bluuebunny/crossref_metadata_2025 huggingface dataset:
Rates and modes of body size evolution in early carnivores and herbivores: a case study from Captorhinidae
Authors: Brocklehurst Neil
Published: January 2016

Body size is an extremely important characteristic, impacting on a variety of ecological and life-history traits. It is therefore important to understand the factors which may affect its evolution, and diet has attracted much interest in this context. A recent study which examined the evolution of the earliest terrestrial herbivores in the Late Carboniferous and Early Permian concluded that in the four herbivorous clades examined there was a trend towards increased body size, and that this increase was more substantial than that observed in closely related carnivorous clades. However, this hypothesis was not based on quantitative examination, and phylogenetic comparative methods provide a more robust means of testing such hypotheses. Here, the evolution of body size within different dietary regimes is examined in Captorhinidae, the most diverse and longest lived of these earliest high fibre herbivores. Evolutionary models were fit to their phylogeny to test for variation in rate and mode of evolution between the carnivorous and herbivorous members of this clade, and an analysis of rate variation throughout the tree was carried out. Estimates of ancestral body sizes were calculated in order to compare the rates and direction of evolution of lineages with different dietary regimes. Support for the idea that the high fibre herbivores within captorhinids are being drawn to a higher adaptive peak in body size than the carnivorous members of this clade is weak. A shift in rates of body size evolution is identified, but this does not coincide with the evolution of high-fibre herbivory, instead occurring earlier in time and at a more basal node. Herbivorous lineages which show an increase in size are not found to evolve at a faster rate than those which show a decrease; in fact, it is those which experience a size decrease which evolve at higher rates. It is possible the shift in rates of evolution is related to the improved food processing ability of the more derived captorhinids rather than a shift in diet, but the evidence for this is circumstantial.
Non-native species in the vascular flora of highlands and mountains of Iceland
Authors: Wasowicz Pawel
Published: January 2016

The highlands and mountains of Iceland are one of the largest remaining wilderness areas in Europe. This study aimed to provide comprehensive and up-to-date data on non-native plant species in these areas and to answer the following questions: (1) How many non-native vascular plant species inhabit highland and mountainous environments in Iceland? (2) Do temporal trends in the immigration of alien species to Iceland differ between highland and lowland areas? (3) Does the incidence of alien species in the disturbed and undisturbed areas within Icelandic highlands differ? (4) Does the spread of non-native species in Iceland proceed from lowlands to highlands? and (5) Can we detect hot-spots in the distribution of non-native taxa within the highlands? Overall, 16 non-native vascular plant species were detected, including 11 casuals and 5 naturalized taxa (1 invasive). Results showed that temporal trends in alien species immigration to highland and lowland areas are similar, but it is clear that the process of colonization of highland areas is still in its initial phase. Non-native plants tended to occur close to man-made infrastructure and buildings including huts, shelters, roads etc. Analysis of spatio-temporal patterns showed that the spread within highland areas is a second step in non-native plant colonization in Iceland. Several statically significant hot spots of alien plant occurrences were identified using the Getis-Ord Gi* statistic and these were linked to human disturbance. This research suggests that human-mediated dispersal is the main driving force increasing the risk of invasion in Iceland’s highlands and mountain areas.
Mixing in a three‐phase system: Enhanced production of oil‐wet reservoirs by CO2 injection
Authors: Jiménez‐Martínez Joaquín , Porter Mark L. , Hyman Jeffrey D. , Carey J. William , Viswanathan Hari S.
Published: January 2016

We recreate three‐phase reservoir conditions (high‐pressure/temperature) using a microfluidics system and show that the use of scCO2 for restimulation operations, such as hydraulic fracturing, can enhance mixing and production. The results inform hydrocarbon extraction from deep shale formations, which has recently generated an energy boom that has lowered hydrocarbon costs. However, production decreases rapidly and methods to increase efficiency or allow restimulation of wells are needed. In our experiments, the presence of residual brine from initial production creates spatiotemporal variability in the system that causes the injected scCO2 to more effectively interact‐mix with trapped hydrocarbon, thereby increasing recovery. We apply volume‐averaging techniques to upscale brine saturation, which allows us to analyze the complex three‐phase system in the framework of well characterized two‐phase systems. The upscaled three‐phase system behaves like a two‐phase system: greater mixing with larger non‐wetting content and higher heterogeneity. The results are contrary to previous observations in water‐wet systems.
A global picture of ionospheric slab thickness derived from GIM TEC and COSMIC radio occultation observations
Authors: Huang He , Liu Libo , Chen Yiding , Le Huijun , Wan Weixing
Published: January 2016

The ionospheric equivalent slab thickness (EST), defined as the ratio of total electron content (TEC) to F2 layer peak electron density (NmF2), describes the thickness of the ionospheric profile. In this study, we retrieve EST from TEC data obtained from Global Ionospheric Map (GIM) and NmF2 retrieved from Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) ionospheric radio occultation data. The diurnal, seasonal, and solar activity variations of global EST are analyzed as the excellent spatial coverage of GIM and COSMIC data. During solstices, daytime EST in the summer hemisphere is larger than that in the winter hemisphere, except in some high‐latitude regions, and the reverse is true for the nighttime EST. The peaks of EST often appear at 0400 local time. The presunrise enhancement in EST appears in all seasons, while the postsunset enhancement in EST is not readily observed in equinox. Both enhancements are attributed to the more remarkable electron density decay of NmF2 compared to that of TEC. The dependence of EST on solar activity is related to the inconsistent solar activity dependences of electron density at different altitudes. Furthermore, it is interesting that EST is enhanced from 0° to 120°E in longitude and 30° to 75°S in latitude during nighttime, just to the east of Weddell Sea Anomaly, during equinox and the Southern Hemisphere summer. This phenomenon is supposed to be related to the effects of geomagnetic declination‐related plasma vertical drifts.
Catchment influence on nitrate and dissolved organic matter in Alaskan streams across a latitudinal gradient
Authors: Harms Tamara K. , Edmonds Jennifer W. , Genet Hélène , Creed Irena F. , Aldred David , Balser Andrew , Jones Jeremy B.
Published: January 2016

Spatial patterns in carbon (C) and nitrogen (N) cycles of high‐latitude catchments have been linked to climate and permafrost and used to infer potential changes in biogeochemical cycles under climate warming. However, inconsistent spatial patterns across regions indicate that factors in addition to permafrost and regional climate may shape responses of C and N cycles to climate change. We hypothesized that physical attributes of catchments modify responses of C and N cycles to climate and permafrost. We measured dissolved organic C (DOC) and nitrate (NO3−) concentrations, and composition of dissolved organic matter (DOM) in 21 streams spanning boreal to arctic Alaska, and assessed permafrost, topography, and attributes of soils and vegetation as predictors of stream chemistry. Multiple regression analyses indicated that catchment slope is a primary driver, with lower DOC and higher NO3− concentration in streams draining steeper catchments, respectively. Depth of the active layer explained additional variation in concentration of DOC and NO3−. Vegetation type explained regional variation in concentration and composition of DOM, which was characterized by optical methods. Composition of DOM was further correlated with attributes of soils, including moisture, temperature, and thickness of the organic layer. Regional patterns of DOC and NO3− concentrations in boreal to arctic Alaska were driven primarily by catchment topography and modified by permafrost, whereas composition of DOM was driven by attributes of soils and vegetation, suggesting that predicting changes to C and N cycling from permafrost‐influenced regions should consider catchment setting in addition to dynamics of climate and permafrost.
Interactions between an Aryl Thioacetate‐Functionalized Zn(II) Porphyrin and Graphene Oxide
Authors: Mao Boyang , Calatayud David G. , Mirabello Vincenzo , Hodges Benjamin J. , Martins José Alberto Ribeiro , Botchway Stanley W. , Mitchels John M. , Pascu Sofia I.
Published: January 2016

The surface modification of graphene oxide (GO) is carried out via the supramolecular functionalization route using a Zn(II)‐porphyrin which is soluble in common organic solvents on basis of long alkyl chains present at the exocyclic positions. This acts as a dispersing agent and decorates the surface of the graphene oxide uniformly, giving rise to a new nanohybrid denoted Zn(II)‐porphyrin@GO. The resulting Zn(II)‐porphyrin@GO nanohybrid forms a stable dispersion in ethanol (as characterized by several different spectroscopic techniques such as UV–vis, Fourier transform infrared, Raman). The morphology of Zn(II)‐porphyrin@GO nanohybrid is investigated by atomic force microscopy (AFM) and transmission electron microscope (TEM)/selected area electron diffraction. Both TEM and AFM measurements indicate that the Zn(II)‐porphyrin self‐assemble onto the surface of graphene oxide sheets. Steady‐state and time‐resolved fluorescence emission studies in the dispersed phase, and as a thin film, point toward the strongly quenched fluorescence emission and lifetime decay, suggesting that energy transfer occurs from the singlet excited state of Zn(II)‐porphyrin unit to GO sheets.
[2+2+2]‐Cyclotrimerization of 1‐Cyclopropyl‐1,6‐diynes with Alkynes: Formation of Cyclopropylarenes.
Authors: Matoušová Eliška , Gyepes Robert , Císařová Ivana , Kotora Martin
Published: January 2016

Cyclotrimerization of 1‐cyclopropyl‐1,6‐diynes with various terminal alkynes was tested under catalytic conditions using rhodium and ruthenium catalysts. We observed that the regioselectivity of the reaction, that is, formation of 1,2‐ or 1,3‐regioisomers, was opposite for the two metals. For the ruthenium complex [Cp*Ru(cod)Cl]‐catalyzed reactions the yields were in many cases high with a strong preference for the formation of 1,3‐substituted regioisomers. In the case of catalysis by the rhodium complex [RhCl(PPh3)3], 1,2‐substituted products were generally preferred, albeit the selectivity was often modest. However, by changing the ligand environment around the central rhodium atom the regioselectivity as well as yields of the products were significantly improved. For example, by using a combination of the rhodium complex [Rh(cod)2BF4] and 1,4‐bis(diphenylphosphino)butane the regioselectivity was changed from 1:1 to 1:12 in favor of the 1,2‐regioisomer. This catalytic system was also applied for synthesis of a substituted 4‐cyclopropyl‐3‐hydroisobenzofuran‐1‐one that could serve as a potential intermediate for preparation of antihypertensive agents.

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Impedance Hyperbolicity in Inkjet‐Printed Graphene Nanocomposites: Tunable Capacitors for Advanced Devices
Authors: Chiolerio Alessandro , Porro Samuele , Bocchini Sergio
Published: January 2016

An easy method for the fabrication of a completely tunable capacitor based on inkjet‐printed hybrid organic systems is here reported. The quantum relativistic properties of graphene‐induce electronic resonances between the polyaniline polymeric matrix and the graphene filler, with extremely long transfer rates. These events induce peculiar physical phenomena due to impedance hyperbolicity, such as voltage‐controlled phase shifting. The apparent capacitance is shown to diverge to infinity having a sign dependent on the frequency sweep direction. Hence devices may be geometrically tuned to operate with desired capacitance (either positive or negative) at the desired frequency. Among various possibilities of theoretical models that can explain the negative capacitance found, the standard space charge accumulation theory is considered and compared to other quantum relativity effects. The discussion of experimental results based on those theories suggests that a new paradigm is required for a comprehensive explanation of the observed phenomena, which include the observation of high‐frequency (MHz) negative capacitance, voltage‐controlled phase shifting, and diverging negative/positive capacitance in correspondence of the characteristic resonance frequency (kHz). The various possibilities of exploiting these peculiar properties in advanced electronic devices are also discussed.
Atomic‐Scale Observation of Oxygen Substitution and Its Correlation with Hole‐Transport Barriers in Cu2ZnSnSe4 Thin‐Film Solar Cells
Authors: Kim Jin Hyun , Choi Si‐Young , Choi Minseok , Gershon Talia , Lee Yun Seog , Wang Wei , Shin Byungha , Chung Sung‐Yoon
Published: January 2016

Kesterite‐type Cu2ZnSn(S,Se)4 has been extensively studied over the past several years, with researchers searching for promising candidates for indium‐ and gallium‐free inexpensive absorbers in high‐efficiency thin‐film solar cells. Many notable experimental and theoretical studies have dealt with the effects of intrinsic point defects, Cu/Zn/Sn nonstoichiometry, and cation impurities on cell performance. However, there have been few systematic investigations elucidating the distribution of oxygen at an atomic scale and the correlation between oxygen substitution and charge transport despite unavoidable incorporation of oxygen from the ambient atmosphere during thin‐film fabrication. Using energy‐dispersive X‐ray spectroscopy, scanning transmission electron microscopy, and electron energy‐loss spectroscopy, the presence of nanoscale layers is directly demonstrated in which oxygen is substantially substituted for Se, near grain boundaries in polycrystalline Cu2ZnSnSe4 films. Density‐functional theory calculations also show that oxygen substitution remarkably lowers the valence band maximum and subsequently widens the overall bandgap. Consequently, anion modification by oxygen can make a major contribution to the formation of a robust barrier blocking the holes from bulk grains into grain boundaries, thereby efficiently attaining electron−hole separation. The findings provide crucial insights into achieving better energy conversion efficiency in kesterite‐based thin‐film solar cells through optimum control of oxidation during the fabrication process.
Dynamic modeling and collocation‐based model reduction of cryogenic air separation units
Authors: Cao Yanan , Swartz Christopher L. E. , Flores‐Cerrillo Jesus , Ma Jingran
Published: January 2016

High purity distillation columns and multi‐stream heat exchangers (MSHXs) are critical units in cryogenic air separation plants. This article focuses on modeling approaches for the primary section of a super‐staged argon plant. A full‐order stage‐wise model for distillation columns in air separation units (ASUs) that considers key process phenomena is presented, followed by a reduced‐order model using a collocation approach. The extent of model reduction that can be achieved without losing significant prediction accuracy is demonstrated. A novel moving boundary model is proposed to handle MSHXs with phase change. Simulation results demonstrate the capability of the proposed model for tracking the phase change occurrence along the length of the heat exchanger. Dynamic simulation studies of the integrated plant show that the thermal integration between the feed and product streams captured in the primary heat exchanger is critical to accurately capture the behavior of ASUs. © 2016 American Institute of Chemical Engineers AIChE J, 62: 1602–1615, 2016
Glochidial infestation by the endangered mollusc Unio crassus in rivers of north‐eastern France: Phoxinus phoxinus and Cottus gobio as primary fish hosts
Authors: Lamand Florent , Roche Kevin , Beisel Jean‐Nicolas
Published: January 2016

The thick‐shelled river mussel Unio crassus is an endangered freshwater bivalve species with a life cycle that includes an obligate glochidial larval stage that attaches to the gills of freshwater fish for several days to months.

Fish hosts were identified in nine north‐eastern French rivers in order to improve unionid conservation management.

Eurasian minnow Phoxinus phoxinus was the most important host at all study sites, with prevalence ranging from 15–100% (122 of 238 individuals infested), and bullhead Cottus gobio usually the second most important (prevalence 0–73%; 37 of 121). Other host species had a relatively low rate of infestation: chub Squalius cephalus (5 of 41), roach Rutilus rutilus (1 of 23), gudgeon Gobio gobio (2 of 50), stone loach Barbatula barbatula (2 of 58) and dace Leuciscus leuciscus (1 of 19). No glochidia were found on spirlin Alburnoides bipunctatus (0 of 24).

Parasitic load usually ranged between one and three per fish (60% of cases), and rarely exceeded 10. First results suggest that U. crassus glochidia influence the weight:length ratio of P. phoxinus but not C. gobio, with infested fish being heavier.

To date, the ecological function of P. phoxinus (and C. gobio) in small streams has been largely underestimated or ignored as the species is small, common and of no interest to anglers. There is increasing evidence, however, that P. phoxinus deserves conservation management owing to the essential role it plays in the reproduction, development and distribution of U. crassus.

Copyright © 2016 John Wiley & Sons, Ltd.
Robust Finite‐Time Control for Linear Time‐Varying Delay Systems With Bounded Control
Authors: Niamsup P. , Phat V. N.
Published: January 2016

This paper develops a novel finite‐time control design for linear systems subject to time‐varying delay and bounded control. Based on the Lyapunov‐like functional method and using a result on bounding estimation of integral inequality, we provide some sufficient conditions for designing state feedback controllers that guarantee the robust finite‐time stabilization with guaranteed cost control. The conditions are obtained in terms of linear matrix inequalities (LMIs), which can be determined by utilizing the MATLAB LMI Control Toolbox. A numerical example is given to show the effectiveness of the proposed method.
An undergraduate laboratory activity on molecular dynamics simulations
Authors: Spitznagel Benjamin , Pritchett Paige R. , Messina Troy C. , Goadrich Mark , Rodriguez Juan
Published: January 2016

Vision and Change [AAAS, 2011] outlines a blueprint for modernizing biology education by addressing conceptual understanding of key concepts, such as the relationship between structure and function. The document also highlights skills necessary for student success in 21st century Biology, such as the use of modeling and simulation. Here we describe a laboratory activity that allows students to investigate the dynamic nature of protein structure and function through the use of a modeling technique known as molecular dynamics (MD). The activity takes place over two lab periods that are 3 hr each. The first lab period unpacks the basic approach behind MD simulations, beginning with the kinematic equations that all bioscience students learn in an introductory physics course. During this period students are taught rudimentary programming skills in Python while guided through simple modeling exercises that lead up to the simulation of the motion of a single atom. In the second lab period students extend concepts learned in the first period to develop skills in the use of expert MD software. Here students simulate and analyze changes in protein conformation resulting from temperature change, solvation, and phosphorylation. The article will describe how these activities can be carried out using free software packages, including Abalone and VMD/NAMD. © 2016 by The International Union of Biochemistry and Molecular Biology, 44:130–139, 2016.
Online Pyrophosphate Assay for Analyzing Adenylation Domains of Nonribosomal Peptide Synthetases
Authors: Kittilä Tiia , Schoppet Melanie , Cryle Max J.
Published: January 2016

Nonribosomal peptide synthetases (NRPSs) produce many important and structurally complex natural products. Because of their architectures, reprogramming NRPSs has long been attempted to access new bioactive compounds. However, detailed characterization of NRPS catalysis and substrate selectivity by adenylation (A) domains is needed to support such efforts. We present a simple coupled NADH/pyrophosphate (PPi ) detection assay for analyzing A domain catalysis in vitro. PPi formation is coupled to the consumption of NADH by four enzymatic steps and is detected spectroscopically (λ=340 nm) for simple analysis. We demonstrate the effectiveness of this assay with several adenylation domains, including a stand‐alone A domain (DltA, cell wall biosynthesis) and an embedded A domain (Tcp10, teicoplanin biosynthesis). Substrate acceptance of the Tcp10 A domain was explored for the first time, thus demonstrating the applicability of the assay for complex, multi‐domain NRPSs.
Metal‐Free Dehydrogenation of Amine‐Boranes by Tunable N‐Heterocyclic Iminoboranes
Authors: Lui Melanie W. , Paisley Nathan R. , McDonald Robert , Ferguson Michael J. , Rivard Eric
Published: January 2016

We report the synthesis of structurally tunable boron complexes supported by N‐heterocyclic imine ligands IPr=N−BR2 (IPr=[(HCNDipp)2C], Dipp=2,6‐iPr2C6H3, R=Cl and/or Ph) that have the ability to abstract dihydrogen from amine‐boranes, and instigate their dehydrocoupling. In one instance, mild heating of the hydrogen addition product IPr=NH−B(Ph)HCl releases H2 to regenerate the starting N‐heterocyclic iminoborane; accordingly IPr=N−B(Ph)Cl can be used as a metal‐free catalyst to promote the dehydrocoupling of MeNH2⋅BH3 to yield N‐methylaminoborane oligomers [MeNH‐BH2]x.
A Puckered Singlet Cyclopentane‐1,3‐diyl: Detection of the Third Isomer in Homolysis
Authors: Ye Jianhuai , Hatano Sayaka , Abe Manabu , Kishi Ryohei , Murata Yusuke , Nakano Masayoshi , Adam Waldemar
Published: January 2016

In the photochemical denitrogenation of 1,4‐diaryl‐2,3‐diazabicyclo[2.2.1]heptane (AZ6) bearing sterically hindered substituents, a curious new absorption band at about 450 nm was observed under low‐temperature matrix conditions, together with the previously well‐characterized planar singlet diradical pl‐1DR6 with λmax=≈580 nm. The 450 nm species was electron paramagnetic resonance (EPR)‐silent. Instead of generating the planar diradical pl‐1DR6 and the precursor azoalkane AZ6 upon warming, the ring‐closed bicyclo[2.1.0]pentane derivative SB6, that is, the AZ6 denitrogenation product was identified. Based on product analysis, low‐temperature spectroscopic observations, high‐level quantum‐mechanical computations, viscosity effect, and laser‐flash photolysis, the puckered singlet diradicaloid puc‐1DR6 was assigned to the new 450 nm absorption. The latter was detected experimentally at the same time as the planar singlet diradical pl‐1DR6. Sterically demanding substituents as well as viscosity impediments were essential for the detection of the experimentally hitherto unknown puckered singlet cyclopentane‐1,3‐diyl diradicaloid puc‐1DR6, that is, the third isomer in homolysis. The present findings should stimulate future work on the mechanistically fascinating stereoselectivity documented in the formation of bicyclo[2.1.0]pentanes during the 2,3‐diazabicyclo[2.2.1]heptane denitrogenation.
Three‐Dimensional Macroassembly of Sandwich‐Like, Hierarchical, Porous Carbon/Graphene Nanosheets towards Ultralight, Superhigh Surface Area, Multifunctional Aerogels
Authors: Zhu Jiayi , Yang Xi , Fu Zhibing , He Junhui , Wang Chaoyang , Wu Weidong , Zhang Lin
Published: January 2016

A new, ultralight, superhigh surface area, multifunctional aerogel, which is macroassembled from sandwich‐like, hierarchical, porous carbon/graphene nanosheets, is described. The multifunctional aerogel was characterized by means of XRD, SEM, TEM, Raman spectroscopy, and UV/Vis absorption spectroscopy. The multifunctional aerogel had an ultralow density of 8 mg cm−3 and a superhigh surface area of 2650 m2 g−1. The multifunctional aerogel was thermal stability and compressible. Meanwhile, the multifunctional aerogel exhibited high capacity for the adsorption of oils and organic solvents, unexpectedly high hydrogen adsorption and good electrochemical performance.
Novel Insights into Structure–Activity Relationships of N‐Terminally Modified PACE4 Inhibitors
Authors: Kwiatkowska Anna , Couture Frédéric , Levesque Christine , Ly Kévin , Beauchemin Sophie , Desjardins Roxane , Neugebauer Witold , Dory Yves L. , Day Robert
Published: January 2016

PACE4 plays important roles in prostate cancer cell proliferation. The inhibition of this enzyme has been shown to slow prostate cancer progression and is emerging as a promising therapeutic strategy. In previous work, we developed a highly potent and selective PACE4 inhibitor, the multi‐Leu (ML) peptide, an octapeptide with the sequence Ac‐LLLLRVKR‐NH2. Here, with the objective of developing a useful compound for in vivo administration, we investigate the effect of N‐terminal modifications. The inhibitory activity, toxicity, stability, and cell penetration properties of the resulting analogues were studied and compared to the unmodified inhibitor. Our results show that the incorporation of a polyethylene glycol (PEG) moiety leads to a loss of antiproliferative activity, whereas the attachment of a lipid chain preserves or improves it. However, the lipidated peptides are significantly more toxic when compared with their unmodified counterparts. Therefore, the best results were achieved not by the N‐terminal extension but by the protection of both ends with the d‐Leu residue and 4‐amidinobenzylamide, which yielded the most stable inhibitor, with an excellent activity and toxicity profile.
MRI monitoring of nanocarrier accumulation and release using Gadolinium‐SPIO co‐labelled thermosensitive liposomes
Authors: Lorenzato Cyril , Oerlemans Chris , van Elk Merel , Geerts Willie J. C. , Denis de Senneville Baudouin , Moonen Chrit , Bos Clemens
Published: January 2016

Encapsulation of anticancer drugs in triggerable nanocarriers can beneficially modify pharmacokinetics and biodistribution of chemotherapeutic drugs, and consequently increase tumor drug concentration and efficacy, while reducing side effects. Thermosensitive liposomes release their contents triggered by hyperthermia, which can be, for example, precisely delivered using an MR Imaging‐guided focused ultrasound procedure. In such a scenario, it is attractive to demonstrate the accumulation of liposomes before applying hyperthermia, as well as to document the release of liposome content using MRI. To address this need, thermosensitive liposomes were developed and characterized, which were doubly loaded by iron oxide nanoparticles and Gd‐chelate, as opposed to loading with a single contrast agent. When intact, the transverse relaxivity of the liposomes is high allowing detection of carriers in tissue. After heating the longitudinal relaxivity steeply increases indicating release of the small molecular contents. By choosing the appropriate MR sequences, availability and release can be evaluated without interference of one contrast agent with the other. Copyright © 2016 John Wiley & Sons, Ltd.
Smart Approach for In Situ One‐Step Encapsulation and Controlled Delivery of a Chemotherapeutic Drug using Metal–Organic Framework–Drug Composites in Aqueous Media
Authors: Adhikari Chandan , Chakraborty Anjan
Published: January 2016

Controlled release of an anticancer drug, doxorubicin (dox), from metal–organic framework (MOF)–drug composites is demonstrated under different external stimuli. 1,3,5‐Benzenetricarboxylic acid (H3BTC) is used as an organic ligand, and iron acetate and zinc nitrate are used as metal sources to synthesize Fe–BTC and Zn–BTC MOFs, which are known to be biocompatible. The in situ formation of MOF–drug composites demonstrates high drug loading capacity compared to conventional methods. The present methodology is devoid of any extra steps for loading the drug after synthesis. Moreover, the drug loading is also independent of pore size of the MOF as the drug molecules are embedded inside the MOF during their in situ formation. The drug release was monitored under external stimuli including change to acidic pH and the presence of biocompatible liposomes for a period of more than 72 h. Steady‐state fluorescence spectroscopy is used to monitor the drug release as a function of time and confocal laser scanning microscopy is used to unravel the post‐release fate of doxorubicin in the presence of liposomes. It is found that drug release rate is higher for the Zn–BTC–dox composite than for the Fe–BTC–dox composite. This is attributed to the stronger binding between dox and Fe‐BTC than that between dox and Zn–BTC. This study highlights a novel approach for the preparation of MOF–drug composites in an aqueous medium for future biomedical applications.
VO2/V2O5:Ag Nanostructures on a DVD as Photoelectrochemical Sensors
Authors: Zheng Jian , Calvillo Laura , Rizzi Gian Andrea , Granozzi Gaetano
Published: January 2016

The electrochemical deposition of a mixed oxide on the Ag nanostructured surface of a commercial digital versatile disc (DVD) is described. The VO2/V2O5 mixture shows interesting photoelectrocatalytic performances under visible‐light illumination after diffusion of the Ag+ ions from the Ag‐DVD substrate through the layer and formation of surface vanadates, which also allows it to be applied as an inexpensive sensing device. The samples were characterized with X‐ray photoemission spectroscopy (XPS), scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), and Raman measurements. The sensing properties towards oxidizable organic substances, such as glucose, were tested.
Grazing exclusion reduced soil respiration but increased its temperature sensitivity in a Meadow Grassland on the Tibetan Plateau
Authors: Chen Ji , Zhou Xuhui , Wang Junfeng , Hruska Tracy , Shi Weiyu , Cao Junji , Zhang Baocheng , Xu Gexi , Chen Yizhao , Luo Yiqi
Published: January 2016

Understanding anthropogenic influences on soil respiration (Rs) is critical for accurate predictions of soil carbon fluxes, but it is not known how Rs responds to grazing exclusion (GE). Here, we conducted a manipulative experiment in a meadow grassland on the Tibetan Plateau to investigate the effects of GE on Rs. The exclusion of livestock significantly increased soil moisture and above‐ground biomass, but it decreased soil temperature, microbial biomass carbon (MBC), and Rs. Regression analysis indicated that the effects of GE on Rs were mainly due to changes in soil temperature, soil moisture, and MBC. Compared with the grazed blocks, GE significantly decreased soil carbon release by 23.6% over the growing season and 21.4% annually, but it increased the temperature sensitivity (Q10) of Rs by 6.5% and 14.2% for the growing season and annually respectively. Therefore, GE may reduce the release of soil carbon from the Tibetan Plateau, but under future climate warming scenarios, the increases in Q10 induced by GE could lead to increased carbon emissions.
Incidence of cancer in patients with chronic heart failure: a long‐term follow‐up study
Authors: Banke Ann , Schou Morten , Videbæk Lars , Møller Jacob E. , Torp‐Pedersen Christian , Gustafsson Finn , Dahl Jordi S. , Køber Lars , Hildebrandt Per R. , Gislason Gunnar H.
Published: January 2016

Aims

With improvement in survival of chronic heart failure (HF), the clinical importance of co‐morbidity is increasing. The aim of this study was to assess the incidence and risk of cancer and all‐cause mortality in a large Danish HF cohort.

Methods and results

A total of 9307 outpatients with verified HF without a prior diagnosis of cancer (27% female, mean age 68 years, 89% with LVEF <45%) were included in the study. A diagnosis of any cancer and all‐cause mortality was obtained from Danish national registries. Outcome was compared with the general Danish population. Overall and type‐specific risk of cancer was analysed in an adjusted Poisson and Cox regression analysis. The 975 diagnoses of cancer in the HF cohort and 330 843 in the background population corresponded to incidence rates per 10 000 patient‐years of 188.9 [95% confidence interval (CI) 177.2–200.6] and 63.0 (95% CI 63.0–63.4), respectively. When stratified by age, incidence rates were increased in all age groups in the HF cohort. Risk of any type of cancer was increased, with an incidence rate ratio of 1.24 (95% CI 1.15–1.33, c < 0.0001). Type‐specific analysis demonstrated an increased hazard ratio for all major types of cancer except for prostate cancer. All‐cause mortality was higher in HF patients with cancer compared with cancer patients from the background population.

Conclusions

Patients with HF have an increased risk of cancer, which persists after the first year after the diagnosis of HF, and their prognosis is worse compared with that of cancer patients without HF.
Transfer of benzo[a]pyrene from microplastics to Artemia nauplii and further to zebrafish via a trophic food web experiment: CYP1A induction and visual tracking of persistent organic pollutants
Authors: Batel Annika , Linti Frederic , Scherer Martina , Erdinger Lothar , Braunbeck Thomas
Published: January 2016

The uptake of microplastic particles and the transfer of potential harmful substances along with microplastics has been studied in a variety of organisms, especially invertebrates. However, the potential accumulation of very small microplastic particles along food webs ending with vertebrate models has not been investigated so far. Therefore, a simple artificial food chain with Artemia sp. nauplii and zebrafish (Danio rerio) was established to analyze the transfer of microplastic particles and associated persistent organic pollutants (POPs) between different trophic levels. Very small (1–20 μm) microplastic particles accumulated in Artemia nauplii and were subsequently transferred to fish. Virgin particles not loaded with POPs did not cause any observable physical harm in the intestinal tracts of zebrafish, although parts of the particles were retained within the mucus of intestinal villi and might even have been taken up by epithelial cells. The transfer of associated POPs was tested with the polycyclic aromatic hydrocarbon benzo[a]pyrene and an ethoxyresorufin-O-deethylase (EROD) assay for CYP1A induction in zebrafish liver as well as via fluorescence analyses. Whereas a significant induction in the EROD assay could not be shown, because of high individual variation and low sensitivity regarding substance concentration, the fluorescence tracking of benzo[a]pyrene indicates that food-borne microplastic-associated POPs may actually desorb in the intestine of fish and are thus transferred to the intestinal epithelium and liver. Environ Toxicol Chem 2016;35:1656–1666. © 2016 SETAC
Generation of mt:egfp transgenic zebrafish biosensor for the detection of aquatic zinc and cadmium
Authors: Liu Lili , Yan Yanchun , Wang Jian , Wu Wei , Xu Lei
Published: January 2016

Zebrafish embryo toxicity testing has become a popular method for detecting environmental pollutions. However, the present research showed that zebrafish embryos exhibited no visible paramorphia, malformation, or mortality when exposed to heavy metals in a range above environmental standard limits, indicating that zebrafish embryos are an imprecise model for monitoring environmental heavy metals concentrations above regulatory limits. Aiming to obtain a biosensor for aquatic heavy metals, a metal-sensitive vector including zebrafish metallothionein (MT) promoter and enhanced green fluorescent protein (EGFP) was reconstructed and microinjected into 1-cell stage zebrafish embryos. The authors obtained an mt:egfp transgenic zebrafish line sensitive to aquatic zinc and cadmium. A quantitative experiment showed that zinc and cadmium treatment significantly induced the expression of EGFP in a dose- and time-dependent manner. In particular, EGFP messenger RNA levels increased remarkably when exposed to heavy metals above the standard limits. The results suggest that the transgenic zebrafish is a highly sensitive biosensor for detecting environmental levels of zinc and cadmium. Environ Toxicol Chem 2016;35:2066–2073. © 2016 SETAC
Integrated simulations of CO2 spreading and pressure response in the multilayer saline aquifer of South Scania Site, Sweden
Authors: Tian Liang , Yang Zhibing , Jung Byeongju , Joodaki Saba , Erlström Mikael , Zhou Quanlin , Niemi Auli
Published: January 2016

An integrated modeling approach/workflow, in which a series of mathematical models of different levels of complexity are applied to evaluate the geological storage capacity of the Scania Site, southwest Sweden, is presented. The storage formation at the site is a layered formation limited by bounding fault zones, and injection is assumed to take place from one existing deep borehole into all layers. A semi‐analytical model for two‐phase flow is first used to evaluate the pressure response and related parameter sensitivity, as well as the first estimates of acceptable injection rates. These results are then used to guide the more detailed numerical simulations that address both pressure response and plume migration. The vertical equilibrium (VE) model is used to obtain a preliminary understanding of the plume migration with a larger number of simulations. Finally the full TOUGH2/ECO2N simulations are performed for the most detailed analyses of pressure responses and plume migration. Throughout, the results of the different modeling approaches are compared to each other. It is concluded that the key limiting factor for the storage capacity at the site in the injection scenario considered is the fast CO2 migration within the high permeability layer. Future studies can address alternative injection scenarios, including using horizontal injection wells and injection to other layers than the high permeability layer.
Canonical NF‐κB signaling in hepatocytes acts as a tumor‐suppressor in hepatitis B virus surface antigen‐driven hepatocellular carcinoma by controlling the unfolded protein response
Authors: Sunami Yoshiaki , Ringelhan Marc , Kokai Enikö , Lu Miao , O'Connor Tracy , Lorentzen Anna , Weber Achim , Rodewald Ann‐Katrin , Müllhaupt Beat , Terracciano Luigi , Gul Sarah , Wissel Sebastian , Leithäuser Frank , Krappmann Daniel , Riedl Petra , Hartmann Daniel , Schirmbeck Reinhold , Strnad Pavel , Hüser Norbert , Kleeff Jörg , Friess Helmut , Schmid Roland M , Geisler Fabian , Wirth Thomas , Heikenwalder Mathias
Published: January 2016

Chronic hepatitis B virus (HBV) infection remains the most common risk factor for hepatocellular carcinoma (HCC). Efficient suppression of HBV viremia and necroinflammation as a result of nucleos(t)ide analogue treatment is able to reduce HCC incidence; nevertheless, hepatocarcinogenesis can occur in the absence of active hepatitis, correlating with high HBV surface antigen (HBsAg) levels. Nuclear factor κB (NF‐κB) is a central player in chronic inflammation and HCC development. However, in the absence of severe chronic inflammation, the role of NF‐κB signaling in HCC development remains elusive. As a model of hepatocarcinogenesis driven by accumulation of HBV envelope polypeptides, HBsAg transgenic mice, which show no HBV‐specific immune response, were crossed to animals with hepatocyte‐specific inhibition of canonical NF‐κB signaling. We detected prolonged, severe endoplasmic reticulum stress already at 20 weeks of age in NF‐κB‐deficient hepatocytes of HBsAg‐expressing mice. The unfolded protein response regulator binding immunoglobulin protein/78‐kDa glucose‐regulated protein was down‐regulated, activating transcription factor 6, and eIF2α were activated with subsequent overexpression of CCAAT/enhancer binding protein homologous protein. Notably, immune cell infiltrates and liver transaminases were unchanged. However, as a result of this increased cellular stress, insufficient hepatocyte proliferation due to G1/S‐phase cell cycle arrest with overexpression of p27 and emergence of ductular reactions was detected. This culminated in increased DNA damage already at 20 weeks of age and finally led to 100% HCC incidence due to NF‐κB inhibition. Conclusion: The role of canonical NF‐κB signaling in HCC development depends on the mode of liver damage; in the case of HBsAg‐driven hepatocarcinogenesis, NF‐κB in hepatocytes acts as a critical tumor suppressor by augmenting the endoplasmic reticulum stress response. (Hepatology 2016;63:1592‐1607)
Macrophage Recruitment Contributes to Regeneration of Mechanosensory Hair Cells in the Zebrafish Lateral Line
Authors: Carrillo Simón A. , Anguita‐Salinas Consuelo , Peña Oscar A. , Morales Rodrigo A. , Muñoz‐Sánchez Salomé , Muñoz‐Montecinos Carlos , Paredes‐Zúñiga Susana , Tapia Karina , Allende Miguel L.
Published: January 2016

In vertebrates, damage to mechanosensory hair cells elicits an inflammatory response, including rapid recruitment of macrophages and neutrophils. While hair cells in amniotes usually become permanently lost, they readily regenerate in lower vertebrates such as fish. Damage to hair cells of the fish lateral line is followed by inflammation and rapid regeneration; however the role of immune cells in this process remains unknown. Here, we show that recruited macrophages are required for normal regeneration of lateral line hair cells after copper damage. We found that genetic ablation or local ablation using clodronate liposomes of macrophages recruited to the site of injury, significantly delays hair cell regeneration. Neutrophils, on the other hand, are not needed for this process. We anticipate our results to be a starting point for a more detailed description of extrinsic signals important for regeneration of mechanosensory cells in vertebrates. J. Cell. Biochem. 117: 1880–1889, 2016. © 2016 Wiley Periodicals, Inc.
The Dietary Flavonoid Fisetin Causes Cell Cycle Arrest, Caspase‐Dependent Apoptosis, and Enhanced Cytotoxicity of Chemotherapeutic Drugs in Triple‐Negative Breast Cancer Cells
Authors: Smith Matthew L. , Murphy Kaylee , Doucette Carolyn D. , Greenshields Anna L. , Hoskin David W.
Published: January 2016

Fisetin (3,3′,4′,7‐tetrahydroxyflavone), a flavonoid found in a number of fruits and vegetables, has diverse biological activities, including cytotoxic effects on cancer cells. In this study, we investigated the effect of fisetin on triple‐negative breast cancer (TNBC) cells. TNBC has a poorer prognosis than other types of breast cancer and treatment options for this disease are limited. Fisetin inhibited the growth of MDA‐MB‐468 and MDA‐MB‐231 TNBC cells, as well as their ability to form colonies, without substantially affecting the growth of non‐malignant cells. In addition, fisetin inhibited the growth of estrogen receptor‐bearing MCF‐7 breast cancer cells and human epidermal growth factor receptor 2‐overexpressing SK‐BR‐3 breast cancer cells. Fisetin inhibited TNBC cell division and induced apoptosis, which was associated with mitochondrial membrane permeabilization and the activation of caspase‐9 and caspase‐8, as well as the cleavage of poly(ADP‐ribose) polymerase‐1. Induction of caspase‐dependent apoptosis by fisetin was confirmed by reduced killing of TNBC cells in the presence of the pan‐caspase inhibitors Z‐VAD‐FMK and BOC‐D‐FMK. Decreased phosphorylation of histone H3 at serine 10 in fisetin‐treated TNBC cells at G2/M phase of the cell cycle suggested that fisetin‐induced apoptosis was the result of Aurora B kinase inhibition. Interestingly, the cytotoxic effect of cisplatin, 5‐fluorouracil, and 4‐hydroxycyclophosphamide metabolite of cyclophosphamide on TNBC cells was increased in the presence of fisetin. These findings suggest that further investigation of fisetin is warranted for possible use in the management of TNBC. J. Cell. Biochem. 117: 1913–1925, 2016. © 2016 Wiley Periodicals, Inc.
Elevation of Brain Magnesium Potentiates Neural Stem Cell Proliferation in the Hippocampus of Young and Aged Mice
Authors: Jia Shanshan , Liu Yunpeng , Shi Yang , Ma Yihe , Hu Yixin , Wang Meiyan , Li Xue
Published: January 2016

In the adult brain, neural stem cells (NSCs) can self‐renew and generate all neural lineage types, and they persist in the sub‐granular zone (SGZ) of the hippocampus and the sub‐ventricular zone (SVZ) of the cortex. Here, we show that dietary‐supplemented ‐ magnesium‐L‐threonate (MgT), a novel magnesium compound designed to elevate brain magnesium regulates the NSC pool in the adult hippocampus. We found that administration of both short‐ and long‐term regimens of MgT, increased the number of hippocampal NSCs. We demonstrated that in young mice, dietary supplementation with MgT significantly enhanced NSC proliferation in the SGZ. Importantly, in aged mice that underwent long‐term (12‐month) supplementation with MgT, MgT did not deplete the hippocampal NSC reservoir but rather curtailed the age‐associated decline in NSC proliferation. We further established an association between extracellular magnesium concentrations and NSC self‐renewal in vitro by demonstrating that elevated Mg2+ concentrations can maintain or increase the number of cultured hippocampal NSCs. Our study also suggests that key signaling pathways for cell growth and proliferation may be candidate targets for Mg2+'s effects on NSC self‐renewal. J. Cell. Physiol. 231: 1903–1912, 2016. © 2016 Wiley Periodicals, Inc.
Signaling and Gene Regulatory Networks Governing Definitive Endoderm Derivation From Pluripotent Stem Cells
Authors: Mohammadnia Abdulshakour , Yaqubi Moein , Pourasgari Farzaneh , Neely Eric , Fallahi Hossein , Massumi Mohammad
Published: January 2016

The generation of definitive endoderm (DE) from pluripotent stem cells (PSCs) is a fundamental stage in the formation of highly organized visceral organs, such as the liver and pancreas. Currently, there is a need for a comprehensive study that illustrates the involvement of different signaling pathways and their interactions in the derivation of DE cells from PSCs. This study aimed to identify signaling pathways that have the greatest influence on DE formation using analyses of transcriptional profiles, protein–protein interactions, protein–DNA interactions, and protein localization data. Using this approach, signaling networks involved in DE formation were constructed using systems biology and data mining tools, and the validity of the predicted networks was confirmed experimentally by measuring the mRNA levels of hub genes in several PSCs‐derived DE cell lines. Based on our analyses, seven signaling pathways, including the BMP, ERK1‐ERK2, FGF, TGF‐beta, MAPK, Wnt, and PIP signaling pathways and their interactions, were found to play a role in the derivation of DE cells from PSCs. Lastly, the core gene regulatory network governing this differentiation process was constructed. The results of this study could improve our understanding surrounding the efficient generation of DE cells for the regeneration of visceral organs. J. Cell. Physiol. 231: 1994–2006, 2016. © 2016 Wiley Periodicals, Inc.