gebhart/patrepeval huggingface dataset:
Procurement and Contract Arrangement (1992)

The client, when seeking to procure and authorise the undertaking of small building works, has a variety of procurement and contract arrangements available. Essentially, any arrangement represents a formal relationship between the two main parties involved in the work, the client and the contractor. The various standard forms of building contract used to confirm the legal relationship are reviewed in Chapter 5. The main differences between the various types of procurement and contractual arrangement feature in the variations of methods used to describe, measure, value and discharge the works. Forms of approach can accommodate a wide range of small building works, from individual construction projects entailing little complexity and with few demands upon resources, to more intricate and demanding construction which require greater, technical and managerial expertise. Works such as these may be arranged informally with a minimum of interrelations between the client and contractor and with little contract documentation, or be procured on a formal level under explicit forms of contract with considerable documentation. Irrespective of differing circumstances, there is usually an appropriate method available.
Analyzing for Co-Localization of Proteins at a Cell Membrane (2004)

Cell-to-cell communication is mediated by molecular interactions at the surface of the cell by soluble ligands released from distant cells or by cell surface molecules on adjacent cells. These interactions lead to activation of intracellular signaling pathways that subsequently can lead to activation of specific genes. This signal transduction process controls cellular activities as diverse as proliferation, differentiation and apoptosis, so we must understand the underlying molecular events in detail in order to understand broader questions related to development, uncontrolled growth in tumors, tissue regeneration and use of stem cells to name a few. Binding of a ligand in the extracellular space to a transmembrane receptor constitutes the first crucial step for activation of a signaling pathway within the cell. This binding can either lead to oligomerization of individual receptors, to reorganization of existing clusters of receptors or to changes in the protein conformations, which in turn results in recruitment of signaling molecules in the cytoplasm. While different membrane receptors activate different downstream signaling pathways, some receptors can activate more than one pathway and a particular pathway can be activated by different receptors. It appears that these processes are regulated either by agonists and antagonists in the extracellular medium, by receptor-receptor interactions in the membrane or by a number of signaling mediators in the cytoplasm of the cell. Our work has focused on understanding how the intermolecular interactions in the membrane can control the signal transduction process: Are there specialized structures on the surface that facilitate receptor-receptor interactions? Do the receptors exist as monomers or pre-existing complexes that enhance the probability of activation? Do different receptors associate in the same domains or are there distinct organizational principles for each receptor type. In order to address these questions, we seek to develop tools that allow us to examine intermolecular interactions and reactions directly on the cell surface, particularly on live cells in culture or in tissue. This review discusses some of the approaches that are currently available and highlights some of the key advantages and disadvantages they represent with particular focus on image cross correlation spectroscopy as a relatively new quantitative tool developed by us to address some of these issues.
Switching Phenomena in Thin Films (1973)

Of the two types of switching phenomena which characterize thin films of amorphous semiconductors, it is now generally acknowledged that memory switching is basically well understood, not only in principle, but in detail. On the other hand, threshold switching has been a subject of some controversy, and a plethora of mechanisms has been proposed. In this paper, equilibrium and high-field characteristics as well as switching properties of threshold-type material are reviewed, and the suggested mechanisms are critically analyzed in the light of recent experimental results.
Modulation of the NMDA receptor by polyamines (1991)

Results of recent biochemical and electrophysiological studies have suggested that a recognition site for polyamines exists as part of the NMDA receptor complex. This site appears to be distinct from previously described binding sites for glutamate, glycine, Mg++,Zn++, and open-channel blockers such as MK-801. The endogenous polyamines spermine and spermidine increase the binding of open-channel blockers and increase NMDA-elicited currents in cultured neurons. These polyamines have been termed agonists at the polyamine recognition site. Studies of the effects of natural and synthetic polyamines on the binding of [3H]MK-801 and on NMDA-elicited currents in cultured neurons have led to the identification of compounds classified as partial agonists, antagonists, and inverse agonists at the polyamine recognition site. Polyamines have also been found to affect the binding of ligands to the recognition sites for glutamate and glycine. However, these effects may be mediated at a site distinct from that at which polyamines act to modulate the binding of open-channel blockers. Endogenous polyamines may modulate excitatory synaptic transmission by acting at the polyamine recognition site of the NMDA receptor. This site could represent a novel therapeutic target for the treatment of ischemia-induced neurotoxicity, epilepsy, and neurodegenerative diseases.
Molecular Modeling Studies on Oxidation of Hexopyranoses by Galactose Oxidase. An Active Site Topology Apparently Designed To Catalyze Radical Reactions, Either Concerted or Stepwise (1996)

Galactose oxidase is a mononuclear copper enzyme which oxidizes primary alcohols to aldehydes using molecular oxygen. A unique type of cross-link between tyrosine 272, an active site copper ligand, and cysteine 228 provides a modified tyrosine radical site which is believed to act as a one-electron redox center. Galactose oxidase is highly selective in its processing of hexopyranose substrates. Turnover of d-galactose is stereospecific for cleavage of the pro-S hydrogen. d-Galactose is an excellent substrate but its C-4 epimer d-glucose is not a substrate and will not even bind at 1 M concentration. Any proposed mechanism for galactose oxidase should be able to account for these stringent hexopyranose substrate specificities. In this paper we report molecular modeling studies of active site binding of postulated radical carbon−hydrogen bond cleavage transition states of d-galactose and d-glucose. Differences in specific enzyme−substrate interactions provide convincing explanations of the pro-S and galactose specificities. In addition, a previously unconsidered concerted radical mechanism appears to be just as plausible as the more standard stepwise radical mechanism via a ketyl radical anion intermediate. Regardless of whether a stepwise or concerted mechanism is operating, the active site appears to be well designed to bind radical transition states and perform radical enzyme catalysis. The detailed models developed here for ground state and transition state enzyme−substrate interactions provide insight to guide mechanistic studies using both radical-probing substrates and site-directed mutagenesis.
Abatacept: a costimulatory inhibitor for treatment of rheumatoid arthritis (2005)

T cell costimulation is believed to be crucial in orchestrating immune responses that lead to inflammation and destruction in rheumatoid arthritis (RA). Abatacept is a novel recombinant CTLA4Ig fusion protein that selectively modulates costimulation via interrupting the CD28:CD80/86 pathway, resulting in downregulation of T cell activation and multiple ensuing effector mechanisms. Abatacept has been shown to be efficacious, either when given alone or in combination with methotrexate, in patients with active RA, including anti-TNF failures. Improvements in clinical signs and symptoms, slowing of radiological progression, and enhancement in patient function and pain have been reported in clinical trials. Infusions were well-tolerated with a favourable safety profile similar to placebo and no appreciable immunogenicity. Abatacept is the first in a new class of biological response modifiers called costimulatory blockers.
Chemically mediated fluorescence yield switching in nitroxide-fluorophore adducts: optical sensors of radical/redox reactions (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemically mediated fluorescence yield switching in nitroxide-fluorophore adducts: optical sensors of radical/redox reactionsNeil V. Blough and Daniel J. SimpsonCite this: J. Am. Chem. Soc. 1988, 110, 6, 1915–1917Publication Date (Print):March 1, 1988Publication History Published online1 May 2002Published inissue 1 March 1988https://pubs.acs.org/doi/10.1021/ja00214a041https://doi.org/10.1021/ja00214a041research-articleACS PublicationsRequest reuse permissionsArticle Views1118Altmetric-Citations172LEARN 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
Preparation, Characterization, and Time-Resolved Fluorometric Application of Silica-Coated Terbium(III) Fluorescent Nanoparticles (2003)

Novel silica-coated terbium(III) chelate fluorescent nanoparticles have been prepared and characterized as a new type of fluorescence probe for highly sensitive time-resolved fluorescence bioassay. The preparation was carried out in a water-in-oil microemulsion containing a strongly fluorescent Tb(3+) chelate, N,N,N(1),N(1)-[2,6-bis(3'-aminomethyl-1'-pyrazolyl)-phenylpyridine]tetrakis(acetate)-Tb(3+), Triton X-100, hexanol, and cyclohexane by controlling hydrolysis of tetraethyl orthosilicate. The nanoparticles are spherical and uniform in size, 42 +/- 3 nm in diameter, strongly fluorescent, and highly photostable and have enough of a long fluorescence lifetime (1.52 ms) for time-resolved fluorescence measurement. A stable and nontoxic method was developed for the surface modification and protein immobilization of the nanoparticles. As a model of application, the nanoparticle-labeled streptavidin was prepared and used in a sandwich-type time-resolved fluoroimmunoassay of human prostate-specific antigen (PSA) by using a 96-well microtiter plate as the solid-phase carrier. The method gives a detection limit of 7.0 pg/mL for the PSA assay.
Methods for the determination of adipose cell size in man and animals (1968)

Four methods for the sizing of adipose cells in small samples of human or animal adipose tissue are compared. These methods depend on the preparation of cell suspensions by incubation of the tissue with collagenase or by prolonged fixation with osmium tetroxide and separation of the fixed cells. A Coulter electronic counter was used to count and size the suspended cells and a Zeiss particle size analyzer for the sizing of cells in photomicrographs. The use of the Coulter counter to count cells in a suspension derived from a known amount of tissue and subjected to osmium tetroxide fixation is recommended for accuracy and general applicability to adipose cells of all sizes in man and animals.
Decreased Cell Surface Charge in Cystic Fibrosis Epithelia (1997)

A colloid titration technique has been used to determine the surface charge of cystic fibrosis (CF) and corresponding non-CF epithelial cells. We have shown that the negative surface charge of CF epithelial cells is significantly reduced in comparison with non-CF cells. This fact may play an important role in CF, where the increased adherence of microorganisms is known to cause chronic lung infection. Neuraminidase treatment removed approximately the same amount of surface charge in both cell lines, indicating no differences in cell surface sialylation. Similar results were obtained by direct measurements of the amount of N-acetylneuraminic acid released by neuraminidase. Therefore, our results indicate that sialic acid residues are not involved in the reduction of the negative surface charge in CF. This conclusion does not support the hypothesis that undersialylation of cell-membrane molecules occurs in cystic fibrosis.
Bacterial Bioreactors for High Yield Production of Recombinant Protein (2006)

We developed a new bacterial expression system that utilizes a combination of attributes (low temperature, induction of an mRNA-specific endoribonuclease causing host cell growth arrest, and culture condensation) to facilitate stable, high level protein expression, almost 30% of total cellular protein, without background protein synthesis. With the use of an optimized vector, exponentially growing cultures could be condensed 40-fold without affecting protein yields, which lowered sample labeling costs to a few percent of the cost of a typical labeling experiment. Because the host cells were completely growth-arrested, toxic amino acids such as selenomethionine and fluorophenylalanine were efficiently incorporated into recombinant proteins in the absence of cytotoxicity. Therefore, this expression system using Escherichia coli as a bioreactor is especially well suited to structural genomics, large-scale protein expressions, and the production of cytotoxic proteins.
Cardiovascular actions of the κ‐agonist, U‐50,488H, in the absence and presence of opioid receptor blockade (1992)

1. The cardiovascular actions of U-50,488H, a kappa-receptor agonist, were studied in rat isolated perfused hearts, and in anaesthetized rats, over concentrations or doses generally above those required to produce kappa-receptor-mediated effects. 2. U-50,488H dose-dependently decreased left-ventricular peak systolic pressure and beating rate in vitro and reduced blood pressure and heart rate in vivo. 3. Over the concentration range of 1-30 microM in vitro, and the dose-range of 0.5-32 mumol kg-1 in vivo, U-50,488H prolonged the P-R, QRS and Q-T intervals of the ECG. 4. The effects of U-50,488H were not antagonized by an opioid receptor antagonist, naloxone (1 microM or 8 mumol kg-1). Similarly, the opioid receptor antagonist, MR 2266, at 8 mumol kg-1 did not significantly reduce the cardiovascular actions of U-50,488H in vivo. 5. The actions of U-50,488H on responses to electrical stimulation were also studied. Over the dose range of 0.5-32 mumol kg-1, U-50,488H altered thresholds and effective refractory period. It had a biphasic action on thresholds for induction of ventricular fibrillation. Thresholds were decreased at lower doses (0.5-4 mumol kg-1) but increased at higher doses (8-32 mumol kg-1). The effects of lower doses were blocked by naloxone. Effective refractory period and threshold pulse width only increased with dose. 6. In conclusion, U-50,488H at high concentration, had direct depressant actions on cardiac contractility, electrical excitability and the ECG. These depressant effects were not antagonized by the opioid receptor antagonists, naloxone and MR 2266, and probably do not involve opioid receptors. Furthermore, some of the observed effects were those expected to result from sodium channel blockade.
Limiting privacy breaches in privacy preserving data mining (2003)

There has been increasing interest in the problem of building accurate data mining models over aggregate data, while protecting privacy at the level of individual records. One approach for this problem is to randomize the values in individual records, and only disclose the randomized values. The model is then built over the randomized data, after first compensating for the randomization (at the aggregate level). This approach is potentially vulnerable to privacy breaches: based on the distribution of the data, one may be able to learn with high confidence that some of the randomized records satisfy a specified property, even though privacy is preserved on average.In this paper, we present a new formulation of privacy breaches, together with a methodology, "amplification", for limiting them. Unlike earlier approaches, amplification makes it is possible to guarantee limits on privacy breaches without any knowledge of the distribution of the original data. We instantiate this methodology for the problem of mining association rules, and modify the algorithm from [9] to limit privacy breaches without knowledge of the data distribution. Next, we address the problem that the amount of randomization required to avoid privacy breaches (when mining association rules) results in very long transactions. By using pseudorandom generators and carefully choosing seeds such that the desired items from the original transaction are present in the randomized transaction, we can send just the seed instead of the transaction, resulting in a dramatic drop in communication and storage cost. Finally, we define new information measures that take privacy breaches into account when quantifying the amount of privacy preserved by randomization.
Microelectrodes on a Silicon Chip for Label-Free Capacitive DNA Sensing (2006)

This paper presents the experimental characterization of two-terminal microfabricated capacitors for microarrays with an electrical sensing of label-free deoxyribonucleic acid (DNA). So far, such a concept has been demonstrated only in experimental setups featuring dimensions much larger than those typical of microfabrication. Therefore, this paper investigates: 1) the compatibility of the silicon microelectronic processes with biological functionalization procedures; 2) the effects of parasitics when electrodes have realistic dimensions; 3) measurement stability and reproducibility; and 4) the possibility of a fully integrated stand-alone device. The obtained results clearly indicate that two-terminal capacitive sensing with fully integrated electronics represents a viable technology for a DNA label-free detection/recognition.
Efficient Entry to Diversely Functionalized Spirocyclic Oxindoles from Isatins through Carbonyl-Addition/Cyclization Reaction Sequences (2006)

A novel approach to diversely functionalized spirocyclic oxindoles has been developed by using different metal-mediated carbonyl-addition/cyclization reaction sequences. Spirocyclization precursors, 2-indolinone-tethered homoallylic alcohols, (buta-1,3-dien-2-yl)methanols, and alpha-allenols have been obtained by regioselective addition of stabilized organoindium reagents to isatins in aqueous environment. Ruthenium-, silver-, and palladium-catalyzed reactions of the above unsaturated alcohol derivatives provided oxaspiro oxindoles.
Near-Infrared Fluorescent Nanoparticles as Combined MR/Optical Imaging Probes (2002)

A number of quantitative three-dimensional tomographic near-infrared fluorescence imaging techniques have recently been developed and combined with MR imaging to yield highly detailed anatomic and molecular information in living organisms (1, 2). Here we describe magnetic nanoparticle based MR contrast agents that have a near-infrared fluorescence (NIRF) that is activated by certain enzymes. The probes are prepared by conjugation of arginyl peptides to cross-linked iron oxide amine (amino-CLIO), either by a disulfide linkage or a thioether linker, followed by the attachment of the indocyanine dye Cy5.5. The NIRF of disulfide-linked conjugate was activated by DTT, while the NIRF of thioether-linked conjugate was activated by trypsin. Fluorescent quenching of the attached fluorochrome occurs in part due to the interaction with iron oxide, as evident by the activation of fluorescence with DTT when nanoparticles that have less than one dye attached per particle. With a SC injection of the probe, axillary and brachial lymph nodes were darkened on MR images and easily delineated by NIRF imaging. The probes may provide the basis for a new class of so-called smart nanoparticles, capable of pinpointing their position through their magnetic properties, while providing information on their environment by optical imaging techniques.
Sodium channel protein expression enhances the invasiveness of rat and human prostate cancer cells (1998)

Expression of Na+ channel protein was analysed in established cell lines of rat and human prostatic carcinoma origin by flow cytometry using a fluorescein-labelled polyclonal antibody. In many cell lines examined, the obtained frequency distribution profiles were bimodal and identified a subpopulation of cells which expressed high levels of Na+ channel protein. A significant positive correlation was demonstrated between the proportion of channel-expressing cells and the functional ability of individual cell lines to invade a basement membrane matrix in vitro. In addition, two transfectant cell lines containing rat prostate cancer genomic DNA were found to express significantly elevated levels of Na+ channel protein when compared with the original benign recipient cell line. Enhanced Na+ channel expression by two metastatic derivatives of these transfectant cells directly correlated with increased invasiveness in vitro. These studies strongly support the hypothesis that expression of Na+ channel protein and the metastatic behaviour of prostatic carcinoma cells are functionally related, either by endowing the membranes of these cells with specialised electrophysiological properties (e.g. enhancing their motility and/or secretory activities) and/or by perturbing endogenous mechanisms regulating ionic homeostasis within the cells.
488. Compounds related to the steroid hormones. Part II. The action of hydrogen bromide on 2-bromo-3-oxo-Δ1-5α-steroids (1961)

G. F. H. Green and A. G. Long, J. Chem. Soc., 1961, 2532 DOI: 10.1039/JR9610002532