bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a rapid and sensitive SPE‐LC‐MS/MS method for the simultaneous estimation of fluoxetine and olanzapine in human plasma
Authors: Gopinath Shanmugam , Kumar Ramadass Satiesh , Alexander Sekar , Danabal Palanisamy 
Published: November 2011

ABSTRACTA high‐performance liquid chromatographic assay with tandem mass spectrometric detection was developed to simultaneously quantify fluoxetine and olanzapine in human plasma. The analytes and the internal standard (IS) duloxetine were extracted from 500 μL aliquots of human plasma through solid‐phase extraction. Chromatographic separation was achieved in a run time of 4.0 min on a Hypersil Gold C18 column (50 × 4.6 mm, 5 µm) using isocratic mobile phase consisting of acetonitrile–water containing 2% formic acid (70:30, v/v), at a flow‐rate of 0.5 mL/min. Detection of analytes and internal standard was performed by electrospray ionization tandem mass spectrometry, operating in positive‐ion and multiple reaction monitoring acquisition mode. The protonated precursor to product ion transitions monitored for fluoxetine, olanzapine and IS were m/z 310.01 → 147.69, 313.15 → 256.14 and 298.1 → 153.97, respectively. The method was validated over the concentration range of 1.00–150.20 ng/mL for fluoxetine and 0.12–25.03 ng/mL for olanzapine in human plasma. The intra‐batch and inter‐batch precision (%CV) across four quality control levels was ≤6.28% for both the analytes. In conclusion, a simple and sensitive analytical method was developed and validated in human plasma. This method is suitable for measuring accurate plasma concentration in bioequivalence study and therapeutic drug monitoring as well, following combined administration. Copyright © 2011 John Wiley & Sons, Ltd.
Stable Analogues of OSB‐AMP: Potent Inhibitors of MenE, the o‐Succinylbenzoate‐CoA Synthetase from Bacterial Menaquinone Biosynthesis
Authors: Lu Xuequan , Zhou Rong , Sharma Indrajeet , Li Xiaokai , Kumar Gyanendra , Swaminathan Subramanyam , Tonge Peter J. , Tan Derek S. 
Published: November 2011

AbstractMenE, the o‐succinylbenzoate (OSB)‐CoA synthetase from bacterial menaquinone biosynthesis, is a promising new antibacterial target. Sulfonyladenosine analogues of the cognate reaction intermediate, OSB‐AMP, have been developed as inhibitors of the MenE enzymes from Mycobacterium tuberculosis (mtMenE), Staphylococcus aureus (saMenE) and Escherichia coli (ecMenE). Both a free carboxylate and a ketone moiety on the OSB side chain are required for potent inhibitory activity. OSB‐AMS (4) is a competitive inhibitor of mtMenE with respect to ATP (Ki=5.4±0.1 nM) and a noncompetitive inhibitor with respect to OSB (Ki=11.2±0.9 nM). These data are consistent with a Bi Uni Uni Bi Ping‐Pong kinetic mechanism for these enzymes. In addition, OSB‐AMS inhibits saMenE with ${K{{{\rm app}\hfill \atop {\rm i}\hfill}}}$=22±8 nM and ecMenE with ${K{{{\rm OSB}\hfill \atop {\rm i}\hfill}}}$=128±5 nM. Putative active‐site residues, Arg222, which may interact with the OSB aromatic carboxylate, and Ser302, which may bind the OSB ketone oxygen, have been identified through computational docking of OSB‐AMP with the unliganded crystal structure of saMenE. A pH‐dependent interconversion of the free keto acid and lactol forms of the inhibitors is also described, along with implications for inhibitor design.
Iron‐Mediated and ‐Catalyzed Metalative Cyclization of Electron‐Withdrawing‐Group‐Substituted Alkynes and Alkenes with Grignard Reagents
Authors: Hata Takeshi , Sujaku Shiro , Hirone Naoki , Nakano Kirihiro , Imoto Junsuke , Imade Haduki , Urabe Hirokazu 
Published: November 2011

AbstractTreatment of ethyl (E)‐5,5‐bis[(benzyloxy)methyl]‐8‐(N,N‐diethylcarbamoyl)‐2‐octen‐7‐ynoate with an iron reagent generated from FeCl2 and tBuMgCl in a ratio of 1:4 (abbreviated as FeCl2/4 tBuMgCl) afforded ethyl [4,4‐bis[(benzyloxy)methyl]‐2‐[(E)‐(N,N‐diethylcarbamoyl)methylene]cyclopent‐1‐yl]acetate in good yield. Deuteriolysis of an identical reaction mixture afforded the bis‐deuterated product ethyl [4,4‐bis[(benzyloxy)methyl]‐2‐[(E)‐(N,N‐diethylcarbamoyl)deuteriomethylene]cyclopent‐1‐yl]deuterioacetate, thus confirming the existence of the corresponding dimetalated intermediate. The latter intermediate can react with halogens or aldehydes to facilitate further synthetic transformations. The amount of FeCl2 was reduced to catalytic levels (10 mol % relative to enyne), and catalytic cyclizations of this sort proceeded with yields comparable to those of the aforementioned stoichiometric reactions. The cyclization of diethyl (E,E)‐2,7‐nonadienedioate with a stoichiometric amount of FeCl2/4 tBuMgCl, followed by the addition of sBuOH as a proton source, afforded a mixture of 2‐(ethoxycarbonyl)‐3‐bicyclo[3.3.0]octanone and its enol form in good yield. The use of aldehyde or ketone in place of sBuOH afforded 2‐(ethoxycarbonyl)‐3‐bicyclo[3.3.0]octanone, which has an additional hydroxyalkyl side chain. Additionally, the metalation of a carbon–carbon unsaturated bond in N,N‐diethyl‐5,5‐bis[(benzyloxy)methyl]‐7,8‐epoxy‐2‐octynamide or (E)‐3,3‐dimethyl‐6‐(N,N‐diethylcarbamoyl)‐5‐hexenyl p‐toluenesulfonate with FeCl2/4 tBuMgCl or FeCl2/4 PhMgBr was followed by an intramolecular alkylation with an epoxide or alkyl p‐toluenesulfonate to afford 5,5‐bis[(benzyloxy)methyl]‐3‐[(E)‐(N,N‐diethylcarbamoyl)methylene]‐1‐cyclohexanol or N,N‐diethyl(3,3‐dimethylcyclopentyl)acetamide after hydrolysis. In both cases, the remaining metalated portion α to the amide group was confirmed by deuteriolysis and could be utilized for an alkylation with methyl iodide.
Well‐Organized Zeolite Nanocrystal Aggregates with Interconnected Hierarchically Micro–Meso–Macropore Systems Showing Enhanced Catalytic Performance
Authors: Yang Xiao‐Yu , Tian Ge , Chen Li‐Hua , Li Yu , Rooke Joanna C. , Wei Ying‐Xu , Liu Zhong‐Min , Deng Zhao , Van Tendeloo Gustaaf , Su Bao‐Lian 
Published: November 2011

AbstractPreparation and characterization of well‐organized zeolitic nanocrystal aggregates with an interconnected hierarchically micro–meso–macro porous system are described. Amorphous nanoparticles in bimodal aluminosilicates were directly transformed into highly crystalline nanosized zeolites, as well as acting as scaffold template. All pores on three length scales incorporated in one solid body are interconnected with each other. These zeolitic nanocrystal aggregates with hierarchically micro–meso–macroporous structure were thoroughly characterized. TEM images and 29Si NMR spectra showed that the amorphous phase of the initial material had been completely replaced by nanocrystals to give a micro–meso–macroporous crystalline zeolitic structure. Catalytic testing demonstrated their superiority due to the highly active sites and the presence of interconnected micro–meso–macroporosity in the cracking of bulky 1,3,5‐triisopropylbenzene (TIPB) compared to traditional zeolite catalysts. This synthesis strategy was extended to prepare various zeolitic nanocrystal aggregates (ZSM‐5, Beta, TS‐1, etc.) with well‐organized hierarchical micro–meso–macroporous structures.
Evidences for the Key Role of Hydrogen Bonds in Nucleophilic Aromatic Substitution Reactions
Authors: Chéron Nicolas , El Kaïm Laurent , Grimaud Laurence , Fleurat‐Lessard Paul 
Published: November 2011

AbstractThe effect of hydrogen bonds on the fate of nucleophilic aromatic substitutions (SNAr) has been studied in silico using a density functional theory approach in the condensed phase. The importance of these hydrogen bonds can explain the “built‐in solvation” model of Bunnett concerning intermolecular processes between halogenonitrobenzenes and amines. It is also demonstrated that it can explain experimental results for a multicomponent reaction (the Ugi–Smiles coupling), involving an intramolecular SNAr (the Smiles rearrangement) as the key step of the process. Modeling reveals that when an intramolecular hydrogen bond is present, it lowers the activation barrier of this step and enables the multicomponent reaction to proceed.
Rotational Spectrum and Internal Dynamics of Tetrahydrofuran–Krypton
Authors: Gou Qian , Feng Gang , Evangelisti Luca , Maris Assimo , Marchini Marianna , Velino Biagio , Caminati Walther 
Published: November 2011

AbstractThe rotational spectrum of the tetrahydrofuran–krypton van der Waals complex has been investigated by pulsed‐jet Fourier transform microwave spectroscopy. The spectra of the 84Kr and 86Kr isotopologues have been assigned and the krypton atom is located nearly over the oxygen atom, almost perpendicular to the COC plane. Each rotational transition is split into two component lines due to, according to the observed Coriolis coupling term between the tunneling states, the residual pseudorotational effects of the ring in the complex. The splitting between the two vibrational sublevels is 87.462(2) and 87.062(2) MHz for the 84Kr and 86Kr isotopologues, respectively. These splittings have been used to determine the barrier to inversion, B2=67 cm−1. The dissociation energy has been estimated to be 3.7 kJ mol−1 from centrifugal distortion effects.
Biomarkers: improving the cost‐effectiveness of biological drugs for autoimmune disorders
Authors: Gurwitz David 
Published: November 2011

AbstractBiological drugs are gradually becoming the treatment of choice for chronic autoimmune diseases. However, their high costs are a key healthcare concern limiting their attractiveness for payers. This can, in part, be offset by implementing drug response biomarkers so that payers will only cover the drugs for patients who are most likely to benefit from them. Identifying such biomarkers in turn depends on the availability of well‐characterized clinical samples. Research collaboration between the pharmaceutical industry, clinicians, and academia is paramount for achieving this goal. Drug Dev Res 72:549–552, 2011. © 2011 Wiley Periodicals, Inc.
Emergence of small‐molecule CXCR4 antagonists as novel immune and hematopoietic system regulatory agents
Authors: Wilson Lawrence J. , Liotta Dennis C. 
Published: November 2011

AbstractThe chemokine CXCR4 receptor is a G‐protein‐coupled receptor that has multiple functions in normal physiologies involving the hematopoietic and immune systems. Although the CXCR4 receptor was initially discovered as one of the co‐receptors involved in human immune deficiency virus (HIV) cell entry, it has also been linked to many central immune system functions through the direct regulation of cell trafficking and adhesion, and is present in many cell types within the body. The receptor ligand combination of CXCL12 (SDF‐1) and CXCR4 underlies pathologies such as HIV infection, cancer metastasis and drug resistance, leukemia progression, rheumatoid arthritis, and lupus. This alternative and widespread functionality has allowed researchers to discover new potential uses for substances that are CXCR4 antagonists. This has resulted in approval of the first CXCR4 antagonist, plerixafor injection (AMD3100), for hematopoietic stem cell mobilization. Newer agents are under clinical evaluation for HIV, cancer, and stem cell mobilization. As these agents are further investigated, new uses and therapeutic interventions for CXCR4 antagonists will be discovered. Drug Dev Res 72:598–602, 2011. © 2011 Wiley Periodicals, Inc.
Anti‐tumor necrosis factor‐α therapies for immune‐mediated and inflammatory skin diseases
Authors: Dessinioti Clio , Stratigos Alexander J. , Katsambas Andreas , Antoniou Christina 
Published: November 2011

AbstractAnti‐tumor necrosis factor‐α (TNF‐α) therapies, also called biologic therapies or immunotherapies, are being used increasingly in dermatology, rheumatology, and gastroenterology in the context of established and emerging indications. Anti‐TNF agents target TNF‐α and include infliximab (a chimeric IgG1 monoclonal antibody), adalimumab (a fully human recombinant IgG1 monoclonal antibody), and etanercept (a dimeric fusion protein of TNFR1 linked to the Fc portion of IgG1). Among skin diseases, only plaque psoriasis represents an approved indication for the use of anti‐TNF‐α agents; however, anti‐TNF therapies have been used as off‐label treatments in a plethora of immune‐mediated or inflammatory cutaneous disorders, such as hidradenitis suppurativa, alopecia areata, pyoderma gangrenosum, and pemphigus vulgaris. In this short review we present accumulating evidence regarding the dual effect of these therapies in inflammatory skin diseases, either resulting in improvement or acting as a paradoxical trigger for their development. The proposed mechanism of action of anti‐TNF treatments on pathogenic key points of these skin conditions is also discussed. Drug Dev Res 72:615–622, 2011. © 2011 Wiley Periodicals, Inc.
Belimumab therapy for systemic lupus erythematosus and potential treatment of rheumatoid arthritis
Authors: Ding Changhai , Li Ran , Xu Jianhua , Cicuttini Flavia , Jones Graeme 
Published: November 2011

AbstractB‐lymphocyte stimulator (BLyS) maintains the survival of B cells, and is elevated in serum or locally in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Belimumab (LymphoStat‐B) is a fully human IgG1λ monoclonal antibody that binds to soluble human BLyS and inhibits its biological activity. It has been developed for therapy for SLE and the potential treatment of other autoimmune diseases. Belimumab was well tolerated in the treatment of SLE for more than 5 years and of RA for more than 24 weeks. In the pooled analyses of two Phase III trials including 1,684 seropositive SLE patients, a statistically significant improvement was observed for the SLE responder index at week 52 for belimumab 1 mg/kg and 10 mg/kg as compared with placebo (46% vs 39%, P = 0.006; 51% vs 39%, P<0.0001, respectively). It modestly reduced the signs and symptoms of RA, most notably in subgroups such as patients with high disease activity, positive rheumatoid factor, and no prior anti‐tumor necrosis factor (TNF) treatment. Belimumab has been approved by the US Food and Drug Administration for the treatment of adult patients with active and seropositive SLE who are receiving standard therapy, but its place in the treatment of RA and other autoimmune diseases remains uncertain. Drug Dev Res 72:623–633, 2011. © 2011 Wiley Periodicals, Inc.
Current management of Behçet's syndrome
Authors: Nowatzky Johannes , Yazici Yusuf 
Published: November 2011

AbstractBehçet's syndrome (BS), or Behçet's disease (BD), is a multisystem inflammatory disorder that mainly affects population clusters along the Old Silk Road; however, it has been reported worldwide. The disease is currently classified as a vasculitis, characterized by sporadic outbreaks. The hallmarks of BS are recurrent, painful oral ulcers. Skin, eyes, central nervous system (CNS), gastrointestinal tract (GI) tract, and other organs may also be involved. CNS, GI, and major vascular involvement can be life‐threatening, and uveitis may lead to blindness. Immunosuppressive and immunomodulatory treatment is the mainstay of therapy for this inflammatory disease. Whereas the most frequently used agents for the treatment of BS have been corticosteroids, colchicine, and azathioprine, the introduction of anti‐tumor necrosis factor (TNF) agents and interferon‐α (IFN‐α) has begun to revolutionize the treatment of Behçet's eye disease and the management of other major organ manifestations. Data from randomized controlled trials (RCTs) showing beneficial effects for some of its disease manifestations are available for azathioprine, colchicine, cyclosporine, etanercept, IFN‐α depot‐methylprednisolone, and others. Currently, an evidence‐based approach to the management of BS is possible only for eye, mucocutaneous, and joint involvement, whereas recommendations for the treatment of gastrointestinal, neurological, and vascular disease remain based on expert opinion. Drug Dev Res 72:647–656, 2011. © 2011 Wiley Periodicals, Inc.
Electrocatalytic Oxidation of Estrogenic Phenolic Compounds at a Nickel‐Modified Glassy Carbon Electrode
Authors: Muna Grace W. , Kaylor Adam , Jaskowski Bonnie , Sirhan Lama R. , Kelley Craig T. 
Published: November 2011

AbstractThis paper demonstrates for the first time, successful electrocatalytic oxidation of electroactive estrogenic phenolic compounds (EPCs) at a nickel‐modified glassy carbon electrode (Ni‐GCE). The electrode was evaluated in terms of electrocatalytic activity, sensitivity, linear dynamic range, limit of detection, and response stability. In comparison to bare glassy carbon electrode, current amplification was observed for EPCs at Ni‐GCE, for example, for a 40 µM estrone at Ni‐GCE was amplified by a factor of 1224. The Ni‐GCE gave good figures of merit with no evidence of electrode fouling. As an example, the limit of detection (S/N=3) for 17β‐estradiol was 100 nM and the response precision (n=5) was 3.4 %.
On the distributed Lagrange multiplier/fictitious domain method for rigid‐particle‐laden flows: a proposition for an alternative formulation of the Lagrange multipliers
Authors: Yiantsios S.G. 
Published: November 2011

SUMMARYThe distributed Lagrange multiplier/fictitious domain method proposed for the direct numerical simulation of particle‐laden flows is considered in this work. First, it is demonstrated that improved accuracy is obtained with a coupled numerical scheme, whereby the pressure and the Lagrange multiplier fields enforcing incompressibility and rigid body motion, respectively, are calculated and applied together. However, the convergence characteristics of the iterative solution of the coupled scheme are poor because symmetric but indefinite and poorly conditioned matrices are produced. An analysis is then presented, which suggests that the cause for the matrix pathologies lies in the interaction of the respective matrix operators enforcing incompressibility and rigid body motion. On the basis of this analysis, an alternative formulation is developed for the Lagrange multipliers, being now composed of a set of forces distributed only on the particle boundary together with a set of couples distributed within the particle core. The new formulation is tested with several types of flows with stationary or moving particles under creeping or finite Reynolds number conditions and it is demonstrated that it produces correct results and better conditioned matrices, thus enabling faster and more reliable convergence of the conjugate gradient method. The analysis and tests, therefore, support the expectation that the proposed formulation is promising and worthy of further study and improvement. Copyright © 2011 John Wiley & Sons, Ltd.
Electric field calculations in brain stimulation based on finite elements: An optimized processing pipeline for the generation and usage of accurate individual head models
Authors: Windhoff Mirko , Opitz Alexander , Thielscher Axel 
Published: November 2011

AbstractThe need for realistic electric field calculations in human noninvasive brain stimulation is undisputed to more accurately determine the affected brain areas. However, using numerical techniques such as the finite element method (FEM) is methodologically complex, starting with the creation of accurate head models to the integration of the models in the numerical calculations. These problems substantially limit a more widespread application of numerical methods in brain stimulation up to now. We introduce an optimized processing pipeline allowing for the automatic generation of individualized high‐quality head models from magnetic resonance images and their usage in subsequent field calculations based on the FEM. The pipeline starts by extracting the borders between skin, skull, cerebrospinal fluid, gray and white matter. The quality of the resulting surfaces is subsequently improved, allowing for the creation of tetrahedral volume head meshes that can finally be used in the numerical calculations. The pipeline integrates and extends established (and mainly free) software for neuroimaging, computer graphics, and FEM calculations into one easy‐to‐use solution. We demonstrate the successful usage of the pipeline in six subjects, including field calculations for transcranial magnetic stimulation and transcranial direct current stimulation. The quality of the head volume meshes is validated both in terms of capturing the underlying anatomy and of the well‐shapedness of the mesh elements. The latter is crucial to guarantee the numerical robustness of the FEM calculations. The pipeline will be released as open‐source, allowing for the first time to perform realistic field calculations at an acceptable methodological complexity and moderate costs. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.
Quantitative effect of the neonatal fontanel on synthetic near infrared spectroscopy measurements
Authors: Dehaes Mathieu , Kazemi Kamran , Pélégrini‐Issac Mélanie , Grebe Reinhard , Benali Habib , Wallois Fabrice 
Published: November 2011

AbstractNear infrared spectroscopy (NIRS) is a functional imaging technique allowing measurement of local cerebral oxygenation. This modality is particularly adapted to critically ill neonates, as it can be used at the bedside and is a suitable and noninvasive tool for carrying out longitudinal studies. However, NIRS is sensitive to the imaged medium and consequently to the optical properties of biological tissues in which photons propagate. In this study, the effect of the neonatal fontanel was investigated by predicting photon propagation using a probabilistic Monte Carlo approach. Two anatomical newborn head models were created from computed tomography and magnetic resonance images: (1) a realistic model including the fontanel tissue and (2) a model in which the fontanel was replaced by skull tissue. Quantitative change in absorption due to simulated activation was compared for the two models for specific regions of activation and optical arrays simulated in the temporal area. A correction factor was computed to quantify the effect of the fontanel and defined by the ratio between the true and recovered change. The results show that recovered changes in absorption were more precise when determined with the anatomical model including the fontanel. The results suggest that the fontanel should be taken into account in quantification of NIRS responses to avoid misinterpretation in experiments involving temporal areas, such as language or auditory studies. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.