gebhart/patrepeval huggingface dataset:
2,2′-Dithiobis(N-ethyl-spermine-5-carboxamide) Is a High Affinity, Membrane-impermeant Antagonist of the Mammalian Polyamine Transport System (1996)

We have synthesized 2,2'-dithiobis(N-ethyl-spermine-5-carboxamide) (DESC), its thiol monomer (MESC), and the mixed MESC-cysteamine disulfide (DEASC) as potential inhibitors of polyamine transport in mammalian cells. DESC was the most potent antagonist of spermine transport in ZR-75-1 human breast cancer cells, with Ki values of 5. 0 +/- 0.7, 80 +/- 31, and 16 +/- 3 microM for DESC, MESC, and DEASC, respectively. DESC also strongly blocked putrescine and spermidine uptake in ZR-75-1 cells (Ki = 1.6 +/- 0.5 and 2.7 +/- 1.1 microM, respectively). While DESC and MESC were purely competitive inhibitors of putrescine transport, DEASC was a mixed competitive/noncompetitive antagonist. Remarkably, DESC was virtually impermeant in ZR-75-1 cells despite its low Ki toward polyamine transport. The marked difference in affinity between DESC and MESC was essentially due to the tail-to-tail juxtaposition of two spermine-like structures, suggesting that dimeric ligands of the polyamine transporter might simultaneously interact with more than one binding site. While DESC strongly decreased the initial rate of [3H]spermidine transport, even a 40-fold molar excess of antagonist could not completely abolish intracellular spermidine accumulation. Moreover, as little as 0.3 microM spermidine fully restored growth in ZR-75-1 cells treated with an inhibitor of polyamine biosynthesis in the presence of 50 microM DESC, thus emphasizing the importance of uptake of trace amounts of exogenous polyamines. Thus, reducing the exogenous supply of polyamines with a potent competitive inhibitor may be kinetically inadequate to block replenishment of the polyamine pool in polyamine-depleted tumor cells that display high transport capacity. These results demonstrate that polyamine analogues cross-linked into a dimeric structure such as DESC interact with high affinity with the mammalian polyamine carrier without being used as substrates. These novel properties provide a framework for the design of specific irreversible inhibitors of the polyamine transporter, which should present advantages over competitive antagonists for an efficient blockade of polyamine transport in tumor cells.
Potent Nonimmunosuppressive Cyclophilin Inhibitors With Improved Pharmaceutical Properties and Decreased Transporter Inhibition (2014)

Nonimmunosuppressive cyclophilin inhibitors have demonstrated efficacy for the treatment of hepatitis C infection (HCV). However, alisporivir, cyclosporin A, and most other cyclosporins are potent inhibitors of OATP1B1, MRP2, MDR1, and other important drug transporters. Reduction of the side chain hydrophobicity of the P4 residue preserves cyclophilin binding and antiviral potency while decreasing transporter inhibition. Representative inhibitor 33 (NIM258) is a less potent transporter inhibitor relative to previously described cyclosporins, retains anti-HCV activity in cell culture, and has an acceptable pharmacokinetic profile in rats and dogs. An X-ray structure of 33 bound to rat cyclophilin D is reported.
Spectral gain behavior of Er-doped fiber with extremely high aluminum concentration (1993)

Erbium-doped fiber amplifiers (EDFAs) are very promising as high gain and low noise optical amplifiers for single-mode fiber communication systems in the 1.55 µm wavelength band. However, wavelength dependence of the gain remains a subject of investigation in some applications, such as long haul transmission with cascaded amplifiers(1) or WDM systems(2). It is well-known that codoping aluminum in the core of the erbium-doped fiber (EDF) is effective to broaden the gain spectrum of the EDFAs.
Control of dorsoventral patterning of somitic derivatives by notochord and floor plate. (1993)

We have examined the effect of implantation of a supernumerary notochord or floor plate on dorsoventral somitic organization. We show that notochord and floor plate are able to inhibit the differentiation of the dorsal somitic derivatives--i.e., axial muscles and dermis--thus converting the entire somite into cartilage, which normally arises only from its ventral part. We infer from these results that the dorsoventral patterning of somitic derivatives is controlled by signals provided by ventral axial structures.
Digital holography for quantitative phase-contrast imaging (1999)

We present a new application of digital holography for phase-contrast imaging and optical metrology. This holographic imaging technique uses a CCD camera for recording of a digital Fresnel off-axis hologram and a numerical method for hologram reconstruction. The method simultaneously provides an amplitude-contrast image and a quantitative phase-contrast image. An application to surface profilometry is presented and shows excellent agreement with contact-stylus probe measurements.
Species Diagnostics Protocols: PCR and Other Nucleic Acid Methods (1996)

Isolation and Purification of Plant Nucleic Acids: Genomic and Chloroplast DNA. Isolation and Purification of Insect DNA Isolation and Purification of Vertebrate DNAs. Statistical Analysis of Arbitrarily Primed PCR Patterns in Molecular Taxonomic Studies. Molecular Identification of Phytopathogenic Viruses. Improved PCR Methods for Identification of Phytopathogenic Viruses. PCR Detection of HIV. The Use of Consensus PCR and Direct Sequence Analysis for the Identification of HPV. The Identification of Dengue Virus Using PCR. The Design and Application of Ribosomal RNA-Targeted, Fluorescent Oligonucleotide Probes for the Identification of Endosymbionts in Protozoa. Subtraction Hybridization for the Isolation of Strain-Specific Rhizobium DNA Probes. The Use of RAPD for Generating Specific DNA Probes for Microorganisms. ITS-RFLP Matching for Identification of Fungi. Specific PCR Primers for the Identification of Endomycorrhizal Fungi. Single-Strand Conformational Polymorphism (SSCP) for the Identification of Endomycorrhizal Fungi. The Use of RAPD for Isolate Identification of Arbuscular Mycorrhizal Fungi. Establishing Relationships Between Closely Related Species Using Total Genomic DNA as a Probe. Detection and Characterization of Leishmania Parasites by DNA-Based Methods: Southern Blotting and PCR. The Molecular Identification of Trypanosomes. Detection and Identification of the Four Malaria Parasite Species Infecting Humans by PCR Amplification. The Use of Degenerate Primers in Conjunction with Strain and Species Oligonucleotides to Classify Onchocerca volvulus. The Use of Synthetic DNA Probes for the Field Identification of Members of the Anopheles gambiae Complex. PCR of the Ribosomal DNA Intergenic SpacerRegions as a Method for Identifying Mosquitoes in the Anopheles gambiae Complex. Restriction Fragment Length Polymorphism (RFLP) Analyses: Distinguishing African and European Honey Bees. Differential Screening for the Isolation of Species-Specific Sequences in the Anopheles farauti Complex. RAPD-PCR with Parasitic Hymenoptera. The Use of Selective Enrichment for the Isolation of Species-Specific DNA Probes for Insects. Index.
Examining the presentation of tumor-associated antigens on peptide-pulsed T2 cells (2013)

Peptide-pulsed T2 cells are routinely used to study T-cell activation by MHC-restricted peptides derived from tumor-associated antigens (TAAs). Nevertheless, the capacity of T2 cells to present antigenic epitopes remains to be precisely quantified, primarily due to the detection limits imposed by available methods. Since naturally-processed TAA-derived epitopes have been shown to be displayed at levels as low as 10-150 copies per cell, highly sensitive detection and quantification techniques are essential to assess the natural degree of T-cell sensitivity. Here, we report the use of soluble, high-affinity T-cell receptors (TCRs) coupled with single-molecule fluorescence microscopy to quantify three reported TAA-derived epitopes on peptide-pulsed T2 cells, dissecting the relationship between concentration of exogenous peptide, number of epitopes presented, and activation of epitope-specific T cells. Our findings indicate that peptide concentrations in the low nanomolar range are required for T2 cells to present TAAs in extents that are comparable to those of malignant cells.
Metal nanocrystal/nitride heterogeneous-stack floating gate memory (2005)

Nonvolatile memories with heterogeneous-stack floating gate of metal nanocrystals and silicon nitride (Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> ) have been fabricated and characterized. The heterogeneous gate stacks showed superior characteristics in retention and low voltage write/erase over single metal nanocrystal memories and/or nitride memories (i.e., MONOS or SONOS). The metal nanocrystals in the stack made low voltage operation possible by the direct tunneling programming, while the nitride layer as an additional charge storage trap layer enabled longer retention time. By making the double stack of Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> -Au-Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> -Au, we could enhance the memory characteristics even further
The Role of Adhesion Molecules in Multiple Myeloma (1992)

Human myeloma plasma cells had been considered to express few surface antigens until recently. The past two International Workshops on Leucocyte Differentiation Antigens have shown that myeloma cells can express a range of surface molecules, and it has become clear that many of these have adhesive functions. The identification of ICAM-1 (CD54) and H-CAM (CD44) on human plasma cells was the initial observation, and other antigens such as N-CAM (CD56) and LFA-3 (CD58) have been confirmed as features of malignant plasma cells in particular. The degree of expression of LFA-1 (CD 11 a) remains to be characterised fully. It seems probable that the loss of some adhesion structures may be associated with increased malignancy and plasma cell leukaemia. At the present time there are few studies relating to the function of these molecules, although homotypic adhesion appears to occur, and it is likely that such studies will shed light on the pathogenesis of myeloma.
Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis (2001)

X-ray structures of two enzymes in the sterol/isoprenoid biosynthesis pathway have been determined in a structural genomics pilot study. Mevalonate-5-diphosphate decarboxylase (MDD) is a single-domain alpha/beta protein that catalyzes the last of three sequential ATP-dependent reactions which convert mevalonate to isopentenyl diphosphate. Isopentenyl disphosphate isomerase (IDI) is an alpha/beta metalloenzyme that catalyzes interconversion of isopentenyl diphosphate and dimethylallyl diphosphate, which condense in the next step toward synthesis of sterols and a host of natural products. Homology modeling of related proteins and comparisons of the MDD and IDI structures with two other experimentally determined structures have shown that MDD is a member of the GHMP superfamily of small-molecule kinases and IDI is similar to the nudix hydrolases, which act on nucleotide diphosphatecontaining substrates. Structural models were produced for 379 proteins, encompassing a substantial fraction of both protein superfamilies. All three enzymes responsible for synthesis of isopentenyl diphosphate from mevalonate (mevalonate kinase, phosphomevalonate kinase, and MDD) share the same fold, catalyze phosphorylation of chemically similar substrates (MDD decarboxylation involves phosphorylation of mevalonate diphosphate), and seem to have evolved from a common ancestor. These structures and the structural models derived from them provide a framework for interpreting biochemical function and evolutionary relationships.
A MEMS electrospray nozzle for mass spectroscopy (2002)

We present our development of a micron-sized MEMS electrospray nozzle and demonstrate its application for electrospray mass spectroscopy (MS). The fabricated and tested micromachined electrospray nozzles are typically 40 /spl mu/m long and with 1-3 /spl mu/m orifice diameters. They also have built-in particle filters. This micromachined nozzle has been successfully interfaced with a mass spectrometer (Finnigan Mat LCQ Ion Trap) to perform standard characterization using a solution of gramicidin S at a flow rate of 50 nL/min and a voltage potential of 4 kV. This MEMS nozzle has demonstrated valid MS analyses with lower flow rates, and it has many advantages over the traditional complex preparation of a glass-capillary.
Cloning and Functional Analysis of the Promoter for KDR/flk-1, a Receptor for Vascular Endothelial Growth Factor (1995)

KDR/flk-1 is one of two receptors for vascular endothelial growth factor, a potent angiogenic peptide. KDR/flk-1 is an early marker for endothelial cell progenitors, and its expression is restricted to endothelial cells in vivo. To investigate the molecular mechanisms regulating expression of KDR/flk-1, we cloned and characterized the promoter of the human KDR/flk-1 gene. The transcription start site was localized by primer extension and ribonuclease protection to a nucleotide 303 base pairs (bp) 5' of the initiation methionine codon. The 5'-flanking sequence is rich in G and C residues and contains five Sp1 elements but no TATA consensus sequence. By reporter gene transfection experiments, we found that approximately 4 kilobases of KDR/flk-1 5'-flanking sequence directed high level luciferase activity in bovine aortic endothelial cells; further deletion analysis revealed positive regulatory elements between bp -225 to -164, -95 to -77, -77 to -60, and +105 to +127. Mutation of an atypical GATA sequence between bp +105 and +127 did not affect promoter activity, suggesting that GATA elements are not essential for the high level promoter activity of this gene. Consistent with endothelial cell-restricted expression of KDR/flk-1 mRNA, we found that the 4-kilobase flanking sequence directed high level promoter activity in endothelial cells but not in other cell types. To our knowledge this is the first report characterizing the KDR/flk-1 promoter. Understanding the KDR/flk-1 promoter will allow us to investigate endothelial cell-specific gene regulation and to uncover methods for targeting gene delivery specifically to endothelial cells.
Xyloglucans in the Primary Cell Wall (1989)

Etude du metabolisme des xyloglucanes incluant leur apparition, leur biosynthese, leur biodegradation, leur organisation et leur role dans la regulation de la croissance
‘The we of me”:The member of the wedding'snovel alliances (1996)

(1996). ‘The we of me”: The member of the wedding's novel alliances. Women & Performance: a journal of feminist theory: Vol. 8, No. 2, pp. 111-135.
Serum Uric Acid Levels Are Associated with Polymorphism in the SAA1 Gene in Chinese Subjects (2012)

The rs12218 SNP in the SAA1 gene was associated with SUA levels in Chinese subjects, indicating that carriers of the T allele of rs12218 have a high risk of hyperuricemia.
ChemInform Abstract: INTRAMOLECULAR 1,3‐DIYL TRAPPING REACTIONS: TOTAL SYNTHESIS OF THE MARINE NATURAL PRODUCT (D,L)‐Δ9(12)‐CAPNELLENE (1982)

Abstract Lithiumalanat reduziert die Carbonsäure (Ia) zu einem Aldehyd (Ib), aus dem das Fulven (II) und weiter mit Azodicarbonsäureester das Diaza‐norbornen (III) entstehen.
Ligand binding assays at equilibrium: validation and interpretation (2010)

The focus of this review paper is factors affecting data interpretation in ligand binding assays under equilibrium conditions. Protocols for determining K(d) (the equilibrium dissociation constant) and K(dA) (the equilibrium inhibitor constant) for receptor ligands are discussed. The basic theory describing the interaction of a radiotracer and an unlabelled competitor ligand with a receptor is developed. Inappropriate experimental design may result in ligand depletion and non-attainment of equilibrium, distorting the calculation of K(d) and K(dA) . Strategies, both theoretical and practical, will be given to avoid and correct such errors, thus leading to the determination of reliable values for these constants. In determining K(dA) from competition binding studies, two additional concepts are discussed. First, the necessity to measure an adequate specific binding signal from the bound radiotracer ligand limits the range of affinity constants that can be measured: a particular set of assay conditions may lead to an upper limit on the apparent affinity of unlabelled ligands. Second, an extension of the basic assay methodology can indicate whether the interaction between the tracer and a test ligand is mediated by a competitive or an allosteric mechanism. Finally, the review ends with a discussion of two factors that are often overlooked: buffer composition and the temperature at which the assay is conducted, and the impact these can have on affinity measurements and the understanding of drug interactions.
The Wallach Rearrangement of Some 4,4′-Disubstituted Azoxybenzenes (1983)

Abstract The treatment of azoxybenzenes bearing electron-withdrawing substituents at 4,4′-positions with sulfuric acid gave the corresponding 2-hydroxyazobenzenes, together with 4′-substituted 4-hydroxyazobenzenes. The treatment of 4,4′-dimethoxyazoxybenzene with p-toluenesulfonic acid and acetic anhydride afforded 4,4′-dimethoxy-3-acetoxyazobenzene and 4,4′-dimethoxy-2-tosyloxyazobenzene as the main rearrangement products.
Drug treatment of functional dyspepsia: a systematic analysis of trial methodology with recommendations for design of future trials. (1996)

Because of suboptimal design and/or unclear presentation of the data, none of the trials provided unequivocal evidence that there is efficacious therapy for the treatment of functional dyspepsia.
Treatment with CD20-specific antibody prevents and reverses autoimmune diabetes in mice (2007)

The precise roles of B cells in promoting the pathogenesis of type 1 diabetes remain undefined. Here, we demonstrate that B cell depletion in mice can prevent or delay diabetes, reverse diabetes after frank hyperglycemia, and lead to the development of cells that suppress disease. To determine the efficacy and potential mechanism of therapeutic B cell depletion, we generated a transgenic NOD mouse expressing human CD20 (hCD20) on B cells. A single cycle of treatment with an antibody specific for hCD20 temporarily depleted B cells and significantly delayed and/or reduced the onset of diabetes. Furthermore, disease established to the point of clinical hyperglycemia could be reversed in over one-third of diabetic mice. Why B cell depletion is therapeutic for a variety of autoimmune diseases is unclear, although effects on antibodies, cytokines, and antigen presentation to T cells are thought to be important. In B cell-depleted NOD mice, we identified what we believe is a novel mechanism by which B cell depletion may lead to long-term remission through expansion of Tregs and regulatory B cells. Our results demonstrate clinical efficacy even in established disease and identify mechanisms for therapeutic action that will guide design and evaluation of parallel studies in patients.
Transcriptional Up-Regulation of GrapevineMLOGenes in Response to Powdery Mildew Infection (2008)

Mildew resistance locus o (MLO) proteins are plant-specific seven-transmembrane (7TM) proteins that are thought to play a role in vesicle trafficking to the plasma membrane. Certain members of the <i>MLO</i> gene family are required for powdery mildew (PM) fungi (Erysiphales) to establish a pathogenic interaction with their plant hosts. Such <i>MLO</i> genes increase in transcription in response to PM infection, and the loss of their function confers broad-spectrum resistance to PM pathogens in barley, tomato, and <i>Arabidopsis thaliana.</i> In this study, a 17-member <i>MLO</i> gene family has been identified in the genome sequence of <i>Vitis vinifera</i>. Fourteen genes of the <i>VvMLO</i> family have been shown to be transcribed at various levels in shoot tips, flower buds, flowers, and leaves. Two <i>VvMLO</i>s increased in transcription in response to the grapevine-adapted PM fungus <i>Erysiphe necator</i>. The predicted polypeptides encoded by these two PM-responsive <i>VvMLOs</i> clustered in the same phylogenetic clade as AtMLO2, AtMLO6, and AtMLO12, proteins that are required by the PM fungus <i>Golovinomyces orontii</i> for causing disease on <i>A. thaliana.</i> The PM-responsiveness of these grapevine genes and their relatedness to <i>AtMLO</i>s suggest that a grapevine <i>MLO</i> gene (or genes) may also be involved in the pathogenesis of <i>E. necator</i>.
Epidermal growth factor receptor binding is affected by structural determinants in the toxin domain of transforming growth factor-alpha-Pseudomonas exotoxin fusion proteins. (1989)

TGF-alpha-PE40 is a hybrid protein composed of transforming growth factor-alpha (TGF-alpha) fused to a 40,000-dalton segment of Pseudomonas exotoxin A (PE40). This hybrid protein possesses the receptor-binding activity of TGF-alpha and the cell-killing properties of PE40. These properties enable TGF-alpha-PE40 to bind to and kill tumor cells that possess epidermal growth factor (EGF) receptors. Unexpectedly, TGF-alpha-PE40 binds approximately 100-fold less effectively to EGF receptors than does native TGF-alpha (receptor-binding inhibition IC50 = 540 and 5.5 nM, respectively). To understand the factors governing receptor binding, deletions and site-specific substitutions were introduced into the PE40 domain of TGF-alpha-PE40. Removal of the N-terminal 59 or 130 amino acids from the PE40 domain of TGF-alpha-PE40 improved receptor binding (IC50 = 340 and 180 nM, respectively) but decreased cell-killing activity. Substitution of alanines for cysteines at positions 265 and 287 within the PE40 domain dramatically improved receptor binding (IC50 = 37 nM) but also decreased cell-killing activity. Similar substitutions of alanines for cysteines at positions 372 and 379 within the PE40 domain did not significantly affect receptor-binding or cell-killing activities. These studies indicate that the PE40 domain of TGF-alpha-PE40 interferes with EGF receptor binding. The cysteine residues at positions 265 and 287 of PE40 are responsible for a major part of this interference.
Sutures and Suture Anchors—Update 2006 (2006)

Surgeons who prefer stronger sutures now have several high-strength suture options from which to choose. Most of the new anchors tested performed very well.