bluuebunny/crossref_metadata_2025 huggingface dataset:
Aluminium chloride promotes tumorigenesis and metastasis in normal murine mammary gland epithelial cells
Authors: Mandriota Stefano J. , Tenan Mirna , Ferrari Paolo , Sappino André‐Pascal
Published: August 2016

Aluminium salts, present in many industrial products of frequent use like antiperspirants, anti‐acid drugs, food additives and vaccines, have been incriminated in contributing to the rise in breast cancer incidence in Western societies. However, current experimental evidence supporting this hypothesis is limited. For example, no experimental evidence that aluminium promotes tumorigenesis in cultured mammary epithelial cells exists. We report here that long‐term exposure to concentrations of aluminium—in the form of aluminium chloride (AlCl3)—in the range of those measured in the human breast, transform normal murine mammary gland (NMuMG) epithelial cells in vitro as revealed by the soft agar assay. Subcutaneous injections into three different mouse strains with decreasing immunodeficiency, namely, NOD SCID gamma (NSG), NOD SCID or nude mice, revealed that untreated NMuMG cells form tumors and metastasize, to a limited extent, in the highly immunodeficient and natural killer (NK) cell deficient NSG strain, but not in the less permissive and NK cell competent NOD SCID or nude strains. In contrast, NMuMG cells transformed in vitro by AlCl3 form large tumors and metastasize in all three mouse models. These effects correlate with a mutagenic activity of AlCl3. Our findings demonstrate for the first time that concentrations of aluminium in the range of those measured in the human breast fully transform cultured mammary epithelial cells, thus enabling them to form tumors and metastasize in well‐established mouse cancer models. Our observations provide experimental evidence that aluminium salts could be environmental breast carcinogens.
A Novel ANO5 Mutation Causing Gnathodiaphyseal Dysplasia With High Bone Turnover Osteosclerosis
Authors: Rolvien Tim , Koehne Till , Kornak Uwe , Lehmann Wolfgang , Amling Michael , Schinke Thorsten , Oheim Ralf
Published: August 2016

Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome that involves an osteopetrosis-like sclerosis of the long bones and fibrous dysplasia–like cemento-osseous lesions of the jawbone. Although the genetic analysis of the respective patients has revealed mutations in the ANO5 gene as an underlying cause, there is still no established consensus regarding the bone status of GDD patients. We report a new case of GDD in a 13-year-old boy with recurrent diaphyseal fractures of the femur, in whom we identified a novel de novo missense mutation in the ANO5 gene, causing a p.Ser500Phe substitution at the protein level. After confirming the presence of GDD-characteristic abnormalities within the jaw bones, we focused on a full osteologic assessment using dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses. We thereby identified increased trabecular bone mass accompanied by elevated serum markers of bone formation and bone resorption. The high turnover bone pathology was further confirmed through the analysis of an iliac crest biopsy, where osteoblast and osteoclast indices were remarkably increased. Taken together, our findings provide evidence for a critical and generalized role of anoctamin-5 (the protein encoded by the ANO5 gene) in skeletal biology. As it is reasonable to speculate that modifying the function of anoctamin-5 might be useful for therapeutically activating bone remodeling, it is now required to analyze its function at a molecular level, for instance in mouse models. © 2016 American Society for Bone and Mineral Research.
Use of Zolpidem and Risk of Acute Pyelonephritis in Women: A Population‐Based Case‐Control Study in Taiwan
Authors: Hsu Fan‐Gen , Sheu Ming‐Jyh , Lin Cheng‐Li , Hsieh Yow‐Wen , Lai Shih‐Wei
Published: August 2016

The aim of this study was to assess a possible correlation between zolpidem use and acute pyelonephritis (APN) in women in Taiwan. Therefore, we performed a case‐control study involving the Taiwan's National Health Insurance Research Database between 2000 and 2011. This study included 3151 female participants aged 20 to 84 years who experienced the first bout of APN (case group) and 6015 randomly selected female participants without APN (control group). Zolpidem use was defined as “current,” “early,” or “late,” if the last remaining 1 tablet for zolpidem was detected within 7 days, between 8 and 14 days, or ≥15 days before the date of APN diagnosis, respectively. The multivariable unconditional logistic regression model was used to calculate the odds ratios (ORs) with 95% confidence intervals (CIs) to assess the correlation between zolpidem use and APN. After adjusting for confounders, the multivariable analysis yielded an adjusted APN OR of 2.2 for participants with current zolpidem use (95%CI 1.7‐2.8) compared with participants who never used zolpidem. The adjusted ORs gradually decreased to 1.4 for participants with early zolpidem use (95%CI 0.8‐2.5) and 1.1 for participants with late zolpidem use (95%CI 0.9‐1.2), but without statistical significance. Only patients with current zolpidem use had a significantly increased relative risk of APN. Additional large confirmatory studies are needed to illustrate a causal relationship. Meanwhile, physicians and pharmacists should be more cautious about the risk of APN when prescribing and dispensing zolpidem in women.
Effective and Green One‐Pot Multicomponent Synthesis of Novel Derivatives of 4H‐Pyrans in the Presence of Hexamethylenetetramine as Catalyst in Water Medium
Authors: Habibi Maysam , Habibi Azizollah , Hakimi Nasab Saber , Dolati Hadi , Mahdavi Seyedeh Mahbobeh
Published: August 2016

Hexamethylenetetramine catalyzes synthesis of new polyfunctionalized 4H‐pyrans by the reaction of aromatic aldehyde, malononitrile, and β‐keto esters via one‐pot three‐component procedure in water medium. Addition of reactants was performed by two methods led to achieve similar results. Using hexamethylenetetramine in catalytic amount not only represents the economic face of the reaction but also due to the use of water, a green and safe reaction condition is organized. Thus, the current strategy provides the benefits of high productivity, convenient operation, and environmental friendliness. The structure of all products were proved by elemental analysis, IR, 1H NMR, and 13C NMR spectroscopy.
Effects of perfusion on DTI and DKI estimates in the skeletal muscle
Authors: De Luca Alberto , Bertoldo Alessandra , Froeling Martijn
Published: August 2016

Purpose

In this study, we evaluated the effects of perfusion of the skeletal muscle on diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI) parameters and their reproducibility.

Methods

Diffusion tensor imaging and DKI models, with and without intravoxel incoherent motion (IVIM) correction, were applied to simulated data at different physiological conditions and signal‐to‐noise ratio levels. Next, the same models were applied to data of the right calf of five healthy volunteers, acquired twice at 3 telsa. For six muscles, we evaluated the correlation of the perfusion signal fraction, with parameters derived from DTI and DKI, and performed repeatability analysis with and without IVIM correction. Additionally, the IVIM correction was compared to a multishell acquisition approach that minimizes perfusion effects on DTI estimates.

Results

Simulations and acquired data showed that DTI and DKI estimates were biased proportionally to the perfusion signal fraction, and that IVIM correction was needed for accurate estimation of the DTI and DKI parameters. However, taking perfusion into account did not improve repeatability.

Conclusion

Blood perfusion has an effect on DTI and DKI estimations, but it can be minimized with IVIM correction or multishell acquisition strategies. Magn Reson Med 78:233–246, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Enhanced performance of ultraviolet organic light‐emitting diode by using graphene oxide and MoO3 dual hole injection layer
Authors: Liu Liming , You Fengjiao , Zheng Qinghong , Mo Bingjie , Zeng Baoqing , Wang Honghang , Zhang Xiaowen , Wei Bin
Published: August 2016

A dual hole injection layer (d‐HIL) composed of graphene oxide (GO) and transition metal oxide MoO3 is constructed and proven to be effectively promotes the radiance and external quantum efficiency (EQE) of ultraviolet organic light‐emitting diode (UV OLED). The device with d‐HIL behaves a maximum radiance of 4.7 mW/cm2 at 237.5 mA/cm2 and EQE of 1.36% at 3.75 mA/cm2, which have been enhanced by 27% and 19%, respectively, in comparison with the coun‐ terpart using conventional MoO3single HIL. The ultraviolet photoelectron spectroscopy elucidates that GO/MoO3 modification to the greatest extent enhances work function. The current‐voltage characteristics and impedance spectroscopy of Hole‐only devices clarify that GO/MoO3 d‐HIL considerably promotes hole injection capacity. Our results indicate that the d‐HIL of GO/MoO3 paves a way for constructing efficient UV OLED.
Dopant‐free back contact silicon heterojunction solar cells employing transition metal oxide emitters
Authors: Wu Weiliang , Bao Jie , Jia Xuguang , Liu Zongtao , Cai Lun , Liu Binhui , Song Jingwei , Shen Hui
Published: August 2016

The present study investigates the electrical properties of transition metal oxide (TMO) emitters in dopant‐free n‐Si back contact solar cells by comparing the properties of solar cells employing three TMOs (WOx, MoOx and V2Ox) with varying electrical properties acting as p‐type contacts. The TMOs are found to induce large band bending in n‐Si, which reduces the injection level dependent interfacial recombination speed Seff and contact resistivity ρc. Among the TMO/n‐Si contacts considered, the V2Ox/n‐Si contact achieves the lowest Seff of 138 cm/s and ρc of 0.034 Ω cm2, providing the significant advantages over heavily doped a‐Si:H(p)/n‐Si contacts. The best device performance was achieved by the V2Ox/n‐Si solar cell, demonstrating an efficiency of 16.59% and an open‐circuit voltage of 610 mV relative to solar cells based on MoOx/n‐Si (15.09%, 594 mV) and WOx/n‐Si (12.44%, 539 mV). Furthermore, the present work is the first to employ WOx, V2Ox and Cs2CO3 in back contact solar cells. The fabrication process employed offers great potential for the mass production of back contact solar cells owing to simple, metal mask patterning with high alignment quality and dopant‐free steps conducted at a lower temperature.
Overview of Oroxylin A: A Promising Flavonoid Compound
Authors: Lu Lu , Guo Qinglong , Zhao Li
Published: August 2016

Oroxylin A is one of the main active components extracted from Scutellariae radix. It has been proved that oroxylin A possesses a broad spectrum of pharmacological functions, including anti‐cancer, antiinflammation, neuroprotective, anti‐coagulation and so on. The pharmacological activity of oroxylin A has been studied in vitro and on animal models, which reflected its promising potency in disease treatment. This review aims to recapitulate the pharmacological function and the molecular mechanisms of oroxylin A, as well as its sources, extraction, synthesis and toxicity study. These data confirmed the therapeutic potential of oroxylin A and provided reference for further development. Copyright © 2016 John Wiley & Sons, Ltd.
The spatiotemporal structure of precipitation in Indian monsoon depressions
Authors: Hunt Kieran M. R. , Turner Andrew G. , Parker David E.
Published: August 2016

Indian monsoon depressions are synoptic‐scale events typically spun up in the Bay of Bengal. They usually last 4–6 days, during which they propagate northwestward across the Indian subcontinent before dissipating over northwest India or Pakistan. They can have a significant effect on monsoon precipitation, particularly in primarily agrarian northern India, and therefore quantifying their structure and variability and evaluating these in numerical weather prediction (NWP) models and general circulation models (GCMs) is of critical importance. In this study, satellite data from CloudSat and recently concluded Tropical Rainfall Measuring Mission (TRMM) missions are used in conjunction with an independently evaluated tracking algorithm to form a three‐dimensional composite image of cloud structure and precipitation within monsoon depressions. The composite comprises 34 depressions from the 1998–2014 TRMM mission and 12 from the 2007–present CloudSat mission and is statistically robust enough to allow significant probing of the spatiotemporal characteristics of moisture and hydrometeor fields. Among the key results of this work are the following: the discovery and characterization of a bimodal, diurnal cycle in surface precipitation; the first picture of the structure of cloud type and density in depressions, showing that deep convection dominates south of the centre and prominent cirrus throughout; the first composite picture of vertical hydrometeor structure in depressions, showing significant precipitation for hundreds of kilometres outside the centre and well past the mid‐troposphere; and a novel discussion of drop‐size distributions (showing significant uniformity across the depression) and the resulting latent heat profiles, showing that average heating rates near the centre can reach 2 K h‐1.
Rapid identification of miglitol and its isomers by electrospray ionization tandem mass spectrometry
Authors: Yin Qiuhong , Wang Lin , Sun Cuirong
Published: August 2016

Rationale

Miglitol (1) derived from 1‐deoxynojirimycin is an iminosugar that is useful in the treatment of type 2 diabetes mellitus. Isomers (2, 3, 4) that differ at the C2 and C3 positions of hydroxyl groups from miglitol are impurities resulting from the synthesis of miglitol. The impurity profile of a drug substance is critical to its safety assessment and is important for monitoring the manufacturing process. Therefore, developing a fast and simple method that can rapidly identify the configuration of miglitol and its isomers (2, 3, 4) is necessary.

Methods

Miglitol (1) and its isomers 2–4 were derivatized with benzoboroxole (o‐hydroxymethyl phenylboronic acid) at room temperature, and the cyclic boronate esters of different configurations were generated. Protonated miglitol and its isomers 2–4, as well as their derivatives, were subjected to collision‐induced dissociation (CID) experiments by using electrospray ionization tandem mass spectrometry (ESI‐MS/MS). Elemental compositions of all the ions were verified by electrospray ion‐trap time‐of‐flight mass spectrometry.

Results

Fragmentation of the protonated miglitol and its isomers gave the same fragment ions at m/z 190 and m/z 146. Both their fragmentation behavior and abundances were similar. Whereas the CID mass spectra of the precursor ions (m/z 322) of cyclic boronate esters showed four characteristic fragment ions, m/z 214 ([M‐C7H8O]−), m/z 196 ([M‐C7H8O‐H2O]−), m/z 151 ([M‐C8H13NO3]−), and m/z 133 ([M‐C8H15NO4]−). The abundances of these fragments are different which are related to the stereostructure of miglitol and its isomers.

Conclusions

A facile method was established for the differentiation of the spatial configuration of miglitol and its isomers using the relative abundances of the fragment ions of boronate esters generated from in‐situ reaction between analytes and benzoboroxole by ESI‐MS/MS. This approach could be used to rapidly identify the stereoisomers and monitor the epimerization of miglitol and its isomers in chemical reactions and manufacturing processes. Copyright © 2016 John Wiley & Sons, Ltd.
Characterization of interaction property of multi‐components in Gardenia jasminoides with aldose reductase by microdialysis combined with liquid chromatography coupled to mass spectrometry
Authors: Wang Lu , Liu Shu , Xing Junpeng , Liu Zhiqiang , Song Fengrui
Published: August 2016

Rationale

An application of microdialysis sampling for evaluation of the interaction property of small molecules to macromolecules is presented. Microdialysis combined with liquid chromatography coupled to quadrupole time‐of‐flight tandem mass spectrometry (LC/QTOF‐MS/MS) was established for the purpose of screening of the multiple bioactive compounds in traditional Chinese medicines (TCMs).

Methods

Microdialysis experiments were performed in vitro using a syringe pump and probes. Separation was achieved via liquid chromatography, and MS analysis was conducted by electrospray ionization quadrupole time‐of‐flight mass spectrometry in negative mode. The interaction property of compounds in TCMs with aldose reductase can be deduced from the comparison of the peak areas in chromatograms using a stable internal standard.

Results

In this work, 23 compounds including iridoids, flavonoids, monoterpenoids, carotenoids and phenolic acids were identified by comparison with reference compounds, characteristic high‐resolution mass spectrometry and the MS/MS fragmentations simultaneously. Binding degrees of 23 compounds in Gardenia jasminoides Eliis (G. jasminoide) with aldose reductase ranged from 13.91% to 66.25%. Also, microdialysis recoveries of 23 compounds in G. jasminoides were determined.

Conclusions

The Interaction properties of 23 compounds in G. jasminoides with aldose reductase were investigated and they are potential bioactive ingredients. Microdialysis coupled to LC/QTOF‐MS/MS can be used for screening of bioactive multicomponents from TCMs with appropriate targets. Copyright © 2016 John Wiley & Sons, Ltd.
Study on diffusion behavior of analyte in an electrospray ionization source
Authors: Gao Fang Yuan , Zhang Ling Yi , Li Xiu Qin , Zhang Wei Bing , Zhang Qing He
Published: August 2016

Rationale

Diffusion of an analyte is one of the main determinants of reduced sensitivity in an electrospray ionization (ESI) source. In this work, the relative responses of compounds and their stable isotope‐labeled (SIL) products in different injection modes were compared to investigate the diffusion behavior of analytes in ESI, without influence of other factors.

Methods

Chloramphenicol (CAP) and D5‐CAP as well as melamine (Mel) and 13C3‐Mel were used to illustrate the diffusion behavior in different operation modes and different ion sources, by comparing their relative responses in infusion mode and flow injection analysis (FIA) mode under variable temperature.

Results

In infusion mode, sample solution was introduced by syringe, and formed a stable and continuous signal. While in FIA mode, because of the huge difference in volume between the sample solution and the mobile phase, it is assumed that analyte ionizes and transmits in the gaseous phase created by the mobile phase. Analytes formed different concentration distributions in the two injection modes. The relative responses of CAP and D5‐CAP increased from 0.81 to 0.98 when the temperature was increased from 300 °C to 650 °C in infusion mode and decreased from 1.37 to 1.17 with increasing temperature in FIA mode. The opposite trends of the two injection modes were also obtained in positive operation modes and ion sources with different configuration.

Conclusions

Opposite variation tendencies of relative responses of model samples and their stable isotope‐labeled products with temperature were observed for infusion and FIA injection modes, indicating different diffusion behaviors in the two injection modes. These results provide a theoretical basis for ion source designing and better understanding of the ESI mechanism. Copyright © 2016 John Wiley & Sons, Ltd.
Non‐tapered PTFE capillary as robust and stable nanoelectrospray emitter for electrospray ionization mass spectrometry
Authors: Jin Di‐Qiong , Zhu Ying , Fang Qun
Published: August 2016

Rationale

The successful implementation of electrospray ionization mass spectrometry (ESI‐MS) largely relies on the physical and chemical properties of electrospray emitters. Current ESI emitters based on pulled glass or fused‐silica capillaries suffer from complicated fabrication procedures and short lifetime because of clogging and breakage problems. ESI emitters with high robustness, easy operation, and low cost are in great demand.

Methods

We proposed to directly use non‐pulled and non‐tapered polytetrafluoroethylene (PTFE) capillaries as nanoelectrospray emitters. We evaluated and studied the performance of PTFE emitters under different flow rates and ESI voltages. Their applications in direct infusion and liquid chromatography (LC)–MS analysis were achieved.

Results

High stable electrospray (relative standard deviation of total ion current intensity <5%) can be obtained at flow rates from 100 nL/min to 1500 nL/min and at ESI voltages from 1.8 kV to 2.9 kV using non‐tapered PTFE emitters. Different types of samples including small‐molecule drugs, peptides, and proteins can be detected with high sensitivity. LC–MS analysis of two model peptides was successfully demonstrated.

Conclusions

We have demonstrated that a non‐tapered PTFE capillary can be a promising ESI emitter for both direct infusion and LC–MS analysis. We envision it could find broad applications in high‐throughput MS analysis fields, such as drug screening and proteomics, where robust and reproducible operations are essentially required. Copyright © 2016 John Wiley & Sons, Ltd.
Development of a suitcase time‐of‐flight mass spectrometer for in situ fault diagnosis of SF6‐insulated switchgear by detection of decomposition products
Authors: Hou Keyong , Li Jinxu , Qu Tuanshuai , Tang Bin , Zhu Liping , Huang Yunguang , Li Haiyang
Published: August 2016

Rationale

Sulfur hexafluoride (SF6) gas‐insulated switchgear (GIS) is an essential piece of electrical equipment in a substation, and the concentration of the SF6 decomposition products are directly relevant to the security and reliability of the substation. The detection of SF6 decomposition products can be used to diagnosis the condition of the GIS.

Methods

The decomposition products of SO2, SO2F2, and SOF2 were selected as indicators for the diagnosis. A suitcase time‐of‐flight mass spectrometer (TOFMS) was designed to perform online GIS failure analysis. An RF VUV lamp was used as the photoelectron ion source; the sampling inlet, ion einzel lens, and vacuum system were well designed to improve the performance.

Results

The limit of detection (LOD) of SO2 and SO2F2 within 200 s was 1 ppm, and the sensitivity was estimated to be at least 10‐fold more sensitive than the previous design. The high linearity of SO2, SO2F2 in the range of 5–100 ppm has excellent linear correlation coefficient R2 at 0.9951 and 0.9889, respectively.

Conclusions

The suitcase TOFMS using orthogonal acceleration and reflecting mass analyzer was developed. It has the size of 663 × 496 × 338 mm and a weight of 34 kg including the battery and consumes only 70 W. The suitcase TOFMS was applied to analyze real decomposition products of SF6 inside a GIS and succeeded in finding out the hidden dangers. The suitcase TOFMS has wide application prospects for establishing an early‐warning for the failure of the GIS. Copyright © 2016 John Wiley & Sons, Ltd.
Surface‐printed microdot array chips coupled with matrix‐assisted laser desorption/ionization mass spectrometry for high‐throughput single‐cell patterning and phospholipid analysis
Authors: Yang Ti , Gao Dan , Jin Feng , Jiang Yuyang , Liu Hongxia
Published: August 2016

Rationale

Single‐cell analysis is very important in several research fields for the heterogeneity of individual cells, which has been well accepted. However, restricted by the size and low content of a single cell, current studies have encountered challenges in high‐throughput, high‐space resolution and sensitivity, and multicomponent analysis. A methodology of a surface‐printed microdot array chip coupled with matrix‐assisted laser desorption ionization mass spectrometry (MALDI‐MS) is presented in this study for high‐throughput single‐cell patterning and phospholipid analysis.

Methods

The poly‐L‐lysine (PLL) used as ink molecule was printed on an oxygen plasma processed indium tin oxide (ITO)‐coated glass slide to form a microdot array by micro‐contact printing technology. The cell array was then formed on the PLL microarray through electrostatic adsorption force. 9‐Aminoacridine (9‐AA) matrix was applied on the cell array before it was analyzed by MALDI‐TOF MS. MALDI mass spectrometry imaging (MALDI‐MSI) was then used for high‐throughput, quick measurement, and multicomponent analysis of the cell array.

Results

The single‐cell capture efficiency of the cell array formed on the PLL microarray was about 40%. Twelve phospholipids were detected at the single‐cell level, and the structures were further confirmed by MS/MS. The MALDI‐MSI of selected ions showed a conformity with the cell array. The relative signal intensity data of selected ions were extracted from every pixel in the image within several minutes. The heterogeneity between individual cells was revealed from the relative signal intensity of phospholipids in 1–3 cells.

Conclusions

Compared to the existing related approaches, high‐throughput, quick measurement, and multicomponent single‐cell analysis have been realized by our method. Through different ink molecules used for micro‐contact printing, the established platform could have the potential to capture and analyze specific cells. Copyright © 2016 John Wiley & Sons, Ltd.
Rapid screening and determination of 11 new psychoactive substances by direct analysis in real time mass spectrometry and liquid chromatography/quadrupole time‐of‐flight mass spectrometry
Authors: Nie Honggang , Li Xianjiang , Hua Zhendong , Pan Wei , Bai Yanping , Fu Xiaofang
Published: August 2016

Rationale

With the amounts and types of new psychoactive substances (NPSs) increasing rapidly in recent years, an excellent high‐throughput method for the analysis of these compounds is urgently needed. In this article, a rapid screening method and a quantitative analysis method for 11 NPSs are described and compared, respectively.

Method

A simple direct analysis in real time mass spectrometry (DART‐MS) method was developed for the analysis of 11 NPSs including three categories of these substances present on the global market such as four cathinones, one phenylethylamine, and six synthetic cannabinoids. In order to analyze these compounds quantitatively with better accuracy and sensitivity, another rapid analytical method with a low limit of detection (LOD) was also developed using liquid chromatography/electrospray ionization quadrupole time‐of‐flight mass spectrometry (LC/QTOFMS).

Results

The 11 NPSs could be determined within 0.5 min by DART‐MS. Furthermore, they could also be separated and determined within 5 min by the LC/QTOFMS method. The two methods both showed good linearity with correlation coefficients (r2) higher than 0.99. The LODs for all these target NPSs by DART‐MS and LC/QTOFMS ranged from 5 to 40 ng mL−1 and 0.1 to 1 ng mL−1, respectively. Confiscated samples, named as “music vanilla” and “bath salt”, and 11 spiked samples were firstly screened by DART‐MS and then determined by LC/QTOFMS.

Conclusions

The identification of NPSs in confiscated materials was successfully achieved, and the proposed analytical methodology could offer rapid screening and accurate analysis results. Copyright © 2016 John Wiley & Sons, Ltd.
Mechanism investigation of HS radical and CS losses from positively charged biradicals of diphenyl sulfides by APCI mass spectrometry
Authors: Cao Xiaoji , Wang Chenlu , Mo Weimin
Published: August 2016

Rationale

Aryl thioethers are potentially useful precursors for constructing various biologically active sulfur‐containing heterocycles. The detailed relationship between the losses of HS radical and CS with the spin multiplicity of positively charged diphenyl sulfide biradicals derived from 3‐iodophenyl phenyl sulfides has not been obtained by tandem mass spectrometry combined with theoretical calculations.

Methods

Collision‐induced dissociation mass spectrometry experiments were carried out using an ion trap mass spectrometer with APCI in positive mode. The MS/MS experiment for dibenzothiophene was performed by CI triple‐quadrupole mass spectrometry in positive ion mode. The accurate masses of fragments were obtained by reflective TOFMS with an EI source. Theoretical calculations were achieved by the density functional theory method at the B3LYP level with the 6−31+G(d, p) basis set in the Gaussian 03 package of programs.

Results

In the fragmentation of positively charged diphenyl sulfide biradicals, losses of HS· and CS were observed, which were proposed to originate from spin multiplicity transformation from a triplet ground state to a singlet excited state and a phenyl radical shift in triplet ground state, respectively. Moreover, a protonated dibenzothiophene intermediate was confirmed to exist in the process of HS radical loss. A linear correlation was established between the product ion abundance from the two competitive losses and the Hammett constants (σ) of substituent groups on the benzene ring.

Conclusions

The eliminations of HS· and CS in the fragmentation of positively charged diphenyl sulfide biradicals were triggered by spin multiplicity transformation from a triplet ground state to a singlet excited state and a phenyl radical shift in a triplet ground state, respectively. Based on theoretical calculations, two competitive neutral losses are thermodynamically controlled. Copyright © 2016 John Wiley & Sons, Ltd.
Two competitive INC‐mediated reactions in the gas‐phase fragmentation of protonated indolyl benzo[b]carbazoles
Authors: Zhang Xiaoping , Jiang Kezhi , Zou Jingfeng , Li Zuguang , Lee Mawrong
Published: August 2016

Rationale

Ion‐neutral complexes (INCs) are intermediates extensively existing in gas‐phase ionic reactions.

Methods

Tandem mass spectrometry (MSn) analysis of indolyl benzo[b]carbazoles was performed on an electrospray ionization quadrupole time‐of‐flight (ESI‐Q‐TOF) mass spectrometer in positive ion mode.

Results

Two competing INC‐mediated reactions were obtained in the fragmentation of protonated indolyl benzo[b]‐carbazoles.

Conclusions

This study enriches our knowledge of the important roles of INCs in the dissociation of indole compounds in the gas phase. Copyright © 2016 John Wiley & Sons, Ltd.
Characterization and application of droplet spray ionization for real‐time reaction monitoring
Authors: Zhang Hong , Li Na , Li Xiao‐di , Jiang Jie , Zhao Dan‐dan , You Hong
Published: August 2016

Rationale

The ionization source for real‐time reaction monitoring has attracted tremendous interest in recent years. We have previously reported a reliable approach in which droplet spray ionization (DSI) was used for monitoring chemical reactions in real‐time. Herein, we systematically investigated the characterization and application of DSI for real‐time reaction monitoring.

Methods

Analyte ions are generated by loading a sample solution onto a corner of a microscope cover glass positioned in front of the MS inlet and applying a high voltage to the sample. The tolerance to positioning, solvent effect, spray angle and spray time were investigated. Extension to real‐time monitoring of macromolecule reactions was also demonstrated by the charge state change of cytochrome c in the presence of acetic acid.

Results

The corner could be positioned within an area of approximately 10 × 6 × 5 mm (x, y, z) in front of the MS inlet. The broad polarities of solvents from methanol to PhF were suitable for DSI. It featured monitoring real‐time changes in reactions on the time scale of seconds to minutes. A real‐time charge state change of cytochrome c was captured.

Conclusions

DSI‐MS features ease of use, durability of the spray platform and reusability of the ion source. Eliminating the need for a sample transport capillary, DSI opens a new avenue for the in situ analysis and real‐time monitoring of short‐lived key reaction intermediates even at subsecond dead times. Copyright © 2016 John Wiley & Sons, Ltd.
A robust two‐stage design identifying the optimal biological dose for phase I/II clinical trials
Authors: Zang Yong , Lee J. Jack
Published: August 2016

We propose a robust two‐stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet‐multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three‐dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose–efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose–toxicity and dose–efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd.
Proton and Hydride Transfer in the Skraup Reaction
Authors: Yamabe Shinichi , Yamazaki Shoko
Published: August 2016

The Skraup reaction affording quinoline was investigated computationally by the use of a model consisting of aniline, glycerol (HO‐CH2‐CH(OH)‐CH2OH) and H3O+ (H2O)7. First, two reaction channels up to the 1,2‐dihydroquinoline were considered. One is the traditional one involving acrolein. The other is for the direct linkage of aniline and glycerol. The channel without acrolein was calculated to be more likely. Second, the oxidation process of 1,2‐dihydroquinoline to quinoline was examined with and without the oxidizing agent, nitrobenzene. With it, the hydride‐shift path was obtained and it is likely energetically. Without it, while the process is feasible in accord with a microwave‐irradiation study, the large activation energy was required in the acid catalyzed either (1,2‐dihydroquinoline + glycerol) or (1,2‐dihydroquinoline + acrolein) reaction. The proton transfer was found to be primary driving force of the Skraup reaction.
Substrate Pre‐Folding and Water Molecule Organization Matters for Terpene Cyclase Catalyzed Conversion of Unnatural Substrates
Authors: Hammer Stephan C. , Syrén Per‐Olof , Hauer Bernhard
Published: August 2016

Terpene cyclase enzymes have recently been challenged with terpene substrate derivatives to generate additional chemical complexity beyond to what is currently found in nature. Herein, molecular dynamics and biocatalysis are used to shed light on the flexibility and inherent limitation of a triterpene cyclase in converting unnatural substrates. Our studies suggest that populating binding modes which allows for concerted reaction pathways is a key element towards an expanded substrate scope and new chemistries displayed by terpene cyclases. Additionally, we show that the spatial organization of water, which is influenced by both the substrate architecture as well as the active site geometry, controls the product selectivity. This highlights that activity and selectivity displayed by terpene cyclases acting on unnatural substrates is particularly difficult to predict, since they depend on various parameters.
Combined ab initio and XPS Investigations of the Electronic Interactions of L–Cysteine Adsorbed on GaAs(1 0 0)
Authors: Juarez María F. , Toader Ana M. , Negrila Catalin , Santos Elizabeth , Lazarescu Valentina
Published: August 2016

The adsorption of L‐cysteine from ethanol solutions on GaAs(1 0 0) surfaces has been studied by XPS and density‐functional theory (DFT). XPS data reveal that the formation of the adsorbate involves preferentially the As‐sites for p‐GaAs(1 0 0) and the Ga‐sites for n‐GaAs(1 0 0). The adsorbed species show different orientations of the functional groups to the surface for the different substrates. DFT calculations performed for both Ga‐dimers and As‐dimers terminated surfaces show that the adsorption is energetically favourable on both substrates. However, the adsorption energy is more negative on top of Ga‐atoms. Here an important contribution for the stabilization of the adsorbate is the interaction of the functional groups with the surface. The parallel orientation found for the Ga‐bound species by DFT calculations is in good agreement with the shift in the binding energy of the NH2/NH3+ species observed by XPS analysis.
Architecture of Directed‐Channel Mesoporous Silica/Titania Shell on Bi‐Alkaline‐Earth Carbonate Particles for Core‐Shell Structure
Authors: Chen Xuncai , Kim Jinsoo , Jung Taesung , Park Jongho , Kim Woo‐Sik
Published: August 2016

A generalized, single‐step synthetic method is outlined for the formation of directed‐channel mesoporous SiO2 or TiO2 shells on bi‐alkaline‐earth carbonate particles to create a core‐shell structure. Cetyltrimethylammonium bromide (CTAB) is used both as the structure‐directing template for the SiO2 and TiO2 shell layer during TEOS and TEOT hydrolysis/condensation and as the mesopore‐channel template in the shell. The resulting core‐shell particles display high properties for the specific surface area and pore volume. In addition, the reaction parameters for the formation of the SiO2 and TiO2 shell during the sol‐gel process are broadly investigated. Consequently, this directed mesoporous core‐shell structure can serve as a platform for further surface modifications to facilitate the rapid translation of particles to a wide range of end applications.
How entrepreneurs leverage institutional intermediaries in emerging economies to acquire public resources
Authors: Armanios Daniel Erian , Eesley Charles E. , Li Jizhen , Eisenhardt Kathleen M.
Published: August 2016

Research summary: Governments in emerging economies often use institutional intermediaries to promote entrepreneurship, and bridge the void between ventures and public funding. While prior literature describes what institutional intermediaries do, it leaves open how intermediaries support different types of entrepreneurs. By comparing science park and non‐science park firms in Beijing and across China, we distinguish which entrepreneurs benefit from certification versus capability‐building through the introduction of two new constructs: skill adequacy and context relevance. Broadly, our study adds insights at the nexus of emerging economies and entrepreneurship research, and to the tie formation and institutional intermediaries literatures.

Managerial summary: A key dilemma facing entrepreneurs is how to finance their ventures. While entrepreneurs in developed economies can seek VC or angel investment, entrepreneurs in emerging economies often need to pursue potential government funding opportunities. Our study highlights three strategies for acquiring government funding. Well‐connected entrepreneurs can leverage their political ties to acquire such funding. Less‐connected entrepreneurs can leverage science parks that in emerging markets are designed to help governments to identify promising ventures. For returnees whose ample experience abroad may not fit with local ways of doing business, gaining science park admission can certify quality and so ease the path to government funding. For technically skilled local entrepreneurs who lack business skills, science parks can help build such skills, which then ease the path to government funding. Copyright © 2016 John Wiley & Sons, Ltd.
Exposure to PM2.5 causes genetic changes in fetal rat cerebral cortex and hippocampus
Authors: Chao Ming‐Wei , Yang Chin‐Hua , Lin Po‐Ting , Yang Yu‐Hsiu , Chuang Yu‐Chen , Chung Meng‐Chi , Tseng Chia‐Yi
Published: August 2016

PM2.5 travels along the respiratory tract and enters systemic blood circulation. Studies have shown that PM2.5 increases the incidence of various diseases not only in adults but also in newborn infants. It causes chronic inflammation in pregnant women and retards fetal development. In this study, pregnant rats were exposed to PM2.5 for extended periods of time and it was found that PM2.5 exposure increased immune cells in mother rats. In addition, cytokines and free radicals rapidly accumulated in the amniotic fluid and indirectly affected the fetuses. The authors collected cerebral cortex and hippocampus samples at E18 and analyzed changes of miRNA levels. Expression levels of cortical miR‐6315, miR‐3588, and miR‐466b‐5p were upregulated, and positively correlated with the genes Pkn2 (astrocyte migration), Gorab (neuritogenesis), and Mobp (allergic encephalomyelitis). In contrast, PM2.5 decreased expression of miR‐338‐5p and let‐7e‐5p, both related to mental development. Further, PM2.5 exposure increased miR‐3560 and let‐7b‐5p in the hippocampus, two proteins that regulate genes Oxct1 and Lin28b that control ketogenesis and glycosylation, and neural cell differentiation, respectively. miR‐99b‐5p, miR‐92b‐5p, and miR‐99a‐5p were decreased, leading to reduced expression of Kbtbd8 and Adam11 which reduced cell mitosis, migration, and differentiation, and inhibited learning abilities and motor coordination of the fetus. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1412–1425, 2017.
Echolocation in humans: an overview
Authors: Thaler Lore , Goodale Melvyn A.
Published: August 2016

Bats and dolphins are known for their ability to use echolocation. They emit bursts of sounds and listen to the echoes that bounce back to detect the objects in their environment. What is not as well‐known is that some blind people have learned to do the same thing, making mouth clicks, for example, and using the returning echoes from those clicks to sense obstacles and objects of interest in their surroundings. The current review explores some of the research that has examined human echolocation and the changes that have been observed in the brains of echolocation experts. We also discuss potential applications and assistive technology based on echolocation. Blind echolocation experts can sense small differences in the location of objects, differentiate between objects of various sizes and shapes, and even between objects made of different materials, just by listening to the reflected echoes from mouth clicks. It is clear that echolocation may enable some blind people to do things that are otherwise thought to be impossible without vision, potentially providing them with a high degree of independence in their daily lives and demonstrating that echolocation can serve as an effective mobility strategy in the blind. Neuroimaging has shown that the processing of echoes activates brain regions in blind echolocators that would normally support vision in the sighted brain, and that the patterns of these activations are modulated by the information carried by the echoes. This work is shedding new light on just how plastic the human brain is. WIREs Cogn Sci 2016, 7:382‐393. doi: 10.1002/wcs.1408

This article is categorized under:

Psychology > Brain Function and Dysfunction

Psychology > Perception and Psychophysics

Neuroscience > Plasticity
How Many Contralateral Carcinomas in Patients with Unilateral Papillary Thyroid Microcarcinoma are Preoperatively Misdiagnosed as Benign?
Authors: Wu Zeng Gui , Yan Xing Qiang , Su Ru Si , Ma Zhao Sheng , Xie Bo Jian , Cao Fei Lin
Published: August 2016

Background

The decision to perform a total thyroidectomy (TT) for unilateral papillary thyroid microcarcinoma (PTMC) with nodules in the contralateral lobe remains controversial. The aim of this study was to investigate the rate of contralateral carcinomas that are preoperatively misdiagnosed as benign.

Methods

From October 2011 to October 2015, a total of 347 patients with unilateral PTMC and contralateral benign nodules who were treated with a TT at a single institution were enrolled. All patients underwent preoperative fine needle aspiration and ultrasonography (US). Clinicopathological features such as age, sex, laterality, tumor size, central lymph node metastases, capsular invasion, TgAb and TPOAb levels, Hashimoto’s thyroiditis, nodule number in both lobes according to preoperative US, and primary carcinoma number in the final postoperative pathology report were all analyzed to investigate the rate and predictive factors of contralateral carcinoma.

Results

A total of 100 patients (28.9 %) were diagnosed with papillary thyroid carcinoma in the contralateral lobe. A multivariate analysis showed that tumor size, nodule number in the contralateral lobe, and multifocality of the primary tumor were all independent predictive factors of contralateral carcinoma in patients with unilateral PTMC and contralateral benign nodules.

Conclusions

According to our findings, the rate at which contralateral carcinomas are preoperatively misdiagnosed as benign is 28.9 %. A TT is essential for unilateral PTMC with a primary tumor size >5 mm, multifocal primary carcinomas or multifocal benign nodules in the contralateral lobe.
Evaluation of commercial soy sauce koji strains of Aspergillus oryzae for γ-aminobutyric acid (GABA) production
Authors: Ab Kadir Safuan , Wan-Mohtar Wan Abd Al Qadr Imad , Mohammad Rosfarizan , Abdul Halim Lim Sarina , Sabo Mohammed Abdulkarim , Saari Nazamid
Published: August 2016

In this study, four selected commercial strains of Aspergillus oryzae were collected from soy sauce koji. These A. oryzae strains designated as NSK, NSZ, NSJ and NST shared similar morphological characteristics with the reference strain (A. oryzae FRR 1675) which confirmed them as A. oryzae species. They were further evaluated for their ability to produce γ-aminobutyric acid (GABA) by cultivating the spore suspension in a broth medium containing 0.4 % (w/v) of glutamic acid as a substrate for GABA production. The results showed that these strains were capable of producing GABA; however, the concentrations differed significantly (P < 0.05) among themselves. Based on the A. oryzae strains, highest GABA concentration was obtained from NSK (194 mg/L) followed by NSZ (63 mg/L), NSJ (51.53 mg/L) and NST (31.66 mg/L). Therefore, A. oryzae NSK was characterized and the sequence was found to be similar to A. oryzae and A. flavus with 99 % similarity. The evolutionary distance (K  nuc) between sequences of identical fungal species was calculated and a phylogenetic tree prepared from the K  nuc data showed that the isolate belonged to the A. oryzae species. This finding may allow the development of GABA-rich ingredients using A. oryzae NSK as a starter culture for soy sauce production.
Opportunities for Collaboration among East Asian and US Law Schools
Authors: SILVER Carole
Published: August 2016

Law schools in East Asia and the US share at least two central challenges. The first relates to globalization and the responsibility of law schools to prepare students to practise in a global environment. The second relates to the contest for control over lawyer licensing that law schools engage in with bar authorities, among others. Is either challenge appropriate for solution through a collaborative approach among law schools from different countries and regions? Research on collaboration identifies the need for a common, shared purpose among collaborators. Local differences make collaboration unlikely with regard to the contest for control, but the goal of developing an approach to prepare students for work in a global environment rises above national differences and is ripe for collaboration.