gebhart/patrepeval huggingface dataset:
Different Mechanisms Mediate Development and Expression of Tolerance and Dependence for Peripheral μ-Opioid Antinociception in Rat (1997)

The mu-opioid [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAMGO) exerts a peripheral antinociceptive effect against prostaglandin E2 (PGE2)-induced mechanical hyperalgesia in the hindpaw of the rat. Tolerance and dependence develop to this effect. We have shown previously that tolerance and dependence can be dissociated and are mediated by different second messenger systems. In the present study, we evaluated whether the same or different second messenger systems mediate the development of this peripheral opioid tolerance or dependence compared with the expression of the loss of antinociceptive effect or rebound opioid antagonist hyperalgesia (i. e., expression of tolerance and dependence). DAMGO-induced tolerance was prevented by pretreatment with the nitric oxide synthase inhibitor NG-methyl-L-arginine (NMLA) but not by the protein kinase C (PKC) inhibitor chelerythrine, the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (ddA), or the calcium chelators 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester (TMB-8) and 2-[(2-bis-[carboxymethyl]amino-5-methylphenoxy)-methyl]-6-methoxy-8-bis [carboxymethyl]aminoquinoline (Quin-2). Once established, however, expression of DAMGO tolerance was acutely reversed by TMB-8 or Quin-2 but not by chelerythrine or NMLA. In contrast, naloxone-precipitated hyperalgesia in DAMGO-tolerant paws, a measure of dependence, was blocked by pretreatment with chelerythrine but not by NMLA, ddA, TMB-8, or Quin-2. Naloxone-precipitated hyperalgesia in DAMGO-tolerant paws was acutely reversed by chelerythrine, ddA, TMB-8, or Quin-2 but not by NMLA. Taken together, these results provide the first evidence that different mechanisms mediate the development and expression of both tolerance and dependence to the peripheral antinociceptive effect of DAMGO. However, although the development of tolerance and dependence are entirely separable, the expression of tolerance and dependence shares common calcium-dependent mechanisms.
Multiple Extracellular Signals Promote Osteoblast Survival and Apoptosis (1997)

Programed cell death (PCD) or apoptosis is a naturally occurring cell suicide pathway induced in a variety of cell types. In many cases, PCD apparently arises as a result of competition for limiting amounts of survival signals. In this study, we have investigated the potential role of growth factors (GF), cytokines, and osteotropic hormones on osteoblast survival in vitro. Our results indicate that in the absence of any of these factors, osteoblasts rapidly undergo PCD, as determined by cell morphology, mitochondrial function, and nuclei fragmentation. Osteoblast survival was promoted by insulin-like growth factor I (IGF-I), IGF-II, insulin, and basic fibroblast growth factor (bFGF). Platelet-derived growth factor had no effect on osteoblast survival, but this GF potentiated the survival-promoting effects of IGF-I, IGF-II, and insulin. A similar effect occurred when bFGF was added in combination with either of the IGFs or insulin. The effects of the IGFs were blocked by αIR-3, an antibody to the type I IGF receptor, whereas the effects of insulin were only partially blocked. This antibody blocked the potentiating effects of platelet-derived growth factor on IGF-I-mediated osteoblast survival, but only partially blocked those of bFGF. Although a 100% survival of osteoblasts was seen in the presence of 2% FCS, the highest level attained by any of the above GF combinations was ∼75%. The monocyte-derived factor, tumor necrosis factor-α (TNFα) was the only agent that enhanced PCD in this study. These results suggest that osteoblast survival is promoted by those GFs sequestrated in bone matrix and that the type I, but not the type II, IGF receptor is involved in the response. Our data also indicate that other unidentified GFs or components of the extracellular matrix may be involved in promoting osteoblast survival and that TNFα may abrogate their effects in vivo. We propose that these GFs may be released from bone matrix during phases of bone resorption and promote osteoblast survival, thereby playing an important role in bone remodeling, and that PCD induced by TNFα may contribute to the bone loss in inflammatory bone disease.
A graph-based system for network-vulnerability analysis (1998)

This paper presents a graph-based approach to network vulnerability analysis. The method is flexible, allowing analysis of attacks from both outside and inside the network. It can analyze risks to a specific network asset, or examine the universe of possible consequences following a successful attack. The graph-based tool can identify the set of attack paths that have a high probability of success (or a low "effort" cost) for the attacker. The system could be used to test the effectiveness of making configuration changes, implementing an intrusion detection system, etc.
A practical protective relay for down-conductor faults (1991)

A practical relay for detecting down-conductor high-impedance ground faults (HIGF) is described, with supporting theory and data from live line tests. The use of the third-harmonic current magnitude and the phase relation to the system voltage is shown to provide useful information for detecting this type of fault. By suppressing ambient harmonics and utilizing only the change in the harmonics, a fault current sensitivity of 1% of the feeder rating is shown to be feasible. Fault detection concepts include harmonic phase sequence components in the three-phase unit. Relays for both single-phase laterals and three-phase circuits are described. Redundant measurement techniques in both versions are shown to enhance the reliability of the system and to contribute to the feasibility of the noted sensitivity.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-κB in mouse skin by blocking IκB kinase activity (2006)

Aberrant expression of cyclooxygenase-2 (COX-2) has been implicated in tumor promotion. Resveratrol, a phytoalexin present in grapes, was reported to inhibit multistage mouse skin carcinogenesis. In the present study, we found that topically applied resveratrol significantly inhibited COX-2 expression induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Resveratrol-suppressed phosphorylation and subsequent degradation of IkappaBalpha, thereby inhibiting activation of nuclear factor-kappaB (NF-kappaB) in TPA-stimulated mouse skin. Pretreatment with resveratrol also suppressed TPA-induced phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 mitogen-activated protein (MAP) kinase. Resveratrol blunted TPA-induced phosphorylation of p65 and its interaction with CBP/p300, rendering NF-kappaB transcriptionally inactive. To get further insights into the molecular basis of NF-kappaB inactivation by resveratrol, we examined the role of IkappaB kinase (IKK) in mediating TPA-induced activation of NF-kappaB and COX-2 expression. TPA treatment led to rapid induction of IKK activity in mouse skin, which was abolished either by resveratrol or an IKK inhibitor Bay 11-7082. Topical application of Bay 11-7082 also abrogated TPA-induced NF-kappaB activation and COX-2 expression, supporting the involvement of IKK in TPA-induced COX-2 expression. Taken together, the above findings suggest that resveratrol targets IKK in blocking TPA-induced NF-kappaB activation and COX-2 expression in mouse skin in vivo.
Maximizing Learner Autonomy Through Reflective Teaching (2013)

In The Bible Christians are likened as salt by Jesus. But if they lose the salt-like flavor and become useless, they will be thrown away, and be trodden under the feet of men. This article aims to analyze the causes and results of the lost taste of salt and explore that Christians, although suffering, yet becoming victorious in a difficult environment, will be blessed, be rich in the taste of salt and live a valued life.
Geographic information systems and cartography (1990)

The GIS phenomenon shows no sign of weakening, but cannot last for ever. The paper addresses the long-term significance of GIS from three perspectives. First, the various application fields are reviewed and used to define four views of GIS. Second, the paper looks at some new and continuing debates in GIS and their significance for cartography. The third section of the paper discusses the search for an intellectual core for GIS, and the role of the US National Science Foundation's National Center for Geographic Information and Analysis.
Diverse Functional Roles of Reactive Cysteines (2012)

Cysteine residues on proteins play key roles in catalysis and regulation. These functional cysteines serve as active sites for nucleophilic and redox catalysis, sites of allosteric regulation, and metal-binding ligands on proteins from diverse classes including proteases, kinases, metabolic enzymes, and transcription factors. In this review, we focus on a few select examples that serve to highlight the multiple functions performed by cysteines, with an emphasis on cysteine-mediated protein activities implicated in cancer. The enhanced reactivity of functional cysteines renders them susceptible to modification by electrophilic species. Toward this end, we discuss recent advancements and future prospects for utilizing cysteine-reactive small molecules as drugs and imaging agents for the treatment and diagnosis of cancer.
First Cross-Coupling Reaction of Potassium Aryltrifluoroborates with Organic Chlorides in Aqueous Media Catalyzed by an Oxime-Derived Palladacycle (2008)

Potassium aryltrifluoroborates are cross-coupled with aryl and heteroaryl chlorides using a 4-hydroxyacetophenone oxime-derived palladacycle as precatalyst, K2CO3 as base, and TBAB as additive in refluxing water under conventional and microwave heating affording the corresponding biphenyls under phosphine-free conditions. For the arylation of allyl and benzyl chlorides, KOH is used as base in acetone-water (3:2) at rt or 50 degrees C using 0.1 mol % Pd loading providing allylbenzenes and diarylmethanes, respectively.
Combined Elemental and Biomolecular Mass Spectrometry Imaging for Probing the Inventory of Tissue at a Micrometer Scale (2012)

Several complementary mass spectrometric imaging techniques allow mapping of various analytes within biological tissue sections. Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) quantitatively detects elements and isotopes with very high sensitivity and a particularly high dynamical range. Matrix-assisted laser desorption/ionization ion mobility mass spectrometry (MALDI-IM-MS) allows a pixel-by-pixel classification and identification of biomolecules. In order to dispose of the healthy hemisphere as an internal calibrant in addition to routinely used external standards, adjacent brain sections of mice with a unilateral 6-OHDA lesion of the medial forebrain bundle were chosen as exemplary samples. We demonstrate a comprehensive way of data acquisition and analysis by coregistering mass spectrometric data on photomicrographs as common reference space and thus providing trimodal spatial information. Registering subsequent planar element maps yielded continuous 3-dimensional data sets. Furthermore, we introduce a correction of MSI data for variable slice thickness applicable to all MSI techniques. In the present case, we observed increased concentrations of iron, manganese, and copper in the lesioned substantia nigra while monounsaturated lipid levels were decreased in the identical region of interest. Our techniques provide new insights into the intricate spatial relationship of morphology and chemistry within tissue.
Diagnosis: Psoriasis or not? What are the clues? (1999)

Psoriasis is a common inflammatory, hyperproliferative skin disorder that affects 1% to 2% of the population of Western Europe and the United States. Because the clinical presentation of psoriasis is varied, many times the definitive diagnosis depends on the histological examination. However, the histological changes of psoriasis are as varied as the clinical presentations. Therefore, a combination of histopathologic features must be present for the diagnosis of psoriasis to be made. In this article, we review the clues for the histopathologic diagnosis of each type and stage of psoriasis, such as psoriasis vulgaris, pustular psoriasis, and erythrodermic psoriasis, as well as the histopathologic differential diagnosis of these entities.
Negative-electron-affinity effect on the surface of chemical-vapor-deposited diamond polycrystalline films (1996)

Strong negative-electron-affinity effects have been observed on the surface of as-grown chemical-vapor-deposited diamond using secondary-electron emission. The samples were randomly oriented polycrystalline diamond films terminated with hydrogen. The effect appears as an intensive peak in the low-energy part of the spectrum of the electron energy distribution and may be described in the model of effective negative electron affinity.
Porcine Malignant Hyperthermia (1990)

Malignant hyperthermia (MH) can be triggered in swine either by stress or by certain anesthetic agents. In humans, MH commonly occurs in patients previously exposed uneventfully to triggering anesthetics. This variability in expressivity of the MH syndrome is a combination of unknown genetic and environmental factors. A hypothesis was tested that a fall in rectal temperature following general anesthesia can prevent the MH syndrome in susceptible patients. Nine littermate Pietrain pigs with MH were exposed to halothane after their rectal temperatures were stabilized at 35 degrees, 36 degrees, and 37 degrees C during thiopental/nitrous oxide anesthesia. The in vivo MH metabolic, cardiopulmonary, and contracture responses were attenuated at the lower rectal temperatures. The effect of varying temperatures on biopsies of skeletal muscle from these animals showed a marked decrease in contracture response to halothane when the muscle was cooled to 25 degrees C. Studies on the Ca2+ uptake process and on Ca2+ channel-Ca2+ release properties of isolated sarcoplasmic reticulum (SR) membranes showed that increasing incubation temperatures from 25 degrees to 38 degrees C increased the Ca2+ uptake rate by the SR Ca2+ pump and also increased the probability of Ca2(+)-induced Ca2+ opening of a Ca2+ channel and the release of stored Ca2+. This study indicates that temperature can have a marked effect on the expressivity of the MH defect at the whole animal, isolated tissue, and fragmented membrane levels of organization. Since many surgical patients' temperatures decrease after induction and anesthesia, this may explain one environmental factor that determines the incidence, rate, and magnitude of the MH syndrome.
Synthesis of Novel Diarylpyrimidine Analogues and Their Antiviral Activity against Human Immunodeficiency Virus Type 1 (2004)

This paper reports the synthesis and the antiviral properties of new diarylpyrimidine (DAPY) compounds as nonnucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis program around this new DAPY series was further optimized to produce compounds displaying improved activity against a panel of eight clinically relevant single and double mutant strains of human immunodeficiency virus type 1 (HIV-1).
Higher Frequency of Certain Cancers inLRRK2G2019S Mutation Carriers With Parkinson Disease (2014)

This multinational study from 5 centers demonstrates that LRRK2 G2019S mutation carriers have an overall increased risk of cancer, especially for hormone-related cancer and breast cancer in women. Larger prospective cohorts or family-based studies investigating associations between LRRK2 mutations and cancer among patients with PD are warranted to better understand the underlying genetic susceptibility between PD and hormone-related cancers.
Cellular activation of latent transforming growth factor beta requires binding to the cation-independent mannose 6-phosphate/insulin-like growth factor type II receptor. (1991)

The activation of latent transforming growth factor beta (LTGF-beta) normally seen in cocultures of bovine aortic endothelial and bovine smooth muscle cells can be inhibited by coculturing the cells with either mannose 6-phosphate (Man-6-P) or antibodies directed against the cation-independent Man-6-P/insulin-like growth factor type II receptor (anti-Man-6-PR). This result was established by measuring the ability of coculture conditioned medium (formed with or without Man-6-P or anti-Man-6-PR) to suppress bovine aortic endothelial cell migration and protease production, activities previously shown to be related to transforming growth factor beta activity. The inhibition by Man-6-P is dose dependent, with maximal inhibition seen at 100 microM and is specific because mannose 1-phosphate and glucose 6-phosphate do not interfere with activation of LTGF-beta. The inhibitory effect of anti-Man-6-PR is also specific and dose dependent; maximal inhibition of activation occurs at 400 micrograms/ml. Control experiments indicate that Man-6-P and anti-Man-6-PR do not interfere with the basal level of migration of bovine aortic endothelial cells, the migration observed when exogenous transforming growth factor beta is added, the activation of transforming growth factor beta by plasmin or transient acidification, and the release of LTGF-beta. Thus, binding to the cation-independent Man-6-P/insulin-like growth factor type II receptor appears to be a requirement for activation of LTGF-beta.
The Linkage Between Protein Folding and Functional Cooperativity: Two Sides of the Same Coin? (2002)

During the course of their biological function, proteins undergo different types of structural rearrangements ranging from local to large-scale conformational changes. These changes are usually triggered by their interactions with small-molecular-weight ligands or other macromolecules. Because binding interactions occur at specific sites and involve only a small number of residues, a chain of cooperative interactions is necessary for the propagation of binding signals to distal locations within the protein structure. This process requires an uneven structural distribution of protein stability and cooperativity as revealed by NMR-detected hydrogen/deuterium exchange experiments under native conditions. The distribution of stabilizing interactions does not only provide the architectural foundation to the three-dimensional structure of a protein, but it also provides the required framework for functional cooperativity. In this review, the statistical thermodynamic linkage between protein stability, functional cooperativity, and ligand binding is discussed.
Promoting Open Innovations in Real Estate Tech (2018)

The LIFULL HOME'S Data Set, which is provided for academic use since November 2015, is being used for research in a variety of fields such as economics, architecture, urban science and so on. In particular, since it contains 83 million object property images and 5.1 million floor plan images, utilization in the computer vision and multimedia field is thriving, and papers using data sets are also adopted at the top conference ICCV 2017 in the image processing field it is. This presentation summarizes the results that have been obtained through the provision of datasets, and shows plans to promote open innovation in the field of real estate technology.
Characterization of the membrane quinoprotein glucose dehydrogenase from Escherichia coli and characterization of a site-directed mutant in which histidine-262 has been changed to tyrosine (1999)

The requirements for substrate binding in the quinoprotein glucose dehydrogenase (GDH) in the membranes of Escherichia coli are described, together with the changes in activity in a site-directed mutant in which His262 has been altered to a tyrosine residue (H262Y-GDH). The differences in catalytic efficiency between substrates are mainly related to differences in their affinity for the enzyme. Remarkably, it appears that, if a hexose is able to bind in the active site, then it is also oxidized, whereas some pentoses are able to bind (and act as competitive inhibitors), but are not substrates. The activation energies for the oxidation of hexoses and pentoses are almost identical. In a previously published model of the enzyme, His262 is at the entrance to the active site and appears to be important in holding the prosthetic group pyrroloquinoline quinone (PQQ) in place, and it has been suggested that it might play a role in electron transfer from the reduced PQQ to the ubiquinone in the membrane. The H262Y-GDH has a greatly diminished catalytic efficiency for all substrates, which is mainly due to a marked decrease in their affinities for the enzyme, but the rate of electron transfer to oxygen is unaffected. During the processing of the PQQ into the apoenzyme to give active enzyme, its affinity is markedly dependent on the pH, four groups with pK values between pH7 and pH8 being involved. Identical results were obtained with H262Y-GDH, showing that His262 it is not directly involved in this process.
Early Detection of Sporadic Pancreatic Cancer (2015)

Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.