gebhart/patrepeval huggingface dataset:
Interaction of Integrin-Linked Kinase and Miniature Chromosome Maintenance 7–Mediating Integrin α7 Induced Cell Growth Suppression (2010)

Mutation of integrin alpha7 (ITGA7) was previously identified in multiple human malignancies. Restoration of ITGA7 expression in prostate cancer and leiomyosarcoma cell lines suppressed tumor growth and cell motility both in vitro and in vivo. In this study, we showed that integrin-linked kinase (ILK) binds with miniature chromosome maintenance 7 (MCM7), a DNA replication licensing protein. A 58-amino acid ILK binding motif was identified in the NH(2)-terminus of MCM7. The expression of ITGA7 induced the phosphorylation of MCM7. Knocking down of ILK abrogated ITGA7-induced MCM7 phosphorylation. ANK, the dominant-negative mutant of ILK, also blocked the phosphorylation of MCM7 induced by ITGA7. The phosphorylation of MCM7 reduced MCM7 chromatin association and inhibited cell growth. A MCM7 mutant that does not bind with ILK did not respond to ITGA7 stimulation, and behaved similarly to a dominant MCM7-negative mutant and neutralized the effect of ITGA7. We conclude that ILK interaction with MCM7 and MCM7 phosphorylation may be a critical event in ITGA7 signaling pathway, leading to tumor suppression.
Protein Phosphatase 5 Is a Major Component of Glucocorticoid Receptor·hsp90 Complexes with Properties of an FK506-binding Immunophilin (1997)

Steroid receptors are recovered from hormone-free cells in multiprotein complexes containing hsp90, p23, an immunophilin, and often some hsp70. The immunophilin, which can be of the FK506- or cyclosporin A-binding class, binds to hsp90 via its tetratricopeptide repeat (TPR) domain, and different receptor heterocomplexes exist depending upon which immunophilin occupies the TPR-binding region of hsp90. We have recently reported that a protein serine/threonine phosphatase that is designated PP5 and contains four TPRs binds to hsp90 and is co-purified with the glucocorticoid receptor (GR) (Chen, M.-S., Silverstein, A. M., Pratt, W. B., and Chinkers, M. (1996) J. Biol. Chem. 271, 32315-32320). In this work, we show that PP5 is recovered with both GR that is nuclear and GR that is cytoplasmic in hormone-free cells. Approximately one-half of the GR.hsp90 heterocomplexes in L cell cytosol contains an immunophilin with high affinity FK506 binding activity, such as FKBP51 or FKBP52, and approximately 35% contains PP5. Only a small (but undetermined) fraction of the native GR.hsp90 heterocomplexes contain the cyclosporin A-binding immunophilin CyP-40. PP5, FKBP52, and CyP-40 exist in separate heterocomplexes with hsp90, and competition binding experiments with the PP5 TPR domain suggest that the three proteins occupy a common binding site on hsp90. A 55-residue connecting region between the N-terminal TPR domain of human PP5 and its C-terminal phosphatase domain has 50% amino acid homology and 22% identity with the central portion of the peptidylprolyl isomerase domain of human FKBP52. Of the 9 residues in this portion of FKBP52 involved in high affinity interactions with FK506, 3 residues are retained and 4 have homologous substitutions in PP5. Although immunoadsorbed PP5 did not bind [3H]FK506, we found that both rabbit PP5 in reticulocyte lysate and purified rat PP5 were specifically retained by an FK506 affinity matrix. Thus, we propose that PP5 possesses properties of an immunophilin with low affinity FK506 binding activity and that it determines a major portion of the native GR heterocomplexes in L cell cytosol.
Candidate‐based proteomics in the search for biomarkers of cardiovascular disease (2004)

The key concept of proteomics (looking at many proteins at once) opens new avenues in the search for clinically useful biomarkers of disease, treatment response and ageing. As the number of proteins that can be detected in plasma or serum (the primary clinical diagnostic samples) increases towards 1000, a paradoxical decline has occurred in the number of new protein markers approved for diagnostic use in clinical laboratories. This review explores the limitations of current proteomics protein discovery platforms, and proposes an alternative approach, applicable to a range of biological/physiological problems, in which quantitative mass spectrometric methods developed for analytical chemistry are employed to measure limited sets of candidate markers in large sets of clinical samples. A set of 177 candidate biomarker proteins with reported associations to cardiovascular disease and stroke are presented as a starting point for such a 'directed proteomics' approach.
Transgenic animals in the evaluation of compound efficacy and toxicity: Will they be as useful as they are novel? (1992)

1. Construction of transgenic mice is predicated upon inserting foreign DNA into native host DNA and having this expressed in the germline. This may be accomplished by nuclear injection, retroviral vectors or use of embryonic stem (ES) cells. 2. Expression of novel structural genes may be reasonably directed by the judicious use of an accompanying promoter/enhancer sequence. Insertion of foreign genes may be designed to result in phenotypic expression of a novel trait or ablation of a native gene or gene product. 3. Resulting transgenic mice offer significant utility as models of human diseases and a unique opportunity for investigating immune and metabolic pathways as well as for exploring mechanisms of development, mutagenesis and teratogenesis. 4. Use of transgenic animals in drug development has considerable potential although realization of this potential will take time. Constructing transgenics is only the first step in a complex series of events culminating in understanding the consequences of imposing novel genetic material on an intact, highly integrated living system. Practical use of transgenic animals will depend upon substantial effort being spent in investigating and validating the phenotypic consequences of gene transfer.
Formation and Structure of Self-Assembled Monolayers (1996)

ADVERTISEMENT RETURN TO ISSUEPREVArticleFormation and Structure of Self-Assembled MonolayersAbraham UlmanView Author Information Department of Chemical Engineering, Chemistry and Materials Science, and the Herman F. Mark Polymer Research Institute, Polytechnic University, Six MetroTech Center, Brooklyn, New York 11201 Cite this: Chem. Rev. 1996, 96, 4, 1533–1554Publication Date (Web):June 20, 1996Publication History Received3 November 1995Revised18 April 1996Published online20 June 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/cr9502357https://doi.org/10.1021/cr9502357research-articleACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views61959Altmetric-Citations6957LEARN 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 SUBJECTS:Adsorption,Alkyls,Gold,Molecules,Monolayers Get e-Alerts
National Optical Astronomy Observatories (NOAO) Infrared Adaptive Optics Program I: General Description (1986)

We describe the general principles behind a polychromatic adaptive optics prograff astronomy which was started at NOAO recently. In this program the atmospheric wavef distortions are measured at visible wavelengths (700nm) using an astronomical object vicinity of the infrared object of interest. The resulting wavefront corrections ar applied to an infrared imaging system which utilizes a two-dimensional detector arra
Flow-Induced Alignment of Fiberlike Supramolecular Self-Assemblies during Organogel Formation with Various Low Molecular Mass Organogelator−Solvent Systems (2002)

Organogelators are small organic molecules that self-assemble at low temperature in long entangled and connected fibers to give birth to a random gel. In this paper, we describe a systematic procedure to prepare easily orientated samples by using a weak flow. We demonstrate that applying a mechanical shear stress during the cooling of a hot isotropic solution of a low molecular mass gelator can lead not only to the alignment of the growing fibers in a parallel fashion within the bulk material but also to centimeter-sized, cylinder-shaped objects displaying strong anisotropic features and well-defined organization at the nanometer level. This work opens exciting ways toward organic materials exhibiting enhanced mechanical, photonic, magnetic, or electronic properties along a given direction.
Neuraminidase Expressed by Streptococcus pneumoniae Desialylates the Lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae : a Paradigm for Interbacterial Competition among Pathogens of the Human Respiratory Tract (2002)

Both Neisseria meningitidis and Haemophilus influenzae are capable of mimicking host structures by decorating their lipopolysaccharides with sialic acid. We show that a neuraminidase expressed by Streptococcus pneumoniae (NanA) is able to desialylate the cell surfaces of both these species, which reside in and possibly compete for the same host niche.
ChemInform Abstract: Synthesis of 2,5‐Disubstituted 3,6‐Diamino‐1,4‐benzoquinones. (1982)

Abstract Das aus Bromanil in bekannter Weise über 2,5‐Dibrom‐3,6‐diamino‐chinon zugängliche Hydrochinon (I) wird mit Säuren oder Säurechloriden (II) in die anellierten Bis‐oxazole (III) umgewandelt.
Photodynamic Therapy for Pancreatic Cancer (2007)

Photodynamic therapy can be an effective treatment of patients with pancreatic cancer, but more extensive preclinical and clinical trials are needed for further improvement in the clinical application of PDT, especially in avoidance of complications during PDT.
Synthesis of 3-Pyridinols. III. Synthesis of Pyridoxine Skeletons from 4-Methyloxazole (1965)

Pyridoxine dimethyl ether (II) and 4-deoxypyridoxine (IV) were synthesized from I by reaction B and C, respectively. V was also derived to pyridoxine via VIII by application of Okamoto's method.
Nanotheranostics of Circulating Tumor Cells, Infections and Other Pathological Features in Vivo (2013)

Many life-threatening diseases are disseminated through biological fluids, such as blood, lymph, and cerebrospinal fluid. The migration of tumor cells through the vascular circulation is a mandatory step in metastasis, which is responsible for ∼90% of cancer-associated mortality. Circulating pathogenic bacteria, viruses, or blood clots lead to other serious conditions including bacteremia, sepsis, viremia, infarction, and stroke. Therefore, technologies capable of detecting circulating tumor cells (CTCs), circulating bacterial cells (CBCs), circulating endothelial cells (CECs), circulating blood clots, cancer biomarkers such as microparticles and exosomes, which contain important microRNA signatures, and other abnormal features such as malaria parasites in biological fluids may facilitate early diagnosis and treatment of metastatic cancers, infections, and adverse cardiovascular events. Unfortunately, even in a disease setting, circulating abnormal cells are rare events that are easily obscured by the overwhelming background material in whole blood. Existing detection methods mostly rely on ex vivo analyses of limited volumes (a few milliliters) of blood samples. These small volumes limit the probability of detecting CTCs, CECs, CBCs and other rare phenomena. In vivo detection platforms capable of continuously monitoring the entire blood volume may substantially increase the probability of detecting circulating abnormal cells and, in particular, increase the opportunity to identify exceedingly rare and potentially dangerous subsets of these cells, such as circulating cancer stem cells (CCSCs). In addition, in vivo detection technologies capable of destroying and/or capturing circulating abnormal cells may inhibit disease progression. This review focuses on novel therapeutic and diagnostic (theranostic) platforms integrating in vivo real-time early diagnosis and nano-bubble based targeted therapy of CTCs, CECs, CBCs and other abnormal objects in circulation. This critical review particularly focuses on nanotechnology-based theranostic (nanotheranostic) approaches, especially in vivo photoacoustic (PA) and photothermal (PT) nanotheranostic platforms. We emphasize an urgent need for in vivo platforms composed of multifunctional contrast nanoagents, which utilize diverse modalities to realize a breakthrough for early detection and treatment of harmful diseases disseminated through the circulation.
Characterization of the testis‐specific promoter region in the human pituitary adenylate cyclase‐activating polypeptide (PACAP) gene (2010)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide localized in the testis at concentration comparable to that found in the brain, suggesting involvement in spermatogenesis. In this study, we identified the human PACAP testis-specific exon (TSE) 10.9 kb upstream from the translational start site and found that the testis-specific transcript of the human PACAP gene was found to be spliced from the TSE into a region of intron 2 without a frameshift. The resulting PACAP precursor has no signal peptide, suggesting that PACAP functions physiologically in an intracrine manner in the testis. The 5'-flanking region of the TSE contains an 80-bp fragment with potent promoter activity in testicular F9 cell. Electrophoresis mobility shift assays showed that proteins from the F9 nuclear extract interacted specifically with the 80-bp fragment. DNA affinity chromatography allowed isolation of the specific proteins bound to the 80-bp fragment, two of which were identified as Poly (ADP-ribose) polymerase-1 (PARP-1) and TIA-1-related protein (TIAR) by mass spectrometry. By using their siRNAs, the depletion of their proteins in F9 cells affected the potent promoter activity of the 80-bp fragment, suggesting that they might be involved in the testis-specific gene expression of PACAP.
PDE4 inhibitors 1999 (1999)

The search for novel phosphodiesterase Type 4 (PDE4) inhibitors remains one of the most active fields within the pharmaceutical industry. Recent progress within the clinical development of PDE4 inhibitors has seen two more compounds progress to Phase III development. However, both Ariflo™ (SB-207499) and roflumilast are being developed principally for the treatment of chronic obstructive pulmonary disease (COPD) rather than asthma. This review also highlights the novel structural classes of PDE4 inhibitors disclosed in the past year’s patent applications and the concentration of effort on the identification of selective PDE4D inhibitors.
Experimental investigation of an eight-qubit unit cell in a superconducting optimization processor (2010)

A superconducting chip containing a regular array of flux qubits, tunable interqubit inductive couplers, an XY-addressable readout system, on-chip programmable magnetic memory, and a sparse network of analog control lines has been studied. The architecture of the chip and the infrastructure used to control it were designed to facilitate the implementation of an adiabatic quantum optimization algorithm. The performance of an eight-qubit unit cell on this chip has been characterized by measuring its success in solving a large set of random Ising spin-glass problem instances as a function of temperature. The experimental data are consistent with the predictions of a quantum mechanical model of an eight-qubit system coupled to a thermal environment. These results highlight many of the key practical challenges that we have overcome and those that lie ahead in the quest to realize a functional large-scale adiabatic quantum information processor.
Regulation of Protein Serine-Threonine Phosphatase Type-2A by Tyrosine Phosphorylation (1992)

Extracellular signals that promote cell growth activate cascades of protein kinases. The kinases are dephosphorylated and deactivated by a single type-2A protein phosphatase. The catalytic subunit of type-2A protein phosphatase was phosphorylated by tyrosine-specific protein kinases. Phosphorylation was enhanced in the presence of the phosphatase inhibitor okadaic acid, consistent with an autodephosphorylation reaction. More than 90% of the activity of phosphatase 2A was lost when thioadenosine triphosphate was used to produce a thiophosphorylated protein resistant to autodephosphorylation. Phosphorylation in vitro occurred exclusively on Tyr307. Phosphorylation was catalyzed by p60v-src, p56lck, epidermal growth factor receptors, and insulin receptors. Transient deactivation of phosphatase 2A might enhance transmission of cellular signals through kinase cascades within cells.
Anti-TNF Antibody Therapy in Rheumatoid Arthritis and the Risk of Serious Infections and Malignancies (2006)

There is evidence of an increased risk of serious infections and a dose-dependent increased risk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy. The formal meta-analysis with pooled sparse adverse events data from randomized controlled trials serves as a tool to assess harmful drug effects.
Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome (2013)

Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumor syndrome that includes susceptibility to pancreatic islet tumors. This syndrome results from mutations in the MEN1 gene, encoding menin. Although menin acts as an oncogenic cofactor for mixed lineage leukemia (MLL) fusion protein-mediated histone H3 lysine 4 methylation, the precise basis for how menin suppresses gene expression and proliferation of pancreatic beta cells remains poorly understood. Here, we show that menin ablation enhances Hedgehog signaling, a proproliferative and oncogenic pathway, in murine pancreatic islets. Menin directly interacts with protein arginine methyltransferase 5 (PRMT5), a negative regulator of gene transcription. Menin recruits PRMT5 to the promoter of the Gas1 gene, a crucial factor for binding of Sonic Hedgehog (Shh) ligand to its receptor PTCH1 and subsequent activation of the Hedgehog signaling pathway, increases repressive histone arginine symmetric dimethylation (H4R3m2s), and suppresses Gas1 expression. Notably, MEN1 disease-related menin mutants have reduced binding to PRMT5, and fail to impart the repressive H4R3m2s mark at the Gas1 promoter, resulting in its elevated expression. Pharmacologic inhibition of Hedgehog signaling significantly reduces proliferation of insulinoma cells, and expression of Hedgehog signaling targets including Ptch1, in MEN1 tumors of mice. These findings uncover a novel link between menin and Hedgehog signaling whereby menin/PRMT5 epigenetically suppresses Hedgehog signaling, revealing it as a target for treating MEN1 tumors.
Mechanisms involved in the differential reduction of omega-3 and omega-6 highly unsaturated fatty acids by structural heart disease resulting in “HUFA deficiency” (2012)

The causes of reduced levels of omega-3 and omega-6 highly unsaturated fatty acids ("HUFA deficiency") in heart failure remain unresolved. HUFA profiles were examined in the serum of 331 patients with failing versus nonfailing heart disease. Arachidonic acid was positively correlated (P < 0.001) with eicosapentaenoic acid (EPA) (r = 0.40) and docosahexaenoic acid (DHA) (r = 0.53) and negatively with palmitic (r = 0.42), palmitoleic (r = 0.38), and oleic acid (r = 0.48). Delta-5 desaturase activity was reduced (P < 0.01) in heart failure patients with low ejection fraction, dilatation, increased wall stress, and reduced heart rate variability (SDNN). In these patients, the reduced (P < 0.01) HUFA and increased palmitic (P < 0.01) and oleic acid (P = 0.05) arose from separate influences involving reduced cardiac contractility (arachidonic acid and palmitic acid predicted by ejection fraction) and chamber dilatation (DHA and oleic acid predicted by end-diastolic diameter). A low DHA (0.2%-0.9% versus 1.4%-3.1%) was associated (P < 0.025) with atrial dilatation (44 ± 8 mm versus 40 ± 8 mm). Equidirectional but less pronounced effects on HUFA were induced by sympathetic activation and (or) insulin resistance (fat and sugar fed to deoxycorticosterone acetate (DOCA)-salt rats) but not by compensated cardiac overload alone (DOCA-salt or aortic constriction), or reduced fatty acid oxidation (CPT-1 inhibition). Based on administration of omega-3 HUFA (OMACOR), dilatation is identified as a target for 1-2 g omega-3 HUFA·day(-1). Interventions for reduced arachidonic acid remain to be explored.
Design and comparison of command shaping methods for controlling residual vibration (2003)

The authors evaluate a signal generation technique for commanding high-performance machines to move without exciting residual vibration. This time-domain input-shaping technique works like a filter that is designed to eliminate decaying sinusoidal resonance responses. It is compared to a variety of filtering techniques and is shown to perform more effectively than any of them. In particular, frequency-domain filter design techniques are less effective for shaping vibration-reducing inputs to systems. The three-impulse shaping sequence offers significant performance advantages in that moves require less time and result in little or no residual vibration. In addition, the response is not sensitive to variations in the system parameters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Role of segment polarity genes in the definition and maintenance of cell states in the Drosophila embryo (1988)

Segment polarity genes are expressed and required in restricted domains within each metameric unit of the Drosophila embryo. We have used the expression of two segment polarity genes engrailed (en) and wingless (wg) to monitor the effects of segment polarity mutants on the basic metameric pattern. Absence of patched (ptc) or naked (nkd) functions triggers a novel sequence of en and wg patterns. In addition, although wg and en are not expressed on the same cells absence of either one has effects on the expression of the other. These observations, together with an analysis of mutant phenotypes during development, lead us to suggest that positional information is encoded in cell states defined and maintained by the activity of segment polarity gene products.