gebhart/patrepeval huggingface dataset:
Homogeneous Assays for Single-Nucleotide Polymorphism Typing Using AlphaScreen (2001)

AlphaScreen technology allows the development of high-throughput homogeneous proximity assays. In these assays, signal is generated when 680 nm laser light irradiates a donor bead in close proximity to an acceptor bead. For the detection of nucleic acids, donor and acceptor beads are brought into proximity by two bridging probes that hybridize simultaneously to a common target and to the generic oligonucleotides attached covalently to the beads. This method allows the detection of as little as 10 amole of a single-stranded DNA target. The combination of AlphaScreen with allele-specific amplification (ASA) and allele-specific hybridization (ASH) has allowed the development of two homogenous single-nucleotide polymorphism (SNP) genotyping platforms. Both types of assay are very robust, routinely giving accurate genotyping results with < 2 ng of genomic DNA per genotype. An AlphaScreen validation study was performed for 12 SNPs by using ASA assays and seven SNPs by using ASH assays. More than 580 samples were genotyped with accuracy >99%. The two assays are remarkably simple, requiring no post-PCR manipulations. Genotyping has been performed successfully in 96- and 384-well formats with volumes as small as 2 microL, allowing a considerable reduction in the amount of reagents and genomic DNA necessary for genotyping. These results show that the AlphaScreen technology can be successfully adapted to high-throughput genotyping.
Modulation of Postendocytic Sorting of G Protein-Coupled Receptors (2002)

Recycling of the mu opioid receptor to the plasma membrane after endocytosis promotes rapid resensitization of signal transduction, whereas targeting of the delta opioid receptor (DOR) to lysosomes causes proteolytic down-regulation. We identified a protein that binds preferentially to the cytoplasmic tail of the DOR as a candidate heterotrimeric GTP-binding protein (G protein)-coupled receptor-associated sorting protein (GASP). Disruption of the DOR-GASP interaction through receptor mutation or overexpression of a dominant negative fragment of GASP inhibited receptor trafficking to lysosomes and promoted recycling. The GASP family of proteins may modulate lysosomal sorting and functional down-regulation of a variety of G protein-coupled receptors.
Psoriasis scales contain C5a as the predominant chemotaxin for monocyte‐derived dendritic cells (2001)

Dendritic cells seem to be of major importance for the pathogenesis of psoriasis. They are increased in number in lesional psoriatic skin which is thought to be due to an increased influx from the peripheral blood regulated by chemotaxins. Using a biological/biochemical approach we have addressed the question whether psoriasis scale extracts contain proteinaceous chemotaxins for dendritic cells. Human monocytes differentiated into dendritic cells by culture with GM-CSF and IL-4 (MoDC) served as responder cells. Chemotactic activity for MoDC was purified by several HPLC-steps. The results of our study show that C5a/C5adesarg is the major chemotactic peptide for MoDC in psoriasis scale extracts. In comparison to other stimuli such as fMLP or monocyte chemotactic peptide 1 (MCP-1) C5a proved to be a most potent and efficient chemotaxin for MoDC. C5a co-eluted with MRP14/calgranulin B which is present in large amounts in psoriasis scale extracts as identified by amino acid sequencing. However, MRP14/calgranulin B did not possess any chemotactic activity for MoDC. Our results provide evidence that C5a/C5adesarg although not specific for dendritic cells seems to be the major chemoattractant for these cells in lesional psoriasis skin.
Field-scale assessment of phytoremediation at a former oil tank battery in Bruderheim, Alberta. (2010)

A 3-yr study to assess the effectiveness of plant-based systems to reduce contaminant levels to environmentally acceptable endpoints (as defined by the Canadian Council of Ministers of the Environment; CCME) was established at a former tank battery near Bruderheim, Alberta. Four treatments (unplanted, unfertilized control; unplanted, fertilized control; a standard cool-season grass/legume mixture; and a locally optimized grass/legume mixture) were compared in a randomized complete block design (n=4). The site was monitored for three years, with soils sampled (0–15 cm and 15-45 cm) at the end of each growing season. Analyses included total petroleum hydrocarbons (TPH), polycyclic aromatic hydrocarbons (PAHs), and CCME PHC-fractions. Plant assessments (species composition, above- and below-ground biomass) also were conducted at the end of each growing season. After three growing seasons, TPH concentrations averaged across the site had been reduced by 62% in the surface and 64% subsurface soils. Reductions in PHC concentrations were generally greater in the plots amended with fertilizer and compost, but were similar in the planted and unplanted plots. Reductions in the F2 (C6-C10) fraction, however, generally occurred more rapidly in the planted treatments. There were no significant differences between the standard and locally optimized plant mixes.
O2 Reduction Mechanism on Non-Noble Metal Catalysts for PEM Fuel Cells. Part I: Experimental Rates of O2 Electroreduction, H2O2 Electroreduction, and H2O2 Disproportionation (2009)

One Fe/N/C cathode electrocatalyst for PEM fuel cells with a nominal loading of 0.2 wt % Fe was prepared by heat-treating at 950 °C in NH3 a nonmicroporous furnace carbon black impregnated with iron acetate. O2 reduction reaction (ORR) occurs on this catalyst with an apparent 4e transfer, while H2O2 electroreduction is sluggish, thereby minimizing the importance of the peroxide electroreduction pathway. It is also shown that H2O2 disproportionates only slowly into H2O and 1/2O2 on this Fe/N/C catalyst. Therefore, the electrochemical−chemical pathway of O2 to H2O2 followed by H2O2 disproportionation is minor during ORR. It is concluded that the present Fe/N/C catalyst reduces O2 to water following mainly a direct 4e pathway. It is also noticed that the initial porosity of the carbon support may drastically influence the ORR mechanism. The same investigation was extended to other M/N/C electrocatalysts, where M = Cr, Mn, Co, Ni, and Cu, prepared according to the same procedure as used for Fe/N/C. A correlation was found between the ORR activity and the activity for H2O2 disproportionation. This is explained by the occurrence of a common rate-limiting intermediate for the two reactions: the oxo-ferryl-like cation radical.
Human Interleukin-3 (IL-3) Induces Disulfide-Linked IL-3 Receptor α- and β-Chain Heterodimerization, Which Is Required for Receptor Activation but Not High-Affinity Binding (1996)

The human interleukin-3 receptor (IL-3R) is a heterodimer that comprises an IL-3 specific alpha chain (IL-3R alpha) and a common beta chain (beta C) that is shared with the receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5. These receptors belong to the cytokine receptor superfamily, but they are structurally and functionally more related to each other and thus make up a distinct subfamily. Although activation of the normal receptor occurs only in the presence of ligand, the underlying mechanisms are not known. We show here that human IL-3 induces heterodimerization of IL-3R alpha and beta c and that disulfide linkage of these chains is involved in receptor activation but not high-affinity binding. Monoclonal antibodies (MAb) to IL-3R alpha and beta c were developed which immunoprecipitated, in the absence of IL-3, the respective chains from cells labelled with 125I on the cell surface. However, in the presence of IL-3, each MAb immunoprecipitated both IL-3R alpha and beta c. IL-3-induced receptor dimers were disulfide and nondisulfide linked and were dependent on IL-3 interacting with both IL-3R alpha and beta c. In the presence of IL-3 and under nonreducing conditions, MAb to either IL-3R alpha or beta c immunoprecipitated complexes with apparent molecular weights of 215,000 and 245,000 and IL-3R alpha and beta c monomers. Preincubation with iodoacetamide prevented the formation of the two high-molecular-weight complexes without affecting noncovalent dimer formation or high-affinity IL-3 binding. Two-dimensional gel electrophoresis and Western blotting (immunoblotting) demonstrated the presence of both IL-3R alpha and beta c in the disulfide-linked complexes. IL-3 could also be coimmunoprecipitated with anti-IL-3R alpha or anti-beta c MAB, but it was not covalently attached to the receptor. Following IL-3 stimulation, only the disulfide-linked heterodimers exhibited reactivity with antiphosphotyrosine antibodies, with beta c but not IL-3R alpha being the phosphorylated species. A model of IL-3R activation is proposed which may be also applicable to the related GM-CSF and IL-5 receptors.
Augmented projections for ptychographic imaging (2013)

Ptychography is a popular technique to achieve diffraction limited resolution images of a two or three dimensional sample using high frame rate detectors. We introduce a relaxation of common projection algorithms to account for instabilities given by intensity and background fluctuations, position errors, or poor calibration using multiplexing illumination. This relaxation introduces an additional phasing optimization at every step that enhances the convergence rate of common projection algorithms. Numerical tests exhibit the exact recovery of the object and the noise when there is high redundancy in the data.
Re-evaluation of amino acid PET studies: can the protein synthesis rates in brain and tumor tissues be measured in vivo? (1993)

The significance of L-[methyl-11C]methionine (11C-Met), L-[1-11C]leucine (11C-Leu) and L-2-[18F]fluorotyrosine (18F-Tyr) for measuring protein synthesis rates in the brain and in tumors by PET was re-evaluated. Tissue uptake and protein incorporation of 3H-Met, 14C-Leu and 18F-Tyr were investigated in mice bearing the FM3A mammary carcinoma. In the control group, the uptake of all three tracers in the brain and FM3A and their incorporation into the acid-precipitable fraction (APF) increased over 60 min. When the protein synthesis in vivo was inhibited by cycloheximide, the incorporation of all three tracers into the APF was significantly reduced to 6%-32% and 3%-11% of the control in the brain and FM3A, respectively. Under these conditions, total uptake of 14C-Leu in the brain and FM3A decreased rapidly, and most of the 14C in the APF was detected as proteins. On the other hand, 3H-Met and 18F-Tyr uptake continued to increase, and significant amounts of radioactivity were incorporated into nonprotein materials. In mice given ouabain to inhibit amino acid transport, total uptake of all three amino acids by FM3A was reduced to 67%-74% of the control 5 min postinjection. These results demonstrate that uptake of the three amino acids is affected by alterations in the amino acid transport system in the brain and tumor tissues, but that only 14C-Leu uptake reflects protein synthesis rates.
Human Platelet-Derived Growth Factor (PDGF): Amino-Terminal Amino Acid Sequence (1983)

Human platelet-derived growth factor (PDGF) obtained from outdated human platelets was subjected to amino-terminal amino acid sequence analysis by automated Edman degradation. Despite the apparent presence of limited proteolytic degradation of the protein derived from this method, the sequence analysis reveals two primary peptide sequences and suggests that active PDGF is composed of two, possibly homologous, peptides linked by a disulfide bond or bonds.
Highly Refractive Glasses to lmprove Electroluminescent Diode Efficiencies (1969)

A series of low‐melting arsenic‐chalcogen‐halogen glasses were developed, with refractive indexes between 2.4 and 2.9. Despite severe thermal expansion mismatch, it was possible to form stable glass domes on planar electroluminescent diodes by using glass compositions which permit strain relief by thermoplastic flow. By reducing internal reflection losses, external efficiencies were routinely increased by factors from 4–6 for , , and diodes, resulting in external efficiencies as high as 7.2% for a solution‐grown diode.
75-nm 3-dB gain-band optical amplification with erbium-doped fluoride fibre amplifiers and distributed Raman amplifiers in 9 × 2.5-Gb/s WDM transmission experiment (1997)

An extremely large 3-dB gain-bandwidth of 75 nm (1531-1606 nm) is achieved employing partially gain-flattened erbium-doped fluoride fiber amplifiers and Raman amplification in the transmission fibres. 9/spl times/2.5 Gb/s WDM transmission is successfully demonstrated using our amplifiers as an in-line- and pre-amplifiers.
Sodium Ion Diffusion in Nafion® Ion Exchange Membranes (1980)

Development of membrane chlor‐alkali cells during this past decade represents a major advancement for commercial electrochemical technology. Chemical engineering applications of separation processes such as this involve diffusional mass transfer that can be treated as a rate process. The chlor‐alkali application includes sodium, chloride, and hydroxyl ions plus water as mobile species in caustic soda and brine solutions and also between immiscible membrane and solution phases. These immiscible phases are brought into contact to allow selective transfer of sodium and water from brine to the caustic solutions. Previous data reported on diffusion through Nafion® membranes,, are difficult to interpret because not only do they involve hydroxide and sodium ion fluxes to give average diffusion coefficients, but also unknown gradients of electrolyte and water concentration are present in the membrane phase. This present work greatly simplifies these problems encountered by isolating and measuring the precise sodium ion self‐diffusion coefficient, , with radio‐tracer techniques in various du Pont Nafion® and EDA modified membranes. It then relates the to equivalent weight, surface treatment, and fabric backing in these membranes. These data for are very important in chlor‐alkali cells because the sodium ion is the major current carrier; therefore, its value can be related to the relative activation energy and voltage drop among similar membranes.
On the Relative Distribution of Cysts of Heterodera schachtii and a Chemical Dressing incorporated with Infected Land by means of a Rototiller (1938)

A field experiment was commenced in Bedfordshire during 1937, when soil infested with cysts of Heterodera schachtii was treated with very heavy dressings of calcium cyanamide. For comparison, a treatment with ammonium sulphate and lime was included. The lay-out was in the form of four randomised blocks of five treatments: control, calcium cyanamide 40, 60 and 80 c.p.a., and ammonium sulphate 80 c.p.a. plus hydrated lime 63 c.p.a. The last dressing contained the same amounts of nitrogen and lime as 80 c.p.a. of calcium cyanamide.
MECHANISMS UNDERLYING THE CORONARY VASODILATION IN THE ISOLATED PERFUSED HEARTS OF RATS SUBMITTED TO ONE WEEK OF HIGH CARBON MONOXIDE EXPOSURE IN VIVO (2002)

We examined the possible mechanisms for carbon monoxide (CO)-induced effects in hearts isolated from Wistar rats exposed for 1 wk to 530 ppm CO. They were treated by daily intraperitoneal injections of either methylene blue (10 mg/kg), glibenclamide (3 mg/kg), or apamin (125 nmol/kg), known to inhibit vasodilatory mechanisms. Hearts were excised, cannulated, and retrogradely perfused through the coronary artery, using the Langendorff method with a constant perfusion pressure. After stabilization, we investigated the degree of resistance to an in vitro transient global low-flow ischemia. One-week CO exposure induced a significant increase in hematocrit and a cardiomegaly, which were not affected by any of these drugs. An enhancement of coronary flow was observed concomitantly with a decrease in ischemic contracture after CO exposure. However, no improvement of contractile recovery was noted. Since methylene blue did not interact with the CO effects, a cGMP signaling pathway can be excluded. On the contrary, as glibenclamide and to a greater extend apamin blocked the vasodilatory effects of CO, we conclude that K+ channels may be involved in these CO effects.
OBSERVATIONS IMPLICATING AN EXTRACELLULAR ENZYMIC MECHANISM OF CONTROL OF BONE MORPHOGENESIS (1974)

Data on physicochemical conditions leading to loss of the bone morphogenetic property of bone matrix in neutral buffer solutions support the concept of an enzymic control mechanism better than a chemical blocking reaction or denaturation. The loss is associated with release of 35 S-labeled constituents and not prevented by ε-amino caproic acid, an inhibitor of cathepsins. The loss is also associated with release of 35 S-cysteine-labeled protein; about 60% of the yield is sustained by the addition of only 3 mmoles/liter of iodoacetic acid. A latent period of about 12 hr, decreased by extraction of bone matrix with CaCl 2 , is characterized by release of protein polysaccharide and other noncollagenous proteins. Release of sialic acid from the bone matrix by neuraminidase at pH 7.4 has no effect upon bone yield. At 2°C, Tris-HCl buffer or ethylenediaminetetraacetic acid extracts noncollagenous proteins without loss of bone yield; at 37°C, pH 7.4, these solutions also activate endogenous enzymes and reduce bone yield. The component of bone matrix responsible for reduction in bone yield is separable from bone matrix by extraction with phosphate buffer, by catheptic digestion of bone matrix in acidic buffer solutions, by sequential chemical extraction of noncollagenous proteins with cold slightly acidic salt solutions or by extraction-denaturation with chloroform-methanol. Detergents neither extinguish nor denature the morphogenetic property but some solubilize or extract degradative enzymes; hexodecyl trimethyl ammonium bromide, at pH 5.0, is positively charged and extracts hydrophobic proteins, including part of the bone morphogenetic property. A special selection of sulfhydryl chemical inhibitors remarkably different from the selection inhibiting known enzymes preserves the bone morphogenetic property of bone matrix; p-chloromercuribenzoate preservation is reversible by chemical reactions with cysteine. Reduction in bone yield in phosphate buffer is not attributable to a chemical block because chloroform-methanol extraction of the agent does not restore bone yield and is not attributable to denaturation because bone yield sustained by p-chloromercuribenzoate is lost by chemical reactions with cysteine. An hypothetical insoluble bone morphogenetic protein (BMP) firmly bound to collagen is degraded by a soluble neutral proteinase (BMPase). Digestion of the hypothetical BMP occurs without loss of the 640-A electron micrographic image of bone collagen, resembles tryptic digestion and is more selective as well as physiologic in action.
Intercom Ontario: a user-centered field trial (2002)

The mandate that Intercom Ontario be a user-centered trial involved the making of a number of choices. This paper describes what these choices were, the rationale behind these choices, their consequences, and the proposed solutions. The objective of the trial is to determine what services the user community in Ontario wants, needs and will use in the emerging electronic superhighway; and to examine the impacts of these solutions in a real world setting and their practicability over the long term. It is expected that the trial will generate knowledge to support all relevant stakeholders: information users as well as information providers at private, public and government levels.
El papel de la OSCE en la prevención y gestión de crisis en Europa (2000)

En primer lugar quisiera expresar mi agradecimiento por la oportunidad que el Centro Superior de Estudios de la Defensa Nacional (CESEDEN) me ofrece para exponer ante una audiencia distinguida y experta en asuntos de seguridad el papel que la Organizacion de Seguridad y Cooperacion en Europa (OSCE) desempena en la seguridad europea. Esta invitacion, que agradezco, es doblemente oportuna. Primero porque en el mes de agosto se cumplira el XXV aniversario de la firma del Acta Final de Helsinki, punto de arranque del llamado <<Proceso de Helsinki)) y de la Conferencia de Seguridad y Cooperacion en Europa (CSCE) que posteriormente dio paso a la organizacion de seguridad mas joven de Europa, la OSCE. Es oportuna tambien porque esta aun reciente la celebracion de la ultima Cumbre de Jefes de Estado y/o de Gobierno en Estambul que ha servido para consolidar el acervo normativo acumulado durante cinco lustros y para relanzar la dimension operativa de la OSCE.
A Stem Cell–Based Approach to Cartilage Repair (2012)

Osteoarthritis (OA) is a degenerative joint disease that involves the destruction of articular cartilage and eventually leads to disability. Molecules that promote the selective differentiation of multipotent mesenchymal stem cells (MSCs) into chondrocytes may stimulate the repair of damaged cartilage. Using an image-based high-throughput screen, we identified the small molecule kartogenin, which promotes chondrocyte differentiation (median effective concentration = 100 nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A, disrupts its interaction with the transcription factor core-binding factor β subunit (CBFβ), and induces chondrogenesis by regulating the CBFβ-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to a stem cell-based therapy for osteoarthritis.
Antibody–drug conjugates as novel anti-cancer chemotherapeutics (2015)

Over the past couple of decades, antibody-drug conjugates (ADCs) have revolutionized the field of cancer chemotherapy. Unlike conventional treatments that damage healthy tissues upon dose escalation, ADCs utilize monoclonal antibodies (mAbs) to specifically bind tumour-associated target antigens and deliver a highly potent cytotoxic agent. The synergistic combination of mAbs conjugated to small-molecule chemotherapeutics, via a stable linker, has given rise to an extremely efficacious class of anti-cancer drugs with an already large and rapidly growing clinical pipeline. The primary objective of this paper is to review current knowledge and latest developments in the field of ADCs. Upon intravenous administration, ADCs bind to their target antigens and are internalized through receptor-mediated endocytosis. This facilitates the subsequent release of the cytotoxin, which eventually leads to apoptotic cell death of the cancer cell. The three components of ADCs (mAb, linker and cytotoxin) affect the efficacy and toxicity of the conjugate. Optimizing each one, while enhancing the functionality of the ADC as a whole, has been one of the major considerations of ADC design and development. In addition to these, the choice of clinically relevant targets and the position and number of linkages have also been the key determinants of ADC efficacy. The only marketed ADCs, brentuximab vedotin and trastuzumab emtansine (T-DM1), have demonstrated their use against both haematological and solid malignancies respectively. The success of future ADCs relies on improving target selection, increasing cytotoxin potency, developing innovative linkers and overcoming drug resistance. As more research is conducted to tackle these issues, ADCs are likely to become part of the future of targeted cancer therapeutics.