gebhart/patrepeval huggingface dataset:
Erythromycin Modulates IL-8 Expression in Normal and Inflamed Human Bronchial Epithelial Cells (1997)

Erythromycin (EM) and its 14-member macrolide analogues have attracted attention for its effectiveness in a variety of airway diseases, including diffuse panbronchiolitis (DPB), sinobronchial syndrome, and chronic sinusitis. However, its mechanisms of action remain unelucidated. We evaluated the effects of several antibiotics on IL-8 expression by normal and transformed human bronchial epithelial cells, an important source of this potent chemokine involved in cell recruitment into the airways. EM and clarithromycin (CAM) uniquely suppressed mRNA levels as well as the release of IL-8 at the therapeutic and noncytotoxic concentrations (% inhibition of IL-8 protein release: 25.0 +/- 5.67% and 37.5 +/- 8.99%, respectively, at 10(-6) M). The other antimicrobes, including a 16-member macrolide josamycin, showed no effect. Bronchial epithelial cells from very peripheral airways as well as from main bronchi were obtained from patients with chronic airway inflammatory diseases, and EM and CAM inhibited IL-8 release from these cells. Among five patients who underwent bronchoscopy before and after macrolide treatment, four showed decreased levels of IL-8 expression in airway epithelium as assessed by reverse transcription and polymerase chain reaction. Our findings showed these 14-member macrolides had inhibitory effect on IL-8 expression in human bronchial epithelial cells, and this new mode of action may have relevance to their clinical effectiveness in airway diseases.
The benefits of bonding: silicon on insulator for bipolar ICs (1994)

The use of silicon on insulator (SOI) is currently restricted to MOS integrated circuits. The author describes a research programme aimed at extending the benefits of SOI to bipolar devices. The process uses twin wafers, electrochemically bonded to produce oxide-isolated active regions of high purity and very low defect density.
Steroidal[3,2-c]pyrazoles. II.1 Androstanes, 19-Norandrostanes and their Unsaturated Analogs (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteroidal[3,2-c]pyrazoles. II.1 Androstanes, 19-Norandrostanes and their Unsaturated AnalogsR. O. Clinton, A. J. Manson, F. W. Stonner, H. C. Neumann, R. G. Christiansen, R. L. Clarke, J. H. Ackerman, D. F. Page, J. W. Dean, W. B. Dickinson, and Clarissa CarabateasCite this: J. Am. Chem. Soc. 1961, 83, 6, 1478–1491Publication Date (Print):March 1, 1961Publication History Published online1 May 2002Published inissue 1 March 1961https://pubs.acs.org/doi/10.1021/ja01467a047https://doi.org/10.1021/ja01467a047research-articleACS PublicationsRequest reuse permissionsArticle Views511Altmetric-Citations113LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Discogenic pain (2004)

aThe Orthopaedic Hospital and Rehabilitation Centre, ORTON, Tenholantie 10, 00280 Helsinki, Finland bFinnish Institute of Occupational Health, Helsinki, Finland cDepartment of Physical Medicine and Rehabilitation, Oulu University Hospital, Oulu, Finland *Corresponding author. Tel.: +358 9 4748 6685; fax: +358 9 4748 2587. E-mail: [email protected] Accepted August 23, 2004.
An apolipoprotein E synthetic peptide targets to lipoproteins in plasma and mediates both cellular lipoprotein interactions in vitro and acute clearance of cholesterol-rich lipoproteins in vivo. (1998)

Apolipoprotein (apo) E mediates lipoprotein binding to cellular lipoprotein receptors. Previously we reported that a synthetic peptide representing a linear dimeric repeat of amino acids 141-155 binds cellular LDL receptors. To prepare an apoE peptide that bound to both cholesterol-rich lipoproteins and lipoprotein receptors, an NH2-terminal acetylated apoE dimer peptide was synthesized. This acetylated peptide preferentially associated with lipoproteins in plasma, whereas nonacylated peptides were poor lipid binders. Acetylated peptide/LDL complexes (molar ratios of 4-5:1) enhanced the interaction of LDL with cultured human fibroblasts by 7-12-fold. Participation by both receptors and cell surface heparin sulfate proteoglycans was observed. When a preformed peptide/125I-LDL complex was injected intravenously into C57BL/6J apoE-deficient mice, its rate of removal was threefold higher than that of 125I-LDL alone. The liver and the spleen were major tissue distribution sites. Intravenous administration of free acetylated peptide resulted in a 30% reduction in total plasma cholesterol within 3-30 min, which reflected a 40-50% and 20-26% reduction in very low density lipoproteins and intermediate density lipoproteins, respectively. Therefore, this peptide selectively associated with cholesterol-rich lipoproteins and mediated their acute clearance in vivo.
The effects of reactive nitrogen intermediates on gene expression inMycobacterium tuberculosis (2003)

Nitric oxide (NO) and related reactive nitrogen intermediates (RNI) are effective antimycobacterial agents and signal-transducing molecules. The present study uses microarray analysis to examine the effects of RNI on Mycobacterium tuberculosis gene expression. A common set of 53 genes was regulated by two chemically distinct nitric oxide donors. For a subset of the RNI-inducible genes, evidence exists suggesting that they may play a role in promoting survival of the tubercle bacillus in the host. Results obtained from studies based on a murine experimental tuberculosis model involving nos2-deficient mice suggest that RNI could regulate M. tuberculosis gene expression in vivo. Finally, there is a remarkable overlap between the RNI-inducible regulon and that previously reported to be regulated by hypoxia; and both reactive nitrogen species and anaerobicity upregulate the expression of one and the same putative two-component regulatory response system. Together, the results of this study provide evidence suggesting that (i) RNI play a role in regulating M. tuberculosis gene expression in vivo; (ii) the reactive nitrogen species upregulate genes that may be conducive to the survival of the tubercle bacillus in the infected host; and (iii) RNI and hypoxia may regulate mycobacterial gene expression via overlapping signal transduction pathways.
γ‐Secretase inhibitors in cancer clinical trials are pharmacologically and functionally distinct (2017)

γ-Secretase inhibitors (GSIs) are being actively repurposed as cancer therapeutics based on the premise that inhibition of NOTCH1 signaling in select cancers is therapeutic. Using novel assays to probe effects of GSIs against a broader panel of substrates, we demonstrate that clinical GSIs are pharmacologically distinct. GSIs show differential profiles of inhibition of the various NOTCH substrates, with some enhancing cleavage of other NOTCH substrates at concentrations where NOTCH1 cleavage is inhibited. Several GSIs are also potent inhibitors of select signal peptide peptidase (SPP/SPPL) family members. Extending these findings to mammosphere inhibition assays in triple-negative breast cancer lines, we establish that these GSIs have different functional effects. We also demonstrate that the processive γ-secretase cleavage pattern established for amyloid precursor protein (APP) occurs in multiple substrates and that potentiation of γ-secretase cleavage is attributable to a direct action of low concentrations of GSIs on γ-secretase. Such data definitively demonstrate that the clinical GSIs are not biological equivalents, and provide an important framework to evaluate results from ongoing and completed human trials with these compounds.
Propofol Concentrations--An Alternative Explanation (1996)

In Response: We thank Dr. Eger for his comments. He proposed another explanation for our finding about concentration differences between plasma and whole blood samples [1]. His suggestion, delay in propofol release from the lipid vesicle used as the vehicle, is a rational explanation for the results observed from constant infusion of propofol. However, such a mechanism cannot explain the results after a bolus injection of propofol. We extracted all propofol by CHCl3 from the plasma samples, regardless of the bound of vehicle lipid [2]. The apparent plasma or blood concentration composes total (released and vehicle entrapped) propofol. If the delay in propofol release from vehicle lipid is true, the immediate separation of plasma would result in higher propofol concentrations than those from storage in plasma. Propofol in its vehicle prevents release to red blood cells (RBCs) when the lipid is cleared from the plasma. However, our results show the opposite. The plasma concentration is higher in the sample with storage for 1 h in the group receiving a bolus injection. From the rapid distribution phase of propofol, the effect of delay in propofol release from the lipid vesicles, used as vehicle, on the distribution of propofol seems negligible. The high lipid solubility of propofol and its distribution in RBCs must be localized mainly in the RBC membrane [3]. Perhaps it would be more appropriate to change the wording from "across" blood cell membrane to "from" blood cell membrane. Shou-Zen Fan, MD, PhD Hsiu-Ying Yu, PhD Yung-Liang Chen, PhD Chien-Chiang Lui, MD, PhD Department of Anesthesiology National Taiwan University Hospital Taipei, Taiwan 10016, Republic of China
The Oligomerization Domain of C4-Binding Protein (C4bp) Acts as an Adjuvant, and the Fusion Protein Comprised of the 19-Kilodalton Merozoite Surface Protein 1 Fused with the Murine C4bp Domain Protects Mice against Malaria (2008)

Highly purified protein antigens are usually poor immunogens; in practice, adjuvants are needed to obtain satisfactory immune responses. Plasmodium yoelii 19-kDa merozoite surface protein 1 (MSP1(19)) is a weak antigen, but mice vaccinated with this antigen in strong adjuvants can survive an otherwise lethal parasite challenge. Fusion proteins comprising this antigen fused to the oligomerization domain of the murine complement inhibitor C4-binding protein (C4bp) and a series of homologues have been produced. These C4bp domains acted as adjuvants for the fused antigen; the MSP1(19)-murine C4bp fusion protein induced protective immunity in BALB/c mice. Because this fusion protein also induced antibodies against circulating murine C4bp, distantly related C4bp oligomerization domains fused to the same antigen were tested. These homologous domains did not induce antibodies against murine C4bp and, surprisingly, induced higher antibody titers against the antigen than the murine C4bp domain induced. These results demonstrate a new adjuvantlike effect of C4bp oligomerization domains.
Biologic properties and enucleation of red blood cells from human embryonic stem cells (2008)

Human erythropoiesis is a complex multistep process that involves the differentiation of early erythroid progenitors to mature erythrocytes. Here we show that it is feasible to differentiate and mature human embryonic stem cells (hESCs) into functional oxygen-carrying erythrocytes on a large scale (10(10)-10(11) cells/6-well plate hESCs). We also show for the first time that the oxygen equilibrium curves of the hESC-derived cells are comparable with normal red blood cells and respond to changes in pH and 2,3-diphosphoglyerate. Although these cells mainly expressed fetal and embryonic globins, they also possessed the capacity to express the adult beta-globin chain on further maturation in vitro. Polymerase chain reaction and globin chain specific immunofluorescent analysis showed that the cells increased expression of beta-globin (from 0% to > 16%) after in vitro culture. Importantly, the cells underwent multiple maturation events, including a progressive decrease in size, increase in glycophorin A expression, and chromatin and nuclear condensation. This process resulted in extrusion of the pycnotic nuclei in up to more than 60% of the cells generating red blood cells with a diameter of approximately 6 to 8 mum. The results show that it is feasible to differentiate and mature hESCs into functional oxygen-carrying erythrocytes on a large scale.
High-efficiency antibody discovery achieved with multiplexed microscopy (2016)

The analysis of secreted antibody from large and diverse populations of B cells in parallel at the clonal level can reveal desirable antibodies for diagnostic or therapeutic applications. By immobilizing B cells in microdroplets with particulate reporters, decoding and isolating them in a microscopy environment, we have recovered panels of antibodies with rare attributes to therapeutically relevant targets. The ability to screen up to 100 million cells in a single experiment can be fully leveraged by accessing primary B-cell populations from evolutionarily divergent species such as chickens.
Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor γ and the retinoid X receptor (1997)

Induction of terminal differentiation represents a promising therapeutic approach to certain human malignancies. The peroxisome proliferator-activated receptor gamma (PPAR gamma) and the retinoid X receptor alpha (RXR alpha) form a heterodimeric complex that functions as a central regulator of adipocyte differentiation. Natural and synthetic ligands for both receptors have been identified. We demonstrate here that PPAR gamma is expressed at high levels in each of the major histologic types of human liposarcoma. Moreover, primary human liposarcoma cells can be induced to undergo terminal differentiation by treatment with the PPAR gamma ligand pioglitazone, suggesting that the differentiation block in these cells can be overcome by maximal activation of the PPAR pathway. We further demonstrate that RXR-specific ligands are also potent adipogenic agents in cells expressing the PPAR gamma/RXR alpha heterodimer, and that simultaneous treatment of liposarcoma cells with both PPAR gamma- and RXR-specific ligands results in an additive stimulation of differentiation. Liposarcoma cell differentiation is characterized by accumulation of intracellular lipid, induction of adipocyte-specific genes, and withdrawal from the cell cycle. These results suggest that PPAR gamma ligands such as thiazolidinediones and RXR-specific retinoids may be useful therapeutic agents for the treatment of liposarcoma.
Analysis of Chondroitin Sulfate/Dermatan Sulfate Chains in Rat Peritoneal Resident Macrophages. (1993)

Chondroitin sulfate/dermatan sulfate (CS/DS) hybrid polymers obtained from rat peritoneal resident macrophages were analyzed by the enzymatic method; CS/DS chains were digested by chondroitinase, and the resultant unsaturated disaccharides were determined by HPLC with fluorometric detection. CS/DS in the resident macrophages are constituted of Di-4S, Di-6S, Di-diSE, Di-diSB and Di-triS.
Survival of recombinant erythropoietin in the circulation: the role of carbohydrates (1989)

Abstract Recombinant human erythropoietin produced in transfected Chinese hamster ovary cells is glycosylated much the same way as the erythropoietin present in human urine. To determine the role of carbohydrates in the stability of recombinant human erythropoietin in vivo, [125I]-labeled recombinant erythropoietin was intravenously infused into rats. The erythropoietin was slowly cleared from the blood with a half-life of approximately two hours. Asialoerythropoietin, which was produced by treatment of recombinant human erythropoietin with sialidase, was found to be cleared rapidly from circulation within ten minutes. These data suggest that the galactose binding protein of hepatic cells is involved in the clearance of asialoerythropoietin. Erythropoietin also contains N-glycans with a few N-acetyllactosamine repeats, which can be enriched by tomato lectin affinity chromatography. The lectin-bound fraction was cleared to a larger extent than was the unfractionated erythropoietin, while the component that did not bind the lectin was found to be stable in the circulation. Authentic N-acetyllactosamine repeats (polylactosaminoglycans) prepared from erythrocytes were similarly rapidly cleared from the circulation to the liver, and this clearance was inhibitable with asialo-alpha 1- acid glycoprotein. These results suggest that (a) the sialic acid of the recombinant erythropoietin is necessary for this glycoprotein hormone to circulate stably and (b) glycoproteins with more than three lactosaminyl repeat units may be cleared by the galactose binding protein of hepatocytes.
Vasodilator therapy in acute myocardial infarction. A comparison of sodium nitroprusside and nitroglycerin. (1975)

Twenty-six patients with complicated acute myocardial infarction were studied in order to compare the hemodynamic effects of sodium nitroprusside (NP) and nitroglycerin (GTN). All patients received NP and 18 of the 26 also received GTN to evaluate both drugs in the same individuals. Both agents produced significant declines in mean arterial pressure, total peripheral resistance (TPR), and heart rate systolic blood pressure product. However, in the 18 patients who received both drugs GTN produced a greater fall (P less than 0.05) in pulmonary capillary wedge pressure (PCW) (25 to 15 mm Hg) than did NP (24 to 17 mm Hg) and a greater increment (P less than 0.01) in (see article) (0.98 to 1.43) than NP (0.98 to 1.16). These data confirm the potent vasodilatory effects of NP and GTN and suggest that NP has a relatively balanced effect on the arterial and venous circulation, and GTN seems to produce more potent venodilatation than arterial dilatation. These observations provide a basis for a more rational choice of vasodilator agents based on initial hemodynamic measurements in complicated acute myocardial infarction.
A segmented matched filter for CDMA code synchronization in systems with Doppler frequency offset (2002)

This paper presents a segmented matched filter (SMF) for codephase acquisition in direct sequence spread spectrum systems. While conventional matched filters provide fast acquisition in the presence of high co-user noise, they are unable to handle significant carrier frequency offset (Doppler). This problem is alleviated by segmentation with non-coherent summation. The paper develops expressions to approximately relate the matched filter partitioning to the pre-detection filter and dwell time integrator of the conventional non-coherent correlator. It also investigates 1-bit versus 2-bit quantization. A mixed-signal application specific integrated circuit (ASIC) has been fabricated to implement a 512 chip SMF with half chip codephase resolution. The paper presents calculated and measured probability density functions (pdf) for the filter output decision variable for 10, 25, and 50 co-users with 0 to 20 kHz Doppler shift. For the example of a GPS receiver, expected acquisition time is shown as a function of multiple access interference and carrier Doppler shift.
High performance interprocessor communication through optical wavelength division multiple access channels (1991)

A multiprocessor system with a large number of nodes can be built at low cost by combining the recent advances in high capacity channels available through optical fiber communication. A highly fault tolerant system is created with good performance characteristics at a reduction in system
Applications of universal context modeling to lossless compression of gray-scale images (2002)

Inspired by theoretical results on universal modeling, a general framework for sequential modeling of gray-scale images is proposed and applied to lossless compression. The model is based on stochastic complexity considerations and is implemented with a tree structure. It is efficiently estimated by a modification of the universal algorithm context. The sequential, lossless compression schemes obtained when the context modeler is used with an arithmetic coder, are tested with a representative set of gray-scale images. The compression ratios are compared with those obtained with state-of-the-art algorithms available in the literature, with the results of the comparison, showing the potential of the proposed approach.
Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy (2001)

The imaging of living cells and tissues using laser-scanning microscopy is offering dramatic insights into the spatial and temporal controls of biological processes. The availability of genetically encoded labels such as green fluorescent protein (GFP) offers unique opportunities by which to trace cell movements, cell signaling or gene expression dynamically in developing embryos. Two-photon laser scanning microscopy (TPLSM) is ideally suited to imaging cells in vivo due to its deeper tissue penetration and reduced phototoxicity; however, in TPLSM the excitation and emission spectra of GFP and its color variants [e.g., CyanFP (CFP); yellowFP (YFP)] are insufficiently distinct to be uniquely imaged by conventional means. To surmount such difficulties, we have combined the technologies of TPLSM and imaging spectroscopy to unambiguously identify CFP, GFP, YFP, and redFP (RFP) as well as conventional dyes, and have tested the approach in cell lines. In our approach, a liquid crystal tunable filter was used to collect the emission spectrum of each pixel within the TPLSM image. Based on the fluorescent emission spectra, supervised classification and linear unmixing analysis algorithms were used to identify the nature and relative amounts of the fluorescent proteins expressed in the cells. In a most extreme case, we have used the approach to separate GFP and fluorescein, separated by only 7 nm, and appear somewhat indistinguishable by conventional techniques. This approach offers the needed ability to concurrently image multiple colored, spectrally overlapping marker proteins within living cells.