gebhart/patrepeval huggingface dataset:
Pulmonary Surfactant Protein D in Sera and Bronchoalveolar Lavage Fluids (1995)

Pulmonary surfactant protein D (SP-D) is a hydrophilic glycoprotein with a reduced molecular mass of 43 kDa and a member of the C-type lectin superfamily, along with mannose-binding proteins and surfactant protein A (SP-A). We have recently prepared monoclonal antibodies against human SP-D and developed an enzyme-linked immunosorbent assay (ELISA). In this study, the levels of SP-D in sera and bronchoalveolar lavage (BAL) fluids of patients with lung diseases were determined by ELISA, using human recombinant SP-D as a standard. We demonstrated that the concentrations of SP-D in sera are prominently increased in patients with idiopathic pulmonary fibrosis (IPF), interstitial pneumonia with collagen disease (IPCD), and pulmonary alveolar proteinosis (PAP). Patients with IPF, IPCD, and PAP exhibited levels of serum SP-D 5.1-fold, 7.2-fold, and 7.0-fold, respectively, of those in healthy volunteers; 91.5% of the patients with IPF, 81.3% with IPCD, and 100% with PAP exhibited serum SP-D levels that exceeded the cut-off value (mean + 2 SD of control value). Serum SP-D levels appeared to reflect the disease activity of IPF and IPCD and the disease severity of PAP. High levels of SP-D in BAL fluids were shown in patients with PAP, but not with IPF and IPCD. We conclude that measurement of SP-D in sera can provide an easily identifiable and useful clinical marker for the diagnosis of IPF, IPCD, and PAP, and can predict the disease activity of IPF and IPCD and the disease severity of PAP.
Effect of dietary fat sources on systemic and intrauterine synthesis of prostaglandins during early pregnancy in gilts1,2 (2003)

The present experiment was conducted to determine the influence of dietary fatty acids C18:2n-6 and C18:3n-3 on the modulation of intrauterine synthesis of prostaglandin E2 (PGE2) and F2alpha (PGF2alpha) during early pregnancy in pigs. Prostaglandin E2 in uterine fluid has been previously reported to be associated with embryo survival and development. Thirty-two Yorkshire-Landrace nulliparous gilts were randomly allocated to four diets containing 5% supplemental fat. The four dietary treatments were: HT, hydrogenated tallow (26.5% C16:0 and 54.8% C18:0); SO, sunflower oil (61.3% C18:2n-6); LO, linseed oil (50.4% C18:3n-3); and SO(CLA), a mixture of sunflower oil and conjugated linoleic acids to provide 20% CLA. Treatments started 2 d after the first pubertal estrus (d -21) and lasted for 36 d (slaughter), which was 15 d after the second estrus (d 0; insemination). Fatty acids and PGE2 were measured in the peripheral blood plasma on d -19, d -7, d 0, and d 14. Fatty acids in endometrial tissues and PGE2 and PGF2alpha in the uterine fluid collected on d 15 were also measured. Concentrations of fatty acids in the plasma reflected the content of fatty acids in the diet as early as d -7. From d -7, PGE2 concentrations in the plasma were higher in gilts fed SO compared with HT (P < 0.05). Plasma PGE2 concentrations were lower (P < 0.01) on d 14 in gilts fed LO compared with HT. Total PGF2alpha contents in the uterine fluid of gilts fed LO were more than 70% lower (P < 0.05) than for the HT group. A similar trend was observed for total PGE2 content and for the ratio PGF2alpha:PGE2, but the effect (LO vs HT) was less marked (P < 0.07 and P < 0.10, respectively). There was no effect of SO or SO(CLA) on total PGE2 contents in the uterine fluid. Dietary enrichment in C18:2n-6 and/or C18:3n-3 for early pregnant gilts can influence fatty acids in plasma and endometrial tissue and can modulate circulatory and intrauterine prostaglandins.
Ownership, responsibility, and the rhetoric of nationalism: A Scottish case (1995)

(1995). Ownership, responsibility, and the rhetoric of nationalism: A Scottish case. Anthropological Forum: Vol. 7, No. 2, pp. 179-191.
Design and operation of a dual laser chromosome sorter (1982)

We describe the design and operation of a dual laser fluorescence activated chromosome sorter that can analyze and sort chromosome suspensions stained with two complementary DNA stains. We used two 18-watt argon-ion lasers to provide maximal excitation of the DNA-specific stains Hoechst 33258 and chromomycin A3. The lasers are focused onto the sample stream by independent optics permitting optimal focusing of any pair of laser wavelengths. We incorporated beam expanders to decrease the energy density on the optics and improve the focal spot uniformity. Adjustable focusing lens holders are used to set the optimal focal spot size. The redesigned sorter separates suspensions of normal human fibroblast chromosomes into 21 fractions and can reliably sort more pure chromosome fractions than was previously possible.
Producing Stable Pyrolysis Liquids from the Oil-Seed Presscakes of Mustard Family Plants: Pennycress (Thlaspi arvense L.) and Camelina (Camelina sativa)† (2010)

Natural oil from non-food oil seeds, such as camelina, jatropha, and pennycress, is increasingly becoming the feedstock of choice for biodiesel production through transesterification to fatty acid methyl esters (FAMEs) and green diesel via catalytic hydrotreating. Unlike the presscakes from food-based feedstocks, such as soy and palm fruits, the residual oil-extracted presscakes are often not suitable for consumption as animal feed. However, their abundance and the fact that these feedstocks are already collected give them a logistic advantage as a bioenergy resource over conventional lignocellulosic biomass, which is yet to be harvested. Vegetable oil-seed presscakes make an ideal thermochemical conversion feedstock because of their inherently high initial calorific value. We carried out fast pyrolysis of the entire value chain of two of the mustard family oil seeds, pennycress and camelina, and found that, at the optimum fast pyrolysis conditions, not only can high-carbon, high-energy liquid fuel intermediates be produced but also these liquids are low-oxygen, stable intermediates that do not oligomerize over time to higher molecular weight or increase in viscosity over time according to the accelerated aging test. Liquid fuel quality was high, with gross calorific value ranging between 29.0 MJ/kg for defatted oil to 34.7 MJ/kg for the whole seed on a dry basis. The corresponding carbon conversion efficiency, defined as feed carbon converted to the liquid pyrolysate, ranged between 60 and 80%. It is envisioned that co-location of a fast pyrolysis process with a green-diesel plant that uses these feedstocks could provide additional gallons of renewable biofuels and a reliable source of aromatic hydrocarbon compounds needed for the formulation of renewable jet fuels.
Enhanced neutralization of human respiratory syncytial virus by mixtures of monoclonal antibodies to the attachment (G) glycoprotein. (1998)

Neutralization of human respiratory syncytial virus (HRSV) by monoclonal antibodies specific for the G protein was evaluated in a microneutralization test. Only certain antibodies showed some degree of neutralization, reflected in a reduction of virus titre (10-20 times maximum), compared with negative controls. In contrast, a pool of antibodies that recognized conserved, group-specific and strain-specific epitopes showed a significant increase in virus neutralization (up to 500-1000 times). By testing binary, tertiary and quaternary combinations, four antibodies were identified which showed maximal effect in the neutralization test. These findings are discussed in terms of the location of antibody binding sites in the G protein primary structure and their relevance for HRSV neutralization and immunobiology.
Fragment-Based Approaches in Drug Discovery and Chemical Biology (2012)

Fragment-based approaches to finding novel small molecules that bind to proteins are now firmly established in drug discovery and chemical biology. Initially developed primarily in a few centers in the biotech and pharma industry, this methodology has now been adopted widely in both the pharmaceutical industry and academia. After the initial success with kinase targets, the versatility of this approach has now expanded to a broad range of different protein classes. Herein we describe recent fragment-based approaches to a wide range of target types, including Hsp90, β-secretase, and allosteric sites in human immunodeficiency virus protease and fanesyl pyrophosphate synthase. The role of fragment-based approaches in an academic research environment is also examined with an emphasis on neglected diseases such as tuberculosis. The development of a fragment library, the fragment screening process, and the subsequent fragment hit elaboration will be discussed using examples from the literature.
Clinical Measures of Central Vision Function in Glaucoma and Ocular Hypertension (1987)

A generalized loss of visual sensitivity, even for foveal targets, has been reported as an early sign of glaucoma. In the present study of central vision, we used relatively simple and rapid clinical tests of color thresholds, color discrimination, and spatial contrast sensitivity to compare the vision of three age-matched groups of patients who had primary open angle glaucoma (n = 33) or ocular hypertension (n = 32) as well as normal subjects (n = 24). The largest sensitivity losses for both glaucoma and ocular hypertensive groups were disclosed by a color threshold test with blue lights designed to isolate the blue-sensitive pathways of the visual system. The loss of sensitivity for both the glaucoma group and the ocular hypertensive group is consistent with recent reports (from postmortem studies of human eyes) of extensive axon death even in the absence of glaucomatous field defects.
N-(4'-hydroxyphenylacetyl)palytoxin: a palytoxin prodrug that can be activated by a monoclonal antibody-penicillin G amidase conjugate. (1992)

Palytoxin (PTX), one of the most toxic nonprotein molecules known, is cytotoxic at picomolar concentrations against a wide variety of cell types. In contrast to most cytotoxins, PTX exerts its activity extracellularly. A method for targeting PTX to tumor cells is described in which a monoclonal antibody-enzyme conjugate activates a PTX prodrug at surfaces of tumor cells. The prodrug, N-(4'-hydroxyphenylacetyl)palytoxin (NHPAP), was prepared by reacting PTX with an active ester of 4-hydroxyphenylacetic acid. NHPAP was 1000 times less toxic than PTX to a panel of carcinoma and lymphoma cell lines. The cytotoxic activity of the combination of penicillin G amidase from Escherichia coli with NHPAP was equal to PTX. Two cell lines that were multidrug resistant showed no enhanced resistance to NHPAP +/- penicillin G amidase. Immunologically specific activation of NHPAP took place when H2981 cells (L6 antigen positive) were treated with the monoclonal antibody conjugate L6-penicillin G amidase followed by NHPAP. This system is distinguished from other prodrug activation schemes, since the released drug exerts its activity extracellularly, has high potency, and may be able to overcome the multidrug resistant phenotype.
Approximate Correspondences in High Dimensions (2007)

Pyramid intersection is an efficient method for computing an approximate partial matching between two sets of feature vectors.We introduce a novel pyramid embedding based on a hierarchy of non-uniformly shaped bins that takes advantage of the underlying structure of the feature space and remains accurate even for sets with high-dimensional feature vectors.The matching similarity is computed in linear time and forms a Mercer kernel.Whereas previous matching approximation algorithms suffer from distortion factors that increase linearly with the feature dimension, we demonstrate that our approach can maintain constant accuracy even as the feature dimension increases.When used as a kernel in a discriminative classifier, our approach achieves improved object recognition results over a state-of-the-art set kernel.
Workplace discrimination and mental retardation: The national EEOC ADA research project (2005)

Using the Integrated Mission System of the Equal Employment Opportunity Commission, the employment discrimination experience of Americans with mental retardation is documented. Researchers compare and contrast the key dimensions of workplace discrimination involving Americans with mental retardation and persons with other physical, sensory, and neurological impairments. Specifically, the researchers examine demographic characteristics of the CPs; the industry designation, location, and size of employers against whom complaints are filed; the nature of discrimination (i.e., type of adverse action) alleged to occur; and the legal outcome or Resolution of these complaints. Chi-square analyses revealed that persons with mental retardation were more likely to encounter discrimination involving matters of involuntary termination (discharge), involuntary resignation (constructive discharge), and harassment. They were less likely to encounter discrimination related to reasonable accommodation, promotion, demotion, and reinstatement. Allegations of employment discrimination by persons with mental retardation were more likely to have merit in comparison to allegations by CPs with other disabilities. Implications for policy and advocacy are addressed.
Inhibition of the Peptidyl-Prolyl-Isomerase Pin1 Enhances the Responses of Acute Myeloid Leukemia Cells to Retinoic Acid via Stabilization of RARα and PML-RARα (2009)

The peptidyl-prolyl-isomerase Pin1 interacts with phosphorylated proteins, altering their conformation. The retinoic acid receptor RARalpha and the acute-promyelocytic-leukemia-specific counterpart PML-RARalpha directly interact with Pin1. Overexpression of Pin1 inhibits ligand-dependent activation of RARalpha and PML-RARalpha. Inhibition is relieved by Pin1-targeted short interfering RNAs and by pharmacologic inhibition of the catalytic activity of the protein. Mutants of Pin1 catalytically inactive or defective for client-protein-binding activity are incapable of inhibiting ligand-dependent RARalpha transcriptional activity. Functional inhibition of RARalpha and PML-RARalpha by Pin1 correlates with degradation of the nuclear receptors via the proteasome-dependent pathway. In the acute myelogenous leukemia cell lines HL-60 and NB4, Pin1 interacts with RARalpha in a constitutive fashion. Suppression of Pin1 by a specific short hairpin RNA in HL-60 or NB4 cells stabilizes RARalpha and PML-RARalpha, resulting in increased sensitivity to the cytodifferentiating and antiproliferative activities of all-trans retinoic acid. Treatment of the two cell lines and freshly isolated acute myelogenous leukemia blasts (M1 to M4) with ATRA and a pharmacologic inhibitor of Pin1 causes similar effects. Our results add a further layer of complexity to the regulation of nuclear retinoic acid receptors and suggest that Pin1 represents an important target for strategies aimed at increasing the therapeutic index of retinoids.
Dissociation rate of antibody-gp120 binding interactions is predictive of V3-mediated neutralization of HIV-1. (1994)

mAbs specific for the V3 loop of HIV-1 are capable of neutralizing laboratory strains of HIV-1 in vitro. In this report we use surface plasmon resonance and biosensor technology to demonstrate that the ability of V3-specific mAbs to neutralize HIV-1(MN) correlated with the dissociation rate constant of the homologous mAb-gp120 binding interaction. mAbs capable of binding diverse strains of gp120 with similar association rate constants exhibited marked differences in the dissociation rate. The dissociation rate, and not the association rate, was found to be predictive of the neutralization capacity of the mAb. Furthermore, synthetic peptides corresponding to the V3 loop of HIV-1(IIIB, MN) yielded quantitatively similar binding kinetic profiles abrogating the need for purified recombinant gp120 protein and potentially facilitating the screening of more diverse isolates. Biosensor immobilized V3 peptides were found to mimic their conformational structure in solution. This offers advantages to peptides studied by ELISA where some degree of denaturation and masking of epitopes can occur upon adsorption of peptides to plastic surfaces. The impact of amino acid substitutions within epitopes on subsequent mAb binding was dissected by observing alterations in dissociation rates. The technique provides rapid kinetic analyses of V3 Ab binding interactions with diverse V3 sequences, facilitating the efficient screening and selection of those most likely to possess the broadest and most potent HIV-1 neutralizing potentials.
Proteases as prognostic markers in cancer. (1996)

It is the ability to invade and metastasize that ultimately determines the prognosis in cancer. Comprising one of the key groups of molecules involved in invasion and metastasis are proteases such as urokinase plasminogen activator and cathepsins B, D, and L, as well as various metalloproteases. These proteases catalyze degradation of the interstitial matrix and basement membranes, allowing cancer cells to invade locally and metastasize to distant sites. If proteases are directly and causally involved in cancer spread, they have the potential to be new prognostic markers in cancer. One of the best examples of a correlation between high levels of a protease in a primary tumor and poor prognosis is urokinase plasminogen activation in breast cancer. In this malignancy, the urokinase plasminogen activator is a strong and independent prognostic marker and may be a marker for axillary node-negative disease. The urokinase plasminogen activator may also be a prognostic marker in other cancers such as gastric, colorectal, lung, bladder, cervical, and ovarian cancers. In a number of studies, cathepsin D has been shown to be a prognostic factor in breast cancer. However, results with cathepsin D, especially when immunocytochemistry is used for its detection, are conflicting. Levels of cathepsin B, cathepsin L, and certain metalloproteases may also supply prognostic data in certain cancers, but results with these proteases are still preliminary.
Multiple kinases and signal transduction. Phosphorylation of the T cell antigen receptor complex. (1987)

Multiple kinases interact at the multicomponent murine T cell antigen receptor. Antigen induces serine phosphorylation of the 21-kDa gamma glycoprotein and tyrosine phosphorylation of p21, a distinct 21-kDa chain. We demonstrate that tyrosine phosphorylation is due to kinase activation, and that all phosphorylated p21 is associated with the antigen receptor. We also show that antigen leads to polyphosphoinositide metabolism and subsequent protein kinase C activation. The two phosphorylation events can be dissociated by protein kinase C depletion, which eliminates phorbol 12-myristate 13-acetate-induced serine but not tyrosine phosphorylation. Activation of a third kinase, cyclic AMP-dependent protein kinase, inhibits both serine and tyrosine events, yet this inhibition can be modulated by addition of the protein kinase C activator, phorbol 12-myristate 13-acetate. Receptor-mediated signal transduction may be understood as the interaction of multiple stimulatory and inhibitory kinase activities.
Antipsychotics Activate mTORC1-Dependent Translation to Enhance Neuronal Morphological Complexity (2014)

Although antipsychotic drugs can reduce psychotic behavior within a few hours, full efficacy is not achieved for several weeks, implying that there may be rapid, short-term changes in neuronal function, which are consolidated into long-lasting changes. We showed that the antipsychotic drug haloperidol, a dopamine receptor type 2 (D₂R) antagonist, stimulated the kinase Akt to activate the mRNA translation pathway mediated by the mammalian target of rapamycin complex 1 (mTORC1). In primary striatal D₂R-positive neurons, haloperidol-mediated activation of mTORC1 resulted in increased phosphorylation of ribosomal protein S6 (S6) and eukaryotic translation initiation factor 4E-binding protein (4E-BP). Proteomic mass spectrometry revealed marked changes in the pattern of protein synthesis after acute exposure of cultured striatal neurons to haloperidol, including increased abundance of cytoskeletal proteins and proteins associated with translation machinery. These proteomic changes coincided with increased morphological complexity of neurons that was diminished by inhibition of downstream effectors of mTORC1, suggesting that mTORC1-dependent translation enhances neuronal complexity in response to haloperidol. In vivo, we observed rapid morphological changes with a concomitant increase in the abundance of cytoskeletal proteins in cortical neurons of haloperidol-injected mice. These results suggest a mechanism for both the acute and long-term actions of antipsychotics.
Analysis of long terminal repeat circle junctions of human immunodeficiency virus type 1 (1990)

Circle junctions of unintegrated human immunodeficiency virus type 1 strain IIIB were analyzed after polymerase chain reaction amplification. Among the 28 colonies sequenced, eight unique circle junction species were detected. Five of the eight species resulted in circle junctions with larger inserts than predicted. A majority of these could result from heterogeneity in generating the U5' long terminal repeat terminus.
Architectural Transcription Factors (1994)

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Continuous Activity Monitoring in Persons at High Risk for Diabetes-Related Lower-Extremity Amputation (2001)

This study evaluated the magnitude and location of activity of diabetic patients at high risk for foot amputation. Twenty subjects aged 64.6 +/- 1.8 years with diabetes, neuropathy, deformity, or a history of lower-extremity ulceration or partial foot amputation were dispensed a continuous activity monitor and a log book to record time periods spent in and out of their homes for 1 week. The results indicate that patients took more steps per hour outside their home, but took more steps per day inside their homes. Although 85% of the patients wore their physician-approved shoes most or all of the time while they were outside their homes, only 15% continued to wear them at home. Focusing on protection of the foot during in-home ambulation may be an important factor on which to focus future multidisciplinary efforts to reduce the incidence of ulceration and amputation. The ability to continuously monitor the magnitude, duration, and time of activity ultimately may assist clinicians in dosing activity just as they dose drugs.
A Decrease in Membrane Tension Precedes Successful Cell-Membrane Repair (2000)

We hypothesized that the requirement for Ca(2+)-dependent exocytosis in cell-membrane repair is to provide an adequate lowering of membrane tension to permit membrane resealing. We used laser tweezers to form membrane tethers and measured the force of those tethers to estimate the membrane tension of Swiss 3T3 fibroblasts after membrane disruption and during resealing. These measurements show that, for fibroblasts wounded in normal Ca(2+) Ringer's solution, the membrane tension decreased dramatically after the wounding and resealing coincided with a decrease of approximately 60% of control tether force values. However, the tension did not decrease if cells were wounded in a low Ca(2+) Ringer's solution that inhibited both membrane resealing and exocytosis. When cells were wounded twice in normal Ca(2+) Ringer's solution, decreases in tension at the second wound were 2.3 times faster than at the first wound, correlating well with twofold faster resealing rates for repeated wounds. The facilitated resealing to a second wound requires a new vesicle pool, which is generated via a protein kinase C (PKC)-dependent and brefeldin A (BFA)-sensitive process. Tension decrease at the second wound was slowed or inhibited by PKC inhibitor or BFA. Lowering membrane tension by cytochalasin D treatment could substitute for exocytosis and could restore membrane resealing in low Ca(2+) Ringer's solution.