gebhart/patrepeval huggingface dataset:
Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580. (1992)

Two non-peptide substance P antagonists exhibit opposite rank orders of potency for the human and rat neurokinin-1 receptors. CP-96,345 shows selectivity for the human receptor, whereas RP67580 shows selectivity for the rat receptor. Amino acid sequence comparison of the two receptors reveals 22 divergent residues. To elucidate the molecular basis for the species selectivity of these antagonists, divergent residues in the human neurokinin-1 receptor were substituted by the rat homologs. Analysis of mutant receptors revealed that substitution of 2 residues (V116L and I290S) in the transmembrane domain of the human neurokinin-1 receptor is both necessary and sufficient to reproduce the antagonist binding affinities of the rat receptor. The nature of these substitutions and the magnitude of the changes in binding affinity suggest that residues 116 and 290 do not interact directly with the antagonist molecules. The present results support a model in which phylogenetically conserved residues interact directly with the antagonists, while phylogenetically divergent residues affect the local helical packing of the receptor. Such a change in local structure would lead to increased binding affinity for one class of antagonists and decreased affinity for another.
Recombinant interleukin-6 protects mice against experimental bacterial infection (1992)

Because of reports of high levels of interleukin-6 (IL-6) in patients during infection, we studied the role of IL-6 in experimental infection. Mice infected with the facultative intracellular pathogen Listeria monocytogenes displayed high levels of IL-6 in their sera and tissues, particularly the spleen, 1 to 3 days after infection. At this time, the IL-6 titers correlated with bacterial numbers in individual mice and in groups of mice given graded doses of Listeria organisms. However, the presence of IL-6 in serum declined after 4 days, even when a large initial dose of bacteria meant that bacterial numbers were still increasing at this time. Recombinant mouse IL-6 injected intraperitoneally before infection protected mice in a dose-dependent manner. It was effective when given 4 h before infection but not when administration was delayed for 24 h postinfection. It is therefore believed that IL-6 plays a role in early priming of the immune response to infection. Its exact function in this model is being investigated.
The Production Processes and Biological Effects of Intravenous Immunoglobulin (2016)

Immunoglobulin is a highly diverse autologous molecule able to influence immunity in different physiological and diseased situations. Its effect may be visible both in terms of development and function of B and T lymphocytes. Polyclonal immunoglobulin may be used as therapy in many diseases in different circumstances such as primary and secondary hypogammaglobulinemia, recurrent infections, polyneuropathies, cancer, after allogeneic transplantation in the presence of infections and/or GVHD. However, recent studies have broadened the possible uses of polyclonal immunoglobulin showing that it can stimulate certain sub-populations of T cells with effects on T cell proliferation, survival and function in situations of lymphopenia. These results present a novel and considerable impact of intravenous immunoglobulin (IVIg) treatment in situations of severe lymphopenia, a situation that can occur in cancer patients after chemo and radiotherapy treatments. In this review paper the established and experimental role of polyclonal immunoglobulin will be presented and discussed as well as the manufacturing processes involved in their production.
Consensus recommendations for the use of 18F-FDG PET as an indicator of therapeutic response in patients in National Cancer Institute Trials. (2006)

Many therapeutic clinical trials have proposed using a measure of metabolic change to assess therapeutic response rather than relying on conventional anatomic measurements of changes in tumor size on CT or MRI. PET assessment of changes in 18F-FDG uptake by tumors is gaining acceptance as such a
New Chiral Phosphorus Ligands for Enantioselective Hydrogenation (2003)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Chiral Phosphorus Ligands for Enantioselective HydrogenationWenjun Tang and Xumu ZhangView Author Information Department of Chemistry, 152 Davey Laboratory, The Pennsylvania State University, University Park, Pennsylvania 16802 Cite this: Chem. Rev. 2003, 103, 8, 3029–3070Publication Date (Web):June 6, 2003Publication History Received29 January 2003Published online6 June 2003Published inissue 1 August 2003https://pubs.acs.org/doi/10.1021/cr020049ihttps://doi.org/10.1021/cr020049iresearch-articleACS PublicationsCopyright © 2003 American Chemical SocietyRequest reuse permissionsArticle Views21217Altmetric-Citations2218LEARN 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 SUBJECTS:Catalysts,Hydrogenation,Ketones,Ligands,Stereoselectivity Get e-Alerts
Synthesis of a linear polyethylene macromonomer and preparation of polystyrene‐graft‐polyethylene copolymers via grafting‐through atom transfer radical polymerization (2007)

Abstract A vinyl‐terminated linear polyethylene (number‐average molecular weight = 1800, weight‐average molecular weight/number‐average molecular weight = 1.7, functionality = 92%) prepared by ethylene coordination polymerization was transformed into a monohydroxy‐terminated linear polyethylene by hydroalumination of the vinyl group with diisobutylaluminum hydride and subsequent oxidation and hydrolysis. This monohydroxy‐terminated linear polyethylene was quantitatively converted into a linear polyethylene macromonomer with a terminal α‐methacrylate group through esterification followed by dehydrobromination. A grafting‐through atom transfer radical polymerization of the α‐methacrylate‐terminated polyethylene and styrene was performed to yield a well‐defined polystyrene‐ graft ‐polyethylene copolymer. The number‐average molecular weight of the graft copolymers, measured by gel permeation chromatography, was lower than the predetermined number‐average molecular weight, presumably because of the intramolecular aggregation of polyethylene side chains. The α‐methacrylate‐terminated polyethylene content and number‐average molecular weight of polystyrene‐ graft ‐polyethylene were determined by 1 H‐NMR. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 105: 3–13, 2007
Integrated Method for Purification and Single-Particle Characterization of Lentiviral Vector Systems by Size Exclusion Chromatography and Tunable Resistive Pulse Sensing (2017)

Elements derived from lentiviral particles such as viral vectors or virus-like particles are commonly used for biotechnological and biomedical applications, for example in mammalian protein expression, gene delivery or therapy, and vaccine development. Preparations of high purity are necessary in most cases, especially for clinical applications. For purification, a wide range of methods are available, from density gradient centrifugation to affinity chromatography. In this study we have employed size exclusion columns specifically designed for the easy purification of extracellular vesicles including exosomes. In addition to viral marker protein and total protein analysis, a well-established single-particle characterization technology, termed tunable resistive pulse sensing, was employed to analyze fractions of highest particle load and purity and characterize the preparations by size and surface charge/electrophoretic mobility. With this study, we propose an integrated platform combining size exclusion chromatography and tunable resistive pulse sensing for monitoring production and purification of viral particles.
Semisynthetic Chemical Modification of the Antifungal Lipopeptide Echinocandin B (ECB): Structure-Activity Studies of the Lipophilic and Geometric Parameters of Polyarylated Acyl Analogs of ECB (1995)

Echinocandin B (ECB) is a lipopeptide composed of a complex cyclic peptide acylated at the N-terminus by linoleic acid. Enzymatic deacylation of ECB provided the peptide "nucleus" as a biologically inactive substrate from which novel ECB analogs were generated by chemical reacylation at the N-terminus. Varying the acyl group revealed that the structure and physical properties of the side chain, particularly its geometry and lipophilicity, played a pivotal role in determining the antifungal potency properties of the analog. Using CLOGP values to describe and compare the lipophilicities of the side chain fragments, it was shown that values of > 3.5 were required for expression of antifungal activity. Secondly, a linearly rigid geometry of the side chain was the most effective shape in enhancing the antifungal potency. Using these parameters as a guide, a variety of novel ECB analogs were synthesized which included arylacyl groups that incorporated biphenyl, terphenyl, tetraphenyl, and arylethynyl groups. Generally the glucan synthase inhibition by these analogs correlated well with in vitro and in vivo activities and was likewise influenced by the structure of the side chain. These structural variations resulted in enhancement of antifungal activity in both in vitro and in vivo assays. Some of these analogs, including LY303366 (14a), were effective by the oral route of administration.
Structural and functional analysis of NADPH-cytochrome P-450 reductase from human liver: complete sequence of human enzyme and NADPH-binding sites (1989)

The complete amino acid sequence of human liver NADPH-cytochrome P-450 reductase has been determined by microsequence analysis and mass spectrometry. The total sequence consists of 676 amino acids initiated by an amino-terminal acetyl group. There is no evidence for posttranslational modifications, including Asn-linked glycosylation. The human enzyme exhibits sequence homology in the range of 92-95% with other mammalian enzymes. Sequence differences were mainly confined to several hydrophilic regions in the NH2-terminal and COOH-terminal domains. Since the human enzyme is immunochemically distinct from the rabbit enzyme despite similar enzymatic properties, it is likely that these variable hydrophilic regions are potential antigenic determinants. The NADPH-depleted enzyme is inactivated by either fluorescein isothiocyanate, a lysine-specific reagent, or 5-(iodoacetamido)fluorescein, a cysteine-specific reagent. In both cases, protection by NADP(H) prevents enzyme inactivation by the reagents. Isolation of fluorescent peptide from 5-(iodoacetamido)fluorescein-inactivated enzyme identified Cys 565 as the specifically NADPH-protected residue.
Report on the TREC 2009 Experiments: Chemical IR Track (2009)

The goal of the first TREC Chemical track was to retrieve documents relevant to a given patent query, within a large collection of patents in chemistry. Regarding this objective, for the Prior Art subtask, our runs performed significantly better that runs submitted by other participating teams. Baseline retrieval methods achieved relatively poor performances (Mean Average Precision = 0.067). Query expansion, driven my chemical named entity recognition resulted in some modest improvement (+2 to 3%). Filtering based on IPC codes did not result in any significant improvement. A re-ranking strategy, based on claims only improved MAP by about 3%. The most effective gain was obtained by using patent citation patterns. Somehow similar to feed-back but restricted to citations, we used patents cited in the retrieved patents in order to boost the retrieval status value of the baseline run. This strategy led to a remarkable improvement (MAP 0.18, +168 %). Nevertheless, as official topics were sampled from the collection disregarding their creation date, our strategy happened to exploit citations of patents which were patented after the topic itself. From a user perspective, such a setting is questionable. We think that future TREC-CHEM competitions should address this issue by using patents filed as recently as possible.
Synthesis of retinals isotopically labelled at positions 11, 12, 14 and 20 (1986)

Abstract Five retinals, having different combinations of 2 H, with one having 2 H and 13 C labels at positions 11, 12, 14 and 20, were obtained with a chemical purity of above 98%, a level of 2 H enrichment greater than 95% and with 13 C enrichment of 99%. The retinals concerned are (20,20,20‐ 2 H 3 )‐, (12,20,20,20‐ 2 H 4 )‐, (12,14,20,20,20‐ 2 H 5 )‐, (11,14‐ 2 H 2 )‐, (12,14‐ 2 H 2 )‐ and (12,14‐ 2 H 2 ,20‐ 13 C)retinal.
Sortase transpeptidases: Insights into mechanism, substrate specificity, and inhibition (2010)

Gram-positive bacteria pose a serious healthcare threat. The growing antibiotic resistance epidemic creates a dire need for new antibiotic targets. The sortase family of enzymes is a promising target for antimicrobial therapy. This review covers the current knowledge of the mechanism, substrate specificity, and inhibitory studies of the Gram-positive bacterial [corrected] enzyme sortase.
Fatty acids and prostate cancer: current status and future challenges. (1999)

In this article the basic biology and function of fatty acids (FAs) will be reviewed. The literature relating to FAs and prostate cancer will be evaluated and possible mechanisms for the mode of action of FAs in the carcinogenesis and progression of prostate cancer will be discussed. In addition, the potential role for specific FAs in the treatment and prevention of prostate cancer will be assessed.
Coxsackievirus B3 Replication Is Reduced by Inhibition of the Extracellular Signal-Regulated Kinase (ERK) Signaling Pathway (2002)

Coxsackievirus B3 (CVB3) is the most common human pathogen for viral myocarditis. We have previously shown that the signaling protein p21(ras) GTPase-activating protein (RasGAP) is cleaved and that mitogen-activated protein kinases (MAPKs) ERK1/2 are activated in the late phase of CVB3 infection. However, the role of intracellular signaling pathways in CVB3-mediated myocarditis and the relative advantages of such pathways to host or virus remain largely unclear. In this study we extended our prior studies by examining the interaction between CVB3 replication and intracellular signaling pathways in HeLa cells. We observed that CVB3 infection induced a biphasic activation of ERK1/2, early transient activation versus late sustained activation, which were regulated by different mechanisms. Infection by UV-irradiated, inactivated virus capable of receptor binding and endocytosis triggered early ERK1/2 activation, but was insufficient to trigger late ERK1/2 activation. By using a general caspase inhibitor (zVAD.fmk) we further demonstrated that late ERK1/2 activation was not a result of CVB3-mediated caspase cleavage. Treatment of cells with U0126, a selective inhibitor of MAPK kinase (MEK), significantly inhibited CVB3 progeny release and decreased virus protein production. Furthermore, inhibition of ERK1/2 activation circumvented CVB3-induced apoptosis and viral protease-mediated RasGAP cleavage. Taken together, these data suggest that ERK1/2 activation is important for CVB3 replication and contributes to virus-mediated changes in host cells. Our findings demonstrate coxsackievirus takeover of a particular host signaling mechanism and uncover a prospective approach to stymie virus spread and preserve myocardial integrity.
The shape of the human lens nucleus with accommodation (2007)

Knowledge about geometric properties such as shape and volume and Poisson's ratio of the nucleus can be used in the mechanical and optical modeling of the accommodation process. Therefore, Scheimpflug imaging was used to determine the shape of the human lens nucleus during accommodation in five subjects. To describe the shape of the nucleus, we fitted a parametric model of the cross-sectional geometry to the gradient of the Scheimpflug images using the Hough transform. The geometric model made it possible to estimate the anterior and the posterior central radius, central thickness, equatorial diameter, and cross-sectional area of the nucleus. Assuming that the nucleus is rotationally symmetric, the volume of the nucleus can be estimated by integrating around the circumference. For all five subjects, the results show that during accommodation the nucleus became more convex and that the central thickness increased whereas the equatorial diameter decreased. This decrease in equatorial diameter of the nucleus with accommodation is in accordance with the Helmholtz accommodation theory. Finally, the volume of the nucleus (on average 35 mm(3)) showed no significant change during accommodation in any of the subjects, presumably due to the fact that the human nucleus consists of incompressible material with a Poisson's ratio that is near .5.
PDGF2/c-sis mRNA Leader Contains a Differentiation-linked Internal Ribosomal Entry Site (D-IRES) (1997)

It has become clear that a given cell type can qualitatively and quantitatively affect the expression of the platelet-derived growth factor B (PDGF2/c-sis) gene at multiple levels. In a previous report, we showed that PDGF2/c-sis 5'-untranslated region has a translational modulating activity during megakaryocytic differentiation of K562 cells. This study points to the mechanism used for this translational modulation. The unusual mRNA leader, which imposes a major barrier to conventional ribosomal scanning, was found to contain an internal ribosomal entry site that becomes more potent in differentiating cells and was termed differentiation-linked internal ribosomal entry site (D-IRES). The D-IRES element defines a functional role for the cumbersome 1022-nucleotide-long mRNA leader and accounts for its uncommon, evolutionary conserved architecture. The differentiation-linked enhancement of internal translation, which provides an additional step to the fine tuning of PDGF2/c-sis gene expression, might be employed by numerous critical regulatory genes with unusual mRNA leaders and might have widespread implications for cellular growth and development.
Forecasting time series with genetic fuzzy predictor ensemble (1997)

This paper proposes a genetic fuzzy predictor ensemble (GFPE) for the accurate prediction of the future in the chaotic or nonstationary time series. Each fuzzy predictor in the GFPE is built from two design stages, where each stage is performed by different genetic algorithms (GA). The first stage generates a fuzzy rule base that covers as many of training examples as possible. The second stage builds fine-tuned membership functions that make the prediction error as small as possible. These two design stages are repeated independently upon the different partition combinations of input-output variables. The prediction error will be reduced further by invoking the GFPE that combines multiple fuzzy predictors by an equal prediction error weighting method. Applications to both the Mackey-Glass chaotic time series and the nonstationary foreign currency exchange rate prediction problem are presented. The prediction accuracy of the proposed method is compared with that of other fuzzy and neural network predictors in terms of the root mean squared error (RMSE).
Los orígenes de las comunidades ciudadanas cristianas : la explicación tardoantigua en la literatura martirial hispana (1998)

Este articulo se pregunta el por que del interes de las iglesias cristianas por escrutar sus origenes y, fundamentalmente, las claves ideologicas que conformaron este fenomeno en la Antiguedad Tardia. A modo de conclusion, se observa una continuidad con la Antiguedad mediante el mantenimiento de las formas de pensamiento clasicas.
Highly efficient electroluminescent materials based on fluorinated organometallic iridium compounds (2001)

We report a class of highly efficient electroluminescent materials based on fluorinated iridium compounds. Using aluminum as the cathode, a device, using fac-tris[5-fluoro-2(5-trifluoromethyl-2-pyridinyl)phenyl-C,N]iridium (Ir-2h) as the luminescent layer, displayed intense electroluminescence at 525 nm with an efficiency of 20 cd/A and a maximum radiance of 4800 cd/m2. Differing from the previously reported Ir(ppy)3, Ir-2h can be used in the undiluted form without the use of a charge-transporting host. This indicates that Ir-2h by itself has good enough charge-transporting properties. Photoluminescence studies at room temperature and 77 K revealed that electroluminescence originates from the metal-to-ligand charge transfer state with a quantum yield of 0.56 for Ir-2h and 0.5 for Ir(ppy)3 in toluene at room temperature. In the thin-film form, photoluminescence quantum yield of Ir-2h is a factor of 10 greater than that of Ir(ppy)3 due to the larger self-quenching effect of Ir(ppy)3.
Microfluidic Synthesis of Cell-Type-Specific Artificial Extracellular Matrix Hydrogels (2013)

Droplet microfluidic technology is applied for the high-throughput synthesis via Michael-type addition of reactive, micrometer-sized poly(ethylene glycol) (PEG) hydrogels ("microgels") with precisely controlled dimension and physicochemical properties. A versatile chemical scheme is used to modify the reactive PEG microgels with tethered biomolecules to tune their bioactive properties for the bioreactor culture and manipulation of various (stem) cell types.
K-ras is an essential gene in the mouse with partial functional overlap with N-ras (1997)

Mammalian ras genes are thought to be critical in the regulation of cellular proliferation and differentiation and are mutated in approximately 30% of all human tumors. However, N-ras and H-ras are nonessential for mouse development. To characterize the normal role of K-ras in growth and development, we have mutated it by gene targeting in the mouse. On an inbred genetic background, embryos homozygous for this mutation die between 12 and 14 days of gestation, with fetal liver defects and evidence of anemia. Thus, K-ras is the only member of the ras gene family essential for mouse embryogenesis. We have also investigated the effect of multiple mutations within the ras gene family. Most animals lacking N-ras function and heterozygous for the K-ras mutation exhibit abnormal hematopoietic development and die between days 10 and 12 of embryogenesis. Thus, partial functional overlap appears to occur within the ras gene family, but K-ras provides a unique and essential function.
Lattice-Gas Automata for the Navier-Stokes Equation (1986)

~e show that a class of deterministic lattice gases with discrete Boolean elements simulates the Navier-Stokes equation, and can be used to design simple, massively parallel computing machines.