gebhart/patrepeval huggingface dataset:
Comparative effects of clarithromycin and erythromycin on the normal intestinal microflora (1991)

10 healthy volunteers received 250 mg of clarithromycin orally q 12 h for 7 days and 10 other volunteers 1000 mg of erythromycin ethylsuccinate orally q 12 h for 7 days. Stool specimens were collected before, during and after antibiotic administration. In the clarithromycin group, the numbers of streptococci and enterobacteria decreased among aerobic microorganisms while in the erythromycin group streptococci, enterococci and enterobacteria decreased and staphylococci increased during antibiotic administration. The anaerobic intestinal microflora was also affected. The alterations were more pronounced in the volunteers receiving erythromycin than in those having clarithromycin.
Modulation of muscle insulin resistance by selective inhibition of GSK-3 in Zucker diabetic fatty rats (2003)

A role for elevated glycogen synthase kinase-3 (GSK-3) activity in the multifactorial etiology of insulin resistance is now emerging. However, the utility of specific GSK-3 inhibition in modulating insulin resistance of skeletal muscle glucose transport is not yet fully understood. Therefore, we assessed the effects of novel, selective organic inhibitors of GSK-3 (CT-98014 and CT-98023) on glucose transport in insulin-resistant muscles of Zucker diabetic fatty (ZDF) rats. Incubation of type IIb epitrochlearis and type I soleus muscles from ZDF rats with CT-98014 increased glycogen synthase activity (49 and 50%, respectively, P < 0.05) but did not alter basal glucose transport (2-deoxyglucose uptake). In contrast, CT-98014 significantly increased the stimulatory effects of both submaximal and maximal insulin concentrations in epitrochlearis (37 and 24%) and soleus (43 and 26%), and these effects were associated with increased cell-surface GLUT4 protein. Lithium enhanced glycogen synthase activity and both basal and insulin-stimulated glucose transport in muscles from ZDF rats. Acute oral administration (2 x 30 mg/kg) of CT-98023 to ZDF rats caused elevations in GSK-3 inhibitor concentrations in plasma and muscle. The glucose and insulin responses during a subsequent oral glucose tolerance test were reduced by 26 and 34%, respectively, in the GSK-3 inhibitor-treated animals. Thirty minutes after the final GSK-3 inhibitor treatment, insulin-stimulated glucose transport was significantly enhanced in epitrochlearis (57%) and soleus (43%). Two hours after the final treatment, insulin-mediated glucose transport was still significantly elevated (26%) only in the soleus. These results indicate that specific inhibition of GSK-3 enhances insulin action on glucose transport in skeletal muscle of the insulin-resistant ZDF rat. This unique approach may hold promise as a pharmacological treatment against insulin resistance of skeletal muscle glucose disposal.
Fluorescent modification of adenosine-containing coenzymes. Biological activities and spectroscopic properties (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFluorescent modification of adenosine-containing coenzymes. Biological activities and spectroscopic propertiesJohn A. Secrist, III, Jorge R. Barrio, Nelson J. Leonard, and Gregorio WeberCite this: Biochemistry 1972, 11, 19, 3499–3506Publication Date (Print):September 12, 1972Publication History Published online1 May 2002Published inissue 12 September 1972https://pubs.acs.org/doi/10.1021/bi00769a001https://doi.org/10.1021/bi00769a001research-articleACS PublicationsRequest reuse permissionsArticle Views928Altmetric-Citations386LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Retinal neurodegeneration: early pathology in diabetes (2000)

Normal vision depends on the normal function of retinal neurons, so vision loss in diabetes must ultimately be explained in terms of altered neuronal function. However to date relatively little attention has been paid to the impact of diabetes on the neural retina. Instead, the focus of most research has been primarily on retinal vascular changes, with the assumption that they cause altered neuronal function and consequently vision loss. An increasing body of evidence suggests that alterations in neuronal function and viability may contribute to the pathogenic mechanisms of diabetic retinopathy beginning shortly after the onset of diabetes. This view arises from neurophysiological, psychometric, histopathological and biochemical observations in humans and experimental animals. The collective evidence from past and recent studies supports the hypothesis that neurodegeneration, together with functional changes in the vasculature, is an important component of diabetic retinopathy. The authors invite other investigators to include the neural retina as a component of their studies so that the pathogenesis of diabetic retinopathy can be understood more clearly.
Lung cancer therapeutics that target signaling pathways: an update (2010)

Claiming more than 150,000 lives each year, lung cancer is the deadliest cancer in the USA. First-line treatments in lung cancer include surgical resection and chemotherapy, the latter of which offers only modest survival benefits at the expense of often severe and debilitating side effects. Recent advances in elucidating the molecular biology of lung carcinogenesis have elucidated novel drug targets, and treatments are rapidly evolving into specialized agents that hone in on specific aspects of the disease. Of particular interest is blocking tumor growth by targeting the physiological processes surrounding angiogenesis, pro-tumorigenic growth factor activation, anti-apoptotic cascades and other cancer-promoting signal transduction events. This article looks at several areas of interest to lung cancer therapeutics and considers the current state of affairs surrounding the development of these therapies.
Identification of the Fusion Peptide of Primate Immunodeficiency Viruses (1989)

Membrane fusion induced by the envelope glycoproteins of human and simian immunodeficiency viruses (HIV and SIVmac) is a necessary step for the infection of CD4 cells and for the formation of syncytia after infection. Identification of the region in these molecules that mediates the fusion events is important for understanding and possibly interfering with HIV/SIVmac infection and pathogenesis. Amino acid substitutions were made in the 15 NH2-terminal residues of the SIVmac gp32 transmembrane glycoprotein, and the mutants were expressed in recombinant vaccinia viruses, which were then used to infect CD4-expressing T cell lines. Mutations that increased the overall hydrophobicity of the gp32 NH2-terminus increased the ability of the viral envelope to induce syncytia formation, whereas introduction of polar or charged amino acids in the same region abolished the fusogenic function of the viral envelope. Hydrophobicity in the NH2-terminal region of gp32 may therefore be an important correlate of viral virulence in vivo and could perhaps be exploited to generate a more effective animal model for the study of acquired immunodeficiency syndrome.
MUTANTS OF ESCHERICHIA COLI K-12 DEFECTIVE IN DNA REPAIR AND IN GENETIC RECOMBINATION (1966)

BACTERIA are readily killed by exposure to ultraviolet light (UV) , presumably as the result of the formation of UV photoproducts in the bacterial DNA. It is also known that pyrimidine dimers are among the photoproducts formed with a high yield, and that bacteria normally contain an efficient mechanism for the repair of DNA containing these products. Pyrimidine dimers are excised from DNA during incubation and can be recovered, still contained within a short oligonucleotide. This excision appears to involve the interruption of single DNA strands, and to be followed by local DNA breakdown and repair synthesis (SETLOW and CARRIER 1964; BOYCE and HOWARD-FLANDERS 1964; PETTIJOHN and HANAWALT 1964). These observations are of interest not only because they reveal the mechanism of an effective and possibly widespread process for the repair of injured DNA, but also because they suggest that local repair can occur in one strand of a double helix. This mechanism for DNA repair may be related to the mechanism of genetic exchange. An insight into the mechanisms of genetic recombination was gained through the discovery that h bacteriophage recombinants can be formed by joining fragments of preexisting phage DNA molecules (MESELSON and WEIGLE 1961). As continuity in the base sequence of the phage genome must be preserved, base pairing between overlapping single strands from each parentel molecule is presumably required as a prelude to the formation of a recombinant ( LEVINTHAL 1959). It has been suggested that the process of recombination may be completed by local DNA repair synthesis on either side of the overlap (MESELSON 1964) and that certain of the enzymes involved may serve in both genetic recombination and in repair after irradiation ( HOWARD-FLANDERS and BOYCE 1964). Further evidence in support of these concepts has been obtained through the isolation of mutants of E. coZi K-12 that have lost the ability to form recombinants when mated with suitable donor strains. As these mutants are able to accept genetic material normafly, it appears that they may be defective in the process of integrating the donor DNA into the recipient chromosome (phenotype symbol Kec-) . Because of the suggested relationship between repair and recombination, the strains were tested for ability to survive exposure to UV, and were found to be highly radiosensitive (CLARK and MARGULIES 1965). After exposure to UV, these mutants degrade their DNA excessively and fail to incorporate labeled thymidine ( CLARK, CHAMBERLIN, BOYCE, and HOWARD-FLANDERS 1966).
Large-area optical design rule checker for logic PSM application (1994)

An aerial optical design rule checker (ODRC) that will handle large areas is used to validate the automatic CAD software used for application of alternating Phase Shift Mask technology to logic devices. An automatic alternating aperture layout algorithm developed internally by Advanced Micro Devices is applied to 0.24 to 0.50 micrometers electrical designs. The layout is then verified for different stepper and defocus values by the ODRC which utilizes the simulated aerial image to compare directly to the electrical design database. Entire databases are handled by fracturing the database into optically isolated areas or by using a sliding window technique. Small areas up to 420 um per side can be done with single processor workstations with at least 512 megabyte of memory. Larger problems require multiprocessor computers with at least 16 gigabyte of memory. Full circuit analysis should be done on systems with at least 64 gigabyte of memory in order to accomplish solving the problem in a reasonable time frame.
Orthotic design and foot impression procedures to control foot alignment (2004)

The traditional theory on subtalar joint neutral position and intrinsic foot deformities for the evaluation and treatment of foot and ankle disorders has been the basis for foot orthotics for many years. Although clinical evaluations have suggested a relationship between subtalar pronation and a variety of lower limb problems, such as shin splints and anterior knee pain, recent research has raised serious concerns about the reliability and validity of the assessment and intervention methods. Results of recent studies in foot biomechanics suggest that the orthosis design to control foot alignment should stabilise the medial apical bony structure of the arch to control the first ray mobility and transmit load through the lateral support structures of the foot, locking the calcaneocuboid joint and decreasing strain in the plantar aponeurosis. The concept of "posting" according to a measured foot deformity is de-emphasised. Reliable foot impression procedures are required to provide appropriate orthotic design and thus management. A prone lying position manipulated foot impression method using polycaprolactone based low temperature thermoplastic material was introduced. Ten (10) subjects were recruited to participate in the reliability tests, which were conducted by 2 orthotists specialized in foot orthotics. Results showed high intrarater and interrater reliability of the measured forefoot width and the navicular height. The reliability of the forefoot-rearfoot relationship was demonstrated by the small variance of the root mean square calculation. Subsequently orthotic intervention can be done in a more consistent manner.
The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic Pain (2010)

From killers to curers: Peptides from cone snail venoms are potential therapeutic agents for the treatment of neuropathic pain. Unfortunately, these peptides suffer from the disadvantage of short biological half-lives and poor activity when taken orally. A new orally active conotoxin was developed to solve these problems.
Cell-Cycle Reentry and Cell Death in Transgenic Mice Expressing Nonmutant Human Tau Isoforms (2005)

Mutations in the microtubule-associated protein tau gene have been linked to neurofibrillary tangle (NFT) formation in several neurodegenerative diseases known as tauopathies; however, no tau mutations occur in Alzheimer's disease, although this disease is also characterized by NFT formation and cell death. Importantly, the mechanism of tau-mediated neuronal death remains elusive. Aged mice expressing nonmutant human tau in the absence of mouse tau (htau mice) developed NFTs and extensive cell death. The mechanism of neuron death was investigated in htau mice, and surprisingly, the presence of tau filaments did not correlate directly with death within individual cells, suggesting that cell death can occur independently of NFT formation. Our observations show that the mechanism of neurodegeneration involved reexpression of cell-cycle proteins and DNA synthesis, indicating that nonmutant tau pathology and neurodegeneration may be linked via abnormal, incomplete cell-cycle reentry.
Mining Individual Life Pattern Based on Location History (2009)

The increasing pervasiveness of location-acquisition technologies (GPS, GSM networks, etc.) enables people to conveniently log their location history into spatial-temporal data, thus giving rise to the necessity as well as opportunity to discovery valuable knowledge from this type of data. In this paper, we propose the novel notion of individual life pattern, which captures individual's general life style and regularity. Concretely, we propose the life pattern normal form (the LP-normal form) to formally describe which kind of life regularity can be discovered from location history; then we propose the LP-Mine framework to effectively retrieve life patterns from raw individual GPS data. Our definition of life pattern focuses on significant places of individual life and considers diverse properties to combine the significant places. LP-Mine is comprised of two phases: the modelling phase and the mining phase. The modelling phase pre-processes GPS data into an available format as the input of the mining phase. The mining phase applies separate strategies to discover different types of pattern. Finally, we conduct extensive experiments using GPS data collected by volunteers in the real world to verify the effectiveness of the framework.
Coupled transcription-polyadenylation in a cell-free system. (1991)

To investigate the relationship between transcription and polyadenylation, an in vitro system has been developed in which endogenously transcribed pre-mRNAs containing functional polyadenylation sites are rapidly and accurately cleaved in a HeLa nuclear extract. Cleavage of endogenously transcribed substrates differed from that of exogenous substrates in that a proximal 3' terminus was not required, the reaction was more tolerant of increased Mg2+ levels, and endogenous substrates were cleaved more efficiently. A promoter dependence for this reaction was suggested by the observation that substrates transcribed by bacteriophage T7 RNA polymerase in the presence of nuclear extract were not cleaved. In addition, analysis of the bovine growth hormone poly(A) site indicated that it is highly efficient in vitro which agrees with previous in vivo data. The availability of an in vitro system in which transcription and polyadenylation are coupled should facilitate analysis of the relation between 3' end processing and RNA polymerase II transcription termination as well as the promoter requirements for polyadenylation.
Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas (1977)

Single agents and combinations of agents were tested for antitumor activity against four transplantable colon tumors in mice. The most impressive anti-tumor activity was obtained with anguidine and the combination of anguidine + 5-FU against colon adenocarcinoma No. 38. Antitumor potentiation was obtained when the combination was injected simultaneously on a Q7d schedule (two experiments), but not on an alternating schedule of administration (3 or 4 days separating injections of the two agents). Anguidine was highly active only in a colon tumor that was very responsive to 5-FU. The correlation between high 5-FU sensitivity and high anguidine sensitivity may be coincidental or could be of predictive value. Other active single agents and combinations of agents against one or more of the colon tumors include 5-FU, 5-FUdR, MeCCNU, BCNU, homoharringtonine, ara-C, Cis-Pt-II, dianhydrogalactitol, piperazinedione, cyclophosphamide; MeCCNU + 5-FU; Adriamycin + 5-FU; Adriamycin + cyclophosphamide; Adriamycin + palmO-ara-C; cyclophosphamide + procarbazine; and 5-FU + palmO-ara-C. (The combination of 5-FU + palmO-ara-C was potentiating only on an alternating schedule.) The results of surgery-chemotherapy adjuvant treatment of metastatic colon tumors established that if an agent or a combination was highly active against moderately advanced tumor masses, this treatment was also highly active after surgery against residual metastatic disease. The converse was also true. That is, if the agent or combination was inactive or marginally active against moderately advanced disease, the treatment was also relatively ineffectual after surgery against residual metastatic disease. Based on surgical-adjuvant experiments with colon tumor No. 26, the following agents and combinations are conditionally recommended: MeCCNU + 5-FU; MeCCNU + Ara-C; cyclophosphamide + Ara-C; BCNU+ 5-FU and MeCCNU. It is also assumed that those agents active against the advanced disease are likely to be active after surgery against residual metastatic cells. Thus, agents highly active against advanced-stage colon adenocarcinoma No. 38 are possible candidates for adjuvant therapy. On this basis, anguidine and anguidine + 5-FU are recommended.
Molecular Characterization Of Hawaii Virus And Other Norwalk-Like Viruses: Evidence For Genetic Polymorphism Among Human Caliciviruses (1994)

Hawaii virus (HV), from a 1971 family outbreak of gastroenteritis, is serotypically distinct from Norwalk virus (NV), recently identified as a human calicivirus by molecular analysis. About 2600 consecutive nucleotides of the HV genome (including those encoding the viral capsid protein) and part of the polymerase region of three other viruses (MDV1, MDV6 and SV7) were sequenced. Comparison of the amino acid sequence of the capsid protein of HV with NV and other human caliciviruses (Toronto virus [TV24], Desert Shield virus [DSV395], and Southampton virus [SHV]) demonstrated the existence of two major genetic groups (genogroups) typified by HV and NV. HV had 76% identity with TV24 and 48% identity with NV, DSV395, or SHV. In addition, comparison of part of the polymerase protein of HV with other human caliciviruses also showed that there were these two genogroups. The large genetic diversity between the capsid sequence of HV and NV is consistent with their serotypic distinctiveness.
Transformation of yeast with synthetic oligonucleotides. (1988)

Genomic DNA of the yeast, Saccharomyces cerevisiae, can be conveniently and specifically altered by transforming spheroplasts or lithium acetate-treated cells directly with synthetic oligonucleotides. Altered forms of iso-1-cytochrome c were generated by transforming a cyc1 mutant with oligonucleotides and selecting for at least partially functional revertants; the oligonucleotides contained a sequence that corrected the cyc1 mutation and produced additional alterations at nearby sites. Transformation has been accomplished with oligonucleotides as short as 20 nucleotides and with amounts as low as 100 micrograms. This method of site-directed mutagenesis in vivo has been used to produce alterations in the NH2-terminal region of iso-1-cytochrome c in which the NH2-terminal methionine is excised and the penultimate residue is acetylated.
Visualizing Interfacial Structure at Non-Common-Atom Heterojunctions with Cross-Sectional Scanning Tunneling Microscopy (2000)

We describe how cross-sectional scanning tunneling microscopy (STM) may be used to image the interfacial bonding across the nearly lattice-matched, non-common-atom GaSb/InAs heterojunction with atomic-scale precision. The method, which takes advantage of the length difference between interfacial and bulk bonds, appears equally applicable to AlSb/InAs and suggests how one might recover the complete structure of either heterojunction from atomic-resolution STM data.
Fusarium polycaprolactone depolymerase is cutinase (1996)

Polycaprolactone (PCL), a synthetic polyester, is degraded by a variety of microorganisms, including some phytopathogens. Many phytopathogens secrete cutinase, a serine hydrolase that degrades cutin, the structural polymer of the plant cuticle. We compared wild-type strains and a cutinase-negative gene replacement mutant strain of Fusarium solani f. sp. pisi (D. J. Stahl and W. Schäfer, Plant Cell 4:621-629, 1992) and a wild-type strain of Fusarium moniliforme to show that Fusarium cutinase is a PCL depolymerase. The wild-type strains, but not the mutant strain, (i) degraded PCL and used it as a source of carbon and energy, (ii) showed induction of secreted PCL depolymerase and an esterase activity of cutinase when grown in the presence of cutin, and (iii) showed induction of PCL depolymerase and an esterase activity of cutinase when grown in the presence of a hydrolysate of PCL, which contains PCL oligomers that are structurally similar to the natural inducers of cutinase. These results together with other details of regulation and conditions for optimal enzyme activity indicate that the Fusarium PCL depolymerase, required for degradation and utilization of PCL, is cutinase.