bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment‐related complications of radiation therapy after radical prostatectomy: comparative effectiveness of intensity‐modulated versus conformal radiation therapy
Authors: Crandley Edwin F. , Hegarty Sarah E. , Hyslop Terry , Wilson David D. , Dicker Adam P. , Showalter Timothy N.
Published: February 2014

Intensity‐modulated radiation therapy (IMRT) is frequently utilized after prostatectomy without strong evidence for an improvement in outcomes compared to conformal radiation therapy (RT). We analyzed a large group of patients treated with RT after radical prostatectomy (RP) to compare complications after IMRT and CRT. The Surveillance, Epidemiology and End Results (SEER)‐Medicare database was queried to identify male Medicare beneficiaries aged 66 years or older who underwent prostatectomy with 1+ adverse pathologic features and received postprostatectomy RT between 1995 and 2007. Chi‐square test was used to compare baseline characteristics between the treatment groups. First complication events, based upon administrative procedure or diagnosis codes occurring >1 year after start of RT, were compared for IMRT versus CRT groups. Propensity score adjustment was performed to adjust for potential confounders. Multivariable Cox proportional hazards models of time to first complication were performed. A total of 1686 patients were identified who received RT after RP (IMRT = 634, CRT = 1052). Patients treated with IMRT were more likely to be diagnosed after 2004 (P < 0.001), have minimally invasive prostatectomy (P < 0.001) and have positive margins (P = 0.019). IMRT use increased over time. After propensity score adjustment, IMRT was associated with lower rate of gastrointestinal (GI) complications, and higher rate of genitourinary‐incontinence complications, compared to CRT. The observed outcomes after IMRT must be considered when determining the optimal approach for postprostatectomy RT and warrant additional study.
Expanding the Potential of G‐Quadruplex Structures: Formation of a Heterochiral TBA Analogue
Authors: Virgilio Antonella , Varra Michela , Scuotto Maria , Capuozzo Antonella , Irace Carlo , Mayol Luciano , Esposito Veronica , Galeone Aldo
Published: February 2014

In order to expand the potential applications of G‐quadruplex structures, we explored the ability of heterochiral oligodeoxynucleotides based on the thrombin‐binding aptamer (TBA) sequence to fold into similar complexes, with particular focus on their resistance in biological environments. A combination of CD and NMR techniques was used. Similarly to TBA, the ODN ggTTggtgtggTTgg (lower case letters indicate L residues) is able to fold into a chair‐like antiparallel G‐quadruplex structure, but has a slightly higher thermal stability. The discovery that heterochiral ODNs are able to form stable G‐quadruplex structures opens up new possibilities for their development in several fields, as aptamers, sensors and, as recently shown, as catalysts for enantioselective reactions.
OMS‐2 for Aerobic, Catalytic, One‐pot Alcohol Oxidation‐Wittig Reactions: Efficient Access to α,β‐Unsaturated Esters
Authors: Kona Jagadeswara R. , King'ondu Cecil K. , Howell Amy R. , Suib Steven L.
Published: February 2014

Manganese oxide octahedral molecular sieve (OMS) materials with well‐defined pores have been extensively studied over two decades due to their intriguing chemical and physical properties. OMS‐2, the synthetic cryptomelane form of manganese oxide, was synthesized by a modified reflux method and was found to be highly active for obtaining α,β‐unsaturated esters (up to 95 % yield and with high diastereoselectivities) from a variety of benzyl, heteroaryl, allyl and alkyl alcohols via one‐pot alcohol oxidation‐Wittig reaction. The transformation utilizes air as the stoichiometric oxidant, and the inexpensive catalyst can be recovered and reused.
Single‐Particle Spectroscopy of Alcohol‐to‐Olefins over SAPO‐34 at Different Reaction Stages: Crystal Accessibility and Hydrocarbons Reactivity
Authors: Qian Qingyun , Ruiz‐Martínez Javier , Mokhtar Mohamed , Asiri Abdullah M. , Al‐Thabaiti Shaeel A. , Basahel Suliman N. , Weckhuysen Bert M.
Published: February 2014

In situ synchrotron‐based IR and UV/Vis micro‐spectroscopy combined with isotopically labeled reactants have been used to identify the different hydrocarbon species formed as well as to assess the activity and accessibility of individual 50 μm‐sized SAPO‐34 crystals. For the methanol‐to‐olefins process, two reaction stages can be distinguished. The first involves the formation of methoxy species, protonated dimethyl ether, and polyalkylated benzene (PAB) carbocations, which do not affect the accessibility of the SAPO‐34 crystal. In addition, methoxy species are very dynamic during this stage. The second stage is related to the formation of polyaromatic (PA) species concentrated in the outer rim of the crystal, which are bulky and interact with the acid sites and thus alter the overall accessibility of the crystal. In contrast, the ethanol‐to‐olefins process only consists of one major stage, as the formation of PAB and PA species cannot be separated. Furthermore, the formation of these species is more internal, and coke formation is mainly concentrated in a layer located in the inner part of the SAPO‐34 crystal.
Monoamine Oxidase–ω‐Transaminase Cascade for the Deracemisation and Dealkylation of Amines
Authors: O'Reilly Elaine , Iglesias Cesar , Turner Nicholas J.
Published: February 2014

Herein we report a one‐pot protocol for the deracemisation of chiral benzylic amines employing a novel monoamine oxidase–ω‐transaminase cascade, allowing access to enantiopure compounds in >99 % ee. We also demonstrate that the same enzymatic cascade can be employed for the dealkylation of secondary amines with >99 % conversion.
Graphene Oxide Catalyzed Dehydration of Fructose into 5‐Hydroxymethylfurfural with Isopropanol as Cosolvent
Authors: Wang Hongliang , Kong Qingqiang , Wang Yingxiong , Deng Tiansheng , Chen Chengmeng , Hou Xianglin , Zhu Yulei
Published: February 2014

The design of green heterogeneous catalysts for the efficient conversion of biomass into platform molecules is a key aim of sustainable chemistry. Graphene oxide prepared from Hummers oxidation of graphite was proven to be a green and efficient carbocatalyst for the dehydration of fructose into 5‐hydroxymethylfurfural (HMF) in some three‐carbon and four‐carbon alcohol mediated solvent systems. HMF was obtained in up to 87 % yield in 90 vol % isopropanol‐mediated DMSO solvent. Some control experiments and analytical data showed that a small number of sulfonic groups and abundance of oxygen‐containing groups (alcohols, epoxides, carboxylates) have an important synergic effect in maintaining the high performance of graphene oxide.
Aerobic Oxidation of Phenols and Related Compounds using Carbon Nanotube–Gold Nanohybrid Catalysts
Authors: Jawale Dhanaji V. , Gravel Edmond , Geertsen Valérie , Li Haiyan , Shah Nimesh , Namboothiri Irishi N. N. , Doris Eric
Published: February 2014

Gold nanoparticles supported on carbon nanotubes were investigated as catalysts in the aerobic oxidation of various substrates (phenols, hydroquinones, catechols, aminophenols, and thiols). The nanohybrid system compares favorably with other supported noble metal catalysts in terms of overall efficacy as it operates at room temperature, under air atmosphere (no external oxidant needed), and can readily be recycled.
Electrochemical Genotyping of Single‐Nucleotide Polymorphisms by using Monobase‐Conjugated Modified Nanoparticles
Authors: Mehdi khoshfetrat Seyyed , Mehrgardi Masoud A.
Published: February 2014

Currently, construction of DNA biosensors for single‐nucleotide polymorphisms (SNPs) genotyping is challenging, particularly in terms of speed and cost. We demonstrate a single platform for genotyping the SNPs by using electrochemical signals of modified nanoparticles (MNPs). To this end, silver and gold nanoparticles (AgNPs and AuNPs) are modified by using cysteine and cysteamine hydrochloride as linkers, respectively. The monobases are subsequently attached to the MNPs through their 5’ phosphate group, forming a phosphoramidate bond with free amino groups of the linkers. Electrooxidation signals of AgNPs and/or 3, 4‐diaminobenzoic acid (DABA) are monitored as analytical signals for SNP genotyping. In the presence of DNA polymerase I (Klenow fragment), the coupling of monobase‐conjugated MNPs (MMNPs) is induced to the mutant sites of duplex DNA, following the Watson–Crick base‐pairing rule, which leads to a substantial change in the signal intensity of MMNPs. The method is able to distinguish complementary targets with a linear dynamic range of 20–1000 pM and 50–1500 pM of mutant DNA, with reliable reproducibility [relative standard deviation (RSD)=5.1 % and stability (RSD=4.2 %). In this study, an accurate, sensitive, fast, and cost‐effective approach for SNP genotyping is introduced.
Rational Design of a Redox‐Labeled Chiral Target for an Enantioselective Aptamer‐Based Electrochemical Binding Assay
Authors: Moreau Julie , Challier Lylian , Lalaoui Noémie , Mavré François , Noël Vincent , Limoges Benoît , Schöllhorn Bernd , Fave Claire
Published: February 2014

A series of redox‐labeled L‐tyrosinamide (L‐Tym) derivatives was prepared and the nature of the functional group and the chain length of the spacer were systematically varied in a step‐by‐step affinity optimization process of the tracer for the L‐Tym aptamer. The choice of the labeling position on L‐Tym proved to be crucial for the molecular recognition event, which could be monitored by cyclic voltammetry and is based on the different diffusion rates of free and bound targets in solution. From this screening approach an efficient electroactive tracer emerged. Comparable dissociation constants Kd were obtained for the unlabeled and labeled targets in direct or competitive binding assays. The enantiomeric tracer was prepared and its enantioselective recognition by the corresponding anti‐D‐Tym aptamer was demonstrated. The access to both enantiomeric tracer molecules opens the door for the development of one‐pot determination of the enantiomeric excess when using different labels with well‐separated redox potentials for each enantiomer.
Rational Design of a Face‐Centred Square‐Cuboid Coordination Cage
Authors: Han Muxin , Michel Reent , Clever Guido H.
Published: February 2014

The simple synthetic conversion of a 90°‐angled bis‐pyridyl ligand into a tripodal tris‐pyridyl ligand leads to the formal transformation of a cubic (a=b=c) into a square‐cuboid (a=b≠c) coordination cage. Mathematical considerations associated with the ligand design, together with X‐ray structure results, NMR spectroscopic and mass spectrometric characterization and molecular modeling of both coordination cages are presented and discussed.
α‐Halogenoacetanilides as Hydrogen‐Bonding Organocatalysts that Activate Carbonyl Bonds: Fluorine versus Chlorine and Bromine
Authors: Koeller Sylvain , Thomas Coralie , Peruch Fréderic , Deffieux Alain , Massip Stéphane , Léger Jean‐Michel , Desvergne Jean‐Pierre , Milet Anne , Bibal Brigitte
Published: February 2014

α‐Halogenoacetanilides (X=F, Cl, Br) were examined as H‐bonding organocatalysts designed for the double activation of CO bonds through NH and CH donor groups. Depending on the halide substituents, the double H‐bond involved a nonconventional CH⋅⋅⋅O interaction with either a HCXn (n=1–2, X=Cl, Br) or a HCAr bond (X=F), as shown in the solid‐state crystal structures and by molecular modeling. In addition, the catalytic properties of α‐halogenoacetanilides were evaluated in the ring‐opening polymerization of lactide, in the presence of a tertiary amine as cocatalyst. The α‐dichloro‐ and α‐dibromoacetanilides containing electron‐deficient aromatic groups afforded the most attractive double H‐bonding properties towards CO bonds, with a NH⋅⋅⋅O⋅⋅⋅HCX2 interaction.
A Versatile and Highly Efficient Method for 1‐Chlorination of Terminal and Trialkylsilyl‐Protected Alkynes
Authors: Gulia Nurbey , Pigulski Bartłomiej , Charewicz Marta , Szafert Sławomir
Published: February 2014

A highly efficient one‐pot procedure for the preparation of 1‐chloroalkynes and 1‐chlorobutadiynes from terminal and trialkylsilyl‐protected precursors is reported. This convenient reaction, proceeding under mild conditions, utilizes N‐chlorosuccinimide as the chlorinating agent and tolerates a range of functional groups.
Steady‐State and Pseudo‐Steady‐State Photocrystallographic Studies on Linkage Isomers of [Ni(Et4dien)(η2‐O,ON)(η1‐NO2)]: Identification of a New Linkage Isomer
Authors: Hatcher Lauren E. , Christensen Jeppe , Hamilton Michelle L. , Trincao Jose , Allan David R. , Warren Mark R. , Clarke Ian P. , Towrie Michael , Fuertes Dr Sara , Wilson Charles C. , Woodall Christopher H. , Raithby Paul R.
Published: February 2014

At temperatures below 150 K, the photoactivated metastable endo‐nitrito linkage isomer [Ni(Et4dien)(η2‐O,ON)(η1‐ONO)] (Et4dien=N,N,N′,N′‐tetraethyldiethylenetriamine) can be generated with 100 % conversion from the ground state nitro‐(η1‐NO2) isomer on irradiation with 500 nm light, in the single crystal by steady‐state photocrystallographic techniques. Kinetic studies show the system is no longer metastable above 150 K, decaying back to the ground state nitro‐(η1‐NO2) arrangement over several hours at 150 K. Variable‐temperature kinetic measurements in the range of 150–160 K show that the rate of endo‐nitrito decay is highly dependent on temperature, and an activation energy of Eact=+48.6(4) kJ mol−1 is calculated for the decay process. Pseudo‐steady‐state experiments, where the crystal is continually pumped by the light source for the duration of the X‐ray experiment, show the production of a previously unobserved, exo‐nitrito‐(η1‐ONO) linkage isomer only at temperatures close to the metastable limit (ca. 140–190 K). This exo isomer is considered to be a transient excited‐state species, as it is only observed in data collected by pseudo‐steady‐state methods.
Effect of Sodium Cation on Metallacycle β‐Hydride Elimination in CO2–Ethylene Coupling to Acrylates
Authors: Jin Dong , Williard Paul G. , Hazari Nilay , Bernskoetter Wesley H.
Published: February 2014

The catalytic conversion of carbon dioxide and olefins into acrylates has been a long standing target, because society attempts to synthesize commodity chemicals in a more economical and sustainable fashion. Although nickel complexes have been known to successfully couple CO2 and ethylene for decades, a key β‐hydride elimination step has proven a major obstacle to the development of a catalytic process. Recent studies have shown that Lewis acid additives can be used to create a lower‐energy pathway for β‐hydride elimination and facilitate a low number of catalytic turnovers. However, the exact manner, in which the Lewis acid promotes β‐hydride elimination remains to be elucidated. Herein, we describe the kinetic and thermodynamic role that commercially relevant and weakly Lewis acidic sodium salts play in promoting β‐hydride elimination from nickelalactones synthesized from CO2 and ethylene. This process is compared to a non‐Lewis acid promoted pathway, and DFT calculations were used to identify differences between the two systems. The sodium‐free isomerization reaction gave a rare CO2‐derived β‐nickelalactone complex, which was structurally characterized.
New Functional Cyclic Aminomethylphosphine Ligands for the Construction of Catalysts for Electrochemical Hydrogen Transformations
Authors: Musina Elvira I. , Khrizanforova Vera V. , Strelnik Igor D. , Valitov Murad I. , Spiridonova Yulia S. , Krivolapov Dmitry B. , Litvinov Igor A. , Kadirov Marsil K. , Lönnecke Peter , Hey‐Hawkins Evamarie , Budnikova Yulia H. , Karasik Andrey A. , Sinyashin Oleg G.
Published: February 2014

Eight‐membered cyclic functional bisphosphines, namely 1,5‐di‐aryl‐3,7‐di(2‐pyridyl)‐1,5‐diaza‐3,7‐diphosphacyclooctanes (aryl=2‐pyridyl, m‐tolyl, p‐tolyl, diphenylmethyl, benzyl, (R)‐(+)‐(α‐methyl)benzyl), with 2‐pyridyl substituents on the phosphorus atoms have been synthesized by condensation of 2‐pyridylphosphine, formaldehyde, and the corresponding primary amine. The structures of some of these bisphosphines have been investigated by X‐ray crystallography. The bisphosphines readily form neutral P,P‐chelate complexes [(κ2‐P,P‐L)MCl2], cationic bis‐P,P‐chelate complexes [(κ2‐P,P‐L)2M]2+, or a five‐coordinate complex [(κ2‐P,P‐L)2NiBr]Br. The electrochemical behavior of two of the nickel complexes, and their catalytic activities in electrochemical hydrogen evolution and hydrogen oxidation, including the fuel‐cell test, have been studied.
Nitrogen and Phosphorus Dual‐Doped Hierarchical Porous Carbon Foams as Efficient Metal‐Free Electrocatalysts for Oxygen Reduction Reactions
Authors: Jiang Hongliang , Zhu Yihua , Feng Qian , Su Yunhe , Yang Xiaoling , Li Chunzhong
Published: February 2014

Despite tremendous progress in developing doped carbocatalysts for the oxygen reduction reaction (ORR), the ORR activity of current metal‐free carbocatalysts is still inferior to that of conventional Pt/C catalysts, especially in acidic media and neutral solution. Moreover, it also remains a challenge to develop an effective and scalable method for the synthesis of metal‐free carbocatalysts. Herein, we have developed nitrogen and phosphorus dual‐doped hierarchical porous carbon foams (HP‐NPCs) as efficient metal‐free electrocatalysts for ORR. The HP‐NPCs were prepared for the first time by copyrolyzing nitrogen‐ and phosphorus‐containing precursors and poly(vinyl alcohol)/polystyrene (PVA/PS) hydrogel composites as in situ templates. Remarkably, the resulting HP‐NPCs possess controllable nitrogen and phosphorus content, high surface area, and a hierarchical interconnected macro‐/mesoporous structure. In studying the effects of the HP‐NPCs on the ORR, we found that the as‐prepared HP‐NPC materials exhibited not only excellent catalytic activity for ORR in basic, neutral, and acidic media, but also much better tolerance for methanol oxidation and much higher stability than the commercial, state‐of‐the‐art Pt/C catalysts. Because of all these outstanding features, it is expected that the HP‐NPC material will be a very suitable catalyst for next‐generation fuel cells and lithium–air batteries. In addition, the novel synthetic method described here might be extended to the preparation of many other kinds of hierarchical porous carbon materials or porous carbon that contains metal oxide for wide applications including energy storage, catalysis, and electrocatalysis.
Pseudotetrahedral Rhodium(I) Complexes
Authors: Geer Ana M. , Julián Alejandro , López José A. , Ciriano Miguel A. , Tejel Cristina
Published: February 2014

A combination of four‐electron donors, such as alkynes, with strongly donating and strong‐field scorpionate ligands is appropriate to create pseudotetrahedral rhodium(I) environments, as found in [Rh(PhBP3)(HCCPh)], which promotes HC bond activation and CC coupling reactions under very smooth conditions.
Stereocontrol by Quaternary Centres: A Stereoselective Synthesis of (−)‐Luminacin D
Authors: Bartlett Nathan , Gross Leona , Péron Florent , Asby Daniel J. , Selby Matthew D. , Tavassoli Ali , Linclau Bruno
Published: February 2014

Very high diastereoselectivity can be achieved by 1,3‐chelation‐controlled allylation of aldehydes that possess a non‐chelating α‐ether substituent, even if the α‐position is a quaternary centre and/or a spiro‐epoxide. This reaction was used as a key step in an enantioselective synthesis of the angiogenesis inhibitor luminacin D.
A NLCG 3‐D Inversion Method of Magnetotellurics with Parallel Structure
Authors: Kun ZHANG , Hao DONG , Jia‐Yong YAN , Qing‐Tian LÜ , Wen‐Bo WEI , Yu‐Xian HE
Published: February 2014

In this paper, we improve and verify the inversion algorithm and parallel computing program of three‐dimensional magnetotelluric sounding, and the program does not require much physical memory and CPU quantity. It makes possible to do three‐dimensional inversion on ordinary PC computers. Throughout nonlinear conjugate gradient algorithm proposed by Newman and Alumbaugh (2000) and preconditioning method proposed by Rodi and Mackie (2001), we improve the preconditioning method add parallel structure, and verify the program with theoretical models. According to the inversion results of measured data in Japanese KAYABE area, we demonstrate the practicality of the algorithm.
Edge Detection in Potential Fields Using Optimal Auto‐Ratios of Vertical Gradients
Authors: Yan‐Guo WANG , Feng‐Xu ZHANG , Cai LIU , Zhu‐Wen WANG , Jin ZHANG
Published: February 2014

Derivative calculation of potential‐fields is widely used in edge detection of geologic bodies. However, the traditional gradient methods are susceptible to noise disturbance, and can lead to instability of results. Besides, the edges of small‐sized geologic bodies are difficult to be detected because of superimposed anomalies. In this paper, we give the definition of auto‐ratios and present a new method for edge detection by using optimal auto‐ratios of vertical derivatives, and elaborate mathematical implication and physical meaning of this method. The model test shows that the method using optimal auto‐ratios of vertical gradients can greatly suppress noise disturbance and accurately detect the edges of geologic bodies which cannot be recognized by traditional edge detection methods. In application, we choose gravity data of the Yalujiang Basin where geological conditions are very complex to test the optimal auto‐ratio method. The results show that the tectonic boundaries recognized by the optimal auto‐ratios of the third‐order vertical derivatives correspond well to distribution characteristics of real geologic bodies, which are in agreement with previous work. And the negative anomaly zones delineated by the auto‐ratios reflect the work area of the Hunjiang coalfield rather well.
Highlights From the 2013 ACCF/AHA Guidelines for the Management of ST‐Elevation Myocardial Infarction and Beyond
Authors: Tamis‐Holland Jacqueline E. , O'Gara Patrick
Published: February 2014

ST‐segment elevation myocardial infarction (STEMI) is considered a cardiology emergency requiring immediate recognition and treatment aimed at successful and early reperfusion to ensure optimal outcomes. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have issued guidelines for the diagnosis and management of patients with acute myocardial infarction since 1990. These guidelines are based on clinical research exploring reperfusion modalities and adjunctive therapies. They are further supported by expert opinion where randomized trial evidence is lacking. In January 2013, the ACCF/AHA released the most recent guidelines for the management of patients with STEMI. This review focuses on the newest and most important recommendations taken from the 2013 ACCF/AHA Guidelines for the Management of STEMI and highlight important new studies that have emerged over the past year.
A Review on Formation and Decay Kinetics of Trihalomethanes in Water of Different Qualities
Authors: Al‐Omari Abbas , Muhammetoglu Ayse , Karadirek Ethem , Jiries Anwar , Batarseh Mufeed , Topkaya Bulent , Soyupak Selcuk
Published: February 2014

Despite the many disadvantages associated with the use of chlorine for disinfecting drinking water, chlorination is still the main method used for this purpose worldwide. Low chlorine concentrations in water distribution systems increase health risks whereas high chlorine concentrations are associated with the formation of disinfection by‐products such as trihalomethanes which are suspected carcinogens. Due to their negative health impacts, trihalomethanes occurrence in finished drinking water has received great attention from researchers and scientists worldwide. This manuscript critically reviews and discusses up to date knowledge on the occurrence of trihalomethanes in chlorinated drinking water and their associated health risks and identifies research gaps. The models for trihalomethane formation and decay have been compiled with special emphasis on the impact of the bromide ion on the total trihalomethane levels and speciation. Furthermore, the fate and transport of trihalomethanes in drinking water supplies and in groundwater have been investigated. Finally, management options for the reduction of trihalomethanes in chlorinated drinking water such as the removal of precursors from raw water, the use of alternative disinfectants and the removal of trihalomethanes from finished drinking water have been critically investigated and discussed.
Removal of Benzoic Acid from Water by Reactive Extraction Using Hollow Fiber Membrane Contactor: Experiment and Modeling
Authors: Agrahari Gunjan Kumar , Verma Nishith , Bhattacharya Prashant K.
Published: February 2014

A commercially available hydrophobic polypropylene based hollow fiber membrane contactor (HFMC: Liquicel® module) was used for the removal of dissolved benzoic acid (BA) from water. The module was operated in liquid–liquid extraction (LLE) mode using BA‐laden water as feed on the lumen side and trioctylamine (TOA) diluted in 1‐octanol as extractant on the shell side of the module. The aqueous and organic streams flowed counter‐currently within the HFMC module. Experiments were carried out under different operating conditions, that is, feed flow rates, extractant flow rates, and initial BA concentrations in the feed. The synthetic wastewater was prepared using BA at concentrations ranging from 150 to 2700 ppm in water, whereas the extractant solution consisted of 0.12 M TOA in 1‐octanol. BA reacted with TOA at the interface of the aqueous and membrane phases, forming a complex that was removed by the organic extractant flowing on the shell side of the module. In this study, up to 95% removal efficiency was obtained using the HFMC operated in the LLE mode. A mathematical model was developed that simulated transport of the bulk aqueous phase and within the pores of the membrane. The model simulation results were found to be in reasonable agreement with the experimental data.
Discovery of 5‐(2‐(Phenylamino)pyrimidin‐4‐yl)thiazol‐2(3H)‐one Derivatives as Potent Mnk2 Inhibitors: Synthesis, SAR Analysis and Biological Evaluation
Authors: Diab Sarah , Teo Theodosia , Kumarasiri Malika , Li Peng , Yu Mingfeng , Lam Frankie , Basnet Sunita K. C. , Sykes Matthew J. , Albrecht Hugo , Milne Robert , Wang Shudong
Published: February 2014

Phosphorylation of eIF4E by human mitogen‐activated protein kinase (MAPK)‐interacting kinases (Mnks) is crucial for human tumourigenesis and development. Targeting Mnks may provide a novel anticancer therapeutic strategy. However, the lack of selective Mnk inhibitors has so far hampered pharmacological target validation and clinical drug development. Herein, we report, for the first time, the discovery of a series of 5‐(2‐(phenylamino)pyrimidin‐4‐yl)thiazole‐2(3H)‐one derivatives as Mnk inhibitors. Several derivatives demonstrate very potent Mnk2 inhibitory activity. The most active and selective compounds were tested against a panel of cancer cell lines, and the results confirm the cell‐type‐specific effect of these Mnk inhibitors. Detailed cellular mechanistic studies reveal that Mnk inhibitors are capable of reducing the expression level of anti‐apoptotic protein Mcl‐1, and of promoting apoptosis in MV4‐11 acute myeloid leukaemia cells.
Sensitivity‐enhanced chemical exchange saturation transfer (CEST) MRI with least squares optimization of Carr Purcell Meiboom Gill multi‐echo echo planar imaging
Authors: Sun Phillip Zhe , Wang Yu , Lu Jie
Published: February 2014

Chemical exchange saturation transfer (CEST) imaging is a novel MRI technique that is sensitive to biomolecules, local pH and temperature, and offers considerable advantages for in vivo applications. However, the magnitude of CEST effect for dilute CEST agents undergoing slow or intermediate chemical exchange is typically small, requiring the use of signal averaging to enhance its sensitivity. Given that T2‐induced signal loss can be normalized by asymmetry analysis, the magnitude of CEST effect is independent of echo time. Therefore, CEST MRI with multi‐echo echo planar imaging (EPI) readout should yield the same CEST effect as conventional single echo acquisition. Importantly, CEST multi‐echo (CESTme) EPI images can be averaged to enhance CEST MRI sensitivity. The goal of this study was to validate CESTme EPI using a creatine–agarose gel CEST phantom with similar T2 as biological tissue. Using least‐squares optimization, we found that the sensitivity of CESTme sequence was significantly higher than that obtained by conventional single echo CEST‐EPI acquisition. Specifically, signal‐to‐noise ratio and contrast‐to‐noise ratio from the proposed CESTme EPI were approximately equivalent to that obtained by doubling the number of signal averages of the standard single echo CEST MRI sequence. In summary, our results demonstrated CESTme EPI for sensitivity‐enhanced CEST imaging. Copyright © 2014 John Wiley & Sons, Ltd.
In vivo near‐infrared fluorescence targeting of T cells: comparison of nanobodies and conventional monoclonal antibodies
Authors: Bannas Peter , Well Lennart , Lenz Alexander , Rissiek Björn , Haag Friedrich , Schmid Joanna , Hochgräfe Katja , Trepel Martin , Adam Gerhard , Ittrich Harald , Koch‐Nolte Friedrich
Published: February 2014

The large size of conventional antibodies impedes tissue penetration and renal elimination, resulting in suboptimal in vivo targeting. Here we assess the utility of nanobodies and nanobody‐Fc‐fusion proteins as alternatives to monoclonal antibodies as theranostics, using T cell ADP–ribosyltransferase 2 (ART2) as a model antigen for specific targeting of lymph nodes. ART2‐specific monovalent nanobody s + 16a (17 kDa), a bivalent Fc‐fusion protein of s + 16a (s + 16‐mFc, 82 kDa), and conventional antibody Nika102 (150 kDa) were labeled with AlexaFluor680. In vitro binding and inhibitory properties of the three AF680 conjugates were assessed by flow cytometry. For in vivo imaging experiments, AF680 conjugates were intravenously injected in mice lacking (KO) or overexpressing (TG) ART2. We monitored circulating and excreted AF680 conjugates in plasma and urine and performed in vivo near‐infrared fluorescence imaging. Nanobody s + 16a680 and s + 16mFc680 labeled and inhibited ART2 on T cells in lymph nodes within 10 min. In contrast, mAb Nika102680 required 2 h for maximal labeling without inhibition of ART2. In vivo imaging revealed specific labeling of ART2‐positive lymph nodes but not of ART2‐negative lymph nodes with all AF680 conjugates. Even though bivalent s + 16mFc680 showed the highest labeling efficiency in vitro, the best lymph node imaging in vivo was achieved with monovalent nanobody s + 16a680, since renal elimination of unbound s + 16a680 significantly reduced background signals. Our results indicate that small single‐domain nanobodies are best suited for short‐term uses, such as noninvasive imaging, whereas larger nanobody‐Fc‐fusion proteins are better suited for long‐term uses, such as therapy of inflammation and tumors. Copyright © 2014 John Wiley & Sons, Ltd.
Anatomical and functional imaging of myocardial infarction in mice using micro‐CT and eXIA 160 contrast agent
Authors: Ashton Jeffrey R. , Befera Nicholas , Clark Darin , Qi Yi , Mao Lan , Rockman Howard A. , Johnson G. Allan , Badea Cristian T.
Published: February 2014

Noninvasive small animal imaging techniques are essential for evaluation of cardiac disease and potential therapeutics. A novel preclinical iodinated contrast agent called eXIA 160 has recently been developed, which has been evaluated for micro‐CT cardiac imaging. eXIA 160 creates strong contrast between blood and tissue immediately after its injection and is subsequently taken up by the myocardium and other metabolically active tissues over time. We focus on these properties of eXIA and show its use in imaging myocardial infarction in mice. Five C57BL/6 mice were imaged ~2 weeks after left anterior descending coronary artery ligation. Six C57BL/6 mice were used as controls. Immediately after injection of eXIA 160, an enhancement difference between blood and myocardium of ~340 HU enabled cardiac function estimation via 4D micro‐CT scanning with retrospective gating. Four hours post‐injection, the healthy perfused myocardium had a contrast difference of ~140 HU relative to blood while the infarcted myocardium showed no enhancement. These differences allowed quantification of infarct size via dual‐energy micro‐CT. In vivo micro‐SPECT imaging and ex vivo triphenyl tetrazolium chloride (TTC) staining provided validation for the micro‐CT findings. Root mean squared error of infarct measurements was 2.7% between micro‐CT and SPECT, and 4.7% between micro‐CT and TTC. Thus, micro‐CT with eXIA 160 can be used to provide both morphological and functional data for preclinical studies evaluating myocardial infarction and potential therapies. Further studies are warranted to study the potential use of eXIA 160 as a CT molecular imaging tool for other metabolically active tissues in the mouse. Copyright © 2014 John Wiley & Sons, Ltd.
In vitro Gd‐DTPA relaxometry studies in oxygenated venous human blood and aqueous solution at 3 and 7 T
Authors: Kalavagunta Chaitanya , Michaeli Shalom , Metzger Gregory J.
Published: February 2014

In vitro T1 and T2* relaxivities (r1 and r2*) of Gd‐DTPA (GaD) in oxygenated human venous blood (OVB) and aqueous solution (AS) at 3 and 7 T were calculated. GaD concentrations ([GaD]) in OVB and AS were prepared in the range 0‐5 mM. All measurements were acquired at 37 ± 2 °C. At both 3 and 7 T, a linear relationship was observed between [GaD] and R1 in both AS and OVB. At 7 T, r1 in AS decreased by 7.5% (p = 0.045) while there was a negligible change in OVB. With respect to R2*, a linear relationship with [GaD] was only observed in AS, while a more complex relationship was observed in OVB; quadratic below and linear above 2 mM at both field strengths. There was a significant increase of over 4‐fold in r2* with GaD in OVB at 7 T (for [GaD] above 2 mM, p <<0.01) as compared with 3 T. Furthermore, in comparison to r1, r2* in AS was less than 2‐fold higher at both field strengths while in OVB it was ~20‐fold and ~90‐fold higher at 3 and 7 T, respectively. This observation emphasizes the importance of r2* knowledge at high magnetic fields, ≥3 T. The comparison between r1 and r2* presented in this work is crucial in the design and optimization of high‐field MRI studies making use of paramagnetic contrast agents. This is especially true in multiple compartment systems such as blood, where r2* dramatically increases while r1 remains relatively constant with increasing magnetic field strength. Copyright © 2014 John Wiley & Sons, Ltd.
Multi‐institutional, randomized, double‐blind, placebo‐controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck
Authors: Allison Ron R. , Ambrad Aaron A. , Arshoun Youssef , Carmel Richard J. , Ciuba Doug F. , Feldman Elizabeth , Finkelstein Steven E. , Gandhavadi Ranjini , Heron Dwight E. , Lane Steven C. , Longo John M. , Meakin Charles , Papadopoulos Dimitrios , Pruitt David E. , Steinbrenner Lynn M. , Taylor Michael A. , Wisbeck William M. , Yuh Grace E. , Nowotnik David P. , Sonis Stephen T.
Published: February 2014

BACKGROUND

The objective of this trial was to determine how a mucoadhesive hydrogel (MuGard), a marketed medical device, would fare when tested with the strictness of a conventional multi‐institutional, double‐blind, randomized, placebo‐controlled study format.

METHODS

A total of 120 subjects planned to receive chemoradiation therapy (CRT) for treatment of head and neck cancers were randomized to receive either MuGard or sham control rinse (SC) during CRT. Subjects completed the validated Oral Mucositis Daily Questionnaire. Weight, opiate use, and World Health Organization (WHO) oral mucositis (OM) scores were recorded. Subjects who dosed at least once daily during the first 2.5 weeks of CRT were included in the efficacy analysis.

RESULTS

Of 120 subjects enrolled, 78 (SC, N = 41; MuGard, N = 37) were eligible for efficacy analysis. Both cohorts were similar in demographics, baseline characteristics, primary tumor type, and planned CRT regimen. MuGard effectively mitigated OM symptoms as reflected by area under the curve of daily patient‐reported oral soreness (P = .034) and WHO scores on the last day of radiation therapy (P = .038). MuGard was also associated with nonsignificant trends related to therapeutic benefit including opioid use duration, and OM scores (WHO criteria) at CRT week 4. Rinse compliance was identical between cohorts. No significant adverse events were reported, and the adverse event incidence was similar between cohorts.

CONCLUSIONS

Testing MuGard, a rinse marketed as a device, in a standard clinical trial format demonstrated its superiority to SC in mitigating OM symptoms, delaying OM progression, and its safety and tolerability. Cancer 2014;120:1433–1440. © 2014 Access Pharmaceuticals, Inc. Cancer published by Wiley Periodicals. Inc. on behalf of American Cancer Society.
Identification of underserved areas for urologic cancer care
Authors: Mossanen Matthew , Izard Jason , Wright Jonathan L. , Harper Jonathan D. , Porter Michael P. , Daratha Kenn B. , Holt Sarah K. , Gore John L.
Published: February 2014

BACKGROUND

The delivery of urologic oncology care is susceptible to regional variation. In the current study, the authors sought to define patterns of care for patients undergoing genitourinary cancer surgery to identify underserved areas for urologic cancer care in Washington State.

METHODS

The authors accessed the Washington State Comprehensive Hospital Abstract Reporting System from 2003 through 2007. They identified patients undergoing radical prostatectomy, radical cystectomy (RC), partial nephrectomy (PN), radical nephrectomy, and transurethral resection of the prostate (TURP). TURP was included for comparison as a reference procedure indicative of access to urologic care. Hospital service areas (HSAs) are where the majority of local patients are hospitalized; hospital referral regions (HRR) are where most patients receive tertiary care. The authors created multivariate hierarchical logistic regression models to examine patient and HSA characteristics associated with the receipt of urologic oncology care out of the HRR for each procedure.

RESULTS

Greater than one‐half of patients went out of their HRR in 7 HSAs (11%) for radical prostatectomy, 3 HSAs (5%) for radical nephrectomy, 10 HSAs (15%) for PN, and 14 HSAs (22%) for RC. No HSAs had high export rates for TURP. Few patient factors were found to be associated with surgical care out of the HRR. High‐export HSAs for PN and RC exhibited lower socioeconomic characteristics than low‐export HSAs, adjusting for HSA population, race, and HSA procedure rates for PN and RC.

CONCLUSIONS

Patients living in areas with lower socioeconomic status have a greater need to travel for complex urologic surgery. Consideration of geographic delineation in the delivery of urologic oncology care may aid in regional quality improvement initiatives. Cancer 2014;120:1565–1571. © 2014 American Cancer Society.
Natural and lesion‐induced decrease in cell proliferation in the medial nucleus of the trapezoid body during hearing development
Authors: Saliu Aminat , Adise Shana , Xian Sandy , Kudelska Kamila , Rodríguez‐Contreras Adrián
Published: February 2014

The functional interactions between neurons and glial cells that are important for nervous system function are presumably established during development from the activity of progenitor cells. In this study we examined proliferation of progenitor cells in the medial nucleus of the trapezoid body (MNTB) located in the rat auditory brainstem. We performed DNA synthesis labeling experiments to demonstrate changes in cell proliferation activity during postnatal stages of development. An increase in cell proliferation correlated with MNTB growth and the presence of S100β‐positive astrocytes among MNTB neurons. In additional experiments we analyzed the fate of newly born cells. At perinatal ages, newly born cells colabeled with the astrocyte marker S100β in higher numbers than when cells were generated at postnatal day 6. Furthermore, we identified newly born cells that were colabeled with caspase‐3 immunohistochemistry and performed comparative experiments to demonstrate that there is a natural decrease in cell proliferation activity during postnatal development in rats, mice, gerbils, and ferrets. Lastly, we found that there is a stronger decrease in MNTB cell proliferation after performing bilateral lesions of the auditory periphery in rats. Altogether, these results identify important stages in the development of astrocytes in the MNTB and provide evidence that the proliferative activity of the progenitor cells is developmentally regulated. We propose that the developmental reduction in cell proliferation may reflect coordinated signaling between the auditory brainstem and the auditory periphery. J. Comp. Neurol. 522:971–985, 2014. © 2013 Wiley Periodicals, Inc.
The 0.96(Bi0.5Na0.5)TiO3 – 0.04BaTiO3 crystal structure: A high‐Q, high‐counting statistics synchrotron diffraction analysis
Authors: Fuentes‐Cobas L. E. , Pardo L. , Montero‐Cabrera M. E. , Plaisier J. R. , García A. , Brebøl K. , Mercadelli E. , Galassi C.
Published: February 2014

A synchrotron powder diffraction experiment, especially designed to shed light on the controversial problem of the crystal structure of 0.96(Bi0.5Na0.5)TiO3 – 0.04BaTiO3, is reported. The investigated material is a key component of the current international search for lead‐free ferro‐piezoelectrics. A wide angular range diffraction pattern was measured in high resolution configuration, with emphasis on trustable counting stastistics in the high‐Q interval. Cc and R3c structural models were tried as primary phases. The obtained experimental results are incompatible with the monoclinic model and clearly favor the rhombohedral symmetry.
Graphite Felt Modified with Bismuth Nanoparticles as Negative Electrode in a Vanadium Redox Flow Battery
Authors: Suárez David J. , González Zoraida , Blanco Clara , Granda Marcos , Menéndez Rosa , Santamaría Ricardo
Published: February 2014

A graphite felt decorated with bismuth nanoparticles was studied as negative electrode in a vanadium redox flow battery (VRFB). The results confirm the excellent electrochemical performance of the bismuth modified electrode in terms of the reversibility of the V3+/V2+ redox reactions and its long‐term cycling performance. Moreover a mechanism that explains the role that Bi nanoparticles play in the redox reactions in this negative half‐cell is proposed. Bi nanoparticles favor the formation of BiHx, an intermediate that reduces V3+ to V2+ and, therefore, inhibits the competitive irreversible reaction of hydrogen formation (responsible for the commonly observed loss of Coulombic efficiency of VRFBs). Thus, the total charge consumed during the cathodic sweep in this electrode is used to reduce V3+ to V2+, resulting in a highly reversible and efficient process.
Energetics of Defects on Graphene through Fluorination
Authors: Xiao Jie , Meduri Praveen , Chen Honghao , Wang Zhiguo , Gao Fei , Hu Jianzhi , Feng Ju , Hu Mary , Dai Sheng , Brown Suree , Adcock Jamie L. , Deng Zhiqun , Liu Jun , Graff Gordon L. , Aksay Ilhan A. , Zhang Ji‐Guang
Published: February 2014

Functionalized graphene sheets (FGSs) comprise a unique member of the carbon family, demonstrating excellent electrical conductivity and mechanical strength. However, the detailed chemical composition of this material is still unclear. Herein, we take advantage of the fluorination process to semiquantitatively probe the defects and functional groups on graphene surface. Functionalized graphene sheets are used as substrate for low‐temperature (<150 °C) direct fluorination. The fluorine content has been modified to investigate the formation mechanism of different functional groups such as CF, CF2, OCF2 and (CO)F during fluorination. The detailed structure and chemical bonds are simulated by density functional theory (DFT) and quantified experimentally by nuclear magnetic resonance (NMR). The electrochemical properties of fluorinated graphene are also discussed extending the use of graphene from fundamental research to practical applications.
Studies on the minor metabolite 6a‐hydroxy‐androstenedione for doping control purposes and its contribution to the steroid profile
Authors: Polet Michael , Van Renterghem Pieter , Van Gansbeke Wim , Van Eenoo Peter
Published: February 2014

Recent publications have shown that the concentrations of minor metabolites such as formestane and 6a‐hydroxy‐androstenedione (6aOHADION) are import parameters, capable of increasing the specificity and efficiency of steroid abuse screening. The importance of such minor metabolites has been recognized for some time, but setting up concentration thresholds is not that straightforward with a single quadrupole gas chromatograph mass spectrometer (GC‐MS) because of the low concentrations; this is especially the case for 6aOH‐ADION. The main aim of this study was to propose a concentration threshold above which the detected 6aOH‐ADION is considered suspicious and isotope ratio mass spectrometry (IRMS) is recommended. Routine doping control samples (2128) from athletes that entered our lab and were not found suspicious for the intake of any doping substance were used to determine the baseline concentrations of 6a‐OH‐ADION. For this purpose, the more sensitive gas chromatography‐tandem mass spectrometry (GC‐MS/MS) was used, capable of quantifying these low concentrations with high reliability. A urinary concentration threshold of 5 ng/mL was set. Concentrations above this threshold are considered suspicious and are forwarded to IRMS for confirmation in routine practice. In addition, an IRMS method was developed, capable of determining the 13C value of 6aOH‐ADION. If a urine sample has an elevated 6aOH‐ADION concentration and normal 13C values for the traditional IRMS target compounds, we are still able to check the 13C value of 6aOH‐ADION. Six excretion studies were executed to stress the applicability of the threshold by visualizing the concentration and δ13C value time profiles of 6aOH‐ADION. Copyright © 2014 John Wiley & Sons, Ltd.