bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of cytochrome P450‐mediated drug–drug interaction potential of orteronel and exposure changes in patients with renal impairment using physiologically based pharmacokinetic modeling and simulation
Authors: Lu Chuang , Suri Ajit , Shyu Wen Chyi , Prakash Shimoga 
Published: September 2014

ABSTRACTOrteronel is a nonsteroidal, selective inhibitor of 17,20‐lyase that was recently in phase 3 clinical development as a treatment for castration‐resistant prostate cancer. In humans, the primary clearance route for orteronel is renal excretion. Human liver microsomal studies indicated that orteronel weakly inhibits CYP1A2, 2C8, 2C9 and 2C19, with IC50 values of 17.8, 27.7, 30.8 and 38.8 µm, respectively, whereas orteronel does not inhibit CYP2B6, 2D6 or 3A4/5 (IC50 > 100 µm). Orteronel also does not exhibit time‐dependent inhibition of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6 or 3A4/5. The results of a static model indicated an [I]/Ki ratio >0.1 for CYP1A2, 2C8, 2C9 and 2C19. Therefore, a physiologically based pharmacokinetic (PBPK) model was developed to assess the potential for drug–drug interactions (DDIs) between orteronel and theophylline, repaglinide, (S)‐warfarin and omeprazole, which are sensitive substrates of CYP1A2, 2C8, 2C9 and 2C19, respectively. Simulation of the area under the plasma concentration–time curve (AUC) of these four CYP substrates in the presence and absence of orteronel revealed geometric mean AUC ratios <1.25. Therefore, in accordance with the 2012 US FDA Draft Guidance on DDIs, orteronel can be labeled a ‘non‐inhibitor’ and further clinical DDI evaluation is not required. In PBPK models of moderate and severe renal impairment, the AUC of orteronel was predicted to increase by 52% and 83%, respectively. These results are in agreement with those of a clinical trial in which AUC increases of 38% and 87% were observed in patients with moderate and severe renal impairment, respectively. Copyright © 2014 John Wiley & Sons, Ltd.
A highly selective and simple fluorescent sensor for mercury (II) ion detection based on cysteamine‐capped CdTe quantum dots synthesized by the reflux method
Authors: Ding Xiaojie , Qu Lingbo , Yang Ran , Zhou Yuchen , Li Jianjun 
Published: September 2014

AbstractCysteamine (CA)‐capped CdTe quantum dots (QDs) (CA–CdTe QDs) were prepared by the reflux method and utilized as an efficient nano‐sized fluorescent sensor to detect mercury (II) ions (Hg2+). Under optimum conditions, the fluorescence quenching effect of CA–CdTe QDs was linear at Hg2+ concentrations in the range of 6.0–450 nmol/L. The detection limit was calculated to be 4.0 nmol/L according to the 3σ IUPAC criteria. The influence of 10‐fold Pb2+, Cu2+ and Ag+ on the determination of Hg2+ was < 7% (superior to other reports based on crude QDs). Furthermore, the detection sensitivity and selectivity were much improved relative to a sensor based on the CA–CdTe QDs probe, which was prepared using a one‐pot synthetic method. This CA–CdTe QDs sensor system represents a new feasibility to improve the detection performance of a QDs sensor by changing the synthesis method. Copyright © 2014 John Wiley & Sons, Ltd.
Simple and sensitive LC‐MS/MS‐based assay for the quantification of dimemorfan in human plasma for use in a pharmacokinetic study
Authors: Tan Hongyi , Peng Jinfu , Pei Qi , Yang Liu , Chen Jun , Guo Chengxian , Hua Ye , Yuan Hong , Yang Guoping 
Published: September 2014

AbstractDimemorfan phosphate has been widely used for 40 years throughout the world for the treatment of coughs. This is the first report on the use of an LC‐MS/MS‐based assay for the determination of dimemorfan in human plasma using estazolam as an internal standard after one‐step protein precipitation with acetonitrile. Chromatographic separation was achieved on a Phenomenex Luna C18 column (3 µm, 50 × 2.0 mm) using a fast gradient method, which involves water and methanol as the mobile phase (both containing 0.1% formic acid). Dimemorfan and estazolam were detected with proton adducts at m/z values of 255.8 → 155.1 and 295.0 → 267.0, respectively, in the selected reaction monitoring positive mode. The linear dynamic range of the assay was 0.04–5.00 ng/mL. The chromatographic run time for each plasma sample was <5 min. The method was proven to be accurate, precise, and repeatable. Finally, the developed method was successfully applied for the determination of dimemorfan in a pharmacokinetic study using healthy Chinese subjects. Copyright © 2014 John Wiley & Sons, Ltd.
Childhood maltreatment and amygdala connectivity in methamphetamine dependence: a pilot study
Authors: Dean Andy C. , Kohno Milky , Hellemann Gerhard , London Edythe D. 
Published: September 2014

AbstractIntroductionChildhood maltreatment, a well‐known risk factor for the development of substance abuse disorders, is associated with functional and structural abnormalities in the adult brain, particularly in the limbic system. However, almost no research has examined the relationship between childhood maltreatment and brain function in individuals with drug abuse disorders.MethodsWe conducted a pilot study of the relationship between childhood maltreatment (evaluated with the Childhood Trauma Questionnaire; Bernstein and Fink 1998) and resting‐state functional connectivity of the amygdala (bilateral region of interest) with functional magnetic resonance imaging in 15 abstinent, methamphetamine‐dependent research participants. Within regions that showed connectivity with the amygdala as a function of maltreatment, we also evaluated whether amygdala connectivity was associated positively with negative affect and negatively with healthy emotional processing.ResultsThe results indicated that childhood maltreatment was positively associated with resting‐state connectivity between the amygdala and right hippocampus, right parahippocampal gyrus, right inferior temporal gyrus, right orbitofrontal cortex, cerebellum, and brainstem. Furthermore, connectivity between the amygdala and hippocampus was positively related to measures of depression, trait anxiety, and emotion dysregulation, and negatively related to self‐compassion and dispositional mindfulness.ConclusionsThese findings suggest that childhood maltreatment may contribute to increased limbic connectivity and maladaptive emotional processing in methamphetamine‐dependent adults, and that healthy emotion regulation strategies may serve as a therapeutic target to ameliorate the associated behavioral phenotype. Childhood maltreatment warrants further investigation as a potentially important etiological factor in the neurobiology and treatment of substance use disorders.
Design, Synthesis, Photophysical Studies and Electrochemistry of Carbazole‐, Oxadiazole‐, and Oxadiazole‐Triarylamine‐Containing Rhenium(I) Diimine Alkynyl Complexes
Authors: Chung Wai‐Kin , Wong Keith Man‐Chung , Yam Vivian Wing‐Wah 
Published: September 2014

AbstractA series of rhenium(I) diimine alkynyl complexes with various electron‐ and hole‐transporting moieties has been synthesized and characterized. Their electronic absorption, emission and electrochemical properties have also been studied.
Palladium‐Catalyzed 2H‐1,2,3‐Triazole‐Directed Oxidative Alkoxylation of Arenes with Alcohols
Authors: Shi Wenjuan , Shi Zhangjie 
Published: September 2014

AbstractA palladium catalyzed ortho‐alkoxylation of aryl CH bond was accomplished with primary and secondary alcohols as alkoxylation reagents and with triazole as new directing group. This transformation has a good functional group tolerance and is not sensitive to moisture and air.
Minimum Amount of Extracting Solvent of (A1A2···At−1)/(A2A3···At) Separation When Using Non‐barren Extracting Solvent
Authors: Cheng Fu‐Xiang , Wu Sheng , Wang Song‐Ling , Zhang Bo , Liu Yan , Liao Chun‐Sheng , Yan Chun‐Hua 
Published: September 2014

AbstractHyperlink extraction technology, by virtue of its remarkable advantage of decreasing the use of chemicals in multi‐component separation, has been extensively employed in rare earth separation industry in China. In hyperlink processes, non‐barren extracting solvent and scrubbing agent solution which contain the component(s) involved in starting feed are employed in order to save both alkali for saponification and acid for scrubbing. Minimum amount of extracting solvent (denoted as Smin) and that of scrubbing agent solution (denoted as Wmin) are important parameters to determine the consumption amounts of alkali and acid for a given countercurrent extraction separation. This article therefore discusses the influence of using non‐barren extracting solvent and scrubbing agent solution on Smin and Wmin of an (A1A2···At−1)/(A2A3···At) separation. The equations for Smin and Wmin are derived, and the variation of the composition of final raffinate as well as that of final extract are determined, which will provide a valuable guidance for the design of hyperlink extraction processes of multi‐component separation, such as rare earths separation.
Formaldehyde‐fixation of platelets for flow cytometric measurement of phosphatidylserine exposure is feasible
Authors: Rochat Sophie , Alberio Lorenzo 
Published: September 2014

AbstractStrong platelet activation results in a redistribution of negatively charged phospholipids from the cytosolic to the outer leaflet of the cellular membrane. Annexin V has a high affinity to negatively charged phospholipids and can be used to identify procoagulant platelets. Formaldehyde fixation can cause factitious Annexin V binding. Our aim was to evaluate a method for fixing platelets avoiding additional Annexin V binding. We induced expression of negatively charged phospholipids on the surface of a fraction of platelets by combined activation with convulxin and thrombin in the presence of Annexin V‐fluorescein isothiocyanate and calcium. Aliquots of resting and activated platelets were fixed with a low concentration, calcium‐free formaldehyde solution. Both native platelets and fixed platelets were analyzed by flow cytometry immediately and after a 24‐h storage at 4°C. We observed that the percentage of Annexin V positive resting platelets ranged from 1.5 to 9.3% for the native samples and from 0.4 to 12.8% for the fixed samples (P = 0.706, paired t‐test). The amount of Annexin V positive convulxin/thrombin activated platelets varied from 12.9 to 35.4% without fixation and from 15.3 to 36.3% after formalin fixation (P = 0.450). After a 24‐h storage at 4°C, Annexin V positive platelets significantly increased both in the resting and in the convulxin/thrombin activated samples of native platelets (both P < 0.001), while results for formalin fixed platelets did not differ from baseline values (P = 0.318 for resting fixed platelets; P = 0.673 for activated fixed platelets). We conclude that platelet fixation with a low concentration, calcium‐free formaldehyde solution does not alter the proportion of Annexin V positive platelets. This method can be used to investigate properties of procoagulant platelets by multicolor flow‐cytometric analysis requiring fixation steps. © 2014 International Society for Advancement of Cytometry
Asymmetric Mannich Reaction of Malonates with Aldimines Using YbIII‐Pybox Complexes Supported on Self‐Assembled Organic–Inorganic Hybrid Silica with an Imidazolium Framework
Authors: Karimi Babak , Jafari Ehsan , Enders Dieter 
Published: September 2014

AbstractYb(OTf)3/iPr‐pybox (3b) immobilized on a self‐assembled organic–inorganic hybrid silica with ionic liquid phase (SAILP) (Catalyst A) behaves as an efficient and recyclable catalyst in the enantioselective Mannich reaction of malonate esters with N‐Boc aldimines to afford the corresponding products in good yields and enantioselectivities. In particular, it has been shown that the use of catalyst A resulted in much superior enantioselectivities in comparison with either 1:2 Yb(OTf)3/3b on a periodic mesoporous organosilica with 10 percent imidazolium framework (catalyst C) or a catalyst comprising 1:1 Yb(OTf)3/3b on SAILP under the same reaction conditions. Catalyst A could be recycled and reused at least four times with only a slight decrease in either catalytic activity or enantioselectivity.
Enhanced Photochemical Sensitivity in Photochromic Diarylethenes Based on a Benzothiophene/Thiophene Nonsymmetrical Structure
Authors: Galangau Olivier , Kimura Yuka , Kanazawa Rui , Nakashima Takuya , Kawai Tsuyoshi 
Published: September 2014

AbstractPhotosensitivity of molecules is one of the central subjects of organic photochemistry. In this article, we present how and why a benzothiophene moiety impacts the photochromic quantum yield for the photochemical pericyclic ring closing of the hexatriene moiety. Two compounds were prepared: a symmetrical one incorporating two fluorenylthiophene units, and its corresponding nonsymmetrical partner, where one of the thiophene units was replaced by a benzothiophene group. Interestingly, the latter presents relatively high cyclization quantum yield (0.74), a value close to the largest one so far reported. Based on crystal structures, VT‐NMR data and DFT calculations, we demonstrate that introducing a benzothiophene in the molecular scaffold induces skeleton stiffening by means of CH–π interactions and steric repulsions, and leads to increased population of the reactive conformer in the ambient conditions.
Solution‐ and Solid‐State Luminescent Borate Complexes Based on a Substituted π‐Conjugated 2‐(6′‐Hydroxy‐5′‐benzofuryl) Scaffold
Authors: Benelhadj Karima , Massue Julien , Retailleau Pascal , Chibani Siwar , Le Guennic Boris , Jacquemin Denis , Ziessel Raymond , Ulrich Gilles 
Published: September 2014

AbstractThis paper describes the synthesis of π‐conjugated fluorophores based either on an anil or a benzoxazole scaffold incorporating a rigid 2‐(6′‐hydroxy‐5′‐benzofuryl) fragment. Their subsequent coordination to a BF2 motif led to highly luminescent BIII complexes called boranils or HBBO borate complexes, respectively. All the new compounds were characterized by NMR spectroscopy, mass spectrometry, and elemental analysis. The study of their optical properties in solution revealed two distinct photophysical behaviors depending on the substitution. Complexes bearing a strong electron‐donating p‐nBu2NC6H4 group displayed a marked internal charge transfer (ICT) leading to a pronounced solvatochromism with λem ranging from 507 to 663 nm and quantum yields of up to 87 %. Alternatively, borate complexes functionalized with p‐tBuC6H4 or p‐OMeC6H4 displayed fluorescence in the visible range that is not influenced by the nature of the solvent. Although the emission of the boranils was quenched in the solid state, HBBO borate complexes displayed intense fluorescence from 489 to 567 nm and quantum yields of up to 23 %. Finally, the excited states of a selection of borate complexes were modeled by using time‐dependent DFT, which allowed calculation of the dipole moments of the dyes in their excited states.
Copper‐Catalyzed Asymmetric Addition to Isatins to give 3‐Hydroxy‐2‐oxindoles by C–H Activation
Authors: Deng Tao , Wang Hongjun , Cai Chun 
Published: September 2014

AbstractA copper‐catalyzed asymmetric addition to isatins to give 3‐hydroxy‐2‐oxindoles by C–H activation with a fluorous bis(oxazoline) as ligand is presented. The corresponding products were obtained in 35–66 % yields with enantioselectivities up to 92 %. The fluorous ligand can be easily recovered and reused at least three times without significant loss in its activity.
An improvement for multidimensional characteristic‐based scheme by using different selected waves
Authors: Fathollahi Reza , Zamzamian Kamiar 
Published: September 2014

SummaryIn this study, an improved multidimensional characteristic‐based (MCB) scheme, used for calculation of incompressible flows via artificial compressibility method, is presented. The new idea uses four different waves instead of traditional waves, which were used in the original MCB scheme corresponding to coordinate axes. In the new selection of waves, the number of compatibility relations is increased to eight, and therefore, more information reaches to each face in order to estimate convective fluxes. Numerical tests show that the new improved MCB scheme is faster in terms of convergence and demonstrates the same accuracy by the older one. Also, it needs less CPU time in comparison with traditional MCB scheme for running the computer code at the same conditions. The new scheme is able to use higher CFL numbers compared with the old MCB scheme. Results obtained by the new proposed method are in good agreement with the benchmark solutions at the wide range of Reynolds numbers. Copyright © 2014 John Wiley & Sons, Ltd.
Consequences of mixing assumptions for time‐variable travel time distributions
Authors: van der Velde Ype , Heidbüchel Ingo , Lyon Steve W. , Nyberg Lars , Rodhe Allan , Bishop Kevin , Troch Peter A. 
Published: September 2014

AbstractThe current generation of catchment travel time distribution (TTD) research, integrating nearly three decades of work since publication of Water's Journey from Rain to Stream, seeks to represent the full distribution in catchment travel times and its temporal variability. Here, we compare conceptualizations of increasing complexity with regards to mixing of water storages and evaluate how these assumptions influence time‐variable TTD estimates for two catchments with contrasting climates: the Gårdsjön catchment in Sweden and the Marshall Gulch catchment in Arizona, USA. Our results highlight that, as long as catchment TTDs cannot be measured directly but need to be inferred from input‐output signals of catchments, the inferred catchment TTDs depend strongly on the underlying assumptions of mixing within a catchment. Furthermore, we found that the conceptualization of the evapotranspiration flux strongly influences the inferred travel times of stream discharge. For the wet and forested Gårdsjön catchment in Sweden, we inferred that evapotranspiration most likely resembles a completely mixed sample of the water stored in the catchment; however, for the drier Marshall Gulch catchment in Arizona, evapotranspiration predominantly contained the younger water stored in the catchment. For the Marshall Gulch catchment, this higher probability for young water in evapotranspiration resulted in older water in the stream compared to travel times inferred with assumptions of complete mixing. New observations that focus on the TTD of the evapotranspiration flux and the actual travel time of water through a catchment are necessary to improve identification of mixing and consequently travel times of stream water. Copyright © 2014 John Wiley & Sons, Ltd.
The Convergence of Fracture Repair and Stem Cells: Interplay of Genes, Aging, Environmental Factors and Disease
Authors: Hadjiargyrou Michael , O'Keefe Regis J 
Published: September 2014

ABSTRACT

The complexity of fracture repair makes it an ideal process for studying the interplay between the molecular, cellular, tissue, and organ level events involved in tissue regeneration. Additionally, as fracture repair recapitulates many of the processes that occur during embryonic development, investigations of fracture repair provide insights regarding skeletal embryogenesis. Specifically, inflammation, signaling, gene expression, cellular proliferation and differentiation, osteogenesis, chondrogenesis, angiogenesis, and remodeling represent the complex array of interdependent biological events that occur during fracture repair. Here we review studies of bone regeneration in genetically modified mouse models, during aging, following environmental exposure, and in the setting of disease that provide insights regarding the role of multipotent cells and their regulation during fracture repair. Complementary animal models and ongoing scientific discoveries define an increasing number of molecular and cellular targets to reduce the morbidity and complications associated with fracture repair. Last, some new and exciting areas of stem cell research such as the contribution of mitochondria function, limb regeneration signaling, and microRNA (miRNA) posttranscriptional regulation are all likely to further contribute to our understanding of fracture repair as an active branch of regenerative medicine. © 2014 American Society for Bone and Mineral Research.
Muscle Torque Relative to Cross-Sectional Area and the Functional Muscle-Bone Unit in Children and Adolescents With Chronic Disease
Authors: Lee Dale Y , Wetzsteon Rachel J , Zemel Babette S , Shults Justine , Organ Jason M , Foster Bethany J , Herskovitz Rita M , Foerster Debbie L , Leonard Mary B 
Published: September 2014

ABSTRACT

Measures of muscle mass or size are often used as surrogates of forces acting on bone. However, chronic diseases may be associated with abnormal muscle force relative to muscle size. The muscle-bone unit was examined in 64 children and adolescents with new-onset Crohn's disease (CD), 54 with chronic kidney disease (CKD), 51 treated with glucocorticoids for nephrotic syndrome (NS), and 264 healthy controls. Muscle torque was assessed by isometric ankle dynamometry. Calf muscle cross-sectional area (CSA) and tibia cortical section modulus (Zp) were assessed by quantitative CT. Log-linear regression was used to determine the relations among muscle CSA, muscle torque, and Zp, adjusted for tibia length, age, Tanner stage, sex, and race. Muscle CSA and muscle torque-relative-to-muscle CSA were significantly lower than controls in advanced CKD (CSA −8.7%, p = 0.01; torque −22.9%, p &lt; 0.001) and moderate-to-severe CD (CSA −14.1%, p &lt; 0.001; torque −7.6%, p = 0.05), but not in NS. Zp was 11.5% lower in advanced CKD (p = 0.005) compared to controls, and this deficit was attenuated to 6.7% (p = 0.05) with adjustment for muscle CSA. With additional adjustment for muscle torque and body weight, Zp was 5.9% lower and the difference with controls was no longer significant (p = 0.09). In participants with moderate-to-severe CD, Zp was 6.8% greater than predicted (p = 0.01) given muscle CSA and torque deficits (R2 = 0.92), likely due to acute muscle loss in newly-diagnosed patients. Zp did not differ in NS, compared with controls. In conclusion, muscle torque relative to muscle CSA was significantly lower in CKD and CD, compared with controls, and was independently associated with Zp. Future studies are needed to determine if abnormal muscle strength contributes to progressive bone deficits in chronic disease, independent of muscle area. © 2014 American Society for Bone and Mineral Research.