gebhart/patrepeval huggingface dataset:
Antioxidant activity of O-protected derivatives of (-)-epigallocatechin-3-gallate: inhibition of soybean and rabbit 15-lipoxygenases (2006)

was protected at all eight phenolic groups as the methyl ether or acetate, propionate or butyrate esters. The synthetic derivatives were examined for antioxidant activities. The compounds were tested as potential diphenylpicrylhydrazyl (DPPH) radical scavengers and as inhibitors of 15-lipoxygenase (15-LO) enzymes from soybeans and rabbit reticulocytes. The O-protected EGCG derivatives were essentially inactive as DPPH scavengers but showed profound inhibiting effects on both types of 15-LO, and the inhibitory effects towards the two enzymes were significantly correlated. The O-protected EGCG derivatives inhibited 15-LO more strongly that EGCG itself. EGCG and its O-protected derivatives were also screened for antibacterial activity against M. tuberculosis.
Vascular endothelial growth factor C expression and lymph node metastasis are regulated by the type I insulin-like growth factor receptor. (2003)

Vascular endothelial growth factor (VEGF)-C is a lymphangiogenic factor implicated in lymphatic metastasis. In this study, we investigated the role of the type I insulin-like growth factor receptor (IGF-IR) in the regulation of VEGF-C expression. We used Lewis lung carcinoma subline M-27 cells transfected with human IGF-IR cDNA. These cells, but not the wild-type cells, expressed VEGF-C mRNA, produced a M(r) 58,000 VEGF-C precursor protein, and secreted a M(r) 29,000 processed form in response to IGF-I. In vivo, they acquired a lymph node metastasizing potential. VEGF-C induction was abolished in cells expressing an IGF-IR with tyrosine-phenylalanine substitutions in the kinase domain, but not in the COOH-terminal domain. The induction was phosphatidylinositol 3'-kinase dependent and, to a lesser extent, mitogen-activated protein kinase signaling dependent, as determined by the use of the respective inhibitors LY294002 (84.6% reduction) and PD98059 (38% reduction). The results identify the IGF-IR as a positive regulator of VEGF-C expression and implicate it in the control of lymphatic metastasis.
Anti-TNF agents in Crohn’s disease (2000)

The current treatment of Crohn's disease is limited by a lack of long-term efficacy of corticosteroid therapy and the associated side effects. Biological treatment strategies aimed at neutralising immune responses, offer new opportunities for the management of chronic inflammatory disorders. In Crohn's disease, anti-TNF agents have taken the lead in development of immune-modulating drugs since TNF is known to be a pivotal cytokine in this illness. Different strategies have been explored aimed at inhibiting TNF but at present, the majority of clinical data have been obtained with monoclonal antihuman TNF antibodies. The chimeric anti-TNF IgG1 antibody infliximab (cA2, Remicade, Centocor) has been proven, in multiple clinical trials, to be an effective and well tolerated therapy for the management of acute Crohn's disease and recently this compound has obtained FDA and European Medicines Evaluation Agency approval. Although there are some concerns about immunogenicity of the anti-TNF antibody resulting in the formation of human antichimeric antibodies (HACA) as well as lymphoproliferative disorders, the clinical benefit in the treatment of refractory Crohn's disease is a major therapeutic breakthrough. Further studies will be needed to establish the role and optimal dosing scheme of anti-TNF antibodies in maintenance of remission, monitor safety in the long run and to evaluate the effectiveness of alternative anti-TNF agents such as the TNF receptor/Fc fusion protein etanercept (Enbrel, Immunex) and TNF synthesis inhibitor thalidomide.
Small molecules that bind the Mdm2 RING stabilize and activate p53 (2012)

p53 is a tumor suppressor that responds to a variety of stresses such as oncogenes and DNA damage by activating its transcriptional targets to allow repair or elimination of damaged cells. In the absence of stress signals, p53 needs to be kept in check and this is achieved by the E3 ligase MDM2. For tumors that retain wild-type p53, therapeutic strategies aimed at removing the inhibitory activity of MDM2 on p53 are under development and to date have focused on drugs that prevent the binding of p53 to MDM2. Here, we report the analysis of a group of synthetic analogs derived from 5-deazaflavin compounds previously identified in a screen as inhibitors of MDM2 autoubiquitination. Using measurement of surface plasmon resonance, we demonstrated that active 5-deazaflavin analogs bind to the MDM2 RING, whereas inactive compounds show no binding. In cellular assays, these active MDM2 RING binding compounds inhibited the ubiquitination of p53, stabilized p53, led to increased expression of p53 targets and caused corresponding cell cycle effects. Deazaflavin analogs therefore function to activate p53 through a novel mechanism, by inhibiting the E3 ligase activity of MDM2 in a manner that involves binding to the MDM2 RING.
Ocular Oxidants and Antioxidant Protection (1998)

Oxidative damage and antioxidant protection in ocular tissues has not been reviewed recently. Metabolism in the eye is of increasing interest because the organ is highly susceptible to damage by sunlight, oxygen, various chemicals, and pollutants. Interest is expected to increase because of an aging Western world population and a continued depletion of stratospheric ozone. Hydrogen peroxide is discussed because it is both a byproduct and a source of free radical reactions and is normally present in the aqueous humor. The metabolism of reactive oxygen species by enzymes, nutrients, pigments, and low molecular weight scavengers is evaluated. Ascorbic acid, because of its high concentration in the eye, is thought to be a primary substrate in ocular protection; progress in determining the mechanisms by which it is recycled and maintained in the useful, reduced state is discussed. Recent information is included about antioxidants not previously known to be present in the eye, and some importance is placed on the properties of the vitreous humor and tear fluid because of the previous lack of emphasis on these.
Adherence of Candida albicans to Silicone Induces Immediate Enhanced Tolerance to Fluconazole (2004)

Wild-type and efflux pump-deficient cells of Candida albicans adhering to silicone were compared with planktonic cells by flow cytometry for their relative resistance to fluconazole (FCZ). Flow cytometry data on cells carrying a fusion of green fluorescent protein to efflux pump promoters confirmed that enhanced tolerance of attached cells to FCZ was due in part to increased expression of CaMDR1 and CDR1 promoters. Within 2 h of their attachment to silicone, the adherent cells demonstrated levels of FCZ tolerance shown by cells from 24-h biofilms. Following their mechanical detachment, this subset of cells retained a four- to eightfold increase in tolerance compared with the tolerance of planktonic cells for at least two generations. Enhanced efflux pump tolerance to FCZ appeared to be induced within the initial 15 min of attachment in a subset of cells that were firmly attached to the substrata.
The clinicopathological significance of heparanase and basic fibroblast growth factor expressions in hepatocellular carcinoma. (2001)

Heparan sulfate plays an essential role for insolubility of the components of extracellular matrix and represents a storage depot for various growth factors. Therefore, heparanase produced by a given tumor may facilitate tumor invasiveness and angiogenesis through the release of heparan sulfate-bound growth factors. Although the growth factors responsible for angiogenesis in hepatocellular carcinoma (HCC) have recently been investigated, the clinicopathological significance of heparanase in connection with basic fibroblast growth factor (bFGF) expression in HCC has not been evaluated so far. Fifty-five patients who had undergone hepatic resection for HCC without preoperative treatment were included in the present study. Expression of heparanase mRNA was evaluated by reverse transcription-PCR, and bFGF was examined by Western blotting using a monoclonal antibody. Tumor angiogenesis was evaluated by immunostaining with a factor VIII-related monoclonal antibody. Expression of heparanase mRNA was detected in 47% of HCCs and was significantly correlated with larger tumor size (P = 0.01), presence of portal vein invasion (P = 0.01), and higher overall tumor invasiveness (P = 0.02). Moreover, its expression was correlated with tumor microvessel density (MVD; P = 0.02). There was a direct correlation between the levels of bFGF proteins and MVD in HCCs (P = 0.0001), and, furthermore, concomitant expression of bFGF and heparanase was associated with higher tumor MVD as compared with expression of either factor alone (P = 0.01). In conclusion, the expression of heparanase in HCC enhances growth, invasion, and angiogenesis of the tumor, and bFGF seems to be a potent angiogenic factor for HCC.
Rational Expectations in Stationary Linear Models (1981)

Linear time series models have come to dominate the macroeconomic literature on rational expectations and equilibrium business cycle theory. But the explicit solution of such models has generally required strong restrictions upon the exogenous process of stochastic shocks (e.g., temporal independence) as well as upon the values of various demand and supply elasticities. This paper exhibits a solution technique, the method of z-transforms, which does not require one to impose such restrictions. The value of this method is illustrated by applying it to completely characterize the symmetric, stationary, rational expectations equilibria of a naive linear model of land speculation. This approach also permits systematic study of the informationally asymmetric equilibria of the model. THIS PAPER develops a method for analyzing rational expectations (RE) equilibria in linear economic models. The methods I shall discuss usually enable one to determine whether or not a given model has a RE equilibrium and, if one exists, to exhibit an explicit expression for the stochastic process of equilibrium prices. The techniques apply to linear models driven by stationary processes of exogenous random shocks.
Avian gut-associated lymphoid tissues and intestinal immune responses to Eimeria parasites. (1996)

Coccidiosis, an intestinal infection caused by intracellular protozoan parasites belonging to several different species of Eimeria, seriously impairs the growth and feed utilization of livestock and poultry. Host immune responses to coccidial infection are complex. Animals infected with Eimeria spp. produce parasite-specific antibodies in both the circulation and mucosal secretions. However, it appears that antibody-mediated responses play a minor role in protection against coccidiosis. Furthermore, there is increasing evidence that cell-mediated immunity plays a major role in resistance to infection. T lymphocytes appear to respond to coccidial infection through both cytokine production and a direct cytotoxic attack on infected cells. The exact mechanisms by which T cells eliminate the parasites, however, remain unclear. Although limited information is available on the intestinal immune system of chickens, gut lymphoid tissues have evolved specialized features that reflect their role as the first line of defense at mucosal surfaces, including both immunoregulatory cells and effector cells. This review summarizes our current understanding of the avian intestinal immune system and mucosal immune responses to Eimeria spp., providing an overview of the complex cellular and molecular events involved in intestinal immune responses to enteric pathogens.
A sensitive ELISPOT assay for detection of CD8+ T lymphocytes specific for HLA class I-binding peptide epitopes derived from influenza proteins in the blood of healthy donors and melanoma patients. (1997)

An enzyme-linked immunospot (ELISPOT) assay was adapted to detect peptide-specific CD8+ T lymphocytes in peripheral blood mononuclear cells (PBMCs). In HLA-A1-, HLA-A2-, and/or HLA-A3-positive individuals, we determined the release of IFN-gamma on a single cell level in response to three different peptide epitopes derived from the influenza matrix protein and nuclear protein containing the HLA-A2.1- and HLA-A1- or HLA-A3-binding motif, respectively. Comparison of the ELISPOT assay with the standard chromium release assay revealed a close correlation between the number of peptide-specific IFN-gamma-releasing T cells in PBMCs and the level of specific cytotoxicity after 14 days of in vitro expansion. The ELISPOT assay detected T cells with specificity for the HLA-A2. 1-binding epitope derived from the matrix protein in 76% of HLA-A2-positive healthy individuals (n = 25); the median frequency was 41 in 10(6) PBMCs. We also detected peptide-specific T cells in 10 of 12 HLA-A2-positive patients with metastatic melanoma with a median frequency of 20.5 in 10(6) PBMCs. In 10 of 24 HLA-A3-positive individuals and in 2 of 14 HLA-A1-positive individuals, peptide-specific T cells for a HLA-A3- and a HLA-A1-binding epitope derived from the nucleoprotein, respectively, were present. In conclusion, the ELISPOT assay may be suitable to monitor a peptide-specific T-cell response in vaccination protocols using peptides derived from tumor or viral antigens.
Preventability of Invasive Pneumococcal Disease and Assessment of Current Polysaccharide Vaccine Recommendations for Adults: United States, 2001–2003 (2006)

Increasing vaccine coverage rates among persons with a current indication may prevent more cases than expanding existing indications. Of the potential new indications studied, the strategy that may prevent most cases is lowering the recommended age for universal vaccination to 50 years.
Syntheseversuche in der Emetin‐Reihe. 3. Mitteilung. 2‐Hydroxy‐hydrobenzo[a]chinolizine (1958)

Abstract The reduction of various 2‐oxo‐1,2,3,4,6,7‐hexahydro‐11b H ‐benzo[a]quinolizines substituted in 3‐position is described. Depending upon the method of reduction and the experimental conditions applied, either a sterically homogeneous carbinol or a mixture of two epimeric carbinols is obtained. Their stereochemistry is discussed. Various derivatives of these alcohols are described.
Tumor-associated macrophages: from basic research to clinical application (2017)

The fact that various immune cells, including macrophages, can be found in tumor tissues has long been known. With the introduction of concept that macrophages differentiate into a classically or alternatively activated phenotype, the role of tumor-associated macrophages (TAMs) is now beginning to be elucidated. TAMs act as "protumoral macrophages," contributing to disease progression. TAMs can promote initiation and metastasis of tumor cells, inhibit antitumor immune responses mediated by T cells, and stimulate tumor angiogenesis and subsequently tumor progression. As the relationship between TAMs and malignant tumors becomes clearer, TAMs are beginning to be seen as potential biomarkers for diagnosis and prognosis of cancers, as well as therapeutic targets in these cases. In this review, we will discuss the origin, polarization, and role of TAMs in human malignant tumors, as well as how TAMs can be used as diagnostic and prognostic biomarkers and therapeutic targets of cancer in clinics.
Targeting neural precursors in the adult brain rescues injured dopamine neurons (2009)

In Parkinson's disease, multiple cell types in many brain regions are afflicted. As a consequence, a therapeutic strategy that activates a general neuroprotective response may be valuable. We have previously shown that Notch ligands support neural precursor cells in vitro and in vivo. Here we show that neural precursors express the angiopoietin receptor Tie2 and that injections of angiopoietin2 activate precursors in the adult brain. Signaling downstream of Tie2 and the Notch receptor regulate blood vessel formation. In the adult brain, angiopoietin2 and the Notch ligand Dll4 activate neural precursors with opposing effects on the density of blood vessels. A model of Parkinson's disease was used to show that angiopoietin2 and Dll4 rescue injured dopamine neurons with motor behavioral improvement. A combination of growth factors with little impact on the vasculature retains the ability to stimulate neural precursors and protect dopamine neurons. The cellular and pharmacological basis of the neuroprotective effects achieved by these single treatments merits further analysis.
Probiotic Lactobacillus reuteri suppress proinflammatory cytokines via c-Jun (2008)

Human TNF and MCP-1 suppression by probiotic L. reuteri was strain-dependent, and the activation of c-Jun and AP-1 represent primary targets for probiotic-mediated suppression of TNF transcription. This report emphasizes the clonal nature of immunoprobiosis and delineation of a specific immunomodulatory mechanism for probiotic strain selection in future inflammatory bowel disease-oriented clinical trials.
Fabrication of ZnSe Nanoparticles in the Apoferritin Cavity by Designing a Slow Chemical Reaction System (2005)

Zinc selenide nanoparticles (ZnSe NPs) were synthesized in the cavity of the cage-shaped protein apoferritin by designing a slow chemical reaction system, which employs tetraaminezinc ion and selenourea. The chemical synthesis of ZnSe NPs was realized in a spatially selective manner from an aqueous solution, and ZnSe cores were formed in almost all apoferritin cavities with little bulk precipitation. Three factors are found to be important for ZnSe NP synthesis in the apoferritin cavity: (1) the threefold channel, which selectively introduces zinc ion into the apoferritin cavity, (2) the apoferritin internal potential, which favors zinc ion accumulation in the cavity, and (3) the nucleation site, which nucleates ZnSe inside the cavity. The characterization of the synthesized ZnSe NPs by X-ray powder diffraction and energy-dispersive spectrometry revealed that the synthesized NPs are a collection of cubic ZnSe polycrystals. It was shown that the 500 degrees C heat treatment for 1 h under nitrogen gas transformed the polycrystalline ZnSe core into a single crystal, and single-crystal ZnSe NPs free of protein were obtained.
A Structural Multi-Mechanism Damage Model for Cerebral Arterial Tissue (2009)

Early stage cerebral aneurysms are characterized by the disruption of the internal elastic lamina. The cause of this breakdown is still not understood, but it has been conjectured to be due to fatigue failure and/or by a breakdown in homeostatic mechanisms in the wall arising from some aspect of the local hemodynamics and wall tension. We propose to model this disruption using a structural damage model. It is built on a previously introduced nonlinear, inelastic multi-mechanism model for cerebral arteries (2005, "An Inelastic Multi-Mechanism Constitutive Equation for Cerebral Arterial Tissue," Biomech. Model. Mechanobiol., 4(4), pp. 235-248), as well as a recent generalization to include the wall anisotropy (2009, "A Structural Multi-Mechanism Constitutive Equation for Cerebral Arterial Tissue," Int. J. Solids Struct., 46(14-15), pp. 2920-2928). The current model includes subfailure damage of the elastin, represented by changes in the tissue mechanical properties and unloaded reference length. A structural model is used to characterize the gradual degradation, failure of elastin, and recruitment of anisotropic collagen fibers. The collagen fibers are arranged in two helically oriented families with dispersion in their orientation. Available inelastic experimental data for cerebral arteries are used to evaluate the constitutive model. It is then implemented in a commercial finite element analysis package and validated using analytical solutions with representative values for cerebral arterial tissue.
Cuckoo Hashing (2001)

We present a simple and efficient dictionary with worst case constant lookup time, equaling the theoretical performance of the classic dynamic perfect hashing scheme of Dietzfelbinger et al. The space usage is similar to that of binary search trees, i.e., three words per key on average. The practicality of the scheme is backed by extensive experiments and comparisons with known methods, showing it to be quite competitive also in the average case.
The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF): International Prospective Validation and Reliability Trial in 402 patients (2011)

Symptomatic burden in myeloproliferative neoplasms is present in most patients and compromises quality of life. We sought to validate a broadly applicable 18-item instrument (Myeloproliferative Neoplasm Symptom Assessment Form [MPN-SAF], coadministered with the Brief Fatigue Inventory) to assess symptoms of myelofibrosis, essential thrombocythemia, and polycythemia vera among prospective cohorts in the United States, Sweden, and Italy. A total of 402 MPN-SAF surveys were administered (English [25%], Italian [46%], and Swedish [28%]) in 161 patients with essential thrombocythemia, 145 patients with polycythemia vera, and 96 patients with myelofibrosis. Responses among the 3 administered languages showed great consistency after controlling for MPN subtype. Strong correlations existed between individual items and key symptomatic elements represented on both the MPN-SAF and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30. Enrolling physicians' blinded opinion of patient symptoms (6 symptoms assessed) were highly correlated with corresponding patients' responses. Serial administration of the English MPN-SAF among 53 patients showed that most MPN-SAF items are well correlated (r > 0.5, P < .001) and highly reproducible (intraclass correlation coefficient > 0.7). The MPN-SAF is a comprehensive and reliable instrument that is available in multiple languages to evaluate symptoms associated with all types of MPNs in clinical trials globally.
The cytoplasmic domain is critical to the tumor suppressor activity of TSLC1 in non-small cell lung cancer. (2003)

The tumor suppressor gene in lung cancer (TSLC1) encodes a membrane glycoprotein containing extensive homology in the extracellular domain with the immunoglobulin-superfamily cell adhesion molecules. The intracellular cytoplasmic domain (CT) contains a protein 4.1 (FERM) binding motif, and a PDZ-interacting motif. Expression of TSLC1 is silenced in non-small cell lung cancer and in other cancers by promoter hypermethylation. Restoration of TSLC1 expression suppresses tumorigenicity of lung cancer cells. We report here the critical role of the FERM-binding and PDZ- interacting domains of TSLC1 in tumor suppressor activity in non-small cell lung cancer. The entire CT domain [amino acid (aa) 398-442], the FERM binding motif (aa 398-410), or the PDZ-interacting motif (aa 432-442) was deleted to generate mutants CT1, CT3, and CT4, respectively. The lung cancer cell line A549, deficient in TSLC1 expression, was stably transfected with the wild-type TSLC1 or the deletion mutants. The cell lines were then injected into athymic (nu/nu) nude mice, and tumor formation at the sites of injection was monitored. A549 cells stably transfected with the empty vector or mutant TSLC1 constructs induced tumors at the sites of injection within 10 days. In contrast, A549 cells expressing wild-type TSLC1 showed the appearance of tumors after 35 days, and the tumors grew substantially slower. A549 cells expressing wild-type TSLC1 also showed suppression of anchorage-independent colony formation in soft agar and markedly increased cell-cell adhesion activity. These results suggest that the cytoplasmic domain of TSLC1 is important in its tumor suppressor activity, and the tumor suppression activity involve protein(s) interacting with the FERM- and PDZ-interacting regions.