bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Coupling at the Ångström Scale
Authors: Dey Krishna Kanti , Pong Frances Ying , Breffke Jens , Pavlick Ryan , Hatzakis Emmanuel , Pacheco Carlos , Sen Ayusman
Published: December 2015

While momentum transfer from active particles to their immediate surroundings has been studied for both synthetic and biological micron‐scale systems, a similar phenomenon was presumed unlikely to exist at smaller length scales due to the dominance of viscosity in the ultralow Reynolds number regime. Using diffusion NMR spectroscopy, we studied the motion of two passive tracers—tetramethylsilane and benzene—dissolved in an organic solution of active Grubbs catalyst. Significant enhancements in diffusion were observed for both the tracers and the catalyst as a function of reaction rate. A similar behavior was also observed for the enzyme urease in aqueous solution. Surprisingly, momentum transfer at the molecular scale closely resembles that reported for microscale systems and appears to be independent of swimming mechanism. Our work provides new insight into the role of active particles on advection and mixing at the Ångström scale.
Chemical Synthesis of Proteins with Non‐Strategically Placed Cysteines Using Selenazolidine and Selective Deselenization
Authors: Reddy Post Sai , Dery Shahar , Metanis Norman
Published: December 2015

Although native chemical ligation has enabled the synthesis of hundreds of proteins, not all proteins are accessible through typical ligation conditions. The challenging protein, 125‐residue human phosphohistidine phosphatase 1 (PHPT1), has three cysteines near the C‐terminus, which are not strategically placed for ligation. Herein, we report the first sequential native chemical ligation/deselenization reaction. PHPT1 was prepared from three unprotected peptide segments using two ligation reactions at cysteine and alanine junctions. Selenazolidine was utilized as a masked precursor for N‐terminal selenocysteine in the middle segment, and, following ligation, deselenization provided the native alanine residue. This approach was used to synthesize both the wild‐type PHPT1 and an analogue in which the active‐site histidine was substituted with the unnatural and isosteric amino acid β‐thienyl‐l‐alanine. The activity of both proteins was studied and compared, providing insights into the enzyme active site.
The Origin of the Reactivity of the Criegee Intermediate: Implications for Atmospheric Particle Growth
Authors: Miliordos Evangelos , Xantheas Sotiris S.
Published: December 2015

The electronic structure of the simplest Criegee intermediate, H2COO, is practically that of a closed shell. On the biradical scale (β), where 0 corresponds to the pure closed shell and 1 to a pure biradical, its β value is only 0.10, suggesting that its ground electronic state is best described as a H2C=Oδ+−Oδ− zwitterion. However, this picture of a nearly inert closed shell contradicts its rich reactivity in the atmosphere. It is shown that the mixing of its ground state with the first triplet excited state, which is a pure biradical state of the type H2C.−O−O., is responsible for the formation of strongly bound products during reactions inducing atmospheric particle growth.
[3,3]‐Sigmatropic Rearrangement/Allylboration/Cyclization Sequence: Enantioenriched Seven‐Membered‐Ring Carbamates and Ring Contraction to Pyrrolidines
Authors: Macé Aurélie , Touchet Sabrina , Andres Patricia , Cossío Fernando , Dorcet Vincent , Carreaux François , Carboni Bertrand
Published: December 2015

The combination of in situ generated α‐isocyanato allylboronic esters and aldehydes afforded seven‐membered‐ring enecarbamates with high levels of diastereo‐ and enantiocontrol. They were easily converted into diversely substituted 1,3‐oxazepan‐2‐ones. An unprecedented rearrangement of 5‐acetoxy‐7‐aryl or styryl derivatives led to tetrasubstituted pyrrolidines. A computational study provides evidence on the feasibility of the proposed mechanism of this unusual ring contraction.
Complementary Iron(II)‐Catalyzed Oxidative Transformations of Allenes with Different Oxidants
Authors: Sabbasani Venkata R. , Lee Hyunjin , Xia Yuanzhi , Lee Daesung
Published: December 2015

Substituent‐ and oxidant‐dependent transformations of allenes are described. Given the profound influence of the substituent on the reactivity of allenes, the subtle differences in allene structures are manifested in the formation of diverse products when reacted with different electrophiles/oxidants. In general, reactions of nonsilylated allenes involve an allylic cation intermediate by forming a C−O bond, at the sp‐hybridized C2, with either DDQ (2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone) or TBHP (tert‐butyl hydroperoxide), along with FeCl2⋅4 H2O (10 mol %). In contrast, silylated allenes favor the formation of propargylic cation intermediates by transferring the allenic hydride to the oxidant, thus generating 1,3‐enynes (E1 product) or propargylic THBP ethers (SN1 product). The formation of these different putative cationic intermediates from nonsilylated and silylated allenes is strongly supported by DFT calculations.
Versatile Aerogel Fabrication by Freezing and Subsequent Freeze‐Drying of Colloidal Nanoparticle Solutions
Authors: Freytag Axel , Sánchez‐Paradinas Sara , Naskar Suraj , Wendt Natalja , Colombo Massimo , Pugliese Giammarino , Poppe Jan , Demirci Cansunur , Kretschmer Imme , Bahnemann Detlef W. , Behrens Peter , Bigall Nadja C.
Published: December 2015

A versatile method to fabricate self‐supported aerogels of nanoparticle (NP) building blocks is presented. This approach is based on freezing colloidal NPs and subsequent freeze drying. This means that the colloidal NPs are directly transferred into dry aerogel‐like monolithic superstructures without previous lyogelation as would be the case for conventional aerogel and cryogel fabrication methods. The assembly process, based on a physical concept, is highly versatile: cryogelation is applicable for noble metal, metal oxide, and semiconductor NPs, and no impact of the surface chemistry or NP shape on the resulting morphology is observed. Under optimized conditions the shape and volume of the liquid equal those of the resulting aerogels. Also, we show that thin and homogeneous films of the material can be obtained. Furthermore, the physical properties of the aerogels are discussed.
Synthesis, In Vitro Biological Evaluation, and Molecular Docking of New Triazoles as Potent Antifungal Agents
Authors: Li Xiang , Liu Chao , Tang Sheng , Wu Qiuye , Hu Honggang , Zhao Qingjie , Zou Yan
Published: December 2015

Based on the structure of the active site of CYP51 and the structure–activity relationships of azole antifungal compounds that we designed in a previous study, a series of 1‐{1‐[2‐(substitutedbenzyloxy)ethyl]‐1H‐1,2,3‐triazol‐4‐yl}‐2‐(2,4‐difluorophenyl)‐3‐(1H‐1,2,4‐triazol‐1‐yl)propan‐2‐ols (6a–n) were designed and synthesized utilizing copper‐catalyzed azide‐alkyne cycloaddition. Preliminary antifungal tests against eight human pathogenic fungi in vitro showed that all the title compounds exhibited excellent antifungal activities with a broad spectrum in vitro. Molecular docking results indicated that the interaction between the title compounds and CYP51 comprised π–π interactions, hydrophobic interactions, and the narrow hydrophobic cleft.
Flexible Hierarchical TiO2/Fe2O3 Composite Membrane with High Separation Efficiency for Surfactant‐Stabilized Oil‐Water Emulsions
Authors: Tan Benny Yong Liang , Juay Jermyn , Liu Zhaoyang , Sun Darren
Published: December 2015

Globally, efficient oil‐water separation for surfactant‐stabilized oil‐water emulsions has been in urgent demand. The current options available for separation are neither sustainable nor resistant to fouling. Herein, we introduce a hierarchically nanostructured TiO2/Fe2O3 composite membrane, which is capable of separating surfactant‐stabilized oil‐water emulsions with high separation efficiency. The high oil rejection rate is contributed by the acquisition of an interconnected delicate network and underwater superoleophobic interface. Meanwhile, its self‐cleaning function promote the facile recovery of the contaminated membrane. Furthermore, the mechanical flexible characteristic of the TiO2/Fe2O3 composite membrane widens its applicability in industrial employment. Thanks to these properties, this novel membrane can be considered as a practical option for treating surfactant‐stabilized oil‐water emulsions.
Polystyrene‐Core–Silica‐Shell Hybrid Particles Containing Gold and Magnetic Nanoparticles
Authors: Tian Jia , Vana Philipp
Published: December 2015

Polystyrene‐core–silica‐shell hybrid particles were synthesized by combining the self‐assembly of nanoparticles and the polymer with a silica coating strategy. The core–shell hybrid particles are composed of gold‐nanoparticle‐decorated polystyrene (PS‐AuNP) colloids as the core and silica particles as the shell. PS‐AuNP colloids were generated by the self‐assembly of the PS‐grafted AuNPs. The silica coating improved the thermal stability and dispersibility of the AuNPs. By removing the “free” PS of the core, hollow particles with a hydrophobic cage having a AuNP corona and an inert silica shell were obtained. Also, Fe3O4 nanoparticles were encapsulated in the core, which resulted in magnetic core–shell hybrid particles by the same strategy. These particles have potential applications in biomolecular separation and high‐temperature catalysis and as nanoreactors.
Intervals for the assessment of measurement agreement: Similarities, differences, and consequences of incorrect interpretations
Authors: Vock Michael
Published: December 2015

Several intervals have been proposed to quantify the agreement of two methods intended to measure the same quantity in the situation where only one measurement per method and subject is available. The limits of agreement are probably the most well‐known among these intervals, which are all based on the differences between the two measurement methods. The different meanings of the intervals are not always properly recognized in applications. However, at least for small‐to‐moderate sample sizes, the differences will be substantial. This is illustrated both using the width of the intervals and on probabilistic scales related to the definitions of the intervals. In particular, for small‐to‐moderate sample sizes, it is shown that limits of agreement and prediction intervals should not be used to make statements about the distribution of the differences between the two measurement methods or about a plausible range for all future differences. Care should therefore be taken to ensure the correct choice of the interval for the intended interpretation.
High throughput chromatography strategies for potential use in the formal process characterization of a monoclonal antibody
Authors: Petroff Matthew G. , Bao Haiying , Welsh John P. , van Beuningen – de Vaan Miranda , Pollard Jennifer M. , Roush David J. , Kandula Sunitha , Machielsen Peter , Tugcu Nihal , Linden Thomas O.
Published: December 2015

High throughput experimental strategies are central to the rapid optimization of biologics purification processes. In this work, we extend common high throughput technologies towards the characterization of a multi‐column chromatography process for a monoclonal antibody (mAb). Scale‐down strategies were first evaluated by comparing breakthrough, retention, and performance (yields and clearance of aggregates and host cell protein) across miniature and lab scale columns. The process operating space was then evaluated using several integrated formats, with batch experimentation to define process testing ranges, miniature columns to evaluate the operating space, and comparison to traditional scale columns to establish scale‐up correlations and verify the determined operating space. When compared to an independent characterization study at traditional lab column scale, the high throughput approach identified the same control parameters and similar process sensitivity. Importantly, the high throughput approach significantly decreased time and material needs while improving prediction robustness. Miniature columns and manufacturing scale centerpoint data comparisons support the validity of this approach, making the high throughput strategy an attractive and appropriate scale‐down tool for the formal characterization of biotherapeutic processes in the future if regulatory acceptance of the miniature column data can be achieved. Biotechnol. Bioeng. 2016;113: 1273–1283. © 2015 Wiley Periodicals, Inc.
Metal–Ligand Misfits: Facile Access to Rhenium–Oxo Corroles by Oxidative Metalation
Authors: Einrem Rune F. , Gagnon Kevin J. , Alemayehu Abraham B. , Ghosh Abhik
Published: December 2015

With the exception of a single accidental synthesis, rhenium corroles are unknown, but of great interest as catalysts and potential radiopharmaceuticals. Oxidative metalation of meso‐triarylcorroles with [Re2(CO)10] in refluxing decalin has provided a facile and relatively high‐yielding route to rhenium(V)–oxo corroles. The complexes synthesized could all be fully characterized by single‐crystal X‐ray structure analyses.
Oxydifluoromethylation of Alkenes by Photoredox Catalysis: Simple Synthesis of CF2H‐Containing Alcohols
Authors: Arai Yusuke , Tomita Ren , Ando Gaku , Koike Takashi , Akita Munetaka
Published: December 2015

We have developed a novel and simple protocol for the direct incorporation of a difluoromethyl (CF2H) group into alkenes by visible‐light‐driven photoredox catalysis. The use of fac‐[Ir(ppy)3] (ppy=2‐pyridylphenyl) photocatalyst and shelf‐stable Hu's reagent, N‐tosyl‐S‐difluoromethyl‐S‐phenylsulfoximine, as a CF2H source is the key to success. The well‐designed photoredox system achieves synthesis of not only β‐CF2H‐substituted alcohols but also ethers and an ester from alkenes through solvolytic processes. The present method allows a single‐step and regioselective formation of C(sp3)–CF2H and C(sp3)−O bonds from C=C moiety in alkenes, such as hydroxydifluoromethylation, regardless of terminal or internal alkenes. Moreover, this methodology tolerates a variety of functional groups.
Cancer susceptibility genes and their potential implication regarding systemic therapy for early‐stage breast cancer
Authors: Karp Judith E. , Wolff Antonio C.
Published: December 2015

The development of leukemia after chemotherapy and/or radiotherapy for breast cancer has been recognized for 4 decades. In this issue, Churpek et al have conducted a retrospective study that expands on a growing body of knowledge for understanding an individual's genetic risk, not only for breast cancer, but also for second cancers such as leukemia.
Effects of Fostamatinib on the Pharmacokinetics of the CYP2C8 Substrate Pioglitazone: Results From In Vitro and Phase 1 Clinical Studies
Authors: Martin Paul , Gillen Michael , Millson David , Oliver Stuart , Brealey Clive , Surry Dominic , Sweeny David , Lau David , Leese Philip
Published: December 2015

Fostamatinib is a prodrug that undergoes gastrointestinal tract dephosphorylation to form the active metabolite, R406. Here we report its cytochrome P450–inducing potential. In vitro, R406 3 and 10 μM induced CYP2C8 to levels representing 53% and 75%, respectively, of the level achieved by the positive control, rifampicin. Induction of other enzymes was minor. The effect of fostamatinib (100 mg twice daily) on the pharmacokinetics of a single oral 30‐mg dose of the CYP2C8 substrate pioglitazone and its metabolite, hydroxy pioglitazone, was then investigated (open‐label, nonrandomized, 2‐period phase I study [n = 15]). Coadministration of fostamatinib and pioglitazone (vs pioglitazone alone) was associated with lower mean maximum plasma concentration values for pioglitazone (geometric least‐squares mean ratio, 82.8; 90% confidence interval, 64.2–106.8) and hydroxy pioglitazone (90.9; 78.6–105.1), an increase in pioglitazone AUC (117.8; 108.4–128.0), a decrease in hydroxy pioglitazone AUC(0–t) (89.7; 78.9–101.9), and an increase in pioglitazone geometric mean t1/2λz (9.4–12.8 hours). No tolerability concerns were identified upon coadministration. These data suggest that although clinical significance has not been formally evaluated, fostamatinib is unlikely to have a clinically significant effect on the pharmacokinetics of pioglitazone (which may be extrapolated to other CYP2C8 substrates). However, vigilance is advised should these agents be prescribed together.
Pharmacokinetics, Safety, and Tolerability of Fevipiprant (QAW039), a Novel CRTh2 Receptor Antagonist: Results From 2 Randomized, Phase 1, Placebo‐Controlled Studies in Healthy Volunteers
Authors: Erpenbeck Veit J. , Vets Eva , Gheyle Lien , Osuntokun Wande , Larbig Michael , Neelakantham Srikanth , Sandham David , Dubois Gerald , Elbast Walid , Goldsmith Paul , Weiss Markus
Published: December 2015

We evaluated the pharmacokinetics (PK), safety, and tolerability of a novel oral CRTh2 antagonist, fevipiprant (QAW039), in healthy subjects. Peak concentrations of fevipiprant in plasma were observed 1‒3 hours postdosing. Concentrations declined in a multiexponential manner, followed by an apparent terminal phase (t1/2, ∼20 hours). Steady state was achieved in 4 days with <2‐fold accumulation. Elimination was partly by renal excretion (≤30% of the dose) and glucuronidation. Food had minimal impact on the PK of fevipiprant, and it was well tolerated at single and multiple oral doses up to 500 mg/day. No dose‐dependent adverse events were observed, and all the events were mild or moderate in severity. Systemic concentrations were sufficiently high to achieve relevant target occupancy, considering in vitro pharmacology data. In summary, the data support further development as a once‐daily oral therapy for allergic diseases.
Strategies for the Controlled Electronic Doping of Colloidal Quantum Dot Solids
Authors: Stavrinadis Alexandros , Konstantatos Gerasimos
Published: December 2015

Over the last several years tremendous progress has been made in incorporating colloidal quantum dot (CQD) solids as photoactive components in optoelectronic devices. A large part of this progress is associated with significant advancements made in controlling the electronic doping of CQD solids. Today, a variety of strategies exists towards that purpose; this Minireview aims to survey the major published works in this subject. Additional attention is given to the many challenges associated with the task of doping CQDs, as well as to the realization of optoelectronic functionalities and applications upon successful light and heavy electronic doping of CQD solids.
Properties of Apolar Solutes in Alkyl Imidazolium‐Based Ionic Liquids: The Importance of Local Interactions
Authors: Lesch Volker , Heuer Andreas , Holm Christian , Smiatek Jens
Published: December 2015

The solvation and the dynamic properties of apolar model solutes in alkyl imidazolium‐based ionic liquids (IL) are studied by using all‐atom molecular dynamics simulations. In regards to specific IL effects, we focused on the often used 1‐ethyl‐3‐methyl imidazolium cation in combination with the anions tetrafluoroborate, acetate, and bis(trifluoromethanesulfonyl)imide. Our findings reveal that the size of the anion crucially influences the accumulation behavior of the cations, which results in modified IL solvation properties. Deviations between the different alkyl imidazolium‐based IL combinations can be also observed with regard to the results for the radial distribution functions, the number of surrounding molecules, and the molecular orientation. The analysis of the van Hove function further shows pronounced differences in the dynamic behavior of the solutes. The simulations verify that the solute mobilities are mainly influenced by the composition of the local solvent shell and the properties of the underlying Lennard–Jones interactions. Additional simulations with regard to modified short‐range dispersion energies for alkyl imidazolium‐based ILs validate our conclusions.
Aqueous Solutions of Ionic Liquids: Microscopic Assembly
Authors: Vicent‐Luna Jose Manuel , Dubbeldam David , Gómez‐Álvarez Paula , Calero Sofia
Published: December 2015

Aqueous solutions of ionic liquids are of special interest, due to the distinctive properties of ionic liquids, in particular, their amphiphilic character. A better understanding of the structure–property relationships of such systems is hence desirable. One of the crucial molecular‐level interactions that influences the macroscopic behavior is hydrogen bonding. In this work, we conduct molecular dynamics simulations to investigate the effects of ionic liquids on the hydrogen‐bond network of water in dilute aqueous solutions of ionic liquids with various combinations of cations and anions. Calculations are performed for imidazolium‐based cations with alkyl chains of different lengths and for a variety of anions, namely, [Br]−, [NO3]−, [SCN]−, [BF4]−, [PF6]−, and [Tf2N]−. The structure of water and the water–ionic liquid interactions involved in the formation of a heterogeneous network are analyzed by using radial distribution functions and hydrogen‐bond statistics. To this end, we employ the geometric criterion of the hydrogen‐bond definition and it is shown that the structure of water is sensitive to the amount of ionic liquid and to the anion type. In particular, [SCN]− and [Tf2N]− were found to be the most hydrophilic and hydrophobic anions, respectively. Conversely, the cation chain length did not influence the results.
Meaning in Life in People with Borderline Personality Disorder
Authors: Marco Jose H. , Pérez Sandra , García‐Alandete Joaquin , Moliner Reyes
Published: December 2015

Low feelings of meaning in life are associated with depression, hopelessness and suicide, substance abuse and emotional dysregulation. The aim of this study is to offer results about the importance of the construct meaning in life in the psychopathology of BPD. In study 1, the sample was made up of 223 participants, 141 participants with BPD and 82 participants with another mental disorder but without BPD. In study 2, the sample was made up of 80 participants with BPD. Study 1 indicated that the participants with BPD had a lower feeling of meaning in life than the participants with mental disorders but without a BPD. Study 2 indicated that meaning in life was highly negatively correlated with the symptoms of BPD. The model composed of emotional dysregulation, and meaning in life was significantly associated with BPD psychopathology. The present study supports the association between meaning in life with the psychopathology of BPD. Copyright © 2015 John Wiley & Sons, Ltd.

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The results of this study suggest that meaning in life is a relevant variable in the psychopathology of BPD

The results of this study suggest that meaning in life is associated with non‐suicide self injuries

This study suggests that current therapies for BPD should focus on increasing the meaning in life in these patients
European wildcat populations are subdivided into five main biogeographic groups: consequences of Pleistocene climate changes or recent anthropogenic fragmentation?
Authors: Mattucci Federica , Oliveira Rita , Lyons Leslie A. , Alves Paulo C. , Randi Ettore
Published: December 2015

Extant populations of the European wildcat are fragmented across the continent, the likely consequence of recent extirpations due to habitat loss and over‐hunting. However, their underlying phylogeographic history has never been reconstructed. For testing the hypothesis that the European wildcat survived the Ice Age fragmented in Mediterranean refuges, we assayed the genetic variation at 31 microsatellites in 668 presumptive European wildcats sampled in 15 European countries. Moreover, to evaluate the extent of subspecies/population divergence and identify eventual wild × domestic cat hybrids, we genotyped 26 African wildcats from Sardinia and North Africa and 294 random‐bred domestic cats. Results of multivariate analyses and Bayesian clustering confirmed that the European wild and the domestic cats (plus the African wildcats) belong to two well‐differentiated clusters (average ФST = 0.159, Rst = 0.392, P > 0.001; Analysis of molecular variance [AMOVA]). We identified from c. 5% to 10% cryptic hybrids in southern and central European populations. In contrast, wild‐living cats in Hungary and Scotland showed deep signatures of genetic admixture and introgression with domestic cats. The European wildcats are subdivided into five main genetic clusters (average ФST = 0.103, Rst = 0.143, P > 0.001; AMOVA) corresponding to five biogeographic groups, respectively, distributed in the Iberian Peninsula, central Europe, central Germany, Italian Peninsula and the island of Sicily, and in north‐eastern Italy and northern Balkan regions (Dinaric Alps). Approximate Bayesian Computation simulations supported late Pleistocene–early Holocene population splittings (from c. 60 k to 10 k years ago), contemporary to the last Ice Age climatic changes. These results provide evidences for wildcat Mediterranean refuges in southwestern Europe, but the evolution history of eastern wildcat populations remains to be clarified. Historical genetic subdivisions suggest conservation strategies aimed at enhancing gene flow through the restoration of ecological corridors within each biogeographic units. Concomitantly, the risk of hybridization with free‐ranging domestic cats along corridor edges should be carefully monitored.
Mycobacterium tuberculosis‐specific CD4+ T‐cell response is increased, and Treg cells decreased, in anthelmintic‐treated patients with latent TB
Authors: Toulza Frederic , Tsang Lillian , Ottenhoff Tom H. M. , Brown Michael , Dockrell Hazel M.
Published: December 2015

In many settings, adults with active or latent tuberculosis will also be coinfected with helminths. Our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity, in a setting where helminth reinfection should not occur. We investigated the potential impact of helminth infection on immune responses to Mycobacterium tuberculosis (Mtb) in patients with latent Mtb infection with or without helminth infection (Strongyloides or Schistosoma), and tested T‐cell responses before and after anthelmintic treatment. The study was performed in migrants resident in the United Kingdom, where reexposure and reinfection following anthelmintic treatment would not occur. The frequency of CD4+IFN‐γ+ T cells was measured following stimulation with Mtb Purified Protein Derivative or ESAT‐6/CFP‐10 antigen, and concentrations of IFN‐γ in culture supernatants measured by ELISA and multiplex bead array. Helminth infection was associated with a lower frequency of CD4+IFN‐γ+ T cells, which increased following treatment. Patients with helminth infection showed a significant increase in CD4+FoxP3+ T cells (Treg) compared to those without helminth infection. There was a decrease in the frequency of Treg cells, and an associated increase in CD4+IFN‐γ+ T cells after the anthelmintic treatment. Here, we show a potential role of Treg cells in reducing the frequency and function of antimycobacterial CD4+IFN‐γ+ T cells, and that these effects are reversed after anthelmintic treatment.
Comparative Synthesis of Cu and Cu2O Nanoparticles from Different Copper Precursors in an Ionic Liquid or Propylene Carbonate
Authors: Marcos Esteban Raquel , Meyer Hajo , Kim Jiyeon , Gemel Christian , Fischer Roland A. , Janiak Christoph
Published: December 2015

Copper metal and copper(I) oxide (cuprite, cuprous oxide) nanoparticles (Cu‐NPs and Cu2O‐NPs) were prepared from different readily available copper salts by means of microwave irradiation in propylene carbonate (PC) or in the ionic liquid (IL) 1‐butyl‐3‐methylimidazolium tetrafluoroborate ([BMIm][BF4]) without addition of extra reducing agents. The nanostructures were studied by high‐angle annular dark field‐scanning transmission electron microscopy, TEM, SEM, and powder XRD. Star‐shaped agglomerated Cu‐NPs with about 45 nm diameter were formed from Cu(BF4)2 in PC. Cu‐NPs with smaller size distributions of 3.1 ± 0.7 nm and 3.7 ± 1.4 nm were obtained when copper(II) bis[1‐(dimethylamino)propan‐2‐olate], Cu[OCH(Me)CH2NMe2]2, was decomposed in PC and in [BMIm][BF4]. Small Cu‐NPs were also obtained from copper(II) acetylacetonate in [BMIm][BF4] with a diameter distribution of 3.3 ± 0.9 nm. Cubic Cu2O nanocubes (Cu2O‐NCs) of 43 ± 15 nm in size could be prepared by using Cu(OAc)2·H2O with [BMIm][BF4]. The size of the Cu2O‐NCs increased on isolation from the neat IL by addition of acetonitrile, which gave NCs of 0.1–0.5 μm in size.
Dimethylzinc‐Mediated Chlorolact­amization of Homoallylic Amines with Chloroform
Authors: Nishida Yuika , Ueda Masafumi , Hayashi Masataka , Takeda Norihiko , Miyata Okiko
Published: December 2015

A novel chlorolactamization reaction of homoallylic amines has been developed. The treatment of homoallylic amines with dimethylzinc in chloroform led to the formation of the corresponding β‐chlorolactams via the Prins‐type cyclization of a carbamoyl chloride intermediate. The results of this study highlight the synthetic utility of chloroform as a source of both carbonyl group and chloride anion.
Influence of thermal behavior of phosphorus compounds on their flame retardant effect in PU rigid foam
Authors: Xu Wei , Wang Guojian
Published: December 2015

Phosphorus‐containing compounds have been widely used as flame retardants for polyurethane rigid foam (PURF). In this work, a number of phosphorus compounds were utilized and studied as flame retardants for PURF, including ammonium polyphosphate, pentaerythritol phosphate, triethyl phosphate, and dimethyl methyl phosphonate. The thermal behavior of flame retardants was thoroughly investigated, such as degradation, vaporization, and the properties of degraded products. The influence of thermal behavior of phosphorus flame retardants on PURF was examined and analyzed. The results indicated that the effect of flame retardant was highly related to their thermal behavior. Phosphorus compounds for gas phase flame retardants were very effective in decreasing the heat release rate and increase limited oxygen index of PURF, while condensed phase flame retardants showed better comprehensive flame retardant effect, such as reducing the toxicity of combustion product. Copyright © 2015 John Wiley & Sons, Ltd.
Effect of different drying methods on the phenolic, flavonoid and volatile compounds of Stevia rebaudiana leaves
Authors: Periche Angela , Castelló María Luisa , Heredia Ana , Escriche Isabel
Published: December 2015

Different drying methods (hot air drying, freeze drying and shade drying) were evaluated to discern the optimal conditions for the preservation of flavonoid, phenolic and volatile compounds in stevia leaves. All the methods applied affected the antioxidant and volatile compounds in dried stevia leaves differently. 2‐Hexenal, hexanal and α‐pinene were the most abundant volatile compounds produced by freeze drying and shade drying (21.1‐19.7; 14.2‐10 and 19.4‐5.04 µg/g, respectively); and furan tetrahydro and α‐pinene (3.2 and 3.1 µg/g, respectively) by air drying. While chlorogenic acid, coumaric acid and sinapic acid were the most abundant phenolic compounds produced by all the drying treatments (with values that ranged between 88.6‐191.8; 41.7‐91.3 and 33.2‐178.5 mg/100g dry weight of stevia, respectively). The content of volatile compounds was higher with shade drying, whereas most flavonoids and phenolic acids had higher concentrations following freeze drying, although some flavonoids and phenolic acids exhibited a higher increment with air drying. There is no best drying treatment, however, freeze drying results in an extract with satisfactory antioxidant properties and good aromatic characteristics. Copyright © 2015 John Wiley & Sons, Ltd.
Analysis of volatile compounds of clove (syzygium aromaticum) buds as influenced by growth phase and investigation of antioxidant activity of clove extracts
Authors: Kasai Hiroko , Shirao Mika , Ikegami‐Kawai Mayumi
Published: December 2015

The volatile compounds originating from fresh clove (Syzygium aromaticum) buds cultivated in a medicinal plant garden located in southern Tokyo were investigated. The volatile compounds originating from fresh clove buds were adsorbed onto polydimethylsiloxane‐coated devices and then analysed using gas chromatography‐mass spectrometry. Sampling was performed at three different development stages of clove buds, i.e., phase I (green), phase II (pink), and phase III (red). In thermal desorption‐gas chromatography‐mass spectrometry procedure volatile compounds: eugenol, β‐caryophyllene, α‐humulene, α‐farnesene, and eugenol acetate were the predominant constituents in most cases. Methyl salicylate, α‐copaene, β‐ocimene, 2‐nonanone, ethyl hexanoate, and acetophenone were additionally found as the buds ripened. Volatile compounds obtained from clove leaves were analysed using the same method, and β‐caryophyllene, eugenol, α‐humulene, 3‐hexen‐1‐ol, 3‐hexen‐1‐yl acetate, and hexyl acetate were identified.

The antioxidant activity of both water and methanol extracts of clove buds and leaves collected from the medicinal plant garden was confirmed using electron spin resonance spectrometry. Scavenging activities against superoxide anion radical and hydroxyl radical were evaluated. Copyright © 2015 John Wiley & Sons, Ltd.
Absolute bioavailability of evacetrapib in healthy subjects determined by simultaneous administration of oral evacetrapib and intravenous [13C8]‐evacetrapib as a tracer
Authors: Cannady Ellen A. , Aburub Aktham , Ward Chris , Hinds Chris , Czeskis Boris , Ruterbories Kenneth , Suico Jeffrey G. , Royalty Jane , Ortega Demetrio , Pack Brian W. , Begum Syeda L. , Annes William F. , Lin Qun , Small David S.
Published: December 2015

This open‐label, single‐period study in healthy subjects estimated evacetrapib absolute bioavailability following simultaneous administration of a 130‐mg evacetrapib oral dose and 4‐h intravenous (IV) infusion of 175 µg [13C8]‐evacetrapib as a tracer. Plasma samples collected through 168 h were analyzed for evacetrapib and [13C8]‐evacetrapib using high‐performance liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameter estimates following oral and IV doses, including area under the concentration‐time curve (AUC) from zero to infinity (AUC[0‐∞]) and to the last measureable concentration (AUC[0‐tlast]), were calculated. Bioavailability was calculated as the ratio of least‐squares geometric mean of dose‐normalized AUC (oral : IV) and corresponding 90% confidence interval (CI). Bioavailability of evacetrapib was 44.8% (90% CI: 42.2–47.6%) for AUC(0‐∞) and 44.3% (90% CI: 41.8–46.9%) for AUC(0‐tlast). Evacetrapib was well tolerated with no reports of clinically significant safety assessment findings. This is among the first studies to estimate absolute bioavailability using simultaneous administration of an unlabeled oral dose with a 13C‐labeled IV microdose tracer at about 1/1000th the oral dose, with measurement in the pg/mL range. This approach is beneficial for poorly soluble drugs, does not require additional toxicology studies, does not change oral dose pharmacokinetics, and ultimately gives researchers another tool to evaluate absolute bioavailability.
Effects of nitrogen sources and metal ions on ethanol fermentation with cadmium‐containing medium
Authors: Xu Qingyun , Wu Mengnan , Hu Jiajun , Gao Min‐Tian
Published: December 2015

This study evaluated ethanol fermentation and its correlation with glutathione (GSH) synthesis under various cadmium‐conditions with different metal ions and nitrogen sources. We found that corn steep liquor (CSL) and yeast extract have differential roles to play in GSH accumulation in cell even though both of them could alleviate the inhibition by cadmium. The different GSH accumulation in cell resulted from the different contents of metal ions in CSL and yeast extract. Intracellular GSH decreased with increasing calcium concentrations, and high calcium concentrations rendered the yeast more tolerant to cadmium stress than the nitrogen sources did. When the mole ratio of calcium to cadmium was 100:1, yeast tolerated 1000 µmol/L cadmium with no decrease in efficiency in ethanol production. As a result, the use of calcium allowed a significant saving of high‐cost nutrient yeast extract with an efficient ethanol production, making the bioconversion of cadmium‐containing biomass into ethanol possible.
Hail climatology in Serbia
Authors: Ćurić Mladjen , Janc Dejan
Published: December 2015

This study investigates the spatial and temporal characteristics of hail frequency in Serbia during the period 1949–2012. Two areas covering the whole territory of Serbia are treated: a complex terrain area (CTA) and a flat terrain area (FTA). Our research shows that the highest hail frequencies were found in the southwestern mountainous part of the country in the warm season. In the cold season, the area of maximum hail frequency lies in the region of the Sava and the Danube rivers. During the warm season, the highest hail frequencies are recorded in May and June and the smallest in August and September. This spatial pattern is influenced by the passages of the prevailing fronts, surface air temperatures and the convection enhancement by the mountains during the year. The trends of mean hail frequency are negative, except for the FTA in the dry season (August–September) and the cold season, in which nonparametric methods do not show any trends. The highest hail frequency area does not show any trend in the warm season, but interdecadal variability is significant. In general, the CTA has a greater mean hail frequency for all treated seasons. In contrast, the FTA has a greater maximum of mean hail frequency per station in the dry (August–September) and cold seasons. Although very small, the territory of Serbia also shows other peculiarities. In the last decade, the FTA has shown a strong positive trend of mean hail frequency as opposed to the CTA. This is due to the fact that the ridge of the Azores high extended over the CTA more frequently than before 2000.
Pressurized liquid extraction followed by liquid chromatography with tandem mass spectrometry to determine pharmaceuticals in mussels
Authors: Núñez Mireia , Borrull Francesc , Pocurull Eva , Fontanals Núria
Published: December 2015

An analytical method based on pressurized liquid extraction and solid‐phase extraction with a mixed‐mode Oasis® MAX sorbent as cleanup, followed by liquid chromatography with electrospray ionization and tandem mass spectrometry was developed and validated for the determination of seven widely used pharmaceuticals in mussel species. The optimization of the pressurized liquid extraction and the solid‐phase extraction parameters is described. The method provided extraction recoveries ranging from 61 to 90%, and limits of detection ranging from 2 to 50 ng/g (dry weight). The repeatability and reproducibility of the method, expressed as relative standard deviation, were lower than 15 and 19%, respectively. The method was successfully applied to the analysis of mussel samples from different locations. The analyses showed that salicylic acid was present in mussels at concentrations up to 177 ng/g (dry weight).
Solid‐phase purification and extraction for the determination of trace neonicotinoid pesticides in tea infusion
Authors: Zhang Minglu , Chen Hongping , Zhu Li , Wang Chuanpi , Ma Guicen , Liu Xin
Published: December 2015

An analytical protocol that includes solid‐phase purification and extraction is successfully developed for the determination of trace neonicotinoid pesticides in tea infusion. The method consists of a purification on amino‐functionalized mesoporous silica SBA‐15 followed by a solid‐phase extraction based on graphene oxide before ultra high performance liquid chromatography with tandem mass spectrometry analysis. Parameters that significantly affected the extraction of the neonicotinoids onto graphene oxide, such as the amount of adsorbent, extraction time, pH, elution solvent, etc. were optimized. The amino‐functionalized mesoporous silica SBA‐15 has been proved to be an efficient adsorbent for removal of polyphenols especially catechins from tea infusion. Graphene oxide exhibits a very rapid adsorption rate (within 10 min) and high adsorption capacities for neonicotinoids at low initial concentration (0.01–0.5 mg/L). The analysis method gave a good determination coefficient (r2 > 0.99) for each pesticide and high recoveries in the range of 72.2–95.0%. Powder X‐ray diffraction, Raman spectroscopy, transmission electron microscopy, and UV‐vis spectroscopy were utilized to identify the structure and morphology of graphene oxide. The adsorption driving force of neonicotinoids on graphene oxide mainly depends on π–π electron donor–acceptor interaction and electrostatic interaction.
Enzymatically Crosslinked Ulvan Hydrogels as Injectable Systems for Cell Delivery
Authors: Morelli Andrea , Betti Margherita , Puppi Dario , Bartoli Cristina , Gazzarri Matteo , Chiellini Federica
Published: December 2015

The present study represents a challenging effort aiming at converting the waste algal biomass Ulva sp. into a source of high added value materials for biomedical applications by means of a clean and sustainable process. Ulvan, a sulphated polysaccharide extracted from Ulva sp., is investigated as in situ gelling material by using the enzyme horseradish peroxidase as catalyst and H2O2 as reagent. The polysaccharide is successfully modified with tyramine units in order to be susceptible to enzymatic recognition and crosslinking through oxidative coupling. The times of gelation of ulvan‐tyramine solutions are optimized by adjusting the amount of H2O2 used for ensuring their practical administration as injectable systems. The rheological properties of the polymeric solutions and the relevant hydrogels evaluated under operative conditions prove to be suitable as injectable in situ forming 3D‐hydrogels. The preliminary biological assays evidence the full cytocompatibility of the developed hydrogels and their feasibility for being used as 3D‐hydrogels for cell delivery.

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Facile Synthesis of Novel Polyethylene‐Based A‐B‐C Block Copolymers Containing Poly(methyl methacrylate) Using a Living Polymerization System
Authors: Song Xiangyang , Ma Qiong , Cai Zhengguo , Tanaka Ryo , Shiono Takeshi , Grubbs Robert B.
Published: December 2015

Ethylene–propylene–methyl methacrylate (MMA) and ethylene–hexene–MMA A‐B‐C block copolymers with high molecular weight (>100 000) are synthesized using fluorenylamide‐ligated titanium complex activated by modified methylaluminoxane and 2,6‐di‐tert‐butyl‐4‐methylphenol for the first time. After diblock copolymerization of olefin is conducted completely, MMA is added and activated by aluminum Lewis acid to promote anionic polymerization. The length of polyolefin and poly (methyl methacrylate) (PMMA) is controllable precisely by the change of the additive amount of olefin and polymerization time, respectively. A soft amorphous polypropylene or polyhexene segment is located between two hard segments of semicrystalline polyethylene and glassy PMMA blocks.

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Memantine and Cognition in Parkinson's Disease Dementia/Dementia With Lewy Bodies: A Meta‐Analysis
Authors: Brennan Laura , Pantelyat Alexander , Duda John E. , Morley James F. , Weintraub Daniel , Wilkinson Jayne R. , Moberg Paul J.
Published: December 2015

Background

The aim of this work was to utilize meta‐analysis in examining the effects of memantine on neuropsychological functioning in patients with Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB).

Methods

Included studies fulfilled these criteria: included objective cognitive measures, a comparison group of participants not taking memantine, and provided sufficient data for calculation of effect size. We examined effect sizes across global cognition and five specific neuropsychological domains. Moderator variables examined included neuropsychological domain, diagnostic cohort (PDD, DLB, or mixed PDD‐DLB cohort), study design (open label or placebo‐controlled), and trial length.

Results

Six publications met inclusion criteria totaling 57 effects. Homogeneity analysis across cognitive domains revealed a small overall effect size (d = 0.25) that was significantly heterogeneous (P < 0.001). Specific neuropsychological domains did not moderate effect size, though. Moderator analysis studies using a mix of DLB and PDD subjects showed larger effects than those that included DLB or PDD patients only. Additionally, open‐label trials had significantly (P < 0.001) larger effect sizes (d = 1.32) than placebo‐controlled trials (d = 0.12).

Conclusions

The present study indicates that effect‐size heterogeneity across studies of memantine in DLB and PDD patients is moderated by diagnostic makeup of the cohort and study design. The small overall effect size noted in placebo‐controlled trials versus open‐label trials indicates that memantine has minimal effects on cognition in PDD and DLB and is unlikely to demonstrate clinically significant improvements in cognition.
Hydrophilic Modification of Polysulfone Ultrafiltration Membranes by Low Temperature Water Vapor Plasma Treatment to Enhance Performance
Authors: Pegalajar‐Jurado Adoracion , Mann Michelle N. , Maynard Matthew R. , Fisher Ellen R.
Published: December 2015

Porous polymeric membranes are used in numerous applications including water filtration systems. Fouling from proteins, toxins, bacteria, and cells present in the water limits membrane utility. Surface modification techniques that retain desired bulk properties while decreasing fouling can effectively extend membrane lifetime. Herein, water vapor plasmas are utilized to create hydrophilic polysulfone ultrafiltration membranes. The permanency of the treatment over two months correlates to covalent incorporation of hydrophilic functional groups into the polymer backbone. Modified membranes show enhanced hydrodynamic characteristics and do not require preconditioning. Thus, water vapor plasma modification provides a potential route to extend ultrafiltration membrane lifetime.
Non‐inferiority and networks: inferring efficacy from a web of data
Authors: Lin Junjing , Gamalo‐Siebers Margaret , Tiwari Ram
Published: December 2015

In the absence of placebo‐controlled trials, the efficacy of a test treatment can be alternatively examined by showing its non‐inferiority to an active control; that is, the test treatment is not worse than the active control by a pre‐specified margin. The margin is based on the effect of the active control over placebo in historical studies. In other words, the non‐inferiority setup involves a network of direct and indirect comparisons between test treatment, active controls, and placebo. Given this framework, we consider a Bayesian network meta‐analysis that models the uncertainty and heterogeneity of the historical trials into the non‐inferiority trial in a data‐driven manner through the use of the Dirichlet process and power priors. Depending on whether placebo was present in the historical trials, two cases of non‐inferiority testing are discussed that are analogs of the synthesis and fixed‐margin approach. In each of these cases, the model provides a more reliable estimate of the control given its effect in other trials in the network, and, in the case where placebo was only present in the historical trials, the model can predict the effect of the test treatment over placebo as if placebo had been present in the non‐inferiority trial. It can further answer other questions of interest, such as comparative effectiveness of the test treatment among its comparators. More importantly, the model provides an opportunity for disproportionate randomization or the use of small sample sizes by allowing borrowing of information from a network of trials to draw explicit conclusions on non‐inferiority. Copyright © 2015 John Wiley & Sons, Ltd.