gebhart/patrepeval huggingface dataset:
Steroid Hormone-Dependent Interaction of Human Progesterone Receptor with its Target Enhancer Element (1988)

We investigated the requirement of steroid hormone for the specific binding of progesterone receptor to its cognate progesterone responsive element (PRE) in cell-free experiments. We prepared unfractionated nuclear extracts from human breast cancer (T47D) cells which are rich in progesterone receptors and used a gel retardation assay to monitor receptor-DNA complex formation. Exposure of receptor to either progesterone, R5020, or the antiprogestin RU38 486 in vivo or in vitro led to the formation of two protein-DNA complexes (1 and 2) which were not detected in nuclear extracts unexposed to hormone. Similar treatment with cortisol or estradiol failed to induce the formation of these complexes. The complexes were specific for PRE, since they could be competed efficiently in binding competition experiments by oligonucleotides containing PRE. A monoclonal antibody which recognizes both A and B forms of human progesterone receptor, interacted with both complexes 1 and 2 and shifted them to slower migrating forms. Another antibody which only recognizes the B form interacted with only complex 1 but not with complex 2, establishing that the complexes 1 and 2 were indeed formed by progesterone receptor forms B and A, respectively. We conclude from the above studies that in vivo or in vitro treatment of nuclear progesterone receptor with either progesterone or R5020 or RU38 486 alone can lead to detection of high affinity complexes formed between the PRE and the receptor present in unpurified nuclear extracts.
Scanning fiber endoscope prototype performance (2004)

Minimally invasive medical procedures require flexible endoscopes that are thinner than existing devices while delivering high resolution images. The scanning fiber endoscope (SFE) described meets these requirements. Prototype SFEs with a 2 mm diameter distal tip envelope and better than 10 micron resolution have been developed.
Effect of broiler age, feed withdrawal, and transportation on levels of coliforms, Campylobacter, Escherichia coli and Salmonella on carcasses before and after immersion chilling (2003)

A study was conducted to determine effects of bird age at slaughter, feed withdrawal, and transportation on levels of coliforms, Campylobacter, Escherichia coli, and Salmonella on carcasses before and after immersion chilling. Broilers were processed at 42, 49, and 56 d of age after a 12-h feed withdrawal period or a 0-h feed withdrawal period (full fed). At each age, broilers were processed from two commercial farms previously identified as Campylobacter positive. One week before slaughter, broilers were gavaged with nalidixic acid-resistant Salmonella. During bleeding, cotton plugs were inserted into the cloaca of each carcass. Whole-carcass rinses (WCR) were performed before and after immersion chilling with 20 ppm sodium hypochlorite, and rinses were analyzed for coliforms, Campylobacter, E. coli and Salmonella. Log10 counts for coliforms, Campylobacter, and E. coli were (P < 0.05) affected by bird age at slaughter. Feed withdrawal (FW) affected only Campylobacter on carcasses of older broilers (56 d of age). Chilling with sodium hypochlorite resulted in log10 reductions of 1.2, 1.3, 1.4, and 0.5 for coliforms, Campylobacter, E. coli, and Salmonella, respectively. Under the conditions of this experiment, it appears that contamination on the exterior of birds entering the processing facility is critical to carcass bacterial counts. Moreover, carcass bacterial counts did not vary when microbial counts of broilers were comparable. FW may increase prechill carcass counts for E. coli and Campylobacter, but it appears to have no effect on postchill carcass counts when sodium hypochlorite is used in the chilling operation.
Deep Convolutional Encoder-Decoder Architecture for Neuronal Structure Segmentation (2018)

Electro microscopic connectomics is a practical application of research direction. It determines whether a nerve is damaged by judging the connectivity of nerves. However, the formidable size of Electro Microscopic (EM) image data generated by serial-section Transmitted Electron Microscopy (ssTEM) severely depends on human annotation, which is impractical. One of the main challenges in connectomics research is to take minimal user intervention into account during neuronal structures automatic segmentation. To address this problem, a network is constructed to segment neuronal structures automatically, which expands receptive field of feature maps. Besides, we also introduce data augmentation method to use the available training data more efficiently. Our model is proposed based on a context network, and its architecture consists of an encoding path that enables feature extraction. The novel introduction of summation-based skip connection is aimed to connect decoding path with encoding path. Finally, real experiments with ISBI EM dataset validate the approach.
Technetium- and rhenium-labeled progestins: synthesis, receptor binding and in vivo distribution of an 11 beta-substituted progestin labeled with technetium-99 and rhenium-186. (1992)

In an effort to develop radiopharmaceuticals useful for the diagnostic imaging of steroid receptor-positive breast tumors, we have radiolabeled an analog of the antiprogestin RU486 (mifepristone), modified to incorporate an N2S2 chelate system in the 11 beta-position, with 99Tc, 99mTc, and 186Re. For the 99Tc-labeled analogs (3), a syn pair and two individual antidiastereomers (linker methylene versus metal-oxo, relative to the N2S2 plane) were isolated. In competitive radiometric binding assays, the syn pair (3syn1,2) had affinity for the progesterone receptor that was 25% that of (promegestone) R5020 (or 161% that of progesterone), and the individual anti-diastereomers had affinities of 47% (3anti1) and 7% (3anti2) that of R5020 (or 303% and 45% that of progesterone). The specific-to-nonspecific binding ratio of the 99mTc (4) and 186Re (5) 11 beta-linked syn systems are 75/25 and 54/46, respectively. In vivo, conjugates 4 and 5 showed progesterone receptor-mediated uptake in rat uterus, but also high uptake in non-target tissues, presumably because of the high lipophilicity of the metal complexes. Modified systems may be useful in vivo as receptor-directed agents for diagnostic imaging or treatment of steroid receptor-positive tumors.
Direct measurement of intracellular free Ca2+ in rat peritoneal macrophages: correlation with oxygen-radical production. (1983)

A novel method has been developed, based on osmotic lysis of intracellular pinocytotic vesicles, to introduce the Ca2+-activated photoprotein obelin into the cytoplasm of rat peritoneal macrophages. The change in osmolarity of the incubating medium necessary to induce lysis of the pinocytotic vesicles did not significantly affect the viability or responsiveness of the cells. The method enabled on average 3 fl of external medium to be introduced into each cell. Macrophages loaded with photoprotein had a resting intracellular Ca2+ concentration of 0.24 +/- 0.02 microM, calculated from the obelin consumption rate. The calcium ionophore, A23187, induced a prolonged rise in intracellular Ca2+ and also stimulated oxygen-radical production, monitored by luminol-dependent chemiluminescence. The chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine, 1 microM, produced a transient increase in cytoplasmic Ca2+ which reached a plateau of 1.2 +/- 0.64 microM (n = 7) and declined with a half-time of approximately 40 sec. Unopsonized particles, latex beads (diameter = 1 micron), did not produce any detectable rise in intracellular Ca2+. Incorporation of a calcium chelator EGTA-ethylene-glycol-bis-(aminoethylether) tetra-acetate--into the cytoplasm abolished the transient intracellular Ca2+ rise induced by chemotactic peptide. Oxygen-radical production was also abolished. However, oxygen radical production induced by unopsonized particles was unaffected by intracellular EGTA. It was concluded that oxygen-radical production detected by chemiluminescence can be triggered by a rise in intracellular Ca2+. Chemotactic peptide induces oxygen-radical production by this mechanism. However, unopsonized particles induce oxygen-radical production by a mechanism independent of a rise in intracellular Ca2+.
Detection of Nitroaromatic Explosives Based on Photoluminescent Polymers Containing Metalloles (2003)

The synthesis, spectroscopic characterization, and fluorescence quenching efficiency of polymers and copolymers containing tetraphenylsilole or tetraphenylgermole with Si-Si, Ge-Ge, and Si-Ge backbones are reported. Poly(tetraphenyl)germole, 2, was synthesized from the reduction of dichloro(tetraphenyl)germole with 2 equivs of Li. Silole-germole alternating copolymer 3 was synthesized by coupling dilithium salts of tetraphenylsilole dianion with dichloro(tetraphenyl)germole. Other tetraphenylmetallole-silane copolymers, 4-12, were synthesized through the Wurtz-type coupling of the dilithium salts of the tetraphenylmetallole dianion and corresponding dichloro(dialkyl)silanes. The molecular weights (M(w)) of these metallole-silane copolymers are in the range of 4000 approximately 6000. Detection of nitroaromatic molecules, such as nitrobenzene (NB), 2,4-dinitrotoluene (DNT), 2,4,6-trinitrotoluene (TNT), and picric acid (PA), has been explored. A linear Stern-Volmer relationship was observed for the first three analytes, but not for picric acid. Fluorescence spectra of polymetalloles or metallole-silane copolymers obtained in either toluene solutions or thin polymer films displayed no shift in the maximum of the emission wavelength. This suggests that the polymetalloles or metallole-silanes exhibit neither pi-stacking of polymer chains nor excimer formation. Fluorescence lifetimes of polymetalloles and metallole-silanes were measured both in the presence and absence of TNT, and tau(o)/tau is invariant. This requires that photoluminescence quenching occurs by a static mechanism.
Regulation of striatal dopamine release by metabotropic glutamate receptors (1998)

In vivo microdialysis in conscious rats was used to assess the effect of metabotropic glutamate receptor stimulation on striatal dopamine release. Local application of the metabotropic glutamate agonist (±)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), via a microdialysis probe, produced a concentration-dependent response: infusion of 50 μM ACPD did not produce a significant effect on extracellular dopamine levels, while application of 100 μM or 500 μM ACPD increased dopamine release by approximately 50% or 100%, respectively. To examine the contribution of impulse flow and multisynaptic mechanisms to the ACPD-induced increase in dopamine release, 500 μM ACPD were coapplied with 2 μM tetrodotoxin (TTX). An increase in extracellular dopamine levels was observed after the application of 500 μM ACPD, despite the presence of TTX. To further study the actions of metabotropic glutamate receptor-stimulation on terminal release characteristics of dopamine, the effect of ACPD on 40 mM K+-stimulated dopamine release was investigated. It was found that application of ACPD reduces dopamine release in response to K+ stimulation. These data suggest that during basal conditions, metabotropic glutamate receptor activation facilitates striatal dopamine release, possibly through presynaptic, impulse-independent mechanisms. However, during conditions of hyperstimulation, activation of metabotropic receptors, in contrast to ionotropic receptors, reduces excess dopamine release. Synapse 28:220–226, 1998. © 1998 Wiley-Liss, Inc.
Handbook of high temperature compounds : properties, production, applications (1990)

Crystal structures thermodynamic properties electric, thermophysical and magnetic properties optical properties mechanical properties chemical properties preparation of powders production of materials powder ignition and explosive hazards toxicity application.
Bioengineering heterodimeric cytokines: turning promiscuous proteins into therapeutic agents (2013)

The interleukin 12 (IL-12) family comprises a group of heterodimeric cytokines that can cope with a great variety of immune conditions as the microenvironment demands. By sharing cytokine and receptor subunits, IL-12 (comprised of p40/p35 subunits), IL-23 (p40/p19), IL-27 (p28/EBI3), and IL-35 (p35/EBI3) represent, as a whole, a highly versatile system participating in controlling the continuum from inflammation to tolerance. Promiscuity, a peculiar feature of those cytokines, is a powerful and economic means of producing individual factors with distinct activities via different combinations of a single set of subunits. Whereas IL-12 and IL-23 have a clearly dominant immunostimulatory functional profile and IL-35 is a potent immunosuppressive agent, IL-27 can exert both adjuvant and regulatory effects, depending on the cytokine milieu. Promiscuity itself, however, may significantly hamper the therapeutic use of heterodimeric cytokines. The subunits of a recombinant cytokine, when administered in its native form, will rapidly dissociate in vivo and reassociate with alternative partners, thus generating different heterodimeric or even homodimeric molecules (i.e., p40/p40) with unwanted effects. As in other areas, bioengineering has provided a formidable tool to overcome the constraints associated with the potential use of IL-12 family cytokines. The generation of several gene constructs expressing IL-12, IL-23, IL-27, IL-35, or even the homodimer p40/p40, in their monomerized, single-chain form has allowed us to unveil the efficacy of those molecules in several experimental settings, including neoplasia, viral infection, chronic inflammation, allergy and autoimmunity. Although work is still needed to obtain an overall picture of therapeutic vs. adverse effects of individual molecules before any use in humans, the new frontiers of bioengineering are now driving the production of completely new combinations of cytokine subunits that may further extend the potential clinical use of such eclectic proteins.
Control of Activity through Oxidative Modification at the Conserved Residue Cys66 of Aryl Sulfotransferase IV (1997)

Oxidation at Cys66 of rat liver aryl suflotransferase IV alters the enzyme's catalytic activity, pH optima and substrate specificity. Although this is a cytosolic detoxification enzyme, the pH optimum for the standard assay substrate 4-nitrophenol is at pH 5.5; upon oxidation, the optimum changes to the physiological pH range. The principal effect of the change in pH optimum is activation, which is manifest by an increase in K'cat without any major influence on substrate binding. In contrast, with tyrosine methyl ester as a substrate, the enzyme's optimum activity occurs at pH 8.0; upon oxidation, it ceases to be a substrate at any pH. The presence of Cys66 was essential for activation to occur, thereby providing a putative reason underlying the conserved nature of this cysteine throughout the phenol sulfotransferase family. Mapping of disulfides by mass spectrometry showed the critical event to be the oxidation of Cys66 to form a disulfide with either Cys232 or glutathione, either one is effective. These results point to a mechanism for regulating the activity of a key enzyme in xenobiotic detoxication during cellular oxidative stress.
Dipeptidyl‐peptidase IV‐β (1998)

Dipeptidyl peptidase IV-beta (DPP IV-beta) is a novel protein which shows a peptidase activity similar to the T-cell-activation antigen CD26. To further characterize this DPP IV-beta and confirm its cell surface expression, we have developed a purification strategy using the CD26- cell line C8166. The purification process includes biotinylation of cell surface proteins before preparation of cell extracts and processing by gel-filtration, ion-exchange and lectin chromatographies. Consistent with the molecular mass of DPP IV-beta estimated by gel-filtration chromatography, the final purified fraction, manifesting a typical DPP IV activity, showed a major biotinylated 75-80-kDa band in SDS/PAGE, thus suggesting the monomeric nature of this enzyme. Kinetic parameters of DPP IV-beta and the sensitivity to a new family of irreversible DPP IV inhibitors, were studied in comparison to CD26. Both enzymes followed a Michaelis kinetics with different Km values for Gly-Pro-NH-Np (NH-Np, para-nitroanilide) hydrolysis (0.28+/-0.05 mM and 0.12+/-0.02 mM). More significant differences were observed in the sensitivity to inhibitors, which exerted a much higher activity on CD26 than on DPP IV-beta. These differences permitted us to study DPP IV-beta expression in CD26-expressing cells, showing the expression of this new enzyme in all lymphoid cells tested, and a rapid enhancement in phytohemagglutinin-stimulated or protein-A-stimulated peripheral blood mononuclear cells. Our results indicate that, although DPP IV-beta and CD26 are coexpressed and manifest a typical DPP IV activity, there are distinct features in their catalytic activities that may confer to each enzyme a complementary role in peptide processing.
A microchip-based DNA purification and real-time PCR biosensor for bacterial detection (2006)

A miniaturized, fully-automated, PCR (polymerase chain reaction)-based detection system has been developed for the rapid detection of bacteria. Monolithic DNA purification/real-time PCR silicon chips were fabricated and tested for their ability to purify and detect the pathogenic bacteria Salmonella typhimurium. Using silica-coated microstructures, nucleic acids could be selectively bound, washed and eluted for subsequent real-time PCR. These microstructures were integrated into a detection microchip containing two distinct regions, one for DNA purification and one for real-time PCR. Using an automated detection platform with integrated microprocessor, pumps, valves, thermocycler and fluorescence detection modules, microchips were used to purify and detect bacterial DNA by real-time PCR amplification using SYBR Green fluorescent dye. As few as 2/spl times/10/sup 3/ S. typhimurium cells could be detected using this system with an average time for detection of 45 min. Detection was augmented by on-chip melting curve analysis capable of differentiating between positive and false-positive results.
Configurable 3D nanoscale high aspect ratio pillars for surface-enhanced Raman spectroscopy (2004)

Configurable Nanoscale-High-Aspect-Ratio-Pillar (NanoHARP) structures were fabricated by a batch process method. Silver thin films were deposited on the top of NanoHARP to form Raman scattering enhancing substrate. By alternating the NanoHARP fabrication recipe and silver thin film deposition thickness, the density as well as the dimensions of the surface matrix is able to be controlled within a wide range. The results of reflectance spectrum and low-temperature electrical conductivity measurements indicate the non-continuous corrugated Ag surface matrix was formed. The Ag-coated nanopillar structure was utilized as the substrate for Surface Enhanced Raman Spectroscopy (SERS) to detect 1nM Rhodamine 6G sample. The characteristic spectrum of Rhodamine 6G was identified successfully and the Raman signal enhancements were observed to vary within 3 orders of magnitude for different nanopillar structures, which is consistent with theoretical predictions. The controllability of the configurations of nanopillars during fabrication enables us to optimize the nano-structure substrate of SERS for specific biomolecules and thus facilitate the ultra-sensitive biomolecule detections.
Regulation of chondroitin sulfate biosynthesis by specific sulfation: acceptor specificity of serum β-GalNAc transferase revealed by structurally defined oligosaccharides (1997)

The relationship between sulfation and polymerization in chondroitin sulfate (CS) biosynthesis has been poorly understood. In this study, we investigated the specificity of bovine serum UDP-GalNAc: CS beta-GalNAc transferase responsible for chain elongation using structurally defined acceptor substrates. They consisted of tetra- and hexasaccharide-serines that were chemically synthesized and various regular oligosaccharides with a GlcA residue at the nonreducing terminus, prepared from chondroitin and CS using testicular hyaluronidase. The enzyme preparation was obtained from fetal bovine serum by means of heparin-Sepharose affinity chromatography. The preparation did not contain the alpha-GalNAc transferase recently demonstrated in fetal bovine serum (Kitagawa et al., J. Biol. Chem., 270, 22190-22195, 1995), that utilizes common acceptor substrates. The beta-GalNAc transferase used as acceptors, two hexasaccharide-serines GlcA beta 1-3GalNAc beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser and GlcA beta 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1-3Gal (4-sulfate) beta 1-3Gal beta 1-4Xyl beta 1-O-Ser, but neither the monosulfated hexasaccharide-serine GlcA beta 1-3GalNAc(4-sulfate) beta 1-4GlcA beta 1-3Gal beta 1-3Gal beta 1-4Xyl beta 1-O-Ser nor tetrasaccharide-serines with or without a sulfate group at C-4 of the third sugar residue Gal-3 from the reducing end. The results indicated that the sulfate group at the Gal-3 C-4 markedly affected the transfer of GalNAc to the terminal GlcA. In addition, a sulfate group at C-4 of the reducing terminal GalNAc of regular tetrasaccharides remarkably enhanced the GalNAc transfer, suggesting that the enzyme recognizes up to the fourth saccharide residue from the nonreducing end. The level of incorporation into a tetra- or hexasaccharide containing a terminal 2-O-sulfated GlcA residue was significant, whereas there was no apparent incorporation into tetra- or hexasaccharides containing a terminal 3-O-sulfated GlcA or penultimate 4,6-O-disulfated GalNAc residue. These results indicated that sulfation reactions play important roles in chain elongation and termination.
CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors (2013)

A human single-chain variable fragment (scFv) antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs). The repertoire was fused to a first-generation T cell receptor ζ (TCRζ)-based chimeric antigen receptor (CAR). We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CAR(v2)) bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CAR(v2) fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR) and the selection context (cell synapse), which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells.Molecular Therapy-Nucleic Acids (2013) 2, e93; doi:10.1038/mtna.2013.19; published online 21 May 2013.
Global financial business and the implications for effective control of money laundering in offshore centres (2002)

Discusses the effect of globalisation of financial markets, especially the effects of international initiatives to improved financial probity and stability in offshore centres, with Jersey as the specific example. Argues that the effect on offshore centres is always positive, and that globalisation in effect makes all financial markets offshore to each other. Focuses on the use of offshore financial centres like Jersey, London, Switzerland and New York by corrupt and powerful public figures to launder stolen money, and briefly suggests how the defences that the international system has to deal with this can be enhanced; no single jurisdiction can hope to manage such situations.