bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Sulfated Cyclofructan 6 and Sulfated Cyclodextrins for the Chiral Separation of Four Basic Pharmaceuticals by Capillary Electrophoresis
Authors: Zhang Yi Jun , Huang Ming Xian , Zhang Yu Ping , Armstrong Daniel Wayne , Breitbach Zachary S. , Ryoo Jae Jeong 
Published: August 2013

ABSTRACTSulfated cyclofructan 6 (S‐CF6) and sulfated cyclodextrins (S‐α‐, β‐, γ‐CDs) are highly selective chiral selectors for the enantioseparation of basic solutes. In this study, S‐CF6 was introduced for the enantiomeric separation of four basic pharmaceuticals (including tamsulosin, tiropramide, bupivacaine, and norephedrine) by capillary electrophoresis (CE), and the enantiomeric separation performance was compared with S‐α‐, β‐, γ‐CDs. The effects of the chiral selector type, chiral selector concentration, operating voltage, and column temperature were examined and optimized. Excellent resolutions were obtained for all solutes on these chiral selectors. Chirality 25:735–742, 2013. © 2013 Wiley Periodicals, Inc.
Numerical simulation of spouting of cylindroid particles in a spouted bed
Authors: Ren Bing , Zhong Wenqi , Jiang Xiaofeng , Jin Baosheng , Yuan Zhulin 
Published: August 2013

AbstractThe hydrodynamic behaviours of cylindroid particles in a spouted bed are studied by three‐dimensionally coupled computational fluid dynamic (CFD) and discrete element method (DEM) model. The cylindroid particles are constructed by multi‐sphere method. The drag coefficient model for non‐spherical particles is employed which shows higher accuracy by comparing the calculated flow pattern and pressure drop distribution data with the experimental measurements and the predicted results with the traditional drag coefficient model for spherical particles. Peak pressure drop, flow pattern, spout diameter and geometry of the fountain are discussed in detail.
Interactions of the Multidrug Resistance Modulators Tariquidar and Elacridar and their Analogues with P‐glycoprotein
Authors: Pajeva Ilza K. , Sterz Katja , Christlieb Matthias , Steggemann Kerstin , Marighetti Federico , Wiese Michael 
Published: August 2013

AbstractTariquidar and elacridar are among the most potent inhibitors of the multidrug resistance transporter P‐glycoprotein (P‐gp), but how they interact with the protein is yet unknown. In this work, we describe a possible way in which these inhibitors interact with P‐gp. We rely on structure–activity relationship analysis of a small group of tariquidar and elacridar analogues that was purposefully selected, designed, and tested. Structural modifications of the compounds relate to the presence or absence of functional groups in the tariquidar and elacridar scaffolds. The activity of the compounds was evaluated by their effects on the accumulation of P‐gp substrates rhodamine 123 and Hoechst 33342 in resistant tumor cells. The data allow estimation of the ability of the compounds to interact with the experimentally proposed R‐ and H‐sites to which rhodamine 123 and Hoechst 33342 bind, respectively. Using an inward‐facing homology model of human P‐gp based on the crystallographic structure of mouse P‐gp, we demonstrate that these binding sites may overlap with the binding sites of the QZ59 ligands co‐crystallized with mouse P‐gp. Based on this SAR analysis, and using flexible alignment and docking, we propose possible binding modes for tariquidar and elacridar. Our results suggest the possibility for the studied compounds to bind to sites that coincide or overlap with the binding sites of rhodamine 123 and Hoechst 33342. These results contribute to further understanding of structure–function relationships of P‐gp and can help in the design of selective and potent P‐gp inhibitors with potential clinical use.
Targets, Structures, and Recent Approaches in Malignant Melanoma Chemotherapy
Authors: Matos Ana Marta , Francisco Ana Paula 
Published: August 2013

AbstractMalignant metastatic melanoma is one of the oncologic diseases with the worst clinical prognosis, due primarily to resistance phenomena against chemotherapeutic agents in current use. However, over the last few years, characterization of the molecular mechanisms involved in the development and progression of the disease has contributed to elucidation of the main pathways by which tissue invasion and metastasis can occur. More importantly, the identification of abnormalities in signaling cascades in melanoma cells has facilitated new therapeutic approaches against malignant melanoma through the design of highly potent and selective drugs with low associated toxicity. Ultimately, recognition of the restricted applicability of new chemotherapies in certain genetic contexts has led to significant improvements in the results of clinical trials, anticipating the existing need for investment in personalized therapies, and taking into account the molecular alterations observed in tumors. Although significant advances have been made in terms of extending the median overall survival rate and improving the quality of life for patients, the mechanisms that compromise in vivo drug efficacy remain poorly understood, particularly those concerning therapeutic resistance phenomena. This review summarizes recently validated targets from the perspective of the medicinal chemistry carried out in the design of the most promising structures.
A Conformational Mimetic Approach for the Synthesis of Carbocyclic Nucleosides as Anti‐HCV Leads
Authors: Kasula Mohan , Balaraju Tuniki , Toyama Massaki , Thiyagarajan Anandarajan , Bal Chandralata , Baba Masanori , Sharon Ashoke 
Published: August 2013

AbstractComputer‐aided approaches coupled with medicinal chemistry were used to explore novel carbocyclic nucleosides as potential anti‐hepatitis C virus (HCV) agents. Conformational analyses were carried out on 6‐amino‐1H‐pyrazolo[3,4‐d]pyrimidine (6‐APP)‐based carbocyclic nucleoside analogues, which were considered as nucleoside mimetics to act as HCV RNA‐dependent RNA polymerase (RdRp) inhibitors. Structural insight gained from the modeling studies revealed the molecular basis behind these nucleoside mimetics. The rationally chosen 6‐APP analogues were prepared and evaluated for anti‐HCV activity. RdRp SiteMap analysis revealed the presence of a hydrophobic cavity near C7 of the nucleosides; introduction of bulkier substituents at this position enhanced their activity. Herein we report the identification of an iodinated compound with an EC50 value of 6.6 μM as a preliminary anti‐HCV lead.
Cytologic subtyping of lung adenocarcinoma by using the proposed International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) adenocarcinoma classification
Authors: Rodriguez Erika F. , Monaco Sara E. , Dacic Sanja 
Published: August 2013

BACKGROUNDThe significance of histologic subtyping of surgically resected lung adenocarcinoma (ADC) was recently proposed by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification. Approximately 70% of lung cancer patients present with advanced disease, and small biopsies or cytology specimens are frequently the only available diagnostic material. It is uncertain whether proposed morphologic subtyping of ADC can be applied to small specimens. The objective of this study was to assess the applicability of morphologic subtyping of ADC on cytologic specimens.METHODSConsecutive, newly diagnosed primary lung ADC specimens from patients with matched surgical resection and cytology specimens (n = 66) were selected for the study. The dominant morphologic pattern was determined according to the IASLC/ATS/ERS classification. The number and percentage of malignant cells in cytology specimens were also evaluated.RESULTSConcordant subtyping of ADC between the dominant pattern on resection and cytology specimens was observed in 26 cases (40%), and was discordant in 32 cases (48%). Concordance increased in specimens that had >200 cells and when correlating with the primary or secondary histologic pattern. The acinar pattern was the most common in concordant cases, whereas discordant cases had a predominantly solid pattern.CONCLUSIONSApplication of the IASLC/ATS/ERS ADC classification to cytologic specimens is challenging and depends on the sufficient cellularity of cytologic preparations. The identification of solid and micropapillary patterns is prognostically important but may be unreliable and difficult on cytology specimens. Future studies are needed to establish reproducible cytologic criteria for the precise subtyping of lung ADC on small specimens. Cancer (Cancer Cytopathol) 2013;121:629–37. © 2013 American Cancer Society.
Effect of Vortioxetine on Cardiac Repolarization in Healthy Adult Male Subjects: Results of a Thorough QT/QTc Study
Authors: Wang Ying , Nomikos George G. , Karim Aziz , Munsaka Melvin , Serenko Michael , Liosatos Maggie , Harris Stuart 
Published: August 2013

ABSTRACTThis double‐blind, randomized, placebo‐ and positive‐controlled, parallel‐group study evaluated the effect of vortioxetine (Lu AA21004), an investigational multimodal antidepressant, on QT interval in accordance with current guidelines of the International Conference on Harmonisation (ICH‐E14). A total of 340 healthy men were randomized to receive 1 of 4 treatments for 14 days: (1) vortioxetine 10 mg once daily (QD), (2) vortioxetine 40 mg QD, (3) placebo QD, or (4) placebo QD on Days 1 through 13 followed by a single dose of moxifloxacin 400 mg (positive control). The primary endpoint was the largest time‐matched, baseline‐adjusted least‐squares (LS) mean difference for the individual‐corrected QT interval (QTcNi [linear]) between vortioxetine and placebo. Alternative QT correction formulas (i.e., Fredericia [QTcF], Bazett [QTcB], Framingham [QTcFm], and QTcNi [nonlinear]) were used as secondary endpoints. The upper bound of the 2‐sided 90% confidence interval around the LS mean difference from placebo for baseline‐adjusted QTcNi (linear), QTcF, QTcB, QTcFm, and QTcNi (nonlinear) did not exceed 10 ms at any time point after multiple doses of vortioxetine 10 mg (therapeutic) or 40 mg (supratherapeutic). Overall, the study results indicate that vortioxetine is unlikely to affect cardiac repolarization in healthy subjects.
Pharmacokinetics of Single‐Dose Dolutegravir in HIV‐Seronegative Subjects With Moderate Hepatic Impairment Compared to Healthy Matched Controls
Authors: Song Ivy H. , Borland Julie , Savina Paul M. , Chen Shuguang , Patel Parul , Wajima Toshihiro , Peppercorn Amanda F. , Piscitelli Stephen C. 
Published: August 2013

AbstractThis study evaluated dolutegravir pharmacokinetics (PK) in subjects with moderate hepatic impairment compared to matched, healthy controls. In this open‐label, parallel‐group study, eight adult subjects with moderate hepatic impairment (Child‐Pugh Score 7–9) and eight healthy subjects matched for gender, age, and body mass index received a single dolutegravir 50‐mg dose. Following dosing, 72‐hour PK sampling was performed to determine total and unbound dolutegravir concentrations. PK parameters were calculated using non‐compartmental analysis. Geometric least squares mean ratios (GMR) and 90% confidence intervals (CIs) in subjects with hepatic impairment versus healthy subjects were generated by analysis of variance. Results showed that PK parameters of total plasma dolutegravir were similar between subject groups. The unbound fraction was higher in subjects with moderate hepatic impairment than in healthy subjects with GMR (90% CI) of 2.20 (1.62, 2.99) for unbound fraction at 3 hours post‐dose and 1.76 (1.23, 2.51) for unbound fraction at 24 hours post‐dose; this correlated with lower serum albumin concentrations and was not considered clinically significant. Dolutegravir was well tolerated in both groups; all adverse events were reported as minor. Although free fraction was increased, no dose adjustment is required for patients treated with dolutegravir who have mild to moderate hepatic impairment.
Number Density of Liquid Inclusions Formed in Frozen Aqueous Electrolyte
Authors: Hashimoto Takuya , Harada Makoto , Nojima Shuichi , Okada Tetsuo 
Published: August 2013

AbstractFrozen aqueous chlorides (≤50 mM) are characterized by using confocal fluorescence microscopy and small angel X‐ray scattering (SAXS). The former method allows us to determine the size of a liquid inclusion formed in the ice matrix at temperatures above the eutectic point of the system (teu). Isolated liquid inclusions of a uniform size are formed when the temperature of a frozen electrolyte increases past teu. The size of the liquid inclusions depends on the observation temperature as well as on the concentration (csalt) and type of salt dissolved in the original unfrozen solution. However, the number density of liquid inclusions is almost constant and independent of these experimental parameters, particularly when an electrolyte is frozen in liquid nitrogen. Salt accumulation can then occur at the imperfections of the ice crystals. The occurrence probability of the imperfections is independent of the nature of an incorporated salt. The amount of a salt confined in each inclusion ranges from 7 to 240 fmol, depending on csalt. SAXS measurements provide information on the size of individual salt crystals formed at temperatures below teu. The radius of gyration of a salt crystal ranges from 2 to 2.8 nm, and does not depend significantly on csalt. Thus, each inclusion is formed from 106–109 nanocrystals, which can act as seeds. When doped ice is prepared at higher temperatures, for example −16 °C, the isolation of liquid inclusions is not sufficient and coalescence occurs more easily upon an increase in temperature or csalt. However, when csalt is lower than 10 mM, the number density of liquid inclusions is almost constant, irrespective of the freezing temperature.
Comparison of Force Fields on the Basis of Various Model Approaches—How To Design the Best Model for the [CnMIM][NTf2] Family of Ionic Liquids
Authors: Köddermann Thorsten , Reith Dirk , Ludwig Ralf 
Published: August 2013

AbstractIn this contribution, we present two new united‐atom force fields (UA‐FFs) for 1‐alkyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide [CnMIM][NTf2] (n=1, 2, 4, 6, 8) ionic liquids (ILs). One is parametrized manually, and the other is developed with the gradient‐based optimization workflow (GROW). By doing so, we wanted to perform a hard test to determine how researchers could benefit from semiautomated optimization procedures. As with our already published all‐atom force field (AA‐FF) for [CnMIM][NTf2] (T. Köddermann, D. Paschek, R. Ludwig, ChemPhysChem­ 2007, 8, 2464), the new force fields were derived to fit experimental densities, self‐diffusion coefficients, and NMR rotational correlation times for the IL cation and for water molecules dissolved in [C2MIM][NTf2]. In the manual force field, the alkyl chains of the cation and the CF3 groups of the anion were treated as united atoms. In the GROW force field, only the alkyl chains of the cation were united. All other parts of the structures of the ions remained unchanged to prevent any loss of physical information. Structural, dynamic, and thermodynamic properties such as viscosity, cation rotational correlation times, and heats of vaporization calculated with the new force fields were compared with values simulated with the previous AA‐FF and the experimental data. All simulated properties were in excellent agreement with the experimental values. Altogether, the UA‐FFs are slightly superior for speed‐up reasons. The UA‐FF speeds up the simulation by about 100 % and reduces the demanded disk space by about 78 %. More importantly, real time and efforts to generate force fields could be significantly reduced by utilizing GROW. The real time for the GROW parametrization in this work was 2 months. Manual parametrization, in contrast, may take up to 12 months, and this is, therefore, a significant increase in speed, though it is difficult to estimate the duration of manual parametrization.
The Semiempirical Quantum Mechanical Scoring Function for In Silico Drug Design
Authors: Lepšík Martin , Řezáč Jan , Kolář Michal , Pecina Adam , Hobza Pavel , Fanfrlík Jindřich 
Published: August 2013

AbstractThis Minireview discusses the latest developments in modern quantum mechanics (QM)‐based computer‐aided drug design, especially using semiempirical QM (SQM) methods. It first tackles biochemical and biophysical quantities and the approaches to their measurements. Protein–ligand affinities are determined mostly by noncovalent interactions. The text thus illustrates how these can be accurately treated with SQM methods. Next, a construction of a modern SQM‐based scoring function is presented and its applications listed. In summary, SQM‐based scoring is a promising modern efficient strategy to be exploited in computer‐aided drug design.
Recover, Recycle, and Reuse: Prove‐Out of Pyrotechnic Illuminants Containing Demilitarized Magnesium
Authors: Sabatini Jesse J. , Moretti Jared D. , Hall Derrick R. , Robert Leon L. 
Published: August 2013

AbstractThe development and prove‐out of yellow‐light‐emitting pyrotechnic illuminants based on recover, recycle, and reuse (R3) technology is described. Magnesium used in this investigation was recovered from four different illuminating pyrotechnic munitions by means of an environmentally friendly demilitarization process. Despite significant differences in the particle size and purity between the four lots of recovered magnesium, the performance of each lot—on evaluation in the M127A1 US Army yellow‐light‐emitting illuminant configuration—exceeded the military requirement and performance of the virgin magnesium‐containing control. All formulations were found to have low sensitivities to various ignition stimuli and possessed high thermal onset temperatures. In addition to the military significance, this demonstrated “green” pyrotechnics technology of using recycled magnesium in illuminating pyrotechnics may also be of interest to the civilian fireworks community.
Chemistry of Heterocyclic 2‐Thiones: In Situ Generation of 3‐(2‐Thiazolin‐2‐yl)thiazolidine‐2‐thione and 1,1′‐Dimethyl‐2,2′‐diimidazolyl Sulfide and Their Coordination to CuI and CuII
Authors: Lobana Tarlok S. , Sultana Razia , Butcher Ray J. , Castineiras Alfonso , Akitsu Takashiro , Fernandez Francisco J. , Vega M. Cristina 
Published: August 2013

AbstractThe chemical reactivity of copper(I) chloride/copper(I) bromide, [CuI(NCCH3)4](BF4), and copper(II) nitrate towards a series of heterocyclic‐2‐thiones under aerobic conditions is described. Thiazolidine‐2‐thione (NC3H5S2) in CH3CN in the presence of copper(I) chloride/bromide and [CuI(NCCH3)4](BF4) was transformed into 3‐(2‐thiazolin‐2‐yl)thiazolidine‐2‐thione (C3H4S2N‐C3H4SN) through C–S bond cleavage and the formation of a C–N bond between two heterocyclic rings. This new thio ligand (C3H4S2N‐C3H4SN) chelates to CuI through N,S‐donor atoms, and the third site is occupied by the halogen atoms (Cl, Br), which leads to the formation of three‐coordinate CuI complexes, [CuIX(κ2‐N,S‐C3H4S2N‐C3H4SN)] [X = Cl (1), Br (2)], and a four‐coordinate N,S‐chelated complex, [CuI(κ2‐N,S‐C3H4S2N‐C3H4SN)2](BF4) (3), is obtained in the presence of BF4–. In each case, the formation of CuSO4·5H2O was also observed. Upon reaction of 1‐methylimidazoline‐2‐thione (N2C4H6S) with [CuI(NCCH3)4](BF4) or copper(II) nitrate in CH3CN or CH3CN/MeOH, respectively, the thio ligand is converted into 1,1′‐dimethyl‐2,2′‐diimidazolyl sulfide (N2C4H5)2S (a thioether), which prefers to bind to CuII (in situ formed) to yield six‐coordinate N,N‐chelated octahedral complexes, namely, {CuII[κ2‐N,N‐(N2C4H5)2S]2(κ1‐OH2)2}X2 [X = BF4 (6), NO3 (7)], with water in the axial positions. The transformation of the thio ligand into 1,1′‐dimethyl‐2,2′‐diimidazolyl sulfide is also observed in its copper(I) chloride reaction in acetonitrile, which yields an N,N‐chelated chloro‐bridged dimer, {CuII2[κ2‐N,N‐(N2C4H5)2S]2(μ‐Cl)2Cl2} (5). Reaction of copper(I) iodide with thiazolidine‐2‐thione and 1‐methylimidazolidine‐2‐thione (N2C4H8S) in acetonitrile yields an iodo‐bridged dimer, [Cu2(κ1‐S‐NC3H5S2)4(μ‐I)2] (4), and a novel polymer, [Cu4(μ3‐I)2(μ‐I)2(μ‐S‐N2C4H8S)2(κ1‐S‐N2C4H8S)]n (8), respectively.
Bis(aryl)acenaphthenequinonediimine Substituent Effect on the Properties and Coordination Environment of Ligands and Their Bis‐Chelate AgI Complexes
Authors: Papanikolaou Panagiotis A. , Gdaniec Maria , Wicher Barbara , Akrivos Pericles D. , Tkachenko Nikolai V. 
Published: August 2013

AbstractThe reaction of a series of Ar–BIAN ligands (Ar = o‐Ph, m‐Cl, m‐CF3, p‐Cl, p‐MeO, and p‐Me–C6H4) with AgNO3 results in the formation of the corresponding bis‐chelate complexes. Substituent groups on the aryl rings seem to offer tunability of the electronic properties of the diimines, also affecting the metal coordination environment through the mono‐coordination or chelation of the nitrate anion as promoted by the substituents p‐MeO, p‐Me, and m‐CF3. The enhanced absorption capacity of the complexes in the visible region in combination with the well‐known redox activity of the ligands and their ability to potentially accommodate a fifth coordinated ligand on the metal center opens a route for the preparation of new silver species of high propensity for catalytic, photocatalytic, and biological applications.
Numerical solution of large and sparse continuous time algebraic matrix Riccati and Lyapunov equations: a state of the art survey
Authors: Benner Peter , Saak Jens 
Published: August 2013

AbstractEfficient numerical algorithms for the solution of large and sparse matrix Riccati and Lyapunov equations based on the low rank alternating directions implicit (ADI) iteration have become available around the year 2000. Over the decade that passed since then, additional methods based on extended and rational Krylov subspace projection have entered the field and proved to be competitive alternatives. In this survey we sketch both types of methods and discuss their advantages and drawbacks. We focus on the continuous time case here, but corresponding results for discrete time problems can for most results be found in the available literature. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Theory and applications of compressed sensing
Authors: Kutyniok Gitta 
Published: August 2013

AbstractCompressed sensing is a novel research area, which was introduced in 2006, and since then has already become a key concept in various areas of applied mathematics, computer science, and electrical engineering. It surprisingly predicts that high‐dimensional signals, which allow a sparse representation by a suitable basis or, more generally, a frame, can be recovered from what was previously considered highly incomplete linear measurements by using efficient algorithms. This article shall serve as an introduction to and a survey about compressed sensing. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)