bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of Recombinant Human Aldehyde Oxidase in Escherichia coli and Optimization of Its Application for the Preparative Synthesis of Oxidized Drug Metabolites
Authors: Rodrigues Diogo , Kittelmann Matthias , Eggimann Fabian , Bachler Thorsten , Abad Sandra , Camattari Andrea , Glieder Anton , Winkler Margit , Lütz Stephan 
Published: March 2014

AbstractRecombinant human aldehyde oxidase (AO) was expressed in Escherichia coli. Different cell disruption methods and conditions of cell culture in shake flasks and bioreactors and of biotransformation on an analytical scale were tested to optimize the synthesis of oxidized AO drug metabolites. The volumetric productivity was increased 24‐fold by optimizing the cell culture conditions. The highest yield was achieved in a 25 L stirred tank bioreactor under non‐oxygen‐limited conditions and high lactose feed rate. Suspensions of highly concentrated and well‐aerated whole cells at neutral pH and relatively low temperatures led to the best conversion. The solvent for the substrate and the buffering agent for the biotransformation had an important effect. In a biotransformation with AO, 210 mg of famciclovir was converted to diacetyl penciclovir a yield of 82 %. The optimized protocol represents a viable method for the preparative synthesis of oxidized AO metabolites of drugs.
Unraveling the Mechanism of Water Oxidation Catalyzed by Nonheme Iron Complexes
Authors: Acuña‐Parés Ferran , Codolà Zoel , Costas Miquel , Luis Josep M. , Lloret‐Fillol Julio 
Published: March 2014

AbstractDensity functional theory (DFT) is employed to: 1) propose a viable catalytic cycle consistent with our experimental results for the mechanism of chemically driven (CeIV) O2 generation from water, mediated by nonheme iron complexes; and 2) to unravel the role of the ligand on the nonheme iron catalyst in the water oxidation reaction activity. To this end, the key features of the water oxidation catalytic cycle for the highly active complexes [Fe(OTf)2(Pytacn)] (Pytacn: 1‐(2′‐pyridylmethyl)‐4,7‐dimethyl‐1,4,7‐triazacyclononane; OTf: CF3SO3) (1) and [Fe(OTf)2(mep)] (mep: N,N′‐bis(2‐pyridylmethyl)‐N,N′‐dimethyl ethane‐1,2‐diamine) (2) as well as for the catalytically inactive [Fe(OTf)2(tmc)] (tmc: N,N′,N′′,N′′′‐tetramethylcyclam) (3) and [Fe(NCCH3)(MePy2CH‐tacn)](OTf)2 (MePy2CH‐tacn: N‐(dipyridin‐2‐yl)methyl)‐N′,N′′‐dimethyl‐1,4,7‐triazacyclononane) (4) were analyzed. The DFT computed catalytic cycle establishes that the resting state under catalytic conditions is a [FeIV(O)(OH2)(LN4)]2+ species (in which LN4=Pytacn or mep) and the rate‐determining step is the OO bond‐formation event. This is nicely supported by the remarkable agreement between the experimental (ΔG≠=17.6±1.6 kcal mol−1) and theoretical (ΔG≠=18.9 kcal mol−1) activation parameters obtained for complex 1. The OO bond formation is performed by an iron(V) intermediate [FeV(O)(OH)(LN4)]2+ containing a cis‐FeV(O)(OH) unit. Under catalytic conditions (CeIV, pH 0.8) the high oxidation state FeV is only thermodynamically accessible through a proton‐coupled electron‐transfer (PCET) process from the cis‐[FeIV(O)(OH2)(LN4)]2+ resting state. Formation of the [FeV(O)(LN4)]3+ species is thermodynamically inaccessible for complexes 3 and 4. Our results also show that the cis‐labile coordinative sites in iron complexes have a beneficial key role in the OO bond‐formation process. This is due to the cis‐OH ligand in the cis‐FeV(O)(OH) intermediate that can act as internal base, accepting a proton concomitant to the OO bond‐formation reaction. Interplay between redox potentials to achieve the high oxidation state (FeVO) and the activation energy barrier for the following OO bond formation appears to be feasible through manipulation of the coordination environment of the iron site. This control may have a crucial role in the future development of water oxidation catalysts based on iron.
The First Heteropentanuclear Extended Metal‐Atom Chain: [Ni+Ru25+Ni2+Ni2+(tripyridyldiamido)4(NCS)2]
Authors: Huang Min‐Jie , Hua Shao‐An , Fu Ming‐Dung , Huang Gin‐Chen , Yin Caixia , Ko Chih‐Hung , Kuo Ching‐Kuo , Hsu Chia‐Hung , Lee Gene‐Hsiang , Ho Kuan‐Yi , Wang Chia‐Hsin , Yang Yaw‐Wen , Chen I‐Chia , Peng Shie‐Ming , Chen Chun‐hsien 
Published: March 2014

AbstractThis study develops the first heteropentametal extended metal atom chain (EMAC) in which a string of nickel cores is incorporated with a diruthenium unit to tune the molecular properties. Spectroscopic, crystallographic, and magnetic characterizations show the formation of a fully delocalized Ru25+ unit. This [Ru2]‐containing EMAC exhibits single‐molecule conductance four‐fold superior to that of the pentanickel complex and results in features of negative differential resistance (NDR), which are unobserved in analogues of pentanickel and pentaruthenium EMACs. A plausible mechanism for the NDR behavior is proposed for this diruthenium‐modulated EMAC.
Silicon‐Directed Rhenium‐Catalyzed Allylic Carbaminations and Oxidative Fragmentations of γ‐Silyl Allylic Alcohols
Authors: Chavhan Sanjay W. , Cook Matthew J. 
Published: March 2014

AbstractA highly regioselective allylic substitution of β‐silyl allylic alcohols has been achieved that provides the branched isomer as a single product. This high level of regiocontrol is achieved through the use of a vinyl silane group that can perform a Hiyama coupling providing 1,3‐disubstituted allylic amines. An unusual oxidative fragmentation product was also observed at elevated temperature that appears to proceed by a Fleming–Tamao‐type oxidation–elimination pathway.
Direct Synthesis of Benzofuro[2,3‐b]pyrroles through a Radical Addition/[3,3]‐Sigmatropic Rearrangement/Cyclization/Lactamization Cascade
Authors: Ueda Masafumi , Ito Yuta , Ichii Yuki , Kakiuchi Maiko , Shono Hiroko , Miyata Okiko 
Published: March 2014

AbstractA straightforward synthetic method for the construction of benzofuro[2,3‐b]pyrrol‐2‐ones by a novel domino reaction through a radical addition/[3,3]‐sigmatropic rearrangement/cyclization/lactamization cascade has been developed. The domino reaction of O‐phenyl‐conjugated oxime ether with an alkyl radical allows the construction of two heterocycles with three stereogenic centers as a result of the formation of two CC bonds, a CO bond, and a CN bond in a single operation, leading to pyrrolidine‐fused dihydrobenzofurans, which are not easily accessible by existing synthetic methods. Furthermore, asymmetric synthesis of benzofuro[2,3‐b]pyrrol‐2‐one derivatives through a diastereoselective radical addition reaction to a chiral oxime ether was also developed.
Chiroptical Phenomena in Reverse Micelles: The Case of (1R,2S)‐Dodecyl (2‐hydroxy‐1‐methyl‐2‐phenylethyl)dimethylammonium Bromide (DMEB)
Authors: Abbate Sergio , Passarello Marco , Lebon France , Longhi Giovanna , Ruggirello Angela , Turco Liveri Vincenzo , Viani Fiorenza , Castiglione Franca , Mendola Daniele , Mele Andrea 
Published: March 2014

ABSTRACT(1R,2S)‐Dodecyl(2‐hydroxy‐1‐methyl‐2‐phenylethyl)dimethylammonium bromide (DMEB) aggregates dispersed in carbon tetrachloride have been investigated by Fourier transform infrared (FT‐IR), vibrational circular dichroism (VCD) and 1H nuclear magnetic resonance (NMR) spectroscopy at various surfactant concentration and water‐to‐surfactant molar ratio. Experimental data indicate that, even at the lowest investigated concentration and in absence of added water, DMEB molecules associate in supramolecular assemblies. At higher DMEB concentration the aggregates can confine water molecules, making it plausible to think that DMEB form reverse micelles and that water molecules are quite uniformly distributed among them and mainly located in the proximity of surfactant head groups. Moreover, the water state in DMEB reverse micelles has been found to be different from that in pure water, due to system‐specific water/surfactant head group interactions. 1H NMR diffusion measurements of both water and DMEB emphasize their joined translational motion characterized by a diffusion rate one order of magnitude lower than that of free molecules. Finally, VCD allowed us to show some characteristics of the association of optically active DMEB molecules as reverse micelles and water confinement inside; namely, we monitored the vibrational optical activity of deuterated hydroxyl bonds of the self‐assembled DMEB molecules and their interaction with D2O molecules. Chirality 26:532–538, 2014.© 2014 Wiley Periodicals, Inc.
The Impact of Tower Internals on Packing Performance
Authors: Schultes Michael 
Published: March 2014

AbstractThe overall tower performance is influenced by the type of both tower internals and random packing. The Raschig GmbH's most recent development is the Raschig Super‐Ring®, the fourth generation of random packings. In 1998, the Raschig Super‐Ring No. 2 was tested at the facilities of Fractional Research Inc. A significantly improved capacity and pressure drop over other random packing was observed without reducing the efficiency. A recent retesting of Raschig Super‐Ring No.2 using new tower internals revealed that the revised tower internals further improved the performance. Raschig has noticeable experience in designing liquid distributors.
Liberation Measurements Used in Upgrading Curves
Authors: Leißner Thomas , Mütze Thomas , Peuker Urs Alexander 
Published: March 2014

AbstractDie Qualität von Aufbereitungsprodukten hängt von den Ergebnissen vieler Teilprozesse ab, zu deren Beschreibung eine Vielzahl von Modellen und Kennwerten existieren. Dieser Artikel stellt eine Erweiterung eines existierenden Modelles vor, mit der ein direkter Vergleich von Teilprozessen auf Basis von Wertstoffausbringen und Bergeausbringen möglich wird. Die Einführung eines neuen Aufschlusskennwertes und eines verbesserten Sortierkennwertes erlauben die Ermittlung der Parameter für Partikelgrößenklassen und damit eine Darstellung über der Partikelgröße als einen für die Aufbereitung wesentlichen Kennwert.
Synthesis and Biological Evaluation of 2‐Substituted‐5‐(4‐nitrophenylsulfonamido)benzoxazoles as Human GST P1‐1 Inhibitors, and Description of the Binding Site Features
Authors: Ertan‐Bolelli Tuğba , Musdal Yaman , Bolelli Kayhan , Yilmaz Serap , Aksoy Yasemin , Yildiz Ilkay , Aki‐Yalcin Esin , Yalcin Ismail 
Published: March 2014

AbstractGlutathione‐S‐transferases (GSTs) are enzymes involved in cellular detoxification by catalyzing the nucleophilic attack of glutathione (GSH) on the electrophilic center of numerous of toxic compounds and xenobiotics, including chemotherapeutic drugs. Human GST P1‐1, which is known as the most prevalent isoform of the mammalian cytosolic GSTs, is overexpressed in many cancers and contributes to multidrug resistance by directly conjugating to chemotherapeutics. It is suggested that this resistance is related to the high expression of GST P1‐1 in cancers, thereby contributing to resistance to chemotherapy. In addition, GSTs exhibit sulfonamidase activity, thereby catalyzing the GSH‐mediated hydrolysis of sulfonamide bonds. Such reactions are of interest as potential tumor‐directed prodrug activation strategies. Herein we report the design and synthesis of some novel sulfonamide‐containing benzoxazoles, which are able to inhibit human GST P1‐1. Among the tested compounds, 2‐(4‐chlorobenzyl)‐5‐(4‐nitrophenylsulfonamido)benzoxazole (5 f) was found as the most active hGST P1‐1 inhibitor, with an IC50 value of 10.2 μM, showing potency similar to that of the reference drug ethacrynic acid. Molecular docking studies performed with CDocker revealed that the newly synthesized 2‐substituted‐5‐(4‐nitrophenylsulfonamido)benzoxazoles act as catalytic inhibitors of hGST P1‐1 by binding to the H‐site and generating conjugates with GSH to form S‐(4‐nitrophenyl)GSH (GS–BN complex) via nucleophilic aromatic substitution reaction. The 4‐nitrobenzenesulfonamido moiety at position 5 of the benzoxazole ring is essential for binding to the H‐site and for the formation of the GST‐mediated GSH conjugate.
Cytotoxic Gold(I) N‐heterocyclic Carbene Complexes with Phosphane Ligands as Potent Enzyme Inhibitors
Authors: Rubbiani Riccardo , Salassa Luca , de Almeida Andreia , Casini Angela , Ott Ingo 
Published: March 2014

AbstractOrganometallic gold complexes with N‐heterocyclic carbene (NHC) ligands have been demonstrating promising properties as novel anticancer agents. Gold(I) NHC complexes containing different phosphanes as secondary ligands were shown to trigger strong cytotoxic effects in cancer cells, and their effective uptake into the cells was quantified by atomic absorption spectroscopy. Moreover, the new compounds strongly inhibited the activity of the seleno‐enzyme thioredoxin reductase (TrxR) and of the zinc‐finger enzyme poly(ADP‐ribose) polymerase 1 (PARP‐1). In the case of TrxR inhibition, their activity depended clearly on the size of the alkyl/aryl residues of phosphorus atoms. Density functional theory (DFT) calculations showed that the AuP bond of the triphenylphosphane complex [AuI(NHC)(PPh3)]I had a lower bond dissociation energy compared to trialkylphosphane complexes [AuI(NHC)(PR3)]I, indicating a higher kinetic reactivity of this particular compound. In fact, [AuI(NHC)(PPh3)]I triggered an enhanced inhibitory activity against PARP‐1.
Disparities of cancer incidence in Michigan's American Indians: Spotlight on breast cancer
Authors: Roen Emily L. , Copeland Glenn E. , Pinagtore Noel L. , Meza Rafael , Soliman Amr S. 
Published: March 2014

BACKGROUNDIn American Indians (AIs), cancer is a leading cause of mortality, yet their disease burden is not fully understood due to unaddressed racial misclassification in cancer registries. This study describes cancer trends among AIs in Michigan, focusing on breast cancer, in a linked data set of Indian Health Service (IHS), tribal, and state cancer registry data adjusted for misclassification.METHODSAI status was based on reported race and linkage to IHS data and tribal registries. Data with complete linkage on all incident cancer cases in Michigan from 1995 to 2004 was used to calculate age‐standardized incidence estimates for invasive all‐site and female breast cancers stratified by racial group. For female breast cancers, stage‐ and age‐specific incidence and percent distributions of early‐ versus late‐stage cancers and age of diagnosis were calculated.RESULTSMore than 50% of all AI cases were identified through IHS and/or tribal linkage. In the linked data, AIs had the lowest rates of all‐sites and breast cancer. For breast cancers, AI women had a greater late‐stage cancer burden and a younger mean age of diagnosis as compared to whites. Although the age‐specific rate for whites was greater than for AI women in nearly all age groups, the difference in hazard ratio increased with increasing age.CONCLUSIONSOur state‐specific information will help formulate effective, tailored cancer prevention strategies to this population in Michigan. The data linkages used in our study are crucial for generating accurate rates and can be effective in addressing misclassification of the AI population and formulating cancer prevention strategies for AI nationwide. Cancer 2014;120:1847–1853. © 2014 American Cancer Society.
Octreotide long‐acting repeatable use among elderly patients with carcinoid syndrome and survival outcomes: A population‐based analysis
Authors: Shen Chan , Shih Ya‐Chen Tina , Xu Ying , Yao James C. 
Published: March 2014

BACKGROUNDOctreotide long‐acting repeatable (LAR) is indicated for the treatment of carcinoid syndrome and diarrhea related to VIPoma, and may delay tumor growth in patients with neuroendocrine tumors (NETs). To the authors' knowledge, the pattern of octreotide LAR use in clinical practice and its impact on survival outcomes has not been well documented.METHODSUsing the Surveillance, Epidemiology, and End Results (SEER)‐Medicare database, the authors identified patients with NET aged ≥ 65 years who were diagnosed between July 1999 and December 2007. Patients with US Food and Drug Administration‐approved indications for octreotide LAR were identified from Medicare claims. Multivariate logistic regression was performed to ascertain factors associated with octreotide LAR use, whereas the Cox proportional hazards model was used to evaluate the impact of octreotide LAR on survival.RESULTSAmong those with Food and Drug Administration‐approved indications, 245 of 4848 patients with distant‐stage disease (51%) and 81 of 807 patients with local/regional disease (10%) initiated treatment with octreotide LAR within 6 months of diagnosis. Multivariate logistic regression indicated that among those with distant‐stage disease, older age (≥ 80 years vs 65‐69 years) (odds ratio [OR], 0.43; 95% confidence interval [95% CI], 0.23‐0.81), female sex (OR, 0.62; 95% CI, 0.40‐0.97), and living in the South (vs Northeast) (OR, 0.36; 95% CI, 0.18‐0.72) were associated with a lower likelihood of using octreotide LAR. The multivariate proportional hazards model showed that octreotide LAR provided a significant 5‐year survival benefit for patients with distant‐stage disease (hazards ratio, 0.61; P ≤ .001), whereas this survival benefit was not shown for the patients with local/regional stage (hazards ratio, 0.88; P = .563).CONCLUSIONSThe results of this retrospective study suggest a possible survival benefit for the use of octreotide LAR in elderly patients with distant‐stage NET with carcinoid syndrome. The results of the current study also suggest that octreotide LAR is underused in this population despite recommended guidelines. Cancer 2014;120:2039–2049. © 2014 American Cancer Society.
Distribution of microsomal prostaglandin E synthase‐1 in the mouse brain
Authors: Eskilsson Anna , Tachikawa Masanori , Hosoya Ken‐ichi , Blomqvist Anders 
Published: March 2014

ABSTRACTPrevious studies in rats have demonstrated that microsomal prostaglandin E synthase‐1 (mPGES‐1) is induced in brain vascular cells that also express inducible cyclooxygenase‐2, suggesting that such cells are the source of the increased PGE2 levels that are seen in the brain following peripheral immune stimulation, and that are associated with sickness responses such as fever, anorexia, and stress hormone release. However, while most of what is known about the functional role of mPGES‐1 for these centrally evoked symptoms is based on studies on genetically modified mice, the cellular localization of mPGES‐1 in the mouse brain has not been thoroughly determined. Here, using a newly developed antibody that specifically recognizes mouse mPGES‐1 and dual‐labeling for cell‐specific markers, we report that mPGES‐1 is constitutively expressed in the mouse brain, being present not only in brain endothelial cells, but also in several other cell types and structures, such as capillary‐associated pericytes, astroglial cells, leptomeninges, and the choroid plexus. Regional differences were seen with particularly prominent labeling in autonomic relay structures such as the area postrema, the subfornical organ, the paraventricular hypothalamic nucleus, the arcuate nucleus, and the preoptic area. Following immune stimulation, mPGES‐1 in brain endothelial cells, but not in other mPGES‐1‐positive cells, was coexpressed with cyclooxygenase‐2, whereas there was no coexpression between mPGES‐1 and cyclooxygenase‐1. These data imply a widespread synthesis of PGE2 or other mPGES‐1‐dependent products in the mouse brain that may be related to inflammation‐induced sickness symptom as well as other functions, such as blood flow regulation. J. Comp. Neurol. 522:3229–3244, 2014. © 2014 Wiley Periodicals, Inc.
Variations in microanatomy of the human cochlea
Authors: Avci Ersin , Nauwelaers Tim , Lenarz Thomas , Hamacher Volkmar , Kral Andrej 
Published: March 2014

ABSTRACTThe human cochlea shows considerable interindividual variability in size and morphology. In order to develop atraumatic cochlear implant (CI) electrodes, high‐precision details of the variability of human anatomy are required. Sixteen human temporal bones were cut around the cochlea in blocks of approximately 3.5 × 3.5 cm. The bones were scanned by using a Skyscan 1173 micro‐computed tomography (μCT) device. Mimics software (Materialise, Leuven, Belgium) was used to segment out the scala tympani (ST) from the μCT images. A three‐dimensional surface model of the segmented area was generated for each cochlea. Cross‐sectional images were taken and analyzed by custom‐designed software in MATLAB. Comparison of different STs showed large variability in cross‐sectional diameter (CSD), vertical trajectory, and height of the ST. Relative standard deviations of the CSD were between 9 and 15%. Heights measured at the center of the ST exceeded those in the modiolar and lateral regions of the scala. At the lateral region, the height decreased significantly at the beginning of the second turn. In the vertical trajectory, critical anatomic features were observed, such as dips, vertical jumps, and peaks. Rosenthal's canal (RC) extended to between 560 and 650°. We found a correlation between the length of the RC and that of the ST. The ST was segmented and the internal dimensions measured by using μCT. We observed large dimensional variability between different STs. These differences could have considerable implications for approaches to the design of CI arrays, especially in terms of their ability to preserve residual hearing during insertion of the electrode array. J. Comp. Neurol. 522:3245–3261, 2014. © 2014 Wiley Periodicals, Inc.
Derivatization and Multidimensional Gas‐Chromatographic Resolution of α‐Alkyl and α‐Dialkyl Amino Acid Enantiomers
Authors: Meinert Cornelia , Meierhenrich Uwe J. 
Published: March 2014

AbstractThe quantitative resolution of amino acid enantiomers is crucial to a number of fields of bioanalytical chemistry, including food and plant analysis, metabolomics, medicinal chemistry, and archeochemistry. The enantioselective analysis of α‐dialkyl amino acids, however, has proven more difficult than for proteinaceous α‐protonated amino acids. Herein, the development of an analytical method capable of base‐line resolving enantiomers of α‐alkyl and α‐dialkyl amino acids in two chromatographic dimensions is reported. It was found that enantiomers of α‐dialkyl amino acids can be readily resolved with the use of an enantioselective Chirasil‐Val stationary phase in the first chromatographic dimension and a polyethylene glycol stationary phase in the second dimension. These data offer new possibilities for the enantioselective resolution and precise quantification of non‐biological α‐dialkyl amino acids. This methodology will subsequently be applied particularly towards enantioselective analyses of samples relevant for understanding of the origin of homochirality on Earth such as meteorites, comets, and interstellar ices.
1,8‐Cineole: Chemical and Biological Oxidation Reactions and Products
Authors: Azerad Robert 
Published: March 2014

AbstractThe products of chemical and biological oxidation (hydroxy, oxo, and acid derivatives) of 1,8‐cineole (3,3‐dimethyl‐2‐oxabicyclo[2.2.2]octane) are reviewed with a focus on the diverse regio‐ and stereoselectivities obtained from this meso monoterpenic compound abundantly present in eucalyptus leaves. Physical properties (melting‐point and specific rotation values) as well as 1H and 13C NMR spectroscopic data of oxidized derivatives have been exhaustively compiled with particular attention on the clarification of some literature inconsistencies owing to different carbon numbering and stereochemical denominations. Analytical and synthetic methods, and formation as metabolites by plants, microorganisms, and animals are also reviewed together with their presently known biological activities.