bluuebunny/crossref_metadata_2025 huggingface dataset:
Urban Political Ecology. Great Promises, Deadlock… and New Beginnings?
Authors: Swyngedouw Erik , Kaika Maria
Published: October 2014

The paper starts from the premise that it is vitally important to recognize that the rapid rate of planetary urbanization is the main driver of environmental change. Indeed, the ‘sustainability’ of contemporary urban life (understood as the expanded reproduction of its socio-physical form and functions) is responsible for 80% of the world’s use of resources and most of the world’s waste. We wish to highlight how these urban origins are routinely ignored in urban theory and practice, and how feeble techno-managerial attempts to produce more ‘sustainable’ forms of urban living are actually heightening the combined and uneven socio-ecological apocalypse that marks the contemporary dynamics of planetary urbanization. This paper is, therefore, not so much concerned with the question of nature IN the city, as it is with the urbanization OF nature, understood as the process through which all forms of nature are socially mobilized, economically incorporated and physically metabolized/transformed in order to support the urbanization process. First, we shall chart the strange history of how the relationship between cities and environments has been scripted and imagined over the last century or so. Second, we shall suggest how the environmental question entered urban theory and practice in the late 20th century. And, finally, we shall explore how and why, despite our growing understanding of the relationship between environmental change and urbanization and a consensual focus on the need for ‘sustainable’ urban development, the environmental conundrum and the pervasive problems it engenders do not show any sign of abating. We shall conclude by briefly charting some of the key intellectual and practical challenges ahead.
Pigeon, Martin; McDonald, David A.; Hoedeman, Olivier y Kishimoto, Satoko (eds.) (2013). Remunicipalización. El retorno del agua a manos públicas
Authors: Vallès Casas Maria
Published: October 2014

Pigeon, Martin; McDonald, David A.; Hoedeman, Olivier y Kishimoto, Satoko (eds.) (2013)Remunicipalización. El retorno del agua a manos públicasAmsterdam: Transnational Institute, 154 p.ISBN 978-94-6228-049-6
Presentació
Authors: Ribas Anna , Saurí David
Published: October 2014

Presentació. Ecologia política i gestió de l'aigua.
Nutritional Status in Patients with Chronic Pancreatitis
Authors: Kucheryavyy Yuriy A. , Andreev Dmitry N.
Published: October 2014

Chronic pancreatitis (CP) is defined as a continuing inflammatory disease of the pancreas that is characterized by irreversible morphological changes often associated with pain and the loss of exocrine and/or endocrine function, which may be clinically relevant. Maldigestion (absolute deficiency of pancreatic enzyme secretion) is a typical complication of CP of any etiology with long anamnesis. Fat malabsorption is considered to be the malnutrition base in CP patients. The purpose of this article is to evaluate the role of nutritive status and nutritive deficiency in CP patients, evaluate diagnostic approaches, correct nutritive status deviation with reference to previous experience, and explore the present situation and possible future perspectives.
Vitamin D - Beyond Bones: Its Relationship to Obesity, Metabolic Syndrome, and Diabetes
Authors: Wongvibulsin Shannon , Vazirani Sondra , Li Zhaoping , Heber David
Published: October 2014

While vitamin D has long been known as an essential nutrient for the prevention of bone disorders, vitamin D deficiency has recently been linked to a number of chronic disease states. This review analyzes the epidemiological, clinical, and mechanistic data concerning the relationship between vitamin D status and obesity, metabolic syndrome (MetS), and diabetes. The increased understanding of the role of vitamin D has promoted researchers to study vitamin D as a potential target for the prevention and treatment of multiple chronic diseases.
Thinking Globally, Acting Locally: Partiality, Preferences and Perspective
Authors: Oddie Graham
Published: October 2014

A rather promising value theory for environmental philosophers combines the well-known fitting attitude (FA) account of value with the rather less well-known account of value as richness. If the value of an entity is proportional to its degree of richness (which has been cashed out in terms of unified complexity and organic unity), then since natural entities, such as species or ecosystems, exhibit varying degrees of richness quite independently of what we happen to feel about them, they also possess differing degrees of mind-independent and subject-independent value. In particular, their value is not dependent on the desires or preferences of humans. The fitting attitudes account of value, at least as it is standardly developed, demands isomorphic evaluative responses on the part of all valuers. In particular, it entails that all valuers should have isomorphic preferences. But this seems absurd. I consider three different strategies with which the fitting attitude theorist can deflect this challenge. The first makes use of an account of non-standard value relations in terms of permissible preference orderings. The second appeals to value appearances and the associated notions of value distance and value perspective. The third involves an account of the ultimate bearers of value as properties, rather than as propositions or states of affairs. These strategies are not all mutually incompatible. While it isn’t possible to combine the first and second strategies, it is possible to combine the first and third strategies, and also to combine the second and the third.
Sur la symétrie présumée entre valeurs et préférences1
Authors: Rossi Mauro
Published: October 2014

Comment pouvons-nous analyser des relations de valeur non standards, comme la parité axiologique, en termes d’attitudes appropriées? Wlodek Rabinowicz suggère que deux choses sont à parité si et seulement si il est à la fois permissible de préférer l’une à l’autre et permissible d’avoir la préférence contraire. Dans un article récent, Johan Gustafsson soutient toutefois que l’analyse de Rabinowicz viole un principe de symétrie entre valeurs et préférences, selon lequel il existe pour toute relation de valeur une relation de préférence correspondante (et vice-versa). À la lumière de ce principe, Gustafsson propose une analyse alternative, selon laquelle deux choses sont à parité si et seulement si il est requis d’entretenir ces choses en parité préférentielle. Dans cet article, j’examine en détail les arguments avancés par Gustafsson contre l’analyse de Rabinowicz et je montre qu’aucun d’eux n’est convaincant.
Value Monism, Richness, And Environmental Ethics
Authors: Kelly Chris
Published: October 2014

The intuitions at the core of environmental ethics and of other neglected value realms put pressure on traditional anthropocentric ethics based on monistic value theories. Such pressure is so severe that it has led many to give up on the idea of monistic value theories altogether. I argue that value monism is still preferable to value pluralism and that, indeed, these new challenges are opportunities to vastly improve impoverished traditional theories. I suggest an alternative monistic theory, Richness Theory, and show how it provides an opportunity to capture the needs of both environmental ethics and of our traditional ethics.
Essence et fondation
Authors: Carnino Pablo
Published: October 2014

L’orthodoxie dans la littérature florissante au sujet de la fondation (grounding) suggère que cette notion ne peut être analysée ou exprimée en terme d’aucune autre. Par ailleurs, le primitivisme à propos de l’essence est considéré comme très plausible depuis l’article influent de Kit Fine à ce sujet1. Cela contraint les philosophes qui emploient ces deux notions à accepter une position doublement primitiviste. Mon objectif principal est de proposer une définition de la fondation en terme d’essence. Je commencerai par présenter la conception positive en question, puis je montrerai la façon dont elle répond à un certain nombre d’objections à son encontre. L’apport d’une telle approche, si elle est couronnée de succès, devrait être évident : les philosophes qui acceptent la fondation comme notion primitive n’auront plus à le faire, pour autant qu’ils emploient déjà la notion d’essence. Pour ceux qui refusaient de parler de fondation sous prétexte que la notion était indéfinissable, la présence d’une définition éliminera ipso facto leur raison d’être sceptique.
Sémantique formelle et engagement ontologique1
Authors: Giraud Thibaut
Published: October 2014

Je montrerai en premier lieu comment et pourquoi la sémantique formelle peut être employée comme un outil pour déterminer l’engagement ontologique d’une théorie : je soutiendrai d’une part que la sémantique doit être prise au sérieux comme apte à décrire la vérifaction des formules du langage; d’autre part, que les engagements ontologiques d’une théorie sont déterminés par ses vérifacteurs. De là, j’exposerai une méthode générale permettant, étant donné un certain type d’ontologie, de construire une sémantique dont les engagements ontologiques sont en accord avec celle-ci. Pour cela, je définirai la notion de cadre ontologique : il s’agit d’une structure telle que toute sémantique cons-truite à partir de cette structure aura un certain engagement ontologique déterminé à l’avance. J’exposerai quatre cadres représentant deux types de nominalisme et deux types de réalisme, et j’esquisserai à partir de ces cadres quatre sémantiques pour les langages du premier ordre.
TORC2-dependent protein kinase Ypk1 phosphorylates ceramide synthase to stimulate synthesis of complex sphingolipids
Authors: Muir Alexander , Ramachandran Subramaniam , Roelants Françoise M , Timmons Garrett , Thorner Jeremy
Published: October 2014

Plasma membrane lipid composition must be maintained during growth and under environmental insult. In yeast, signaling mediated by TOR Complex 2 (TORC2)-dependent protein kinase Ypk1 controls lipid abundance and distribution in response to membrane stress. Ypk1, among other actions, alleviates negative regulation of L-serine:palmitoyl-CoA acyltransferase, upregulating production of long-chain base precursors to sphingolipids. To explore other roles for TORC2-Ypk1 signaling in membrane homeostasis, we devised a three-tiered genome-wide screen to identify additional Ypk1 substrates, which pinpointed both catalytic subunits of the ceramide synthase complex. Ypk1-dependent phosphorylation of both proteins increased upon either sphingolipid depletion or heat shock and was important for cell survival. Sphingolipidomics, other biochemical measurements and genetic analysis demonstrated that these modifications of ceramide synthase increased its specific activity and stimulated channeling of long-chain base precursors into sphingolipid end-products. Control at this branch point also prevents accumulation of intermediates that could compromise cell growth by stimulating autophagy.
FRET Imaging by Laser Scanning Cytometry on Large Populations of Adherent Cells
Authors: Doan‐Xuan Quang‐Minh , Szalóki Nikoletta , Tóth Katalin , Szöllősi János , Bacso Zsolt , Vámosi György
Published: October 2014

The application of FRET (fluorescence resonance energy transfer) sensors for monitoring protein‐protein interactions under vital conditions is attracting increasing attention in molecular and cell biology. Laser‐scanning cytometry (LSC), a slide‐based sister procedure to flow cytometry, provides an opportunity to analyze large populations of adherent cells or 2‐D solid tissues in their undisturbed physiological settings. Here we provide an LSC‐based three‐laser protocol for high‐throughput ratiometric FRET measurements utilizing cyan and yellow fluorescent proteins as a FRET pair. Membrane labeling with Cy5 dye is used for cell identification and contouring. Pixel‐by‐pixel and single‐cell FRET efficiencies are calculated to estimate the extent of the molecular interactions and their distribution in the cell populations examined. We also present a non‐high‐throughput donor photobleaching FRET application, for obtaining the required instrument parameters for ratiometric FRET. In the biological model presented, HeLa cells are transfected with the ECFP‐ or EYFP‐tagged Fos and Jun nuclear proteins, which heterodimerize to form active AP1 transcription factor. Curr. Protoc. Cytom. 70:2.23.1‐2.23.29. © 2014 by John Wiley & Sons, Inc.
Asymmetric braking and dawnward deflection of dipolarization fronts: Effects of ion reflection
Authors: Zhou Xu‐Zhi , Angelopoulos Vassilis , Liu Jiang , Runov Andrei , Pan Dong‐Xiao
Published: October 2014

Dipolarization fronts (DFs), earthward propagating structures in the Earth's magnetotail with sharp enhancements of the northward magnetic field, can reflect and accelerate ions in the ambient plasma sheet. The ion reflection and acceleration process, which generates earthward flows ahead of the DF, also imposes a dynamic pressure on the DF to decelerate its earthward motion. It has been shown that the ion reflection process is not symmetric, with stronger ion accelerations at the evening side of the DF than at its morning side, which implies dawn‐dusk asymmetric reaction of the ambient plasma and consequently dawnward deflection of DFs. In this paper, we examine this scenario in detail, by carrying out statistical studies based on Time History of Events and Macroscale Interactions during Substorms observations from 2008 to 2011. We demonstrate the important role of the ion reflection process in the longstanding problems regarding DF evolution and bursty flow braking in the near‐Earth plasma sheet.
Inferring methane fluxes at a larch forest using Lagrangian, Eulerian, and hybrid inverse models
Authors: Ueyama Masahito , Takanashi Satoru , Takahashi Yoshiyuki
Published: October 2014

Measuring methane (CH4) flux at upland forests is challenging due to high levels of heterogeneity in upscaling chamber measurements and the detection limits of currently available micrometeorological methods. We estimated CH4 fluxes in an upland forest from vertical concentration profiles using three different inverse multilayer models: the Lagrangian localized near field theory, Eulerian, and hybrid Lagrangian‐Eulerian models. The approach could estimate spatially representative fluxes, and use of higher gradients within canopies than above them could minimize uncertainties associated with sensor noises. Comparing fluxes by the models and measurements by the micrometeorological hyperbolic relaxed eddy accumulation and chamber methods, daytime fluxes were reasonably reproduced, but nighttime fluxes were overestimated most likely due to an underestimation of stable conditions and storage effects. The models and measurements show that the forest acted as a CH4 sink during the study period, and the soil acted as the dominant sink. The estimated sink increased with increasing soil temperatures and decreasing soil water content. The CH4 sink estimated during the study period were 1.5 ± 0.2 nmol m−2 s−1 by the micrometeorological method, 2.4 ± 0.5 nmol m−2 s−1 by chambers, 2.8 ± 1.1 nmol m−2 s−1 by the Lagrangian model, 2.7 ± 1.0 nmol m−2 s−1 by the Eulerian model, and 3.7 ± 2.8 nmol m−2 s−1 by the hybrid model. The performance of the Lagrangian and hybrid models increased when the CH4 sink/source was assumed to only exist in the soil.
Abacavir
Authors: Zhang Zhi‐Yi
Published: October 2014

Abacavir (brand name: Ziagen), [(1
S
,4
R
)‐4‐[2‐amino‐6‐(cyclopropylamino)purin‐9‐yl]cyclopent‐2‐en‐1‐yl]methanol, is a reverse transcriptase inhibitor often used in combination with other drugs to treat HIV‐1 infection. In vitro, the drug undergoes alcohol dehydrogenase (ADH)‐mediated oxidation to form carboxylic acid metabolite and phosphorylation in lymphocytes. The oxidative biotransformation has been associated to the drug‐induced adverse effect, whereas the phosphorylation postulated to augment the antiviral action. In vivo, abacavir exhibited extensive liver metabolism and the major metabolites identified were carboxylic acid and
O
‐glucuronide. Abacavir and the related substances were recovered in excreta completely, with majority in urine. Therefore, the principal mechanism of abacavir clearance in humans is hepatic metabolism, comprising ADH‐mediated oxidation and O‐glucuronidation conjugated with the β,γ‐unsaturated hydroxyl group.
Aliskiren
Authors: Gao Ruina
Published: October 2014

Aliskiren is a direct renin inhibitor used for the treatment of hypertension. Primary metabolic pathway of aliskiren in humans is shown. Metabolites are formed by O‐desmethylation and further oxidation, O‐dealkylation and further glucuronidation, amide hydrolysis and further lactone formation, aromatic hydroxylation, and N‐acetylation.
Amiodarone
Authors: Yuan Tao
Published: October 2014

Amiodarone is an antiarrhythmic drug used to treat supraventricular and ventricular arrhythmias. In vitro and in vivo metabolic pathways of amiodarone in humans are shown. Two major metabolites, mono‐
N
‐desethyl amiodarone and 3′‐hydroxyl‐mono‐
N
‐desethyl amiodarone, and two minor metabolites, di‐
N
‐desethyl amiodarone and deaminated amiodarone, were detected in plasma of patients orally receiving amiodarone.
Aniracetam
Authors: Yu Yang
Published: October 2014

Aniracetam is a pyrrolidinone derivative used as a cognition enhancer for the treatment of Alzheimer's disease and other neurodegenerative conditions. In vivo metabolic pathways of aniracetam in rats, dogs, and humans are shown. After oral and i.v. administrations of [
14
C]‐aniracetam to human subjects, approximately 84, 0.8, and 11% of the radioactive dose was recovered in urine, feces, and expired air (as
14
CO
2
), respectively, within 48 h. Approximately 70% of the dose was metabolized to 4‐
p
‐anisamidobutyric acid and excreted via urine. The remaining 30% of the dose was metabolized to 2‐pyrrolidinone and anisic acid. Further hydroxylation and oxidation of 2‐pyrrolidinone yielded 5‐hydroxy‐2‐pyrrolidinone and succinimide. Anisic acid was excreted mainly as glycine and glucuronide conjugates in urine.
Atazanavir
Authors: Xu Lin
Published: October 2014

Atazanavir, an HIV‐1 protease inhibitor, was extensively metabolized in humans and mice. Primary metabolic pathways in mice and humans were similar and they included hydroxylation, N‐dealkylation, dehydrogenation, hydrolysis, and glucuronide or sulfate conjugations. Monohydroxylated metabolite (
6
) was the major circulating metabolite in humans.
Benazepril
Authors: Xu Lin
Published: October 2014

Benazepril is an ethyl ester prodrug of benazeprilat to improve its bioavailability. Two primary biotransformation pathways were observed. Benazepril metabolized extensively to benazeprilat via ester hydrolysis, acyglucuronide conjugates of benazepril, and benazeprilat.
Carvedilol
Authors: Yang Yong , Yu Jinghua
Published: October 2014

Carvedilol is a nonselective β‐blocker/α‐blocker used in the treatment of mild to moderate congestive heart failure. The in vitro metabolism of carvedilol was investigated in dog, rat, and human liver microsomes, human intestinal microsomes, as well as recombinant human cytochrome P450, and UDP‐glucuronosyltransferases. O‐Demethylation and aryl hydroxylation were major metabolic reactions, which were catalyzed by CYP2C9, 2D6, 1A2, 3A4, and 2E1. O‐Glucuronidation was catalyzed mainly by UGT1A1, 2B4, and 2B7. The metabolism of [
14
C]‐carvedilol was studied in healthy male volunteers after a single oral dose of 50 mg. The mean total radioactivity recovered in urine represented 82% of the administered dose. Carvedilol was extensively metabolized and the unchanged drug in urine accounted for <2% of the dose.
N
‐Glucuronide conjugate at the nitrogen of the carbazol substructure was identified as the major metabolite. Other minor metabolic reactions observed include oxidative ether cleavage of side chain, O‐demethylation, O‐glucuronide/sulfate conjugation, and aryl hydroxylation.
Cidofovir
Authors: Zhong Kan
Published: October 2014

Cidofovir is an analog of deoxycytidine monophosphate with potent antiherpesvirus activity. The in vitro metabolism of cidofovir was investigated with the human T cells. It was metabolized via phosphorylation to form cidofovir phosphate, cidofovir diphosphate (the active form), and cidofovir‐phosphocholine. The long intracellular half‐lives of these phosphorylated metabolites are responsible for the prolonged action of cidofovir. The metabolism of [
14
C]‐cidofovir was investigated in rabbits, rats, and monkeys. Seven days after an intravenous administration of [
14
C]‐cidofovir in cynomolgus monkeys, urinary recovery was >90% of the total radioactive dose. Cidofovir accounted for 98% of the urinary radioactivity, and cidofovir phosphocholine was the only metabolite detected.
Erlotinib
Authors: Xie Cen
Published: October 2014

Erlotinib is a small‐molecule epidermal growth factor receptor inhibitor used to treat refractory locally advanced and metastatic cell lung cancer. Rapid absorption of the administered [
14
C‐quinazoline]‐erlotinib was observed in four healthy male volunteers after a single oral dose of 100 mg. Erlotinib was extensively metabolized in humans with <2% of the unmetabolized parent recovered. Primary metabolic reactions included O‐demethylation, oxidation of the acetylene moiety, aryl hydroxylation, and the subsequent conjugation of the phenolic metabolites. Further metabolism of the primary metabolites was also observed. Phase II conjugation of the oxidative metabolites yielded glucuronides and sulfate as minor metabolites. Major fecal metabolites detected were the carboxylic acid from oxidation of an O‐demethylation metabolite (29% of the administered radioactivity) and an O‐demethylation metabolite (21%).
Ezlopitant
Authors: Prakash Chandra
Published: October 2014

Ezlopitant, (2
S
,3
S
)‐2‐benzhydryl‐
N
‐[(5‐isopropyl‐2‐methoxy‐phenyl)methyl]quinuclidin‐3‐amine, is a neurokinin receptor antagonist. It is extensively metabolized in humans, as no unchanged drug was detected in urine and feces. The metabolic pathways were due to oxidation and dehydrogenation at the isopropyl group, O‐demethylation, oxidative dealkylation of the 2‐benzhydryl‐1‐aza‐bicyclo[2.2.2]oct‐3‐yl moiety, and oxidation at the quincludine moiety.
Sildenafil
Authors: Gao Chunying
Published: October 2014

Sildenafil is a potent and selective inhibitor of type 5 phosphodiesterase. It is used mainly for erectile dysfunction treatment. Piperazine
N
‐desmethyl sildenafil and pyrazole
N
‐desmethyl sildenafil were identified as the main circulating metabolites in human after both intravenous and oral administration of [
14
C]‐sildenafil. In human feces, sildenafil was not detected. Piperazine
N
‐desmethyl sildenafil, piperazine ring‐opening product, and 15 other minor metabolites were detected. Among them, the piperazine ring‐opening metabolite was the major component in fecal extracts from human, accounting for 22% of the dose. In human urine, the aliphatic hydroxylated metabolite was identified to be a major component (41% of the urinary radioactivity and 5% of the administered radioactivity). Eight other radioactive components were detected in urine, each accounting for <2% of the dose.
Finasteride
Authors: Du Jiangbo
Published: October 2014

Finasteride is a 5α‐reductase type II inhibitor used in the treatment of benign prostatic hyperplasia and pattern baldness. After oral administration in healthy human volunteers, 39 and 57% of the administered [
14
C]‐finasteride dose were recovered in urine and feces, respectively. Less than 1% of the finasteride dose was excreted unchanged. The metabolite ω‐hydroxy finasteride was the major circulating metabolite (12% of the total radioactivity), and finasteride‐ω‐oic acid was the major metabolite detected in urine (18%). Further metabolites observed were 6α‐OH finasteride and its glucuronide conjugate, and the glucuronide conjugate of the acid metabolite.
Flunitrazepam
Authors: Zhou Xin
Published: October 2014

Flunitrazepam is a potent hypnotic, sedative, and amnestic drug used to treat severe insomnia. The metabolic and excretion profiles of flunitrazepam were studied in human volunteers after administration of 2.0 mg. A total of eight primary urinary metabolites were observed. Major metabolic pathways observed were N‐demethylation, 3‐hydroxylation, nitro‐reduction, and further N‐acetylation of the amino group, yielding N‐desmethylflunitrazepam, 3‐hydroxy‐flunitrazepam, 7‐aminoflunitrazepam, and 7‐acetamidoflunitrazepam, respectively. These metabolites were also detected in plasma. A combination of these reactions yielded 7‐aminodesmethylflunitrazepam, 7‐acetamidodesmethylflunitrazepam, 3‐hydroxy‐7‐aminoflunitrazepam, and 3‐hydroxy‐7‐acetamidoflunitrazepam.
Sertraline
Authors: Yu Jinghua
Published: October 2014

Sertraline is an antidepressant of the selective serotonin reuptake inhibitor class. N‐Desmethylation was the primary metabolic reaction found in humans. Oxidative deamination (sertraline ketone) and
N
‐methyl carboxylation products were also detected. The phase II metabolite detected was sertraline
N
‐carbamoyl glucuronide.
Buspirone
Authors: Zhong Kan
Published: October 2014

Buspirone is a potent and selective 5‐HT
1A
receptor partial agonist. It is used to treat anxiety disorders. After a single oral dose (20 mg) of [
14
C/
15
N]‐buspirone to human subjects, urine samples were collected and, approximately, 50% of the radioactivity was recovered. An
N
‐dealkylation metabolite is the most abundant metabolite in human urine, accounting for 38% of the
14
C excreted. Three major metabolic routes were identified: hydroxylation at C‐5 on pyrimidine ring, hydroxylation at C‐6′ on bicyclo ring, and N‐dealkylation.
Berberine
Authors: Chen Meixia
Published: October 2014

Berberine is an isoquinoline alkaloid drug used orally for various parasitic and fungal infections. The metabolism of berberine was investigated in urine of 12 healthy male volunteers. After an oral administration of 300 mg, seven metabolites were identified in urine. The primary metabolic reactions were opening of the dioxolane ring and O‐demethylation. The identified metabolites included sulfate or glucuronide conjugates of the phase I metabolites.
Sumatriptan
Authors: Chen Meixia
Published: October 2014

Sumatriptan is a serotonin agonist used to treat headache, nausea, sensitivity to light and sound, and other migraine symptoms. The metabolism of [
14
C]‐sumatriptan was studied in healthy male volunteers after an oral administration. The major metabolite was sumatriptan carboxylic acid (oxidative deamination catalyzed by MAO‐A and further oxidation). Its glucuronide conjugate was present as a minor metabolite.
Zibotentan
Authors: Zhou Xin
Published: October 2014

Zibotentan is an endothelin receptor antagonist used to treat castration‐resistant prostate cancer. The disposition and metabolism of zibotentan were investigated in healthy subjects following a single oral dose of 15‐mg [
14
C]‐zibotentan. Unchanged drug was the primary circulating radioactive component. About 82% of the radioactivities were eliminated in urine. Major metabolites found in plasma, urine, and feces were despyrazine zibotentan by N‐dealkylation, hydroxymethyl zibotentan, hydroxyl zibotentan (hydroxylation at the oxadiazol moiety), biaryl acid zibotentan, and despyrazine biaryl acid zibotentan. CYP3A4 was the major isoform that mediated the biotransformation of zibotentan.
(2
S
)‐Pterosin
A
Authors: Chen Meixia
Published: October 2014

(2
S
)‐Pterosin A is a sesquiterpene natural product found in bracken. It exhibits antihypoglycemic activity. Metabolism of (2
S
)‐pterosin A was investigated in male Wistar rats following an oral dose. Primary metabolic reactions included the oxidation of the hydroxyethyl moiety to the corresponding acid, oxidation/decarboxylation of the hydroxymethyl moiety of the cyclopentanyl ring, hydroxylation of the cyclopentanyl ring, hydroxylation/oxidation of the C‐13 benzylic methyl group, lactonization, and glucuronide conjugation. Numerous metabolites were derived from these primary and secondary metabolic reactions.
Antipyrine
Authors: Liu Ying
Published: October 2014

Antipyrine is a pain reliever with both analgesic and antipyretic activities. After a single oral dose of 1200 mg antipyrine to humans, aryl hydroxylation, hydroxylation of the methyl‐pyrazole moiety, and
N
‐demethylation were initial phase I metabolic reactions. Phase II metabolites of antipyrine were also identified in human urine. Glucuronide conjugation was the predominant phase II metabolic pathway of antipyrine in humans.
Paclitaxel
Authors: Xu Qiufang
Published: October 2014

Paclitaxel is a taxoid mitotic inhibitor used in the therapy of breast, ovarian, and lung cancers. In vivo metabolism of paclitaxel was studied in a female patient with severe renal impairment and recurrent ovarian cancer following intravenous injection of [3H]‐paclitaxel. About 53% of the radioactive dose was excreted in feces, which was mainly composed of mono‐ and dihydroxylated metabolites. Unchanged drug excreted in urine and feces accounted for 2% and 6% of the total dose, respectively. The major metabolite detected in feces was 6α‐hydroxypaclitaxel, whereas 3′‐p‐hydroxypaclitaxel, 3′‐
p
,6α‐dihydroxypaclitaxel, baccatin, and 10‐deacetylbaccatin were minor metabolites identified.
Thalidomide
Authors: Penner Natasha
Published: October 2014

Thalidomide is mainly eliminated via spontaneous hydrolysis in vivo. Degradation products containing the intact phthalimide moiety exhibited teratogenic activity.
Ranitidine
Authors: Ding Juefang
Published: October 2014

Ranitidine is a histamine H2‐receptor antagonist that inhibits stomach acid production. It is commonly used in the treatment of peptic ulcer disease and gastroesophageal reflux disease. In human, approximately 68% of the intravenous (i.v.) dose and 27% of the oral dose were excreted unchanged in urine in the first 24 h. Early metabolite profiling data showed that 7 and 9% of the dose were recovered as metabolites, respectively. Limited human metabolism of ranitidine was evidenced, with metabolites ranitidine
N
‐oxide, ranitidine
S
‐oxide, and desmethylranitidine accounting for only 4, 1, and 1% of the dose, respectively.
Roflumilast
Authors: Yu Jinghua
Published: October 2014

Roflumilast is a selective, long‐acting inhibitor of the enzyme PDE4 for the treatment of chronic obstructive pulmonary disease such as asthma. The excretion of roflumilast in humans after oral or intravenous (i.v.) administration occurred mainly as urinary metabolites (70% of the dose). The fecal elimination accounted for approximately 20% of the dose. Human metabolism studies showed that roflumilast was extensively metabolized via both phase I and phase II reactions. The major metabolite found in human plasma was roflumilast
N
‐oxide. Its formation was catalyzed mainly by CYP3A4 and 1A2. Major metabolites identified in urine were glucuronides of roflumilast N‐oxide and of a monohydroxylated roflumilast.
Nevirapine
Authors: Zhou Xin
Published: October 2014

Nevirapine is a non‐nucleoside reverse transcriptase inhibitor used to treat HIV‐1 infection and AIDS. The biotransformation of nevirapine was conducted in eight healthy male volunteers after oral dose of [
14
C]‐nevirapine. At maximum plasma concentration, parent compound accounted for 75% of the circulating radioactivity. CYP metabolism, glucuronide conjugation, and urinary excretion of glucuronidated metabolites represent the primary metabolic route. Metabolites 3‐hydroxy nevirapine (1%), 12‐hydroxy nevirapine (0.6%), glucuronide of 2‐hydroxy nevirapine (19%), glucuronide of 3‐hydroxy nevirapine (26%), glucuronde of 8‐hydroxy nevirapine (1%), glucuronide of 12‐hydroxy nevirapine (24%), and 12‐carboxy nevirapine (2%) were detected in urine. Two mercapturates were also detected in the urine of HIV‐positive patients undergoing standard antiretroviral chemotherapy.
3‐
n
‐Butylphthalide
Authors: Xingxing Diao
Published: October 2014

3‐
n
‐Butylphthalide (NBP) is one of the chemical constituents in celery oil. It exhibits pharmacological properties that are useful in the treatment of hypertension. The metabolism and excretion of NBP were studied in four healthy Chinese male volunteers after a single oral administration of 200 mg. A total of 23 metabolites were observed in human plasma and urine. Pharmacokinetics data revealed the presence of four major side‐chain hydroxylated metabolites in human plasma. The biological activities of these metabolites were higher than that of NBP. Other minor phase I metabolic reactions were opening of the lactone ring, aryl hydroxylation, and β‐oxidation. Numerous phase II metabolites (glucuronide and sulfate conjugates) were also identified. About 82% of the administered dose was excreted in human urine. Predominant metabolic pathways of NBP were ω‐carboxylation followed by acyl glucuronide conjugation and glucuronide conjugation of monohydroxylated NBP.
Famitinib
Authors: Xie Cen
Published: October 2014

Famitinib is a multitargeted receptor tyrosine kinase inhibitor under clinical development for the treatment of carcinoma. The metabolism and excretion of famitinib were investigated in cancer patients after repeated oral administration. Famitinib was extensively metabolized, and the primary routes of oxidative metabolism were N‐desethylation, oxidative deamination, oxidative defluorination, hydrogenation, indolylidene or methylpyrrolo‐dihydropyridone hydroxylation, and N‐oxidation.
N
‐Desethylfamitinib was further oxidative defluorinated, hydroxylated at indolylidene, and hydrogenated. The hydrogenated metabolites were further hydroxylated at the exocyclic methylene. The hydroxyl metabolites or the parent drug underwent subsequent phase II conjugations, including sulfates and glucuronides. In addition, two cysteine conjugates were detected. The unchanged famitinib was the predominant component in circulation. At steady state, the daily recovery of famitinib and the identified major metabolites was 14% of the administered dose in urine and 56% in feces.
Flutamide
Authors: Zhou Xin
Published: October 2014

Flutamide is an oral nonsteroidal antiandrogen drug primarily used to treat prostate cancer. The in vivo metabolism of flutamide was studied in patients with prostate cancer receiving oral dosing (125 mg, thrice daily). Circulating metabolites detected were a side‐chain monohydroxylation metabolite and the amide hydrolysis metabolite and its
N
‐acetyl conjugate. Major metabolites found in urine were side‐chain mono‐ and trihydroxylation metabolites, and the further aryl hydroxylation product of the amide hydrolysis metabolite. Nitro‐reduction to the corresponding amine was also an important metabolic reaction. In a separate human metabolism study, after an oral dose of 250‐mg flutamide, sulfate, GSH, and glucuronide conjugates of flutamide and its hydroxylated metabolites were also identified in urine.
Gemopatrilat
Authors: Meng Jian
Published: October 2014

Gemopatrilat is a vasopeptidase inhibitor involved in the regulation of cardiovascular functions. It is used for the treatment of cardiovascular and renal diseases. Metabolism of [
14
C]‐gemopatrilat was studied in humans after oral administration. Major metabolites in the non‐dithiothreitol (DDT)‐reduced plasma were the amine‐side chain hydrolysis product and its
N
‐acetylated analog, and
S
‐methyl gemopatrilat and its dimmer. They combined to account for above 30% of the administered radioactivity. The majority of unextractable radioactivity in plasma was identified after DDT reduction as gemopatrilat, apparently bound to sulfhydryl groups of plasma proteins by reversible disulfide bonds. Radioactivity recovered in human urine was 59%. Major metabolites in urine were (
S
)‐2‐thiomethyl‐3‐phenylpropionic acid, the cysteine disulfide adduct of gemopatrilat and its acyl glucuronide,
S
‐methyl gemopatrilat and its acyl glucuronide. Radioactivity recovered in feces was 19%. Gemopatrilat was extensively metabolized, as it was not detected in urine and feces.
Lurasidone
Authors: Du Jiangbo
Published: October 2014

Lurasidone is a new second‐generation antipsychotic used in the treatment of schizophrenia and bipolar disorder. The in vitro metabolism of [
14
C]‐lurasidone was investigated in liver microsomes and hepatocytes from mice, rats, rabbits, dogs, monkeys, and humans. Hydroxylation of cyclohexane ring or the norbornane ring, sulfur oxidation (yielded lurasidone S‐oxide and sulfone), and oxidative N‐dealkylation were the major metabolic pathways observed. Lurasidone sulfoxide was the major in vitro metabolite in all species. Other primary metabolic reactions observed in vivo were the opening of the thiazole ring (and S‐methylation), di‐ and trihydroxylations, and glucuronide conjugation. Combination of these metabolic reactions also yielded numerous secondary metabolites.
Sulindac
Authors: Du Jiangbo
Published: October 2014

Sulindac is a nonsteroidal anti‐inflammatory drug of the arylalkanoic acid class. It is used to reduce pain caused by arthritis, bursitis, gout, and tendinitis. The biotransformation of sulindac was investigated in rats, dogs, monkeys, and humans. The primary metabolic reactions were S‐oxidation of parent sulfoxide moiety to the corresponding sulfone and reversible reduction of sulfoxide to the sulfide. Sulindac sulfide is the pharmacologically active form of sulindac. Other metabolic reactions observed were the hydration of the parent double bond and methyl hydroxylation. Sulindac and its metabolites were also transformed as acyl glucuronide conjugates in urine.
Vabicaserin
Authors: Xie Cen
Published: October 2014

Vabicaserin is a potent 5‐hydroxytryptamine 2C receptor full agonist. It is currently under development for the treatment of psychotic symptoms. Vabicaserin was extensively metabolized in humans after oral administration of nonradiolabeled material. The primary biotransformation pathway of vabicaserin in humans was carbamoyl glucuronidation. The systemic exposure ratios of the carbamoyl glucuronide to parent drug ranged from 20 to 29. Minor plasma metabolites were isomers of hydroxyl vabicaserin, vabicaserin imine, vabicaserin nitrone, hydroxyl vabicaserin glucuronide, didehydrohydroxyl vabicaserin glucuronide, and hydroxyl vabicaserin imine. The urinary metabolic profile was similar to plasma profile, except that a hydroxyl vabicaserin carbamoyl glucuronide and two vabicaserin N‐glucuronides were observed in the urine.
Highly Stretchable Conductors Integrated with a Conductive Carbon Nanotube/Graphene Network and 3D Porous Poly(dimethylsiloxane)
Authors: Chen Mengting , Zhang Ling , Duan Shasha , Jing Shilong , Jiang Hao , Li Chunzhong
Published: October 2014

Here, a novel and facile method is reported for manufacturing a new stretchable conductive material that integrates a hybrid three dimensional (3D) carbon nanotube (CNT)/reduced graphene oxide (rGO) network with a porous poly(dimethylsiloxane) (p‐PDMS) elastomer (pPCG). This reciprocal architecture not only alleviates the aggregation of carbon nanofillers but also significantly improves the conductivity of pPCG under large strains. Consequently, the pPCG exhibits high electrical conductivity with a low nanofiller loading (27 S m−1 with 2 wt% CNTs/graphene) and a notable retention capability after bending and stretching. The simulation of the mechanical properties of the p‐PDMS model demonstrates that an extremely large applied strain (εappl) can be accommodated through local rotations and bending of cell walls. Thus, after a slight decrease, the conductivity of pPCG can continue to remain constant even as the strain increases to 50%. In general, this architecture of pPCG with a combination of a porous polymer substrate and 3D carbon nanofiller network possesses considerable potential for numerous applications in next‐generation stretchable electronics.
A mechanistic approach to tracing anthropometric charts: The extended mechanistic growth function method
Authors: Spada Elena , Gilli Giulio , Coscia Alessandra , Milani Silvano
Published: October 2014

Objectives

The Extended Mechanistic Growth Function (EMGF) method (Clementi et al. [1999]: Am J Med Genet 87:317–323) is a possible alternative to the Cole and Green LMS method ([1992] Stat Med 11:1305‐1319) to construct cross‐sectional anthropometric charts. It differs from the technique used by Kuczmarski et al. ([2002]: Vital Health Stat 11:1–190) to trace the CDC growth charts in that all centiles are simultaneously fitted with a single function. The aim of this study is to show how an EMGF model can be designed.

Methods

To illustrate the structure and properties of the EMGF method, the data of the Italian Neonatal Study (Bertino et al. [2010]: J Pediatr Gastroenterol Nutr 51:353–361) were analyzed. The dataset included the birth weight of 45,272 single liveborn babies with gestational ages ranging from 23 to 42 weeks. The EMGF method consists of three steps. In the preliminary step, selected age‐dependent raw centiles of the anthropometric trait are computed. In the smoothing step, all centiles are simultaneously fitted with a growth function extended with the inclusion of a few extra parameters. In the transformation step, estimates of the age‐dependent L (skewness), M (median), and S (coefficient of variation) parameters are derived.

Results

A four‐parameter generalized logistic function, extended with five parameters to model between‐sex differences, distance between centiles and their slope, was found to fit the raw centiles of birth weight distribution with a residual standard deviation of 51.3 g.

Conclusions

The EMGF method represents a bridge to link cross‐sectional and longitudinal studies and allows us to identify milestones of the median growth in a population in the same way used for individual profiles. Am. J. Hum. Biol. 27:175–183, 2015. © 2014 Wiley Periodicals, Inc.
Effects of obligatory training and prior training experience on attitudes towards performing basic life support: a questionnaire survey
Authors: Matsubara Hiroki , Enami Miki , Hirose Keiko , Kamikura Takahisa , Nishi Taiki , Takei Yutaka , Inaba Hideo
Published: October 2014

Aim

To determine the effect of Japanese obligatory basic life support training for new driver's license applicants on their willingness to carry out basic life support.

Methods

We distributed a questionnaire to 9,807 participants of basic life support courses in authorized driving schools from May 2007 to April 2008 after the release of the 2006 Japanese guidelines. The questionnaire explored the participants' willingness to perform basic life support in four hypothetical scenarios: cardiopulmonary resuscitation on one's own initiative; compression‐only cardiopulmonary resuscitation following telephone cardiopulmonary resuscitation; early emergency call; and use of an automated external defibrillator. The questionnaire was given at the beginning of the basic life support course in the first 6‐month term and at the end in the second 6‐month term.

Results

The 9,011 fully completed answer sheets were analyzed. The training significantly increased the proportion of respondents willing to use an automated external defibrillator and to perform cardiopulmonary resuscitation on their own initiative in those with and without prior basic life support training experience. It significantly increased the proportion of respondents willing to carry out favorable actions in all four scenarios. In multiple logistic regression analysis, basic life support training and prior training experiences within 3 years were associated with the attitude. The analysis of reasons for unwillingness suggested that the training reduced the lack of confidence in their skill but did not attenuate the lack of confidence in detection of arrest or clinical judgment to initiate a basic life support action.

Conclusions

Obligatory basic life support training should be carried out periodically and modified to ensure that participants gain confidence in judging and detecting cardiac arrest.
Unmodified and esterified Kraft lignin‐filled polyethylene composites: Compatibilization by free‐radical grafting
Authors: Hu Lei , Stevanovic Tatjana , Rodrigue Denis
Published: October 2014

In this study, the effectiveness of free‐radical grafting as a compatibilization method applied to composites containing Kraft lignin (KL) and esterified lignin was comparatively investigated. Maleated lignin (ML) was first obtained via esterification of KL with maleic anhydride. KL and ML were respectively incorporated into high density polyethylene (HDPE) up to 60% wt and dicumyl peroxide was used as a free‐radical generator. The influence of lignin esterification and free‐radical grafting on the morphological, mechanical, and thermal properties of lignin‐based composites was studied. The incorporation of lignins into HDPE resulted in poor mechanical strength because of low compatibility. Morphological and mechanical evidences indicate improved compatibility between lignins and HDPE following free‐radical grafting. The free‐radical scavenging properties of KL allowed better compatibilization of KL‐based composites compared with ML‐based composites. In addition, thermal analysis results showed that free‐radical grafting increases the thermal stability of ML‐based composites. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41484.
Einfluss der Einbaudicke auf die Festigkeit und Dauerhaftigkeit von zementgebundenem Vergussbeton
Authors: Breitenbücher Rolf , Benra Melanie
Published: October 2014

In der Richtlinie “Herstellung und Verwendung von zementgebundenem Vergussbeton und Vergussmörtel” des Deutschen Ausschusses für Stahlbeton [1] ist die Einbauhöhe für Vergussbetone auf das 25‐fache des Größtkorns beschränkt. Hintergrund sind Befürchtungen, dass sich der Beton bei größeren Einbaudicken so stark erwärmt, dass Festigkeitseinbußen, Mikrorisse und Beeinträchtigungen der Dauerhaftigkeit wie ein eingeschränkter Frostwiderstand oder eine potenzielle sekundäre Ettringitbildung auftreten.

In einem Forschungsprojekt, gefördert vom Deutschen Beton‐ und Bautechnik‐Verein E.V., wurden am Lehrstuhl für Baustofftechnik der Ruhr‐Universität Bochum die potenziellen Auswirkungen einer höheren Temperatur während der Erhärtung von Vergussbetonen mit großen Einbauhöhen auf die Festigkeit und Dauerhaftigkeit untersucht. Es zeigte sich, dass bei der derzeit begrenzten Einbauhöhe mehr oder weniger die gleichen thermischen Randbedingungen vorlagen wie bei größeren Einbauhöhen und sich keine signifikanten Auswirkungen auf die Festbetoneigenschaften zeigten [2].

Influence of casting thickness on the strength and durability of cementitious grouting concrete

In the Guideline ”Production and use of cementitious grouting concrete and grouting mortar" [1] by the German Committee for Structural Concrete, the casting thickness is limited to 25‐times of the maximum aggregate size. Background are concerns that concrete with a larger thickness heats up so intensively that loss in strength, microcracking and impairment of durability as e.g. reduced frost resistance or potential secondary ettringite formation become relevant.

In a research project, sponsored by the German Society for Concrete and Construction Technology, the Institute for Building Materials of the Ruhr‐University Bochum examined the effects of higher temperatures during hydratation of the cementitious grouting concrete with higher installation thickness on its strength and durability. It was found that, with the currently limited thickness, more or less the same thermal conditions are existent as with larger heights. Thus no impairs on the properties of hardened concrete could be observed [2].