gebhart/patrepeval huggingface dataset:
Orphanin FQ inhibits capsaicin‐induced thermal nociception in monkeys by activation of peripheral ORL1 receptors (2002)

1. Orphanin FQ (OFQ), an endogenous peptide for ORL1 receptors, has been identified. Although the actions of OFQ have much in common with those of opioid peptides at the cellular level, behavioral studies in rodents seem conflicting. 2. The aim of this study was to investigate the potential pronociceptive or antinociceptive function of peripheral ORL1 receptors in primates. Experiments were conducted to verify whether local administration of OFQ can attenuate capsaicin-induced nociception and whether peripheral ORL1 receptors selectively mediate the local action of OFQ in monkeys. 3. Capsaicin (100 microg) was administered subcutaneously in the tail to locally evoke a nociceptive response (thermal allodynia/hyperalgesia), which was manifested as a reduced tail-withdrawal latency in normally innocuous 46 degreeC warm water. 4. Co-administration of OFQ (1--30 microg) with capsaicin in the tail dose-dependently inhibited thermal nociception. However, a locally effective dose of OFQ (30 microg), when applied in the back, did not inhibit capsaicin-induced nociception. 5. OFQ-induced local antinociception was antagonized by a small dose (10 microg) of J-113397, a selective ORL1 receptor antagonist, in the tail. Similarly, s.c. administration of 10 microg of J-113397 in the back did not antagonize local antinociception of OFQ. 6. In addition, s.c. administration of either OFQ or J-113397 in the tail alone did not change its thermal nociceptive threshold. Local administration of opioid receptor antagonists selective for mu, kappa, and delta opioid receptors did not antagonize OFQ-induced local antinociception. Local administration of J-113397 also did not interfere with the local actions of mu, kappa, and delta opioid agonists in the tail. 7. These results provide the first functional evidence that activation of peripheral ORL1 receptors produces thermal antinociception in primates and this action is independent of antinociception produced at classical opioid receptors.
The Management of Chronic Heart Failure (1996)

Heart failure is a complex of symptoms — fatigue, shortness of breath, and congestion — that are related to the inadequate perfusion of tissue during exertion and often to the retention of fluid. Its primary cause is an impairment of the heart's ability to fill or empty the left ventricle properly.The management of heart failure can no longer be confined to the relief of symptoms. The processes that contribute to left ventricular dysfunction may progress independently from the development of symptoms (Figure 1). Treatment to prevent or delay the progression of left ventricular dysfunction may therefore be quite different . . .
Apolipoprotein A-I Mimetic Peptide Retains Function After Oxidant Exposure (2008)

Mechanical integrity of arteries is vital for maintaining compensatory mechanisms under physiologic conditions, and changes in vessel structure (and consequently, vessel mechanical properties) are hallmarks of the progression of pathologic states. Oxidative stress can (1) induce endothelial dysfunction by interfering with nitric oxide (NO) signaling pathways relevant to vasodilation/vasoconstriction of arteries, and (2) alter atherosclerotic plaque composition by oxidation of constituents or by interruption of reverse cholesterol transport from plaques.
Photodynamic Therapy With Verteporfin for Choroidal Neovascularization Caused by Age-related Macular Degeneration (1999)

Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm2, no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified.
Inhibition of insulin-like growth factor I receptor expression in neuroblastoma cells induces the regression of established tumors in mice. (1998)

Several lines of evidence now indicate that type 1 insulin-like growth factor receptor (IGF1R) function may be particularly important in the pathogenesis of the pediatric cancer neuroblastoma. Modulating the expression of specific genes involved in neuroblastoma tumorigenesis could provide a much needed alternative treatment strategy for poor prognosis disease. We now report construction of an antisense expression vector to the IGF1R that markedly reduces cellular IGF1R levels and inhibits the proliferation and clonogenicity of neuroblastoma cells in vitro but not that of IGF1R null cells. This antitumor activity is associated with the induction of apoptotic cell death in transfected cells, as measured by annexin V staining and flow cytometry. Direct injection of this vector into established tumors growing in syngeneic mice results in a marked inhibition of tumor growth with complete and durable tumor regression in one-half of the animals. This effect appears to be immunologically mediated in that vector injection of neuroblastoma tumors growing in severe combined immunodeficiency mice results in only modest delay of tumor growth. Our results suggest that inhibition of IGF1R expression by direct intratumoral delivery of an antisense construct could provide a novel therapeutic approach in the management of poor prognosis neuroblastoma.
Hyperpolarized gases--a new type of MR contrast agents? (1997)

The nuclear spin polarization of noble gases can be strongly enhanced by laser optical pumping followed by electron-nuclear polarization transfer. Direct optical pumping of metastable 3He atoms has been shown to produce enormous polarization in the order of 0.4-0.6. This is about 10(5) times greater than the polarization of water protons at thermal equilibrium used at conventional MR imaging. We demonstrate that hyperpolarized 3He gas can be applied to nuclear MR imaging of human organs with air-filled spaces. In vivo 3He MR experiments were performed in a whole-body MR scanner with a superconducting magnet ramped down to 0.8 T and at 1.5 T using a double resonant Helmholtz coil operating at 63.6 and 48.6 MHz for 1H and 3He, respectively. Anatomical details of the lungs of a volunteer were visualized with the FLASH technique demonstrating the potential of the method for fast imaging of airways in the human body and for pulmonary ventilation studies.
Identification of TOSO/FAIM3 as an Fc receptor for IgM (2009)

Fc receptors specifically bind to the Fc region of Igs to mediate the unique functions to each class of Igs. To identify a novel Fc receptor for IgM, we searched expressed sequence tag database for molecules containing Ig domains with homology to those of known Fc receptors for IgM, Fcalpha/muR and polymeric Ig receptor. As a result, we identified TOSO/Fas apoptotic inhibitory molecule 3 (FAIM3) as a possible Fc receptor for IgM. HeLa cells transfected with a TOSO/FAIM3-expression vector bound to IgM but not IgG and were able to internalize IgM-conjugated beads but not IgG-conjugated beads, suggesting that TOSO/FAIM3 is indeed a receptor for IgM (FcmuR). FcmuR protein was expressed predominantly on B-lineage cells; expression of the Fcmr transcripts was observed from the pre-B-cell stage and maintained thereafter during B-cell development. These results identify TOSO/FAIM3 as a receptor for IgM and suggest that FcmuR may serve as an uptake receptor for IgM-opsonized antigens by B cells.
The Liver: Biology and Pathobiology. (1983)

INTRODUCTION Organizational PriciplesEmbryonic Development of the Liver THE CELLS Gap and Tight Junctions in Liver:Composition, Regulation, and FunctionMotor MoleculesGene Regulation and In Vivo Function of Liver Transcription FactorsThe Hepatocyte Plasma Membrane:Organization, Differentiation, Biogenesis,and TurnoverHepatocyte Basolateral Membrane Organic Anion TransportersThe Hepatocyte Surface:Dynamic PolarityThe Endoplasmic Reticulum and Golgi Complex in Secretory Membrane TransportMolecular Mechanisms of Hepatocellular Vesicle FormationReceptor-Mediated EndocytosisPeroxisomal Assembly, Biology, and Disease Relationship SECTION A: HEPATOCYTE:METABOLISM Integrated Cell Function:ApoptosisFundamentals of Cellular OsmoregulationRoles of Intracellular Proteolysis in Hepatocyte Cell-Cycle,Aging, and Programmed Cell DeathRegulation of Hepatic Cholesterol HomeostasisLeptin and the LiverHypoxic, Ischemic, and Reperfusion Injury to LiverProtective Mechanisms Against Reactive oxygen SpeciesDisorders of Bilirubin MetabolismThe PorphyriasCopper Metabolism and the LiverThe Liver and Iron SECTION B:BILE SECRETION The Biology of the Bile CanaliculusConjugate Export Pumps of the Multidrug Resistance Protein (MRP) Family in LiverGenetic Defects of Canalicular TransportHormonal Regulation of Bile SecretionNucleotide Transport and Regulation of Bile FormationThe Pathobiology of Biliary Epithelia SECTION C:SINUSOIDAL CELLS Endothelial and Pit CellsHepatic Stellate Cells:Morphology, Function, and Regulation SECTION D:EXTRACELLULAR MATRIX The Extracellular Matrix of the LiverIntegrins INTERRELATED CELL FUNCTIONS Role of Inositol Trisphosphate and Diacylglycerol in the Regulation of Liver FunctionSynthesis of an Signaling Through D-3 PhosphoinositidesInsulin and Other Growth FactorsCyclic AMP Signaling in the Liver:Coupling Transcription to Psysiology and ProliferationCA2+ Signaling in the LiverNitric Oxide in the LiverInterleukin-6 Signaling During the Acute-Phase Response of the LiverInnate Immune Sensing and the Toll-Like ReceptorsLiver RegenerationHepatocyte Growth Factor:Its Role in Hepatic Growth and Pathobiology THE ORGANRELATION TO OTHER ORGANSHepatic EncephalopathyAlterations of the Kidney in Liver Disease PATHOBIOLOGIC ANLYSISMolecular Pathophysiology of Membrane Transport Function in CholestasisThe Biology of Portal Hypertension1-Antitrypsin DeficiencyPathophysiology of Liver FibrosisAlcoholic and Nonalcoholic SteatohepatitisSchistosomiasis:A Model of Immunologically Mediated Liver DiseaseImmune Mechanisms of Viral Clearance, and Disease Pathogenesis During Viral HepatitisEpidemiology, Natural History, and Prevention of Viral HepatitisMolecular Bases of Hepatitis B and Hepatitis C Related Chronic Liver DiseaseMolecular Biology of Hepatitis VirusesLiver Transplantation:Factors Affecting the Balance Between Tolerance and Rejection in Experimental ModelsViral Hepatitis:Antiviral Therapy HORIZONSTissue Engineering of the LiverA Genomic View of Hepatology:Th
The Natural History of Complex Regional Pain Syndrome (2009)

This study shows that although CRPS is a progressive disease, after 1 year, the majority of the signs and symptoms were well developed and although many variables worsen over the course of the illness, the majority demonstrated only moderate increases with disease duration.
Molecular events in the induction of a nonresponsive state in interleukin 2-producing helper T-lymphocyte clones. (1987)

Exposure of normal interleukin 2 (IL-2)-producing helper T-cell clones to antigen and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-treated antigen-presenting cells results in proliferative unresponsiveness to subsequent stimulation with antigen and normal antigen-presenting cells. In the present study, we have examined the molecular events that accompany the induction of this unresponsive state. T cells stimulated in this manner failed to produce IL-2, but interleukin 3, interferon-gamma, and IL-2 receptors were partially induced and T-cell receptor beta mRNA was fully induced. Although T-cell unresponsiveness correlated with an IL-2 production defect, addition of IL-2 during the induction phase failed to prevent development of the unresponsive state. The critical biochemical event appeared to be an increase in intracellular calcium. Removal of calcium from the medium prevented induction of the unresponsive state, whereas addition of the calcium ionophore ionomycin induced unresponsiveness as well as all of the related partial activation events. Thus, an increase in intracellular calcium under nonmitogenic conditions appears to initiate an alternative activation program that prevents the T cell from producing IL-2 in response to subsequent normal activation signals. The significance of this in vitro model for tolerance induction in vivo is discussed.
Clinicopathological significance of LAT1 and ASCT2 in patients with surgically resected esophageal squamous cell carcinoma (2016)

High expression of LAT1 and ASCT2 correlates with metastasis and invasion. Accordingly, these proteins could serve as prognostic biomarkers and therapeutic targets for treating patients with surgically resectable ESCC. J. Surg. Oncol. 2016;113:381-389. © 2016 Wiley Periodicals, Inc.
Selective G Protein Coupling by C-C Chemokine Receptors (1996)

The C-C chemokines are major mediators of chemotaxis of monocytes and some T cells in inflammatory reactions. The pathways by which the C-C chemokine receptors activate phospholipase C (PLC) were investigated in cotransfected COS-7 cells. The C-C chemokine receptor-1 (CKR-1), the MCP-1 receptor-A (MCP-1Ra), and MCP-1Rb can reconstitute ligand-induced accumulation of inositol phosphates with PLC beta2 in a pertussis toxin-sensitive manner, presumably through G beta gamma released from the Gi proteins. However, these three receptors demonstrated different specificity in coupling to the alpha subunits of the Gq class. While none of the receptors can couple to Galphaq/11, MCP-1Rb can couple to both Galpha14 and Galpha16, but its splicing variant, MCP-1Rb, cannot. Since MCP-1Ra and -b differ only in their C-terminal intracellular domains, the C-terminal ends of MCP-1Rs determine G protein coupling specificity. CKR-1 can couple to Galpha14 but not to Galpha16, suggesting some of the C-C chemokine receptors, unlike the C-X-C chemokine receptors, discriminate against Galpha16, a hematopoietic-specific Galpha subunit. The intriguing specificity in coupling of the Gq class of G proteins implies that the chemokines may be involved in some distinct functions in vivo. The commonality of the chemokine receptors in coupling to the Gi-Gbetagamma-PLC beta2 pathway provides a potential target for developing broad spectrum anti-inflammatory drugs.
Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Oxysterols block transport by binding to Insig (2007)

Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells.
Control of radiation-induced pneumopathy and lung fibrosis by angiotensin-converting enzyme inhibitors and an angiotensin II type 1 receptor blocker (2000)

ACE inhibitors and one AII type 1 receptor blocker were effective in protecting lungs from radiation-induced pneumonitis and the development of lung fibrosis in two models of rat radiation injury. In the first series of experiments (unilateral irradiation), those ACE inhibitors containing a sulphydryl radical were more effective than those without it. This observation led to the question of whether this protective effect is related to inhibition of AII synthesis or rather to some of the collateral pharmacologic properties of these drugs, such as anti-oxidation or protease inhibition. The AII receptor blocker, however, was shown to be equally effective, if not better, in its antifibrotic capacity than any ACE inhibitor with or without an SH radical, reaffirming the role of AII in modulation of collagen synthesis.
Constructing gene models from accurately predicted exons: an application of dynamic programming (1994)

This paper presents a computationally efficient algorithm, the Gene Assembly Program III (GAP III), for constructing gene models from a set of accurately-predicted 'exons'. The input to the algorithm is a set of clusters of exon candidates, generated by a new version of the GRAIL coding region recognition system. The exon candidates of a cluster differ in their presumed edges and occasionally in their reading frames. Each exon candidate has a numerical score representing its 'probability' of being an actual exon. GAP III uses a dynamic programming algorithm to construct a gene model, complete or partial, by optimizing a predefined objective function. The optimal gene models constructed by GAP III correspond very well with the structures of genes which have been determined experimentally and reported in the Genome Sequence Database (GSDB). On a test set of 137 human and mouse DNA sequences consisting of 954 true exons, GAP III constructed 137 gene models using 892 exons, among which 859 (859/954 = 90%) are true exons and 33 (33/892 = 3%) are false positive. Among the 859 true positives, 635 (74%) match the actual exons exactly, and 838 (98%) have at least one edge correct. GAP III is computationally efficient. If we use E and C to represent the total number of exon candidates in all clusters and the number of clusters, respectively, the running time of GAP III is proportional to (E x C).
Inhibition of Rabbit Brain Prolyl Endopeptidase by N‐Benzyloxycarbonyl‐Prolyl‐Prolinal, a Transition State Aldehyde Inhibitor (1983)

Prolyl endopeptidase cleaves peptide bonds on the carboxyl side of proline residues within a peptide chain. The enzyme readily degrades a number of neuropeptides including substance P, neurotensin, thyrotropin-releasing hormone, and luteinizing hormone-releasing hormone. The finding that the enzyme is inhibited by benzyloxycarbonyl-prolyl-proline, with a Ki of 50 microM, prompted the synthesis of benzyloxycarbonyl-prolyl-prolinal as a potential transition state analog inhibitor. Rabbit brain prolyl endopeptidase was purified to homogeneity for these studies. The aldehyde was found to be a remarkably potent inhibitor of prolyl endopeptidase with a Ki of 14 nM. This Ki is more than 3000 times lower than that of the corresponding acid or alcohol. By analogy with other transition state inhibitors, it can be assumed that binding of the prolinal residue to the S1 subsite and the formation of a hemiacetal with the active serine of the enzyme greatly contribute to the potency of inhibition. The specificity of the inhibitor is indicated by the finding that a variety of proteases were not affected at concentrations 150 times greater than the Ki for prolyl endopeptidase. The data indicate that benzyloxycarbonyl-prolyl-prolinal is a specific and potent inhibitor of prolyl endopeptidase and that consequently it should be of value in in vivo studies on the physiological role of the enzyme.
Humoral immune response in disease‐free advanced melanoma patients after vaccination with melanoma‐associated gangliosides (1991)

Several studies have shown that melanoma-associated gangliosides are immunogenic in melanoma patients and that antibodies against them have a favorable prognostic effect. Our study aims at characterizing the humoral immune response in disease-free, advanced melanoma patients vaccinated with a total ganglioside fraction extracted from pooled metastases of human melanoma, containing as major gangliosides GM3 and GD3, and as minor ones GM2 and GD2. Prior to vaccination, all patients were made disease-free by surgical removal of skin, lymph-node or other distant metastases. Repeated vaccinations were carried out intradermally with gangliosides either in the native form in buffered solution, or in the form of liposomes. Serum samples were collected at regular intervals and assayed by ELISA for the presence of specific IgG and IgM antiganglioside antibodies. Selected samples were tested by immunostaining on thin-layer plates to specify the ganglioside species involved in the reactivity. Out of 32 evaluable patients, 17 presented a significant increase in antibody titer, mostly of the IgG isotype, which was maximal between 2 and 4 months after starting injections of gangliosides, and gradually disappeared within 1 year. No significant difference could be seen between the group of 20 patients treated with native gangliosides and the group of 12 vaccinated with the gangliosides in liposomes. All gangliosides seemed to be immunogenic, but GM2 and GD2 were somewhat more reactive. The disease-free intervals for the patients who showed an antibody response to the treatment were significantly higher (p less than 0001) than those of the non-responding group, as compared by the Kaplan-Meier method.
Is Radar Cardiography (RCG) Possible? (2019)

In this paper, we propose a novel concept of Radar Cardiography (RCG). We demonstrate the ability to achieve precise heartbeat measurement wirelessly using advanced radar signal processing technique. We show that the reconstructed heartbeat waveform matches the reference electrocardiography (ECG) signal. We propose a new heartbeat monitoring method, in which we isolate cardiovascular activity from strong respiratory-inference in the 3-Dimensional (3-D) spaces: azimuth, elevation, and depth. With significant pulse signal-to-noise-ratio (SNR) improvement compared to the conventional radar approach, heart-rate variability (HRV) analysis using radar is therefore possible.
Aberrant methylation of heparan sulfate glucosamine 3-O-sulfotransferase 2 genes as a biomarker in colorectal cancer. (2010)

These results may show the possibility of early detection for CRC by examining 3OST2 gene methylation status in DNA extracted from stool.
Sensors for detecting biological agents (2008)

Biological agents including viruses, bacteria, and other naturally occurring pathogenic organisms, along with the toxins they produce, are considered far harder to detect and defend against than chemical agents. Here we provide an overview of the predominant molecular sensing technologies for the detection of these agents. This includes biosensing strategies based upon use of antibodies, genomic analysis, biochemical testing, other recognition interactions, and cellular-based responses. We survey some popular sensing approaches, illustrate them with current examples showing how they have been applied, and discuss their intrinsic benefits and potential liabilities. Lastly, within the context of security applications, some approaches for integrating sensing technologies into field-portable devices are discussed.
Recent Progress in Aqueous Lithium‐Ion Batteries (2012)

Abstract Building a low‐carbon society supported by sustainable energy is a worldwide topic. The aqueous lithium‐ion battery (LIB) has been demonstrated to be one of the most promising stationary power sources for sustainable energies such as wind and solar power. The aqueous LIB may solve both the safety problem associated with the lithium‐ion batteries which use highly toxic and flammable organic solvents, and the poor cycling life associated with commercialized aqueous rechargeable batteries including lead‐acid and nickel‐metal‐hydride systems. During the past decades, many efforts have been made to improve the performance of the aqueous lithium‐ion battery. The present work reviews the latest advances in the exploration and development of battery systems and relative materials. Also the main approaches, achievements, and challenges in this field are briefly commented on and discussed.