gebhart/patrepeval huggingface dataset:
Discovery and Development of Aurora Kinase Inhibitors as Anticancer Agents (2009)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTDiscovery and Development of Aurora Kinase Inhibitors as Anticancer AgentsJohn R. Pollard* and Michael MortimoreView Author Information Vertex Pharmaceuticals (Europe) Ltd., 88 Milton Park, Abingdon, Oxfordshire OX14 4RY, U.K.* To whom correspondence should be addressed. Phone: 44 (0) 1235 438800. Fax: 44 (0) 1235 820440. E-mail: [email protected]Cite this: J. Med. Chem. 2009, 52, 9, 2629–2651Publication Date (Web):March 25, 2009Publication History Received25 September 2008Published online25 March 2009Published inissue 14 May 2009https://doi.org/10.1021/jm8012129Copyright © 2009 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views7997Altmetric-Citations154LEARN 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 InReddit Read OnlinePDF (1020 KB) Get e-AlertsSUBJECTS:Cells,Genetics,Inhibition,Inhibitors,Peptides and proteins Get e-Alerts
Antagonist Muscle Inhibition During Voluntary and Automatic Movements Does Not Appear to Involve the Same Neural Pathways (1996)

Motor Control Research Laboratory, Physical Therapy Department, The University of Montana, Missoula, Mont. Support by NIH-R15 NS30664-01A1, Murdock Charitable Trust, and The University of Montana.
Supramolekulare Phosphorylierung kationischer Alkohole mit 3‐Arylindol‐4‐carboxamidin‐Struktur (1994)

Supramolecular Phosphorylation of Cationic Alcohols with a 3‐Arylindole‐4‐carboxamidine Framework Recently we reported on the synthesis of 8‐phenylnaphthalene‐1‐carboxamidines equipped with nucleophilic side chains ( 1, 2 ). In the protonated state these compounds were able to coordinate phosphoric acid diesters as ion‐pair complexes and to react with them in a quasi‐intramolecular way. In comparison with noncharged alcohols high‐rate enhancements of phosphorylation could be achieved. Now we describe the synthesis of analogous amidinium alcohols constructed from a 3,4‐disubstituted indole framework. Due to the five‐membered ring of the indole the angle between the substituents of 4 and 5 is extended compared to the naphthalene derivatives 1 and 2 . As a result from this structural change a slight increase of the phosphorylation rate of 4 is observed.
GREM1 is expressed in the cancer-associated myofibroblasts of basal cell carcinomas (2017)

Cancer-associated fibroblasts (CAFs) play important roles in cancer progression through their complex interactions with cancer cells. The secreted bone morphogenetic protein antagonist, gremlin1 (GREM1) is expressed by the CAFs of basal cell carcinomas (BCCs), and promotes the growth of cancer cells. In this study, we investigated the expression of GREM1 mRNAs in various benign and malignant skin tumors, including various BCC subtypes. Analysis by RNA in situ hybridization (ISH) revealed that fibroblasts in the scar tissue expressed GREM1 and α-smooth muscle actin (α-SMA), whereas resident fibroblasts in the dermis of the normal skin did not express GREM1. Real-time polymerase chain reaction analysis showed significantly higher GREM1 expression in skin cancers and pilomatricomas (PMCs) than in other benign skin tumors. Tissue microarrays analyzed by RNA ISH for GREM1 expression also demonstrated that 23% of BCCs, 42% of squamous cell carcinomas, 20% of melanomas, and 90% of PMCs were positive for GREM1 expression, whereas trichoepitheliomas, eccrine poromas, hidradenomas, and spiradenomas were negative for GREM1 expression. Most BCCs that were GREM1 expression positive were of desmoplastic or mixed subtypes, and GREM1 expression was localized to activated myofibroblasts at the tumoral-stromal interface. Interestingly, most PMCs harbored GREM1-expressing fibroblasts, probably because of the inflammatory responses caused by foreign body reactions to keratin. Additionally, in BCCs, stromal GREM1 expression had a strong correlation with CD10 expression. In conclusion, GREM1 is frequently expressed by myofibroblasts in scars or in the stroma of basal cell carcinomas, suggesting that GREM1 expression can be a marker for activated myofibroblasts in the cancer stroma or in scar tissue.
Elastography (2002)

Intravascular ultrasound elastography is a method for measuring the local elastic properties of coronary atherosclerotic plaques using intravascular ultrasound (IVUS). Mechanical properties of the different tissues within a plaque are measured through strain. In the last decade, several groups have applied elastography intravascularly with various levels of success. In this paper, the approaches of the different research groups will be discussed and the focus will be on our approach to the application of intravascular elastography.
A reprogrammable gate array and applications (1993)

A field-programmable gate array (FPGA) can implement thousands of gates of logic, has no up-front fixed costs, and can be programmed in a few minutes by writing into on-chip static memory is described. This kind of FPGA can be reprogrammed any number of times, providing a versatile platform for rapid hardware implementation. Reprogrammable technology allows software-like design methodologies to be applied to logic design. The construction of this kind of FPGA, design tradeoffs, and examples of applications that take advantage of reprogrammability are examined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A chromosome 14-specific human satellite III DNA subfamily that shows variable presence on different chromosomes 14. (1992)

We describe a new subfamily of satellite III DNA (pTRS-63), which, by a combination of in situ hybridization to human metaphase chromosomes and analysis of a panel of somatic cell hybrids, is shown to be specific for human chromosome 14. This DNA has a basic 5-bp repeating unit of diverged GGAAT which is tandemly repeated and organized into either one of two distinct higher-order structures of 5 kb (designated the "L" form) or 4.8 kb (designated the "S" form). In addition, a third (Z) form, representing no detectable levels of this satellite III subfamily, is found. Results from five somatic cell hybrid lines and from a number of informative human individuals suggest that, on any one chromosome 14, only one of the three forms may exist. Subchromosomally, this sequence has been mapped to the p11 region and is distal to the domain occupied by another previously described satellite III subfamily (pTRS-47) found on chromosome 14. The pTRS-63 sequence described adds to the understanding of the structural organization of the short arm of human chromosome 14 and should be useful for the investigation of the molecular etiology of the frequently occurring t(13q14q) and t(14q21q) Robertsonian translocations.
A Strategy for Constructing Large Protein Interaction Maps Using the Yeast Two-Hybrid System:Regulated Expression Arrays and Two-Phase Mating (2003)

Maps representing the binary interactions among proteins have become valuable tools for understanding how proteins work together to mediate biological processes. One of the most effective methods for detecting biologically important protein interactions has been the yeast two-hybrid system. Here we present an efficient two-hybrid strategy to facilitate construction of protein interaction maps on a genome-wide scale. The strategy begins with two arrays of yeast expressing known proteins fused to either a DNA binding domain (BD), or a transcription activation domain (AD). The fusion proteins are conditionally expressed using regulated promoters that can be repressed during construction and amplification of the yeast arrays. Interaction assays are conducted in two phases. In the first phase, small pools of AD strains are mated with the array of BD strains. In the second phase, individual BD strains are mated with appropriate subsets of the AD array corresponding to positive pools in the first phase. This strategy has several advantages over previously described approaches, including the ability to detect interactions with proteins that inhibit yeast growth or that activate transcription as BD fusions. Moreover, by minimizing the number of mating operations and sequencing reactions needed to test large sets of binary interactions, this strategy is more efficient than either matrix or library screening approaches. We also present a three-dimensional pooling scheme to further increase the efficiency of large-scale two-hybrid analyses.
Induction of vascular endothelial growth factor expression by prostaglandin E2 and E1 in osteoblasts. (1994)

PGE1 and PGE2 are potent stimulators of bone formation. Osteogenesis is strongly dependent on angiogenesis. Vascular endothelial growth factor (VEFG), a secreted endothelial cell-specific mitogen, has been implicated in physiological and pathological angiogenesis. The aim of this study was to examine the possible role of VEGF in PG stimulation of bone formation. We found that in rat calvaria-derived osteoblast-enriched cells and in the osteoblastic RCT-3 cell line PGE2 and E1 increased VEGF mRNA and protein levels. The increased expression of VEGF mRNA produced by PGE2 was rapid (maximal at 1 h), transient (declined by 3 h), potentiated by cycloheximide, and abolished by actinomycin D. PGE2 had no effect on VEGF mRNA stability, suggesting transcriptional regulation of VEGF expression by PGF2. Rp-cAMP, a cAMP antagonist, suppressed VEGF mRNA induced by PGE2, indicating cAMP mediation. The upregulation of VEGF expression by PGE2 in the preosteoblastic RCT-1 cells was potentiated by treatment with retinoic acid, which induces the differentiation of these cells. The upregulation of VEGF mRNA by PGE2 was inhibited by dexamethasone treatment. In addition, Northern blot analysis showed that VEGF mRNA is expressed in adult rat tibia. In summary, we documented, for the first time, the expression of VEGF in osteoblasts and in bone tissue. Stimulation of VEGF expression by PGs and its suppression by glucocorticoids, which, respectively, stimulate and suppress bone formation, strongly implicate the involvement of VEGF in bone metabolism.
Early evolution of histone mRNA 3′ end processing (2007)

The replication-dependent histone mRNAs in metazoa are not polyadenylated, in contrast to the bulk of mRNA. Instead, they contain an RNA stem-loop (SL) structure close to the 3' end of the mature RNA, and this 3' end is generated by cleavage using a machinery involving the U7 snRNP and protein factors such as the stem-loop binding protein (SLBP). This machinery of 3' end processing is related to that of polyadenylation as protein components are shared between the systems. It is commonly believed that histone 3' end processing is restricted to metazoa and green algae. In contrast, polyadenylation is ubiquitous in Eukarya. However, using computational approaches, we have now identified components of histone 3' end processing in a number of protozoa. Thus, the histone mRNA stem-loop structure as well as the SLBP protein are present in many different protozoa, including Dictyostelium, alveolates, Trypanosoma, and Trichomonas. These results show that the histone 3' end processing machinery is more ancient than previously anticipated and can be traced to the root of the eukaryotic phylogenetic tree. We also identified histone mRNAs from both metazoa and protozoa that are polyadenylated but also contain the signals characteristic of histone 3' end processing. These results provide further evidence that some histone genes are regulated at the level of 3' end processing to produce either polyadenylated RNAs or RNAs with the 3' end characteristic of replication-dependent histone mRNAs.
Functional Architecture of the Nicotinic Acetylcholine Receptor: From Electric Organ to Brain (1991)

International audience
Inorganic glasses, glass-forming liquids and amorphizing solids (2007)

Abstract We take familiar inorganic oxide glasses and non-oxide glasses and the liquids from which they derive to review the current understanding of their atomic structure, ranging from the local environments of individual atoms to the long-range order which can cover many interatomic distances. The structural characteristics of important glasses and melts, like silicates, borates, alumino-silicates, halides and chalcogenides, are drawn from the results of recent spectroscopy and scattering experiments. The techniques include Nuclear Magnetic Resonance (NMR) and X-ray Absorption Fine Structure (XAFS), Neutron Scattering (NS) and Small- and Wide-angle X-ray Scattering measurements (SAXS/WAXS), and are often combined with computer simulation experiments in order to obtain detailed images of structure and diffusion in the glassy as well as in the molten state. We then review the current understanding of relaxation in glasses, liquids and polyamorphic states. This includes phenomenological models and theories of relaxation in different dynamical regimes, spectroscopic studies of atomic-scale mechanisms of viscous flow in inorganic glass-formers and the signatures of relaxational behaviour embedded in the low-frequency vibrational dynamics of glasses including the Boson peak and the Two-Level Systems (TLS) that control conformational transformation. We conclude this review by extending concepts of the dynamics of the glass transition from the supercooled liquid in order to understand the solid-state amorphization of crystals under temperature and pressure and to determine the thermodynamic limits of the crystalline and glassy state. Acknowledgements The authors thank the following for helpful discussions: Bruce Aitken, Austen Angell, Punit Boolchand, Uli Buchenau, Jűrgen Horbach, Jorge Íñiguez, Himanshu Jain, Alexander Kolobov, Philipp Maass, Florian Menau, Alexandra Navrotsky, Peter Poole, Andrei Sokolov, Yann Vaills and Martin Wilding. One of the authors (GNG) acknowledges the support of the Higher Education Funding Council for Wales through the Centre for Advanced Functional Materials and Devices. Both authors are grateful to the International Materials Institute on New Functionality in Glass – NSF Grant No. DMR-0409588 – for support in writing this review. One author (SS) also acknowledges support of NSF Grant No. DMR-0603933 for the preparation of this review.
Fisco, poder y monarquía en los albores de la Modernidad. Castilla, 1504-1525 (2004)

En la presente tesis doctoral se analiza la evolucion hacendistica de Castilla entre el periodo transcurrido desde el fallecimiento de Isabel la Catolica y la salida de la revuelta comunera. En aquellos anos, y como consecuencia de la particular dinamica dinastica que se creo tras 1504, el reino asistio a un periodo de inestabilidad caracterizado por dos elementos basicos: afirmacion de poderes particulares y sujecion de estos a un discurso de docilidad frente a la propia Corona. Asimismo, aquellas decadas tambien se caracterizaron por la existencia de una conflictividad general fruto de lo asentado desde principios del sido XVI. La tesis doctoral se divide en dos partes bien diferenciadas. En la primera de ellas se analiza la hacienda ordinaria de Castilla a partir de cuatro capitulos, siempre en relacion con las estructuras de credito que caracterizaban aquel sistema fiscal: el primero de ellos traza la evolucion de los tributos tanto a nivel general como particular; el segundo, a su vez, se centra en el analisis del gasto. El tercero se esfuerza por definir los circuitos financieros fundamentales para la consecucion de credito. Finalmente, se realiza un amplio estudio sociologico de los organismos encargados del gobierno de la hacienda real de Castilla. La segunda parte de la tesis tiene como objetivo el analisis de la evolucion politica y fiscal de Castilla. Concretamente, se analiza la politica hacendistica en relacion con el desarrollo del poder a partir de capitulos que recogen etapas fundamentales en el devenir de Castilla; a saber, crisis dinastica acaecida tras 1504, reordenacion a partir de los acuerdos de Blois y Cortes de Madrid de 1510, segunda regencia de Cisneros, la epoca comunera y el posterior periodo de reformas politicas y administrativas.
Epidural spinal electrical stimulation in severe angina pectoris. (1988)

The short term effects of epidural spinal electrical stimulation were studied in 10 patients with angina pectoris of New York Heart Association functional class III or IV. The antianginal pharmacological treatment given at entry to the study was regarded as optimal and was not changed during the study. The effects of epidural spinal electrical stimulation were measured by repeated bicycle ergometer tests. Treatment with epidural spinal electrical stimulation increased the patients' working capacity, decreased ST segment depression, increased time to angina, and reduced the recovery time. The observed effects did not seem to be correlated with any changes in myocardial oxygen demand during epidural spinal electrical stimulation and were additional to the benefits of the pharmacological treatment.
Evolutionary relationship of archaebacteria, eubacteria, and eukaryotes inferred from phylogenetic trees of duplicated genes. (1989)

All extant organisms are though to be classified into three primary kingdoms, eubacteria, eukaryotes, and archaebacteria. The molecular evolutionary studies on the origin and evolution of archaebacteria to date have been carried out by inferring a molecular phylogenetic tree of the primary kingdoms based on comparison of a single molecule from a variety of extant species. From such comparison, it was not possible to derive the exact evolutionary relationship among the primary kingdoms, because the root of the tree could not be determined uniquely. To overcome this difficulty, we compared a pair of duplicated genes, elongation factors Tu and G, and the alpha and beta subunits of ATPase, which are thought to have diverged by gene duplication before divergence of the primary kingdoms. Using each protein pair, we inferred a composite phylogenetic tree with two clusters corresponding to different proteins, from which the evolutionary relationship of the primary kingdoms is determined uniquely. The inferred composite trees reveal that archaebacteria are more closely related to eukaryotes than to eubacteria for all the cases. By bootstrap resamplings, this relationship is reproduced with probabilities of 0.96, 0.79, 1.0, and 1.0 for elongation factors Tu and G and for ATPase subunits alpha and beta, respectively. There are also several lines of evidence for the close sequence similarity between archaebacteria and eukaryotes. Thus we propose that this tree topology represents the general evolutionary relationship among the three primary kingdoms.
Sequence-specific 5mC detection in live cells based on the TALE-split luciferase complementation system (2018)

We established a method for converting TALE-DNA binding to luminescence, by combining a TALE and a split luciferase system. Furthermore, using a methylation-sensitive TALE, sequence-specific 5mC detection of genomic DNA was achieved in live cells. This study provides a new strategy for exploring the biological functions of 5mC.
Polysaccharides in Lichens and Fungi. I. Antitumour Active Polysaccharides of Gyrophora esculenta MIYOSHI and Lasallia papulosa (ACH.) LANO (1968)

A marked inhibiting effect against implanted sarcoma 180 was shown by the so far unknown glucan of a lichen, Gyrophora esculenta MIYOSHI. The glucan was isolated in a pure state and proved to be a partially acylated β-1, 6-glucan. The antitumour active component of another lichen, Lasallia papulosa (ACH.) LLANO, has been almost established to be identical with that of G. esculenta.
Differential expression of cathepsins B and L compared with matrix metalloproteinases and their respective inhibitors in rheumatoid arthritis and osteoarthritis: A parallel investigation by semiquantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry (1998)

The data indicate a more pronounced expression of MMP mRNA compared with cysteine proteinases in RA. The higher levels of cathepsin B and L proteins in RA synovial lining cells compared with OA are consistent with previous studies that assert a post-transcriptional up-regulation of these enzymes in RA.
Gambling heuristic on a chord ring (2005)

Chord routing is greedy and non-symmetric, and is based on a skiplist-like data structure, whose entries are known as fingers. This work explores the benefits arising from a modified greedy lookup strategy that, without introducing any additional communication overhead, simply exploits the implicit symmetry knowledge intrinsic to the highly structured Chord ring. Through extensive simulation on a dynamic peer environment, we show a practical and feasible solution that actually boosts DHT lookup performance under a wide range of scenarios.
A double‐blinded, randomized, methylprednisolone‐controlled study on the efficacy of oclacitinib in the management of pruritus in cats with nonflea nonfood‐induced hypersensitivity dermatitis (2019)

Oclacitinib appears to be effective for treating pruritus and lesions in cats with NFNFIHD, albeit methylprednisolone seemed to perform better.
Salivary Agglutinin Inhibits HIV Type 1 Infectivity through Interaction with Viral Glycoprotein 120 (2003)

Salivary agglutinin (SAG) is a high molecular mass glycoprotein (340 kDa) that plays important roles in innate immunity. SAG has been found to specifically inhibit HIV-1 infectivity and to bind to virus through the envelope protein gp120. Although SAG binds to gp120 of the virus, the exact nature of this binding has not been characterized. Using surface plasmon resonance technology, we have found that SAG interacts with recombinant envelopes derived from diverse HIV-1 isolates with K(D) values ranging from 10(-7) to 10(-10) M, comparable to gp120-sCD4 binding. Furthermore, SAG binding to gp120 is Ca(2+) dependent. sCD4 prebound to gp120 failed to abrogate SAG binding, suggesting a distinct mechanism for SAG inhibition of HIV-1 infectivity. Inhibition by monoclonal antibodies specific for carbohydrates also implicates the involvement of carbohydrates in the interaction between SAG and gp120. These results argue that the anti-HIV-1 activity of SAG is due to carbohydrate-mediated binding to gp120. A demonstration that SAG is related to lung scavenger receptor, gp-340, further suggests the roles of SAG in preventing pathogen invasion at the entry portal and raises its potential as an anti-HIV-1 drug candidate.