gebhart/patrepeval huggingface dataset:
Human immunodeficiency virus-infected macrophages produce soluble factors that cause histological and neurochemical alterations in cultured human brains. (1991)

We wanted to establish an in vitro human model for AIDS-associated dementia and pursue the hypothesis that this disease process may be a result of soluble factors produced by HIV-infected macrophages. Human brain aggregates were prepared from nine different brain specimens, and were treated with supernatants from in vitro HIV-infected macrophages (SI), uninfected macrophages (SU), infected T cells, or macrophage-conditioned media from four AIDS patients. Seven of nine treated brains exposed to SI showed peripheral rarefaction after 1 wk of incubation that by ultrastructural analysis showed cytoplasmic vacuolation. Aggregates from two of three brain cultures treated with SI for 3 wk became smaller, an approximately 50% decrease in size. The degree of apparent toxicity in brains exposed to patient-derived macrophage supernatants paralleled the proportion of macrophages found to be expressing HIV p24. Ultrastructural abnormalities were not observed in brains treated with supernatants from HIV-infected T cells, uninfected macrophages, or LPS-activated macrophages. Levels of five neurotransmitter amino acids were decreased in comparison to the structural amino acid leucine. These findings suggest that HIV-infected macrophages, infected both in vitro as well as derived from AIDS patients' peripheral blood, produce factors that cause reproducible histochemical, ultrastructural, and functional abnormalities in human brain aggregates.
Development and In Vitro Characterization of a New Immunoassay of Cardiac Troponin T (1992)

We describe a new one-step enzyme immunoassay of troponin T that uses two specific monoclonal antibodies and streptavidin-coated tubes as the solid phase. The monoclonal antibodies were obtained by conventional hybridoma technology, with human troponin T as antigen. The identity of the cardiac troponin T antigen was confirmed by analysis of the amino acid composition and by partial sequence analysis. The specificity of the monoclonal antibodies for cardiac troponin T was proved by immunoblot analysis and displacement curves. The capture antibody is labeled with biotin. The second antibody is conjugated to horseradish peroxidase (EC 1.11.1.7). The assay [Enzymun-TestR system (Boehringer Mannheim GmbH)] is performed in only 90 min at room temperature; the measuring range for troponin T is 0.1 to 15 micrograms/L. The assay shows excellent between-run precision (CV = 3.3-4.9%).
Incorporation of thioether building blocks into an αvβ3‐specific RGD peptide: Synthesis and biological activity (2003)

We report the design, synthesis, and binding affinities of a family of thioether analogues of the alpha(v)beta(3)-specific compound c[(Mpa)RGDD(tBuG)C]-NH(2). The synthesis of the thioether building blocks is scalable and produced the desired products in good yields. The linear peptides were synthesized on solid supports, followed by cyclization in solution. Our analogues demonstrate interesting binding data to the isolated receptors. In particular, the peptide c[NH-Arg-Gly-Asp-Asp-(tBuG)-Cys(S-CH(2)-CO)]NH(2) (1) exhibits differences in binding when compared to the parent compound and demonstrates potent affinity to the alpha(v)beta(3) and alpha(5)beta(1) receptors while having reduced binding to the alpha(IIb)beta(3) receptor. This result combined with the replacement of the disulfide with a thioether makes this compound interesting for further development.
Route Decision Behaviour in a Commuting Scenario: Simple Heuristics Adaptation and Effect of Traffic Forecast (2004)

One challenge to researchers dealing with traffic management is to find efficient ways to model and predict traffic flow. Due to the social nature of traffic, most of the decisions are not independent. Thus, in traffic systems the inter-dependence of actions leads to a high frequency of implicit co-ordination decisions. Although there are already systems designed to assist drivers in these tasks (broadcast, Internet, etc.), such systems do not consider or even have a model of the way drivers decide. Our research goal is the study of commuting scenarios, drivers' decision-making, its influence on the system as a whole, and how simulation can be used to understand complex traffic systems. The present paper addresses two key issues: simulation of driver decision-making, and the role of a traffic forecast component. The former is realised by a nave model for the route choice adaptation, where commuters behaviour is based on heuristics they evolve. The second issue is realised via a traffic control system which perceives drivers' decisions and returns a forecast, thus allowing drivers to decide the actual route selection. For validation, we use empirical data from real experiments and show that the heuristics drivers evolve lead to a situation similar to that obtained in the real experiments. As for the forecast scenario, our results confirm that a traffic system in which a large share of drivers reacts to the forecast will not develop into equilibrium. However, a more stable situation arises by introducing some individual tolerance to sub-optimal forecasts.
Glycan Array Screening Reveals a Candidate Ligand for Siglec-8* (2004)

Sialic acid-binding immunoglobulin-like lectin 8 (Siglec-8) is selectively expressed on human eosinophils, basophils, and mast cells, where it regulates their function and survival. Previous studies demonstrated sialic acid-dependent binding of Siglec-8 but failed to reveal significant substructure specificity or high affinity of that binding. To test a broader range of potential ligands, a Siglec-8-Ig chimeric protein was tested for binding to 172 different glycan structures immobilized as biotinylated glycosides on a 384-well streptavidin-coated plate. Of these, approximately 40 structures were sialylated. Among these, avid binding was detected to a single defined glycan, NeuAcalpha2-3(6-O-sulfo)Galbeta1-4[Fucalpha1-3]GlcNAc, also referred to in the literature as 6'-sulfo-sLex. Notably, neither unsulfated sLex (NeuAcalpha2-3Galbeta1-4[Fucalpha1-3]GlcNAc) nor an isomer with the sulfate on the 6-position of the GlcNAc residue (6-sulfo-sLex, NeuAcalpha2-3Galbeta1-4[Fucalpha1-3](6-O-sulfo)GlcNAc) supported detectable binding. Subsequent secondary screening was performed using surface plasmon resonance. Biotin glycosides immobilized on streptavidin biosensor chips were exposed to Siglec-8-Ig in solution. Whereas surfaces derivatized with sLex and 6-sulfo-sLex failed to support detectable Siglec-8 binding, 6'-sulfo-sLex supported significant binding with a Kd of 2.3 microm. In a separate test of binding specificity, aminopropyl glycosides were covalently immobilized at different concentrations on activated (N-hydroxysuccinimidyl) glass surfaces (Schott-Nexterion Slide H). Subsequent exposure to Siglec-8-Ig precomplexed with fluorescein isothiocyanate anti-human Fc resulted in fluorescent signals at immobilized concentrations of 6'-sulfo-sLex of <5 pmol/spot. In contrast, sLex and 6-sulfo-sLex did not support any Siglec-8 binding at the highest concentration tested (300 pmol/spot). We conclude that Siglec-8 binds preferentially to the sLex structure bearing an additional sulfate ester on the galactose 6-hydroxyl.
Fetal phenotypic expression by adult rat hepatocytes on collagen gel/nylon meshes. (1979)

Hepatocytes from adult rats were maintained in primary culture for up to 10-13 days on nylon meshes coated with a thin layer of rat tail collagen gel. Their ultrastructure closely resembled that of the liver parenchymal cell in vivo, but hepatocytes in late culture exhibited a pronounced buildup of microfilaments beneath their apical cell surface. Hepatocytes in early and late cultures secreted albumin, transferrin, and alpha1-acid glycoprotein into the medium; they exhibited a 7- to 10-fold induction of tyrosine aminotransferase activity by dexamethasone; and they expressed an alkaline phosphatase that was similar to that of normal rat liver with respect to its inhibition by the liver enzyme inhibitor L-homoarginine. In addition, the hepatocytes in culture demonstrated phenotypic changes characteristic of fetal liver parenchymal cells. These changes, which paralleled an increase in DNA synthesis, included the expression of and linear increase in the activity of the fetal liver cell enzyme gamma-glutamyl transpeptidase, an increased production of alpha1-fetoprotein, and a change in the substrate specificity of fructose-bisphosphate aldolase to that of the fetal liver isozyme.
A simple learning strategy for high-speed quadrocopter multi-flips (2009)

We describe a simple and intuitive policy gradient method for improving parametrized quadrocopter multi-flips by combining iterative experiments with information from a first-principles model. We start by formulating an N-flip maneuver as a five-step primitive with five adjustable parameters. Optimization using a low-order first-principles 2D vertical plane model of the quadrocopter yields an initial set of parameters and a corrective matrix. The maneuver is then repeatedly performed with the vehicle. At each iteration the state error at the end of the primitive is used to update the maneuver parameters via a gradient adjustment. The method is demonstrated at the ETH Zurich Flying Machine Arena testbed on quadrotor helicopters performing and improving on flips, double flips and triple flips.
Identification and characterization of a novel surface antigen gene induced in mast cells activated through the high affinity IgE receptor (1995)

In an effort to isolate novel genes involved in inflammation and/or mast cell activation, we have used a combination of differential screening and subtractive hybridization to isolate genes whose expression are induced upon activation of a transformed rat mast cell line. One of the isolated clones, pMCA-32, contained an open reading frame of 278 amino acids that included a putative hydrophobic transmembrane domain, a cysteine rich Ig-like extracellular domain, and a cytoplasmic domain containing three consensus SH2-domain phosphotyrosine binding sites. The MCA-32 gene is also highly conserved between rat and mouse, with the two coding regions being 73% identical. Although the MCA-32 coding region did not contain an obvious signal peptide, MCA-32 protein was detected on the surface of rat mast cells, and the cloned cDNA produced a cell surface protein when expressed in COS-7 cells. MCA-32 RNA from both mouse and rat undergoes alternative splicing, producing an mRNA containing an in-frame deletion of the TM domain, suggesting that a form of MCA-32 protein may be secreted. MCA-32 mRNA expression was up-regulated upon activation of RBL-2H3 cells and was highly abundant in primary peritoneal mast cells. Expression of MCA-32 RNA was only observed in primary and transformed mast cells from rat, while in the mouse MCA-32, RNA was also produced in significant amounts by a number of transformed monocyte cell lines. Thus, MCA-32 is a novel surface protein whose structure and expression suggest roles in the development and/or activation of mast cells and monocytes.
Homologous upstream sequences near Epstein-Barr virus promoters. (1983)

The sequence of the 17,166-base-pair EcoRI C fragment of Epstein-Barr virus DNA, cell line B95-8, was determined. In vitro transcription was used to identify three RNA polymerase II promoters within this fragment of the virus. Cytoplasmic poly(A)+ RNAs starting at these points were demonstrated in B95-8 cells induced into virus production with 12-O-tetradecanoylphorbol 13-acetate. Uninduced B95-8 cells contained much less of these RNAs. The upstream sequences near the three promoters show striking homologies that may be involved in transcriptional control.
6-Methyl-2,4-Disubstituted Pyridazin-3(2H)-ones: A Novel Class of Small-Molecule Agonists for Formyl Peptide Receptors (2009)

Following a ligand-based drug design approach, a potent mixed formyl peptide receptor 1 (FPR1) and formyl peptide receptor-like 1 (FPRL1) agonist (14a) and a potent and specific FPRL1 agonist (14x) were identified. These compounds belong to a large series of pyridazin-3(2H)-one derivatives substituted with a methyl group at position 6 and a methoxy benzyl at position 4. At position 2, an acetamide side chain is essential for activity. Likewise, the presence of lipophilic and/or electronegative substituents in the position para to the aryl group at the end of the chain plays a critical role for activity. Affinity for FPR1 receptors was evaluated by measuring intracellular calcium flux in HL-60 cells transfected with FPR1, FPRL1, and FPRL2. Agonists were able to activate intracellular calcium mobilization and chemotaxis in human neutrophils. The most potent chemotactic agent (EC(50) = 0.6 microM) was the mixed FPR/FPRL1 agonist 14h.
Mechanisms Involved in Targeted Gene Replacement in Mammalian Cells (2000)

The "ends-out" or omega (Omega)-form gene replacement vector is used routinely to perform targeted genome modification in a variety of species and has the potential to be an effective vehicle for gene therapy. However, in mammalian cells, the frequency of this reaction is low and the mechanism unknown. Understanding molecular features associated with gene replacement is important and may lead to an increase in the efficiency of the process. In this study, we investigated gene replacement in mammalian cells using a powerful assay system that permits efficient recovery of the product(s) of individual recombination events at the haploid, chromosomal mu-delta locus in a murine hybridoma cell line. The results showed that (i) heteroduplex DNA (hDNA) is formed during mammalian gene replacement; (ii) mismatches in hDNA are usually efficiently repaired before DNA replication and cell division; (iii) the gene replacement reaction occurs with fidelity; (iv) the presence of multiple markers in one homologous flanking arm in the replacement vector did not affect the efficiency of gene replacement; and (v) in comparison to a genomic fragment bearing contiguous homology to the chromosomal target, gene targeting was only slightly inhibited by internal heterology (pSV2neo sequences) in the replacement vector.
Central Object of the 30 Doradus Nebula, a Supermassive Star (1981)

R136 (HD 38268) is the central object of the 30 Doradus Nebula, a giant region of ionized hydrogen in the Large Magellanic Cloud. Observations of R136 at low and high spectral resolution with the International Ultraviolet Explorer reveal a peculiar hot object with a massive stellar wind. An outflow speed of 3500 kilometers per second and a temperature of approximately 60,000 K are indicated by the spectra. The bulk of the observed ultraviolet radiation must come from R136a, the brightest and bluest component of R136. Its absolute visual magnitude and observed temperature imply a luminosity about 10(8) times that of the sun. Most of the ionizations produced in 30 Doradus are provided by this peculiar object. If RI36a is a dense cluster of very hot stars, about 30 stars of classes O3 and WN3 exist in a region estimated to have a diameter of less than 0.1 parsec. This is inconsistent with the ultraviolet line spectrum and the evidence for optical variability. An alternative interpretation of the observations is that the radiation from R136a is dominated by a single superluminous object with the following approximate properties: luminosity and temperature as given above, a radius 100 times that of the sun, a mass 2500 times that of the sun, and a loss rate of 10(-3.5) solar masses per year. Model interior calculations for hydrogen-burning stars are consistent with these parameters. Such stars, however, are expected to be unstable, and this may account for the massive stellar wind.
Nucleosides. XV. Decarboxylative elimination of 2'-deoxynucleoside uronic acids (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleosides. XV. Decarboxylative elimination of 2'-deoxynucleoside uronic acidsJiri Zemlicka, Robert Gasser, Joseph V. Freisler, and Jerome P. HorwitzCite this: J. Am. Chem. Soc. 1972, 94, 9, 3213–3218Publication Date (Print):May 1, 1972Publication History Published online1 May 2002Published inissue 1 May 1972https://pubs.acs.org/doi/10.1021/ja00764a053https://doi.org/10.1021/ja00764a053research-articleACS PublicationsRequest reuse permissionsArticle Views308Altmetric-Citations33LEARN 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
Small fragments of herpesvirus DNA with transforming activity contain insertion sequence-like structures. (1984)

A 737-base-pair fragment of herpes simplex virus type 2 DNA with morphological-transforming ability was identified by transfecting into rodent cells deleted fragments of the left-hand end of the Bgl II N fragment region (map position 0.58-0.625), which were constructed in vitro. The transforming sequences lie within the coding region for a Mr 61,000 protein, but the fragment itself does not appear to specify a viral polypeptide. Contained within the transforming fragment are sequences that can be drawn as a stem-loop structure flanked by direct repeats, similar to an insertion sequence-like element. An insertion sequence-like structure was also found in a small fragment of human cytomegalovirus DNA that has transforming activity. Possible mechanisms of herpesvirus transformation are discussed.
Use of liquid chromatography/tandem mass spectrometric molecular fingerprinting for the rapid structural identification of pharmaceutical impurities (2009)

Use of liquid chromatography/tandem mass spectrometric (LC/MS(n)) molecular fingerprinting is systematically demonstrated as a very effective tool for rapid structural elucidation of pharmaceutical impurities through a case study in which three isomers of betamethasone sodium phosphate (BSP) were rapidly identified as degradants formed due to the D-homoannular ring expansion of the steroid core structure of BSP in the solid state. The rapid structural elucidation of these degradants was achieved by matching or closely matching the UV profiles, molecular weights, and more importantly the fragmentation patterns obtained from the LC/MS(n) (n = 1 to 3) analysis of their enzyme-catalyzed hydrolytic products, respectively, with those of a D-homoannular isomer of betamethasone available in our LC/MS(n) molecular fingerprint database. This strategy of using LC/MS(n) molecular fingerprinting to obtain high-confidence structures of unknown species is then validated by structure verification through one- (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) experiments.
The pathophysiology of multiple sclerosis⋮ the mechanisms underlying the production of symptoms and the natural history of the disease (1999)

The pathophysiology of multiple sclerosis is reviewed, with emphasis on the axonal conduction properties underlying the production of symptoms, and the course of the disease. The major cause of the negative symptoms during relapses (e.g. paralysis, blindness and numbness) is conduction block, caused largely by demyelination and inflammation, and possibly by defects in synaptic transmission and putative circulating blocking factors. Recovery from symptoms during remissions is due mainly to the restoration of axonal function, either by remyelination, the resolution of inflammation, or the restoration of conduction to axons which persist in the demyelinated state. Conduction in the latter axons shows a number of deficits, particularly with regard to the conduction of trains of impulses and these contribute to weakness and sensory problems. The mechanisms underlying the sensitivity of symptoms to changes in body temperature (Uhthoff's phenomenon) are discussed. The origin of 'positive' symptoms, such as tingling sensations, are described, including the generation of ectopic trains and bursts of impulses, ephaptic interactions between axons and/or neurons, the triggering of additional, spurious impulses by the transmission of normal impulses, the mechanosensitivity of axons underlying movement-induced sensations (e.g. Lhermitte's phenomenon) and pain. The clinical course of the disease is discussed, together with its relationship to the evolution of lesions as revealed by magnetic resonance imaging and spectroscopy. The earliest detectable event in the development of most new lesions is a breakdown of the blood-brain barrier in association with inflammation. Inflammation resolves after approximately one month, at which time there is an improvement in the symptoms. Demyelination occurs during the inflammatory phase of the lesion. An important mechanism determining persistent neurological deficit is axonal degeneration, although persistent conduction block arising from the failure of repair mechanisms probably also contributes.
Expression of nitric oxide synthase III in human thyroid follicular cells: evidence for increased expression in hyperthyroidism (1997)

Nitric oxide mediates a wide array of cellular functions in many tissues. It is generated by three known isoforms of nitric oxide synthases (NOS). Recently, the endothelial isoform, NOSIII, was shown to be abundantly expressed in the rat thyroid gland and its expression increased in goitrous glands. In this study, we analyzed whether NOSIII is expressed in human thyroid tissue and whether levels of expression vary in different states of thyroid gland function. Semiquantitative RT-PCR was used to assess variations in NOSIII gene expression in seven patients with Graves' disease, one with a TSH-receptor germline mutation and six hypothyroid patients (Hashimoto's thyroiditis). Protein expression and subcellular localization were determined by immunohistochemistry (two normal thyroids, five multinodular goiters, ten hyperthyroid patients and two hypothyroid patients). NOSIII mRNA was detected in all samples: the levels were significantly higher in tissues from hyperthyroid patients compared with euthyroid and hypothyroid patients. NOSIII immunoreactivity was detected in vascular endothelial cells, but was also found in thyroid follicular cells. In patients with Graves' disease, the immunostaining was diffusely enhanced in all follicular cells. A more intense signal was observed in toxic adenomas and in samples obtained from a patient with severe hyperthyroidism due to an activating mutation in the TSH receptor. In multinodular goiters, large follicles displayed a weak signal whereas small proliferative follicles showed intense immunoreactivity near the apical plasma membrane. In hypothyroid patients, NOSIII immunoreactivity was barely detectable. In summary, NOSIII is expressed both in endothelial cells and thyroid follicular cells. The endothelial localization of NOSIII is consistent with a role for nitric oxide in the vascular control of the thyroid. NOSIII expression in thyroid follicular cells and the variations in its immunoreactivity suggest a possible role for nitric oxide in thyrocyte function and/or growth.