gebhart/patrepeval huggingface dataset:
Tissue Engineering of a Differentiated Cardiac Muscle Construct (2002)

Cardiac tissue engineering is an emerging field. The suitability of engineered heart tissue (EHT) for both in vitro and in vivo applications will depend on the degree of syncytoid tissue formation and cardiac myocyte differentiation in vitro, contractile function, and electrophysiological properties. Here, we demonstrate that cardiac myocytes from neonatal rats, when mixed with collagen I and matrix factors, cast in circular molds, and subjected to phasic mechanical stretch, reconstitute ring-shaped EHTs that display important hallmarks of differentiated myocardium. Comparative histological analysis of EHTs with native heart tissue from newborn, 6-day-old, and adult rats revealed that cardiac cells in EHTs reconstitute intensively interconnected, longitudinally oriented, cardiac muscle bundles with morphological features resembling adult rather than immature native tissue. Confocal and electron microscopy demonstrated characteristic features of native differentiated myocardium; some of these features are absent in myocytes from newborn rats: (1) highly organized sarcomeres in registry; (2) adherens junctions, gap junctions, and desmosomes; (3) a well-developed T-tubular system and dyad formation with the sarcoplasmic reticulum; and (4) a basement membrane surrounding cardiac myocytes. Accordingly, EHTs displayed contractile characteristics of native myocardium with a high ratio of twitch (0.4 to 0.8 mN) to resting tension (0.1 to 0.3 mN) and a strong beta-adrenergic inotropic response. Action potential recordings demonstrated stable resting membrane potentials of -66 to -78 mV, fast upstroke kinetics, and a prominent plateau phase. The data indicate that EHTs represent highly differentiated cardiac tissue constructs, making EHTs a promising material for in vitro studies of cardiac function and tissue replacement therapy.
A New Method for Coarse-Grained Elastic Normal-Mode Analysis (2006)

In this paper, we report a new method for coarse-grained elastic normal-mode analysis. The purpose is to overcome a long-standing problem in the conventional analysis called the tip effect that makes the motional patterns (eigenvectors) of some low-frequency modes irrational. The new method retains the merits of a conventional method such as not requiring lengthy initial energy minimization, which always distorts structures, and also delivers substantially more accurate low-frequency modes with no tip effect for proteins of any size. This improvement of modes is crucial for certain types of applications such as structural refinement or normal-mode-based sampling.
Characterization of the human cytochrome P450 isozymes responsible for styrene metabolism. (1993)

The rate of formation of styrene glycol from styrene was compared in human, rat and mouse liver microsomes. At a low styrene concentration (0.085 mM), the rates decreased in the order, mouse > rat > human; at a high concentration (1.85 mM), the order was rat > mouse > human. The forms of cytochrome P450 that are responsible for transforming styrene to styrene glycol were determined by vaccinia virus-mediated cDNA expression of individual P450 forms in cultured cells. Of the 10 human P450 forms studied, CYP2B6 was the most effective in forming of styrene glycol, followed by CYP1A2, CYP2E1 and CYP2C8; the human P450s CYP3A3, CYP3A4 and CYP3A5 also catalysed metabolism, but were much less active; and CYP2A6, CYP2C9 and CYP2D6 had little detectable activity. CYP1A1 from mouse liver was more active in forming styrene glycol than mouse CYP1A2; the latter was less active than human CYP1A2. CYP2B1 from rat liver was more active than rat CYP2B2 or CYP2B6 from human liver. The rate of styrene glycol formation was higher in lung microsomes from smokers than in those from current nonsmokers.
Optical limiting effect in a two-photon absorption dye doped solid matrix (1995)

We recently reported a new lasing dye, trans-4-[p-(N-ethyl-N-hydroxylethylamino)styryl]-N-methylpyridinium tetraphenylborate (ASPT), which has also been shown to possess a strong two-photon absorption (TPA) and subsequent frequency upconversion fluorescence behavior when excited with near infrared laser radiation. Based on the TPA mechanism, a highly efficient optical limiting performance has been demonstrated in a 2 cm long ASPT-doped epoxy rod pumped with 1.06 μm Q-switched laser pulses at 50–250 MW/cm2 intensity levels. The measured nonlinear absorption coefficient reached 6 cm/GW for the tested sample of dopant concentration d0=4×10−3 M/L. The molecular TPA cross section of ASPT in the epoxy matrix is estimated as σ2=2.5×10−18 cm4/GW or σ2′=4.7×10−46 cm4/photon/s, respectively. Two-photon pumped cavity lasing is also observed in an ASPT-doped polymer rod.
Introduction (2005)

In March 2001, on the BBC Radio 4 Today program, a report was presented discussing a new seven-category class scheme being used in the British Census. Listeners were invited to the BBC website to see what class they were in. Within a few days there were over 50,000 hits on the site, a record for this sort of thing. At least for the segment of the British population that listens to the BBC morning news, class remains a salient issue.
Anti-cytokine antibodies as carrier proteins. Prolongation of in vivo effects of exogenous cytokines by injection of cytokine-anti-cytokine antibody complexes. (1993)

Anti-cytokine antibodies that block interactions between cytokines and cytokine receptors have been used to inhibit endogenous cytokine function. However, injection of mice with mixtures of IL-4 and either of two neutralizing anti-IL-4 mAb, at a cytokine/anti-cytokine mAb molar ratio of approximately 2:1, enhances and prolongs in vivo IL-4 activity, as measured by induction of increased spleen cell Ia expression. Although splenocyte Ia expression returns to baseline two days after mice are injected with free IL-4, soluble IL-4-anti-IL-4 mAb complexes still induce several-fold increases in Ia expression 3 days after injection. Complexes that contain as little as 400 ng of IL-4 have considerable in vivo stimulatory activity, and a maximal effect on splenocyte Ia expression is induced by injection of 2 micrograms of complexed IL-4. The stimulatory effect of IL-4-containing complexes on splenocyte Ia expression can be blocked by increasing the ratio of anti-IL-4 mAb to IL-4, by injection of anti-IL-4R mAb, and by in vivo aggregation of the complexes. Complexes of IL-4 with a non-neutralizing anti-IL-4 mAb do not have increased IL-4 agonist activity in vivo. These observations are most consistent with the possibility that neutralizing anti-IL-4 mAb act as carrier proteins that increase the in vivo half-life of IL-4 by preventing its excretion, and possibly, by preventing modification of its active site. The enhanced agonist effect of IL-4-anti-IL-4 mAb complexes is not unique; complexes of IL-3 with a neutralizing anti-IL-3 mAb have a greatly increased ability, compared with free IL-3, to stimulate mucosal mastocytosis, and complexes of IL-7 with a neutralizing anti-IL-7 mAb have a greatly increased ability, compared with free IL-7 or IL-7 complexed with a non-neutralizing anti-IL-7 mAb, to stimulate an increase in pre-B cell number. These observations suggest that complexes of cytokines and neutralizing anti-cytokine mAb may provide a generally useful way to increase the magnitude and duration of cytokine effects in vivo.
Laser‐mediated gene transfer in rice (1995)

We report an effective system for introducing exogenous DNA into cells of embryonic calli of Oryza sativa L. cv. Japonica. Plant cells were pretreated in hypertonic buffer to draw some of the water from the cells and were then put into medium of less negative osmotic potential containing exogenous DNA and treated immediately with a laser microbeam (λ=355 nm) to puncture holes in the cell wall and membrane. The pretreatment of the cells generated a gradient of osmotic pressure between the inside and outside of the cells, which facilitated the uptake of material into cells through the laser perforations. Bright yellow‐green fluorescence could be detected inside cells that had been bathed in a solution containing the fluorescent molecule calcein. β‐Glucuronidase (GUS) genes were successfully introduced into rice cells as indicated by gene expression both in post‐treated cells and in plantlets derived from kanamycin‐resistant calli that had been treated by this method.
Explanatory supplement to the Astronomical Almanac (1993)

original Explanatory to the and the and Nautical Almanac was published in 1961 and revised in 1974. In 1981 the series of publications titled The Ephemeris and the American and Nautical Almanac were continued under the single title The Almanac. Thus, the title of the new edition of the Explanatory Supplement. In the 1970s it was recognized that there was a need to revise the planetary and lunar ephemerides, the FK4 star catalog, the time scales, the System of Constants and the Theory of Nutation. In 1984 all these revisions were introduced using the new standard epoch J2000.0, thus making the original Explanatory Supplement out of date. Hence, the new version was prepared based on the FK5 star catalog, the IAU (1976) System of Constants, the new time scales, including those adopted in 199 1, the IAU (1980) Theory, of Nutation, and the DE200/LE200 ephemerides. Improvements since 1984 have also been incorporated. Current values of astrometric and planetary data are included. Explanatory to the Almanac provides a detailed description of the means of performing practical astronomy or spherical astronomy. It shows how computations for the Astronomical Almanac are performed and the underlying information required by someone using that publication or wanting to perform related computations. It is intended to be a reference volume for anybody working with accurate positional astronomical data and anyone interested in investigations of the solar system.
Graphene based gene transfection (2011)

Graphene as a star in materials research has been attracting tremendous attentions in the past few years in various fields including biomedicine. In this work, for the first time we successfully use graphene as a non-toxic nano-vehicle for efficient gene transfection. Graphene oxide (GO) is bound with cationic polymers, polyethyleneimine (PEI) with two different molecular weights at 1.2 kDa and 10 kDa, forming GO-PEI-1.2k and GO-PEG-10k complexes, respectively, both of which are stable in physiological solutions. Cellular toxicity tests reveal that our GO-PEI-10k complex exhibits significantly reduced toxicity to the treated cells compared to the bare PEI-10k polymer. The positively charged GO-PEI complexes are able to further bind with plasmid DNA (pDNA) for intracellular transfection of the enhanced green fluorescence protein (EGFP) gene in HeLa cells. While EGFP transfection with PEI-1.2k appears to be ineffective, high EGFP expression is observed using the corresponding GO-PEI-1.2k as the transfection agent. On the other hand, GO-PEI-10k shows similar EGFP transfection efficiency but lower toxicity compared with PEI-10k. Our results suggest graphene to be a novel gene delivery nano-vector with low cytotoxicity and high transfection efficiency, promising for future applications in non-viral based gene therapy.
Anterior dentition and relationships of the early Eocene omomyids Arapahovius advena and Teilhardina demissa, sp. nov. (1995)

Two dentaries from the Wasatchian Willwood Formation of the Bighorn Basin, Wyoming, constitute the first evidence of the anterior teeth of the omomyid Arapahovius advena . Another specimen, preserving intact crowns of nearly all the lower teeth, represents a derived new species of Teilhardina. The two species appear to be closely related and provide evidence on the interrelationships of diminutive omomyids. Arapahovius and Anemorhysis are sister taxa that probably evolved from a derived species of Teilhardina.
Comparison of straight chain and cyclic unnatural amino acids embedded in the core of staphylococcal nuclease (1997)

We have determined by X-ray crystallography the structures of several variants of staphylococcal nuclease with long flexible straight chain and equivalent length cyclic unnatural amino acid side chains embedded in the protein core. The terminal atoms in the straight side chains are not well defined by the observed electron density even though they remain buried within the protein interior. We have previously observed this behavior and have suggested that it may arise from the addition of side-chain vibrational and oscillational motions with each bond as a side chain grows away from the relatively rigid protein main chain and/or the population of multiple rotamers (Wynn R, Harkins P, Richards FM. Fox RO. 1996. Mobile unnatural amino acid side chains in the core of staphylococcal nuclease. Protein Sci 5:1026-1031). Reduction of the number of degrees of freedom by cyclization of a side chain would be expected to constrain these motions. These side chains are in fact well defined in the structures described here. Over-packing of the protein core results in a 1.0 A shift of helix 1 away from the site of mutation. Additionally, we have determined the structure of a side chain containing a single hydrogen to fluorine atom replacement on a methyl group. A fluorine atom is intermediate in size between methyl group and a hydrogen atom. The fluorine atom is observed in a single position indicating it does not rotate like methyl hydrogen atoms. This change also causes subtle differences in the packing interactions.
Platelet-activating Factor Acetylhydrolase, and Not Paraoxonase-1, Is the Oxidized Phospholipid Hydrolase of High Density Lipoprotein Particles (2003)

Paraoxonase-1 (PON1), an high density lipoprotein (HDL)-associated organophosphate triesterase, suppresses atherosclerosis in an unknown way. Purified PON1 protects lipoprotein particles from oxidative modification and hydrolyzes pro-atherogenic oxidized phospholipids and the inflammatory mediator platelet-activating factor (PAF). We find human PON1 acted as a phospholipase A(2) but not as a phospholipase C or D through cleavage of phosphodiester bonds as expected. PON1 requires divalent cations, but EDTA did not block the phospholipase A(2) activity of PON1. In contrast, a serine esterase inhibitor abolished phospholipase activity even though PON1 has no active-site serine residues. PAF acetylhydrolase, an oxidized phospholipid phospholipase A(2), is a serine esterase associated with specific HDL particles. Western blotting did not reveal detectable amounts of PAF acetylhydrolase in PON1 preparations, although very low amounts of PAF acetylhydrolase might still account for PON1 phospholipase A(2) activity. We revised the standard PON1 purification by first depleting HDL of PAF acetylhydrolase to find PON1 purified in this way no longer hydrolyzed oxidized phospholipids or PAF. Serum from a donor with an inactivating mutation in the PAF acetylhydrolase gene did not hydrolyze oxidized phospholipids or PAF, yet displayed full paraoxonase activity. We conclude that PAF acetylhydrolase is the sole phospholipase A(2) of HDL and that PON1 has no phospholipase activity toward PAF or pro-atherogenic oxidized phospholipids.
3-day treatment with azithromycin 1.5% eye drops versus 7-day treatment with tobramycin 0.3% for purulent bacterial conjunctivitis: multicentre, randomised and controlled trial in adults and children (2006)

Azithromycin 1.5% for 3 days was as effective and as safe as tobramycin for 7 days. Furthermore, more azithromycin than tobramycin patients presented an early clinical cure at Day 3. Due to its twice daily dosing regimen for 3 days, azithromycin represents a step forward in the management of purulent bacterial conjunctivitis, especially in children.
Elimination of murine erythroleukemic stem cells with a novel anti‐erythroid antibody conjugated to ricin a‐chain: A model for studies of bone‐marrow transplantation therapy (1986)

We have produced a rat monoclonal antibody (MAb) MAE15 (IgG), specific for murine erythroid cells, using a murine erythroid cell line as immunogen. This MAb specifically binds to the surface of normal and neoplastic murine erythroid cells. Murine mature erythrocytes and non-erythroid cells as well as rat and human erythroid and non-erythroid cells are not recognized by MAb MAE15. Immunoblotting analysis and mixed precipitation in agar gel showed MAb MAE15 to be specific for murine epitope of 69 kDa antigen of erythroblasts (Ag-Eb), an interspecies antigenic marker of nucleated red cells and reticulocytes. A conjugate (immunotoxin) was prepared, comprising ricin A-chain and MAb MAE15. The immunotoxin inhibited protein synthesis of murine erythroleukemic Ag-Eb-positive K-2 cells and completely inhibited (at the concentration of 2 X 10(-7) M) spleen colony formation by erythroleukemic stem cells of the Ag-Eb-positive RAL cell line. Approximately 35% of the murine normal stem-cell (CFU-S) population was not affected by the immunotoxin at the concentration of 2 X 10(-7) M. This experimental system may be a convenient model for studies of bone marrow transplantation therapy of erythroleukemias.
Identification of NY-ESO-1 Peptide Analogues Capable of Improved Stimulation of Tumor-Reactive CTL (2000)

Expression of NY-ESO-1 in a high proportion of different human tumors makes this protein a very attractive vaccine target. NY-ESO-1 peptides, recognized by HLA-A2-restricted CTL, have recently been described. However, it remains unclear how efficiently tumors generate these epitopes, and whether peptide analogues can be used for optimal expansion and activation of NY-ESO-1-specific HLA-A2-restricted CTL. By generating unique CTL clones, we demonstrate that NY-ESO-1-positive tumor cells are efficiently killed by HLA-A2-restricted CTL specific for the peptide epitope NY-ESO-1 157-165. Presentation of this epitope is not affected by the presence or absence of the proteasome subunits low molecular proteins 2 and 7 and is not blocked by proteasome inhibitors, while it is impaired in the TAP-deficient cell line LBL 721.174. NY-ESO-1 157-165 peptide analogues were compared for their antigenicity and immunogenicity using PBL from melanoma patients. Three peptides, containing the carboxyl-terminal cysteine substituted for either valine, isoleucine, or leucine, were recognized at least 100 times more efficiently than the wild-type peptide by specific CTL. Peptide analogues were capable of stimulating the expansion of NY-ESO-1-specific CTL from PBL of melanoma patients much more efficiently than wild-type peptide. These findings define the processing requirements for the generation of the NY-ESO-1 157-165 epitope. Identification of highly antigenic NY-ESO-1 peptide analogues may be important for the development of vaccines capable of expanding NY-ESO-1-specific CTL in cancer patients.
The Lung: Scientific Foundations (1991)

Section Titles I. General Biologic Processes II. Strategies for Understanding the Lung in Health and Disease III. Major Components IV. Integrated Morphology: Growth and Form V. Integrated Physiology and Pathophysiology VI. The Fetal, Perinatal, Postnatal, and Aging Lung VII. Lung Injury, Defense and Repair VIII. Special Environments and Interventions
Energy Transfer Studies of the Distances between the Colchicine, Ruthenium red, and BisANS Binding Sites on Calf Brain Tubulin (1994)

Fluorescence energy transfer experiments were performed in order to measure the spatial separation between the colchine and Ruthenium Red binding sites, the high-affinity bisANS and Ruthenium Red sites, and the allocolchicine and high-affinity bisANS sites on calf brain tubulin. Energy transfer was observed between both colchicine and allocolchicine and Ruthenium Red, resulting in a distance of 40-45 A between these sites on the tubulin molecule. No detectable energy transfer could be observed when allocolchicine was used as fluorescence donor and bisANS as acceptor or when bisANS was used as donor and Ruthenium Red as acceptor. This indicates that the distance of separation between the allocolchicine and bisANS sites is greater than 50 A, while that between the bisANS and Ruthenium Red sites is greater than 72 A. On the basis of these and previous distance measurements (Ward & Timasheff, 1988), two triangles of binding sites have been defined (colchicine-bisANS-E-site and colchicine-bisANS-Ruthenium Red). Since the dihedral angle between them is not known, a schematic model has been drawn with all the sites located in a single plane.(ABSTRACT TRUNCATED AT 250 WORDS)
Purification and characterization of sialyl-Le(a)-carrying mucins of human bile; evidence for the presence of MUC1 and MUC3 apoproteins. (1994)

Purification of sialyl-Le(a)-carrying mucins from primary human bile by trichloroacetic acid precipitation, delipidation, and gel filtration in guanidinium chloride gave three separable fractions, one of which was further purified by affinity chromatography. These fractions, named SBG1 (for soluble bile glycoprotein), SBG2, and SBG3 had molecular masses of > 1100, 800-950, and 100-250 kDa, respectively, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Their mucin characteristics were indicated by a high carbohydrate content, ranging from 74 to 95%. The carbohydrate compositions indicated the presence of very long fucosylated polylactosamine chains. Amino acid analyses showed high abundance of serine and threonine in all three fractions (19-36%), confirming their mucin-like nature. Immunochemical analyses of deglycosylated samples detected the MUC1 mucin apoprotein in SBG2 and the MUC3 protein in SBG1. To our knowledge, this is the first report of a MUC3 mucin being purified. This mucin showed no significant reduction in size upon trypsin treatment or disulfide bond reduction and alkylation. Gel filtration of three samples of secondary bile showed that the size distribution of sialyl-Le(a)-carrying glycoproteins was similar to that found in primary bile, and immunochemical analysis showed that the MUC1 protein was present in all three samples. In one sample an additional fraction was isolated, which was insoluble in 6 M guanidinium chloride, but was solubilized upon reduction and alkylation. mRNAs from gallbladder epithelia were analyzed in Northern blot hybridizations showing that the MUC1 and MUC3 but not the MUC2 mucin apoprotein genes were expressed.
Cloning of a Novel Member of the UDP-Galactose:β-N-Acetylglucosamine β1,4-Galactosyltransferase Family, β4Gal-T4, Involved in Glycosphingolipid Biosynthesis (1998)

A novel putative member of the human UDP-galactose:beta-N-acetylglucosamine beta1,4-galactosyltransferase family, designated beta4Gal-T4, was identified by BLAST analysis of expressed sequence tags. The sequence of beta4Gal-T4 encoded a type II membrane protein with significant sequence similarity to other beta1,4-galactosyltransferases. Expression of the full coding sequence and a secreted form of beta4Gal-T4 in insect cells showed that the gene product had beta1,4-galactosyltransferase activity. Analysis of the substrate specificity of the secreted form revealed that the enzyme catalyzed glycosylation of glycolipids with terminal beta-GlcNAc; however, in contrast to beta4Gal-T1, -T2, and -T3, this enzyme did not transfer galactose to asialo-agalacto-fetuin, asialo-agalacto-transferrin, or ovalbumin. The catalytic activity of beta4Gal-T4 with monosaccharide acceptor substrates, N-acetylglucosamine as well as glucose, was markedly activated in the presence of alpha-lactalbumin. The genomic organization of the coding region of beta4Gal-T4 was contained in six exons. All intron/exon boundaries were similarly positioned in beta4Gal-T1, -T2, and -T3. beta4Gal-T4 represents a new member of the beta4-galactosyltransferase family. Its kinetic parameters suggest unique functions in the synthesis of neolactoseries glycosphingolipids.