gebhart/patrepeval huggingface dataset:
Purification, Characterization, and Subunit Structure of Rat Core 1 β1,3-Galactosyltransferase (2002)

The O-linked oligosaccharides (O-glycans) in mammalian glycoproteins are classified according to their core structures. Among the most common is the core 1 disaccharide structure consisting of Galbeta1-->3GalNAcalpha1-->Ser/Thr, which is also the precursor for many extended O-glycan structures. The key enzyme for biosynthesis of core 1 O-glycan from the precursor GalNAc-alpha-Ser/Thr is UDP-Gal:GalNAc-alpha-Ser/Thr beta3-galactosyltransferase (core1 beta3-Gal-T). Core 1 beta3-Gal-T activity, which requires Mn2+, was solubilized from rat liver membranes and purified 71,034-fold to apparent homogeneity (>90% purity) in 5.7% yield by ion exchange chromatography on SP-Sepharose, affinity chromatography on immobilized asialo-bovine submaxillary mucin, and gel filtration chromatography on Superose 12. The purified enzyme is free of contaminating glycosyltransferases. Two peaks of core 1 beta3-Gal-T activity were identified in the final step on Superose 12. One peak of activity contained protein bands on non-reducing SDS-PAGE of approximately 84- and approximately 86-kDa disulfide-linked dimers, whereas the second peak of activity contained monomers of approximately 43 kDa. Reducing SDS-PAGE of these proteins gave approximately 42- and approximately 43-kDa monomers. Both the 84/86-kDa dimers and the 42/43-kDa monomers have the same novel N-terminal sequence. The purified enzyme, which is remarkably stable, has an apparent Km for UDP-Gal of 630 microm and an apparent Vmax of 206 micromol/mg/h protein using GalNAcalpha1-O-phenyl as the acceptor. The reaction product was generated using asialo-bovine submaxillary mucin as an acceptor; treatment with O-glycosidase generated the expected disaccharide Galbeta1-->3GalNAc. These studies demonstrate that activity of the core 1 beta1,3-Gal-T from rat liver is contained within a single, novel, disulfide-bonded, dimeric enzyme.
Nuclease activity of 1,10-phenanthroline-copper. New conjugates with low molecular weight targeting ligands (1993)

The chemical nuclease activity of 1,10-phenanthroline-copper depends on DNA sequence because the coordination complex has affinity for DNA. In order to target this efficient nucleolytic activity, it is essential to override its inherent specificity. The minimal size of ligands capable of redirecting the specificity has been investigated. A conjugate (HOP) prepared by alkylating Hoechst dye 33258 with 5-(iodoacetamido)-1,10-phenanthroline has a greater preference for A-T-rich regions than the unsubstituted 1,10-phenanthroline-copper complex, reflecting the specificity of this A-T-specific minor-groove binder. However, since quaternizing the dye with 5-(iodoacetamido)-1,10-phenanthroline increases its affinity for DNA, the specificity of cleavage by the conjugate is less than the binding selectivity of the dye. Linking 1,10-phenanthroline with the peptide of the helix-turn-helix domain of the Trp repressor specificity results in a conjugate with greater reactivity for the operator sequence than the unsubstituted complex. The intrinsic affinity of the 1,10-phenanthroline-Cu can only be partially overridden by the conformationally unstable peptide. Attachment of 1,10-phenanthroline to a deoxyoligonucleotide complementary to a single-stranded loop of RNA successfully targets the scission of the chemical nuclease. Cleavage sites are observed not only contiguous to the site of hybridization but also at nonadjacent sequence positions. The latter set of sites must be close in space to the 5' end of the hybridized deoxyoligonucleotide.
Structural mimicry of a native protein by a minimized binding domain (1997)

The affinity between molecules depends both on the nature and presentation of the contacts. Here, we observe coupling of functional and structural elements when a protein binding domain is evolved to a smaller functional mimic. Previously, a 38-residue form of the 59-residue B-domain of protein A, termed Z38, was selected by phage display. Z38 contains 13 mutations and binds IgG only 10-fold weaker than the native B-domain. We present the solution structure of Z38 and show that it adopts a tertiary structure remarkably similar to that observed for the first two helices of B-domain in the B-domain/Fc complex [Deisenhofer, J. (1981) Biochemistry 20, 2361-2370], although it is significantly less stable. Based on this structure, we have improved on Z38 by designing a 34-residue disulfide-bonded variant (Z34C) that has dramatically enhanced stability and binds IgG with 9-fold higher affinity. The improved stability of Z34C led to NMR spectra with much greater chemical shift dispersion, resulting in a more precisely determined structure. Z34C, like Z38, has a structure virtually identical to the equivalent region from native protein A domains. The well-defined hydrophobic core of Z34C reveals key structural features that have evolved in this small, functional domain. Thus, the stabilized two-helix peptide, about half the size and having one-third of the remaining residues altered, accurately mimics both the structure and function of the native domain.
Modulation of Hepatocarcinoma Cell Morphology and Activity by Parylene-C Coating on PDMS (2010)

We demonstrated for the first time the modulation of HepG2 cells' behavior in relation to the intrinsic physical properties of PDMS and ParC, enabling the local modulation of cell spreading in a 2D or 3D manner by simple microfabrication techniques. This work will provide promising insights into the development of cell-based platforms that have many applications in the field of in vitro liver tissue engineering, pharmacology and therapeutics.
The reaction of thioimides with phosphorus ylides (1991)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe reaction of thioimides with phosphorus ylidesJohn E. Bishop, John F. O'Connell, and Henry RapoportCite this: J. Org. Chem. 1991, 56, 17, 5079–5091Publication Date (Print):August 1, 1991Publication History Published online1 May 2002Published inissue 1 August 1991https://pubs.acs.org/doi/10.1021/jo00017a017https://doi.org/10.1021/jo00017a017research-articleACS PublicationsRequest reuse permissionsArticle Views1676Altmetric-Citations55LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Hippocampal Volume and Depression: A Meta-Analysis of MRI Studies (2004)

Hippocampal volume is reduced in patients with unipolar depression, maybe as a consequence of repeated periods of major depressive disorder. Bipolar patients did not seem to show a reduction in hippocampal volume, but this has been much less investigated.
Hydrodynamic resistance of single confined moving drops in rectangular microchannels (2008)

We integrate a sensitive microfluidic comparator into a T-junction device and report measurements of the excess pressure drop due to a single moving droplet confined in a rectangular microchannel. We specifically focus on drops that are not coated with surfactants and study the effects of drop size, droplet viscosity and capillary number on their hydrodynamic resistance. In the capillary number range of ≈ 10−3–10−2, we find two distinct regimes for hydrodynamic resistance behavior based on drop size. In regime I associated with small drops (drop length/channel width ∼ <4), we find that the pressure drop is independent of the drop size and the capillary number, and depends weakly on the ratio of the viscosities of the two immiscible phases. In regime II, associated with large drops (drop length/channel width > ∼4), depending on the viscosity ratio of the two phases, the hydrodynamic resistance could increase, decrease or remain unchanged with drop size. We present a simple model that qualitatively captures these experimental trends. This model reveals that the pressure drop in regime I is dominated by the dissipation due to the end caps, and in regime II by both the end caps and the central body of the droplet. Such fundamental understanding will enable the design of large-scale energy-efficient fluidic circuits by minimizing the overall pressure drop in a network and may also provide insights into controlling droplet traffic to build functional passively-driven two-phase microfluidic technologies.
Field Day for a Boy Soldier (1979)

ONMYPALM, my father's medals, dead as he, cover the so-called lines of head, heart, and life. I say medals, but there are only two; my hand is not very big, even now, and the medals feel heavy. never wore my mother says with attenuated gentleness. Wrapped in coarse tissue paper that smelled of almonds and soot, they tarnished in a shallow little white box of glossy cardboard such as might have enclosed condoms. Once I found and polished them when playing soldiers in a peaked cap and silver-buttoned blazer buckled tight with two belts, one around my waist, the other over my left shoulder make a Sam Browne. He let me flaunt them for an hour, then with a taut face, as if in some jubilant pain, made me wrap them up and give them back. That was during World War Two, when we pinned swastika flags the map of World War One, his war, the backdrop his four-year rise from private sergeant, his wounding not long before the Armistice, when he was honor ably broken upward. I half-salute him with the other hand, remembering from some manual how look him straight in the eye when at the proper distance and (how did it go exactly?) to raise the hand smartly until the tip of the forefinger touches the lower part of the headdress or forehead above the right eye. ... Trying reach him, be in his world, I dredged up and learned by heart some peculiar things. It amused him have a small boy, his, shoot him a stiffer-than-stiff salute. If only he could see me now. The full-blown etiquette of military compliments eludes me; holding the salute until he returns it?except he is no longer at the proper distance?I am frozen at attention. The bronze one hangs from a ring. Its ribbon is red in the center, with green and violet on either side, shaded make the colors of two rainbows; but what holds my eye is the winged figure of Victory, prim in a toga, one hand uplifted cup sky as if testing spring water. The head looks detach able. The feet have begun melt, I can't think why, unless the figure is standing in the mud of the trenches. The side of the face in shadow has a halo, not above but alongside. The brass medal is all action, though, with St. George on horseback trampling the eagle shield of the enemy powers, and a skull and cross-bones (for good measure), while the sun lifts above all like an extension of the ribbon's orange watered center. If he ever wore them, he must have had the king's head outward, so 22
Covalent attachment of functionalized lipid bilayers to planar waveguides for measuring protein binding to biomimetic membranes (1995)

A new method is presented for measuring sensitively the interactions between ligands and their membrane-bound receptors in situ using integrated optics, thus avoiding the need for additional labels. Phospholipid bilayers were attached covalently to waveguides by a novel protocol, which can in principle be used with any glass-like surface. In a first step, phospholipids carrying head-group thiols were covalently immobilized onto SiO2-TiO2 waveguide surfaces. This was accomplished by acylation of aminated waveguides with the heterobifunctional crosslinker N-succinimidyl-3-maleimidopropionate, followed by the formation of thioethers between the surface-grafted maleimides and the synthetic thiolipids. The surface-attached thiolipids served as hydrophobic templates and anchors for the deposition of a complete lipid bilayer either by fusion of lipid vesicles or by lipid self-assembly from mixed lipid/detergent micelles. The step-by-step lipid bilayer formation on the waveguide surface was monitored in situ by an integrated optics technique, allowing the simultaneous determination of optical thickness and one of the two refractive indices of the adsorbed organic layers. Surface coverages of 50-60% were calculated for thiolipid layers. Subsequent deposition of POPC resulted in an overall lipid layer thickness of 45-50 A, which corresponds to the thickness of a fluid bilayer membrane. Specific recognition reactions occurring at cell membrane surfaces were modeled by the incorporation of lipid-anchored receptor molecules into the supported bilayer membranes. (1) The outer POPC layer was doped with biotinylated phosphatidylethanolamine. Subsequent specific binding of streptavidin was optically monitored. (2) A lipopeptide was incorporated in the outer POPC monolayer. Membrane binding of monoclonal antibodies, which were directed against the peptide moiety of the lipopeptide, was optically detected. The specific antibody binding correlated well with the lipopepitde concentration in the outer monolayer.
Tetrahydrouridine, cytidine analogues, and hemoglobin F (1985)

Abstract 5‐Azacytidine (azaC) has previously been shown to raise Hb F levels in the repeatedly phlebotomized baboon (PCV: around 20%). The administration of tetrahydrouridine (THU), an inhibitor of the enzymatic conversion of azaC to 5‐azauridine, made it possible to reduce the amount of azaC and also of 2‐deoxy‐5‐azacytidine (d‐azaC) by more than 90% and still achieve maximal Hb F elevations. However, the granulocytopenia, usually occurring after 5‐azaC, was not altered by the lowering of the dosages in the presence of THU. Thus, the granulocytopenia is not due to 5‐azauridine or other catabolic products resulting from deamination. It is also unlikely that it is caused by a direct influence of azaC on RNA since d‐azaC also causes granulocytopenia. The persistence of reticulocytosis throughout the treatment with azaC or d‐azaC makes it appear likely that the observed increase in Hb F levels to more than 60% of total hemoglobin is not due to a cytotoxic effect on erythropoiesis resulting in a shift of cell populations toward greater immaturity, but to a direct influence of the drug on the regulation of γ globin chain production.
Motion Compensated Component Color Coding (1982)

We develop and evaluate motion compensation schemes for predictive coding of the component color television signal. Algorithms are discussed for estimation of motion of each color component (luminance and chrominance) separately as well as in combination. Techniques for switching of the predictors for individual components are proposed and simulated. Simulations show that it is sufficient to estimate parameters of motion based only on the luminance and use them for motion-based prediction and switching the predictors for both the luminance and chrominance. Thus, only one motion estimator and prediction switch is needed for the three components of the color signal. Compression capability of motion compensation is scene dependent, in some video conference type of scenes, bit rate is reduced by as much as 60 percent compared to conditional replenishment coding.
Automatically labeling video data using multi-class active learning (2003)

Labeling video data is an essential prerequisite for many vision applications that depend on training data, such as visual information retrieval, object recognition, and human activity modelling. However, manually creating labels is not only time-consuming but also subject to human errors, and eventually, becomes impossible for a very large amount of data (e.g. 24/7 surveillance video). To minimize the human effort in labeling, we propose a unified multiclass active learning approach for automatically labeling video data. We include extending active learning from binary classes to multiple classes and evaluating several practical sample selection strategies. The experimental results show that the proposed approach works effectively even with a significantly reduced amount of labeled data. The best sample selection strategy can achieve more than a 50% error reduction over random sample selection.
Fluorous Oligosaccharide Synthesis Using a Novel Fluorous Protective Group (2001)

The Bfp (bisfluorous chain type propanoyl) group, a novel fluorous protecting reagent, was able to be prepared easily. The Bfp group was readily introduced to carbohydrate, was removed in high yield, and was recyclable after cleavage. Use of the Bfp group made it possible to synthesize a tetrasaccharide by minimal column chromatography purification. Each synthetic intermediate was able to be easily purified by using only simple fluorous-organic solvent extraction and was monitored by NMR, mass spectroscopy, and TLC.
Aberrant MHC class II expression in mouse joints leads to arthritis with extraarticular manifestations similar to rheumatoid arthritis (2006)

Genetic susceptibility to rheumatoid arthritis (RA) is associated with certain MHC class II molecules. To clarify the role of these determinants in RA, we generated the D1CC transgenic mouse that expressed genes involved in antigen processing and presentation by the MHC class II pathway in joints. The class II transactivator, which was transcribed from the rat collagen type II promoter and enhancer, directed the expression of these genes. In D1CC mice congenic for the H-2(q) (DBA/1) background, small amounts of bovine collagen type II in adjuvant induced reproducibly an inflammatory arthritis resembling RA. Importantly, these stimuli had no effect in DBA/1 mice. Eighty-nine percent of D1CC mice developed chronic disease with joint swelling, redness, and heat in association with synovial proliferation as well as pannus formation and mononuclear infiltration of synovial membranes. Granulomatous lesions resembling rheumatoid nodules and interstitial pneumonitis also were observed. As in patients with RA, anticyclic citrullinated peptide antibodies were detected during the inflammatory stage. Finally, joints in D1CC mice displayed juxtaarticular demineralization, severe joint space narrowing, and erosions, which led to ankylosis, but without the appearance of osteophytes. Thus, aberrant expression of MHC class II in joints facilitates the development of severe erosive inflammatory polyarthritis, which is very similar to RA.
Immunogenicity of a Human Immunodeficiency Virus (HIV) Polytope Vaccine Containing Multiple HLA A2 HIV CD8+Cytotoxic T-Cell Epitopes (1999)

Compelling evidence now suggests that alphabeta CD8 cytotoxic T lymphocytes (CTL) have an important role in preventing human immunodeficiency virus (HIV) infection and/or slowing progression to AIDS. Here, we describe an HIV type 1 CTL polyepitope, or polytope, vaccine comprising seven contiguous minimal HLA A2-restricted CD8 CTL epitopes conjoined in a single artificial construct. Epitope-specific CTL lines derived from HIV-infected individuals were able to recognize every epitope within the construct, and HLA A2-transgenic mice immunized with a recombinant virus vaccine coding for the HIV polytope also generated CTL specific for different epitopes. Each epitope in the polytope construct was therefore processed and presented, illustrating the feasibility of the polytope approach for HIV vaccine design. By simultaneously inducing CTL specific for different epitopes, an HIV polytope vaccine might generate activity against multiple challenge isolates and/or preempt the formation of CTL escape mutants.
G9a inhibition potentiates the anti-tumour activity of DNA double-strand break inducing agents by impairing DNA repair independent of p53 status (2016)

Cancer cells often exhibit altered epigenetic signatures that can misregulate genes involved in processes such as transcription, proliferation, apoptosis and DNA repair. As regulation of chromatin structure is crucial for DNA repair processes, and both DNA repair and epigenetic controls are deregulated in many cancers, we speculated that simultaneously targeting both might provide new opportunities for cancer therapy. Here, we describe a focused screen that profiled small-molecule inhibitors targeting epigenetic regulators in combination with DNA double-strand break (DSB) inducing agents. We identify UNC0638, a catalytic inhibitor of histone lysine N-methyl-transferase G9a, as hypersensitising tumour cells to low doses of DSB-inducing agents without affecting the growth of the non-tumorigenic cells tested. Similar effects are also observed with another, structurally distinct, G9a inhibitor A-366. We also show that small-molecule inhibition of G9a or siRNA-mediated G9a depletion induces tumour cell death under low DNA damage conditions by impairing DSB repair in a p53 independent manner. Furthermore, we establish that G9a promotes DNA non-homologous end-joining in response to DSB-inducing genotoxic stress. This study thus highlights the potential for using G9a inhibitors as anti-cancer therapeutic agents in combination with DSB-inducing chemotherapeutic drugs such as etoposide.
Small-Molecule Selectin Inhibitor Protects Against Liver Inflammatory Response After Ischemia and Reperfusion (1997)

A small-molecule selectin inhibitor (TBC-1269) had a protective effect in livers subjected to 90 minutes of warm hepatic ischemia and 6 hours of reperfusion by decreasing neutrophil infiltration, migration and subsequent tissue damage. The best protective effect was achieved when the compound was administered 15 minutes before reperfusion. These findings offer a new therapeutic alternative for protection against ischemia and reperfusion injury.
Proteases for Processing Proneuropeptides into Peptide Neurotransmitters and Hormones (2008)

Peptide neurotransmitters and peptide hormones, collectively known as neuropeptides, are required for cell-cell communication in neurotransmission and for regulation of endocrine functions. Neuropeptides are synthesized from protein precursors (termed proneuropeptides or prohormones) that require proteolytic processing primarily within secretory vesicles that store and secrete the mature neuropeptides to control target cellular and organ systems. This review describes interdisciplinary strategies that have elucidated two primary protease pathways for prohormone processing consisting of the cysteine protease pathway mediated by secretory vesicle cathepsin L and the well-known subtilisin-like proprotein convertase pathway that together support neuropeptide biosynthesis. Importantly, this review discusses important areas of current and future biomedical neuropeptide research with respect to biological regulation, inhibitors, structural features of proneuropeptide and protease interactions, and peptidomics combined with proteomics for systems biological approaches. Future studies that gain in-depth understanding of protease mechanisms for generating active neuropeptides will be instrumental for translational research to develop pharmacological strategies for regulation of neuropeptide functions. Pharmacological applications for neuropeptide research may provide valuable therapeutics in health and disease.