gebhart/patrepeval huggingface dataset:
The Anti-inflammatory Effect of Subconjunctival Bevacizumab on Chemically Burned Rat Corneas (2009)

Purpose: To investigate the effect of bevacizumab in a model of corneal inflammation. Materials and Methods: Epithelium from the cornea and limbus was completely removed using 100% alcohol in rats. Bevacizumab (1.25 mg/0.05 ml) or normal saline was subconjunctivally injected. One week later, corneas were examined and subjected to hematoxylin-eosin and immunofluorescent staining for VEGF. Expression of IL-2, IFN-γ, IL-6, and TGF-β 1 were analyzed by ELISA. Results: Bevacizumab showed a borderline reduction in corneal neovascularization (11.0 ± 4.8% and 18.0 ± 10.0% in the bevacizumab and control groups, respectively; p = 0.054), while the extent of epithelialization was not affected (5.0 ± 3.4% and 6.1 ± 5.2% in the bevacizumab and control groups, respectively; p = 0.715). The infiltration of inflammatory cells was reduced (99.3 ± 22.3 cells/× 400 in the bevacizumab-injected corneas and 182.3 ± 58.0 cells/× 400 in the controls; p = 0.013). The levels of IL-2, IFN-γ, and IL-6 were decreased in the rats with the bevacizumab injections (44 ± 6 and 79 ± 9 pg/ml for IL-2 in the bevacizumab-injected group and control, respectively, p = 0.025; 45 ± 5 and 67 ± 6 pg/ml for IFN-γ in the bevacizumab-injected group and controls, respectively, p = 0.043; 45 ± 6 and 75 ± 8 pg/ml for IL-6 in the bevacizumab-injected group and controls, respectively, p = 0.030). Conclusions: Bavacizumab showed a reduction in inflammatory cell infiltration and cytokines in chemically burned rat corneas.
Early Induction of Apoptosis in Hematopoietic Cell Lines After Exposure to Flavopiridol (1998)

Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4: 120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bax protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority.
Synthesis of 2‐monoglycerides by alcoholysis of palm oil and tuna oil using immobilized lipases (2003)

Abstract Commercial immobilized lipases were used for the synthesis of 2‐monoglycerides (2‐MG) by alcoholysis of palm and tuna oils with ethanol in organic solvents. Several parameters were studied, i.e. , the type of immobilized lipases, water activity, type of solvents and temperatures. The optimum conditions for alcoholysis of tuna oil were at a water activity of 0.43 and a temperature of 60 °C in methyl‐ tert ‐butyl ether for ∼12 h. Although immobilized lipase preparations from Pseudomonas sp. and Candida antarctica fraction B are not 1, 3‐regiospecific enzymes, they were considered to be more suitable for the production of 2‐MG by the alcoholysis of tuna oil than the 1, 3‐regiospecific lipases (Lipozyme RM IM from Rhizomucor miehei and lipase D from Rhizopus delemar ). With Pseudomonas sp. lipase a yield of up to 81% 2‐MG containing 80% PUFA (poly‐unsaturated fatty acids) from tuna oil was achieved. The optimum conditions for alcoholysis of palm oil were similar as these of tuna oil alcoholysis. However, lipase D immobilized on Accurel EP100 was used as catalyst at 40 °C with shorter reaction times (&lt;12 h). This lead to a yield of ∼60% 2‐MG containing 55.0‐55.7% oleic acid and 18.7‐21.0% linoleic acid.
Pembrolizumab Plus Pegylated Interferon alfa-2b or Ipilimumab for Advanced Melanoma or Renal Cell Carcinoma: Dose-Finding Results from the Phase Ib KEYNOTE-029 Study (2018)

<b>Purpose:</b> Pembrolizumab monotherapy, ipilimumab monotherapy, and pegylated interferon alfa-2b (PEG-IFN) monotherapy are active against melanoma and renal cell carcinoma (RCC). We explored the safety and preliminary antitumor activity of pembrolizumab combined with either ipilimumab or PEG-IFN in patients with advanced melanoma or RCC.<b>Experimental Design:</b> The phase Ib KEYNOTE-029 study (ClinicalTrials.gov, NCT02089685) included independent pembrolizumab plus reduced-dose ipilimumab and pembrolizumab plus PEG-IFN cohorts. Pembrolizumab 2 mg/kg every 3 weeks (Q3W) plus 4 doses of ipilimumab 1 mg/kg Q3W was tolerable if ≤6 of 18 patients experienced a dose-limiting toxicity (DLT). The target DLT rate for pembrolizumab 2 mg/kg Q3W plus PEG-IFN was 30%, with a maximum of 14 patients per dose level. Response was assessed per RECIST v1.1 by central review.<b>Results:</b> The ipilimumab cohort enrolled 22 patients, including 19 evaluable for DLTs. Six patients experienced ≥1 DLT. Grade 3 to 4 treatment-related adverse events occurred in 13 (59%) patients. Responses occurred in 5 of 12 (42%) patients with melanoma and 3 of 10 (30%) patients with RCC. In the PEG-IFN cohort, DLTs occurred in 2 of 14 (14%) patients treated at dose level 1 (PEG-IFN 1 μg/kg/week) and 2 of 3 (67%) patients treated at dose level 2 (PEG-IFN 2 μg/kg/week). Grade 3 to 4 treatment-related adverse events occurred in 10 of 17 (59%) patients. Responses occurred in 1 of 5 (20%) patients with melanoma and 2 of 12 (17%) patients with RCC.<b>Conclusions:</b> Pembrolizumab 2 mg/kg Q3W plus ipilimumab 1 mg/kg Q3W was tolerable and provided promising antitumor activity in patients with advanced melanoma or RCC. The maximum tolerated dose of pembrolizumab plus PEG-IFN had limited antitumor activity in this population. <i>Clin Cancer Res; 24(8); 1805-15. ©2018 AACR</i>.
Endothelin induction of inositol phospholipid hydrolysis, sarcomere assembly, and cardiac gene expression in ventricular myocytes. A paracrine mechanism for myocardial cell hypertrophy (1990)

The present study examined the effects of endothelin-1 on phosphoinositide hydrolysis, diacylglycerol formation, and the induction of myocardial cell hypertrophy utilizing a well characterized cultured neonatal rat myocardial cell model. In this system, a hypertrophic response can be assessed by increases in myocardial cell size, an increase in the assembly of an individual contractile protein (myosin light chain-2) into organized contractile units, accumulation of contractile proteins, the activation of a program of immediate early gene expression, and the induction of genes encoding contractile and embryonic proteins (Iwaki, K., Sukhatme, V., Shubeita, H.E., Chien, K.R., (1990) J. Biol. Chem. 265, 13809-13817). Utilizing these criteria, the present study documents that stimulation with endothelin-1 can produce myocardial cell hypertrophy, induce the expression and release of ANF in ventricular cells, and can activate the transcription of cardiac-specific genes. In addition, endothelin-1 stimulates phosphoinositide hydrolysis and the accumulation of diacylglycerol. It is proposed that endothelin-1 stimulation may represent an important paracrine mechanism for the in vivo regulation of cardiac growth and hypertrophy.
Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration (2018)

Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE. Graft-derived cells survived well, extensively migrated into different subfields of the hippocampus, and differentiated into distinct subclasses of inhibitory interneurons expressing various calcium-binding proteins and neuropeptides. Moreover, grafting of hiPSC-MGE cells after SE mediated several neuroprotective and antiepileptogenic effects in the host hippocampus, as evidenced by reductions in host interneuron loss, abnormal neurogenesis, and aberrant mossy fiber sprouting in the dentate gyrus (DG). Furthermore, axons from graft-derived interneurons made synapses on the dendrites of host excitatory neurons in the DG and the CA1 subfield of the hippocampus, implying an excellent graft-host synaptic integration. Remarkably, seizure-suppressing effects of grafts were significantly reduced when the activity of graft-derived interneurons was silenced by a designer drug while using donor hiPSC-MGE cells expressing designer receptors exclusively activated by designer drugs (DREADDs). These results implied the direct involvement of graft-derived interneurons in seizure control likely through enhanced inhibitory synaptic transmission. Collectively, the results support a patient-specific MGE cell grafting approach for treating TLE.
Evolvability of random polypeptides through functional selection within a small library (2002)

A directed evolution with phage-displayed random polypeptides of about 140 amino acid residues was followed until the sixth generation under a selection based on affinity to a transition state analog for an esterase reaction. The experimental design deliberately limits the observation to only 10 clones per generation. The first generation consists of three soluble random polypeptides and seven arbitrarily chosen clones from a previously constructed library. The clone showing the highest affinity in a generation was selected and subjected to random mutagenesis to generate variants for the next generation. Even within only 10 arbitrarily chosen polypeptides in each of the generations, there are enough variants in accord to capacity of binding affinity. In addition, the binding capacity of the selected polypeptides showed a gradual continuous increase over the generation. Furthermore, the purified selected random polypeptides exhibited a gradual but significant increase in esterase activity. The ease of the functional development within a small sequence variety implies that enzyme evolution is prompted even within a small population of random polypeptides.
Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype (2011)

CD44(+)CD24(-/low) and ALDH1(+) phenotypes seem to identify CSC with distinct levels of differentiation. It seems that the paramount method and biomarkers that identify breast CSC within the distinct molecular subtypes need to be better explored, because it is pivotal to translate the CSC concept to clinical practice. In the future, the recognition of reliable markers to distinguish the CSC pool in each molecular subtype will be decisive for the development of specific target therapies.
Friend Turns Foe: Transformation of Anti-Inflammatory HDL to Proinflammatory HDL during Acute-Phase Response (2010)

High-density lipoprotein (HDL) is a major carrier of cholesterol in the blood. Unlike other lipoproteins, physiological functions of HDL influence the cardiovascular system in favorable ways except when HDL is modified pathologically. The cardioprotective mechanism of HDL is mainly based on reverse cholesterol transport, but there has been an emerging interest in the anti-inflammatory and antioxidant roles of HDL. These latter activities of HDL are compromised in many pathological states associated with inflammation. Further, abnormal HDL can become proinflammatory contributing to oxidative damage. In this paper, we discuss the functional heterogeneity of HDL, how alterations in these particles in inflammatory states result in loss of both antioxidant activity and reverse cholesterol transport in relation to atherosclerosis, and the need for assays to predict its functionality.
A Double-Blind, Placebo-Controlled Study of the Omega-3 Fatty Acid Docosahexaenoic Acid in the Treatment of Major Depression (2003)

This trial failed to show a significant effect of DHA monotherapy in subjects with major depression.
Targeting the IL-15 Receptor with an Antagonist IL-15 Mutant/Fcγ2a Protein Blocks Delayed-Type Hypersensitivity (1998)

Owing to shared receptor components, the biologic activities of IL-15 are similar to those of IL-2. However, the patterns of tissue expression of IL-2/IL-2R alpha and IL-15/IL-15R alpha differ. The development of agents targeting the receptor and signaling elements of IL-15 may provide a new perspective for treatment of diseases associated with expression of IL-15/IL-15R. We designed, genetically constructed, and expressed a receptor site-specific IL-15 antagonist by mutating glutamine residues within the C terminus of IL-15 to aspartic acid and genetically linked this mutant IL-15 to murine Fc gamma2a. These mutant IL-15 proteins specifically bind to the IL-15R, competitively inhibit IL-15-triggered cell proliferation, and do not activate the STAT-signaling pathway. Because the receptor site-specific antagonist IL-15 mutant/Fc gamma2a fusion proteins had a prolonged t(1/2) in vivo and the potential for destruction of IL-15R+ leukocytes, we examined the immunosuppressive activity of this agent. An IL-15 mutant/Fc gamma2a fusion protein markedly attenuated Ag-specific delayed-type hypersensitivity responses and decreased leukocyte infiltration within the delayed-type hypersensitivity sites. These findings suggest that 1) IL-15/IL-15R+ cells are crucial to these T cell-dependent immune responses, and 2) treatment with IL-15 mutant/Fc gamma2a protein may ameliorate T cell-dependent immune/inflammatory diseases.
Synthesis of 5-(tert-alkyl)resorcinols (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 5-(tert-alkyl)resorcinolsS. J. Dominianni, C. W. Ryan, and C. W. DeArmittCite this: J. Org. Chem. 1977, 42, 2, 344–346Publication Date (Print):January 1, 1977Publication History Published online1 May 2002Published inissue 1 January 1977https://pubs.acs.org/doi/10.1021/jo00422a037https://doi.org/10.1021/jo00422a037research-articleACS PublicationsRequest reuse permissionsArticle Views457Altmetric-Citations30LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A 9.9 G-10.8 Gb/s rate-adaptive clock and data-recovery with no external reference clock for WDM optical fiber transmission (2003)

A 9.9-10.8 Gb/s rate adaptive clock and data recovery circuit with 1:16 DMUX are integrated in 0.5 /spl mu/m SiGe BiCMOS. A dual-input voltage-controlled oscillator incorporates a fast and a slow tracking loop with a DC gain enhancer. The chip exhibits 2 mUIrms jitter generation and 0.45 UIpp jitter tolerance in a 4-80 MHz range. Power dissipation is 1.45 W from a 3.3 V supply.
Virtual reality crowd simulation: effects of agent density on user experience and behaviour (2018)

Agent-based crowd simulations are used for modelling building and space usage, allowing designers to explore hypothetical real-world scenarios, including extraordinary events such as evacuations. Existing work which engages virtual reality (VR) as a platform for crowd simulations has been primarily focussed on the validation of simulation models through observation; the use of interactions such as gaze to enhance a sense of immersion; or studies of proxemics. In this work, we extend previous studies of proxemics and examine the effects of varying crowd density on user experience and behaviour. We have created a simulation in which participants walk freely and perform a routine manual task, whilst interacting with agents controlled by a typical social force simulation model. We examine and report the effects of crowd density on both affective state and behaviour. Our results show a significant increase in negative affect with density, measured using a self-report scale. We further show significant differences in some aspects of user behaviours, using video analysis, and discuss how our results relate to VR simulation design for mixed human–agent scenarios.
<title>Excimer-laser-produced plasma studies</title> (1990)

The interaction of an Excimer laser with an aluminum surface was studied by a characterization of the blowoff plasma plume. The SDIOIMLI Two-Meter Laser, operating at XeF and KrF wavelengths, was used to illuminate mm sized spots on aluminum targets at fluences of 400 - 1250 J/cm2 for 1 .8 ps. The resultant plasma was characterized by numerous techniques. The temperature of the plasma as a function of distance out in the plume was measured by both a modified line reversal technique and spectral methods. The absolute ion density was measured as a function of distance out in the plume by a laser absorption technique. The temperature in the blowoff plasma plume was found to be relatively constant, dropping by approximately 50% in 1 cm. The density, however, fell by an order of magnitude in the same distance. The measured results agree with predictions from the 2-D Hydrocode STREAK.
Metabotropic glutamate receptors: an original family of G protein‐coupled receptors (1993)

In 1985, we discovered a new glutamate receptor which was coupled to phospholipase C via a G protein and which was later termed metabotropic glutamate receptor (mGluR). In this review, both the diversity of mGluRs and the cellular events they control are discussed, as well as their roles in physiological regulation and brain function.
Botulinum toxin injections for adults with overactive bladder syndrome (2011)

Intravesical botulinum toxin appears to be an effective therapy for refractory OAB symptoms, but as yet little controlled trial data exist on benefits and safety compared with other interventions, or with placebo. Further robust data are required on long term outcomes, safety, and optimal dose of botulinum toxin for OAB.
Linking genetic susceptibility to Crohnʼs disease with Th17 cell function: IL-22 serum levels are increased in Crohnʼs disease and correlate with disease activity and IL23R genotype status (2007)

The Th17 cytokine IL-22 is expressed at high levels in CD and correlates with disease activity, offering a better separation between active and inactive CD than IL-6 and TNF-alpha. IL23R genotypes influence IL-22 serum expression, linking genetic CD susceptibility to Th17 cell function for the first time.
Three-Dimensional Structure Determination of a Protein Supercomplex That Oxidizes Methane to Formaldehyde in Methylococcus capsulatus (Bath) (2006)

The oxidation of methane to methanol in methanotrophs is catalyzed by the enzyme methane monooxygenase (MMO). Two distinct forms of this enzyme exist, a soluble cytoplasmic MMO (sMMO) and a membrane-bound particulate form (pMMO). The active protein complex termed pMMO-C was purified recently from Methylococcus capsulatus (Bath). The complex consists of pMMO hydroxylase and an additional component pMMO-R, which was proposed to be the reductase for the pMMO complex. Further study of this complex has led here to the proposal that the pMMO-R is in fact methanol dehydrogenase, the subsequent enzyme in the methane oxidation pathway by methanotrophs. We describe here the biochemical and biophysical characterization of a stable purified complex of pMMO hydroxylase (pMMO-H) with methanol dehydrogenase (MDH) and report the first three-dimensional (3D) structure, determined by cryoelectron microscopy and single particle analysis to approximately 16 A resolution. The 3D structure reported here provides the first insights into the supramolecular organization of pMMO with MDH. These studies of pMMO-MDH complexes have provided further understanding of the structural basis for the particular functions of the enzymes in this system which might also be of relevance to the complete process of methane oxidation by methanotrophs under high copper concentration in the environment.
Qualification of Reactor Physics Toolset for a Thorium-Fuelled CANDU Reactor (2010)

AECL has developed enhanced versions of the reactor physics computer codes for analysis of CANDU® reactors and the ACR-1000™. The central codes that comprise the analysis toolset are WIMS-AECL (a lattice code), RFSP (a core code) and MCNP5 (a Monte Carlo code). The toolset, with ENDF/B-VI nuclear data, has been validated for application to the ACR-1000 design. In addition to comparisons of code predictions against relevant experiments conducted in AECL’s ZED-2 critical facility, advanced methods based on cross-section sensitivity/uncertainty (S/U) analysis were used to extend the results of bias and uncertainty in reactivity coefficients, derived from analysis of ZED-2 tests, to the ACR-1000 reactor. The validation of this toolset with ENDF/B-VII nuclear data is proposed for application to analysis of a Thorium-fuelled CANDU Reactor (TCR). The TCR is based on the Enhanced CANDU 6™ (EC6™) reactor [1] and would operate with a fuel design that incorporates both low-enriched uranium (LEU) oxide and thorium oxide fuel elements in the same fuel bundle to achieve enhanced fuel and core performance with thorium fuel. For the initial TCR toolset qualification, important reactor physics phenomena would be validated using several relevant ZED-2 experiments performed in the past. Results from experiments with a variety of oxide fuels are available, including plutonium/thorium (Pu/Th), 233U/Th, 235U/Th, LEU and CANDU-MOX (containing a mixture of plutonium, uranium and dysprosium to simulate the reactor physics affects of fuel burnup). Taken together along with other relevant experimental data, these experiments would be expected to address the important isotopes and many phenomena for the TCR and to enable the validation of the reactor physics toolset for this design. Additional confirmatory experiments would reduce uncertainties. This paper describes the qualification process, including validation, which is proposed to support the use of the reactor physics toolset for the TCR.