bluuebunny/crossref_metadata_2025 huggingface dataset:
Topographic separation of fornical fibers associated with the anterior and posterior hippocampus in the human brain: An MRI‐diffusion study
Authors: Christiansen Kat , Metzler‐Baddeley Claudia , Parker Greg D. , Muhlert Nils , Jones Derek K. , Aggleton John P. , Vann Seralynne D.
Published: November 2016

Background and Objective

Evidence from rat and nonhuman primate studies indicates that axons comprising the fornix have a characteristic topographical organization: projections from the temporal/anterior hippocampus mainly occupy the lateral fornix, whereas the more medial fornix contains fibers from the septal/posterior hippocampus. The aim of this study was to investigate whether the same topographical organization exists in the human brain.

Methods

Using high angular resolution diffusion MRI‐based tractography at 3T, subdivisions of the fornix were reconstructed in 40 healthy adults by selecting fiber pathways from either the anterior or the posterior hippocampus.

Results

The tract reconstructions revealed that anterior hippocampal fibers predominantly comprise the lateral body of the fornix, whereas posterior fibers make up the medial body of the fornix. Quantitative analyses support this medial:lateral distinction in humans, which matches the topographical organization of the fornix in other primates.

Conclusion

This novel tractography protocol enables the separation of fornix fibers from anterior and posterior hippocampal regions in the human brain and, hence, provides a means by which to compare functions associated with different sets of connections along the longitudinal axis of the hippocampus.
Migration of breast cancer cell lines in response to pulmonary laminin 332
Authors: Carpenter Philip M. , Sivadas Priyanka , Hua Spencer S. , Xiao Cally , Gutierrez Alyssa B. , Ngo Tuan , Gershon Paul D.
Published: November 2016

Because tumor cell motility is a requirement for metastasis, we hypothesized that lung tissue harbors substances that induce tumor cell migration. MCF‐7 breast carcinoma cells exposed to small airway epithelial cells and conditioned medium exhibited dose‐dependent tumor cell migration. Among the extracellular matrix proteins in the conditioned medium identified by mass spectrometry, laminin 332 (LM332) had the greatest contribution to the migration of MCF‐7 cells. Immunoblotting and immunohistochemistry for LM332‐specific chains identified LM332 in the lung and in pulmonary epithelial cells. Antibodies to either LM332 or its integrin receptor inhibited MCF‐7 motility, and knockdown of LM332 chains also reduced its migration‐inducing activity. Taken together, these findings implicate LM332 as a component of lung tissue that can induce motility in breast carcinoma cells that have been transported to lung during metastasis. Earlier studies on LM332 in tumor progression have examined LM332 expression in tumor cells. This investigation, in comparison, provides evidence that the tumor promoting potential of LM332 may originate in the lung microenvironment rather than in tumor cells alone. Furthermore, this study provides evidence that the motility‐inducing properties of the microenvironment can reside in epithelial cells. The findings raise the possibility that LM332 plays a role in the pulmonary metastases of breast carcinoma and may provide a target for antimetastasis therapy.
Pregnane X receptors regulate CYP2C8 and P‐glycoprotein to impact on the resistance of NSCLC cells to Taxol
Authors: Chen Yan , Huang Wandan , Chen Feiyu , Hu Guoping , Li Fenglei , Li Jianhua , Xuan Aiguo
Published: November 2016

Cytochrome P450 2C8 (CYP2C8) is one of the enzymes that primarily participate in producing metabolisms of medications and P‐glycoprotein (P‐gp) has been regarded as one of the important molecules in chemotherapeutically induced multidrug resistance (MDR). In addition, the pregnane X receptor (PXR) is involved in regulating both CYP2C8 and P‐gp. We aim to research the effect of PXR on Taxol‐resistant non–small‐cell lung cancer (NSCLC cells) via regulating CYP2C8 and P‐gp. NSCLC cells were treated with SR12813, LY335979, or PXR siRNA. Cell counting kit (CCK‐8) assay was used to detect cell vitality. Colony formation assay was used to observe cell proliferation. Western blotting, real‐time polymerase chain reaction (RT‐PCR), and immunofluorescence staining were conducted to analyze the expressions of PXR, CYP2C8, and P‐gp. Taxol and its metabolic products were detected by high‐performance liquid chromatography (HPLC). The expression of PXR in A549 cell line was higher than that in other cell lines. The accumulation of PXR was observed in the nucleus after cells were treated with SR12813. Besides, SR12813 induced higher expressions of CYP2C8 and P‐gp proteins. We also discovered that pretreatment with SR12813 reversed the inhibition of cell viability and proliferation after the Taxol treatment in comparison to the SR12813 untreated group. Furthermore, the hydroxylation products of Taxol analyzed by HPLC were increased in comparison to the SR12813 untreated group, indicating that high expressions of CYP2C8 and P‐gp enhanced the resistance of A549 cells to Taxol. For cells treated with PXR siRNA, cell viability, cell proliferation, and Taxol metabolites were significantly reduced after the Taxol treatment in comparison to the siRNA‐negative group. The cell viability, cell proliferation, and Taxol metabolites were regulated by the expressions of PXR, P‐gp, and CYP2C8. That is, PXR expression has an important effect on the resistance of NSCLC cells to Taxol via upregulating P‐gp and CYP2C8.
Development of particle swarm optimization–support vector regression (PSO‐SVR) coupled with microwave plasma torch–atomic emission spectrometry for quality control of ginsengs
Authors: Ying Yangwei , Jin Wei , Yu Haixiang , Yu Bingwen , Shan Jin , Lv Shaowu , Zhu Dan , Jin Qinhan , Mu Ying
Published: November 2016

As people have become more focused on their own health, the role of ginseng for medical uses has begun to receive substantial interest. However, the quality control of ginseng remains in question because different species vary considerably in this respect. In this paper, particle swarm optimization–support vector regression combined with microwave plasma torch–atomic emission spectrometry (MPT‐AES) was used, for the first time, for quality control of ginseng. To build calibration models, quantitative determination of target element concentrations in ginseng samples was conducted by MPT‐AES because ginseng quality was closely related to the place of origin and can thus be judged by the elemental composition. Characteristic spectral lines were extracted via principal component analysis to reduce the computational effort and improve the representativeness of the input variables. Two heuristic algorithms, particle swarm optimization and a genetic algorithm, were selected to optimize the parameters (eg, c, g, and ε) that were extremely significant in the construction of the support vector regression (SVR) models. Another linear regression approach, partial least squares regression (PLSR), was also used and compared. The comparisons were based on evaluation indexes, namely, the root mean square error and the squared correlation coefficient (R2). A significant difference between SVR and PLSR showed that SVR outperformed PLSR in such a multivariate regression problem. The acquired results showed that particle swarm optimization was slightly better than a genetic algorithm. In conclusion, the proposed MPT‐AES combined with particle swarm optimization–support vector regression is appropriate for quantitative elemental analysis and further application in the quality control of ginseng.
Getting the Most out of Solar Irradiation: Efficient Use of Polychromatic Light for Water Splitting
Authors: Taştan Ümit , Ziegenbalg Dirk
Published: November 2016

To increase the fraction of utilizable polychromatic light, a new reactor concept was developed and manufactured by using rapid prototyping technologies. Investigation of the prototypes revealed enhancements of the photocurrent by up to one order of magnitude, when TiO2 was used as the photoanode in combination with commercially available photovoltaic cells. The reported concept is scalable and an easy transfer to technical scale is expected from a technological as well as an economical perspective. Experimental results underline the conclusion that to achieve efficient overall use of solar irradiation both the material as well as the reactor/process must be considered. Combining these complementary approaches allows largest possible optimization potential. With respect to ongoing research, the concept also breaks ground for the development of catalysts.
Iron(II), Cobalt(II), Nickel(II), and Zinc(II) Silylene Complexes: Reaction of the Silylene [iPrNC(NiPr2)NiPr]2Si with FeBr2, CoBr2, NiBr2⋅MeOCH2CH2OMe, ZnCl2, and ZnBr2
Authors: Baus Johannes A. , Mück Felix M. , Schneider Heidi , Tacke Reinhold
Published: November 2016

Reaction of the donor‐stabilized silylene [iPrNC(NiPr2)NiPr]2Si (1) with FeBr2, CoBr2, NiBr2⋅MeOCH2CH2OMe, ZnCl2, and ZnBr2 afforded the respective transition‐metal silylene complexes 4–8, the formation of which can be described in terms of a Lewis acid/base reaction (4, 5, 7, 8) or a nucleophilic substitution reaction (6). However, the reactivity profile of silylene 1 is not only based on its strong Lewis base character; the different coordination modes of the two guanidinato ligands (4–6 vs. 7 and 8) add an additional reactivity facet. The paramagnetic compounds 4 and 5 and the diamagnetic compounds 6⋅THF, 7, and 8⋅0.5 Et2O were structurally characterized by single‐crystal X‐ray diffraction. In addition, compound 6⋅THF was studied by 15N and 29Si solid‐state NMR spectroscopy, and 7 and 8 were characterized by NMR spectroscopic studies in the solid state (15N, 29Si) and in solution (1H, 13C, 29Si). Compounds 4–8 represent very rare examples of FeII, CoII, NiII, and ZnII silylene complexes. Four‐coordinate silicon(II) compounds with an SiN3M skeleton (M=Fe, Co, Ni) and M in the formal oxidation state +2 (4–6) have not yet been reported, and five‐coordinate silicon(II) compounds with an SiN4Zn skeleton (7, 8) are also unprecedented.
Catalytic Emulsion Based on Janus Nanosheets for Ultra‐Deep Desulfurization
Authors: Xia Lixin , Zhang Hairan , Wei Zhichao , Jiang Yi , Zhang Ling , Zhao Jie , Zhang Junhui , Dong Li , Li Erni , Ruhlmann Laurent , Zhang Qian
Published: November 2016

Catalytic Janus nanosheets were synthesized by using an anion‐exchange reaction between heteropolyacids (HPAs) and the modified ionic‐liquid (IL) moieties of Janus nanosheets. Their morphology and surface properties were characterized by using SEM, energy‐dispersive spectroscopy (EDS), FTIR spectroscopy, and X‐ray photoelectron spectroscopy (XPS) studies. Because of their inherent Janus structure, the nanosheets exhibited good amphipathic character with ILs and oil to form a stable ILs‐in‐oil emulsion. Therefore, these Janus nanosheets can be used as both emulsifiers and catalysts to perform emulsive desulfurization. During this process, sulfur‐containing compounds at the interface could be easily oxidized and efficiently removed from a model oil. Application of this Janus emulsion brings an efficient, useful, and green procedure to the desulfurization process. Compared with the desulfurization catalyzed by using HPAs in a conventional two‐phase system, the sulfur removal of dibenzothiophene (DBT) achieved in a Janus emulsion system was improved from 68 to 97 % within 1.5 h. Moreover, this emulsion system could be demulsified easily by simple centrifugation to recover both the nanosheets and the ILs. Owing to the good structural stability of the Janus nanosheets, the sulfur removal efficiency of DBT could still reach 99.9 % after the catalytic nanosheets had been recycled at least six times.
Reactions Catalysed by a Binuclear Copper Complex: Relay Aerobic Oxidation of N‐Aryl Tetrahydroisoquinolines to Dihydroisoquinolones with a Vitamin B1 Analogue
Authors: Liu Yuxia , Wang Chao , Xue Dong , Xiao Miao , Liu Jiao , Li Chaoqun , Xiao Jianliang
Published: November 2016

N‐Aryl tetrahydroisoquinolines were oxidised to dihydroisoquinolones through the relay catalysis of a binuclear paddle‐wheel copper complex and a vitamin B1 analogue with oxygen as oxidant. Mechanistic studies revealed that the copper catalyst oxidises amines to the corresponding iminium salts, which are then oxygenated to lactam products by catalysis of the vitamin B1 analogue.
Iridium versus Iridium: Nanocluster and Monometallic Catalysts Carrying the Same Ligand Behave Differently
Authors: Cano Israel , Martínez‐Prieto Luis M. , Chaudret Bruno , van Leeuwen Piet W. N. M.
Published: November 2016

A specific secondary phosphine oxide (SPO) ligand (tert‐butyl(phenyl)phosphine oxide) was employed to generate two iridium catalysts, an Ir–SPO complex and IrNPs (iridium nanoparticles) ligated with SPO ligands, which were compared mutually and with several supported iridium catalysts with the aim to establish the differences in their catalytic properties. The Ir–SPO‐based catalysts showed totally different activities and selectivities in the hydrogenation of various substituted aldehydes, in which H2 is likely cleaved by a metal–ligand cooperation, that is, the SPO ligand and a neighboring metal centre operate in tandem to activate the hydrogen molecule. In addition, the supported IrNPs behave very differently from both Ir–SPO catalysts. This study exemplifies perfectly the advantages and disadvantages related to the use of the main types of catalysts, and thus the dissimilarities between them.
Service with a smile: A source of emotional exhaustion or performance incentive in call‐centre employees
Authors: Picard Karel , Cossette Michel , Morin Denis
Published: November 2016

This study examines the relationships between emotional labour (surface acting, deep acting, and natural expression of positive emotions) and emotional exhaustion and service performance among 215 call centre employees. Of the hypotheses concerning the relation between the three emotional regulation strategies to emotional exhaustion and to service performance, only natural expression of positive emotion is significantly related to both consequences. Results also suggest that neuroticism moderates the link between deep acting and emotional exhaustion: employees with low levels of neuroticism seem more emotionally exhausted when they use deep acting. Copyright © 2016 ASAC. Published by John Wiley & Sons, Ltd.
Immunotherapy approaches in the treatment of malignant brain tumors
Authors: Dunn‐Pirio Anastasie M. , Vlahovic Gordana
Published: November 2016

Glioblastoma is the most common malignant primary brain tumor. Despite standard‐of‐care treatment, consisting of maximal surgical resection followed by chemoradiation, both morbidity and mortality associated with this disease remain very poor. Therefore, there is an urgent need for more efficacious and well tolerated therapies. Advancing knowledge of the intricate interplay between malignant gliomas and the immune system, coupled with the recent launch of immunotherapy research for other cancers, has led to a veritable increase in immunotherapy investigation for glioblastoma and other malignant gliomas. This clinical review highlights the recent breakthroughs in cancer immunotherapy and the complex correlation of the immune system with primary brain tumors, with special attention to multiple immunotherapy modalities currently being investigated for malignant glioma, including peptide vaccines, dendritic cell vaccines, oncolytic viruses, chimeric T‐cell receptors, and checkpoint inhibitors. Cancer 2017;123:734–50. © 2016 American Cancer Society.
Clinical and genetic determinants of ovarian metastases from colorectal cancer
Authors: Ganesh Karuna , Shah Ronak H. , Vakiani Efsevia , Nash Garrett M. , Skottowe Hugh P. , Yaeger Rona , Cercek Andrea , Lincoln Anne , Tran Christina , Segal Neil H. , Reidy Diane L. , Varghese Anna , Epstein Andrew S. , Sonoda Yukio , Chi Dennis , Guillem Jose , Temple Larissa , Paty Philip , Hechtman Jaclyn , Shia Jinru , Weiser Martin , Aguilar Julio Garcia , Kemeny Nancy , Berger Michael F. , Saltz Leonard , Stadler Zsofia K.
Published: November 2016

BACKGROUND

Ovarian metastases from colorectal cancer (OM‐CRC) often are unresponsive to chemotherapy and are associated with poor survival. To the authors' knowledge, the clinicopathologic and genomic predictors of OM‐CRC are poorly characterized and optimal clinical management remains unclear.

METHODS

Women with a histopathological diagnosis of OM‐CRC who were treated at Memorial Sloan Kettering Cancer Center from 1999 to 2015 were identified. Next‐generation somatic mutation profiling (Memorial Sloan Kettering‐Integrated Mutation Profiling of Actionable Cancer Targets [MSK‐IMPACT]) was performed on 38 OM‐CRC cases, including 21 matched tumor pairs/trios. Regression models were used to analyze variables associated with progression‐free survival and overall survival (OS).

RESULTS

Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS), SMAD family member 4 (SMAD4), and neurotrophic receptor tyrosine kinase 1 (NTRK1) mutations were more frequent in cases of OM‐CRC than in instances of CRC occurring without OM. SMAD4 and lysine methyltransferase 2D (KMT2D) mutations were associated with reduced OS. Matched multisite tumor sequencing did not identify OM‐specific genomic alterations. Of the 195 patients who underwent oophorectomy for OM‐CRC (median age, 49 years with a progression‐free survival of 9.4 months and an OS of 23 months from oophorectomy), 76% had extraovarian metastasis (EOM). In multivariable analysis, residual disease after surgery (R2 resection) was associated with worse survival. Patients with EOM were less likely to achieve R0/R1 surgical resection status (complete macroscopic resection without clinical/radiological evidence of disease) (48% vs 94%). However, if R0/R1 resection status was achieved, both patients with (35.9 months vs 12 months) and without (43.2 months vs 14.5 months) EOM were found to have better OS. Among 114 patients with R0/R1 resection status, 23 (20%) had no disease recurrence, including 10 patients (9%) with > 3 years of follow‐up.

CONCLUSIONS

Loss‐of‐function alterations in SMAD4 are frequent and predictive of worse survival in patients with OM‐CRC. Similar to oligometastatic CRC to the lung or liver, surgical resection of OM‐CRC is associated with a better outcome only if all macroscopic metastatic disease is resected. Cancer 2017;123:1134–1143. © 2016 American Cancer Society.
Identification of Outer and Inner Nickel Particles in a Mesoporous Support: How the Channels Modify the Reducibility of Ni/SBA‐15 Catalysts
Authors: Rodriguez‐Gomez Alberto , Caballero Alfonso
Published: November 2016

Two different nickel supported on SBA‐15 catalytic systems have been prepared by means of impregnation (Ni/SBA‐15‐ImU) and deposition‐precipitation (Ni/SBA‐15‐DP) methodologies. Upon calcination, Ni/SBA‐15DP presents a well‐developed nickel phyllosilicate phase, which after reduction gives rise to a dispersed and homogeneous metallic phase, mainly located inside the 5 nm in diameter mesoporous structure of the support. On the contrary, as evidenced by XRD and a double temperature programmed reduction (TPR) peak, the Ni/SBA‐15‐ImU catalyst presents two different NiO phases, which after reduction in hydrogen generate nickel particles in a wide range of sizes. In situ XAS and XPS have unambiguously showed that the distinct TPR profiles obtained for each system are related with particles located in and out the mesoporous structure of the SBA‐15 channels. The particles inside the porous are more difficult to reduce, clearly showing a kind of confinement effect of the SBA‐15 mesostructure, modifying the reducibility of the NiO phase.
Dynamics of Novel Photoactive AgCl Microstars and Their Environmental Applications
Authors: Simmchen Juliane , Baeza Alejandro , Miguel‐Lopez Albert , Stanton Morgan M. , Vallet‐Regi Maria , Ruiz‐Molina Daniel , Sánchez Samuel
Published: November 2016

In the field of micromotors many efforts have been taken to find a substitute for peroxide as fuel. While most approaches turn towards other toxic high energy chemicals such as hydrazine, we introduce here an energy source that is widely used in nature: light. Light is an ideal source of energy and some materials, such as AgCl, have the inherent property to transform light energy for chemical processes, which can be used to achieve propulsion. In the case of silver chloride, one process observed after light exposure is surface modification, which leads to the release of ions, generating chemo‐osmotic gradients. Here we present endeavors to use those processes to propel uniquely shaped micro‐objects of microstar morphology with a high surface‐to‐volume ratio, study their dynamics and present approaches to go towards real environmental applications.
Co‐SiO2 Nanocomposite Catalysts for COx‐Free Hydrogen Production by Ammonia Decomposition
Authors: Hu Xiu‐Cui , Wang Wei‐Wei , Gu Ying‐Qiu , Jin Zhao , Song Qi‐Sheng , Jia Chun‐Jiang
Published: November 2016

High‐surface‐area Co‐SiO2 nanocomposites were synthesized by a simple two‐step procedure with activated carbon as the template. These materials catalyze the decomposition of ammonia to produce COx‐free hydrogen. The fresh and used catalysts were characterized by various techniques including X‐ray diffraction, N2 adsorption–desorption, and transmission electron microscopy. Furthermore, temperature‐programmed reduction by hydrogen combined with the corresponding in situ XRD analysis was performed to investigate the redox properties of the as‐prepared catalysts. The strong interaction between the cobalt species and silica can effectively prevent the active cobalt nanoparticles from agglomerating during calcination and the ammonia decomposition reaction. The ammonia reaction rate reached about 7000 mol NH3 molCo−1 h−1 with a very high GHSV of 124 000 cm3 gcat−1 h−1 at 600 °C; this rate was maintained for 48 h without any observable deactivation of the as‐obtained Co‐SiO2 nanocomposite catalyst.
Detection of Dopamine by a Biomimetic Electrochemical Sensor Based on Polythioaniline‐Bridged Gold Nanoparticles
Authors: Tertiş Mihaela , Florea Anca , Adumitrăchioaie Alina , Cernat Andreea , Bogdan Diana , Barbu‐Tudoran Lucian , Jaffrezic Renault Nicole , Săndulescu Robert , Cristea Cecilia
Published: November 2016

A new biomimetic electrochemical sensor was developed for the detection of dopamine based on a glassy carbon electrode modified with electrochemically generated gold nanoparticles. The preparation of the polymer is simple and cost‐effective, achieving the polymerization of thioaniline and generation of gold nanoparticles in a single step by cyclic voltammetry, in the presence of the target molecule, dopamine. After extraction, the imprinted polymer exhibits high sensitivity and selectivity for dopamine. Moreover, the developed imprinted polymer film allows the fast, direct detection of dopamine without the need of a redox mediator. The formation of a self‐assembled monolayer of the monomer prior to electropolymerization ensures the adherence of the film onto the electrode surface, conferring good stability to the sensor (over two weeks). Cyclic voltammetry, electrochemical impedance spectroscopy, atomic force microscopy, scanning electron microscopy, and energy dispersive X‐ray spectroscopy were used for the complete characterization of the developed sensor, and differential pulse voltammetry was used for its testing.
Nutrients influence the thermal ecophysiology of an intertidal macroalga: multiple stressors or multiple drivers?
Authors: Colvard Nicholas , Helmuth Brian
Published: November 2016

Urbanization of coastlines is leading to increased introduction of nutrients from the terrestrial environment to nearshore habitats. While such nutrient influxes can be detrimental to coastal marine organisms due to increased eutrophication and subsequent reduced oxygen, they could also have positive effects (i.e., increased food availability) on species that are nitrogen‐limited such as macroalgae. Nutrient enrichment in this environment thus has the potential to counteract some of the negative impacts of increasing temperatures, at least for some species. Characterizing the physiological response of organisms to simultaneous changes in multiple drivers such as these is an important first step in predicting how global climate change may lead to ecological responses at more local levels. We evaluated how nutrient enrichment (i.e., nitrogen availability) affected the growth of Fucus vesiculosus, a foundational macroalgal species in the North Atlantic rocky intertidal zone, and found that nutrient‐enriched algal blades showed a significant increase in tissue growth compared to individuals grown under ambient conditions. We further quantified net photosynthesis by ambient and nutrient‐enriched tissues at saturating irradiance over a range of temperature conditions (6–30°C). Respiration was unaffected by nutrient treatment; however, there was a significant increase in photosynthetic oxygen production for nutrient‐enriched tissue compared to ambient, but only at elevated (≥18°C) temperatures. This study contributes to a growing body of literature showing the complexity of responses to changes in multiple drivers, and highlights the importance of studying the impacts of global climate change within the context of more local environmental conditions.
The strength of the association between heterozygosity and probability of interannual local recruitment increases with environmental harshness in blue tits
Authors: Ferrer Esperanza S. , García‐Navas Vicente , Sanz Juan José , Ortego Joaquín
Published: November 2016

The extent of inbreeding depression and the magnitude of heterozygosity–fitness correlations (HFC) have been suggested to depend on the environmental context in which they are assayed, but little evidence is available for wild populations. We combine extensive molecular and capture–mark–recapture data from a blue tit (Cyanistes caeruleus) population to (1) analyze the relationship between heterozygosity and probability of interannual adult local recruitment and (2) test whether environmental stress imposed by physiologically suboptimal temperatures and rainfall influence the magnitude of HFC. To address these questions, we used two different arrays of microsatellite markers: 14 loci classified as neutral and 12 loci classified as putatively functional. We found significant relationships between heterozygosity and probability of interannual local recruitment that were most likely explained by variation in genomewide heterozygosity. The strength of the association between heterozygosity and probability of interannual local recruitment was positively associated with annual accumulated precipitation. Annual mean heterozygosity increased over time, which may have resulted from an overall positive selection on heterozygosity over the course of the study period. Finally, neutral and putatively functional loci showed similar trends, but the former had stronger effect sizes and seemed to better reflect genomewide heterozygosity. Overall, our results show that HFC can be context dependent, emphasizing the need to consider the role of environmental heterogeneity as a key factor when exploring the consequences of individual genetic diversity on fitness in natural populations.
Anticancer, Azonafide‐Inspired Fluorescent Ligands and Their Rhenium(I) Complexes for Cellular Imaging
Authors: Langdon‐Jones Emily E. , Jones Ariana B. , Williams Catrin F. , Hayes Anthony J. , Lloyd David , Mottram Huw J. , Pope Simon J. A.
Published: November 2016

Two dipicolyamino‐conjugated anthracene‐1,9‐dicarboximide fluorophores and their corresponding ReI complexes have been synthesised and photophysically examined. All species were fluorescent in the visible region at about 490 nm with lifetimes up to 16 ns. The anticancer potency of the ligands and complexes was demonstrated across a range of cancer cell lines (LOVO, PC3, A549, MCF‐7). Cell imaging studies with MCF7 cells and Schizosaccharomyces pombe show that these fluorophores exhibit variable intracellular localisation patterns that are structure‐dependent.
RhIII‐Catalyzed CF3‐Carbenoid C‐7 Functionalization of Indolines
Authors: Iagafarova Irina E. , Vorobyeva Daria V. , Loginov Dmitry A. , Peregudov Alexander S. , Osipov Sergey N.
Published: November 2016

An efficient method for the CF3‐carbenoid C‐7 functionalization of N‐pyrimidylindolines has been developed. This protocol uses readily available methyl 3,3,3‐trifluoro‐2‐diazopropionate as a cross‐coupling partner and smoothly proceeds under chelation‐controlled RhIII catalysis. The reactions provide the indoline products with high regioselectivity within a few hours and allow for the introduction of both the CF3 and carboxylate functions at the C‐7 position.
Synthesis of CF2H‐Substituted Pyrazolines by [3+2] Cycloaddition between CF2HCHN2 and Electron‐Deficient Alkenes
Authors: Li Jue , Yu Xin‐Ling , Cossy Janine , Lv Song‐Yang , Zhang Hai‐Long , Su Fu , Mykhailiuk Pavel K. , Wu Yong
Published: November 2016

CF2H‐substituted pyrazolines were synthesized by [3+2] cycloaddition between in situ generated CF2HCHN2 and electron‐deficient alkenes. The representative CF2H‐substituted pyrazoline was easily oxidized into the CF2H‐substituted pyrazole, which are important in agrochemistry.
Polyoxometalate‐Mediated Lignin Oxidation for Efficient Enzymatic Production of Sugars and Generation of Electricity from Lignocellulosic Biomass
Authors: Zhao Xuebing , Ding Yi , Du Bo , Zhu J. Y. , Liu Dehua
Published: November 2016

Conversion of lignocellulosic biomass to various renewable fuels, chemicals, materials, and electricity has attracted more and more interest in recent decades to decrease the dependence on fossil resources and reduce net CO2 emissions. Herein, we have developed an integrated process of biomass pretreatment for enzymatic hydrolysis of cellulose coupled with electricity generation with polyoxometalates (POMs) and ferric ion as electron mediators and proton carriers. The pretreatment is a “charging” process, and the re‐oxidation of the POMs is effectively a “discharging” process. The pretreated substrate showed a good enzymatic digestibility (≈80 % cellulose conversion) within a short incubation period (<24 h). Fe3+ was screened as a cheap, effective liquid mediator to transfer electrons to air, which is the terminal electron acceptor in the “discharging” process. The highest output power densities of 10.8 and 12.4 mW cm−2 were obtained for discharging of reduced H3PMo12O40 and H4PMo11VO40, respectively. This power density is 5000–6000 times higher than that of phenol‐fueled microbial fuel cells, and 10 times higher than that of a recently reported direct biomass fuel cell with an air cathode covered with Pt catalyst. Moreover, this work also provides a conceptual combination of a direct biomass fuel cell and a redox flow cell, which can be flexibly switched between electricity generation from biomass and stationary energy storage.
Weighted sum rate maximization in MIMO interfering broadcast channels exploiting virtual per‐user power constraints
Authors: Masoumzadeh M. , Sabahi M. F. , Forouzan A. R.
Published: November 2016

In this paper, we consider the weighted sum rate (WSR) maximization problem in a partially coordinated multiple‐input multiple‐output multicell broadcast channel with constraints on base stations' transmit powers where the communication is based on dirty paper coding. To be able to obtain a computationally efficient solution for this non‐convex optimization problem, we solve it by a fast algorithm for WSR maximization under per‐user power constraints. The main idea is to define virtual per‐user power constraints that add up to the per‐base station power budgets in each cell and optimize the per‐user power constraints to maximize the WSR. We propose two computationally efficient power allocation algorithms to find the per‐user power constraints, namely, the waterfilling‐based power update and the gradient descent–based power update algorithms. In the latter one, we find a closed‐form expression for the derivative of the maximum of WSR wrt the per‐user power constraints resulting in a considerable reduction in the complexity. The resulting algorithms are computationally efficient, and our simulation results show that they achieve significantly higher bit rates than the current algorithms at the same signal‐to‐noise power ratio.
A Quasi‐experimental Approach to the Multinationality‐performance Relationship: An Application to Learning‐by‐exporting
Authors: Chang Sea‐Jin , Chung Jaiho
Published: November 2016

Research summary

This article introduces the propensity score matching method and the difference‐in‐differences approach as an innovative way to create a quasi‐experimental setting. By controlling for endogeneity, these methods more precisely capture the dynamic effect of strategy adoption. When used in tandem, these empirical methodologies can shed light on the multinationality‐performance relationship that has generated mixed findings to date, mainly due to methodological limitations. We compare and contrast propensity score matching and the difference‐in‐differences approach with alternative methodologies that attempt to handle endogeneity, while applying them specifically to the learning‐by‐exporting hypothesis, a classic case of the multinationality‐performance relationship. We find strong evidence that export does indeed improve firm productivity, more so when firms have higher learning opportunities.

Managerial summary

Firms increasingly become multinational by pursuing international markets. However, it is not clear whether international strategy really improves firm performance, since the observed positive relationship may be driven by the fact that better performing firms pursue international strategy. This poses an important managerial issue since managers need to be certain about the causal impact of strategic choices. We compare and contrast various methodologies that help establish the causal relationship between international strategy and firm performance. Using a quasi‐experimental method, we find strong evidence that international strategy through exporting does indeed improve firm productivity based on learning from exporting activities and, further, that such learning is greater when exporting firms have higher learning opportunities. Copyright © 2016 Strategic Management Society.
Institutional Complementarity and Substitution as an Internationalization Strategy: The Emergence of an African Multinational Giant
Authors: Luiz John , Stringfellow Dustin , Jefthas Anthea
Published: November 2016

Research Summary

We examine the internationalization decisions made by one of Africa's most successful companies, South African Breweries, as it underwent a period of aggressive expansion. We see processes of both institutional complementarity and substitution at different phases and with different motives. At first it sought countries that played to its strength, namely the knowledge of doing business in environments of institutional uncertainty, but later it pursued an institutional diversification strategy whereby it attempted to minimize its institutional risk exposure. As it became larger, its aspirations increased too, and its over‐exposure to emerging market institutional risk saw it engage in institutional substitution into advanced countries. Through this phased international process, it was able to develop its internal assets, and this enabled the moves into developed markets.

Managerial summary

We demonstrate that firms can exploit their knowledge of ‘weak’ institutional settings and turn it into a source of advantage as they internationalize into locations with similar institutional ‘weaknesses.’ Using the case of one of Africa's most successful multinational enterprises, we illustrate the value gained from initially capitalizing upon institutional complementarity (utilizing the comparative advantage linked to institutional know‐how) by exploiting the experience of the home country's environment into similar settings. Over time and through learning‐by‐doing, pressure arose to diversify the risk linked with over‐exposure to institutional uncertainty and country risk, and this was associated with the process of institutional substitution into more advanced countries. We see emerging multinational learning and building its capabilities by leveraging its understanding of its home country institutional environment. Copyright © 2016 John Wiley & Sons, Ltd.
Africa: The New Frontier for Global Strategy Scholars
Authors: Mol Michael J. , Stadler Christian , Ariño Africa
Published: November 2016

Context matters in the global strategy literature. We discuss how Africa, as a setting that received limited attention in the past, offers opportunity to challenge existing theory and develop new insights. The overall goal is to ask: What will the field of global strategic management look like once we have engaged with Africa in a similar manner as we have done with other emerging economies? We also introduce the papers published in this special issue and highlight directions for future research. Copyright © 2016 John Wiley & Sons, Ltd.
Religious Hospitals and Patient Choice
Authors: Sawicki Nadia N.
Published: November 2016

Recent media reports have drawn widespread attention to the experiences of patients who are denied reproductive services at Catholic hospitals. For some patients, such as those experiencing miscarriage, denial of appropriate treatment can lead to serious health consequences. However, many patients are unaware of the limitations on services available at religiously affiliated health care institutions. As a result, patients’ ability to make informed and autonomous decisions about where to seek treatment is hindered. There are currently no federal or state laws requiring health care institutions to inform patients directly of the full scope of medical services they are unable to provide on the basis of religion or conscience. Given religious hospitals’ significant role in the provision of health care in the United States, it is essential that patients be clearly informed about institutional limitations on care. This goal would be best served by adopting a federal disclosure law similar to the Patient Self‐Determination Act.
Getting a Sporting Chance: Title IX and the Intergenerational Transmission of Health
Authors: Schulkind Lisa
Published: November 2016

We know that healthier mothers tend to have healthier infants, but we do not know how much of that relationship reflects the intergenerational transmission of genetic attributes versus environmental influences. From a policy perspective, it is crucial to understand which environmental influences are important and whether investments in one generation affect outcomes for the next. I use variation in the implementation of Title IX to measure the effects of increased athletic opportunities on the health of infants. Babies born to women with greater athletic opportunities as teenagers have babies that are healthier at birth. They are less likely to be born of low or very low birthweight and have higher Apgar scores. Copyright © 2016 John Wiley & Sons, Ltd.
Validation of the prognostic value of histologic scoring systems in primary sclerosing cholangitis: An international cohort study
Authors: de Vries Elisabeth M. G. , de Krijger Manon , Färkkilä Martti , Arola Johanna , Schirmacher Peter , Gotthardt Daniel , Goeppert Benjamin , Trivedi Palak J. , Hirschfield Gideon M. , Ytting Henriette , Vainer Ben , Buuren Henk R. van , Biermann Katharina , Harms Maren H. , Chazouilleres Olivier , Wendum Dominique , Kemgang Astrid D. , Chapman Roger W. , Wang Lai Mun , Williamson Kate D. , Gouw Annette S. H. , Paradis Valerie , Sempoux Christine , Beuers Ulrich , Hübscher Stefan G. , Verheij Joanne , Ponsioen Cyriel Y.
Published: November 2016

Histologic scoring systems specific for primary sclerosing cholangitis (PSC) are not validated. We recently determined the applicability and prognostic value of three histological scoring systems in a single PSC cohort. The aim of this study was to validate their prognostic use and reproducibility across a multicenter PSC cohort. Liver biopsies from PSC patients were collected from seven European institutions. Histologic scoring was performed using the Nakanuma, Ishak, and Ludwig scoring systems. Biopsies were independently scored by six liver pathologists for interobserver agreement. The prognostic value of clinical, biochemical, and all three histologic scoring systems on predicting composite endpoints 1 (PSC‐related death and liver transplantation), 2 (liver transplantation), and 3 (liver‐related events), was assessed using univariable and multivariable Cox proportional hazards modeling. A total of 119 PSC patients were identified, and the median follow‐up was 142 months. During follow‐up, 31 patients died (20 PSC‐related deaths), 31 patients underwent liver transplantation, and 35 patients experienced one or more liver‐related events. All three staging systems were independent predictors of endpoints 2 and 3 (Nakanuma system: hazard ratio [HR], 3.16 [95% confidence interval (CI), 1.49‐6.68] for endpoint 2 and HR, 2.05 [95% CI, 1.17‐3.57] for endpoint 3; Ishak system: HR, 1.55 [95% CI, 1.10‐2.18] for endpoint 2 and HR, 1.43 [95% CI, 1.10‐1.85] for endpoint 3; Ludwig system: HR, 2.62 [95% CI, 1.19‐5.80] for endpoint 2 and HR, 2.06 [95% CI, 1.09‐3.89] for endpoint 3). Only the Nakanuma staging system was independently associated with endpoint 1: HR, 2.14 (95% CI, 1.22‐3.77). Interobserver agreement was moderate for Nakanuma stage (κ = 0.56) and substantial for Nakanuma component fibrosis (κ = 0.67), Ishak stage (κ = 0.64), and Ludwig stage (κ = 0.62). Conclusion: We confirm the independent prognostic value and demonstrate for the first time the reproducibility of staging disease progression in PSC using the Nakanuma, Ishak, and Ludwig staging systems. The Nakanuma staging system—incorporating features of chronic biliary disease—again showed the strongest predictive value. (Hepatology 2017;65:907‐919).
Identification and validation of an eight‐gene expression signature for predicting high Fuhrman grade renal cell carcinoma
Authors: Wan Fangning , Zhu Yao , Han Chengtao , Xu Qinghua , Wu Junlong , Dai Bo , Zhang Hailiang , Shi Guohai , Gu Weijie , Ye Dingwei
Published: November 2016

Clear cell renal cell carcinoma (ccRCC) is a malignancy with heterogeneous outcomes. Currently, renal mass biopsies are commonly employed to extract disease characteristics and aid prognosis. Although the pathological diagnosis of malignant disease is accurate in contemporary reports, the classification of Fuhrman grade using biopsy specimens remains far from promising. To generate a gene signature to distinguish high‐grade ccRCC, we used the cancer genome atlas (TCGA) database to develop a gene expression signature for distinguishing high‐grade (G3/4) from low‐grade (G1/2) disease. The expression profile was further validated for performance and clinical use in 283 frozen renal cancer samples and 127 ex vivo renal mass biopsy samples, respectively. The area under curve (AUC) was used to quantify discriminative ability and was compared using the De‐long test. Using the discovery dataset, we identified a 24‐gene signature for high‐grade disease with an AUC of 0.884. After applied to the development dataset, an eight‐gene profile was defined and achieved an AUC of 0.823. Accuracy of eight‐gene panel was maintained in the renal mass biopsies (RMB) samples (AUC = 0.821). In summary, using three‐stage design, we validated an eight‐gene expression signature for predicting high Fuhrman grade of ccRCC. This tool may help to reveal the characteristics of ccRCC biopsy specimens.
Drug loaded nanoparticle coating on totally bioresorbable PLLA stents to prevent in‐stent restenosis
Authors: Zhao Jian , Mo Zhichao , Guo Fangfang , Shi Donglu , Han Qian Qian , Liu Qing
Published: November 2016

Biodegradable polymer poly (dl‐lactide) (PDLLA) has been used as drug coating material for drug‐eluting stents due to its excellent biocompatibility and sustained drug release ability. However, the uniform thin layer drug eluting coating on a stent not only inhibits the blood vessel's smooth muscle cell overgrowth but also delay the endotheliation process which is often associated with the occurrence of acute thrombosis. Therefore, in this study, we developed a novel coating method using PDLLA nanoparticles (NPs) as a coating to overcome this issue. The average 300 nm sized sirolimus‐loaded PDLLA nanoparticles were prepared by a conventional emulsion solvent evaporation method. A low temperature plasma polymerization technology to graft hydrophilic polymers on to poly (l‐lactide) stent was used to increase the surface coating efficiency of nanoparticles on the stent. Results showed that sirolimus‐loaded nanoparticles can be successfully coated on to the stents with sustained drug release properties. In vitro cell culture study showed the drug loaded nanoparticle coating effectively inhibited the proliferation of smooth muscle cells while still allowed a faster proliferation of endothelial cells, suggesting that the new NP coated bioresorbable stents have the potential to reduce both the occurrence of in‐stent restenosis and acute thrombosis. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 88–95, 2018.
A comparative study of software programmes for cross‐sectional skeletal muscle and adipose tissue measurements on abdominal computed tomography scans of rectal cancer patients
Authors: van Vugt Jeroen L.A. , Levolger Stef , Gharbharan Arvind , Koek Marcel , Niessen Wiro J. , Burger Jacobus W.A. , Willemsen Sten P. , de Bruin Ron W.F. , IJzermans Jan N.M.
Published: November 2016

Background

The association between body composition (e.g. sarcopenia or visceral obesity) and treatment outcomes, such as survival, using single‐slice computed tomography (CT)‐based measurements has recently been studied in various patient groups. These studies have been conducted with different software programmes, each with their specific characteristics, of which the inter‐observer, intra‐observer, and inter‐software correlation are unknown. Therefore, a comparative study was performed.

Methods

Fifty abdominal CT scans were randomly selected from 50 different patients and independently assessed by two observers. Cross‐sectional muscle area (CSMA, i.e. rectus abdominis, oblique and transverse abdominal muscles, paraspinal muscles, and the psoas muscle), visceral adipose tissue area (VAT), and subcutaneous adipose tissue area (SAT) were segmented by using standard Hounsfield unit ranges and computed for regions of interest. The inter‐software, intra‐observer, and inter‐observer agreement for CSMA, VAT, and SAT measurements using FatSeg, OsiriX, ImageJ, and sliceOmatic were calculated using intra‐class correlation coefficients (ICCs) and Bland–Altman analyses. Cohen's κ was calculated for the agreement of sarcopenia and visceral obesity assessment. The Jaccard similarity coefficient was used to compare the similarity and diversity of measurements.

Results

Bland–Altman analyses and ICC indicated that the CSMA, VAT, and SAT measurements between the different software programmes were highly comparable (ICC 0.979–1.000, P < 0.001). All programmes adequately distinguished between the presence or absence of sarcopenia (κ = 0.88–0.96 for one observer and all κ = 1.00 for all comparisons of the other observer) and visceral obesity (all κ = 1.00). Furthermore, excellent intra‐observer (ICC 0.999–1.000, P < 0.001) and inter‐observer (ICC 0.998–0.999, P < 0.001) agreement for all software programmes were found. Accordingly, excellent Jaccard similarity coefficients were found for all comparisons (mean ≥ 0.964).

Conclusions

FatSeg, OsiriX, ImageJ, and sliceOmatic showed an excellent agreement for CSMA, VAT, and SAT measurements on abdominal CT scans. Furthermore, excellent inter‐observer and intra‐observer agreement were achieved. Therefore, results of studies using these different software programmes can reliably be compared.