bluuebunny/crossref_metadata_2025_split huggingface dataset:
An evaluation of the CYP2D6 and CYP3A4 inhibition potential of metoprolol metabolites and their contribution to drug–drug and drug–herb interaction by LC‐ESI/MS/MS
Authors: Borkar Roshan M. , Bhandi Murali Mohan , Dubey Ajay P. , Ganga Reddy V. , Komirishetty Prashanth , Nandekar Prajwal P. , Sangamwar Abhay T. , Kamal Ahmed , Banerjee Sanjay K. , Srinivas R. 
Published: March 2016

AbstractThe aim of the present study was to evaluate the contribution of metabolites to drug–drug interaction and drug–herb interaction using the inhibition of CYP2D6 and CYP3A4 by metoprolol (MET) and its metabolites. The peak concentrations of unbound plasma concentration of MET, α‐hydroxy metoprolol (HM), O‐desmethyl metoprolol (ODM) and N‐desisopropyl metoprolol (DIM) were 90.37 ± 2.69, 33.32 ± 1.92, 16.93 ± 1.70 and 7.96 ± 0.94 ng/mL, respectively. The metabolites identified, HM and ODM, had a ratio of metabolic area under the concentration–time curve (AUC) to parent AUC of ≥0.25 when either total or unbound concentration of metabolite was considered. In vitro CYP2D6 and CYP3A4 inhibition by MET, HM and ODM study revealed that MET, HM and ODM were not inhibitors of CYP3A4‐catalyzed midazolam metabolism and CYP2D6‐catalyzed dextromethorphan metabolism. However, DIM only met the criteria of >10% of the total drug related material and <25% of the parent using unbound concentrations. If CYP inhibition testing is solely based on metabolite exposure, DIM metabolite would probably not be considered. However, the present study has demonstrated that DIM contributes significantly to in vitro drug–drug interaction. Copyright © 2016 John Wiley & Sons, Ltd.
Dimethyloxalylglycine may be enhance the capacity of neural‐like cells in treatment of Alzheimer disease
Authors: Ghasemi Moravej Fahimeh , Vahabian Mehrangiz , Soleimani Asl Sara 
Published: March 2016

AbstractAlthough using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats.
A novel small molecule, Rosline, inhibits growth and induces caspase‐dependent apoptosis in human lung cancer cells A549 through a reactive oxygen species‐dependent mechanism
Authors: Zhao Ting , Feng Yang , Jin Wenling , Pan Hui , Li Haizhou , Zhao Yang 
Published: March 2016

AbstractChemical screening using synthetic small molecule libraries has provided a huge amount of novel active molecules. It generates lead compound for drug development and brings focus on molecules for mechanistic investigations on many otherwise intangible biological processes. In this study, using non‐small cell lung cancer cell A549 to screen against a structurally novel and diverse synthetic small molecule library of 2,400 compounds, we identified a molecule named rosline that has strong anti‐proliferation activity on A549 cells with a 50% cell growth inhibitory concentration (IC50) of 2.87 ± 0.39 µM. We showed that rosline treatment increased the number of Annexin V‐positive staining cell, as well as G2/M arrest in their cell cycle progression. Further, we have demonstrated that rosline induces a decrease of mitochondrial membrane potential (Δφm) and an increase of caspases 3/7 and 9 activities in A549 cells, although having no effect on the activity of caspase 8. Moreover, we found that rosline could induce the production of reactive oxygen species (ROS) and inhibit the phosphorylation of signaling molecule Akt in A549 cells. Alternatively, an antioxidant N‐acetyl‐L‐cysteine (NAC) significantly attenuated rosline's effects on the mitochondrial membrane potential, caspases 3/7 and 9 activities, cell viabilities and the phosphorylation of Akt. Our results demonstrated that ROS played an important role in the apoptosis of A549 cells induced by rosline.
Reactivity of 2,1‐Benzisoxazole in Palladium‐Catalyzed Direct Arylation with Aryl Bromides
Authors: Aidene Mohand , Belkessam Fatma , Soulé Jean‐François , Doucet Henri 
Published: March 2016

AbstractThe Pd‐catalyzed direct arylation of 2,1‐benzisoxazole with aryl bromides to access 3‐arylbenzoisoxazoles proceeds in moderate‐to‐high yields with 1 mol % Pd(OAc)2 or 2 mol % PdCl(C3H5)(dppb) (dppb=1,4‐bis(diphenylphosphino)butane) as the catalysts and KOAc as an inexpensive base. A wide variety of (hetero)aryl bromides have been employed successfully. Moreover, arylations followed by benzisoxazole ring opening allowed the preparation of 2‐aminobenzophenones in only two steps.
Base‐Catalyzed Condensation of Levulinic Acid: A New Biorefinery Upgrading Approach
Authors: Faba Laura , Díaz Eva , Ordóñez Salvador 
Published: March 2016

AbstractThe base‐catalyzed condensation of levulinic acid (LA) under mild conditions (0.1 MPa, 323 K, 0.45 mol L−1 aq solution of levulinic acid, catalyst/reactant=1:24 wt.) was proposed as a new approach for the upgrading of this molecule by using mixed oxides as catalysts. Three products were identified: α‐angelica lactone (AL) and two aldol condensation adducts, LA–LA and AL–LA. These last ones (obtained with selectivities higher than 90 % at 30 % conversion upon using MgZr) present high value as fuel and chemical precursors. The distribution of basic and acidic sites on the catalyst governs the performance and selectivity of the catalyst, whereas the stability of the catalyst in the reaction media determines the deactivation behavior. Bulk MgZr oxides present a good balance of these properties.
Beyond Clusters: Supramolecular Networks Self‐Assembled from Nanosized Silver Clusters and Inorganic Anions
Authors: Wang Zhi , Li Xiao‐Yu , Liu Li‐Wei , Yu Si‐Qi , Feng Zhen‐Yu , Tung Chen‐Ho , Sun Di 
Published: March 2016

AbstractAssembly of small clusters into rigid bodies with precise shape and symmetry has been witnessed by the significant advances in cluster‐based metal–organic frameworks (MOFs), however, nanosized silver cluster based MOFs remain largely unexplored. Herein, two anion‐templated silver clusters, CO3@Ag20 and SO4@Ag22, were ingeniously incorporated into a 2D sql lattice (1, [CO3@Ag20(iPrS)10(NO3)8(DMF)2]n) and an unprecedented 3D two‐fold interpenetrated dia network (2, [SO4@Ag22(iPrS)12(NO3)6⋅2 NO3]n), respectively, under mild solvothermal conditions. Their atomically precise structures were confirmed by single‐crystal X‐ray diffraction analysis and further consolidated by IR spectroscopy, thermogravimetric analysis (TGA), and elemental analysis. Each drum‐like CO3@Ag20 cluster is extended by twelve NO3− ions to form the 2D sql lattice of 1, whereas each ball‐shaped SO4@Ag22 cluster with a twisted truncated tetrahedral geometry is pillared by four [Ag6(NO3)3] triangular prisms to form the 3D interpenetrated dia network of 2. Notably, 2 is the first interpenetrated 3D MOF constructed from silver clusters. These results demonstrate the dual role of the anions, which not only internally act as anion templates to induce the formation of silver thiolate clusters but also externally extend the cluster units into the rigid networks. The photoluminescent and electrochemical properties of 2 are discussed in detail.
Multichromophoric π‐Conjugation: Modular Design for Gated and Cascade Energy Transfer
Authors: Park Byung Gyu , Hong Dae Ho , Lee Ho Yong , Lee Milim , Lee Dongwhan 
Published: March 2016

AbstractMultichromophore arrays allow for cascade energy transfer. As an isoelectronic analogue of indacenyl, bis(triazolo)benzene features a fused tricyclic skeleton that rigidly places two π‐extended triazoles in close proximity. Such triazole‐based fluorophores behave as electronically independent modules in the ground states, but become tightly coupled upon photoexcitation for highly efficient excitation energy transfer (EET) that can be gated by external stimuli. Taking this donor–acceptor fluorophore system a step further, we have designed and implemented a cascade EET. Here, the initial excitation takes part in a circular relay to arrive at the longest‐wavelength emitting site as the final destination. Modularly constructed triazoloarenes should serve as versatile platforms for chemically controlled optical signaling.
Emergent Catalytic Behavior of Self‐Assembled Low Molecular Weight Peptide‐Based Aggregates and Hydrogels
Authors: Tena‐Solsona Marta , Nanda Jayanta , Díaz‐Oltra Santiago , Chotera Agata , Ashkenasy Gonen , Escuder Beatriu 
Published: March 2016

AbstractWe report a series of short peptides possessing the sequence (FE)n or (EF)n and bearing l‐proline at their N‐terminus that self‐assemble into high aspect ratio aggregates and hydrogels. We show that these aggregates are able to catalyze the aldol reaction, whereas non‐aggregated analogues are catalytically inactive. We have undertaken an analysis of the results, considering the accessibility of catalytic sites, pKa value shifts, and the presence of hydrophobic pockets. We conclude that the presence of hydrophobic regions is indeed relevant for substrate solubilization, but that the active site accessibility is the key factor for the observed differences in reaction rates. The results presented here provide an example of the emergence of a new chemical property caused by self‐assembly, and support the relevant role played by self‐assembled peptides in prebiotic scenarios. In this sense, the reported systems can be seen as primitive aldolase I mimics, and have been successfully tested for the synthesis of simple carbohydrate precursors.
A Thermo‐ and Photo‐Switchable Ruthenium Initiator For Olefin Metathesis
Authors: Sashuk Volodymyr , Danylyuk Oksana 
Published: March 2016

AbstractA ruthenium carbene complex bearing azobenzene functionality is reported. The complex exists in the form of two isomers differing by the size of the chelate ring. Both isomers were isolated by applying kinetic or thermodynamic control during the synthesis and characterized by X‐ray diffraction analysis. The isomerization of the complex was studied by UV/Vis spectroscopy. The stable isomer was tested as a catalyst in olefin metathesis. The complex was activated at about 100 °C to promote ring‐closing and ring‐opening polymerization metathesis reactions. The activation took place also at room temperature under middle ultraviolet radiation.
ChemInform Abstract: AVPO4F (A: Li, K): A 4 V Cathode Material for High‐Power Rechargeable Batteries.
Authors: Fedotov Stanislav S. , Khasanova Nellie R. , Samarin Aleksandr Sh. , Drozhzhin Oleg A. , Batuk Dmitry , Karakulina Olesia M. , Hadermann Joke , Abakumov Artem M. , Antipov Evgeny V. 
Published: March 2016

AbstractPhase pure KVPO4F is prepared by firing equimolar amounts of VPO4 and KHF2 under Ar (600 °C, 1 h).
Entwicklungen und Trends in der industriellen Prozessanalytik für Life‐Science‐Anwendungen
Authors: Gerlach Martin , Gross Reinhard , Steckenreiter Thomas , Traenkle Jens , Tulke Albert 
Published: March 2016

AbstractProzessanalytik und die ihr zugrundeliegende Prozessanalysentechnik müssen auf die spezifischen Anforderungen an Prozesse in der Life‐Science‐Industrie eingehen, um dort künftig umfassend eingesetzt zu werden. Dies hängt einerseits mit den vielfältigen regulatorischen Anforderungen zusammen, aber auch mit der Komplexität und anderen Herausforderungen der einzelnen Mess‐ und Regelaufgaben. Beispiele für aktuell erzielte Ergebnisse werden im vorliegenden Beitrag vorgestellt. Echtzeitinformationen – gegebenenfalls auch stoffspezifisch – als Grundlage eines besseren Prozessverständnisses und einer überlegenen, automatisierten Prozessführung zu gewinnen, gehört dabei zu den wichtigsten Anforderungen.
Developments in slurry flow modelling in a historical perspective
Authors: Wilson Kenneth , Sellgren Anders 
Published: March 2016

AbstractDurand's slurry flow model attempted to find a single formula for sand‐size particles and larger, but Babcock's data showed that a single formula could not apply. A subsequent group of models is based on Wilson's layered force‐balance analysis of slurry flows applied to friction losses and deposition limit. Models based on variants of this analysis include those by Shook and others at the Saskatchewan Research Council (SRC). Early versions of Wilson's model relied on particle fall velocity to find friction losses, but the classical iterative method of finding fall velocity has now been replaced by a direct method. This is based on the shear Reynolds number of the particle, which can be expressed in terms of the better known Archimedes number. Thus, calculations of slurry friction and limit of deposition involve two principal parameters: the Archimedes number and the diameter ratio d/D.
Concentration and velocity profiles of sediment‐water mixtures using the drift flux model
Authors: Goeree Joep C. , Keetels Geert H. , Munts Edwin A. , Bugdayci Hassan H. , van Rhee Cees 
Published: March 2016

AbstractIn this paper, the concentration and velocity profiles of sediment water mixtures for open‐channel flows are modelled numerically and validated with experimental results. A continuum approach, the drift flux model, is used. The mixture consists of volume fractions with different particle sizes. Hindered settling is taken into account with the closure relation of Richardson and Zaki. Transport equations are used for sediment transport. Turbulence is modelled with the LES (large eddy simulation) WALE model. The discretization of the transport and Navier‐Stokes equations is done with the finite volume method. The Navier‐Stokes equations are solved using a fractional step method. The numerical results are compared with experimental results concerning open‐channel flows.
Hierarchical Co3O4 Nanowires as Binder Free Electrodes for Reversible Lithium Storage
Authors: Zhang Zichao , Li Li , Ren Quan , Xu Qi , Cao Bingqiang 
Published: March 2016

AbstractTo develop a long cycle life and good rate capability electrode, tricobalt tetraoxide (Co3O4) nanowires with hierarchical structure composed of ultra‐small nanoparticles are directly grown on nickel foam current collector. The size of the nanoparticles is about 10 nm. They are synthesized via a facile hydrothermal route followed by calcination and evaluated as an anode of binder‐free lithium‐ion batteries. The concentration of reactant and duration of reaction are considered as important synthesis parameters. Co3O4 nanowires electrode exhibits excellent electrochemical performance including outstanding cycling performance, a high reversible discharge capacity and good rate capability, owing to the hierarchical architecture composed of micro‐/nanostructures. After rate capacity performance measurements, a capacity of 1060.1 mAh·g−1 is retained. At a rate of 500 mA·g−1, a reversible capacity remains stable as high as 957 mAh·g−1. The enhanced performance is owing to the hierarchical structure of the nanowires and good contact with the substrate which can make electrons efficiently transport from Co3O4 nanowires to the current collectors. The mesoporous structure may facilitate the lithium ion diffusion and mitigate the internal mechanical stress induced by volume variations of the electrode upon cycling, which lead to outstanding electrochemical performance.
Synthesis and Improved Properties of Hypergolic Boronium‐Based Ionic Liquids
Authors: Li Xingye , Lu Huijie , Wang Qi , Huang Jinglun , Nie Fude , Li Haibo , Chen Fu‐Xue 
Published: March 2016

AbstractA series of asymmetric monoimidazolium dihydroboronium‐based ionic liquids (ILs) were synthesized from amine‐boranes. All the resulting ILs were fully characterized by 1H and 13C NMR, IR spectroscopy, elemental analysis or high resolution mass spectrum. Compared with the symmetric bisimidazolium dihydroboronium‐based ILs, these new ILs exhibited improved properties with shorter ignition delay times (IDs), higher densities, and lower phase transition temperature showing the promising application potential as green propellants.
Alkylation of Staurosporine to Derive a Kinase Probe for Fluorescence Applications
Authors: Disney Alexander J. M. , Kellam Barrie , Dekker Lodewijk V. 
Published: March 2016

AbstractThe natural product staurosporine is a high‐affinity inhibitor of nearly all mammalian protein kinases. The labelling of staurosporine has proven effective as a means of generating protein kinase research tools. Most tools have been generated by acylation of the 4′‐methylamine of the sugar moiety of staurosporine. Herein we describe the alkylation of this group as a first step to generate a fluorescently labelled staurosporine. Following alkylation, a polyethylene glycol linker was installed, allowing subsequent attachment of fluorescein. We report that this fluorescein–staurosporine conjugate binds to cAMP‐dependent protein kinase in the nanomolar range. Furthermore, its binding can be antagonised with unmodified staurosporine as well as ATP, indicating it targets the ATP binding site in a similar fashion to native staurosporine. This reagent has potential application as a screening tool for protein kinases of interest.
Synthesis and Biological Evaluation of New (−)‐Englerin Analogues
Authors: López‐Suárez Laura , Riesgo Lorena , Bravo Fernando , Ransom Tanya T. , Beutler John A. , Echavarren Antonio M. 
Published: March 2016

AbstractWe report the synthesis and biological evaluation of a series of (−)‐englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier‐to‐synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth‐inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).
Detection of PIK3CA mutations, including a novel mutation of V344G in exon 4, in metastatic lung adenocarcinomas: A retrospective study of 115 FNA cases
Authors: Allison Derek B. , Lilo Mohammed T. , Geddes Susan , Pallavajjalla Aparna , Askin Frederic , Gabrielson Edward , Zheng Gang , Li Qing Kay 
Published: March 2016

BACKGROUNDPhosphatidylinositol‐4,5‐bisphosphate 3‐kinase catalytic subunit alpha (PIK3CA) mutations and amplification are detected in 1% of primary lung adenocarcinomas (ADCs) and in 38% of primary lung squamous cell carcinomas. Alterations of PIK3CA in metastatic non–small cell lung carcinoma (NSCLC), however, are still not fully understood. This study investigated PIK3CA alterations in metastatic ADCs and correlated the findings with those for other commonly tested molecular abnormalities via fine‐needle aspiration (FNA) and small‐core biopsy materials.METHODSThis study identified 115 FNA cases of metastatic lung ADC with standard lung cancer panel analysis by targeted next‐generation sequencing and fluorescence in situ hybridization at the Johns Hopkins Medical Institute over a 12‐month period. The panel included mutational analysis of PIK3CA, AKT, BRAF, EGFR, ERBB2, KRAS, and NRAS genes and tests of rearrangements for ALK and ROS1 genes.RESULTSA PIK3CA mutation was detected in 7 of 115 cases of metastatic ADC (6.1%). The majority of the mutations were located in exon 9 or exon 20; however, a mutation in exon 1 was seen in 1 case. Furthermore, p.V344G in exon 4 was detected in 2 cases. Among cases with PIK3CA mutations, 4 had coexisting EGFR mutations, whereas 2 had a coexisting BRAF or KRAS mutation.CONCLUSIONSSeveral common mutations as well as a novel mutation in the PIK3CA gene were observed in metastatic NSCLC (particularly ADC). The unique role, however, of PIK3CA mutations in metastatic NSCLC and the clinical implications need to be further investigated. Cancer Cytopathol 2016;124:485–92. © 2016 American Cancer Society.
mTOR kinase is needed for the development and stabilization of dendritic arbors in newly born olfactory bulb neurons
Authors: Skalecka Agnieszka , Liszewska Ewa , Bilinski Robert , Gkogkas Christos , Khoutorsky Arkady , Malik Anna R. , Sonenberg Nahum , Jaworski Jacek 
Published: March 2016

ABSTRACTNeurogenesis is the process of neuron generation, which occurs not only during embryonic development but also in restricted niches postnatally. One such region is called the subventricular zone (SVZ), which gives rise to new neurons in the olfactory bulb (OB). Neurons that are born postnatally migrate through more complex territories and integrate into fully functional circuits. Therefore, differences in the differentiation of embryonic and postnatally born neurons may exist. Dendritogenesis is an important process for the proper formation of future neuronal circuits. Dendritogenesis in embryonic neurons culturedin vitrowas shown to depend on the mammalian target of rapamycin (mTOR). Still unknown, however, is whether mTOR could regulate the dendritic arbor morphology of SVZ‐derived postnatal OB neurons under physiological conditionsin vivo. The present study usedin vitrocultured and differentiated SVZ‐derived neural progenitors and found that both mTOR complex 1 and mTOR complex 2 were required for the dendritogenesis of SVZ‐derived neurons. Furthermore, using a combination ofin vivoelectroporation of neural stem cells in the SVZ and genetic and pharmacological inhibition of mTOR, it was found that mTOR was crucial for the growth of basal and apical dendrites in postnatally born OB neurons under physiological conditions and contributed to the stabilization of their basal dendrites. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1308–1327, 2016