bluuebunny/crossref_metadata_2025 huggingface dataset:
Broadband low‐frequency electromagnetic waves in the inner magnetosphere
Authors: Chaston C. C. , Bonnell J. W. , Kletzing C. A. , Hospodarsky G. B. , Wygant J. R. , Smith C. W.
Published: September 2015

A prominent yet largely unrecognized feature of the inner magnetosphere associated with particle injections, and more generally geomagnetic storms, is the occurrence of broadband electromagnetic field fluctuations over spacecraft frame frequencies (fsc) extending from effectively zero to fsc ≳ 100  Hz. Using observations from the Van Allen Probes we show that these waves most commonly occur premidnight but are observed over a range of local times extending into the dayside magnetosphere. We find that the variation of magnetic spectral energy density with fsc obeys
over several decades with a spectral breakpoint at fb ≈ 1 Hz. The values for α are lognormally distributed with α = 1.9 ± 0.6 for fsc < fb and α = 2.9 ± 0.6 for fsc > fb. A is a function of geomagnetic activity with the largest values observed over intervals of decreasing Dst index during the main phase of geomagnetic storms. At these times these waves are nearly always present in the nightside inner magnetosphere and are commonly observed from L = 3 outward. The observed variation of the electric to magnetic field amplitude with fsc is well described by a dispersive Alfvén wave model under the assumption that fsc is primarily a consequence of the Doppler shift of plasma frame structures moving over the spacecraft. The robust anticorrelation between the time rate change of the Dst index and wave spectral energy density coupled with the ability of dispersive Alfvén waves to drive transverse ion acceleration suggests that these waves may boost ion energy density in the inner magnetosphere and intensify the ring current during storm times.
An objective method for the assessment of fluid injection‐induced seismicity and application to tectonically active regions in central California
Authors: Goebel T. H. W. , Hauksson E. , Aminzadeh F. , Ampuero J.‐P.
Published: September 2015

Changes in seismicity rates, whether of tectonic or of induced origin, can readily be identified in regions where background rates are low but are difficult to detect in seismically active regions. We present a novel method to identify likely induced seismicity in tectonically active regions based on short‐range spatiotemporal correlations between changes in fluid injection and seismicity rates. The method searches through the entire parameter space of injection rate thresholds and determines the statistical significance of correlated changes in injection and seismicity rates. Applying our method to Kern County, central California, we find that most earthquakes within the region are tectonic; however, fluid injection contributes to seismicity in four different cases. Three of these are connected to earthquake sequences with events above M4. Each of these sequences followed an abrupt increase in monthly injection rates of at least 15,000 m3. The probability that the seismicity sequences and the abrupt changes in injection rates in Kern County coincide by chance is only 4%. The identified earthquake sequences display low Gutenberg‐Richter b values of ∼0.6–0.7 and at times systematic migration patterns characteristic for a diffusive process. Our results show that injection‐induced pressure perturbations can influence seismic activity at distances of 10 km or more. Triggering of earthquakes at these large distances may be facilitated by complex local geology and faults in tectonically active regions. Our study provides the first comprehensive, statistically robust assessment of likely injection‐induced seismicity within a large, tectonically active region.
Design and Evaluation of Bilayer Matrix Tablet of Metoprolol Tartrate and Lisinopril Maleate
Authors: Ijaz Hira , Qureshi Junaid , Danish Zeeshan , Zaman Muhammad , Abdel‐Daim Mohamed , Bashir Irfan
Published: September 2015

The objective of study was to design bilayer matrix tablet of metoprolol tartrate and lisinopril maleate. The direct compression method was used for preparation of both layers. Precompression and postcompression parameters were evaluated. USP Type II dissolution apparatus was used for the in vitro drug release study using 0.1 N HCl for immediate release of lisinopril maleate layer for 2 h and phosphate buffer at pH 6.8 for 10 h for metoprolol tartrate sustained layer. In vitro data were fitted into various kinetic models. Precompression parameters showed good flow properties of powder blend. Postcompression parameters were within compendia range. L7 (2% SSG and 3% CC‐Na) was selected for formulation of immediate release layer that showed 91.6% drug release after 10 min, and for sustained release formulation, M4 (9% pectin, 9% acacia, and 20% Eudragit L100) showed 92.5% drug release for 10 h. Most formulations of sustained layer followed Higuchi drug release kinetics. Bilayer matrix tablet of metoprolol tartrate and lisinopril maleate can be formulated for the treatment of postmyocardial infarction.
Core–Shell Magnetic Molecularly Imprinted Polymer Prepared for Selectively Removed Indole from Fuel Oil
Authors: Yang Wenming , Niu Dandan , Ni Xiaoni , Zhou Zhiping , Xu Wanzhen , Huang Weihong
Published: September 2015

Magnetic molecularly imprinted polymers (MMIPs) were synthesized for selective recognition and rapid enrichment of indole from a model fuel. The MMIPs were synthesized by precipitation polymerization and a surface molecular imprinting technique, using indole as the template molecule, Fe3O4 nanoparticles as magnetically susceptible components, methylacrylic acid as the functional monomer, and ethylene glycol dimethacrylate as a cross‐linker. The properties of the MMIPs were characterized by Fourier‐transform infrared spectroscopy, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, and thermogravimetric analysis. The adsorption capacity of indole–molecularly imprinted polymers (MIPs) was 50.25 mg g−1 at 303 K and reached adsorption equilibrium in a short time. Experimental data were modeled with a pseudo–second‐order, Langmuir isotherm model. The selective adsorption performance of MIPs was favorable.
Reduced integration and differentiation of the imitation network in autism: A combined functional connectivity magnetic resonance imaging and diffusion‐weighted imaging study
Authors: Fishman Inna , Datko Michael , Cabrera Yuliana , Carper Ruth A. , Müller Ralph‐Axel
Published: September 2015

Objective

Converging evidence indicates that brain abnormalities in autism spectrum disorder (ASD) involve atypical network connectivity, but few studies have integrated functional with structural connectivity measures. This multimodal investigation examined functional and structural connectivity of the imitation network in children and adolescents with ASD, and its links with clinical symptoms.

Methods

Resting state functional magnetic resonance imaging and diffusion‐weighted imaging were performed in 35 participants with ASD and 35 typically developing controls, aged 8 to 17 years, matched for age, gender, intelligence quotient, and head motion.

Results

Within‐network analyses revealed overall reduced functional connectivity (FC) between distributed imitation regions in the ASD group. Whole brain analyses showed that underconnectivity in ASD occurred exclusively in regions belonging to the imitation network, whereas overconnectivity was observed between imitation nodes and extraneous regions. Structurally, reduced fractional anisotropy and increased mean diffusivity were found in white matter tracts directly connecting key imitation regions with atypical FC in ASD. These differences in microstructural organization of white matter correlated with weaker FC and greater ASD symptomatology.

Interpretation

Findings demonstrate atypical connectivity of the brain network supporting imitation in ASD, characterized by a highly specific pattern. This pattern of underconnectivity within, but overconnectivity outside the functional network is in contrast with typical development and suggests reduced network integration and differentiation in ASD. Our findings also indicate that atypical connectivity of the imitation network may contribute to ASD clinical symptoms, highlighting the role of this fundamental social cognition ability in the pathophysiology of ASD. Ann Neurol 2015;78:958–969
Simvastatin and vitamin D for migraine prevention: A randomized, controlled trial
Authors: Buettner Catherine , Nir Rony‐Reuven , Bertisch Suzanne M. , Bernstein Carolyn , Schain Aaron , Mittleman Murray A. , Burstein Rami
Published: September 2015

Objective

The aim of this work was to assess efficacy and tolerability of simvastatin plus vitamin D for migraine prevention in adults with episodic migraine.

Methods

We performed a randomized, double‐blind, placebo‐controlled trial with a 12‐week baseline period and 24‐week intervention period in 57 adults with episodic migraine. Participants were randomly assigned to simvastatin 20 mg tablets twice‐daily plus vitamin D3 1,000 international units capsules twice‐daily or matching placebo tablets and capsules.

Results

Compared to placebo, participants using simvastatin plus vitamin D3 demonstrated a greater decrease in number of migraine days from the baseline period to intervention weeks 1 to 12: a change of –8.0 (interquartile range [IQR]: −15.0 to −2.0) days in the active treatment group versus +1.0 (IQR: −1.0 to + 6.0) days in the placebo group, p < 0.001; and to intervention weeks 13 to 24: a change of −9.0 (IQR: −13 to −5) days in the active group versus +3.0 (IQR: −1.0 to + 5.0) days in the placebo group, p < 0.001. In the active treatment group, 8 patients (25%) experienced 50% reduction in the number of migraine days at 12 weeks and 9 (29%) at 24 weeks postrandomization. In comparison, only 1 patient (3%) in the placebo group (p = 0.03) experienced such a reduction. Adverse events were similar in both active treatment and placebo groups.

Interpretation

The results demonstrate that simvastatin plus vitamin D is effective for prevention of headache in adults with episodic migraine. Given statins' ability to repair endothelial dysfunction, this economical approach may also reduce the increased risk for vascular diseases among migraineurs. Ann Neurol 2015;78:970–981
TPM3 deletions cause a hypercontractile congenital muscle stiffness phenotype
Authors: Donkervoort Sandra , Papadaki Maria , de Winter Josine M. , Neu Matthew B. , Kirschner Janbernd , Bolduc Véronique , Yang Michele L. , Gibbons Melissa A. , Hu Ying , Dastgir Jahannaz , Leach Meganne E. , Rutkowski Anne , Foley A. Reghan , Krüger Marcus , Wartchow Eric P. , McNamara Elyshia , Ong Royston , Nowak Kristen J. , Laing Nigel G. , Clarke Nigel F. , Ottenheijm Coen A. C. , Marston Steven B. , Bönnemann Carsten G.
Published: September 2015

Objective

Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions ΔE218 and ΔE224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient.

Methods

The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca2+ sensitivity of thin filaments reconstituted with recombinant Tpm3.12 ΔE218 and ΔE224.

Results

Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca2+ sensitivity and altered cross‐bridge cycling kinetics in ΔE224 fibers. In vitro motility studies showed a two‐fold increase in Ca2+ sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations.

Interpretation

These data indicate that Tpm3.12 deletions ΔE218 and ΔE224 result in increased Ca2+ sensitivity of the troponin–tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin‐binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on‐state. The mutations destabilize the off‐state and result in excessively sensitized excitation–contraction coupling of the contractile apparatus. This work expands the phenotypic spectrum of TPM3‐related disease and provides insights into the pathophysiological mechanisms of the actin–tropomyosin complex. Ann Neurol 2015;78:982–994
Describing many‐body bosonic waveguide scattering with the truncated Wigner method
Authors: Dujardin Julien , Engl Thomas , Urbina Juan Diego , Schlagheck Peter
Published: September 2015

We consider quasi‐stationary scattering of interacting bosonic matter waves in one‐dimensional waveguides, as they arise in guided atom lasers. We show how the truncated Wigner (tW) method, which corresponds to the semiclassical description of the bosonic many‐body system on the level of the diagonal approximation, can be utilized in order to describe such many‐body bosonic scattering processes. Special emphasis is put on the discretization of space at the exact quantum level, in order to properly implement the semiclassical approximation and the tW method, as well as on the discussion of the results to be obtained in the continuous limit.

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Organized Aggregation of Porphyrins in Lipid Bilayers for Third Harmonic Generation Microscopy
Authors: Cui Liyang , Tokarz Danielle , Cisek Richard , Ng Kenneth K. , Wang Fan , Chen Juan , Barzda Virginijus , Zheng Gang
Published: September 2015

Nonlinear optical microscopy has become a powerful tool for high‐resolution imaging of cellular and subcellular composition, morphology, and interactions because of its high spatial resolution, deep penetration, and low photo‐damage to tissue. Developing specific harmonic probes is essential for exploiting nonlinear microscopic imaging for biomedical applications. We report an organized aggregate of porphyrins (OAP) that formed within lipidic nanoparticles showing fingerprint spectroscopic properties, structure‐associated second harmonic generation, and superradiant third harmonic generation. The OAP facilitated harmonic microscopic imaging of living cells with significantly enhanced contrast. The structure‐dependent switch between harmonic (OAP‐intact) and fluorescence (OAP‐disrupted) generation enabled real‐time multi‐modality imaging of the cellular fate of nanoparticles. Robustly produced under various conditions and easily incorporated into pre‐formed lipid nanovesicles, OAP provides a biocompatible nanoplatform for harmonic imaging.
Electron–Proton Decoupling in Excited‐State Hydrogen Atom Transfer in the Gas Phase
Authors: Miyazaki Mitsuhiko , Ohara Ryuhei , Daigoku Kota , Hashimoto Kenro , Woodward Jonathan R. , Dedonder Claude , Jouvet Christophe , Fujii Masaaki
Published: September 2015

Hydrogen‐release by photoexcitation, excited‐state‐hydrogen‐transfer (ESHT), is one of the important photochemical processes that occur in aromatic acids and is responsible for photoprotection of biomolecules. The mechanism is described by conversion of the initial state to a charge‐separated state along the O(N)‐H bond elongation, leading to dissociation. Thus ESHT is not a simple H‐atom transfer in which a proton and a 1s electron move together. Here we show that the electron‐transfer and the proton‐motion are decoupled in gas‐phase ESHT. We monitor electron and proton transfer independently by picosecond time‐resolved near‐infrared and infrared spectroscopy for isolated phenol–(ammonia)5, a benchmark molecular cluster. Electron transfer from phenol to ammonia occurred in less than 3 picoseconds, while the overall H‐atom transfer took 15 picoseconds. The observed electron‐proton decoupling will allow for a deeper understanding and control of of photochemistry in biomolecules.
Redox Modulation of PTEN Phosphatase Activity by Hydrogen Peroxide and Bisperoxidovanadium Complexes
Authors: Lee Chang‐Uk , Hahne Gernot , Hanske Jonas , Bange Tanja , Bier David , Rademacher Christoph , Hennig Sven , Grossmann Tom N.
Published: September 2015

PTEN is a dual‐specificity protein tyrosine phosphatase. As one of the central tumor suppressors, a thorough regulation of its activity is essential for proper cellular homeostasis. The precise implications of PTEN inhibition by reactive oxygen species (e.g. H2O2) and the subsequent structural consequences remain elusive. To study the effects of PTEN inhibition, bisperoxidovanadium (bpV) complexes serve as important tools with the potential for the treatment of nerve injury or cardiac ischemia. However, their mode of action is unknown, hampering further optimization and preventing therapeutic applications. Based on protein crystallography, mass spectrometry, and NMR spectroscopy, we elucidate the molecular basis of PTEN inhibition by H2O2 and bpV complexes. We show that both molecules inhibit PTEN via oxidative mechanisms resulting in the formation of the same intramolecular disulfide, therefore enabling the reactivation of PTEN under reductive conditions.
Methionine: a green and efficient promoter for copper‐catalyzed Sonogashira cross‐coupling reactions
Authors: Hajipour Abdol R. , Mohammadsaleh Fatemeh
Published: September 2015

In the presence of amino acids as environmentally friendly ligands, CuI‐catalyzed Sonogashira cross‐coupling of various aryl halides with phenylacetylene was conducted to afford the corresponding internal alkynes. l‐Methionine was found to be useful for this palladium‐free and amine‐free coupling reaction. It was also found that the solvent system plays an important role in this reaction, and significantly affects the product formation and reaction rate. Sonogashira coupling of aryl iodides and aryl bromides in dimethylsulfoxide or dimethylformamide gave the coupled products in good to excellent yields. Copyright © 2015 John Wiley & Sons, Ltd.
Printability of elastomer latex for additive manufacturing or 3D printing
Authors: Lukić Maria , Clarke Jane , Tuck Christopher , Whittow William , Wells Garry
Published: September 2015

Additive manufacturing, sometimes referred to as 3D printing is a new, rapidly developing technology which has the potential to revolutionize fabrication of certain high value, complex products. Until now conventional elastomers have not been widely used in the additive manufacturing process. The goal of our work was to determine the feasibility of additive manufacturing using ink jet printing of elastomeric latex materials. Particle size, viscosity, and surface tension were measured for five different latex materials—poly(2‐chloro‐1,3‐butadiene), carboxylated styrene‐butadiene rubber, carboxylated butadiene‐acrylonitrile copolymer, natural rubber, and prevulcanized natural rubber. The XSBR latex was predicted as the one most likely to be printable. Printing trials carried out with the XSBR as the ink proved it to be printable, although technical problems of agglomeration and print head clogging need to be addressed and both the material and process need to be optimized for consistent printing to be achieved. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42931.
Multicomponent One‐pot Reactions Towards the Synthesis of Stereoisomers of Dipicolylamine Complexes
Authors: Raje Sakthi , Gurusamy Sureshbabu , Koner Abhishek , Mehrotra Sonam , Jennifer Samson Jegan , Vasudev Prema G. , Butcher Ray J. , Angamuthu Raja
Published: September 2015

Reported are multi‐component one‐pot syntheses of chiral complexes [M(LROR′)Cl2] or [M(LRSR′)Cl2] from the mixture of an N‐substituted ethylenediamine, pyridine‐2‐carboxaldehyde, a primary alcohol or thiol and MCl2 utilizing in‐situ formed cyclized Schiff bases where a C−O bond, two stereocenters, and three C−N bonds are formed (M=Zn, Cu, Ni, Cd; R=Et, Ph; R′=Me, Et, nPr, nBu). Tridentate ligands LROR′ and LRSR′ comprise two chiral centers and a hemiaminal ether or hemiaminal thioether moiety on the dipicolylamine skeleton. Syn‐[Zn(LPhOMe)Cl2] precipitates out readily from the reaction mixture as a major product whereas anti‐[Zn(LPhOMe)Cl2] stays in solution as minor product. Both syn‐[Zn(LPhOMe)Cl2] and anti‐[Zn(LPhOMe)Cl2] were characterized using NMR spectroscopy and mass spectrometry. Solid‐state structures revealed that syn‐[Zn(LPhOMe)Cl2] adopted a square pyramidal geometry while anti‐[Zn(LPhOMe)Cl2] possesses a trigonal bipyramidal geometry around the Zn centers. The scope of this method was shown to be wide by varying the components of the dynamic coordination assembly, and the structures of the complexes isolated were confirmed by NMR spectroscopy, mass spectrometry, and X‐ray crystallography. Syn complexes were isolated as major products with ZnII and CuII, and anti complexes were found to be major products with NiII and CdII. Hemiaminals and hemiaminal ethers are known to be unstable and are seldom observed as part of cyclic organic compounds or as coordinated ligands assembled around metals. It is now shown, with the support of experimental results, that linear hemiaminal ethers or thioethers can be assembled without the assistance of Lewis acidic metals in the multi‐component assembly, and a possible pathway of the formation of hemiaminal ethers has been proposed.
Clinical and Cognitive Characteristics Associated with Mathematics Problem Solving in Adolescents with Autism Spectrum Disorder
Authors: Oswald Tasha M. , Beck Jonathan S. , Iosif Ana‐Maria , McCauley James B. , Gilhooly Leslie J. , Matter John C. , Solomon Marjorie
Published: September 2015

Mathematics achievement in autism spectrum disorder (ASD) has been understudied. However, the ability to solve applied math problems is associated with academic achievement, everyday problem‐solving abilities, and vocational outcomes. The paucity of research on math achievement in ASD may be partly explained by the widely‐held belief that most individuals with ASD are mathematically gifted, despite emerging evidence to the contrary. The purpose of the study was twofold: to assess the relative proportions of youth with ASD who demonstrate giftedness versus disability on applied math problems, and to examine which cognitive (i.e., perceptual reasoning, verbal ability, working memory) and clinical (i.e., test anxiety) characteristics best predict achievement on applied math problems in ASD relative to typically developing peers. Twenty‐seven high‐functioning adolescents with ASD and 27 age‐ and Full Scale IQ‐matched typically developing controls were assessed on standardized measures of math problem solving, perceptual reasoning, verbal ability, and test anxiety. Results indicated that 22% of the ASD sample evidenced a mathematics learning disability, while only 4% exhibited mathematical giftedness. The parsimonious linear regression model revealed that the strongest predictor of math problem solving was perceptual reasoning, followed by verbal ability and test anxiety, then diagnosis of ASD. These results inform our theories of math ability in ASD and highlight possible targets of intervention for students with ASD struggling with mathematics. Autism Res 2016, 9: 480–490. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.
Nonidentical twins: Comparison of frequentist and Bayesian lasso for Cox models
Authors: Zucknick Manuela , Saadati Maral , Benner Axel
Published: September 2015

One important task in translational cancer research is the search for new prognostic biomarkers to improve survival prognosis for patients. The use of high‐throughput technologies allows simultaneous measurement of genome‐wide gene expression or other genomic data for all patients in a clinical trial. Penalized likelihood methods such as lasso regression can be applied to such high‐dimensional data, where the number of (genomic) covariables is usually much larger than the sample size. There is a connection between the lasso and the Bayesian regression model with independent Laplace priors on the regression parameters, and understanding this connection has been useful for understanding the properties of lasso estimates in linear models (e.g. Park and Casella,). In this paper, we study the lasso in the frequentist and Bayesian frameworks in the context of Cox models. For the Bayesian lasso we extend the approach by Lee et al. (). In particular, we impose the lasso penalty only on the genome features, but not on relevant clinical covariates, to allow the mandatory inclusion of important established factors. We investigate the models in high‐ and low‐dimensional simulation settings and in an application to chronic lymphocytic leukemia.
Simulation and prediction of protein production in fed‐batch E. coli cultures: An engineering approach
Authors: Calleja Daniel , Kavanagh John , de Mas Carles , López‐Santín Josep
Published: September 2015

An overall model describing the dynamic behavior of fed‐batch E. coli processes for protein production has been built, calibrated and validated. Using a macroscopic approach, the model consists of three interconnected blocks allowing simulation of biomass, inducer and protein concentration profiles with time. The model incorporates calculation of the extra and intracellular inducer concentration, as well as repressor–inducer dynamics leading to a successful prediction of the product concentration. The parameters of the model were estimated using experimental data of a rhamnulose‐1‐phosphate aldolase‐producer strain, grown under a wide range of experimental conditions. After validation, the model has successfully predicted the behavior of different strains producing two different proteins: fructose‐6‐phosphate aldolase and ω‐transaminase. In summary, the presented approach represents a powerful tool for E. coli production process simulation and control. Biotechnol. Bioeng. 2016;113: 772–782. © 2015 Wiley Periodicals, Inc.
Sphingolipids contribute to acetic acid resistance in Zygosaccharomyces bailii
Authors: Lindahl Lina , Genheden Samuel , Eriksson Leif A. , Olsson Lisbeth , Bettiga Maurizio
Published: September 2015

Lignocellulosic raw material plays a crucial role in the development of sustainable processes for the production of fuels and chemicals. Weak acids such as acetic acid and formic acid are troublesome inhibitors restricting efficient microbial conversion of the biomass to desired products. To improve our understanding of weak acid inhibition and to identify engineering strategies to reduce acetic acid toxicity, the highly acetic‐acid‐tolerant yeast Zygosaccharomyces bailii was studied. The impact of acetic acid membrane permeability on acetic acid tolerance in Z. bailii was investigated with particular focus on how the previously demonstrated high sphingolipid content in the plasma membrane influences acetic acid tolerance and membrane permeability. Through molecular dynamics simulations, we concluded that membranes with a high content of sphingolipids are thicker and more dense, increasing the free energy barrier for the permeation of acetic acid through the membrane. Z. bailii cultured with the drug myriocin, known to decrease cellular sphingo­lipid levels, exhibited significant growth inhibition in the presence of acetic acid, while growth in medium without acetic acid was unaffected by the myriocin addition. Furthermore, following an acetic acid pulse, the intracellular pH decreased more in myriocin‐treated cells than in control cells. This indicates a higher inflow rate of acetic acid and confirms that the reduction in growth of cells cultured with myriocin in the medium with acetic acid was due to an increase in membrane permeability, thereby demonstrating the importance of a high fraction of sphingolipids in the membrane of Z. bailii to facilitate acetic acid resistance; a property potentially transferable to desired production organisms suffering from weak acid stress. Biotechnol. Bioeng. 2016;113: 744–753. © 2015 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.
Liver transplantation for secondary liver tumours
Authors: Lerut J , Foss A
Published: September 2015

Cautious expansion of indications for liver transplantation
Metabolic routes along digestive system of licorice: multicomponent sequential metabolism method in rat
Authors: Zhang Lei , Zhao Haiyu , Liu Yang , Dong Honghuan , Lv Beiran , Fang Min , Zhao Huihui
Published: September 2015

This study was conducted to establish the multicomponent sequential metabolism (MSM) method based on comparative analysis along the digestive system following oral administration of licorice (Glycyrrhiza uralensis Fisch., leguminosae), a traditional Chinese medicine widely used for harmonizing other ingredients in a formulae. The licorice water extract (LWE) dissolved in Krebs–Ringer buffer solution (1 g/mL) was used to carry out the experiments and the comparative analysis was performed using HPLC and LC‐MS/MS methods. In vitro incubation, in situ closed‐loop and in vivo blood sampling were used to measure the LWE metabolic profile along the digestive system. The incubation experiment showed that the LWE was basically stable in digestive juice. A comparative analysis presented the metabolic profile of each prototype and its corresponding metabolites then. Liver was the major metabolic organ for LWE, and the metabolism by the intestinal flora and gut wall was also an important part of the process. The MSM method was practical and could be a potential method to describe the metabolic routes of multiple components before absorption into the systemic blood stream. Copyright © 2015 John Wiley & Sons, Ltd.
Association of DNA methyltransferases expression with global and gene‐specific DNA methylation in colorectal cancer cells
Authors: Sarabi Mostafa Moradi , Naghibalhossaini Fakhraddin
Published: September 2015

There are conflicting reports regarding the association between DNA methyltransferases (DNMTs) expression and global or gene‐specific DNA methylation in colorectal cancer (CRC) cells. To correlate DNMTs expression with DNA methylation, we quantified DNMT1, DNMT3A and DNMT3B mRNA levels in five CRC cell lines (HCT116, LS180, HT29/219, Caco2 and SW742) by real‐time reverse‐transcriptase polymerase chain reaction (PCR) assay. In addition, we examined the global 5‐methyl cytosine levels and the methylation patterns of 12 CpG islands in these CRC cells by enzyme‐linked immunosorbent assay and methylation‐specific PCR methods, respectively. The average expression levels of three DNMTs in HCT116, Caco2, HT29/219 and SW742, relative to the expression level in LS180 (taken to be 1), were 90·1, 31·6, 2·66 and 1·86. Our data indicated that overall about 1·45%, 1·03%, 0·98%, 0·86% and 0·85% of the cytosines were methylated in the genome of HCT116, Caco2, HT29/219, SW742 and LS180 cells, respectively. The 5‐mC percentages were positively correlated with the relative cellular DNMTs expression in five CRC cell lines as verified by Pearson correlation test. However, we found no positive correlation between mRNA expression of DNMTs and gene promoter hypermethylation in these cells. Our results suggest that cellular DNMT expression is positively correlated with global DNA methylation level but not with regional DNA hypermethylation at each locus. Copyright © 2015 John Wiley & Sons, Ltd.
Harnessing Enzymatic Promiscuity in Myxochelin Biosynthesis for the Production of 5‐Lipoxygenase Inhibitors
Authors: Korp Juliane , König Stefanie , Schieferdecker Sebastian , Dahse Hans‐Martin , König Gabriele M. , Werz Oliver , Nett Markus
Published: September 2015

The siderophore myxochelin A is a potent inhibitor of human 5‐lipoxygenase (5‐LO). To clarify whether the iron‐chelating properties of myxochelin A are responsible for this activity, several analogues of this compound were generated in the native producerPyxidicoccus fallaxby precursor‐directed biosynthesis. Testing in a cell‐free assay unveiled three derivatives with bioactivity comparable with that of myxochelin A. Furthermore, it became evident that inhibition of 5‐LO by myxochelins does not correlate with their iron affinities.
Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti‐Pr specificity
Authors: Shapiro Roman , Chin‐Yee Ian , Lam Selay
Published: September 2015

Key Clinical Message

Severe cold agglutinin disease with hemodynamic compromise requires rapid stabilization of the autoimmune hemolytic anemia as a bridge to the immunosuppressive effect of rituximab. Herein, we describe eculizumab treatment of severe complement‐mediated hemolysis in a patient whose hemodynamic status deteriorated in spite of supportive blood transfusions and therapeutic plasma exchange.
Turn‐On Ratiometric Fluorescent Probe for Selective Discrimination of Cr3+ from Fe3+ in Aqueous Media for Living Cell Imaging
Authors: Rasheed Lubna , Yousuf Muhammad , Youn Il Seung , Yoon Taeseung , Kim Kwang‐Youn , Seo Young‐Kyo , Shi Genggongwo , Saleh Muhammad , Hur Jin‐Hoe , Kim Kwang S.
Published: September 2015

Pyrene‐based turn‐on ratiometric fluorescent probe 1 demonstrates high sensitivity and exceptional selectivity toward Cr3+ in the presence of other metals, including Fe3+ in aqueous media. Interaction of Cr3+ with probe 1 brings pyrene moieties close enough to have better aligned π–π stacking, thus enhancing the excimer peak many fold. On the other hand, the interaction of Fe3+ with probe 1 brings forth a negligible difference in stacking, resulting in an insignificant change in fluorescence intensity. Exceptional selectivity of probe 1 with Cr3+ over Fe3+ and other metals has been confirmed by theoretical studies in addition to experimental results. Imaging of HeLa cells observed by confocal fluorescence microscopy reveals that probe 1 can be used to monitor Cr3+ in live cells to map its subcellular distribution.
Ex‐Situ Kinetic Investigations of the Formation of the Poly‐Oxo Cluster U38
Authors: Falaise Clément , Volkringer Christophe , Hennig Christoph , Loiseau Thierry
Published: September 2015

The ex‐situ qualitative study of the kinetic formation of the poly‐oxo cluster U38, has been investigated after the solvothermal reaction. The resulting products have been characterized by means of powder XRD and scanning electron microscopy (SEM) for the solid phase and UV/Vis, X‐ray absorption near edge structure (XANES), extended X‐ray absorption fine structure (EXAFS), and NMR spectroscopies for the supernatant liquid phase. The analysis of the different synthesis batches, stopped at different reaction times, revealed the formation of spherical crystallites of UO2 from t=3 h, after the formation of unknown solid phases at an early stage. The crystallization of U38 occurred from t=4 h at the expense of UO2, and is completed after t=8 h. Starting from pure uranium(IV) species in solution (t=0–1 h), oxidation reactions are observed with a UIV/UVI ratio of 70:30 for t=1–3 h. Then, the ratio is inversed with a UIV/UVI ratio of 25/75, when the precipitation of UO2 occurs. Thorough SEM observations of the U38 crystallites showed that the UO2 aggregates are embedded within. This may indicate that UO2 acts as reservoir of uranium(IV), for the formation of U38, stabilized by benzoate and THF ligands. During the early stages of the U38 crystallization, a transient crystallized phase appeared at t=4 h. Its crystal structure revealed a new dodecanuclear moiety (U12), based on the inner hexanuclear core of {U6O8} type, decorated by three additional pairs of dinuclear U2 units. The U12 motif is stabilized by benzoate, oxalates, and glycolate ligands.
A Cationic MOF with High Uptake and Selectivity for CO2 due to Multiple CO2‐Philic Sites
Authors: Wang Hai‐Hua , Shi Wen‐Juan , Hou Lei , Li Gao‐Peng , Zhu Zhonghua , Wang Yao‐Yu
Published: September 2015

The reaction of N‐rich pyrazinyl triazolyl carboxyl ligand 3‐(4‐carboxylbenzene)‐5‐(2‐pyrazinyl)‐1H‐1,2,4‐triazole (H2cbptz) with MnCl2 afforded 3D cationic metal–organic framework (MOF) [Mn2(Hcbptz)2(Cl)(H2O)]Cl⋅DMF⋅0.5 CH3CN (1), which has an unusual (3,4)‐connected 3,4T1 topology and 1D channels composed of cavities. MOF 1 has a very polar framework that contains exposed metal sites, uncoordinated N atoms, narrow channels, and Cl− basic sites, which lead to not only high CO2 uptake, but also remarkably selective adsorption of CO2 over N2 and CH4 at 298–333 K. The multiple CO2‐philic sites were identified by grand canonical Monte Carlo simulations. Moreover, 1 shows excellent stability in natural air environment. These advantages make 1 a very promising candidate in post‐combustion CO2 capture, natural‐gas upgrading, and landfill gas‐purification processes.
Thermochromism of CuI Tetrakisguanidine Complexes: Reversible Activation of Metal‐to‐Ligand Charge‐Transfer Bands
Authors: Wiesner Sven , Wagner Arne , Hübner Olaf , Kaifer Elisabeth , Himmel Hans‐Jörg
Published: September 2015

Tetranuclear, intensely blue‐coloured CuI complexes were synthesised in which two Cu2X3− units (X=Br or I) are bridged by a dicationic GFA (guanidino‐functionalised aromatic) ligand. The UV/Vis spectra show a large metal‐to‐ligand charge‐transfer (MLCT) band around 638 nm. The tetranuclear “low‐temperature” complexes are in a temperature‐dependent equilibrium with dinuclear CuI “high‐temperature” complexes, which result from the reversible elimination of two CuX groups. A massive thermochromism effect results from the extinction of the strong MLCT band upon CuX elimination with increasing temperature. For all complexes, quantum chemical calculations predict a small and method‐dependent energy difference between the possible electronic structures, namely CuI and dicationic GFA ligand (closed‐shell singlet) versus CuII and neutral GFA ligand (triplet or broken‐symmetry state). The closed‐shell singlet state is disfavoured by hybrid‐DFT functionals, which mix in exact Hartree–Fock exchange, and is favoured by larger basis sets and consideration of a polar medium.
Light‐Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy
Authors: Szymanski Wiktor , Ourailidou Maria E. , Velema Willem A. , Dekker Frank J. , Feringa Ben L.
Published: September 2015

Cancer treatment suffers from limitations that have a major impact on the patient’s quality of life and survival. In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported herein. Analogues of the clinically used chemotherapeutic agents vorinostat, panobinostat, and belinostat were designed with a photoswitchable azobenzene moiety incorporated into their structure. The most promising compound exhibits high inhibitory potency in the thermodynamically less stable cis form and a significantly lower activity for the trans form, both in terms of HDAC activity and proliferation of HeLa cells. This approach offers a clear prospect towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy.
Glyconanomaterials for Combating Bacterial Infections
Authors: Ramström Olof , Yan Mingdi
Published: September 2015

Bacterial infections constitute an increasing problem to human health in response to build‐up of resistance to present antibiotics and sluggish development of new pharmaceuticals. However, a means to address this problem is to pinpoint the drug delivery to—and into—the bacteria. This results in a high local concentration of the drug, circumventing the increasingly high doses otherwise necessary. Combined with other effectors, such as covalent attachment to carriers, rendering the drugs less degradable, and the combination with efflux inhibitors, old drugs can be revived. In this context, glyconanomaterials offer exceptional potential, since these materials can be tailored to accommodate different effectors. In this Concept article, we describe the different advantages of glyconanomaterials, and point to their potential in antibiotic “revitalization”.
A Programmed DNA Marker Based on Bis(4‐ethynyl‐1,8‐naphthalimide) and Three‐Methane‐Bridged Thiazole Orange
Authors: Mao Yueyuan , Liu Keyin , Chen Liang , Cao Xinhua , Yi Tao
Published: September 2015

Two large conjugated naphthalimide derivatives with or without three‐methane‐bridged thiazole orange (TO3; i.e., compounds 1 a and 2 a, respectively) were designed and synthesized. The fluorescence of the naphthalimide group in compound 1 a at λ=532 nm initially decreased and that for the TO3 group at λ=655 nm increased sequentially upon adding Salmon testes (St) DNA. In contrast, without the TO3 group, the fluorescence intensity of compound 2 a monotonously decreased in response to the addition of DNA. The non‐monotonic change in the fluorescence for compound 1 a could be divided into two linear sections with two different wavelengths in the range of 0<Rb/1 a<1.2 and 1.2 <Rb/1 a<6.0 (Rb/1 a=[base pair]/[1 a]). Thus, compound 1 a can be regarded as a programmed responding molecule for DNA, which can semi‐quantitatively determine the concentration of DNA over a large concentration range from the standard fluorescence curve of compound 1 a at different wavelengths when bound with DNA. Furthermore, the binding modes of compounds 1 a and 2 a with StDNA were studied by using CD spectroscopy and melting temperature (Tm) testing. The results showed that compound 1 a interacts with StDNA through multi‐interactions including weak intercalation, weak minor groove binding, and inter‐dye interactions, whereas compound 2 a bound with DNA through simultaneous intercalation and minor groove binding.
New Aggregation‐Induced Emitters: Tetraphenyldistyrylbenzenes
Authors: Freudenberg Jan , Rominger Frank , Bunz Uwe H. F.
Published: September 2015

The synthesis of five novel distyrylbenzene (DSB) derivatives, featuring a central tetraphenylbenzene core, is reported. The targets show aggregation‐induced emission (AIE), which, however, is substituent‐dependent. For the pure hydrocarbon and derivatives that do not carry (+M) or (−M) substituents, classic AIE behavior is observed, that is, the DSBs are non‐fluorescent in solution, but are highly fluorescent in cold matrices, upon aggregate formation in poor solvents and in the solid, crystalline state. If aldehyde or dibutylamino groups are attached in the para‐position of the DSB unit, non‐classic AIE‐phores result. These are fluorescent both in dilute solution as well as in the solid state. Prolonged irradiation of the targets leads to benzotetraphene derivatives by a double cyclization.
Design, Synthesis, and Conformational Analysis of Proposed β‐Turn Mimics from Isoxazoline‐Cyclopentane Aminols
Authors: Memeo Misal Giuseppe , Mella Mariella , Montagna Valentina , Quadrelli Paolo
Published: September 2015

Constrained aminols from oxazanorbornene derivatives have the geometrical features to be used as β‐turn inducers. Four different stereoisomers were prepared and spectroscopically characterized (MD calculations, NMR‐titration and VT‐NMR experiments). Temperature coefficients in DMSO are indicative for the existence of an intramolecular hydrogen bond. Chirooptical properties revealed a β‐turn arrangement of all the synthesized compounds, where, depending on the absolute configuration of the cyclopentane spacer, they can be labeled as left‐ or right‐handed turns.
Highly Regioselective Palladium‐Catalyzed Carboxylation of Allylic Alcohols with CO2
Authors: Mita Tsuyoshi , Higuchi Yuki , Sato Yoshihiro
Published: September 2015

Various allylic alcohols were carboxylated in the presence of a catalytic amount of PdCl2 and PPh3 using ZnEt2 as a stoichiometric transmetalation agent under a CO2 atmosphere (1 atm). This carboxylation proceeded in a highly regioselective manner to afford branched carboxylic acids predominantly. The β,γ‐unsaturated carboxylic acid thus obtained was successfully converted into an optically active γ‐butyrolactone, a known intermediate of (R)‐baclofen.
Cationic Cobalt(III)‐Catalyzed Aryl and Alkenyl CH Amidation: A Mild Protocol for the Modification of Purine Derivatives
Authors: Liang Yujie , Liang Yu‐Feng , Tang Conghui , Yuan Yizhi , Jiao Ning
Published: September 2015

A cationic cobalt(III)‐catalyzed direct CH amidation of unactivated (hetero)arenes and alkenes by using 1,4,2‐dioxazol‐5‐ones as the amidating reagent has been developed. This transformation proceeds efficiently under external oxidant‐free conditions with a broad substrate scope. Moreover, 6‐arylpurine compounds, which often exhibit high potency in antimycobacterial, cytostatic, and anti‐HCV activities, can be smoothly amidated, thus offering a mild protocol for their late stage functionalization.
Synthesis and Characterization of Fluorinated Polyimide Derived from 3,3′‐Diisopropyl‐4,4′‐diaminodiphenyl‐3′′,4′′‐difluorophenylmethane
Authors: Huang Xiaohua , Mei Mei , Liu Chanjuan , Pei Xianglin , Wei Chun
Published: September 2015

A novel aromatic diamine monomer, 3,3′‐diisopropyl‐4,4′‐diaminodiphenyl‐3′′,4′′‐difluorophenylmethane (PAFM), was successfully synthesized by coupling of 2‐isopropylaniline and 3,4‐difluorobenzaldehyde. The aromatic diamine was adopted to synthesize a series of fluorinated polyimides by polycondensation with various dianhydrides: pyromellitic dianhydride (PMDA), 3,3′,4,4′‐biphenyltetracarboxylic dianhydride (BPDA), 4,4′‐oxydiphthalic anhydride (ODPA) and 3,3′,4,4′‐benzophenone tetracarboxylic dianhydride (BTDA) via the conventional one‐step method. These polyimides presented excellent solubility in common organic solvents, such as N,N‐dimethylformamide (DMF), N,N‐dimethyl acetamide (DMAc), dimethyl sulfoxide (DMSO), N‐methyl‐2‐pyrrolidone (NMP), chloroform (CHCl3), tetrahydrofuran (THF) and so on. The glass transition temperatures (Tg) of fluorinated polyimides were in the range of 260–306°C and the temperature at 10% weight loss in the range of 474–502°C. Their films showed the cut‐off wavelengths of 330–361 nm and higher than 80% transparency in a wavelength range of 385–463 nm. Moreover, polymer films exhibited low dielectric properties in the range of 2.76–2.96 at 1 MHz, as well as prominent mechanical properties with tensile strengths of 66.7–97.4 MPa, a tensile modulus of 1.7–2.1 GPa and elongation at break of 7.2%–12.9%. The polymer films also showed outstanding hydrophobicity with the contact angle in the range of 91.2°–97.9°.
Synthesis, Structural Characterization and Reactivity of a Bis(phosphine)(silyl) Platinum(II) Complex
Authors: Li Yonghua , Zeng Wenjin , Lai Wenyong , Shimada Shigeru , Wang Shi , Wang Lianhui , Huang Wei
Published: September 2015

Treatment of 1,2‐C6H4(SiH3)(SiH3) (1) with Pt(dmpe)(PEt3)2 (dmpe=Me2PCH2CH2PMe2) in the ratio of 1:1 leads to the complex {1,2‐C6H4(SiH2)(SiH2)}PtII (dmpe) (2), which can react with proton organic reagent bearing hydroxy group with low steric hindrance to form a tetra‐alkoxy substituted silyl platinum(II) compound (3). Compounds 2 and 3 are the very rare examples of silyl transition‐metal complexes derived from this chelating hydrosilane ligand. To the best of our knowledge, there are only 6 examples of silyl metal complexes prepared from this ligand with such structural features registered in the Cambridge Structural Database, among them, only one silyl platinum(II) compound is presented. The structures of complexes 2 and 3 were unambiguously determined by multinuclear NMR spectroscopic studies and single crystal X‐ray analysis.