gebhart/patrepeval huggingface dataset:
Amyotrophic Lateral Sclerosis Mutations Have the Greatest Destabilizing Effect on the Apo- and Reduced Form of SOD1, Leading to Unfolding and Oxidative Aggregation (2005)

Mutant forms of Cu,Zn-superoxide dismutase (SOD1) that cause familial amyotrophic lateral sclerosis (ALS) exhibit toxicity that promotes the death of motor neurons. Proposals for the toxic properties typically involve aberrant catalytic activities or protein aggregation. The striking thermodynamic stability of mature forms of the ALS mutant SOD1 (Tm>70 degrees C) is not typical of protein aggregation models that involve unfolding. Over 44 states of the polypeptide are possible, depending upon metal occupancy, disulfide status, and oligomeric state; however, it is not clear which forms might be responsible for toxicity. Recently the intramolecular disulfide has been shown to be required for SOD1 activity, leading us to examine these states of several disease-causing SOD1 mutants. We find that ALS mutations have the greatest effect on the most immature form of SOD1, destabilizing the metal-free and disulfide-reduced polypeptide to the point that it is unfolded at physiological temperatures (Tm<37 degrees C). We also find that immature states of ALS mutant (but not wild type) proteins readily form oligomers at physiological concentrations. Furthermore, these oligomers are more susceptible to mild oxidative stress, which promotes incorrect disulfide cross-links between conserved cysteines and drives aggregation. Thus it is the earliest disulfide-reduced polypeptides in the SOD1 assembly pathway that are most destabilized with respect to unfolding and oxidative aggregation by ALS-causing mutations.
Microbial transformationsd. 19. Asymmetric dihydroxylation of the remote double bond of geraniol: a unique stereochemical control allowing easy access to both enantiomers of geraniol-6,7-diol (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMicrobial transformationsd. 19. Asymmetric dihydroxylation of the remote double bond of geraniol: a unique stereochemical control allowing easy access to both enantiomers of geraniol-6,7-diolX. M. Zhang, A. Archelas, and R. FurstossCite this: J. Org. Chem. 1991, 56, 12, 3814–3817Publication Date (Print):June 1, 1991Publication History Published online1 May 2002Published inissue 1 June 1991https://doi.org/10.1021/jo00012a010Request reuse permissionsArticle Views226Altmetric-Citations34LEARN 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 (551 KB) Get e-Alertsclose Get e-Alerts
Bragg gratings in an acrylate polymer consisting of periodic polymer-dispersed liquid-crystal planes (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTBragg gratings in an acrylate polymer consisting of periodic polymer-dispersed liquid-crystal planesR. L. Sutherland, L. V. Natarajan, V. P. Tondiglia, and T. J. BunningCite this: Chem. Mater. 1993, 5, 10, 1533–1538Publication Date (Print):October 1, 1993Publication History Published online1 May 2002Published inissue 1 October 1993https://pubs.acs.org/doi/10.1021/cm00034a025https://doi.org/10.1021/cm00034a025research-articleACS PublicationsRequest reuse permissionsArticle Views1414Altmetric-Citations324LEARN 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
Association of Betel Nut with Carcinogenesis: Revisit with a Clinical Perspective (2012)

Betel nut (BN), betel quid (BQ) and products derived from them are widely used as a socially endorsed masticatory product. The addictive nature of BN/BQ has resulted in its widespread usage making it the fourth most abused substance by humans. Progressively, several additives, including chewing tobacco, got added to simple BN preparations. This addictive practice has been shown to have strong etiological correlation with human susceptibility to cancer, particularly oral and oropharyngeal cancers.The PUBMED database was searched to retrieve all relevant published studies in English on BN and BQ, and its association with oral and oropharyngeal cancers. Only complete studies directly dealing with BN/BQ induced carcinogenesis using statistically valid and acceptable sample size were analyzed. Additional relevant information available from other sources was also considered.This systematic review attempts to put in perspective the consequences of this widespread habit of BN/BQ mastication, practiced by approximately 10% of the world population, on oral cancer with a clinical perspective. BN/BQ mastication seems to be significantly associated with susceptibility to oral and oropharyngeal cancers. Addition of tobacco to BN has been found to only marginally increase the cancer risk. Despite the widespread usage of BN/BQ and its strong association with human susceptibility to cancer, no serious strategy seems to exist to control this habit. The review, therefore, also looks at various preventive efforts being made by governments and highlights the multifaceted intervention strategies required to mitigate and/or control the habit of BN/BQ mastication.
SC‐0051, a 2‐benzoyl‐cyclohexane‐1,3‐dione bleaching herbicide, is a potent inhibitor of the enzyme p‐hydroxyphenylpyruvate dioxygenase (1993)

Growth inhibition of Lemna gibba plantlets by the bleaching herbicide, SC-0051 (2-(2-chloro-4-methanesulfonylbenzoyl)-1,3-cyclohexanedione)) was alleviated by the addition of homogentisic acid to the growth medium. Homogentisic acid is a key intermediate in the biosynthesis of tyrosine-derived plant quinones as well as in tyrosine metabolism. The herbicide prevented the incorporation of radioactivity from [14C]tyrosine into lipophilic plant metabolites and, in rat liver extracts, the herbicide inhibited the conversion of tyrosine to homogentisic acid. The enzyme p-hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27) from both Zea mays seedlings and liver tissues, was found to be subject to strong inhibition by SC-0051. Inhibition of plant quinone biosynthesis is a new mode of herbicidal action. One of the consequences of quinone depletion in plants by SC-0051. Inhibition of plant quinone biosynthesis is a new mode of herbicidal action. One of the consequences of quinone depletion in plants in vivo is apparently an indirect inhibition of phytoene desaturation. The enzyme phytoene desaturase itself, however, is not afflicted by the herbicide.
Fundamental limitations in antennas (1981)

Four fundamental limitations in antennas have been identified in the areas of: electrically small antennas, superdirective antennas, superresolution antennas, and high-pin antennas. All exhibit roughly exponential increase in cost factors with performance increase beyond the robust range. This paper reviews these limitations. Electrically small antennas are analyzed via spherical mode theory, with the antenna enclosed in a virtual sphere. Minimum Q varies inversely as the cube of sphere radius in radian wavelengths when the radius is much less than the latter. This limits the achievable bandwidth. Superdirective apertures require a constraint; the optimization is generally intractable except for line sources. Superdirective arrays have spacing below half-wavelength, and for small spacings a constraint is desirable to limit Q, tolerances, efficiency, sidelobes, etc. This is accomplished by expressing constrained directivity as a ratio of two Hermilian quadratic forms, for which a solution exists. Array Q varies exponentially with directivity so only modest increases are practical. Superresolution arrays use maximum entropy processes to improve spatial frequency resolution for short samples (short arrays), analogous to spectral analysis processing. An amplitude-tapered autocorrelation function is extended by linear least square prediction and autoregression; the latter contributes filter poles. This extension is with minimum added information, hence maximum entropy. In contrast to superdirective arrays which are all zero functions, superresolution maximum entropy uses an all pole function. Results are dependent upon the sampling subarray size and upon signal/noise (S/N). Required S/N increases exponentially with inverse angular resolution. Achievable gain of high-gain reflector antennas is limited by cost of the structure. For random surface errors maximum gain is proportional to the mechanical tolerance ratio (antenna diameter/1σ tolerance) squared. Since cost increases rapidly with diameter and with tolerance ratio this comprises a gain limitation. Current best reflectors have maximum gain in the range of 90 to 100 dB.
Recombinant Immunocytokines Targeting the Mouse Transferrin Receptor:  Construction and Biological Activities (1998)

Localized cytokine therapies with recombinant monoclonal antibody-cytokine fusion proteins, designated immunocytokines, have become of increasing interest for tumor immunotherapy, since they direct immunomodulatory cytokines into the tumor microenvironment. To investigate their mechanisms of action in a variety of syngeneic tumor models, recombinant mouse cytokines IL2 and GM-CSF were engineered as fusion proteins to the carboxyl terminus of a chimeric rat/mouse antitransferrin receptor antibody, ch17217 and expressed in stable-transfected Chinese hamster ovary cells. The recombinant immunocytokines were readily purified by affinity chromatography and their binding characteristics were identical to those shown for the ch17217 antibody. The IL2 immunocytokine had an activity similar to recombinant mouse IL2, whereas the GM-CSF immunocytokine had enhanced cytokine activity relative to recombinant mouse GM-CSF. The clearance rates of ch17217 and the GM-CSF and IL2 immunocytokines were relatively similar with elimination phases (t1/2alpha) of 1.8 h and distribution phases (t1/2beta) of 83, 88, and 91 h, respectively. Both immunocytokines demonstrated effective antitumor activity by suppressing the growth of hepatic metastases of mouse neuroblastoma and pulmonary metastases of mouse colon carcinoma in syngeneic A/J and BALB/c mice, respectively. These results indicate that biologically effective IL2 and GM-CSF immunocytokines combine the targeting ability of an antitransferrin receptor monoclonal antibody with the immunomodulatory functions of each cytokine. Because of the universal expression of the transferrin receptor on mouse tumor cell lines, these constructs should prove useful to determine their efficacy in a wide variety of syngeneic mouse tumor models and to perform detailed studies of their modes of action.
The effects of resveratrol and SIRT1 activation on dystrophic cardiomyopathy (2015)

The muscular dystrophies, which cause progressive weakening of the skeletal muscles, are frequently associated with cardiomyopathy. In fact, the leading cause of mortality in patients with Duchenne muscular dystrophy, the most common and most severe type of muscular dystrophy, is heart failure due to cardiomyopathy. Therefore, more effective methods for treating cardiomyopathy are expected to improve long-term outcomes for patients with Duchenne muscular dystrophy. Our recent preclinical data show that treatment with the SIRT1 activator resveratrol is beneficial for dystrophic cardiomyopathy. We examined the effects of resveratrol treatment in two different models of muscular dystrophy: dystrophin-deficient mdx mice and δ-sarcoglycan-deficient TO-2 hamsters. In both models, resveratrol suppressed cardiac hypertrophy, preserved cardiac function, and reduced tissue fibrosis in the diseased heart. Importantly, resveratrol significantly improved survival in TO-2 hamsters. Resveratrol also attenuated skeletal muscle pathology in mdx mice. These promising results indicate resveratrol's potential for clinical translation to treat cardiomyopathy in patients with muscular dystrophies.
Probing Cellular Chemistry in Biological Systems with Microelectrodes (2006)

Over the past 20 years, the technological impediments to fabricating electrodes of micrometer dimensions have been largely overcome. These small electrodes can be readily applied to probe chemical events at the surface of tissues or individual biological cells; they can even be used to monitor concentration changes within intact animals. These measurements can be made on rapid time scales and with minimal perturbation of the system under study. Several recent applications have provided important insights into chemical processes at cells and in tissues. Examples include molecular flux measurements at the surface of single cells and through skin-which can offer insights into oxidative stress, exocytosis, and drug delivery-and real-time brain neurotransmitter monitoring in living rats, which reveals correlations between behavior and molecular events in the brain. Such findings can promote interdisciplinary collaborations and may lead to a broader understanding of the chemical aspects of biology.
Indigenous gut microbiota and probiotics in paediatric coeliac disease (2008)

Coeliac disease (CD) is the commonest immune-mediated enteropathy characterized by a permanent intolerance to cereal gluten proteins. This disease can present at any age with a variety of clinical features, but typical cases often do so in early childhood with small intestinal injury and signs of malabsorption. CD aetiology involves genetic, immunologic and environmental factors. The ingestion of gluten is responsible for CD symptoms and signs. Epidemiological and clinical data also suggest that other environmental factors can contribute to the risk of CD development, including the pattern of infant nutrition and the incidence of infections in early life. Breast-feeding seems to exert a protective role against CD development and greatly influence the gut microbial composition. Indigenous gut microbes are thought to play pivotal roles in the development of the gut barrier function and oral tolerance to dietary antigens. Early exposure to a beneficial microbiota is related to a lower incidence of diverse immune-related diseases (e.g. atopic and autoimmune diseases). Alterations in the composition of the gut microbiota have also been associated with CD presentation in children. These evidences suggest that a balanced composition of the gut microbiota or the presence of specific beneficial bacteria might protect against CD. In this scenario, it can be hypothesised that the administration of probiotics and/or prebiotics in early life could help to regulate the intestinal permeability limiting the access of antigens to the submucosa and contribute to the regulation and fine-tuning of the immune system leading to oral tolerance to gluten.
Effects of slaughter age on meat tenderness and USDA carcass maturity scores of beef females (1995)

Two experiments were conducted to determine the effect of carcass maturity on meat palatability using concentrate-fed cattle of known history and to determine the relationship of chronological age to carcass maturity scores. Yearling heifers (n = 28) and 2-yr-old cows (n = 25) of similar breed groups were fed a high-energy-density diet for 90 d before slaughter. Longissimus muscle Instron peak load (Warner-Bratzler shear force) did not differ between age groups; but, fail elongation was higher for the 2-yr-old cows (P < .05). Overall tenderness ratings were lower for the 2-yr-old cows; however, the magnitude of the tenderness difference between age groups was small (.4 units on an 8-point scale). There was 10-fold more variation in tenderness within each age group than there was between age groups. Carcass maturity scores and chronological age were compared for heifers and cows (n = 249) ranging in age from 1.7 to 13.9 yr. Carcass maturity scores increased with increasing chronological age at a much faster rate than indicated by USDA. The following chronological age groups most accurately reflected the chronological age associated with each USDA carcass maturity class: A, 9 to 24 mo; B, 24 to 36 mo; C, 36 to 48 mo; D, 48 to 60 mo; E, > 60 mo. These results indicate that efforts to control variation in tenderness would be more effective if they targeted factors that have a greater effect on meat tenderness than does maturity class. Moreover, our results indicate that cows may grade lower at a given age than what USDA standards imply.
Potential Synergies and Challenges in Refining Cellulosic Biomass to Fuels, Chemicals, and Power (2003)

Lignocellulosic biomass such as agricultural and forestry residues and dedicated crops provides a low-cost and uniquely sustainable resource for production of many organic fuels and chemicals that can reduce greenhouse gas emissions, enhance energy security, improve the economy, dispose of problematic solid wastes, and improve air quality. A technoeconomic analysis of biologically processing lignocellulosics to ethanol is adapted to project the cost of making sugar intermediates for producing a range of such products, and sugar costs are predicted to drop with plant size as a result of economies of scale that outweigh increased biomass transport costs for facilities processing less than about 10,000 dry tons per day. Criteria are then reviewed for identifying promising chemicals in addition to fuel ethanol to make from these low cost cellulosic sugars. It is found that the large market for ethanol makes it possible to achieve economies of scale that reduce sugar costs, and coproducing chemicals promises greater profit margins or lower production costs for a given return on investment. Additionally, power can be sold at low prices without a significant impact on the selling price of sugars. However, manufacture of multiple products introduces additional technical, marketing, risk, scale-up, and other challenges that must be considered in refining of lignocellulosics.
The crtE gene in Erwinia herbicola encodes geranylgeranyl diphosphate synthase. (1992)

A cluster of genes essential for the biosynthesis of carotenoids in Erwinia herbicola has been isolated and characterized [Armstrong, G.A., Alberti, M. & Hearst, J. E. (1990) Proc. Natl. Acad. Sci. USA 87, 9975-9979]. Related gene clusters are found in other carotenoid-producing bacteria. Two of these genes, crtB and crtE, have been assigned to enzymes responsible for conversion of geranylgeranyl diphosphate (GGPP) to prephytoene diphosphate and prephytoene diphosphate to phytoene, respectively. We isolated crtE from the Er. herbicola cluster by PCR amplification and cloned the coding region into the Escherichia coli expression vector pARC306N. Es. coli JM101 was transformed with the expression plasmid, and transformants were assayed for GGPP synthase and phytoene synthase activity. Extracts from JM101/pSM145 accumulated [14C]GGPP when incubated with [14C]isopentenyl diphosphate and farnesyl diphosphate, whereas similar incubations with [3H]GGPP did not yield prephytoene diphosphate or phytoene. Thus, crtE encodes GGPP synthase.
Cardiovascular and hemodynamic parameters in women following prolonged CGRP inhibition using LBR-101, a monoclonal antibody against CGRP (2014)

Sustained CGRP inhibition was not associated with hemodynamic or ECG changes in a population at an increased age risk for cardiovascular events.
CC-122, a pleiotropic pathway modifier, mimics an interferon response and has antitumor activity in DLBCL (2015)

Cereblon (CRBN), a substrate receptor of the Cullin 4 RING E3 ubiquitin ligase complex, is the target of the immunomodulatory drugs lenalidomide and pomalidomide. Recently, it was demonstrated that binding of these drugs to CRBN promotes the ubiquitination and subsequent degradation of 2 common substrates, transcription factors Aiolos and Ikaros. Here we report that CC-122, a new chemical entity termed pleiotropic pathway modifier, binds CRBN and promotes degradation of Aiolos and Ikaros in diffuse large B-cell lymphoma (DLBCL) and T cells in vitro, in vivo, and in patients, resulting in both cell autonomous as well as immunostimulatory effects. In DLBCL cell lines, CC-122-induced degradation or short hairpin RNA-mediated knockdown of Aiolos and Ikaros correlates with increased transcription of interferon (IFN)-stimulated genes independent of IFN-α, -β, and -γ production and/or secretion and results in apoptosis in both activated B-cell (ABC) and germinal center B-cell DLBCL cell lines. Our results provide mechanistic insight into the cell-of-origin independent antilymphoma activity of CC-122, in contrast to the ABC subtype selective activity of lenalidomide.
CD200‐FC, a novel antiarthritic biologic agent that targets proinflammatory cytokine expression in the joints of mice with collagen‐induced arthritis (2008)

CD200-Fc is an effective therapeutic agent in established CIA that targets proinflammatory cytokine expression in the joint without any obvious systemic immunosuppressive effects. Our findings indicate that CD200-Fc has considerable potential as a novel therapeutic agent in rheumatoid arthritis in humans.
Genital Human Papillomavirus Infections in Patients Attending an Inner-City STD Clinic (1991)

One hundred and sixteen consecutive women attending a Baltimore City STD clinic were studied for the prevalence of human papillomavirus (HPV) infection of the genital tract using three criteria: presence of clinically recognized (visible) genital warts, cytopathologic evidence suggestive of HPV infection in a Papanicolaou smear, and analysis of cervical scrapes for genital tract HPV genomic sequences by Southern hybridization. The women were young (median age: 22 years) and more than 80% had a history of one or more STDs. The prevalences were 17% for visible warts, 41% for cytologic findings suggestive of HPV infection, and 12% for HPV DNA in cervical scrapes. Comparing the results of the three techniques, HPV DNA was found significantly more often in cytopathology-positive women than in cytopathology-negative women (18% vs. 5%, P = 0.05) and in women with visible warts than in women without visible warts (29% vs. 6%, P = 0.01). Visible warts were more common in women with HPV-DNA-positive cervical scrapes than in HPV-negative women (50% vs. 14%, P = .01). Although 52% of women were judged as infected by at least one of the three criteria, only 4% were infected by using all three criteria. The prevalence of infection was 23% if cytopathology alone was excluded as evidence of HPV infection. These results indicate the difficulty in an accurate estimation of the prevalence of HPV infections, even in a high-risk population.