bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel Highly Energetic Pyrazoles: N‐Trinitromethyl‐Substituted Nitropyrazoles
Authors: Dalinger Igor L. , Vatsadze Irina A. , Shkineva Tatyana K. , Kormanov Alexandr V. , Struchkova Marina I. , Suponitsky Kyrill Yu. , Bragin Anatoly A. , Monogarov Konstantin A. , Sinditskii Valery P. , Sheremetev Aleksei B.
Published: June 2015

A new family of energetic compounds, nitropyrazoles bearing a trinitromethyl moiety at the nitrogen atom of the heterocycle, was designed. The desirable high‐energy dense oxidizers 3,4‐dinitro‐ and 3,5‐dinitro‐1‐(trinitromethyl)pyrazoles were synthesized in good yields by destructive nitration of the corresponding 1‐acetonylpyrazoles. All of the prepared compounds were fully characterized by multinuclear NMR and IR spectroscopy, as well as by elemental analysis. Single‐crystal X‐ray diffraction studies show remarkably high density. Impact sensitivity tests and thermal stability measurements were also performed. All of the pyrazoles possess positive calculated heats of formation and exhibit promising energetic performance that is the range of 1,3,5‐trinitroperhydro‐1,3,5‐triazine and pentaerythritol tetranitrate. The new pyrazoles exhibit positive oxygen balance and are promising candidates for new environmentally benign energetic materials.
Relationship between cold winters over Northern Asia and the subsequent hot summers over mid‐lower reaches of the Yangtze River valley under global warming
Authors: Qiao Shaobo , Gong Zhiqiang , Feng Guolin , Qian Zhonghua
Published: June 2015

Under global warming, cold winters over Northern Asia are highly correlated with the subsequent hot summers over middle and lower reaches of the Yangtze River valley (MLYRV). This high correlation may result from an oceanic bridge's effect in the Western Pacific. The mechanism may be described as follows: the atmospheric circulation anomalies of cold winters corresponds with a simultaneous warmer Western Pacific warm pool (WPWP) by decreasing surface latent heat fluxes. The warmer sea surface temperature (SST) can persist and move eastward gradually to the subsequent summer through the oceanic processes, and thus in turn affect the hot days (HDs) over MLYRV.
Optimization of coordinated signal settings for hook‐turn intersections
Authors: Bie Yiming , Liu Zhiyuan , Lu Linjun
Published: June 2015

Hook turn (HT) is a unique traffic regulation rule for right‐turning vehicles at intersections (in the system where driving is on the left), which was proposed in Melbourne to improve the safety level and operational efficiency of intersections. However, existing coordination plans for HT intersections are fixed and determined empirically, which restricts the further improvements of the efficiency. In this paper, mathematical models are developed for the calculation of the average vehicle delay, with consideration of the spillback phenomenon of HT vehicles in waiting areas. The platoon dispersion model is used to describe the traffic movements between coordinated intersections. With the aim of minimizing average delay of all vehicles, a mixed nonlinear integer model is developed for the optimal coordination plan, which is solved by a genetic algorithm due to the complexity of the model. Finally, a numerical example is built based on three HT intersections in downtown Melbourne, to verify the proposed methodology. Based on a comparison with the current signal plan, the optimal signal plan can significantly reduce the average delay as well as the number of spillbacks, in both the peak hour and off‐peak hour cases. Copyright © 2015 John Wiley & Sons, Ltd.
Decision Pattern Analysis as a General Framework for Studying Individual Differences in Decision Making
Authors: Jackson Simon A. , Kleitman Sabina , Stankov Lazar , Howie Pauline
Published: June 2015

This paper investigated decision pattern analysis (DPA) as a general and standard framework for studying individuals' consistent decision making behavior within and between contexts. DPA classifies decisions on the basis of judgement accuracy and the goal orientation of the decided‐upon action. Over repeated decisions, patterns of individuals' decision behavior are described by five variables: competence, optimality, recklessness, hesitancy and decisiveness. A fictitious medical decision making test and three standard cognitive ability tests (extended with confidence ratings and a ‘submit answer for marking’ decision) were used to investigate the psychometric properties of these DPA variables. Internal consistency of the decision patterns ranged from good to excellent. Convergent validity was assessed via cognitive abilities, metacognitive confidence and a control criterion imposed on confidence that determines the decision to be made: the point of sufficient certainty. Personality variables were included to assess discriminant validity. As hypothesised, cognitive abilities showed positive correlations with competence and optimality. High confidence, low points of sufficient certainty and a greater discrepancy between them were associated with higher decisiveness and recklessness, and lower hesitancy. Personality measures showed mixed and generally weak correlations with the DPA variables. These convergent and discriminant results also held after controlling for all variables in regression. The results provide preliminary psychometric support for DPA as a general framework of behavioral decision making. DPA has the potential to be exploited in many contexts for uses that, to date, have been unachievable in a psychometrically valid manner. Copyright © 2015 John Wiley & Sons, Ltd.
Fermentation broth components influence droplet coalescence and hinder advanced biofuel recovery during fermentation
Authors: Heeres Arjan S. , Schroën Karin , Heijnen Joseph J. , van der Wielen Luuk A. M. , Cuellar Maria C.
Published: June 2015

Developments in synthetic biology enabled the microbial production of long chain hydrocarbons, which can be used as advanced biofuels in aviation or transportation. Currently, these fuels are not economically competitive due to their production costs. The current process offers room for improvement: by utilizing lignocellulosic feedstock, increasing microbial yields, and using cheaper process technology. Gravity separation is an example of the latter, for which droplet growth by coalescence is crucial. The aim of this study was to study the effect of fermentation broth components on droplet coalescence. Droplet coalescence was measured using two setups: a microfluidic chip and regular laboratory scale stirred vessel (2 L). Some fermentation broth components had a large impact on droplet coalescence. Especially components present in hydrolysed cellulosic biomass and mannoproteins from the yeast cell wall retard coalescence. To achieve a technically feasible gravity separation that can be integrated with the fermentation, the negative effects of these components on coalescence should be minimized. This could be achieved by redesign of the fermentation medium or adjusting the fermentation conditions, aiming to minimize the release of surface active components by the microorganisms. This way, another step can be made towards economically feasible advanced biofuel production.
Engineering surface hydrophobicity improves activity of Bacillus thermocatenulatus lipase 2 enzyme
Authors: Tang Ting , Yuan Chongli , Hwang Hyun‐Tae , Zhao Xuebing , Ramkrishna Doraiswami , Liu Dehua , Varma Arvind
Published: June 2015

Bacillus thermocatenulatus lipase 2 (BTL2) is a promising industrial enzyme used in biodiesel production. Although BTL2 has high thermostability and good resistance to organic solvents, the activity of BTL2 is suboptimal for industrial processes. To improve BTL2 activity, we engineered BTL2 lipase by modulating hydrophobicity of its lid domain. Through site‐directed mutagenesis, we constructed three mutants, namely Y225F+S232A, S232A+T236V and Q185L, to cover all uncharged hydrophilic amino acids within the lid domain. Activities of these mutants were characterized. Our findings suggest that one mutant (Y225F+S232A) showed ∼35% activity increase in catalyzing heterogeneous hydrolytic reactions relevant for industrial applications. A mathematical framework was established to account for different molecular events that contribute to the observed apparent catalytic activities. Increases in hydrophobicity of lid domains were associated with increased interfacial adsorption of lipases and lower molecular enzymatic activities. The measured apparent activities of lipases include contributions from both events. Lid hydrophobicity can thus result in different changes in lipase activities depending on the mutation site. Our work demonstrates the feasibility of increasing BTL2 activity by modulating the hydrophobicity of lid domains and provides some guidelines for further improving BTL2 activity.
Method for generation of peptide‐specific igy antibodies directed to Staphylococcus aureus extracellular fibrinogen binding protein epitope
Authors: Walczak Maciej , Grzywa Renata , Łupicka‐Słowik Agnieszka , Skoreński Marcin , Bobrek Kamila , Nowak Daria , Boivin Stephane , Brown Eric L. , Oleksyszyn Józef , Sieńczyk Marcin
Published: June 2015

The IgY antibodies offer an attractive alternative to mammalian IgGs in research, diagnosis and medicine. The isolation of immunoglobulin Y from the egg yolks is efficient and economical, causing minimal suffering to animals. Here we present the methodology for the production of IgY antibodies specific to Staphylococcus aureus fibrinogen binding protein (Efb) and its peptidyl epitope (spanning residues 127–140). The Efb is an extracellular, adhesion protein which binds both human fibrinogen and complement C3 protein thus contributing to the high infectious potential of this pathogen. The selected epitope of Efb protein is responsible for the interaction with C3. The immunochemical characterization of both anti‐Efb and epitope‐specific IgY antibodies revealed their similar avidity, titer, and reactivity profile, although some differences in the hen's immune response to administered antigens is discussed. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 552–559, 2015.
Case-mix analysis and variation in rates of non-surgical treatment of older women with operable breast cancer
Authors: Morgan J , Richards P , Ward S , Francis M , Lawrence G , Collins K , Reed M , Wyld L
Published: June 2015

Background

Non-surgical management of older women with oestrogen receptor (ER)-positive operable breast cancer is common in the UK, with up to 40 per cent of women aged over 70 years receiving primary endocrine therapy. Although this may be appropriate for frailer patients, for some it may result in treatment failure, contributing to the poor outcomes seen in this age group. Wide variation in the rates of non-operative management of breast cancer in older women exists across the UK. Case mix may explain some of this variation in practice.

Methods

Data from two UK regional cancer registries were analysed to determine whether variation in treatment observed between 2002 and 2010 at hospital and clinician level persisted after adjustment for case mix. Expected case mix-adjusted surgery rates were derived by logistic regression using the variables age, proxy Charlson co-morbidity score, deprivation quintile, method of cancer detection, tumour size, stage, grade and node status.

Results

Data on 17 129 women aged 70 years or more with ER-positive operable breast cancer were analysed. There was considerable variation in rates of surgery at both hospital and clinician level. Despite adjusting for case mix, this variation persisted at hospital level, although not at clinician level.

Conclusion

This study demonstrates variation in selection criteria for older women for operative treatment of early breast cancer, indicating that some older women may be undertreated or overtreated, and may partly explain the inferior disease outcomes in this age group. It emphasizes the urgent need for evidence-based guidelines for treatment selection criteria in older women with breast cancer.
Simultaneous quantification of atenolol and chlorthalidone in human plasma by ultra‐performance liquid chromatography–tandem mass spectrometry
Authors: Shah Jaivik V. , Patel Daxesh P. , Shah Priyanka A. , Sanyal Mallika , Shrivastav Pranav S.
Published: June 2015

A simple, sensitive and reproducible ultra‐performance liquid chromatography–tandem mass spectrometry method has been developed for the simultaneous determination of atenolol, a β‐adrenergic receptor‐blocker and chlorthalidone, a monosulfonamyl diuretic in human plasma, using atenolol‐d7 and chlorthalidone‐d4 as the internal standards (ISs). Following solid‐phase extraction on Phenomenex Strata‐X cartridges using 100 μL human plasma sample, the analytes and ISs were separated on an Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm) column using a mobile phase consisting of 0.1% formic acid–acetonitrile (25:75, v/v). A tandem mass spectrometer equipped with electrospray ionization was used as a detector in the positive ionization mode for both analytes. The linear concentration range was established as 0.50–500 ng/mL for atenolol and 0.25–150 ng/mL for chlorthalidone. Extraction recoveries were within 95–103% and ion suppression/enhancement, expressed as IS‐normalized matrix factors, ranged from 0.95 to 1.06 for both the analytes. Intra‐batch and inter‐batch precision (CV) and accuracy values were 2.37–5.91 and 96.1–103.2%, respectively. Stability of analytes in plasma was evaluated under different conditions, such as bench‐top, freeze–thaw, dry and wet extract and long‐term. The developed method was superior to the existing methods for the simultaneous determination of atenolol and chlorthalidone in human plasma with respect to the sensitivity, chromatographic analysis time and plasma volume for processing. Further, it was successfully applied to support a bioequivalence study of 50 mg atenolol + 12.5 mg chlorthalidone in 28 healthy Indian subjects. Copyright © 2015 John Wiley & Sons, Ltd.
Foldamers as Anticancer Therapeutics: Targeting Protein–Protein Interactions and the Cell Membrane
Authors: Fahs Sara , Patil‐Sen Yogita , Snape Timothy J.
Published: June 2015

Targeting important protein–protein interactions involved in carcinogenesis or targeting the cell membrane of a cancer cell directly are just two of the ways in which foldamers (oligomeric molecules that fold into distinct shapes in solution) hold considerable potential in the treatment of cancer. From mimicking the local topography of the helical compound of interest by using covalently constrained foldamers to mimicking the topography of the natural helix such that the positions of key functional motifs are in an identical spatial orientation to match those presented by the original α‐helix, synthetic foldamers have been used to mimic the natural foldamers that interact with proteins or the cell membrane. These targeted approaches have become established over a timeframe of more than a decade, and they continue to be included in the assortment of cancer targets being studied and the arsenal of chemotherapy compounds in development. These approaches are reviewed herein.
Renal denervation for the treatment of hypertension: Making a new start, getting it right
Authors: Weber Michael A. , Kirtane Ajay , Mauri Laura , Townsend Raymond R. , Kandzari David E. , Leon Martin B.
Published: June 2015

The renal nerves contribute to hypertension through effects in the kidney that enhance sodium retention and renin secretion, and by effects in the central nervous system that increase systemic sympathetic activity. Therefore, targeting the renal nerves provides a logical basis for treating hypertension. Several trials of renal denervation––achieved by applying radiofrequency energy through catheters placed in the renal arteries–– have been completed. Clinical results have been inconsistent, however, partly because of factors related to the ablation technique and partly because these studies have been performed in patients with the inadequately defined clinical condition of “treatment‐resistant hypertension.” This statement now explains our conclusion that future studies of renal denervation should be guided by the established randomized, controlled clinical trial designs used for studying antihypertensive drugs and other treatments for hypertension. © 2015 Wiley Periodicals, Inc.
Prenatal diagnosis of X‐linked adrenoleukodystrophy associated with isolated pericardial effusion
Authors: Traficante Giovanna , Biagiotti Roberto , Andreucci Elena , Di Tommaso Mariarosaria , Provenzano Aldesia , Cariati Ettore , Giglio Sabrina
Published: June 2015

Key Clinical Message

This is the first reported case of fetal pericardial effusion in association with X‐linked adrenoleukodystrophy and hypocortisolism from a nonautoimmune cause. Our hypothesis is that in experienced hands and after accurate genetic counseling, isolated pericardial effusion can constitute an indication for a severe metabolic disease.
A case of delayed hemothorax with an inferior phrenic artery injury detected and treated endovascularly
Authors: Yamanashi Keiji , Nakao Shota , Idoguchi Koji , Matsuoka Tetsuya
Published: June 2015

Key Clinical Message

We report the rare case of delayed hemothorax (DHX) with an inferior phrenic artery (IPA) injury due to blunt thoracic trauma. Our case suggests that DHX almost always occurs early after injury, and endovascular treatment is an effective procedure for traumatic hemothorax including DHX.
The Carbocation: A Forgotten Lewis Acid Catalyst
Authors: Naidu Veluru Ramesh , Ni Shengjun , Franzén Johan
Published: June 2015

A Lewis acid that has received negligible attention as a catalyst is the carbocation. The carbocation is isoelectronic to boron and owes its Lewis acidity to a low‐lying empty pC orbital. In terms of reactivity and stability carbocations are very versatile Lewis acids, from the extremely unstable methylium cation to the water‐stable tris(N,N‐dimethylaniline) methylium ion (crystal violet). Although the Lewis acid properties of carbocations have been extensively studied since the discovery of the tropolium ion more than 130 years ago there is only a handful examples on the application of carbocations as Lewis acid catalysts. Herein, the research on triarylmethylium (trityl)‐cation catalysis is summarized. In light of the reports the trityl ion emerges as a highly efficient and highly versatile Lewis acid catalyst capable of catalyzing different classes of reactions often with high selectivity and low catalyst loadings (for some reactions down to ppm levels).
Effect of Cobalt Particle Size on Acetone Steam Reforming
Authors: Sun Junming , Zhang He , Yu Ning , Davidson Stephen , Wang Yong
Published: June 2015

Carbon‐supported cobalt nanoparticles with different particle sizes were synthesized and characterized by complementary characterization techniques such as X‐ray diffraction, N2 sorption, acetone temperature‐programmed desorption, transmission electron microscopy, and CO chemisorption. Using acetone steam reforming reaction as a probe reaction, we revealed a volcano‐shape curve of the intrinsic activity (turnover frequency of acetone) and the CO2 selectivity as a function of the cobalt particle size with the highest activity and selectivity observed at a particle size of approximately 12.8 nm. Our results indicate that the overall performance of acetone steam reforming is related to a combination of particle‐size‐dependent acetone decomposition, water dissociation, and the oxidation state of the cobalt nanoparticles.
Heterogeneous Catalyst of Mixed K Compounds/Ca‐Al‐Graphite Oxide for the Transesterification of Soybean Oil to Biodiesel
Authors: Sun Chuanjia , Qiu Fengxian , Yang Dongya , Ye Bin
Published: June 2015

A novel heterogeneous solid base catalyst was prepared by loading of Ca‐Al‐graphite oxide with mixed potassium salts and applied in the transesterification of soybean oil with methanol to produce biodiesel. The catalysts were characterized by Hammett indicators, X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X‐ray spectrometry, and transmission electron microscopy. The effects of the methanol‐to‐oil molar ratio, catalyst amount, reaction temperature, stirring rate, and reaction time were investigated to optimize the transesterification reaction conditions. Moreover, the prepared catalyst retains its activity after being used for four cycles. In particular, the solid base catalyst can be effectively and easily separated from the reaction system, which may provide significant benefits for the development of an environmentally benign and continuous process for preparing biodiesel.
Design and Preparation of a Lithium‐rich Layered Oxide Cathode with a Mg‐Concentration‐Gradient Shell for Improved Rate Capability
Authors: Yu Ruizhi , Wang Gang , Wang Xianyou , Wang Di , Wen Weicheng , Shu Hongbo , Yang Xiukang
Published: June 2015

A spherical core–shell lithium‐rich layered oxide material Li1.5Mn0.75Ni0.20Mg0.05O2+δ (CSLM) with a Mg‐concentration‐gradient shell is rationally designed and synthesized through a co‐precipitation method. The physicochemical and electrochemical properties of the CSLM cathode material are systematically investigated, and compared with the conventional Li1.5Mn0.75Ni0.25O2+δ (CL) cathode material. The electrochemical tests demonstrate that the CSLM cathode material exhibits better cycle stability and rate capability. The Li/CSLM cell delivers an excellent cycling performance with a capacity retention of 96.4 % after 100 cycles at 0.5 C. Moreover, at a high rate of 10 C, the Li/CSLM cell can still exhibit a high discharge capacity of 141.1 mAh g−1, as compared with 58.9 mAh g−1 for the Li/CL cell. Thus, lithium‐rich layered oxide material Li1.5Mn0.75Ni0.20Mg0.05O2+δ with a Mg‐concentration‐gradient shell is a promising cathode material for advanced lithium‐ion batteries.
The Structure and Conformation of (CH3)3CSNO
Authors: Canneva Antonela , Erben Mauricio F. , Romano Rosana M. , Vishnevskiy Yury V. , Reuter Christian G. , Mitzel Norbert W. , Della Védova Carlos O.
Published: June 2015

The gas‐phase molecular structure of (CH3)3CSNO was investigated by using electron diffraction, allowing the first experimental geometrical parameters for an S‐nitrosothiol species to be elucidated. Depending on the orientation of the SNO group, two conformers (anti and syn) are identified in the vapor of (CH3)3CSNO at room temperature, the syn conformer being less abundant. The conformational landscape is further scrutinized by using vibrational spectroscopy techniques, including gas‐phase and matrix‐isolation IR spectroscopy, resulting in a contribution of ca. 80:20 for the anti:syn abundance ratio, in good agreement with the computed value at the MP2(full)/cc‐pVTZ level of approximation. The UV/Vis and resonance Raman spectra also show the occurrence of the conformational equilibrium in the liquid phase, with a moderate post‐resonance Raman signature associated with the 350 nm electronic absorption.
A Tetraferrocenyl‐Resorcinarene Cavitand as a Redox‐Switchable Host of Ammonium Salts
Authors: Ruiz‐Botella Sheila , Vidossich Pietro , Ujaque Gregori , Vicent Cristian , Peris Eduardo
Published: June 2015

Tetraannulation of a resorcinarene‐octaamino cavitand with ferrocenecarboxaldehyde allows the preparation of a tetrabenzimidazole‐resorcinarene cavitand with four ferrocenyl moieties directly linked to the C2 atom of the imidazole units. Oxidation of the four ferrocenyl moieties produces important structural modifications of the molecule, as indicated by DFT calculations performed for the neutral and tetraoxidized forms of the cavitand. By means of 1H NMR spectroscopic analysis, the encapsulating properties of the new tetraferrocenyl‐resorcinarene cavitand toward a series of ammonium salts were evaluated, and a clear cutoff point in binding affinity with respect to size was observed. Cyclic voltammetric studies allowed us to estimate the relative association constants for the neutral and oxidized forms of the cavitand, thus indicating that the guest was bound to the neutral (reduced) state of the cavitand and was released from the oxidized form. These redox‐addressable conformational and binding properties of the resorcinarene‐tetraferrocenyl cavitand constitute all the necessary features of a redox‐switchable molecular gripper. By means of mass‐spectrometric analysis, we could unambiguously confirm the molar stoichiometry of the host–guest complex (1:1) and assess the strong guest encapsulation, as indicated by triggering the covalent coupling between host and guest in the gas phase.
Group 2 Catalysis for the Atom‐Efficient Synthesis of Imidazolidine and Thiazolidine Derivatives
Authors: Arrowsmith Merle , Hill Michael S. , Kociok‐Köhn Gabriele
Published: June 2015

A wide variety of functionalised imidazolidine‐2‐ones and ‐thiones, 2‐imino‐imidazolidines and thiazolidine‐2‐thiones have been synthesised under very mild reaction conditions by using simple and cost‐effective alkaline earth bis(amide) precatalysts, [Ae{N(SiMe3)2}2(THF)2] (Ae=Mg, Ca, Sr). The reactions ensue with 100 % atom efficiency as one‐pot cascades from simple, commercially available terminal alkyne and heterocumulene reagents. The reactions take place through the initial assembly of propargylamidines, which are utilised in subsequent cyclisation reactions through addition of the isocyanate, isothiocyanate and, in one case, carbon disulfide reagents. This reactivity is deduced to take place through a well‐defined sequence of heterocumulene hydroacetylenation and alkyne hydroamidation steps, which are all mediated at the alkaline earth centre. The rate and regioselectivity of the cyclisation reactions are, thus, found to be heavily dependent upon the identity of the catalytic alkaline earth centre employed. Similarly, the selectivity of the reactions was observed to be profoundly affected by stereoelectronic variations in the individual substrates, albeit by a similar Group 2‐centred reaction mechanism in all cases studied.
Observation of Diastereomeric Interconversions of β‐Sulfinylsubporphyrins as Evidence for Bowl Inversion
Authors: Yoshida Kota , Osuka Atsuhiro
Published: June 2015

B‐Methoxy β‐(4‐methoxyphenylsulfinyl)subporphyrin and B‐phenyl β‐(4‐methoxyphenylsulfinyl)subporphyrin were synthesized by oxidation of the corresponding β‐sulfanylsubporphyrins with m‐chloroperbenzoic acid and were separated into diastereomers, respectively. B‐Methoxy subporphyrin diastereomers were interconverted to each other in methanol or ethanol, whereas such interconversion was not observed for B‐phenyl subporphyrin diastereomers even at high temperature. Diastereomeric interconversions of B‐methoxy subporphyrins were dramatically accelerated by addition of trifluoroacetic acid. These results suggest that the diastereomeric interconversions of B‐methoxy subporphyrins, namely, their bowl inversions, proceed via a mechanism involving protonation‐induced generation of subporphyrin borenium cations followed by nucleophilic attacks by alcohols.
Chiral Iodine‐Catalyzed Dearomatizative Spirocyclization for the Enantioselective Construction of an All‐Carbon Stereogenic Center
Authors: Zhang Dong‐Yang , Xu Lue , Wu Hua , Gong Liu‐Zhu
Published: June 2015

The first enantioselective dearomatizative spirocyclization of 1‐hydroxy‐N‐aryl‐2‐naphthamide derivatives has been accomplished by chiral organoiodine catalysis to stereoselectively create an all‐carbon stereogenic center, providing a straightforward approach to access spirooxindole derivatives in good yields and with high to excellent levels of enantioselectivity. Chiral hypervalent phenyl‐λ3‐iodanes generated in situ from the oxidation of the chiral phenyl iodine actually participate in the asymmetric oxidative dearomatizative spirocyclization reaction.
Amide as Terminal Groups: Synthesis and Properties as New Tolane‐Type Liquid Crystals
Authors: Zhang Hong , Hong Fengying , Zhu Dezhao , Xia Zhengce , Wu Hongxiang , Wang Hui , Zeng Zhuo
Published: June 2015

A series of novel tolane‐type liquid crystals with amide group as terminal group have been prepared. The terminal amide groups were modified, and the influence of these structural parameters on liquid crystal phases was investigated by polarizing optical microscope (POM) and differential scanning calorimetry (DSC). Three of these new compounds exhibit nematic phase, good thermal stabilities. In general, these liquid crystals with amide as end groups have high melting points and phase transition temperatures, which result from the hydrogen bonds. Based on theoretical calculations, these new molecules with strong electron donating amide as end group have narrower HOMO‐LUMO energy gap and higher dipole moment than tolane.
Comparison of a Homemade Bacuri Shell Activated Carbon With Carbon Nanotubes for Food Dye Removal
Authors: Saucier Caroline , Adebayo Matthew A. , Lima Eder C. , Prola Lizie D. T. , Thue Pascal S. , Umpierres Cibele S. , Puchana‐Rosero Mayerly J. , Machado Fernando M.
Published: June 2015

The shell of bacuri together with inorganic components [red mud + lime + KOH + KAl(SO4)2 + Al(OH)3] at different ratios of 1.0 (BC‐1.0), 1.5 (BC‐1.5), and 2.0 (BC‐2.0) were pyrolized at 1073 K. To complete the chemical activation process, the inorganic components were leached from the carbonaceous matrix through acidification with 6 M HCl under reflux to obtain ABC‐1.0, ABC‐1.5 and ABC‐2.0. ABC‐1.5 showed the highest adsorption capacity among these adsorbents. Fourier transform IR spectroscopy, scanning electron microscopy, N2 adsorption/desorption curves and X‐ray diffraction were used to characterize BC‐1.5 (precursor) and ABC‐1.5 (activated carbon). The analyses indicate that the majority of the inorganic compounds were leached from the carbonaceous matrix, resulting in an activated carbon with a high surface area and pore volume, suitable for dye adsorption. The sorption capacity of ABC‐1.5 was compared with multi‐walled carbon nanotubes (MWCNT) for removal of Brilliant Blue food dye (BB‐FCF) from aqueous solutions. The general order kinetic model described well the adsorption process. The maximum amounts of BB‐FCF removed at 323 K were 647.9 and 231.5 mg g−1 for ABC‐1.5 and MWCNT, respectively. In addition, ABC‐1.5 and MWCNT were applied for the treatment of two simulated effluents.
Epidermal growth factor receptor exon 20 insertions in advanced lung adenocarcinomas: Clinical outcomes and response to erlotinib
Authors: Naidoo Jarushka , Sima Camelia S. , Rodriguez Katherine , Busby Natalie , Nafa Khedoudja , Ladanyi Marc , Riely Gregory J. , Kris Mark G. , Arcila Maria E. , Yu Helena A.
Published: June 2015

BACKGROUND

Epidermal growth factor receptor (EGFR) exon 20 insertions (exon20ins) represent approximately 10% of EGFR‐mutant lung adenocarcinomas, and are associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Clinical outcomes in comparison with patients with sensitizing EGFR mutations are not well established.

METHODS

Patients with stage IV lung adenocarcinomas with EGFR exon20ins were identified through routine molecular testing. Clinicopathologic data were collected. Overall survival (OS) was measured from the diagnosis of stage IV disease, and in patients treated with EGFR TKIs, the time to progression (TTP) on erlotinib was measured.

RESULTS

One thousand eight hundred and eighty‐two patients with stage IV lung adenocarcinomas were identified: 46 patients had EGFR exon20ins (2%), and 258 patients had an EGFR exon 19 deletion (exon19del)/L858R point mutation (14%). Among 11 patients with lung adenocarcinomas with EGFR exon20ins who received erlotinib, 3 patients (27%) had a partial response (FQEA, 1; ASV, 1; and unknown variant, 1). TTP for patients with EGFR exon20ins and patients with EGFR exon19del/L858R on erlotinib were 3 and 12 months, respectively (P < .01). Responses to chemotherapy were similar for patients with lung adenocarcinomas with EGFR exon20ins and patients with lung adenocarcinomas with EGFR exon19del/L858R. Median OS from the diagnosis of stage IV disease for patients with EGFR exon20ins and patients with EGFR exon19del/L858R was 26 months (95% confidence interval, 19 months‐not reached n = 46) and 31 months (95% confidence interval, 28‐33 months; n = 258), respectively (P = .53).

CONCLUSIONS

The majority of patients with advanced lung adenocarcinomas harboring EGFR exon20ins do not respond to EGFR TKI therapy. Standard chemotherapy should be used as first‐line therapy. These patients have an OS similar to that of patients with sensitizing EGFR mutations. Individuals with certain variants such as FQEA and ASV may respond to erlotinib. Cancer 2015;121:3212–3220. © 2015 American Cancer Society.
Eudaimonic well‐being and tumor norepinephrine in patients with epithelial ovarian cancer
Authors: Davis Lauren Z. , Slavich George M. , Thaker Premal H. , Goodheart Michael J. , Bender David P. , Dahmoush Laila , Farley Donna M. , Markon Kristian E. , Penedo Frank J. , Lubaroff David M. , Cole Steve W. , Sood Anil K. , Lutgendorf Susan K.
Published: June 2015

BACKGROUND

The impact of psychological well‐being on the physiologic processes involved in cancer progression remains unclear. Prior research has implicated adrenergic signaling in tumor growth and metastasis. Given that adrenergic signaling is influenced by both positive and negative factors, the authors examined how 2 different aspects of well‐being (eudaimonic and positive affect) and psychological distress were associated with tumor norepinephrine (NE) in patients with ovarian cancer.

METHODS

A total of 365 women with suspected ovarian cancer completed psychosocial assessments before surgery and clinical information was obtained from medical records. Study inclusion was confirmed after histological diagnosis. Tumor NE was measured in frozen tissue samples using high‐performance liquid chromatography with electrochemical detection. Confirmatory factor analysis was used to model eudaimonic well‐being, positive affect, and psychological distress, and structural equation modeling was used to examine associations between these factors and tumor NE.

RESULTS

Eudaimonic well‐being, positive affect, and psychological distress, modeled as distinct but correlated constructs, best fit the data (ie, compared with unitary or 2‐factor models) (root mean square error of approximation, 0.048; comparative fit index, 0.982; and standardized root‐mean‐squared residual, 0.035). Structural equation modeling analysis that included physical well‐being, stage of disease, histology, psychological treatment history, beta‐blocker use, and caffeine use as covariates was found to have good model fit (root mean square error of approximation, 0.052; comparative fit index, 0.955; and standardized root‐mean‐squared residual, 0.036) and demonstrated that eudaimonic well‐being was related to lower tumor NE (β = ‐.24 [P = .045]). In contrast, no effects were found for positive affect or psychological distress.

CONCLUSIONS

Eudaimonic well‐being was found to be associated with lower tumor NE, independent of positive affect and psychological distress. Because adrenergic signaling is implicated in tumor progression, increasing eudaimonic well‐being may improve both psychological and physiologic resilience in patients with ovarian cancer. Cancer 2015;121:3435–43. © 2015 American Cancer Society.
Comments on the recently published “Guidelines for the cytopathologic diagnosis of epithelioid and mixed‐type malignant mesothelioma”
Authors: Hjerpe Anders , Dobra Katalin
Published: June 2015

Recently published guidelines describe how a specific diagnosis based on effusions can be obtained in most patients with malignant mesothelioma. The high positive predictive value makes biopsy sampling redundant in these patients and allows an earlier diagnosis.
Rational Design and Synthesis of a Highly Porous Copper‐Based Interpenetrated Metal–Organic Framework for High CO2 and H2 Adsorption
Authors: Bose Purnandhu , Bai Linyi , Ganguly Rakhesh , Zou Ruqiang , Zhao Yanli
Published: June 2015

Interpenetrated metal–organic frameworks (MOFs) are often observed to show lower porosity than their non‐interpenetrating analogues. It would be highly desirable if the interpenetrated MOFs could still provide high stability, high rigidity, and optimal pore size for applications. In this work, an asymmetrical tricarboxylate organic linker was rationally designed for the construction of a copper(II)‐based microporous MOF with a twofold interpenetrated structure of Pt3O4 topology. In spite of having structural interpenetration, the activated MOF shows high porosity with a Brunauer–Emmett–Teller surface area of 2297 m2 g−1, and high CO2 (15.7 wt % at 273 K and 1 bar) and H2 uptake (1.64 wt % at 77 K and 1 bar).
An Aggregation‐Induced Emission‐Active Macrocycle: Illusory Topology of the Penrose Stairs
Authors: He Zikai , Wang Erjing , Lam Jacky W. Y. , Li Yang , Lin Zhenyang , Tang Ben Zhong
Published: June 2015

The facile synthesis of a tetraphenylethene‐based macrocycle having aggregation‐induced emission characteristics and that expresses illusory topology of the Penrose stairs is presented. As a result of the twisted chirality (P or M) of the tetraphenylethene unit and the axial chirality of the macrocyclic linkage (R or S), the macrocycle exhibits two absolute configurations whose interconversion is energetically favorable as revealed by theoretical calculations.
Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for human leukocyte antigen B (HLA‐B) genotype and allopurinol dosing: 2015 update
Authors: Saito Y , Stamp LK , Caudle KE , Hershfield MS , McDonagh EM , Callaghan JT , Tassaneeyakul W , Mushiroda T , Kamatani N , Goldspiel BR , Phillips EJ , Klein TE , Lee MTM
Published: June 2015

The Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA‐B*58:01 Genotype and Allopurinol Dosing was originally published in February 2013. We reviewed the recent literature and concluded that none of the evidence would change the therapeutic recommendations in the original guideline; therefore, the original publication remains clinically current. However, we have updated the Supplemental Material and included additional resources for applying CPIC guidelines into the electronic health record. Up‐to‐date information can be found at PharmGKB (http://www.pharmgkb.org).
Addressing fear, fighting complacency
Authors: Pergam SA
Published: June 2015

Nature has us wired instinctively to be cautious of things that are unknown or unfamiliar. Children may fear the dark, but even as adults we remain afraid of things that go bump in the night.
Neonatal drug therapy: The first frontier of therapeutics for children
Authors: Allegaert K , van den Anker J
Published: June 2015

Knowledge about the safe and effective use of medicines in neonates has increased substantially but has resulted in few label changes. Drugs developed for use in adults are reshaped and tailored to specific neonatal indications. However, the use of drugs in neonates should not only mirror adult pharmacotherapy, but should be driven by their own specific needs. Therefore, building collaborative networks may assist to develop a newborn‐driven research agenda addressing their clinical needs and diseases.
Human Ontogeny of Drug Transporters: Review and Recommendations of the Pediatric Transporter Working Group
Authors: Brouwer KLR , Aleksunes LM , Brandys B , Giacoia GP , Knipp G , Lukacova V , Meibohm B , Nigam SK , Rieder M , de Wildt SN ,   on behalf of the Pediatric Transporter Working Group
Published: June 2015

The critical importance of membrane‐bound transporters in pharmacotherapy is widely recognized, but little is known about drug transporter activity in children. In this white paper, the Pediatric Transporter Working Group presents a systematic review of the ontogeny of clinically relevant membrane transporters (e.g., SLC, ABC superfamilies) in intestine, liver, and kidney. Different developmental patterns for individual transporters emerge, but much remains unknown. Recommendations to increase our understanding of membrane transporters in pediatric pharmacotherapy are presented.
Catalytic Production of Branched Small Alkanes from Biohydrocarbons
Authors: Oya Shin‐ichi , Kanno Daisuke , Watanabe Hideo , Tamura Masazumi , Nakagawa Yoshinao , Tomishige Keiichi
Published: June 2015

Squalane, C30 algae‐derived branched hydrocarbon, was successfully converted to smaller hydrocarbons without skeletal isomerization and aromatization over ruthenium on ceria (Ru/CeO2). The internal CH2CH2 bonds located between branches are preferably dissociated to give branched alkanes with very simple distribution as compared with conventional methods using metal‐acid bifunctional catalysts.
Computationally efficient multidimensional analysis of complex flow cytometry data using second order polynomial histograms
Authors: Zaunders John , Jing Junmei , Leipold Michael , Maecker Holden , Kelleher Anthony D. , Koch Inge
Published: June 2015

Many methods have been described for automated clustering analysis of complex flow cytometry data, but so far the goal to efficiently estimate multivariate densities and their modes for a moderate number of dimensions and potentially millions of data points has not been attained. We have devised a novel approach to describing modes using second order polynomial histogram estimators (SOPHE). The method divides the data into multivariate bins and determines the shape of the data in each bin based on second order polynomials, which is an efficient computation. These calculations yield local maxima and allow joining of adjacent bins to identify clusters. The use of second order polynomials also optimally uses wide bins, such that in most cases each parameter (dimension) need only be divided into 4–8 bins, again reducing computational load. We have validated this method using defined mixtures of up to 17 fluorescent beads in 16 dimensions, correctly identifying all populations in data files of 100,000 beads in <10 s, on a standard laptop. The method also correctly clustered granulocytes, lymphocytes, including standard T, B, and NK cell subsets, and monocytes in 9‐color stained peripheral blood, within seconds. SOPHE successfully clustered up to 36 subsets of memory CD4 T cells using differentiation and trafficking markers, in 14‐color flow analysis, and up to 65 subpopulations of PBMC in 33‐dimensional CyTOF data, showing its usefulness in discovery research. SOPHE has the potential to greatly increase efficiency of analysing complex mixtures of cells in higher dimensions. © 2015 International Society for Advancement of Cytometry
Developmental nicotine exposure enhances inhibitory synaptic transmission in motor neurons and interneurons critical for normal breathing
Authors: Jaiswal Stuti J. , Buls Wollman Lila , Harrison Caitlyn M. , Pilarski Jason Q. , Fregosi Ralph F.
Published: June 2015

Nicotine exposure in utero negatively affects neuronal growth, differentiation, and synaptogenesis. We used rhythmic brainstems slices and immunohistochemistry to determine how developmental nicotine exposure (DNE) alters inhibitory neurotransmission in two regions essential to normal breathing, the hypoglossal motor nucleus (XIIn), and preBötzinger complex (preBötC). We microinjected glycine or muscimol (GABAA agonist) into the XIIn or preBötC of rhythmic brainstem slices from neonatal rats while recording from XII nerve roots to obtain XII motoneuron population activity. Injection of glycine or muscimol into the XIIn reduced XII nerve burst amplitude, while injection into the preBötC altered nerve burst frequency. These responses were exaggerated in preparations from DNE animals. Quantitative immunohistochemistry revealed a significantly higher GABAA receptor density on XII motoneurons from DNE pups. There were no differences in GABAA receptor density in the preBötC, and there were no differences in glycine receptor expression in either region. Nicotine, in the absence of other chemicals in tobacco smoke, alters normal development of brainstem circuits that are critical for normal breathing. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 337–354, 2016
Detection of silent cells, synchronization and modulatory activity in developing cellular networks
Authors: Hjorth Johannes J.J. , Dawitz Julia , Kroon Tim , Pires Johny , Dassen Valerie J. , Berkhout Janna A. , Emperador Melero Javier , Nadadhur Aish G. , Alevra Mihai , Toonen Ruud F. , Heine Vivi M. , Mansvelder Huibert D. , Meredith Rhiannon M.
Published: June 2015

Developing networks in the immature nervous system and in cellular cultures are characterized by waves of synchronous activity in restricted clusters of cells. Synchronized activity in immature networks is proposed to regulate many different developmental processes, from neuron growth and cell migration, to the refinement of synapses, topographic maps, and the mature composition of ion channels. These emergent activity patterns are not present in all cells simultaneously within the network and more immature “silent” cells, potentially correlated with the presence of silent synapses, are prominent in different networks during early developmental periods. Many current network analyses for detection of synchronous cellular activity utilize activity‐based pixel correlations to identify cellular‐based regions of interest (ROIs) and coincident cell activity. However, using activity‐based correlations, these methods first underestimate or ignore the inactive silent cells within the developing network and second, are difficult to apply within cell‐dense regions commonly found in developing brain networks. In addition, previous methods may ignore ROIs within a network that shows transient activity patterns comprising both inactive and active periods. We developed analysis software to semi‐automatically detect cells within developing neuronal networks that were imaged using calcium‐sensitive reporter dyes. Using an iterative threshold, modulation of activity was tracked within individual cells across the network. The distribution pattern of both inactive and active, including synchronous cells, could be determined based on distance measures to neighboring cells and according to different anatomical layers. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 357–374, 2016
dictyBase 2015: Expanding data and annotations in a new software environment
Authors: Basu Siddhartha , Fey Petra , Jimenez‐Morales David , Dodson Robert J. , Chisholm Rex L.
Published: June 2015

dictyBase is the model organism database for the social amoeba Dictyostelium discoideum and related species. The primary mission of dictyBase is to provide the biomedical research community with well‐integrated high quality data, and tools that enable original research. Data presented at dictyBase is obtained from sequencing centers, groups performing high throughput experiments such as large‐scale mutagenesis studies, and RNAseq data, as well as a growing number of manually added functional gene annotations from the published literature, including Gene Ontology, strain, and phenotype annotations. Through the Dicty Stock Center we provide the community with an impressive amount of annotated strains and plasmids. Recently, dictyBase accomplished a major overhaul to adapt an outdated infrastructure to the current technological advances, thus facilitating the implementation of innovative tools and comparative genomics. It also provides new strategies for high quality annotations that enable bench researchers to benefit from the rapidly increasing volume of available data. dictyBase is highly responsive to its users needs, building a successful relationship that capitalizes on the vast efforts of the Dictyostelium research community. dictyBase has become the trusted data resource for Dictyostelium investigators, other investigators or organizations seeking information about Dictyostelium, as well as educators who use this model system. genesis 53:523–534, 2015. © 2015 Wiley Periodicals, Inc.