gebhart/patrepeval huggingface dataset:
Pharmacokinetics of tramadol and its three main metabolites in healthy male and female volunteers (2007)

By using a high-performance liquid chromatography method, the pharmacokinetics of the tramadol (T) and its three main metabolites, O-desmethyltramadol (M1), N-desmethyltramadol (M2) and O,N-didesmethyltramadol (M5) was studied in healthy male and female Iranian volunteers after oral administration of two 50 mg tramadol hydrochloride tablets. The related pharmacokinetic parameters such as C(max), T(max), AUC((0-t)), AUC((0-infinity)), T(1/2) and Cl/F were calculated and compared between the two genders. No significant differences were found in the systemic exposure and pharmacokinetic of tramadol, M1 and M2 while there were significant differences in AUCs of M5 in the two genders. It was concluded that to get a more accurate result, the gender dependency of T and its metabolites might be studied in specific phenotypes.
Approximate Pattern Matching Under Uncertainty in Geospatial Semantic Graphs. (2014)

Abstract not provided.
The application of DNA and RNA G-quadruplexes to therapeutic medicines (2011)

The intriguing structural diversity in folded topologies available to guanine-rich nucleic acid repeat sequences have made four-stranded G-quadruplex structures the focus of both basic and applied research, from cancer biology and novel therapeutics through to nanoelectronics. Distributed widely in the human genome as targets for regulating gene expression and chromosomal maintenance, they offer unique avenues for future cancer drug development. In particular, the recent advances in chemical and structural biology have enabled the construction of bespoke selective DNA based aptamers to be used as novel therapeutic agents and access to detailed structural models for structure based drug discovery. In this critical review, we will explore the important underlying characteristics of G-quadruplexes that make them functional, stable, and predictable nanoscaffolds. We will review the current structural database of folding topologies, molecular interfaces and novel interaction surfaces, with a consideration to their future exploitation in drug discovery, molecular biology, supermolecular assembly and aptamer design. In recent years the number of potential applications for G-quadruplex motifs has rapidly grown, so in this review we aim to explore the many future challenges and highlight where possible successes may lie. We will highlight the similarities and differences between DNA and RNA folded G-quadruplexes in terms of stability, distribution, and exploitability as small molecule targets. Finally, we will provide a detailed review of basic G-quadruplex geometry, experimental tools used, and a critical evaluation of the application of high-resolution structural biology and its ability to provide meaningful and valid models for future applications (255 references).
The Generation of Th Memory in Neonates Versus Adults: Prolonged Primary Th2 Effector Function and Impaired Development of Th1 Memory Effector Function in Murine Neonates (2001)

Immunization during the neonatal period often results in Th2-biased secondary responses. To understand the regulation of this phenomenon, we have examined all phases of Th development, from the generation of primary effectors to the duration of the primary effector stage to the production of memory effector function. First, we had previously reported that although primary responses in the neonatal lymph nodes are mature, mixed Th1/Th2-like, primary responses in the spleens of the same animals are exclusively Th2-like. To determine whether Th2-dominant secondary responses are due to the Th2-polarized primary function in the spleen, neonates were splenectomized before immunization. Even in the absence of primary neonatal splenic responses, the secondary responses of neonates were Th2 dominant. Thus, the overwhelmingly Th2 primary responses in the neonatal spleen are not required to generate Th2-dominant memory in the lymph nodes. Second, we have compared the kinetics of the primary response phase in neonates and adults. In adults, Ag-specific Th2 function disappeared rapidly from both the lymph nodes and spleen. In contrast, primary Th2 function persisted out to 5 wk in both neonatal organs. Third, the generation of Th memory responses was examined in animals initially immunized as neonates and in adults. These experiments demonstrated that neonates are selectively impaired in the development of Th1 memory effector function. Together, these results indicate that neonates are biased to Th2 function at all phases of an immune response.
The Endocannabinoid System: Drug Targets, Lead Compounds, and Potential Therapeutic Applications (2005)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTThe Endocannabinoid System: Drug Targets, Lead Compounds, and Potential Therapeutic ApplicationsDidier M. Lambert and Christopher J. FowlerView Author Information Unité de Chimie Pharmaceutique et de Radiopharmacie, Université Catholique de Louvain, Avenue Mounier, 73, UCL-CMFA 73.40, B-1200 Brussels, Belgium, and Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87 Umeå, Sweden Cite this: J. Med. Chem. 2005, 48, 16, 5059–5087Publication Date (Web):July 19, 2005Publication History Received31 January 2005Published online19 July 2005Published inissue 1 August 2005https://pubs.acs.org/doi/10.1021/jm058183thttps://doi.org/10.1021/jm058183treview-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views3823Altmetric-Citations279LEARN 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-Alertsclose SUBJECTS:Agonists,Inhibitors,Peptides and proteins,Receptors,Rodent models Get e-Alerts
Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. (1999)

GDNF exerts both histologic and functional neuroprotective effects on rod photoreceptors in the rd/rd mouse. Thus rescue was demonstrated in an animal model of inherited retinal degeneration in which the gene defect was located within the rods themselves, similar to most forms of human retinitis pigmentosa. GDNF represents a candidate neurotrophic factor for palliating some forms of hereditary human blindness.
Phase II Trial of Bevacizumab and Irinotecan in Recurrent Malignant Glioma (2007)

The combination of bevacizumab and irinotecan is an active regimen for recurrent grade III-IV glioma with acceptable toxicity.
Effect of DNA Complexation and Freeze-Drying on the Physicochemical Characteristics of Cationic Liposomes (2000)

We describe the use of saccharides, such as sorbitol, mannitol, sucrose, maltodextrin, and dextran, as cyoprotectants for freeze-drying cationic liposomes. Saccharides can protect liposomes either by interacting with phospholipid headgroups or by forming an amorphous glass surrounding the vesicles, thus preventing aggregation, mechanical rupture of membrane, fusion of liposomes, and drug leakage. We have particularly considered liposome characteristics, such as size, zeta potential, and ability in complexing DNA, before and after freeze-drying. Our study indicates that cationic liposomes are able to maintain liposome characteristics after lyophilization and rehydration and maintain the ability to complex DNA even if the strength of the interaction forces was of lower intensity with respect to liposomes before lyophilization.
Latent factor representations of dynamic networks with applications in cyber-security (2020)

Dynamic networks frequently arise in nature, representing, for example, neuronal connectivity in the brain, internet connections between computers, and human interactions within social networks. Motivated by specific characteristics of computer networks, this thesis gives novel contributions to three important branches of statistical analysis of dynamic graphs: modelling of connectivity events, graph clustering, and link prediction. Nodes and edges within the network will be assumed to have latent, unobserved characteristics, estimated using statistical latent factor models. The first part of this work proposes edge-based models for individual connection events. A model for dynamic network evolution based on the Pitman-Yor process is proposed, which is used for network-wide anomaly detection. Furthermore, a model for classification of periodic arrivals in event time data is proposed, to separate human and automated activity within individual edges. Correct classification of these two types of activity is fundamental for effective intrusion detection. In its second part, this work proposes novel methodologies for graph clustering. Finding nodes with similar connectivity patterns is important for reliable network monitoring. A model for simultaneous estimation of the latent dimension and number of communities in spectral clustering is proposed, under a generalised random dot product graph interpretation of the stochastic blockmodel. The model is then extended to allow for heterogeneous within-community degree distributions, proposing a novel spectral clustering algorithm under the degree corrected stochastic blockmodel. Finally, in the third part of this thesis, link prediction methods are discussed. The ability to correctly associate anomaly scores with the connections in a network is crucial for the cyber-defence of an organisation. In this work, it is demonstrated that random dot product graphs are a powerful and scalable tool for link prediction in large graph. Furthermore, an extension of the popular Poisson matrix factorisation model is proposed, which correctly models binary matrices and allows the effects of nodal covariates to be estimated. Scalable inferential techniques are also discussed. Overall, this work gives contributions towards a unified model for cyber-security applications, in a Bayesian framework, with the ultimate aim to dynamically predict the connectivity of IP addresses, or users and hosts, in a computer network.
Novel Electrochemical Studies of Ionic Liquids (2002)

Room-temperature ionic liquids (ILs) have been proposed as alternative solvents for organic synthesis, separations, and electrochemical applications. Here, we report studies that probe the electrochemical and solvation properties of a tetraalkylammonium (methyltributylammonium bis(trifluoromethylsulfon)imide, M3BNIm) and an imidazolium (1-butyl-3-methylimidazolium hexafluorophosphate, BMIPF6) based ionic liquid. It is demonstrated that despite impurities, the cathodic limit at a Pt electrode is enhanced for the tetraalkylammonium-based IL. Electrogenerated chemiluminescence of tris(2,2‘-bipyrindinyl)ruthenium (Ru(bpy)32+) was observed in both ionic liquids, and differences in the response were interpreted in terms of the solvent reactivity and polarity. As ILs have been proposed as alternatives to organic solvents in extraction processes, an understanding of the relative lipophilicity of the IL ions and the equilibrium potential difference established across the IL/water interface is of fundamental relevance. Here, electrochemical measurements at a conventionally polarized liquid−liquid interface (water/1,2-dichloroethane) were used to determine the relative lipophilicity of the IL constituent ions. From formal ion transfer potential values ( ) obtained, the standard ionic partition coefficients could be estimated. The polarizability of the neat ionic liquid/water interface was investigated. From these studies, it can be seen that BMIPF6 is hydrophilic while M3BNIm is moderately hydrophobic. The significance of the potential difference established across the IL/water interface is discussed.
Properties of extracellular superoxide dismutase from human lung (1984)

A further characterization of human extracellular superoxide dismutase is reported. The study was especially aimed at the interaction with substances known to interfere with CuZn superoxide dismutase and other superoxide dismutases. Extracellular superoxide dismutase is efficiently inhibited by cyanide and is about 3 times more sensitive than is human CuZn superoxide dismutase. The sensitivity to azide is much lower, but still about 3 times higher than that of human CuZn superoxide dismutase. Extracellular superoxide dismutase is about as rapidly inactivated by hydrogen peroxide as is CuZn superoxide dismutase. The sensitivity to diethyldithiocarbamate is very high and more than an order of magnitude larger than that of CuZn superoxide dismutase. Sodium dodecyl sulphate, under conditions suggested as being suitable for distinguishing between the insensitive CuZn superoxide dismutase and the sensitive Mn superoxide dismutase, efficiently inactivated extracellular superoxide dismutase. No antigenic similarities between extracellular superoxide dismutase and CuZn superoxide dismutase could be demonstrated. Anti-(extracellular superoxide dismutase) did not bind CuZn superoxide dismutase, and anti-(CuZn superoxide dismutase) did not bind extracellular superoxide dismutase.
A fluorescent metal sensor based on macrocyclic chelation (2001)

The ethylenediamine functionalized quinacridone derivatives 3a–c display an orange fluorescence (λem(max) = 558 nm) which is quenched upon addition of coordinating metal ions by formation of a macrocyclic chelate bringing metal ion and fluorophore in close proximity to one another.
Vascular Cell Components of the Medullary Arteries in Binswanger’s Disease Brains (2000)

The proliferation of collagen fibrils in the media and adventitia of the blood vessels in BD brains was not specific to small arteries and arterioles but also occurred in the pericapillary spaces. Pericapillary sclerosis, smooth muscle cell proliferation in the terminal arterioles, and their morphological transformation in the proximal arteries may alter the shear rates and thus cause profound microcirculatory disturbances in BD brains.
Cyclic Oligomers of Polycarbonates and Polyesters (2006)

Recent chemistry has been developed for the efficient preparation of oligomeric cyclic esters and carbonates. The current techniques have made it possible to prepare hundreds of kilograms of the cyclic oligomers per batch, and have made these materials available for study. Both methods of synthesis have been studied mechanistically. Purification to polymerization quality has been simply achieved in both cases, with selective reactions for removal of linear oligomers. The cyclic oligomers melt at 130–180°C (polyesters) or 180–200°C (polycarbonates), and have melt viscosities about 4 orders of magnitude lower than the parent high molecular weight polymers. Polymerization of the cyclic oligomers has been achieved with a variety of initiators, and using various techniques. Polymerization can be complete within minutes, and leads to very high molecular weight polyesters or polycarbonates without formation of byproducts, and with essentially no exotherm. The ring opening chemistry facilitates a variety of new copolymer reactions, and has made the fabrication of composite structures with very high fiber loadings possible.
Mechanical response of red blood cells entering a constriction (2014)

Most work on the dynamic response of red blood cells (RBCs) to hydrodynamic stress has focused on linear velocity profiles. Relatively little experimental work has examined how individual RBCs respond to pressure driven flow in more complex geometries, such as the flow at the entrance of a capillary. Here, we establish the mechanical behaviors of healthy RBCs undergoing a sudden increase in shear stress at the entrance of a narrow constriction. We pumped RBCs through a constriction in a microfluidic device and used high speed video to visualize and track the flow behavior of more than 4400 RBCs. We show that approximately 85% of RBCs undergo one of four distinct modes of motion: stretching, twisting, tumbling, or rolling. Intriguingly, a plurality of cells (∼30%) exhibited twisting (rotation around the major axis parallel to the flow direction), a mechanical behavior that is not typically observed in linear velocity profiles. We present detailed statistical analyses on the dynamics of each motion and demonstrate that the behavior is highly sensitive to the location of the RBC within the channel. We further demonstrate that the observed tumbling, twisting, and rolling rotations can be rationalized qualitatively in terms of rigid body mechanics. The detailed experimental statistics presented here should serve as a useful resource for modeling of RBC behavior under physiologically important flow conditions.
THE BRAIN LESION OF GOLDTHIOGLUCOSE OBESITY (1965)

The development of hypothalamic lesions due to goldthioglucose are described. The initial extensive necrotic lesion occurs in close to 100 per cent of animals injected with LD(50). Within 2 weeks the necrotic material has been removed and a narrow scar results. After a lapse of several months, the scar is often difficult to visualize, especially in animals that have not developed obesity. The ventromedial nucleus is not the center of the lesion. The nucleus is preserved in some instances, and partially or completely destroyed in others, depending on the extent of the lesion. The more prominent scar in the obese animals correlates with the larger initial lesion necessary for the complete bilateral destruction of the ventromedial nucleus which is known to be a prerequisite for the development of hypothalamic obesity. Thus, contrary to earlier suggestions, goldthioglucose does not localize specifically in the cells of the ventromedial nucleus.
Increased Numbers of CD4+ and CD8+ T Cells in Lesional Skin of Cats with Allergic Dermatitis (1998)

The aim of this study was to characterize T cells in the skin of cats with an allergic dermatitis histologically compatible with atopic dermatitis, since T cells play an important role in the pathogenesis of atopic dermatitis in humans. We observed a significantly greater number of T cells in lesional skin of domestic short-haired cats with allergic dermatitis (n = 10; median age 5.8 years) than in the skin of healthy control animals (n = 10; median age 5.0 years). In the skin of the healthy control animals, one or two CD4+ cells and no CD8+ cells were found. A predominant increase of CD4+ T cells and a CD4+/CD8+ ratio (mean +/- SD: 3.9 +/- 2.0) was found in the lesional skin of 10 cats with allergic dermatitis. The CD4+/CD8+ cell ratio in the skin of healthy control animals could not be determined because of the absence of CD8+ cells. The CD4+/CD8+ cell ratio in the peripheral blood of 10 cats with allergic dermatitis (mean +/- SD: 1.9 +/- 0.4) did not differ significantly from that in 10 healthy control animals (2.2 +/- 0.4). The CD4+/CD8+ cell ratio and predominance of CD4+ T cells in the lesional skin of cats with allergic dermatitis is comparable to that found in atopic dermatitis in humans. In addition, the observed increase of CD4+ T cells in the nonlesional skin of cats with allergic dermatitis compared to the skin of healthy cats is similar to what is seen in humans. Cytokines produced by T cells and antigen-specific T cells are important mediators in the inflammatory cascade resulting in atopic dermatitis in humans. This study is a first step to investigate their role in feline allergic dermatitis.
Organic–Inorganic Hybrid Scintillator for Neutron Detection Fabricated by Sol–Gel Method (2008)

Novel scintillating materials for neutron detection were fabricated by using the sol-gel method.The scintillating materials comprised borosilicate glass and poly(ethylene glycol) (PEG).The scintillation characteristics were examined under He irradiation, and it was found that the scintillation intensity increased with the concentration of PEG.It also increased linearly with the concentration of fluor 2-(4-tert-butylphenyl)-5-(4-biphenylyl)-1,3,4-oxadiazole (B-PBD).Furthermore, the scintillation intensity of the best sample was comparable to that of the commercially available plastic scintillator BC-454.It was shown that a fluor with larger solubility in the starting solution would further improve the scintillation property.
Identification and hypotensive activity of proadrenomedullin N‐terminal 20 peptide (PAMP) (1994)

Proadrenomedullin N-terminal 20 peptide (PAMP) is a candidate for a novel biologically active peptide processed from an adrenomedullin precursor. Using a radioimmunoassay for human PAMP, major and minor immunoreactive PAMPs were purified from porcine adrenal medulla and complete amino acid sequences were determined. The major immunoreactive peptide was PAMP itself with an amidated carboxy terminus. The minor one was determined to be PAMP[5-20]. An intravenous bolus injection of human PAMP in anesthetized rats caused a rapid and strong hypotensive effect in a dose dependent manner. The present data indicate that PAMP is an endogenous biologically active peptide which is processed from adrenomedullin precursor.
Isolation of targeted AAV2 vectors from novel virus display libraries (2006)

Random peptide ligands displayed on viral capsids are emerging tools for selection of targeted gene transfer vectors even without prior knowledge of the potential target cell receptor. We have previously introduced adeno-associated viral (AAV)-displayed peptide libraries that ensure encoding of displayed peptides by the packaged AAV genome. A major limitation of these libraries is their contamination with wild-type (wt) AAV. Here we describe a novel and improved library production system that reliably avoids generation of wt AAV by use of a synthetic cap gene. Selection of targeted AAV vectors from wt-containing and the novel wt-free libraries on cell types with different permissivity for wt AAV2 replication suggested the superiority of the wt-free library. However, from both libraries highly specific peptide sequence motifs were selected which improved transduction of cells with moderate or low permissivity for AAV2 replication. Strong reduction of HeLa cell transduction compared to wt AAV2 and only low level transduction of non-target cells by some selected clones showed that not only the efficiency but also the specificity of gene transfer was improved. In conclusion, our study validates and improves the unique potential of virus display libraries for the development of targeted gene transfer vectors.
Functionalized Derivatives of Hyaluronic Acid Oligosaccharides: Drug Carriers and Novel Biomaterials (1994)

Oligosaccharides derived from hyaluronic acid (HA), a naturally occurring linear polysaccharide composed of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid, can be chemically modified to introduce a pendant amine-like functionality (patent application pending). Covalent attachment of steroidal and nonsteroidal antiinflammatory drugs to functionalized HA oligosaccharides was accomplished with the incorporation of hydrolytically labile bonds. Further derivatization of the pendant group with homobifunctional crosslinkers allowed the introduction of covalent crosslinks. Chemically-modified HA oligosaccharides were unambiguously characterized in solution by high-resolution 1H NMR spectroscopy.