gebhart/patrepeval huggingface dataset:
The secreted form of a melanocyte membrane‐bound glycoprotein (Pmel17/gp100) is released by ectodomain shedding (2009)

Ectodomain shedding is a proteolytic mechanism by which a transmembrane protein is converted into a secreted form. Pmel17/gp100 is a melanocyte‐specific membrane‐bound glycoprotein that has amyloid characteristics and forms fibrillar structures in melanosomes after a complex sequence of post‐translational processing and trafficking events, including cleavage by a furin‐like proprotein convertase (PC). A secreted form of Pmel17 (termed sPmel17) was also thought to be released due to cleavage by a PC. We used multidisciplinary approaches to demonstrate that sPmel17 is released by ectodomain shedding at the juxtamembrane and/or intramembrane motif and to show that this is independent of cleavage by a PC. We further show that sPmel17 consists of 2 fragments linked by disulfide bonds and that the shedding is inhibited at low temperature but not by metalloproteinase inhibitors. Moreover, treatment with a phorbol ester or a calmodulin inhibitor induces Pmel17 shedding. We also refine the reactivity of HMB50 and NKI/beteb, 2 monoclonal antibodies commonly used as melanoma‐specific markers. The fact that those antibodies require physically separated domains of Pmel17 sheds interesting light on its 3‐dimensional conformation. We conclude that sPmel17 is released by regulated proteolytic ectodomain shedding.—Hoashi, T., Tamaki, K., Hearing, V. J. The secreted form of a melanocyte membrane‐bound glycoprotein (Pmel17/ gp100) is released by ectodomain shedding. FASEB J. 24, 916–930 (2010). www.fasebj.org
Imaging of bronchodilator effects in COPD with hyperpolarised 3He and 1H MRI (2013)

Introduction A combination of hyperpolarised 3 He and 1 H MRI can provide high spatial resolution images of lung ventilation and blood perfusion, and measurements of lung emphysema. Objective To assess regional lung function response to bronchodilator in COPD. Methods 10 patients with moderate to severe COPD (NICE guidelines) were scanned using 3 He and 1 H MRI, before and after bronchodilator on two occasions. Quantitative MRI measures of ventilation, blood perfusion, apparent diffusion coefficient (ADC) and lung volume were calculated regionally and for the whole lung. Statistical analysis was carried out on the global measures. Results After bronchodilator there was a significant decrease in global lung volume suggesting reduced air trapping. No other global MRI measures showed significant change. However, regional changes in ventilation and perfusion were seen after bronchodilator; different lung regions showed different responses, which may account for the lack of significant change globally. Mean 3 He ADC demonstrated excellent test-retest repeatability at baseline and inverse correlation with DLCO, suggesting that ADC is a reliable measure of emphysematous destruction which shows no change with bronchodilator. Conclusion Lung ventilation and perfusion assessment with 3 He and 1 H MRI showed regional variations in response to bronchodilator which were masked by whole lung measurements in this group of patients with moderate to severe COPD.
Subsecond Induction of α4 Integrin Clustering by Immobilized Chemokines Stimulates Leukocyte Tethering and Rolling on Endothelial Vascular Cell Adhesion Molecule 1 under Flow Conditions (2000)

Leukocyte recruitment to target tissue is initiated by weak rolling attachments to vessel wall ligands followed by firm integrin-dependent arrest triggered by endothelial chemokines. We show here that immobilized chemokines can augment not only arrest but also earlier integrin-mediated capture (tethering) of lymphocytes on inflamed endothelium. Furthermore, when presented in juxtaposition to vascular cell adhesion molecule 1 (VCAM-1), the endothelial ligand for the integrin very late antigen 4 (VLA-4, alpha4beta1), chemokines rapidly augment reversible lymphocyte tethering and rolling adhesions on VCAM-1. Chemokines potentiate VLA-4 tethering within <0.1 s of contact through Gi protein signaling, the fastest inside-out integrin signaling events reported to date. Although VLA-4 affinity is not altered upon chemokine signaling, subsecond VLA-4 clustering at the leukocyte-substrate contact zone results in enhanced leukocyte avidity to VCAM-1. Endothelial chemokines thus regulate all steps in adhesive cascades that control leukocyte recruitment at specific vascular beds.
Occurrence of Uncommon Infinite Chains Consisting of Edge-Sharing Octahedra in a Porous Metal Organic Framework-Type Aluminum Pyromellitate Al4(OH)8[C10O8H2] (MIL-120): Synthesis, Structure, and Gas Sorption Properties (2009)

A new metal organic framework (MOF)-type aluminum pyromellitate or Al4(OH)8[C10O8H2]·4.8−5H2O (called MIL-120) has been hydrothermally synthesized at 210 °C for 24 h. Its structure was analyzed by single-crystal microdiffraction using the synchrotron radiation beamline at ID13 station (ESRF, Grenoble). It consists of infinite chains of aluminum centers in octahedral coordination connected to each other through the pyromellitate linker. The structural feature is the existence of the AlO2(OH)4 octahedra linked to each other via a common edge consisting of two μ2-hydroxo groups, along the [102] direction. The different positions of the common edge in the two distinct Al crystallographical sites induce a cis−trans connection mode of the octahedral units, and zigzag chains are generated. All the carboxylate groups of the pyromellitate molecules are perpendicularly connected to the inorganic chains, and it results in the formation of channels running along the c axis (5.4 × 4.7 Å), in which water molecules are encapsulated. 27Al solid state NMR revealed two well resolved signals with two distinct quadrupolar coupling constants (CQ = 8.07 and 4.77 MHz) related to two Al sites. Brunnauer-Emmett-Teller (BET) surface area is 308(4) m2 g−1 (Langmuir: 432(1) m2 g−1). H2 adsorption is 1.3 wt % at 77 K and 3 MPa. CH4 or CO2 adsorptions are 1.8 mmol g−1 and 4.8 mmol g−1, respectively, at 303 K (under 1 MPa).
Induction of foxP3 + Regulatory T Cells in the Periphery of T Cell Receptor Transgenic Mice Tolerized to Transplants (2004)

Abstract Transplantation tolerance can be induced in mice by grafting under the cover of nondepleting CD4 plus CD8 or CD154 mAbs. This tolerance is donor Ag specific and depends on a population of CD4+ regulatory T cells that, as yet, remain poorly defined in terms of their specificity, origin, and phenotype. Blocking of the Ag-specific response in vitro with an anti-CD4 mAb allowed T cells from monospecific female TCR-transgenic mice against the male Ag Dby, presented by H-2Ek, to express high levels of foxP3 mRNA. foxP3 induction was dependent on TGF-β. The nondepleting anti-CD4 mAb was also able to induce tolerance in vivo in such monospecific TCR-transgenic mice, and this too was dependent on TGF-β. As in conventional mice, acquired tolerance was dominant, such that naive monospecific T cells were not able to override tolerance. Splenic T cells from tolerant mice proliferated normally in response to Ag, and secreted IFN-γ and some IL-4, similar to control mice undergoing primary or secondary graft rejection. High levels of foxP3 mRNA, and glucocorticoid-induced TNFR superfamily member 18 (GITR)+ CD25+ T cells were found within the tolerated skin grafts of long-term tolerant recipients. These data suggest that regulatory T cells maintaining transplantation tolerance after CD4 Ab blockade can be induced de novo through a TGF-β-dependent mechanism, and come to accumulate in tolerated grafts.
Electric Shock Devices and Their Effects on the Human Body (1990)

Stun guns, shock batons and cattle prods are electric shock devices which can be used as weapons against the human body. Stun guns cause temporary incapacitation of the body whereas the other devices do not. The electrical outputs of examples of each type of device were measured using a digital storage oscilloscope at the moment when the device was discharged across resistors chosen to simulate the resistance of the human body. The outputs from the stun guns and the non-incapacitating devices have characteristic waveform shapes and magnitudes: significantly, the peak current from the stun guns is two orders of magnitude greater than from the other devices. To understand the possible hazardous effects of these outputs on the human body, the output parameters were related to the available information on the effects of electric currents on the human body and on the electro-immobilization of farm animals.
Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids (2005)

Long-chain unsaturated fatty acids, such as linoleic acid, show antibacterial activity and are the key ingredients of antimicrobial food additives and some antibacterial herbs. However, the precise mechanism for this antimicrobial activity remains unclear. We found that linoleic acid inhibited bacterial enoyl-acyl carrier protein reductase (FabI), an essential component of bacterial fatty acid synthesis, which has served as a promising target for antibacterial drugs. Additional unsaturated fatty acids including palmitoleic acid, oleic acid, linolenic acid, and arachidonic acid also exhibited the inhibition of FabI. However, neither the saturated form (stearic acid) nor the methyl ester of linoleic acid inhibited FabI. These FabI-inhibitory activities of various fatty acids and their derivatives very well correlated with the inhibition of fatty acid biosynthesis using [(14)C] acetate incorporation assay, and importantly, also correlated with antibacterial activity. Furthermore, the supplementation with exogenous fatty acids reversed the antibacterial effect of linoleic acid, which showing that it target fatty acid synthesis. Our data demonstrate for the first time that the antibacterial action of unsaturated fatty acids is mediated by the inhibition of fatty acid synthesis.
Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex (1982)

The development of stimulus selectivity in the primary sensory cortex of higher vertebrates is considered in a general mathematical framework. A synaptic evolution scheme of a new kind is proposed in which incoming patterns rather than converging afferents compete. The change in the efficacy of a given synapse depends not only on instantaneous pre- and postsynaptic activities but also on a slowly varying time-averaged value of the postsynaptic activity. Assuming an appropriate nonlinear form for this dependence, development of selectivity is obtained under quite general conditions on the sensory environment. One does not require nonlinearity of the neuron's integrative power nor does one need to assume any particular form for intracortical circuitry. This is first illustrated in simple cases, e.g., when the environment consists of only two different stimuli presented alternately in a random manner. The following formal statement then holds: the state of the system converges with probability 1 to points of maximum selectivity in the state space. We next consider the problem of early development of orientation selectivity and binocular interaction in primary visual cortex. Giving the environment an appropriate form, we obtain orientation tuning curves and ocular dominance comparable to what is observed in normally reared adult cats or monkeys. Simulations with binocular input and various types of normal or altered environments show good agreement with the relevant experimental data. Experiments are suggested that could test our theory further.
Normal bronchial epithelial cell expression of glutathione transferase P1, glutathione transferase M3, and glutathione peroxidase is low in subjects with bronchogenic carcinoma. (2000)

Normal bronchial epithelial cells (NBECs) are at risk for damage from inhaled and endogenous oxidative species and from epoxide metabolites of inhaled polycyclic aromatic hydrocarbons. Epidemiological and in vitro data suggest that interindividual variation in this risk may result from variation in NBEC expression of enzymes that inactivate reactive species by conjugating them to glutathione. Quantitative competitive reverse transcription-PCR was used to measure mRNA levels of glutathione transferases (GSTs) and glutathione peroxidases (GSHPxs) in primary NBECs from subjects with or without bronchogenic carcinoma. Mean expression levels (mRNA/10(3) beta-actin mRNA) in NBECs from 23 subjects without bronchogenic carcinoma compared to those from 11 subjects with bronchogenic carcinoma respectively (in parentheses) were: mGST (26.0, 6.11), GSTM3 (0.29, 0.09), combined GSTM1,2,4,5 (0.98, 0.60), GSTT1 (0.84, 0.76), GSTP1 (287, 110), GSHPx (140, 62.1), and GSHPxA (0.43, 0.34). Levels of GSTP1, GSTM3, and GSHPx were significantly (P < 0.05) lower in NBECs from subjects with bronchogenic carcinoma. Further, the gene expression index formed by multiplying the values for mGST x GSTM3 x GSHPx x GSHPxA x GSTP1 had a sensitivity (90%) and specificity (76%) for detecting NBECs from bronchogenic carcinoma subjects that was better than any individual gene. In cultured NBECs derived from eight individuals without bronchogenic carcinoma and incubated under identical conditions such that environmental effects were minimized, the mean level of expression and degree of interindividual variation for each gene evaluated was less than that observed in primary NBECs. Data from these studies support the hypotheses that (a) interindividual variation in risk for bronchogenic carcinoma results in part from interindividual variation in NBEC expression of antioxidant genes; (b) gene expression indices will better identify individuals at risk for bronchogenic carcinoma than individual gene expression values; and (c) both hereditary and environmental exposures contribute to the level of and interindividual variation in gene expression observed in primary NBECs. Many epidemiological studies have been designed to evaluate risk associated with polymorphisms or gene expression levels of putative susceptibility genes based on measurements in surrogate tissues, such as peripheral blood lymphocytes. Based on data presented here, it will be important to include the assessment of NBECs in future studies. Measurement of antioxidant gene expression in NBECs may identify the 5-10% of individuals at risk for bronchogenic carcinoma. Bronchoscopic sampling of NBECs from smokers and ex-smokers then will allow susceptible individuals to be entered into surveillance and/or chemoprevention studies.
Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States (2017)

Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant <i>Enterobacteriaceae</i> (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among <i>Enterobacteriaceae</i> bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (<i>cps</i>), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among <i>Klebsiella pneumoniae</i>, <i>Enterobacter</i> spp., and <i>Escherichia coli</i> bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were <i>K. pneumoniae</i> and 92% produced <i>K. pneumoniae</i> carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing <i>K. pneumoniae</i> (KPC-<i>Kp</i>). The <i>wzi154</i> allele, corresponding to <i>cps-2</i>, was present in 93% of KPC-3-<i>Kp</i>, whereas KPC-2-<i>Kp</i> had greater <i>cps</i> diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-<i>Kp</i> had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-<i>Kp</i> bacteremia (adjusted odds ratio [aOR], 2.58; <i>P</i> = 0.045), cancer (aOR, 3.61, <i>P</i> = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; <i>P</i> = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.
Effect of Anodal Versus Cathodal Transcranial Direct Current Stimulation on Stroke Rehabilitation (2013)

A brief course of 2 types of tDCS stimulation is superior to sham stimulation in enhancing the effect of rehabilitation training to improve motor recovery after stroke.
GPER-mediated proliferation and estradiol production in breast cancer-associated fibroblasts (2014)

Cancer-associated fibroblasts (CAFs) are crucial co-mediators of breast cancer progression. Estrogen is the predominant driving force in the cyclic regulation of the mammary extracellular matrix, thus potentially affecting the tumor-associated stroma. Recently, a third estrogen receptor, estrogen (G-protein-coupled) receptor (GPER), has been reported to be expressed in breast CAFs. In this study, GPER was detected by immunohistochemical analysis in stromal fibroblasts of 41.8% (59/141) of the primary breast cancer samples. GPER expression in CAFs isolated from primary breast cancer tissues was confirmed by immunostaining and RT-PCR analyses. Tamoxifen (TAM) in addition to 17β-estradiol (E₂) and the GPER agonist G1 activated GPER, resulting in transient increases in cell index, intracellular calcium, and ERK1/2 phosphorylation. Furthermore, TAM, E₂, and G1 promoted CAF proliferation and cell-cycle progression, both of which were blocked by GPER interference, the selective GPER antagonist G15, the epidermal growth factor receptor (EGFR) inhibitor AG1478, and the ERK1/2 inhibitor U0126. Importantly, TAM as well as G1 increased E₂ production in breast CAFs via GPER/EGFR/ERK signaling when the substrate of E₂, testosterone, was added to the medium. GPER-induced aromatase upregulation was probably responsible for this phenomenon, as TAM- and G1-induced CYP19A1 gene expression was reduced by GPER knockdown and G15, AG1478, and U0126 administration. Accordingly, GPER-mediated CAF-dependent estrogenic effects on the tumor-associated stroma are conceivable, and CAF is likely to contribute to breast cancer progression, especially TAM resistance, via a positive feedback loop involving GPER/EGFR/ERK signaling and E₂ production.
Antitumor activity, and antiangiogenic activity of nanoparticle albumin-bound nab-rapamycin in combination with nab-paclitaxel. (2009)

Abstract Abstract #3125 Background: Rapamycin inhibits downstream signals from the mammalian target of rapamycin (mTOR), a known kinase member of a signaling pathway that promotes tumor growth. Rapamycin's poor aqueous solubility and poor chemical stability have limited its development as an intravenous (IV) anticancer agent. Nab-rapamycin utilizes the albumin-bound technology to allow for IV administration of rapamycin and has demonstrated dose-linear pharmacokinetics and safety up to 90 mg/kg with effective antitumor activity at 40 mg/kg against a human panel of tumor xenografts. This study investigated the efficacy of combined therapy with nab-paclitaxel (Abraxane®) utilizing invasive human breast (MDA-MB-231) and colon (HT29) cancer xenograft models.&amp;#x2028; Material and Methods: Xenograft transplants using luciferase-tagged MDA-MB-231 cells were implanted into mammary fatpad of SCID mice and allowed to reach 460 mm3 in size prior to IV administration of saline (vehicle, n = 9); nab-rapamycin, 3x wkly for 2 wks at 40 mg/kg (nab-rap-2W; n = 8); nab-rapamycin, 3x wkly for 4 wks at 40 mg/kg (nab-rap-4W; n = 8); Abraxane, qdx5 at 30 mg/kg (ABX; n = 8); nab-rap-2W + ABX (n = 9); or nab-rap-4W + ABX (n = 8). HT29 xenografts were also treated with nab-rap-4W (n = 8) and nab-rap-4W + ABX (10 mg/kg, qdx5, IP, n = 8). The in vivo antiangiogenic effect of nab-rapamycin was evaluated using the standard in vivo chick chorioallantoic membrane (CAM) assay with 3-day old embryos (n = 18).&amp;#x2028; Results: Relative to vehicle controls, nab-rap-2W (P &amp;lt; 0.00011), nab-rap-4W (P &amp;lt; 0.0001), and ABX (P &amp;lt; 0.0001) were effective against MDA-MB-231 tumor xenograft models with tumor growth inhibition (TGI) of 60%, 66%, and 73% respectively. Additive antitumor effects were observed with combination of nab-rapamycin + ABX with TGI of 81% and 86% for nab-rap-2W + ABX and nab-rap-4W + ABX groups, respectively. For HT29 tumors, the combination of ABX and nab-rapamycin also showed greater TGI (89%) compared to nab-rapamycin alone (81%). In the chick CAM assay, nab-rapamycin demonstrated antiangiogenic efficacy at doses of 10 µg and above without affecting embryo viability.&amp;#x2028; Conclusions: Combination therapy of nab-rapamycin and Abraxane was more effective at inhibiting breast and colon xenograft tumor growth than single therapy of either drug. The enhanced antitumor activity seen with combined nab-rapamycin-Abraxane may in part be due to the observed antiangiogenic activity of nab-rapamycin. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3125.
Fundamentals of tertiary oil recovery. Pt. 1. Why tertiary recovery (1976)

Secondary recovery projects initiated annually by Atlantic Richfield Co. in the U.S. show a general trend somewhat characteristic of all U.S. producers. Why did the number of project starts decline. Simply because there was a lack of prospects for Atlantic Richfield to apply waterflooding economically. This raises the question of what is the next step to maintain U.S. oil producing rates. One answer is to recover a third crop of oil from those fields which have already undergone secondary recovery. It is becoming evident that tertiary recovery must be undertaken while the existing wells and surface equipment are still intact and usable. Very few prospects are expected to be so profitable that economics will permit redrilling of wells and replacement of surface equipment, but tertiary recovery will be applicable to many of the existing oil fields. Engineers and production personnel at all organizational levels must make an effort to recognize those fields under their supervision which are candidates for tertiary recovery applications.
Role of lysophosphatidylcholine in T-lymphocyte activation: involvement of phospholipase A2 in signal transduction through protein kinase C. (1992)

2-Lysophosphatidylcholine (lysoPtdCho), a product of the hydrolysis of phosphatidylcholine catalyzed by phospholipase A2, greatly potentiates the activation of human resting T lymphocytes that is induced by a membrane-permeant diacylglycerol plus a calcium ionophore, as determined by the expression of the alpha subunit of the interleukin 2 receptor and thymidine incorporation into DNA. LysoPtdCho per se is inactive unless both diacylglycerol and a calcium ionophore are present. This effect of lysoPtdCho is also observed when diacylglycerol is replaced by a tumor-promoting phorbol ester. Other lysophosphatides including lysophosphatidylserine, lysophosphatidylinositol, and lysophosphatidic acid are inert except for lysophosphatidylethanolamine, which is far less effective than lysoPtdCho. Tracer experiments with radioactive choline indicate that, when T lymphocytes are stimulated with an antigenic signal, lysoPtdCho is indeed produced in a time-dependent fashion, although the concentration of this lysophospholipid accumulated remains to be quantitated. It suggests that phospholipase A2 is directly involved in the signal transduction pathway through protein kinase C to induce long-term cellular responses.