gebhart/patrepeval huggingface dataset:
Silica induces apoptosis in macrophages and the release of interleukin-1 α and interleukin-1β (1993)

Resident adherent peritoneal cells selectively released high amounts of interleukin-1 (IL-1) activity when treated with silica. The use of anti-IL-1 antisera showed that both IL-1 alpha and IL-1 beta were present in supernatants of silica-treated macrophages. In contrast, intracellular IL-1 activity was totally neutralized by anti-IL-1 alpha antibodies and was easily converted into the mature IL-1 alpha form by autolysis in cytoplasmic extracts. Anion exchange chromatography clearly separated the two IL-1 species present in supernatants of silica-stimulated macrophages. Natural IL-1 beta was further characterized by chromatofocalization; it had an apparent isoelectric point, pI, in the range 8.3-8.6. In agreement with previous findings showing that IL-1 beta was released only by apoptotic cells, we have found that silica-treated macrophages underwent apoptosis. This was demonstrated by the characteristic laddering electrophoretic pattern of DNA extracted from silica-treated cells and by the morphology of macrophage nuclei stained with the DNA-specific dye DAPI. In addition, quantification of apoptotic cells was performed by a flow cytometric analysis based on the reduction of cellular DNA content exhibited by apoptotic cells. Treatment of macrophages with silica, therefore, results in an active process that promotes the processing and liberation of IL-1 beta.
Protection of erythrocytes from human complement–mediated lysis by membrane-targeted recombinant soluble CD59: a new approach to PNH therapy (2005)

Paroxysmal nocturnal hemoglobinuria (PNH) results from the expansion of a hematopoietic clone that is deficient in glycosylphosphatidylinositol-anchored molecules. PNH is characterized by chronic hemolysis with acute exacerbations due to the uncontrolled activity of complement on PNH cells, which lack the inhibitor of homologous complement, CD59. Symptoms include severe fatigue, hemoglobinuria, esophageal spasm, erectile dysfunction, and thrombosis. We report the use of a novel synthetically modified recombinant human CD59, rhCD59-P, a soluble protein that attaches to cell membranes. In vitro treatment of PNH erythrocytes with rhCD59-P resulted in levels of CD59 equivalent to normal erythrocytes and effectively protected erythrocytes from complement-mediated hemolysis. The administration of rhCD59-P to CD1 mice resulted in levels of CD59 on erythrocytes, which protected them from complement-mediated lysis. Thus, rhCD59-P corrects the CD59 deficiency in vitro and can bind to erythrocytes in an in vivo murine model, protecting the cells from the activity of human complement, and represents a potential therapeutic strategy in PNH.
Mining Discriminative Patterns for Classifying Trajectories on Road Networks (2010)

Classification has been used for modeling many kinds of data sets, including sets of items, text documents, graphs, and networks. However, there is a lack of study on a new kind of data, trajectories on road networks. Modeling such data is useful with the emerging GPS and RFID technologies and is important for effective transportation and traffic planning. In this work, we study methods for classifying trajectories on road networks. By analyzing the behavior of trajectories on road networks, we observe that, in addition to the locations where vehicles have visited, the order of these visited locations is crucial for improving classification accuracy. Based on our analysis, we contend that (frequent) sequential patterns are good feature candidates since they preserve this order information. Furthermore, when mining sequential patterns, we propose to confine the length of sequential patterns to ensure high efficiency. Compared with closed sequential patterns, these partial (i.e., length-confined) sequential patterns allow us to significantly improve efficiency almost without losing accuracy. In this paper, we present a framework for frequent pattern-based classification for trajectories on road networks. Our comparative study over a broad range of classification approaches demonstrates that our method significantly improves accuracy over other methods in some synthetic and real trajectory data.
Comparison of the Effects of Transforming Growth Factor α and Epidermal Growth Factor on Gastrointestinal Proliferation and Hormone Release (1996)

Epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) bind to a common receptor and are both present in the normal gastrointestinal tract. Although many studies have examined their function in isolation, there is little information directly comparing their actions. We examined the relative potency of TGF alpha and EGF in stimulating 3H-thymidine uptake into primary rat hepatocytes at various doses in vitro and on the crypt cell production rate (CCPR) within the gastrointestinal tract when infused intravenously at 49 nmol/kg/day into rats receiving total parenteral nutrition. In vitro, maximal stimulatory activity was similar in EGF- and TGF alpha-treated cells, however, the dose of EGF required to stimulate 3H-thymidine uptake to 50% of maximal levels was only one third of that required using TGF alpha. In vivo, EGF and TGF alpha significantly increased the weight and proliferative indices throughout the gastrointestinal tract. The response (as determined by CCPR) was about 80% higher in animals which had received EGF when compared to animals receiving TGF alpha. Treatment with EGF also caused significant rises in plasma PYY, enteroglucagon and gastrin levels, whereas the equivalent dose of TGF alpha only caused a significant rise in plasma gastrin levels. We conclude that TGF-alpha, like EGF, is trophic to the entire gastrointestinal tract of the rat, however, it is a less effective mitogen, and has differential hormonal effects.
Adenosine-5'-triphosphate (ATP) supplementation improves low peak muscle torque and torque fatigue during repeated high intensity exercise sets (2012)

Supplementation with 400 mg ATP/d for 15 days tended to reduce muscle fatigue and improved a participant's ability to maintain a higher force output at the end of an exhaustive exercise bout.
lec32 Is a New Mutation in Chinese Hamster Ovary Cells That Essentially Abrogates CMP-N-acetylneuraminic Acid Synthetase Activity (1995)

LEC29.Lec32 is a glycosylation mutant that was isolated from a selection of mutagenized Chinese hamster ovary (CHO) cells for lectin resistance. Compared with LEC29 CHO cells, the double mutant exhibited an unusually high sensitivity to the toxic lectin, ricin, indicating increased exposure of galactose residues on cell surface carbohydrates. Structural analysis of LEC29.Lec32 cellular glycoproteins showed a nearly complete lack of sialic acid residues. Genetic analysis demonstrated that the lec32 mutation is recessive and novel. Biochemical analysis showed that the mutant cells contained less than 5% of the cytidine 5'-monophosphate N-acetylneuraminic acid (CMP-NeuAc) present in parental CHO cells (1.6 nmol/mg of cell protein). A sensitive radiochemical assay used to measure CMP-NeuAc synthetase activity showed that the properties of this enzyme in parental CHO cells were essentially identical to those of CMP-NeuAc synthetase in various mammalian tissues. However, no CMP-NeuAc synthetase activity was detected in LEC29.Lec32 extracts. Mixing experiments provided no evidence for an inhibitor in the mutant CHO cells, and two revertants, which expressed only the LEC29 phenotype, had normal CMP-NeuAc synthetase levels. The combined evidence indicates that the lec32 mutation resides in either the structural gene encoding CMP-NeuAc synthetase or in a gene that regulates the production of active enzyme.
Clinical Importance of Hepatic Cytochrome P450 in Drug Metabolism (1995)

(1995). Clinical Importance of Hepatic Cytochrome P450 in Drug Metabolism. Drug Metabolism Reviews: Vol. 27, No. 3, pp. 397-417.
Insights into the molecular nature of magnesium homeostasis (2004)

Magnesium is an important cofactor for many biological processes, such as protein synthesis, nucleic acid stability, or neuromuscular excitability. Extracellular magnesium concentration is tightly regulated by the extent of intestinal absorption and renal excretion. Despite the critical role of magnesium handling, the exact mechanisms mediating transepithelial transport remained obscure. In the past few years, the genetic disclosure of inborn errors of magnesium handling revealed several new proteins along with already known molecules unexpectedly involved in renal epithelial magnesium transport, e.g., paracellin-1, a key player in paracellular magnesium and calcium reabsorption in the thick ascending limb or the gamma-subunit of the Na(+)-K(+)-ATPase in the distal convoluted tubule. In this review, we focus on TRPM6, an ion channel of the "transient receptor potential (TRP) gene family, which, when mutated, causes a combined defect of intestinal magnesium absorption and renal magnesium conservation as observed in primary hypomagnesemia with secondary hypocalcemia.
Development of a monoclonal antibody specific for the COOH-terminal of beta-amyloid 1-42 and its immunohistochemical reactivity in Alzheimer's disease and related disorders. (1994)

The beta-amyloid peptide (beta AP) has been characterized by protein sequencing techniques as a 39-43 amino acid protein with heterogeneous COOH-termini. Controversy exists regarding the predominant form of beta AP in neuritic plaques (NP) and cerebral vasculature of Alzheimer's disease (AD) brain. A monoclonal antibody was developed that selectively recognizes the free COOH-terminal of beta AP 1-42 but not beta AP species with shorter or longer COOH-termini. Brain sections from AD and related disorders were examined using this antibody. In AD samples, the antibody stained diffuse amyloid and NP cores, many intraneuronal and extraneuronal neurofibrillary tangles (NFT), but not cerebrovascular amyloid. Pick and Lewy bodies lacked immunoreactivity. These findings suggest that beta AP 1-42 is present in early and mature amyloid deposits and NFT, but that species of beta AP other than 1-42 comprise human vascular deposits.
Isolation and Culture of Hippocampal Neurons from Prenatal Mice (2012)

Primary cultures of rat and murine hippocampal neurons are widely used to reveal cellular mechanisms in neurobiology. By isolating and growing individual neurons, researchers are able to analyze properties related to cellular trafficking, cellular structure and individual protein localization using a variety of biochemical techniques. Results from such experiments are critical for testing theories addressing the neural basis of memory and learning. However, unambiguous results from these forms of experiments are predicated on the ability to grow neuronal cultures with minimum contamination by other brain cell types. In this protocol, we use specific media designed for neuron growth and careful dissection of embryonic hippocampal tissue to optimize growth of healthy neurons while minimizing contaminating cell types (i.e. astrocytes). Embryonic mouse hippocampal tissue can be more difficult to isolate than similar rodent tissue due to the size of the sample for dissection. We show detailed dissection techniques of hippocampus from embryonic day 19 (E19) mouse pups. Once hippocampal tissue is isolated, gentle dissociation of neuronal cells is achieved with a dilute concentration of trypsin and mechanical disruption designed to separate cells from connective tissue while providing minimum damage to individual cells. A detailed description of how to prepare pipettes to be used in the disruption is included. Optimal plating densities are provided for immuno-fluorescence protocols to maximize successful cell culture. The protocol provides a fast (approximately 2 hr) and efficient technique for the culture of neuronal cells from mouse hippocampal tissue.
B7-1 Engagement of Cytotoxic T Lymphocyte Antigen 4 Inhibits T Cell Activation in the Absence of CD28 (1998)

Ligation of cytotoxic T lymphocyte antigen 4 (CTLA4) appears to inhibit T cell responses. Four mechanisms have been proposed to explain the inhibitory activity of CTLA4: competition for B7-1 and B7-2 binding by CD28; sequestration of signaling molecules away from CD28 via endocytosis; delivery of a signal that antagonizes a CD28 signal; and delivery of a signal that antagonizes a T cell receptor (TCR) signal. As three of these potential mechanisms involve functional antagonism of CD28, an experimental model was designed to determine whether CTLA4 could inhibit T cell function in the absence of CD28. TCR transgenic/recombinase activating gene 2-deficient/CD28-wild-type or CD28-deficient mice were generated and immunized with an antigen-expressing tumor. Primed T cells from both types of mice produced cytokines and proliferated in response to stimulator cells lacking B7 expression. However, whereas the response of CD28+/+ T cells was augmented by costimulation with B7-1, the response of the CD28-/- T cells was strongly inhibited. This inhibition was reversed by monoclonal antibody against B7-1 or CTLA4. Thus, CTLA4 can potently inhibit T cell activation in the absence of CD28, indicating that antagonism of a TCR-mediated signal is sufficient to explain the inhibitory effect of CTLA4.
NOVEL NANOFIBER-BASED GRAFT FOR HEART VALVE REPLACEMENT (2012)

Creating a functional heart valve graft that lasts a lifetime is one of the main targets of cardiovascular tissue engineering. While processed conventional collagen-based heart valves have been used for many years, they eventually fail because of inadequate cell infiltration and insufficient replacement of graft material by tissue remodeling. To overcome the graft failure due to inadequate tissue remodeling and growth, an improved graft material was created by incorporating type I collagen protein with mechanical robust silk fibroin, and hemocompatible synthetic elastic polymer poly(glycerol-sebacate) (PGS). The central hypothesis of this project was: Electrospun grafts created from composites of type I collagen, silk fibroin, and PGS are stable, less thrombogenic and more readily available than the conventionally used collagen-based grafts for aortic heart valve replacement. The aim was to fabricate a graft material that mimicked the composition, structure and mechanical properties of native heart valve tissue, and to promote the formation of an intact non-thrombogenic endothelial cell layer. In this study, an improved heart valve material composed of type I collagen, silk fibroin, and PGS was developed. The homogeneity of blended composites was demonstrated using Fourier transform spectroscopy. Tensile stress, strain, and elastic modulus of the electrospun mats were measured by an Instron mechanical tester. The elastic moduli were between 2.3 - 5.0 Mpa, tensile stresses ranged from 0.8 to 1.5 Mpa, and strains were of 30% - 70%. These values were similar to those reported for native heart valves. Suture retention tests showed a highest 0.32N pull-out force at the single-loop suture site in electrospun mats with 4.5:4.5:1 collagen, silk fibroin and PGS weight ratio (PFC mats). Functional test of PFC mats demonstrated a slow degradation rate as compared to other collagen-based grafts. Cells adhered to and proliferated on PFC mats. Endothelial cells were observed to form tight junctions on the material. Several studies with isolated platelets showed the PFC mats were less thrombogenic in comparison to collagen hydrogels and structurally similar electrospun collagen mats. In summary, this work demonstrated PFC mats provided strong, slowly degradable, and non-thrombogenic grafts that promoted cell adhesion and growth. Therefore, PFC mats could be used as a functional and durable heart valve replacement.
Management of Ocular Injuries (1977)

Optometry and Vision Science is the most authoritative source for current developments in optometry, physiological optics, and vision science. This frequently cited monthly scientific journal has served primary eye care practitioners for more than 75 years, promoting vital interdisciplinary exchange among optometrists and vision scientists worldwide. Official Journal of the American Academy of Optometry.
Two silencers regulate the tissue-specific expression of the collagen II gene. (1990)

Collagen II, the major component of cartilage, is synthesized primarily by chondrocytes and by certain cells in the eye. Previously, we have studied the regulatory regions of the collagen II gene by DNA transfection assays (Horton, W., Miyashita, T., Kohno, K., and Yamada, Y. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8864-8868). These studies show that both the promoter and an enhancer sequence in the first intron are required for high transcriptional activity in chondrocytes. These elements do not show significant activity in cells which do not synthesize collagen II, such as in muscle cells and fibroblasts. In this report, we have constructed plasmids containing various deletions of the promoter of the collagen II gene, fused to a reporter gene for chloramphenicol acetyltransferase (CAT) and transfected them into both chick embryonic fibroblasts and HeLa cells. We have found that silencer elements in the collagen II promoter region reduce CAT activity 11-fold in fibroblasts, while not affecting the enhancer-mediated transcription in chondrocytes. Deletions in the promoter showed that most of the silencing activity was localized in two sites, between -360 and -460 base pairs and between -620 and -700 base pairs. Furthermore, a fragment containing these two sequences in a thymidine kinase promoter CAT construct reduced the activity of the promoter in an orientation independent fashion. Sequence analysis revealed that the two silencer regions are homologous and contain consensus motifs for silencer elements found in other genes. Gel retardation experiments showed that nuclear factors from HeLa cells bind specifically to a DNA fragment containing the silencer, whereas chondrocyte nuclear extracts did not show any activity. Thus, our study indicates that the expression of the collagen II gene is controlled by both negative and positive elements to ensure that the gene is only expressed in suitable cells.
Combined Effects of Glandless Genes gl2 and gl3 on Pigment Glands in the Cotton Plant (1960)

Synopsis Two genes, gl 2 and gl 3 , were found responsible for glandlessness (absence of pigment glands) in the cotton plant, Gossypium hirsutum L. A third gene, gl 1 , is inherited independently and is masked by the action of gl 2 and gl 3 . Glandlessness is recessive in the seedling stage but partially dominant in the mature stage. Glandless cottonseed, previously found associated with absence of gossypol and other pigments, promises to be of economic value to the cottonseed crushing industry.
Silicon Field Emitter Arrays (2001)

Chapter 5 discusses silicon field emitter arrays (FEA) and their fabrication, emission characteristics and various circuit elements that are made possible with the semiconducting FEA material. It also examines some practical issues concerning the stability and reliability of silicon field emitter arrays.
Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report (2016)

Patients with relapsed or refractory non-Hodgkin lymphoma have a dismal prognosis. Chimeric Antigen Receptor (CAR)-modified T cells (CART cells) that targeted CD20 were effective in a phase I clinical trial for patients with advanced B-cell lymphomas. We performed a phase IIa trial to further assess the safety and efficacy of administering autologous anti-CD20 CART (CART-20) cells to patients with refractory or relapsed CD20<sup>+</sup> B-cell lymphoma. Eleven patients were enrolled, and seven patients underwent cytoreductive chemotherapy to debulk the tumors and deplete the lymphocytes before receiving T-cell infusions. The overall objective response rate was 9 of 11 (81.8%), with 6 complete remissions (CRs) and 3 partial remissions; no severe toxicity was observed. The median progression-free survival lasted for >6 months, and 1 patient had a 27-month continuous CR. A significant inverse correlation between the levels of the <i>CAR</i> gene and disease recurrence or progression was observed. Clinically, the lesions in special sites, specifically the spleen and testicle, were refractory to CART-20 treatment. Collectively, these results together with our data from phase I strongly demonstrated the feasibility and efficacy of CART-20 treatment in lymphomas and suggest large-scale patient recruitment in a future study. This study was registered at www.clinicaltrials.org as NCT01735604.
Improved recognition of native‐like protein structures using a combination of sequence‐dependent and sequence‐independent features of proteins (1999)

We describe the development of a scoring function based on the decomposition P(structure|sequence) ∝ P(sequence|structure) *P(structure), which outperforms previous scoring functions in correctly identifying native-like protein structures in large ensembles of compact decoys. The first term captures sequence-dependent features of protein structures, such as the burial of hydrophobic residues in the core, the second term, universal sequence-independent features, such as the assembly of β-strands into β-sheets. The efficacies of a wide variety of sequence-dependent and sequence-independent features of protein structures for recognizing native-like structures were systematically evaluated using ensembles of ≈30,000 compact conformations with fixed secondary structure for each of 17 small protein domains. The best results were obtained using a core scoring function with P(sequence|structure) parameterized similarly to our previous work (Simons et al., J Mol Biol 1997;268:209–225] and P(structure) focused on secondary structure packing preferences; while several additional features had some discriminatory power on their own, they did not provide any additional discriminatory power when combined with the core scoring function. Our results, on both the training set and the independent decoy set of Park and Levitt (J Mol Biol 1996;258:367–392), suggest that this scoring function should contribute to the prediction of tertiary structure from knowledge of sequence and secondary structure. Proteins 1999;34:82–95. © 1999 Wiley-Liss, Inc.
Protein Sequence Databases (2001)

Abstract The comprehensive, annotated and curated protein sequence databases – the PIR‐International Protein Sequence Database and SWISS‐PROT – support genome annotation, protein functional and structural analysis, proteomics, and phylogenetic studies. The databases are widely available, either free or by subscription, and are augmented by a variety of useful tools and related databases.
Antioxidant and Antitumor Activity of Ganoderma lucidum (Curt.: Fr.) P. Karst.Reishi (Aphyllophoromycetideae) from South India (2000)

Antioxidant and antitumor properties of Ganoderma lucidum (Curt.: Fr.) P. Karst. (Aphyllophoromycetideae) from tropical South India were investigated. A methanol extract of the mushroom showed marked superoxide radical scavenging, hydroxyl radical scavenging, and lipid peroxidation inhibiting activities. The superoxide scavenging activity of the extract was significantly high. The aqueous extract also showed marked hydroxyl radical scavenging and superoxide radical scavenging activity. Hydroxyl radical scavenging activity of the extract was significantly high. However, the aqueous extract did not inhibit lipid peroxidation. Neither methanol nor aqueous extract showed any appreciable antitumor activity against ascites tumor. However, the extracts exhibited significant antitumor activity against solid tumor induced by Ehrlich's ascites carcinoma cells. The results of the investigations indicate that G. lucidum strains occurring in tropical South India possessed significant antioxidant and antitumor properties. The findings suggest the potent therapeutic use of South Indian strains of G. lucidum.