gebhart/patrepeval huggingface dataset:
Polyphenol mixtures of Euphorbia supina the inhibit invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells (2015)

The Korean prostrate spurge Euphorbia supina is abundant in polyphenols and has been used as a folk medicine in Korea against a variety of diseases. Thus, we aimed to investigate the effect of polyphenol mixtures of Korean Euphorbia supina (PES) on the invasion and metastasis of highly metastatic breast cancer MDA-MB-231 cells. Firstly, PES showed no cytotoxicity on cancer cells and endothelial cells (ECs) at the doses of 0.1-10 µg/ml, but showed significant cytotoxicity from 50 µg/ml. Thus, we performed subsequent experiments with PES at doses up to 5 µg/ml. PES dose‑dependently suppressed epithelial-mesenchymal transition by downregulating the mesenchymal markers, Snail1 and N-cadherin, showing significant inhibition from 1 and 5 µg/ml, respectively. In addition, PES significantly inhibited MMP-9 activity and LOX release induced by TNF-α at 5 µg/ml. Then, we determined the effect of PES on the expression of adhesion molecules and VE-cadherin phosphorylation. The results showed that PES effectively reduced TNF-α-mediated VCAM-1 expression but not ICAM expression both in the MDA-MB-231 cells and ECs, resulting in the reduced adhesion of MDA-MB-231 to ECs. Finally, PES effectively inhibited MDA-MB-231 cell invasion through ECs, suggesting that PES may serve as a therapeutic agent against cancer metastasis with minimal cytotoxicity to normal cells.
T Cell Tolerance Induced by Cross-Reactive TCR Ligands Can Be Broken by Superagonist Resulting in Anti-Inflammatory T Cell Cytokine Production (2005)

Cross-reactive activation of potentially autoreactive T cells by high-affinity nonself ligands may be important in breaking self-tolerance in autoimmunity. In a mouse transgenic for a cross-reactive TCR, we have previously shown that a hyper-stimulating altered peptide ligand, L144, induced unresponsiveness to the self peptide, proteolipid protein 139-151. In this study, we demonstrate that a superagonist ligand can break T cell tolerance induced by the lower affinity cognate Ag. T cells tolerant to the cognate ligand, Q144, responded to superagonist, L144, by proliferation and the production of mainly IL-4 and IL-10 in vitro. In contrast, T cells that were tolerized to the superagonist were unable to respond to any peptide that cross-reacted with the transgenic TCR. Low-dose immunization with the superagonist L144 was able to break tolerance to the cognate ligand in vivo and resulted in a blunted proliferative response with production of Th2 cytokines.
A Cost Comparison of Management of Chronic Hepatitis B and Its Associated Complications in Hong Kong and Singapore (2004)

This study confirms that CHB and its liver disease complications are a significant economic burden to the healthcare budgets of Hong Kong and Singapore, and indicates that effective therapy that arrests or reverses the progression of liver disease would be highly cost-effective.
Physical and Electrical Properties of Thin Doped Silicon Films Obtained by Low Temperature Smart Cut and Solid Phase Epitaxy (2013)

International audience
Prenatal diagnosis of marfan syndrome: Identification of a fibrillin‐1 mutation in chorionic villus sample (1995)

Marfan syndrome (MFS) is one of the most common heritable connective tissue disorders and is caused by mutations in a gene coding for fibrillin-1. All but one of over 30 published mutations have been unique and specific prenatal diagnostics can only be provided to families with a previously established mutation. We have earlier identified a 366 bp deletion of fibrillin mRNA in a three-generation British Marfan family. An affected female in the family together with her husband sought prenatal diagnosis. Chorionic villus sampling was performed at 11.5 weeks of gestation and total RNA was directly extracted from the sample. After reverse transcription and polymerase chain reaction (PCR) of the cDNA, the same deletion was identified in the chorionic villus sample (CVS) and the mother's sample in agarose gel electrophoresis. The fetal origin of the CVS was confirmed with polymorphic markers. In addition to the mutation analysis, CVS cells of the proband and a control fetus were cultured for biochemical studies of fibrillin polypeptides. The results of the biochemical investigation were in concordance with the molecular analysis.
Discovery of Branebrutinib (BMS-986195): A Strategy for Identifying a Highly Potent and Selective Covalent Inhibitor Providing Rapid in Vivo Inactivation of Bruton’s Tyrosine Kinase (BTK) (2019)

Bruton's tyrosine kinase (BTK), a non-receptor tyrosine kinase, is a member of the Tec family of kinases and is essential for B cell receptor (BCR) mediated signaling. BTK also plays a critical role in the downstream signaling pathways for the Fcγ receptor in monocytes, the Fcε receptor in granulocytes, and the RANK receptor in osteoclasts. As a result, pharmacological inhibition of BTK is anticipated to provide an effective strategy for the clinical treatment of autoimmune diseases such as rheumatoid arthritis and lupus. This article will outline the evolution of our strategy to identify a covalent, irreversible inhibitor of BTK that has the intrinsic potency, selectivity, and pharmacokinetic properties necessary to provide a rapid rate of inactivation systemically following a very low dose. With excellent in vivo efficacy and a very desirable tolerability profile, 5a (branebrutinib, BMS-986195) has advanced into clinical studies.
Mechanism of CRISPR-RNA guided recognition of DNA targets inEscherichia coli (2015)

In bacteria and archaea, short fragments of foreign DNA are integrated into Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) loci, providing a molecular memory of previous encounters with foreign genetic elements. In Escherichia coli, short CRISPR-derived RNAs are incorporated into a multi-subunit surveillance complex called Cascade (CRISPR-associated complex for antiviral defense). Recent structures of Cascade capture snapshots of this seahorse-shaped RNA-guided surveillance complex before and after binding to a DNA target. Here we determine a 3.2 Å x-ray crystal structure of Cascade in a new crystal form that provides insight into the mechanism of double-stranded DNA binding. Molecular dynamic simulations performed using available structures reveal functional roles for residues in the tail, backbone and belly subunits of Cascade that are critical for binding double-stranded DNA. Structural comparisons are used to make functional predictions and these predictions are tested in vivo and in vitro. Collectively, the results in this study reveal underlying mechanisms involved in target-induced conformational changes and highlight residues important in DNA binding and protospacer adjacent motif recognition.
Nanofiber Fuel Cell MEAs with a PtCo/C Cathode (2019)

PtCo/C and Pt/C catalyst powders were incorporated into electrospun nanofiber and conventional sprayed cathode membrane-electrode-assemblies (MEAs) at a fixed electrode loading of 0.1 mgPt/cm<sup>2</sup>. The binder for PtCo/C nanofiber cathodes and Pt/C nanofiber anodes was a mixture of Nafion and poly(acrylic acid) (PAA), whereas the sprayed electrode MEAs utilized a neat Nafion binder. The structure of electrospun fibers was analyzed by scanning transmission electron microscopy (STEM) and energy-dispersive X-ray spectroscopy (EDS), which showed that the fibers were ~30% porous with a uniform distribution of catalyst and binder in the axial and radial fiber directions. The initial performance of nanofiber MEAs at 80°C was 20% better than the sprayed electrode MEA (a maximum power density of 1,045 mW/cm<sup>2</sup> vs. 869 mW/cm<sup>2</sup>). The benefit of the nanofiber electrode morphology was most evident at end-of-test (after a metal dissolution accelerated stress test), where power densities dropped by only 8%, after 30,000 square wave voltage cycles (0.6 V to 0.95 V), as compared to a 35% drop in the maximum power for the sprayed electrode MEA. The use of a recovery protocol improved the initial performance of a nanofiber MEA by ~13%, to 1,070 mW/cm<sup>2</sup> at 0.65 V, and increased the power after a metal dissolution stress test by 5–10% (e.g. 840 mW/cm<sup>2</sup> at 0.65 V after 30,000 voltage cycles). At rated power, the nanofiber MEA generated more than 1,000 mW/cm<sup>2</sup> at 99°C and a pressure of 250 kPa<sub>abs</sub>. The high performance and durability of PtCo/C nanofiber cathode MEAs is due to the combined effects of a highly active cathode catalyst and the unique nanofiber electrode morphology, where there is a uniform distribution of catalyst and binder (no agglomeration) and short transport pathways across the submicron diameter fibers (which lowers gas transfer resistance and facilitates water removal from the cathode).
Predicting HIV-1 broadly neutralizing antibody epitope networks using neutralization titers and a novel computational method (2014)

Computational methods were implemented to rapidly survey protein structures and predict epitope networks associated with response to individual monoclonal antibodies, which resulted in the identification and deeper understanding of immunological hotspots targeted by broadly neutralizing HIV-1 antibodies.
Metal vapour synthesis of bis{1,3-bis(trimethylsilyl)cyclopentadienyl}-calcium, -strontium, and -barium compounds; X-ray structures of [M{η-C5H3-1,3-(SiMe3)2}2(thf)](M = Ca, Sr; thf = tetrahydrofuran) (1988)

Cocondensation of C5H4(SiMe3)2, hexane, and metal vapour at –196 °C yields M{C5H3-1,3-(SiMe3)2}2[M = Ca (1), Sr (2), and Ba (3)] which reversibly bind tetrahydrofuran (thf); X-ray structure determinations on the adducts [M{η-C5H3-1,3-(SiMe3)2}2(thf)], [M = Ca (4) Sr, (5)] show they are monomeric bent metallocenes, M–C, M–O 2.662(10)–2.718(9), 2.310(9), (4), 2.78(4)–2.84(5), 2.49(3)Å, (5); Centroid–M–Centroid, 139.1, (4), 134°, (5).
Neutral sphingomyelinase 2 is required for HIV-1 maturation (2023)

HIV-1 assembly occurs at the inner leaflet of the plasma membrane (PM) in highly ordered membrane microdomains. The size and stability of membrane microdomains is regulated by activity of the sphingomyelin hydrolase neutral sphingomyelinase 2 (nSMase2) that is localized primarily to the inner leaflet of the PM. In this study, we demonstrate that pharmacological inhibition or depletion of nSMase2 in HIV-1-producer cells results in a block in the processing of the major viral structural polyprotein Gag and the production of morphologically aberrant, immature HIV-1 particles with severely impaired infectivity. We find that disruption of nSMase2 also severely inhibits the maturation and infectivity of other primate lentiviruses HIV-2 and simian immunodeficiency virus, has a modest or no effect on nonprimate lentiviruses equine infectious anemia virus and feline immunodeficiency virus, and has no effect on the gammaretrovirus murine leukemia virus. These studies demonstrate a key role for nSMase2 in HIV-1 particle morphogenesis and maturation.
Compact UHF antenna for precise measurement of respiratory signal in PET scanners (2019)

Measuring internal organ movement is always challenging. Most sensors are categorized for surface-skin motion detection (electrically or mechanically). In this paper, a CW Doppler radar system with compact antenna is proposed for measuring internal respiratory motion directly. In this approach a low gain compact linear and circular patch antenna are implemented based on high dielectric constant material. The acquired data while doing PET/CT scan presents more realistic motion detector with better accuracy and more reliability compare to the other techniques.
[A problem with ESR dosimetry utilizing human tooth enamel in low dose region]. (1990)

Experiments were made to determine the dependence of CO3(3-) signal intensity on radiation dose in the low dose region from 3.1 x 10(-4) C/kg to 865.6 x 10(-4) C/kg. After all human tooth enamel samples were crushed into 350-500 micrometers particles, they were irradiated with 60Co gamma rays. Irradiated samples were measured with the ESR instrument, and the CO3(3-) signal appearance and the true signal have been determined. It is confirmed that the relation between the true intensity of the CO3(3-) signal and the exposure have linearity from 25.0 x 10(-4) C/kg to 865.6 x 10(-4) C/kg. It is difficult to confirm this in the case of less than 25.0 x 10(-4) C/kg due to the effect of organic signal and noise.
Net acid transport by isolated perfused inner medullary collecting ducts (1990)

The isolated perfused tubule technique was used to study net acid transport in rat terminal inner medullary collecting duct (IMCD) segments. The stop-flow luminal pH [measured fluorometrically with the acidic form of the pH-sensitive dye 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in the lumen] fell 0.35 units below the bath pH in tubules from control rats and 0.53 units below the bath in tubules from deoxycorticosterone-treated rats. Tubules from control rats absorbed bicarbonate and secreted ammonium against concentration gradients, although at low rates. In control rats, 10(-8) M vasopressin added to the bath increased bicarbonate absorption almost threefold. Treatment of rats in vivo with deoxycorticosterone significantly increased the rate of bicarbonate absorption in vitro. In vivo NH4Cl loading also significantly increased bicarbonate absorption. Staining microdissected tubules with acridine orange confirmed that the perfused segments lacked intercalated cells. We conclude that the terminal IMCD spontaneously acidifies the lumen despite an absence of intercalated cells. Bicarbonate absorption appears to be regulated by the same factors that affect net acidification in other collecting duct segments.
α2-Adrenoceptor Blockade Potentiates the Effect of Duloxetine on Sneeze Induced Urethral Continence Reflex in Rats (2010)

Findings support the concept that combination therapy with alpha(2)-adrenoceptor antagonists may be an effective, novel strategy to reinforce the clinical efficacy of serotonin and norepinephrine reuptake inhibitors for stress urinary incontinence.
Overestimation of minimal model glucose effectiveness in presence of insulin response is due to undermodeling (1998)

Glucose effectiveness is an important determinant of glucose tolerance that can be derived from minimal model analysis of an intravenous glucose tolerance test (IVGTT). However, recent evidence suggests that glucose effectiveness is overestimated by minimal model analysis. Here we compare a new model-independent estimate of glucose effectiveness with the minimal model estimate by reanalyzing published data in which insulin-dependent diabetic subjects were each given IVGTTs under two conditions (Quon, M. J., C. Cochran, S. I. Taylor, and R. C. Eastman. Diabetes 43: 890-896, 1994). In one case, a basal insulin level was maintained (BI-IVGTT). In the second case, a dynamic insulin response was recreated (DI-IVGTT). Our results show that minimal model glucose effectiveness is very similar to the model-independent measurement during a BI-IVGTT but is three times higher during a DI-IVGTT. To investigate the causes of minimal model overestimation in the presence of a dynamic insulin response, Monte Carlo simulation studies on a two-compartment model of glucose kinetics with various insulin response patterns were performed. Results suggest that minimal model overestimation is due to single-compartment representation of glucose kinetics that results in a critical oversimplification in the presence of increasingly dynamic insulin secretion patterns.
Deciphering Protein Kinase Specificity Through Large-Scale Analysis of Yeast Phosphorylation Site Motifs (2010)

Phosphorylation is a universal mechanism for regulating cell behavior in eukaryotes. Although protein kinases target short linear sequence motifs on their substrates, the rules for kinase substrate recognition are not completely understood. We used a rapid peptide screening approach to determine consensus phosphorylation site motifs targeted by 61 of the 122 kinases in Saccharomyces cerevisiae. By correlating these motifs with kinase primary sequence, we uncovered previously unappreciated rules for determining specificity within the kinase family, including a residue determining P-3 arginine specificity among members of the CMGC [CDK (cyclin-dependent kinase), MAPK (mitogen-activated protein kinase), GSK (glycogen synthase kinase), and CDK-like] group of kinases. Furthermore, computational scanning of the yeast proteome enabled the prediction of thousands of new kinase-substrate relationships. We experimentally verified several candidate substrates of the Prk1 family of kinases in vitro and in vivo and identified a protein substrate of the kinase Vhs1. Together, these results elucidate how kinase catalytic domains recognize their phosphorylation targets and suggest general avenues for the identification of previously unknown kinase substrates across eukaryotes.
Electronic system for optical shutter control (1976)

A versatile electronic system for accurate shutter control in optical experiments is described in detail. Digital and analog circuitry is used to provide automatic timing, exposure control, manual operation, and remote programmability.
Fluorescence of the KH molecule (1974)

in ab­sorption and in emission. We report here the first study of KH fluorescence, excited by both a pulsed tunable dye laser and by the lines of a cw argon ion laser. With the ability to excite fluorescence in this class of molecules, one can look forward to obtaining increasingly refined structural information on the excited state (such as the variation in dipole moment as a function of vibrational level) through fluorescence interference techniques,
Conformational kinetics of methyl nitrite. I. NMR spectral evidence for statistical intramolecular vibrational redistribution (1984)

Pressure dependent rate constants for syn⇄anti conformational exchange in gaseous methyl nitrite and in gaseous methyl nitrite–CO2 mixtures have been obtained from line shape analyses of 1H NMR spectra. The pressure dependence of the exchange rates is consistent with a specific reaction rate constant of ∼1×109/s which agrees with RRKM calculations demonstrating that intramolecular vibrational redistribution is occurring at the statistical limit in methyl nitrite molecules with ∼12 kcal/mol of internal vibrational energy. At 12 kcal/mol methyl nitrite has a state density of ∼160/cm−1. These results indicate strong anharmonic and/or Coriolis coupling between vibrational levels. Bimolecular rate data for methyl nitrite and methyl nitrite–CO2 mixtures are consistent with a collisional efficiency βp for CO2 of 0.95(8) for activation of syn–anti conformational exchange at 258.8 K.
MC4R biased signalling and the conformational basis of biological function selections (2022)

The MC4R, a GPCR, has long been a major target for obesity treatment. As the most well-studied melanocortin receptor subtype, the evolutionary knowledge pushes the drug development and structure-activity relationship (SAR) moving forward. The past decades have witnessed the evolution of scientists' view on GPCRs gradually from the control of a single canonical signalling pathway via a bilateral 'active-inactive' model to a multi-state alternative model where the ligands' binding affects the selection of the downstream signalling. This evolution brings the concept of biased signalling and the beginning of the next generation of peptide drug development, with the aim of turning from receptor subtype specificity to signalling pathway selectivity. The determination of the value structures of the MC4R revealed insights into the working mechanism of MC4R activation upon binding of agonists. However, new challenge has risen as we seek to unravel the mystery of MC4R signalling selection. Thus, more biased agonists and ligands with representative biological functions are needed to solve the rest of the puzzle.
Thoracic Spine Manipulation in Individuals With Subacromial Impingement Syndrome Does Not Immediately Alter Thoracic Spine Kinematics, Thoracic Excursion, or Scapular Kinematics: A Randomized Controlled Trial (2015)

Therapy, level 1b-.
CR3 (αM β2; CD11b/CD18) restores IgG-dependent phagocytosis in transfectants expressing a phagocytosis-defective Fc γRIIA (CD32) tail-minus mutant (1996)

Previous studies have suggested that complement receptors cooperate with Fc receptors to mediate Ab-dependent effector functions. In the present study, we tested the capacity of complement receptor type 3 (CR3; alphaM beta2; CD11b/CD18) to participate in Fc gammaRIIA (CD32)-mediated phagocytosis. To test this hypothesis, we transfected a phagocytosis-defective tail-minus mutant of Fc gammaRIIA into fibroblasts that did or did not express CR3. As controls, cells exposed to the transfection protocol but not expressing either CR3 or Fc gammaRIIA constructs were also selected. Expression of cell surface receptors was confirmed by both flow cytometry and fluorescence microscopy. Cells were tested for their ability to bind and internalize IgG-opsonized erythrocytes and for surface proximity of CR3 and Fc gammaRIIA using resonance energy transfer techniques. Resonance energy transfer studies showed a physical proximity between CR3 and Fc gammaRIIA on cell surfaces. Cells expressing only the tail-minus mutant of Fc gammaRIIA were unable to internalize erythrocytes but showed significant binding ability. In contrast, cells expressing both mutant Fc gammaRIIA and CR3 internalized opsonized erythrocytes. These results show that CR3 can complement the phagocytic function of defective Fc gammaRIIA. These data suggest that CR3 is capable of transducing a phagocytic signal generated by Fc gammaRIIA recognition events that mediates internalization of IgG-opsonized targets.
Technical challenges in exploiting the web as a business resource (2005)

In this talk, I'll describe some recent indicators suggesting that businesses are on the cusp of operational exploitation of the web as a decision support resource. From consumer research and purchasing behavior to enterprise brand tracking, intelligence gathering, and advertising, the web is suddenly on everybody's mind - not as an exciting future possibility, but as an exploitable resource. I'll describe some technological approaches to employing this resource, talk about what's possible today, and describe some challenges for the future. As a running example, I'll cover IBM's WebFountain system: its architecture, analytical model, and applications.
A high-resolution spectrometer based on a compact planar two dimensional photonic crystal cavity array (2012)

We demonstrate a compact spectrometer based on an array of high-quality-factor photonic crystal nanocavities, coupled via a planar two-dimensional waveguide. This architecture enables spectral analysis of incident light with resolution as high as the bandwidth of the cavity mode–0.3 nm at 840 nm for our device. The design is easily extended to the visible and deep-infrared spectral ranges. The two-dimensional cavity array can be mated to commercial two-dimensional optical detector arrays, creating a compact and high-resolution spectrometer suitable for a range of applications including materials and chemical analysis.