gebhart/patrepeval huggingface dataset:
Targeting the Warburg Effect That Arises in Tumor Cells Expressing Membrane Type-1 Matrix Metalloproteinase (2011)

Hypoxia inducible factor-1 (HIF-1) is a key transcription factor required for cellular adaptation to hypoxia, although its physiological roles and activation mechanisms during normoxia have not been studied sufficiently. The Warburg effect, which is a hallmark of malignant tumors that is characterized by increased activity of aerobic glycolysis, accompanies activation of HIF-1 during normoxia. Besides tumor cells that have multiple genetic and epigenetic alterations, normal macrophages also use glycolysis for ATP production by depending upon elevated HIF-1 activity even during normoxia. We recently found that activity of factor inhibiting HIF-1 (FIH-1) is specifically suppressed in macrophages by a nonproteolytic activity of membrane type-1 matrix metalloproteinase (MT1-MMP/MMP-14). Thus, MT1-MMP expressed in macrophages plays a significant role in regulating HIF-1 activity during normoxia. In the light of this finding, we examined here whether MT1-MMP contributes to the Warburg effect of tumor cells. All the tumor cell lines that express MT1-MMP exhibit increased glycolytic activity, and forced expression of MT1-MMP in MT1-MMP-negative tumor cells is sufficient to induce the Warburg effect. The cytoplasmic tail of MT1-MMP mediates the stimulation of aerobic glycolysis by increasing the expression of HIF-1 target genes. Specific intervention of the MT1-MMP-mediated activation of HIF-1 in tumor cells retarded tumor growth in mice. Systemic administration of a membrane-penetrating form of the cytoplasmic tail peptide in mice to inhibit HIF-1 activation competitively also exhibited a therapeutic effect on tumors.
Design of shapes for precise image registration (1998)

This correspondence deals with the problem of designing planar shapes for subpixel image registration. Basic theoretical considerations are shown to lead to a lower bound on location accuracy. Optimal registration marks achieving this bound are discussed. These optimal designs, however, require very high printing or etching resolution and are inherently very sensitive to variations in the image sampling model (like scaling of grid size and rotation). More robust, optimal and suboptimal "topology-preserving" registration marks are then introduced and analyzed.
Fluorescence transmission through 1-D and 2-D periodic metal films (2004)

We study the transmission of fluorescence through periodically modulated metal films. In one-dimensional corrugated films, transmission is mediated by coherent scattering of surface plasmons directly excited by fluorophores on the surface. This scattering is shown to be a two-dimensional problem in that diffraction orders along both axes are obtained with well-defined states of polarization. In films consisting of two-dimensional arrays of sub-wavelength apertures, an additional mechanism exists in the direct transmission of fluorescence through the apertures, which is the dominant mechanism of transmission as shown by measurement of the radiation pattern from these structures.
Knowledge-Based Temporal Abstraction in Clinical-Management Tasks (1994)

We describe a general method for abstracting higherlevel, interval-based concepts from time-stamped clinical data, the knowledge-based temporal-abstraction [KBTA] method. We focus on the knowledge representation, knowledge acquisition and knowledge reuse and sharing aspects of the KBTA method. We describe five mechanisms which solve the five tasks composing the KBTA method, and four types of knowledge necessary for instantiating these mechanisms in a particular domain. We present an example of instantiating the KBTA method in the domain of monitoring insulin-dependent diabetes patients. 1. The Temporal-Abstraction Task There are several desired features for a method solving the TA task. The input and output parameter values might be of different types (e.g., numbers, symbols) and abstraction levels (e.g., BLOOD GLUCOSE LEVEL 74; GLUCOSE STATE = LOW). Input data might arrive out of temporal order, and interpretations should be revised accordingly. Several alternate interpretations might need to be maintained and followed. From the knowledge-representation aspect, acquiring necessary knowledge from domain experts should be facilitated, as well as maintenance of that knowledge. Reusing the domain-independent abstraction knowledge for solving the TA task in other domains should be possible, as well as sharing some of the domain-specific knowledge with other tasks in the same domain.
An Insertion Mutation That Distorts Antibody Binding Site Architecture Enhances Function of a Human Antibody (2011)

ABSTRACT The structural and functional significance of somatic insertions and deletions in antibody chains is unclear. Here, we demonstrate that a naturally occurring three-amino-acid insertion within the influenza virus-specific human monoclonal antibody 2D1 heavy-chain variable region reconfigures the antibody-combining site and contributes to its high potency against the 1918 and 2009 pandemic H1N1 influenza viruses. The insertion arose through a series of events, including a somatic point mutation in a predicted hot-spot motif, introduction of a new hot-spot motif, a molecular duplication due to polymerase slippage, a deletion due to misalignment, and additional somatic point mutations. Atomic resolution structures of the wild-type antibody and a variant in which the insertion was removed revealed that the three-amino-acid insertion near the base of heavy-chain complementarity-determining region (CDR) H2 resulted in a bulge in that loop. This enlarged CDR H2 loop impinges on adjacent regions, causing distortion of the CDR H1 architecture and its displacement away from the antigen-combining site. Removal of the insertion restores the canonical structure of CDR H1 and CDR H2, but binding, neutralization activity, and in vivo activity were reduced markedly because of steric conflict of CDR H1 with the hemagglutinin antigen. IMPORTANCE Antibody diversification through VDJ gene recombination, junctional variation, and somatic hypermutation has clear importance for the generation of mature, high-affinity antibodies. Between 1.3 and 6.5% of antibody variable gene sequences have been reported to contain insertions or deletions, but their structural and functional significance remains less well defined. The pandemic influenza virus hemagglutinin antibody 2D1 data suggest that somatic insertions and deletions in antibody genes contribute important structural and functional features. We predict that such features can be critical for affinity and functional maturation of the human antibody repertoire.
Transient RNAi Induction against Endogenous Genes in Arabidopsis Protoplasts Using in Vitro-Prepared Double-Stranded RNA (2005)

RNA interference is a powerful technique for suppressing gene functions in many eukaryotes including plants. Here we show that introduction of double-stranded RNA into Arabidopsis protoplasts leads to marked silencing of endogenous genes, as observed previously for transgenes [Biosci. Biotechnol. Biochem., 67, 2674-2677 (2003)]. This simple system should be useful for functional analysis of genes involved in fundamental cellular processes.
Binding of EBNA-1 to DNA creates a protease-resistant domain that encompasses the DNA recognition and dimerization functions (1992)

The Epstein-Barr virus nuclear antigen EBNA-1 is essential for replication of the viral DNA during latency. EBNA-1 binds as a dimer to palindromic recognition sequences within the plasmid origin of replication, ori-P. In this study, proteinase K susceptibility has been used to further characterize the DNA-binding domain of EBNA-1. Limited protease digestion of EBNA-1 (amino acids 408 to 641) generated a smaller DNA-binding species that had a degree of inherent protease resistance. When EBNA-1 was preincubated with a specific DNA probe, the protease resistance of the smaller binding species increased 100-fold, suggesting that the conformation of EBNA-1 changes on binding. The protease-resistant species comprised an 18-kDa polypeptide that was further cleaved at high levels of protease to 11- and 5.4-kDa products. A model of the proposed protease-resistant domain structure is presented. Constructions carrying serial, internal deletions across the 18-kDa domain were created. Each of the deletions perturbed dimerization ability and abolished DNA binding. These studies suggest that the DNA-binding and dimerization motifs of EBNA-1 lie within a conformationally discrete domain whose overall integrity is necessary for EBNA-1-DNA interaction.
X-ray Crystal Structure of the Fe-Only Hydrogenase (CpI) from Clostridium pasteurianum to 1.8&nbsp;Angstrom Resolution (1998)

A three-dimensional structure for the monomeric iron-containing hydrogenase (CpI) from Clostridium pasteurianum was determined to 1.8 angstrom resolution by x-ray crystallography using multiwavelength anomalous dispersion (MAD) phasing. CpI, an enzyme that catalyzes the two-electron reduction of two protons to yield dihydrogen, was found to contain 20 gram atoms of iron per mole of protein, arranged into five distinct [Fe-S] clusters. The probable active-site cluster, previously termed the H-cluster, was found to be an unexpected arrangement of six iron atoms existing as a [4Fe-4S] cubane subcluster covalently bridged by a cysteinate thiol to a [2Fe] subcluster. The iron atoms of the [2Fe] subcluster both exist with an octahedral coordination geometry and are bridged to each other by three non-protein atoms, assigned as two sulfide atoms and one carbonyl or cyanide molecule. This structure provides insights into the mechanism of biological hydrogen activation and has broader implications for [Fe-S] cluster structure and function in biological systems.
Reactivities of Stable Rotamers. XLII. Generation and Fates of Rotameric [1-(9-Fluorenyl)-2-naphthyl]methyl Radicals (1999)

Abstract The title radical rotamers were generated by thermolyses of the corresponding t-butyl peroxycarboxylates or photolyses of the corresponding 2(1H)-thioxo-1-pyridyl carboxylates. Products from the t-butyl peroxyesters were t-butoxy compounds, dimers, and colligation products with a benzyl radical, when the reactions were carried out in toluene. In carbon tetrachloride, chlorine-abstraction products and colligation products with a trichloromethyl radical were obtained in addition to the dimers. Photolyses of the 2(1H)-thioxo-1-pyridyl esters afforded expected products, the dimers and 2-pyridylthio derivatives. Generally, the differences from one rotamer to another cause minor differences in the distribution of the products. The small differences are attributed to the steric effects which operate at the site where the radical is produced.
Preparation of difluoroaminodifluorophosphine (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of difluoroaminodifluorophosphineKim Cohn, James E. Smith, and Ronald SteenCite this: J. Am. Chem. Soc. 1970, 92, 21, 6359–6360Publication Date (Print):October 1, 1970Publication History Published online1 May 2002Published inissue 1 October 1970https://pubs.acs.org/doi/10.1021/ja00724a056https://doi.org/10.1021/ja00724a056research-articleACS PublicationsRequest reuse permissionsArticle Views36Altmetric-Citations3LEARN 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
Evolución de la gestión del conflicto y la negociación en España. Factores interpersonales y culturales (1999)

El proposito de este trabajo ha sido examinar e integrar los resultados obtenidos sobre la gestion del conflicto y la negociacion a partir de las investigaciones realizadas en Espana. Con este objetivo se han analizado los siguientes aspectos: a) Las conductas de gestion del conflicto, b) los procesos emocionales implicados en dichas conductas, c) las condiciones sociales en las que se dan las mismas, y d) la influencia de aspectos culturales en los procesos de negociacion y mediacion. Los resultados obtenidos han mostrado la relevancia de estos factores en la gestion del conflicto, confirmandose que la percepcion de los negociadores sobre su conducta se ve afectada por el estado afectivo y emocional en el que se encuentren. A su vez, las condiciones de presencia social y las expectativas de eficacia de los negociadores pueden influir en los resultados de la negociacion. Finalmente, se confirma que los estilos de integracion y dominacion han sido los mas utilizados por los negociadores espanoles en la gestion del conflicto, mostrandose al mismo tiempo la incidencia de los aspectos culturales sobre dichas conductas.
SIT Image sensor: Design considerations and characteristics (1986)

This paper concerns a new solid-state imaging device using a static induction transistor (SIT). The device has a single SIT/pixel structure previously proposed by Nishizawa et al. The authors developed a new serial readout area array configuration suitable for standard TV format, and its operational characteristics have been analyzed using a simplified model. Image sensors consisting of 170(H) × 124(V) pixels were fabricated using a combined SIT and MOS process, and their measured characteristics agree well with the analysis. Signal current as large as 94 µA was obtained at an exposure value of 0.17 lx . s without any output amplifier, and it is expected that sensitivity will be improved with a decrease in the charge storage capacitance of the SIT gate.
Modulation of Human β-Defensin-2 Transcription in Pulmonary Epithelial Cells by Lipopolysaccharide-Stimulated Mononuclear Phagocytes Via Proinflammatory Cytokine Production (2003)

Human beta-defensin (hBD)-2, a cationic antimicrobial peptide primarily induced in epithelial cells in response to inflammatory stimuli, plays an important role in host defense. To elucidate the expression mechanism of hBD-2 in the lung, we investigated the modulation of hBD-2 transcription in pulmonary epithelial cells by mononuclear phagocytes stimulated with LPS. Coculture of A549 pulmonary epithelial cells with Mono-Mac-6 monocytic cells in the presence of Escherichia coli LPS markedly up-regulated hBD-2 promoter activity, whereas A549 alone did not respond to LPS to activate the hBD-2 promoter. Furthermore, IL-1beta and TNF-alpha in the culture supernatants from LPS-stimulated monocytic cells activated the hBD-2 promoter in A549 cells. Of note, IL-1beta was more potent than TNF-alpha in this effect. In addition, a mutation of the NF-kappaB site at -200 (pkappaB1 site) completely abolished this IL-1beta- and TNF-alpha-induced hBD-2 promoter activation, whereas NF-kappaB inhibitors (MG-132 and helenalin) strongly suppressed it. Moreover, electrophoretic mobility shift assay suggested that NF-kappaB, consisting of p65-p50 heterodimer, could bind to the pkappaB1 site in cytokine-stimulated A549 cells. Interestingly, flow cytometric analysis revealed that A549 cells expressed CD14 but lacked Toll-like receptor 4, which may account for the hyporesponsiveness of A549 cells to LPS. Taken together, these results suggest that hBD-2 expression in pulmonary epithelial cells is modulated by NF-kappaB via the actions of IL-1beta and TNF-alpha produced by LPS-stimulated mononuclear phagocytes.
Nosocomial Spread of Linezolid-Resistant, Vancomycin-ResistantEnterococcus faecium (2002)

To the Editor: Vancomycin-resistant enterococci have become important nosocomial pathogens in the United States. Since November 1995, rectal swabs for surveillance for vancomycin-resistant enterococci have been collected twice weekly from adult patients admitted to the liver, kidney, and pancreas transplantation unit at our institution.1 Recently, linezolid-resistant, vancomycin-resistant Enterococcus faecium was isolated from seven patients at our institution. All isolates carried the vanA gene and were resistant to linezolid (minimal inhibitory concentration [MIC], 16 μg per milliliter), ampicillin, penicillin, gentamicin, streptomycin, and vancomycin and were susceptible to quinupristin–dalfopristin and the investigational agents oritavancin (MIC, 1 μg per milliliter) and tigecycline (MIC, . . .
Multilayered Oxide Interphase Concept for Ceramic‐Matrix Composites (1998)

Hi‐Nicalon/SiC minicomposite specimens containing three oxide interphase layers (amorphous SiO 2 , monoclinic ZrO 2 , and amorphous SiO 2 ) were prepared by chemical vapor deposition. The minicomposites exhibited graceful composite failure behavior with reasonable load‐carrying capability in room‐temperature tensile tests. Much of the composite behavior and load‐carrying capability was retained even after matrix precracking and subsequent oxidation in air at 960°C for 10 h. In both the as‐prepared and oxidized specimens, crack deflection and fiber pull‐out occurred preferentially within the multilayered interphase region. The potential merits and uncertainties associated with this multilayered oxide interphase approach were discussed in the context of designing environmentally durable interfaces for ceramic‐matrix composites.
Photocatalytic Reduction of CO2 with Re-Pyridyl-NHCs (2015)

A series of Re(I) pyridyl N-heterocyclic carbene (NHC) complexes have been synthesized and examined in the photocatalytic reduction of CO2 using a simulated solar spectrum. The catalysts were characterized through NMR, UV-vis, cyclic voltammetry under nitrogen, and cyclic voltammetry under carbon dioxide. The complexes were compared directly with a known benchmark catalyst, Re(bpy) (CO)3Br. An electron-deficient NHC substituent (PhCF3) was found to promote catalytic activity when compared with electron-neutral and -rich substituents. Re(PyNHC-PhCF3) (CO)3Br was found to exceed the CO production of the benchmark Re(bpy) (CO)3Br catalyst (51 vs 33 TON) in the presence of electron donor BIH and photosensitizer fac-Ir(ppy)3. Importantly, Re(PyNHC-PhCF3) (CO)3Br was found to function without a photosensitizer (32 TON) at substantially higher turnovers than the benchmark catalyst Re(bpy) (CO)3Br (14 TON) under a solar simulated spectrum.
Transmission of high speed electrical signals in a Josephson package (1983)

It is proposed that Josephson circuit chips are housed in a three-dimensional, card-on-board package operated near 4.2K. In this technology logic signals travel on matched, low-loss, superconducting transmission lines and through low resistance but inductive package connectors. In an experiment designed to model closely the electrical environment of this package, the waveform of a Josephson driver signal was measured before and after propagation through a card-to-card path in the package. The measurements were made on-chip using Josephson sampling techniques. The degradation in risetime of a 125ps driver signal was less than 20ps; crosstalk to a parallel path through the package was less than 2%. The inductances of right angle and pluggable micropin connectors were determined using an impedance current split experiment. Measured values of about 100pH and 250pH respectively are in good agreement with numerical calculations.
Concise total syntheses of dl-camptothecin and related anticancer drugs (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConcise total syntheses of dl-camptothecin and related anticancer drugsWang Shen, Craig A. Coburn, William G. Bornmann, and Samuel J. DanishefskyCite this: J. Org. Chem. 1993, 58, 3, 611–617Publication Date (Print):January 1, 1993Publication History Published online1 May 2002Published inissue 1 January 1993https://pubs.acs.org/doi/10.1021/jo00055a012https://doi.org/10.1021/jo00055a012research-articleACS PublicationsRequest reuse permissionsArticle Views1217Altmetric-Citations116LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Targeted Delivery of RNAi Therapeutics With Endogenous and Exogenous Ligand-Based Mechanisms (2010)

Lipid nanoparticles (LNPs) have proven to be highly efficient carriers of short-interfering RNAs (siRNAs) to hepatocytes in vivo; however, the precise mechanism by which this efficient delivery occurs has yet to be elucidated. We found that apolipoprotein E (apoE), which plays a major role in the clearance and hepatocellular uptake of physiological lipoproteins, also acts as an endogenous targeting ligand for ionizable LNPs (iLNPs), but not cationic LNPs (cLNPs). The role of apoE was investigated using both in vitro studies employing recombinant apoE and in vivo studies in wild-type and apoE(-/-) mice. Receptor dependence was explored in vitro and in vivo using low-density lipoprotein receptor (LDLR(-/-))-deficient mice. As an alternative to endogenous apoE-based targeting, we developed a targeting approach using an exogenous ligand containing a multivalent N-acetylgalactosamine (GalNAc)-cluster, which binds with high affinity to the asialoglycoprotein receptor (ASGPR) expressed on hepatocytes. Both apoE-based endogenous and GalNAc-based exogenous targeting appear to be highly effective strategies for the delivery of iLNPs to liver.