when such mismatches and the directing junction are on the same side of the DSB site. Studies at HIS4 confirmed the predicted influence of the bias in junction resolution on the conversion gradient, type of mismatch repair, and frequency of aberrant 5:3 segregation, as well as the predicted relationship between mismatch repair and crossing over.

Divergent Chiron Approach for the First Total Synthesis of (+)-Pseudonocardide A, (+)-Pseudonocardide C and an epimer of ent-Pseudonocardide D

2021 ◽  
Author(s):  
Kapil Sharma ◽  
Naresh Surineni ◽  
Sayani Das ◽  
Shivajirao L. Gholap
Keyword(s):  
Total Synthesis ◽  
Salient Features

A concise and divergent chiron approach for the first total synthesis of (+)-Pseudonocardide A, (+)-Pseudonocardide C and an epimer of ent-Pseudonocardide D is reported starting from D-ribose. The salient features...

scholarly journals Hohe Myopie und Innenschielen: ein Update zum Heavy-Eye-Syndrom

2020 ◽  
Vol 6 (4) ◽  
pp. 178-179
Author(s):  
Santa Heede ◽  
Stephan Johannes Linke
Keyword(s):  
Differential Diagnosis ◽  
Current Literature ◽  
Surgical Techniques ◽  
Rectus Muscle ◽  
Pulley System ◽  
Important Type ◽  
Hohe Myopie ◽  
Salient Features

Heavy eye syndrome is an important type of myopia-induced strabismus. We provide an overview of heavy eye syndrome, from its history to its most salient features. The theory of the orbital and rectus muscle pulley system as it relates to heavy eye syndrome and the prevailing theories on the pathophysiology of heavy eye syndrome in the current literature are discussed. We also highlight the presentation of heavy eye syndrome, its typical features on imaging, and differential diagnosis. Finally, we provide an overview on the management of heavy eye syndrome, including a description of several current surgical techniques.

scholarly journals The Ethics of Touch and the Importance of Nonhuman Relationships in Animal Agriculture

2021 ◽  
Vol 34 (2) ◽  
Author(s):  
Steve Cooke
Keyword(s):  
Stress Reduction ◽  
Animal Ethics ◽  
Physiological Responses ◽  
Animal Agriculture ◽  
Nonhuman Animals ◽  
Social Animals ◽  
Reduction Methods ◽  
Salient Features

AbstractAnimal agriculture predominantly involves farming social animals. At the same time, the nature of agriculture requires severely disrupting, eliminating, and controlling the relationships that matter to those animals, resulting in harm and unhappiness for them. These disruptions harm animals, both physically and psychologically. Stressed animals are also bad for farmers because stressed animals are less safe to handle, produce less, get sick more, and produce poorer quality meat. As a result, considerable efforts have gone into developing stress-reduction methods. Many of these attempt to replicate behaviours or physiological responses that develop or constitute bonding between animals. In other words, humans try to mitigate or ameliorate the damage done by preventing and undermining intraspecies relationships. In doing so, the wrong of relational harms is compounded by an instrumentalisation of trust and care. The techniques used are emblematic of the welfarist approach to animal ethics. Using the example of gentle touching in the farming of cows for beef and dairy, the paper highlights two types of wrong. First, a wrong done in the form of relational harms, and second, a wrong done by instrumentalising relationships of care and trust. Relational harms are done to nonhuman animals, whilst instrumentalisation of care and trust indicates an insensitivity to morally salient features of the situation and a potential character flaw in the agents that carry it out.

The Utah paradigm of skeletal physiology: what is it?

2001 ◽  
Vol 14 (04) ◽  
pp. 179-184 ◽  
Author(s):  
H. M. Frost
Keyword(s):  
Muscle Strength ◽  
Mechanical Strain ◽  
Postnatal Growth ◽  
Tissue Level ◽  
Second Step ◽  
Load Bearing ◽  
Salient Features ◽  
Utah Paradigm ◽  
Strain Dependent

SummaryAn elegant design stratagem for an organ intended to carry loads for life without fracturing, rupturing or wearing out would make those loads determine the organ's strength. It seems load-bearing mammalian bones, joints, fascia, ligaments and tendons do exactly that. Physiologists begin to understand how they do it, and that led to the Utah paradigm of skeletal physiology. Those adaptations occur in two major steps. The first step creates the genetically predetermined newborn skeleton with its anatomical relationships and biologic machinery. The second step adds to the first one all postnatal adaptations to mechanical and other challenges that would affect an organ's strength, size, architecture and composition. During postnatal growth, increasing loads make tissue-level biologic mechanisms correspondingly increase the strength of such organs. Mechanical strain-dependent signals help to control that process, which muscle strength, muscle anatomy and neuromuscular physiology strongly influence. Its problems seem to cause or help to cause numerous skeletal and some extraskeletal disorders. A Table in the article lists examples of them.This article summarizes salient features of the Utah paradigm, which includes both facts and some meanings inferred from them. Other times and people must resolve any questions about those meanings and about the devils that can lie in the details. Parenthetically, instead of the accuracy of the facts on which that paradigm stands, the above questions usually concern the different meanings people can infer from facts, and whether particular facts and ideas would be relevant to a particular issue.

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