bluuebunny/crossref_metadata_2025 huggingface dataset:
The intelligent anatomy spotter: A new approach to incorporate higher levels of Bloom's taxonomy
Authors: Choudhury Bipasha , Gouldsborough Ingrid , Shaw Frances L.
Published: December 2015

The spotter test is an assessment that has been used widely to test practical knowledge of anatomy. Traditional spotter formats often focus solely on knowledge recall, in addition to being an onerous marking burden on staff where consistency in marking free text responses can be questioned. First‐year optometry students at the University of Manchester study the functional anatomy of the eye in the first semester of their first year. Included in the assessment of this unit is a spotter examination worth 45% of the total unit mark. Due to the factors listed above, a new spotter format was designed. Students had to answer three questions per specimen where the answers to the questions were the labeled structures themselves (A, B, C, or D). They had to work out the answer to the question and then work out which of the labeled structures was the correct structure, negating the “cueing effect” of standard multiple choice questions. Examination results were analyzed over a six‐year period (control groups 2008/2009, 2009/2010, 2010/2011; treatment groups 2011/2012, 2012/2013, 2013/2014). There were no significant differences between marks obtained for the new spotter format when compared with the traditional format. The new format spotter tested comprehension rather than just knowledge, and facilitated marking because subjectiveness was erased, and less time was spent determining whether an answer was correct or not. Anat Sci Educ 9: 440–445. © 2015 American Association of Anatomists.
Development of realistic shortest path algorithm considering lane changes
Authors: Yang Inchul , Kim Hyung Jin , Jeon Woo Hoon , Kim Hyunmyung
Published: December 2015

Lane changes occur as many times as turning movements are needed while following a designated path. The cost of a route with many lane changes is likely to be more expensive than that with less lane changes, and unrealistic paths with impractical lane changes should be avoided for drivers' safety. In this regard, a new algorithm is developed in this study to find the realistic shortest path considering lane changing. The proposed algorithm is a modified link‐labeling Dijkstra algorithm considering the effective lane‐changing time that is a parametric function of the prevailing travel speed and traffic density. The parameters were estimated using microscopic traffic simulation data, and the numerical test demonstrated the performance of the proposed algorithm. It was found that the magnitude of the effect of the effective lane‐changing time on determining the realistic shortest path is nontrivial, and the proposed algorithm has capability to exclude links successfully where the required lane changes are practically impossible. Copyright © 2015 John Wiley & Sons, Ltd.
Student voice and the community forum: finding ways of ‘being heard’ at an alternative school for disenfranchised young people
Authors: Baroutsis Aspa , Mills Martin , McGregor Glenda , te Riele Kitty , Hayes Debra
Published: December 2015

Opportunities for students to speak and to be heard are important elements of democratic schooling processes but research into student voice has shown that a culture of silence is a more common feature of schooling. Efforts to re‐engage young people in learning often recognise the importance of schooling processes that provide them with opportunities to participate meaningfully in schooling dialogues. This paper describes attempts to provide such opportunities for young people in an alternative school, who had been marginalised in mainstream schooling. Research was conducted over a period of 18 months, utilising a range of data collection methods, including interviews, observations, photography and the collection of artefacts, such as school documents. Drawing particularly on data related to a daily community forum, the paper explores how this routine afforded opportunities for student voice. The three‐part structure of the forum produced a range of effects, including: a discussion of issues related to local and wider community news as well as college announcements; a check‐in where each member of the community voiced their readiness (or otherwise) for the day's learning; and a sign‐up process that incorporated informed decision making about the day's learning sessions. It is argued that the intentions that underpin the community forum are important and relevant in all forms of schooling, not just alternative programmes, but these intentions can produce unintended effects.
Rethinking assessment in a digital age: opportunities, challenges and risks
Authors: Timmis Sue , Broadfoot Patricia , Sutherland Rosamund , Oldfield Alison
Published: December 2015

While it is frequently argued that assessment sits at the heart of the learning process, in practice assessment often remains narrowly focused on qualifications and reporting achievements, driven by institutional and societal aspirations and tensions such as accountability and economic well being. Yet, the need for assessment to account for the knowledge, skills, dispositions and attitudes necessary to equip young people for a changing and increasingly digital world is also increasingly acknowledged. Based on our recent research review, this article critically examines the role of technology enhanced assessment (or TEA). We argue that while technology offers many potentially creative opportunities for innovation and for rethinking assessment purposes, there are also numerous risks and challenges. In particular we highlight ethical concerns over social exclusion and new forms of digital dividedness and the increasing risks associated with big data and the rise of learning analytics. Finally, we note that much research and innovation happens in silos, where policy, research and practice on assessment, technology enhanced assessment and ethical and political concerns are not linked up. We conclude that there needs to be a much more wide‐ranging, critical and nuanced discussion in educational and policy circles so that debates about the potential of technology can be linked to improving assessment in the light of the range of social and political challenges that such progress presents. We end with some critical questions for policy, practice and research communities, which we offer as a starting point for future thinking and ways forward.
(RS)‐Propranolol: enantioseparation by HPLC using newly synthesized (S)‐levofloxacin‐based reagent, absolute configuration of diastereomers and recovery of native enantiomers by detagging
Authors: Alwera Shiv , Bhushan Ravi
Published: December 2015

Diastereomers of (RS)‐propranolol were synthesized using (S)‐levofloxacin‐based new chiral derivatizing reagents (CDRs). Levofloxacin was chosen as the pure (S)‐enantiomer for its high molar absorptivity (εo ∼ 24000) and availability at a low price. Its ‐COOH group had N‐hydroxysuccinimide and N‐hydroxybenzotriazole, which acted as good leaving groups during nucleophilic substitution by the amino group of the racemic (RS)‐propranolol; the CDRs were characterized by UV, IR, 1H‐NMR, high resolution mass spectrometry (HRMS) and carbon, hydrogen, nitrogen, and sulphur fundamental elemental components analyser (CHNS). Diastereomers were separated quantitatively using open column chromatography; absolute configuration of the diastereomers was established and the reagent moiety was detagged under microwave‐assisted acidic conditions. (S)‐ and (R)‐propranolol as pure enantiomers and (S)‐levofloxacin were separated, isolated and characterized. Optimized lowest‐energy structures of the diastereomers were developed using Gaussian 09 Rev. A.02 program and hybrid density functional B3LYP with 6‐31G* basis set (based on density functional theory) for explanation of elution order and configuration. In addition, RP HPLC conditions for separation of diastereomers were optimized with respect to pH, concentration of buffer, flow rate of mobile phase and nature of organic modifier. HPLC separation method was validated as per International Conference on Harmonization guidelines. With the systematic application of various analytical techniques, absolute configuration of the diastereomers (and the native enantiomers) of (RS)‐propranolol was established. Copyright © 2016 John Wiley & Sons, Ltd.
Novel rapid liquid chromatography tandem masspectrometry method for vemurafenib and metabolites in human plasma, including metabolite concentrations at steady state
Authors: Vikingsson Svante , Strömqvist Malin , Svedberg Anna , Hansson Johan , Höiom Veronica , Gréen Henrik
Published: December 2015

A novel, rapid and sensitive liquid chromatography tandem–mass spectrometry method for quantification of vemurafenib in human plasma, that also for the first time allows for metabolite semi‐quantification, was developed and validated to support clinical trials and therapeutic drug monitoring. Vemurafenib was analysed by precipitation with methanol followed by a 1.9 min isocratic liquid chromatography tandem masspectrometry analysis using an Acquity BEH C18 column with methanol and formic acid using isotope labelled internal standards. Analytes were detected in multireaction monitoring mode on a Xevo TQ. Semi‐quantification of vemurafenib metabolites was performed using the same analytical system and sample preparation with gradient elution. The vemurafenib method was successfully validated in the range 0.5–100 μg/mL according to international guidelines. The metabolite method was partially validated owing to the lack of commercially available reference materials. For the first time concentration levels at steady state for melanoma patients treated with vemurafenib is presented. The low abundance of vemurafenib metabolites suggests that they lack clinical significance. Copyright © 2016 John Wiley & Sons, Ltd.
A highly efficient and sensitive LC‐MS/MS method for the determination of afatinib in human plasma: application to a metabolic stability study
Authors: Kadi Adnan A. , Abdelhameed Ali S. , Darwish Hany W. , Attwa Mohamed W. , Al‐Shakliah Nasser S.
Published: December 2015

Afatinib (AFT) is a new tyrosine kinase inhibitor approved for the treatment of nonsmall cell lung cancer. In the present study, a simple, specific, rapid and sensitive liquid chromatography tandem mass‐spectrometric method for the quantification of AFT in human plasma, was developed and validated. Chromatographic separation of the analytes was accomplished on a reversed‐phase Luna®‐PFP 100 Å column (50 × 2.0 mm; 3.0 μm) maintained at ambient temperature. Isocratic elution was carried out using acetonitrile–water (40:60, v/v) containing 10 mm ammonium formate buffer (pH 4.5) adjusted with formic acid at a flow rate of 0.4 mL min−1. The analytes were monitored by electrospray ionization in positive ion multiple reaction monitoring mode. The method yields a linear calibration plot (r2 = 0.9997) from a quantification range of 0.5–500 ng mL−1 with the lower limit of quantification and lower limit of detection of 1.29 and 0.42 ng mL−1, respectively. The intra‐ and inter‐day precision and accuracy were estimated and found to be in the ranges of 1.53–4.11% for precision and −2.80–0.38% for accuracy. Finally, quantification of afatinib in a metabolic stability study in rat liver microsomes was achieved through the proposed method. Copyright © 2016 John Wiley & Sons, Ltd.
Pre‐concentration of trace amount of bisphenol A in water samples by palm leaf ash and determination with high‐performance liquid chromatography
Authors: Sohrabi Razieh , Bahramifar Nader , Javadian Hamedreza , Agarwal Shilpi , Gupta Vinod Kumar
Published: December 2015

Palm leaf ash was characterized and used as low‐cost adsorbent for solid‐phase extraction and preconcentration of bisphenol A (BPA) in real water samples. Analysis of BPA was carried out using HPLC involving Eurospher 100–5‐C18 (25 cm × 4.5 mm, particle size 5 μm) column and water–acetonitrile (40:60, v/v) as mobile phase. The adsorption was achieved quantitatively at a pH of 6 with elution by 3 mL acetonitrile. The limits of detection and enrichment factor were 0.02 μg L−1 and 333, respectively. Under optimum conditions the relative standard deviation (RSD) was 2% (n = 10). Comparison of qualification criteria of presented preconcentration procedure with other research indicated that palm leaf ash adsorbent was better than many of the adsorbents in terms of cost and reusability. Also, the limit of detection, precision and enrichment factor were comparable and even better than the previously reported methods. Finally, the efficiency of method was computed by determination of trace amounts of BPA in sea, river, mineral and tap waters with recoveries of 93.3–105.5% and RSDs of 0.61–3.12%.. Briefly, the developed solid‐phase extraction and Preparative layer chromatography (PLC) methods may be used for bisphenol A monitoring in any environmental water sample. Copyright © 2016 John Wiley & Sons, Ltd.
Development and validation of SPMMTE HPLC method for analysis of profens from human plasma
Authors: Hussain Afzal , Al‐Ajmi Mohamed F. , Amir Samira , Ali Imran
Published: December 2015

A fast, selective and reproducible solid‐phase membrane microtip extraction (SPMMTE) HPLC method has been developed and validated for the analyses of ibuprofen, ketoprofen, and flurbiprofen from human plasma. The analysis was carried out on a C18 (150 × 4.6 mm; 5 μm) column. The mobile phase used was water–acetonitrile (55:45, v/v) adjusted to pH 3.0 using trifluoroacetic acid, at a flow rate 0.5 mL/min with a detection wavelength of 225 nm. The values for the capacity factors for the profen samples ranged from 0.47 to 1.50. The values for the selectivity factor (α) for ketoprofen–flurbiprofen, flurbiprofen–ibuprofen and ibuprofen–ketoprofen combinations from human plasma samples were 1.99, 1.00 and 2.10, respectively. The resolution factors (Rs) for ketoprofen–flurbiprofen, flurbiprofen–ibuprofen and ibuprofen–ketoprofen from plasma samples were 3.00, 1.50 and 4.10, respectively. The percentage recoveries of ibuprofen, ketoprofen, and flurbiprofen from human plasma were 75–85%. All of the profens were separated within 7.0 min, indicating a relatively fast method. During the development of the SPMMTE procedure the parameters of pH, contact time, desorption and types of solvents were optimized. The final method was also found to be efficient, effective and inexpensive. Copyright © 2016 John Wiley & Sons, Ltd.
The Casein Kinase 2‐Dependent Phosphorylation of NS5A Domain 3 from Hepatitis C Virus Followed by Time‐Resolved NMR Spectroscopy
Authors: Secci Erica , Luchinat Enrico , Banci Lucia
Published: December 2015

Hepatitis C virus (HCV) chronically affects millions of individuals worldwide. The HCV nonstructural protein 5A (NS5A) plays a critical role in the viral assembly pathway. Domain 3 (D3) of NS5A is an unstructured polypeptide responsible for the interaction with the core particle assembly structure. Casein kinase 2 (CK2) phosphorylates NS5A‐D3 at multiple sites that have mostly been predicted and only observed indirectly. In order to identify the CK2‐dependent phosphorylation sites, we monitored the reaction between NS5A‐D3 and CK2 in vitro by time‐resolved NMR. We unambiguously identified four serine residues as substrates of CK2. The apparent rate constant for each site was determined from the reaction curves. Ser408 was quickly phosphorylated, whereas the three other serine residues reacted more slowly. These results provide a starting point from which to elucidate the role of phosphorylation in the mechanisms of viral assembly—and in the modulation of the viral activity—at the molecular level.
A New Way Forward in Cancer Drug Discovery: Inhibiting the SWI/SNF Chromatin Remodelling Complex
Authors: Zinzalla Giovanna
Published: December 2015

Mutations in subunits of the SWI/SNF chromatin remodelling complex are found in 20 % of human cancers. At face value, this would appear to indicate that this multiprotein complex is a potent tumour suppressor. However, it has recently emerged that some mutations in the SWI/SNF complex can have a gain‐of‐function effect and that in other tumours, such as pancreatic cancer, leukaemia, and breast cancer, the wild‐type complex is used to drive cancer. Thus, paradoxically, this “tumour suppressor” has become an attractive target for developing anticancer agents. The SWI/SNF complex makes several protein–protein interactions both within the complex and with a wide range of transcription factors, and targeting these protein–protein interactions is emerging as the best approach to modulating the activity of the complex selectively.
Light‐Activated Reversible Imine Isomerization: Towards a Photochromic Protein Switch
Authors: Berbasova Tetyana , Santos Elizabeth M. , Nosrati Meisam , Vasileiou Chrysoula , Geiger James H. , Borhan Babak
Published: December 2015

Mutants of cellular retinoic acid‐binding protein II (CRABPII), engineered to bind all‐trans‐retinal as an iminium species, demonstrate photochromism upon irradiation with light at different wavelengths. UV light irradiation populates the cis‐imine geometry, which has a high pKa, leading to protonation of the imine and subsequent “turn‐on” of color. Yellow light irradiation yields the trans‐imine isomer, which has a depressed pKa, leading to loss of color because the imine is not protonated. The protein‐bound retinylidene chromophore undergoes photoinduced reversible interconversion between the colored and uncolored species, with excellent fatigue resistance.
Rationale and indications for coronary chronic total occlusion interventions
Authors: Vo M. N. , Rinfret S.
Published: December 2015

Chronic total occlusions (CTOs) are commonly found in patients with coronary artery disease and are considered the “final frontier” of coronary intervention. Despite growing interest in percutaneous coronary intervention (PCI) of CTOs along with advances in techniques and equipment, attempt rates remain low. This is most likely due to the fact that CTO PCI remains technically challenging and requires higher resource utilization. Furthermore, there remains controversy regarding the actual clinical benefit of successful CTO PCI. However, there have been a growing number of studies reporting short‐ and long‐term outcomes of CTO revascularization. We therefore sought to review the evidence and potential clinical benefits of successful CTO PCI.

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Hybrid approach to treatment of atrial fibrillation
Authors: Ong C. S. , Kofidis T.
Published: December 2015

Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice. For years, there has been much interest and much is written with regard to the integrated or hybrid multidisciplinary approach toward cardiovascular care. The hybrid approach has been established in many centers, mostly with respect to ischemic heart disease. However, it is only a new and upcoming trend toward the use of a hybrid approach to treating cardiac arrhythmias. This hybrid approach to treating AF, while not the prevalent practice, is supported by medical literature. This review article examines the hybrid approach to treatment of AF, its benefits, disadvantages, and safety, as well as the long‐term results, based on current available literature. The hybrid approach to treatment of AF, combining surgical epicardial, and catheter endocardial ablation, showed a higher success rate compared to either technique alone. The increasing cooperation and professional intimacy between cardiologists and cardiothoracic surgeons are likely to continue and the hybrid approach, with its benefits while bearing in mind its limitations, may become the gold standard for treatment of drug‐resistant AF for the coming decade and beyond.

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Convenient Access to Fluorescent Probes by Chemoselective Acylation of Hydrazinopeptides: Application to the Synthesis of the First Far‐Red Ligand for Apelin Receptor Imaging
Authors: Margathe Jean‐François , Iturrioz Xavier , Regenass Pierre , Karpenko Iuliia A. , Humbert Nicolas , de Rocquigny Hugues , Hibert Marcel , Llorens‐Cortes Catherine , Bonnet Dominique
Published: December 2015

Herein, we develop a convenient method to facilitate the solution‐phase fluorescent labelling of peptides based on the chemoselective acylation of α‐hydrazinopeptides. This approach combines the advantages of using commercially available amine‐reactive dyes and very mild conditions, which are fully compatible with the chemical sensitivity of the dyes. The usefulness of this approach was demonstrated by the labelling of apelin‐13 peptide. Various fluorescent probes were readily synthesized, enabling the rapid optimization of their affinities for the apelin receptor. Thus, the first far‐red fluorescent ligand with sub‐nanomolar affinity for the apelin receptor was characterized and shown to track the receptor efficiently in living cells by fluorescence confocal microscopy.
Homoleptic Two‐Coordinate Silylamido Complexes of Chromium(I), Manganese(I), and Cobalt(I)
Authors: Werncke C. Gunnar , Suturina Elizaveta , Bunting Philip C. , Vendier Laure , Long Jeffrey R. , Atanasov Mihail , Neese Frank , Sabo‐Etienne Sylviane , Bontemps Sébastien
Published: December 2015

Anionic two‐coordinate complexes of first‐row transition‐metal(I) centres are rare molecules that are expected to reveal new magnetic properties and reactivity. Recently, we demonstrated that a N(SiMe3)2− ligand set, which is unable to prevent dimerisation or extraneous ligand coordination at the +2 oxidation state of iron, was nonetheless able to stabilise anionic two‐coordinate FeI complexes even in the presence of a Lewis base. We now report analogous CrI and CoI complexes with exclusively this amido ligand and the isolation of a [MnI{N(SiMe3)2}2]22− dimer that features a Mn−Mn bond. Additionally, by increasing the steric hindrance of the ligand set, the two‐coordinate complex [MnI{N(Dipp)(SiMe3)}2]− was isolated (Dipp=2,6‐iPr2‐C6H3). Characterisation of these compounds by using X‐ray crystallography, NMR spectroscopy, and magnetic susceptibility measurements is provided along with ligand‐field analysis based on CASSCF/NEVPT2 ab initio calculations.
Controlled Multi‐functionalization Facilitates Targeted Delivery of Nanoparticles to Cancer Cells
Authors: Hudlikar Manish S. , Li Xiuru , Gagarinov Ivan A. , Kolishetti Nagesh , Wolfert Margreet A. , Boons Geert‐Jan
Published: December 2015

A major objective of nanomedicine is to combine in a controlled manner multiple functional entities into a single nanoscale device to target particles with great spatial precision, thereby increasing the selectivity and potency of therapeutic drugs. A multifunctional nanoparticle is described for controlled conjugation of a cytotoxic drug, a cancer cell targeting ligand, and an imaging moiety. The approach is based on the chemical synthesis of polyethylene glycol that at one end is modified by a thioctic acid for controlled attachment to a gold core. The other end of the PEG polymers is modified by a hydrazine, amine, or dibenzocyclooctynol moiety for conjugation with functional entities having a ketone, activated ester, or azide moiety, respectively. The conjugation approach allowed the controlled attachment of doxorubicin through an acid‐labile hydrazone linkage, an Alexa Fluor dye through an amide bond, and a glycan‐based ligand for the cell surface receptor CD22 of B‐cells using strain promoted azide‐alkyne cycloaddition. The incorporation of the ligand for CD22 led to rapid entry of the nanoparticle by receptor‐mediated endocytosis. Covalent attachment of doxorubicin via hydrazone linkage caused pH‐responsive intracellular release of doxorubicin and significantly enhanced the cytotoxicity of nanoparticles. A remarkable 60‐fold enhancement in cytotoxicity of CD22 (+) lymphoma cells was observed compared to non‐ targeted nanoparticles.
Bis‐Sulfonyl O,C,O‐Chelated Metallylenes (Ge, Sn) as Adjustable Ligands for Iron and Tungsten Complexes
Authors: Deak Noémi , Petrar Petronela M. , Mallet‐Ladeira Sonia , Silaghi‐Dumitrescu Luminiţa , Nemeş Gabriela , Madec David
Published: December 2015

The synthesis and characterization of an E2CE2 bis‐sulfonyl aryl pincer ligand and its efficiency for the stabilization of compounds containing low‐valent Group 14 elements (Ge and Sn) are reported. Complexation reaction of these metallylenes with iron or tungsten complexes resulted in the modulation of the oxygen atoms of the sulfonyl groups implicated in the stabilization of the Group 14 elements, demonstrating the original adjustable character of the bis‐sulfonyl O2S‐C‐SO2 aryl pincer.
Cascade Mn‐Mediated γ‐Alkylation/oxa‐Michael Addition of Enones with 1,3‐Dicarbonyls
Authors: Liu Xiaoguang , Chen Xiaohong , Mohr Justin T.
Published: December 2015

A radical‐based strategy for regioselective γ‐C−C bond formation/oxa‐conjugate addition, forming the tetrahydrobenzofuran core common to many bioactive natural products is described. The technique utilizes readily available enone derivatives and 1,3‐dicarbonyl compounds as coupling partners in an oxidative formal [3+2] cycloaddition mediated by MnIII. The transformation delivers polycyclic products in good yields and proceeds with complete regiocontrol and excellent stereoselectivity. Sterically encumbered substrates are notably well‐tolerated and bond formation occurs readily to form neopentyl and all‐carbon quaternary centers in good yields. Several stereo‐ and chemoselective transformations of the products are described.
Solubility Switching of Metallophthalocyanines and Their Larger Derivatives upon Encapsulation
Authors: Kondo Kei , Akita Munetaka , Yoshizawa Michito
Published: December 2015

Metallophthalocyanines (MPcs) are very useful pigments but scarcely soluble without appropriate functional groups in common solvents. Herein, we report that bent polyaromatic amphiphiles act as excellent solubilizing reagents for nonfunctionalized MPcs and larger MPc derivatives (e.g., CuPc, perhalogenated CuPcs, Cu‐naphthalocyanine, CuPc polymers, and double‐decker MPcs) in neutral water upon encapsulation. The resultant MPc nanocomposites display high stability towards heat and pH change. More importantly, the encapsulated MPcs can be released by simple protocols under mild conditions both into a bulk solvent and onto glass or polymer plates.
Energy balance in viscous liquid containing a bubble: Rise due to buoyancy
Authors: Zawala Jan
Published: December 2015

The total energy balance of a system consisting of a bubble (radius 0.74 mm) freely rising in viscous liquid under the action of buoyancy was considered. Values of bubble acceleration, local and terminal velocities, and shape deformations calculated by numerically solving the Navier‐Stokes equation are compared with experimentally determined values. Additionally, the energies of the system associated with bubble motion (kinetic, potential, and rate of viscous energy dissipation), obtained from simulations, are given. On the basis of energy balances obtained for the system, two independent relations describing the motion of a bubble (Lagrange and Joseph equations) were used to show that, for steady‐state conditions, the constant (terminal) velocity of the bubble is a result of balance between buoyancy force and the drag originating from energy dissipation due to fluid viscosity. According to the calculations performed, the discrepancy between the expected and actual results of the Lagrange and Joseph equations for the system considered was ∼1 %. The estimated added mass coefficient was in close agreement with expected theoretical value for deformed spheres, and increased with decreasing tube radius.
Energy and paper recycling: Modelling the time and energy requirements for low consistency batch repulping
Authors: Saville Frank , Martinez Mark , Olson James
Published: December 2015

An analytical model for low‐consistency repulping linking pulp material properties, consistency, temperature, and rotor and vat geometry is provided, which allows for accurate prediction of the time and energy required for repulping in both a 0.25 m3 laboratory‐scale repulper and a 15 m3 industrial‐scale repulper. The model assumes that all deflaking work is done by the repulper rotor in the rotor‐swept volume by turbulence generated by the rotor and that no deflaking occurs in the rest of the vat. Rotor shaft power is split linearly between the breakup of waste paper and dissipation by turbulence. Comparing the model predictions and experimental data for different pulp types, vat fill levels, and pulp suspension consistencies yields a correlation of R2 = 0.99 between all experimental results and the model predictions given the condition of fully turbulent (Reynolds‐independent) repulper rotor operation. The efficiency of the laboratory repulper is reduced from that predicted by the model for very low vat fill levels. This is due to a loss of effectiveness of the baffles at these low levels as indicated by solid body motion of the suspension and reduced rotor power number. This indicates that thorough mixing is a requirement to maximize repulping efficiency. Repulping time and energy savings can be accomplished by increasing the suspension consistency and the rotor‐swept volume/vat volume ratio by either increasing rotor size or reducing vat volume, all while ensuring complete mixing and circulation in the vat.
Development of Highly Potent GAT1 Inhibitors: Synthesis of Nipecotic Acid Derivatives by Suzuki–Miyaura Cross‐Coupling Reactions
Authors: Petrera Marilena , Wein Thomas , Allmendinger Lars , Sindelar Miriam , Pabel Jörg , Höfner Georg , Wanner Klaus T.
Published: December 2015

A new series of potent and selective mGAT1 inhibitors has been identified, featuring a nipecotic acid residue and an N‐butenyl linker with a 2‐biphenyl residue at the ω‐position. Docking, combined with MD calculations, revealed a binding mode for the new compounds similar to that of tiagabine, the only mGAT1 inhibitor currently approved as antiepileptic drug. For the synthesis, a Suzuki–Miyaura cross‐coupling reaction was used as a key step by which variously substituted biaryl subunits were assembled. Biological evaluation revealed several compounds that possess binding affinities and inhibitory potencies toward mGAT1, together with subtype selectivities against mGAT2–mGAT4 that were similar to or even higher than those for tiagabine. A derivative carrying the 2′,4′‐dichloro‐2‐biphenyl moiety attached to N‐but‐3‐enylnipecotic acid at the terminal position of the linker chain was found to be the most potent binder, with the racemic form of the compound displaying a binding affinity of 8.05±0.13 (pKi), while the R enantiomer exhibited an affinity value of 8.33±0.06 (pKi).
Using “residual” FNA rinse and body fluid specimens for next‐generation sequencing: An institutional experience
Authors: Wei Shuanzeng , Lieberman David , Morrissette Jennifer J. D. , Baloch Zubair W. , Roth David B. , McGrath Cindy
Published: December 2015

BACKGROUND

Tissue specimens are typically considered optimal for molecular testing; however, in the current era of personalized medicine, cytopathology specimens are increasingly recognized as potential sources for molecular testing. This is often accomplished by using cell block specimens and/or fine‐needle aspiration (FNA) smear preparations. In this study, the authors investigated the feasibility, performance, and quality of “residual” FNA rinse and body effusion fluids used for next‐generation sequencing (NGS).

METHODS

Sequence data were generated from 17 malignancies in 16 patients from 13 FNA (10 lymph nodes, 1 lung, and 2 bone lesions) and 4 effusion (3 pleural and 1 pericardial) specimens. Malignancies included carcinomas (lung, breast, ovarian, and unknown primary), melanoma, and myeloma. Paired NGS testing was performed in 7 patients who had surgical biopsy or cell block specimens available. Routinely processed residual FNA rinse material and body fluids were used for DNA extraction and NGS (targeted gene panel).

RESULTS

NGS was successfully performed on all 17 specimens. A significant amount of DNA was obtained from the residual FNA rinse (176.3 ng/μL) compared with the paired cell block slides (10.6 ng/μL). Two of the 10 lung adenocarcinomas (20%) demonstrated epidermal growth factor receptor (EGFR) mutations, including 1 leucine‐to‐arginine substitution at codon 858 (L858R) in exon 21 and 1 codon 2235_2249 deletion (resulting in an in‐frame deletion of 5 amino acids from position 746 to 750 [glutamic acid, leucine, arginine, glutamic acid, and alanine]; E746_A750del) in exon 19. Three KRAS [Kirsten rat sarcoma viral oncogene homolog] mutations, 1 BRAF (v‐Raf murine sarcoma viral oncogene homolog B1) mutation, and 1 NRAS (neuroblastoma RAS viral oncogene homolog) mutation were identified in the remaining lung adenocarcinomas. Patients who underwent paired testing demonstrated 100% concordant mutations.

CONCLUSIONS

Targeted NGS can be performed on residual FNA rinse and body fluid specimens. This approach is particularly important when a paucicellular cell block or biopsy specimen is encountered. Cancer Cytopathol 2016;124:324–29. © 2015 American Cancer Society.
The coefficient of variation as a measure of spectrophotometric repeatability
Authors: Centore Paul
Published: December 2015

The mean color difference from the mean (MCDM) is a standard measure of spectrophotometric repeatability. This article proposes a supplementary measure: the coefficient of variation (CoV), which is the ratio of the standard deviation of the measured reflectances to their mean. The CoV is calculated from the same repeated sample measurements as the MCDM. Unlike the MCDM, the CoV depends only on physical quantities, and not on perceptual quantities; furthermore, a CoV is defined for each wavelength. This article analyzes data from six different spectrophotometer–sample combinations. An important empirical result is that the CoV is nearly constant across wavelengths, except when the reflectance at a particular wavelength is less than about 5%, in which case, measurement variability is markedly greater. Because the MCDM tends to lose this fact through averaging, the CoV is recommended as an adjunct to the MCDM for spectrophotometer analysis and development. The CoV analysis also provides evidence that samples’ surface geometry is a major factor in measurement variability. © 2015 Wiley Periodicals, Inc. Col Res Appl, 41, 571–579, 2016
Aggregation Behavior of Several Ionic Liquids in Molecular Solvents of Low Polarity—Indication of a Bimodal Distribution
Authors: Cade Elise A. , Petenuci João , Hoffmann Markus M.
Published: December 2015

The structure and dynamics of ion pairing and aggregation is studied by concentration‐ and temperature‐dependent measurements of 1H and 19F self‐diffusion coefficients, viscosity, and conductivity for the following five solutions: 1‐alkyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)amide ([Cnmim][NTf2], n=2, 4, 6) in dichloromethane (CH2Cl2), and [C6mim][NTf2] in tetrahydrofuran (THF) and chlorobenzene (C6H5Cl). The temperature dependence of these properties at constant IL concentrations follows the Arrhenius law for all five solutions. The IL‐concentration dependence of the respective activation energies obtained from the Arrhenius analysis is nonlinear in the case of conductivity, but indicates linear relationships for viscosity and self‐diffusion. All five solutions studied display average solute radius maxima as plotted against IL concentration. The maximum average solute radii follow an order of solvents of CHCl3>C6H5Cl>CH2Cl2≈THF, which corresponds to the order of increasing solvent dielectric constant. The observed trends in the physical properties of these solutions indicate the development of a bimodal distribution of solute size with increasing IL concentration. Specifically, the presence of aggregates is supported by the analysis of the conductivity data and the observation of the same self‐diffusion coefficients for the cation and anion. The concurrent presence of freely dissolved ions is supported by the obtained average solute radii that do not exceed the radii of the corresponding ion pairs.
Catalysts Encapsulated in Molecular Machines
Authors: Pan Tiezheng , Liu Junqiu
Published: December 2015

Smart catalysts offer the control of chemical processes and sequences of transformations, and catalysts with unique catalytic behavior can afford chiral products or promote successive polymerization. To meet advanced demands, the key to constructing smart catalysts is to incorporate traditional catalytic functional groups with trigger‐induced factors. Molecular machines with dynamic properties and particular topological structures have typical stimulus‐responsive features. In recent years, scientists have made efforts to utilize molecular machines (molecular switches, rotaxanes, motors, etc.) as scaffolds to develop smart catalysts. This Minireview focuses on the achievements of developing catalysts encapsulated in molecular machines and their remarkable specialties. This strategy is believed to provide more potential applications in switchable reactions, asymmetric synthesis, and processive catalysis.
Direct Conversion of Cellulose into Ethyl Lactate in Supercritical Ethanol–Water Solutions
Authors: Yang Lisha , Yang Xiaokun , Tian Elli , Lin Hongfei
Published: December 2015

Biomass‐derived ethyl lactate is a green solvent with a growing market as the replacement for petroleum‐derived toxic organic solvents. Here we report, for the first time, the production of ethyl lactate directly from cellulose with the mesoporous Zr‐SBA‐15 silicate catalyst in a supercritical mixture of ethanol and water. The relatively strong Lewis and weak Brønsted acid sites on the catalyst, as well as the surface hydrophobicity, were beneficial to the reaction and led to synergy during consecutive reactions, such as depolymerization, retro‐aldol condensation, and esterification. Under the optimum reaction conditions, ∼33 % yield of ethyl lactate was produced from cellulose with the Zr‐SBA‐15 catalyst at 260 °C in supercritical 95:5 (w/w) ethanol/water.
Metal‐Free Chemoselective Oxidative Dehomologation or Direct Oxidation of Alcohols: Implication for Biomass Conversion
Authors: Kim Sun Min , Shin Hun Yi , Kim Dong Wan , Yang Jung Woon
Published: December 2015

A transition metal‐free, chemoselective reaction was performed using the sodium tert‐butoxide–oxygen (NaOtBu–O2) system, resulting in either oxidative dehomologation or direct oxidation of alcohols. In particular, the newly developed protocol may be used to predict the major product formed, which depends on alkyl chain length of the alcohols and reaction conditions. The rational mechanism of this transformation was also demonstrated by performing an 18O isotopic labelling experiment. This protocol presents a straightforward method for biomass conversion of a lignin model compound to phenol and benzoic acid.
Throughput maximization in electromagnetic energy harvesting cognitive radio sensor networks
Authors: Ergul Ozgur , Alagoz Fatih , Akan Ozgur B.
Published: December 2015

In the near future, billions of wireless devices are expected to be operational. To enable the required machine to machine communications, two major problems must be addressed. How to obtain the required spectrum efficiency, and how to deliver the required power to these devices. The most promising answers to these questions are cognitive radio and energy harvesting, respectively. Energy harvesting enables deployment of sensors and devices without having to worry about their battery lifetime. Cognitive radio increases the utilization of spectrum by accessing unused spectrum dynamically. Energy harvesting from electromagnetic waves is suitable for these low power, low cost devices used in machine to machine communications because only minimal additional hardware is required for such energy harvesting. With this idea as the starting point, we first present an analysis on how much throughput can be obtained from a cognitive, electromagnetic energy harvesting wireless network. Then, we show when and how cooperation among network nodes may increase performance. We believe that our results will provide insight for the development of future cooperative cognitive energy harvesting networks. Copyright © 2015 John Wiley & Sons, Ltd.
Processes of change in Acceptance and Commitment Therapy and Applied Relaxation for long‐standing pain
Authors: Kemani M.K. , Hesser H. , Olsson G.L. , Lekander M. , Wicksell R.K.
Published: December 2015

Background

The utility of cognitive behavioural (CB) interventions for chronic pain has been supported in numerous studies. This includes Acceptance and Commitment Therapy (ACT), which has gained increased empirical support. Previous research suggests that improvements in pain catastrophizing and psychological inflexibility are related to improvements in treatment outcome in this type of treatment. Although a few studies have evaluated processes of change in CB‐interventions, there is a particular need for mediation analyses that use multiple assessments to model change in mediators and outcome over time, and that incorporate the specified timeline between mediator and outcome in the data analytic model.

Methods

This study used session‐to‐session assessments to evaluate if psychological inflexibility, catastrophizing, and pain intensity mediated the effects of treatment on pain interference. Analyses were based on data from a previously conducted randomized controlled trial (n = 60) evaluating the efficacy of ACT and Applied Relaxation (AR). A moderated mediation model based on linear mixed models was used to analyse the data.

Results

Neither catastrophizing nor pain intensity mediated changes in pain interference for any of the treatments. In contrast, psychological inflexibility mediated effects on outcome in ACT but not in AR.

Conclusions

Results add to previous findings illustrating the role of psychological inflexibility as a mediator in ACT.
The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain
Authors: van der Wal S.E.I. , van den Heuvel S.A.S. , Radema S.A. , van Berkum B.F.M. , Vaneker M. , Steegers M.A.H. , Scheffer G.J. , Vissers K.C.P.
Published: December 2015

Introduction

The neuroinflammatory response plays a key role in several pain syndromes. Intravenous (iv) lidocaine is beneficial in acute and chronic pain. This review delineates the current literature concerning in vitro mechanisms and in vivo efficacy of iv lidocaine on the neuroinflammatory response in acute and chronic pain.

Databases and data treatment

We searched PUBMED and the Cochrane Library for in vitro and in vivo studies from July 1975 to August 2014. In vitro articles providing an explanation for the mechanisms of action of lidocaine on the neuroinflammatory response in pain were included. Animal or clinical studies were included concerning iv lidocaine for acute or chronic pain or during inflammation.

Results

Eighty‐eight articles regarding iv lidocaine were included: 36 in vitro studies evaluating the effect on ion channels and receptors; 31 animal studies concerning acute and chronic pain and inflammatory models; 21 clinical studies concerning acute and chronic pain.

Low‐dose lidocaine inhibits in vitro voltage‐gated sodium channels, the glycinergic system, some potassium channels and Gαq‐coupled protein receptors. Higher lidocaine concentrations block potassium and calcium channels, and NMDA receptors. Animal studies demonstrate lidocaine to have analgesic effects in acute and neuropathic pain syndromes and anti‐inflammatory effects early in the inflammatory response. Clinical studies demonstrate lidocaine to have advantage in abdominal surgery and in some neuropathic pain syndromes.

Conclusions

Intravenous lidocaine has analgesic, anti‐inflammatory and antihyperalgesic properties mediated by an inhibitory effect on ion channels and receptors. It attenuates the neuroinflammatory response in perioperative pain and chronic neuropathic pain.
Dynamic weight bearing as a non‐reflexive method for the measurement of abdominal pain in mice
Authors: Laux‐Biehlmann A. , Boyken J. , Dahllöf H. , Schmidt N. , Zollner T.M. , Nagel J.
Published: December 2015

Background

Chronic pelvic pain (CPP) is a high burden for patients and society. It affects 15–24% of women in reproductive age and is an area of high unmet medical need. CPP can be caused by a wide range of visceral diseases such as abdominal infections, gastrointestinal or gynaecological diseases like endometriosis. Despite the high medical need for this condition, pharmacological approaches are hampered by the limited number of available methods for the behavioural evaluation of pain in inflammation‐driven animal models of pelvic pain.

Methods

The dynamic weight bearing (DWB) system was used for the evaluation of spontaneous behaviour changes in the zymosan‐induced peritonitis mouse model. Inflammatory mediator levels were evaluated in peritoneal lavage and their correlation with the behavioural endpoints was assessed. We evaluated the effect on behavioural endpoints of the selective cyclooxygenase‐2 (COX‐2) inhibitor celecoxib and the Nav1.8 blocker A‐803467.

Results

The presence of a relief posture, characterized by a significantly increased weight distribution towards the front paws, was observed following intraperitoneal injection of zymosan. A positive correlation was detected between PGE2 levels in the peritoneal lavage and DWB endpoints. In addition, zymosan‐induced weight bearing changes were reverted by celecoxib and A‐803467.

Conclusions

This study described for the first time the use of DWB as a non‐subjective and non‐reflexive method for the evaluation of inflammatory‐driven abdominal pain in a mouse model.
Experimental pain impairs recognition memory irrespective of pain predictability
Authors: Forkmann K. , Schmidt K. , Schultz H. , Sommer T. , Bingel U.
Published: December 2015

Background

Pain is hardwired to signal threat and tissue damage and therefore automatically attracts attention to initiate withdrawal or defensive behaviour. This well‐known interruptive function of pain interferes with cognitive functioning and is modulated by bottom‐up and top‐down variables. Here, we applied predictable or unpredictable painful heat stimuli simultaneously to the presentation of neutral images to investigate (I) whether the predictability of pain modulated its effect on the encoding of images (episodic memory) and (II) whether subjects remember that certain images have been previously presented with pain (source memory).

Methods

Twenty‐four healthy subjects performed a categorization task in which 80 images had to be categorized into living or non‐living objects. We compared the processing and encoding of these images during cued and non‐cued pain trials as well as cued and non‐cued pain‐free trials. Effects on recognition performance and source memory for pain were immediately tested using a surprise recognition task.

Results

Painful thermal stimulation impaired recognition accuracy (d′, recollection, familiarity). This negative effect of pain was positively correlated with the individual expectation of pain interference and the attentional avoidance of pain‐related words. However, the interruptive effect of pain was not modulated by the predictability of pain. Source memory for painful stimulation was at chance level, indicating that subjects did not explicitly remember that images had been paired with pain.

Conclusions

Targeting negative expectations and a maladaptive attentional bias for pain‐related material might help reducing frequently reported pain‐induced cognitive impairments.