bluuebunny/crossref_metadata_2025 huggingface dataset:
Current-induced spin–orbit torque magnetization switching in a MnGa/Pt film with a perpendicular magnetic anisotropy
Authors: Ranjbar Reza , Suzuki Kazuya Z. , Sasaki Yuta , Bainsla Lakhan , Mizukami Shigemi
Published: November 2016

Current-induced magnetization switching is demonstrated in a micron sized Hall bar consisting of Pt-capped ultrathin ferrimagnetic MnGa films. The films showed a low magnetization M
s ≃ 150 kA/m and a large perpendicular magnetic anisotropy (PMA) field

T, indicating a PMA thickness t product

mJ/m2, which is relatively larger than those reported for other material films with PMA. Magnetization switching induced by an in-plane electrical current was examined with the application of an in-plane magnetic field. The phase diagram of the switching current vs the in-plane magnetic field is qualitatively consistent with that of the torque due to the spin-Hall effect in the Pt layer.
Production of cytotoxic compounds in dedifferentiated cells ofJatropha curcasL. (Euphorbiaceae)
Authors: Ovando-Medina Isidro , Pérez-Díaz Leny P. , Ruiz-González Sonia , Salvador-Figueroa Miguel , Urbina-Reyes Marcos E. , Adriano-Anaya Lourdes
Published: November 2016

This study addresses thein vitroculture as an alternative to obtain compounds with cytotoxic activity from the medicinal plantJatropha curcas(Euphorbiaceae). We determined the presence of cytotoxic compounds in both whole plants and dedifferentiated cells. We evaluated the effect of auxin, cytokinins and light on callus induction in cotyledon explants. We found that the most effective combination to induce callus was the auxin 2,4-D (5 mM) with the cytokinin 6-BAP (2.5 mM), on Murashige-Skoog medium in darkness. We compared the callogenic potential among accessions from different geographic origins, finding that ARR-251107-MFG7 is most prone to form callus. The roots ofJ. curcasgrown in field produced a compound chromatographically similar to the cytotoxic diterpene jatrophone. The profile of compounds extracted from the dedifferentiated cells was similar to that of the whole plant, including a relatively abundant stilbene-like compound. This study contributes to the future establishment of protocols to produce anti-cancer compounds fromJ. curcascultivated in vitro.
Non-target effects of a glyphosate-based herbicide on Common toad larvae (Bufo bufo, Amphibia) and associated algae are altered by temperature
Authors: Baier Fabian , Gruber Edith , Hein Thomas , Bondar-Kunze Elisabeth , Ivanković Marina , Mentler Axel , Brühl Carsten A. , Spangl Bernhard , Zaller Johann G.
Published: November 2016

Background

Glyphosate-based herbicides are the most widely used pesticides in agriculture, horticulture, municipalities and private gardens that can potentially contaminate nearby water bodies inhabited by amphibians and algae. Moreover, the development and diversity of these aquatic organisms could also be affected by human-induced climate change that might lead to more periods with extreme temperatures. However, to what extent non-target effects of these herbicides on amphibians or algae are altered by varying temperature is not well known.

Methods

We studied effects of five concentrations of the glyphosate-based herbicide formulation Roundup PowerFlex (0, 1.5, 3, 4 mg acid equivalent glyphosate L−1as a one time addition and a pulse treatment of totally 4 mg a.e. glyphosate L−1) on larval development of Common toads (Bufo bufo, L.; Amphibia: Anura) and associated algae communities under two temperature regimes (15 vs. 20 °C).

Results

Herbicide contamination reduced tail growth (−8%), induced the occurrence of tail deformations (i.e. lacerated or crooked tails) and reduced algae diversity (−6%). Higher water temperature increased tadpole growth (tail and body length (tl/bl) +66%, length-to-width ratio +4%) and decreased algae diversity (−21%). No clear relation between herbicide concentrations and tadpole growth or algae density or diversity was observed. Interactive effects of herbicides and temperature affected growth parameters, tail deformation and tadpole mortality indicating that the herbicide effects are temperature-dependent. Remarkably, herbicide-temperature interactions resulted in deformed tails in 34% of all herbicide treated tadpoles at 15 °C whereas no tail deformations were observed for the herbicide-free control at 15 °C or any tadpole at 20 °C; herbicide-induced mortality was higher at 15 °C but lower at 20 °C.

Discussion

These herbicide- and temperature-induced changes may have decided effects on ecological interactions in freshwater ecosystems. Although no clear dose-response effect was seen, the presence of glyphosate was decisive for an effect, suggesting that the lowest observed effect concentration (LOEC) in our study was 1.5 mg a.e. glyphosate L−1water. Overall, our findings also question the relevance of pesticide risk assessments conducted at standard temperatures.
The abundance of large, piscivorous Ferox Trout (Salmo trutta) in Loch Rannoch, Scotland
Authors: Thorne Alastair , MacDonald Alisdair I. , Thorley Joseph L.
Published: November 2016

Background

Ferox Trout are large, long-lived piscivorous Brown Trout (Salmo trutta). Due to their exceptionally large size, Ferox Trout are highly sought after by anglers while their life-history strategy, which includes delayed maturation, multiphasic growth and extended longevity, is of interest to ecological and evolutionary modelers. However, despite their recreational and theoretical importance, little is known about the typical abundance of Ferox Trout.

Methods

To rectify this situation a 16 year angling-based mark-recapture study was conducted on Loch Rannoch, which at 19 km2is one of the largest lakes in the United Kingdom.

Results

A hierarchical Bayesian Jolly-Seber analysis of the data suggest that if individual differences in catchability are negligible the population of Ferox Trout in Loch Rannoch in 2009 was approximately 71 fish. The results also suggest that a single, often unaccompanied, highly-experienced angler was able to catch roughly 8% of the available fish on an annual basis.

Discussion

It is recommended that anglers adopt a precautionary approach and release all trout with a fork length ≥400 mm caught by trolling in Loch Rannoch. There is an urgent need to assess the status of Ferox Trout in other lakes.
Cancer Survivorship: New Challenge in Cancer Medicine
Authors: Rowland Julia H.
Published: November 2016

Overview

As the population of cancer survivors continues to increase, so too has attention to the long‐term care needs of these individuals after treatment ends. While most survivors adapt well post‐treatment, many experience lingering effects of their illness. In some cases, these effects become permanent and raise challenges to recovery and adaptation. In this chapter, we outline some of the common persistent sequelae of cancer and their management and review the emerging guidelines for survivorship care planning. Models of follow‐up care after cancer are discussed, along with the needs and support of informal cancer caregivers in this process. Recommendations for future directions in survivorship research and care are provided.
What's in a Name? The Impact of Fair Trade Claims on Product Price
Authors: Marconi Nicholas G. , Hooker Neal H. , DiMarcello Nicholas
Published: November 2016

Agribusinesses use credence claims reporting the sustainability of products and supply chains. One example, fair trade, relies on a diverse set of third party standards and certification organizations. Food marketing data are used to compare products launched between 1999 and 2013 in the coffee, tea, and chocolate categories. Out of 3,257 observations making a reference to fair trade, 2,745 were certified. The other items follow certain fair trade practices or support fair trade. Many products claim both fair trade and organic (congruent claim). Fairtrade Labeling Organizations – International (FLO‐I) certifiers dominate, but Fair Trade USA (breaking from FLO‐I in 2012) is important. A double hurdle hedonic regression model explores the relationship between claims and suggested retail price in the United States, Canada, and European Union over two periods (1999–2011 and 2012–2013). Two models are run, one aggregating non‐FLO‐I members and one accounting for each individual certifier. The models (first hurdle) are not able to identify factors explaining which products are certified. Results suggest (second hurdle) that after controlling for congruent claims, having a fair trade claim certified by certain third parties significantly raises the price (above an uncertified product). In particular FLO‐I certification leads to a higher price in all models in both periods. Conversely, there is a range of premia for non‐FLO‐I certifiers, not all statistically significant. Implications for stakeholders are advanced. [EconLit citations: D40, L15, L66].
Relationship between Children's BMI and Parents’ Preferences for Kids’ Yogurts with and without Front of Package Health Signals
Authors: Colson Gregory , Grebitus Carola
Published: November 2016

Childhood obesity has emerged as a critical national policy issue in many countries. One challenge in combating childhood obesity via induced shifts toward a healthier diet is that the majority of food consumed by younger children is purchased or prepared by someone else, i.e., a parent. Hence, it is critical to design initiatives and marketing efforts aimed at affecting parents' purchases of healthy foods for their children. In this study, we focus on the potential of front‐of‐package health labels specifically designed to signal to parents those foods that are healthy for children. We report results of a choice experiment administered to 733 parents. In the experiments, branded and unbranded yogurts marketed to children are considered with different health labels. In our analysis, we control for the child's body mass index (BMI) to assess how labels affect parents' food choices in the context of varying BMI data for the children. We also include whether parents worried about their children's eating patterns react differently to the labeling. Results from two multinomial logit models indicate that parents prefer and are more likely to purchase yogurts with a label denoting the food is a healthy choice for children. Critically, we find parents with children who are overweight or obese, and hence already in the high‐risk category due to their body weight, are most affected by the labels. Overall, results indicate that health labels can be an effective signal and marketing effort to nudge parents of overweight or obese children toward healthier food purchase. [EconLit citations: D12, I1, Q18].
Information Content of USDA Rice Reports and Price Reactions of Rice Futures
Authors: McKenzie Andrew M. , Darby Jessica L.
Published: November 2016

Rice is a predominant food staple in many regions of the world, and it is important to determine how efficiently the U.S. rice market helps to ensure world food security. This question can be answered by gauging the price discovery performance of the U.S. rice futures market and the economic usefulness of the U.S. government's supply and demand forecasts. So, to this end, we employ two event study approaches: (1) to examine variability in returns on report‐release days as compared to returns on pre‐ and post‐report days, and (2) to regress price reactions on changes in usage and production information. It is found that the USDA provides the rice futures markets with valuable information and rice futures respond to the information in an economically consistent manner.
Stabilitätsanforderungen von Elektrokatalysatoren für die Sauerstoffentwicklung: der Weg zu einem grundlegenden Verständnis und zur Minimierung der Katalysatordegradation
Authors: Spöri Camillo , Kwan Jason Tai Hong , Bonakdarpour Arman , Wilkinson David P. , Strasser Peter
Published: November 2016

Dieser Aufsatz befasst sich mit den technischen Herausforderungen, wissenschaftlichen Grundlagen, neuen Entwicklungen und Perspektiven auf dem Gebiet der Stabilität und Degradation von OER‐Katalysatoren (OER=Sauerstoffentwicklungsreaktion) an Elektrolyseuranoden in saurer Umgebung. Vorrangig wird der Betrieb auf Basis von Membran‐Elektrode‐Einheiten betrachtet. Zuerst wird der Begriff “Katalysatorstabilität” diskutiert; weitere Themen sind die aktuellen Leistungsziele sowie die Hauptmechanismen der Katalysatordegradation und Strategien zu deren Verminderung. Anschließend werden geeignete In‐situ‐Methoden für die Untersuchung der Katalysatordegradation bewertet und Entwicklungen bei der Abstimmung der OER‐Katalysatorstabilität beschrieben. Abschließend wird die Bedeutung allgemeingültiger Kennzahlen für die Stabilität diskutiert, und es wird ein umfassender beschleunigter Alterungstest vorgeschlagen, der vergleichbare Leistungsdaten für verschiedene Laborbedingungen und Katalysatortypen liefert. Ziel ist es, die Beziehungen zwischen Struktur, Zusammensetzung und Stabilität von OER‐Katalysatoren bei verschiedenen Betriebsbedingungen aufzuzeigen.
Risk of second primary cancer in patients treated with radiotherapy for rectal cancer
Authors: Martling A , Smedby K E , Birgisson H , Olsson H , Granath F , Ekbom A , Glimelius B
Published: November 2016

Background

Many patients with rectal cancer receive radiotherapy (RT) to reduce the risk of local recurrence. Radiation may give rise to adverse effects, including second primary cancers. In view of the divergent results of previous studies, the present study evaluated the risk of second primary cancer following RT in all randomized RT rectal cancer trials conducted in Sweden and in the Swedish ColoRectal Cancer Registry (SCRCR).

Methods

Patients included in five randomized trials and the SCRCR were linked to the Swedish Cancer Registry. Cox regression models estimated the hazard ratio (HR) of second primary cancer among patients who received RT compared with those who did not.

Results

A total of 13 457 patients were included in this study; 7024 (52·2 per cent) received RT and 6433 (47·8 per cent) had surgery alone. Overall, no increased risk of second primary cancer was observed with RT (HR 1·03; 95 per cent c.i. 0·92 to 1·15), independently of follow-up time and location within or outside of the irradiated volume. In the randomized trials, with longer follow-up (maximum 31 years), a slight increase was observed outside of (HR 1·33, 1·01 to 1·74) but not within (HR 1·11, 0·73 to 1·67) the irradiated volume. Irradiated men had a lower risk of prostate cancer than those treated with surgery alone (HR 0·68, 0·51 to 0·91).

Conclusion

Overall, there was no increased risk of second primary cancer following RT for rectal cancer within or outside of the irradiated volume up to 20 years of follow-up. Men with rectal cancer who received RT had a reduced risk of prostate cancer.
SCAI/CCAS/SPA expert consensus statement for anesthesia and sedation practice: Recommendations for patients undergoing diagnostic and therapeutic procedures in the pediatric and congenital cardiac catheterization laboratory
Authors: Odegard Kirsten C. , Vincent Robert , Baijal Rahul , Daves SuAnne , Gray Robert , Javois Alex , Love Barry , Moore Phil , Nykanen David , Riegger Lori , Walker Scott G. , Wilson Elizabeth C.
Published: November 2016

Current practice of sedation and anesthesia for patients undergoing pediatric congenital cardiac catheterization laboratory (PCCCL) procedures is known to vary among institutions, a multi‐society expert panel with representatives from the Congenital Heart Disease Council of the Society for Cardiovascular Angiography and Interventions (SCAI), the Society for Pediatric Anesthesia (SPA) and the Congenital Cardiac Anesthesia Society (CCAS) was convened to evaluate the types of sedation and personnel necessary for procedures performed in the PCCCL. The goal of this panel was to provide practitioners and institutions performing these procedures with guidance consistent with national standards and to provide clinicians and institutions with consensus‐based recommendations and the supporting references to encourage their application in quality improvement programs. Recommendations can neither encompass all clinical circumstances nor replace the judgment of individual clinicians in the management of each patient. The science of medicine is rooted in evidence, and the art of medicine is based on the application of this evidence to the individual patient. This expert consensus statement has adhered to these principles for optimal management of patients requiring sedation and anesthesia. What follows are recommendations for patient monitoring in the PCCCL regardless of whether minimal or no sedation is being used or general anesthesia is being provided by an anesthesiologist. © 2016 Wiley Periodicals Inc.
Orbital Engineering: Photoactivation of an Organofunctionalized Polyoxotungstate
Authors: Cameron Jamie M. , Fujimoto Satomi , Kastner Katharina , Wei Rong‐Jia , Robinson David , Sans Victor , Newton Graham N. , Oshio H. Hiroki
Published: November 2016

Tungsten‐based polyoxometalates (POMs) have been employed as UV‐driven photo‐catalysts for a range of organic transformations. Their photoactivity is dependent on electronic transitions between frontier orbitals and thus manipulation of orbital energy levels provides a promising means of extending their utility into the visible regime. Herein, an organic–inorganic hybrid polyoxometalate, K6[P2W17O57(PO5H5C7)2]⋅6 C4H9NO, was found to exhibit enhanced redox behaviour and photochemistry compared to its purely inorganic counterparts. Hybridization with electron‐withdrawing moieties was shown to tune the frontier orbital energy levels and reduce the HOMO–LUMO gap, leading to direct visible‐light photoactivation of the hybrid and establishing a simple, cheap and effective approach to the generation of visible‐light‐activated hybrid nanomaterials.
Point‐to‐Point Ultra‐Remote Asymmetric Control with Flexible Linker
Authors: Kawasaki Tsuneomi , Ishikawa Yasuyuki , Minato Yoshihiro , Otsuka Takashi , Yonekubo Shigeru , Sato Itaru , Shibata Takanori , Matsumoto Arimasa , Soai Kenso
Published: November 2016

An ultra‐remote intramolecular (point‐to‐point) asymmetric control through 38 bonds (1,39‐asymmetric induction) has been achieved by using the principle of direct supramolecular orientation of catalytic and reactive moieties in asymmetric autocatalysis. We found the highly stereoselective diisopropylzinc addition reaction using designed molecules possessing pyrimidine sites at each terminal of a conformationally flexible simple methylene chain.
Prostate cancer: Developing novel approaches to castration‐sensitive disease
Authors: Francini Edoardo , Taplin Mary‐Ellen
Published: November 2016

Although androgen‐deprivation therapy (ADT) remains the mainstay of castration‐sensitive prostate cancer (CSPC) therapy, the disease's heterogeneity and the limited duration of the response have chaperoned the introduction of chemotherapy and the investigation of novel hormonal targeted agents in this setting. Combinations of ADT plus chemotherapy or novel hormonal therapies are being tested at various stages of CSPC with promising results. Furthermore, immunotherapy and experimental drugs are also being actively investigated in this setting. Intriguing multimodality strategies, chiefly deployed for early‐stage disease with the aim of maximizing the efficacy and duration of the response, are being explored and may become valid therapeutic options in the future. Ultimately, striking a balance between the clinical gains of these combinations and possibly increased toxicity and reduced quality of life will be necessary. The development of precision medicine and accurate biomarkers is fundamental to progress. Cancer 2017;29–42. © 2016 American Cancer Society.
Principles of Chromatography
Authors: Mallik Buddhadeb , Chakravarti Bulbul , Chakravarti Deb N.
Published: November 2016

Chromatography in its many different forms is an indispensable separation technique for purification or analysis of one or multiple components from a mixture that may contain a variety of simple as well as complex molecules. This unit is focused on a specific type of chromatography known as liquid chromatography (LC), with particular reference to separation of proteins. The theory of chromatography is discussed in the context of partition of the components of a mixture between a solid stationary phase and a liquid mobile phase. Although very useful for chromatographic separation of small molecules, considerable deviation is observed in the case of separation of proteins. The principles of three commonly used chromatographic techniques for separation of proteins, such as size exclusion, ion exchange, and affinity chromatography, are discussed. The unit is expected to be useful for biologists and biochemists, as well as engineers involved in downstream bioprocessing. © 2016 by John Wiley & Sons, Inc.
MHC‐Peptide Tetramers to Visualize Antigen‐Specific T Cells
Authors: Altman John D. , Davis Mark M.
Published: November 2016

Mature T lymphocytes of the CD8 or CD4 classes bear αβ T cell receptors (TCR) that are specific for a molecular complex consisting of a major histocompatibility complex class I or II (MHC class I or II) molecule bound to a unique self or foreign peptide. Until recently, methods for monitoring antigen‐specific T cell immune responses were restricted primarily to functional assays based on limiting dilution analysis, because the lack of specific molecular reagents to identify clonal T cells obviated approaches to identify and enumerate specific T cells. Development of efficient methods to express and refold MHC class I molecules with synthetic peptides coincided with identification of specific protein sequences that provide the substrate for enzymatic biotinylation. This combination has led to the development of a straightforward method for generating synthetic TCR ligands, making them tetravalent to provide increased avidity, and labeling them through a streptavidin moiety with useful fluorescent tags such as allophycocyanin or R‐phycoerythrin. This unit describes the preparation of MHC class I/peptide tetramers in detail, including bacterial expression and refolding of the MHC class I light chain, β2‐microglobulin (β2m), as well as the formation of a complex consisting of the MHC class I heavy chain of interest, β2m, and a chosen peptide. © 2016 by John Wiley & Sons, Inc.
Induction and Quantification of NETosis
Authors: Carmona‐Rivera Carmelo , Kaplan Mariana J.
Published: November 2016

Neutrophil extracellular traps (NET) are web‐like structures composed of nuclear material and neutrophil granular proteins that are released to the extracellular space after specific microbial or sterile inflammatory stimuli. NETosis is a specific type of cell death that ensues when neutrophils extrude NETs. It is important to develop validated standards to induce and quantify NETs in order to accurately compare results between laboratories and advance the understanding of this biological process and its implications in health and disease. This unit presents methods for isolating human neutrophils from peripheral blood and inducing NETs through various types of stimulation that rely on the production of reactive oxygen species from NADPH oxidase or mitochondria. Alternative methods are also described for low‐ and high‐throughput quantification of NETs. © 2016 by John Wiley & Sons, Inc.
Isolation and Characterization of Exosomes from Cultures of Tissue Explants and Cell Lines
Authors: Mincheva‐Nilsson Lucia , Baranov Vladimir , Nagaeva Olga , Dehlin Eva
Published: November 2016

Exosomes are specialized, nanometer‐sized extracellular vesicles of endosomal origin actively secreted into the extracellular space by a variety of cells under normal and pathological conditions. Exosomes have recently emerged as important intercellular communicators and modulators of diverse mechanisms and cellular responses. Characterization of their composition and function will open possibilities for new diagnostic methods and promising therapeutic approaches based on nanobiology. This unit provides a standard isolation procedure for purification of exosomes based on density gradient ultracentrifugation with sucrose. The process of isolating exosomes relies on obtaining proper source fluids/supernatants as well as qualitative and quantitative assessment of the isolated vesicles. The methodological procedures here can be divided in three parts: (1) pre‐isolation procedures aiming to obtain fluids containing exosomes, with a focus on protocols for organ explants and cell cultures; (2) a procedure for exosome isolation with several gradient alternatives; and (3) post‐isolation procedures for estimating the purity and yield of the exosomal fraction. © 2016 by John Wiley & Sons, Inc.
Fluorescence‐Based Microplate Assays for In Vitro Assessment of Mitochondrial Toxicity, Metabolic Perturbation, and Cellular Oxygenation
Authors: Hynes James , Carey Conn , Will Yvonne
Published: November 2016

High‐throughput in vitro cell metabolism assays are of particular use for identification and delineation of mitochondrial toxicity and related metabolic perturbation. Here, a panel of fluorescence‐based metabolism assays are described for measuring oxygen consumption, glycolytic flux, and cellular oxygenation. They can be applied to analysis of both isolated mitochondria and cell models. Sample data are presented illustrating how these protocols can be used to examine drug treatment, the interplay between oxidative and glycolytic ATP generation, and the impact of cell oxygenation on this balance. Descriptions are provided on how these measurements can be applied to 3D systems and how they can be multiplexed with other relevant metabolic readouts. Mitochondrial isolation and cell permeabilization protocols are also provided. © 2016 by John Wiley & Sons, Inc.
Properties of Space Charge Distributions and Conduction Current in XLPE and LDPE under DC High Electric Field
Authors: KATO TSUYOSHI , ONOZAWA RYO , MIYAKE HIROAKI , TANAKA YASUHIRO , TAKADA TATSUO
Published: November 2016

Space charge behavior and conduction current in polyethylene under dc stress were investigated. One of the reasons for the different breakdown property in cross‐linked polyethylene (XLPE) from that in low‐density polyethylene (LDPE) may be based on the existence of cross‐linking by‐products in XLPE. Furthermore, a thermal history in cross‐linking process for XLPE may also cause of the difference. It is generally accepted that the existence of the cross‐linking by‐products increase the conduction current in XLPE under dc stress. It is also said that an anneal treatment in air atmosphere may affect to the electrical properties under dc stress. Therefore, we investigated the effect of the cross‐linking by‐products and the anneal treatment on space charge behavior and conduction current in polyethylene under dc stress. In our research, it is thought that the increasing dissipation power in XLPE is the cause of the breakdown in it under dc stress. Therefore, to calculate the dissipation power in the bulk of test sample, we measured the space charge distribution and the external circuit current simultaneously. Based on the results, we discussed the reason of the difference of the space charge properties in XLPE and LDPE focusing on the cross‐linking by‐products and the oxidation of the test samples.
NLRP12 negatively regulates proinflammatory cytokine production and host defense against Brucella abortus
Authors: Silveira Tatiana N. , Gomes Marco Túlio R. , Oliveira Luciana S. , Campos Priscila C. , Machado Gabriela G. , Oliveira Sergio C.
Published: November 2016

Brucella abortus is the causative agent of brucellosis, which causes abortion in domestic animals and undulant fever in humans. This bacterium infects and proliferates mainly in macrophages and dendritic cells, where it is recognized by pattern recognition receptors (PRRs) including Nod‐like receptors (NLRs). Our group recently demonstrated the role of AIM2 and NLRP3 in Brucella recognition. Here, we investigated the participation of NLRP12 in innate immune response to B. abortus. We show that NLRP12 inhibits the early production of IL‐12 by bone marrow‐derived macrophages upon B. abortus infection. We also observed that NLRP12 suppresses in vitro NF‐κB and MAPK signaling in response to Brucella. Moreover, we show that NLRP12 modulates caspase‐1 activation and IL‐1β secretion in B. abortus infected‐macrophages. Furthermore, we show that mice lacking NLRP12 are more resistant in the early stages of B. abortus infection: NLRP12−/− infected‐mice have reduced bacterial burdens in the spleens and increased production of IFN‐γ and IL‐1β compared with wild‐type controls. In addition, NLRP12 deficiency leads to reduction in granuloma number and size in mouse livers. Altogether, our findings suggest that NLRP12 plays an important role in negatively regulating the early inflammatory responses against B. abortus.
B‐cell activation with CD40L or CpG measures the function of B‐cell subsets and identifies specific defects in immunodeficient patients
Authors: Marasco Emiliano , Farroni Chiara , Cascioli Simona , Marcellini Valentina , Scarsella Marco , Giorda Ezio , Piano Mortari Eva , Leonardi Lucia , Scarselli Alessia , Valentini Diletta , Cancrini Caterina , Duse Marzia , Grimsholm Ola , Carsetti Rita
Published: November 2016

Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B‐cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B‐cell functions in infancy and throughout childhood. We show that T‐independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T‐dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system.
Analysis of 3D multi‐layer microfluidic gradient generator
Authors: Ha Jang Ho , Kim Tae Hyeon , Lee Jong Min , Ahrberg Christian D. , Chung Bong Geun
Published: November 2016

We developed a three‐dimensional (3D) simple multi‐layer microfluidic gradient generator to create molecular gradients on the centimeter scale with a wide range of flow rates. To create the concentration gradients, a main channel (MC) was orthogonally intersected with vertical side microchannel (SC) in a 3D multi‐layer microfluidic device. Through sequential dilution from the SC, a spatial gradient was generated in the MC. Two theoretical models were created to assist in the design of the 3D multi‐layer microfluidic gradient generator and to compare its performance against a two‐dimensional equivalent. A first mass balance model was used to predict the steady‐state concentrations reached, while a second computational fluid dynamic model was employed to predict spatial development of the gradient by considering convective as well as diffusive mass transport. Furthermore, the theoretical simulations were verified through experiments to create molecular gradients in a 3D multi‐layer microfluidic gradient generator.
The bioenergy potential of Natura 2000 – a synergy between climate change mitigation and biodiversity protection
Authors: Van Meerbeek Koenraad , Ottoy Sam , de Andrés García María , Muys Bart , Hermy Martin
Published: November 2016

Climate change and biodiversity loss are two of the greatest challenges of the 21st century. To date, actions proposed by the international community to address these problems have largely been conducted in a piecemeal fashion. Conservation biologists advocate for low‐intensity management in temperate protected areas to maintain and restore biodiversity. Low‐input, high‐diversity biomass from such areas has been proposed as a promising alternative bioenergy feedstock. Here, we show that there is a vast unexploited biomass‐for‐bioenergy potential present in Natura 2000, the European nature conservation network. Spanning 7.5 million hectares (ha), non‐forest ecosystems within Natura 2000 have a biomass production of 17.9 teragrams (Tg) of dry matter annually. The conversion of this biomass to bioenergy will not lead to the displacement of food production systems, thereby avoiding 12.5 Tg of carbon dioxide equivalent greenhouse‐gas emissions and circumventing between 1.2 and 2.8 million ha of indirect land‐use change. The use of conservation biomass as bioenergy feedstock clearly offers the opportunity to reconcile biodiversity goals and climate‐change mitigation.
Relationship between HMF intake and SMF formation in vivo: An animal and human study
Authors: Pastoriza de la Cueva Silvia , Álvarez Juana , Végvári Ákos , Montilla‐Gómez Javier , Cruz‐López Olga , Delgado‐Andrade Cristina , Rufián‐Henares José A.
Published: November 2016

Scope

5‐Hydroxymethylfurfural (HMF) is a furanic compound produced in heat‐processed foods by nonenzymatic browning reactions. HMF has been demonstrated to be hepato‐ and nephrotoxic in animals with a link to its metabolite 5‐sulfooxymethylfurfural (SMF). To date little is known about either the formation of SMF from ingested HMF or the formation of DNA adducts in animals or human beings.

Methods and results

To assess SMF in vivo formation, we first performed a study in mice treated with high/low doses of oral HMF. We found increased concentrations of SMF in plasma and DNA SMF‐adducts in leukocytes, hepatic tissue, and kidneys by means of LC–MS/MS, but no spatial formation in such tissues was observed by MALDI‐MS imaging technology due to low sensitivity. In a second experiment, we measured the exposure to HMF in a Spanish preadolescent population. We analyzed the concentration of HMF metabolites (plasma, urine) and measured, for the first time, the presence of SMF in plasma and DNA SMF‐adducts in leukocytes.

Conclusion

This study provides the first evidence that oral HMF is readily transformed into SMF in vivo, giving rise to the formation of DNA adducts in a direct relation with HMF intake, both in animals and human beings.
Meeting Report From the Prostate Cancer Foundation Scientific Working Group on Radium‐223
Authors: Miyahira Andrea K. , Morris Michael , Soule Howard R. ,   PCF Radium‐223 Scientific Working Group
Published: November 2016

INTRODUCTION

The Prostate Cancer Foundation (PCF) convened a Scientific Working Group Meeting on Radium‐223 on September 8, 2016, at The Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan Kettering Cancer Center.

METHODS

The meeting was attended by 18 investigators with expertise in radium‐223, bone biology, molecular imaging, biomarkers, and prostate cancer clinical trials. The goal of this meeting was to discuss the known and unknown surroundings the therapeutic effects of the bone targeting agent radium‐223, in bone metastatic prostate cancer therapy, and to outline the most critical studies needed to improve the clinical use of this agent.

RESULTS

Three major topic areas were discussed: (1) the basic science of radium; (2) immuno‐adjuvant properties of radium therapy; and (3) high impact clinical trials and correlative science.

DISCUSSION

This article reviews the major topics discussed at the meeting for the purpose of accelerating studies that will improve the use of radium‐223 in the treatment of prostate cancer patients. Prostate 77:245–254, 2017. © 2016 Wiley Periodicals, Inc.
Theory of time‐dependent nonequilibrium transport through a single molecule in a nonorthogonal basis set
Authors: Dražić Miloš S. , Cerovski Viktor , Zikic Radomir
Published: November 2016

A microscopic theory of nonequilibrium electronic transport under time‐dependent bias through a molecule (or quantum dot) embedded between two semi‐infinite metallic electrodes is developed in a nonorthogonal single‐particle basis set using an ab initio formalism of Green's functions. The equilibrium zeroth order electron Green's function and self‐energy are corrected by the corresponding time‐inhomogeneous dynamical contributions derived in the Hartree approximation in a steady‐state linear‐response regime. Nonorthogonality contributes to dynamical response by introducing terms related to the central region‐electrode interface, which appears only in the time‐dependent case. The expression for current is also derived, where a nonorthogonality‐induced dynamical correction gives an additional current that is not present in the orthogonal description. It is shown that the obtained expression for current is gauge‐invariant and demonstrated that the omission of the additional current violates charge conservation. The additional current term vanishes in an orthogonal basis set.
Adding fish images taken in other countries to the biodiversity database of a Japanese public museum, with report of range extension of Labrisomus jenkinsi from the Pacific coast of Costa Rica
Authors: Miyazaki Yusuke , Murase Atsunobu , Sahara Ryosuke , Angulo Arturo , Senou Hiroshi
Published: November 2016

Many biodiversity databases have been launched in recent years. Various species of certain developed taxa, such as fish, quadrupeds, and butterflies, are currently able to be photographically identified, in particular for ecological and biogeographic studies. However, there are problems that result from registration of images from countries with different primary languages. In this study, we provide an example of the challenges associated with registering fish images, specifically one case that has functioned as a voucher for the range extension of Labrisomus jenkinsi (Heller and Snodgrass, 1903) (Perciformes: Labrisomidae) from the Galapagos Islands to the Pacific coast of Costa Rica. The fish image database in question belongs to a Japanese public museum [the Kanagawa Prefectural Museum of Natural History; the online version (FishPix) is provided by the museum and the National Museum of Nature and Science]. We propose that there are problems associated with image registration caused by using different languages. Furthermore, these challenges should be a common subject for discussion among museums as they attempt to accumulate biodiversity data from citizens in the future.
Metropolitan Regions as a Changing Policy Concept in a Comparative Perspective
Authors: Fricke Carola
Published: November 2016

In Europe, metropolitan policies emerge in a multi-scalar system of supranational, national and regional scales. Besides national policies on metropolitan issues, more and more European policies address metropolitan regions. They propose varying attributes of what characterizes a metropolitan region, for instance, defining them as functional and statistical areas, or as nodes for European spatial development. These conceptualizations of metropolitan regions have implications for institutional forms of metropolitan governance. However, existing research has not yet comparatively explored the development of metropolitan concepts in national and supranational policy contexts. This paper compares the changing concepts of metropolitan regions in the European Union, France and Germany. It raises the question of how different policies conceptualize metropolitan regions. Thereby, the paper proposes a comparative perspective on concepts in policies addressing metropolitan regions, such as policy documents, planning strategies, regulations or reports. It analyses shifts in metropolitan policies by describing the change of concepts and the reference to frames of spatial development such as polycentricity, competitiveness or integrated development. Three analytical perspectives contribute to understanding the change of metropolitan policies. First, the comparison of concepts in different national and supranational policy contexts develops an understanding of metropolitan regions beyond national specificities. Second, a historical comparison contributes to understanding changes in metropolitan concepts since the late 1990s. And third, analysing the development of metropolitan policies comparatively explores similarities of concepts and frames between policy contexts, despite differences in institutional settings.
Inflammatory, cardio-metabolic and diabetic profiling of chronic schizophrenia
Authors: Balõtšev R. , Koido K. , Vasar V. , Janno S. , Kriisa K. , Mahlapuu R. , Ljubajev U. , Parksepp M. , Veiksaar P. , Volke V. , Lang A. , Haring L. , Zilmer M. , Vasar E.
Published: November 2016

Background

There is a growing interest in low-grade inflammatory and metabolic alterations in patients with chronic schizophrenia (SCH).

Methods

Inflammatory (tumor-necrosis factor-α [TNF-α], interferon-γ [IFN-γ], interleukins [IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10], monocyte chemo-attractant protein-1 [MCP-1]) and growth factors (vascular endothelial growth factor [VEGF], epidermal growth factor [EGF]) were measured in blood serum samples of 105 SCH patients and 148 control subjects (CS). Simultaneously the clinical biomarkers (C-reactive protein [CRP], triglycerides [TG], low-density lipoprotein [LDL-c] and high-density lipoprotein [HDL-c] cholesterol, glycated hemoglobin [HbA1c]) were measured, and body mass index (BMI) was calculated for patients.

Results

Several cyto-/chemokines (IFN-γ, MCP-1, IL-2, IL-6, IL-8 and IL-10) were significantly (P < 0.0000001) elevated in SCH patients compared to CS. Odds ratios, obtained from logistic regression analyses, were significantly elevated for IL-2, IL-6, IL-10, INF-γ, and decreased for TNF-α in SCH group. Among the patients, higher IL-2, IL-6, INF-γ and lower MCP-1 levels as well as male gender were together significant (P < 0.000001) predictors of higher HbA1c levels, and TG/HDL-c parameter was associated with ratios of INF-γ/IL-10 (P = 0.004), and INF-γ/IL-4 (P = 0.049), HbA1c (P = 0.005), INF-γ (P = 0.009), as well as LDL-c (P = 0.02) levels.

Conclusions

IL-2, IL-6, IL-10 and IFN-γ were the most significant SCH-related markers among the measured cytokines in our patient group. Furthermore, significant associations between pro-/anti-inflammatory imbalance and HbA1c as well as cardio-metabolic risk marker (TG/HDL-c) were observed, indicating higher risks of diabetes and cardiovascular diseases among SCH patients.
Are major depression and bipolar disorder neuropsychologically distinct? A meta-analysis of comparative studies
Authors: Samamé C. , Szmulewicz A.G. , Valerio M.P. , Martino D.J. , Strejilevich S.A.
Published: November 2016

Background

Neuropsychological deficits are present in both major depression and bipolar disorder. So far, however, reports directly comparing these mood disorders with regard to cognitive outcomes have been scant and yielded inconsistent results. This work aims to combine the findings of comparative studies of cognition in major depression and bipolar disorder in order to explore whether these neuropsychiatric conditions present with distinct cognitive features.

Methods

The main online databases were extensively searched to retrieve reports assessing neurocognitive functioning in two groups of mood disorder patients, one with major depressive disorder and another with bipolar disorder, both in the same phase of illness. Between-group effect sizes for cognitive variables were obtained from selected studies and pooled by means of meta-analytic procedures.

Results

During euthymia, a significant overall effect size (Hedges’g = 0.64, P < 0.001) favoring major depressive disorder was found for verbal memory as assessed with list learning tests, whereas no significant between-group differences were found for the remaining variables analyzed. During depressive episodes, similar cognitive outcomes were observed between groups.

Conclusion

At present, it is not possible to postulate specific neuropsychological profiles for major depression and bipolar disorder in light of available evidence. It remains to be ascertained whether the differences found for verbal memory constitute an expression of distinct underlying mechanisms or whether they are best explained by sample characteristics or differential exposure to variables with a negative impact on cognition.
Use of atomoxetine and suicidal ideation in children and adolescents: Results of an observational cohort study within general practice in England
Authors: Davies M. , Coughtrie A. , Layton D. , Shakir S.A.S.
Published: November 2016

Aim

To investigate the association between atomoxetine, a drug used in the treatment of Attention Deficit Hyperactivity Disorder (ADHD), and suicidal ideation, within a cohort of 2–18-year-old patients in England.

Methods

The study was conducted using the observational cohort technique of Modified prescription event monitoring (M-PEM). Patients prescribed atomoxetine were identified from dispensed prescriptions issued by primary care physicians. A customised postal GP questionnaire was used to capture outcome data for suicidal ideation. A matched pair cohort analysis was performed within patients to compare the risk of suicidal ideation in the period after starting atomoxetine with the risk prior to starting atomoxetine; this was stratified by age and concomitant use of methylphenidate. Additional information on patient characteristics, and events of interest was also collected; individual cases of suicidal ideation were qualitatively assessed for drug relatedness.

Results

Of the final cohort (n = 4509); 85.5% male (n = 3857), median age 11 years (IQR: 9,14). Primary prescribing indication for atomoxetine was ADHD (n = 4261, 94.6%). Almost a quarter of the cohort had been co-prescribed methylphenidate. Results of the matched pair cohort analysis indicated that the period after starting atomoxetine was not associated with an increase in the incidence of suicidal ideation compared to the period prior to starting treatment (RR: 0.71; CI: 0.48–1.07; P-value: 0.104). Individual case assessment of suicidal ideation suggested a causal association within a number of cases.

Conclusions

This study found no evidence of an increased risk of suicidal ideation during treatment with atomoxetine, compared to the period prior to starting treatment. Amongst age specific subgroups, this risk may change. Nonetheless, individual case assessment suggested a causal relationship in some patients, hence physicians need to be aware of the possibility of developing this event, and furthermore consider how best to detect it in this paediatric population. This study demonstrates the importance of combining quantitative statistical analyses with a qualitative case series assessment.