cometadata/datacite-rtg-text-other-reclassification-records huggingface dataset:
Dysopsonin Activity of Serum DNA-Binding Proteins Favorable for Gene Delivery
Creators: name: Yuan, X.
name: Huang, L.
name: Frick, A.
name: Liu, F.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Naked DNA is regarded as the safest and simplest method of gene delivery. However, normally intravenously injected naked plasmid DNA is rapidly eliminated from the blood. It has been hypothesized that opsonins, a category of serum DNA-binding proteins (SDBPs), label the injected plasmid DNA as foreign so that it may be recognized and rapidly removed from the bloodstream by liver nonparenchymal cells. Contrary to the hypothesis, our data indicate that some SDBPs across multiple species may have important dysopsonin properties, acting to reduce liver uptake. Formation of SDBP and DNA complexes was observed by agarose gel electrophoresis. An in vivo study involving hepatic artery and portal vein occlusion in a mouse model confirmed the activity of serum diminishing liver uptake of DNA. Data using hydrodynamic gene transfer in the mouse liver and in situ transfection in the mouse lung revealed that serum proteins bound to DNA do not affect the biological activity of the plasmid DNA. We have identified several SDBPs with potential dysopsonin properties. The SDBPs with dysopsonin properties and DNA complexes may be further modified and ultimately be developed into a novel DNA carrier system favorable for systemic gene delivery.
1 Brief an [Johann Caspar Lavater]
Brief an Lavater ...
Creators: name: Hauff, Immanuel Ferdinand Friedrich
Publisher: name: [s.n.]
Year: 1784

description: von Immanuel Ferd[inand] Fried[rich] Hauff
description: Hauff: Kandidat der Philosophie im theologischen Stift in Tübingen
Hepatobiliary Disposition of Troglitazone and Metabolites in Rat and Human Sandwich-Cultured Hepatocytes: Use of Monte Carlo Simulations to Assess the Impact of Changes in Biliary Excretion on Troglitazone Sulfate Accumulation
Creators: name: Lee, J. K.
name: Abe, K.
name: Brouwer, K. L. R.
name: Lim, C.
name: Marion, T. L.
name: Pollock, G. M.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: This study examined the hepatobiliary disposition of troglitazone (TGZ) and metabolites [TGZ sulfate (TS), TGZ glucuronide (TG), and TGZ quinone (TQ)] over time in rat and human sandwich-cultured hepatocytes (SCH). Cells were incubated with TGZ; samples were analyzed for TGZ and metabolites by liquid chromatography-tandem mass spectrometry. SCH mimicked the disposition of TGZ/metabolites in vivo in rats and humans; TGZ was metabolized primarily to TS and to a lesser extent to TG and TQ. In human SCH, the biliary excretion index (BEI) was negligible for TGZ and TQ, ∼16% for TS, and ∼43% for TG over the incubation period; in rat SCH, the BEI for TS and TG was ∼13 and ∼41%, respectively. Hepatocyte accumulation of TS was extensive, with intracellular concentrations ranging from 132 to 222 μM in rat SCH; intracellular TGZ concentrations ranged from 7.22 to 47.7 μM. In human SCH, intracellular TS and TGZ concentrations ranged from 136 to 160 μM and from 49.4 to 84.7 μM, respectively. Pharmacokinetic modeling and Monte Carlo simulations were used to evaluate the impact of modulating the biliary excretion rate constant (Kbile) for TS on TS accumulation in hepatocytes and medium. Simulations demonstrated that intracellular concentrations of TS may increase up to 3.1- and 5.7-fold when biliary excretion of TS was decreased 2- and 10-fold, respectively. It is important to note that altered hepatobiliary transport and the extent of hepatocyte exposure may not always be evident based on medium concentrations (analogous to systemic exposure in vivo). Pharmacokinetic modeling/simulation with data from SCH is a useful approach to examine the impact of altered hepatobiliary transport on hepatocyte accumulation of drug/metabolites.
Photofragmentation beam splitters for matter-wave interferometry
Creators: name: Dörre, Nadine
name: Rodewald, Jonas
name: Geyer, Philipp
name: von Issendorff, Bernd
name: Haslinger, Philipp
name: Arndt, Markus
Publisher: name: arXiv
Year: 2014
Subjects: subject: Atomic Physics (physics.atom-ph)
subject: Optics (physics.optics)
subject: Quantum Physics (quant-ph)
subject: FOS: Physical sciences

description: Extending the range of quantum interferometry to a wider class of composite nanoparticles requires new tools to diffract matter waves. Recently, pulsed photoionization light gratings have demonstrated their suitability for high mass matter-wave physics. Here we extend quantum interference experiments to a new class of particles by introducing photofragmentation beam splitters into time-domain matter-wave interferometry. Photofragmentation gratings can act on objects as different as van der Waals clusters and biomolecules which are thermally unstable and often resilient to single-photon ionization. We present data that demonstrate this coherent beam splitting mechanism with clusters of hexafluorobenzene and we show single-photon depletion gratings based both on fragmentation and ionization for clusters of vanillin.
title: Burnout und dessen Prädiktoren bei Lehrenden der Sekundarstufe in Österreich während der COVID-19-Pandemie
Creators: name: Neumann, Matthias
Year: 2021

description: Das Burnout-Syndrom, charakterisiert durch emotionale Erschöpfung, Depersonalisation und reduzierter persönlicher Leistungsfähigkeit, gilt unter Lehrkräften als weit verbreitet. Die Covid-19-Pandemie sorgt für eine starke Veränderung der schulischen Arbeitsbedingungen und bringt für Lehrpersonen zusätzliche, neue Herausforderungen mit sich. Die vorliegende quantitative Online-Studie untersuchte anhand von einer 351 Lehrerenden umfassenden Stichprobe Burnout und dessen Prädiktoren bei Lehrenden der Sekundarstufe in Österreich unter COVID-19-Bedingungen. Zur Messung der Symptomatik kam das Maslach Burnout-Inventory – Educators Survey (MBI-ES) zum Einsatz. Nach üblicher Klassifikation zeigten sich in der Stichprobe hohe Werte bei 50.7% in der Skala emotionale Erschöpfung, 20.8% in der Skala Depersonalisation und 3.5% in der Skala reduzierte persönlicher Leistungsfähigkeit. Lehrende von Hauptgegenständen zeigten hierbei im Schnitt eine höhere Symptomatik als jene von Nebengegenständen. Entgegen den Erwartungen waren weder Geschlecht, noch Alter oder die Jahre an Berufserfahrung bedeutende Prädiktoren für Burnout. Im Gegensatz dazu erwiesen sich im Einklang mit bisherigen Forschungsergebnissen ein hohes Arbeitsvolumen, eine geringe Lehrenden-Selbstwirksamkeit und ein hohes Niveau an wahrgenommenem Stress als potente Prädiktoren für eine ausgeprägte Burnout-Symptomatik. Auf Basis der Ergebnisse wird für eine baldige Implementierung universeller Burnout-Interventionsprogramme für Lehrende plädiert.
description: Burnout, a syndrome characterized by emotional exhaustion, depersonalization and reduced personal accomplishment, is known to be highly prevalent among educators. The COVID-19 pandemic drastically altered the working conditions for school teachers and confronted them with additional and unfamiliar challenges. The current quantitative online study comprised a sample of 351 teachers and investigated burnout and its predictors among secondary school teachers in Austria during COVID-19 conditions. The Maslach Burnout-Inventory – Educators Survey (MBI-ES) served as a measure for burnout symptoms. According to a widespread classification system of the MBI-ES, 50.7% of the sample can be categorized as high in emotional exhaustion, 20.8% in depersonalization and 3.5% in reduced personal accomplishment. Teachers of main subjects showed greater symptoms than those of subsidiary subjects. Contrary to the expectations, neither sex nor age or the amount of job experience emerged as predictors of burnout. However, in line with previous research, low levels of teacher self-efficacy and high levels of perceived stress turned out to be potent predictors of burnout. On the basis of these results, an early implementation of universal burnout intervention programs for teachers is recommended.
Inhibition of I B Kinase-  Protects Dopamine Neurons Against Lipopolysaccharide-Induced Neurotoxicity
Creators: name: Qian, L.
name: Shi, J. S.
name: Flood, P. M.
name: Zhang, F.
name: Gao, H. M.
name: Hong, J. S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Parkinson's disease (PD) is a progressive neurological disorder characterized by a selective loss of dopamine (DA) neurons in the substantia nigra (SN). Although current therapy can control symptoms of this disorder, there is no effective therapy available to halt its progression. Recently, neuroinflammation has been recognized as an important contributor to the pathogenesis of PD, and nuclear factor-κB (NF-κB) plays a key role in regulating neuroinflammation. Hence, the modulation of NF-κB pathway may have therapeutic potential for PD. Activation of NF-κB depends on the phosphorylation of its inhibitor, IκB, by the specific IκB kinase (IKK) subunit IKK-β. Compound A (7-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-5-[(3S)-3-piperidinyl]-1, 4-dihydro-2H-pyrido[2,3-d][1,3]oxazin-2-one hydrochloride), a potent and selective inhibitor of IKK-β, has recently been reported to provide cardioprotection through specific suppression of NF-κB signaling. The present study, for the first time, elucidates neuroprotective effects of compound A. Daily subcutaneous injection of compound A (1 mg/kg) for 7 days inhibited the activation of microglia induced by nigral stereotaxic injection of lipopolysaccharide (LPS) and significantly attenuated LPS-induced loss of DA neurons in the SN. In vitro mechanistic studies revealed that neuroprotective effects of compound A were mediated by 1) suppressing the activity of microglial NADPH oxidase and decreasing the production of reactive oxygen species, and 2) inhibiting NF-κB-mediated gene transcription of various proinflammatory mediators in microglia via IKK-β suppression. These findings indicate that compound A afforded potent neuroprotection against LPS-induced neurodegeneration through selective inhibition of NF-κB activation and may be of potential benefit in the treatment of PD.
SPIRITS OF LIFE AND PERCEPTION. GREEK AND ARABIC LEGACIES IN ALBERT THE GREAT'S EARLY THEOLOGY AND NATURAL PHILOSOPHY
Creators: name: MERONI, MICHELE
Publisher: name: Universit� degli Studi di Milano
Year: 2021

description: Among his contemporaries, Albert the Great (1200-1280) stands out for his extensive knowledge of philosophical and medical sources from the Islamic Word. The dissertation investigates the role of Albert's Arabic sources in his doctrine of spirit, a key concept straddling medicine and natural philosophy, in the broader context of his psychophysiology. The main purpose of the research is to provide a study of the reception of sources such as Avicenna (De anima, De animalibus, Canon), Qusta ibn Luqa (De differentia spiritus et animae) and other Arabic authors (Averroes, al-Ghazali and al-Magusi), shedding light on their relevance for Albert's own understanding of spiritus. Prefaced by a methodological introduction and a first chapter devoted to the relationship between philosophy and medicine, the dissertation provides a comparison between Albert's position on the role of spirit in his early theological works with his mature works (Aristotelian paraphrases), focusing especially on the Parva Naturalia. The research revolves around two main areas of interest: life- and perception-related phenomena, highlighting how Albert's understanding of the causal role of spirit changes over the years, thus moving away from his first conception in the early theological works, strongly influenced by his Arabic sources. A typical feature of Albert's psychophysiology of life-related phenomena in the Aristotelian paraphrases is the introduction of the concept of spirit in plants, a unique case among Albert's contemporaries. The second part of the dissertation deals with the role of spirits in sense perception and cognitive activities, with a special focus on dreams, divinatory dreams, and prophecy, where the influence of the Arabic (also, Hebrew) philosophical tradition is crucial.
Overexpression of Cytochrome P450 Epoxygenases Prevents Development of Hypertension in Spontaneously Hypertensive Rats by Enhancing Atrial Natriuretic Peptide
Creators: name: Yang, G.
name: Xiao, X.
name: Zeldin, D. C.
name: Xiao, B.
name: Li, X.
name: Yu, X.
name: Wang, D. W.
name: Yan, J.
name: Voltz, J. W.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Cytochrome P450 (P450)-derived epoxyeicosatrienoic acids (EETs) exert well recognized vasodilatory, diuretic, and tubular fluid-electrolyte transport actions that are predictive of a hypotensive effect. The study sought to determine the improvement of hypertension and cardiac function by overexpressing P450 epoxygenases in vivo. Long-term expression of CYP102 F87V or CYP2J2 in spontaneously hypertensive rats (SHR) was mediated by using a type 8 recombinant adeno-associated virus (rAAV8) vector. Hemodynamics was measured by a Millar Instruments, Inc. (Houston, TX) microtransducer catheter, and atrial natriuretic peptide (ANP) mRNA levels were tested by real-time polymerase chain reaction. Results showed that urinary excretion of 14,15-EET was increased at 2 and 6 months after injection with rAAV-CYP102 F87V and rAAV-CYP2J2 compared with controls (p < 0.05). During the course of the 6-month study, systolic blood pressure significantly decreased in P450 epoxygenase-treated rats, but the CYP2J2-specific inhibitor C26 blocked rAAV-CYP2J2-induced hypotension and the increase in EET production. Cardiac output was improved by P450 epoxygenase expression at 6 months (p < 0.05). Furthermore, cardiac collagen content was reduced in P450 epoxygenase-treated rats. ANP mRNA levels were up-regulated 6- to 14-fold in the myocardium, and ANP expression was significantly increased in both myocardium and plasma in P450 epoxygenase-treated rats. However, epidermal growth factor (EGF) receptor antagonist 4-(3′-chloroanilino)-6,7-dimethoxy-quinazoline (AG-1478) significantly attenuated the increase in the EET-induced expression of ANP in vitro. These data indicate that overexpression of P450 epoxygenases attenuates the development of hypertension and improves cardiac function in SHR, and that these effects may be mediated, at least in part, by ANP via activating EGF receptor.
Quanta of Geometry: Noncommutative Aspects
Creators: name: Chamseddine, Ali H.
name: Connes, Alain
name: Mukhanov, Viatcheslav
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Physics - Theory (hep-th)
subject: General Relativity and Quantum Cosmology (gr-qc)
subject: Quantum Algebra (math.QA)
subject: FOS: Physical sciences
subject: FOS: Mathematics

description: In the construction of spectral manifolds in noncommutative geometry, a higher degree Heisenberg commutation relation involving the Dirac operator and the Feynman slash of real scalar fields naturally appears and implies, by equality with the index formula, the quantization of the volume. We first show that this condition implies that the manifold decomposes into disconnected spheres which will represent quanta of geometry. We then refine the condition by involving the real structure and two types of geometric quanta, and show that connected spin-manifolds with large quantized volume are then obtained as solutions. The two algebras M_2(H) and M_4(C) are obtained which are the exact constituents of the Standard Model. Using the two maps from M_4 to S^4 the four-manifold is built out of a very large number of the two kinds of spheres of Planckian volume. We give several physical applications of this scheme such as quantization of the cosmological constant, mimetic dark matter and area quantization of black holes.
description: 4 pages. Title modified. Letter rewritten to be understandable by a wider audience. To appear in Physical Review Letters
IMMUNOMODULATORY EFFECTS OF PIDOTIMOD IN PATIENTS HOSPITALIZED FOR COMMUNITY-ACQUIRED PNEUMONIA
Creators: name: GARZIANO, MICAELA
Publisher: name: Universit� degli Studi di Milano
Year: 2017

description: Introduzione: Il pidotimod (PDT) � una molecola dipeptidica di sintesi ad azione immunomodulante. Tale composto � studiato gi� da diversi anni con incoraggianti risultati a carico sia del sistema immunitario innato che adattativo. Studi in vitro ed in vivo ne hanno gi� dimostrato i benefici effetti nel trattamento di molte patologie. Col nostro studio abbiamo voluto porre l?accento sugli effetti del PDT associato alla terapia antibiotica standard in pazienti ospedalizzati per polmonite contratta in comunit� (CAP). Metodi: 36 pazienti ospedalizzati per CAP, di cui 20 bambini e 16 adulti, sono stati arruolati nello studio secondo specifici criteri di inclusione. I pazienti sono stati suddivisi in due gruppi di trattamento, al primo � stato somministrato PDT associato alla terapia antibiotica standard, al secondo la sola terapia antibiotica. I campioni di sangue sono stati prelevati a diverse tempistiche, i bambini sono stati prelevati al momento dell?arruolamento (T0), a 3 e 5 giorni dall? inizio della terapia (T3 e T5), e a 7 giorni dalla fine della somministrazione farmacologica (T21), Gli adulti sono stati invece prelevati al momento dell?arruolamento (T0), e rispettivamente a 1, 3, e 5 giorni dall?inizio della terapia (T1, T3, T5). Le PBMC sono state isolate da sangue periferico e stimolate in presenza di pneumococco. Dopo 3 ore di stimolazione una parte delle cellule � stata utilizzata per l?estrazione dell?RNA per la valutazione dell?espressione di specifici geni coinvolti nella risposta antibatterica; mentre dopo 18 ore di stimolazione le restanti cellule sono state marcate per le analisi citofluorimetriche. Risultati: I risultati ottenuti nei bambini hanno evidenziato un?azione del PDT su cellule denritiche, dove modula l?espressione di marker di attivazione e molecole costimolatorie quali HLA DRII, CD80 e CD86; e monociti, sui quali incrementa l?espressione del TLR2. Inoltre il gruppo trattato con PDT manifesta anche un?incremento nella secrezione di citochine proinfiammatorie TNF? e IL-12. Negli adulti � stato anche osservato un aumento nell? espressione del TLR4 a livello dei monociti, mentre nessuna differenza � stata osservata nella secrezione delle citochine proinfiammatorie. In aggiunta, in entrambi i gruppi si � osservata una modulazione nell? espressione di geni coinvolti nella risposta infiammatoria e antimicrobica. Conclusioni: Questi risultati confermano gli effetti immunomodulanti del PDT gi� descritti in letteratura, nonch� i benefici della molecola associata alla terapia antibiotica standard nei pazienti affetti da CAP, grazie alla sua azione a livello dell?immunit� innata.
46 Briefe, 3 Beilagen an Johann Caspar Lavater
Brief an Lavater ...
Creators: name: Hasenkamp, Johann Gerhard
Publisher: name: [s.n.]
Year: 1771

description: von Johann Gerhard Hasenkamp
description: Davon 3 Briefe undatiert (Nr. 197, 202 und 244); 2 Briefe ohne Jahr, nachträglich mit Bleistift ergänzt (Nr. 198 und 200), 1 Brief undatiert, Monat und Jahr mit Bleistift ergänzt (Nr. 199); 1 Brief ohne Jahr (Nr. 201)
description: Davon 1 Brief mit Notiz versehen: "Dieser im Hasenkampischen Nachlasse im Original und Copie gefundene Brief scheint nicht abgegangen zu sein, da er sich im Lavaterschen Nachlasse nicht findet. Ich füge ihn daher hiermit im Original in denselben ein.", signiert M. Goebel, 28.4.1847 (Nr. 199)
description: Davon 1 Brief an Unbekannt ("Herr Doctor, Herr und Gönner") (Nr. 205), 2 Kopien von Briefen Hasenkamps an Friedrich Christoph Oetinger für Lavater (Nr. 207-208, als Beilagen zu Nr. 210); 1 Brief an den Bruder Friedrich Arnold Hasenkamp, von diesem mit Notiz weitergeleitet an Lavater (Nr. 229); 1 Brief vrmtl. an Samuel Collenbusch (Nr. 239); 2 Briefe mitadressiert an Johann Konrad Pfenninger (Nr. 242 und 243)
description: Nr. 219 ist vrmtl. Fortsetzung von Nr. 218 und Nr. 222 von Nr. 220
description: Mit Auszug aus einem Brief von Woltersdorf, Berlin, vrmtl. Theodor Karl Georg Woltersdorf (1727-1806) in Nr. 228; mit Auszug aus einem Brief von Samuel Collenbusch in Nr. 229
description: Davon 1 Brief mit Anmerkungen von Samuel Collenbusch (Nr. 221)
description: Davon 1 Brief mit Ergänzungen von späterem Datum (Nr. 208)
description: Mit Selbstbiographie Hasenkamps in Nr. 212 und 213
description: Beilage: Nachbemerkung (Ergänzung) zu S. 5 der Selbstbiographie in Nr. 213, dat. 25.12.1772-1.1.1773 (Nr. 212)
description: Beilage: Anmerkungen über die Frankfurter Rezension der Lavaterschen Predigten über den Prophet Jonas, dat. Duisburg, 13.5.1773 (Nr. 217)
description: Beilage a: "Gebeth-Lied, um Stärkung des Glaubens", annotierter Druck (Nr. 245)
9 Briefe, 1 Beilage an [Johann Caspar] Lavater
Brief an Lavater ...
Creators: name: Haugwitz, Christian Heinrich Curt von
Publisher: name: [s.n.]
Year: 1775

description: von [Christian Heinrich] Curt [von] Haugwitz
description: Davon 1 Brief ohne Monat und Jahr (Nr. 250)
description: Davon 1 Brief mit Beischrift von Eberhard Gaupp (Nr. 256)
description: Beilage: Äußerung und Vorschlag des Herrn Freyherrn Curt von Haugwitz an Herrn Christoph Kaufman, dat. Schaffhausen, 9.7.1780 (Nr. 257)
Sulindac and Its Metabolites Inhibit Multiple Transport Proteins in Rat and Human Hepatocytes
Creators: name: Lee, J. K.
name: Brouwer, K. L. R.
name: Paine, M. F.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Sulindac is a commonly used nonsteroidal anti-inflammatory drug. This study tested the hypothesis that sulindac-mediated drug–drug interactions and/or hepatotoxicity may be caused, in part, by inhibition of proteins responsible for the hepatic transport of drugs and/or bile acids by sulindac and/or sulindac metabolites [sulindac sulfone (S-sulfone) and sulindac sulfide (S-sulfide)]. The uptake and excretion of model substrates, [3H]taurocholate (TC), [3H]estradiol 17-β-glucuronide (E217G), and nitrofurantoin (NF), were investigated in rat and human suspended and sandwich-cultured hepatocytes (SCH). In suspended rat hepatocytes, S-sulfone and S-sulfide inhibited Na+-dependent TC initial uptake (IC50 of 24.9 ± 6.4 and 12.5 ± 1.8 μM, respectively) and Na+-independent E217G initial uptake (IC50 of 12.1 ± 1.6 and 6.3 ± 0.3 μM, respectively). In rat SCH, sulindac metabolites (100 μM) decreased the in vitro biliary clearance (Clbiliary) of TC, E217G, and NF by 38 to 83%, 81 to 97%, and 33 to 57%, respectively; S-sulfone and S-sulfide also decreased the TC and NF biliary excretion index by 39 to 55%. In suspended human hepatocytes, S-sulfone and S-sulfide inhibited Na+-dependent TC initial uptake (IC50 of 42.2 and 3.1 μM, respectively); S-sulfide also inhibited the TC Clbiliary in human SCH. Sulindac/metabolites markedly inhibited hepatic uptake and biliary excretion of E217G by 51 to 100% in human SCH. In conclusion, sulindac and metabolites are potent inhibitors of the uptake and biliary clearance of bile acids in rat and human hepatocytes and also inhibit substrates of rat breast cancer resistance protein, rat and human organic anion-transporting polypeptides, and human multidrug resistance-associated protein 2. Inhibition of multiple hepatic transport proteins by sulindac/metabolites may play an important role in clinically significant sulindac-mediated drug–drug interactions and/or liver injury.
Two Flavonolignans from Milk Thistle (Silybum marianum) Inhibit CYP2C9-Mediated Warfarin Metabolism at Clinically Achievable Concentrations
Creators: name: Brantley, S. J.
name: Paine, M. F.
name: Kroll, D. J.
name: Oberlies, N. H.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2010

description: Milk thistle (Silybum marianum) is a popular herbal product used for hepatoprotection and chemoprevention. Two commercially available formulations are the crude extract, silymarin, and the semipurified product, silibinin. Silymarin consists of at least seven flavonolignans, of which the most prevalent are the diastereoisomers silybin A and silybin B; silibinin consists only of silybin A and silybin B. Based on a recent clinical study showing an interaction between a silymarin product and the CYP2C9 substrate losartan, the CYP2C9 inhibition properties of silybin A and silybin B and corresponding regioisomers, isosilybin A and isosilybin B, were evaluated using human liver microsomes (HLMs), recombinant CYP2C9 (rCYP2C9) enzymes, and the clinically relevant probe, (S)-warfarin. Silybin B was the most potent inhibitor in HLMs, followed by silybin A, isosilybin B, and isosilybin A (IC50 of 8.2, 18, 74, and >100 μM, respectively). Next, silybin A and silybin B were selected for further characterization. As with HLMs, silybin B was more potent than silybin A toward rCYP2C9*1 (6.7 versus 12 μM), rCYP2C9*2 (9.3 versus 19 μM), and rCYP2C9*3 (2.4 versus 9.3 μM). Using a matrix of five substrate (1–15 μM) and six inhibitor (1–80 μM) concentrations and HLMs, both diastereoisomers inhibited (S)-warfarin 7-hydroxylation in a manner described best by a mixed-type inhibition model (Ki values of 4.8 and 10 μM for silybin B and silybin A, respectively). These observations, combined with the high systemic silibinin concentrations (>5–75 μM) achieved in a phase I study involving prostate cancer patients, prompt clinical evaluation of a potential warfarin-milk thistle interaction.
Decoherence of an entangled state of a strongly-correlated double quantum dot structure through tunneling processes
Creators: name: Büsser, C. A.
name: de Vega, I.
name: Heidrich-Meisner, F.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Mesoscale and Nanoscale Physics (cond-mat.mes-hall)
subject: FOS: Physical sciences

description: We consider two quantum dots described by the Anderson-impurity model with one electron per dot. The goal of our work is to study the decay of a maximally entangled state between the two electrons localized in the dots. We prepare the system in a perfect singlet and then tunnel-couple one of the dots to leads, which induces the non-equilibrium dynamics. We identify two cases: if the leads are subject to a sufficiently large voltage and thus a finite current, then direct tunneling processes cause decoherence and the entanglement as well as spin correlations decay exponentially fast. At zero voltage or small voltages and beyond the mixed-valence regime, virtual tunneling processes dominate and lead to a slower loss of coherence. We analyze this problem by studying the real-time dynamics of the spin correlations and the concurrence using two techniques, namely the time-dependent density matrix renormalization group method and a master-equation method. The results from these two approaches are in excellent agreement in the direct-tunneling regime for the case in which the dot is weakly tunnel-coupled to the leads. We present a quantitative analysis of the decay rates of the spin correlations and the concurrence as a function of tunneling rate, interaction strength, and voltage.
description: 16 pages, 11 figures, revised version as published
IMMUNOPROFILE IN EFFUSION CYTOLOGY
Creators: name: PINTO DA  CUNHA, MARIA NAZARE'
Publisher: name: Universit� degli Studi di Milano
Year: 2010

description: BACKGROUND: Cytology has a crucial role for diagnosing pleural and abdominal effusions. A prompt accurate diagnosis has both prognostic and therapeutic significance. However, cell morphology alone is not always sufficient to formulate such a diagnosis. In human medicine, immunocytochemistry of effusion cytology has now standardized procedures that provide reliable insights into various diagnostic dilemmas. OBJECTIVE: To describe the method of immunocytochemistry in effusion cytology and to estimate the value of a panel of markers in identifying cells in canine and feline effusions. MATERIALS AND METHODS: Human, feline and canine mesothelial cells were isolated in culture. Western?blot (WB) analysis was used to ascertain antibody cross?reactivity for all the markers, with the exception of HBME?1. Forty?four cytospined or smeared effusion specimens from dogs and cats with a cytological diagnosis of reactive effusion or malignancy of non?hematopoietic origin were stained with a standard panel of Vimentin, Cytokeratin (CK) AE1/AE3, CK 5/6 and HBME?1 as mesothelial cell markers; desmin as mesothelial cell malignancy marker; and CK7/CK20 as a marker of metastasis. Malignancy was confirmed by histologic evaluation; non?malignant conditions were confirmed by follow?up. Sensitivities, specificities and predictive values were calculated. RESULTS: The WB analysis confirmed the specific crossreactivity of the human antibodies for canine and feline proteins in mesothelial tissue. No significant differences were found between canine and feline results. Vimentin/cytokeratin coexpression had a sensitivity of 79% and a specificity of 92%, HBME?1 had 89% sensitivity and 23% specificity, and CK5/6 had 26% sensitivity and 100% specificity for mesothelial cells. Desmin had only 20% specificity for benign mesothelial cells, while CK7?/CK20+ had a specificity of 79% and sensitivity of 30% for metastatic cells on effusions. CONCLUSION: Immunocytochemistry can be applied in effusion samples, and valuable results can be obtained. The most useful marker, with the highest overall accuracy for the identification of mesothelial cells in effusion, is the Vim/CK coexpression, being CK5/6 the more specific and HBME?1 the more sensitive antibody. Desmin is not useful for discriminating between benign and malignant mesothelial cells. The coordinate expression of CK7?/CK20+ has not proved to be useful on the identification of metastatic cells on effusions.
The mass-metallicity relation of zCOSMOS galaxies at z ~ 0.7, its dependence on SFR, and the existence of massive low-metallicity galaxies
Creators: name: Maier, C.
name: Ziegler, B. L.
name: Lilly, S. J.
name: Contini, T.
name: Montero, E. Perez
name: Lamareille, F.
name: Bolzonella, M.
name: Floc'h, E. Le
Publisher: name: arXiv
Year: 2014
Subjects: subject: Astrophysics of Galaxies (astro-ph.GA)
subject: FOS: Physical sciences

description: (Abridged) The knowledge of the number and of the physical nature of low-metallicity massive galaxies is crucial for the determination and interpretation of the mass-metallicity relation (MZR). Using VLT-ISAAC near-infrared (NIR) spectroscopy of 39 zCOSMOS z~0.7 galaxies, we have measured Halpha and [NII] emission line fluxes for galaxies with [OII], Hbeta and [OIII] available from VIMOS optical spectroscopy. The NIR spectroscopy enables us to break the degeneracy of the R23 method to derive unambiguously O/H gas metallicities, and also SFRs from extinction corrected Halpha. Using, as a benchmark, the position in the D4000 vs. [OIII]/Hbeta diagram of galaxies with reliable O/Hs from NIR spectroscopy, we were able to break the lower/upper branch R23 degeneracy of additional 900 zCOSMOS z~0.7 galaxies. Additionally, the Halpha-based SFR measurements were used to find the best SFR calibration based on [OII] for the zCOSMOS z~0.7 galaxies without Halpha measurements. We find a fraction of 19% of lower mass 9.5
description: Accepted for publication in A&A; clarifying Appendix added
A class of Hamilton-Jacobi equations on Banach-Finsler manifolds
Creators: name: Jaramillo, J. A.
name: Jimenez-Sevilla, M.
name: Rodenas-Pedregosa, J. L.
name: Sanchez-Gonzalez, L.
Publisher: name: arXiv
Year: 2014
Subjects: subject: Functional Analysis (math.FA)
subject: Analysis of PDEs (math.AP)
subject: Differential Geometry (math.DG)
subject: FOS: Mathematics
subject: 58B10, 58B20, 46T05, 46T20, 46B20, 35R01

description: The concept of subdifferentiability is studied in the context of $C^1$ Finsler manifolds (modeled on a Banach space with a Lipschitz $C^1$ bump function). A class of Hamilton-Jacobi equations defined on $C^1$ Finsler manifolds is studied and several results related to the existence and uniqueness of viscosity solutions are obtained.
description: 24 pages
Antagonist Functional Selectivity: 5-HT2A Serotonin Receptor Antagonists Differentially Regulate 5-HT2A Receptor Protein Level In Vivo
Creators: name: Kroeze, W. K.
name: Yadav, P. N.
name: Farrell, M. S.
name: Roth, B. L.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Dysregulation of the 5-HT2A receptor is implicated in both the etiology and treatment of schizophrenia. Although the essential role of 5-HT2A receptors in atypical antipsychotic drug actions is widely accepted, the contribution of 5-HT2A down-regulation to their efficacy is not known. We hypothesized that down-regulation of cortical 5-HT2A receptors contributes to the therapeutic action of atypical antipsychotic drugs. To test this hypothesis, we assessed the effect of chronically administered antipsychotics (clozapine, olanzapine, and haloperidol) and several 5-HT2A antagonists [ketanserin, altanserin, α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol (M100907), α-phenyl-1-(2-phenylethyl)-4-piperidinemethano ({"type":"entrez-nucleotide","attrs":{"text":"M11939","term_id":"169356","term_text":"M11939"}}M11939), 4-[(2Z)-3-{[2-(dimethylamino)ethoxy]amino}-3-(2-fluorophenyl)prop-2-en-1-ylidene]cyclohexa-2,5-dien-1-one (SR46349B), and pimavanserin], on the phencyclidine (PCP)-induced hyperlocomotor response and cortical 5-HT2A receptor levels in C57BL/6J mice. Clozapine and olanzapine, but not haloperidol, induced receptor down-regulation and attenuated PCP-induced locomotor responses. Of the selective 5-HT2A antagonists tested, only ketanserin caused significant receptor protein down-regulation, whereas SR46349B up-regulated 5-HT2A receptors and potentiated PCP-hyperlocomotion; the other 5-HT2A receptor antagonists were without effect. The significance of these findings with respect to atypical antipsychotic drug action is discussed.
Intrinsic alignments of galaxies in the MassiveBlack-II simulation: analysis of two-point statistics
Creators: name: Tenneti, Ananth
name: Singh, Sukhdeep
name: Mandelbaum, Rachel
name: Di Matteo, Tiziana
name: Feng, Yu
name: Khandai, Nishikanta
Publisher: name: arXiv
Year: 2014
Subjects: subject: Cosmology and Nongalactic Astrophysics (astro-ph.CO)
subject: FOS: Physical sciences

description: The intrinsic alignment of galaxies with the large-scale density field is an important astrophysical contaminant in upcoming weak lensing surveys. We present detailed measurements of the galaxy intrinsic alignments and associated ellipticity-direction (ED) and projected shape ($w_{g+}$) correlation functions for galaxies in the cosmological hydrodynamic MassiveBlack-II (MB-II) simulation. We carefully assess the effects on galaxy shapes, misalignment of the stellar component with the dark matter shape and two-point statistics of iterative weighted (by mass and luminosity) definitions of the (reduced and unreduced) inertia tensor. We find that iterative procedures must be adopted for a reliable measurement of the reduced tensor but that luminosity versus mass weighting has only negligible effects. Both ED and $w_{g+}$ correlations increase in amplitude with subhalo mass (in the range of $10^{10} - 6.0\times 10^{14}h^{-1}M_{\odot}$), with a weak redshift dependence (from $z=1$ to $z=0.06$) at fixed mass. At $z \sim 0.3$, we predict a $w_{g+}$ that is in reasonable agreement with SDSS LRG measurements and that decreases in amplitude by a factor of $\sim 5$--18 for galaxies in the LSST survey. We also compared the intrinsic alignments of centrals and satellites, with clear detection of satellite radial alignments within their host halos. Finally, we show that $w_{g+}$ (using subhalos as tracers of density) and $w_{δ+}$ (using dark matter density) predictions from the simulations agree with that of non-linear alignment models (NLA) at scales where the 2-halo term dominates in the correlations (and tabulate associated NLA fitting parameters). The 1-halo term induces a scale dependent bias at small scales which is not modeled in the NLA model.
description: 25 pages, 27 figures, revised after referee comments, accepted for publication in MNRAS
Quantum Periods For Certain Four-Dimensional Fano Manifolds
Creators: name: Coates, Tom
name: Galkin, Sergey
name: Kasprzyk, Alexander
name: Strangeway, Andrew
Publisher: name: arXiv
Year: 2014
Subjects: subject: Algebraic Geometry (math.AG)
subject: Symplectic Geometry (math.SG)
subject: FOS: Mathematics
subject: 14J45, 14N35 (Primary), 14J33 (Secondary)

description: We collect a list of known four-dimensional Fano manifolds and compute their quantum periods. This list includes all four-dimensional Fano manifolds of index greater than one, all four-dimensional toric Fano manifolds, all four-dimensional products of lower-dimensional Fano manifolds, and certain complete intersections in projective bundles.
description: 44 pages. Includes results of computer algebra calculations and full source code: see the Appendices and the ancillary files. v2: typos corrected, explained connections to the work of Batyrev--Ciocan-Fontanine--Kim--van Straten. v3: fixed strange problem with PDF generation
Fermi-LAT gamma-ray anisotropy and intensity explained by unresolved Radio-Loud Active Galactic Nuclei
Creators: name: Di Mauro, Mattia
name: Cuoco, Alessandro
name: Donato, Fiorenza
name: Siegal-Gaskins, Jennifer M.
Publisher: name: arXiv
Year: 2014
Subjects: subject: High Energy Astrophysical Phenomena (astro-ph.HE)
subject: High Energy Physics - Phenomenology (hep-ph)
subject: FOS: Physical sciences

description: Radio-loud active galactic nuclei (AGN) are expected to contribute substantially to both the intensity and anisotropy of the isotropic gamma-ray background (IGRB). In turn, the measured properties of the IGRB can be used to constrain the characteristics of proposed contributing source classes. We consider individual subclasses of radio-loud AGN, including low-, intermediate-, and high-synchrotron-peaked BL Lacertae objects, flat-spectrum radio quasars, and misaligned AGN. Using updated models of the gamma-ray luminosity functions of these populations, we evaluate the energy-dependent contribution of each source class to the intensity and anisotropy of the IGRB. We find that collectively radio-loud AGN can account for the entirety of the IGRB intensity and anisotropy as measured by the Fermi Large Area Telescope (LAT). Misaligned AGN provide the bulk of the measured intensity but a negligible contribution to the anisotropy, while high-synchrotron-peaked BL Lacertae objects provide the dominant contribution to the anisotropy. In anticipation of upcoming measurements with the Fermi-LAT and the forthcoming Cherenkov Telescope Array, we predict the anisotropy in the broader energy range that will be accessible to future observations.
description: 27 pages, 29 figures. This version matches the published version, minor changes only
title: Flächengerechte Mobilität in Wien
Creators: name: Lorenz, Pascal
Year: 2021

description: In den letzten Jahren wurde im öffentlichen Diskurs zur Verteilung der öffentlichen Flächen immer öfter der Begriff der Flächengerechtigkeit verwendet, ohne diesen da-bei genauer zu definieren. Ziel dieser Arbeit war es deshalb die Fragen „Was ist Flä-chengerechtigkeit?“ und „Ist die Mobilität in Wien flächengerecht?“ zu beantworten. Untersucht wurde hierfür ein beispielhaftes Projektgebiet im 8. und 16. Wiener Ge-meindebezirk. Der ersten Frage wurde anhand einer gründlichen Literaturrecherche nachgegangen, wobei besonders die Werke von Rawls („A Theory of Justice“), Lefebv-re („Le droit à la ville“), Harvey („Social Justice and the city“) und Soja („Seeking Spatial Justice“) im Fokus standen. Ergebnis dieser Recherche war, dass Flächengerechtig-keit ein undefinierter Begriff ist und daher im Diskurs überproportional oft gebraucht wurde. Zeitgleich wurde eine Digitalisierung des Untersuchungsgebiet mit Hilfe eines Luftbilds und des Programms Arc GIS Pro durchgeführt, bei der die Flächen des öf-fentlichen Raums in verschiedene Nutzungsklassen unterteilt wurde. Zur Beantwor-tung der zweiten Frage wurden die Ergebnisse dieser Erhebung zuerst statistisch ausgewertet und im Anschluss mit der theoretischen Grundlage verknüpft. Obwohl Rawls, Lefebvre, Harvey und Soja eine qualitative Herangehensweise zur Eingren-zung des Begriffs „Flächengerechtigkeit“ wählten, und dadurch die Beurteilung der erhobenen Flächen schwerfällt, lässt sich die Verteilung der Flächen im Untersu-chungsgebiet nicht als gerecht bewerten. Nichtsdestotrotz ist eine genauere Ausei-nandersetzung mit dem Begriff der Flächengerechtigkeit notwendig, um ihn allge-meingültig zu definieren und die Beurteilung öffentlicher Räume zu erleichtern.
Mechanisms Underlying Differences in Systemic Exposure of Structurally Similar Active Metabolites: Comparison of Two Preclinical Hepatic Models
Creators: name: Paine, M. F.
name: Tidwell, R. R.
name: Wang, M. Z.
name: Brouwer, K. L. R.
name: Pollack, G. M.
name: Yan, G. Z.
name: Hall, J. E.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: Selection of in vitro models that accurately characterize metabolite systemic and hepatobiliary exposure remains a challenge in drug development. In the present study, mechanisms underlying differences in systemic exposure of two active metabolites, furamidine and 2,5-bis (5-amidino)-2-pyridyl furan (CPD-0801), were examined using two hepatic models from rats: isolated perfused livers (IPLs) and sandwich-cultured hepatocytes (SCH). Pafuramidine, a prodrug of furamidine, and 2,5-bis [5-(N-methoxyamidino)-2-pyridyl] furan (CPD-0868), a prodrug of CPD-0801, were selected for investigation because CPD-0801 exhibits greater systemic exposure than furamidine, despite remarkable structural similarity between these two active metabolites. In both IPLs and SCH, the extent of conversion of CPD-0868 to CPD-0801 was consistently higher than that of pafuramidine to furamidine over time (at most 2.5-fold); area under the curve (AUC) of CPD-0801 in IPL perfusate and SCH medium was at least 7-fold higher than that of furamidine. Pharmacokinetic modeling revealed that the rate constant for basolateral (liver to blood) net efflux (kA_net efflux) of total formed CPD-0801 (bound + unbound) was 6-fold higher than that of furamidine. Hepatic accumulation of both active metabolites was extensive (>95% of total formed); the hepatic unbound fraction (fu,L) of CPD-0801 was 5-fold higher than that of furamidine (1.6 versus 0.3%). Incorporation of fu,L into the pharmacokinetic model resulted in comparable kA_net efflux,u between furamidine and CPD-0801. In conclusion, intrahepatic binding markedly influenced the disposition of these active metabolites. A higher fu,L explained, in part, the enhanced perfusate AUC of CPD-0801 compared with furamidine in IPLs. SCH predicted the disposition of prodrug/metabolite in IPLs.
Carrier-free Raman manipulation of trapped neutral atoms
Creators: name: Reimann, René
name: Alt, Wolfgang
name: Macha, Tobias
name: Meschede, Dieter
name: Thau, Natalie
name: Yoon, Seokchan
name: Ratschbacher, Lothar
Publisher: name: arXiv
Year: 2014
Subjects: subject: Atomic Physics (physics.atom-ph)
subject: Quantum Physics (quant-ph)
subject: FOS: Physical sciences

description: We experimentally realize an enhanced Raman control scheme for neutral atoms that features an intrinsic suppression of the two-photon carrier transition, but retains the sidebands which couple to the external degrees of freedom of the trapped atoms. This is achieved by trapping the atom at the node of a blue detuned standing wave dipole trap, that acts as one field for the two-photon Raman coupling. The improved ratio between cooling and heating processes in this configuration enables a five times lower fundamental temperature limit for resolved sideband cooling. We apply this method to perform Raman cooling to the two-dimensional vibrational ground state and to coherently manipulate the atomic motion. The presented scheme requires minimal additional resources and can be applied to experiments with challenging optical access, as we demonstrate by our implementation for atoms strongly coupled to an optical cavity.
description: 12 pages, 5 figures
NADPH Oxidase Pathway Is Involved in Aortic Contraction Induced by A3 Adenosine Receptor in Mice
Creators: name: Tilley, S. L.
name: Mustafa, S. J.
name: El-Awady, M. S.
name: Ansari, H. R.
name: Fil, D.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2011

description: The NADPH oxidase (Nox) subunits 1, 2 (gp91 phox), and 4 are the major sources for reactive oxygen species (ROS) in vascular tissues. In conditions such as ischemia-reperfusion and hypoxia, both ROS and adenosine are released, suggesting a possible interaction. Our aim in this study was to examine the A3 adenosine receptor (A3AR)-induced vascular effects and its relation to ROS and Nox1, 2, and 4 using aortic tissues from wild-type (WT) and A3AR knockout (A3KO) mice. The selective A3AR agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IBMECA) (10−10–10−5 M) induced contraction of the aorta from WT but not from A3KO mice, and this contraction was inhibited by the Nox inhibitor apocynin (10−5 M) and the ROS scavengers superoxide dismutase-polyethylene glycol and catalase-polyethylene glycol (100 U/ml each). Cl-IBMECA-induced contraction was not affected by the mast cell degranulator compound 48/80 (100 μg/ml) or the stabilizer cromolyn sodium (10−4 M). In addition, Cl-IBMECA (10−7 M) increased intracellular ROS generation by 35 ± 14% in WT but not in A3KO aorta, and this increase was inhibited by apocynin (10−5 M), diphenyleneiodonium chloride (10−5 M), and the A3AR antagonist 3-propyl-6-ethyl-5-[(ethylthio)carbonyl]-2 phenyl-4-propyl-3-pyridine carboxylate (MRS1523) (10−5 M). Furthermore, Cl-IBMECA selectively increased the protein expression of the Nox2 subunit by 150 ± 15% in WT but not in A3KO mice without affecting either Nox1 or 4, and this increase was inhibited by apocynin. The mRNA of Nox2 was unchanged by Cl-IBMECA in either WT or A3KO aortas. In conclusion, A3AR enhances ROS generation, possibly through activation of Nox2, with subsequent contraction of the mouse aorta.
The Relationships between Anatomical Brain Structure and Risky Behaviors
Creators: name: Jung, Wi Hoon
name: Aydogan, Gökhan
name: Kable, Joe
name: Linnér, Richard Karlsson
name: Daviet, Remi
name: Nave, Gideon
name: Koellinger, Philipp D.
Publisher: name: OSF Registries
Year: 2020
Subjects: Brain
Drinking
Risk tolerance
Risky behaviors
Smoking
UK Biobank

description: We plan to empirically test the relationship between anatomical differences in specific brain regions and behavioral outcomes related to risky behaviour in the field. Specifically, we want to identify neuro-anatomical differences (i.e. cortical thickness, gray and white matter volume) that are robustly associated to risky behaviour (RB) across several domains. Attitudes toward risk substantially differ across individuals. Given their importance in decisions related to health and financial outcomes, risk attitudes have received much attention in economics and related fields in the social sciences. Thus, we believe that the results will be informative for a broader audience, and specifically to scientists in the realms of biology, psychology, neuroscience, social science and business. In this study, we plan to address the following research questions: (1) Are specific brain areas more strongly linked to risky behaviour (RB) than expected by chance? (2) Is it possible to predict RB from anatomical brain structure? (3) Do brain images add predictive accuracy for RB to that obtained from socio-demographic and other variables?