cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Synthesis and structure-activity relationships of pyridoxal-6-arylazo-5?-phosphate and phosphonate derivatives as P2 receptor antagonists
Creators: name: Kim, Heaok
name: Burnstock, Geoffrey
name: Rychkov, Alexei
name: Kim, Yong-Chul
name: Yoburn, Joshua
name: Jacobson, Kenneth A.
name: King, Brian F.
name: Camaioni, Emidio
name: Wildman, Scott S.
name: Ziganshin, Airat U.
name: Ji, Xiao-duo
name: Harden, T. Kendall
name: Boyer, Jos L.
name: Mohanram, Arvind
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 1998

description: Novel analogs of the P2 receptor antagonist pyridoxal-5′-phosphate-6-phenylazo-2′,4′-disulfonate (PPADS) were synthesized. Modifications were made through functional group substitution on the sulfophenyl ring and at the phosphate moiety through the inclusion of phosphonates, demonstrating that a phosphate linkage is not required for P2 receptor antagonism. Substituted 6-phenylazo and 6-naphthylazo derivatives were also evaluated. Among the 6-phenylazo derivatives, 5′-methyl, ethyl, propyl, vinyl, and allyl phosphonates were included. The compounds were tested as antagonists at turkey erythrocyte and guinea-pig taenia coli P2Y1 receptors, in guinea-pig vas deferens and bladder P2X1 receptors, and in ion flux experiments by using recombinant rat P2X2 receptors expressed in Xenopus oocytes. Competitive binding assay at human P2X1 receptors in differentiated HL-60 cell membranes was carried out by using [35S]ATP-γ-S. A 2′-chloro-5′-sulfo analog of PPADS (C14H12O9N3ClPSNa), a vinyl phosphonate derivative (C15H12O11N3PS2Na3), and a naphthylazo derivative (C18H14O12N3PS2Na2), were particularly potent in binding to human P2X1 receptors. The potencies of phosphate derivatives at P2Y1 receptors were generally similar to PPADS itself, except for the p-carboxyphenylazo phosphate derivative C15H13O8N3PNa and its m-chloro analog C15H12O8N3ClPNa, which were selective for P2X vs. P2Y1 receptors. C15H12O8N3ClPNa was very potent at rat P2X2 receptors with an IC50 value of 0.82 μM. Among the phosphonate derivatives, [4-formyl-3-hydroxy-2-methyl-6-(2-chloro-5-sulfonylphenylazo)-pyrid-5-yl]methylphosphonic acid (C14H12-O8N3ClPSNa) showed high potency at P2Y1 receptors with an IC50 of 7.23 μM. The corresponding 2,5-disulfonylphenyl derivative was nearly inactive at turkey erythrocyte P2Y1 receptors, whereas at recombinant P2X2 receptors had an IC50 value of 1.1 μM. An ethyl phosphonate derivative (C15H15O11N3PS2Na3), whereas inactive at turkey erythrocyte P2Y1 receptors, was particularly potent at recombinant P2X2 receptors.
DREADDs: novel tools for drug discovery and development
Creators: name: Roth, Bryan L.
name: Lee, Hyeong-Min
name: Giguere, Patrick M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Since the invention of the first designer receptors exclusively activated by designer drugs (DREADDs), these engineered G protein-coupled receptors (GPCRs) have been widely applied in investigations of biological processes and behaviors. DREADD technology has emerged as a powerful tool with great potential for drug discovery and development. DREADDs can facilitate the identification of druggable targets and enable researchers to explore the activities of novel drugs against both known and orphan GPCRs. Here, we discuss how DREADDs can be used as novel tools for drug discovery and development.
Rectifiable-Reifenberg and the Regularity of Stationary and Minimizing Harmonic Maps
Creators: name: Naber, Aaron
name: Valtorta, Daniele
Publisher: name: arXiv
Year: 2015
Subjects: subject: Differential Geometry (math.DG)
subject: Analysis of PDEs (math.AP)
subject: FOS: Mathematics

description: In this paper we study the regularity of stationary and minimizing harmonic maps $f:B_2(p)\subseteq M\to N$ between Riemannian manifolds. If $S^k(f)\equiv\{x\in M: \text{ no tangent map at $x$ is }k+1\text{-symmetric}\}$ is $k^{th}$-stratum of the singular set of $f$, then it is well known that $\dim S^k\leq k$, however little else about the structure of $S^k(f)$ is understood in any generality. Our first result is for a general stationary harmonic map, where we prove that $S^k(f)$ is $k$-rectifiable. In the case of minimizing harmonic maps we go further, and prove that the singular set $S(f)$, which is well known to satisfy $\dim S(f)\leq n-3$, is in fact $n-3$-rectifiable with uniformly {\it finite} $n-3$-measure. An effective version of this allows us to prove that $|\nabla f|$ has estimates in $L^3_{weak}$, an estimate which is sharp as $|\nabla f|$ may not live in $L^3$. The above results are in fact just applications of a new class of estimates we prove on the {\it quantitative} stratifications $S^k_{ε,r}(f)$ and $S^k_ε(f)\equiv S^k_{ε,0}(f)$. Roughly, $S^k_ε\subseteq M$ is the collection of points $x\in S^k_ε$ for which no ball $B_r(x)$ is $ε$-close to being $k+1$-symmetric. We show that $S^k_ε$ is $k$-rectifiable and satisfies the Minkowski estimate $Vol(B_r\,S_ε^k)\leq C r^{n-k}$. The proofs require a new $L^2$-subspace approximation theorem for stationary harmonic maps, as well as new $W^{1,p}$-Reifenberg and rectifiable-Reifenberg type theorems. These results are generalizations of the classical Reifenberg, and give checkable criteria to determine when a set is $k$-rectifiable with uniform measure estimates. The new Reifenberg type theorems may be of some independent interest.
description: Some more details added in the proofs
Issues with time--distance inversions for supergranular flows
Creators: name: Švanda, Michal
Publisher: name: arXiv
Year: 2015
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: Aims. Recent studies showed that time--distance inversions for flows start to be dominated by a random noise at a depth of only a few Mm. It was proposed that the ensemble averaging might be a solution to learn about the structure of the convective flows, e.g., about the depth structure of supergranulation. Methods. Time--distance inversion is applied to the statistical sample of ~$10^4$ supergranules, which allows to regularise weakly about the random-noise term of the inversion cost function and hence to have a much better localisation in space. We compare these inversions at four depths (1.9, 2.9, 4.3, and 6.2 Mm) when using different spatio-temporal filtering schemes in order to gain confidence about these inferences. Results. The flows inferred by using different spatio-temporal filtering schemes are different (even by the sign) even-though the formal averaging kernels and the random-noise levels are very similar. The inverted flows alterates its sign several times with depth. It is suggested that this is due to the inaccuracies in the forward problem that are possibly amplified by the inversion. It is possible that also other time--distance inversions are affected by this issue.
description: 8 pages, 5 figures, 2 tables, accepted for publication in Astronomy & Astrophysics
Interactive effect of silicon application and Azospirillum brasilense inoculation on wheat nutrient uptake and accumulation combined with N application rates
Creators: name: Galindo, Fernando Shintate
name: Pagliari, Paulo Humberto
name: Buzetti, Salatiér
name: Rodrigues, Willian Lima
name: Fernandes, Guilherme Carlos
name: Biagini, Antônio Leonardo Campos
name: Marega, Evelyn Maria Rocha
name: Jalal, Arshad
name: Filho, Marcelo Carvalho Minhoto Teixeira
Publisher: name: Taylor & Francis
Year: 2023
Subjects: subject: Microbiology
subject: FOS: Biological sciences
subject: Genetics
subject: Pharmacology
subject: Biotechnology
subject: Environmental Sciences not elsewhere classified
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: Biological Sciences not elsewhere classified
subject: Plant Biology
subject: Computational Biology

description: This study was developed to investigate the interactive effect of silicon (Si) application and the inoculation of plant growth promoting bacteria (PGPB) Azospirillum brasilense on wheat nutrient uptake and accumulation on biomass and grains when combined with nitrogen (N) application rates. The study was set up in a Rhodic Hapludox under no-till system, located in Selvíria, state of Mato Grosso do Sul, Brazil (tropical Savannah region). Treatments were tested in a randomized complete block design with four replicates, arranged in a full factorial design 2 × 2 × 5 and included: i) two soil amendment sources (Ca and Mg silicate as Si source and dolomitic limestone); ii) two seed inoculation (with and without A. brasilense) and iii) five N application rates applied as side-dress (0, 50, 100, 150 and 200 kg ha−1). Increasing N application rates positively influenced wheat nutrition with increased nutrient and Si uptake in shoot. Calcium and Mg silicate positively influenced wheat nutrition with greater shoot Si and grain N, P, K, B, Cu, Fe, Mn, Zn and Si uptake. In addition, Si was the third and sixth element most absorbed in wheat shoot and grain respectively. Inoculation with A. brasilense was found to increase nutrient uptake with greater shoot K and S and grain N, P, K, Mg, S, B, Cu, Mn, Zn and Si uptake. Azospirillum brasilense inoculation provided greater N uptake, with an increase of 5.8 and 8.9% on shoot and grain uptake.
title: Novel strategies for the detection of ragwort poisoning in horses
Creators: name: Elizabeth Moore, Rowan
Publisher: name: University of Liverpool Repository
Year: 2023

description: Toxic pyrrolizidine alkaloids (PAs) are produced by flowering plant species throughout the world, including ragwort (Senecio jacobea). In animals, PAs are metabolised within the liver to form their corresponding dehydro-PAs or pyrroles. These compounds are highly reactive and are capable of alkylating and cross-linking DNA and proteins to lead to characteristic molecular and cellular insult within the liver. There are presently no metllOds for tlle definitive diagnosis of ragwort poisoning in animals. If biomarkers for ragwort poisoning could be identified in dIe early stages of ingestion dlen the onset of irreversible patllology might be preventable. The goal of this study was to explore methods for the detection and analysis of pyrrole-peptide and pyrrole-protein adducts· in vitro and to investigate techniques facilitating the identification of changes in equine blood as a result of PA poisoning in Vivo. Initial experiments aimed to elucida~e dIe range of responses of model proteins to alh.'ylating agents ill tll/ro. Intact mass analysis of dIe proteins by l-dimensional gel electrophoresis (lD-GE) and quadtupole-time-of-flight mass spectrometry (Q-ToF MS) demonstrated that different reagents are capable of distinctly modifying proteins, and that these reagents have varying degrees of specificity for dIe sulphydryl group of cysteine residues. Matri.x-assisted laser desorption/ionisation (MALDI)-ToF MS revealed the particular regions of proteins which were targeted by reagents and demonstrated that peptide adduct detection could be enhanced by guanidination of lysine-terminated peptides.
Metrics with Prescribed Ricci Curvature on Homogeneous Spaces
Creators: name: Pulemotov, Artem
Publisher: name: arXiv
Year: 2015
Subjects: subject: Differential Geometry (math.DG)
subject: Analysis of PDEs (math.AP)
subject: FOS: Mathematics

description: Let $G$ be a compact connected Lie group and $H$ a closed subgroup of $G$. Suppose the homogeneous space $G/H$ is effective and has dimension 3 or higher. Consider a $G$-invariant, symmetric, positive-semidefinite, nonzero (0,2)-tensor field $T$ on $G/H$. Assume that $H$ is a maximal connected Lie subgroup of $G$. We prove the existence of a $G$-invariant Riemannian metric $g$ and a positive number $c$ such that the Ricci curvature of $g$ coincides with $cT$ on $G/H$. Afterwards, we examine what happens when the maximality hypothesis fails to hold.
description: 11 pages
Kinematics of classical Cepheids in the Nuclear Stellar Disk
Creators: name: Matsunaga, N.
name: Fukue, K.
name: Yamamoto, R.
name: Kobayashi, N.
name: Inno, L.
name: Genovali, K.
name: Bono, G.
name: Baba, J.
name: Fujii, M. S.
name: Kondo, S.
name: Ikeda, Y.
name: Hamano, S.
name: Nishiyama, S.
name: Nagata, T.
name: Aoki, W.
name: Tsujimoto, T.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: Classical Cepheids are useful tracers of the Galactic young stellar population because their distances and ages can be determined from their period-luminosity and period-age relations. In addition, the radial velocities and chemical abundance of the Cepheids can be derived from spectroscopic observations, providing further insights into the structure and evolution of the Galaxy. Here, we report the radial velocities of classical Cepheids near the Galactic Center, three of which were reported in 2011, the other reported for the first time. The velocities of these Cepheids suggest that the stars orbit within the Nuclear Stellar Disk, a group of stars and interstellar matter occupying a region of 200 pc around the Center, although the three-dimensional velocities cannot be determined until the proper motions are known. According to our simulation, these four Cepheids formed within the Nuclear Stellar Disk like younger stars and stellar clusters therein.
description: Accepted for publication in ApJ; 8 pages, 7 figures, 6 tables
Eventual quasi-linearity of the Minkowski length
Creators: name: Soprunov, Ivan
name: Soprunova, Jenya
Publisher: name: arXiv
Year: 2014
Subjects: subject: Combinatorics (math.CO)
subject: Metric Geometry (math.MG)
subject: FOS: Mathematics
subject: 52B20

description: The Minkowski length of a lattice polytope $P$ is a natural generalization of the lattice diameter of $P$. It can be defined as the largest number of lattice segments whose Minkowski sum is contained in $P$. The famous Ehrhart theorem states that the number of lattice points in the positive integer dilates $tP$ of a lattice polytope $P$ behaves polynomially in $t\in\mathbb{N}$. In this paper we prove that for any lattice polytope $P$, the Minkowski length of $tP$ for $t\in\mathbb{N}$ is eventually a quasi-polynomial with linear constituents. We also give a formula for the Minkowski length of coordinates boxes, degree one polytopes, and dilates of unimodular simplices. In addition, we give a new bound for the Minkowski length of lattice polygons and show that the Minkowski length of a lattice triangle coincides with its lattice diameter.
description: 13 pages, 1 figure; minor corrections, to appear in European Journal of Combinatorics
title: The myco sterols of yeast
Creators: name: Brundrit, Dennis
Publisher: name: University of Liverpool Repository
Year: 2023

description: The naturally occurring secondary alcohols, known as the sterols, are classified biologically as zoosterols, phytosterols, and mycosterols, according to the source, animal, vegetable, or fungoid, from which they are obtained. The discovery that irradiation with short wave-length ultra-violet light confers powerful anti-rachitic properties on ergosterol, the principal member of the mycosterol sub-division, has given a great. impetus to the study of these compounds and of their derivatives. Mycosterols are mainly derived from the non-saponifiable matter in the fats of yeast and of ergot of rye, both of which contain complex mixtures of the individuals of this group. The separation of these mixtures has frequently been, attempted. and the isolation of many new sterols has been claimed, but the views of the various investigators are in such conflict that an independent and complete examination has become necessary.
Coulomb bound states and resonances due to groups of Ca dimers adsorbed on suspended graphene
Creators: name: Saffarzadeh, Alireza
name: Kirczenow, George
Publisher: name: arXiv
Year: 2015
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: The electronic bound states and resonances in the vicinity of the Dirac point energy due to the adsorption of calcium dimers on a suspended graphene monolayer are explored theoretically using density functional theory (DFT) and an improved extended Hückel model that includes electrostatic potentials. The Mulliken atomic charges and the electrostatic potentials are obtained from DFT calculations and reveal charge transfer from the Ca dimers to the graphene which is responsible for the emergence of resonant states in the electronic spectrum. The number of resonant states increases as the number of adsorbed dimers is increased. We find a bound "atomic-collapse" state in the graphene local density of states, as has been observed experimentally [Wang \textit{et al.}, Science {\bf 340}, 734 (2013)]. We find the formation of the atomic-collapse state and its population with electrons to require fewer adsorbed Ca dimers than in the experiment, possibly due to the different spacing between dimers and the dielectric screening by a boron nitride substrate in the experiment. We also predict the onset of filling of a second atomic-collapse state with electrons when six Ca dimers are adsorbed on the suspended graphene monolayer. Experiments testing these predictions would be of interest.
description: 9 pages, 6 figures
Atractides (Atractides) talinarostris Cook 1967
Creators: name: Pešić, Vladimir
name: Chatterjee, Tapas
name: Bordoloi, Sabitry
Publisher: name: Zenodo
Year: 2010
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Arachnida
Trombidiformes
Hygrobatidae
Atractides
Atractides talinarostris

description: Atractides (Atractides) talinarostris Cook, 1967
Records from the study area: Maharashtra—Cook (1967); Prasad (1974); Pešić & Ranga Reddy (2009).
Habitat: Interstitial of streams; probably hyporheophilous.
Distribution: India.
description: Published as part of Pešić, Vladimir, Chatterjee, Tapas & Bordoloi, Sabitry, 2010, A checklist of the water mites (Acari: Hydrachnidia) of India, with new records and description of one new species, pp. 1-54 in Zootaxa 2617 (1) on page 26, DOI: 10.11646/zootaxa.2617.1.1, http://zenodo.org/record/197964
title: Indirect methods of obtaining activity and mobility of structure-borne sound sources
Creators: name: Höller, Christoph
Publisher: name: University of Liverpool Repository
Year: 2014

description: The work reported in this thesis focuses on the development of indirect methods for the experimental determination of important source parameters for structure-borne sound source characterization. In the first part of the thesis, matrix inversion methods for the determination of blocked forces are investigated. A simplified measurement procedure is proposed which offers a solution to the two major challenges to these methods, namely the acquisition of the FRF matrix and the problems associated with matrix inversion. The proposed procedure involves a free, low-mobility receiver plate which is modelled numerically. Calculated FRFs are used together with measured velocity responses to inversely determine the blocked forces. It is found that while the method has great potential in principle, in practice the accurate modelling of the receiver plate is of critical importance. In the second part of the thesis, three formulations are considered for the indirect determination of source mobility. Instead of performing measurements on the source in the free state, the source mobility is obtained from measurements made in-situ. This approach is beneficial if the source is difficult to suspend, or if it contains non-linear structural elements. The three formulations are validated numerically and experimentally. It is found that the methods can quantify source mobilities of single-contact and multi-contact sources from in-situ measurements. However, typical measurement errors, such as background noise or inaccuracies in sensor positioning, can significantly reduce the accuracy and reliability of the methods. In the final part of the thesis, the reception plate method for the determination of the power injected by a high-mobility source into a low-mobility receiver is reviewed, and a source substitution method proposed as a development. The substitution method circumvents problems that may arise when the reception plate method is applied to coupled walls and floors. A special focus of investigation is on the calibration of the receiver structure. It is found that the calibration can be performed with shaker or hammer, and that an average calibration factor may be used. The source substitution method thus offers a potential alternative to the reception plate method, for application with coupled plates.
Expanding the scope of drug repurposing in pediatrics: The Children's Pharmacy Collaborative™
Creators: name: Muratov, Eugene
name: Janzen, William P.
name: Fourches, Denis
name: Sarrimanolis, Zafeira
name: Corey, Seth J.
name: Farag, Sherif
name: Blatt, Julie
name: Tropsha, Alexander
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2014

description: Drug repurposing is the use of “old” drugs for new indications, avoiding the need for time- and cost-intensive toxicity studies. This approach should be particularly attractive for pediatrics, but its use in this population has been limited. One obstacle has been the lack of a comprehensive database of drugs for which there already is at least one indication in children. We describe the development of The Children’s Pharmacy Collaborative™, which should grow over time, serve as a resource for professionals and families, and stimulate drug repurposing efforts for a range of pediatric disorders.
Atractides (Atractides) vayitriensis Cook 1967
Creators: name: Pešić, Vladimir
name: Chatterjee, Tapas
name: Bordoloi, Sabitry
Publisher: name: Zenodo
Year: 2010
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Arachnida
Trombidiformes
Hygrobatidae
Atractides
Atractides vayitriensis

description: Atractides (Atractides) vayitriensis Cook, 1967
Records from the study area: Kerala—Cook (1967); Prasad (1974).
Habitat: Mountain streams.
Distribution: India.
description: Published as part of Pešić, Vladimir, Chatterjee, Tapas & Bordoloi, Sabitry, 2010, A checklist of the water mites (Acari: Hydrachnidia) of India, with new records and description of one new species, pp. 1-54 in Zootaxa 2617 (1) on page 26, DOI: 10.11646/zootaxa.2617.1.1, http://zenodo.org/record/197964
CYP4F Enzymes Are the Major Enzymes in Human Liver Microsomes That Catalyze the O-Demethylation of the Antiparasitic Prodrug DB289 [2,5-Bis(4-amidinophenyl)furan-bis-O-methylamidoxime]
Creators: name: Saulter, J. Y.
name: Bridges, A. S.
name: Parkinson, O. T.
name: Zeldin, D. C.
name: Hall, J. E.
name: Hall, M.
name: Paine, M. F.
name: Wang, M. Z.
name: Cheung, Y.-L.
name: Boykin, D. W.
name: Tidwell, R. R.
name: Usuki, E.
name: Allen, J. L.
name: Parkinson, A.
name: Loewen, G.
name: Stephens, C. E.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2006

description: DB289 [2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime] is biotransformed to the potent antiparasitic diamidine DB75 [2,5-bis(4-amidinophenyl) furan] by sequential oxidative O-demethylation and reductive N-dehydroxylation reactions. Previous work demonstrated that the N-dehydroxylation reactions are catalyzed by cytochrome b5/NADH-cytochrome b5 reductase. Enzymes responsible for catalyzing the DB289 O-demethylation pathway have not been identified. We report an in vitro metabolism study to characterize enzymes in human liver microsomes (HLMs) that catalyze the initial O-demethylation of DB289 (M1 formation). Potent inhibition by 1-aminobenzotriazole confirmed that M1 formation is catalyzed by P450 enzymes. M1 formation by HLMs was NADPH-dependent, with a Km and Vmax of 0.5 μM and 3.8 nmol/min/mg protein, respectively. Initial screening showed that recombinant CYP1A1, CYP1A2, and CYP1B1 were efficient catalysts of M1 formation. However, none of these three enzymes was responsible for M1 formation by HLMs. Further screening showed that recombinant CYP2J2, CYP4F2, and CYP4F3B could also catalyze M1 formation. An antibody against CYP4F2, which inhibited both CYP4F2 and CYP4F3B, inhibited 91% of M1 formation by HLMs. Two inhibitors of P450-mediated arachidonic acid metabolism, HET0016 (N-hydroxy-N′-(4-n-butyl-2-methylphenyl)formamidine) and 17-octadecynoic acid, effectively inhibited M1 formation by HLMs. Inhibition studies with ebastine and antibodies against CYP2J2 suggested that CYP2J2 was not involved in M1 formation by HLMs. Additionally, ketoconazole preferentially inhibited CYP4F2, but not CYP4F3B, and partially inhibited M1 formation by HLMs. We conclude that CYP4F enzymes (e.g., CYP4F2, CYP4F3B) are the major enzymes responsible for M1 formation by HLMs. These findings indicate that, in human liver, members of the CYP4F subfamily biotransform not only endogenous compounds but also xenobiotics.
Human Enteric Microsomal CYP4F Enzymes O-Demethylate the Antiparasitic Prodrug Pafuramidine
Creators: name: Hall, J. E.
name: Tidwell, R. R.
name: Zeldin, D. C.
name: Wu, J. Q.
name: Paine, M. F.
name: Wang, M. Z.
name: Bridges, A. S.
name: Kornbluth, S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: CYP4F enzymes, including CYP4F2 and CYP4F3B, were recently shown to be the major enzymes catalyzing the initial oxidative O-demethylation of the antiparasitic prodrug pafuramidine (DB289) by human liver microsomes. As suggested by a low oral bioavailability, DB289 could undergo first-pass biotransformation in the intestine, as well as in the liver. Using human intestinal microsomes (HIM), we characterized the enteric enzymes that catalyze the initial O-demethylation of DB289 to the intermediate metabolite, M1. M1 formation in HIM was catalyzed by cytochrome P450 (P450) enzymes, as evidenced by potent inhibition by 1-aminoben-zotriazole and the requirement for NADPH. Apparent Km and Vmax values ranged from 0.6 to 2.4 μM and from 0.02 to 0.89 nmol/min/mg protein, respectively (n = 9). Of the P450 chemical inhibitors evaluated, ketoconazole was the most potent, inhibiting M1 formation by 66%. Two inhibitors of P450-mediated arachidonic acid metabolism, HET0016 (N-hydroxy-N′-(4-n-butyl-2-methylphenyl)formamidine) and 17-octadecynoic acid, inhibited M1 formation in a concentration-dependent manner (up to 95%). Immunoinhibition with an antibody raised against CYP4F2 showed concentration-dependent inhibition of M1 formation (up to 92%), whereas antibodies against CYP3A4/5 and CYP2J2 had negligible to modest effects. M1 formation rates correlated strongly with arachidonic acid ω-hydroxylation rates (r2 = 0.94, P < 0.0001, n = 12) in a panel of HIM that lacked detectable CYP4A11 protein expression. Quantitative Western blot analysis revealed appreciable CYP4F expression in these HIM, with a mean (range) of 7 (3–18) pmol/mg protein. We conclude that enteric CYP4F enzymes could play a role in the first-pass biotransformation of DB289 and other xenobiotics.
Human Health in Space Travel: Limitations and Opportunities
Creators: name: Tang, Bill
Publisher: name: The University of Texas at Austin
Year: 2022
Subjects: spaceflight
aerospace medicine
space biology
oxidative stress
DNA damage
galactic cosmic ray

description: Space travel presents unique environmental challenges that enact molecular, cellular, and physiological changes across many regions within the human body. Specifically, the high energy and variable mass of the particles from space radiation present new and unexplored consequences in which astronauts will be at greater risk of deleterious health effects beyond Earth's protective magnetosphere. Longer missions beyond low Earth orbit will result in greater doses of space radiation, increasing the risk of developing degenerative tissue diseases from the accumulation of genetic mutations and high oxidative stress. This thesis maps the findings of space-related biological research on humans and animals exposed to spaceflight effects –to present the risks associated with spaceflight, health responses to these risks, and the mitigative strategies that can be applied to counteract deleterious health effects and ensure successful spaceflight missions in the future.
Monotonic Abstraction Techniques: from Parametric to Software Model Checking
Creators: name: Alberti, Francesco
name: Ghilardi, Silvio
name: Sharygina, Natasha
Publisher: name: arXiv
Year: 2014
Subjects: subject: Logic in Computer Science (cs.LO)
subject: Software Engineering (cs.SE)
subject: FOS: Computer and information sciences

description: Monotonic abstraction is a technique introduced in model checking parameterized distributed systems in order to cope with transitions containing global conditions within guards. The technique has been re-interpreted in a declarative setting in previous papers of ours and applied to the verification of fault tolerant systems under the so-called "stopping failures" model. The declarative reinterpretation consists in logical techniques (quantifier relativizations and, especially, quantifier instantiations) making sense in a broader context. In fact, we recently showed that such techniques can over-approximate array accelerations, so that they can be employed as a meaningful (and practically effective) component of CEGAR loops in software model checking too.
description: In Proceedings MOD* 2014, arXiv:1411.3453
Unmasking Problems in Rural Health Planning
Creators: name: Fitzwilliams, Jeannette
name: Fitzwilliams, Jeannette
Publisher: name: Unknown
Year: 1979
Subjects: subject: Community/Rural/Urban Development
subject: Health Economics and Policy
subject: Public Economics
subject: Research Methods/ Statistical Methods
subject: rural health regions
subject: rural health funding
subject: rural health data

description: Separating regional health statistics into smaller geographic segments will help local planning agencies identify and deal with health needs of rural people. National and regional averages for key health planning variables mask rural problems because these variables differ widely within and among regions. Further, health service areas (HSAs) are more rural than the national average would indicate. Better health care planning and delivery require the following adjustments: (1) use of disaggregated data, (2) flexibility in regulations, (3) adjustment of funding formulas, (4) establishment of subarea councils, (5) identification of major HSA rural types, and (6) improvement of data for small rural areas.
Atractides (Atractides) yukii Cook 1967
Creators: name: Pešić, Vladimir
name: Chatterjee, Tapas
name: Bordoloi, Sabitry
Publisher: name: Zenodo
Year: 2010
Subjects: Biodiversity
Taxonomy
Animalia
Arthropoda
Arachnida
Trombidiformes
Hygrobatidae
Atractides
Atractides yukii

description: Atractides (Atractides) yukii Cook, 1967
Records from the study area: Maharashtra—Cook (1967); Prasad (1974); Pešić & Ranga Reddy (2009); Uttaranchal—Kumar & Dobriyal (1992).
Habitat: Streams; probably hyporheophilous.
Distribution: India, Nepal.
description: Published as part of Pešić, Vladimir, Chatterjee, Tapas & Bordoloi, Sabitry, 2010, A checklist of the water mites (Acari: Hydrachnidia) of India, with new records and description of one new species, pp. 1-54 in Zootaxa 2617 (1) on page 26, DOI: 10.11646/zootaxa.2617.1.1, http://zenodo.org/record/197964
Soliton models for thick branes
Creators: name: Peyravi, Marzieh
name: Riazi, Nematollah
name: Lobo, Francisco S. N.
Publisher: name: arXiv
Year: 2015
Subjects: subject: General Relativity and Quantum Cosmology (gr-qc)
subject: High Energy Physics - Phenomenology (hep-ph)
subject: High Energy Physics - Theory (hep-th)
subject: FOS: Physical sciences

description: In this work, we present new soliton solutions for thick branes in $4+1$ dimensions. In particular, we consider brane models based on the sine-Gordon ($SG$), $φ^{4}$ and $φ^{6}$ scalar fields, which have broken $Z_{2}$ symmetry in some cases, and are responsible for supporting and stabilizing the thick branes. The origin of the symmetry breaking in these models resides in the fact that the modified scalar field potential may have non-degenerate vacuua. These vacuua determine the cosmological constant on both sides of the brane. We also study the geodesic equations along the fifth dimension, in order to explore the particle motion in the neighbourhood of the brane. Furthermore, we examine the stability of the thick branes, by determining the sign of the $w^2$ term in the expansion of the potential for the resulting Schrodinger-like equation, where $w$ is the 5-dimensional coordinate. It turns out that the $φ^4$ brane is stable, while there are unstable modes for certain ranges of the model parameters in the SG and $φ^6$ branes.
description: 15 pages, 9 figures. V2: 18 pages; discussion on the brane stability and references added. Accepted for publication in the European Physical Journal C
title: Parkour and the city: the role of human mobility in place-making
Creators: name: Otchie, Michael
Publisher: name: University of Liverpool Repository
Year: 2014

description: The intention of this thesis is to frame the emerging discipline of parkour into the context of architectural research. The thesis takes into consideration a range of research methods including interviews, literature and film reviews, and filmmaking exercises. The subject of the documentary films produced for this study, are a series of tours of the city of Liverpool that are carried out by practitioners of parkour, so-called traceurs, and university architecture students. By using these tours of Liverpool as case studies, the research project provides a novel approach to understanding the multi-sensory qualities of urban spaces, and builds upon practices found within the emerging field of sensory-ethnography. These tours are used as a means to gather qualitative data that extends beyond verbal responses, as physical interactions between individuals and their surroundings are documented and analysed. The use of filmmaking techniques within this piece of research allows for it to build upon pre-existing practices found within the culture associated with parkour. By examining video filmmaking as a tool for documenting the relationship between traceurs and city spaces, this research study makes reference to the growth of the parkour movement via Internet based social networks and the proliferation of digital videos. The thesis concludes with a novel approach for understanding traceurs as an architectural figure, akin to the concept of the flâneur, which has significance for the interrogating multiple layers of meaning within contemporary urban space. The study also provides support for critically examining the development of subject knowledge and epistemological knowledge in relation to architecture and the body.
title: The relationship between formulaic sequences and EFL reading comprehension
Creators: name: Babaee Khou, Moloud
Publisher: name: University of Liverpool Repository
Year: 2023

description: The main focus of this study was to investigate the relationship between recognition and understanding of formulaic sequences (FSs) and L2 reading comprehension. It also sought to find out whether the interaction between recognition and understanding of these sequences affects reading comprehension. In addition, six secondary hypotheses were examined. They investigated the relationships between recognition and understanding of formulaic sequences and the frequency of occurrence of the target sequences in the BNC and the subjects' overall English proficiency and their sex.
Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in Freshly Isolated Rat Hepatocytes
Creators: name: Perry, J. L.
name: Bow, D. A. J.
name: Brouwer, K. L. R.
name: Miller, D. S.
name: Pritchard, J. B.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Freshly isolated hepatocytes are widely accepted as the “gold standard” for providing reliable data on drug uptake across the sinusoidal (basolateral) membrane. However, the suitability of freshly isolated hepatocytes in suspension to assess efflux by canalicular (apical) proteins or predict biliary excretion in the intact organ is unclear. After collagenase digestion, hepatocytes rapidly lose polarity, but localization of canalicular transport proteins in the first few hours after isolation has not been well characterized. In this study, immunostaining and confocal microscopy have provided, for the first time, a detailed examination of canalicular transport protein localization in freshly isolated rat hepatocytes fixed within 1 h of isolation and in cells cultured for 1 h. Organic anion transporting polypeptide 1a1 (Oatp1a1) was expressed in all hepatocytes and distributed evenly across the basolateral membrane; there was no evidence for colocalization of Oatp1a1 with P-glycoprotein (P-gp) or multidrug resistance-associated protein 2 (Mrp2). In contrast, P-gp and Mrp2 expression was lower than Oatp1a1 and confined to junctions between adjacent cells, intracellular compartments, and “legacy” network structures at or near the cell surface. P-gp and Mrp2 staining was more predominant in regions adjacent to former canalicular spaces, identified by zonula occludens-1 staining. Functional analysis of rat hepatocytes cultured for 1 h demonstrated that the fluorescent anion and Mrp2 substrate, 5-(and-6)-carboxy-2′,7′-dichlorofluorescein (CDF), accumulated in cellular compartments; compartmental accumulation of CDF was sensitive to (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-[[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK571, Mrp inhibitor) and was not observed in hepatocytes isolated from Mrp2-deficient rats. Drug efflux from freshly isolated hepatocytes as an estimate of apical efflux/biliary excretion would give an inaccurate assessment of true apical elimination and, as such, should not be used to make in vivo extrapolations.
Bayesian leave-one-out cross-validation approximations for Gaussian latent variable models
Creators: name: Vehtari, Aki
name: Mononen, Tommi
name: Tolvanen, Ville
name: Sivula, Tuomas
name: Winther, Ole
Publisher: name: arXiv
Year: 2014
Subjects: subject: Computation (stat.CO)
subject: Machine Learning (stat.ML)
subject: FOS: Computer and information sciences

description: The future predictive performance of a Bayesian model can be estimated using Bayesian cross-validation. In this article, we consider Gaussian latent variable models where the integration over the latent values is approximated using the Laplace method or expectation propagation (EP). We study the properties of several Bayesian leave-one-out (LOO) cross-validation approximations that in most cases can be computed with a small additional cost after forming the posterior approximation given the full data. Our main objective is to assess the accuracy of the approximative LOO cross-validation estimators. That is, for each method (Laplace and EP) we compare the approximate fast computation with the exact brute force LOO computation. Secondarily, we evaluate the accuracy of the Laplace and EP approximations themselves against a ground truth established through extensive Markov chain Monte Carlo simulation. Our empirical results show that the approach based upon a Gaussian approximation to the LOO marginal distribution (the so-called cavity distribution) gives the most accurate and reliable results among the fast methods.
Multidrug Resistance-Associated Protein 2 Is Primarily Responsible for the Biliary Excretion of Fexofenadine in Mice
Creators: name: Bridges, A. S.
name: Patel, N. J.
name: Zamek-Gliszczynski, M. J.
name: Tian, X.
name: Raub, T. J.
name: Li, J.
name: Nezasa, K.-i.
name: Brouwer, K. L. R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: Previous studies implicated P-glycoprotein (P-gp) as the major transport protein responsible for the biliary excretion of fexofenadine (FEX). However, FEX biliary excretion was not impaired in P-gp- or Bcrp-knockout mice, and Mrp2-deficient rats. The present study tested the hypothesis that species differences exist in the transport protein primarily responsible for FEX biliary excretion between mice and rats. Livers from Mrp2-knockout (Mrp2KO) mice and Mrp2-deficient (TR−) rats were perfused in a single-pass manner with 0.5 μM FEX. GF120918 (10 μM) was employed to inhibit P-gp and Bcrp. The biliary excretion rate of FEX was decreased 85% in Mrp2KO relative to wild-type mice (18.4 ± 2.2 vs. 122 ± 34 pmol/min/g liver). In mice, more than 50% of FEX unbound intrinsic biliary clearance (CLbile, int = 3.0 ml/hr/g liver) could be attributed to Mrp2 (Mrp2-dependent CLbile, int ~ 1.7 ml/hr/g liver), with P-gp and Bcrp playing a minor role (P-gp- and Bcrp-dependent CLbile, int ~ 0.3 ml/hr/g liver). Approximately one-third of FEX CLbile, int was attributed to unidentified mechanisms in mice. In contrast to mice, FEX biliary excretion rate (245 ± 38 and 250 ± 25 pmol/min/g liver) and CLbile, int (9.72 ± 2.5 and 6.49 ± 0.68 ml/hr/g liver) were comparable between Mrp2-deficient (TR−) and control Wistar rats, respectively, suggesting that unidentified transport mechanism(s) can completely compensate for the loss of Mrp2 function in rats. Mrp2 clearly plays a major role in FEX biliary excretion in mice. In conclusion, remarkable species differences exist in FEX hepatobiliary transport mechanisms.
The First Aspartic Acid of the DQxD Motif for Human UDP-Glucuronosyltransferase 1A10 Interacts with UDP-Glucuronic Acid during Catalysis
Creators: name: Redinbo, M. R.
name: Goldman, A.
name: Finel, M.
name: Patana, A.-S.
name: Zielinska, A. K.
name: Miller, G. P.
name: Radominska-Pandya, A.
name: Miley, M. J.
name: Bratton, S. M.
name: Xiong, Y.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2007

description: All UDP-glucuronosyltransferase enzymes (UGTs) share a common cofactor, UDP-glucuronic acid (UDP-GlcUA). The binding site for UDP-GlcUA is localized to the C-terminal domain of UGTs on the basis of amino acid sequence homology analysis and crystal structures of glycosyltransferases, including the C-terminal domain of human UGT2B7. We hypothesized that the 393DQMD-NAK399 region of human UGT1A10 interacts with the glucuronic acid moiety of UDP-GlcUA. Using site-directed mutagenesis and enzymatic analysis, we demonstrated that the D393A mutation abolished the glucuronidation activity of UGT1A10 toward all substrates. The effects of the alanine mutation at Q394, D396, and K399 on glucuronidation activities were substrate-dependent. Previously, we examined the importance of these residues in UGT2B7. Although D393 (D398 in UGT2B7) is similarly critical for UDP-GlcUA binding in both enzymes, the effects of Q394 (Q399 in UGT2B7) to Ala mutation on activity were significant but different between UGT1A10 and UGT2B7. A model of the UDP-GlcUA binding site suggests that the contribution of other residues to cosubstrate binding may explain these differences between UGT1A10 and UGT2B7. We thus postulate that D393 is critical for the binding of glucuronic acid and that proximal residues, e.g., Q394 (Q399 in UGT2B7), play a subtle role in cosubstrate binding in UGT1A10 and UGT2B7. Hence, this study provides important new information needed for the identification and understanding of the binding sites of UGTs, a major step forward in elucidating their molecular mechanism.
Apparent Differences in Mechanisms of Harmol Sulfate Biliary Excretion in Mice and Rats
Creators: name: Brouwer, K. L. R.
name: Nezasa, K.-i.
name: Hoffmaster, K. A.
name: Zamek-Gliszczynski, M. J.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2008

description: Previous experiments demonstrated that the biliary excretion of harmol sulfate (HS) was mediated by Bcrp, and not by Mrp2 or P-glycoprotein in mice. However, recent reports suggested that species differences in hepatic canalicular transport mechanisms for a given substrate exist between mice and rats. In the present study, biliary excretion of HS was examined in perfused livers from mice and rats in the absence or presence of the P-glycoprotein and Bcrp inhibitor, GF120918. As expected, in mouse liver perfusions the biliary excretion of HS was decreased ~3.5-fold by GF120918, consistent with previous reports of Bcrp-mediated HS biliary excretion. However, despite sufficient hepatic unbound concentrations of GF120918 to achieve extensive inhibition of Bcrp, the biliary excretion of HS was not decreased significantly in rats (50 ± 12 vs. 41 ± 6 %). In summary, biliary excretion of HS was mediated by a GF120918-sensitive mechanism in mice, previously elucidated as Bcrp. In contrast the pathway responsible for HS biliary excretion in rats was not impaired by GF120918. Thus, transport mechanism(s) responsible for harmol sulfate biliary excretion appear to differ between mice and rats.
title: Morbus Osler. Morbus Osler - Mehr als nur Nasenbluten.
Creators: name: Ärztliches Zentrum Für Qualität In Der Medizin (ÄZQ)
Publisher: name: Bundesärztekammer (BÄK); Kassenärztliche Bundesvereinigung (KBV); Ärztliches Zentrum für Qualität in der Medizin (ÄZQ)
Year: 2013
Subjects: subject: 610 Medical sciences; Medicine

description: Kurzinformation für Patienten
title: Self-compassion and coping in gay men
Creators: name: Beard, Kieron
Publisher: name: University of Liverpool Repository
Year: 2014

description: Dissertation submitted in partial fulfillment of Doctorate in Clinical Psychology. Includes three chapters; a narrative literature review of coping with minority stress in gay men, empirical study exploring the the benefits of self-compassion for well-being in gay men and a expanded discussion chapter.
CSI 2264: Characterizing Young Stars in NGC 2264 with Short-Duration, Periodic Flux Dips in their Light Curves
Creators: name: Stauffer, John
name: Cody, Ann Marie
name: McGinnis, Pauline
name: Rebull, Luisa
name: Hillenbrand, Lynne A.
name: Turner, Neal J.
name: Carpenter, John
name: Plavchan, Peter
name: Carey, Sean
name: Terebey, Susan
name: Morales-Calderón, María
name: Alencar, Silvia H. P.
name: Bouvier, Jerome
name: Venuti, Laura
name: Hartmann, Lee
name: Calvet, Nuria
name: Micela, Giusi
name: Flaccomio, Ettore
name: Song, Inseok
name: Gutermuth, Rob
name: Barrado, David
name: Vrba, Frederick J.
name: Covey, Kevin
name: Padgett, Debbie
name: Herbst, William
name: Gillen, Edward
name: Lyra, Wladimir
name: Guimaraes, Marcelo Medeiros
name: Bouy, Herve
name: Favata, Fabio
Publisher: name: arXiv
Year: 2015
Subjects: subject: Solar and Stellar Astrophysics (astro-ph.SR)
subject: FOS: Physical sciences

description: We identify nine young stellar objects (YSOs) in the NGC 2264 star-forming region with optical {\em CoRoT} light curves exhibiting short-duration, shallow, periodic flux dips. All of these stars have infrared (IR) excesses that are consistent with their having inner disk walls near the Keplerian co-rotation radius. The repeating photometric dips have FWHM generally less than one day, depths almost always less than 15%, and periods (3
description: 38 pages emulateapj; 30 figures; 5 tables. Accepted to AJ
title: Wind Streamline Ambiguity Removal of Microwave Scatterometer Data
Creators: name: Zaepfel, Hans W.
Publisher: name: Old Dominion University
publisherIdentifier: https://ror.org/04zjtrb98
publisherIdentifierScheme: ROR
Year: 1986

description: There is a class of satellite microwave scatterometers that return oceanographic information which includes wind vectors with directional ambiguity. The first part of the ambiguity removal process is to reduce the data to a directional ambiguity of 180°. This thesis shows that wind direction change contains the information required for streamline ambiguity removal and that syntactic pattern recognition techniques can be used to locate the areas of wind direction change. Spreading the information along the areas of wind direction change results in the removal of the streamline ambiguity. The algorithm is implemented and the results are presented showing that it is a good candidate for removing streamline ambiguity.