gebhart/patrepeval huggingface dataset:
Recombinant Human Adenovirus: Targeting to the Human Transferrin Receptor Improves Gene Transfer to Brain Microcapillary Endothelium (2000)

Some inborn errors of metabolism due to deficiencies of soluble lysosomal enzymes cause global neurodegenerative disease. Representative examples include the infantile and late infantile forms of the ceroid lipofuscinoses (CLN1 or CLN2 deficiency, respectively) and mucopolysaccharidoses type VII (MPS VII), a deficiency of beta-glucuronidase. Treatment of the central nervous system component of these disorders will require widespread protein or enzyme replacement, either through dissemination of the protein or through dissemination of a gene encoding it. We hypothesize that transduction of brain microcapillary endothelium (BME) with recombinant viral vectors, with secretion of enzyme product basolaterally, could allow for widespread enzyme dissemination. To achieve this, viruses should be modified to target the BME. This requires (i) identification of a BME-resident target receptor, (ii) identification of motifs targeted to that molecule, (iii) the construction of modified viruses to allow for binding to the target receptor, and (iv) demonstrated transduction of receptor-expressing cells. In proof of principal experiments, we chose the human transferrin receptor (hTfR), a molecule found at high density on human BME. A nonamer phage display library was panned for motifs which could bind hTfR. Forty-three clones were sequenced, most of which contained an AKxxK/R, KxKxPK/R, or KxK motif. Ten peptides representative of the three motifs were cloned into the HI loop of adenovirus type 5 fiber. All motifs tested retained their ability to trimerize and bind transferrin receptor, and seven allowed for recombinant adenovirus production. Importantly, the fiber-modified viruses facilitated increased gene transfer (2- to 34-fold) to hTfR expressing cell lines and human brain microcapillary endothelia expressing high levels of endogenous receptor. Our data indicate that adenoviruses can be modified in the HI loop for expanded tropism to the hTfR.
Fructose ingestion acutely elevates blood pressure in healthy young humans (2008)

Overconsumption of fructose, particularly in the form of soft drinks, is increasingly recognized as a public health concern. The acute cardiovascular responses to ingesting fructose have not, however, been well-studied in humans. In this randomized crossover study, we compared cardiovascular autonomic regulation after ingesting water and drinks containing either glucose or fructose in 15 healthy volunteers (aged 21-33 yr). The total volume of each drink was 500 ml, and the sugar content 60 g. For 30 min before and 2 h after each drink, we recorded beat-to-beat heart rate, arterial blood pressure, and cardiac output. Energy expenditure was determined on a minute-by-minute basis. Ingesting the fructose drink significantly increased blood pressure, heart rate, and cardiac output but not total peripheral resistance. Glucose ingestion resulted in a significantly greater increase in cardiac output than fructose but no change in blood pressure and a concomitant decrease in total peripheral resistance. Ingesting glucose and fructose, but not water, significantly increased blood pressure variability and decreased cardiovagal baroreflex sensitivity. Energy expenditure increased by a similar amount after glucose and fructose ingestion, but fructose elicited a significantly greater increase in respiratory quotient. These results show that ingestion of glucose and fructose drinks is characterized by specific hemodynamic responses. In particular, fructose ingestion elicits an increase in blood pressure that is probably mediated by an increase in cardiac output without compensatory peripheral vasodilatation.
Fluorescent low density lipoprotein for observation of dynamics of individual receptor complexes on cultured human fibroblasts. (1981)

The visible wavelength excited fluorophore 3,3'-dioctadecylindocarbocyanine iodide (Dil[3]) was incorporated into human low density lipoprotein (LDL) to form the highly fluorescent LDL derivative dil(3)-LDL. Dil(3)-LDL binds to normal human fibroblasts and to human fibroblasts defective in LDL receptor internalization but does not bind to LDL receptor-negative human fibroblasts at 4 degrees C or 37 degrees C. It is internalized rapidly at 37 degrees C by normal fibroblasts and depresses the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) in a manner similar to that of LDL. It is prevented from binding to the LDL receptor by an excess of unlabeled LDL or by heparin sulfate. Identical distributions of dil(3)-LDL are observed on cells by either indirect immunofluorescence with fluorescein-labeled antibody or directly by dil(3) fluorescence. Upwards of 45 molecules of dil(3) are incorporated per molecule of LDL without affecting binding to the receptor. This labeling renders individual molecules visible by their fluorescence and enables the derivative to be used in dynamic studies of LDL-receptor motion on living fibroblasts by standard fluorescence techniques at low LDL receptor density. Observations with this derivative indicate that the LDL-receptor complex is immobilized on the surface of human fibroblasts but, when free of this linkage, undergoes a Brownian motion consistent with theory.
2-Mercapto-N-(azolyl)benzenesulphonamides. I. Synthesis of N-(1,1-dioxo-1,4,2-benzodithiazin-3-yl)guanidines and their transformations into 2-mercapto-N-(5-amino-1,2,4-triazol-3-yl) benzenesulphonamide derivatives with potential anti-HIV or anticancer activity. (1997)

N-(1,1-Dioxo-1,4,2-benzodithiazin-3-yl)-N'-R3-guanidines [IIa-IIo] were prepared from the corresponding 3-methylthio-1,4,2-benzodithiazine 1,1-dioxide derivatives [Ia-Id]. Depending on electronic effects of R3 substituents, hydrazinolysis of the benzodithiazinylguanidines [II] afforded the following derivatives in good yields: either 2-mercapto-N-(5-amino-1,2,4-triazol-3-yl)benzenesulphonamides [IIIa-IIIc] (82-90% yields for R3 = H, Bu and Bzl) or 2-mercapto-N-[5-(R3-amino)-1,2,4-triazol-3-yl]benzenesulphonamides [IIIa-IIIm] (42-80% yields for R3 = Ph or substituted phenyl). The mechanism of the reaction has been suggested. Preliminary screening data indicated that compounds [IIId, IIIf-IIIi, IIIk] exhibit moderate anti-HIV-1 activity, and compounds [IIIe, IIIj, III l] anticancer activity.
Gastrointestinal expression and partial cDNA cloning of murine Muc2 (1999)

To help us investigate the role of mucin in the protection of the colonic epithelium in the mouse, we aimed to identify the murine colonic mucin (MCM) and its encoding gene. We isolated MCM, raised an anti-MCM antiserum, and studied the biosynthesis of MCM in the gastrointestinal tract. Isolated MCM resembled other mucins in physicochemical properties. Anti-MCM recognized MCM as well as rat and human MUC2 on Western blots, interacting primarily with peptide epitopes, indicating that MCM was identical to murine Muc2. Using anti-MCM and previously characterized anti-human and anti-rat MUC2 antibodies, we identified a murine Muc2 precursor in the colon of approximately 600 kDa, which appeared similar in size to rat and human MUC2 precursors. Western blotting, immunoprecipitation of metabolically labeled mucins, and immunohistochemistry showed that murine Muc2 was expressed in the colon and the small intestine but was absent in the stomach. To independently identify murine Muc2, we cloned a cDNA fragment from murine colonic mRNA, encoding the 302 NH2-terminal amino acids of murine Muc2. The NH2 terminus of murine Muc2 showed 86 and 75% identity to the corresponding rat and human MUC2 peptide sequences, respectively. Northern blotting with a murine Muc2 cDNA probe showed hybridization to a very large mRNA, which was expressed highly in the colon and to some extend in the small intestine but was absent in the stomach. In situ hybridization showed that the murine Muc2 mRNA was confined to intestinal goblet cells. In conclusion, by two independent sets of experiments we identified murine Muc2, which appears homologous to rat and human MUC2. Because Muc2 is prominently expressed in the colon, it is most likely to be the predominant mucin in the colonic mucus layer.
Sulfur poisoning of catalysts. Quarterly progress report, 1 April--30 June 1976. [Methanol synthesis from H and CO] (1976)

Progress is reported on an experimental study of the poisoning of catalysts used in methanol synthesis by sulfur-containing gases (hydrogen sulfide, thiophene, carbonyl sulfide). The changes in catalyst surface composition when the catalyst was exposed to hydrogen sulfide were determined by Auger electron spectroscopy. Thiophene is less deleterious than hydrogen sulfide. Values of the poisoning rate constant with hydrogen sulfide as a feedstock contaminant are nearly identical for the LPP catalysts examined, but are about an order of magnitude smaller for HPP catalysts. The capture of hydrogen sulfide by the catalyst appears to be extremely efficient. (LTN)
Sensitivity analysis of line correspondence (1995)

This correspondence shows that line and point correspondences can obtain orientation with the same accuracy, and that when using line correspondence, using more matching lines does not guarantee that the orientation error can be reduced. Orientation detection using line correspondence is very sensitive to errors in image location. We provide a sensitivity analysis of line correspondence, and conditions which lead to orientation sensitivity due to errors in image location. The orientation error using line correspondence due to offset from the image center is obtained analytically. A method for selecting three matching lines, such that orientation is not sensitive to image location errors and using more matching edges to improve the accuracy of orientation is given. Finally three examples are given to illustrate the concepts and support the theoretical results. The first example shows that an orientation with reasonable accuracy may be obtained by using three matching lines. The second example demonstrates that both point and line correspondences can obtain orientation with the same accuracy. The last example supports experimentally the result regarding the orientation error using line correspondence due to offset of the image center and lens distortion.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Controlled release of human immunoglobulin G. 1. Release kinetics studies (1999)

The release of human immunoglobulin G (IgG) using ethylene-vinyl acetate copolymer (EVAc) as a polymer carrier was studied by fabricating them into two commercially available dosage forms: slab and microsphere. A first-order flux decay model and two hierarchical models concerned with the mass transfer coefficient on the slab surface were used to describe the mechanism of release kinetics and the results compared. These models gave insight to some of the important physical parameters of drug release such as the diffusion coefficient, time constant of release, and initial flux. It was found that the release mechanism varies with time, and hence no single model can be used to predict the release profile for the entire period of study. A controlled release study by matrix coating was also done. The results obtained were utilized to examine the suitability of a particular dosage form (matrix geometry) of IgG for clinical applications. The release data compared with the standard methods of IgG therapy proves localized drug delivery to be a major boon for immunodeficient patients.
Low-dose deoxycoformycin in lymphoid malignancy. (1985)

Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase (ADA), was explored for its antineoplastic potential in 28 patients with advanced lymphoid malignancy. Both normal and malignant B lymphocytes have low levels of ADA activity, and low doses of dCF profoundly inhibit this enzyme in the peripheral blood of patients with chronic lymphocytic leukemia (CLL). The low doses of dCF administered in this trial (4 mg/m2) were not associated with prohibitive toxicity. Five of 28 patients had an objective response. Four additional patients had clinical improvement. No significant difference in the pretreatment ADA activity existed between responding patients and treatment failures. The demonstration of responses to dCF following failure on standard alkylating agents suggests that dCF may not be cross-resistant with current agents used to treat CLL. Additional studies should be pursued using low-dose dCF in patients with advanced malignancy.
A Nonpeptidic Sulfonamide Inhibits the p53−mdm2 Interaction and Activates p53-Dependent Transcription in mdm2-Overexpressing Cells (2004)

The evaluation of a sulfonamide inhibitor of the p53-mdm2 interaction is presented. The compound was identified using 3D database searching techniques based on a computationally derived pharmacophore model of mdm2 binding. It inhibits the physical interaction of recombinant p53 and mdm2 in vitro and increases p53-dependent transcription in an mdm2-overexpressing cell line.
Pleiotropic defects in ataxia-telangiectasia protein-deficient mice (1996)

We have generated a mouse model for ataxia-telangiectasia by using gene targeting to generate mice that do not express the Atm protein. Atm-deficient mice are retarded in growth, do not produce mature sperm, and exhibit severe defects in T cell maturation while going on to develop thymomas. Atm-deficient fibroblasts grow poorly in culture and display a high level of double-stranded chromosome breaks. Atm-deficient thymocytes undergo spontaneous apoptosis in vitro significantly more than controls. Atm-deficient mice then exhibit many of the same symptoms found in ataxia-telangiectasia patients and in cells derived from them. Furthermore, we demonstrate that the Atm protein exists as two discrete molecular species, and that loss of one or of both of these can lead to the development of the disease.
385. The synthesis and properties of 2 : 7-disubstituted 1 : 2 : 3 : 4-tetrahydroisoquinolines (1949)

M. H. Beeby and F. G. Mann, J. Chem. Soc., 1949, 1799 DOI: 10.1039/JR9490001799
Mobile Radio Communications: Second and Third Generation Cellular and WATM Systems: 2nd (1999)

This comprehensive all-in-one reference work covers the fundamental physical aspects of mobile communications and explains the latest techniques employed in second and third generation digital cellular mobile radio systems. Mobile radio communications technology has progressed rapidly and it is now capable of the transmission of voice, data and image signals. This new edition reflects the current state-of-the-art by featuring: * Expanded and updated sections on voice compression techniques, interleaving and channel coding methods, quaternary frequency shift keying, continuous phase modulation methods, Viterbi equalisation and slow frequency hopping as well as extended coverage of the GSM system. * Three new chapters on wireless multimedia, third generation systems and on WATM respectively As in the first edition, this latest volume continues to cover important topics such as radio propagation, multiple access methods and, on a higher level, cordless telecommunications and teletraffic issues. This book will prove invaluable to mobile communication engineers, designers, researchers, and students in the design, operation and research of second and third generation systems and wireless LANs.
Bottleneck Characterization of Dynamic Web Site Benchmarks (2002)

The absence of benchmarks for Web sites with dynamic content has been a major impediment to research in this area. We describe three benchmarks for evaluating the performance of Web sites with dynamic content. The benchmarks model three common types of dynamic-content Web sites with widely varying application characteristics: an online bookstore, an auction site, and a bulletin board. For each benchmark we describe the design of the database, the interactions provided by the Web server, and the workloads used in analyzing the performance of the system. We have implemented these three benchmarks with commonly used open-source software. In particular, we used the Apache Web server, the PHP scripting language, and the MySQL relational database. Our implementation is therefore representative of the many dynamic content Web sites built using these tools. Our implementations are available freely from our Web site for other researchers to use. We present a performance evaluation of our implementations of these three benchmarks on contemporary commodity hardware. Our performance evaluation focused on finding and explaining the bottleneck resources in each benchmark. For the online bookstore, the CPU on the database was the bottleneck, while for the auction site and the bulletin board the CPU on the front-end Web server was the bottleneck. In none of the benchmarks was the network between the front-end and the back-end a bottleneck. With amounts of memory common by today’s standards, neither the main memory nor the disk proved to be a limiting factor in terms of performance for any of the benchmarks. 1.
Two types of Ia-positive T cells. Synthesis and exchange of Ia antigens. (1980)

Two distinct types of Ia-positive T cells have been described. One type represents a blastoid T cell responding from stimulation by mitogens, antigens, and in allogeneic and autologous mixed lymphocyte culture reactions. This is a large cell that is strongly positive for Ia antigens as measured by a variety of different antisera. The other general type is a smaller cell with a lower expression of Ia antigens that is found at low levels in normal peripheral blood and is markedly elevated in various pathological states. It also rises rapidly after inoculation with tetanus toxoid and PPD in sensitized individuals. This cell does not incorporate thymidine and is enriched in the Tgamma fraction; it can be markedly concentrated from normal lymphocytes, and current evidence indicates that it is a T cell. The marked elevation of this cell in the blood of patients with rheumatoid arthritis is of special interest. Considerable evidence indicates that, at least in certain instances, the Ia antigens are synthetized by the cells that carry them. Incorporation of labeled amino acid experiments and the in vitro translation results presented above indicate this. However, the ready exchange of Ia antigens between cells in the experiments described indicates that uptake from other cells may be a significant source.
Alcaligenes eutrophus Possesses a Second Pyruvate Dehydrogenase (E1) (1996)

Two gene loci, which hybridized with pdhA, the structural gene of the E1 component of the Alcaligenes eutrophus pyruvate dehydrogenase complex [Hein, S. & Steinbüchel, A. (1994) J. Bacteriol. 176, 4394-4408], were identified on two nonrelated A. eutrophus chromosomal BamHI fragments by using a pdhA-specific DNA probe. These data indicated that A. eutrophus possesses, beside PdhA, two additional distinct pyruvate dehydrogenases (E1). A 6.8-kbp genomic BamHI fragment of A. eutrophus was cloned, and sequence analysis of a 3.896-kbp region revealed the structural gene pdhE (2.694 kbp) for a second pyruvate dehydrogenase (E1), which was not clustered with structural genes for other components of 2-oxo acid dehydrogenase complexes. The A. eutrophus pdhE gene product (898 amino acid residues) exhibited significant similarities to the E1 components of the pyruvate dehydrogenase complexes of A. eutrophus, Neisseria meningitidis, Escherichia coli and Azotobacter vinelandii, which are also composed of only one type of subunit. Heterologous expression of pdhE in the aceEF deletion mutant E. coli YYC202 was demonstrated by spectrometric detection of enzyme activities and by phenotypic complementation to acetate prototrophy. These complementation studies indicated that the E1 component of the A. eutrophus pyruvate dehydrogenase complex can be replaced by a functionally active pdhE gene product.
Microbial Baeyer−Villiger Oxidation:  Stereopreference and Substrate Acceptance of Cyclohexanone Monooxygenase Mutants Prepared by Directed Evolution (2006)

[reaction: see text] An array of random mutants of cyclohexanone monooxygenase (CHMO) from Acinetobacter sp. NCIMB 9871 was screened against a library of structurally diverse ketones for modifications in the substrate acceptance profile and stereopreference of the enzymatic Baeyer-Villiger biooxidation. While the set of mutant biocatalysts was initially evolved for the enantiocomplementary oxidation of 4-hydroxycyclohexanone, improved and/or divergent stereoselectivities were observed for several substrates. In addition, expanded substrate acceptance to facilitate biotransformation of sterically demanding ketones was found.
A peptide that inhibits hydroxyapatite growth is in an extended conformation on the crystal surface (1998)

Proteins play an important role in the biological mechanisms controlling hard tissue development, but the details of molecular recognition at inorganic crystal interfaces remain poorly characterized. We have applied a recently developed homonuclear dipolar recoupling solid-state NMR technique, dipolar recoupling with a windowless sequence (DRAWS), to directly probe the conformation of an acidic peptide adsorbed to hydroxyapatite (HAP) crystals. The phosphorylated hexapeptide, DpSpSEEK (N6, where pS denotes phosphorylated serine), was derived from the N terminus of the salivary protein statherin. Constant-composition kinetic characterization demonstrated that, like the native statherin, this peptide inhibits the growth of HAP seed crystals when preadsorbed to the crystal surface. The DRAWS technique was used to measure the internuclear distance between two 13C labels at the carbonyl positions of the adjacent phosphoserine residues. Dipolar dephasing measured at short mixing times yielded a mean separation distance of 3.2 +/- 0.1 A. Data obtained by using longer mixing times suggest a broad distribution of conformations about this average distance. Using a more complex model with discrete alpha-helical and extended conformations did not yield a better fit to the data and was not consistent with chemical shift analysis. These results suggest that the peptide is predominantly in an extended conformation rather than an alpha-helical state on the HAP surface. Solid-state NMR approaches can thus be used to determine directly the conformation of biologically relevant peptides on HAP surfaces. A better understanding of peptide and protein conformation on biomineral surfaces may provide design principles useful for the modification of orthopedic and dental implants with coatings and biological growth factors that are designed to enhance biocompatibility with surrounding tissue.
Monolithic Wavelength Converters for High-Speed Packet-Switched Optical Networks (2007)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> This paper describes the design and demonstration of advanced 40-Gb/s return-to-zero (RZ) tunable all-optical wavelength converter technologies for use in packet-switched optical networks. The device designs are based on monolithic integration of a delayed interference Mach–Zehnder interferometer (MZI) semiconductor optical amplifier (SOA) wavelength converter with a sampled-grating distributed Bragg reflector tunable laser and an on-chip waveguide delay. Experimental results are presented demonstrating error-free wavelength conversion with 1-dB power penalty at 40-Gb/s data rates. By incorporating label modulation functionality on-chip along with a fast tunable 40-Gb/s wavelength converter, fully monolithic packet-forwarding chips are realized that are capable of simultaneous error-free wavelength conversion of 40-Gb/s payloads, remodulation of 10-Gb/s packet headers, and data routing through fast wavelength switching. </para>