gebhart/patrepeval huggingface dataset:
Cell cultures derived from Wilms' tumour animal model. (1987)

Several cell cultures were established from a transplantable Wistar/Furth rat Wilms' tumour. Following cloning by the limiting dilutions method, three morphologically distinct types of cells were identified and preserved for further study of growth regulation in the nephroblastoma model.
An Automated and Multiplexed Method for High Throughput Peptide Immunoaffinity Enrichment and Multiple Reaction Monitoring Mass Spectrometry-based Quantification of Protein Biomarkers (2009)

There is an urgent need for quantitative assays in verifying and validating the large numbers of protein biomarker candidates produced in modern "-omics" experiments. Stable isotope standards with capture by anti-peptide antibodies (SISCAPA) has shown tremendous potential to meet this need by combining peptide immunoaffinity enrichment with quantitative mass spectrometry. In this study, we describe three significant advances to the SISCAPA technique. First, we develop a method for an automated magnetic bead-based platform capable of high throughput processing. Second, we implement the automated method in a multiplexed SISCAPA assay (nine targets in one assay) and assess the performance characteristics of the multiplexed assay. Using the automated, multiplexed platform, we demonstrate detection limits in the physiologically relevant ng/ml range (from 10 microl of plasma) with sufficient precision (median coefficient of variation, 12.6%) for quantifying biomarkers. Third, we demonstrate that enrichment of peptides from larger volumes of plasma (1 ml) can extend the limits of detection to the low pg/ml range of protein concentration. The method is generally applicable to any protein or biological specimen of interest and holds great promise for analyzing large numbers of biomarker candidates.
The Driver and the Passengers (2000)

The Driver and the Passengers"Georgie's nerves felt like they were carrying an electric current.A hopeless sense of rage and desperation had been lying inside of him for a long time, and quitting smoking was only helping to extenuate it.Sitting in the back of Derek's father's car, he felt like he had shot his life, and now it was crumbling-slowly but more rapidly all the time.But sitting in the back of the car listening to classic rock on the radio was tolerable, despite his nicotine craving.As long as the car ride continued as it had been, he knew he'd be all right.Jordan sat in the backseat with Georgie.Georgie was glad Jordan was his brother because he was a good kid that pretty much had things put together.Jordan's girlfriend May sat in the front seat smoking a cigarette she had bummed from Derek.Georgie was scared of May because she was pretty and blonde and dangerous somehow.A real dish was how Georgie would describe her.Derek drove his father's old Cadillac and wore Oakley's and smoked a cigarette.Georgie liked Derek because the two of them didn't have to talk about important things all the time or even talk at all if they didn't want to.The four kids stared out the windows of the car as they crossed the bridge that led to the big city.Georgie was the only one out of high school, and he was aware of that, and it bothered him.He was glad that nobody was talking, but then May ruined the silence."I don't like this song."She turned off Supertramp and put on one of the popular stations.Georgie felt his rage flare up.As a general rule, people were not supposed to touch the radio in other people's cars with out permission, but Derek didn't say anything.When the next song came on Derek changed the station back to classic rock."Hey, that was ... " "I don't care.I control the radio, and 1 hate that song," Derek interrupted her."Why don't we just turn off the radio and talk?" May asked.
A Simple Glycol Nucleic Acid (2005)

A glycol nucleic acid (GNA) with an acyclic propylene glycol phosphodiester backbone forms stable antiparallel duplexes following the Watson-Crick base pairing rules.
Biomass fast pyrolysis in fluidized bed : product cleaning by in-situ filtration (2006)

This thesis is dedicated to the subject of fast pyrolysis in a fluid bed reactor. A large part of the work is related to reactor design aspects of fast pyrolysis, a subject that has not been considered sufficiently. Past research efforts were focussed mainly on the kinetics of wood pyrolysis and the testing of different reactor types by measuring the bio-oil yield as a function of the reactor temperature.
The Effects of Surgical Fracture Fixation on the Systemic Inflammatory Response to Major Trauma (2005)

Early stabilization of major long bone fractures is beneficial in reducing the incidence of acute respiratory distress syndrome and multiple organ failure, both of which are caused by activation of the systemic inflammatory response. This activation results in tissue recruitment of and injury by circulating polymorphonuclear leukocytes. The reasons for clinical benefits of early fracture stabilization in major trauma are unknown. Published studies indicate that fracture surgery increases the posttraumatic inflammatory response. Major surgery to stabilize fractures carries a higher complication rate when performed on patients whose hypovolemic shock is not fully corrected. Thus, fracture care should be tailored to the patient, not dictated by the injured bone. Understanding the impact of fracture surgery on the systemic inflammatory response to major trauma is necessary to refine treatment and to apply it optimally to all patients.
Nutritional correlates and dynamics of diabetes in the Nile rat (Arvicanthis niloticus): a novel model for diet-induced type 2 diabetes and the metabolic syndrome (2010)

The Nile rat fed typical rodent diets develops hyperinsulinemia that precedes hyperglycemia (insulin resistance) leading to diet-induced type 2 diabetes associated with hypertriglyceridemia, hypercholesterolemia, and hypertension. Dietary modulation affected growth rate (weight gain and central adiposity) to impact disease progression. This rodent model represents a novel system of gene-diet interactions affecting energy utilization that can provide insight into the prevention and treatment of the type 2 diabetes and Metabolic Syndrome.
Studies on the chirality of sulfoxidation catalyzed by bacterial flavoenzyme cyclohexanone monooxygenase and hog liver FAD-containing monooxygenase (1982)

The stereochemical outcome of oxygen transfer to the sulfur moiety of aryl alkyl sulfides catalyzed by two flavoenzyme monooxygenases has been determined by resolution of sulfoxide product enantionmers on a high-pressure liquid chromatography column [Pirkle, W. H., Finn, J. M. Schreiner, J. L., & Hamper, B. C. (1981) J. Am. Chem. Soc. 103, 3964-3966] containing a 3,5-dinitrobenzoyl-D-phenylglycine chiral stationary phase. With 4-tolyl ethyl sulfide as substrate, cyclohexanone monooxygenase from Acinetobacter produces predominantly the (S)-(-)-sulfoxide (82% S, 18% R), a modest enantioselectivity. In contrast, the flavin adenine dinucleotide (FAD) containing a monooxygenase purified from hog liver microsomes carries out sulfoxidation to yield the (R)-(+)-sulfoxide enantiomer as major product (95% R, 5% S). The presence of the minor sulfoxide enantiomer in each case appears to be due to incomplete chiral processing by each enzyme and not to a competing, achiral, nonenzymic sulfoxidation process. The mammalian FAD-containing monooxygenase also oxygenates the divalent sulfur of the antiarthritic drug sulindac sulfide to yield a single dextrorotatory isomer of the sulfoxide prodrug. Analysis of the chiral outcome of sulfoxidation catalyzed by rat liver microsomes indicated that phenobarbital treatment increases the capacity for S-(-)-oxygenation of 4-tolyl ethyl sulfide, suggesting that the phenobarbital-induced cytochrome P-450 isoenzymes catalyze formation of the (S)-(-)-sulfoxide preferentially, a surmise validated in the following paper [Waxman, D. J., Light, D. R., & Walsh, C. (1982) Biochemistry (following paper in this issue)]. With sulindac sulfide as substrate, though, both control and phenobarbital-induced microsomes catalyze sulfoxidation to yield the same (+)-sulfoxide enantiomer generated by the purified FAD-containing monoxygenase, suggesting a low degree of participation by the cytochrome P-450 isozymes in sulfoxidation of this compound.
Reactive oxygen intermediates as regulators of TNF-α production in rat lung inflammation induced by silica (1996)

Exposure to mineral dusts such as silica has been associated with progressive pulmonary inflammation and fibrosis. There is evidence that the release of reactive oxygen intermediates (ROI) and cytokines by alveolar macrophages (AM) is involved in lung injury associated with silica exposure. However, the chronology and relationship between these two mediators are poorly understood. In this study, an animal model of silicosis has been used, allowing simultaneous follow-up of lung histopathologic state, AM TNF-alpha production at the protein (biologic assay) and mRNA (reverse transcriptase-PCR) levels, and the release of ROI (luminol-dependent chemiluminescence), after bronchoalveolar lavages. In particular, it has been shown that intratracheal instillation of silica (50 mg/kg) in rats led to fibrosis characterized by cellular interstitial infiltrates with granulomas, and in AM, it led to 1) an early and continuous increase in 12-O-tetradecanoylphorbol-13-acetate- or zymosan-triggered ROI production (days 1, 3, 14, and 28 post-treatment), and 2) a rise of TNF-alpha mRNA expression and protein secretion on days 3 and 14. A free radical scavenger pretreatment (N-ter-butyl-alpha-phenylnitrone) reversed lung histopathologic changes and decreased AM ROI production and TNF-alpha expression at the level of mRNA. These findings suggest that ROI production is an important primary event determining the silica-induced inflammatory process. ROI may act in an autocrine or paracrine manner and regulate TNF-alpha production by a mechanism promoting gene expression. The critical role of this cytokine in the pathogenesis of silicosis was confirmed by anti-TNF-alpha Ab treatment.
Viremia in Acute Herpes Zoster (2009)

The detection of VZV DNA in the serum and peripheral blood mononuclear cells of all 25 zoster patients documents that viremia is a common manifestation of herpes zoster. Sorivudine cream appears to be a safe and well-tolerated adjuvant therapy; however, further phase 2 studies are needed to determine its clinical efficacy for the treatment of herpes zoster. Trials registration. ClinicalTrials.gov identifier: NCT00652184.
Generation and characterization of LymphoStat‐B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator (2003)

A fully human monoclonal antibody has been isolated that binds to BLyS with high affinity and neutralizes human BLyS bioactivity in vitro and in vivo. Administration of this antibody to cynomolgus monkeys resulted in B cell depletion in spleen and lymph node. This antibody may prove therapeutically useful in the treatment of autoimmune diseases in humans.
A Preorganized Active Site in the Crystal Structure of the Tetrahymena Ribozyme (1998)

Group I introns possess a single active site that catalyzes the two sequential reactions of self-splicing. An RNA comprising the two domains of the Tetrahymena thermophila group I intron catalytic core retains activity, and the 5.0 angstrom crystal structure of this 247-nucleotide ribozyme is now described. Close packing of the two domains forms a shallow cleft capable of binding the short helix that contains the 5' splice site. The helix that provides the binding site for the guanosine substrate deviates significantly from A-form geometry, providing a tight binding pocket. The binding pockets for both the 5' splice site helix and guanosine are formed and oriented in the absence of these substrates. Thus, this large ribozyme is largely preorganized for catalysis, much like a globular protein enzyme.
Effects of Limited Aeration and of the ArcAB System on Intermediary Pyruvate Catabolism in Escherichia coli (2000)

The capacity of Escherichia coli to adapt its catabolism to prevailing redox conditions resides mainly in three catabolic branch points involving (i) pyruvate formate-lyase (PFL) and the pyruvate dehydrogenase complex (PDHc), (ii) the exclusively fermentative enzymes and those of the Krebs cycle, and (iii) the alternative terminal cytochrome bd and cytochrome bo oxidases. A quantitative analysis of the relative catabolic fluxes through these pathways is presented for steady-state glucose-limited chemostat cultures with controlled oxygen availability ranging from full aerobiosis to complete anaerobiosis. Remarkably, PFL contributed significantly to the catabolic flux under microaerobic conditions and was found to be active simultaneously with PDHc and cytochrome bd oxidase-dependent respiration. The synthesis of PFL and cytochrome bd oxidase was found to be maximal in the lower microaerobic range but not in a delta ArcA mutant, and we conclude that the Arc system is more active with respect to regulation of these two positively regulated operons during microaerobiosis than during anaerobiosis.
cql: Flat file database query language (1994)

cql is a UNIX system tool that applies C style query expressions to flat file databases. In some respects it is yet another addition to the toolbox of programmable file filters: grep [Hume88], sh [Bour78][BK89], awk [AKW88], and perl [Wall]. However, by restricting its problem domain, cql takes advantage of optimizations not available to these more general purpose tools. This paper describes the cql data description and query language, query optimizations, and provides comparisons with other tools. 1 Introduction Flat file databases are common in UNIX system environments. They consist of newline terminated records with a single character that delimits fields within each record. Well known examples are /etc/passwd and /etc/group, and more recently the sablime [CF88] MR databases and cia [Chen89] abstraction databases. There are two basic flat file database operations: update -- delete, add or modify records query -- scan for records based on field selection function For the most...
Inflammatory Bowel Disease (2015)

Ethiopian Jews migrating to Israel are at risk of developing IBD. Larger cohorts are needed to determine the relative importance of environmental and genetic factors that cause IBD in these patients.
Suppression of STING Associated with LKB1 Loss in KRAS-Driven Lung Cancer (2018)

<i>KRAS</i>-driven lung cancers frequently inactivate <i>TP53</i> and/or <i>STK11/LKB1</i>, defining tumor subclasses with emerging clinical relevance. Specifically, <i>KRAS</i>-<i>LKB1</i> (KL)-mutant lung cancers are particularly aggressive, lack PD-L1, and respond poorly to immune checkpoint blockade (ICB). The mechanistic basis for this impaired immunogenicity, despite the overall high mutational load of <i>KRAS</i>-mutant lung cancers, remains obscure. Here, we report that LKB1 loss results in marked silencing of stimulator of interferon genes (STING) expression and insensitivity to cytoplasmic double-strand DNA (dsDNA) sensing. This effect is mediated at least in part by hyperactivation of DNMT1 and EZH2 activity related to elevated S-adenylmethionine levels and reinforced by DNMT1 upregulation. Ectopic expression of STING in KL cells engages IRF3 and STAT1 signaling downstream of TBK1 and impairs cellular fitness, due to the pathologic accumulation of cytoplasmic mitochondrial dsDNA associated with mitochondrial dysfunction. Thus, silencing of STING avoids these negative consequences of LKB1 inactivation, while facilitating immune escape. SIGNIFICANCE: Oncogenic <i>KRAS</i>-mutant lung cancers remain treatment-refractory and are resistant to ICB in the setting of LKB1 loss. These results begin to uncover the key underlying mechanism and identify strategies to restore STING expression, with important therapeutic implications because mitochondrial dysfunction is an obligate component of this tumor subtype.<i>See related commentary by Corte and Byers, p. 16</i>.<i>This article is highlighted in the In This Issue feature, p. 1</i>.
Complement receptor 2–mediated targeting of complement inhibitors to sites of complement activation (2003)

In a strategy to specifically target complement inhibitors to sites of complement activation and disease, recombinant fusion proteins consisting of a complement inhibitor linked to a C3 binding region of complement receptor (CR) 2 were prepared and characterized. Natural ligands for CR2 are C3 breakdown products deposited at sites of complement activation. Fusion proteins were prepared consisting of a human CR2 fragment linked to either the N terminus or C terminus of soluble forms of the membrane complement inhibitors decay accelerating factor (DAF) or CD59. The targeted complement inhibitors bound to C3-opsonized cells, and all were significantly more effective (up to 20-fold) than corresponding untargeted inhibitors at protecting target cells from complement. CR2 fusion proteins also inhibited CR3-dependent adhesion of U937 cells to C3 opsonized erythrocytes, indicating a second potential anti-inflammatory mechanism of CR2 fusion proteins, since CR3 is involved in endothelial adhesion and diapedesis of leukocytes at inflammatory sites. Finally, the in vivo validity of the targeting strategy was confirmed by the demonstration that CR2-DAF, but not soluble DAF, targets to the kidney in mouse models of lupus nephritis that are associated with renal complement deposition.
Phase I-II Study of Gemcitabine and Fluorouracil as a Continuous Infusion in Patients With Pancreatic Cancer (1999)

The MTD of gemcitabine when combined with 5-FU via PVI on this schedule was 1,000 mg/m2/ wk; however, on the basis of administered dose-intensity, the recommended dose for additional investigation is 900 mg/m2. This combination chemotherapy regimen was well tolerated and showed promising antitumor activity in the treatment of pancreatic cancer.
Novel concept for ultracompact polarization splitter-rotator based on silicon nanowires (2011)

A novel concept for an ultracompact polarization splitter-rotator is proposed by utilizing a structure combining an adiabatic taper and an asymmetrical directional coupler. The adiabatic taper structure is singlemode at the input end while it becomes multimode at the other end. When light propagates along the adiabatic taper structure, the TM fundamental mode launched at the narrow end is efficiently (close to 100%) converted to the first higher-order TE mode at the wide end because of the mode coupling between them. By using an asymmetrical directional coupler that has two adjacent waveguides with different core widths, the first higher-order TE mode is then coupled to the TE fundamental mode of the adjacent narrow waveguide. On the other hand, the input TE polarization does not change when it goes through the adiabatic taper structure. In the region of the asymmetrical directional coupler, the TE fundamental mode in the wide waveguide is not coupled to the adjacent narrow waveguide because of phase mismatch. In this way, TE- and TM- polarized light are separated while the TM fundamental mode is also converted into the TE fundamental mode. A design example of the proposed polarization splitter-rotator is given by using silicon-on-insulator nanowires and the total length of the device is less than 100μm. Furthermore, only a one-mask process is needed for the fabrication process, which is compatible with the standard fabrication for the regular photonic integrated circuits based on SOI nanowires.
Abstract 14725: Effect of SAR236553/REGN727 Fully Human Monoclonal Anti-Proprotein Convertase Subtilisin/Kexin Type 9 Antibody on Plasma Lipoprotein(a) Concentrations: Pooled Analysis from Three Phase 2 Studies (NCT:01266876; 01288469; 01288443) (2012)

Background: Lipoprotein (a) [Lp(a)], an LDL-like lipoprotein with apolipoprotein (a) covalently bound to the existing apoB protein, increases the risk of CV disease. Only apheresis and high- dose n...
Delivery of Full-Length Factor VIII Using a piggyBac Transposon Vector to Correct a Mouse Model of Hemophilia A (2014)

Viral vectors have been used for hemophilia A gene therapy. However, due to its large size, full-length Factor VIII (FVIII) cDNA has not been successfully delivered using conventional viral vectors. Moreover, viral vectors may pose safety risks, e.g., adverse immunological reactions or virus-mediated cytotoxicity. Here, we took advantages of the non-viral vector gene delivery system based on piggyBac DNA transposon to transfer the full-length FVIII cDNA, for the purpose of treating hemophilia A. We tested the efficiency of this new vector system in human 293T cells and iPS cells, and confirmed the expression of the full-length FVIII in culture media using activity-sensitive coagulation assays. Hydrodynamic injection of the piggyBac vectors into hemophilia A mice temporally treated with an immunosuppressant resulted in stable production of circulating FVIII for over 300 days without development of anti-FVIII antibodies. Furthermore, tail-clip assay revealed significant improvement of blood coagulation time in the treated mice. piggyBac transposon vectors can facilitate the long-term expression of therapeutic transgenes in vitro and in vivo. This novel gene transfer strategy should provide safe and efficient delivery of FVIII.
Cell Docking in Double Grooves in a Microfluidic Channel (2009)

Microstructures that generate shear-protected regions in microchannels can rapidly immobilize cells for cell-based biosensing and drug screening. Here, a two-step fabrication method is used to generate double microgrooves with various depth ratios to achieve controlled double-level cell patterning while still providing shear protection. Six microgroove geometries are fabricated with different groove widths and depth ratios. Two modes of cell docking are observed: cells docked upstream in sufficiently deep and narrow grooves, and downstream in shallow, wide grooves. Computational flow simulations link the groove geometry and bottom shear stress to the experimental cell docking patterns. Analysis of the experimental cell retention in the double grooves demonstrates its linear dependence on inlet flow speed, with slope inversely proportional to the sheltering provided by the groove geometry. Thus, double-grooved microstructures in microfluidic channels provide shear-protected regions for cell docking and immobilization and appear promising for cell-based biosensing and drug discovery.
Lymphotactin Acts as an Innate Mucosal Adjuvant (1999)

Lymphotactin (Lptn) is a C chemokine produced predominantly by NK and CD8-positive (CD8+) T cells including gammadelta TCR-positive (TCR+) intraepithelial lymphocytes. Lptn is chemotactic for NK and T cells and likely plays an important role in maintaining the integrity of the epithelium and in mucosal immune responses. In this study, we characterized the immune responses to OVA given intranasally with Lptn to mice. This regimen enhanced OVA-specific serum Ab responses and Ab titers in mucosal secretions. Lptn also enhanced OVA-specific Ab-forming cells in mucosal and systemic compartments. CD4-positive (CD4+) T cells isolated from mucosal compartments and spleens of mice intranasally immunized with OVA plus Lptn displayed higher OVA-specific proliferative responses and greater synthesis of IFN-gamma, IL-2, IL-4, IL-5, IL-6, and IL-10 than did CD4+ T cells from mice given OVA without Lptn. These studies indicate that Lptn has adjuvant properties and suggest that Lptn present in the mucosa has the potential to enhance mucosal and systemic Ab responses through help provided by Th1- and Th2-type cells to link the initial innate signals of the mucosa with the acquired immune system.