bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiangiogenic and Toxic Effects of Genistein, Usnic Acid, and Their Copper Complexes in Zebrafish Embryos at Different Developmental Stages
Authors: Draut Heidrun , Rehm Tobias , Begemann Gerrit , Schobert Rainer
Published: December 2016

Angiogenesis plays a major role in the normal embryonic development and in diseases such as cancer. Drugs that control angiogenesis are an alternative way to tackle this disease. The polyphenols usnic acid (3), genistein (5), and daidzein (6) were tested for antiangiogenic and unwanted effects in zebrafish embryos whose blood vessel system resembles that of mammals. The established tyrosine kinase inhibitors axitinib (1) and tyrphostin AG490 (2) were included for comparison. All compounds except 6 caused distinct antiangiogenic effects such as a concentration‐dependent reduction of intersegmental vessels, dorsal longitudinal anastomotic vessels, subintestinal veins and secondary sprouts. As side effects, pericardial oedema and the impairment of blood flow were observed. Usnic acid (3), genistein (5) and Cu(II)‐genisteinate (7) gave rise to a curvature of the spine. Compounds 5 and 7 also induced cell death in the head of the embryos at higher doses. All effects were more pronounced when the compounds had been applied at an early stage (24 hpf) rather than at 48 hpf. The copper complexes 4 and 7 showed a stronger antiangiogenic effect than the free ligands 3 and 5. The genistein complex 7 was antiangiogenic at doses so low that side effects were tolerable, and thus it may be a potential anticancer drug candidate.
Chemical Composition, Antimicrobial and Insecticidal Activities of Flowers Essential Oils of Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm. from Martinique Island
Authors: Kerdudo Audrey , Ellong Emy Njoh , Burger Pauline , Gonnot Vanessa , Boyer Laurent , Chandre Fabrice , Adenet Sandra , Rochefort Katia , Michel Thomas , Fernandez Xavier
Published: December 2016

Alpinia species, used as ornamental plants and flavoring agents, are renowned for their therapeutic properties and their subsequent use in traditional medicines throughout the world. Alpinia zerumbet (Pers.) B.L.Burtt & R.M.Sm. is the most common Alpinia species encountered in Martinique. Several essential oils (EOs) obtained by hydrodistillation of A. zerumbet flowers collected in various locations on the island at different seasons were analysed to evaluate the influence of the collection period and area on the EOs’ chemical compositions and to assess their bioactivity. A combination of GC‐FID and GC/MS techniques was used to examine the volatile constituents, leading to the identification of a total of 71 components accounting for 97.8 – 99.3% of the respective total GC‐FID areas: among them, nineteen compounds were characterized for the first time in A. zerumbet EOs. The antimicrobial activity of these EOs was assessed against eight bacterial, yeast and fungal strains and two multi‐resistant strains: some significant bacteriostatic and fungistatic activities of A. zerumbet flower oils were evidenced. Finally, an interesting insecticidal activity of the flower EO was highlighted for the first time against Aedes aegypti.
Enhancement of Ag‐Based Plasmonic Photocatalysis in Hydrogen Production from Ammonia Borane by the Assistance of Single‐Site Ti‐Oxide Moieties within a Silica Framework
Authors: Verma Priyanka , Kuwahara Yasutaka , Mori Kohsuke , Yamashita Hiromi
Published: December 2016

Ag nanoparticles (NPs) have gained great attention owing to their interesting plasmonic properties and efficient catalysis under visible‐light irradiation. In this study, an Ag‐based plasmonic catalyst supported on mesoporous silica with isolated and tetrahedrally coordinated single‐site Ti‐oxide moieties, namely, Ag/Ti‐SBA‐15, was designed with the purpose of utilizing the broad spectral range of solar energy. The Ti‐SBA‐15 support allows the deposition of small Ag NPs with a narrow size distribution. The chemical structure, morphology, and optical properties of the prepared catalyst were characterized by techniques such as UV/Vis, FT extended X‐ray absorption fine structure, and X‐ray photoelectron spectroscopy, field‐emission SEM, TEM, and N2 physisorption studies. The catalytic activity of Ag/Ti‐SBA‐15 in hydrogen production from ammonia borane by hydrolysis was significantly enhanced in comparison with Ag/SBA‐15 without Ti‐oxide moieties and Ag/TiO2/SBA‐15 involving agglomerated TiO2, both in the dark and under light irradiation. Improved electron transfer under light irradiation caused by the creation of heterojunctions between Ag NPs and Ti‐oxide moieties explains the results obtained in the present study.
C3‐Symmetric Boron Lewis Acid with a Cage‐Shape for Chiral Molecular Recognition and Asymmetric Catalysis
Authors: Konishi Akihito , Nakaoka Koichi , Maruyama Hikaru , Nakajima Hideto , Eguchi Tomohiro , Baba Akio , Yasuda Makoto
Published: December 2016

Chiral Lewis acids play an important role in the precise construction of various types of chiral molecules. Here, a cage‐shaped borate 2 was designed and synthesized as a chiral Lewis acid that possesses a unique C3‐symmetric structure composed of three homochiral binaphthyl moieties. The highly symmetrical structure of 2 with homochirality was clearly elucidated by X‐ray crystallographic analysis. The peculiar chiral environment of 2⋅THF exhibited chiral recognition of some simple amines and a sulfoxide. Moreover, the application of 2⋅THF to hetero‐Diels–Alder reactions as a chiral Lewis‐acid catalyst afforded the enantioselective products, which were obtained through an entropy‐controlled pathway according to the analysis of the relationship between optical yield and reaction temperature. In particular, the robust chiral reaction field of 2⋅THF allowed the first example of an asymmetric hetero‐Diels–Alder reaction with a simple diene despite the requirement of high temperature.
Cell Surface Nano‐modulation for Non‐invasive in vivo Near‐IR Stem Cell Monitoring
Authors: Shin Woo Jung , Shin Seung Won , Yuk Ji Soo , Amornkitbamrung Lunjakorn , Jang Min Su , Song In Hyun , Choi Soon Won , Kang Insung , Lee Jin Young , Bae Hojae , Kang Kyung‐Sun , Um Soong Ho
Published: December 2016

A stem cell tracking system is in high demand for the determination of cell destinations and for the validation of cell therapeutic efficacy in regenerative transplantation. To date, near‐infrared (NIR) imaging technology has received considerable attention in cell behavior monitoring, owing to its patient compatibility, easy accessibility and cost effectiveness. Conventionally, in vivo cell tracking has been visualized by direct in‐cell staining with NIR, where it may be achieved by complicated genetic engineering. Such genetic amendment techniques have suffered from serious challenges, which can destroy a cell's metabolism and can accidentally incur unexpected carcinoma. Herein we demonstrate a novel cell nano‐modulation method for noninvasive stem cell monitoring. It is simply achieved by conjugating stem cells with lipid‐supported, NIR‐tagged, polymeric nanoparticles. These engineered cells, which are designated as NIR‐labeled light‐emitting stem cells (LESCs), maintain their biochemical functionality (i.e., differentiation, quantum efficacy, etc.) even after conjugation. LESCs were used for in situ stem cell monitoring at inoculation sites. It is speculated that the LESC technique could provide a new preparative methodology for in vivo cell tracking in advanced diagnostic medicine, where cell behavior is a critical issue.
Uncertainty quantification of inflow boundary condition and proximal arterial stiffness–coupled effect on pulse wave propagation in a vascular network
Authors: Brault Antoine , Dumas Laurent , Lucor Didier
Published: December 2016

This work aims at quantifying the effect of inherent uncertainties from cardiac output on the sensitivity of a human compliant arterial network response based on stochastic simulations of a reduced‐order pulse wave propagation model. A simple pulsatile output form is used to reproduce the most relevant cardiac features with a minimum number of parameters associated with left ventricle dynamics. Another source of significant uncertainty is the spatial heterogeneity of the aortic compliance, which plays a key role in the propagation and damping of pulse waves generated at each cardiac cycle. A continuous representation of the aortic stiffness in the form of a generic random field of prescribed spatial correlation is then considered. Making use of a stochastic sparse pseudospectral method, we investigate the sensitivity of the pulse pressure and waves reflection magnitude over the arterial tree with respect to the different model uncertainties. Results indicate that uncertainties related to the shape and magnitude of the prescribed inlet flow in the proximal aorta can lead to potent variation of both the mean value and standard deviation of blood flow velocity and pressure dynamics due to the interaction of different wave propagation and reflection features. Lack of accurate knowledge in the stiffness properties of the aorta, resulting in uncertainty in the pulse wave velocity in that region, strongly modifies the statistical response, with a global increase in the variability of the quantities of interest and a spatial redistribution of the regions of higher sensitivity. These results will provide some guidance in clinical data acquisition and future coupling of arterial pulse wave propagation reduced‐order model with more complex beating heart models.
A comprehensive and scalable middleware for Ambient Assisted Living based on cloud computing and Internet of Things
Authors: Gomes Berto de Tácio Pereira , Muniz Luiz Carlos Melo , da Silva e Silva Francisco José , Ríos Luis Eduardo Talavera , Endler Markus
Published: December 2016

Ambient Assisted Living (AAL) main goal is the development of health monitoring systems for patients with chronic diseases and elderly people through the use of body, home, and environmental sensors that increase their degree of independence and mobility. A comprehensive software infrastructure for AAL systems should be able to cover scenarios involving several patient mobility levels, locations, and physical and cognitive abilities. Cloud computing can provide to AAL systems the ability to extend the limited processing power of mobile devices, but its main role is to integrate all stakeholders through the storage and processing of health data and the orchestration of healthcare business logic. On the other hand, the Internet of Things (IoT) provides the ability to connect sensors and actuators, integrating and making them available through the Internet. This paper presents the Mobile‐Hub/Scalable Data Distribution Layer, a middleware for AAL based on cloud computing and IoT. We discuss how this middleware can handle the requirements of the main health monitoring scenarios and present results that demonstrate the ability to opportunistically discover and connect with sensors in a timely manner and the scalability necessary for handling the connection and data processing of many connected patients.
Validation of a microdose probe drug cocktail for clinical drug interaction assessments for drug transporters and CYP3A
Authors: Prueksaritanont T , Tatosian DA , Chu X , Railkar R , Evers R , Chavez‐Eng C , Lutz R , Zeng W , Yabut J , Chan GH , Cai X , Latham AH , Hehman J , Stypinski D , Brejda J , Zhou C , Thornton B , Bateman KP , Fraser I , Stoch SA
Published: December 2016

A microdose cocktail containing midazolam, dabigatran etexilate, pitavastatin, rosuvastatin, and atorvastatin has been established to allow simultaneous assessment of a perpetrator impact on the most common drug metabolizing enzyme, cytochrome P450 (CYP)3A, and the major transporters organic anion‐transporting polypeptides (OATP)1B, breast cancer resistance protein (BCRP), and MDR1 P‐glycoprotein (P‐gp). The clinical utility of these microdose cocktail probe substrates was qualified by conducting clinical drug interaction studies with three inhibitors with different in vitro inhibitory profiles (rifampin, itraconazole, and clarithromycin). Generally, the pharmacokinetic profiles of the probe substrates, in the absence and presence of the inhibitors, were comparable to their reported corresponding pharmacological doses, and/or in agreement with theoretical expectations. The exception was dabigatran, which resulted in an approximately twofold higher magnitude for microdose compared to conventional dosing, and, thus, can be used to flag a worst‐case scenario for P‐gp. Broader application of the microdose cocktail will facilitate a more comprehensive understanding of the roles of drug transporters in drug disposition and drug interactions.
Engineering Favorable Morphology and Structure of Fe‐N‐C Oxygen‐Reduction Catalysts through Tuning of Nitrogen/Carbon Precursors
Authors: Gupta Shiva , Zhao Shuai , Ogoke Ogechi , Lin Ye , Xu Hui , Wu Gang
Published: December 2016

Structures and morphologies of Fe‐N‐C catalysts are believed to be crucial because of the number of active sites and local bonding structures governing the overall catalyst performance for the oxygen reduction reaction (ORR). However, the knowledge how to rationally design catalysts is still lacking. By combining different nitrogen/carbon precursors, including polyaniline (PANI), dicyandiamide (DCDA), and melamine (MLMN), we aim to tune catalyst morphology and structure to facilitate the ORR. Instead of the commonly studied single precursors, multiple precursors were used during the synthesis; this provides a new opportunity to promote catalyst activity and stability through a likely synergistic effect. The best‐performing Fe‐N‐C catalyst derived from PANI+DCDA is superior to the individual PANI or DCDA‐derived ones. In particular, when compared to the extensively explored PANI‐derived catalysts, the binary precursors have an increased half‐wave potential of 0.83 V and an enhanced electrochemical stability in challenging acidic media, indicating a significantly increased number of active sites and strengthened local bonding structures. Multiple key factors associated with the observed promotion are elucidated, including the optimal pore size distribution, highest electrochemically active surface area, presence of dominant amorphous carbon, and thick graphitic carbon layers with more pyridinic nitrogen edge sites likely bonded with active atomic iron.
Mass Cytometry of Follicular Lymphoma Tumors Reveals Intrinsic Heterogeneity in Proteins Including HLA‐DR and a Deficit in Nonmalignant Plasmablast and Germinal Center B‐Cell Populations
Authors: Wogsland Cara Ellen , Greenplate Allison Rae , Kolstad Arne , Myklebust June Helen , Irish Jonathan Michael , Huse Kanutte
Published: December 2016

Background

Follicular lymphoma (FL) is an indolent non‐Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the nonmalignant B‐cell and T‐cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B‐cell heterogeneity.

Methods

Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, nonmalignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue.

Results

Diversity in cellular phenotype between tumors was greater for the malignant B cells than for nonmalignant B or T cells. The malignant B‐cell population bore little phenotypic similarity to any healthy B‐cell subset, and unexpectedly clustered closer to naïve B‐cell populations than GC B‐cell populations. Among the nonmalignant B cells within FL tumors, a significant lack of GC and plasmablast B cells was observed relative to tonsil controls. In contrast, nonmalignant T cells in FL tumors were present at levels similar to their cognate tonsillar T‐cell subsets.

Conclusion

Mass cytometry revealed that diverse HLA‐DR expression on FL cells within individual tumors contributed greatly to tumor heterogeneity. Both malignant and nonmalignant B cells in the tumor bore little phenotypic resemblance to healthy GC B cells despite the presence of T follicular helper cells in the tumor. These findings suggest that ongoing signaling interactions between malignant B cells and intra‐tumor T cells shape the tumor microenvironment. © 2016 International Clinical Cytometry Society
Development of a pathway model to assess the exposure of European pine trees to pine wood nematode via the trade of wood
Authors: Douma J. C. , van der Werf W. , Hemerik L. , Magnusson C. , Robinet C.
Published: December 2016

Pine wood nematode (PWN), Bursaphelenchus xylophilus, is a threat for pine species (Pinus spp.) throughout the world. The nematode is native to North America, and invaded Japan, China, Korea, and Taiwan, and more recently Portugal and Spain. PWN enters new areas through trade in wood products. Once established, eradication is not practically feasible. Therefore, preventing entry of PWN into new areas is crucial. Entry risk analysis can assist in targeting management to reduce the probability of entry. Assessing the entry of PWN is challenging due to the complexity of the wood trade and the wood processing chain. In this paper, we develop a pathway model that describes the wood trade and wood processing chain to determine the structure of the entry process. We consider entry of PWN through imported coniferous wood from China, a possible origin of Portuguese populations, to Europe. We show that exposure increased over years due to an increase in imports of sawn wood. From 2000 to 2012, Europe received an estimated 84 PWN propagules from China, 88% of which arose from imported sawn wood and 12% from round wood. The region in Portugal where the PWN was first reported is among those with the highest PWN transfer per unit of imported wood due to a high host cover and vector activity. An estimated 62% of PWN is expected to enter in countries where PWN is not expected to cause the wilt of pine trees because of low summer temperatures (e.g., Belgium, Sweden, Norway). In these countries, PWN is not easily detected, and such countries can thus serve as potential reservoirs of PWN. The model identifies ports and regions with high exposure, which helps targeting monitoring and surveillance, even in areas where wilt disease is not expected to occur. In addition, we show that exposure is most efficiently reduced by additional treatments in the country of origin, and/or import wood from PWN‐free zones. Pathway modelling assists plant health managers in analyzing risks along the pathway and planning measures for enhancing biosecurity.
Bee communities along a prairie restoration chronosequence: similar abundance and diversity, distinct composition
Authors: Tonietto Rebecca K. , Ascher John S. , Larkin Daniel J.
Published: December 2016

Recognition of the importance of bee conservation has grown in response to declines of managed honey bees and some wild bee species. Habitat loss has been implicated as a leading cause of declines, suggesting that ecological restoration is likely to play an increasing role in bee conservation efforts. In the midwestern United States, restoration of tallgrass prairie has traditionally targeted plant community objectives without explicit consideration for bees. However, restoration of prairie vegetation is likely to provide ancillary benefits to bees through increased foraging and nesting resources. We investigated community assembly of bees across a chronosequence of restored eastern tallgrass prairies and compared patterns to those in control and reference habitats (old fields and prairie remnants, respectively). We collected bees for 3 yr and measured diversity and abundance of in‐bloom flowering plants, vegetation structure, ground cover, and surrounding land use as predictors of bee abundance and bee taxonomic and functional diversity. We found that site‐level variables, but not site type or restoration age, were significant predictors of bee abundance (bloom diversity,P = 0.004; bare ground cover,P = 0.02) and bee diversity (bloom diversity,P = 0.01). There were significant correlations between overall composition of bee and blooming plant communities (Mantel test,P = 0.002), and both plant and bee assemblages in restorations were intermediate between those of old fields and remnant prairies. Restorations exhibited high bee beta diversity, i.e., restored sites’ bee assemblages were taxonomically and functionally differentiated from each other. This pattern was strong in younger restorations (<20 yr old), but absent from older restorations (>20 yr), suggesting restored prairie bee communities become more similar to one another and more similar to remnant prairie bee communities over time with the arrival of more species and functional groups of bees. Our results indicate that old fields, restorations, and remnants provide habitat for diverse and abundant bee communities, but continued restoration of old fields will help support and conserve bee communities more similar to reference bee communities characteristic of remnant prairies.
Ecohydrological transformation in the Dry Chaco and the risk of dryland salinity: Following Australia's footsteps?
Authors: Marchesini Victoria A. , Giménez Raúl , Nosetto Marcelo D. , Jobbágy Esteban G.
Published: December 2016

During the last century, the massive conversion of Australian dry forests to crops and pastures triggered the massive soil and groundwater degradation process known as dryland salinity. Currently, South American Chaco's dry forests are undergoing a similar transformation, leading global deforestation rates. The goal of this study was to review existing ecohydrological information about natural and cultivated systems in the Chaco to assess the dryland salinity risks. We review deep soil water, salt stocks, and groundwater recharge from agriculture or native dry forests stands located in a precipitation range of 450–1100 mm. We complement this with water table level records and geoelectric profiles together with personal observations. We use data from 15 Australian studies for comparison. Strong salt leaching, especially after 20 years of forest clearance, indicates the onset of deep drainage following forest conversion to agriculture in the Dry Chaco. Water stocks were more than double in the cleared stands compared to their dry forest pairs, and recharge rates were up to two order magnitude higher in agricultural areas. Although lower atmospheric salt deposition, younger sediments, and relatively high water‐consuming agricultural systems in the Dry Chaco attenuate salinization risks compared to Australia, the very flat topography and related shallow water table levels of the South American region could make groundwater recharge and salt mobilization processes more widespread and difficult to manage. The lack of awareness among the general public, farmers, and decision makers about this issue amplifies the problem, making land management plans for the Argentine dry forest territories essential.
Projecting impacts of climate change on habitat availability in a macrophyte dominated Chalk River
Authors: House A. R. , Thompson J. R. , Roberts C. , de Smeth K. , Old G. , Acreman M. C.
Published: December 2016

Climate change will impact fluvial ecosystems through changes in the flow regime. Physical habitat is an established measure of a river's ecological status when assessing changes to flow. Yet, it requires extensive datasets, is site specific, and does not account for dynamic processes; shortcomings that the use of hydrological and hydraulic models may alleviate. Here, simulated flows along a 600 m reach of the River Lambourn, Boxford, UK, were extracted from the 1D MIKE 11 hydraulic component of an integrated MIKE SHE model of the Centre for Ecology & Hydrology River Lambourn Observatory. In‐channel seasonal macrophyte growth and management through cutting alter water levels, represented in the hydraulic model by manipulating channel bed roughness (Manning's n). Assessment of climate change used outputs from the UK Climate Projections 2009 ensemble of global climate models for the 2080s. River discharge outputs were disaggregated to provide velocity and depth profiles across 41 cross sections along the reach. These were integrated with habitat suitability criteria for brown trout (Salmo trutta) to generate a measure of available physical habitat. The influence of macrophyte growth caused the habitat‐discharge relationship to be unusable in evaluating the sensitivity of brown trout to flow changes. Instead, projected time series were used to show an overall reduction in habitat availability, more for adult than juvenile trout. Results highlighted the impact of weed cutting, and its potential role in mitigating both flood risk and the ecological impacts of climate change. The use of a hydraulic model to assess physical habitat availability has worldwide applicability.
Plant‐herbivore synchrony and selection on plant flowering phenology
Authors: Fogelström Elsa , Olofsson Martin , Posledovich Diana , Wiklund Christer , Dahlgren Johan P. , Ehrlén Johan
Published: December 2016

Temporal variation in natural selection has profound effects on the evolutionary trajectories of populations. One potential source of variation in selection is that differences in thermal reaction norms and temperature influence the relative phenology of interacting species. We manipulated the phenology of the butterfly herbivore Anthocharis cardamines relative to genetically identical populations of its host plant, Cardamine pratensis, and examined the effects on butterfly preferences and selection acting on the host plant. We found that butterflies preferred plants at an intermediate flowering stage, regardless of the timing of butterfly flight relative to flowering onset of the population. Consequently, the probability that plant genotypes differing in timing of flowering should experience a butterfly attack depended strongly on relative phenology. These results suggest that differences in spring temperature influence the direction of herbivore‐mediated selection on flowering phenology, and that climatic conditions can influence natural selection also when phenotypic preferences remain constant.
Invasive exotic shrub modifies a classic animal‐habitat relationship and alters patterns of vertebrate seed predation
Authors: Guiden Peter W. , Orrock John L.
Published: December 2016

Recent evidence suggests that invasive exotic plants can provide novel habitats that alter animal behavior. However, it remains unclear whether classic animal‐habitat associations that influence the spatial distribution of plant‐animal interactions, such as small mammal use of downed woody debris, persist in invaded habitats. We removed an invasive exotic shrub (buckthorn, Rhamnus cathartica) from 7 of 15 plots in Wisconsin. In each plot, we deployed 200 tagged Quercus rubra seeds in November 2014. After five months, tags were recovered to track spatial patterns of small mammal seed predation. Most recovered tags were associated with consumed seeds (95%); live‐trapping, ancillary camera‐trapping, and previous behavioral studies suggest that white‐footed mice (Peromyscus leucopus) were responsible for most seed predation. In habitats without R. cathartica, most seed predation occurred near woody debris. In habitats with R. cathartica, small mammals rarely consumed seeds near woody debris, and seed predation occurred farther from the plot center and was less spatially clustered. Our results illustrate that invasive exotic shrubs can disrupt an otherwise common animal‐habitat relationship. Failing to account for changes in habitat use may diminish our ability to predict animal distributions and outcomes of species interactions in novel habitats created by invasive exotic plants.
Crystal Structures and Spin‐Crossover Behavior of Iron(II) Complexes with Chiral and Racemic Ligands
Authors: Sekimoto Yusuke , Karim Mohammad Razaul , Saigo Naoto , Ohtani Ryo , Nakamura Masaaki , Hayami Shinya
Published: December 2016

Chiral iron(II) complexes, [Fe{(R)‐L}2(NCS)2] (1) and [Fe{(S)‐L}2(NCS)2] (2), and racemic complex [Fe(rac)‐L)2(NCS)2] (3) {L = α‐methyl‐N‐(2‐pyridinylmethylene)cyclohexanemethanamine} were synthesized. Their structures and magnetic properties were investigated by X‐ray crystallography, magnetic susceptibility measurements, and Mössbauer spectroscopy. Complexes 1 and 2 crystallize in the trigonal system with space group P3121 and P3221, respectively. All complexes exhibit spin‐crossover (SCO) behavior and light induced excited spin state trapping (LIESST) effects at 532 nm. Complexes 1 and 2 show similar gradual SCO behavior, and complex 3 shows more gradual SCO, which seems to be a result of the different crystal packing, as complex 3 is the symmetric isomer but 1 and 2 are asymmetric.
Sunflow: Sunlight Drives Fast and Green Photochemical Flow Reactions in Simple Microcapillary Reactors – Application to Photoredox and H‐Atom‐Transfer Chemistry
Authors: Nauth Alexander M. , Lipp Alexander , Lipp Benjamin , Opatz Till
Published: December 2016

“Sunflow“ – The combination of a microcapillary reactor in continuous flow mode with sunlight as the most sustainable energy source imaginable was applied to a range of photoredox and H‐atom‐transfer reactions making them both fast and green.
Nickel(II)‐Catalyzed Enantioselective 1,3‐Dipolar Cycloaddition of Nitrones with α,β‐Unsaturated Acylcarboxylates
Authors: Xie Lei , Yu Xuan , Li Jiaqi , Zhang Zhenhua , Qin Zhaohai , Fu Bin
Published: December 2016

The highly enantioselective 1,3‐dipolar cycloaddition of nitrones with α,β‐unsaturated acylcarboxylates was realized for the first time by using a chiral bis(indano‐oxazoline)‐based Ni complex. The reaction proceeded smoothly under mild conditions and provided isoxazolidines with three contiguous stereocenters in high yields with excellent diastereoselectivities (>20:1 dr) and enantioselectivities (up to 99 % ee). The reaction was scaled up to the gram scale, and the products were readily transformed into γ‐amino alcohols and other potentially bioactive compounds.
Conceptualizing delta forms and processes in Arctic coastal environments
Authors: Bendixen Mette , Kroon Aart
Published: December 2016

Climate warming in the Arctic directly causes two opposite changes in Arctic coastal systems: increased melt‐water discharge through rivers induces extra influx of sediments and extended open water season increases wave impact which reworks and erodes the shores. A shoreline change analysis along the southern coast of Disko Island in western Greenland was conducted with aerial photographs and satellite images from 1964, 1985, and 2012. The decadal morphologic evolution of this 85 km section showed that large parts of the coast had undergone very limited changes. However, two deltas were highly dynamic and popped up as hotspots.

The Tuapaat delta and Skansen delta showed large progradation rates (1.5 and 7 m/yr) and migration of the adjacent barriers and spits. The dynamic behavior at the delta mouths was mainly caused by classic delta channel lobe switching at one delta (Tuapaat), and by a breach of the fringing spit at the other delta (Skansen). The longshore and cross‐shore transports are responsible for reworking the sediment with a result of migrating delta mouths and adjacent subaqueous mouth bars. Seaward progradation of the deltas is limited due to the steep nature of the bathymetry in Disko Bay.

Finally, a schematic conceptual overview of processes and associated morphological responses for deltas in Arctic environments is presented, including the climate drivers affecting delta evolution. Copyright © 2016 John Wiley & Sons, Ltd.
Characterization of oil and water accommodated fractions used to conduct aquatic toxicity testing in support of the Deepwater Horizon oil spill natural resource damage assessment
Authors: Forth Heather P. , Mitchelmore Carys L. , Morris Jeffrey M. , Lipton Joshua
Published: December 2016

The Deepwater Horizon blowout resulted in the release of millions of barrels of crude oil. As part of the Trustees’ Natural Resource Damage Assessment, a testing program was implemented to evaluate the toxicity of Deepwater Horizon oil and oil/dispersant mixtures to aquatic organisms from the Gulf of Mexico. Because of the variety of exposures that likely occurred, the program included 4 Deepwater Horizon oils, which encompassed a range of weathering states, and 3 different oil-in-water mixing methods, for a total of 12 unique water accommodated fractions (WAFs). The present study reports on the chemical characteristics of these 4 Deepwater Horizon oils and 12 WAFs. In addition, to better understand exposure chemistry, an examination was conducted of the effects of WAF preparation parameters—including mixing energy, starting oil composition, and oil-to-water mixing ratios—on the chemical profiles and final concentrations of these 12 WAFs. The results showed that the more weathered the starting oil, the lower the concentrations of the oil constituents in the WAF, with a shift in composition to the less soluble compounds. In addition, higher mixing energies increased the presence of insoluble oil constituents. Finally, at low to mid oil-to-water mixing ratios, the concentration and composition of the WAFs changed with changing mixing ratios; this change was not observed at higher mixing ratios (i.e., >1 g oil/L). Ultimately, the present study provides a basic characterization of the oils and WAFs used in the testing program, which helps to support interpretation of the more than 500 Deepwater Horizon Natural Resource Damage Assessment toxicity testing results and to enable a comparison of these results with different tests and with the field. Environ Toxicol Chem 2017;36:1450–1459. © 2016 SETAC
AVIX: An Improved VIX Based on Stochastic Interest Rates and an Adaptive Screening Mechanism
Authors: Zheng Zhenlong , Jiang Zhengyun , Chen Rong
Published: December 2016

An improved model‐free implied variation index (AVIX) is proposed in this article. The AVIX is developed under a generalized semi‐martingale process with stochastic interest rates. An adaptive option screening mechanism is proposed to accommodate different market conditions. The effect of dividend protection is also considered. An empirical study of the China 50 ETF option market suggests that the AVIX is a better barometer of aggregate implied variation and investor sentiment than the traditional VIX. It reacts to market changes more rapidly and more sensitively. The AVIX also contains more information about future volatility and provides a more efficient forecast of future realized volatility. © 2016 Wiley Periodicals, Inc. Jrl Fut Mark 37:374–410, 2017
The role of the hippocampus in generalizing configural relationships
Authors: Berens Sam C. , Bird Chris M.
Published: December 2016

The hippocampus has been implicated in integrating information across separate events in support of mnemonic generalizations. These generalizations may be underpinned by processes at both encoding (linking similar information across events) and retrieval (“on‐the‐fly” generalization). However, the relative contribution of the hippocampus to encoding‐ and retrieval‐based generalizations is poorly understood. Using fMRI in humans, we investigated the hippocampal role in gradually learning a set of spatial discriminations and subsequently generalizing them in an acquired equivalence task. We found a highly significant correlation between individuals’ performance on a generalization test and hippocampal activity during the test, providing evidence that hippocampal processes support on‐the‐fly generalizations at retrieval. Within the same hippocampal region there was also a correlation between activity during the final stage of learning (when all associations had been learnt but no generalization was required) and subsequent generalization performance. We suggest that the hippocampus spontaneously retrieves prior events that share overlapping features with the current event. This process may also support the creation of generalized representations during encoding. These findings are supportive of the view that the hippocampus contributes to both encoding‐ and retrieval‐based generalization via the same basic mechanism; retrieval of similar events sharing common features. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.
What training and skills will the ecotoxicologists of the future require?
Authors: Harris Meagan J , Huggett Duane B , Staveley Jane P , Sumpter John P
Published: December 2016

Students and academic researchers conduct a diverse range of studies that add to the growing body of ecotoxicology research. Once an academic researcher entertains an applied research topic, there is potential for that research to be used in local, state, or federal regulatory decision or action. The ability of regulatory decision makers to use academic studies to inform decisions is dependent on: 1) the relevance of the experiment to regulatory decisions, 2) the reliability of the laboratory and the study itself, and 3) quality reporting of data such that study relevance and reliability are evident. The purpose of this brief communication is to highlight actions that can be taken by Society of Environmental Toxicology and Chemistry members to enhance the usability of academic research studies in regulatory decision making by promoting training, partnerships, and communication. Integr Environ Assess Manag 2017;13:580–584. © 2016 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC)

Key Points

Academic ecotoxicology studies may be considered for use in regulatory decision making, regardless of the authors’ intent for such studies to be used in this context. For academic studies to be useful for regulatory purposes, the study needs to be relevant and reliable; reporting of sufficient information for the evaluation of these attributes is critical. Training students on the topics of regulatory relevance and data reliability will lead to improvements in the applicability of academic research for regulatory decision making. Cross-sector partnerships (among academia, business, and government) provide learning and teaching opportunities for all participants.
Diagnostic and prognostic role of cell‐free DNA testing for colorectal cancer patients
Authors: Bedin Chiara , Enzo Maria Vittoria , Del Bianco Paola , Pucciarelli Salvatore , Nitti Donato , Agostini Marco
Published: December 2016

Circulating cell‐free DNA (cfDNA) was found in increased amounts in cancer patients and tumor‐associated molecular alteration can be detected in cancer patient's samples. For this reason, the cfDNA analysis is actually considered as a new concept of liquid biopsy. We evaluated the presence and integrity of plasma cfDNA by ALU‐based qPCR and the methylation profile of OSMR and SFRP1 genes promoter in a large cohort of colorectal cancer (CRC) patients (n = 114) in comparison to healthy subjects (n = 56) and patients with adenomatous lesions (n = 22). Moreover, we studied the prognosis value focusing on histopathological staging and survival. The cfDNA concentration and the integrity index were increased in CRC patients. The ALU83 and ALU244 fragment dosage showed a moderate discriminant capacity between CRC patients and controls and CRC and adenoma patients. Especially, cfDNA was significantly higher in CRC patients at advanced histopathological stage. In addition, the increased cfDNA level was associated with poor prognosis. A comparison of methylation profile in matched tissue and plasma on 25 CRC patients was performed and only three mismatched cases were observed. A lower methylation quantification was observed in cfDNA than tissue DNA. The cfDNA methylation frequency was statistically different in controls, adenoma and CRC patients and this frequency increased with the histopathological stage of tumor. The adenoma and CRC patients methylated cfDNA showed a higher quantity of ALU83 and ALU244. An integrated approach, combining the detection of ALU fragments and cancer type‐specific epigenetic alteration, can improve diagnostic efficiency and better define the prognostic value for CRC disease.
Frequency and clinical correlates of elevated plasma Epstein‐Barr virus DNA at diagnosis in peripheral T‐cell lymphomas
Authors: Haverkos Bradley M. , Huang Ying , Gru Alejandro , Pancholi Preeti , Freud Aharon G. , Mishra Anjali , Ruppert Amy S. , Baiocchi Robert A. , Porcu Pierluigi
Published: December 2016

Epstein‐Barr virus (EBV)‐encoded RNAs (EBER) in tumor tissue and cell‐free plasma EBV‐DNA (pEBVd) are detected in EBV‐associated lymphomas. Studies have suggested that EBER+ peripheral T‐cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre‐treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV‐assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14–37%) were pre‐treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd− patients. EBER‐ISH was performed on 10 pEBVd+ and 35 pEBVd− tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd− patients were also EBER+. With median follow up of 24 months (range 1–96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd− patients (13 vs. 72 months; p = 0.04). In our retrospective study, pre‐treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL.
BRCA1/2‐negative hereditary triple‐negative breast cancers exhibit BRCAness
Authors: Domagala Pawel , Hybiak Jolanta , Cybulski Cezary , Lubinski Jan
Published: December 2016

BRCA1/2‐associated breast cancers are sensitive to poly(ADPribose) polymerase (PARP) inhibitors and platinum compounds mainly due to their deficiency in DNA repair via homologous recombination (HR). However, approximately only 15% of triple‐negative breast cancers (TNBCs) are BRCA1/2‐associated. TNBCs that exhibit BRCAness (a phenotype reflecting impaired HR in BRCA1/2‐negative tumors) are also regarded sensitive to PARP inhibitors and platinum compounds. Thus, we hypothesized that hereditary BRCA1/2‐negative TNBCs may exhibit BRCAness. To find a subset of hereditary BRCA1/2‐negative TNBCs among 360 TNBCs, we first identified a group of 41 hereditary TNBCs by analyzing the family histories of the patients. Next, we tested this group for the presence of germline BRCA1/2 mutations, and finally, we compared the expression levels of 120 genes involved in HR and five other major mechanisms of DNA damage repair between BRCA1/2‐associated and BRCA1/2‐negative subgroups of hereditary TNBCs using real‐time PCR arrays. Approximately 73% of the hereditary TNBCs were BRCA1/2‐associated and 27% were BRCA1/2‐negative. The expression levels of the analyzed genes showed no significant differences between these two subgroups indicating the BRCAness of the BRCA1/2‐negative hereditary TNBCs and thereby distinguishing a novel subset of TNBCs as a potential target for PARP inhibitors or platinum‐based therapy. The results show the significance of family history in selecting patients with TNBC for therapies directed at incompetent DNA repair (e.g., PARP inhibitors and/or platinum‐based therapies) and indicate that a relatively simple strategy for broadening the target group for these modes of treatment is to identify patients with hereditary TNBCs.
Spheroid model for functional osteogenic evaluation of human adipose derived stem cells
Authors: Gurumurthy Bhuvaneswari , Bierdeman Patrick C. , Janorkar Amol V.
Published: December 2016

3D culture systems have the ability to mimic the natural microenvironment by allowing better cell–cell interactions. We have prepared an in vitro 3D osteogenic cell culture model using human adipose derived stem cells (hASCs) cultured atop recombinant elastin‐like polypeptide (ELP) conjugated to a charged polyelectrolyte, polyethyleneimine (PEI). We demonstrate that hASCs cultured atop the ELP–PEI coated tissue culture polystyrene (TCPS) formed 3D spheroids and exhibited superior differentiation toward osteogenic lineage compared to the traditional two dimensional (2D) monolayer formed atop uncoated TCPS. Live/dead viability assay confirmed >90% live cells at the end of the 3‐week culture period. Over the same culture period, higher protein content was observed in 2D monolayer than 3D spheroids, as the 2D environment allowed continued proliferation, while 3D spheroids underwent contact‐inhibited growth arrest. The normalized alkaline phosphatase (ALP) activity, which is an indicator for early osteogenic differentiation was higher for 3D spheroids. The normalized osteocalcin (OCN) production, which is an indicator for osteogenic maturation was also higher for 3D spheroids while 2D monolayer had no noticeable OCN production. On day 22, increased Alizarin red uptake by 3D spheroids showed greater mineralization activity than 2D monolayer. Taken together, these results indicate a superior osteogenic differentiation of hASCs in 3D spheroid culture atop ELP–PEI coated TCPS surfaces than the 2D monolayer formed on uncoated TCPS surfaces. Such enhanced osteogenesis in 3D spheroid stem cell culture may serve as an alternative to 2D culture by providing a better microenvironment for the enhanced cellular functions and interactions in bone tissue engineering. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1230–1236, 2017.
When size matters: differences in demineralized bone matrix particles affect collagen structure, mesenchymal stem cell behavior, and osteogenic potential
Authors: Dozza B. , Lesci I. G. , Duchi S. , Della Bella E. , Martini L. , Salamanna F. , Falconi M. , Cinotti S. , Fini M. , Lucarelli E. , Donati D.
Published: December 2016

Demineralized bone matrix (DBM) is a natural, collagen‐based, osteoinductive biomaterial. Nevertheless, there are conflicting reports on the efficacy of this product. The purpose of this study was to evaluate whether DBM collagen structure is affected by particle size and can influence DBM cytocompatibility and osteoinductivity. Sheep cortical bone was ground and particles were divided in three fractions with different sizes, defined as large (L, 1–2 mm), medium (M, 0.5–1 mm), and small (S, <0.5 mm). After demineralization, the chemical–physical analysis clearly showed a particle size‐dependent alteration in collagen structure, with DBM‐M being altered but not as much as DBM‐S. DBM‐M displayed a preferable trend in almost all biological characteristics tested, although all DBM particles revealed an optimal cytocompatibility. Subcutaneous implantation of DBM particles into immunocompromised mice resulted in bone induction only for DBM‐M. When sheep MSC were seeded onto particles before implantation, all DBM particles were able to induce new bone formation with the best incidence for DBM‐M and DBM‐S. In conclusion, the collagen alteration in DBM‐M is likely the best condition to promote bone induction in vivo. Furthermore, the choice of 0.5–1 mm particles may enable to obtain more efficient and consistent results among different research groups in bone tissue‐engineering applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1019–1033, 2017.