gebhart/patrepeval huggingface dataset:
Localization and Regulation of Thyrotropin Receptors within Lipid Rafts (2003)

The TSH receptor (TSHR) is a prototypic G protein-coupled receptor with a large extracellular domain. We have previously demonstrated homophilic interactions of TSHRs and their existence as constitutive oligomers. However, we have also shown that TSH itself promotes the formation of receptor monomers. We hypothesized, therefore, that TSHR monomers induced by TSH ligand may move into lipid rafts before effective TSH-induced signaling by bringing the cognate signaling molecules resident in such rafts together with the TSHRs. Thus, we aimed to determine whether the TSHRs would partition into these lipid rafts. The B subunit of cholera toxin (CTxB) binds to lipid raft-enriched GM1 ganglioside and has been widely exploited to visualize lipid rafts. Using such a method, we demonstrated the presence of these GM1-enriched lipid microdomains in Chinese hamster ovary cells by using CTxB labeled with a red dye (Alexa 594). To provide evidence for the presence of TSHRs in lipid rafts, we stained Chinese hamster ovary cells expressing TSHRGFP with labeled CTxB. Our results demonstrated that the TSHRGFP complexes localized to GM1-enriched lipid raft microdomains as evidenced by colocalization of the green fluorescent protein tag with the labeled CTxB. Hence, we concluded that a significant proportion of TSHRs were constitutively associated with lipid rafts. Furthermore, upon activation of these stained raft-receptor complexes with increasing concentrations of TSH, we observed that the raft-receptor complexes decreased significantly. The relevance of such receptor movement out of the rafts suggested that these may be the receptors critical in the initiation of signal transduction
Cardiac imaging using gated magnetic resonance. (1984)

To overcome the limitations of magnetic resonance (MR) cardiac imaging using nongated data acquisition, three methods for acquiring a gating signal, which could be applied in the presence of a magnetic field, were tested: an air-filled plethysmograph, a laser-Doppler capillary perfusion flowmeter, and an electrocardiographic gating device. The gating signal was used for timing of MR imaging sequences (IS). Application of each gating method yielded significant improvements in structural MR image resolution of the beating heart, although with both plethysmography and laser-Doppler velocimetry it was difficult to obtain cardiac images from the early portion of the cardiac cycle due to an intrinsic delay between the ECG R wave and peripheral detection of the gating signal. Variations in the temporal relationship between the R wave and plethysmographic and laser-Doppler signals produced inconsistencies in the timing of IS. Since the ECG signal is virtually free of these problems, the preferable gating technique is IS synchronization with an electrocardiogram. The gated images acquired with this method provide sharp definition of internal cardiac morphology and can be temporarily referenced to end diastole and end systole or intermediate points.
Analysis of site-directed mutations in human pro-alpha 2(I) collagen which block cleavage by the C-proteinase. (1990)

We have used site-directed mutagenesis to obtain human pro alpha 2(I) cDNAs containing novel mutations designed to inhibit cleavage at the C-proteinase site. Deletion of six relatively conserved amino acids which surround the cleavage site did not interfere with assembly of the triple helix in transfected rat cells, but blocked cleavage of the constituent mutated chains by endogenous C-proteinase. Substitution for a conserved Asp, which forms part of the Ala-Asp bond cleaved by C-proteinase, also blocked cleavage by endogenous C-proteinase. The conserved Asp is, therefore, a necessary component of the C-proteinase cleavage site. Incubation in vitro with a purified mouse C-proteinase, confirmed both mutations to be resistant to cleavage by high concentrations of the physiologically relevant enzyme. Mutant pro alpha 2(I) chains, resistant to cleavage by C-proteinase in culture media, were processed in cell layers by a different protease which cleaved telopeptide domains. Naturally occurring mutations at the C-proteinase site have not been described in human patients. The mutations characterized here, further define the C-proteinase cleavage site and provide reagents which may be informative when introduced into transgenic mice.
Truncation in CCND1 mRNA alters miR-16-1 regulation in mantle cell lymphoma (2008)

Cyclin D1 (CCND1) is a well-known regulator of cell-cycle progression. It is overexpressed in several types of cancer including breast, lung, squamous, neuroblastoma, and lymphomas. The most well-known mechanism of overexpression is the t(11;14)(q13;q32) translocation found in mantle cell lymphoma (MCL). It has previously been shown that truncated CCND1 mRNA in MCL correlates with poor prognosis. We hypothesized that truncations of the CCND1 mRNA alter its ability to be down-regulated by microRNAs in MCL. MicroRNAs are a new class of abundant small RNAs that play important regulatory roles at the posttranscriptional level by binding to the 3' untranslated region (UTR) of mRNAs blocking either their translation or initiating their degradation. In this study, we have identified the truncation in CCND1 mRNA in MCL cell lines. We also found that truncated CCND1 mRNA leads to increased CCND1 protein expression and increased S-phase cell fraction. Furthermore, we demonstrated that this truncation alters miR-16-1 binding sites, and through the use of reporter constructs, we were able to show that miR-16-1 regulates CCND1 mRNA expression. This study introduces the role of miR-16-1 in the regulation of CCND1 in MCL.
Interferon induced in human leukocytes by mitogens: production, partial purification and characterization (1980)

Interferon was induced in leukocyte suspensions from human buffy coats by exposure to phytohemagglutinin P, concanavalin A (Con A) and staphylococcal enterotoxin A, under a variety of cell culture conditions. Con A was found to rapidly (within 12 h) induce high yields of antiviral activity (1.5 units/1000 cells). Lesser yields were obtained with the other two mitogens studied. The interferon was partially purified to a spec. act. around 10(5.3) units/mg protein, by batch adsorption on controlled-pore glass (CPG) beads and desorption by ethylene glycol. This material was characterized as containing mainly gamma-type interferon. Specifically on gel filtration, a fraction of 45000 daltons was obtained which could account for virtually all antiviral activity present in the starting material. Furthermore, the ethylene glycol-eluted antiviral activity was acid-labile, serologically distinct from alpha and beta-type interferon and strictly species-specific (no activity detectable on any of the available cell species sensitive to alpha and beta-type interferon). The crude culture supernatant also contained some antiviral activity which resembled beta-type interferon in that it adsorbed to CPG, could be desorbed by pH 2 buffer, was acid-resistant and could be neutralized by a specific anti-fibroblast interferon antiserum. The CPG/ethylene glycol-purified gamma-type interefron preparation was found to inhibit the growth of certain lymphoblastoid cells (Daudi and Molt-4). It also potentiated natural killer activity of fresh donor lymphocytes. In both respects, the gamma-type interferon preparation was not significantly more active than preparations of alpha and beta-interferon of similar antiviral potency.
Strong luminescence induced by elastic deformation of piezoelectric crystals (2013)

The luminescence induced by elastic deformation of solids, called the phenomenon of elastico-mechanoluminescence (EML), is observed in several materials. For applied pressure in the range of 17 MPa, certain crystals emit intense EML, which can be seen in day light with naked eye. In the present paper, we explore that, as the piezoelectric constant near the photo-generated electric dipoles formed by trapping of charge carriers in crystals is several times higher as compared to that at normal sites, the piezoelectrically induced detrapping of charge carriers and EML emission may take place for less value of the pressure applied onto the crystals.
Enhanced expression of a glyceraldehyde-3-phosphate dehydrogenase gene in human lung cancers. (1987)

We have shown that a Mr 37,000 protein whose expression is strongly enhanced in human lung cancer tissues is the subunit of glyceraldehyde-3-phosphate (GAPDH, EC 1.2.1.12). We have isolated a GAPDH complementary DNA from human lung cancer cells and deduced the complete amino acid sequence of the encoded protein. The structure of the lung cancer GAPDH is identical to that of liver GAPDH. In addition, we have found that GAPDH mRNA expression is markedly increased in human lung cancer tissues. These results disclose a molecular basis of increased glycolysis in cancer cells and reveal an important role of energy creating reaction in cancer cell growth.
Bioartificial Polymeric Materials Obtained from Blends of Synthetic Polymers with Fibrin and Collagen (1991)

A new class of biomaterials, called "bioartificial polymeric materials", was prepared blending a segmented polyurethane (PU) with fibrinogen (FBNG); and poly(acrylic acid) (PAA), poly(acrylamide) (PAAM), poly(vinyl alcohol) (PVAL), with collagen (CLG), respectively. The PU-FBNG material was processed through a spraying, phase-inversion technique to fabricate porous tubular conduits. FBNG was subsequently converted into covalently cross-linked fibrin (FBN) through the action of thrombin (Th), fibrin-stabilizing factor (FSF), and calcium ions. Differential scanning calorimetry (DSC) showed the cross-linked blend was more stable than native cross-linked FBN. Tensile behaviors of the PU-FBN materials closely matched those of a natural artery on varying the ratio PU/FBN. Implantation experiments in the rat model showed a mature internal capsule and good tissue organization of PU-FBN (50%) grafts in the regenerated arterial wall. However, 50% of FBN did not assure adequate mechanical resistance, and aneurysmal changes were seen in some grafts. DSC of CLG-based materials, processed by casting, showed that the synthetic component offered definite advantage compared to the CLG denaturation temperature, particularly noticeable for CLG-PAA and CLG-PVAL blends. Material advantages and drawbacks are discussed.
Anticonvulsant Nature of Marihuana Smoking (1975)

Marihuana smoking, in conjunction with therapeutic doses of phenobarbital and diphenylhydantoin, was apparently necessary for controlling seizures in one 24-year-old epileptic patient.
Postoperative Adjuvant Dendritic Cell–Based Immunotherapy in Patients with Relapsed Glioblastoma Multiforme (2008)

Adjuvant DC-based immunotherapy for patients with relapsed GBM is safe and can induce long-term survival. A trend to PFS improvement was shown in the faster vaccination schedule. The importance of age and a minimal residual disease status at the start of the vaccination is underscored.
Melatonin Administration to Blind People: Phase Advances and Entrainment (1991)

The purpose of this study was to test the phase-shifting and entraining effects of melatonin in human subjects. Five totally blind men were found in a previous study to have free-running endogenous melatonin rhythms. Their rhythms were remarkably stable, so that any deviation from the predicted phase was readily detectable. After determination of their free-running period and phase, they were given exogenous melatonin (5 mg) at bedtime (2200 hr) for 3 weeks, in a double-blind, placebo-controlled trial. The effects on the endogenous melatonin rhythm were assessed at intervals ranging from several days to 2 weeks. Exogenous administration of melatonin phase-advanced their endogenous melatonin rhythms. In three of the subjects, cortisol was shown to be phase-shifted in tandem with the melatonin rhythm. A sixth subject [one of the coauthors (JS)] was previously found to have free-running cortisol and temperature rhythms and was plagued by recurrent insomnia and daytime sleepiness. He had tried unsuccessfully to entrain his rhythms for over 10 years. After he took melatonin (7 mg at 2100 hr), his insomnia and sleepiness resolved. Determination of his endogenous melatonin rhythm after about a year of treatment demonstrated endogenous rhythms that appeared normally entrained. The treatment of blind people with free-running rhythms has many advantages for demonstrating chronobiological effects of hormones or drugs.
Distributed Estimation and Control of Algebraic Connectivity Over Random Graphs (2014)

In this paper, we propose a distributed algorithm for the estimation and control of the connectivity of ad-hoc networks in the presence of a random topology. First, given a generic random graph, we introduce a novel stochastic power iteration method that allows each node to estimate and track the algebraic connectivity of the underlying expected graph. Using results from stochastic approximation theory, we prove that the proposed method converges almost surely (a.s.) to the desired value of connectivity even in the presence of imperfect communication scenarios. The estimation strategy is then used as a basic tool to adapt the power transmitted by each node of a wireless network, in order to maximize the network connectivity in the presence of realistic medium access control (MAC) protocols or simply to drive the connectivity toward a desired target value. Numerical results corroborate our theoretical findings, thus illustrating the main features of the algorithm and its robustness to fluctuations of the network graph due to the presence of random link failures.
Rapid gradient‐echo imaging (2012)

Gradient-echo sequences are widely used in magnetic resonance imaging (MRI) for numerous applications ranging from angiography to perfusion to functional MRI. Compared with spin-echo techniques, the very short repetition times of gradient-echo methods enable very rapid 2D and 3D imaging, but also lead to complicated "steady states." Signal and contrast behavior can be described graphically and mathematically, and depends strongly on the type of spoiling: fully balanced (no spoiling), gradient spoiling, or radiofrequency (RF)-spoiling. These spoiling options trade off between high signal and pure T(1) contrast, while the flip angle also affects image contrast in all cases, both of which can be demonstrated theoretically and in image examples. As with spin-echo sequences, magnetization preparation can be added to gradient-echo sequences to alter image contrast. Gradient-echo sequences are widely used for numerous applications such as 3D perfusion imaging, functional MRI, cardiac imaging, and MR angiography.
Directed Evolution of a Cytochrome P450 Monooxygenase for Alkane Oxidation (2001)

Cytochrome P450 monooxygenase BM-3 (EC 1.14.14.1) hydroxylates fatty acids with chain lengths between C12 and C18. It is also known to oxidize the corresponding alcohols and amides. However, it is not known to oxidize alkanes. Here we report that P450 BM-3 oxidizes octane, which is four carbons shorter and lacks the carboxylate functionality of the shortest fatty acid P450 BM-3 is known to accept, to 4-octanol, 3-octanol, 2-octanol, 4-octanone, and 3-octanone. The rate is much lower than for oxidation of the preferred fatty acid substrates. In an effort to explore the plasticity and mechanisms of substrate recognition in this powerful biocatalyst, we are using directed evolution − random mutagenesis, recombination, and screening − to improve its activity towards saturated hydrocarbons. A spectrophotometric assay has been validated for high throughput screening, and two generations of laboratory evolution have yielded variants displaying up to five times the specific activity of wild-type P450 BM-3.
Simultaneous Pharmacokinetic Screening of a Mixture of Compounds in the Dog Using API LC/MS/MS Analysis for Increased Throughput (1997)

ADVERTISEMENT RETURN TO ISSUELetterNEXTSimultaneous Pharmacokinetic Screening of a Mixture of Compounds in the Dog Using API LC/MS/MS Analysis for Increased ThroughputJudd Berman, Kathy Halm, Kim Adkison, and Joel ShafferView Author Information Glaxo Wellcome, Five Moore Drive, Research Triangle Park, North Carolina 27709 Cite this: J. Med. Chem. 1997, 40, 6, 827–829Publication Date (Web):March 14, 1997Publication History Received8 October 1996Published online14 March 1997Published inissue 1 March 1997https://pubs.acs.org/doi/10.1021/jm960702shttps://doi.org/10.1021/jm960702srapid-communicationACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views761Altmetric-Citations118LEARN 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 SUBJECTS:Antagonists,Metabolism,Mixtures,Pharmacokinetics,Plasma Get e-Alerts
Apache Hadoop YARN: Moving beyond MapReduce and Batch Processing with Apache Hadoop 2 (2014)

This book is a critically needed resource for the newly released Apache Hadoop 2.0, highlighting YARN as the significant breakthrough that broadens Hadoop beyond the MapReduce paradigm. From the Foreword by Raymie Stata, CEO of Altiscale The Insiders Guide to Building Distributed, Big Data Applications with Apache Hadoop YARN Apache Hadoop is helping drive the Big Data revolution. Now, its data processing has been completely overhauled: Apache Hadoop YARN provides resource management at data center scale and easier ways to create distributed applications that process petabytes of data. And now in Apache Hadoop YARN, two Hadoop technical leaders show you how to develop new applications and adapt existing code to fully leverage these revolutionary advances. YARN project founder Arun Murthy and project lead Vinod Kumar Vavilapalli demonstrate how YARN increases scalability and cluster utilization, enables new programming models and services, and opens new options beyond Java and batch processing. They walk you through the entire YARN project lifecycle, from installation through deployment. Youll find many examples drawn from the authors cutting-edge experiencefirst as Hadoops earliest developers and implementers at Yahoo! and now as Hortonworks developers moving the platform forward and helping customers succeed with it. Coverage includes YARNs goals, design, architecture, and componentshow it expands the Apache Hadoop ecosystem Exploring YARN on a single node Administering YARN clusters and Capacity Scheduler Running existing MapReduce applications Developing a large-scale clustered YARN application Discovering new open source frameworks that run under YARN
Detection of Normal and Chimeric Nucleophosmin in Human Cells (1999)

In anaplastic large-cell lymphoma (ALCL), the (2;5) chromosomal translocation creates a fusion gene encoding the 80-kD NPM-ALK hybrid protein. This report describes three new monoclonal antibodies, two of which recognize, by Western blotting, the N-terminal portion of NPM present in the NPM-ALK fusion protein and also in two other NPM fusion proteins (NPM-RARalpha and NPM-MLF1). The third antibody recognizes the C-terminal portion (deleted in NPM-ALK) and reacts only with wild-type NPM. The three antibodies immunostain wild-type NPM (in paraffin-embedded normal tissue samples) in cell nuclei and in the cytoplasm of mitotic cells. Cerebral neurones, exceptionally, show diffuse cytoplasmic labeling. In contrast to normal tissues, the two antibodies against the N-terminal portion of NPM labeled the cytoplasm of neoplastic cells, in four ALK-positive ALCL, reflecting their reactivity with NPM-ALK fusion protein, whereas the antibody to the C-terminal NPM epitope labeled only cell nuclei. Immunocytochemical labeling with these antibodies can therefore confirm that an ALK-positive lymphoma expresses NPM-ALK (rather than a variant ALK-fusion protein) and may also provide evidence for chromosomal anomalies involving the NPM gene other than the classical (2;5) translocation.
Desorption electrospray ionization mass spectrometry (2015)

AccessScience is an authoritative and dynamic online resource that contains incisively written, high-quality educational material covering all major scientific disciplines. An acclaimed gateway to scientific knowledge, AccessScience is continually expanding the ways it can demonstrate and explain core, trustworthy scientific information that inspires and guides users to deeper knowledge.
Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK (2015)

Monoclonal antibodies can block cellular interactions that negatively regulate T-cell immune responses, such as CD80/CTLA-4 and PD-1/PD1-L, amplifying preexisting immunity and thereby evoking antitumor immune responses. Ibrutinib, an approved therapy for B-cell malignancies, is a covalent inhibitor of BTK, a member of the B-cell receptor (BCR) signaling pathway, which is critical to the survival of malignant B cells. Interestingly this drug also inhibits ITK, an essential enzyme in Th2 T cells and by doing so it can shift the balance between Th1 and Th2 T cells and potentially enhance antitumor immune responses. Here we report that the combination of anti-PD-L1 antibody and ibrutinib suppresses tumor growth in mouse models of lymphoma that are intrinsically insensitive to ibrutinib. The combined effect of these two agents was also documented for models of solid tumors, such as triple negative breast cancer and colon cancer. The enhanced therapeutic activity of PD-L1 blockade by ibrutinib was accompanied by enhanced antitumor T-cell immune responses. These preclinical results suggest that the combination of PD1/PD1-L blockade and ibrutinib should be tested in the clinic for the therapy not only of lymphoma but also in other hematologic malignancies and solid tumors that do not even express BTK.
Drug Releasing Polymer Thin Films: New Era of Surface-Mediated Drug Delivery (2010)

Polymer films and coatings are among the popular and most successful tools to modulate surface properties of biomaterials, specifically tissue responses and fouling behavior. Over the past decade, a novel opportunity has been widely investigated, namely utility of surface coatings in surface-mediated drug delivery. In these applications, deposited polymer films act as both a coating to modulate surface properties and a reservoir for active therapeutic cargo. The field has recently accelerated beyond the proof-of-concept reports toward delivering practical solutions and established technologies for biomedical applications. This review briefly summarizes the recent successes of polymer thin films, specifically those constructed by sequential polymer deposition technique, in surface-mediated drug delivery.
Effect of CYP2D6 metabolizer status on the disposition of the (+) and (−) enantiomers of perhexiline in patients with myocardial ischaemia (2007)

Perhexiline's pharmacokinetics exhibit significant enantioselectivity in CYP2D6 extensive/intermediate and poor metabolizers, with both enantiomers displaying polymorphic and saturable metabolism via CYP2D6. Clinical use of rac-perhexiline may be improved by developing specific enantiomer target plasma concentration ranges.