gebhart/patrepeval huggingface dataset:
Occurrence of antigenic (species-specific?) partially 3-O-methylated heteromannans in cell wall and soluble cellular (nonwall) components of Coccidioides immitis mycelia (1983)

Skin test-active, phenol-soluble, water-soluble (PSWS) extracts of Coccidioides immitis whole, defatted mycelia were compared with skin test-active, alkali-soluble, water-soluble (ASWS) extracts of mycelial cell walls. Both PSWS and ASWS extracts contained partially 3-O-methylated mannan. Composition analysis of both PSWS and ASWS extracts indicated mannose and glucose as major components, whereas 3-O-methylmannose and galactose were minor constituents. These heteromannans and glucans could be obtained from cell walls by extraction with either mild acid or alkali, but not with aqueous phenol. We therefore conclude that the PSWS extracts which were obtainable from whole mycelia but not from cell walls represent cellular (i.e., periplasmic, membrane associated, or cytoplasmic), nonwall polymers. Both PSWS and ASWS mycelial extracts and their gel filtration fractions reacted with rabbit antispherule serum, but with little cross-reactivity. However, alkali treatment of higher-molecular-weight PSWS extract polymers yielded products that cross-reacted with serological identity with low-molecular-weight components of ASWS extracts of mycelial walls, indicating that cell walls and cellular polymers share antigenic determinants. Finally, gel filtration of PSWS extracts on Sephacryl S-200 and Sepharose CL 4B yielded fractions that reacted with serological identity with one or more components of mycelial cytosol, mycelial culture filtrate and autolysate coccidioidins, and spherulin.
Photochemistry and Photobiology of Furocoumarin Hydroperoxides Derived from Imperatorin: Novel Intercalating Photo‐Fenton Reagents for Oxidative DNA Modification by Hydroxyl Radicals* (1996)

ABSTRACT Photochemical and photobiological properties of the im‐peratorin‐derived furocoumarin hydroperoxides la, la', 2a and 2a’have been investigated. Irradiation (350 nm) of the hydroperoxide 2a’afforded the alcohol 2b (2%), a diastereomeric mixture of the hydroxy epoxide 2c (40%; diastereomeric ratio = 80:20) and the epoxide 2d (8%). The formation of these products was rationalized in terms of homolysis of the hydroperoxide bond initiated by intramolecular energy transfer from the photoexcited furocoumarin chromophore. The quantum yields for the photolytic decomposition of hydroperoxides were estimated to be in the range of 0.03–0.85 and decreased in the order 2a ≫ 2a′≫ 1a′≥ 1a. The involvement of hydroxyl radicals in these reactions was established by trapping experiments with benzene and spectroscopic evidence was obtained by EPR spin trapping with 5,5‐di‐methylpyrroline‐ N ‐oxide. Fluorescence titration, DNA melting and linear dichroism studies of furocoumarins indicated that these compounds undergo efficient com‐plexation and also intercalation into the DNA. The binding parameters K (intrinsic binding constant) and l/n (frequency of binding sites) of complexes between furocoumarin derivatives and DNA were determined to be in the range of 3900–23 900 M ‐ l and 0.017–0.045. The pho‐toreaction of la’and lb’with 2′‐deoxyguanosine (dGuo) afforded exclusively 7,8‐dihydro‐8‐oxo‐2′‐deoxy‐guanosine (8‐oxodGuo), presumably through singlet oxygen, which was formed in a type II photooxidation process. In contrast, the hydroperoxide 2a oxidized dGuo to oxazo‐lone as major and 8‐oxodGuo as minor products through hydroxyl radicals, which were generated from 2a under photolytic conditions. Interestingly, the photoreactions of furocoumarins with salmon testes DNA showed that the highly reactive (φ= 0.85) hydroperoxide 2a is also most efficient in inducing the mutagenic DNA oxidation product 8‐oxodGuo. Hence, the novel furocoumarin hydroperoxide 2a constitutes the first intercalating photo‐Fen‐ton reagent and serves as convenient hydroxyl radical source for genotoxicity studies.
Eosinophilic inflammation in cough variant asthma (1998)

Eosinophils are considered to play a central pathogenetic role in asthma. We previously reported that sputum eosinophilia was observed in patients with cough variant asthma (CVA), as well as in "classic" asthma with wheezing. This study was undertaken to further investigate the involvement of eosinophils in CVA. The serum eosinophil cationic protein (ECP) level, the percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and the number of eosinophils in bronchial biopsy specimen were examined in 14 patients with CVA, 21 with classic asthma, and in seven healthy controls. For the two asthmatic groups, the clinical severity was classified with scores of 1-3. Pulmonary function and bronchial responsiveness were not significantly different between the patients with classic asthma and those with CVA. BAL, tissue eosinophil and serum ECP were all significantly increased in both classic asthma and CVA when compared with the controls but were not different between classic asthma and CVA. In both groups of asthmatics, the clinical severity significantly correlated with serum ECP and tissue eosinophils. In conclusion, eosinophilic inflammation is involved in cough variant asthma as well as in classic asthma. Anti-inflammatory treatment may be essential in patients with CVA, as in those with classic asthma.
Automated inspection of solder bumps using visual signatures of specular image-highlights (2003)

The author describes a technique for automated inspection of solder bumps by analyzing spatial features and intensity characteristics of image highlights. It is based on high-contrast imaging of specular soldered surfaces against a reflective background using dark-field illumination for selective enhancement of surface topography. Bright-field images of these surfaces are also analyzed to resolve ambiguities in the defect-identification process. The reflectance of solder is studied, for the estimation of corresponding signatures of image specularities, which provide information about surface curvature, metallurgical constituents and topographic discontinuities. During inspection, a specular highlight in the run-time image is mapped into a feature space of reduced dimensionalities for comparison against the features of typical signatures. Based on this principle, visual inspection systems have been designed and implemented for high-speed detection of defective solder bumps and leadless ceramic chip carriers and metallized advanced VLSI wafers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Targeted Replacement of the Mouse Apolipoprotein E Gene with the Common Human APOE3 Allele Enhances Diet-induced Hypercholesterolemia and Atherosclerosis (2021)

Apolipoprotein (apo) E, a constituent of several lipoproteins, is a ligand for the low density lipoprotein receptor, and this interaction is important for maintaining cholesterol and triglyceride homeostasis. We have used a gene replacement strategy to generate mice that express the human apoE3 isoform in place of the mouse protein. The levels of apoE mRNA in various tissues are virtually the same in the human apoE3 homozygous (3/3) mice and their littermates having the wild type mouse allele (+/+). Total cholesterol and triglyceride levels in fasted plasma from the 3/3 mice were not different from those in the +/+ mice, when maintained on a normal (low fat) chow diet. We found, however, notable differences in the distribution of plasma lipoproteins and apolipoprotein E between the two groups: beta-migrating lipoproteins and plasma apoB100 levels are decreased in the 3/3 mice, and the apoE distribution is shifted from high density lipoproteins to larger lipoprotein particles. In addition, the fractional catabolic rate of exogenously administered remnant particles without apoE was 6-fold slower in the 3/3 mice compared with the +/+ mice. When the 3/3 and +/+ animals were fed a high fat/high cholesterol diet, the 3/3 animals responded with a dramatic increase (5-fold) in total cholesterol compared with the +/+ mice (1.5-fold), and after 12 weeks on this same diet the 3/3 animals developed significantly (at least 13-fold) larger atherosclerotic plaques in the aortic sinus area than the +/+ animals. Thus the structural differences between human APOE3 and mouse ApoE proteins are sufficient to cause an increased susceptibility to dietary-induced hypercholesterolemia and atherosclerosis in the 3/3 mice.
Development of a Polyclonal-Antibody-Based Immunohistochemical Method for the Detection of Type 2 Porcine Circovirus in Formalin-Fixed, Paraffin-Embedded Tissue (1999)

An immunohistochemical method for the detection of type 2 porcine circovirus (PCV2) in paraffin-embedded tissue was developed. Rabbits were inoculated with purified PCV2 to obtain a polyclonal antiserum. Antiserum was applied to sections of porcine tissue that contained lesions consistent with postweaning multisystemic wasting syndrome and in which PCV2 genome had been demonstrated by in situ hybridization. In all cases (18/18), the density and distribution of positive cells detected by in situ hybridization or immunohistochemistry were identical. The immunohistochemical method is more rapid and less expensive than in situ hybridization and is thus more suitable for routine diagnostic use.
Lyme borreliosis: host responses to Borrelia burgdorferi (1991)

The chronic inflammatory condition that develops after infection by B. burgdorferi is a complex process resulting from host responses to a limited number of organisms. Amplification mechanisms driven by potent proinflammatory molecules, i.e., IL-1, may explain the vigorous response to a paucity of organisms. Spirochete dissemination to distant locations involves adherence to and penetration across endothelium and may be facilitated by host responses that increase vessel permeability. The apparent lack of tissue tropism in Lyme disease is reflected in the organism's ability to adhere to different eucaryotic cell types in vitro and the wide distribution of B. burgdorferi in various organs of infected humans and experimentally infected animals. While phagocytosis and complement activation have been observed in vitro, the specific immune response that develops in humans is inefficient in eradicating the organisms, which may possess some mechanism(s) to evade this response. There is significant evidence for host autoreactivity based on antigenic cross-reactivity between the 41-kDa flagellar subunit and stress proteins of the spirochetes and endogenous host cell components. Although the outer surface proteins appear to be suitable candidates as targets for vaccination in animal studies, fundamental differences in the immune response to spirochetal components may preclude their use in humans.
Disease-associated mutations in CIAS1 induce cathepsin B–dependent rapid cell death of human THP-1 monocytic cells (2006)

Mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene are associated with a spectrum of autoinflammatory diseases, including familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile neurologic, cutaneous, articular syndrome, also known as neonatal-onset multisystem inflammatory disease. CIAS1 encodes cryopyrin, a protein that localizes to the cytosol and functions as pattern recognition receptor. Cryopyrin also participates in nuclear factor-kappaB regulation and caspase-1-mediated maturation of interleukin 10. In this study, we showed that disease-associated mutations in CIAS1 induced rapid cell death of THP-1 monocytic cells. The features of cell death, including 7-AAD staining, the presence of cellular edema, and early membrane damage resulting in lactate dehydrogenase (LDH) release, indicated that it was more likely to be necrosis than apoptosis, and was effectively blocked with the cathepsin B-specific inhibitor CA-074-Me. CA-074-Me also suppressed induced by disease-associated mutation lysosomal leakage and mitochondrial damage. In addition, R837, a recently identified activator of cryopyrin-associated inflammasomes, induced cell death in wild type CIAS1-transfected THP-1 cells. These results indicated that monocytes undergo rapid cell death in a cathepsin B-dependent manner upon activation of cryopyrin, which is also a specific phenomenon induced by disease-associated mutation of CIAS1.
Design and Implementation of a Performance Management System at Johnson Space Center. (1982)

Efficient and reliable manipulation of biological particles is crucial in medical diagnosis and chemical synthesis. Inertial microfluidic devices utilizing passive hydrodynamic forces in the secondary flow have drawn considerable attention for their high throughputs, low costs, and harmless particle manipulation. However, as the dominant mechanism, the inertial lift force is difficult to quantitatively analyze because of the uncertainties of its magnitude and direction. The equilibrium position of particles varies along the migration process, thus inducing the instabilities of particle separation. Herein, we present a designable inertial microfluidic chip combining a spiral channel with periodic expansion structures for the sheathless separation of particles with different sizes. The stable vortex-induced lift force arising from the periodic expansion and the Dean drag force significantly enhanced the focusing process and determined the final equilibrium position. The experimental results showed that over 99% of target particles could be isolated with the high target sample purity of 86.12%. In the biological experiment, 93.5% of the MCF-7, 89.5% of the Hela, and 88.6% of the A549 cells were steadily recovered with excellent viabilities to verify the potential of the device in dealing with biological particles over a broad range of throughputs. The device presented in this study can further serve as a lab-on-chip platform for liquid biopsy and diagnostic analysis.
Hybrid Receptors Formed by Insulin Receptor (IR) and Insulin-like Growth Factor I Receptor (IGF-IR) Have Low Insulin and High IGF-1 Affinity Irrespective of the IR Splice Variant (2006)

Insulin receptor (IR) and insulin-like growth factor I receptor (IGF-IR) are both from the same subgroup of receptor tyrosine kinases that exist as covalently bound receptor dimers at the cell surface. For both IR and IGF-IR, the most described forms are homodimer receptors. However, hybrid receptors consisting of one-half IR and one-half IGF-IR are also present at the cell surface. Two splice variants of IR are expressed that enable formation of two isoforms of the IGF-IR/IR hybrid receptor. In this study, these two splice variants of hybrid receptors were studied with respect to binding affinities of insulin, insulin-like growth factor I (IGF-I), and insulin-like growth factor II (IGF-II). Unlike previously published data, in which semipurified receptors have been studied, we found that the two hybrid receptor splice variants had similar binding characteristics with respect to insulin, IGF-I, and IGF-II binding. We studied both semipurified and purified hybrid receptors. In all cases we found that IGF-I had at least 50-fold higher affinity than insulin, irrespective of the splice variant. The binding characteristics of insulin and IGF-I to both splice variants of the hybrid receptors were similar to classical homodimer IGF-IR.
Myristyl acylation of the tumor necrosis factor alpha precursor on specific lysine residues. (1992)

NH2-terminal glycine myristyl acylation is a cotranslational modification that affects both protein localization and function. However, several proteins that lack NH2-terminal glycine residues, including the interleukin 1 (IL-1) precursors, also contain covalently linked myristate. To date, the site(s) of acylation of these proteins has not been determined. During an evaluation of IL-1 acylation, it was observed that [3H]myristate-labeled human monocyte lysates contained a prominent 26-kD myristylated protein, which was identified as the tumor necrosis factor alpha (TNF) precursor protein on the basis of specific immune precipitation. Radioimmunoprecipitates from the supernates of labeled monocytes indicated that the processed or mature 17-kD form of TNF does not contain myristate, suggesting that the site of acylation occurs within the 76-amino acid propiece of the precursor molecule. As the TNF precursor does not contain an NH2-terminal glycine, we hypothesized that myristyl acylation occurs on the N-epsilon-NH2 groups of lysine, of which two are present in the propiece (K19K20). Synthetic peptides were designed to include all seven lysine residues present within the entire 26-kD TNF precursor, and used in an in vitro myristyl acylation assay containing peptide, myristyl-CoA, and monocyte lysate as a source of enzyme. Analysis of reaction products by reverse phase high performance liquid chromatography and gas phase sequencing demonstrated the exclusive myristyl acylation of K19 and K20, consistent with the presence in monocytes of a specific lysyl N-epsilon-NH2-myristyl transferase activity. The acylated lysine residues are located immediately downstream from a hydrophobic, probable membrane-spanning segment of the propiece. Specific myristyl acylation of the TNF propiece may facilitate membrane insertion or anchoring of this critical inflammatory mediator.
Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy (2002)

MGH Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA ∗Tel.: +1-617-726-2338; fax: +1-617-724-2719 E-mail: [email protected]
Design and fabrication of compliant micromechanisms and structures with negative Poisson's ratio (2002)

This paper describes a new way to design and fabricate compliant micromechanisms and material structures with negative Poisson's ratio (NPR). The design of compliant mechanisms and material structures is accomplished in an automated way using a numerical topology optimization method. The procedure allows the user to specify the elastic properties of materials or the mechanical or geometrical advantages of compliant mechanisms and returns the optimal structures. The topologies obtained by the numerical procedure require practically no interaction by the engineer before they can be transferred to the fabrication unit. Fabrication is carried out by patterning a sputtered silicon on a PECVD-glass with a laser micromachining set-up. Subsequently the structures are etched into the underlying PECVD-glass and the glass are underetched, all in one two-step RIE process. The components are tested using a probe placed on an xy-stage. This fast prototyping allows newly developed topologies to be fabricated and tested within the same day.
Determining the frequency of heteropteran predation on sweetpotato whitefly and pink bollworm using multiple ELISAs (1994)

Abstract The gut contents of field‐collected, predaceous Heteroptera were assayed for the presence of eggs of the sweetpotato whitefly, Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) and the pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae) using multiple enzyme‐linked immunosorbent assays (ELISAs). Of seven species examined, Geocoris species and Orius tristicolor (Say) were the most frequent predators of sweetpotato whitefly with 32–39% of the individuals tested over the whole season scoring positive for whitefly antigens. With the exception of Lygus hesperus Knight, a major insect pest as well as a predator, the frequency of predation on pink bollworm eggs was much lower (0.7–14.3% positive over the season). Relatively few predators tested positive for both antigens (0.3–12.5%).
Learning to Understand Phrases by Embedding the Dictionary (2016)

Distributional models that learn rich semantic word representations are a success story of recent NLP research. However, developing models that learn useful representations of phrases and sentences has proved far harder. We propose using the definitions found in everyday dictionaries as a means of bridging this gap between lexical and phrasal semantics. Neural language embedding models can be effectively trained to map dictionary definitions (phrases) to (lexical) representations of the words defined by those definitions. We present two applications of these architectures: reverse dictionaries that return the name of a concept given a definition or description and general-knowledge crossword question answerers. On both tasks, neural language embedding models trained on definitions from a handful of freely-available lexical resources perform as well or better than existing commercial systems that rely on significant task-specific engineering. The results highlight the effectiveness of both neural embedding architectures and definition-based training for developing models that understand phrases and sentences.
NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis (2013)

Background— In diabetes mellitus, vascular complications such as atherosclerosis are a major cause of death. The key underlying pathomechanisms are unclear. However, hyperglycemic oxidative stress derived from NADPH oxidase (Nox), the only known dedicated enzyme to generate reactive oxygen species appears to play a role. Here we identify the Nox1 isoform as playing a key and pharmacologically targetable role in the accelerated development of diabetic atherosclerosis. Methods and Results— Human aortic endothelial cells exposed to hyperglycemic conditions showed increased expression of Nox1, oxidative stress, and proinflammatory markers in a Nox1-siRNA reversible manner. Similarly, the specific Nox inhibitor, GKT137831, prevented oxidative stress in response to hyperglycemia in human aortic endothelial cells. To examine these observations in vivo, we investigated the role of Nox1 on plaque development in apolipoprotein E–deficient mice 10 weeks after induction of diabetes mellitus. Deletion of Nox1, but not Nox4, had a profound antiatherosclerotic effect correlating with reduced reactive oxygen species formation, attenuation of chemokine expression, vascular adhesion of leukocytes, macrophage infiltration, and reduced expression of proinflammatory and profibrotic markers. Similarly, treatment of diabetic apolipoprotein E–deficient mice with GKT137831 attenuated atherosclerosis development. Conclusions— These studies identify a major pathological role for Nox1 and suggest that Nox1-dependent oxidative stress is a promising target for diabetic vasculopathies, including atherosclerosis.
The relationship between in vitro cellular aging and in vivo human age. (1976)

Differences between early and late passage cell cultures on the organelle and macromolecular levels have been attributed to cellular "aging". However, concern has been expressed over whether changes in diploid cell populations after serial passage in vitro accurately reflect human cellular aging in vivo. Studies were therefore undertaken to determine if significant differences would be observed in the in vitro lifespans of skin fibroblast cultures from old and young normal, non-hospitalized volunteers and to examine if parameters that change with in vitro "aging" are altered as a function of age in vivo. Statistically signigificant (P less than 0.05) decreases were found in the rate of fibroblast migration, onset of cell culture senescence, in vitro lifespan, cell population replication rate, and cell number at confluency of fibroblast cultures derived from the old donor group when compared to parallel cultures from young donors. No significant differences were observed in modal cell volumes and cellular macromolecular contents. The differences observed in cell cultures from old and young donors were quantitatively and qualitatively distinct from those cellular alterations observed in early and late passage WI-38 cells (in vitro "aging"). Therefore, although early and late passage cultures of human diploid cells may provide an important cell system for examining loss of replicative potential, fibroblast cultures derived from old and young human donors may be a more appropriate model system for studying human cellular aging.