gebhart/patrepeval huggingface dataset:
Epoxyeicosanoids as mediators of neurogenic vasodilation in cerebral vessels (2009)

Epoxyeicosatrienoic acids (EETs) are potent vasodilators produced from arachidonic acid by cytochrome P-450 (CYP) epoxygenases and metabolized to vicinal diols by soluble epoxide hydrolase (sEH). In the brain, EETs are produced by astrocytes and the vascular endothelium and are involved in the control of cerebral blood flow (CBF). Recent evidence, however, suggests that epoxygenases and sEH are present in perivascular vasodilator nerve fibers innervating the cerebral surface vasculature. In the present study, we tested the hypothesis that EETs are nerve-derived relaxing factors in the cerebral circulation. We first traced these fibers by retrograde labeling in the rat to trigeminal ganglia (TG) and sphenopalatine ganglia (SPG). We then examined the expression of CYP epoxygenases and sEH in these ganglia. RT-PCR and Western blot analysis identified CYP2J3 and CYP2J4 epoxygenase isoforms and sEH in both TG and SPG, and immunofluorescence double labeling identified CYP2J and sEH immunoreactivity in neuronal cell bodies of both ganglia. To evaluate the functional role of EETs in neurogenic vasodilation, we elicited cortical hyperemia by electrically stimulating efferent cerebral perivascular nerve fibers and by chemically stimulating oral trigeminal fibers with capsaicin. Cortical blood flow responses were monitored by laser-Doppler flowmetry. Local administration to the cortical surface of the putative EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (30 mumol/l) attenuated CBF responses to electrical and chemical stimulation. These results suggest that EETs are produced by perivascular nerves and play a role in neurogenic vasodilation of the cerebral vasculature. The findings have important implications to such clinical conditions as migraine, vasospasm after subarachnoid hemorrhage, and stroke.
High-Resolution Mapping of Ventricular Scar (2016)

Mapping with small closely spaced electrode catheters can improve mapping resolution within areas of low voltage.
Cell guidance by ultrafine topography in vitro (1991)

Laser holography and microelectronic fabrication techniques have been employed to make grating surfaces in fused quartz with ultrafine period (260 nm) in an attempt to mimic the topography of aligned fibrillar extracellular matrix (ECM), which, in the past, has been shown to affect the behaviour of cells in vitro and in vivo. The alignment of BHK cells, MDCK cells and chick embryo cerebral neurones on 260 nm period grating surfaces (130 nm grooves separated by 130 nm) of various depths (100, 210 and 400 nm) was examined. While all gratings aligned BHK cell populations, the degree of alignment was dependent on depth. The response of single MDCK cells to the grating patterns was both to align precisely to the direction of the gratings, and to elongate; only their elongation was depth-dependent. MDCK cells that were part of epithelial cell islands, and the outgrowth of neurites from chick embryo neurones, were mainly unaffected by the grating surfaces. It is clear that topography on this scale can control cell behaviour, but guidance of this type is strongly dependent on cell type and cell-cell interactions.
Paramagnetic relaxation reagents. Alternatives or complements to lanthanide shift reagents in nuclear magnetic resonance spectral analysis (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTParamagnetic relaxation reagents. Alternatives or complements to lanthanide shift reagents in nuclear magnetic resonance spectral analysisGeorge C. Levy and Richard A. KomoroskiCite this: J. Am. Chem. Soc. 1974, 96, 3, 678–681Publication Date (Print):February 1, 1974Publication History Published online1 May 2002Published inissue 1 February 1974https://pubs.acs.org/doi/10.1021/ja00810a007https://doi.org/10.1021/ja00810a007research-articleACS PublicationsRequest reuse permissionsArticle Views631Altmetric-Citations56LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Probing the Active Site of Human Manganese Superoxide Dismutase:  The Role of Glutamine 143, (1998)

Structural and biochemical characterization of the nonliganding residue glutamine 143 near the manganese of human Mn superoxide dismutase (hMnSOD), a homotetramer of 22 kDa, reveals a functional role for this residue. In the wild-type protein, the side-chain amide group of Gln 143 is about 5 A from the metal and is hydrogen-bonded to Tyr 34, which is a second prominent side chain adjacent to the metal. We have prepared the site-specific mutant of hMnSOD with the conservative replacement of Gln 143 --> Asn (Q143N). The crystal structure of Q143N shows that the side-chain amide nitrogen of residue 143 is 1.7 A more distant from the manganese than in the wild-type enzyme. The Tyr 34 side-chain hydroxyl in Q143N is also moved to become 0.6 A more distant from the metal due to an additional water molecule. Differential scanning calorimetry showed that Q143N is slightly more stable than the wild-type enzyme with Tm for the main unfolding transition increased by 2 degrees C to 90.7 degrees C. Pulse radiolysis and stopped-flow spectrophotometry reveal that unlike wild-type hMnSOD, which is strongly inhibited by peroxide, Q143N MnSOD exhibits no product inhibition even at concentrations of O2. - in the millimolar range, and its catalysis follows Michaelis kinetics with no evidence of cooperativity. However, the overall catalytic activity of this mutant was decreased 2-3 orders of magnitude compared with the wild-type MnSOD, which can account for its lack of product inhibition. Q143N MnSOD lacked the visible absorption spectrum typical of wild-type Mn(III)SOD. Also, unlike the wild-type Mn(III)SOD, which is electron paramagnetic resonance (EPR) silent, Q143N MnSOD has a complex EPR spectrum with many resonances in the region below 2250 G. We conclude that the Gln 143 --> Asn mutation has increased the reduction potential of manganese to stabilize Mn(II), indicating that Gln 143 has a substantial role in maintaining a reduction potential favorable for the oxidation and reduction cycles in the catalytic disproportionation of superoxide. A solvent hydrogen isotope effect near 2 for kcat in catalysis by Q143N hMnSOD indicates rate-contributing proton transfers to form product hydroperoxide anion or hydrogen peroxide. The data demonstrate a prominent role for Gln 143 in maintaining the microenvironment of the manganese and in efficient catalysis of superoxide dismutation to oxygen and hydrogen peroxide.
Volume rendering of abdominal aortic aneurysms (1997)

One well known application area of volume rendering is the reconstruction and visualization of output from medical scanners like computed tomography (CT). 2D greyscale slices produced by these scanners can be reconstructed and displayed onscreen as a 3D model. Volume visualization of medical images must address two important issues. First, it is difficult to segment medical scans into individual materials based only on intensity values. Second, although greyscale images are the normal method for displaying medical volumes, these types of images are not necessarily appropriate for highlighting regions of interest within the volume. Studies of the human visual system have shown that individual intensity values are difficult to detect in a greyscale image. In these situations colour is a more effective visual feature. We addressed both problems during the visualization of CT scans of abdominal aortic aneurysms. We have developed a classification method that empirically segments regions of interest in each of the 2D slices. We use a perceptual colour selection technique to identify each region of interest in both the 2D slices and the 3D reconstructed volumes. The result is a colourized volume that the radiologists are using to rapidly and accurately identify the locations and spatial interactions of different materials from their scans. Our technique is being used in an experimental post operative environment to help to evaluate the results of surgery designed to prevent the rupture of the aneurysm. In the future, we hope to use the technique during the planning of placement of support grafts prior to the actual operation.
Phosphoinositide-Regulated Kinases and Phosphoinositide Phosphatases (2001)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhosphoinositide-Regulated Kinases and Phosphoinositide PhosphatasesNick R. Leslie, Ricardo M. Biondi, and Dario R. AlessiView Author Information MRC Protein Phosphorylation Unit and Division of Signal Transduction Therapy, Department of Life Sciences, University of Dundee, Dundee DD1 5EH, U.K. Cite this: Chem. Rev. 2001, 101, 8, 2365–2380Publication Date (Web):July 20, 2001Publication History Received19 January 2001Published online20 July 2001Published inissue 1 August 2001https://pubs.acs.org/doi/10.1021/cr000091ihttps://doi.org/10.1021/cr000091iresearch-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views753Altmetric-Citations81LEARN 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:Cell and molecular biology,Cells,Hydrophobicity,Peptides and proteins,Post-translational modification Get e-Alerts
Targeted Inhibition of Mutant IDH2 in Leukemia Cells Induces Cellular Differentiation (2013)

A number of human cancers harbor somatic point mutations in the genes encoding isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2). These mutations alter residues in the enzyme active sites and confer a gain-of-function in cancer cells, resulting in the accumulation and secretion of the oncometabolite (R)-2-hydroxyglutarate (2HG). We developed a small molecule, AGI-6780, that potently and selectively inhibits the tumor-associated mutant IDH2/R140Q. A crystal structure of AGI-6780 complexed with IDH2/R140Q revealed that the inhibitor binds in an allosteric manner at the dimer interface. The results of steady-state enzymology analysis were consistent with allostery and slow-tight binding by AGI-6780. Treatment with AGI-6780 induced differentiation of TF-1 erythroleukemia and primary human acute myelogenous leukemia cells in vitro. These data provide proof-of-concept that inhibitors targeting mutant IDH2/R140Q could have potential applications as a differentiation therapy for cancer.
A corner finding algorithm for image analysis and registration (1982)

In our algorithm the gradient of 8 (the gra-dient direction) in a grey level image is employed for detecting candidates for corner points. Two theorems show that this quantity attains a local maximum at a corner point. Two approaches, median filtering and Hough transform are used effectively to distinguish corner points from noise points. The corner points formed by our algorithm are used in interframe matching.
A mouse model of the atopic eczema/dermatitis syndrome by repeated application of a crude extract of house‐dust mite Dermatophagoides farinae (2003)

Repeated painting of Dermatophagoides extract produced IgE-associated AEDS-like lesions on the skin of NC mice.
Baroreflex: A New Therapeutic Target in Human Stroke? (2009)

We suggest therefore that the modifying of autonomic functions may have important therapeutic implications in acute ischemic as well as in hemorrhagic stroke.
Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin. (1987)

The biological latency of serum transforming growth factor-beta (TGF-beta) was shown to be due to the interaction of TGF-beta with a specific serum binding protein. This binding protein was affinity labeled with 125I-TGF-beta, and its Mr and subunit structure were determined using sodium dodecyl sulfate-gel electrophoresis and gel filtration chromatography. Its Mr is reminiscent of that of the serum protease inhibitor, alpha 2-macroglobulin (alpha 2M). Immunoprecipitation of the 125I-TGF-beta-binding protein complex by a specific anti-alpha 2M antibody, and the formation of identical complexes between 125I-TGF-beta and purified alpha 2M, confirmed that alpha 2M is the TGF-beta-binding protein in serum. Immunoblot analysis showed that endogenous serum TGF-beta is also bound to alpha 2M. However, in contrast to added 125I-TGF-beta, the majority of the endogenous TGF-beta is linked to alpha 2M covalently. Alpha 2M and acid-activated TGF-beta co-eluted from a Superose 6 fast protein liquid chromatography column, confirming that the interaction of TGF-beta with alpha 2M accounts for the latency of serum TGF-beta. It is proposed that alpha 2M may serve an important multifunctional role at sites of inflammation by scavenging both active peptides and proteases that are released by platelets at the site of injury.
Increasing transduction efficiency of recombinant murine retrovirus vectors by initiation of endogenous reverse transcription: potential utility for genetic therapies (1995)

Reverse transcription of retroviral genomic RNA in a target cell is influenced by cellular factors, including the concentration of deoxyribonucleoside triphosphates (dNTPs). In addition, recent data have demonstrated that reverse transcription can be driven within human immunodeficiency virus type 1 virions, prior to infection of a cell, by increasing extracellular concentrations of dNTPs. In attempts to increase the transduction efficiency of recombinant murine leukemia virus vectors, endogenous reverse transcription was initiated within cell-free, recombinant murine leukemia virus virions in the presence of relatively high concentrations of dNTPs. As a result, the expression of transduced genes via these retroviral vectors was increased approximately 10-fold by treatment of virions with dNTPs. Combined with our previous data, these observations suggest that virion-associated DNA synthesis can occur in diverse groups of retroviruses and positively alter retroviral infectivity. As such, these manipulations may be useful for increasing the efficiency of retrovirus-mediated gene delivery.
Alterations of epigenetics and microRNAs in cancer and cancer stem cell (2014)

Epigenetics is an acquired modification of methylation and/or acetylation of chromatin DNA or histone proteins, which regulates downstream gene expression. Epigenetic alterations can be induced by aging, chronic inflammation and viral infection. Aberrant DNA methylation and/or histone modification at the CpG island promoter may induce inactivation of tumor suppressor genes and play critical roles in the initiation and progression of human cancer. In silico analysis is essential to investigate putative genetic and epigenetic elements of tumor suppressor genes such as Rb1 gene. This may contribute genetic and epigenetic information modulating tissue-specific transcripts and expression levels of genes Genome-wide analysis of DNA methylation by BeadChip assay is quite useful to identify aberrantly methylated genes in human cancers. HIST1H3J, POU4F2, SHOX2, PHKG2, TLX3, and HOXA7 were identified as aberrantly methylated genes in human papillary thyroid cancers by genome-wide analysis of DNA methylation. In addition, papillary thyroid cancers with preferential methylation were significantly associated with mutations of the BRAF/RAS oncogenes. These hypermethylated genes may constitute potential biomarkers for papillary thyroid cancer
Anodically Electrodeposited Iridium Oxide Films (AEIROF) from Alkaline Solutions for Electrochromic Display Devices (1989)

Anodically electrodeposited iridium oxide films from alkaline solutions were investigated for application to electrochromic devices. Micro-crystalline (diameter: 15Å) films obtained by the electrolysis of aqueous alkaline solutions containing iridium chloride, oxalic acid and potassium carbonate showed good electrochromic reaction reversibility. The coloration efficiency of the films was about one third that of typical evaporated tungsten oxide films, and the response rate measured by the amount of injected charge was about double. The cycle lives of the cells, composed of electrodeposited films, 1M H 3 PO 4 -NaOH (pH=3∼5), and an activated carbon cloth, were more than 8 × 10 6 with a 0.6 V, 1 Hz continuous square wave.
Field Responsive Polymers (1999)

Microwave absorbing materials can advantageously be obtained using conducting polymers. Among those polymers, soluble ones are of interest as they can be processed and mixed with insulating polymers using classical techniques such as spin-coating, molding or extrusion. Nevertheless, final electrical properties and stability over time will depend on structural characteristics of the polymer (monomer, comonomer, defects content, chain length, crystallinity) and also on the details of processing techniques. Effect of structural properties of polymers on electrical or optical properties have been studied in detail in order to go further in applications. Main results of these studies are presented in this paper.
Sampling From the Proteome to the Human Leukocyte Antigen-DR (HLA-DR) Ligandome Proceeds Via High Specificity (2016)

Comprehensive analysis of the complex nature of the Human Leukocyte Antigen (HLA) class II ligandome is of utmost importance to understand the basis for CD4(+)T cell mediated immunity and tolerance. Here, we implemented important improvements in the analysis of the repertoire of HLA-DR-presented peptides, using hybrid mass spectrometry-based peptide fragmentation techniques on a ligandome sample isolated from matured human monocyte-derived dendritic cells (DC). The reported data set constitutes nearly 14 thousand unique high-confident peptides,i.e.the largest single inventory of human DC derived HLA-DR ligands to date. From a technical viewpoint the most prominent finding is that no single peptide fragmentation technique could elucidate the majority of HLA-DR ligands, because of the wide range of physical chemical properties displayed by the HLA-DR ligandome. Our in-depth profiling allowed us to reveal a strikingly poor correlation between the source proteins identified in the HLA class II ligandome and the DC cellular proteome. Important selective sieving from the sampled proteome to the ligandome was evidenced by specificity in the sequences of the core regions both at their N- and C- termini, hence not only reflecting binding motifs but also dominant protease activity associated to the endolysosomal compartments. Moreover, we demonstrate that the HLA-DR ligandome reflects a surface representation of cell-compartments specific for biological events linked to the maturation of monocytes into antigen presenting cells. Our results present new perspectives into the complex nature of the HLA class II system and will aid future immunological studies in characterizing the full breadth of potential CD4(+)T cell epitopes relevant in health and disease.
Therapeutic potential of non-competitive, subtype-selective metabotropic glutamate receptor ligands (2002)

AbstractMetabotropic glutamate (mGlu) receptors have progressively evolved from the status of a ‘solution looking for problems’ to being the focus of major drug discovery programmes in an increasing number of large pharmaceutical companies. The steady increase in interest for these targets was primarily due to their relatively recent discovery and consequently, to the lack of selective systemically-active ligands to allow precise assessment of their physiological role and therapeutical potential. Fortunately, strong faith in the potential of modulatory receptors of the major excitatory transmitters in the mammalian brain, glutamate, led tenacious pioneers to design molecules which have been extremely useful to validate valuable targets for medicinal chemistry development. In addition, the increasing use of recently available high-throughput functional assays allowed the identification of ligands for these targets with novel mechanisms of action. This review will concentrate on recent progress in the field, focussing on novel pharmacological agents acting non-competitively as allosteric modulators of the mGlu receptors and on their potential use as therapeutic agents.Keywordsallosteric modulatoranxietyinverse agonistmetabotropic glutamate (mGlu) receptormigraineneuropathic painnon-competitive ligandsschizophrenia
SOBRE LA FORTALEZA DE MULA. APORTE DOCUMENTAL (1998)

This paper has discovered a record of the construction of the fortress at Mula (Murcia), written by its architect, the morisco (a moslem convert to christianity). Luis Fajardo, The document provides valuable information about the state of the works. diferent expenses, the search Jor materials, etc. It also raises the intriguiny question of the possible existence of an older christian castle, before Fajardo.
Atypical Sleep in Ventilated Patients (2013)

Analysis of polysomnographic data revealed profound deficiencies in standard scoring criteria due to a predominance of atypical polysomnographic findings in ventilated patients. The revised scoring scheme proved reliable in sleep staging and may serve as a building block in future work.
Origin of Photovoltage and Photocurrent in the Nanoporous Dye-Sensitized Electrochemical Solar Cell (1999)

The essential role of the dark equilibrium potential is discussed for charge separation and the photovoltaic functioning of the title cell. A quantitative model is presented for the potential distribution in the sponge-type title cell. The unique screening process for the photogenerated electrons is discussed that facilitates their extremely long lifetime since the screening ions cannot function as recombination centers. A general analogy is pointed out for the photovoltaic functioning of the sponge-type electrochemical solar cell and of a conventional single-crystal solid-state solar cell.