bluuebunny/crossref_metadata_2025 huggingface dataset:
Age‐Dependent Levels of 5‐Methyl‐, 5‐Hydroxymethyl‐, and 5‐Formylcytosine in Human and Mouse Brain Tissues
Authors: Wagner Mirko , Steinbacher Jessica , Kraus Theo F. J. , Michalakis Stylianos , Hackner Benjamin , Pfaffeneder Toni , Perera Arshan , Müller Markus , Giese Armin , Kretzschmar Hans A. , Carell Thomas
Published: July 2015

The absolute levels of 5‐hydroxymethylcytosine (hmC) and 5‐methylcytosine (mC) in human brain tissues at various ages were determined. Additionally, absolute levels of 5‐formylcytosine (fC) in adult individuals and cytosine modification levels in sorted neurons were quantified. These data were compared with age‐related fC, hmC, and mC levels in mouse brain samples. For hmC, an initial steady increase is observed, which levels off with age to a final steady‐state value of 1.2 % in human brain tissue. This level is nearly twice as high as in mouse cerebral cortex. In contrast, fC declines rapidly with age during early developmental stages, thus suggesting that while hmC is a stable epigenetic mark, fC is more likely an intermediate of active DNA demethylation during early brain development. The trends in global cytosine modification dynamics during the lifespan of an organism are conserved between humans and mice and show similar patterns in different organs.
One‐pot Unsymmetrical Ketone Synthesis Employing a Pyrrole‐Bearing Formal Carbonyl Dication Linchpin Reagent
Authors: Heller Stephen T. , Newton James N. , Fu Tingting , Sarpong Richmond
Published: July 2015

A one‐pot procedure for the synthesis of unsymmetrical ketones utilizing a pyrrole‐bearing carbonyl linchpin reagent (carbonyl linchpin N,O‐dimethylhydroxylamine pyrrole; CLAmP) is reported. In contrast to other carbonyl dielectrophile equivalents, CLAmP enables the synthesis of ketones from a variety of organolithium and Grignard reagents. The electrophilic nature of CLAmP enables the addition of less reactive as well as thermally unstable nucleophiles. CLAmP was designed to form kinetically stable tetrahedral intermediates upon the addition of organometallic nucleophiles. Evidence for the existence of persistent tetrahedral intermediates was obtained through in situ IR studies.
Acid–Base Pairs in Lewis Acidic Zeolites Promote Direct Aldol Reactions by Soft Enolization
Authors: Lewis Jennifer D. , Van de Vyver Stijn , Román‐Leshkov Yuriy
Published: July 2015

Hf‐, Sn‐, and Zr‐Beta zeolites catalyze the cross‐aldol condensation of aromatic aldehydes with acetone under mild reaction conditions with near quantitative yields. NMR studies with isotopically labeled molecules confirm that acid‐base pairs in the Si‐O‐M framework ensemble promote soft enolization through α‐proton abstraction. The Lewis acidic zeolites maintain activity in the presence of water and, unlike traditional base catalysts, in acidic solutions.
Dimeric TADDOL Phosphoramidites in Asymmetric Catalysis: Domino Deracemization and Cyclopropanation of Sulfonium Ylides
Authors: Klimczyk Sebastian , Misale Antonio , Huang Xueliang , Maulide Nuno
Published: July 2015

A gold‐catalyzed asymmetric cyclopropanation of unactivated olefins with sulfonium ylides in the presence of a bimetallic catalyst with a novel dimeric TADDOL‐phosphoramidite ligand is reported. This transformation allows a rare gold‐catalyzed dynamic deracemization of chiral racemic substrates, where the same catalyst is responsible for several synergistic tasks in solution. The products are useful building blocks in synthesis and enable expeditious access to natural products.
Substrate‐Tuned Catalysis of the Radical S‐Adenosyl‐L‐Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis
Authors: Ji Xinjian , Li Yongzhen , Ding Wei , Zhang Qi
Published: July 2015

NosL is a radical S‐adenosyl‐L‐methionine (SAM) enzyme that converts L‐Trp to 3‐methyl‐2‐indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2‐amino‐3‐(benzofuran‐3‐yl)propanoic acid (ABPA), we clearly demonstrated that the 5′‐deoxyadenosyl (dAdo) radical‐mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L‐Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical‐mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities.
Direct Imaging of Highly Anisotropic Photogenerated Charge Separations on Different Facets of a Single BiVO4 Photocatalyst
Authors: Zhu Jian , Fan Fengtao , Chen Ruotian , An Hongyu , Feng Zhaochi , Li Can
Published: July 2015

Spatially resolved surface photovoltage spectroscopy (SRSPS) was employed to obtain direct evidence for highly anisotropic photogenerated charge separation on different facets of a single BiVO4 photocatalyst. Through the controlled synthesis of a single crystal with preferentially exposed {010} facets, highly anisotropic photogenerated hole transfer to the {011} facet of single BiVO4 crystals was observed. The surface photovoltage signal intensity on the {011} facet was 70 times stronger than that on the {010} facets. The influence of the built‐in electric field in the space charge region of different facets on the anisotropic photoinduced charge transfer in a single semiconductor crystal is revealed.
A Molecular Platform for Multistate Near‐Infrared Electrochromism and Flip‐Flop, Flip‐Flap‐Flop, and Ternary Memory
Authors: Cui Bin‐Bin , Tang Jian‐Hong , Yao Jiannian , Zhong Yu‐Wu
Published: July 2015

A diruthenium complex with a redox‐active amine bridge has been designed, synthesized, and studied by single‐crystal X‐ray analysis and DFT and TDDFT calculations. It shows three well‐separated redox processes with exclusive near‐infrared (NIR) absorbance at each redox state. The electropolymerized film of a related vinyl‐functionalized complex displays multistate NIR electrochromism with low operational potential, good contrast ratio, and long retention time. Flip‐flop, flip‐flap‐flop, and ternary memories have been realized by using the obtained film (ca. 15–20 nm thick) with three electrochemical inputs and three NIR optical outputs that each displays three levels of signal intensity.
Synergistic Catalysis: Metal/Proton‐Catalyzed Cyclization of Alkynones Toward Bicyclo[3.n.1]alkanones
Authors: Zhu Shifa , Zhang Qiaohui , Chen Kai , Jiang Huanfeng
Published: July 2015

A highly efficient and practical synergistically metal/proton‐catalyzed Conia–ene reaction for the synthesis of bicyclo[3.n.1]alkanones has been developed. This synergistic catalysis was successfully utilized in modifying natural compounds such as methyl dihydrojasmonate, α,β‐thujone, and 5α‐cholestan‐3‐one. Furthermore, the bridged carbonyl group of bicyclo[3.2.1]alkanones could be easily attacked by nucleophiles to give the ring‐opened cycloheptenone products or bicyclo[4.2.1]amide in excellent yields. These reactions provide rapid access to a diverse range of cyclic structures from simple starting materials or naturally occurring compounds.
Synthesis and properties of cross‐linked polymers from epoxidized rubber seed oil and triethylenetetramine
Authors: Abduh Muhammad Yusuf , Iqbal Muhammad , Picchioni Francesco , Manurung Robert , Heeres Hero J.
Published: July 2015

A series of epoxidized oils were prepared from rubber seed, soybean, jatropha, palm, and coconut oils. The epoxy content varied from 0.03 to 7.4 wt %, in accordance with the degree of unsaturation of the oils (lowest for coconut, highest for rubber seed oil). Bulk polymerization/curing of the epoxidized oils with triethylenetetramine (in the absence of a catalyst) was carried out in a batch setup (1 : 1 molar ratio of epoxide to primary amine groups, 100°C, 100 rpm, 30 min) followed by casting of the mixture in a steel mold (180°C, 200 bar, 21 h) and this resulted in cross‐linked resins. The effect of relevant pressing conditions such as time, temperature, pressure, and molar ratio of the epoxide and primary amine groups was investigated and modeled using multivariable nonlinear regression. Good agreement between experimental data and model were obtained. The rubber seed oil‐derived polymer has a Tg of 11.1°C, a tensile strength of 1.72 MPa, and strain at break of 182%. These values are slightly higher than for commercial epoxidized soybean oil (Tg of 6.9°C, tensile strength of 1.11 MPa, and strain at break of 145.7%). However, the comparison highlights the potential for these novel resins to be used at industrial/commercial level. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42591.
Uniform mPEG‐b‐PMETAC enables pH‐responsive delivery of insulin
Authors: Li Zongjun , Zhang Yifei , Lu Diannan , Liu Zheng
Published: July 2015

A cationic block copolymer (mPEG‐b‐PMETAC) with uniform molecular weight was synthesized using atom transfer radical polymerization. Insulin was reversibly encapsulated by mPEG‐b‐PMETAC via electrostatic interaction. The secondary and tertiary structures of insulin during the assembly and delivery processes were monitored by circular dichroism and fluorescence spectrum. The effects of pH and salt concentration on encapsulation were examined, respectively. Enhanced stability of the encapsulated insulin against proteolysis by trypsin and chymotrypsin was demonstrated. Insulin can be encapsulated and delivered from an mPEG‐b‐PMETAC assembly by tuning the pH and ionic strength, which determines the electrostatic interaction between insulin and the polymer. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42596.
Nitrile rubber/hindered phenol exterminated hyperbranched polyester materials with improved damping and mechanical performance
Authors: Yang Yuan , Zhao Yun‐Feng , Zhan Mao‐Sheng , Wang Jian‐Yue , Zhao Chuan , Liu Xiao‐Yan , Zhang Ji‐Hua
Published: July 2015

Hindered phenol exterminated hyperbranched polyester (mHBP) is fabricated by esterification reaction. The mHBP is introduced into nitrile rubber (NBR) to prepare NBR/mHBP blends. Structure, damping and mechanical properties of NBR/mHBP blends are investigated by Fourier transform infrared spectroscopy (FTIR), 1H‐NMR, dynamic mechanical thermal analyzer (DMTA), and tensile tester. FTIR spectra of the blends illustrate the intermolecular hydrogen bonding between the NBR and mHBP, contributing to the improvement of damping and mechanical properties. The results indicate that, with the increasing mHBP content, the Tg of the blends shifted to a higher temperature with a broadening temperature range and improved mechanical properties, showing an application in adjusting the Tg and temperature range without decreasing of loss factor. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42605.
Chemical and bonding effects of exposing uncured PBI‐NBR insulation to ambient conditions
Authors: Parry Shawn , Pancoast Justin , Mildenhall Scott
Published: July 2015

Uncured Polybenzimidazole‐Nitrile Butadiene Rubber (PBI‐NBR) insulation experiences altered chemical and bonding phenomena if exposed to ambient conditions while in a sheet‐stock configuration. Multiple lots of a PBI‐NBR formulation exposed to ambient and slightly elevated temperature (100°F) conditions experience bonding degradation when vulcanized to a metal substrate. Chemical analyses show that tallow amine (clay particle surfactant) accumulates at the surface of uncured NBR as a function of ambient and 100°F exposure time. Additionally, thin film analyses suggest surface oxidation of NBR polymers when exposed to the ambient environment. Mechanical and chemical observations imply a correlation between vulcanized bonding performance with tallow amine diffusion and polymer surface reaction. The diffusion and reactivity of chemical species found in the PBI‐NBR formulation has implications to other fields employing these components. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42636.
Immunohistochemical Studies of Cytoskeletal and Extracellular Matrix Components in Dogfish Scyliorhinuscanicula L. Notochordal Cells
Authors: Restović Ivana , Vukojević Katarina , Paladin Antonela , Saraga‐Babić Mirna , Bočina Ivana
Published: July 2015

Immunofluorescence and immunohistochemical techniques were used to define the distribution of cytoskeletal (cytokeratin 8, vimentin) and extracellular matrix components (collagen type I, collagen type II, hyaluronic acid, and aggrecan) and bone morphogenetic proteins 4 and 7 (BMP4 and BMP7) in the notochord of the lesser spotted dogfish Scyliorhinus canicula L. Immunolocalization of hyaluronic acid was observed in the notochord, vertebral centrum, and neural and hemal arches, while positive labeling to aggrecan was observed in the ossified centrum, notochord, and the perichondrium of the hyaline cartilage. Type I collagen was observed in the mineralized cartilage of the vertebral bodies, the notochord, the fibrocartilage of intervertebral disc, and the perichondrium. A positive labeling to type II collagen was observed in the inner part of the cartilaginous vertebral centrum and the notochord, as well as in the neural arch and muscle tissue, but there was no appreciable labeling of the hyaline cartilage. The presence of both BMP4 and BMP7 was seen in the mineralized vertebral centrum, notochordal cells, and neural arch. The notochordal cells expressed both cytokeratin 8 and vimentin, but predominantly vimentin. Hyaluronic acid, collagen type I, and collagen type II expression confirmed the presence of a mixture of notochordal and fibrocartilaginous tissue in the intervertebral disc, while BMPs confirmed the presence of an ossification in the cartilaginous skeleton of the spotted dogfish. Anat Rec, 298:1700–1709, 2015. © 2015 Wiley Periodicals, Inc.
Utility of the Child Behavior Checklist as a Screener for Autism Spectrum Disorder
Authors: Havdahl K. Alexandra , von Tetzchner Stephen , Huerta Marisela , Lord Catherine , Bishop Somer L.
Published: July 2015

The Child Behavior Checklist (CBCL) has been proposed for screening of autism spectrum disorders (ASD) in clinical settings. Given the already widespread use of the CBCL, this could have great implications for clinical practice. This study examined the utility of CBCL profiles in differentiating children with ASD from children with other clinical disorders. Participants were 226 children with ASD and 163 children with attention‐deficit/hyperactivity disorder, intellectual disability, language disorders, or emotional disorders, aged 2–13 years. Diagnosis was based on comprehensive clinical evaluation including well‐validated diagnostic instruments for ASD and cognitive testing. Discriminative validity of CBCL profiles proposed for ASD screening was examined with area under the curve (AUC) scores, sensitivity, and specificity. The CBCL profiles showed low discriminative accuracy for ASD (AUC 0.59–0.70). Meeting cutoffs proposed for ASD was associated with general emotional/behavioral problems (EBP; mood problems/aggressive behavior), both in children with and without ASD. Cutoff adjustment depending on EBP‐level was associated with improved discriminative accuracy for school‐age children. However, the rate of false positives remained high in children with clinical levels of EBP. The results indicate that use of the CBCL profiles for ASD‐specific screening would likely result in a large number of misclassifications. Although taking EBP‐level into account was associated with improved discriminative accuracy for ASD, acceptable specificity could only be achieved for school‐age children with below clinical levels of EBP. Further research should explore the potential of using the EBP adjustment strategy to improve the screening efficiency of other more ASD‐specific instruments. Autism Res 2015. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Zugspannungs‐Dehnungs‐Beziehung für UHPFRC in Anlehnung an DAfStb‐Richtlinie Stahlfaserbeton
Authors: Oettel Vincent , Empelmann Martin
Published: July 2015

Im Gegensatz zur einaxialen Betondruckfestigkeit, die sich relativ einfach an Zylindern oder Würfeln ermitteln lässt, ist die Erfassung der zentrischen Betonzugfestigkeit wesentlich aufwendiger, da die Lasteinleitung mit Schwierigkeiten verbunden ist. Daher bietet sich die indirekte Ermittlung der zentrischen Zugfestigkeit über einen Biegezugversuch an. In diesem Fall muss jedoch die im Biegezugversuch bestimmte Kraft‐Verformungs‐Kurve in eine Zugspannungs‐Dehnungs‐Linie umgerechnet werden. Um das Zugspannungs‐Dehnungs‐Verhalten von ultrahochfestem Faserbeton (UHPFRC) zu untersuchen, wurden am iBMB, Fachgebiet Massivbau der TU Braunschweig, 4‐Punkt‐Biegeversuche mit Standard‐Biegebalken 15/15/70 cm aus ultrahochfestem Fein‐ oder Grobkornbeton mit unterschiedlichen Faserschlankheiten und ‐gehalten durchgeführt. Aufbauend auf den Versuchsergebnissen wurde, in Anlehnung an die DAfStb‐Richtlinie Stahlfaserbeton, eine Zugspannungs‐Dehnungs‐Beziehung für UHPFRC hergeleitet und mit der Finite‐Elemente‐Methode (FEM) validiert.

Tensile Stress‐Strain Relationship for UHPFRC on the basis of DAfStb‐Richtlinie Stahlfaserbeton

The concrete compressive strength can be easily determined by using cylinders or cubes, whilst determing the axial concrete tensile strength is much more complex due to its load instruction. Therefore, the axial tensile strength can be determined indirectly by bending test. In this case, however, the load‐displacement curve determined of the bending test has to be converted into a tensile stress‐strain curve. In order to analyse the tensile stress‐strain behavior of ultra‐high performance fiber reinforced concrete (UHPFRC), the iBMB, Division of Concrete Construction of the TU Braunschweig, has conducted 4‐point bending tests with standard bending beams 15/15/70 cm made of UHPFRC‐mortar or UHPFRC‐concrete which differed in fiber slenderness and fiber content. A tensile stress‐strain relation for UHPFRC based on the DAfStb‐Richtlinie Stahlfaserbeton was derived from the experimental results and finally validated by applying the finite element method (FEM).
Betonbau bei chemischem Angriff – neue DBV‐Arbeitshilfen
Authors: Siebert Björn
Published: July 2015

In verschiedenen Anwendungsgebieten ist der Baustoff Beton hohen Beanspruchungen von außen, z. B. durch betonaggressive Wässer, ausgesetzt, die die Dauerhaftigkeit des Bauwerks beeinträchtigen können. Für einen chemischen Angriff in natürlichen Böden und Grundwässern bestehen normative Vorgaben, um den Angriffsgrad anhand der Art und Konzentration der angreifenden Stoffe in Expositionsklassen einzustufen. Ob und inwieweit die Einstufungen für Böden und Grundwässer auch auf andere Bereiche mit chemischem Angriff auf Beton, z. B. Kraftwerksbau, Abwasseranlagen, Biogasanlagen etc., zu übertragen sind, ist stets im Einzelfall zu überprüfen.

Um Beton mit einem für die jeweilige Exposition adäquaten chemischen Widerstand auszustatten, sind in der Regel die betontechnologischen Vorgaben der einschlägigen Regelwerke ausreichend. Bei besonders starker Beanspruchung werden darüber hinaus zusätzliche Maßnahmen erforderlich, die sowohl die Betontechnologie als auch die Bauausführung betreffen können. Über die Art und den Umfang solcher im jeweiligen Anwendungsgebiet zusätzlich erforderlichen Maßnahmen wird in der Fachwelt kontrovers diskutiert.

Diese Problemstellungen in der Praxis aufgreifend, hat der Deutsche Beton‐ und Bautechnik‐Verein E.V. neue Arbeitshilfen herausgegeben, in denen auf die derzeitige Vorgehensweise bei der Bewertung des chemischen Angriffsgrads in unterschiedlichen Anwendungsgebieten des Betonbaus und bei der Festlegung geeigneter Schutzprinzipien eingegangen wird.

Concrete structures under chemical attack – new DBV Guide to Good Practice

In various fields of application concrete is highly stressed by the environmental exposure, e. g. by aggressive water, which may affect the durability of the structure. There are normative guidelines dealing with the chemical attack in natural soil and ground water which allow a classification of the attack in exposition classes on basis of the type and concentration of the corrosive substances. Whether and to what extent the classification criteria for soils and groundwater are transferable to other areas with chemical attack on concrete, e. g. power plants, wastewater treatment plants, biogas plants, etc. must always be checked individually.

In order to provide concrete with an adequate chemical resistance, the requirements for the concrete technology according to the general standards and regulations are usually sufficient. For particularly high stresses additional measures are needed which can affect both the concrete technology and the construction. A controversial debate among experts exists with respect to the type and extent of such measures required in the respective field of application.

With focus on these practical issues, the German Society for Concrete and Construction Technology (DBV) has published a new Guide to Good Practice which provides the common procedure for the evaluation of a chemical attack on concrete in different fields of application and deals with appropriate protection principles.
Does it help that efficacy has been proven once we start discussing (added) benefit?
Authors: Koch Armin , Ziert Yvonne
Published: July 2015

Since the introduction of benefit assessment to support reimbursement decisions in Germany there seems to be the impression that totally distinct methodology and strategies for decision making would apply in the field of drug licensing and reimbursement. In this article, the position is held that, while decisions may differ due to differing mandates of drug licensing and reimbursement bodies, the underlying strategies are quite similar. For this purpose, we briefly summarize the legal basis for decision making in both fields from a methodological point of view, and review two recent decisions about reimbursement regarding grounds for approval. We comment on two examples, where decision making was based on the same pivotal studies in the licensing and reimbursement process. We conclude that strategies in the field of reimbursement are (from a methodological standpoint) until now more liberal than established rules in the field of drug licensing, but apply the same principles. Formal proof of efficacy preceding benefit assessment can thus be understood as a gatekeeper against principally wrong decision making about efficacy and risks of new drugs in full recognition that more is needed. We elaborate on the differences between formal proof of efficacy on the one hand and the assessment of benefit/risk or added benefit on the other hand, because it is important for statisticians to understand the difference between the two approaches.
Assessing the predictive power of newly added biomarkers
Authors: Wang Zhanfeng , Luo Xiangyu , Chang Yuan‐chin I.
Published: July 2015

As medical research and technology advance, there are always new biomarkers found and predictive models proposed for improving the diagnostic performance of diseases. Therefore, in addition to the existing biomarkers and predictive models, how to assess new biomarkers becomes an important research problem. Many classification performance measures, which are usually based on the performance on the whole cut‐off values, were applied directly to this type of problems. However, in a medical diagnosis, some cut‐off points are more important, such as those points within the range of high specificity. Thus, as the partial area under the ROC curve to the area under ROC curve, we study the partial integrated discriminant improvement (pIDI) for evaluating the predictive ability of a newly added marker at a prespecified range of cut‐offs. Theoretical property of estimate of the proposed measure is reported. The performance of this new measure is then compared with that of the partial area under an ROC curve. The numerical results use synthesized are presented, and a liver cancer dataset is used for demonstration purposes.
Validation of a liquid chromatography‐triple quadrupole mass spectrometric method for the determination of 5‐nitro‐5′‐hydroxy‐indirubin‐3′‐oxime (AGM‐130) in human plasma and its application to microdose clinical trial
Authors: Park Min‐Ho , Lee Yun Young , Cho Kyung Hee , La Sookie , Lee Hee Joo , Yim Dong‐Seok , Ban Sooho , Park Moon‐Young , Kim Yong‐Chul , Kim Yoon‐Gyoon , Shin Young G.
Published: July 2015

A liquid chromatography–triple quadrupole mass spectrometric (LC‐MS/MS) method was developed and validated for the determination of 5‐nitro‐5′‐hydroxy‐indirubin‐3′‐oxime (AGM‐130) in human plasma to support a microdose clinical trial. The method consisted of a liquid–liquid extraction for sample preparation and LC‐MS/MS analysis in the positive ion mode using TurboIonSprayTM for analysis. d3‐AGM‐130 was used as the internal standard. A linear regression (weighted 1/concentration) was used to fit calibration curves over the concentration range of 10–2000 pg/mL for AGM‐130. There were no endogenous interference components in the blank human plasma tested. The accuracy at the lower limit of quantitation was 96.6% with a precision (coefficient of variation, CV) of 4.4%. For quality control samples at 30, 160 and 1600 pg/mL, the between run CV was ≤5.0 %. Between‐run accuracy ranged from 98.1 to 101.0%. AGM‐130 was stable in 50% acetonitrile for 168 h at 4°C and 6 h at room temperature. AGM‐130 was also stable in human plasma at room temperature for 6 h and through three freeze–thaw cycles. The variability of selected samples for the incurred sample reanalysis was ≤12.7% when compared with the original sample concentrations. This validated LC‐MS/MS method for determination of AGM‐130 was used to support a phase 0 microdose clinical trial. Copyright © 2015 John Wiley & Sons, Ltd.
Validation of a sensitive HPLC/fluorescence method for assessment of ciprofloxacin levels in plasma and prostate microdialysate samples from rats
Authors: Zimmermann Estevan Sonego , Torres Bruna Gaelzer Silva , Dalla Costa Teresa
Published: July 2015

Chronic bacterial prostatitis treatment consists of broad‐spectrum antibiotic therapy for long periods of time. Drug penetration into the prostate makes the treatment a challenged. Ciprofloxacin is one of the most prescribed drugs for this treatment. A liquid chromatography with fluorescence detection method was developed and validated for determining ciprofloxacin concentrations in two different matrices: plasma and prostate microdialysate. Ciprofloxacin was separated on a C18 column eluted with a mobile phase constituted of a mixture of 0.4% aqueous triethylamine:methanol:acetonitrile (75:15:10, v/v/v) and 0.4% aqueous triethylamine:acetonitrile (88:12, v/v) for microdialysate and plasma samples, respectively. Linearity was obtained over a concentration range of 5–1000 ng/mL (microdialysate) and 10–2000 ng/mL (plasma), with coefficients of determination ≥0.9956. Precision was determined from the analysis of six quality control samples and showed RSD values <11.1 and 7.4% for intra and inter‐assay precision, respectively. The accuracy ranged from 85.6 to 114.3%. The method was applied to a preliminary pharmacokinetic study to investigate ciprofloxacin concentrations in prostate, sampled by microdialysis, and plasma after a 7 mg/kg intravenous dose to Wistar rats. The method showed high sensitivity using only protein precipitation as plasma sample clean‐up and was successfully applied to investigate ciprofloxacin prostate penetration. Copyright © 2015 John Wiley & Sons, Ltd.
Metabolic shifts induced by human H460 cells in tumor‐bearing mice
Authors: Liu Linsheng , Wang Yaqiong , Zheng Tian , Cao Bei , Li Mengjie , Shi Jian , Aa Nan , Wang Xinwen , Zhao Chunyan , Aa Jiye , Wang Guangji
Published: July 2015

Tumor markers are most popularly used in diagnosis of various cancers clinically. However, the confounding factors of individual background diversities, such as genetics, food preferences, living styles, physical exercises, etc., greatly challenge the identification of tumor markers. Study of the metabolic impact of inoculated tumors on model animals can facilitate the identification of metabolomic markers relevant to tumor insult. In this study, serum metabolites from nude mice (n = 14) inoculated with human H460 cells (human nonsmall cell lung carcinoma) were profiled using gas chromatography time‐of‐flight mass spectrometry. The mice with inoculated tumors showed an obviously different metabolic pattern from the control; identification of the discriminatory metabolites suggested the metabolic perturbation of free fatty acids, amino acids, glycolysis and tricarboxylic acid (TCA) cycle turnover. The significantly decreased TCA intermediates, free fatty acids, 3‐hydroxybutyric acid and fluctuating amino acids (t‐test, p < 0.05) in serum of tumor‐bearing mice characterized the metabolic impact of local inoculated H460 tumor cells on the whole system. This indicates that they are candidate metabolomic markers for translational study of lung cancer, clinically. Copyright © 2015 John Wiley & Sons, Ltd.
Achieving Exceptional Photocatalytic Activity and Selectivity through a Well‐Controlled Short‐Ordered Structure: A Case Study of NaxTaOy⋅n H2O
Authors: Su Yiguo , Lang Junyu , Du Chunfang , Bian Fenggang , Wang Xiaojing
Published: July 2015

The present work reports the preparation of a short‐ordered NaxTaOy⋅n H2O catalyst that exhibits exceptional and highly efficient photocatalytic reactivity toward aerobic oxidation relative to its crystalline counterpart. Synchrotron radiation wide‐angle X‐ray scattering and transmission electron microscopy results indicated that the as‐synthesized catalyst shows short‐ordered features with well‐controlled short‐range ordering limits and defect chemistry. The short‐ordered structure of NaxTaOy⋅n H2O predicted large amounts of defective centers and high surface areas that may play critical roles in visible‐light harvesting and photocatalytic aerobic oxidation. This work may provide a novel strategy for the development of short‐ordered catalytic systems with well‐controlled defect chemistry that exhibit highly efficient photocatalytic properties.
Photoelectrocatalytic Oxidation of Methyl Orange on a TiO2 Nanotubular Anode Using a Flow Cell
Authors: José Martín de Vidales María , Mais Laura , Sáez Cristina , Cañizares Pablo , Walsh Frank C. , Rodrigo Manuel A. , Rodrigues Christiane de Arruda , Ponce de León Carlos
Published: July 2015

Methyl orange from water was removed by photocatalytic anodic oxidation using a titanium dioxide array surface. The coating was prepared by anodizing a titanium plate in an ethylene glycol electrolyte‐containing NH4F followed by heat treatment to realize a photocatalytic surface under UV light. Scanning electron microscopy imaging showed that the array coating consisted of closely spaced nanotubes perpendicular to the titanium plate. The aqueous solution of methyl orange was circulated through a rectangular channel flow cell containing the coated anode. The effects of electrolyte flow rate and applied potential on the oxidation rate and efficiency were evaluated. At higher mean linear flow rates, the efficiency of the oxidation process improved, indicating a mass transport‐controlled process. At more positive applied potentials, the TiO2 structure deteriorated resulting in a lower oxidation efficiency.
Optimization of Titania Post‐Necking Treatment of TaON Photoanodes to Enhance Water‐Oxidation Activity under Visible‐Light Irradiation
Authors: Gujral Satnam Singh , Simonov Alexandr N. , Higashi Masanobu , Abe Ryu , Spiccia Leone
Published: July 2015

A post‐necking treatment of porous screen‐printed TaON films with titania is optimized to improve their photocatalytic activity for water oxidation under visible‐light irradiation (λ>400 nm). Post‐necking was achieved by applying TiCl4 solutions in ethanol or water, or Ti(iOPr)2(acac)2 (acac=acetylacetonate) in isopropanol to the films, followed by calcination at 450 °C in air. Under voltammetric and chronoamperometric conditions in Na2SO4 (0.1 M, pH 6), a 25‐fold enhancement in oxidative photocurrent densities is achieved upon post‐necking of TaON by using ethanolic TiCl4, whereas aqueous TiCl4 and Ti(iOPr)2(acac)2 precursors afforded improvements of eight‐ and sixfold, respectively. SEM and electrochemical impedance spectroscopy studies confirm that post‐necking improves the interconnectivity of the particles and facilitates charge transfer within the photoanode and at the electrode–electrolyte interface. The highest improvement in activity was achieved by using ethanolic TiCl4 to deposit 10–20 wt % TiO2 on the TaON films, whereas higher loadings deteriorated the performance.
Shape‐Controlled Growth of Carbon Nanostructures: Yield and Mechanism
Authors: Ma Yao , Sun Xiao , Yang Nianjun , Xia Junhai , Zhang Lei , Jiang Xin
Published: July 2015

Carbon nanostructures with precisely controlled shapes are difficult materials to synthesize. A facet‐selective‐catalytic process was thus proposed to synthesize polymer‐linked carbon nanostructures with different shapes, covering straight carbon nanofiber, carbon nano Y‐junction, carbon nano‐hexapus, and carbon nano‐octopus. A thermal chemical vapor deposition process was applied to grow these multi‐branched carbon nanostructures at temperatures lower than 350 °C. Cu nanoparticles were utilized as the catalyst and acetylene as the reaction gas. The growth of those multi‐branched nanostructures was realized through the selective growth of polymer‐like sheets on certain indexed facets of Cu catalyst. The vapor–facet–solid (VFS) mechanism, a new growth mode, has been proposed to interpret such a growth in the steps of formation, diffusion, and coupling of carbon‐containing oligomers, as well as their final precipitation to form nanostructures on the selective Cu facets.
Interpreted Recognition Process: A Highly Sensitive and Selective Luminescence Chemosensor
Authors: Zhang Huabin , Hu Ping , Zhang Qikai , Huang Mingdong , Lu Can‐Zhong , Malgras Victor , Yamauchi Yusuke , Zhang Jian , Du Shao‐Wu
Published: July 2015

A luminescence‐sensing process based on coordination compound [H2N(CH3)2]3[Tb(dipic)3] was developed. It shows fast response (within 1 min), high selectivity, and is ultrasensitive to detect Fe3+ or Cr3+ in aqueous solution and living cells (KSV values are calculated to be 3.6×104 L mol−1 for Fe3+ and 1.9×104 L mol−1 for Cr3+). The whole recognition process has been witnessed through electrospray ionization mass spectrometry (ESI‐MS) analysis, and the ligand‐transfer‐induced luminescence‐quenching mechanism is interpreted. This work contributes to extend the potential applications of lanthanide coordination compounds (LnCCs) in the fields of biological and environmental technologies.
Single‐Site Zeolite‐Anchored Organoiridium Carbonyl Complexes: Characterization of Structure and Reactivity by Spectroscopy and Computational Chemistry
Authors: Martinez‐Macias Claudia , Chen Mingyang , Dixon David A. , Gates Bruce C.
Published: July 2015

A family of HY zeolite‐supported cationic organoiridium carbonyl complexes was formed by reaction of Ir(CO)2(acac) (acac=acetylacetonate) to form supported Ir(CO)2 complexes, which were treated at 298 K and 1 atm with flowing gas‐phase reactants, including C2H4, H2, 12CO, 13CO, and D2O. Mass spectrometry was used to identify effluent gases, and infrared and X‐ray absorption spectroscopies were used to characterize the supported species, with the results bolstered by DFT calculations. Because the support is crystalline and presents a nearly uniform array of bonding sites for the iridium species, these were characterized by a high degree of uniformity, which allowed a precise determination of the species involved in the replacement, for example, of one CO ligand of each Ir(CO)2 complex with ethylene. The supported species include the following: Ir(CO)2, Ir(CO)(C2H4)2, Ir(CO)(C2H4), Ir(CO)(C2H5), and (tentatively) Ir(CO)(H). The data determine a reaction network involving all of these species.
Concise Total Synthesis of Ivorenolide B
Authors: Ungeheuer Felix , Fürstner Alois
Published: July 2015

An expeditious route to the potential immunosuppressive lead compound ivorenolide B (1) is described, which relies on the formation of the distinctive 1,3‐diyne subunit embedded into the 17‐membered framework of this target by ring‐closing alkyne metathesis (RCAM). This key transformation was accomplished with the aid of the molybdenum alkylidyne complex 7, which turned out to be compatible with the acid sensitive propargylic alcohol substituents as well as the terminal alkyne unit present in the cyclization precursor. As the presence of such functionality had been detrimental for alkyne metathesis until very recently, this example illustrates the excellent application profile of this new catalyst as well as the rapidly increasing scope of the transformation. Its structural outreach can be further increased by subjecting cyclo‐1,3‐diynes to appropriate post‐metathetic transformations, most notably with the help of alkynophilic gold or palladium catalysts. This aspect is illustrated by the conversion of the model compound 4 into various cyclophane products.
Efficient Synthesis of Differentiated syn‐1,2‐Diol Derivatives by Asymmetric Transfer Hydrogenation–Dynamic Kinetic Resolution of α‐Alkoxy‐Substituted β‐Ketoesters
Authors: Monnereau Laure , Cartigny Damien , Scalone Michelangelo , Ayad Tahar , Ratovelomanana‐Vidal Virginie
Published: July 2015

Asymmetric transfer hydrogenation was applied to a wide range of racemic aryl α‐alkoxy‐β‐ketoesters in the presence of well‐defined, commercially available, chiral catalyst RuII–(N‐p‐toluenesulfonyl‐1,2‐diphenylethylenediamine) and a 5:2 mixture of formic acid and triethylamine as the hydrogen source. Under these conditions, dynamic kinetic resolution was efficiently promoted to provide the corresponding syn α‐alkoxy‐β‐hydroxyesters derived from substituted aromatic and heteroaromatic aldehydes with a high level of diastereoselectivity (diastereomeric ratio (d.r.)>99:1) and an almost perfect enantioselectivity (enantiomeric excess (ee)>99 %). Additionally, after extensive screening of the reaction conditions, the use of RuII‐ and RhIII‐tethered precatalysts extended this process to more‐challenging substrates that bore alkenyl‐, alkynyl‐, and alkyl substituents to provide the corresponding syn α‐alkoxy‐β‐hydroxyesters with excellent enantiocontrol (up to 99 % ee) and good to perfect diastereocontrol (d.r.>99:1). Lastly, the synthetic utility of the present protocol was demonstrated by application to the asymmetric synthesis of chiral ester ethyl (2S)‐2‐ethoxy‐3‐(4‐hydroxyphenyl)‐propanoate, which is an important pharmacophore in a number of peroxisome proliferator‐activated receptor α/γ dual agonist advanced drug candidates used for the treatment of type‐II diabetes.
Chiral Memory in Silylium Ions
Authors: Ducos P. , Liautard V. , Robert F. , Landais Y.
Published: July 2015

The configurational stability of the chiral silicon center in Lewis base‐stabilized silyliums has been studied. Complete retention of configuration at silicon is observed at low temperature in silylium ions stabilized by lone‐pair interactions. In contrast, loss of chiral memory is observed with systems involving π‐interactions. Epimerization of the silicon center was observed by simply allowing equilibration of the diastereomeric silyliums at RT or by adding a catalytic amount of a chelating solvent. Conditions for the transfer of axial chirality to Si‐centered chirality were shown to rely on the strength of the Lewis base‐silylium ion interaction.
Oil‐CO2 minimum miscible pressure (MMP) determination using a stimulated smart approach
Authors: Zargar Ghassem , Bagheripour Parisa , Asoodeh Mojtaba , Gholami Amin
Published: July 2015

Multi‐contact miscible displacement of reservoir petroleum by injection of the relatively inexpensive carbon dioxide (CO2) gas represents one of the most efficient currently available techniques of enhanced oil recovery. Experimental determination of optimal injection pressure, known as minimum miscible pressure (MMP), is very costly, laborious, and time‐intensive. Therefore, the quest for a quick, cost‐effective, and accurate way of determining MMP is inevitable. In this study an improved approach was followed to predict oil‐CO2 MMP. First, input/output data are transformed to a higher correlated data space using an alternative condition expectation (ACE) algorithm to reduce complexity of the problem for a generalized regression neural network (GRNN). Then, transformed data are introduced to the GRNN to construct a model for estimation of MMP. Eventually, a hybrid genetic algorithm‐pattern search technique is employed for optimizing the GRNN and producing more accurate estimations. This model was constructed using worldwide experimental data from open literature. The performance of the constructed model was assessed by introducing experimental data from Iran Oils as test data. A comparison between the current study and previous models, including outstanding correlations and intelligent systems, demonstrated the superiority of the proposed model.
Solvent extraction of phenol from aqueous solution with benzyl 2‐ethylhexyl sulfoxide as a novel extractant
Authors: Wang Shixiong , Shi Deqiang , Yang Ruisi , Xu Yan , Guo Hong , Yang Xiangjun
Published: July 2015

In this paper, we synthesized a novel structure of sulfoxide, benzyl 2‐ethylhexyl sulfoxide (BSO), and evaluated its performance for extracting phenol. The influences of several variables on phenol extraction were investigated, including equilibrium time, pH value, temperature, and salts in the aqueous phase. It was found the BSO dissolved in kerosene was an effective extractant for the recovery of phenol from an aqueous solution at pH = 2. The transfer mechanism of phenol into the organic phase was proved to be the solvation reaction by BSO through hydrogen bonds as a phenol: BSO 1:1 complex. The temperature variation tests showed that the extraction process is exothermic, and phenol extraction efficiency decreased with increased reaction temperature. Phenol could be efficiently stripped from the loaded organic phase with a sodium hydroxide solution. The results obtained establish that the BSO/kerosene system has potential for practical applications in the recovery of phenol from aqueous solutions.
Prospects of β‐Secretase Inhibitors for the Treatment of Alzheimer’s Disease
Authors: Ghosh Arun K. , Tang Jordan
Published: July 2015

β‐Secretase continues to be an attractive drug discovery target for the therapeutic intervention of Alzheimer’s disease (AD). This enzyme plays a critical role in the production of neurotoxic β‐amyloid (Aβ) peptides in the brain. Over the years, extensive research efforts have led to the development of many promising classes of inhibitors against this protease. Many small‐molecule, peptidomimetic, and nonpeptide β‐secretase inhibitors have now overcome the key challenging development hurdles such as selectivity and brain penetration. A number of inhibitors have also shown further promise in reducing brain Aβ and rescuing cognitive decline in animal models. Recently, several β‐secretase inhibitors have entered into preclinical and phase I studies, and at least one of these inhibitors has advanced to phase II/III human trials. The outlook on β‐secretase inhibitor drugs for the treatment of AD patients is discussed herein.
Implementation and Characterization of Flow Injection in Dissolution Dynamic Nuclear Polarization NMR Spectroscopy
Authors: Chen Hsueh‐Ying , Hilty Christian
Published: July 2015

The use of dissolution dynamic nuclear polarization (D‐DNP) offers substantially increased signals in liquid‐state NMR spectroscopy. A challenge in realizing this potential lies in the transfer of the hyperpolarized sample to the NMR detector without loss of hyperpolarization. Here, the use of a flow injection method using high‐pressure liquid leads to improved performance compared to the more common gas‐driven injection, by suppressing residual fluid motions during the NMR experiment while still achieving a short injection time. Apparent diffusion coefficients are determined from pulsed field gradient echo measurements, and are shown to fall below 1.5 times the value of a static sample within 0.8 s. Due to the single‐scan nature of D‐DNP, pulsed field gradients are often the only choice for coherence selection or encoding, but their application requires stationary fluid. Sample delivery driven by a high‐pressure liquid will improve the applicability of these types of D‐DNP advanced experiments.
Carbon‐Based Materials for Lithium‐Ion Batteries, Electrochemical Capacitors, and Their Hybrid Devices
Authors: Yao Fei , Pham Duy Tho , Lee Young Hee
Published: July 2015

A rapidly developing market for portable electronic devices and hybrid electrical vehicles requires an urgent supply of mature energy‐storage systems. As a result, lithium‐ion batteries and electrochemical capacitors have lately attracted broad attention. Nevertheless, it is well known that both devices have their own drawbacks. With the fast development of nanoscience and nanotechnology, various structures and materials have been proposed to overcome the deficiencies of both devices to improve their electrochemical performance further. In this Review, electrochemical storage mechanisms based on carbon materials for both lithium‐ion batteries and electrochemical capacitors are introduced. Non‐faradic processes (electric double‐layer capacitance) and faradic reactions (pseudocapacitance and intercalation) are generally explained. Electrochemical performance based on different types of electrolytes is briefly reviewed. Furthermore, impedance behavior based on Nyquist plots is discussed. We demonstrate the influence of cell conductivity, electrode/electrolyte interface, and ion diffusion on impedance performance. We illustrate that relaxation time, which is closely related to ion diffusion, can be extracted from Nyquist plots and compared between lithium‐ion batteries and electrochemical capacitors. Finally, recent progress in the design of anodes for lithium‐ion batteries, electrochemical capacitors, and their hybrid devices based on carbonaceous materials are reviewed. Challenges and future perspectives are further discussed.
Measuring disease levels in myeloma using flow cytometry in combination with other laboratory techniques: Lessons from the past 20 years at the Leeds Haematological Malignancy Diagnostic Service
Authors: Rawstron Andy C. , de Tute Ruth M. , Haughton J. , Owen Roger G.
Published: July 2015

People with myeloma who obtain a good response to treatment have a better survival if sensitive molecular or flow‐cytometric techniques show no detectable minimal residual disease (MRD). The application of MRD techniques to clinical trials is now considered to be increasingly important because treatment approaches are sufficiently effective that using survival outcomes is slowing down the identification of the best new treatments. The articles in this issue consider the laboratory requirements for harmonization of MRD analysis by flow cytometry but there are practical considerations that are also important in implementing a myeloma MRD assay in the cytometry laboratory. In particular, it is important to consider when to request, and how best to utilize, a bone marrow aspirate sample because the procedure is invasive and the cells obtained are valuable for a number of different investigations. This brief article considers some experience obtained over two decades of implementing a service for MRD detection, initially as a scientific bolt‐on to clinical trials through to a routine clinical diagnostic assay. © 2015 International Clinical Cytometry Society