gebhart/patrepeval huggingface dataset:
Stackable Layers: An Architecture for File System Development (1991)

This thesis proposes the stackable layers method of file system design. This approach constructs file systems from a number of independently developed layers. Each layer is bounded by a symmetric interface, syntactically identical above and below. Layers combine in stacks, linear or tree-shaped collections, each layer building on the functionality of those beneath it. Stackable filing improves file system development in several ways. Stacking encourages code re-use by building upon already existing layers. Incremental improvement is possible by substitution of existing layers. The layer interface is extensible, allowing new operations to be easily added by third-parties. Each operation is carefully described, permitting existin...
Epistatic mutations in PUMA BH3 drive an alternate binding mode to potently and selectively inhibit anti-apoptotic Bfl-1 (2017)

Overexpression of anti-apoptotic Bcl-2 family proteins contributes to cancer progression and confers resistance to chemotherapy. Small molecules that target Bcl-2 are used in the clinic to treat leukemia, but tight and selective inhibitors are not available for Bcl-2 paralog Bfl-1. Guided by computational analysis, we designed variants of the native BH3 motif PUMA that are > 150-fold selective for Bfl-1 binding. The designed peptides potently trigger disruption of the mitochondrial outer membrane in cells dependent on Bfl-1, but not in cells dependent on other anti-apoptotic homologs. High-resolution crystal structures show that designed peptide FS2 binds Bfl-1 in a shifted geometry, relative to PUMA and other binding partners, due to a set of epistatic mutations. FS2 modified with an electrophile reacts with a cysteine near the peptide-binding groove to augment specificity. Designed Bfl-1 binders provide reagents for cellular profiling and leads for developing enhanced and cell-permeable peptide or small-molecule inhibitors.
Alternative pathway therapy for urea cycle disorders (1998)

In man the major pathway for the disposal of waste nitrogen is the urea cycle; in inborn errors of this pathway, nitrogen flux is reduced. As a result there is accumulation of ammonia and glutamine with disordered metabolism of other amino acids. Nitrogen homeostasis can be restored in these patients with a low-protein diet combined with compounds that create alternative pathways for nitrogen excretion. The introduction of these compounds has been a major advance in the management of these inborn errors and as a result the outcome, particularly for those treated early, has improved.
Apoptosis and Emphysema (2003)

Keywords: chronic obstructive pulmonary disease, COPD; matrix metalloprotease, MMP; vascular endothelial growth factor, VEGF
Clinical Measurements Using Fiber Optics And Optrodes (1984)

Fiber optics, optrodes, and fluorescence spectroscopy have been combined to form the new technology of remote fiber fluorimetry (RFF). Both in-vivo and in-vitro clinical measurements can be made by using this technique. The optrode, a fiber termination with preselected chemical or physical properties, is attached to the distal end of the optical fiber so that specific, in-situ measurements can be made. RFF systems for pH, blood pressure, oxygen, and carbon dioxide are being completed, and other optrodes are in the development stages.
소규모 사업장 대상 스마트 작업환경관리 서비스 모델 제안 (2021)

Objectives: The purpose of this study is to propose a smart work environment management service model that can measure and maintain work environments in real time.
Methods: How existing private consignment business is being carried out was identified and a simpler method was applied to the model.
Results: Common support was provided according to the Korea Standard Industrial Classification. Hazards suitable for the relevant industry classification were selected and information on safety and health education, etc. was provided. Theme-specific support provides services focusing on hazards that can be measured through applications. Hazards are evaluated by applying new standards divided into ‘Good’, ‘Average’, ‘Inadequate’, and ‘Faulty’.
Conclusions: This model is designed to help employers identify health and safety conditions in small businesses where it is difficult to hire health and safety professionals. Using the app proposed in this study, anyone can easily measure their work environment at any time.
The Relative Effects of Selective Intra-arterial and Intravenous Vasopressin Infusion (1976)

The relative effects of selective intra-arterial and intravenous infusions of vasopressin were evaluated in 16 normotesive dogs. One group was infused via the left gastric artery, one was infused via a peripheral vein, and a control group was not infused. Flow to the stomach and bowel was reduced by an average of 73% and 45%, respectively. There was no significant difference between selective intra-arterial and intravenous infusions with regard to their effects on visceral flow or their systemic parameters. Control animals demonstrated only minor variations from base-line flow.
No-New-Neurons Dogma Loses Ground (1998)

NEUROBIOLOGYBoth popular and scientific wisdom have held that the brain neurons we form when we're young have to last a lifetime because adult brains can't make new neurons. But last week, a research team reported in the Proceedings of the National Academy of Sciences that adult marmoset monkeys make new neurons in the hippocampus, a part of the brain associated with learning and memory. Although previous work had shown that lower species produce brain neurons throughout their lives, some neuroscientists have hailed the new result, because it is the first evidence that the same may be true for primates--perhaps even humans. If further work confirms that the adult human brain can make new neurons, and if these cells join existing functional networks in the brain, it may open the door to repairing brain damage from disease or trauma by enhancing new neuron formation.
Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis. (1992)

The Golgi apparatus (complex) is at the center stage of important functions of processing and transport of plasma membrane, lysosomal, and secreted proteins. The involvement of the Golgi apparatus in the pathogenesis of chronic degenerative diseases of neurons is virtually unknown. In the present study, fragmentation and atrophy of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis (ALS), has been detected with organelle specific antibodies. Approximately 30% of motor neurons in five ALS patients showed a fragmented Golgi apparatus whereas only about 1% of motor neurons from seven controls with neurologic or systemic disease showed a similar change. Morphometric studies are consistent with the hypothesis that the alteration of the Golgi apparatus is an early event in the pathogenesis of the neuronal degeneration in ALS. Immunocytochemical studies with antibodies against alpha tubulin, tau, and phosphorylated subunits of neurofilament polypeptides did not disclose differences in the staining of neurons with fragmented or normal Golgi apparatus, suggesting that the alteration of the organelle is not secondary to a gross lesion of the cytoskeleton. However, these observations do not rule out the hypothesis that the fragmentation of the Golgi apparatus is secondary to subtle changes of the polypeptides involved in the attachment of membranes of the organelle to the cytoskeleton.
Adipose-Derived Stem Cells on Hyaluronic Acid–Derived Scaffold (2012)

Human ASCs on an HA-derived scaffold may be used as a source of keratocytes to regenerate extracellular matrix-like material in situations where the cornea stroma has been compromised.
Epidermal growth factor receptor (EGFR) expression in prostatic adenocarcinoma after hormonal therapy: A fluorescence in situ hybridization and immunohistochemical analysis (2008)

We found that EGFR gene expression was detectable in 35% of this large series of hormone-treated prostate cancer, and that EGFR protein is frequently expressed in tissue from these patients. EGFR over-expression may serve as a reasonable target for therapeutic intervention in this otherwise difficult to treat subset of prostate cancer.
Endocytic uptake of nonenzymatically glycosylated proteins is mediated by a scavenger receptor for aldehyde-modified proteins. (1988)

Long term incubation of proteins with glucose, named the Maillard reaction (Maillard, L. C. (1912) C. R. Acad. Sci. (Paris) 154, 66-68), gives rise to advanced glycosylation end product (AGE) with fluorescence, color, as well as cross-linked properties. The receptor-mediated endocytosis of AGE-proteins by macrophages was reported (Vlassara, H., Brownlee, M., and Cerami, A. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 5588-5592). The present study on the binding of AGE-bovine serum albumin (BSA) to rat peritoneal macrophages and sinusoidal liver cells demonstrated the presence of a saturable, high affinity receptor for AGE-BSA with Kd = 2.4 x 10(-7) M (macrophages) and 2.1 x 10(-7) M (sinusoidal cells). The cellular binding of AGE-BSA and its endocytic uptake by these cells were competitively inhibited by BSA preparations modified with aliphatic aldehydes such as formaldehyde or glycolaldehyde, ligands known to be specific for a scavenger receptor for aldehyde-modified proteins (Horiuchi, S., Murakami, M., Takata, K., and Morino, Y. (1986). J. Biol. Chem. 261, 4962-4966). These ligands also had a profound in vivo effect on the plasma clearance of 125I-AGE-BSA as well as its hepatic uptake. Thus, endocytic uptake of AGE-proteins by macrophages appeared to be mediated by a scavenger receptor for aldehyde-modified proteins. This provides evidence for the biological importance of the scavenger receptor in eliminating senescent macromolecules from the circulation.
Sequence and Structural Elements at the 3′ Terminus of Bovine Viral Diarrhea Virus Genomic RNA: Functional Role during RNA Replication (1999)

Bovine viral diarrhea virus (BVDV), a member of the genus Pestivirus in the family Flaviviridae, has a positive-stranded RNA genome consisting of a single open reading frame and untranslated regions (UTRs) at the 5' and 3' ends. Computer modeling suggested the 3' UTR comprised single-stranded regions as well as stem-loop structures-features that were suspected of being essentially implicated in the viral RNA replication pathway. Employing a subgenomic BVDV RNA (DI9c) that was shown to function as an autonomous RNA replicon (S.-E. Behrens, C. W. Grassmann, H. J. Thiel, G. Meyers, and N. Tautz, J. Virol. 72:2364-2372, 1998) the goal of this study was to determine the RNA secondary structure of the 3' UTR by experimental means and to investigate the significance of defined RNA motifs for the RNA replication pathway. Enzymatic and chemical structure probing revealed mainly the conserved terminal part (termed 3'C) of the DI9c 3' UTR containing distinctive RNA motifs, i.e., a stable stem-loop, SL I, near the RNA 3' terminus and a considerably less stable stem-loop, SL II, that forms the 5' portion of 3'C. SL I and SL II are separated by a long single-stranded intervening sequence, denoted SS. The 3'-terminal four C residues of the viral RNA were confirmed to be single stranded as well. Other intramolecular interactions, e.g., with upstream DI9c RNA sequences, were not detected under the experimental conditions used. Mutagenesis of the DI9c RNA demonstrated that the SL I and SS motifs do indeed play essential roles during RNA replication. Abolition of RNA stems, which ought to maintain the overall folding of SL I, as well as substitution of certain single-stranded nucleotides located in the SS region or SL I loop region, gave rise to DI9c derivatives unable to replicate. Conversely, SL I stems comprising compensatory base exchanges turned out to support replication, but mostly to a lower degree than the original structure. Surprisingly, replacement of a number of residues, although they were previously defined as constituents of a highly conserved stretch of sequence of the SS motif, had little effect on the replication ability of DI9c. In summary, these results indicate that RNA structure as well as sequence elements harbored within the 3'C region of the BVDV 3' UTR create a common cis-acting element of the replication process. The data further point at possible interaction sites of host and/or viral proteins and thus provide valuable information for future experiments intended to identify and characterize these factors.
Induction of apoptotic cell death in human colorectal carcinoma cell lines by a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug: independence from COX-2 protein expression. (1997)

Cyclooxygenase (COX) catalyzes the conversion of arachidonic acid to prostaglandin H2. The inducible isoform, COX-2, promotes colorectal tumorigenesis, and nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit this isoform are chemopreventive in murine models of intestinal tumorigenesis. To establish a mechanism for their chemopreventive properties, we examined the effect of a COX-2-selective inhibitor, NS-398, on two colorectal carcinoma cell lines: HT29, which was found to express COX-2 protein constitutively; and S/KS, which did not express detectable levels of COX-2 protein. NS-398 had a dose-dependent antiproliferative effect on each cell line (IC50, 82.0 +/- 10.1 microM for HT29 and 78.6 +/- 11.1 microM for S/KS), and this was due to the induction of apoptosis. Cell cycle parameters were unaffected by NS-398 treatment. The ability of NS-398 to induce apoptosis provides a potential mechanism by which COX-2-selective inhibitors are chemopreventive and also indicates their potential as chemotherapeutic agents for colorectal cancer. That this effect was independent of COX-2 protein expression suggests that COX-2-selective NSAIDs may, like nonselective NSAIDs, be antineoplastic in the absence of COX-2.
Heterologous expression and functional properties of amiloride high affinity (NHE-1) and low affinity (NHE-3) isoforms of the rat Na/H exchanger (1993)

Recent molecular cloning studies have identified four distinct members (NHE-1,-2,-3,-4) of the Na/H exchanger gene family that are expressed in a tissue-specific pattern. To examine some of their functional properties, full-length cDNAs for two of these isoforms, rat NHE-1 and NHE-3, were stably transfected in Na/H exchanger-deficient Chinese hamster ovary cells (AP-1) and assayed for transport activity by measuring amiloride-inhibitable H(+)-activated 22Na+ influx. Pharmacological analyses revealed that the activity of NHE-1 was substantially more sensitive to inhibition by amiloride and its analogues than NHE-3. Similarly, both isoforms were differentially sensitive to inhibition by cimetidine, clonidine, and harmaline; agents also known to inhibit the activity of the Na/H exchanger. Their rank order of potency for NHE-1 was cimetidine > harmaline > or = clonidine whereas the reverse order was observed for NHE-3. The isoforms were also distinguished by their kinetic properties. While the extracellular Na+ (Na+o) dependence of both isoforms showed simple, saturating Michaelis-Menten kinetics, NHE-1 exhibited a 2-fold lower affinity for Na+o than NHE-3, with apparent KNa values of 10.0 +/- 1.4 and 4.7 +/- 0.6 mM, respectively. In contrast to Na+o, intracellular H+ (H+i) activated both isoforms by a positive cooperative mechanism. However, NHE-1 had a 2-fold higher apparent affinity for H+i compared to NHE-3, with half-maximal activation values of pK 6.75 +/- 0.05 and 6.45 +/- 0.08, respectively. Other external cations also interacted with both exchangers. Li+o and H+o inhibited 22Na+ influx by both isoforms with similar kinetics. In contrast, K+o inhibited 22Na+ influx by NHE-1, but had no effect on NHE-3. Thus NHE-1 and -3 exhibited diverse functional properties when expressed in the same cell type. Furthermore, the functional properties associated with NHE-3 closely mimicked those described for the apical membrane Na/H exchanger of renal proximal tubules, suggesting that these proteins are molecularly identical.
Efficacy and Mechanism-of-Action of a Novel Superagonist Interleukin-15: Interleukin-15 Receptor αSu/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma (2013)

ALT-803, a complex of an interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein, was found to exhibit significantly stronger in vivo biologic activity on NK and T cells than IL-15. In this study, we show that a single dose of ALT-803, but not IL-15 alone, eliminated well-established 5T33P and MOPC-315P myeloma cells in the bone marrow of tumor-bearing mice. ALT-803 treatment also significantly prolonged survival of myeloma-bearing mice and provided resistance to rechallenge with the same tumor cells through a CD8(+) T-cell-dependent mechanism. ALT-803 treatment stimulated CD8(+) T cells to secrete large amounts of IFN-γ and promoted rapid expansion of CD8(+)CD44(high) memory T cells in vivo. These memory CD8(+) T cells exhibited ALT-803-mediated upregulation of NKG2D (KLRK1) but not PD-1 (PDCD1) or CD25 (IL2RA) on their cell surfaces. ALT-803-activated CD8(+) memory T cells also exhibited nonspecific cytotoxicity against myeloma and other tumor cells in vitro, whereas IFN-γ had no direct effect on myeloma cell growth. ALT-803 lost its antimyeloma activity in tumor-bearing IFN-γ knockout mice but retained the ability to promote CD8(+)CD44(high) memory T-cell proliferation, indicating that ALT-803-mediated stimulation of CD8(+)CD44(high) memory T cells is IFN-γ-independent. Thus, besides well-known IL-15 biologic functions in host immunity, this study shows that IL-15-based ALT-803 could activate CD8(+)CD44(high) memory T cells to acquire a unique innate-like phenotype and secrete IFN-γ for nonspecific tumor cell killing. This unique immunomodulatory property of ALT-803 strongly supports its clinical development as a novel immunotherapeutic agent against cancer and viral infections.
Allergic bronchial asthma due to Dermatophagoides pteronyssinus hypersensitivity can be efficiently treated by inoculation of allergen-antibody complexes. (1990)

Antigen-antibody complexes were made from allergens of the common house dust mite, Dermatophagoides pteronyssinus (Dpt) and an excess of purified autologous specific antibodies. These complexes have been used to treat Dpt-hypersensitive patients who suffered from chronic bronchial asthma. Clinical symptoms and medication intake were followed by filling in diary cards. Peak expiratory flow, measured four times a day, was also followed. Intradermal skin tests and bronchial challenge tests were performed with allergen together with an evaluation of nonspecific bronchial reactivity. Specific IgE and IgG antibodies were assayed after separation from the bulk of serum immunoglobulins by immunoadsorption. The study was carried out over two years according to a double-blind protocol. Intradermal inoculation of antigen-antibody complexes resulted in a marked reduction of both clinical and medication scores. No systemic side-effects were observed and only mild wheal and flare reactions were noted at the injection site. The treatment showed a drastic reduction of specific skin and bronchial reactivities with only marginal effects on nonspecific bronchial reactivity. Concentrations of specific IgE antibodies decreased significantly during the first weeks of treatment and remained at these lower values throughout the study. Specific IgG antibodies actually decreased in the majority of treated patients. The total amount of allergen used in this study was less than 1% of the amount currently used for conventional hyposensitization with the same allergen. These findings show that antigen-antibody complex inoculation is an efficient and safe means of treating allergic bronchial asthma and that the mechanism of action is likely to differ from conventional hyposensitization.
Novel Selective Orally Active CRTH2 Antagonists for Allergic Inflammation Developed from in Silico Derived Hits (2006)

Hits from an in silico derived focused library for CRTH2 were transformed into highly selective antagonists with favorable ADME properties. Oral administration of 4-bromo-2-(1-phenyl-1H-pyrazole-4-carbonyl)phenoxyacetic acid (19) inhibited peribronchial eosinophilia and mucus cell hyperplasia in a mouse model of allergic asthma, supporting the therapeutic potential of this novel compound class. In addition, this selective pharmacological tool compound provides further evidence for CRTH2 as a relevant therapeutic target for treatment of Th2- and eosinophil-related inflammation.
Tissue Handling for Genome-Wide Expression Analysis: A Review of the Issues, Evidence, and Opportunities (2007)

Studies have consistently shown that frozen tissue yields more intact RNA than formalin-fixed, paraffin-embedded tissue. The chemical modification, cross-linking, and fragmentation caused by formalin fixation often render RNA unsuitable for microarray analysis. Thus, when expression analysis involving hundreds or more than 1000 gene markers is contemplated, pathologists should consider freezing a specimen within half an hour (preferably within minutes) of surgical resection and storing it at -80 degrees C or below. In coming years, pathologists will need to work closely with oncologists and other clinicians to determine when saving frozen tissue for microarray expression analysis is both practical and necessary. In select cases, the benefit of implementing a few extra tissue-handling steps may improve diagnostic and prognostic capability.
Immobilization of immunoglobulins on silica surfaces. Kinetics of immobilization and influence of ionic strength (1985)

The kinetics of, and the influence of ionic strength on, the immobilization of rabbit immunoglobulin G (IgG) on different types of well-characterized silica surfaces were investigated. Adsorptive immobilization was compared with covalent attachment via thiol-disulphide exchange reactions. The amount of immobilized IgG on five different types of silica surfaces as a function of IgG concentration, at two different ionic strengths, was determined. The IgG-solid-surface interaction involved different types of interaction forces, depending on the surface chemistry of the solid surface. The solid-surface chemistry is an important parameter determining the immobilized amount of IgG. When conditions for covalent attachment of IgG to the surfaces were fulfilled, the IgG showed high affinity and the immobilized amount of IgG showed a fast saturation. Changes in ionic strength showed no significant influence on the kinetics of immobilization on these surfaces. The amount of covalently attached IgG was partially ionic-strength-dependent, indicating that adsorptive interactions were involved. The results are of fundamental interest for the development of new immunosensors based on surface-concentration-measuring devices.
Cross‐linking of collagen in the presence of oxidizing lipid (1978)

Gelatin films containing unsaturated lipid have been exposed to ultraviolet and visible irradiation. No sign of paramagnetism could be detected in the films, although the gelatin was undergoing cross-linking reactions. The addition of nitroxyl-forming radical scavengers decreased the rate of cross-linking as did addition of ascorbic acid to the reacting mixture. Nitroxyls could not be detected in the gels, however. The conclusion is drawn that the main reaction in the cross-linking reaction of collagen is a condensation of amino groups and extrinsic or intrinsic carbonyl groups. The extrinsic aldehydes are formed in the autoxidation of unsaturated lipid.