gebhart/patrepeval huggingface dataset:
Disposition of 5-Aminosalicylic Acid from 5-Aminosalicylic Acid-Delivering Drugs during Accelerated Intestinal Transit in Healthy Volunteers (1989)

In eight healthy volunteers accelerated intestinal transit time was induced with bisacodyl, and urinary and faecal excretion of sulphasalazine, olsalazine, 5-aminosalicylic acid (5-ASA), and acetyl-5-ASA was studied after a single oral dose of 3.3 mmol sulphasalazine, olsalazine, Pentasa, and Salofalk and 2.6 mmol of Asacol. The faecal and urinary excretion of acetyl-5-ASA was lowest after intake of sulphasalazine and olsalazine and highest after intake of Pentasa and Salofalk. The figures for Asacol were intermediate. This indicates insufficient release of 5-ASA from sulphasalazine and olsalazine. When the results of this study are compared with those of a previous study without accelerated transit time, the disposition of 5-ASA from all the 5-ASA-delivering drugs is influenced unfavourably by an accelerated gut transit but most pronounced in the case of sulphasalazine, olsalazine, and Asacol. The impaired release from the azo compounds sulphasalazine and olsalazine is a result of far less complete splitting of the diazo bond.
Folate receptor mediated DNA delivery into tumor cells: potosomal disruption results in enhanced gene expression. (1994)

We have used a particular folate receptor, which is overexpressed in tumor cells, for targeted DNA delivery into these cell types. This folate receptor internalizes folate through caveolae by a process named potocytosis, which is distinct from endocytosis, through clathrin-coated pits. When folate conjugated to poly-L-lysine was used to deliver the E. coli beta-galactosidase gene into tumor cells overexpressing the folate receptor, only low levels of beta-galactosidase activity were detectable. When a replication-defective adenovirus was coincubated with the DNA/folate complexes, 20 to 30% of the cells stained blue with X-gal and a 1000-fold increase of beta-galactosidase activity was observed. Thus, for high efficient DNA delivery and gene expression via the caveolae system, a potosomal disruption agent is needed. Furthermore, folate-mediated DNA delivery is restricted to tumor cells that highly overexpress the folate receptor, which will permit future development of tumor cell-specific delivery of toxic genes for cancer gene therapy.
Grafting Bimodal Polymer Brushes on Nanoparticles Using Controlled Radical Polymerization (2012)

RAFT (reversible addition–fragmentation chain transfer) polymerization has been widely used to synthesize different polymer architectures such as polymer brushes on nanoparticles for incorporation into polymer nanocomposites. It is believed that these polymer brushes, with the same chemistry as the matrix polymer, can be employed to improve filler dispersion by compatibilizing unfavorable enthalpic interactions between the inorganic nanoparticles and their organic host matrices. However, monomodal brush graft nanoparticles are found to aggregate into a range of isotropic and anisotropic morphologies, formed due to a delicate balance between enthalpic and entropic interfacial interactions. This coupling of enthalpy and entropy leaves only a small window of graft densities and molecular weights to obtain randomly dispersed filler morphologies. These issues can be countered by using a bimodal polymer brush that contains a small number of long homopolymer chains that can entangle, and a high density of short brushes that screens the particle/particle attraction, thereby aiding in decoupling the interfacial enthalpic and entropic interactions. In the present work, we demonstrate a robust step-by-step technique using RAFT polymerization to synthesize these bidisperse/bimodal polymer brush-anchored nanoparticles. A layer of dense brush of the first population was initially prepared using surface-initiated RAFT polymerization from colloidal silica nanoparticles. After cleavage of the chain transfer agent from the first population of chain ends, a second RAFT agent was attached onto the silica nanoparticles and then a monomer, which may be the same or different from the first brush, was polymerized. This versatile and widely applicable route enables us to independently control the molecular variables of the attached chains, such as composition, molecular weights and graft densities of the individual populations. The bimodal brush-grafted colloidal silica nanoparticles show superior dispersion and interaction with a homopolymer matrix when compared to monomodal brush-grafted particles.
PEI-g-chitosan, a Novel Gene Delivery System with Transfection Efficiency Comparable to Polyethylenimine in Vitro and after Liver Administration in Vivo (2005)

Polyethylenimine-graft-chitosan (PEI-g-chitosan) was synthesized by performing cationic polymerization of aziridine in the presence of water-soluble oligo-chitosan (M(n) = 3400). The absolute molecular weight and chemistry of the PEI-g-chitosan obtained were characterized using GPC, 13C and 1H NMR, respectively. The results indicated that all the amines of chitosan were grafted with oligo-PEI, and the average length of the oligo-PEI side chains was determined by the feed molar ratio of aziridne/amine in chitosan. PEI-g-chitosan of M(n) = 7400 with a polydispersity index (PDI) of 1.50, and PEI side chains of M(n) = 206 was prepared for gene delivery. Gel electrophoresis showed that DNA migration was retarded completely at a N/P ratio of 2.5/1, indicating good DNA condensation capability of PEI-g-chitosan. The sizes and the zeta-potentials of the complexes of PEI-g-chitosan/DNA were characterized. The cytotoxicity of PEI-g-chiotsan was evaluated, and the results reflected that PEI-g-chitosan had a lower cytotoxicity than PEI (25 K). Gene transfection efficiency of PEI-g-chitosan in HepG2, HeLa, and primary hepatocytes cells and after administration in the common bile duct of rat liver was determined. Remarkably, PEI-g-chitosan showed a higher transfection efficiency than that of PEI (25 K) both in vitro and in vivo. The systematic distribution and the distribution in liver of the gene expression of the complexes of PEI-chitosan/DNA were determined as well.
Kinetics and Thermodynamics of Hydrogen Oxidation and Oxygen Reduction in Hydrophobic Room-Temperature Ionic Liquids (2009)

In this study 1-dodecyl-3-methylimidazolium (C(12)mim) bis(pentafluoroethylsulfonyl)imide (BETI) and 1-dodecylimidazolium (C(12)im) BETI hydrophobic room-temperature ionic liquids (RTILs) were synthesized and used as proton-conducting electrolytes in a nonhumidified feed gas electrochemical cell. The ionic conductivities of C(12)mimBETI and C(12)imBETI were similar and increased linearly with an increase in temperature from 20 to 130°C. However, when used in the electrochemical system the protic water-equilibrated C(12)imBETI had a larger maximum current and power density compared to the aprotic water-equilibrated C(12)mimBETI. The effect of water content on the reaction rates and thermodynamics of these hydrophobic RTILs was also examined. The efficiency of the C(12)mimBETI increased upon removal of water while that of the C(12)imBETI decreased in efficiency when water was removed. The water structure in these RTILs was examined using attenuated total internal reflection Fourier transform IR spectroscopy and depended on the chemical structure of the cation. These studies give further insight into the possible mechanism of proton transport in these RTIL systems.
Glimpses of a Tiny RNA World (2001)

Naturally tiny regulatory RNAs of about 22 nucleotides were first identified from
 Caenorhabditis elegans genetics. Artificially induced RNAs of this size are also an intermediate in RNA interference, and both such RNAs use a common biochemical processing pathway. Now three groups have shown that there is an entire world of tiny RNAs that had almost escaped detection until now. These tiny RNAs are likely to regulate the translation of other mRNAs during development and, like the intermediates in RNAi, may be subject to amplification and systemic spread.
Detailed Analysis Concerning the Biodistribution and Metabolism of Human Calcitonin-Derived Cell-Penetrating Peptides (2008)

The interest in using small peptides for therapeutic and diagnostic in vivo applications is based on several advantageous features such as good penetration into tissues and rapid clearance from the body. Because of their size, they can easily be synthesized chemically. The recently discovered cell-penetrating peptides (CPP) and among them CPP derived from the native peptide hormone human calcitonin (hCT) could meet these requirements. Therefore, they are nowadays widely used as delivery vectors for a variety of bioactive molecules. However, the knowledge about the distribution and metabolism of CPP in vivo is very limited. Hence, evaluation of the pharmacological features of any promising peptide is a crucial challenge in its development process. Herein, we studied the in vivo radiopharmacology of (68)Ga radiolabeled DOTA-modified, hCT-derived CPP in rats using small animal PET. Furthermore, the arterial blood at different time points and urine were analyzed for radio-metabolites. It was shown that d-amino acid modifications of the sequence hCT(9-32) resulted in an increased in vivo stability and lower retention in the kidney cortex of this peptide.
Cognitive impairment and oxidative stress in the elderly: Results of epidemiological studies (2000)

Cognitive impairment is a major component of age-related dementing diseases and it has been suggested that it could share the same pathological pathways with neurodegenerative processes and cerebrovascular lesions. The free radical theory of ageing could be one of these pathways. Implication of free radical damage in processes related to cerebral ageing is a good argument in favour of the hypothesis that antioxidants may protect against cognitive impairment. Observational studies (mostly cross-sectional) of relationships between cognitive impairment and antioxidant status are based on the evaluation of dietary intake or on the levels of carotenoids, selenium and vitamins A, C and E in plasma or red blood cells. More convincing results were obtained on vitamin C and carotenoids. Despite some limitations, the comparison between results obtained in various populations is becoming increasingly informative and these studies argue for a protective effect of antioxidants on cognitive performance.
Lipid Peroxidation and Resistance to Oxidation in Patients with Type 2 Diabetes Mellitus (2004)

We investigated lipid peroxidation, resistance of plasma and red blood cells to oxidation, and antioxidant defense system in erythrocytes and sera in patients with type 2 diabetes mellitus. One group included newly diagnosed 20 patients and the other included 20 patients treated with oral antidiabetic agents (OAD). Twenty healthy subjects served as controls. Serum and red blood cell malondialdehyde (MDA), glutathione (GSH), resistance to oxidation, and plasma thiol (total -SH) levels were measured. In addition, glycated hemoglobin, serum fructosamine, uric acid, total protein, total cholesterol, triglyceride and glucose levels were determined. Although newly diagnosed patients had higher serum and erythrocyte MDA levels than those of controls, the highest levels of MDA were determined in patients treated with OAD. MDA levels after exposing to oxidation increased in OAD group more than in newly diagnosed patients. Total -SH and erythrocyte GSH levels of the both diabetic groups were lower than controls. These results show that serum and erythrocyte lipid peroxidation was increased in diabetic patients. The sera of the patients showed a decreased resistance against oxidation. We therefore suggest that the effect of increased free radicals may be prevented by antioxidant systems in early stages of type 2 diabetes but in advanced stages this relationship is impaired owing to decreased antioxidant activity. Decreased red blood cell GSH and serum total -SH levels may be due to a compensation mechanism of the antioxidants.
Profile of a mammalian sperm receptor1,2 (1990)

Complementary molecules on the surface of eggs and sperm are responsible for species-specific interactions between gametes during fertilization in both plants and animals. In this essay, several aspects of current research on the mouse egg receptor for sperm, a zona pellucida glycoprotein called ZP3, are addressed. These include the structure, synthesis, and functions of the sperm receptor during oogenesis and fertilization in mice. Several conclusions are drawn from available information. These include (I) ZP3 is a member of a unique class of glycoproteins found exclusively in the extracellular coat (zona pellucida) of mammalian eggs. (II) ZP3 gene expression is an example of oocyte-specific and, therefore, sex-specific gene expression during mammalian development. (III) ZP3 is a structural glycoprotein involved in assembly of the egg extracellular coat during mammalian oogenesis. (IV) ZP3 is a sperm receptor involved in carbohydrate-mediated gamete recognition and adhesion during mammalian fertilization. (V) ZP3 is an inducer of sperm exocytosis (acrosome reaction) during mammalian fertilization. (VI) ZP3 participates in the secondary block to polyspermy following fertilization in mammals. (VII) The extracellular coat of other mammalian eggs contains a glycoprotein that is functionally analogous to mouse ZP3. The unique nature, highly restricted expression, and multiple roles of ZP3 during mammalian development make this glycoprotein a particularly attractive subject for investigation at both the cellular and molecular levels.
High-Performance Liquid Chromatography of Pyridylamino Derivatives of Unsaturated Disaccharides Produced from Chondroitin Sulfate Isomers by Chondroitinases1 (1984)

A sensitive method was developed for the separation and quantitation of four unsaturated disaccharides (delta Di-0S, delta Di-4S, delta Di-6S, and delta Di-diS) by high performance liquid chromatography. The unsaturated disaccharides were coupled with a fluorescent compound, 2-aminopyridine. Complete separation of the resulting pyridylamino derivatives was achieved on a column of muBondapak-C18 with 8 mM KH2PO4-Na2HPO4 (pH 6.0)/methanol (30/l, by volume) as a mobile phase. There was a linear relationship between the fluorescence emission (peak height), and the amount of each authentic disaccharide used for the coupling reaction. This method was applied to analyze commercially available chondroitin sulfates A and C, dermatan sulfate, and urinary glycosaminoglycans obtained from patients with mucopolysaccharidosis after digestion with chondroitinases. The data indicated that the present method is useful for the separation and quantitation of nmol-pmol levels of the unsaturated disaccharides produced from chondroitin sulfate isomers by chondroitinases and can be used for their structural characterization.
Therapeutic Synergy Between Irinotecan and 5-Fluorouracil against Human Tumor Xenografts (2004)

The optimal therapeutic synergy was achieved when irinotecan was administered 24 h before 5-Flurouracil. Sensitivity to this combination was associated with poor differentiation status, higher cyclin A index, recruitment of cells into S phase, and induction of Bax expression and apoptosis.
The Jahn–Teller instability of fivefold degenerate states in icosahedral molecules (1990)

The linear H⊗(g⊕2h) Jahn–Teller problem, relevant to the instability of icosahedral molecules in fivefold degenerate states, is analyzed in detail for the first time. The method of the isostationary function is used to identify all the extrema of the corresponding potential energy surface. Depending on one single mode-splitting parameter, two different coupling regimes are possible, favoring either pentagonal or trigonal minima. The saddle points on interconversion paths between equivalent minima are identified and the topology of the low-energy regions of the surface is determined. The results are found to be in agreement with the epikernel principle. In addition the symmetry characteristics of the principal warping term under the SO(5) symmetry group of electronic space are assigned.
Neutralization of Circulating Vascular Endothelial Growth Factor (VEGF) by Anti-VEGF Antibodies and Soluble VEGF Receptor 1 (sFlt-1) Induces Proteinuria (2003)

There are about 2.5 million glomeruli in the kidneys each consisting of a barrel of glomerular basement membrane surrounded by glomerular endothelial cells on the inside and glomerular epithelial cells with established foot processes (podocytes) on the outside. Defects in this filtration apparatus lead to glomerular vascular leak or proteinuria. The role of vascular endothelial growth factor (VEGF) in the regulation of glomerular vascular permeability is still unclear. Recent studies indicate that patients receiving anti-VEGF antibody therapy may have an increased incidence of proteinuria. In a different setting, pregnancies complicated by preeclampsia are associated with elevated soluble VEGF receptor 1 protein (sFlt-1), endothelial cell dysfunction and proteinuria. These studies suggest that neutralization of physiologic levels of VEGF, a key endothelial survival factor, may lead to proteinuria. In the present study, we evaluated the potential of anti-VEGF neutralizing antibodies and sFlt-1 in the induction of proteinuria. Our studies demonstrate that anti-VEGF antibodies and sFlt-1 cause rapid glomerular endothelial cell detachment and hypertrophy, in association with down-regulation of nephrin, a key epithelial protein in the glomerular filtration apparatus. These studies suggest that down-regulation or neutralization of circulating VEGF may play an important role in the induction of proteinuria in various kidney diseases, some forms of cancer therapy and also in women with preeclampsia.
Theoretical investigations of novel nucleic acid bases (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTheoretical investigations of novel nucleic acid basesAndrew R. Leach and Peter A. KollmanCite this: J. Am. Chem. Soc. 1992, 114, 10, 3675–3683Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://doi.org/10.1021/ja00036a016RIGHTS & PERMISSIONSArticle Views118Altmetric-Citations34LEARN 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 InReddit PDF (1 MB) Get e-Alerts Get e-Alerts
Matrix vesicles in osteomalacic hypophosphatasia bone contain apatite-like mineral crystals. (1997)

Hypophosphatasia, a heritable disease characterized by deficient activity of the tissue nonspecific isoenzyme of alkaline phosphatase (TNSALP), results in rickets and osteomalacia. Although identification of TNSALP gene defects in hypophosphatasia establishes a role of ALP in skeletal mineralization, the precise function remains unclear. The initial site of mineralization (primary mineralization) normally occurs within the lumen of TNSALP-rich matrix vesicles (MVs) of growth cartilage, bone, and dentin. We investigated whether defective calcification in hypophosphatasia is due to a paucity and/or a functional failure of MVs secondary to TNSALP deficiency. Nondecalcified autopsy bone and growth plate cartilage from five patients with perinatal (lethal) hypophosphatasia were studied by nondecalcified light and electron microscopy to assess MV numbers, size, shape, and ultrastructure and whether hypophosphatasia MVs contain apatite-like mineral, as would be the case if these MVs retained their ability to concentrate calcium and phosphate internally despite a paucity of TNSALP in their investing membranes. We found that hypophosphatasia MVs are present in approximately normal numbers and distribution and that they are capable of initiating internal mineralization. There is retarded extravesicular crystal propagation. Thus, in hypophosphatasia the failure of bones to calcify appears to involve a block of the vectorial spread of mineral from initial nuclei within MVs, outwards, into the matrix. We conclude that hypophosphatasia MVs can concentrate calcium and phosphate internally despite a deficiency of TNSALP activity.
Imaging Modalities for Aortic Endografting (1997)

One of the most fundamental and influential differences between conventional surgery and endovascular grafting for aortic aneurysm is the central role of imaging in every aspect of management. This review summarizes five imaging techniques for aortic endografting: intravascular ultrasound, contrast angiography, conventional computed tomography (CT), spiral CT with image processing, and magnetic resonance angiography (MRA). External ultrasound and intravascular ultrasound have important relevance to endovascular aortic surgery. Artifacts of arteriography include magnification, thrombus effect, fore-shortening of tortuosity, loss of luminal detail, parallax error, and projection errors. Conventional CT scans have artifacts and difficulties also. Diameter measurement by CT suffers from methodology errors and observer variability. If conventional CT and angiography are used for endovascular aortic graft planning, both should be obtained since neither alone provides sufficient data. The use of spiral CT scanning and computerized image processing has clearly aided the preoperative definition of aneurysm morphology both in terms of dimensional accuracy and by adding diagnostic information. MRA is capable of producing three-dimensional images, axial sections, and longitudinal projections in any plane. It can detect blood flow without contrast medium, but gadolinium enhances MRA by avoiding the "signal dropout" artifact. Technology exists to provide new forms of imaging for endovascular surgery that combines three-dimensional models with on-line image data in a process called "data fusion." This may offer improved ease and accuracy for conducting endovascular procedures in the future.
Two-dimensional test data compression for scan-based deterministic BIST (2002)

A novel architecture for scan-based mixed mode BIST is presented. To reduce the storage requirements for the deterministic patterns it relies on a two-dimensional compression scheme, which combines the advantages of known vertical and horizontal compression techniques. To reduce both the number of patterns to be stored and the number of bits to be stored for each pattern, deterministic test cubes are encoded as seeds of an LFSR (horizontal compression), and the seeds are again compressed into seeds of a folding counter sequence (vertical compression). The proposed BIST architecture is fully compatible with standard scan design, simple and flexible, so that sharing between several logic cores is possible. Experimental results show that the proposed scheme requires less test data storage than previously published approaches providing the same flexibility and scan compatibility.