gebhart/patrepeval huggingface dataset:
A pH-Sensitive Fluor, CypHer <sup>TM</sup> 5, Used to Monitor Agonist-Induced G Protein-Coupled Receptor Internalization in Live Cells (2002)

G protein-coupled receptors (GPCRs) are the largest family of proteins involved in transmembrane signal transduction and are actively studied because of their suitability as therapeutic small-molecule drug targets. Agonist activation of GPCRs almost invariably results in the receptor being desensitized. One of the key events in receptor desensitization is the sequestration of the receptor from the cell surface into acidic intracellular endosomes. Therefore, a convenient, generic, and noninvasive monitor of this process is desirable. A novel, pH-sensitive, red-excited fluorescent dye, CypHer 5, was synthesized. This dye is non-fluorescent at neutral pH and is fluorescent at acidic pH. Anti-epitope antibodies labeled with this dye were internalized in an agonist concentration- and time-dependent manner, following binding on live cells to a range of GPCRs that had been modified to incorporate the epitope tags in their extracellular N-terminal domain. This resulted in a large signal increase over background. When protonated, the red fluorescence of CypHer 5 provides a generic reagent suitable for monitoring the internalization of GPCRs into acidic vesicles. This approach should be amenable to the study of many other classes of cell surface receptors that also internalize following stimulation.
Multiple cytokines activate phosphatidylinositol 3-kinase in hemopoietic cells. Association of the enzyme with various tyrosine-phosphorylated proteins. (1994)

Activation of phosphatidylinositol (PI) 3-kinase is a common sequel to tyrosine kinase activation and appears to be essential for tyrosine kinases to induce proliferation. Since multiple hemopoietic growth factors activate tyrosine kinases, we investigated whether these growth factors activate PI 3-kinase. We show that interleukin-3 (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), granulocyte-macrophage colony stimulating factor (GM-CSF), and steel factor (SLF) all activate PI 3-kinase. These cytokines increased the amount of PI 3-kinase activity that could be immunoprecipitated with anti-phosphotyrosine antibodies from the MC-9 mast cell line or from the hemopoietic progenitor cell line FDC-P1. Increases in this assay frequently correlate with PI 3-kinase activation in vivo. To determine directly whether these factors activate PI 3-kinase in vivo, we measured the levels of 3-phosphorylated inositol phospholipids in intact 32P-labeled MC-9 cells. IL-3, IL-4, IL-5, GM-CSF, and SLF all caused increased synthesis of the PI 3-kinase products phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with a relative potency of SLF >> IL-3 > IL-5, GM-CSF > IL-4. In contrast, IL-4 caused the largest increase in the in vitro anti-phosphotyrosine immune complex PI 3-kinase assay. Thus, the in vitro assay does not accurately reflect in vivo activation of PI 3-kinase. Cytokine treatment did not stimulate tyrosine phosphorylation of either the 85-kDa regulatory subunit or the 110-kDa catalytic subunit of PI 3-kinase and is therefore not required for activation of PI 3-kinase by these factors. Cytokine treatment did induce PI 3-kinase to associate with other tyrosine-phosphorylated proteins in a cytokine-specific manner. PI 3-kinase associated with c-kit after SLF stimulation, a 170-kDa protein after IL-4 stimulation, and a 70-kDa protein after treatment with IL-3 or GM-CSF. Thus, multiple hemopoietic growth factors that act through different types of receptors activate PI 3-kinase in vivo and induce factor-specific interactions of PI 3-kinase with other tyrosine-phosphorylated proteins.
Comparative integromics on FZD7 orthologs: Conserved binding sites for PU.1, SP1, CCAAT-box and TCF/LEF/SOX transcription factors within 5'-promoter region of mammalian FZD7 orthologs (2007)

Canonical WNT signals are transduced through Frizzled (FZD) family receptor and LRP5/LRP6 co-receptor to upregulate MYC, CCND1, FGF20, JAG1, WISP1 and DKK1 genes, while non-canonical WNT signals are transduced through FZD family receptor and PTK7/ROR2/RYK co-receptor to activate RHOA/RHOU/RAC/CDC42, JNK, PKC, NFAT and NLK signaling cascades. FZD7, expressed in the normal gastrointestinal tract, is upregulated in esophageal cancer, gastric cancer, colorectal cancer, and hepatocellular carcinoma. Here, chimpanzee FZD7 and cow Fzd7 genes were identified and characterized by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee FZD7 and cow Fzd7 genes were identified within NW_001232110.1 and AC173037.2 genome sequences, respectively. Chimpanzee FZD7 and cow Fzd7 showed 100% and 97.2% total-amino-acid identity with human FZD7. All of the nine amino-acid residues substituted between human FZD7 and human FzE3 were identical to those of human FZD7 in chimpanzee, cow, mouse and rat FZD7 orthologs. Functional analyses using FzE3 with multiple cloning artifacts and/or sequencing errors are invalid. FZD7 orthologs were seven-transmembrane proteins with extracellular Frizzled domain, leucine zipper motif around the 5th transmembrane domain, and cytoplasmic DVL- and PDZ-binding motifs. Ser550 and Ser556 of FZD7 orthologs were putative aPKC phosphorylation sites. Dimerization and Ser550/556 phosphorylation were predicted as regulatory mechanisms for the signaling through FZD7. Transcriptional start site of human FZD7 gene was 735-bp upstream of NM_003507.1 RefSeq 5'-end. In addition to gastrointestinal cancer, hepatocellular cancer and pancreatic cancer, human FZD7 mRNAs were expressed in blastocysts, undifferentiated embryonic stem (ES) cells, ES-derived endodermal progenitors, ES-derived neural progenitors, fetal cochlea, retinal pigment epithelium, olfactory epithelium, regenerating liver, and multiple sclerosis. Comparative genomics analyses revealed that the binding sites for PU.1, SP1/Krüppel-like, CCAAT-box, and TCF/LEF/SOX transcription factors were conserved among 5'-promoter regions of mammalian FZD7 orthologs.
Reaction of serine proteases with substituted isocoumarins: discovery of 3,4-dichloroisocoumarin, a new general mechanism based serine protease inhibitor (1985)

The mechanism-based inactivations of a number of serine proteases, including human leukocyte (HL) elastase, cathepsin G, rat mast cell proteases I and II, several human and bovine blood coagulation proteases, and human factor D by substituted isocoumarins and phthalides which contain masked acyl chloride or anhydride moieties, are reported. 3,4-Dichloroisocoumarin, the most potent inhibitor investigated here, inactivated all the serine proteases tested but did not inhibit papain, leucine aminopeptidase, or beta-lactamase. 3,4-Dichloroisocoumarin was fairly selective toward HL elastase (kobsd/[I] = 8920 M-1 s-1); the inhibited enzyme was quite stable to reactivation (kdeacyl = 2 X 10(-5) s-1), while enzymes inhibited by 3-acetoxyisocoumarin and 3,3-dichlorophthalide regained full activity upon standing. The rate of inactivation was decreased dramatically in the presence of reversible inhibitors or substrates, and ultraviolet spectral measurements indicate that the isocoumarin ring structure is lost upon inactivation. Chymotrypsin A gamma is totally inactivated by 1.2 equiv of 3-chloroisocoumarin or 3,4-dichloroisocoumarin, and approximately 1 equiv of protons is released upon inactivation. These results indicate that these compounds react with serine proteases to release a reactive acyl chloride moiety which can acylate another active site residue. These are the first mechanism-based inhibitors reported for many of the enzymes tested, and 3,4-dichloroisocoumarin should find wide applicability as a general serine protease inhibitor.
A Novel Inhibitory Receptor (ILT3) Expressed on Monocytes, Macrophages, and Dendritic Cells Involved in Antigen Processing (1997)

Immunoglobulin-like transcript (ILT) 3 is a novel cell surface molecule of the immunoglobulin superfamily, which is selectively expressed by myeloid antigen presenting cells (APCs) such as monocytes, macrophages, and dendritic cells. The cytoplasmic region of ILT3 contains putative immunoreceptor tyrosine-based inhibitory motifs that suggest an inhibitory function of ILT3. Indeed, co-ligation of ILT3 to stimulatory receptors expressed by APCs results in a dramatic blunting of the increased [Ca2+]i and tyrosine phosphorylation triggered by these receptors. Signal extinction involves SH2-containing protein tyrosine phosphatase 1, which is recruited by ILT3 upon cross-linking. ILT3 can also function in antigen capture and presentation. It is efficiently internalized upon cross-linking, and delivers its ligand to an intracellular compartment where it is processed and presented to T cells. Thus, ILT3 is a novel inhibitory receptor that can negatively regulate activation of APCs and can be used by APCs for antigen uptake.
The single-chain form of tissue-type plasminogen activator has catalytic activity: studies with a mutant enzyme that lacks the cleavage site (1989)

Tissue-type plasminogen activator (t-PA), the serine protease responsible for catalyzing the production of plasmin from plasminogen at the site of blood clots, is synthesized as a single-chain polypeptide precursor. Proteolytic cleavage at the C-terminal side of Arg275 generates a two-chain form of the enzyme whose subunits are held together by a single disulfide bond. We have measured the activities of both forms of the wild-type enzyme, as well as that of a mutant enzyme (Arg275----Gly), created by oligonucleotide-directed mutagenesis, that cannot be cleaved into a two-chain form. Both types of single-chain t-PAs are enzymatically active and exhibit identical Vmax and Km values when assayed with synthetic peptide substrates, indicating that the single amino acid change had no effect on the amidolytic activity of the enzyme. However, cleavage of wild-type t-PA into the two-chain form results in increased activity both on a peptide substrate and on the natural substrates Lys- and Glu-plasminogen in the absence or presence of stimulation by soluble fibrin. The enhanced activity is due to a 3-5-fold increase in the Vmax of the cleaved enzyme, rather than to any change in the Km values for the various substrates. During incubation with plasminogen, the single-chain form of wild-type t-PA is converted to the two-chain form by plasmin generated during the reaction. This conversion, from the less active form of the enzyme, results in a reaction that displays biphasic kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)
Reactive NUMA (1997)

This paper proposes and evaluates a new approach to directory-based cache coherence protocols called Reactive NUMA (R-NUMA). An R-NUMA system combines a conventional CC-NUMA coherence protocol with a more-recent Simple-COMA (S-COMA) protocol. What makes R-NUMA novel is the way it dynamically reacts to program and system behavior to switch between CC-NUMA and S-COMA and exploit the best aspects of both protocols. This reactive behavior allows each node in an R-NUMA system to independently choose the best protocol for a particular page, thus providing much greater performance stability than either CC-NUMA or S-COMA alone. Our evaluation is both qualitative and quantitative. We first show the theoretical result that R-NUMA's worst-case performance is bounded within a small constant factor (i.e., two to three times) of the best of CC-NUMA and S-COMA. We then use detailed execution-driven simulation to show that, in practice, R-NUMA usually performs better than either a pure CC-NUMA or pure S-COMA protocol, and no more than 57% worse than the best of CC-NUMA and S-COMA, for our benchmarks and base system assumptions.
Required role of focal adhesion kinase (FAK) for integrin-stimulated cell migration (1999)

FAK localizes to sites of transmembrane integrin receptor clustering and facilitates intracellular signaling events. FAK-null (FAK-) fibroblasts exhibit a rounded morphology, defects in cell migration, and an elevated number of cell-substratum contact sites. Here we show that stable re-expression of epitope-tagged FAK reversed the morphological defects of the FAK- cells through the dynamic regulation of actin structures and focal contact sites in fibronectin (FN) stimulated cells. FAK re-expressing fibroblasts (clones DA2 and DP3) exhibit a characteristic fibrillar shape and display indistinguishable FN receptor-stimulated migration properties compared to normal fibroblasts. Expression of various FAK mutants in the FAK- cells showed that FAK kinase activity, the Tyr-397/SH2 domain binding site, and the first proline-rich SH3 binding region in the FAK C-terminal domain were individually needed to promote full FAK-mediated FAK- cell migration to FN whereas direct paxillin binding to FAK was not required. Expression of the FAK Phe-397 mutant did not promote FAK- cell migration and overexpression of p50(csk) in DA2 cells inhibited migration to FN suggesting that Src-family PTKs play important roles in FAK-mediated motility events. Expression of the FAK C-terminal domain, FRNK, promoted FAK dephosphorylation at Tyr-397 and potently blocked FAK-mediated cell migration. This dominant-negative effect of FRNK was reversed by a point mutation (Leu-1034 to Ser) which prevented FRNK localization to focal contact sites. Our results show that FAK functions as a key regulator of fibronectin receptor stimulated cell migration events through the recruitment of both SH2 and SH3 domain-containing signaling proteins to sites of integrin receptor clustering.
Release of prostaglandins and monohydroxy and trihydroxy metabolites of linoleic and arachidonic acids by adult and fetal aortae and ductus arteriosus. (1985)

The conversion of arachidonic acid (20:4) to prostaglandins by vascular tissue is important in the adult because of the antithrombotic effect of prostacyclin and in the fetus because of the vasodilatory effect of prostaglandin (PG) E2 on the ductus arteriosus. We have shown that vascular tissue converts various polyunsaturated fatty acids to monohydroxy and trihydroxy metabolites derived from hydroperoxides, which may be involved in regulating prostaglandin synthesis. We have now measured the amounts of these hydroperoxide metabolites, as well as those of prostaglandins, released from slices of rat, rabbit and bovine aortae, as well as from fetal calf aorta and ductus arteriosus. The major oxygenated polyunsaturated fatty acid metabolite formed by rat and bovine blood vessels was 6-oxo-PGF1 alpha. Fetal calf aorta and ductus arteriosus produced about five times as much 6-oxo-PGF1 alpha as adult bovine aorta. Much smaller amounts of the cyclooxygenase products, PGE2, 12-hydroxy-5,8,10-heptadecatrienoic acid, 11-hydroxy-5,8,12,14-icosatetraenoic acid (11-hydroxy-20:4), and 15-hydroxy-20:4, were released by aortae. Small amounts of the lipoxygenase product, 12-hydroxy-20:4, were also detected. Substantial amounts of free and esterified monohydroxy and trihydroxy metabolites of linoleic acid (18:2) were detected, especially in rat and rabbit aortae. Rabbit aorta, which had low cyclooxygenase activity, formed more oxygenated 18:2 metabolites than 20:4 metabolites. Indomethacin did not inhibit the formation of the 18:2 metabolites, indicating that cyclooxygenase was not involved. Neither exogenous 13-hydroxy-18:2 nor trihydroxyoctadecenoic acid was incorporated to a large extent into lipids from vascular endothelial or smooth muscle cells, suggesting that the esterified 18:2 oxygenation products had arisen mainly via direct oxygenation of lipids.
Process development for the production of prebiotic galacto‐oligosaccharides from lactose using β‐galactosidase from <i>Lactobacillus</i> sp. (2007)

Galacto-oligosaccharides (GOS) are formed from lactose in discontinuous mode of conversion using beta-galactosidase from Lactobacillus sp. (beta-gal). The discontinuous process was optimized for technical application with regard to GOS yield, enzyme preparation, reaction temperature and substrate source. It proved to be advantageous to directly apply the crude cell-free enzyme extract for the conversion, since similar GOS yields and composition were obtained as when using the pure enzyme preparation, but expensive purification could be avoided. Reaction temperature was lowered to 17 degrees C to limit microbial contamination when using technical substrates. Thereby GOS yield decreased from 30% to 28% of total sugars and enzyme demand increased 2.7-fold. Whey permeate was compared to buffered lactose solution as a substrate source. The initial reaction rate was found to be 1.8 times higher for the whey permeate substrate; however, GOS yield was slightly lower (approximately 25% of total sugar at 17 degrees C) mainly due to smaller amounts of allolactose[beta-D-Galp-(1-->6)-D-Glc] and the trisaccharide beta-D-Galp-(1-->6)-D-Lac formed.
A CMOS resistive feedback single to differential low noise amplifier with multiple-tuner-outputs for a digital TV tuner (2009)

A CMOS resistive feedback single to differential low noise amplifier (S-to-D LNA) with single-ended multiple tuner outputs (MTOs) is implemented for a digital TV (DTV) tuner using a 0.18-m CMOS process. In order to achieve wideband output balancing with high gain, low noise figure (NF) and high linearity, the S-to-D LNA exploiting the resistive feedback with enhanced loop gain is proposed. The proposed S-to-D LNA also has single-ended MTOs which are made by combining the differential output of the S-to-D LNA without second-order distortion for supporting multiple tuner and multiple stream applications. This leads the excellent IIP2 at both differential output and single-ended MTOs of the proposed S-to-D LNA. A voltage gain of 19.5 dB, an average NF of 2.4 dB, an IIP3 of -2 dBm and an IIP2 of 26 dBm are obtained at differential output. At single-ended MTOs, a voltage gain of 12.5 dB, an average NF of 2.9 dB, an IIP3 of -1.5 dBm and an IIP2 of 25 dBm are obtained.
Redesigning the replenishment process of medical supplies in hospitals with RFID (2010)

Purpose The purpose of this paper is to present a case study of a hospital nursing unit that has evaluated and approved a two‐bin “e‐kanban” replenishment system based on passive high frequency radio‐frequency identification (RFID) technology. Design/methodology/approach The case study analysis is based on both qualitative and quantitative data that were collected using semi‐structured interviews, on‐site observations and experience from previous implementations. The data and simulation analysis presented in this paper were validated by key respondents thereby increasing their reliability. Findings Results indicate that implementing the e‐kanban RFID solution in conjunction with the redesign of the ward floor and of the roles and functions can substantially improve business and operational performance. The most important benefits for the hospital are derived from the time saved from non‐value‐added activities that can be transferred to patient care activities and the significant reduction of on‐hand inventory at distributed storage locations. The solution is considered an alternative that requires less initial investment than RFID‐enabled cabinets used in the replenishment of consignment and high‐value supplies in operating rooms and cardiac catheterization laboratories. Research limitations/implications There is a need to conduct further research on RFID supply chain management (SCM) applications in the healthcare sector as this area holds a great potential for performance improvements. Additionally, there is a need to conduct more in‐depth research into the isolated impact of RFID technology in comparison to the change management and process redesign that it generates. One key limitation of this research is the case study approach based on a single case. This paper, therefore provides direction for practitioners on how to assess RFID's potential impact in the healthcare supply chain. Originality/value While most of the research on RFID in healthcare sector focuses on active RFID technology for asset management, this research presents a novel RFID application and contributes to our understanding of RFID's potential in intra‐organizational SCM processes.
Wireless charging system with magnetic field shaping for electric vehicles (2013)

A wireless charging system with magnetic field shaping is proposed. The magnetic field of wireless power transmission is shaped by an innovated structure of resonator, which is named as Shaped Magnetic Field Resonator (SMFR). The magnetic field is shaped within the zone of active transmission and the magnetic flux density is greatly reduced outside the zone of active transmission. Therefore, the Electromagnetic Interference (EMI) to adjacent electric devices is drastically diminished. The high temperature effect of shielding material induced by eddy current on the shielding material is also improved. Besides, the transfer efficiency can be improved. The numerical analysis (Finite Element Analysis) of the proposed resonators by electromagnetic simulation software is carried out for analyzing the shaped magnetic field. Finally, the proposed system is implemented to validate the feasibility.
Computer-Assisted Coregistration of Multislice SPECT and MR Brain Images by Fixed External Fiducials (1993)

We have developed and validated in a phantom a method of computer-assisted coregistration using multislice SPECT and MR images. Reusable fiducial markers were fabricated from nylon-based plastic and consist of two parts: a base that remains fixed to the skin with adhesive between scans and a removable, spherical cavity insert that can be filled with contrast agents appropriate for multiple imaging modalities. Markers external and internal to a three-dimensional brain phantom provided a means of quantifying the method's accuracy. A computer algorithm was used to derive transformation matrices for image sets by minimizing the root mean squared deviations obtained for multiple permutations (n = 10) of increasing numbers (range 3-11) of external SPECT/MRI point pairs. As defined by the average +/- SEM mean residual deviations of noncoregistered internal fiducials, the minimal accuracy was 2.4 +/- 0.3 mm (no marker > 3.6 mm) for three coregistration points and did not improve beyond seven to eight fiducials (2.2 +/- 0.1 mm; no marker > 3.2 mm). The method's true accuracy is likely to be better than estimates of minimal accuracy, however, since such measures reflect surmountable random errors in fiducial location. With use of identical MRI (or SPECT) data sets, measures of intraoperator (0.5 +/- 0.1 and 0.5 +/- 0.1 mm, respectively) and interoperator (0.5 +/- 0.3 and 0.8 +/- 0.1 mm) reliability were also obtained, establishing the method as highly reproducible and objective. Preliminary results in a human subject suggest its feasibility for clinical studies.