gebhart/patrepeval huggingface dataset:
Maternal serum levels of type I and type III procollagen peptides in pre-eclamptic pregnancy (2001)

Objective : To compare maternal serum levels of two markers of collagen synthesis, procollagen I carboxy-terminal peptide (PICP) and procollagen III amino-terminal peptide (PIIINP), in patients with pre-eclampsia and in controls. Methods : PICP and PIIINP were measured by radioimmunoassay in maternal serum samples from patients diagnosed with pre-eclampsia at 32 weeks' gestation or later and in controls from the same period of gestation. For PICP, 37 cases and 36 controls were studied; for PIIINP, 12 cases and 19 controls were studied. Results : Both PICP and PIIINP levels were significantly elevated in patients with pre-eclampsia. PICP and PIIINP levels were, on average, 20% and 80% higher than in controls, respectively. Conclusions : These results are in agreement with previous findings that maternal serum levels of PICP and PIIINP are mildly elevated in patients with pre-eclampsia. These markers are unlikely to be useful in the prediction of pre-eclampsia.
Orthogonal Self-Assembled Monolayers: Alkanethiols on Gold and Alkane Carboxylic Acids on Alumina (1989)

This work demonstrates the practicality of forming two self-assembled monolayers (SAMs), independently but simultaneously, by adsorption of two different adsorbates from a common solution onto a substrate exposing two different materials at its surface. The experimental procedure and the degree of independence achieved in the resulting SAMs are illustrated by examination of monolayers obtained by adsorption of alkanethiols on gold and alkane carboxylic acids on alumina. This procedure provides a method for modifying the surface characteristics of microlithographically generated patterns and offers a versatile technique for controlling solid-vapor and solid-liquid interfacial properties in systems having patterns with dimensions of the order of 1 micrometer.
Tumor chemosensitivity conferred by inserted herpes thymidine kinase genes: paradigm for a prospective cancer control strategy. (1986)

The lack of highly exploitable biochemical differences between normal tissues and some tumors can theoretically be circumvented by a strategy utilizing gene insertion prophylactically to create tissue mosaicism for drug sensitivity, thereby ensuring that any tumor arising clonally will differ from part of the normal cell population. Elements of the strategy were tested with neoplastic BALB/c murine cell lines bearing the herpes thymidine kinase gene. Exposure to the herpes thymidine kinase-specific substrate 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine ablated the clonogenic potential of the cells in vitro, and administration of this drug to BALB/c mice bearing tumors produced by the cell lines uniformly induced complete regression of the tumors. The observed responses to therapy imply that the strategy may prove valuable when the genetic technology needed for its human implementation becomes available.
Inhibition of the IL-2-inducible tyrosine kinase (Itk) activity: a new concept for the therapy of inflammatory skin diseases (2010)

T-cell-mediated processes play an essential role in the pathogenesis of several inflammatory skin diseases such as atopic dermatitis, allergic contact dermatitis and psoriasis. The aim of this study was to investigate the role of the IL-2-inducible tyrosine kinase (Itk), an enzyme acting downstream of the T-cell receptor (TCR), in T-cell-dependent skin inflammation using three approaches. Itk knockout mice display significantly reduced inflammatory symptoms in mouse models of acute and subacute contact hypersensitivity (CHS) reactions. Systemic administration of a novel small molecule Itk inhibitor, Compound 44, created by chemical optimization of an initial high-throughput screening hit, inhibited Itk's activity with an IC50 in the nanomolar range. Compound 44 substantially reduced proinflammatory immune responses in vitro and in vivo after systemic administration in two acute CHS models. In addition, our data reveal that human Itk, comparable to its murine homologue, is expressed mainly in T cells and is increased in lesional skin from patients with atopic dermatitis and allergic contact dermatitis. Finally, silencing of Itk by RNA interference in primary human T cells efficiently blocks TCR-induced lymphokine secretion. In conclusion, Itk represents an interesting new target for the therapy of T-cell-mediated inflammatory skin diseases.
Classical Major Histocompatibility Complex Class I Molecules in Motoneurons: New Actors at the Neuromuscular Junction (2009)

Major histocompatibility complex (MHC) class I molecules have fundamental functions in the immune system. Recent studies have suggested that these molecules may also have non-immune functions in the nervous system, in particular related to synaptic function and plasticity. Because adult motoneurons express mRNAs for MHC class I molecules, we have examined their subcellular expression pattern in vivo and their role for the synaptic connectivity of these neurons. We observed immunoreactivity for classical MHC class I (Ia) protein in motoneuron somata, but the predominant expression was found in axons and presynaptically at neuromuscular junctions (NMJs). Peripheral nerve lesion induced a strong increase of motoneuron MHC class Ia (H2-K(b)/D(b)) mRNA, indicating a role for MHC class Ia molecules during regeneration. Accordingly, there was an accumulation of MHC class Ia proteins at the cut ends and in growth cones of motor axons after lesion. In K(b-/-)D(b-/-) mice (lacking MHC class Ia molecules), the time course for recovery of grip ability in reinnervated muscles was significantly delayed. Muscles from K(b-/-)D(b-/-) mice displayed an increased density and a disturbed distribution of NMJs and fewer terminal Schwann cells/NMJ compared with wild-type mice. A population of Schwann cells in sciatic nerves expressed the paired Ig receptor B, which binds to MHC class I molecules. These results provide the first evidence that neuronal MHC class Ia molecules are present in motor axons, that they are important for organization of NMJs and motor recovery after nerve lesion, and that their actions may be mediated via Schwann cells.
New Family of Argyrodite Thioantimonate Lithium Superionic Conductors (2019)

We report on a new family of argyrodite lithium superionic conductors, as solid solutions Li<sub>6+<i>x</i></sub>M<sub><i>x</i></sub>Sb<sub>1-<i>x</i></sub>S<sub>5</sub>I (M = Si, Ge, Sn), that exhibit superionic conductivity. These represent the first antimony argyrodites to date. Exploration of the series using a combination of single crystal X-ray and synchrotron/neutron powder diffraction, combined with impedance spectroscopy, reveals that an optimal degree of substitution (<i>x</i>), and substituent induces slight S<sup>2-</sup>/I<sup>-</sup> anion site disorder-but more importantly drives Li<sup>+</sup> cation site disorder. The additional, delocalized Li-ion density is located in new high energy lattice sites that provide intermediate interstitial positions (local minima) for Li<sup>+</sup> diffusion and activate concerted ion migration, leading to a low activation energy of 0.25 eV. Excellent room temperature ionic conductivity of 14.8 mS·cm<sup>-1</sup> is exhibited for cold-pressed pellets-up to 24 mS·cm<sup>-1</sup> for sintered pellets-among the highest values reported to date. This enables all-solid-state battery prototypes that exhibit promising properties. Furthermore, even at -78 °C, suitable bulk ionic conductivity of the electrolyte is retained (0.25 mS·cm<sup>-1</sup>). Selected thioantimonate iodides demonstrate good compatibility with Li metal, sustaining over 1000 h of Li stripping/plating at current densities up to 0.6 mA·cm<sup>-2</sup>. The significantly enhanced Li ion conduction and lowered activation energy barrier with increasing site disorder reveals an important strategy toward the development of superionic conductors.
Molecular heterogeneity of Fc alpha receptors detected by receptor-specific monoclonal antibodies (1992)

Fc alpha receptors (Fc alpha R) were isolated from a human monocytic cell line and used to raise four mAb with receptor specificity. The antibodies were used to identify the types of white blood cells that express Fc alpha R and the molecular heterogeneity of the receptor molecules. Nonpolymorphic epitopes, outside of the Fc alpha-binding site, were recognized only on blood cells of granulocyte and monocyte/macrophage lineages. The molecules identified, both by the antibodies and by the IgA ligand, were glycoproteins ranging in relative molecular mass from 55 to 75 kDa. However, one antibody detected a subpopulation of Fc alpha R molecules characterized by relatively restricted size heterogeneity. A complex glycosylation pattern was revealed by the resolution of discrete 32- and 36-kDa molecular species after removal of N-linked oligosaccharides and by evidence for O-linked carbohydrate moieties on at least a portion of the Fc alpha R molecules. In biosynthetic studies, all four anti-Fc alpha R antibodies and the IgA ligand bound a single 32-kDa core protein present in tunicamycin-treated cells, and the exceptional antibody again recognized molecules with relatively restricted glycosylation in the nontreated cells. These antibodies and native IgA ligands thus provide complementary reagents for definition of the complex structure and function of Fc alpha R in systemic IgA antibody responses.
Documenting and Evaluating Oral Language Development in the Classroom. (1996)

These comments were made by parents discussing the necessity of creating a school-wide program of documenting and evaluating oral language. They articulate two very real concerns common to parents and educators alike: How is oral language valued and evaluated in the classroom? Concerns such as these confirm that it is not enough for teachers to simply expound the virtues of oral language or even to place check marks on report cards. In order to insure that oral language be given its rightful place in the curriculum, teachers must implement validated programs that contain documentation and evaluation.
Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide exchanger (1993)

Hepatocyte growth factor/scatter factor (HGF/SF) induces mitogenesis and cell dissociation upon binding to the protein-tyrosine kinase receptor encoded by the MET proto-oncogene (p190MET). The signal transduction pathways downstream from the receptor activation are largely unknown. We show that HGF/SF activates Ras protein. HGF/SF stimulation of metabolically labeled A549 cells raised the amount of Ras-bound radiolabeled guanine nucleotides by over 5-fold. Furthermore, following HGF/SF stimulation of these cells, 50% of Ras was in the GTP-bound active state. The uptake by Ras of radiolabeled GTP was also increased by 5-fold following HGF/SF stimulation in digitonin-permeabilized A549 cells. Moreover, HGF/SF treatment of A549 cells leads to stimulation of the cytosolic Ras-guanine nucleotide exchange activity, measured as accelerated release of [3H]GDP from purified recombinant Ras protein in vitro, in a dose- and time-dependent manner. Likewise, treatment with the protein-tyrosine kinase inhibitor 3-(1',4'-dihydroxytetralyl)methylene-2-oxindole of GTL-16 cells (featuring a p190MET receptor constitutively active) significantly decreased the cytosolic Ras-guanine nucleotide exchange activity. These data demonstrate that HGF/SF activates Ras protein by shifting the equilibrium toward the GTP-bound state and increases the uptake of guanine nucleotides by Ras, through mechanism(s) including the activation of a Ras-guanine nucleotide exchanger.
MUC1 Glycoforms in Breast Cancer (1996)

A highly immunogenic peptide motif within the tandem repeat domain of MUC1 mucin is assumed to be exposed during development of breast cancer due to altered O-glycosylation. To elucidate the structural aspects of these changes, we have isolated and analysed the integrated or secretory MUC1 glycoforms from carcinoma cell lines or solid tumors and from human milk. The buoyant densities measured in CsCl gradients for MUC1 glycoforms from cancer cells revealed heterogeneity of the physicochemical species and a significant reduction of their carbohydrate contents compared to MUC1 from skim milk. Immunoreactivity patterns of MUC1 glycoforms from tumor or T47D cells exhibited a lack of fucosylated Lewis blood-group-related antigens and the appearance of core-type antigen sialyl(NeuGl)-TF, Gal beta 1-3(NeuGl alpha 2-6)GalNAc. Structural chemistry of MUC1 oligosaccharides demonstrated that the cancer-associated glycoforms carry mainly sialylated trisaccharides NeuAc alpha 2-3Gal Beta 1-3GalNAc or NeuAc alpha 2-6(Gal beta l-3)GalNAc, exhibit a concomitant decrease in the ratio of GlcNAc/GalNAc, a reduction or disappearance of L-fucose, and a partial substitution of N-acetylneuraminic acid by the N-glycolylated variant. On comparison to the secretory MUC1 in human milk, the glycoforms on human milk fat globule membranes showed apparently identical patterns of O-linked oligosaccharides with a preponderance of neutral polylactosamino-glycans. During serum-free cultivation of T47D cells over 4 weeks, the expression of secretory MUC1 glycoforms was inconsistent based on the decreasing contents of sialic acid and on the concomitant increase of immunodetectable TF antigen.
Synthesis and antiinflammatory activity of a series of 2-aroyl-1,1a,2,6b-tetrahydrocycloprop[b]indole-1-carboxylic acids (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and antiinflammatory activity of a series of 2-aroyl-1,1a,2,6b-tetrahydrocycloprop[b]indole-1-carboxylic acidsWilliam J. Welstead Jr., Harold F. Stauffer Jr., and Lawrence F. SancilioCite this: J. Med. Chem. 1974, 17, 5, 544–547Publication Date (Print):May 1, 1974Publication History Published online1 May 2002Published inissue 1 May 1974https://pubs.acs.org/doi/10.1021/jm00251a019https://doi.org/10.1021/jm00251a019research-articleACS PublicationsRequest reuse permissionsArticle Views492Altmetric-Citations42LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Lactobacillus buchneri strain NRRL B-30929 converts a concentrated mixture of xylose and glucose into ethanol and other products (2007)

Lactobacillus buchneri strain NRRL B-30929 was isolated from a fuel ethanol production facility. This heterofermentative, facultative anaerobe can utilize xylose as a sole carbon source and tolerates up to 12% ethanol. Carbohydrate utilization (API, Biomerieux) and Phenotype Microarrays (PM, Biolog) analyses indicated that the strain is able to metabolize a broad spectrum of carbon sources including various monosaccharides (C5 and C6), disaccharides and oligosaccharides, with better rates under anaerobic conditions. In pH-controlled bioreactors, the bacterium consumed xylose and glucose simultaneously at high concentrations (125 g L(-1), pH 6.0). The major fermentation products were lactate (52 g L(-1)), acetate (26 g L(-1)) and ethanol (12 g L(-1)). The strain ferments glucose alone (pH 4.0) into lactate and ethanol with a molar ratio of 1.03:1. This strain will be further explored via genetic engineering for potential applications in biomass conversion.
Epitope Mapping of Broadly Neutralizing HIV-2 Human Monoclonal Antibodies (2012)

Recent studies have shown that natural infection by HIV-2 leads to the elicitation of high titers of broadly neutralizing antibodies (NAbs) against primary HIV-2 strains (T. I. de Silva, et al., J. Virol. 86:930-946, 2012; R. Kong, et al., J. Virol. 86:947-960, 2012; G. Ozkaya Sahin, et al., J. Virol. 86:961-971, 2012). Here, we describe the envelope (Env) binding and neutralization properties of 15 anti-HIV-2 human monoclonal antibodies (MAbs), 14 of which were newly generated from 9 chronically infected subjects. All 15 MAbs bound specifically to HIV-2 gp120 monomers and neutralized heterologous primary virus strains HIV-2(7312A) and HIV-2(ST). Ten of 15 MAbs neutralized a third heterologous primary virus strain, HIV-2(UC1). The median 50% inhibitory concentrations (IC(50)s) for these MAbs were surprisingly low, ranging from 0.007 to 0.028 μg/ml. Competitive Env binding studies revealed three MAb competition groups: CG-I, CG-II, and CG-III. Using peptide scanning, site-directed mutagenesis, chimeric Env constructions, and single-cycle virus neutralization assays, we mapped the epitope of CG-I antibodies to a linear region in variable loop 3 (V3), the epitope of CG-II antibodies to a conformational region centered on the carboxy terminus of V4, and the epitope(s) of CG-III antibodies to conformational regions associated with CD4- and coreceptor-binding sites. HIV-2 Env is thus highly immunogenic in vivo and elicits antibodies having diverse epitope specificities, high potency, and wide breadth. In contrast to the HIV-1 Env trimer, which is generally well shielded from antibody binding and neutralization, HIV-2 is surprisingly vulnerable to broadly reactive NAbs. The availability of 15 human MAbs targeting diverse HIV-2 Env epitopes can facilitate comparative studies of HIV/SIV Env structure, function, antigenicity, and immunogenicity.
ADAM12 Is a Four-leafed Clover (2006)

The ADAMs (a disintegrin and metalloprotease) comprise a family of multidomain proteins with metalloprotease, cell adhesion, and signaling activities. Human ADAM12, which is implicated in diseases such as cancer, is expressed in two splice forms, the transmembrane ADAM12-L and the shorter and soluble ADAM12-S. ADAM12 is synthesized as a zymogen with the prodomain keeping the metalloprotease inactive through a cysteine-switch mechanism. Maturation and activation of the protease involves the cleavage of the prodomain in the trans-Golgi or possibly at the cell surface by a furin-peptidase. The aim of the present study was to determine the fate of the prodomain following furin cleavage. Here we demonstrate that, following cleavage of the human ADAM12-S prodomain in the trans-Golgi by a furin-peptidase, the prodomain remains non-covalently associated with the mature molecule. Accordingly, both the 68-kDa mature form of ADAM12-S and the 25-kDa prodomain could be detected using domain-specific antisera in immunoprecipitation and Western blot analyses of human serum ADAM12 and purified recombinant human ADAM12. Using electron microscopy after negative staining we have furthermore obtained the first visualization of a full-length ADAM molecule, human ADAM12-S, and report that it appears to be a compact clover composed of four globular domains, one of which is the prodomain. Finally, our data demonstrate that the presence of the metalloprotease domain appears to be sufficient for the prodomain to remain associated with the mature ADAM12-S. Thus, we conclude that the prodomain of human ADAM12-S is an integral domain of the mature molecule and as such might have specific biological functions in the extracellular space.
The Amino Acid at the X Position of an Asn-X-Ser Sequon Is an Important Determinant of N-Linked Core-glycosylation Efficiency (1996)

N-Linked glycosylation is a common form of protein processing that can profoundly affect protein expression, structure, and function. N-Linked glycosylation generally occurs at the sequon Asn-X-Ser/Thr, where X is any amino acid except Pro. To assess the impact of the X amino acid on core glycosylation, rabies virus glycoprotein variants were generated by site-directed mutagenesis with each of the 20 common amino acids substituted at the X position of an Asn-X-Ser sequon. The efficiency of core glycosylation at the sequon in each variant was quantified in a rabbit reticulocyte lysate cell-free translation system supplemented with canine pancreas microsomes. The presence of Pro at the X position completely blocked core glycosylation, whereas Trp, Asp, Chi, and Leu were associated with inefficient core glycosylation. The other variants were more efficiently glycosylated, and several were fully glycosylated. These findings demonstrate that the X amino acid is an important determinant of N-linked core-glycosylation efficiency.
CD99 Signals Caspase-Independent T Cell Death (2001)

Death signaling by Fas and TNF receptors plays a major role in the control of activated mature T cells. However, the nature of the death receptors, which may be used by the immune system to control T cells that have not acquired susceptibility to Fas ligand or TNF, is not established. In this study, we demonstrate that engagement of distinct epitopes on CD99 rapidly induces T cell death by a novel caspase-independent pathway. A new mAb to these CD99 epitopes, Ad20, induces programmed cell death of transformed T cells as determined by morphological changes, phosphatidylserine exposure on the cell surface, and uptake of propidium iodide. In general, ligation of CD99 induced kinetically faster and more profound death responses as compared with the impact of anti-Fas and TNF-related apoptosis-inducing ligand (TRAIL). Ad20-induced programmed cell death was observed with seven of eight T cell lines examined, and notably, only two of these were distinctly responsive to anti-Fas and TRAIL. CD99-mediated death signaling proceeded independently of functional CD3, CD4, CD45, and p56(lck), revealed distinctions from CD47-mediated T cell death responses, and was not influenced by interference with CD47 signaling. In contrast to the effect on transformed T cell lines, Ad20-induced death responses were not observed with normal peripheral T cells. Thus, our data suggest that CD99 is linked to a novel death pathway that may have biologic relevance in control of early T cells.
The Role of Lipid Metabolism in the Pathogenesis of Alcoholic and Nonalcoholic Hepatic Steatosis (2010)

Hepatic steatosis is now understood to play an important role in the development of advanced liver disease. Alcoholic and nonalcoholic fatty liver each begin with the accumulation of lipids in the liver. Lipid accumulation in the liver can occur through maladaptations of fatty acid uptake (either through dietary sources or from fat tissue), fatty acid synthesis, fatty acid oxidation, or export of lipids from the liver. Alterations in mechanisms of fatty acid uptake through both dietary uptake and lipolysis in adipose tissue can contribute to the pathogenesis of both disorders, as can effects on fatty acid transporters. Effects on lipid synthesis in alcoholic and nonalcoholic fatty liver involve the endoplasmic reticulum (ER) stress response, homocysteine metabolism pathway, and different transcription factors regulating genes in the lipid synthesis pathway. Fatty acid oxidation, through effects on AMP-activated protein kinase (AMPK), adiponectin, peroxisome proliferator-activated receptors (PPARs), and mitochondrial function is predominantly altered in alcoholic liver disease, although studies suggest that activation of this pathway may improve nonalcoholic fatty liver disease. Finally, changes in fatty acid export, through effects on apolipoprotein B and microsomal transport protein are seen in both diseases. Thus, the similarities and differences in the mechanism of fat accumulation in the liver in nonalcoholic and alcoholic liver disease are explored in detail.