bluuebunny/crossref_metadata_2025 huggingface dataset:
Furan [MAK Value Documentation in German language, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: May 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated furan [110‐00‐9]. All toxicity endpoints have been considered and publications are described in detail.

Genotoxicity data show only a secondary genotoxic effect at high doses and no effect at low doses. Therefore, furan is classified as a primary non‐genotoxic carcinogen. As a maximum concentration at the workplace (MAK value) can be derived from available studies, furan was reclassified from Category 2 into Category 4 for carcinogens.

There are no long‐term inhalation studies available to derive a MAK value. In a 13‐week study with rats, subcapsular inflammation and apoptosis in the liver of unclear relevance for humans were observed at 0.12 mg/kg body weight/day with a NOAEL of 0.03 mg/kg body weight/day. These may be adaptive effects and were not observed in a two‐year study or its interim investigations. A physiologically based pharmacokinetic model predicted the burden in human livers to be about three‐fold lower compared with rats. The NOAEL of 0.03 mg/kg body weight/day was scaled to a concentration at the workplace and a MAK value of 0.02 ml/m
3
was derived, also taking into account the lower liver dose in humans.

The MAK value was derived from a systemic NOAEL; therefore, furan is classified in Peak Limitation Category II with the default excursion factor of 2 as sufficient toxicokinetic data are not available, especially for the reactive metabolite cis‐2‐butene‐1,4‐dial.

Model calculations show that dermal absorption would contribute substantially to the systemic toxicity and furan continues to be designated with an „H“.

Because there are no studies on developmental toxicity, furan is assigned to Pregnancy Risk Group D.

There are no data on sensitization.
1‐Decanol [MAK Value Documentation in German language, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: May 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated 1‐decanol [112‐30‐1] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Critical effects are irritation and the tumour‐promoting potential on the skin. Neither appropriate data in humans nor inhalation or oral studies of 1‐decanol with animals are available for derivation of a MAK value. An 8‐week feeding study in Wistar rats with the structurally related 1‐dodecanol resulted in a NOAEL of 100 mg/kg body weight and day. The same NOAEL is assumed for 1‐decanol. From this NOAEL, the concentration in workplace air was calculated according to the Commission's procedure to be 245 mg 1‐decanol/m3. However, as 1‐decanol is irritating and there are no studies of effects in the respiratory tract, a comparison with structurally‐related substances is indicated as well. The RD50values of 45 ml/m3and 50 ml/m3for 2‐ethylhexanol and 1‐octanol, respectively, are rather similar, which can also be assumed for 1‐decanol. Because of its similar irritating potency, the MAK value for 1‐decanol has been established at 10 ml/m3in analogy to 2‐ethylhexanol. As local effects are critical, the substance is assigned to Peak Limitation Category I. The excursion factor of 2 is set in analogy to 2‐ethylhexanol. From a synopsis of all data, 1‐decanol is classified in Pregnancy Risk Group C, despite the small difference between MAK value and NOAEC of 15 ml/m3for developmental toxicity. 1‐Decanol is not mutagenic in bacteria. There are no long‐term studies with 1‐decanol. Papillomas, squamous cell carcinomas and severe skin irritation occurred after 60‐week application to the skin of the mouse following initiation with 7,12‐dimethylbenz[a]anthracene. The maximum skin absorption of 10 mg is less than 25% of the systemically tolerable amount of 660 mg which is taken up by inhalation at the MAK value. There are no positive clinical findings of contact sensitization from 1‐decanol, nor are such effects expected from the structure and the comparison with homologous alcohols. Data for sensitization of the airways are not available.
2‐Phenoxyethanol [MAK Value Documentation in German language, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: May 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has re‐evaluated 2‐phenoxyethanol [122‐99‐6], considering all toxicity endpoints. Available publications and study reports are described in detail.

In a 14‐day inhalation study with rats, critical effects of 2‐phenoxyethanol were hyperplasia, degeneration and metaplasia of the respiratory epithelium in the nasal cavity beginning at 246 mg/m
3
. The NOAEC was 48.2 mg/m
3
(8.4 ml/m
3
). Since 2014, the Commission uses an empirical approach to set maximum concentrations at the workplace (MAK values) for substances with critical effects on the upper respiratory tract or the eyes. Based on this approach, a MAK value of 1 ml/m
3
has been derived. The assignment to Peak Limitation Category I, because local effects are critical, and the excursion factor of 2 have been confirmed.

No developmental toxicity was detected in rats (oral) or rabbits (dermal) up to doses of 1000 or 600 mg/kg body weight and day, resp. In an oral two‐generation study in mice, the NOAEL for foetotoxicity was about 400 mg/kg body weight and day. The differences between the NOAEL for rats, mice and rabbits scaled to an inhalation concentration at the workplace and the MAK value are considered so large that damage to the embryo or foetus is unlikely when the MAK value is observed. Therefore, classification in Pregnancy Risk Group C is confirmed.

2‐Phenoxyethanol is not regarded to be genotoxic or carcinogenic. Sensitization is not expected based on results of animal studies and experience in humans. Skin contact is not expected to contribute significantly to the systemic toxicity.
4‐Nitrobenzoesäure [MAK Value Documentation in German language, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: May 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated 4‐nitrobenzoic acid [62‐23‐7]. Available study reports and publications are described in detail. 4‐Nitro)benzoic acid caused a statistically significantly increased incidence of adenomas and of the sum of adenomas and carcinomas of the clitoris gland in female F344 rats in an oral, 2‐year carcinogenicity study at doses of 60 mg/kg body weight and day and above. The incidence of adenomas and the sum of adenomas and carcinomas was above the range limit of the historical controls of the contract laboratory. As 4‐nitrobenzoic acid is a metabolite of 4‐nitrotoluene, which also induced tumors of the clitoral gland as well as tumors in other organs, 4‐nitrobenzoic acid is classified in analogy to 4‐nitrotoluene in Carcinogen Category 3B. 4‐Nitrobenzoic acid has a weak mutagenic potency in vitro. It did not induce micronuclei in vivo or in vitro. There are no suitable data in humans to derive a MAK value. In rats, a 15‐month study and a 2‐year study resulted in a NOAEL of 60 mg/kg and day for delayed body weight gain in the females. Toxicokinetic scaling results in a concentration of 147 mg/m3in workplace air. The LOAEC for local effects on the olfactory epithelium of rats in a 14‐day study is 150 mg/m3, the NOAEC 20 mg/m3. Since 2014, the Commission uses an empirical approach to set MAK values for substances with critical effects on the upper respiratory tract or the eyes. Based on this approach, a MAK value of 1 mg/m3for the inhalable fraction was derived. The dose of 60 mg/kg body weight and day which resulted in increased incidences of clitoral gland tumors corresponds to a concentration which is about 150 times higher than the MAK value. In view of the evaluation of carcinogenicity, this margin is considered to be sufficiently large. As local effects are critical, the substance is assigned to Peak Limitation Category I. The difference between NOAEC and LOAEC is large, thus an excursion factor of 2 has been established. 4‐Nitrobenzoic acid is assigned to Pregnancy Risk Group D as the available data for prenatal toxicity are insufficient. Skin absorption does not contribute significantly to systemic toxicity and 4‐nitrobenzoic acid is not expected to lead to contact sensitization.
Diphenylamin, octyliert (Benzolamin, N‐Phenyl‐, Reaktionsprodukte mit 2,4,4‐Trimethylpenten) [MAK Value Documentation in German language, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: May 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated octylated diphenylamine [
68411‐46‐1
] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. The critical effect of octylated diphenylamine is hepatotoxicity after repeated gavage administration to rats. Octylated diphenylamine is a UVCB‐substance, a substance of unknown or variable composition, complex reaction products or biological materials. A representative composition is not known. Thus, a MAK value could not be derived and the substance is classified in Section II b of the List of MAK and BAT Values. The substance is not genotoxic. Carcinogenicity studies and data on the potential of contact sensitization in humans are not available. The substance is not a contact sensitizer in guinea pigs. Skin contact is not expected to contribute significantly to systemic toxicity.
N,N‐Bis(2‐ethylhexyl)‐((1,2,4‐triazol‐1‐yl)methyl)amin [MAK Value Documentation in German language, 2017]
Authors: Hartwig A. ,   MAK Commission
Published: May 2017

The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has evaluated N,N‐Bis(2‐ethylhexyl)‐((1,2,4‐triazol‐1‐yl)methyl)amine [
91273‐04‐0
] to derive a maximum concentration at the workplace (MAK value), considering all toxicity endpoints. Available unpublished study reports and publications are described in detail. N,N‐Bis(2‐ethylhexyl)‐((1,2,4‐triazol‐1‐yl)methyl)amine is corrosive to the skin of rabbits and results in irritation of the stomach after gavage administration in rats. Therefore, a local irritation potential is to be assumed. There are no inhalation studies availabe and no read‐across substance could be found. Thus, a MAK value could not be derived and the substance is classified in Section II b of the List of MAK and BAT Values. N,N‐Bis(2‐ethylhexyl)‐((1,2,4‐triazol‐1‐yl)methyl)amine is not genotoxic. Carcinogenicity studies are not available. Maximization tests in guinea pigs reveal a skin sensitizing potential and the substance is designated with „Sh“. Skin contact is not expected to contribute significantly to systemic toxicity.
Optimization Methods For Chemists and Chemometricians
Authors: Eijsbouts Corneel J.G. , Postma Geert J. , Buydens Lutgarde M. C.
Published: May 2017

Optimization problems are abundant in analytical chemistry, while the field of computational science is bringing new optimization methods. These methods differ in strategy, sufficient for some to work very well on one optimization problem, while others are costly, inefficient, or fail at all at finding the optimum. From the chemist's point of view, it can be said that for each optimization problem there exists a suitable method to find the optimum or an acceptable solution.

For problems that can be calculated with a differentiable formula, a method that uses the derivative can find the optimum probably very fast. Problems with multiple local optima are best solved with global optimizers, while for simple problems with only one optimum, a local method is more efficient. Some problems are noisy in the solution, others are too complex to optimize and are better tackled by just trying to find a really good solution instead of the best. This article provides an overview of the established classical and new nonclassical and experimental optimization techniques and highlights the mechanics of the techniques to give an understanding of which technique can be used best for the optimization problem at hand.
Charged Particle Activation Analysis: Applications
Authors: Erramli Hassane , Bounagui Omar El
Published: May 2017

Radioactivation methods in general are essential for trace analysis because of their accuracy; among these methods, charged particle activation analysis (CPAA) is especially suitable for the determination of light elements such as boron, carbon, nitrogen, and oxygen at trace levels in materials. CPAA can also be used advantageously for other heavier elements, if needed, and sometimes be a complement to neutron activation analysis, or even competes with it.

The CPAA is the best reference method because of its high sensitivity and selectivity. It permits the determination of the total concentration, regardless of the chemical state. The surface contamination can be eliminated by etching after irradiation, and absolute concentrations can be obtained by direct comparison with known compounds. There are no matrix effects and no need for reference samples.

In this article, we have described and discussed, in more detail, the principle and some applications of CPAA. Examples are given of typical applications of CPAA technique such as the study of the oxygen profiling in Czochralski‐silicon (Cz‐Si) substrates submitted to a rapid thermal annealing (RTA) and the study of the oxygen behavior in thermally treated Cz‐Si by combining CPAA with ion channeling.

Helium behavior in irradiated UO2is an important role in the mechanical stability of nuclear fuels during and after its use in nuclear power plants. Helium migration mechanisms in bulk uranium dioxide (UO2) have already been the subject of theoretical studies, but there is a lack of experimental data relating to the most stable location in the crystal.

The question of the helium behavior in silicon carbide 6H–SiC single crystals has been studied at the atomic scale by numerical simulations, but no experiment has been carried out to assess the results hitherto. The measurements have shown that a portion of the He is located in the interstitial tetrahedral sites as predicted by the numerical simulations.
Solution‐Processed Monolayer Organic Crystals for High‐Performance Field‐Effect Transistors and Ultrasensitive Gas Sensors
Authors: Peng Boyu , Huang Shuyun , Zhou Zhiwen , Chan Paddy Kwok Leung
Published: May 2017

This work innovatively develops a dual solution‐shearing method utilizing the semiconductor concentration region close to the solubility limit, which successfully generates large‐area and high‐performance semiconductor monolayer crystals on the millimeter scale. The monolayer crystals with poly(methyl methacrylate) encapsulation show the highest mobility of 10.4 cm2 V−1 s−1 among the mobility values in the reported solution‐processed semiconductor monolayers. With similar mobility to multilayer crystals, light is shed on the charge accumulation mechanism in organic field‐effect transistors (OFETs), where the first layer on interface bears the most carrier transport task, and the other above layers work as carrier suppliers and encapsulations to the first layer. The monolayer crystals show a very low dependency on channel directions with a small anisotropic ratio of 1.3. The positive mobility–temperature correlation reveals a thermally activated carrier transport mode in the monolayer crystals, which is different from the band‐like transport mode in multilayer crystals. Furthermore, because of the direct exposure of highly conductive channels, the monolayer crystal based OFETs can sense ammonia concentrations as low as 10 ppb. The decent sensitivity indicates the monolayer crystals are potential candidates for sensor applications.
Ultrahigh and Selective SO2 Uptake in Inorganic Anion‐Pillared Hybrid Porous Materials
Authors: Cui Xili , Yang Qiwei , Yang Lifeng , Krishna Rajamani , Zhang Zhiguo , Bao Zongbi , Wu Hui , Ren Qilong , Zhou Wei , Chen Banglin , Xing Huabin
Published: May 2017

The efficient capture of SO2 is of great significance in gas‐purification processes including flue‐gas desulfurization and natural‐gas purification, but the design of porous materials with high adsorption capacity and selectivity of SO2 remains very challenging. Herein, the selective recognition and dense packing of SO2 clusters through multiple synergistic host–guest and guest–guest interactions by controlling the pore chemistry and size in inorganic anion (SiF62−, SIFSIX) pillared metal–organic frameworks is reported. The binding sites of anions and aromatic rings in SIFSIX materials grasp every atom of SO2 firmly via Sδ+···Fδ− electrostatic interactions and Oδ−···Hδ+ dipole–dipole interactions, while the guest–guest interactions between SO2 molecules further promote gas trapping within the pore space, which is elucidated by first‐principles density functional theory calculations and powder X‐ray diffraction experiments. These interactions afford new benchmarks for the highly efficient removal of SO2 from other gases, even if at a very low SO2 concentration. Exceptionally high SO2 capacity of 11.01 mmol g−1 is achieved at atmosphere pressure by SIFSIX‐1‐Cu, and unprecedented low‐pressure SO2 capacity is obtained in SIFSIX‐2‐Cu‐i (4.16 mmol g−1 SO2 at 0.01 bar and 2.31 mmol g−1 at 0.002 bar). More importantly, record SO2/CO2 selectivity (86–89) and excellent SO2/N2 selectivity (1285–3145) are also achieved. Experimental breakthrough curves further demonstrate the excellent performance of these hybrid porous materials in removing low‐concentration SO2.
Electron Hopping Across Hemin‐Doped Serum Albumin Mats on Centimeter‐Length Scales
Authors: Amdursky Nadav , Wang Xuhua , Meredith Paul , Riley D. Jason , Payne David J. , Bradley Donal D. C. , Stevens Molly M.
Published: May 2017

Exploring long‐range electron transport across protein assemblies is a central interest in both the fundamental research of biological processes and the emerging field of bioelectronics. This work examines the use of serum‐albumin‐based freestanding mats as macroscopic electron mediators in bioelectronic devices. In particular, this study focuses on how doping the protein mat with hemin improves charge‐transport. It is demonstrated that doping can increase conductivity 40‐fold via electron hopping between adjacent hemin molecules, resulting in the highest measured conductance for a protein‐based material yet reported, and transport over centimeter length scales. The use of distance‐dependent AC impedance and DC current–voltage measurements allows the contribution from electron hopping between adjacent hemin molecules to be isolated. Because the hemin‐doped serum albumin mats have both biocompatibility and fabrication simplicity, they should be applicable to a range of bioelectronic devices of varying sizes, configurations, and applications.
Synthesis of Dibenzo[hi,st]ovalene and Its Amplified Spontaneous Emission in a Polystyrene Matrix
Authors: Paternò Giuseppe M. , Chen Qiang , Wang Xiao‐Ye , Liu Junzhi , Motti Silvia G. , Petrozza Annamaria , Feng Xinliang , Lanzani Guglielmo , Müllen Klaus , Narita Akimitsu , Scotognella Francesco
Published: May 2017

A large number of graphene molecules, or large polycyclic aromatic hydrocarbons (PAHs), have been synthesized and display various optoelectronic properties. Nevertheless, their potential for application in photonics has remained largely unexplored. Herein, we describe the synthesis of a highly luminescent and stable graphene molecule, namely a substituted dibenzo[hi,st]ovalene (DBO 1), with zigzag edges and elucidate its promising optical‐gain properties by means of ultrafast transient absorption spectroscopy. Upon incorporation of DBO into an inert polystyrene matrix, amplified stimulated emission can be observed with a relatively low power threshold (ca. 60 μJ cm−2), thus highlighting its high potential for lasing applications.
Chemical Recognition of Active Oxygen Species on the Surface of Oxygen Evolution Reaction Electrocatalysts
Authors: Yang Chunzhen , Fontaine Olivier , Tarascon Jean‐Marie , Grimaud Alexis
Published: May 2017

Owing to the transient nature of the intermediates formed during the oxygen evolution reaction (OER) on the surface of transition metal oxides, their nature remains largely elusive by the means of simple techniques. The use of chemical probes is proposed, which, owing to their specific affinities towards different oxygen species, unravel the role played by these species on the OER mechanism. For that, tetraalkylammonium (TAA) cations, previously known for their surfactant properties, are introduced, which interact with the active oxygen sites and modify the hydrogen bond network on the surface of OER catalysts. Combining chemical probes with isotopic and pH‐dependent measurements, it is further demonstrated that the introduction of iron into amorphous Ni oxyhydroxide films used as model catalysts deeply modifies the proton exchange properties, and therefore the OER mechanism and activity.
A Simple Nanocellulose Coating for Self‐Cleaning upon Water Action: Molecular Design of Stable Surface Hydrophilicity
Authors: Huang Shu , Wang Dayang
Published: May 2017

Coating solid surfaces with cellulose nanofibril (CNF) monolayers via physical deposition was found to keep the surfaces free of a variety of oils, ranging from viscous engine oil to polar n‐butanol, upon water action. The self‐cleaning function was well correlated with the unique molecular structure of the CNF, in which abundant surface carboxyl and hydroxy groups are uniformly, densely, and symmetrically arranged to form a polar corona on a crystalline nanocellulose strand. This isotropic core–corona configuration offers new and easily adoptable guidance to design self‐cleaning surfaces at the molecular level. Thanks to its excellent self‐cleaning behavior, the CNF coating converted conventional meshes into highly effective membranes for oil–water separation with no prior surface treatment required.
Hyperconjugation Is the Source of Helicity in Perfluorinatedn‐Alkanes
Authors: Cormanich Rodrigo A. , O'Hagan David , Bühl Michael
Published: May 2017

Hyperconjugative, steric, and electrostatic effects were evaluated as possible sources of the helicity in linear perfluorinated alkanes through analysis of natural bond orbitals and classical electrostatics. Contrary to previous rationalizations, which indicate dominating steric or electrostatic effects, this analysis indicates that hyperconjugative stabilization through σCC→σ*CFinteractions are the underlying driving force for the origin of the observed helicity in perfluoroalkanes.
Catalysis of Extracellular Deamination by a FAD‐Linked Oxidoreductase after Prodrug Maturation in the Biosynthesis of Saframycin A
Authors: Song Li‐Qiang , Zhang Ying‐Ying , Pu Jin‐Yue , Tang Man‐Cheng , Peng Chao , Tang Gong‐Li
Published: May 2017

The biosynthesis of antibiotics in bacteria is usually believed to be an intracellular process, at the end of which the matured compounds are exported outside the cells. The biosynthesis of saframycin A (SFM‐A), an antitumor antibiotic, requires a cryptic fatty acyl chain to guide the construction of a pentacyclic tetrahydroisoquinoline scaffold; however, the follow‐up deacylation and deamination steps remain unknown. Herein we demonstrate that SfmE, a membrane‐bound peptidase, hydrolyzes the fatty acyl chain to release the amino group; and SfmCy2, a secreted oxidoreductase covalently associated with FAD, subsequently performs an oxidative deamination extracellularly. These results not only fill in the missing steps of SFM‐A biosynthesis, but also reveal that a FAD‐binding oxidoreductase catalyzes an unexpected deamination reaction through an unconventional extracellular pathway in Streptmyces bacteria.
Silver(III)⋅⋅⋅Silver(III) Interactions that Stabilize the syn Form in a Porphyrin Dimer Upon Oxidation
Authors: Singh Akhil Kumar , Khan Firoz Shah Tuglak , Rath Sankar Prasad
Published: May 2017

The interaction between two AgII porphyrins, connected covalently through a highly flexible ethane bridge, in a metalloporphyrin dimer has been investigated upon stepwise oxidation. X‐ray structure determination of one and two‐electron oxidized complexes has clearly revealed only metal‐centered oxidation that results in short Ag−N (porphyrin) distance with large distortion in the porphyrin macrocycle. The 2e‐oxidized complex exhibits significant metallophilic interaction in the form of a close AgIII⋅⋅⋅AgIII contact that brings two porphyrin rings more cofacial with syn‐conformation, which would otherwise stabilize in an anti‐form. The interaction also leads to an intense emission peak at 546 nm at 77 K in the photoluminescence study.
Total Synthesis of Dictyodendrins by the Gold‐Catalyzed Cascade Cyclization of Conjugated Diynes with Pyrroles
Authors: Matsuoka Junpei , Matsuda Yuka , Kawada Yuiki , Oishi Shinya , Ohno Hiroaki
Published: May 2017

In total and formal syntheses of dictyodendrins B, C, E, and F, the key step involved the direct construction of the pyrrolo[2,3‐c]carbazole core by the gold‐catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki–Miyaura coupling), C2 (addition to an aldehyde), N3 (alkylation), and C5 positions (Ullman coupling) provided divergent access to dictyodendrins.
Thermal Disproportionation of Oxo‐Functionalized Graphene
Authors: Grote Fabian , Gruber Christoph , Börrnert Felix , Kaiser Ute , Eigler Siegfried
Published: May 2017

Graphene production by wet chemistry is an ongoing scientific challenge. Controlled oxidation of graphite introduces oxo functional groups; this material can be processed and converted back to graphene by reductive defunctionalization. Although thermal processing yields conductive carbon, a ruptured and undefined carbon lattice is produced as a consequence of CO2 formation. This thermal process is not understood, but it is believed that graphene is not accessible. Here, we thermally process oxo‐functionalized graphene (oxo‐G) with a low (4–6 %) and high degree of functionalization (50–60 %) and find on the basis of Raman spectroscopy and transmission electron microscopy performed at atomic resolution (HRTEM) that thermal processing leads predominantly to an intact carbon framework with a density of lattice defects as low as 0.8 %. We attribute this finding to reorganization effects of oxo groups. This finding holds out the prospect of thermal graphene formation from oxo‐G derivatives.
Allyl‐Palladium‐Catalyzed Ketone Dehydrogenation Enables Telescoping with Enone α,β‐Vicinal Difunctionalization
Authors: Chen Yifeng , Huang David , Zhao Yizhou , Newhouse Timothy R.
Published: May 2017

The telescoping of allyl‐palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.
Ga(III) complex with morin for kidney cancer cell labelling
Authors: Sentkowska Aleksandra , Kilian Krzysztof , Kopeć Maciej , Pyrzyńska Krystyna , Cheda Łukasz
Published: May 2017

The formation of a complex between Ga(III) and morin (3,5,7,2′,4′‐pentahydroxyflavone) was studied. UV–visible, infrared and mass spectroscopies were used to characterize the complex. The stoichiometric ratio for the reaction between metal ion and flavonoid was determined using the methods of Yoe–Jones and Job, which confirmed that a 1:1 Ga–morin complex was formed (estimated binding constant = 2.31 × 104 l mol−1). It was found that the coordination to Ga(III) occurs through the carbonyl oxygen atom and the 3‐OH group of the morin molecule. According to developed conditions, complexation reaction with 68Ga was performed and the complex was used to label kidney cancer cells (CAKI‐1, CAKI‐2, ACHN and 786‐O). The knowledge gained from this study should be useful for the development of new radiopharmaceuticals for diagnostic purposes containing 68Ga.
Bis‐benzimidazolium‐palladium system catalyzed Suzuki‐Miyaura coupling reaction of aryl bromides under mild conditions
Authors: Lin Yi‐Rang , Chiu Chien‐Cheng , Chiu Huai‐Tsu , Lee Dong‐Sheng , Lu Ta‐Jung
Published: May 2017

Bis‐benzimidazolium salts were prepared successfully from commercially available and inexpensive o‐phenylenediamine through a series of simple reactions. The bis‐NHC‐Pd complexes prepared in situ can catalyze Suzuki‐Miyaura cross‐coupling reaction under very mild conditions in aqueous media with excellent yields. The efficiency of this reaction is demonstrated by its compatibility with a range of functional groups. Di‐ortho‐substituted biaryls could be accomplished in 89–99% yields. Moreover, the rigorous exclusion of air or moisture is not required in these transformations.
Polymer‐supported palladium: A hybrid system for multifunctional catalytic application
Authors: Taher Abu , Choudhary Meenakshi , Nandi Debkumar , Siwal Samarjeet , Mallick Kaushik
Published: May 2017

Polymer‐supported palladium was synthesized by applying a single‐step wet chemical synthesis route and the resultant composite material was characterized by means of various techniques. Infrared and UV–visible spectra provided information on the chemical structure of the polymer. Microscopy techniques showed the general morphology of the polymer. The oxidation state of palladium was determined using the X‐ray photoelectron spectroscopy method. The synthesized material was applied as a heterogeneous catalyst for the Heck coupling reaction and also as an electrocatalyst for the oxidation of cysteine.
Attenuation of Follicular Helper T Cell–Dependent B Cell Hyperactivity by Abatacept Treatment in Primary Sjögren's Syndrome
Authors: Verstappen Gwenny M. , Meiners Petra M. , Corneth Odilia B. J. , Visser Annie , Arends Suzanne , Abdulahad Wayel H. , Hendriks Rudi W. , Vissink Arjan , Kroese Frans G. M. , Bootsma Hendrika
Published: May 2017

Objective

To assess the effect of abatacept (CTLA‐4Ig), which limits T cell activation, on homeostasis of CD4+ T cell subsets and T cell–dependent B cell hyperactivity in patients with primary Sjögren's syndrome (SS).

Methods

Fifteen patients with primary SS treated with abatacept were included. Circulating CD4+ T cell and B cell subsets were analyzed by flow cytometry at baseline, during the treatment course, and after treatment was completed. CD4+ effector T cell subsets and Treg cells were identified based on expression of CD45RA, CXCR3, CCR6, CCR4, CXCR5, programmed death 1, inducible costimulator (ICOS), and FoxP3. Serum levels of anti‐SSA/anti‐SSB and several T cell–related cytokines were measured. Expression of ICOS and interleukin‐21 (IL‐21) protein was examined in parotid gland tissue at baseline and after treatment. Changes in laboratory parameters and associations with systemic disease activity (EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]) over time were analyzed using generalized estimating equations.

Results

Abatacept selectively reduced percentages and numbers of circulating follicular helper T (Tfh) cells and Treg cells. Other CD4+ effector T cell subsets were unaffected. Furthermore, expression of the activation marker ICOS by circulating CD4+ T cells and expression of ICOS protein in parotid gland tissue declined. Reduced ICOS expression on circulating Tfh cells correlated significantly with lower ESSDAI scores during treatment. Serum levels of IL‐21, CXCL13, anti‐SSA, and anti‐SSB decreased. Among circulating B cells, plasmablasts were decreased by treatment. After cessation of treatment, all parameters gradually returned to baseline.

Conclusion

Abatacept treatment in patients with primary SS reduces circulating Tfh cell numbers and expression of the activation marker ICOS on T cells. Lower numbers of activated circulating Tfh cells contribute to attenuated Tfh cell–dependent B cell hyperactivity and may underlie the efficacy of abatacept.
The impact of stereoscopic imagery and motion on anatomical structure recognition and visual attention performance
Authors: Remmele Martin , Schmidt Elena , Lingenfelder Melissa , Martens Andreas
Published: May 2017

Gross anatomy is located in a three‐dimensional space. Visualizing aspects of structures in gross anatomy education should aim to provide information that best resembles their original spatial proportions. Stereoscopic three‐dimensional imagery might offer possibilities to implement this aim, though some research has revealed potential impairments that may result from observing stereoscopic visualizations, such as discomfort. However, possible impairments of working memory such as decreased visual attention performance due to applying this technology in gross anatomy education have not yet been investigated. Similarly, in gross anatomy education the impact of stereoscopic imagery on learners’ recognition of anatomical‐spatial relationships and the impact of different presentation formats have only been investigated in a small number of studies. In this study, the performance of 171 teacher trainees working on the anatomy of hearing was examined, either with non‐stereoscopic or stereoscopic imagery. Static and dynamic picture presentations were applied. Overall, benefits for stereoscopic imagery on estimating anatomical‐spatial relations were found. The performance on a visual attention test indicates that the impact of stereoscopic visualizations on the human cognitive system varies more from person to person compared to non‐stereoscopic visualizations. In addition, combinations of temporarily moving pictures and stereoscopic imagery lead to decreased visual attention performance compared to combinations of moving pictures and non‐stereoscopic imagery. Anat Sci Educ 11: 15–24. © 2017 American Association of Anatomists.
Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer
Authors: Aronsson M , Carlsson P , Levin L-Å , Hager J , Hultcrantz R
Published: May 2017

Background

Colorectal cancer screening can decrease morbidity and mortality. However, there are widespread differences in the implementation of programmes and choice of strategy. The primary objective of this study was to estimate lifelong costs and health outcomes of two of the currently most preferred methods of screening for colorectal cancer: colonoscopy and sensitive faecal immunochemical test (FIT).

Methods

A cost-effectiveness analysis of colorectal cancer screening in a Swedish population was performed using a decision analysis model, based on the design of the Screening of Swedish Colons (SCREESCO) study, and data from the published literature and registries. Lifelong cost and effects of colonoscopy once, colonoscopy every 10 years, FIT twice, FIT biennially and no screening were estimated using simulations.

Results

For 1000 individuals invited to screening, it was estimated that screening once with colonoscopy yielded 49 more quality-adjusted life-years (QALYs) and a cost saving of €64 800 compared with no screening. Similarly, screening twice with FIT gave 26 more QALYs and a cost saving of €17 600. When the colonoscopic screening was repeated every tenth year, 7 additional QALYs were gained at a cost of €189 400 compared with a single colonoscopy. The additional gain with biennial FIT screening was 25 QALYs at a cost of €154 300 compared with two FITs.

Conclusion

All screening strategies were cost-effective compared with no screening. Repeated and single screening strategies with colonoscopy were more cost-effective than FIT when lifelong effects and costs were considered. However, other factors such as patient acceptability of the test and availability of human resources also have to be taken into account.
Effect of lamotrigine on seizure development in a rat pentylenetetrazole kindling model
Authors: Chen Yishu , He Xiaokuo , Sun Qianqian , Fang Ziyan , Zhou Liemin
Published: May 2017

Introduction

Epileptogenesis is a process of seizure development. Lamotrigine is a novel antiepileptic drug which is also used for antiepileptogenic research. Kindling models are recommended as potentially useful tools for antiepileptogenic treatment discovery. However, previous studies demonstrated that the antiepileptogenic effect of lamotrigine is controversial in the electrical kindling model. Chemical kindling such as with pentylenetetrazole is another kindling model. The aims of this study were to examine whether lamotrigine could prevent the development of seizure in pentylenetetrazole kindling rats.

Methods

Female rats were kindled by subconvulsive doses of pentylenetetrazole (35 mg/kg) once every other day for 15 times. Thereafter, the kindled rats received different doses of lamotrigine (5, 10 and 20 mg/kg) before pentylenetetrazole to observe the anticonvulsant effect. For the antiepileptogenic experiment, rats were kindled as the same way while pretreated (1 h) with different doses of lamotrigine (5, 10 and 20 mg/kg) before each injection of pentylenetetrazole. After a washout period for 1 week, the rats were administrated with pentylenetetrazole again for 3 times. The seizures were recorded each time. Later it was in vivo electrophysiological experiments followed with histologic analysis.

Results

For the anticonvulsant experiment lamotrigine dose‐dependently suppressed pentylenetetrazole‐induced seizures. Here, 20 mg/kg of lamotrigine pretreatment significantly blocked the seizure development in rats for their seizure stages remained longer in 1–3 during the kindling phase. Mean seizure stages or generalized seizure durations in the 10 and 20 mg/kg lamotrigine pretreated groups were significantly lower or shorter when received 3 times of pentylenetetrazole after the washout period. Electrophysiological study also demonstrated 20 mg/kg of lamotrigine pretreatment obviously eliminated increased population spike amplitude in hippocampus. However, different doses of lamotrigine pretreatment could not alleviate severity of hippocampal neuronal damage.

Conclusions

The results suggest that adequate doses of lamotrigine can prevent seizure development in the pentylenetetrazole kindling rat model.
Spinal epidural hematoma following a thoracic epidural in a child with sickle cell disease
Authors: Sathyamoorthy Madhankumar , Walker Benjamin , Rhodes Melissa M. , Eriator Ike
Published: May 2017

Key Clinical Message

Acute liver dysfunction in the perioperative period may increase the risk of epidural hematoma in a patient with a neuraxial catheter. Coagulation testing needs to be carefully monitored in these patients. An epidural hematoma should be ruled out urgently by CT or MRI in cases of a persistent motor block.
N‐Heterocyclic Phosphenium Complex of Manganese: Synthesis and Catalytic Activity in Ammonia Borane Dehydrogenation
Authors: Gediga Micheal , Feil Christoph M. , Schlindwein Simon H. , Bender Johannes , Nieger Martin , Gudat Dietrich
Published: May 2017

A neutral N‐heterocyclic phosphenium complex of manganese was synthesised by a metathesis approach and characterised by IR, NMR, and XRD studies. The short P−Mn distance suggests a substantial metal–ligand double bond character. Reaction with a hydride produced an anionic phosphine complex, which was also characterised by IR and NMR spectroscopy and, after anion exchange, a single‐crystal XRD study. Protonation of the anion occurs at the metal to yield a neutral phosphine metal carbonyl hydride, which releases dihydrogen upon irradiation with UV light. These reactions confirm the electrophilic nature of the phosphenium ligand and suggest that the title complex might undergo reactions displaying metal–ligand cooperativity. Surprisingly, reaction with ammonia borane (AB) did not proceed under transfer hydrogenation of the Mn=P double bond but through the catalytic dehydrogenation of AB. The phosphenium complex behaves here as a class II catalyst, which dehydrogenates AB to NH2BH2 that was trapped with cyclohexene. Computational model studies led to the identification of two possible catalytic cycles, which differ in the regioselectivity of the initial AB activation step. In one case, the activation proceeds as cooperative transfer hydrogenation of the Mn=P bond, whereas in the other case a H+/H− pair is transferred to the phosphorus atom and a nitrogen atom of the phosphenium unit, resulting in a ligand‐centred reaction in which the metal fragment acts merely as stabilising substituent. Unexpectedly, this pathway, which constitutes a new reaction mode for phosphenium complexes, seems to be better in accord with experimental findings on the course of the catalysis.
Electron Transfer of Cytochrome c on Surface‐Enhanced Raman Scattering–Active Substrates: Material Dependence and Biocompatibility
Authors: Li Junbo , Cheng Weina , Wang Xiaolei , Zhang Haijing , Jin Jing , Ji Wei , Han Xiao Xia , Zhao Bing
Published: May 2017

Surface‐enhanced Raman spectroscopy (SERS) represents a powerful approach for studying the structure and reaction of proteins in fundamental and applied sciences. The surface properties of SERS‐active materials determine important parameters such as Raman enhancement ability, biocompatibility, and electronic communication between supports and proteins. Here, electron transfer (ET) of Cyt c on noble metals and transition metals is investigated by SERS spectroscopy. The results here indicate that the ET occurs from the reduced state of Cyt c to silver substrate, depending on the laser wavelengths. Nickel and cobalt can directly transfer electrons to the oxidized state of Cyt c, which enables a reductive activity of these transition metal nanoparticles (NPs). This study demonstrates the role of transition metals as electron donors for Cyt c and has proved that the charge transfer theory for SERS is applicable for explanation of the ET between Cyt c and Ag NPs.
Ratiometric Fluorescent Probes for the Detection of Reactive Oxygen Species
Authors: Andina Diana , Leroux Jean‐Christophe , Luciani Paola
Published: May 2017

Reactive oxygen species (ROS) are endogenously produced oxidants with various functions ranging from host defense to signaling. These transient species can cause severe damage to the body when their production is dysregulated or when environmental factors elevate their concentrations. To study their effects and prevent oxidative harm, tools capable of monitoring ROS in cells and tissue in a sensitive and selective fashion are required. In this Review, a summary of existing ratiometric probes is provided, together with a critical discussion of selected examples.
A Two‐Step Synthesis of 2‐Spiropiperidines
Authors: Griggs Samuel D. , Thompson Nathan , Tape Daniel T. , Fabre Marie , Clarke Paul A.
Published: May 2017

A general two‐step synthesis of 2‐spiropiperidines has been developed. δ‐Amino‐β‐ketoesters can be reacted with cyclic ketones to generate 2‐spiropiperidines in good to excellent yields. The 2‐spiropiperidines formed occupy an under‐explored region of 3D‐chemical space and are novel scaffolds for use in drug discovery programs. These 2‐spiropiperidines can be further functionalised to generate small highly sp3‐rich structures, which exhibit an excellent likeness to lead‐molecules in drug discovery.
Safety and efficacy of DOACs vs acenocoumarol in patients undergoing catheter ablation of atrial fibrillation
Authors: Vlachos Konstantinos , Efremidis Michael , Bazoukis George , Letsas Konstantinos P. , Saplaouras Athanasios , Georgopoulos Stamatis , Karamichalakis Nikolaos , Rokiza Aikaterini , Sakellaropoulou Antigoni , Kolokathis Angelos Michail , Efremidis Theodoros , Asvestas Dimitrios , Sideris Antonios
Published: May 2017

Background

Thromboembolic complications can be life‐threatening during atrial fibrillation (AF) catheter ablation. The aim of our study was to evaluate the safety and efficacy of continuous treatment using direct oral anticoagulants (DOACs) as an alternative to uninterrupted acenocoumarol for periprocedural anticoagulation.

Hypothesis

Continuous treatment with DOACs has similar safety and efficacy compared to acenocoumarol.

Methods

We enrolled 474 patients (mean age, 58 years; 68.4% male) undergoing AF catheter ablation between June 2013 and December 2016. All patients were equally assigned to take acenocoumarol (group 1, 136 patients) or DOACs (group 2, 338 patients) for ≥2 months before the procedure. We compared thromboembolic and bleeding complications between the 2 groups.

Results

Our analysis showed no significant difference in major and minor complications between the 2 patient groups. Specifically, 3 of 136 patients (2.2%) using uninterrupted acenocoumarol had a major complication (1 patient [0.7%] had transient ischemic attack resolved 8 hours later, 1 [0.7%] had pericardial tamponade, and 1 [0.7%] had a subcapsular renal hematoma) and 2 patients (1.4%) had minor complications (1 [0.7%] pseudoaneurysm and 1 [0.7%] groin hematoma). In group 2, 1 of 338 patients (0.3%) had a major complication (transient ischemic attack). In the same group, 7 patients (2.1%) had a minor complication (1 patient [0.3%] presented with pseudoaneurysm, 4 [1.2%] with pericardial effusion <1 cm, 1 [0.3%] femoral arteriovenous fistula between the femoral artery and femoral vein, and 1 [0.7%] groin hematoma).

Conclusions

DOACs and acenocoumarol have similar safety and effectiveness regarding thromboembolic complications prevention without increasing bleeding complications.
Mass Production of Monodisperse Carbon Microspheres with Size‐Dependent Supercapacitor Performance via Aqueous Self‐Catalyzed Polymerization
Authors: Yu Qiang , Guan Doudou , Zhuang Zechao , Li Jiantao , Shi Changwei , Luo Wen , Zhou Liang , Zhao Dongyuan , Mai Liqiang
Published: May 2017

A facile, aqueous, self‐catalyzed polymerization method has been developed for the mass production of monodisperse phenolic resin and carbon microspheres. The synthesis is mainly based on the self‐catalyzed reaction between phenol derivatives and the hydrolysis products of hexamethylenetetramine (HMTA). The obtained phenolic resin spheres have a tunable size of 0.8–6.0 μm, depending on the type of phenol and HMTA/phenol ratio. Treating the phenolic resin with steam at an elevated temperature results in monodisperse carbon microspheres with abundant micropores, high surface area, and rich surface functionality. The resultant carbon spheres exhibit a size‐dependent electrical double‐layer capacitor performance; the capacitance increases with decreasing particle size. The nitrogen and oxygen codoped carbon spheres with the smallest size (≈600 nm) deliver a high specific capacitance (282 F g−1 at 0.5 A g−1), excellent rate capability (170 F g−1 at 20 A g−1), and outstanding cycling stability (95.3 % capacitance retention after 10 000 cycles at 5 A g−1). This study provides a new avenue for the mass production of monodisperse carbon microspheres.
Emerging Targets of Diuretic Therapy
Authors: Cheng C‐J , Rodan AR , Huang C‐L
Published: May 2017

Diuretics are commonly prescribed for treatment in patients with hypertension, edema, or heart failure. Studies on hypertensive and salt‐losing disorders and on urea transporters have contributed to better understanding of mechanisms of renal salt and water reabsorption and their regulation. Proteins involved in the regulatory pathways are emerging targets for diuretic and aquaretic therapy. Integrative high‐throughput screening, protein structure analysis, and chemical modification have identified promising agents for preclinical testing in animals. These include WNK‐SPAK inhibitors, ClC‐K channel antagonists, ROMK channel antagonists, and pendrin and urea transporter inhibitors. We discuss the potential advantages and side effects of these potential diuretics.