gebhart/patrepeval huggingface dataset:
Mapping Insulin/GLUT4 Circuitry (2011)

One of the most important metabolic actions of insulin is catalysing glucose uptake into skeletal muscle and adipose tissue. This is accomplished via activation of the phosphatidylinositol-3-kinase/Akt signalling pathway and subsequent translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. As such, this represents an ideal system for studying the convergence of signal transduction and protein trafficking. The GLUT4 translocation process is complex, but can be dissected into at least four discrete trafficking steps. This raises the question as to which of these is the major regulated step in insulin-stimulated GLUT4 translocation. Numerous molecules have been reported to regulate GLUT4 trafficking. However, with the exception of TBC1D4, the molecular details of these distal signalling arms of the insulin signalling network and how they modify distinct steps of GLUT4 trafficking have not been established. We discuss the need to adopt a more global approach to expand and deepen our understanding of the molecular processes underpinning this system. Strategies that facilitate the generation of detailed models of the entire insulin signalling network will enable us to identify the critical nodes that control GLUT4 traffic and decipher emergent properties of the system that are not currently apparent.
Manipulation of Self-Assembled Structures of Magnetic Beads for Microfluidic Mixing and Assaying (2004)

We present an original concept of manipulation of magnetic microbeads in a microchannel. It is based on the dynamic motion of a self-assembled structure of ferrimagnetic beads that are retained within a microfluidic flow using a local alternating magnetic field. The latter induces a rotational motion of the magnetic particles, thereby strongly enhancing the fluid perfusion through the magnetic structure that behaves as a dynamic random porous medium. The result is a very strong particle-liquid interaction that can be controlled by adjusting the magnetic field frequency and amplitude, as well as the liquid flow rate, and is at the basis of very efficient liquid mixing. The principle is demonstrated using a microfluidic chip made of poly(methyl methacrylate) with integrated soft ferromagnetic plate structures. The latter are part of an electromagnetic circuit and serve to locally apply a magnetic field over the section of the microchannel. Starting from a laminar flow pattern of parallel fluorescein dye and nonfluorescent liquid streams, we demonstrate a 95% mixing efficiency using a mixing length of only 400 microm and at liquid flows of the order of 0.5 cm/s. We anticipate that the intense interaction between the fluid and magnetic particles with functionalized surfaces holds large potential for the development of future bead-based assays.
Polarization independent InP WDM multiplexer/demultiplexer module (1998)

We report the design, fabrication, packaging, and characterization of a polarization independent integrated optical InP multiplexer/demultiplexer module. The device is based on a vertically etched diffractive grating and separates four channels with 4 spacing in the 1.55 /spl mu/m window. An n/sup -//n/sup +/-InP layer structure with very low birefringence results in a shift of the passbands between transverse electric (TE) and transverse magnetic (TM) polarization of less than 0.1 nm. With a self-aligned flip-chip mounting technique light is optically coupled from the input and output waveguides to an array of lensed single mode fibers with a coupling efficiency of more than 80%. The packaging includes temperature control that allows fine tuning of the channel passbands over 5 nm. Optical crosstalk is always better than -17 dB and fiber to fiber losses of 15 dB are achieved. The module has been successfully implemented in a 4/spl times/2.5 Gb/s WDM transmission system.
Design of buffer exchange surfaces and sensor chips for biosensor chip mass spectrometry (2002)

The feasibility of buffer exchange in biosensor chip mass spectrometry, along with the construction of base sensor chips and use of alternative chip chemistries, is demonstrated in this work. Beta-2-microglobulin (beta2m) was used as an analyte and captured in the first flow cell (FC1) on the sensor chip surface by an immobilized anti-beta2m antibody. Low pH buffer was then used to elute the captured analyte from the flow cell and route it to a second flow cell (FC2) downstream that served as a cation exchanger that retains the analyte. Following additional washes in FC1, the analyte present in FC2 was either eluted with a higher pH buffer (to demonstrate the possibility of elution into a downstream trypsin flow cell), or it was subjected to matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis to verify its presence in FC2. In a separate experiment, a gold-sputtered glass slide (base chip) was activated through a formation of 11-mercaptoundecanoic acid self-assembled monolayer and via reaction with 1,1"-carbonyldiimidazole. The activated chip was placed manually into the biosensor and two surfaces (flow cells) were derivatized with antibodies to beta2m and cystatin C (cysC). To evaluate the chip performance, diluted human urine aliquot was injected over the flow cells. Following the surface plasmon resonance analysis, the chip was MALDI-TOF MS analyzed, yielding signals from beta2m and cysC from their respective flow cells. Artifacts arising from the surface chemistries were not observed in the analysis.
T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition (2017)

Programmed cell death-1 (PD-1) is a coinhibitory receptor that suppresses T cell activation and is an important cancer immunotherapy target. Upon activation by its ligand PD-L1, PD-1 is thought to suppress signaling through the T cell receptor (TCR). By titrating PD-1 signaling in a biochemical reconstitution system, we demonstrate that the co-receptor CD28 is strongly preferred over the TCR as a target for dephosphorylation by PD-1-recruited Shp2 phosphatase. We also show that CD28, but not the TCR, is preferentially dephosphorylated in response to PD-1 activation by PD-L1 in an intact cell system. These results reveal that PD-1 suppresses T cell function primarily by inactivating CD28 signaling, suggesting that costimulatory pathways play key roles in regulating effector T cell function and responses to anti-PD-L1/PD-1 therapy.
Apoptosis of T Cells Mediated by Ca 2+ -Induced Release of the Transcription Factor MEF2 (1999)

T cell receptor (TCR)-induced apoptosis of thymocytes is mediated by calcium-dependent expression of the steroid receptors Nur77 and Nor1. Nur77 expression is controlled by the transcription factor myocyte enhancer factor 2 (MEF2), but how MEF2 is activated by calcium signaling is still obscure. Cabin1, a calcineurin inhibitor, was found to regulate MEF2. MEF2 was normally sequestered by Cabin1 in a transcriptionally inactive state. TCR engagement led to an increase in intracellular calcium concentration and the dissociation of MEF2 from Cabin1, as a result of competitive binding of activated calmodulin to Cabin1. The interplay between Cabin1, MEF2, and calmodulin defines a distinct signaling pathway from the TCR to the Nur77 promoter during T cell apoptosis.
Quantification of Cholesterol Tracers by Gas Chromatography-Negative Ion Chemical Ionization Mass Spectrometry (1996)

Because of its high sensitivity, gas chromatography negative ion chemical ionization mass spectrometry (GC-NCI-MS) is a potentially valuable analytical tool for the study of cholesterol metabolism. Of several derivatives prepared for potential use in tracer studies pentafluorobenzoyl cholesterol was selected because it formed rapidly at ambient temperature and was stable for long periods, could be detected at a level of 1 fmol, and yielded a mass spectrum in which the molecular ion was the principal component. Hexadeuterated cholesterol tracer ([26,26,26,27,27,27-2H6]cholesterol) could be detected in dilutions up to 2700 in unlabeled cholesterol by selected ion monitoring with a coefficient of variation averaging 3.2%. In seven normal subjects tracer cholesterol was infused intravenously and plasma cholesterol enrichment was determined after 4 h. The measured rapidly miscible cholesterol pool was 391.0 +/- 38.6 mg cholesterol/kg. Negative ion mass spectrometry of pentafluorobenzyol cholesterol will facilitate analysis of both small amounts of natural cholesterol and labeled cholesterol in applications where sensitivity is critical.
Direct Mass Spectrometry Analysis of Biofluid Samples Using Slug‐Flow Microextraction Nano‐Electrospray Ionization (2014)

Direct mass spectrometry (MS) analysis of biofluids with simple procedures represents a key step in the translation of MS techniques to clinical and point-of-care applications. The current study reports the development of a single-step method using slug-flow microextraction and nano-electrospray ionization for MS analysis of organic compounds in blood and urine. High sensitivity and quantitation precision have been achieved in the analysis of therapeutic and illicit drugs in 5 μL samples. Real-time chemical derivatization has been incorporated for analyzing anabolic steroids. The monitoring of enzymatic functions has also been demonstrated with cholinesterase in wet blood. The reported study encourages the future development of disposable cartridges, which function with simple operation to replace the traditional complex laboratory procedures for MS analysis of biological samples.
Three-dimensional surface imaging by multi-frequency phase shift profilometry with angle and pattern modeling for system calibration (2016)

In this paper, we present a 3D surface imaging system based on the well-known phase shift profilometry. To yield the analytical solutions, four shifted phases and three high carrier frequencies are used to compute the phase map and reduce the noises that are caused by the inherent optical aberrations and external influences, e.g. different illumination light sources, uneven intensity distribution and automatic image processing algorithms. To reduce the system noise, we propose to model the pattern of the calibration grid in a virtual space. To obtain the modeled pattern, we use a plane to intercept the rays that are modeled by the proposed angle modeling method. In the world coordinate system, the angle and the pattern are computed based on the calibration data. A registration method is used to transform the modeled pattern in the virtual space to the ideal pattern in the world coordinate system by computing the least squared errors between the true points in the modeled pattern and the measured points in the practical pattern. The modeled (true) points are used for re-calibration of the 3D imaging system. Experimental results showed that the measurement accuracy increases considerably and the MSE is reduced from 0.95 mm to 0.65 mm (32% average error decrease) after replacing the measured points with the true points for calibration.
Cognitive effects after epidural vs general anesthesia in older adults. A randomized trial (1995)

<h3>Objective.</h3> —To compare the effect of epidural vs general anesthesia on the incidence of long-term cognitive dysfunction after total knee replacement surgery in older adults. <h3>Design.</h3> —Randomized controlled clinical trial. <h3>Setting.</h3> —Orthopedic specialty academic hospital. <h3>Patients.</h3> —A total of 262 patients undergoing elective primary total knee replacement with a median age of 69 years; 70% women. <h3>Intervention.</h3> —Random assignment to either epidural or general anesthesia. <h3>Main Outcome Measures.</h3> —A thorough neuropsychological assessment was performed preoperatively and repeated at 1 week and 6 months postoperatively. Cognitive outcome was assessed by within-patient change on 10 tests of memory, psychomotor, and language skills. Prospective standardized surveillance for cardiovascular complications was performed to allow simultaneous assessment of anesthetic effects on cognitive and cardiovascular outcomes. <h3>Results.</h3> —The two groups were similar at baseline in terms of age, sex, comorbidity, and cognitive function. There were no significant differences between the epidural and general anesthesia groups in within-subject change from baseline on any of the 10 cognitive test results at either 1 week or 6 months. Overall, 5% of patients showed a long-term clinically significant deterioration in cognitive function. There was no difference between the anesthesia groups in the incidence of major cardiovascular complications (3% overall). <h3>Conclusions.</h3> —The type of anesthesia, general or epidural, does not affect the magnitude or pattern of postoperative cognitive dysfunction or the incidence of major cardiovascular complications in older adults undergoing elective total knee replacement. This is the largest trial of the effects of general vs regional anesthesia on cerebral function reported to date, with more than 99% power to detect a clinically significant difference on any of the neuropsychological tests. (<i>JAMA</i>. 1995;274:44-50)
Optimizing Display, Analysis, Interpretation and Utility of Self-Monitoring of Blood Glucose (SMBG) Data for Management of Patients with Diabetes (2007)

Given reliable measures of glucose variability, one can apply a strategy to progressively reduce glucose variability and then increase the intensity of therapy so as to reduce median blood glucose and hence A1c, while minimizing the risk of hypoglycemia.
The catalyzed reaction of .alpha.,.beta.-unsaturated esters with various hydrosilanes (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe catalyzed reaction of .alpha.,.beta.-unsaturated esters with various hydrosilanesKenji Takeshita, Yoshio Seki, Kazuaki Kawamoto, Shinji Murai, and Noboru SonodaCite this: J. Org. Chem. 1987, 52, 22, 4864–4868Publication Date (Print):October 1, 1987Publication History Published online1 May 2002Published inissue 1 October 1987https://pubs.acs.org/doi/10.1021/jo00231a008https://doi.org/10.1021/jo00231a008research-articleACS PublicationsRequest reuse permissionsArticle Views1321Altmetric-Citations67LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Association of phosphatidylinositol 3-kinase with a specific sequence of the T cell receptor zeta chain is dependent on T cell activation. (1994)

The T cell antigen receptor (TCR).CD3 complex contains several distinct but related signal transduction modules termed "Reth motifs": one each in the cytoplasmic domains of CD3-gamma, -delta, and -epsilon chains and three in the CD3-zeta polypeptide (zeta A, zeta B, and zeta C). Cross-linking of individual motifs expressed in chimeric molecules leads to early and late T cell activation events. Although the activated T cell receptor associates with nonreceptor tyrosine kinases, the sites of interaction with kinases and other potential effector molecules have not been fully mapped. Here we show that phosphatidylinositol 3-kinase (PI 3-kinase) preferentially associated with the zeta chain membrane proximal motif zeta A. Maximal PI 3-kinase/zeta A association occurred following TCR.CD3 activation and was dependent upon phosphorylation of both tyrosine residues in zeta A. The association of PI 3-kinase was specific for zeta A and could be ranked zeta A >> zeta C > zeta B. Phosphorylation of the zeta A motif on tyrosine residues occurred in response to TCR.CD3 cross-linking in vivo. These results indicate that T cell activation leads to assembly of an intracellular signaling complex: recruitment of a tyrosine kinase, phosphorylation of zeta A, and association of PI 3-kinase. These data also support a model in which different Reth motifs of the TCR.CD3 complex recruit distinct signal transduction molecules. Thus, the subdomains of the T cell antigen receptor zeta chain may serve different roles during T cell maturation and antigen-driven activation.
Mn porphyrin-based SOD mimic, MnTnHex-2-PyP5+, and non-SOD mimic, MnTBAP3−, suppressed rat spinal cord ischemia/reperfusion injuryviaNF-κB pathways (2014)

Herein we have demonstrated that both superoxide dismutase (SOD) mimic, cationic Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)), and non-SOD mimic, anionic Mn(III) meso-tetrakis(4-carboxylatophenyl)porphyrin (MnTBAP(3-)), protect against oxidative stress caused by spinal cord ischemia/reperfusion via suppression of nuclear factor kappa B (NF-κB) pro-inflammatory pathways. Earlier reports showed that Mn(III) N-alkylpyridylporphyrins were able to prevent the DNA binding of NF-κB in an aqueous system, whereas MnTBAP(3-) was not. Here, for the first time, in a complex in vivo system-animal model of spinal cord injury-a similar impact of MnTBAP(3-), at a dose identical to that of MnTnHex-2-PyP(5+), was demonstrated in NF-κB downregulation. Rats were treated subcutaneously at 1.5 mg/kg starting at 30 min before ischemia/reperfusion, and then every 12 h afterward for either 48 h or 7 days. The anti-inflammatory effects of both Mn porphyrins (MnPs) were demonstrated in the spinal cord tissue at both 48 h and 7 days. The downregulation of NF-κB, a major pro-inflammatory signaling protein regulating astrocyte activation, was detected and found to correlate well with the suppression of astrogliosis (as glial fibrillary acidic protein) by both MnPs. The markers of oxidative stress, lipid peroxidation and protein carbonyl formation, were significantly reduced by MnPs. The favorable impact of both MnPs on motor neurons (Tarlov score and inclined plane test) was assessed. No major changes in glutathione peroxidase- and SOD-like activities were demonstrated, which implies that none of the MnPs acted as SOD mimic. Increasing amount of data on the reactivity of MnTBAP(3-) with reactive nitrogen species (RNS) (.NO/HNO/ONOO(-)) suggests that RNS/MnTBAP(3-)-driven modification of NF-κB protein cysteines may be involved in its therapeutic effects. This differs from the therapeutic efficacy of MnTnHex-2-PyP(5+) which presumably occurs via reactive oxygen species and relates to NF-κB thiol oxidation; the role of RNS cannot be excluded.
Acid base catalytic mechanism of the dihydropyrimidine dehydrogenase from pH studies. (1993)

Primary deuterium (NADPH(D)), solvent deuterium, and multiple isotope effects and the pH dependence of kinetic parameters have been used to probe the mechanism of the dihydropyrimidine dehydrogenase from pig liver. Isotope effect and pH-rate data suggest a rate-determining reductive half-reaction in which reduction of the flavin by NADPH has only a minor rate limitation (DV approximately D(V/KNADPH) approximately 1.1), while protonation of the flavin at N-1 occurring in a step following reduction is slow (D2OV = 3, while D2O(V/KNADPH) = 2). An enzymatic general acid with a pK of 8.2 is required to protonate N-1 of the flavin. In the second half-reaction, uracil is reduced at C-6 by flavin and protonated on the opposite face at C-5 by an enzymatic general acid with a pK of 9. The hydride transfer from N-5 of the flavin to C-5 of uracil is facilitated by an enzymatic general base with a pK of 5.6 that accepts a proton from N-1 of the flavin. There is also evidence from the pH dependence of V and the V/K for reduced dinucleotide substrates that a second enzyme residue with a pK of 6.4 must be unprotonated for optimum activity, but is not essential for activity. None of the functional groups reflected in the V/KNADPH pH-rate profile have a role in binding, while both of those observed in the V/Kuracil profile have a role in binding as shown by the pH dependence of the dissociation constants for the competitive inhibitors ATP-ribose and 2,6-dihydroxypyridine.
Core-Clickable PEG-Branch-Azide Bivalent-Bottle-Brush Polymers by ROMP: Grafting-Through and Clicking-To (2010)

The combination of highly efficient polymerizations with modular "click" coupling reactions has enabled the synthesis of a wide variety of novel nanoscopic structures. Here we demonstrate the facile synthesis of a new class of clickable, branched nanostructures, polyethylene glycol (PEG)-branch-azide bivalent-brush polymers, facilitated by "graft-through" ring-opening metathesis polymerization of a branched norbornene-PEG-chloride macromonomer followed by halide-azide exchange. The resulting bivalent-brush polymers possess azide groups at the core near a polynorbornene backbone with PEG chains extended into solution; the structure resembles a unimolecular micelle. We demonstrate copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click-to" coupling of a photocleavable doxorubicin (DOX)-alkyne derivative to the azide core. The CuAAC coupling was quantitative across a wide range of nanoscopic sizes (∼6-∼50 nm); UV photolysis of the resulting DOX-loaded materials yielded free DOX that was therapeutically effective against human cancer cells.
Comparative analysis of Gold Codes with PN codes using correlation property in CDMA technology (2012)

In a spread spectrum modulation system all users of the channel transmit information at the same time over the whole channel. Because information transmitted this way simply resembles noise, it is hard to intercept and therefore it offers high security. This techniques have a number of advantages over other multiplexing systems includes better frequency efficiency, power utilization and noise flexibility. This paper is prepared on the basis of aims on study of correlation properties among Gold code sequence and ordinary pseudo noise codes sequence. This paper however is also simulation of production of speared signal and re produce the original message signals. Two Gold Codes sequences and two Pseudo Noise sequences are to determine which is a better means for modulating the given message signal in terms of better noise immunity and security with the help of MATLAB.
Total Syntheses of Vancomycin and Eremomycin Aglycons (1998)

Controlling the elements of planar and axial chirality are the principal challenges in the synthesis of the aglycon of vancomycin. Vancomycin is the prototypical member of the glycopeptide family of antibiotics which are effective for the treatment of infections by methicillin-resistant Staphylococcus aureus. The first total syntheses of the vancomycin and eremomycin aglycons provide insight into the influence of structure on kinetic and thermodynamic control of atropselective macrocyclizations.
Mcl-1 deficiency results in peri-implantation embryonic lethality (2000)

We disrupted the Mcl-1 locus in murine ES cells to determine the developmental roles of this Bcl-2 family member. Deletion of Mcl-1 resulted in peri-implantation embryonic lethality. Mcl-1(-/-) embryos do not implant in utero, but could be recovered at E3.5-4.0. Null blastocysts failed to hatch or attach in vitro, indicating a trophectoderm defect, although the inner cell mass could grow in culture. Of note, Mcl-1(-/-) blastocysts showed no evidence of increased apoptosis, but exhibited a delay in maturation beyond the precompaction stage. This model indicates that Mcl-1 is essential for preimplantation development and implantation, and suggests that it has a function beyond regulating apoptosis.