bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficient Phthalimide Copolymer‐Based Bulk Heterojunction Solar Cells: How the Processing Additive Influences Nanoscale Morphology and Photovoltaic Properties
Authors: Xin Hao , Guo Xugang , Ren Guoqiang , Watson Mark D. , Jenekhe Samson A.
Published: March 2012

The power conversion efficiency of poly(N‐(2‐ethylhexyl)‐3,6‐bis(4‐dodecyloxythiophen‐2‐yl)phthalimide) (PhBTEH)/fullerene bulk heterojunction solar cells improves from 0.43 to 4.1% by using a processing additive. The underlying mechanism for the almost 10‐fold enhancement in solar cell performance is found to be inhibition of fullerene intercalation into the polymer side chains and regulation of the relative crystallization/aggregation rates of the polymer and fullerene. An optimal interconnected two‐phase morphology with 15–20 nm domains is obtained when a processing additive is used compared with 100–300 nm domains without the additive. The results demonstrate that a processing additive provides an effective means of controlling both the fullerene intercalation in polymer/fullerene blends and the domain sizes of their phase‐separated nanoscale morphology.
Sherwood–Rayleigh parameterization for evaporation in the presence of surfactant monolayers
Authors: Bower S. M. , Saylor J. R.
Published: March 2012

Presented here is an experimental investigation of the effects of several surfactant monolayers on evaporation driven by natural convection in the air above a water surface. Experiments were performed in a controlled laboratory setting with tanks of heated water for the following cases: (1) a clean water surface, and for surfaces covered with monolayers of (2) oleyl alcohol, (3) stearic acid, and (4) stearyl alcohol. Evaporation rates were measured using a laser‐based method, and the Sherwood and Rayleigh numbers, Sh and Ra, were computed from the data. Power law scalings of the form Sh = B·Ram were developed for each case which yielded, essentially, m = 1/3 for all four surface conditions. The oleyl alcohol and stearic acid conditions give essentially the same value for B as for the clean surface case. For stearyl alcohol, B is smaller than for all other surface conditions; this result is attributed to the ability of the stearyl alcohol monolayer to inhibit evaporation by blocking the passage of water molecules through the monolayer: the barrier effect. The surface temperature is measured in this work enabling a separation of the effect of surfactants on evaporation due to a reduction in surface temperature from their effect on evaporation due to a true barrier effect. This has not been accomplished heretofore. © 2012 American Institute of Chemical Engineers AIChE J, 59: 303–315, 2013
Synthesis and Biological Evaluation of 1‐Phenyl‐1,2,3,4‐dihydroisoquinoline Compounds as Tubulin Polymerization Inhibitors
Authors: Zheng Can‐Hui , Chen Jun , Liu Jia , Zhou Xiao‐Tian , Liu Na , Shi Duo , Huang Jing‐Jing , Lv Jia‐Guo , Zhu Ju , Zhou You‐Jun
Published: March 2012

A series of 1‐phenyl‐3,4‐dihydroisoquinoline derivatives and several 1‐phenyl‐1,2,3,4‐tetrahydroisoquinoline, 1‐phenyl‐isoquinoline analogues were synthesized, and their cytotoxicity and tubulin polymerization inhibitory activity were evaluated. The 1‐phenyl‐3,4‐dihydroisoquinoline compounds were found to be potential tubulin polymerization inhibitors. Compound 5n, bearing a 3′OH and 4′OCH3 substituted 1‐phenyl B‐ring, was shown to confer optimal bioactivity. The single‐crystal structure of 5n was further determined by X‐ray diffraction, and the binding mode of 5n to tubulin was obtained by molecular docking, which can explain the structure–activity relationships. The studies presented here provide a new structural type for the development of novel antitumor agents.
Fleet size determination for a truckload distribution center
Authors: Huang Shan‐Huen , Yang Ta‐Hui , Tang Ching‐Hui
Published: March 2012

This work presents an analysis of the fleet size determination problem for a truckload distribution center in which each customer requests multi‐truckload services. A transformation is made to define this problem as a cutting stock problem which can be resolved by finding the proper set of patterns beneficial for an NP‐hard (non‐deterministic polynomial‐time hard) problem. The genetic algorithm (GA) is combined with cutting stock techniques to solve the problem. Experiments are carried out testing two types of problems, with and without time‐window constraints. To verify the solution quality obtained with the proposed approach, the problem is also solved using only GA. It is shown that the proposed approach can significantly improve the GA solution by 14.68%. Copyright © 2012 John Wiley & Sons, Ltd.
FRET microscopy in the living cell: Different approaches, strengths and weaknesses
Authors: Padilla‐Parra Sergi , Tramier Marc
Published: March 2012

New imaging methodologies in quantitative fluorescence microscopy, such as Förster resonance energy transfer (FRET), have been developed in the last few years and are beginning to be extensively applied to biological problems. FRET is employed for the detection and quantification of protein interactions, and of biochemical activities. Herein, we review the different methods to measure FRET in microscopy, and more importantly, their strengths and weaknesses. In our opinion, fluorescence lifetime imaging microscopy (FLIM) is advantageous for detecting inter‐molecular interactions quantitatively, the intensity ratio approach representing a valid and straightforward option for detecting intra‐molecular FRET. Promising approaches in single molecule techniques and data analysis for quantitative and fast spatio‐temporal protein‐protein interaction studies open new avenues for FRET in biological research.
Scanning image correlation spectroscopy
Authors: Digman Michelle A. , Gratton Enrico
Published: March 2012

Molecular interactions are at the origin of life. How molecules get at different locations in the cell and how they locate their partners is a major and partially unresolved question in biology that is paramount to signaling. Spatio‐temporal correlations of fluctuating fluorescently tagged molecules reveal how they move, interact, and bind in the different cellular compartments. Methods based on fluctuations represent a remarkable technical advancement in biological imaging. Here we discuss image analysis methods based on spatial and temporal correlation of fluctuations, raster image correlation spectroscopy, number and brightness, and spatial cross‐correlations that give us information about how individual molecules move in cells and interact with partners at the single molecule level. These methods can be implemented with a standard laser scanning microscope and produce a cellular level spatio‐temporal map of molecular interactions.
Nonparametric confidence intervals for the ratio of marginal hazard rates of paired survival times
Authors: Jin Huan , Zhao Naiqing , Tu Dongsheng
Published: March 2012

Paired survival times with potential censoring are often observed from two treatment groups in clinical trials and other types of clinical studies. The ratio of marginal hazard rates may be used to quantify the treatment effect in these studies. In this paper, a recently proposed nonparametric kernel method is used to estimate the marginal hazard rate, and the method of variance estimates recovery (MOVER) is used for the construction of the confidence intervals of a time‐dependent hazard ratio based on the confidence limits of a single marginal hazard rate. Two methods are proposed: one uses the delta method and another adopts the transformation method to construct confidence limits for the marginal hazard rate. Simulations are performed to evaluate the performance of the proposed methods. Real data from two clinical trials are analyzed using the proposed methods.
Ursolic acid directly promotes protein accretion in myotubes but does not affect myoblast proliferation
Authors: Figueiredo Vandré Casagrande , Nader Gustavo A.
Published: March 2012

Ursolic acid (UA) has been recently proposed as a potential candidate for the treatment of muscle wasting conditions because of its protein sparring/anabolic effects. Despite this finding, it is unknown whether this response is the consequence of a direct effect on the muscle fibre or if it is mediated by neural or other systemic factors. In the present study, we sought to determine if UA has direct effects in skeletal muscle cells, whether it can increase myoblast proliferation and whether UA can become myotoxic at higher doses. Our results demonstrate that UA directly promoted protein accretion in cultured myotubes but did not modulate myoblast proliferation. At higher doses, UA compromised cell viability in both myoblasts and myotubes. We conclude that the anabolic properties of UA seen in vivo and in vitro are likely a direct effect on the muscle cell, but at higher doses, the benefits decline in favour of a myotoxic outcome. Copyright © 2012 John Wiley & Sons, Ltd.
UV Radiation Induces Genome‐Mediated, Site‐Specific Cleavage in Viral Proteins
Authors: Wigginton Krista Rule , Menin Laure , Sigstam Therese , Gannon Greg , Cascella Michele , Hamidane Hisham Ben , Tsybin Yury O. , Waridel Patrice , Kohn Tamar
Published: March 2012

Much research has been dedicated to understanding the molecular basis of UV damage to biomolecules, yet many questions remain regarding the specific pathways involved. Here we describe a genome‐mediated mechanism that causes site‐specific virus protein cleavage upon UV irradiation. Bacteriophage MS2 was disinfected with 254 nm UV, and protein damage was characterized with ESI‐ and MALDI‐based FT‐ICR, Orbitrap, and TOF mass spectroscopy. Top‐down mass spectrometry of the products identified the backbone cleavage site as Cys46–Ser47 in the virus capsid protein, a location of viral genome–protein interaction. The presence of viral RNA was essential to inducing backbone cleavage. The similar bacteriophage GA did not exhibit site‐specific protein cleavage. Based on the major protein fragments identified by accurate mass analysis, a cleavage mechanism is proposed by radical formation. The mechanism involves initial oxidation of the Cys46 side chain followed by hydrogen atom abstraction from Ser47 Cα. Computational protein QM/MM studies confirmed the initial steps of the radical mechanism. Collectively, this study describes a rare incidence of genome‐induced protein cleavage without the addition of sensitizers.
A Flavoprotein Monooxygenase that Catalyses a Baeyer–Villiger Reaction and Thioether Oxidation Using NADH as the Nicotinamide Cofactor
Authors: Jensen Chantel N. , Cartwright Jared , Ward Jonathan , Hart Sam , Turkenburg Johan P. , Ali Sohail T. , Allen Michael J. , Grogan Gideon
Published: March 2012

A gene from the marine bacterium Stenotrophomonas maltophilia encodes a 38.6 kDa FAD‐containing flavoprotein (Uniprot B2FLR2) named S. maltophilia flavin‐containing monooxygenase (SMFMO), which catalyses the oxidation of thioethers and also the regioselective Baeyer–Villiger oxidation of the model substrate bicyclo[3.2.0]hept‐2‐en‐6‐one. The enzyme was unusual in its ability to employ either NADH or NADPH as nicotinamide cofactor. The KM and kcat values for NADH were 23.7±9.1 μM and 0.029 s−1 and 27.3±5.3 μM and 0.022 s−1 for NADPH. However, kcat/KM value for the ketone substrate in the presence of 100 μM cofactor was 17 times greater for NADH than for NADPH. SMFMO catalysed the quantitative conversion of 5 mM ketone in the presence of substoichiometric concentrations of NADH with the formate dehydrogenase cofactor recycling system, to give the 2‐oxa and 3‐oxa lactone products of Baeyer–Villiger reaction in a ratio of 5:1, albeit with poor enantioselectivity. The conversion with NADPH was 15 %. SMFMO also catalysed the NADH‐dependent transformation of prochiral aromatic thioethers, giving in the best case, 80 % ee for the transformation of p‐chlorophenyl methyl sulfide to its R enantiomer. The structure of SMFMO reveals that the relaxation in cofactor specificity appears to be accomplished by the substitution of an arginine residue, responsible for recognition of the 2′‐phosphate on the NADPH ribose in related NADPH‐dependent FMOs, with a glutamine residue in SMFMO. SMFMO is thus representative of a separate class of single‐component, flavoprotein monooxygenases that catalyse NADH‐dependent oxidations from which possible sequences and strategies for developing NADH‐dependent biocatalysts for asymmetric oxygenation reactions might be identified.
Meta‐analysis of complications in aortic valve replacement: Comparison of Medtronic‐Corevalve, Edwards‐Sapien and surgical aortic valve replacement in 8,536 patients
Authors: Jilaihawi Hasan , Chakravarty Tarun , Weiss Robert E. , Fontana Gregory P. , Forrester James , Makkar Raj R.
Published: March 2012

Background: We sought to establish the complication rates following transcatheter aortic valve replacement (TAVR) in the context of high risk and octogenarian surgical aortic valve replacement (SAVR) in the contemporary literature, and to critically analyze population characteristics and outcomes. Methods: TAVR studies were selected from nonoverlapping series and SAVR studies for comparison if they met similar entry criteria. Bayesian meta‐analytic methods were employed. Results: For the 5024 TAVR and 3512 SAVR patients included in the study, TAVR subjects had greater baseline renal impairment (P < 0.001), a higher incidence of prior myocardial infarction (P = 0.032) and respiratory disease (P = 0.005) and a higher logistic EuroSCORE (P = 0.039). There were no significant differences observed in complications studied in SAVR and TAVR: 30 day mortality (9% vs 8.5%, P = 0.31), 1 year mortality (18.4% vs 22.8%, P = 0.65), 30 day stroke (2.4% vs 2.6%, P = 0.72), new permanent pacemaker (5.9% vs 12.1%, P = 0.055) and dialysis inception (2.4% vs 4.1%, P = 0.70). We also compared demographics and outcomes between the two types of transcatheter valves. Apart from some variation in functional status, there were no significant differences at baseline with different TAVR designs. The only difference in complications was the need for pacemaker insertion, higher with the Medtronic‐Corevalve than with the Edwards‐Sapien design (24.5% vs 5.9% P < 0.0001). Conclusions: Complications for elderly and high risk aortic stenosis patients being treated by TAVR appear comparable to those selected for SAVR in the real‐world. © 2012 Wiley Periodicals, Inc.
Carbon–Carbon Bond Formation by Ligand‐free Cross‐Coupling Reaction Using Palladium Catalyst Supported on Synthetic Adsorbent
Authors: Monguchi Yasunari , Sakai Keita , Endo Koichi , Fujita Yuki , Niimura Masaru , Yoshimura Masatoshi , Mizusaki Tomoteru , Sawama Yoshinari , Sajiki Hironao
Published: March 2012

A palladium catalyst supported on a commercial synthetic adsorbent, DIAION HP20, could be employed for the crosscoupling reactions of aryl halides with organoboronic acids (Suzuki–Miyaura reaction), alkenes (Mizoroki–Heck reaction), and alkynes (Sonogashira reaction) in a ligand‐free manner. 10 % Pd/HP20 was highly active as the catalyst at approximately the same level as 10 % palladium on carbon (10 % Pd/C) for many of the reactions, and was especially effective for the Suzuki–Miyaura reaction using bromoaniline derivatives without the N‐protection and Sonogashira reaction of the heteroaryl iodides. As a stable supply and certain quality of HP20 are available as an industrial product, 10 % Pd/HP20 would be in practical use for a variety of cross‐coupling reactions and hydrogenation as the substitute for 10 % Pd/C, which is dependent on charcoal as a natural product.
Kinetics of Isothermal Ethanol Adsorption onto a Carbon Molecular Sieve under Conventional and Microwave Heating
Authors: Adnadjević B. K. , Jovanović J. D.
Published: March 2012

The isothermal kinetics of ethanol adsorption from aqueous solution onto a zeolite type carbon molecular sieve (CMS‐3A) under conventional heating (CH) and microwave heating (MWH) was investigated. The adsorption kinetics is described by the model of a phase‐boundary controlled reaction for both heating modes. The activation energy (Ea) for the adsorption process under MWH is lower than under CH while the preexponential factor (lnA) is higher. Ethanol adsorption is a kinetically complex process whose complexity changes with the mode of heating. The established decrease in Ea and increase in lnA under MWH compared to CH is explained with the increase in the ground vibrational level of the – OH twisting vibrations in the ethanol molecule and with the decrease in its anharmonicity factor which is caused by the selective resonant transfer of energy from CMS‐3A to the OH oscillators.
Geometric and Electronic Structures of Phenoxyl Radicals Hydrogen Bonded to Neutral and Cationic Partners
Authors: Orio Maylis , Jarjayes Olivier , Baptiste Benoit , Philouze Christian , Duboc Carole , Mathias Jenny‐Lee , Benisvy Laurent , Thomas Fabrice
Published: March 2012

Two di‐tert‐butylphenols incorporating an N‐methylbenzimidazole moiety in the ortho or para position have been synthesised (MeOH and pMeOH, respectively). Their X‐ray structures evidence a hydrogen bond between the phenolic proton and the iminic nitrogen atom, whose nature is intra‐ and intermolecular, respectively. The present studies demonstrate that MeOH is readily oxidised by an intramolecular PET mechanism to form the hydrogen‐bonded phenoxyl‐N‐methylbenzimidazolium system (MeOH).+, whereas oxidation of pMeOH occurs by intermolecular PET, affording the neutral phenoxyl benzimidazole (pMeO). system. The deprotonations of MeOH and pMeOH yield the corresponding phenolate species (MeO)− and (pMeO)−, respectively, whilst that of the previously reported HOH (analogous to MeOH but lacking the N‐methyl group) produces an unprecedented hydrogen‐bonded phenol benzimidazolate species, as evidenced by its X‐ray structure. The latter is believed to be in equilibrium in solution with its tautomeric phenolate form, as suggested by NMR, electrochemistry and DFT studies. The one‐electron oxidations of the anions occur by a simple ET process affording phenoxyl radical species, whose electronic structure has been studied by HF‐EPR spectroscopy and DFT calculations. In particular, analysis of the g1 tensor shows the order 2.0079>2.0072>2.0069>2.0067 for (MeO)., (HO)., (MeOH).+ and (HOH).+, respectively. (MeO). exhibits the largest g1 tensor (2.0079), consistent with the absence of intramolecular hydrogen bond. The g1 tensor of (HO). is intermediate between those of (MeOH).+ and (MeO). (g1=2.0072), indicating that the phenoxyl oxygen is hydrogen‐bonded with a neutral benzimidazole partner.
Near‐IR Excitation Transfer and Electron Transfer in a BF2‐Chelated Dipyrromethane–Azadipyrromethane Dyad and Triad
Authors: El‐Khouly Mohamed E. , Amin Anu N. , Zandler Melvin E. , Fukuzumi Shunichi , D'Souza Francis
Published: March 2012

A molecular dyad and triad, comprised of a known photosensitizer, BF2‐chelated dipyrromethane (BDP), covalently linked to its structural analog and near‐IR emitting sensitizer, BF2‐chelated tetraarylazadipyrromethane (ADP), have been newly synthesized and the photoinduced energy and electron transfer were examined by femtosecond and nanosecond laser flash photolysis. The structural integrity of the newly synthesized compounds has been established by spectroscopic, electrochemical, and computational methods. The DFT calculations revealed a molecular‐clip‐type structure for the triad, in which the BDP and ADP entities are separated by about 14 Å with a dihedral angle between the fluorophores of around 70°. Differential pulse voltammetry studies have revealed the redox states, allowing estimation of the energies of the charge‐separated states. Such calculations revealed a charge separation from the singlet excited BDP (1BDP*) to ADP (BDP.+‐ADP.−) to be energetically favorable in nonpolar toluene and in polar benzonitrile. In addition, the excitation transfer from the singlet BDP to ADP is also envisioned due to good spectral overlap of the BDP emission and ADP absorption spectra. Femtosecond laser flash photolysis studies provided concrete evidence for the occurrence of energy transfer from 1BDP* to ADP (in benzonitrile and toluene) and electron transfer from BDP to 1ADP* (in benzonitrile, but not in toluene). The kinetic study of energy transfer was measured by monitoring the rise of the ADP emission and revealed fast energy transfer (ca. 1011 s−1) in these molecular systems. The kinetics of electron transfer via 1ADP*, measured by monitoring the decay of the singlet ADP at λ=820 nm, revealed a relatively fast charge‐separation process from BDP to 1ADP*. These findings suggest the potential of the examined ADP–BDP molecules to be efficient photosynthetic antenna and reaction center models.
Total Synthesis of Exiguamines A and B Inspired by Catecholamine Chemistry
Authors: Sofiyev Vladimir , Lumb Jean‐Philip , Volgraf Matthew , Trauner Dirk
Published: March 2012

The evolution of a total synthesis of the exiguamines, two structurally unusual natural products that are highly active inhibitors of indolamine‐2,3‐dioxygenase (IDO), is described. The ultimately successful strategy involves advanced cross‐coupling methodology and features a potentially biosynthetic tautomerization/electrocyclization cascade reaction that forms two heterocycles and installs a quaternary ammonium ion in a single synthetic operation.
Synthesis of 2‐ and 2,7‐Functionalized Pyrene Derivatives: An Application of Selective CH Borylation
Authors: Crawford Andrew G. , Liu Zhiqiang , Mkhalid Ibraheem A. I. , Thibault Marie‐Hélène , Schwarz Nicolle , Alcaraz Gilles , Steffen Andreas , Collings Jonathan C. , Batsanov Andrei S. , Howard Judith A. K. , Marder Todd B.
Published: March 2012

An efficient synthetic route to 2‐ and 2,7‐substituted pyrenes is described. The regiospecific direct CH borylation of pyrene with an iridium‐based catalyst, prepared in situ by the reaction of [{Ir(μ‐OMe)cod}2] (cod=1,5‐cyclooctadiene) with 4,4′‐di‐tert‐butyl‐2,2′‐bipyridine, gives 2,7‐bis(Bpin)pyrene (1) and 2‐(Bpin)pyrene (2, pin=OCMe2CMe2O). From 1, by simple derivatization strategies, we synthesized 2,7‐bis(R)‐pyrenes with R=BF3K (3), Br (4), OH (5), B(OH)2 (6), and OTf (7). Using these nominally nucleophilic and electrophilic derivatives as coupling partners in Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig cross‐coupling reactions, we obtained 2,7‐bis(R)‐pyrenes with R=(4‐CO2C8H17)C6H4 (8), Ph (9), C≡CPh (10), C≡C[{4‐B(Mes)2}C6H4] (11), C≡CTMS (12), C≡C[(4‐NMe2)C6H4] (14), C≡CH (15), N(Ph)[(4‐OMe)C6H4] (16), and R=OTf, R′=C≡CTMS (13). Lithiation of 4, followed by reaction with CO2, yielded pyrene‐2,7‐dicarboxylic acid (17), whilst borylation of 2‐tBu‐pyrene gave 2‐tBu‐7‐Bpin‐pyrene (18) selectively. By similar routes (including Negishi cross‐coupling reactions), monosubstituted 2‐R‐pyrenes with R=BF3K (19), Br (20), OH (21), B(OH)2 (22), [4‐B(Mes)2]C6H4 (23), B(Mes)2 (24), OTf (25), C≡CPh (26), C≡CTMS (27), (4‐CO2Me)C6H4 (28), C≡CH (29), C3H6CO2Me (30), OC3H6CO2Me (31), C3H6CO2H (32), OC3H6CO2H (33), and O(CH2)12Br (34) were obtained from 2. These derivatives are of synthetic and photophysical interest because they contain donor, acceptor, and conjugated substituents. The crystal structures of compounds 4, 5, 7, 12, 18, 19, 21, 23, 26, and 28–31 have also been obtained from single‐crystal X‐ray diffraction data, revealing a diversity of packing modes, which are described in the Supporting Information. A detailed discussion of the structures of 1 and 2, their polymorphs, solvates, and co‐crystals is reported separately.
Increasing Profitability by Accelerated Product‐ and Process Development with Modular and Scalable Apparatuses
Authors: Brodhagen Andreas , Grünewald Marcus , Kleiner Matthias , Lier Stefan
Published: March 2012

Die zunehmende Fokussierung der chemischen Industrie in Europa auf Spezialitätenprodukte erfordert neue, ganzheitliche Ansätze bei der Produkt‐ und Verfahrensentwicklung. Durch modulare und skalierbare Apparatekonzepte lässt sich eine rasche und kostengünstige Anpassung der Produktionskapazität an Marktentwicklungen erzielen. Am Beispiel einer Fallstudie für ein Spezialitätenprodukt werden die Einflüsse der schnellen Marktanpassung auf die Wirtschaftlichkeit und damit Wettbewerbsfähigkeit dargestellt und bewertet. Die Kapitalwertanalyse zeigt, dass insbesondere die Verkürzung des Zeitbedarfs von der Produktentwicklung bis zur fertigen Produktionsanlage durch smarte Produktionstechnologien zu einer Erhöhung der Wirtschaftlichkeit führt.
Shorter Time‐to‐Market with Micro‐Conti Processes
Authors: Grundemann Laura , Schoenitz Martin , Scholl Stephan
Published: March 2012

Traditional process development consists of four main phases resulting in time‐consuming and cost‐intensive launches for new products and processes. By employing microprocess technology, transferring batch to continuous processes or setting up a continuous process for low to medium production capacities from scratch becomes technically feasible. Since volumetric flow rates on lab‐scale are often similar to production rates, the scale‐up factor is low. Thus, individual development phases can be omitted reducing the time‐to‐market for new products and/or processes. Based on two case studies, the development phase of micro‐conti processes is described and conclusions are drawn regarding the 50 % idea as laid down in the Tutzing theses.
Ionic Liquid Modified Resin for the Adsorptive Removal of Dibutyl Phthalate: Equilibrium, Kinetic, and Thermodynamic Studies
Authors: Qureshi Umair A. , Solangi Amber R. , Memon Saima Q. , Taqvi Syed I. H. , Memon Najma
Published: March 2012

This study evaluated the adsorptive properties of dibutyl phthalate (DBP) on room temperature ionic liquid (RTIL) modified XAD‐4 resin. The modified RTIL‐XAD 4 sorbent was characterized by FTIR. Effect of varying experimental conditions such as pH, contact time, temperature, shaking speed, concentrations, and interfering species were investigated by batch adsorption experiments. Adsorption was found to be most favorable at pH 6 within 30 min. Experimental data were evaluated in terms of kinetic, equilibrium, and thermodynamic modeling. Kinetics of the sorption was found to follow pseudo second order rate equation whereas Freundlich and D–R isotherms were the most suitable models to explain sorption phenomenon. Thermodynamically sorption was endothermic, irreversible, and spontaneous in nature.
Exploring the Anticancer Activity of Functionalized Isoindigos: Synthesis, Drug‐like Potential, Mode of Action and Effect on Tumor‐Induced Xenografts
Authors: Wee Xi Kai , Yang Tianming , Go Mei Lin
Published: March 2012

Meisoindigo has been used as an indirubin substitute for the treatment of chronic myeloid leukemia (CML) for several years. In view of its poor solubility and erratic absorption, several investigations have focused on developing analogues with more desirable physicochemical profiles. Here, we investigated the structure–activity relationship (SAR) of meisoindigo with respect to its antiproliferative activity on leukemic K562 cells and found that appending a phenalkyl side chain onto the lactam NH resulted in analogues that retained good activity. Furthermore, analogues in which the phenyl ring was substituted with a basic heterocycle were significantly more soluble than meisoindigo while retaining acceptable antiproliferative profiles. The most promising analogue (E)‐1‐(2‐(4‐methylpiperazin‐1‐yl)ethyl)‐[3,3′‐biindolinylidene]‐2,2′‐dione (5‐4) is more potent than meisoindigo across a panel of malignant cells, with at least 40 times greater solubility than meisoindigo, little or no tendency to aggregate in solution and capable of significantly extending the lifespans of animals with K562 induced xenografts. Mechanistically, it induced apoptotic cell death and disrupted the progression of K562 cells from the G1 to G2 phase. Taken together, our findings highlighted the feasibility of addressing the physicochemical deficits of the isoindigo scaffold by systematic modifications which was achieved without overt loss of growth inhibitory activity.
Optimized synthesis of 100 nm diameter magnetoliposomes with high content of maghemite particles and high MRI effect
Authors: Garnier Boris , Tan Sisareuth , Miraux Sylvain , Bled Emilie , Brisson Alain R.
Published: March 2012

Magnetoliposomes are liposomes surrounding an iron oxide core, which are used as contrast enhancing agents in magnetic resonance imaging (MRI). One method for producing magnetoliposomes consists of hydration of a lipid film with citrate‐coated iron oxide particles followed by extrusion. Two parameters are of major importance for in vivo applications of magnetoliposomes, namely their size, which must be small, optimally around 100 nm diameter, in order to ensure their prolonged circulation in the bloodstream, and their iron content, which must be maximal for generating high MRI effect. We studied the formation of magnetoliposomes by passive encapsulation of maghemite (γ‐Fe2O3) particle suspensions of varying concentrations, with the objective of producing magnetoliposomes of small size and high iron content. The iron to lipid ratio was used to determine the iron content of the magnetoliposomes after the successive purification steps and cryo‐TEM was used to characterize their size, their homogeneity and the efficiency of purification. The size of citrate‐coated maghemite clusters was found to be of critical importance for obtaining magnetoliposomes smaller than 200 nm. We were able to reproducibly synthesize magnetoliposomes of 100 nm diameter with high iron content –up to 77 particles per liposome (5.6 moles iron per mole lipid) – and high r2 MRI relaxivity – up to 320 m m−1 . s−1. The magnetoliposomes present improved characteristics compared with previous reports. Future research will focus on using these magnetoliposomes as drug delivery systems for in vivo diagnostics or therapeutics applications. Copyright © 2011 John Wiley & Sons, Ltd.
Further data supporting that paclitaxel‐associated acute pain syndrome is associated with development of peripheral neuropathy
Authors: Reeves Brandi N. , Dakhil Shaker R. , Sloan Jeff A. , Wolf Sherry L. , Burger Kelli N. , Kamal Arif , Le‐Lindqwister Nguyet A. , Soori Gamini S. , Jaslowski Anthony J. , Kelaghan Joseph , Novotny Paul J. , Lachance Daniel H. , Loprinzi Charles L.
Published: March 2012

BACKGROUND:

Paclitaxel causes an acute pain syndrome (P‐APS), occurring within days after each dose and usually abating within days. Paclitaxel also causes a more classic peripheral neuropathy, which steadily increases in severity with increasing paclitaxel total doses. Little detail is available regarding the natural history of these 2 syndromes, or any relationship between them, although a recent publication does provide natural history data about weekly paclitaxel, supporting an association between the severity of P‐APS and eventual peripheral neuropathy symptoms.

METHODS:

Patients entering this study were about to receive paclitaxel and carboplatin every 3 weeks. Daily questionnaires were completed for the first week after every chemotherapy dose, and European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire, Chemotherapy‐Induced Peripheral Neuropathy 20‐item instruments were completed weekly.

RESULTS:

The P‐APS severity peaked on day 4 after the initial chemotherapy dose, with 12%, 29%, 23%, and 36% of patients having maximal pain scores of 0, 1 to 4, 5 or 6, or 7 to 10 during the first week after the first dose of therapy, respectively. Patients with P‐APS scores of 0 to 4 with the first dose of chemotherapy had less eventual sensory neuropathy than did patients with P‐APS scores of 5 to 10 (P = 0.001). With regard to the more peripheral neuropathy, sensory neuropathy was more problematic than was either motor or autonomic neuropathy. Numbness and tingling were more common components of the sensory neuropathy than was pain.

CONCLUSIONS:

Patients with worse P‐APS severities appear to have more eventual chemotherapy‐induced peripheral neuropathy. This provides support for the concept that P‐APS is a form of nerve pathology. Cancer 2012. © 2012 American Cancer Society.
A note from history: Landmarks in history of cancer, part 4
Authors: Hajdu Steven I.
Published: March 2012

In the second half of the 19th century, most cancer patients were cared for by surgeons who exerted ascesis and limited their operations to 1 or 2 specific areas. To assist surgeons and other physicians in caring for their patients, pathologists described newly discovered entities, refined the microscopic classification of tumors, and introduced the grading of cancers. The discoveries of Rontgen and the Curies revolutionized the diagnosis and treatment of cancers. The search for the cause of cancers extended to infectious organisms, chemicals, and radioactive materials. The 50 years covered in this review formed the groundwork for the coordinated, specialized care of cancer patients at institutions dedicated to render the most promising treatment. Cancer 2012. © 2012 American Cancer Society.
p38 mitogen‐activated protein kinase signaling, ERCC1 expression, and viability of lung cancer cells from never or light smoker patients
Authors: Planchard David , Camara‐Clayette Valérie , Dorvault Nicolas , Soria Jean‐Charles , Fouret Pierre
Published: March 2012

BACKGROUND:

Expression of DNA‐repair proteins and activated mitogen‐activated protein kinases (MAPKs) may differ according to smoking status. The authors investigated whether p38 MAPK activity contributed to the viability of cisplatin in lung cancer cell lines from never or light smokers and to ERCC1 mRNA expression.

METHODS:

Activated p38 MAPK was tested as a predictor for ERCC1 levels in 117 lung adenocarcinomas. Cell viabilities of NCI‐H1975, NCI‐H1793, NCI‐H1650, and NCI‐H1651 cell lines, derived from never or light smokers, were measured after treatment with the p38 MAPK inhibitor SB202190 and cisplatin. The role of p38α (MAPK14) and p38β (MAPK11) isoforms and ERCC1 was evaluated using RNA interference.

RESULTS:

ERCC1 protein‐level expression was predicted by activated p38 MAPK in lung adenocarcinoma tissues. The p38‐specific inhibitor SB202190 strongly decreased cell viability (43%‐63%). SB202190 plus cisplatin significantly decreased cell viability in every cell line, including cisplatin‐resistant NCI‐H1793. Genetic inhibition, targeting both MAPK11 and MAPK14, reduced the viability of the different cell lines: down‐regulation of p38β accounted for most of this effect. Cisplatin's effect was greater after MAPK11 down‐regulation for NCI‐H1651, and MAPK14 down‐regulation for NCI‐H1650. In addition, both SB202190 and MAPK11 inhibition reduced excision repair cross‐complementing 1 mRNA levels.

CONCLUSIONS:

Lung cancer cells from never or light smokers rely on p38 MAPK signaling for survival. MAPK11 is involved in that pathway and might contribute to ERCC1 expression. Sensitization to cisplatin can be achieved by pharmacological inhibition of p38 MAPK signaling. Cancer 2012. © 2012 American Cancer Society.
Ethical aspects of participation in the Database of Genotypes and Phenotypes of the National Center for Biotechnology Information
Authors: Peppercorn Jeffrey , Shapira Iuliana , Deshields Teressa , Kroetz Deanna , Friedman Paula , Spears Patricia , Collyar Deborah E. , Shulman Lawrence N. , Dressler Lynn , Bertagnolli Monica M.
Published: March 2012

BACKGROUND:

The rapid pace of genetics research, coupled with evolving standards for informed consent, can create ethical challenges regarding future use of tissue or information from completed clinical trials. The Cancer and Leukemia Group B (CALGB) Oncology Cooperative Group was faced with an ethical dilemma regarding sharing genetic data from a completed genome‐wide association study (GWAS) that was conducted as part of a large, multicenter breast cancer clinical trial with a national database: the Database of Genotypes and Phenotypes National Center for Biotechnology Information (dbGaP).

METHODS:

The CALGB Ethics Committee conducted a series of multidisciplinary meetings and teleconferences involving patient advocates, bioethicists, clinical researchers, and clinical oncologists to evaluate the ethical issues raised by this case and to identify lessons for improving informed consent to future genetics research in oncology trials.

RESULTS:

The Ethics Committee recommended that GWAS data be provided to dbGaP consistent with documented consent for future use of tissue among trial participants. Ethical issues, including adequacy of informed consent to future research, limitations of privacy in modern genetics research, the potential impact of population‐based genetics research on health disparities, and recontact of research participants for clinical care or further research, were identified as major ethical considerations in this area.

CONCLUSIONS:

Although modern standards for informed consent should not prohibit research or sharing of data consistent with participant's intent and the public interest, there is an urgent need for national consensus on the appropriate use of archived tissue and standardized informed consent for future research among cancer clinical trial participants. Cancer 2012. © 2012 American Cancer Society.
Pure and mixed fibrolamellar hepatocellular carcinomas differ in natural history and prognosis after complete surgical resection
Authors: Malouf Gabriel G. , Brugières Laurence , Le Deley Marie‐Cécile , Faivre Sandrine , Fabre Monique , Paradis Valérie , Aerts Isabelle , Le Tourneau Christophe , Dreyer Chantal , Branchereau Sophie , Belghiti Jacques , Raymond Eric
Published: March 2012

BACKGROUND:

The purpose of the current study was to describe pure and mixed fibrolamellar hepatocellular carcinoma (FL‐HCC).

METHODS:

Consecutive patients with pure and mixed FL‐HCC were identified from a central pathological review using Edmondson's criteria. Clinical, pathological, and epigenetic characteristics of patients who underwent curative surgery were evaluated. Overall and disease‐free survival as well as patterns of disease recurrence were examined. Methylation levels of L1 retrotransposon (LINE‐1) repetitive elements and Ras association domain family 1A gene (RASSF1) promoter were also assessed using pyrosequencing.

RESULTS:

Forty of 53 patients with a median age of 22 years (range, 9 years‐;65 years) met the criteria for analysis. Central pathological review found that 30 patients (75%) had pure and 10 patients (25%) had mixed FL‐HCC. Pure FL‐HCC typically occurred in patients aged < 30 years. These patients often presented with lymph node metastasis at the time of diagnosis and frequently experienced extrahepatic recurrences (n = 16). Conversely, mixed FL‐HCC appeared to resemble to classic HCC, occurring in patients aged > 40 years and frequently involving the liver as the primary site of disease recurrence. With a median follow‐up of 7.8 years, the median overall survival from the time of diagnosis in all patients was 6.4 years (range, 3.2 years‐12 years). Multivariate analysis found that the risk of death was increased in patients with higher American Joint Committee on Cancer disease stages (P = .003) and those with mixed FL‐HCC (P = .03). Methylation analysis of LINE‐1 repetitive elements and RASSF1 promoter revealed different methylation levels between pure and mixed FL‐HCC, suggesting a different epigenetic background.

CONCLUSIONS:

Pure and mixed FL‐HCC display distinct clinical presentations and epigenetic backgrounds leading to different prognoses and as such may be regarded as separate clinical entities. Cancer 2012. © 2012 American Cancer Society.
Novel Fe3+‐Based 1H MRI β‐Galactosidase Reporter Molecules
Authors: Yu Jian‐Xin , Gulaka Praveen K. , Liu Li , Kodibagkar Vikram D. , Mason Ralph P.
Published: March 2012

There is increasing interest in the development of reporter agents to reveal enzyme activity in vivo using imaging in small animals. We have previously demonstrated the feasibility of detecting lacZ gene activity using the commercially available 3,4‐cyclohexenoesculetin‐β‐D‐galactopyranoside (S‐Gal) as a 1H MRI reporter. Specifically, β‐galactosidase (β‐gal) releases the aglycone, which forms a magnetic resonance contrast‐inducing paramagnetic precipitate in the presence of Fe3+. Contrast was primarily T2‐weighted signal loss, but T1 effects were also observed. Since T1‐contrast generally provides signal enhancement as opposed to loss, it appeared attractive to explore whether analogues could be generated with enhanced characteristics. We now report the design and synthesis of novel analogues together with characterization of 1H MRI contrast based on both T1 and T2 response to β‐gal activity in vitro for the lead agent.
Self‐Limited Reaction‐Diffusion in Nanostructured Substrates: Surface Coverage Dynamics and Analytic Approximations to ALD Saturation Times
Authors: Yanguas‐Gil Angel , Elam Jeffrey W.
Published: March 2012

We present a general model based on a time‐dependent, reaction–diffusion equation to determine the dosing times and coverage profiles in structured substrates during atomic layer deposition (ALD). We first derive expressions comprising a non‐linear diffusion–reaction equation coupled to a surface kinetic equation. In their non‐dimensional forms, these equations show that coverage dynamics during ALD in nanostructured substrates depend only on two non‐dimensional parameters, the Damkoler and precursor excess (number of molecules per surface site in the nanostructure) numbers. Using the assumptions of molecular flow in a circular pore, we derive a general, analytic equation to predict saturation exposure times. To demonstrate the utility of our model, we derive additional expressions incorporating a precursor loss term relevant to predicting exposure times during ozone‐based ALD. Because our model makes no assumptions about the diffusion coefficient or sample geometry, it can easily be adapted to describe a broad range of ALD systems such as trenches and vias, anodized alumina, or aerogels under almost any conditions including molecular, viscous, and transition flow regimes
Using knowledge of development to promote recovery of function after brain damage
Authors: Michel George F.
Published: March 2012

Knowledge of normal development of brain–behavior relations plays an important role in understanding how the plasticity of the nervous system can be used to promote recovery of function following brain damage. Aspects of the other articles in this issue are used in justification of the value of such developmental knowledge. Also, the development of amblyopia and its remediation in adulthood is discussed as a model for developing other techniques for ensuring recovery of function after stroke. Although the articles in this issue establish an excellent context for improving actual recovery of function (rather than compensation for deficits), much still needs to be discovered about how we can use developmental knowledge, along with knowledge of the plasticity of the nervous system, to improve remediation techniques. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 54:350‐356, 2012.
Ecohydrological ‘indicators of alteration’ – a robust measure of change in dune slacks
Authors: Robins N S , Jones M L M
Published: March 2012

Coastal dunes support a biodiverse wetland habitat, dune slacks, which depend on a seasonally fluctuating, but near‐surface, groundwater level. Any long‐term change in the hydrological regime will impact the ecology. Analysis of long‐term water level hydrographs, using a methodology prescribed for surface water flow gauging data, provides a set of ecohydrological ‘indicators of alteration’. These indicators collectively form a robust quantified measure of change that provides a basis for assessing the ecological impact that may result from a changed hydrological regime. This method was tested using monthly frequency water level data from three west coast UK coastal dunes, over periods of up to 37 years. Mean hydrological variables derived from the hydrographs were compared pre‐impact and post‐impact for a variety of perturbations: medium‐term climate variation and pre‐shoreline and post‐shoreline erosion. The method provided a valid quantification of hydrological change. The low frequency of water‐level data measurements compared with continuous flow‐gauge data precluded analysis of change in inter‐annual variability or perturbation (coefficients of variability) because of the likelihood of missed extreme flood and drought. Principal components analysis was used to identify associations between hydrological indicators and highlighted redundancy among some indicators such as measures of frequency and duration but orthogonality, i.e. independence, of others such as mean water levels and duration of drought. The hydrological effects of climatic variation over a 37‐year period, of management interventions and erosion events that occurred at the three coastal dunes were small compared with the likely impact from projected climate change predictions. Copyright © 2012 John Wiley & Sons, Ltd.
Diaryl‐Substituted Perylene Bis(imides): Synthesis, Separation, Characterization and Comparison of Electrochemical and Optical Properties of 1,7‐ and 1,6‐Regioisomer
Authors: Dey Somnath , Efimov Alexander , Lemmetyinen Helge
Published: March 2012

A series of diaryl‐substituted perylene bis(imides) (PBIs) containing electron‐donating and ‐withdrawing aryl groups in the bay region (1‐, 6‐, 7‐ and/or 12‐positions of the perylene core) were synthesized by Suzuki coupling reaction. The corresponding regioisomers, namely, 1,7‐ and 1,6‐regioisomer, were separated from the mixture by conventional column chromatography without any need of recrystallization. All the individual regioisomers were fully characterized by 1H NMR and HRMS spectroscopy. The compounds were studied by optical spectroscopy and electrochemical techniques. The optical and electrochemical properties of 1,7‐regioisomer are slightly different from the 1,6‐regioisomer of the respective diaryl‐PBI. Significant redshift and broadening of the absorption and emission maxima were observed in all synthesized PBIs depending upon the electronic nature of the attached aryl group. This is very first time such large series of 1,6‐diarylperylenetetracarboxydiimides with their corresponding 1,7‐regioisomers were synthesized, separated, characterized and studied in detail.
Pyridine‐Substituted BODIPY as Fluorescent Probe for Hg2+
Authors: Wagner Sally , Brödner Kerstin , Coombs Benjamin A. , Bunz Uwe H. F.
Published: March 2012

Dialkynylated BODIPYs bearing pyridine or dibutylaniline substituents have been synthesized, and their photophyisical properties in the presence of different metal ions have been studied. 4‐Pyridyl substitution gives a highly selective fluorescence probe for HgII ions.
Controlled Reactions of 2,3‐Allenoates with a 1,3‐Diketone Catalyst Effect
Authors: Fang Zhao , Fu Chunling , Ma Shengming
Published: March 2012

Two types of reactions of 2,3‐allenoates with 1,3‐diketones under different reaction conditions are described: under palladium catalysis, the relatively electron‐rich C=C bonds are attacked to afford ethyl (2E)‐4‐acyl‐2‐alkyl‐4‐aryl‐6‐oxohept‐2‐enoates exclusively with dicyclohexyl(2,4,6‐trimethoxyphenyl)phosphane as the ligand; under Cu(OAc)2 catalysis, 4‐[R–C(=O)–]‐(LB‐Phos) 3,5‐dialkyl‐3‐(2‐oxo‐2‐arylethyl)furan‐2(3H)‐one products are formed unexpectedly through intramolecular reaction at the electron‐deficient C=C bond.