gebhart/patrepeval huggingface dataset:
Non‐selective conductance in calcium channels of frog muscle: calcium selectivity in a single‐file pore. (1984)

Voltage-clamp studies were carried out to compare currents through Ca2+ channels (ICa) with Na+ currents (Ins) through a non-selective cation conductance blocked by micromolar concentrations of external Ca2+. The gating of both currents was found to have similar time and voltage dependence. The amplitudes of ICa and Ins varied widely, but Ins was always large in fibres with large ICa, and small in fibres with small ICa. Both ICa and Ins were blocked by the specific Ca2+ channel blocker nifedipine, with half-blockage concentrations that were virtually identical (KD = 0.9 microM for ICa and 0.7 microM for Ins). ICa and Ins were also equally sensitive to block by diltiazem (KD = 80 microM). These parallels between Ins and ICa are most easily explained if Ins flows through Ca2+ channels. Apparently, Ca2+ channels bear high-affinity Ca2+-binding sites, and are highly permeable to monovalent cations when Ca2+ is absent. Ba2+ currents (IBa) and ICa were measured in external solutions containing mixtures of Ba2+ and Ca2+. IBa is blocked by Ca2+, as is Ins. Adding Ba2+ to Ca2+ produces only small or no increases in current, as if Ba2+ is only sparingly permeant when Ca2+ is present. Membrane currents in Ba2+/Ca2+ mixtures show anomalous mole-fraction behaviour, suggesting that Ca2+ channels are single-file, multi-ion pores. Complex current transients are observed under maintained depolarizations in Na+/Ca2+ and Ba2+/Ca2+ mixtures. They suggest that in ion mixtures, Ca2+ channels transport Ca2+ in preference to Na+ and Ba2+. Hence Ca2+ channels are selective for Ca2+, even though current amplitudes suggest that the Na+ or Ba2+ permeabilities in the absence of Ca2+ are as high as, or higher than, the Ca2+ permeability. We conclude that the selective permeability of Ca2+ channels depends on the presence of Ca2+. In model calculations, our observations are explained as a consequence of Ca2+ channels being single-file pores. It is proposed that Ca2+ channels derive much of their ion selectivity from high-affinity Ca2+ binding sites located in an otherwise unselective aqueous pore.
Chemiluminescent reactions of lucigenin. 1. Reactions of lucigenin with hydrogen peroxide (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTChemiluminescent reactions of lucigenin. 1. Reactions of lucigenin with hydrogen peroxideRichard Maskiewicz, Dotsevi Sogah, and Thomas C. BruiceCite this: J. Am. Chem. Soc. 1979, 101, 18, 5347–5354Publication Date (Print):August 1, 1979Publication History Published online1 May 2002Published inissue 1 August 1979https://pubs.acs.org/doi/10.1021/ja00512a040https://doi.org/10.1021/ja00512a040research-articleACS PublicationsRequest reuse permissionsArticle Views710Altmetric-Citations72LEARN 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
A Technique for Expressing Eukaryotic Genes in Bacteria (1980)

Methods are described that allow efficient expression in Escherichia coli of cloned eukaryotic genes. The methods require that the coding sequence of the gene in question be available in a form uninterrupted by intervening sequences (for example, as a complementary DNA clone). The gene products are synthesized unfused to other amino acid sequences. The genetic manipulations are simple, and require the plasmids described and commercially available enzymes.
Nonvolatile reprogrammable logic elements using hybrid resonant tunneling diode–giant magnetoresistance circuits (2001)

We have combined resonant interband tunneling diodes (RITDs) with giant magnetoresistance (GMR) elements so that the GMR element controls the switching current and stable operating voltage points of the hybrid circuit. Parallel and series combinations demonstrate continuous or two-state tunability of the subsequent RITD-like current–voltage characteristic via the magnetic field response of the GMR element. Monostable–bistable transition logic element operation is demonstrated with a GMR/RITD circuit in both the dc limit and clocked operation. The output of such hybrid circuits is nonvolatile, reprogrammable, and multivalued.
Histidine 103 in Fra2 Is an Iron-Sulfur Cluster Ligand in the [2Fe-2S] Fra2-Grx3 Complex and Is Required for in Vivo Iron Signaling in Yeast (2010)

The BolA homologue Fra2 and the cytosolic monothiol glutaredoxins Grx3 and Grx4 together play a key role in regulating iron homeostasis in Saccharomyces cerevisiae. Genetic studies indicate that Grx3/4 and Fra2 regulate activity of the iron-responsive transcription factors Aft1 and Aft2 in response to mitochondrial Fe-S cluster biosynthesis. We have previously shown that Fra2 and Grx3/4 form a [2Fe-2S](2+)-bridged heterodimeric complex with iron ligands provided by the active site cysteine of Grx3/4, glutathione, and a histidine residue. To further characterize this unusual Fe-S-binding complex, site-directed mutagenesis was used to identify specific residues in Fra2 that influence Fe-S cluster binding and regulation of Aft1 activity in vivo. Here, we present spectroscopic evidence that His-103 in Fra2 is an Fe-S cluster ligand in the Fra2-Grx3 complex. Replacement of this residue does not abolish Fe-S cluster binding, but it does lead to a change in cluster coordination and destabilization of the [2Fe-2S] cluster. In vivo genetic studies further confirm that Fra2 His-103 is critical for control of Aft1 activity in response to the cellular iron status. Using CD spectroscopy, we find that ∼1 mol eq of apo-Fra2 binds tightly to the [2Fe-2S] Grx3 homodimer to form the [2Fe-2S] Fra2-Grx3 heterodimer, suggesting a mechanism for formation of the [2Fe-2S] Fra2-Grx3 heterodimer in vivo. Taken together, these results demonstrate that the histidine coordination and stability of the [2Fe-2S] cluster in the Fra2-Grx3 complex are essential for iron regulation in yeast.
Fracture Properties of Kerogen and Importance for Organic-Rich Shales (2013)

International audience
Botulinum Toxin: Novel Treatment for Dramatic Urethral Dilatation Associated With Dysfunctional Voiding (1997)

No AccessJournal of UrologyPediatric Urology1 Jul 1997Botulinum Toxin: Novel Treatment for Dramatic Urethral Dilatation Associated With Dysfunctional Voiding George F. Steinhardt, Shahida Naseer, and Oscar A. Cruz George F. SteinhardtGeorge F. Steinhardt , Shahida NaseerShahida Naseer , and Oscar A. CruzOscar A. Cruz View All Author Informationhttps://doi.org/10.1097/00005392-199707000-00067AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Botulinum Toxin: Novel Treatment for Dramatic Urethral Dilatation Associated With Dysfunctional Voiding." The Journal of Urology, 158(1), pp. 190–191 References 1 : Therapy with botulinum toxin. In: Strabismus: Other Therapies. Edited by . New York: Marcel Dekker1993: 109. Google Scholar 2 : Botulinum-A toxin as a treatment of detrusor-sphincter dyssynergia: a prospective study in 24 spinal cord injury patients.. J. Urol.1996; 155: 1023. Link, Google Scholar 3 : Dysfunctional voiding: diagnosis and management. In: Urology Annual 1994. Edited by . New York: W. W. Norton Medical Books1994: 261. Google Scholar 4 : Serum antibody production to botulinum A toxin.. Ophthalmology1993; 100: 1861. Google Scholar From the Departments of Surgery (Urology), Pediatrics and Ophthalmology, St. Louis University School of Medicine, St. Louis, Missouri.© 1997 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited ByVricella G, Campigotto M, Coplen D, Traxel E and Austin P (2014) Long-Term Efficacy and Durability of Botulinum-A Toxin for Refractory Dysfunctional Voiding in ChildrenJournal of Urology, VOL. 191, NO. 5S, (1586-1591), Online publication date: 1-May-2014.Franco I, Landau-Dyer L, Isom-Batz G, Collett T and Reda E (2007) The Use of Botulinum Toxin A Injection for the Management of External Sphincter Dyssynergia in Neurologically Normal ChildrenJournal of Urology, VOL. 178, NO. 4S, (1775-1780), Online publication date: 1-Oct-2007.Franco I (2018) Overactive Bladder in Children. Part 2: ManagementJournal of Urology, VOL. 178, NO. 3, (769-774), Online publication date: 1-Sep-2007.Jørgensen B (2018) Editorial CommentJournal of Urology, VOL. 176, NO. 1, (330-331), Online publication date: 1-Jul-2006.Mokhless I, Gaafar S, Fouda K, Shafik M and Assem A (2018) Botulinum A Toxin Urethral Sphincter Injection in Children With Nonneurogenic Neurogenic BladderJournal of Urology, VOL. 176, NO. 4S, (1767-1770), Online publication date: 1-Oct-2006. Volume 158Issue 1July 1997Page: 190-191 Advertisement Copyright & Permissions© 1997 by American Urological Association, Inc.MetricsAuthor Information George F. Steinhardt More articles by this author Shahida Naseer More articles by this author Oscar A. Cruz More articles by this author Expand All Advertisement PDF DownloadLoading ...
Evolution of new nonantibody proteins via iterative somatic hypermutation (2004)

B lymphocytes use somatic hypermutation (SHM) to optimize immunoglobulins. Although SHM can rescue single point mutations deliberately introduced into nonimmunoglobulin genes, such experiments do not show whether SHM can efficiently evolve challenging novel phenotypes requiring multiple unforeseeable mutations in nonantibody proteins. We have now iterated SHM over 23 rounds of fluorescence-activated cell sorting to create monomeric red fluorescent proteins with increased photostability and far-red emissions (e.g., 649 nm), surpassing the best efforts of structure-based design. SHM offers a strategy to evolve nonantibody proteins with desirable properties for which a high-throughput selection or viable single-cell screen can be devised.
Development of a Novel Trans-Lentiviral Vector That Affords Predictable Safety (2000)

Lentiviral vectors derived from human immunodeficiency virus type 1 (HIV-1) hold great promise for gene therapy. However, the possibility of generating replication-competent retrovirus (RCR) through genetic recombination raises concerns for safety. Here we describe a novel HIV-based packaging system (trans-lentiviral) that splits gag/gag-pol into two parts: One that expresses gag/gag-pro and another that expresses reverse transcriptase and integrase as fusion partners of viral protein R (Vpr). Using a sensitive assay developed to specifically detect recombinant lentiviral DNA mobilization, we demonstrated that the trans-lentiviral vector prevents the generation of recombinants that contain a functional gag-pol structure, while the lentiviral vector generates env-minus recombinant lentivirus that mobilizes recombinant genomes to other cells when pseudotyped with an exogenous envelope. Since an intact gag-pol structure is absolutely required for retroviral DNA mobilization and RCR, the trans-lentiviral vector design significantly reduces this risk. Moreover, it makes it possible to assess the risk of RCR and DNA mobilization using an in vitro assay that monitors trans-lentiviral vector stocks for the regeneration of the gag-pol structure. Therefore, the trans-lentiviral vector design will ensure the greatest predictable level of safety for the clinical application of retroviral vectors, including HIV-based vectors.
Control of Kinetic Properties of AMPA Receptor Channels by Nuclear RNA Editing (1994)

AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor channels mediate the fast component of excitatory postsynaptic currents in the central nervous system. Site-selective nuclear RNA editing controls the calcium permeability of these channels, and RNA editing at a second site is shown here to affect the kinetic aspects of these channels in rat brain. In three of the four AMPA receptor subunits (GluR-B, -C, and -D), intronic elements determine a codon switch (AGA, arginine, to GGA, glycine) in the primary transcripts in a position termed the R/G site, which immediately precedes the alternatively spliced modules "flip" and "flop." The extent of editing at this site progresses with brain development in a manner specific for subunit and splice form, and edited channels possess faster recovery rates from desensitization.
Translation-lookaside buffer consistency (1990)

Nine solutions to the cache consistency problem for shared-memory multiprocessors with multiple translation-lookaside buffers (TLBs) are described. A TLB's function is defined, and it is shown how TLB inconsistency arises in uniprocessor and multiprocessor architectures. The problem of TLB consistency is solved in a uniprocessor and in multiprocessors with a shared bus, virtual-address caches, and hardware cache consistency. Solutions that can be implemented in multiprocessors with more general interconnection networks and without hardware cache consistency are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
HER-2 Positive Breast Cancer: What Else Beyond Trastuzumab-Based Therapy? (2008)

HER-2 is a tyrosine kinase receptor which is overexpressed in 20-25% of breast cancer patients and is associated with poor prognosis. Trastuzumab, a humanized monoclonal antibody directed against the HER-2 receptor, used alone or in combination with chemotherapy, has shown significant clinical benefit in improving survival in metastatic patients, as well as halving the recurrence rate and improving survival in early breast cancer. Even with these impressive results, the reality is that not all patients will benefit form this therapy, and in those who do, resistance to trastuzumab can often develop within 1 year of treatment initiation. Beyond trastuzumab therapy, a "second wave" of monoclonal antibodies and tyrosine kinase inhibitors has emerged. These drugs have variable properties including: 1) dual inhibition against EGFR and HER-2, such as lapatinib, HKI-272 and pertuzumab; 2) anti-angiogenesis such as bevacizumab and pazopanib; 3) anti-mTOR action such as Temsirolimus; and 4) anti-Hsp90 such as 17-AAG. When used in combination with trastuzumab, or with cytotoxic chemotherapy, or as single agents, these new anti-HER-2 strategies bear the potential of arresting the tumorigenesis process. In this article, we present the current strategies in the treatment of breast cancer patients who overexpress HER-2, with particular focus on new tyrosine kinase inhibitors that can be used in combination with or after trastuzumab therapy.
Similarities between Neurologic Effects of L-Dopa and of Apomorphine (1970)

L-DOPA is a precursor for the biosynthesis of both melanins and catecholamines. Both groups of substances are diminished within the Parkinsonian brain.1 2 3 L-dopa administration might therefore increase both melanins and catecholamines.4 The side effects of L-dopa were assigned to dopamine instead of melanin5 because they paralleled the effects of apomorphine, which has chemical similarities to dopamine6 and activates dopaminergic receptors in laboratory animals.6 7 8 The therapeutic effects of L-dopa might also be assigned to dopamine if they could be duplicated by apomorphine.4 , 9 , 10 We have found that subcutaneous administration of apomorphine to patients with selected neurologic disorders has temporarily changed the neurologic . . .
Generation of Functional Hepatocytes From Human Embryonic Stem Cells Under Chemically Defined Conditions That Recapitulate Liver Development (2009)

We have developed a robust and efficient method to differentiate pluripotent stem cells into hepatic cells, which exhibit characteristics of human hepatocytes. Our approach should facilitate the development of clinical grade hepatocytes for transplantation and for research on drug discovery.
Purification and Some Properties of Bilirubin Oxidase ofMyrothecium verrucariaMT-1 (1982)

Journal Article Purification and Some Properties of Bilirubin Oxidase of Myrothecium verrucaria MT-1 Get access Noriaki Tanaka, Noriaki Tanaka Department of Agricultural Chemistry, College of Agriculture, University of Osaka Prefecture, Sakai, Osaka 591, Japan Search for other works by this author on: Oxford Academic Google Scholar Sawao Murao Sawao Murao Department of Agricultural Chemistry, College of Agriculture, University of Osaka Prefecture, Sakai, Osaka 591, Japan Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 46, Issue 10, 1 October 1982, Pages 2499–2503, https://doi.org/10.1080/00021369.1982.10865459 Published: 01 October 1982 Article history Received: 16 March 1982 Published: 01 October 1982
Type 1 And Type 2 Diabetic Patients Display Different Patterns of Cellular Microparticles (2002)

The development of vasculopathies in diabetes involves multifactorial processes including pathological activation of vascular cells. Release of microparticles by activated cells has been reported in diseases associated with thrombotic risk, but few data are available in diabetes. The aim of the present work was to explore the number and the procoagulant activity of cell-derived microparticles in type 1 and 2 diabetic patients. Compared with age-matched control subjects, type 1 diabetic patients presented significantly higher numbers of platelet and endothelial microparticles (PMP and EMP), total annexin V-positive blood cell microparticles (TMP), and increased levels of TMP-associated procoagulant activity. In type 2 diabetic patients, only TMP levels were significantly higher without concomitant increase of their procoagulant activity. Interestingly, in type 1 diabetic patients, TMP procoagulant activity was correlated with HbA(1c), suggesting that procoagulant activity is associated with glucose imbalance. These results showed that a wide vesiculation process, resulting from activation or apoptosis of several cell types, occurs in diabetes. However, diabetic patients differ by the procoagulant activity and the cellular origin of microparticles. In type 1 diabetic patients, TMP-procoagulant activity could be involved in vascular complications. Moreover, its correlation with HbA(1c) reinforces the importance of an optimal glycemic control in type 1 diabetes.
Tyrosine kinase receptors in the control of epithelial growth and morphogenesis during development (1993)

The c-ros, c-met and c-neu genes encode receptor-type tyrosine kinases and were originally identified because of their oncogenic potential. However, recent progress in the analysis of these receptors and their respective ligands indicate that they do not mediate exclusively mitogenic signals. Rather, they can induce cell movement, differentiation or morphogenesis of epithelial cells in culture. Interestingly, the discussed receptors are expressed in embryonal epithelia, whereas direct and indirect evidence shows that the corresponding ligands are produced in mesenchymal cells. In development, signals given by mesenchymal cells are major driving forces for differentiation and morphogenesis of epithelia; embryonal epithelia are generally unable to differentiate without the appropriate mesenchymal factors. The observed activities of these receptor/ligand systems in cultured cells and their expression patterns indicate that they regulate epithelial differentiation and morphogenesis also during embryogenesis and suggest thus a molecular basis for mesenchymal epithelial interactions.
A neural probabilistic language model (2003)

A goal of statistical language modeling is to learn the joint probability function of sequences of words in a language. This is intrinsically difficult because of the curse of dimensionality: a wor...
Effect of N-Terminal Truncation and Solution Conditions on Chemokine Dimer Stability:  Nuclear Magnetic Resonance Structural Analysis of Macrophage Inflammatory Protein 1β Mutants (1998)

Chemokines (chemotactic cytokines) are a family of immune system proteins, several of which have been shown to block human immunodeficiency virus (HIV) infection in various cell types. While the solved structures of most chemokines reveal protein dimers, evidence has accumulated for the biological activity of individual chemokine monomers, and a debate has arisen regarding the biological role of the chemokine dimer. Concurrent with this debate, several N-terminal truncations and modifications in the CC subfamily of chemokines have been shown to have functional significance, in many cases antagonizing their respective receptors and in some cases retaining the ability to block HIV entry to the cell. As the dimer interface of CC chemokines is located at their N-terminus, a structural study of N-terminally truncated chemokines will address the effect that this type of mutation has on the dimer-monomer equilibrium. We have studied the structural consequences of N-terminal truncation in macrophage inflammatory protein 1 beta (MIP-1 beta), a CC chemokine that has been shown to block HIV infection. Examination of nuclear magnetic resonance (NMR) spectra of a series of N-terminally truncated MIP-1 beta variants reveals that these proteins possess a range of ability to dimerize. A mutant beginning at amino acid Asp6 [termed MIP(6)] has near wild-type dimer properties, while further truncation results in weakened dimer affinity. The mutant MIP(9) (beginning with amino acid Thr9) has been found to exist solely as a folded monomer. Relaxation measurements yield a rotational correlation time of 8.6 +/- 0.1 ns for wild-type MIP-1 beta and 4.5 +/- 0.1 ns for the MIP(9) mutant, consistent with a wild-type dimer and a fully monomeric MIP(9) variant. The presence of physiological salt concentration drastically changes the monomer-dimer equilibrium for both wild-type and most mutant proteins, heavily favoring the dimeric form of the protein. These results have implications for structure-function analysis of existing chemokine mutants as well as for the larger debate regarding the biological existence and activity of the chemokine dimer.
Monoclonal Antibody to Rat CD63 Detects Different Molecular Forms in Rat Tissue (1998)

From mice immunized with rat endothelial cell membranes, we isolated several hybridomas secreting monoclonal antibodies (MAbs) to a 45-kDa glycoprotein expressed on the surface of cultured cells. One of these antibodies, 523-14A, was purified and used for immunoaffinity chromatography, Western blotting, and immunohistochemistry. The glycoprotein containing the antigen for MAb 523-14A, gp45, was isolated from rat lung endothelial cell membranes using wheat germ agglutinin and antibody affinity chromatography sequentially. Mass spectrometry of tryptic peptides from gel purified bands identified gp45 as rat CD63, a member of the transmembrane-4 superfamily. Western blot analyses of tissues from F344 rats showed that kidney, spleen, uterus, and ovaries expressed CD63 at high levels. Thymus, salivary gland, testicles, intestines, pancreas, and adrenals expressed lower amounts. Tissue cell types expressing CD63 were also examined and the results showed that, in addition to the expected expression on lymphoid cells, CD63 was expressed on many epithelial and muscle cells as well. The mobility of CD63 on SDS-PAGE varied widely, indicative of molecular masses ranging from 45 kDa in some tissues to nearly 60 kDa in others.