gebhart/patrepeval huggingface dataset:
Polymorphonuclear leukocyte function triggered through the high affinity Fc receptor for monomeric IgG. (1987)

While it is extensively documented that gamma-interferon (IFN-gamma) is a potent stimulator of cells of the monocyte lineage, relatively little is known about its effects on granulocytes. We and others have found that immunoglobulin G (IgG) antibody-dependent cell cytotoxicity (ADCC) by polymorphonuclear cells (PMN) is significantly enhanced in a dose-dependent fashion by 16 hours incubation with recombinant IFN-gamma, resulting in 2- to 16-fold increases in ADCC. Incubation of PMN with lipopolysaccharide for 16 hours did not augment ADCC. Since IFN-gamma enhancement of ADCC is accompanied by increased expression of Fc receptors, we used monoclonal antibodies to compare control and IFN-gamma treated PMN for expression of the high affinity Fc receptor for monomeric IgG1 (FcgRI) and the PMN receptor for polymeric IgG (FcgR1o). Freshly isolated PMN or PMN cultured without IFN-gamma expressed FcgR1o but not detectable quantities of FcgRI. However, while FcgR1o were not increased on IFN-gamma-treated PMN, these cells expressed moderate amounts of FcgRI. To determine whether FcgRI contributed to PMN function, heteroantibodies consisting of Fab 3G8 or Fab 32 linked to Fab anti-target antibody were produced. ADCC of untreated PMN was promoted only by Fab 3G8 heteroantibody, whereas IFN-gamma-treated PMN killed through both FAB 3G8 and Fab 32 heteroantibodies. Thus, FcgRI can be induced on PMN by IFN-gamma, can mediate cytotoxicity by these cells, and probably accounts for the IFN-gamma stimulation of ADCC.
Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth (2005)

Colorectal carcinoma (CRC) is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRC-derived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.
Absorption and Excretion of Drugs. XXX. Absorption of Barbituric Acid Derivatives from Rat Stomach. (1967)

The absorption of the unionized forms of barbituric acid derivatives from rat stomach was found to be a first order process and varied with the differences in the chemical structures. N-methylation and O-S displacement markedly affected the gastric absorption. The mediated physicochemical factor was partition coefficient to organic solvent. Effect of pH of drug solution also influenced the absorption of especially readily absorbed derivatives. In respect to ionized forms, the similarity in rate constants was observed among all series of derivatives, and the mechanism involved was assumed to be a physical diffusion through pores. From these observations, it was concluded that all types of barbituric acid derivatives are absorbed from rat stomach by a relatively simple physical process, which is in good agreement with pH-partition process suggested by Brodie, et al.
Six novel deleterious and three neutral mutations in the gene encoding the alpha-subunit of hexosaminidase A in non-Jewish individuals. (1992)

Initial investigations demonstrated that only 3/34 "Tay-Sachs chromosomes" in 22 unrelated, non-Jewish patients or carriers of some form of GM2-gangliosidosis (7 black and 15 non-Jewish Caucasian) had either of the two mutations commonly found in the Jewish population. To determine the nature and incidence of the alterations in this non-Jewish population we have utilized PCR, single-strand conformation polymorphism analysis and sequencing to detect new mutations in genomic DNA. Fourteen primer sets have been utilized to analyze 80% of the coding region and 23/26 splice sites of the gene coding for the alpha chain of hexosaminidase A. Presumed deleterious mutations were discovered in 17/34 chromosomes believed to be carrying a beta-hexosaminidase A alpha-subunit gene mutation. Ten had abnormalities which have been described previously. In the remaining 24 Tay-Sachs disease alleles, six novel mutations predicted to be deleterious were discovered. These include two small deletions (a single-base frameshift and a three-base deletion removing an amino acid), two different nonsense mutations, an initiation codon mutation (ATG----GTG), and a missense mutation (Arg499Cys) in a highly conserved residue. In addition, three presumed nondeleterious mutations were found.
Effector Memory T Cells, Early Metastasis, and Survival in Colorectal Cancer (2005)

The role of tumor-infiltrating immune cells in the early metastatic invasion of colorectal cancer is unknown.
Cystic fibrosis transmembrane conductance regulator protein repair as a therapeutic strategy in cystic fibrosis (2010)

An improved understanding of the molecular mechanisms underlying the basic genetic defect in cystic fibrosis have led to new treatment strategies to repair the mutant protein.
Koilocytes indicate a role for human papilloma virus in breast cancer (2009)

As koilocytes are known to be the precursors of some HPV-associated cervical cancer, it follows that HPVs may be causally associated with breast cancer.
Mathematical modeling of retinal birefringence scanning (1999)

Retinal birefringence scanning (RBS) is a new technique that is used to detect the fixation of the eye remotely and noninvasively. The method is based on analysis of polarization changes induced by the retina. In this study, the principles of RBS were mathematically modeled to facilitate a better understanding of the origins of the signals obtained. Stokes vector analysis and Mueller matrix multiplication were augmented with Poincaré sphere representation. The cornea was modeled as a linear retarder. The foveal area was modeled as a radially symmetric birefringent medium. The model accurately predicted the frequency and phase of RBS signals obtained during central and paracentral fixation. The signal that indicates central fixation during RBS likely results from a combination of the radial birefringence of the Henle fibers and the overlying corneal birefringence.
ANN based current control of a VSI fed AC machine using line coordinates (2005)

This paper presents an implementation of a continually on-line trained artificial neural network (COT-ANN) for an induction machine's current loop control using a DSP based system. A reduction in the computation time compared to previous implementations makes the system a viable alternative to standard PI controlled current loops. Some simulations are presented and the results are later confirmed by experimental tests.
Rheological characterization of the gel point: a new interpretation (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRheological characterization of the gel point: a new interpretationRene Muller, Eric Gerard, Pascal Dugand, Paul Rempp, and Yves GnanouCite this: Macromolecules 1991, 24, 6, 1321–1326Publication Date (Print):March 1, 1991Publication History Published online1 May 2002Published inissue 1 March 1991https://pubs.acs.org/doi/10.1021/ma00006a017https://doi.org/10.1021/ma00006a017research-articleACS PublicationsRequest reuse permissionsArticle Views2201Altmetric-Citations120LEARN 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
The extended active site of guinea pig liver transglutaminase. (1975)

The catalytic activities of guinea pig liver transglutaminase toward glutamine-containing peptide derivatives of three series have been studied. These series include: (a) formylheptapeptides of the basic structure, HCO-GLY3-L-Gln-Gly3. A single L-leucine residue was systematically substituted for glycine at a different position in each peptide; (b) formyltripeptides of the basic structure, HCO-Gly-L-Gln-Gly. L-Leucine was substituted for glycine in each position and in both positions; (c) various N-acyl derivatives of the dipeptide, L-Gln-Gly. Comparison of the values of the kinetic constants for methylamine incorporation and for hydroxylamine incorporation with the peptide derivatives shows that the length of the peptide chain has a pronounced influence on catalysis, as does the position of the leucine residue in the longer chain peptide derivatives. The kcat/Km(app) values for each substrate calculated from data for methylamine incorporation and from those for hydroxylamine incorporation were found to be in good agreement. However, both the observed maximum velocity and the apparent Michaelis constant for each peptide derivative were significantly larger for hydroxylamine incorporation than for methylamine incorporation. Interpretation of these findings as evidence for a normal catalytic mechanism for each amine incorporation reaction and for the limiting nature of deacylation to methylamine is discussed. Two observations caution against such an interpretation. These are the significantly higher inhibitor constants found fo formylhexaglycine and for several other competitive inhibitors in the hydroxylamine incorporation reaction, and earlier findings of higher turnover values with hyroxylamine in cases were acylation appears to be limiting for methylamine incorporation. Methods of preparation, supporting analytical data and properties of the peptide intermediates, the peptides, and their derivatives used in this study are presented in the miniprint supplement immediately following this paper.
Decreased membrane complement regulators in the retinal pigmented epithelium contributes to age‐related macular degeneration (2012)

Dysregulated complement is thought to play a central role in age-related macular degeneration (AMD) pathogenesis, but the specific mechanisms have yet to be determined. In maculae of AMD specimens, we found that the complement regulatory protein, CD59, was increased in regions of uninvolved retinal pigmented epithelium (RPE) of early AMD, but decreased in the RPE overlying drusen and in geographic atrophy, an advanced form of AMD. While CD46 immunostaining was basolaterally distributed in the RPE of unaffected controls, it was decreased in diseased areas of early AMD samples. Since oxidized low-density lipoproteins (oxLDL) collect in drusen of AMD and are a known complement trigger, we treated ARPE-19 cells with oxLDL and found that cellular CD46 and CD59 proteins were decreased by 2.9- and nine-fold (p < 0.01), respectively. OxLDLs increased complement factor B mRNA and Bb protein, but not factor D, I or H. OxLDLs increased C3b, but not C3a, C5 or C5b-9. C5b-9 was increased by 27% (p < 0.01) when the medium was supplemented with human serum, which was sufficient to induce poly(ADP-ribose) polymerase cleavage, a marker of apoptosis. The decreased levels of CD46 and CD59 were in part explained by their release in exosomal and apoptotic membranous particles. In addition, CD59 was partially degraded through activation of IRE1α. Collectively, these results suggest that a combination of impaired complement regulators results in inadequately controlled complement by the RPE in AMD that induces RPE damage.
Isolation, characterization, and physical mapping of a pseudorabies virus mutant containing antigenically altered gp50 (1984)

A pseudorabies virus variant ( mar197 -1) containing a mutation in a viral glycoprotein with a molecular weight of 50,000 ( gp50 ) was isolated by selecting for resistance to a neurtralizing monoclonal antibody ( MCA50 -1) directed against gp50 . This mutant was completely resistant to neutralization with MCA50 -1 in the presence or absence of complement, and was therefore defined as a mar (monoclonal-antibody-resistant) mutant. The mutation did not affect neutralization with polyvalent immune serum. The mar197 -1 mutant synthesized and processed gp50 normally, but the mutation prevented the binding and immunoprecipitation of gp50 by MCA50 -1. Thus, the mutation was within the structural portion of the gp50 gene affecting the epitope of the monoclonal antibody. The mutation was mapped by marker rescue with cloned pseudorabies restriction enzyme fragments to the short region of the pseudorabies genome between 0.813 and 0.832 map units. This is equivalent to a 2.1-kilobase-pair region.
2D Differential In-gel Electrophoresis for the Identification of Esophageal Scans Cell Cancer-specific Protein Markers (2002)

The reproducibility of conventional two-dimensional (2D) gel electrophoresis can be improved using differential in-gel electrophoresis (DIGE), a new emerging technology for proteomic analysis. In DIGE, two pools of proteins are labeled with 1-(5-carboxypentyl)-1'-propylindocarbocyanine halide (Cy3) N-hydroxy-succinimidyl ester and 1-(5-carboxypentyl)-1'-methylindodi-carbocyanine halide (Cy5) N-hydroxysuccinimidyl ester fluorescent dyes, respectively. The labeled proteins are mixed and separated in the same 2D gel. 2D DIGE was applied to quantify the differences in protein expression between laser capture microdissection-procured esophageal carcinoma cells and normal epithelial cells and to define cancer-specific and normal-specific protein markers. Analysis of the 2D images from protein lysates of approximately 250,000 cancer cells and normal cells identified 1038 protein spots in cancer cell lysates and 1088 protein spots in normal cell lysates. Of the detected proteins, 58 spots were up-regulated by >3-fold and 107 were down-regulated by >3-fold in cancer cells. In addition to previously identified down-regulated protein annexin I, tumor rejection antigen (gp96) was found up-regulated in esophageal squamous cell cancer. Global quantification of protein expression between laser capture-microdissected patient-matched cancer cells and normal cells using 2D DIGE in combination with mass spectrometry is a powerful tool for the molecular characterization of cancer progression and identification of cancer-specific protein markers.
Rates of imine formation from acetone and some N,N-dimethyl vicinal diamines (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRates of imine formation from acetone and some N,N-dimethyl vicinal diaminesJack Hine and Yueting ChouCite this: J. Org. Chem. 1981, 46, 4, 649–652Publication Date (Print):February 1, 1981Publication History Published online1 May 2002Published inissue 1 February 1981https://pubs.acs.org/doi/10.1021/jo00317a001https://doi.org/10.1021/jo00317a001research-articleACS PublicationsRequest reuse permissionsArticle Views502Altmetric-Citations25LEARN 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
Linagliptin: A thorough Characterization beyond Its Clinical Efficacy (2013)

Linagliptin, one of the five dipeptidyl peptidase-4 inhibitors available, has recently entered the market both in the US and in most European countries for treatment of type 2 diabetes mellitus. It presents a xanthine-based structure, and is characterized by unique pharmacokinetics, with non-linear profile, long terminal half-life allowing prolonged exposure to the drug. It is eliminated predominately through the intestinal tract and only minimally into urine, so that it can be administered, without any dose adjustment, in conditions of renal impairment. Linagliptin is effective in modifying all parameters of hyperglycemia either in monotherapy, or as add-on therapy, together with metformin or a sulfonylurea. It also exhibits a good tolerability profile with few side effects, absence (when used in monotherapy), or low risk (when in combination with a sulfonylurea) of hypoglycemia. More importantly it has a weight neutral effect. A comprehensive report of the literature on linagliptin is provided, paying attention in particular to preclinical studies, interactions with other drugs, safety and tolerability, and results obtained in animal models that highlight properties of linagliptin suggestive of potential additional uses. Particularly promising appear the data demonstrating a positive effect of linagliptin on metabolic dysfunction and renal and/or cardiovascular damage together with more recently reported effects of linagliptin on tissue repair and neuroprotection.
Severity of gliosis in Pick's disease and frontotemporal lobar degeneration: tau-positive glia differentiate these disorders (2003)

Frontotemporal dementia is a term used to characterize diverse neuropathological conditions that can present with the same clinical phenotype. Five different neuropathologies underlie this disorder. However, consistent frontal and/or temporal neuronal loss and gliosis characterize all cases, the majority having no obvious pathological inclusions. Because neuronal loss and gliosis are consistent features across all cases, the present study aimed to determine the relationship between neuronal loss, gliosis and, for cases with abnormal tau inclusions, intracellular tau deposition. Formalin-fixed brain specimens from sporadic cases with frontotemporal dementia (eight with tau-positive Pick bodies, five with frontotemporal lobar degeneration without inclusions) were compared with those from non-diseased controls (n = 5). Brain specimens were cut into 3 mm coronal slices for evaluation and tissue samples from the superior frontal gyrus were taken for microscopic analysis. Immuno histochemistry for glia-specific proteins (astrocytic glial fibrillary acidic protein and microglial major histocompatibility complex II) and different tau epitopes was performed on 50 microm free-floating sections. Gross patterns of brain atrophy were analysed and upper and lower layer pyramidal neurons and glial cell numbers were quantified. A disease severity scheme was devised using the degree of gross macroscopic frontal and temporal atrophy to establish the relationship between the gliosis and neurodegeneration. In this small sample, the patterns of gross atrophy could be grouped reliably into four stages of severity. These stages were the same across disease groups and correlated with volume- corrected pyramidal neuron densities. In cases with Pick bodies, disease stage also correlated with duration, providing further evidence that these stages represent the progression of degeneration in this limited sample. Whereas there were, on average, many more reactive astrocytes in the cases with Pick bodies than in those with frontotemporal lobar atrophy, there was significant overlap between cases in the degree of astrocytosis. However, a large proportion of the astrocytes in Pick's disease displayed phosphorylated tau immunoreactivity, whereas no tau-positive astrocytes were found in frontotemporal lobar degeneration. The pattern and degree of microglia activation were similar in all the dementia cases analysed, with considerably more activated microglia accumulating in white matter. In this small sample, the abundance of white matter microglia at early disease stages suggests a prominent role for this cell type in the neurodegenerative process. In frontotemporal lobar degeneration, a significant proportion of the activated white matter microglia were tau-2-immunoreactive, suggesting direct involvement in axonal degeneration, possibly via immune processes.
Decreased and aberrant nuclear lamin expression in gastrointestinal tract neoplasms (1999)

Reduced expression of nuclear lamins, sometimes together with aberrant, cytoplasmic immunoreactivity is common in gastrointestinal neoplasms. Altered lamin expression may be a biomarker of malignancy in the gastrointestinal tract.
Coronary Artery Bypass Grafting in Patients with Left Ventricular Dysfunction (2006)

Although patients with LV dysfunction had higher mortality and morbidity, CABG could be done in these high-risk patients with acceptable results.
Deuterium Magic Angle Spinning Studies of Substrates Bound to Cytochrome P450 (1999)

We report solid-state deuterium magic angle spinning NMR spectra of perdeuterated adamantane bound to the active site of microcrystalline cytochrome P450cam (CP450cam) in its resting state. CP450cam contains a high-spin ferric (Fe3+) heme in the resting state; the isotropic shift was displaced from the diamagnetic value and varied with temperature consistent with Curie-law dependence. A nondeuterated competitive tighter binding ligand, camphor, was used to displace the adamantane-bound species. This addition resulted in the disappearance of the hyperfine-shifted signal associated with a perdeuterated adamantane bound to CP450cam, while signals presumably associated with adamantane bound to other cavities persisted. We simulated the deuterium spinning side-band intensities for the enzyme-bound species using dipolar hyperfine coupling as the only anisotropic interaction; the deuterium quadrupolar interaction was apparently averaged due to a fast high-symmetry motion. These data provide direct support for previous proposals that substrates are conformationally mobile on the time scale of enzymatic turnover. The simulations suggested that the adamantane binds with an average metal-deuterium distance of 6.2 (+/-0.2) A, corresponding to a dipolar coupling constant of 6.5 (+/-0.5) kHz.