gebhart/patrepeval huggingface dataset:
Hierarchical self-assembly of chiral rod-like molecules as a model for peptide β-sheet tapes, ribbons, fibrils, and fibers (2001)

A generic statistical mechanical model is presented for the self-assembly of chiral rod-like units, such as beta-sheet-forming peptides, into helical tapes, which with increasing concentration associate into twisted ribbons (double tapes), fibrils (twisted stacks of ribbons), and fibers (entwined fibrils). The finite fibril width and helicity is shown to stem from a competition between the free energy gain from attraction between ribbons and the penalty because of elastic distortion of the intrinsically twisted ribbons on incorporation into a growing fibril. Fibers are stabilized similarly. The behavior of two rationally designed 11-aa residue peptides, P(11)-I and P(11)-II, is illustrative of the proposed scheme. P(11)-I and P(11)-II are designed to adopt the beta-strand conformation and to self-assemble in one dimension to form antiparallel beta-sheet tapes, ribbons, fibrils, and fibers in well-defined solution conditions. The energetic parameters governing self-assembly have been estimated from the experimental data using the model. The 8-nm-wide fibrils consist of eight tapes, are extremely robust (scission energy approximately 200 k(B)T), and sufficiently rigid (persistence length l(fibril) approximately 20-70 microm) to form nematic solutions at peptide concentration c approximately 0.9 mM (volume fraction approximately 0.0009 vol/vol), which convert to self-supporting nematic gels at c > 4 mM. More generally, these observations provide a new insight into the generic self-assembling properties of beta-sheet-forming peptides and shed new light on the factors governing the structures and stability of pathological amyloid fibrils in vivo. The model also provides a prescription of routes to novel macromolecules based on a variety of self-assembling chiral units, and protocols for extraction of the associated energy changes.
Pulling Teeth: Striking for the Check-Off in the Halifax Shipyards, 1944 (1989)

In 1937 nova SCOTIA CREATED A legislative precedent in the field of Canadian labour relations. For the first time a provincial Trade Union Act gave organized workers the right to have union dues automatically deducted from their paycheques, a procedure known as the check-off.1 Yet many employers continued actively to oppose principles of union security. In 1944, Halifax Shipyards Limited, a shipbuilding subsidiary of the Montreal-based Dominion Coal and Steel Company, challenged the legality of the check-off, triggering a month-long walkout of 3,000 workers at yards in Halifax and Dartmouth. During the strike, an embattled Local No. 1, Industrial Union of Marine and Shipbuilding Workers of Canada (Canadian Congress of Labour), overcame worker apathy and federal government indifference to win a Nova Scotia Supreme Court decision upholding its claim to the check-off. Until this landmark ruling in early 1945, union security in Nova Scotia as stipulated in the Trade Union Act remained a hollow promise. Case studies of labour disputes from this period are surprisingly rare given the high frequency and vehemence of wartime strikes.2 Although Laurel Sefton MacDowell's study of the 1941-2 Kirkland Lake gold miners' strike shows how utterly ruthless business and government could be in resisting union recognition, those affected at Kirkland Lake represented a small group of workers in one of the few economic sectors that actually curtailed its wartime operations.3 Most
Purification of an outer capsid glycoprotein of neonatal calf diarrhea virus and preparation of its antisera (1983)

An outer capsid glycoprotein, VP 7, was purified from a bovine rotavirus, neonatal calf diarrhea virus, by isoelectric focusing in glycerol gradients after disruption of the outer capsid. Its isoelectric point was found to be about 4.5. Guinea pigs were immunized with this VP 7 preparation. The antisera possessed both neutralizing and hemagglutination-inhibiting activities as well as complement-fixing activity, suggesting that VP 7 is a protein involved in hemagglutination and initiation of infection. When these antisera were reacted with a simian rotavirus, their antibody titers were low by hemagglutination-inhibiting and complement-fixing assays, but one serum neutralized the simian rotavirus as efficiently as it did homologous neonatal calf diarrhea virus.
FRIEDREICH'S ATAXIA: A CLINICAL AND GENETIC STUDY OF 90 FAMILIES WITH AN ANALYSIS OF EARLY DIAGNOSTIC CRITERIA AND INTRAFAMILIAL CLUSTERING OF CLINICAL FEATURES (1981)

The clinical features of 115 patients from 90 families with Friedreich's ataxia are described. Onset of symptoms was before the age of 25 (mean 10.52) years in all the index cases. An analysis of early cases suggested that limb and truncal ataxia and absent tendon reflexes in the legs were the only consistent diagnostic criteria within five years of presentation. Dysarthria, signs of pyramidal tract dysfunction in the legs and loss of joint position and vibration sense are not necessarily present during the first five years of symptoms, but appear to develop eventually in all cases. Scoliosis and ECG evidence of cardiomyopathy were found in over two-thirds of the patients studied; pes cavus, distal amyotrophy, optic atrophy, nystagmus and deafness were all less frequent. The disorder was gradually progressive in all cases. The mean age of losing the ability to walk was 25 years; 95 per cent were chair-bound by the age of 44 years. About 10 per cent of the patients had diabetes mellitus which was controlled by oral hypoglycaemic drugs in one quarter. Diabetes appeared to be associated with a higher incidence of optic atrophy and deafness. Diabetes also clustered within sibships; the risk of an individual with Friedreich's ataxia developing diabetes if an affected sib has it is over 40 per cent. Similarly, cardiomyopathy ran true within affected members of the same sibship, but there were instances of discordance which suggest that the development of the non-neurological features of Friedreich's ataxia may be controlled by modifying genes rather than heterogeneity of the main gene. Segregation analysis and an increased consanguinity rate amongst parents of patients (5.55 per cent) confirmed that this disorder is of autosomal recessive inheritance. A study of 101 first degree relatives of the patients with Friedreich's ataxia failed to demonstrate any neurological or electrocardiographic abnormalities which could be ascribed to the heterozygous state.
Demonstration That CFTR Is a Chloride Channel by Alteration of Its Anion Selectivity (1991)

Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3',5'-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide greater than chloride greater than iodide greater than fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide greater than bromide greater than chloride greater than fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.
Randomized Multicenter Phase II Trial of a Biweekly Regimen of Fluorouracil and Leucovorin (LV5FU2), LV5FU2 Plus Cisplatin, or LV5FU2 Plus Irinotecan in Patients With Previously Untreated Metastatic Gastric Cancer: A Fédération Francophone de Cancérologie Digestive Group Study—FFCD 9803 (2004)

Of the three regimens tested, the combination of LV5FU2-irinotecan is the most promising and will be assessed in a phase III trial.
Fhit-nucleotide Specificity Probed with Novel Fluorescent and Fluorogenic Substrates (2000)

Fhit, a member of the histidine triad superfamily of nucleotide-binding proteins, binds and cleaves diadenosine polyphosphates and functions as a tumor suppressor in human epithelial cancers. Function of Fhit in tumor suppression does not require diadenosine polyphosphate cleavage but correlates with the ability to form substrate complexes. As diadenosine polyphosphates are at lower cellular concentrations than mononucleotides, we sought to quantify interactions between Fhit and competitive inhibitors with the use of diadenosine polyphosphate analogs containing fluorophores in place of one nucleoside. Appp-S-(7-diethylamino-4-methyl-3-(4-succinimidylphenyl)) coumarin (ApppAMC), Appp-S-(4-4-difluoro-5,7-dimethyl-4-bora-3a, 4a-diaza-s-indacine-3-yl) methylaminoacetyl (ApppBODIPY), and GpppBODIPY, synthesized in high yield, are effective Fhit substrates, producing AMP or GMP plus fluorophore diphosphates. GpppBODIPY cleavage is accompanied by a 5.4-fold increase in fluorescence because BODIPY fluorescence is quenched by stacking with guanine. Titration of unlabeled diadenosine polyphosphates, inorganic pyrophosphate, mononucleotides, and inorganic phosphate into fluorescent assays provided values of K(m) and K(I) as competitive inhibitors. The data indicate that Fhit discriminates between good substrates via k(cat) and against cellular competitors in equilibrium binding terms. Surprisingly, pyrophosphate competes better than purine mononucleotides.
mGlu5 receptor antagonists and their therapeutic potential (2008)

Background: Glutamate mediates its effects via ionotropic and metabotropic glutamate (mGlu) receptors. mGlu receptors are G protein-coupled receptors that are classified into three clusters, group I-III. This review focuses on the mGlu5 receptors of group I. mGlu5 receptors are highly expressed in limbic brain regions and are located postsynaptically. Objective: Following the discovery of the prototypical negative allosteric modulator MPEP, the therapeutic potential of mGlu5 receptors has been steadily explored and expanded. This review highlights present developments in drug discovery and the therapeutic potential of negative allosteric modulators. Methods: Material evaluated ranged from patents to published literature, but also included information that is available from public-accessible websites. Results/conclusion: Based on the wide and consistent effects of prototypical antagonists, such as MPEP, it is concluded that mGlu5 receptor antagonists have treatment potential for both peripheral and central nervous system disorders ranging from psychiatric, neurological to neuromuscular, including illnesses with no apparent nervous system link, such as cancer.
A protective role of 1,25-dihydroxyvitamin D3 in chemically induced rat colon carcinogenesis (1992)

The intriguing observation has been made that 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] receptors are present in tissues not involved in calcium homeostasis and that 1,25(OH)2D3 exerts an antiproliferative, differentiation-promoting action in a variety of cancer cell lines, including cells of the large intestine. It was therefore deemed of interest to study 1,25(OH)2D3 expression and biological activity in a murine model of colon carcinogenesis. Colon carcinogenesis was induced in male rats by the sequential administration of 1,2-dimethylhydrazine dihydrochloride (DMH). Levels and binding characteristics of 1,25(OH)2D3 receptors were assessed in control and DMH-treated rat colonic mucosal high-speed supernatants. In concurrent studies, 1,25(OH)2D3 was administered (s.c., 400 ng/rat) prior to, together with and after DMH challenge and the activity of ornithine decarboxylase (ODC), a growth-related DMH-induced enzyme, was determined in colonic cytosols. Serum Ca2+ levels were measured concurrently. Rats submitted to identical treatment schedules were killed 10 weeks after termination of DMH administration and the whole colon was opened and examined for tumors. The results show that (i) rat colonic mucosa possesses a single class of high-affinity 1,25(OH)2D3 receptors; (ii) DMH administration provokes a marked reduction (50%) in 1,25(OH)2D3 binding sites without affecting Kd values; (iii) DMH administered concurrently with 1,25(OH)2D3 suppressed the vitamin D-induced hypercalcemia and restored serum Ca2+ concentrations to basal levels; and (iv) 1,25(OH)2D3 delivered prior to DMH challenge obliterated the typical DMH-induced early colonic ODC activity peak and markedly reduced (50%) the number of colon adenocarcinomas. The present findings indicate that a colon-specific potent carcinogen interferes with the biological expression of 1,25(OH)2D3 and that vitamin D administered prior to a carcinogenic insult is able to reduce significantly the incidence of colon tumors, presumably acting as an antiproliferative or differentiation-promoting agent.
Non-alcoholic fatty liver disease: a brief review (2004)

The term 'non-alcoholic fatty liver disease' (NAFLD) includes cases with steatosis alone and those with non-alcoholic steatohepatitis (NASH). Usually there are no signs or symptoms, sometimes fatigue or pain, and apart from hepatomegaly the condition is revealed by abnormal liver biochemistry or by abdominal ultrasound. Most cases are associated with overweight or diabetes. Liver enzymes are usually elevated, especially GGT, ASAT and ALAT. Other conditions, including alcohol abuse and autoimmune hepatitis, have to be excluded. The diagnosis of steatosis can be made with ultrasound or CT scan. A liver biopsy is often needed to exclude other disease and to assess inflammation and fibrosis. Cirrhosis can develop. NAFLD is usually caused by two 'hits': the 'first hit' is peripheral insulin resistance, causing steatosis. The 'second hit' is caused by reactive oxygen species, inducing vicious cycles leading to inflammation. Weight loss, metformin or thiazolidinediones can improve NAFLD by increasing insulin sensitivity. Radical scavengers such as vitamin E, betaine and perhaps also urodeoxycholic acid may improve the hepatitis component. Further studies on treatment are needed.
Improved Semantic Parsers For If-Then Statements (2016)

Digital personal assistants are becoming both more common and more useful. The major NLP challenge for personal assistants is machine understanding: translating natural language user commands into an executable representation. This paper focuses on understanding rules written as If-Then statements, though the techniques should be portable to other semantic parsing tasks. We view understanding as structure prediction and show improved models using both conventional techniques and neural network models. We also discuss various ways to improve generalization and reduce overfitting: synthetic training data from paraphrase, grammar combinations, feature selection and ensembles of multiple systems. An ensemble of these techniques achieves a new state of the art result with 8% accuracy improvement.
ChemInform Abstract: The Heterolytic and the Homolytic Cleavage of the Oxygen‐Nitrogen Bond in O,N‐Diacylarylhydroxylamines. (1988)

Abstract The kinetics of the thermolysis of the two O,N‐diacylhydroxylamines (Ia), (Ib) in different solvents and at different temp. leading to the respective products (II) + (III) or (IV) are studied.
A Potential Role for Dendritic Cell/Macrophage-Expressing DPP4 in Obesity-Induced Visceral Inflammation (2012)

Dipeptidyl peptidase-4 (DDP4) inhibitors target the enzymatic degradation of incretin peptides and represent a major advance in the treatment of type 2 diabetes. DPP4 has a number of nonenzymatic functions that involve its interaction with adenosine deaminase (ADA) and other extracellular matrix proteins. Here, we assessed the nonenzymatic role of DPP4 in regulating dendritic cell (DC)/macrophage-mediated adipose inflammation in obesity. Both obese humans and rodents demonstrated increased levels of DPP4 expression in DC/macrophage cell populations from visceral adipose tissue (VAT). The DPP4 expression increased during monocyte differentiation to DC/macrophages and with lipopolysaccharide (LPS)-induced activation of DC/macrophages. The DPP4 colocalized with membrane-bound ADA on human DCs and enhanced the ability of the latter to stimulate T-cell proliferation. The DPP4 interaction with ADA in human DC/macrophages was competitively inhibited by the addition of exogenous soluble DPP4. Knockdown of DPP4 in human DCs, but not pharmacologic inhibition of their enzymatic function, significantly attenuated the ability to activate T cells without influencing its capacity to secrete proinflammatory cytokines. The nonenzymatic function of DPP4 on DC may play a role in potentiation of inflammation in obesity by interacting with ADA. These findings suggest a novel role for the paracrine regulation of inflammation in adipose tissue by DPP4.
Sequence comparison between the phosphoprotein mRNAs of human and bovine respiratory syncytial viruses identifies a divergent domain in the predicted protein (1992)

The nucleotide and deduced amino acid sequences of the phosphoprotein (P) mRNA of bovine respiratory syncytial virus (BRSV) strain A51908 have been determined. The P mRNA is 860 nucleotides long with a single large open reading frame and the encoded polypeptide is 241 amino acids long. Comparison with the corresponding sequences of human respiratory syncytial virus (HRSV) subgroups A and B revealed 72 to 74% identity at the nucleotide level, and 81% at the amino acid level. The P protein contains a single divergent domain (37% amino acid identity) flanked by highly conserved domains (87% amino acid identity). The 3' end non-coding region is 47 nucleotides shorter than the corresponding region of HRSV. Comparison of the P mRNA sequences of two strains of BRSV (A51908 and FS-1) showed that there was extensive sequence identity at both the nucleotide (97%) and amino acid (97.9%) levels.
CATALYST GOES VIRAL (2010)

RETURN TO ISSUEPREVNewsNEXTCATALYST GOES VIRALNANOTECHNOLOGY: Material grown on a virus template performs better than catalysts grown conventionallyBETHANY HALFORDCite this: Chem. Eng. News 2010, 88, 24, 13Publication Date (Print):June 14, 2010Publication History Published online27 March 2011Published inissue 14 June 2010https://doi.org/10.1021/cen-v088n024.p013Copyright © 2010 AMERICAN CHEMICAL SOCIETYArticle Views5Altmetric-Citations-LEARN 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 (510 KB) SUBJECTS:Catalysts,Nanowires,Viruses Get e-Alerts
Rat retinal pigment epithelial cells express an inducible form of nitric oxide synthase and produce nitric oxide in response to inflammatory cytokines and activated T cells. (1994)

In this report we show that rat retinal pigment epithelial (RPE) cells express an inducible form of nitric oxide synthase (iNOS) and secrete high levels of nitric oxide (NO.) when co-cultured with activated lymphocytes. We have previously shown that cultured rat RPE cells suppress syngeneic lymphocyte proliferation, an effect attributed to prostaglandin E2 (PGE2) secretion by the RPE cells. However supernatants from such co-cultures were also found to contain high levels of nitrite (NO2-), the stable end-product of NO. synthesis. RPE cell secretion of NO. was stimulated by the cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), an effect enhanced by endotoxin [lipopolysaccharide (LPS)], reduced by the competitive inhibitor of L-arginine metabolism, NG-monomethyl-L-arginine (L-NMMA) and inhibited by cycloheximide. These effects were dose dependent. Using reverse transcription (RT)/PCR a product of 1398 bp was amplified which showed sequence identity with iNOS cloned from rat vascular smooth muscle. Northern blot analysis of total RNA extracted from rat RPE before and after cytokine stimulation showed induction of a 4.5 kb (kilobase) transcript which hybridized with a 1398 bp (base pair) polymerase chain reaction (PCR)-generated cDNA probe derived from the sequence of rat RPE cell iNOS. These results indicate RPE cells express an inducible form of nitric oxide synthase (NOS) and that high levels of NO. may be produced locally in the eye by the RPE in the presence of activated lymphocytes. Given the cytostatic and cytotoxic properties of this molecule, NO. may play an important role as an inducible mediator of immunosuppressive mechanisms within the microenvironment of the eye at the site of lymphocyte activation.
The Diagnosis of Strep Throat in Adults in the Emergency Room (1981)

Adult patients who presented to an urban emergency room complaining of a sore throat had cultures and clinical information recorded. Models were constructed, using logistic regression analysis, of both a positive culture for Group A beta streptococcus and a positive guess by a resident. The model of a positive culture consisted of four variables--tonsillar exudates, swollen tender anterior cervical nodes, lack of a cough, and history of fever. Patients with all 4 variables had a 56% probability of a positive culture; 3 variables, 32%; 2 variables, 15%; 1 variable, 6.5%; and 0 variables, 2.5%. The model of a positive guess by a resident demonstrated an over-reliance on physical exam and an underuse of history. The model of a positive culture allows stratification of patients to assist clinicians in the management strategies.
Electrical Remodeling of the Atria in Congestive Heart Failure (2003)

Atrial remodeling due to CHF is characterized by structural changes, abnormalities of conduction, sinus node dysfunction, and increased refractoriness. These abnormalities may be responsible in part for the increased propensity for AF in CHF.