gebhart/patrepeval huggingface dataset:
Regulation of Dimethylarginine Dimethylaminohydrolase (DDAH) in Rat Preglomerular Vascular Smooth Muscle Cells (PGVSMCs) by Reactive Oxygen Species (ROS) (2008)

DDAH degrades asymmetric dimethylarginine (ADMA) which is an endogenous NOS inhibitor and risk factor for cardiovascular disorders. We tested the hypothesis that ROS regulate the transcription, translation or activity of DDAH. We created a stable rat PGVSMC line overexprissing p22 phox (S‐p22 phox ) using a p22 phox ‐pcDNA4/HisMax construct (a generous gift from Kathy Griendling). Quantitative real time PCR and Western blotting confirmed a marked increase in p22 phox mRNA and protein of 4.7±0.6 and 2.3±0.5 fold, (p&lt;0.01), compared to wild type cells (WT). S‐p22 phox cells had elevated superoxide and hydrogen peroxid generation (2.3±0.09 fold and 1.8±0.1 fold p&lt;0.01). The mRNAs for DDAH ‐1 and ‐2 were increased by 2.8 ± 0.2 and 1.8 ± 0.1 fold in S‐p22 phox cells p&lt; 0.01). DDAH‐2 promoter activity, determined by transient transfection and luciferase assay, was 4.1 fold increased in S‐p22 phox cells (p &lt; 0.01). Interestingly, both DDAH‐1 and ‐2 proteins were significantly lower in S‐p22 phox cells (0.9±0.2 and 0.9±0.1 fold; p&lt;0.01), yet β‐actin was not different. DDAH activity measured by a colorimetric assay (Kidney Int. 72:886–9, 2007) was reduced by 62±2% in S‐p22 phox (p&lt;0.01). The results reveal for the first time an important effect but complex of p22 phox – dependent ROS generation on DDAH. Thus, ROS upregulate the expression of DDAH‐1 and ‐2 genes via activating a promoter, at least for DDAH‐2, yet downregulate both DDAH‐1 and ‐2 proteins and their enzyme activity. This is a specific effect since ROS do not change the expression of cell structure proteins. These findings in PGVSMCs provide a novel regulatory pathway whereby ROS may modulate renal hemodynamics, and thereby BP and salt homeostasis.
Bioerodible Polymers for Ocular Drug Delivery (1998)

Development of ophthalmic drug-delivery systems has always been challenging. The commonly used route for drug delivery to the anterior segment of the eye has been the conjunctival cul-de-sac. Because of drawbacks associated with this route, new approaches have been investigated for delivery of drugs to the eye by means of polymeric delivery systems. Development of controlled drug-release devices has been a major step forward in this respect. Bioerodible polymers have been at the forefront of such systems. They are very important because they eliminate the need for removing the implant after complete drug release. Bioerodible polymers have been divided into three classes based on their mechanism of hydrolysis: Type I--hydrolysis of crosslinked hydrogels; Type II--solubilization by ionization or hydrolysis of linear polymers; and Type III--biodegradation by backbone cleavage. Polymers from all three classes are discussed in detail in this review.
Evaluation of the mTOT inhibitor, rapamycin in dogs with spontaneously derived osteosarcoma: A focus on preclinical pharmacokinetics and pharmacodynamics (2007)

C87 There is great interest in the development of mTOR inhibitors as anti-cancer therapies. mTOR functions as the nutrient sensor of the cell controlling protein translation, integral in cancer development and progression. The inhibition of mTOR is possible with Rapamycin, initially developed as an immunosuppressant for transplant patients, and novel analogues, known collectively as rapalogs. Although there are currently many treatment trials evaluating Rapamycin and rapalogs, the correlation of dose, pharmacodynamic modulation, response and benefit for these agents is poorly underestood. Furthermore, an understanding of optimal combinations of mTOR inhibitors with other cancer treatments is lacking. The complexity of questions related to the dose, exposure, dose-target, and benefit of a new cancer agent requires sophisticated and innovative model systems. Pet dogs that have naturally developed cancer may be such a model system. As such a preclinical dose escalation study in pet dogs with osteosarcoma was initiated to address questions of Rapamycin pharmacokinetics and its relationship to tumoral and PBMC correlative pharmacodynamics. This study was conducted through the Comparative Oncology Trials Consortium, a multi-institutional translational cancer therapy effort, led by the NCI, that integrates naturally occurring cancers seen in pet dogs into the development path of new cancer drugs. Dogs were administered paraenteral Rapamycin daily for an 8-day exposure starting at 0.01 mg/kg and finishing at 0.08 mg/kg. Biopsies were collected both pre and post treatment to assess mTOR pathway inhibition using modulation of 4EBP1 and S6K phosphorylation. Rapamycin was found to be safe and tolerable in tumor bearing dogs at doses relevant to typical human doses. There were two > grade 3 toxicities recorded but neither was attributable to the study drug. Hematologic and biochemical assessment was performed weekly for the 15-day study period and no significant toxicities reported. The tolerability of parenteral rapamycin in dogs will support the inclusion of dogs in future studies of mTOR inhibition. Pharmacokinetic and pharmacodynamic assessments are currently being performed. This study was designed as a necessary prequel for currently planned studies that will assess the activity of mTOR inhibition in osteosarcoma and future studies that will define optimal combinations of mTOR inhibition with both conventional and novel cancer treatments for sarcomas and other cancers.
Inflammatory breast cancer: a model for investigating cluster-based dissemination (2017)

Metastases claim more than 90% of cancer-related patient deaths and are usually seeded by a subset of circulating tumor cells shed off from the primary tumor. In circulation, circulating tumor cells are found both as single cells and as clusters of cells. The clusters of circulating tumor cells, although many fewer in number, possess much higher metastatic potential as compared to that of individual circulating tumor cells. In this review, we highlight recent insights into molecular mechanisms that can enable the formation of these clusters-(a) hybrid epithelial/mesenchymal phenotype of cells that couples their ability to migrate and adhere, and (b) intercellular communication that can spatially coordinate the cluster formation and provide survival signals to cancer cells. Building upon these molecular mechanisms, we also offer a possible mechanistic understanding of why clusters are endowed with a higher metastatic potential. Finally, we discuss the highly aggressive Inflammatory Breast Cancer as an example of a carcinoma that can metastasize via clusters and corroborates the proposed molecular mechanisms.
ChemInform Abstract: An Alternative Solid‐Phase Approach To C1‐Oxytocin. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
New volatile marker test to detect colorectal lesions (2015)

2050-6414 (e)
SQSTM1Mutations in French Patients With Frontotemporal Dementia or Frontotemporal Dementia With Amyotrophic Lateral Sclerosis (2013)

Although the frequency of the mutations is low in our series (4 of 188 patients [2%]), our results, similar to those already reported, support a direct pathogenic role of p62 in different types of FTD.
Design of Optimum Plate-Fin Natural Convective Heat Sinks (2003)

The effort described herein extends the use of least-material single rectangular plate-fin analysis to multiple fin arrays, using a composite Nusselt number correlation. The optimally spaced least-material array was also found to be the globally best thermal design. Comparisons of the thermal capability of these optimum arrays, on the basis of total heat dissipation, heat dissipation per unit mass, and space claim specific heat dissipation, are provided for several potential heat sink materials. The impact of manufacturability constraints on the design and performance of these heat sinks is briefly discussed.
ChemInform Abstract: Organolanthanoid‐Centered Hydroamination/Cyclization of Aminoolefins. Expedient Oxidative Access to Catalytic Cycles. (1990)

Abstract The readily accessible (Cp)2Sm(THF)2 and (Cp)2Sm catalysts catalyze the hydroamination/cyclization of a variety of aminoolefins such as (I).
Synthesis and characterization of bulky aryl derivatives of the heavier Main Group 3 elements (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis and characterization of bulky aryl derivatives of the heavier Main Group 3 elementsMark A. Petrie, P. P. Power, H. V. Rasika Dias, Karin Ruhlandt-Senge, Krista M. Waggoner, and Rudolf J. WehmschulteCite this: Organometallics 1993, 12, 4, 1086–1093Publication Date (Print):April 1, 1993Publication History Published online1 May 2002Published inissue 1 April 1993https://pubs.acs.org/doi/10.1021/om00028a025https://doi.org/10.1021/om00028a025research-articleACS PublicationsRequest reuse permissionsArticle Views1136Altmetric-Citations95LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
CHFR methylation strongly correlates with methylation of DNA damage repair and apoptotic pathway genes in non-small cell lung cancer. (2015)

DNA methylation occurs commonly in non-small cell lung cancer (NSCLC). We sought to determine the frequency and relationship of methylation of key genes involved in the pathways of mitotic checkpoint control, DNA damage repair, apoptosis, and growth factor signaling in these patients. We analyzed the DNA methylation status of eight genes (CHFR, FANCF, MGMT, p16, DAPK, ASC or TMS-1, RAR-B, and CRBP1) using nested methylation-specific PCR (MSP) on over 314 paraffin-embedded, human non-small cell lung cancer samples. We determined the methylation frequency of each gene in addition to the association of the methylation of each gene with other members of the panel. Methylation was a common event in these samples. Our methylation analysis showed frequencies of methylation of 10% for CHFR, 14% for FANCF, 30% for MGMT, 29% for p16, 17% for DAPK, 33% for ASC, 38% for RAR-B, and 7% for CRBP1. There was a strong correlation between methylation of the mitotic G2-M checkpoint gene, CHFR, and methylation of other genes in our panel involved in DNA damage repair (FANCF and MGMT) and apoptosis (DAPK and ASC) but not with other genes in our panel, including p16 (the G1-S checkpoint gene), CRBP1, or RAR-B. In addition, MGMT methylation strongly correlated with the pro-apoptotic gene, ASC. There are distinct associations of methylated genes in non-small cell lung cancer involving DNA damage repair, apoptosis, and the G2-M mitotic checkpoint control. Further studies are warranted to determine whether these methylation patterns have implications for prognosis in addition to prediction of response to chemotherapeutic agents commonly used in the treatment of non-small cell lung cancer, such as radiotherapy and platinum- or taxane-based chemotherapy.
Search for an additional, heavy Higgs boson in the $$H\rightarrow ZZ$$ H → Z Z decay channel at $$\sqrt{s} = 8\;\text{ TeV }$$ s = 8 TeV in $$pp$$ p p collision data with the ATLAS detector (2016)

A search is presented for a high-mass Higgs boson in the [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] decay modes using the ATLAS detector at the CERN Large Hadron Collider. The search uses proton-proton collision data at a centre-of-mass energy of 8 TeV corresponding to an integrated luminosity of 20.3 fb[Formula: see text]. The results of the search are interpreted in the scenario of a heavy Higgs boson with a width that is small compared with the experimental mass resolution. The Higgs boson mass range considered extends up to [Formula: see text] for all four decay modes and down to as low as 140 [Formula: see text], depending on the decay mode. No significant excess of events over the Standard Model prediction is found. A simultaneous fit to the four decay modes yields upper limits on the production cross-section of a heavy Higgs boson times the branching ratio to [Formula: see text] boson pairs. 95 % confidence level upper limits range from 0.53 pb at [Formula: see text] GeV to 0.008 pb at [Formula: see text] GeV for the gluon-fusion production mode and from 0.31 pb at [Formula: see text] GeV to 0.009 pb at [Formula: see text] GeV for the vector-boson-fusion production mode. The results are also interpreted in the context of Type-I and Type-II two-Higgs-doublet models.
Finite element analysis of abdominal aortic aneurysms: geometrical and structural reconstruction with application of an anisotropic material model (2014)

Journal Article Finite element analysis of abdominal aortic aneurysms: geometrical and structural reconstruction with application of an anisotropic material model Get access David Roy, David Roy 1University of Montréal Hospital – Research Centre, Tour Viger, 900 rue St-Denis, Montréal, Canada H2X 0A9, david.roy.5@umontreal.ca Search for other works by this author on: Oxford Academic Google Scholar Gerhard A. Holzapfel, Gerhard A. Holzapfel 2Graz University of Technology, Institute of Biomechanics, Kronesgasse 5-I, 8010 Graz, Austria, holzapfel@tugraz.at Search for other works by this author on: Oxford Academic Google Scholar Claude Kauffmann, Claude Kauffmann 3University of Montréal Hospital – Research Centre, Tour Viger, 900 rue St-Denis, Montréal, Canada H2X 0A9 *Corresponding author: gilles.soulez.chum@ssss.gouv.qc.caclaude.kauffmann@gmail.com Search for other works by this author on: Oxford Academic Google Scholar Gilles Soulez Gilles Soulez 3University of Montréal Hospital – Research Centre, Tour Viger, 900 rue St-Denis, Montréal, Canada H2X 0A9 *Corresponding author: gilles.soulez.chum@ssss.gouv.qc.caclaude.kauffmann@gmail.com Search for other works by this author on: Oxford Academic Google Scholar IMA Journal of Applied Mathematics, Volume 79, Issue 5, October 2014, Pages 1011–1026, https://doi.org/10.1093/imamat/hxu037 Published: 08 September 2014 Article history Received: 04 July 2014 Accepted: 04 July 2014 Published: 08 September 2014
Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen (2016)

PEGylation of biomolecules is a major approach to increase blood stream half-life, stability and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives due to high molecular mass and stability toward proteases, however their size lowers to some extent their potential because of a reduced ability to penetrate tissues, especially those of tumor origin. Fab or otherwise engineered smaller fragments are an alternative but are less stable and are much less well retained in circulation. We have here investigated the effects of various PEGylations on the binding properties and in vivo half-life of Fab fragments derived from the enzymatic splitting of Trastuzumab. We find that PEGylation increases the half-life of the molecules but also strongly affects the ability to recognize the target antigen in a way that is dependent on the extent and position of the chemical modification. Data thus support the concept that polyethylene glycol (PEG) conjugation on Trastuzumab Fabs increases half-life but reduces their affinity and this is a fine balance, which must be carefully considered for the design of strategies based on the use of antibody fragments.
ChemInform Abstract: CAPTO‐DATIVE SUBSTITUENT EFFECTS. PART 8. BRIDGED DEHYDRODIMERISATION AS A GENERAL METHOD OF SYNTHESIS: C4‐BRIDGING WITH α‐TERT‐BUTYLMERCAPTOACRYLONITRILE (1981)

Abstract Die direkte Dehydrodimerisierung der aus den Substraten (I) entstehenden Radikale (IV) wird in Gegenwart von Radicophilen ‐ die gleichzeitig elektrophile und nucleophile Radikale addieren (sog.
A simulation of cellular system growth and its effect on urban in-building parasitic frequency reuse (1999)

Indoor parasitic cellular systems reuse the same frequencies as outdoor cellular (macrocellular) systems to provide wireless communications inside a building or campus. This paper provides a simulation strategy to determine future channel availability that is possible between in-building and outdoor cellular systems that share the same radio spectrum. Capacity that is currently available inside an urban office building is first derived from field-strength measurements of all the channels in the macrocellular system made inside the building. We then create a simulation that determines the effect of a growing outdoor cellular system on in-building frequency reuse. Future in-building frequency reuse is predicted over a 6-yr timeline in 3-mo intervals and includes the effect of height above ground inside the building. Results show that indoor reuse is practical as long as interference levels of about -85 dBm can be tolerated from the outdoor macrocellular system.
Rate equation analysis of digital pulse modulation in strongly injection-locked semiconductor microring lasers (2020)

Digital pulse modulation of strongly injection-locked whistle-geometry semiconductor ring lasers is investigated. Specifically, we address the problem of optical output signal distortion due to transient behavior of the laser in response to picosecond input pulses of injection current. Pulse modulation of a 2-&mu;m-diameter strongly injection-locked whistlegeometry ring laser with up to 50 GHz repetition rate and substantially suppressed transient emission tails is demonstrated in numerical modeling for a sequence of triangular injection current pulses of picosecond duration.
ChemInform Abstract: Experiments Directed Towards Synthesis of Complex Glycosphingolipids: Ganglio‐ganglioside GQ1b1. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Cytotoxicity and thermomechanical behavior of biomedical shape-memory polymer networks post-sterilization (2008)

Shape-memory polymers (SMPs) are being increasingly proposed for use in biomedical devices. This paper investigates the cytotoxicity, surface characteristics and thermomechanics of two acrylate-based SMP networks as a function of sterilization using a minimal essential media elution test, FTIR-ATR and dynamic mechanical analysis (DMA). Networks sterilized by low-temperature plasma elicited a cytotoxic response and are shown to completely destroy the cell monolayer. FTIR-ATR analysis showed evidence of surface oxidation with an increase and broadening of the absorbance peak from approximately 3500 to 3100 cm(-1), which is associated with an increase in hydroxyl groups. DMA revealed small, but statistically significant, differences in reduction of the glass transition temperatures of both networks when sterilized with gamma irradiation. One network showed an increase in rubbery modulus, which is an indication of crosslink density, after gamma irradiation. Lastly, practical sterilization concerns of SMP devices are discussed in light of the different methods.
JAK2 Inhibitors for the Treatment of Myeloprolifertive Disorders. (2006)

Abstract The molecular pathogenesis of the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocytosis, and myelofibrosis with myeloid metaplasia has been conclusively linked to a single mutation in JAK2 (Janus Associated Kinase 2). A G-T transversion event in exon 14 that translates into a substitution of phenylalanine for valine at amino residue 617 leads to constitutive activation of JAK2V617F in a majority of these MPD cases. Assays in several laboratories indicate that between 90–100% of patients with polycythemia vera harbor this allele. Because the JAK2.V617F gain-of-function mutant affects such a large patient population, pharmacologically targeting the mutated JAK2 is highly clinically relevant. In order to address this unmet clinical need we designed and synthesized a series of structurally novel compounds for their capacity to inhibit JAK2.V617F. Compounds were identified which potently inhibited JAK2 enzyme, with enzymatic IC50s as low as 1 nM. Subsets of this group were subsequently identified which were highly selectivity against undesirable off-target kinases, including up to 100X selectivity versus the highly homologous JAK3 kinase. Compounds were then advanced into in vitro assays in JAK2.V617F transformed cell lines in which compounds were identified with proliferation EC50s as low as 60 nM (representative compounds listed in Table below). Compounds from this series were subsequently shown to be orally available and efficacious in rodent models of MPD driven disease. Conclusion: TargeGen has synthesized a series of JAK2.V617F inhibitors with promising potency, selectivity and pharmaceutical properties for utility in the treatment of myeloproliferative disorders. Representative JAK2 Inhibitors Compound Primary Target Selectivity Profile Cell EC50 JAK2 IC50 JAK2 vs JAK3 (X-fold selectivity) BaF3:JAK2.V617F TG101192 3.8 15 140 TG101209 6 28 279 TGs101348 12.5 83 297 JAK Inhibitor I (Calbiochem) 10 1.5 320
Identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y (2010)

Nucleosomal incorporation of specialized histone variants is an important mechanism to generate different functional chromatin states. Here, we describe the identification and characterization of two novel primate-specific histone H3 variants, H3.X and H3.Y. Their messenger RNAs are found in certain human cell lines, in addition to several normal and malignant human tissues. In keeping with their primate specificity, H3.X and H3.Y are detected in different brain regions. Transgenic H3.X and H3.Y proteins are stably incorporated into chromatin in a similar fashion to the known H3 variants. Importantly, we demonstrate biochemically and by mass spectrometry that endogenous H3.Y protein exists in vivo, and that stress stimuli, such as starvation and cellular density, increase the abundance of H3.Y-expressing cells. Global transcriptome analysis revealed that knockdown of H3.Y affects cell growth and leads to changes in the expression of many genes involved in cell cycle control. Thus, H3.Y is a novel histone variant involved in the regulation of cellular responses to outside stimuli.