gebhart/patrepeval huggingface dataset:
Serine and Threonine β-Lactones:  A New Class of Hepatitis A Virus 3C Cysteine Proteinase Inhibitors (2002)

Hepatitis A virus (HAV) 3C enzyme is a cysteine proteinase essential for viral replication and infectivity and represents a target for the development of antiviral drugs. A number of serine and threonine beta-lactones were synthesized and tested against HAV 3C proteinase. The D-N-Cbz-serine beta-lactone 5a displays competitive reversible inhibition with a K(i) value of 1.50 x 10(-6) M. Its enantiomer, L-N-Cbz-serine beta-lactone 5b is an irreversible inactivator with k(inact) = 0.70 min(-1), K(Iota) = 1.84 x 10(-4) M and k(inact)/K(Iota) = 3800 M(-1) min(-1). Mass spectrometry and HMQC NMR studies using (13)C-labeled 5b show that inactivation of the enzyme occurs by nucleophilic attack of the cysteine thiol (Cys-172) at the beta-position of the oxetanone ring. Although the N-Cbz-serine beta-lactones 5a and 5b display potent inhibition, other related analogues with an N-Cbz side chain, such as the five-membered ring homoserine gamma-lactones 14a and 14b, the four-membered ring beta-lactam 33, 2-methylene oxetane 34, cyclobutanone 36, and 3-azetidinone 39, fail to give significant inhibition of HAV 3C proteinase, thus demonstrating the importance of the beta-lactone ring for binding.
The sensitivity of halobacteria to antibiotics (1984)

Eleven species of the genera Halobacterium, Halococcus and the recently proposed Haloarcula were tested by the macro-broth dilution method for their sensitivity to 20 antibiotics with different modes of action. The most active were bacitracin, erythromycin, haloquinone, rifampicin and novobiocin. Resistant mutants of H. mediterranei to bacitracin, chloramphenicol and josamycin were obtained with frequencies of spontaneous mutation between 10−4 and 10−7.
A Chinese hamster cDNA encoding a protein essential for phosphatidylserine synthase I activity. (1991)

A phosphatidylserine-auxotrophic mutant of cultured Chinese hamster ovary (CHO) cells, PSA-3, is defective in phosphatidylserine synthase I activity. Transfection of PSA-3 cells with a cDNA expression library of CHO-K1 (the parent of PSA-3) yielded a phosphatidylserine-prototrophic transformant with normal phosphatidylserine synthase I activity. Using a cDNA segment retrieved from the transformant as a probe, a cDNA clone (pssA) responsible for phosphatidylserine prototrophy was isolated from the original cDNA library by colony filter hybridization. Introduction of the pssA cDNA into PSA-3 cells restored the phosphatidylserine content, and the resultant transformant exhibited 15-fold higher specific phosphatidylserine synthase I activity than CHO-K1 cells. The nucleotide sequence of the pssA cDNA contained a single long open reading frame capable of encoding a protein of 471 amino acid residues with several putative membrane-spanning domains. Our results indicated that the pssA cDNA encodes an integral membrane protein essential for phosphatidylserine synthase I activity.
Cyclic voltammetric oxidation of tetra-tert-butyltetrahedrane (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic voltammetric oxidation of tetra-tert-butyltetrahedraneMarye Anne Fox, Kay A. Campbell, Siegfried Huenig, Horst Berneth, Gunther Maier, Klaus Albert Schneider, and Klaus Dieter MalschCite this: J. Org. Chem. 1982, 47, 18, 3408–3412Publication Date (Print):August 1, 1982Publication History Published online1 May 2002Published inissue 1 August 1982https://doi.org/10.1021/jo00139a005RIGHTS & PERMISSIONSArticle Views93Altmetric-Citations24LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Transformation of encapsulated Streptococcus pneumoniae (1986)

We describe the high-efficiency transformation of several virulent, encapsulated isolates of Streptococcus pneumoniae. Transformation was effected by the induction of competence with competence factor and was apparently the result both of inducing noncompetent recipients and overcoming the inhibition imposed by the capsule.
The Maize Regulatory Gene B-Peru Contains a DNA Rearrangement That Specifies Tissue-Specific Expression Through Both Positive and Negative Promoter Elements (1998)

The B-Peru allele of the maize b regulatory gene is unusual relative to most b alleles in that it is expressed in the aleurone layer of the seed. It is also expressed in a subset of plant vegetative tissues. Transgenic maize plants containing the B-Peru gene with the first 710 bases of upstream sequence conferred the same levels of aleurone expression as nontransgenic B-Peru plants, but no pigment was made in vegetative tissues. Transient transformation assays in aleurone tissue localized the aleurone-specific promoter to the first 176 bases of the B-Peru upstream region and identified two critically important regions within this fragment. Mutation of either region alone reduced expression greater than fivefold. Surprisingly, the double mutation actually increased expression to twice the native promoter level. Our results suggest that these two critical sequences, which lie close together in the promoter, may form a negative regulatory element. Several lines of evidence suggest that the B-Peru promoter arose through the translocation of an existing aleurone-specific promoter to the b locus. Immediately upstream of the aleurone-specific promoter elements and in the opposite orientation to the b coding sequence is a pseudogene sequence with strong similarity to a known class of proteins. Our findings that novel aleurone-specific promoter sequences of the B-Peru transcription factor are found adjacent to part of another gene in a small insertion are quite unexpected and have interesting evolutionary implications.
Lumbar Modic Changes—A Comparison Between Findings at Low- and High-Field Magnetic Resonance Imaging (2012)

There was a significant difference between low- and high-field MRI regarding the overall prevalence of any Modic change, but this had opposite directions for types 1 and 2: type 2 dominated in high field and conversely in high field [corrected]. The type of MRI unit should be taken into consideration when diagnosing patients with Modic changes
Chronic oral nicotine treatment protects against striatal degeneration in MPTP‐treated primates (2006)

The present studies were done to investigate the effect of long-term nicotine treatment against nigrostriatal damage in non-human primates. Monkeys were administered nicotine in drinking water for 6 months to provide chronic but intermittent delivery as with smoking. Plasma nicotine levels ranged from 10 to 15 ng/mL, which were within the range in cigarette smokers. Animals were then lesioned with low doses of the dopaminergic neurotoxin MPTP for several months while nicotine was continued. The results showed that levels of striatal tyrosine hydroxylase, dopamine transporter, vesicular monoamine transporter, dopamine and nicotinic receptors were greater in nicotine-treated MPTP-lesioned primates than in lesioned animals not receiving nicotine. Nicotine had no effect in unlesioned animals. Monoamine oxidase activity was similar in unlesioned and lesioned animals treated with or without nicotine, suggesting that nicotine did not exert its effects through changes in MPTP or dopamine metabolism. MPTP-induced cell loss in the substantia nigra was unaffected by nicotine treatment, indicating that nicotine acts at the striatal level to restore/maintain dopaminergic function. These data further support the possibility that nicotine contributes to the lower incidence of Parkinson's disease in smokers.
C-reactive protein in patients with COPD, control smokers and non-smokers (2005)

CRP levels are raised in COPD patients without clinically relevant IHD and independent of cigarette smoking, and reduced in patients with COPD using ICS. CRP may be a systemic marker of the inflammatory process that occurs in patients with COPD.
Using the Dallas Pain Questionnaire to Classify Individuals With Low Back Pain in a Working Population (2002)

The Dallas Pain Questionnaire discriminated between different groups of persons with low back pain. The proposed classification uses a short, simple practical tool to assess different levels of low back pain.
Prokaryotic genome regulation: multifactor promoters, multitarget regulators and hierarchic networks (2010)

The vast majority of experimental data have been accumulated on the transcription regulation of individual genes within a single model prokaryote, Escherichia coli, which form the well-established on-off switch model of transcription by DNA-binding regulatory proteins. After the development of modern high-throughput experimental systems such as microarray analysis of whole genome transcription and the Genomic SELEX search for the whole set of regulation targets by transcription factors, a number of E. coli promoters are now recognized to be under the control of multiple transcription factors, as in the case of eukaryotes. The number of regulation targets of a single transcription factor has also been found to be more than hitherto recognized, ranging up to hundreds of promoters, genes or operons for several global regulators. The multifactor promoters and the multitarget transcription factors can be assembled into complex networks of transcription regulation, forming hierarchical networks.
Novel glutamatergic drugs for the treatment of mood disorders (2013)

Mood disorders are common and debilitating, resulting in a significant public health burden. Current treatments are only partly effective and patients who have failed to respond to trials of existing antidepressant agents (eg, those who suffer from treatment-resistant depression [TRD]) require innovative therapeutics with novel mechanisms of action. Although neuroscience research has elucidated important aspects of the basic mechanisms of antidepressant action, most antidepressant drugs target monoaminergic mechanisms identified decades ago. Glutamate, the major excitatory neurotransmitter in the central nervous system, and glutamatergic dysfunction has been implicated in mood disorders. These data provide a rationale for the pursuit of glutamatergic agents as novel therapeutic agents. Here, we review preclinical and clinical investigations of glutamatergic agents in mood disorders with a focus on depression. We begin with discussion of evidence for the rapid antidepressant effects of ketamine, followed by studies of the antidepressant efficacy of the currently marketed drugs riluzole and lamotrigine. Promising novel agents currently in development, including N-methyl-D-aspartate (NMDA) receptor modulators, 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) receptor modulators, and drugs with activity at the metabotropic glutamate (mGlu) receptors are then reviewed. Taken together, both preclinical and clinical evidence exists to support the pursuit of small molecule modulators of the glutamate system as novel therapeutic agents in mood disorders. It is hoped that by targeting neural systems outside of the monoamine system, more effective and perhaps faster acting therapeutics can be developed for patients suffering from these disabling disorders.
Membrane folate-binding proteins are responsible for folate-protein conjugate endocytosis into cultured cells (1993)

Folate-protein conjugates have been shown to bind to and enter HeLa and KB cells by receptor-mediated endocytosis [Leamon and Low (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 5572-5576]. Although these cells contain a membrane folate-binding protein (FBP) involved in the uptake of free folate, no studies have been conducted to evaluate whether the folate-protein conjugates enter cells via the same protein. To address this issue, HeLa cell monolayers were treated with folate-labelled 125I-RNAase under various conditions characteristic of FBP-mediated folate uptake. Folate-labelled 125I-RNAase was found to bind to cells with high affinity (Kd = 24 nM), and like the free vitamin, its binding could be competitively blocked by excess free folate. Furthermore, binding could be reversed by either washing the cells with acid/saline, pH 3.0, or by treating the cells with phosphatidyl-inositol-specific phospholipase C, an enzyme known to release FBP from cell surfaces. Because cells pretreated with anti-FBP serum were unable to bind folate conjugates, and since the same antiserum identified a single 65 kDa band reminiscent of FBPs found in many other tissues, we conclude that a classical FBP is responsible for the uptake of folate-protein conjugates by receptor-bearing cells.
Isolation of a Marek's disease virus (MDV) recombinant containing the lacZ gene of Escherichia coli stably inserted within the MDV US2 gene (1991)

We have isolated a stable, recombinant Marek's disease virus (MDV) containing the lacZ gene of Escherichia coli inserted into the unique short region of the genome. The nucleotide sequence of the insertion site indicates that it lies within a sequence homologous to the US2 gene of herpes simplex virus. Stable insertion of the lacZ gene into the MDV US2 gene indicates that the site is nonessential for MDV growth in cell culture.
Targeting the phosphatidylinositol 3-kinase/Akt pathway for enhancing breast cancer cells to radiotherapy. (2003)

The phosphatidylinositol 3-kinase (PI-3K)/Akt pathway, regulated by its upstream growth factor receptor tyrosine kinases, plays a critical role in promoting cell proliferation and inhibiting cell death. The aim of this study was to determine whether the PI-3K/Akt activity contributes to the resistance of human breast cancer cells to ionizing radiation and whether inhibition of the PI-3K/Akt pathway could sensitize human breast cancer cells to radiotherapy. To determine a causal relationship between the activity of Akt and radioresistance in human breast cancer cells, MCF7 cells, transfected with constitutively active H-Ras (RadG12V) or constitutively active Akt, were chosen for analysis of the cell clonogenic survival fraction and induction of apoptosis after ionizing radiation. The PI-3K-specific inhibitor LY294002 was used to examine whether inhibition of PI-3K could sensitize these cells to radiation treatment. Our results indicate that the expression of constitutively active Ras (which activated Akt in a PI-3K-dependent manner) and the expression of constitutively active Akt (which caused a PI-3K-independent activation of Akt) each increased cellular resistance to radiation. Inhibition of PI-3K with LY294002 reverted the constitutively active Ras-mediated radioresistance but not the constitutively active Akt-mediated radioresistance. Our data suggest that Akt may be a potential target for enhancing the response to radiotherapy in patients with breast cancer.
Prevention of atrial fibrillation by inter-atrial septum pacing guided by electrophysiological testing, in patients with delayed interatrial conduction (2002)

Atrial septal pacing in combination with antiarrhythmic drug therapy reduced the incidence of PAF in pts with prolonged inter-atrial conduction times. Pace mapping of the IAS is an attractive technique to assess the shortest atrial activation time between HRA and distal CS. Whether placement of the atrial lead based on the shortest HRA--distal CS time is the best place in the IAS to prevent PAF still remains to be proven.
Crystallinity and the effect of ionizing radiation in polyethylene. I. Crosslinking and the crystal core (1975)

Abstract An extensive study has been carried out on the effect of ionizing radiation on polyethylene in the form of solution‐grown single crystals to follow up preceding investigations which had indicated that the radiation‐induced effects along the fold surfaces could be significantly different from those within the crystal interior. In this first part of the series, radiation‐induced crosslinking was investigated in the case of “crystal core” material. This material, obtained by removal of the fold surface by oxidative degradation with ozone, consists of isolated foldfree crystal layers of dicarboxylic acids of uniform length, the length itself depending on the fold length of the starting crystal. This “core material” was irradiated by γ rays and the effect of crosslinking was followed by GPC analysis by recording the development of dimer, trimer, etc., peaks in the chromatograms. For a given dose, the fractional amount of crosslinked material is independent of the chain length. This, together with other effects described, provides unambiguous evidence that crosslinking occurs at the chain ends or, in other words, that there is no crosslinking within the interior of the paraffinoid lattice. Further, no permanent scission was observed to occur within the lattice, at least in amounts detectable by the present molecular weight measurements. The obvious significance of these effects for radiation studies on paraffinoid substances in general, beyond those of the present long‐chain dicarboxylic acids, is discussed prior to utilizing them in the study of chain‐folded polyethylene crystals in the following parts of the series.
Nucleotide sequence of an infectious molecularly cloned genome of ground squirrel hepatitis virus (1984)

We have determined the complete nucleotide sequence of an infectious cloned genome of ground squirrel hepatitis virus (GSHV), a nonpathogenic member of the hepadnavirus group. The genome is 3,311 base pairs long and contains the major open reading frames described for the related human and woodchuck hepatitis B viruses (HBV and WHV, respectively). These reading frames include genes for the major structural proteins (the surface and core antigens), unassigned open reading frames (A and B), the longer of which is presumed to encode the viral DNA polymerase, and an open reading frame preceding and continuous with the surface antigen gene. The arrangement of these open reading frames is similar to that encountered in the genomes of HBV and WHV: all of the reading frames are encoded on the same strand, they are positioned in the same fashion with respect to each other, and a large portion (at least 51%) of the genome can be translated in two reading frames. Comparisons of the predicted translational products of the three mammalian hepadnaviruses reveal 78% amino acid homology between the proteins of GSHV and WHV and 43% homology between those of GSHV and HBV. In addition, a perfect direct repeat of 10 to 11 base pairs, separated by ca. 46 to 223 base pairs, is present in the three mammalian viruses and in duck hepatitis B virus; the position of the repeats near the 5' termini of the two strands of virion DNA suggests a role in viral replication.
αvβ3 Itegrin pathway controls glioma radioresistance through ILK. (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5180 

We have previously demonstrated that factors involved in adhesion signalling pathways control radioresistance of human glioma cell lines. The aim of this study was to dissect out the involvement of the biological pathways controlling adhesion and invasion, in the radioresistance mechanisms of glioblastoma cells. We first demonstrated that plating two radiosensitive glioblastoma cell lines (U251 and SF767 cells) on fibronectin and vitronectin induced a significant increase of cell survival after irradiation of these cells due to an inhibition of the radiation-induced mitotic cell death. In the same extend, inhibiting αvβ3 and αvβ5 integrin- which are mainly expressed in these glioma cell lines- with specific inhibitors radiosensitizes radioresistant U87 and SF763 cells. We next explored which integrins are involved in this adhesion-dependant radioresistance pathways by silencing β3 and β5 integrin with specific siRNA and demonstrate that αvβ3 controls the radioresistance of U87 cells. αvβ3 and αvβ5 integrins mainly signal throught the integrin-linked kinase (ILK) or focal adhesion kinase (FAK). By silencing these two proteins with specific siRNA, we showed that ILK but not FAK mediates this adhesion-dependant radioresistance pathway throught Akt and RhoB. Our results bring to light for the first time that adhesion is not only a factor of glioma agressivness but also a factor of resistance to treatment particularly radiotherapy. They also strongly suggest that it could be of great interest to target this pathway to increase the efficiency of radiotherapy for human glioblastoma.
Design and performance tradeoffs in clustered video servers (2002)

We investigate the suitability of clustered architectures for designing scalable multimedia servers. Specifically, we evaluate the effects of: (i) architectural design of the cluster; (ii) the size of the unit of data interleaving; and (iii) read ahead buffering and scheduling on the real time performance guarantees provided by the server. To analyze the effects of these parameters, we develop an analytical model of clustered multimedia servers, and then validate it through extensive simulations, The results of our analysis have formed the basis of our prototype implementation based on an RS/6000 Scalable Parallel (SP) machine. We briefly describe the prototype and discuss some implementation details.
Methods of evaluating hair growth (2003)

For decades, scientists and clinicians have examined methods of measuring scalp hair growth. With the development of drugs that stem or even reverse the miniaturization of androgenetic alopecia, there has been a greater need for reliable, economical and minimally invasive means of measuring hair growth and, specifically, response to therapy. We review the various methods of measurement described to date, their limitations and value to the clinician. In our opinion, the potential of computer-assisted technology in this field is yet to be maximized and the currently available tools are less than ideal. The most valuable means of measurement at the present time are global photography and phototrichogram-based techniques (with digital image analysis) such as the 'TrichoScan'. Subjective scoring systems are also of value in the overall assessment of response to therapy and these are under-utilized and merit further refinement.