bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric Formal Synthesis of Azadirachtin
Authors: Mori Naoki , Kitahara Takeshi , Mori Kenji , Watanabe Hidenori
Published: October 2015

An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley’s synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right‐hand segment starting from the known 5‐hydroxymethyl‐2‐cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the α‐oxidation of the six‐membered lactone followed by methanolysis.
Linking Semiconductor Nanocrystals into Gel Networks through All‐Inorganic Bridges
Authors: Singh Amita , Lindquist Beth A. , Ong Gary K. , Jadrich Ryan B. , Singh Ajay , Ha Heonjoo , Ellison Christopher J. , Truskett Thomas M. , Milliron Delia J.
Published: October 2015

For colloidal semiconductor nanocrystals (NCs), replacement of insulating organic capping ligands with chemically diverse inorganic clusters enables the development of functional solids in which adjacent NCs are strongly coupled. Yet controlled assembly methods are lacking to direct the arrangement of charged, inorganic cluster‐capped NCs into open networks. Herein, we introduce coordination bonds between the clusters capping the NCs thus linking the NCs into highly open gel networks. As linking cations (Pt2+) are added to dilute (under 1 vol %) chalcogenidometallate‐capped CdSe NC dispersions, the NCs first form clusters, then gels with viscoelastic properties. The phase behavior of the gels for variable [Pt2+] suggests they may represent nanoscale analogues of bridged particle gels, which have been observed to form in certain polymer colloidal suspensions.
The Structure of a Plant Tyrosinase from Walnut Leaves Reveals the Importance of “Substrate‐Guiding Residues” for Enzymatic Specificity
Authors: Bijelic Aleksandar , Pretzler Matthias , Molitor Christian , Zekiri Florime , Rompel Annette
Published: October 2015

Tyrosinases and catechol oxidases are members of the class of type III copper enzymes. While tyrosinases accept both mono‐ and o‐diphenols as substrates, only the latter substrate is converted by catechol oxidases. Researchers have been working for decades to elucidate the monophenolase/diphenolase specificity on a structural level and have introduced an early hypothesis that states that the reason for the lack of monophenolase activity in catechol oxidases may be its structurally restricted active site. However, recent structural and biochemical studies of this enzyme class have raised doubts about this theory. Herein, the first crystal structure of a plant tyrosinase (from Juglans regia) is presented. The structure reveals that the distinction between mono‐ and diphenolase activity does not depend on the degree of restriction of the active site, and thus a more important role for amino acid residues located at the entrance to and in the second shell of the active site is proposed.
Over‐Oxidation as the Key Step in the Mechanism of the MoCl5‐Mediated Dehydrogenative Coupling of Arenes
Authors: Schubert Moritz , Franzmann Peter , Wünsche von Leupoldt Anica , Koszinowski Konrad , Heinze Katja , Waldvogel Siegfried R.
Published: October 2015

Molybdenum pentachloride is an unusually powerful reagent for the dehydrogenative coupling of arenes. Owing to the high reaction rate using MoCl5, several labile moieties are tolerated in this transformation. The mechanistic course of the reaction was controversially discussed although indications for a single electron transfer as the initial step were found recently. Herein, based on a combined study including synthetic investigations, electrochemical measurements, EPR spectroscopy, DFT calculations, and mass spectrometry, we deduct a highly consistent mechanistic scenario: MoCl5 acts as a one‐electron oxidant in the absence of TiCl4 and as two‐electron oxidant in the presence of TiCl4, but leads to an over‐oxidized intermediate in both cases, which protects it from side reactions. In the course of aqueous work‐up the reagent waste (MoIII/IV species) acts as reducing agent generating the desired organic C−C coupling product.
Using Signal Processing Diagnostics to Improve Public Sector Evaluations
Authors: Matthews Mark
Published: October 2015

False positive test results that overstate intervention impacts can distort and constrain the capability to learn and adapt in governance, and are therefore best avoided. This article considers the benefits of using the Bayesian techniques used in signal processing and machine learning to identify cases of these false positive test results in public sector evaluations. These approaches are increasingly used in medical diagnosis—a context in which (like public policy) avoiding false positive and false negative test results in the evidence base is very important. The findings from a UK National Audit Office review of evaluation quality are used to illustrate how a Bayesian diagnostic framework for use in public sector evaluations could be developed.
Abatacept Inhibition of T Cell Priming in Mice by Induction of a Unique Transcriptional Profile That Reduces Their Ability to Activate Antigen‐Presenting Cells
Authors: Patakas Agapitos , Ji Rui‐Ru , Weir William , Connolly Sean E. , Benson Robert A. , Nadler Steven G. , Brewer James M. , McInnes Iain B. , Garside Paul
Published: October 2015

Objective

To determine at the phenotypic, functional, and transcriptional levels whether abatacept, a CTLA‐4Ig molecule that binds with high affinity to CD80/86 on antigen‐presenting cells (APCs) and is used to treat rheumatoid arthritis, induces a state of immunologic tolerance in T cells and dendritic cells in mice.

Methods

We investigated the capacity of abatacept to regulate the development of antigen‐specific immunologic tolerance in vivo using murine models of priming and tolerance to generate highly purified antigen‐specific T cell populations and CD11c+ APCs. These were combined with detailed immunologic and full genome transcriptional analyses.

Results

We found that abatacept inhibited T cell activation, but did not render T cells anergic or lead to the generation of Treg cells. However, it induced a sustained inhibition of T cell activation due to the inability of these cells to progress through the cell cycle following T cell receptor stimulation. We also observed that this state was accompanied by an inhibition of dendritic cell activation due to their reduced licensing by T cells.

Conclusion

This study provides detailed insight into the mode of action of abatacept, demonstrating that its effectiveness is not due to the induction of T cell tolerance, but rather to a sustained inhibition of T cell activation that results in reduced functionality of APCs, with significant implications for its clinical application.
Brief Report: Six‐Week Treatment of Axial Spondyloarthritis Patients With an Optimal Dose of Nonsteroidal Antiinflammatory Drugs: Early Response to Treatment in Signal Intensity on Magnetic Resonance Imaging of the Sacroiliac Joints
Authors: Varkas G. , Jans L. , Cypers H. , Van Praet L. , Carron P. , Elewaut D. , Van den Bosch F.
Published: October 2015

Objective

To evaluate the early effect of full‐dose nonsteroidal antiinflammatory drugs (NSAIDs) on the extent and intensity of bone marrow edema of the sacroiliac (SI) joints on magnetic resonance imaging (MRI) in axial spondyloarthritis (SpA).

Methods

A single‐center, 6‐week study of a cohort of consecutive patients with clinically suspected axial SpA was conducted. A total of 117 patients were screened. Forty patients who were diagnosed as having axial SpA and had presented with a positive MRI of the SI joints as defined by the Assessment of SpondyloArthritis international Society (ASAS) criteria were considered for a followup MRI after 6 weeks of an optimal dose of NSAIDs. Twenty patients completed the study. Disease activity was monitored by determining the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score every 2 weeks and the Bath Ankylosing Spondylitis Functional Index score at baseline and week 6. NSAID intake was assessed by the ASAS NSAID index. Primary end points were improvement in bone marrow edema of the SI joints on MRI and BASDAI response at week 6.

Results

Approximately one‐third of eligible patients newly diagnosed as having axial SpA were unable to continue the full‐dose NSAID schedule. The median NSAID index was 97% in patients who completed the study. There was a reduction of 1.1 units (10.5%) in mean Spondyloarthritis Research Consortium of Canada (SPARCC) scores at week 6 in comparison to baseline (P = 0.032). Overall, only 30% of the patients (6 of 20) had a minimal clinically important difference of ≥2.5 in SPARCC score. However, 80% of the patients displayed high‐intensity lesions on STIR images at baseline, which decreased significantly at week 6 (P = 0.011). There was a significant decrease in the relative intensity of the region of interest (P = 0.007) and a mean decrease of 0.6 in the BASDAI score per 2 weeks of therapy (P = 0.001). Only 29.4% of the patients met the BASDAI criteria for 50% improvement (BASDAI50) at week 6.

Conclusion

Our findings indicate a high level of dropout among patients receiving full‐dose NSAID therapy in daily practice. In those who tolerated NSAID therapy, there was no clinically relevant decrease in SPARCC scores and low BASDAI50 response. However, we found a decrease in signal intensity of bone marrow edema of the SI joints as an early response to 6 weeks of optimal NSAID therapy in patients newly presenting with axial SpA.
A Highly K+‐Selective Fluorescent Probe – Tuning the K+‐Complex Stability and the K+/Na+ Selectivity by Varying the Lariat‐Alkoxy Unit of a Phenylaza[18]crown‐6 Ionophore
Authors: Schwarze Thomas , Schneider Radu , Riemer Janine , Holdt Hans‐Jürgen
Published: October 2015

A desirable goal is to synthesize easily accessible and highly K+/Na+‐selective fluoroionophores to monitor physiological K+ levels in vitro and in vivo. Therefore, highly K+/Na+‐selective ionophores have to be developed. Herein, we obtained in a sequence of only four synthetic steps a set of K+‐responsive fluorescent probes 4, 5 and 6. In a systematic study, we investigated the influence of the alkoxy substitution in ortho position of the aniline moiety in π‐conjugated aniline‐1,2,3‐triazole‐coumarin‐fluoroionophores 4, 5 and 6 [R=MeO (4), EtO (5) and iPrO (6)] towards the K+‐complex stability and K+/Na+ selectivity. The highest K+‐complex stability showed fluoroionophore 4 with a dissociation constant Kd of 19 mm, but the Kd value increases to 31 mm in combined K+/Na+ solutions, indicating a poor K+/Na+ selectivity. By contrast, 6 showed even in the presence of competitive Na+ ions equal Kd values (KdK+=45 mm and KdK+/Na+=45 mm) and equal K+‐induced fluorescence enhancement factors (FEFs=2.3). Thus, the fluorescent probe 6 showed an outstanding K+/Na+ selectivity and is a suitable fluorescent tool to measure physiological K+ levels in the range of 10–80 mm in vitro. Further, the isopropoxy‐substituted N‐phenylaza[18]crown‐6 ionophore in 6 is a highly K+‐selective building block with a feasible synthetic route.
Cytoplasmic injection of murine zygotes with Sleeping Beauty transposon plasmids and minicircles results in the efficient generation of germline transgenic mice
Authors: Garrels Wiebke , Talluri Thirumala R. , Ziegler Maren , Most Ilka , Forcato Diego O. , Schmeer Marco , Schleef Martin , Ivics Zoltán , Kues Wilfried A.
Published: October 2015

Transgenesis in the mouse is an essential tool for the understanding of gene function and genome organization. Here, we describe a simplified microinjection protocol for efficient germline transgenesis and sustained transgene expression in the mouse model employing binary Sleeping Beauty transposon constructs of different topology. The protocol is based on co‐injection of supercoiled plasmids or minicircles, encoding the Sleeping Beauty transposase and a transposon construct, into the cytoplasm of murine zygotes. Importantly, this simplified injection avoids the mechanical penetration of the vulnerable pronuclear membrane, resulting in higher survival rates of treated embryos and a more rapid pace of injections. Upon translation of the transposase, transposase‐catalyzed transposition into the genome results in stable transgenic animals carrying monomeric transgenes. In summary, cytoplasmic injection of binary transposon constructs is a feasible, plasmid‐based, and simplified microinjection method to generate genetically modified mice. The modular design of the components allows the multiplexing of different transposons, and the generation of multi‐transposon transgenic mice in a single step.
Genetic fusion of single‐chain variable fragments to partial spider silk improves target detection in micro‐ and nanoarrays
Authors: Thatikonda Naresh , Delfani Payam , Jansson Ronnie , Petersson Linn , Lindberg Diana , Wingren Christer , Hedhammar My
Published: October 2015

Immobilizing biomolecules with retained functionality and stability on solid supports is crucial for generation of sensitive immunoassays. However, upon use of conventional immobilization strategies, a major portion of the biomolecules (e.g. antibodies) frequently tends to lose their bioactivity. In this study, we describe a procedure to immobilize human single‐chain variable fragment (scFv) via genetic fusion to partial spider silk, which have a high tendency to adhere to solid supports. Two scFvs, directed towards serum proteins, were genetically fused to partial spider silk proteins and expressed as silk fusion proteins in E. coli. Antigen binding ability of scFvs attached to a partial silk protein denoted RC was investigated using microarray analysis, whereas scFvs fused to the NC silk variant were examined using nanoarrays. Results from micro‐ and nanoarrays confirmed the functionality of scFvs attached to both RC and NC silk, and also for binding of targets in crude serum. Furthermore, the same amount of added scFv gives higher signal intensity when immobilized via partial spider silk compared to when immobilized alone. Together, the results suggest that usage of scFv‐silk fusion proteins in immunoassays could improve target detection, in the long run enabling novel biomarkers to be detected in crude serum proteomes.
Adherence to Mediterranean diet and risk of cancer: an updated systematic review and meta‐analysis of observational studies
Authors: Schwingshackl Lukas , Hoffmann Georg
Published: October 2015

The aim of the present systematic review and meta‐analysis of observational studies was to gain further insight into the effects of adherence to Mediterranean Diet (MD) on overall cancer mortality, incidence of different types of cancer, and cancer mortality risk in cancer survivors. Literature search was performed using the electronic databases PubMed, and EMBASE until 2 July 2015. We included either cohort (for specific tumors only incidence cases were used) or case–control studies. Study specific risk ratios, hazard ratios, and odds ratios (RR/HR/OR) were pooled using a random effect model. The updated review process showed 23 observational studies that were not included in the previous meta‐analysis (total number of studies evaluated: 56 observational studies). An overall population of 1,784,404 subjects was included in the present update. The highest adherence score to an MD was significantly associated with a lower risk of all‐cause cancer mortality (RR: 0.87, 95% CI 0.81–0.93, I2 = 84%), colorectal cancer (RR: 0.83, 95% CI 0.76–0.89, I2 = 56%), breast cancer (RR: 0.93, 95% CI 0.87–0.99, I2=15%), gastric cancer (RR: 0.73, 95% CI 0.55–0.97, I2 = 66%), prostate cancer (RR: 0.96, 95% CI 0.92–1.00, I2 = 0%), liver cancer (RR: 0.58, 95% CI 0.46–0.73, I2 = 0%), head and neck cancer (RR: 0.40, 95% CI 0.24–0.66, I2 = 90%), pancreatic cancer (RR: 0.48, 95% CI 0.35–0.66), and respiratory cancer (RR: 0.10, 95% CI 0.01–0.70). No significant association could be observed for esophageal/ovarian/endometrial/and bladder cancer, respectively. Among cancer survivors, the association between the adherence to the highest MD category and risk of cancer mortality, and cancer recurrence was not statistically significant. The updated meta‐analyses confirm a prominent and consistent inverse association provided by adherence to an MD in relation to cancer mortality and risk of several cancer types.
Sorafenib for the treatment of advanced hepatocellular carcinoma with extrahepatic metastasis: a prospective multicenter cohort study
Authors: Nakano Masahito , Tanaka Masatoshi , Kuromatsu Ryoko , Nagamatsu Hiroaki , Tajiri Nobuyoshi , Satani Manabu , Niizeki Takashi , Aino Hajime , Okamura Shusuke , Iwamoto Hideki , Shimose Shigeo , Shirono Tomotake , Koga Hironori , Torimura Takuji ,   the Kurume Liver Cancer Study Group of Japan
Published: October 2015

Sorafenib, an oral multikinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC) treatment. However, its therapeutic effect in advanced HCC patients with extrahepatic metastasis remains uncertain. This study aimed to prospectively assess the efficacy, safety, and survival risk factors and evaluate the prognostic impact of sorafenib treatment in advanced HCC patients with or without extrahepatic metastasis. Between May 2009 and March 2014, 312 consecutive advanced HCC patients who received sorafenib were enrolled in this study. We evaluated their characteristics and compared the clinical outcomes of those with and without extrahepatic metastasis. Of the enrolled patients, 245 (81%) received sorafenib treatment for more than 1 month, with a median duration of 3.6 months. Eighteen patients demonstrated partial response to sorafenib therapy, 127 had stable disease, and 134 had progressive disease at the first radiologic assessment. The median survival time (MST) and progression‐free survival (PFS) were 10.3 and 3.6 months, respectively. Multivariate analysis identified gender, Child‐Pugh class, baseline serum des‐gamma‐carboxy prothrombin level, and treatment duration as independent risk factors for survival. Extrahepatic metastasis was detected in 178 patients. However, the MST, PFS, and therapeutic effect were comparable between patients with and without extrahepatic metastasis. The independent risk factors for decreased overall survival in patients with extrahepatic metastasis were similar to those affecting all patients. Our results indicated that sorafenib could be administered for hepatic reserve and as long‐term treatment for advanced HCC patients regardless of their extrahepatic metastasis status.
Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high‐risk prostate cancer patients with worse survival following radiation therapy
Authors: Jacobs Corbin , Tumati Vasu , Kapur Payal , Yan Jingsheng , Xie Xian‐Jin , Hannan Raquibul , Hsieh Jer‐Tsong , Kim Dong Wook Nathan , Saha Debabrata
Published: October 2015

Decreased expression of tumor suppressor DAB2IP is linked to aggressive cancer and radiation resistance in several malignancies, but clinical survival data is largely unknown. We hypothesized that pretreatment DAB2IP reduction would predict worse prostate cancer‐specific survival (PCSS). Immunohistochemistry of pretreatment biopsies was scored by an expert genitourinary pathologist. Other endpoints analyzed include freedom from biochemical failure (FFBF), castration resistance‐free survival (CRFS), and distant metastasis‐free survival (DMFS). Seventy‐nine patients with NCCN‐defined high‐risk prostate cancer treated with radiotherapy from 2005 to 2012 at our institution were evaluated. Twenty‐eight percent (22/79) of pretreatment biopsies revealed DAB2IP‐reduction. The median follow up times were 4.8 years and 5.3 years for patients in the DAB2IP‐reduced group and DAB2IP‐retained group, respectively. Patients with reduced DAB2IP demonstrated worse outcome compared to patients retaining DAB2IP, including FFBF (4‐year: 34 vs. 92%; P < 0.0001), CRFS (4‐year: 58 vs. 96%; P = 0.0039), DMFS (4‐year: 58 vs. 100%; P = 0.0006), and PCSS (5‐year: 83 vs. 100%; P = 0.0102). Univariate analysis showed T stage, N stage, and Gleason score were statistically significant variables. Pretreatment tumor DAB2IP status remained significant in multivariable analyses. This study suggests that about one‐fourth of men with high‐risk prostate cancer have decreased tumor expression of DAB2IP. This subpopulation with reduced DAB2IP has a suboptimal response and worse malignancy‐specific survival following radiation therapy and androgen deprivation. DAB2IP loss may be a genetic explanation for the observed differences in aggressive tumor characteristics and radiation resistance. Further study into improving treatment response and survival in this subpopulation is warranted.
A Tough Nanocomposite Aerogel of Manganese Oxide and Polyaniline as an Electrode for a Supercapacitor
Authors: Liang Meiying , Liu Xinhua , Li Wenjun , Wang Qigang
Published: October 2015

A tough aerogel electrode of manganese oxide and polyaniline was prepared by in situ gelation, freeze‐drying, and heat treatment on carbon cloth. The porous structure endows the final aerogel electrode with high electrochemical performance even at high current density and excellent cycling stability.
Pull‐out strength of anchor pins for brickwork masonry and earth block masonry / Auszugsfestigkeit von Verpressankern für Ziegel‐ und Lehmsteinmauerwerk
Authors: Miccoli Lorenzo , Fontana Patrick , Paganoni Sara , D’Ayala Dina
Published: October 2015

In this paper results of the experimental testing performed on brick masonry and earth block masonry are presented. The paper outlines the development of the testing procedures for two different types of anchors. For this purpose, two experimental campaigns of pull‐out tests on masonry corner connections strengthened by metallic rod grouted were carried out. Experimental results proved that the implemented testing procedures are suitable to determine the most recurring failure modes of the anchor pins. Moreover, a procedure is proposed to estimate the capacity of grouted anchor pins based on experimental studies.
Flexural tensile tests with vertically perforated clay unit masonry with thin layer mortar / Biegezugversuche an Planziegelmauerwerk
Authors: Fehling Ekkehard , Ismail Mohammed , Samaan Samer , Meyer Udo
Published: October 2015

As part of the EU project, INSYSME – INnovative SYStems for earthquake resistant Masonry Enclosures in reinforced concrete buildings – to optimise infill masonry the German project partners carried out an initial part of the project on flexural strength testing of high‐tech clay block masonry in accordance with DIN EN 1052‐2. In this a wide range of modern products was considered which at present is regulated in Germany by means of general building authority approvals. The test results show that the specifications for flexural tensile strength of high‐tech clay block masonry in DIN EN 1996 are very conservative in most cases.
Employ mindfulness to improve services, support student success
Authors: Bedrossian Louise
Published: October 2015

As academic‐year demands peak again, it is especially important to re‐evaluate strategies for effective delivery of services, student success, and also professional achievement. Employing mindfulness strategies can benefit the work of both service providers and students.
Create a process for video captioning that ensures access for deaf, hard‐of‐hearing students
Authors: Carey Trudy
Published: October 2015

Videos are a great way to involve students in the learning experience, but when they aren't closed‐captioned, deaf and hard‐of‐hearing students are excluded from participation. It is a challenge to work with faculty to convince them that the videos they show in their classes must be captioned to provide access.
The in vivo and in vitro phase I metabolism of FYL‐67, a novel oxazolidinone antibacterial drug, studied by LC‐MS/MS
Authors: Sang Zitai , Long Haiyue , Yang Tao , Ye Weiwei , Yang Xiaoyan , Chen Gong , Wang Zhenling , Luo Youfu
Published: October 2015

In our previous study, FYL‐67, a novel linezolid analogue with the morpholinyl ring replaced by a 4‐(pyridin‐2‐yl)‐1H‐pyrazol‐1‐yl group, was demonstrated to own an excellent activity against Gram‐positive organisms,such as methicillin‐resistant Staphylococcus aureus (MRSA). However, metabolic biotransformation was not investigated. This study was performed to identify the phase I metabolites of FYL‐67 using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). The chemical structures were confirmed by comparison with corresponding chemical standards obtained internal. Primary elucidation of the metabolic pathway of FYL‐67 in vitro was performed using liver preparations (microsomes and hepatocytes) from rats and humans, and SD (Sprague Dawley, rat, rattus norvegicus) rats were used for the study of in vivo approach. To the end, two metabolites (M1 and M2) were detected after in vitro as well as in vivo experiments. Based on LC‐MS/MS analyses, the metabolites were demonstrated to be 5‐(aminomethyl)‐3‐(3‐fluoro‐4‐(4‐(pyridin‐2‐yl)‐1H‐pyrazol‐1‐yl)phenyl)oxazolidin‐2‐one (M1) and 3‐(3‐fluoro‐4‐(4‐(pyridin‐2‐yl)‐1H‐pyrazol‐1‐yl)phenyl)‐5‐(hydroxymethyl)oxazolidin‐2‐one (M2). Amide hydrolysis at acetyl group of FYL‐67 leading to the formation of M1 was observed and suggested to play a major role in both in vivo and in vitro phase I metabolism of FYL‐67. M1 was demonstrated to undergo a further oxidation to form M2. In addition, the results indicated no species difference existing between rats and humans. The outcomes of our research can be utilized for the development and validation of the analytical method for the quantification of FYL‐67 as well as its metabolites in biological samples. Furthermore, it is helpful to conduct studies of pharmacodynamics and toxicodynamics. Copyright © 2015 John Wiley & Sons, Ltd.
Winners always win: growth of a wide range of plant species from low to future high CO2
Authors: Temme Andries A. , Liu Jin Chun , Cornwell William K. , Cornelissen Johannes H. C. , Aerts Rien
Published: October 2015

Evolutionary adaptation to variation in resource supply has resulted in plant strategies that are based on trade‐offs in functional traits. Here, we investigate, for the first time across multiple species, whether such trade‐offs are also apparent in growth and morphology responses to past low, current ambient, and future high CO2 concentrations. We grew freshly germinated seedlings of up to 28 C3 species (16 forbs, 6 woody, and 6 grasses) in climate chambers at 160 ppm, 450 ppm, and 750 ppm CO2. We determined biomass, allocation, SLA (specific leaf area), LAR (leaf area ratio), and RGR (relative growth rate), thereby doubling the available data on these plant responses to low CO2. High CO2 increased RGR by 8%; low CO2 decreased RGR by 23%. Fast growers at ambient CO2 had the greatest reduction in RGR at low CO2 as they lost the benefits of a fast‐growth morphology (decoupling of RGR and LAR [leaf area ratio]). Despite these shifts species ranking on biomass and RGR was unaffected by CO2, winners continued to win, regardless of CO2. Unlike for other plant resources we found no trade‐offs in morphological and growth responses to CO2 variation, changes in morphological traits were unrelated to changes in growth at low or high CO2. Thus, changes in physiology may be more important than morphological changes in response to CO2 variation.
Macroscale intraspecific variation and environmental heterogeneity: analysis of cold and warm zone abundance, mortality, and regeneration distributions of four eastern US tree species
Authors: Prasad Anantha M.
Published: October 2015

I test for macroscale intraspecific variation of abundance, mortality, and regeneration of four eastern US tree species (Tsuga canadensis, Betula lenta, Liriodendron tulipifera, and Quercus prinus) by splitting them into three climatic zones based on plant hardiness zones (PHZs). The primary goals of the analysis are to assess the differences in environmental heterogeneity and demographic responses among climatic zones, map regional species groups based on decision tree rules, and evaluate univariate and multivariate patterns of species demography with respect to environmental variables. I use the Forest Inventory Analysis (FIA) data to derive abundance, mortality, and regeneration indices and split the range into three climatic zones based on USDA PHZs: (1) cold adapted, leading region; (2) middle, well‐adapted region; and (3) warm adapted, trailing region. I employ decision tree ensemble methods to assess the importance of environmental predictors on the abundance of the species between the cold and warm zones and map zonal variations in species groups. Multivariate regression trees are used to simultaneously explore abundance, mortality, and regeneration in tandem to assess species vulnerability. Analyses point to the relative importance of climate in the warm adapted, trailing zone (especially moisture) compared to the cold adapted, leading zone. Higher mortality and lower regeneration patterns in the warm trailing zone point to its vulnerability to growing season temperature and precipitation changes that could figure more prominently in the future. This study highlights the need to account for intraspecific variation of demography in order to understand environmental heterogeneity and differential adaptation. It provides a methodology for assessing the vulnerability of tree species by delineating climatic zones based on easily available PHZ data, and FIA derived abundance, mortality, and regeneration indices as a proxy for overall growth and fitness. Based on decision tree rules, ecologically meaningful variations in species abundance among the climatic zones can be related to environmental variability and mapped.
Predator‐driven elemental cycling: the impact of predation and risk effects on ecosystem stoichiometry
Authors: Leroux Shawn J. , Schmitz Oswald J.
Published: October 2015

Empirical evidence is beginning to show that predators can be important drivers of elemental cycling within ecosystems by propagating indirect effects that determine the distribution of elements among trophic levels as well as determine the chemical content of organic matter that becomes decomposed by microbes. These indirect effects can be propagated by predator consumptive effects on prey, nonconsumptive (risk) effects, or a combination of both. Currently, there is insufficient theory to predict how such predator effects should propagate throughout ecosystems. We present here a theoretical framework for exploring predator effects on ecosystem elemental cycling to encourage further empirical quantification. We use a classic ecosystem trophic compartment model as a basis for our analyses but infuse principles from ecological stoichiometry into the analyses of elemental cycling. Using a combined analytical‐numerical approach, we compare how predators affect cycling through consumptive effects in which they control the flux of nutrients up trophic chains; through risk effects in which they change the homeostatic elemental balance of herbivore prey which accordingly changes the element ratio herbivores select from plants; and through a combination of both effects. Our analysis reveals that predators can have quantitatively important effects on elemental cycling, relative to a model formalism that excludes predator effects. Furthermore, the feedbacks due to predator nonconsumptive effects often have the quantitatively strongest impact on whole ecosystem elemental stocks, production and efficiency rates, and recycling fluxes by changing the stoichiometric balance of all trophic levels. Our modeling framework predictably shows how bottom‐up control by microbes and top‐down control by predators on ecosystems become interdependent when top predator effects permeate ecosystems.
Conducting Wave Investigation by Multichannel Surface EMG
Authors: KOSUGE TOMOHIRO , ITAKURA NAOAKI , MITO KAZUYUKI
Published: October 2015

Muscular activity is investigated by analyzing the action potential generated by motor units. The multichannel surface electromyogram (EMG) is used to analyze the conduction of muscle potential, which is recorded as the interference electric potential generated by motor units. The multichannel surface EMG includes waveforms that conduct in several channels (conducting waves). We believe that it may be possible to analyze the changes in surface muscle potential caused by muscular activity so as to examine the composition of conducting waves in the multichannel surface EMG. Thus, in this paper, we propose a new method of analyzing the multichannel surface EMG. The proposed method involves quantitatively searching for all conducting waves that appear in the multichannel surface EMG in order to calculate the similarity of the waveforms. Using this method, which is referred to as the multichannel method for conducting waves (m‐ch method), various types of data for each wave, including the conduction velocity and amplitude, across channels can be examined. Using the m‐ch method, we analyzed the multichannel surface EMG in subjects holding a load. We also examined the changes in the composition of the conducting waves. We believe that muscular activity can be analyzed based on conducting waves from a surface EMG.
A Fundamental Study of Polarimetric GB‐SAR for Nondestructive Inspection of Internal Damage in Concrete Walls
Authors: TAKAHASHI KAZUNORI , OKAMURA SAIKA , SATO MOTOYUKI
Published: October 2015

Damages on the surfaces of concrete buildings can easily be detected by visual inspection and can be repaired. However, damages inside walls need nondestructive inspection techniques to be detected, located, and identified. There has been a great demand for such techniques particularly after the 3.11 Great East Japan Earthquake. Ground‐based synthetic aperture radar (GB‐SAR) is a technique that can be potentially used for inspection of concrete walls in a nondestructive and noncontacting manner. The paper reports a fundamental experiment with a polarimetric GB‐SAR system to detect internal damage in a concrete specimen caused by horizontal loading simulating earthquakes. The results show that the system does not have enough resolution to visualize individual defects, and that the effect of steel rebars installed inside the concrete is so strong that it masks weak responses. However, polarimetric analysis demonstrated the capability to minimize the effect of rebars by rearranging polarization basis and to extract weak responses. In particular, internal damages could be detected by observing the volume scattering component in this experiment.
Tissue factor expression by myeloid cells contributes to protective immune response against Mycobacterium tuberculosis infection
Authors: Venkatasubramanian Sambasivan , Tripathi Deepak , Tucker Torry , Paidipally Padmaja , Cheekatla Satyanarayana , Welch Elwyn , Raghunath Anjana , Jeffers Ann , Tvinnereim Amy R. , Schechter Melissa E , Andrade Bruno B , Mackman Nizel , Idell Steven , Vankayalapati Ramakrishna
Published: October 2015

Tissue factor (TF) is a transmembrane glycoprotein that plays an essential role in hemostasis by activating coagulation. TF is also expressed by monocytes/macrophages as part of the innate immune response to infections. In the current study, we determined the role of TF expressed by myeloid cells during Mycobacterium tuberculosis (M. tb) infection by using mice lacking the TF gene in myeloid cells (TFΔ) and human monocyte derived macrophages (MDMs). We found that during M. tb infection, a deficiency of TF in myeloid cells was associated with reduced inducible nitric oxide synthase (iNOS) expression, enhanced arginase 1 (Arg1) expression, enhanced IL‐10 production and reduced apoptosis in infected macrophages, which augmented M. tb growth. Our results demonstrate that a deficiency of TF in myeloid cells promotes M2‐like phenotype in M .tb infected macrophages. A deficiency in TF expression by myeloid cells was also associated with reduced fibrin deposition and increased matrix metalloproteases (MMP)‐2 and MMP‐9 mediated inflammation in M. tb infected lungs. Our studies demonstrate that TF expressed by myeloid cells has newly recognized abilities to polarize macrophages and to regulate M. tb growth.
Facile One‐Pot Route toward Water‐Soluble Lanthanide–Copper–Glycinehydrox­imate 15‐Metallacrown‐5 Complexes
Authors: Katkova Marina A. , Zabrodina Galina S. , Muravyeva Maria S. , Shavyrin Andrey S. , Baranov Evgeny V. , Khrapichev Alexandr A. , Ketkov Sergey Yu.
Published: October 2015

Among the Ln[15MCCuRha‐5] metallacrowns (MC; Rha = R‐substituted hydroximate ligands), the simple glycinehydroximate (Glyha) complex is presented as the primary model for studying various aspects of the guest interaction with the LnIII ion. We report a one‐pot synthesis of several glycinehydroximate LnL[15MCCuGlyha‐5] derivatives in the presence of calcium compounds. The complexes with bidentate nitrate ion Nd(NO3)[15MCCuIIGlyha‐5](NO3)2 (1), bidentate acetate Y(CH3COO)[15MCCuIIGlyha‐5](NO3)2 (2), bridging nitrate La(NO3)[15MCCuIIGlyha‐5](NO3)2 (3), and bidentate lactate Gd(CH3CHOCOO)[15MCCuIIGlyha‐5]Cl2 [4(Gd)] have been prepared and characterized by X‐ray analysis. The lactate was chosen as an example of the essential oxy‐anions that exist as metabolites in all living organisms. We examined the lanthanide‐induced NMR spectroscopy shifting ability of a series of lactate 4(Ln) metallacrown complexes (Ln = La, Y, Ce, Pr, Nd, Sm, Eu, Gd, Tb, or Dy). The corresponding GdIII complex was characterized by 1H NMR spectroscopy relaxometric techniques in aqueous media.
Tridentate Aryloxy‐Based Titanium Catalysts towards Ethylene Oligomerization and Polymerization
Authors: Audouin Hugo , Bellini Rosalba , Magna Lionel , Mézailles Nicolas , Olivier‐Bourbigou Hélène
Published: October 2015

A series of tridentate aryloxy‐based ligands were synthesized and characterized for their coordination behaviour towards TiIV. Coordination studies revealed that the nature of the central atom (amine vs. ether) and the type of bridging spacer (aromatic vs. aliphatic) are important aryloxy ligand parameters and influence the ligand coordination mode and the formation of stable titanium complexes. This series of titanium complexes were evaluated in ethylene oligomerization and polymerization after activation with methylaluminoxane (MAO) and showed the preferential formation of polyethylene. In some cases, the formation of a small amount of 1‐hexene suggests the existence of several catalytic centres in the reaction mixture.
Facile Large‐Scale Synthesis of 5‐ and 6‐Carboxyfluoresceins: Application for the Preparation of New Fluorescent Dyes
Authors: Hammershøj Peter , Kumar E. K. Pramod , Harris Pernille , Andresen Thomas L. , Clausen Mads H.
Published: October 2015

A series of fluorescein dyes have been prepared from a common precursor through a very simple synthetic procedure, giving access to important precursors for fluorescent probes. The method has proven an efficient access to regioisomerically pure 5‐ and 6‐carboxyfluoresceins on a large scale, in good yields, and with high regioisomeric purity. Furthermore, we have applied the method to the development of a new type of mixed fluorescein derivatives of 5‐carboxyfluorescein. We have demonstrated the scope of the procedure by synthesizing a new type of double chromophore within the fluoro‐Jade family.
Effects of insular stimulation on thermal nociception
Authors: Denis D.J. , Marouf R. , Rainville P. , Bouthillier A. , Nguyen D.K.
Published: October 2015

Background

Electrical stimulation used for brain mapping in the postero‐superior insula can evoke pain. The effects of prolonged high frequency insular stimulation on pain thresholds are unknown.

Objective/Hypothesis

Prolonged high frequency insular stimulation, by virtue of its inhibitory properties on networks, could decrease thermal nociception.

Methods

Epileptic subjects had electrodes implanted in the insular cortex for the purpose of epileptic focus resection. Thermal and pressure nociceptive thresholds were tested bilaterally on the forearm on two consecutive days. Randomly assigned double‐blind high frequency (150 Hz) insular stimulation took place for 10 min before pain testing either on the first day or on the second day.

Results

Six subjects (three females; mean age of 35 years) were included. Insular stimulation increased heat pain threshold on the ipsilateral (p = 0.003; n = 6) and contralateral sides (p = 0.047; n = 6). Differences in cold pain threshold did not reach statistical significance (ipsilateral: p = 0.341, contralateral: p = 0.143; n = 6), but one subject had a profound decrease in both heat and cold pain responses. Pressure pain threshold was not modified by insular stimulation (ipsilateral: p = 0.1123; contralateral: p = 0.1192; n = 6). Two of the three subjects who had a postero‐superior operculo‐insulectomy developed central pain with contralateral thermal nociceptive deficit.

Conclusions

High frequency inhibitory postero‐superior insular stimulation may have the potential to decrease thermal nociception. Together with previous studies, our data support the notion that the integrity of this brain region is necessary for thermal but not pressure nociceptive processing.
A hydrogeomorphic assessment of twenty‐first century floods in the UK
Authors: Foulds Simon A. , Macklin Mark G.
Published: October 2015

The occurrence of devastating floods in the British uplands during the first two decades of the twenty‐first century poses two key questions: (1) are recent events unprecedented in terms of their frequency and magnitude; and (2) is climate and/or land‐use change driving the apparent upturn in flooding? Conventional methods of analysing instrumental flow records cannot answer these questions because upland catchments are usually ungauged, and where records do exist they rarely provide more than 30–40 years of data. In this paper we analyse all lichen‐dated upland flood records in the United Kingdom (UK) to establish the longer‐term context and causes of recent severe flooding. Our new analysis of torrential sedimentary deposits shows that twenty‐first century floods are not unprecedented in terms of both their frequency (they were more frequent before 1960) and magnitude (the biggest events occurred during the seventeenth–nineteenth centuries). However, in some areas recent floods have either equalled or exceeded the largest historical events. The majority of recent floods have been triggered by torrential summer downpours related to a marked negative phase of the summer North Atlantic Oscillation (NAO) between 2007 and 2012. It is of concern that historical data suggests there is far more capacity in the North Atlantic climate system to produce wetter and more prolonged flood‐rich periods than hitherto experienced in the twenty‐first century. Looking forwards, an increased likelihood of weather extremes due to climate change means that geomorphological based flood series extensions must be placed at the centre of flood risk assessment in the UK uplands and in similar areas worldwide. Copyright © 2015 John Wiley & Sons, Ltd.
Interleukin‐25 initiates Th2 differentiation of human CD4+ T cells and influences expression of its own receptor
Authors: Bredo Graeme , Storie Jessica , Shrestha Palikhe Nami , Davidson Courtney , Adams Alexis , Vliagoftis Harissios , Cameron Lisa
Published: October 2015

Human CRTh2+ Th2 cells express IL‐25 receptor (IL‐25R) and IL‐25 has been shown to potentiate production of Th2 cytokines. However, regulation of IL‐25R and whether it participates in Th2 differentiation of human cells have not been examined. We sought to characterize IL‐25R expression on CD4+ T cells and determine whether IL‐25 plays a role in Th2 differentiation. Naïve human CD4+ T cells were activated in the presence of IL‐25, IL‐4 (Th2 conditions) or both cytokines to assess their relative influence on Th2 differentiation. For experiments with differentiated Th2 cells, CRTh2‐expressing cells were isolated from differentiating cultures. IL‐25R, GATA3, CRTh2 and Th2 cytokine expression were assessed by flow cytometry, qRT‐PCR and ELISA. Expression of surface IL‐25R was induced early during Th2 differentiation (2 days). Addition of IL‐25 to naïve CD4+ T cells revealed that it induces expression of its own receptor, more strongly than IL‐4. IL‐25 also increased the proportions of IL‐4‐, GATA3‐ and CRTh2‐expressing cells and expression of IL‐5 and IL‐13. Activation of differentiated CRTh2+ Th2 cells through the TCR or by CRTh2 agonist increased surface expression of IL‐25R, though re‐expression of CRTh2 following TCR downregulation was impeded by IL‐25. These data suggest that IL‐25 may play various roles in Th2 mediated immunity. We establish here it regulates expression of its own receptor and can initiate Th2 differentiation, though not as strongly as IL‐4.
Molecular basis of the regulation of iron homeostasis in fission and filamentous yeasts
Authors: Brault Ariane , Mourer Thierry , Labbé Simon
Published: October 2015

When iron load exceeds that needed by fission and filamentous yeasts, iron‐regulatory GATA‐type transcription factors repress genes encoding iron acquisition systems. In contrast, under iron starvation, optimization of cellular iron utilization is coordinated by a specialized regulatory subunit of the CCAAT‐binding factor that fosters repression of genes encoding iron‐using proteins. Despite these findings, there is still limited knowledge concerning the mechanisms by which these iron‐responsive regulators respond to high‐ or low‐iron availability. To provide a framework for understanding common and distinct properties of iron‐dependent transcriptional regulators, a repertoire of their functional domains in different fungal species is presented here. In addition, discovery of interacting partners of these iron‐responsive factors contributes to provide additional insight into their properties. © 2015 IUBMB Life, 67(11):801–815, 2015
Overproduction of reactive oxygen species and activation of MAPKs are involved in apoptosis induced by PM2.5 in rat cardiac H9c2 cells
Authors: Cao Jing , Qin Gang , Shi Ruizan , Bai Feng , Yang Guangzhao , Zhang Mingsheng , Lv Jiyuan
Published: October 2015

Epidemiological studies show a positive correlation between the air levels of fine particulate matter (PM2.5) and cardiovascular disorders, but how PM2.5 affects cardiomyocytes has not been studied in great deal. The aim of the present study was to obtain an insight into the links among intracellular levels of reactive oxygen species (ROS), apoptosis and mitogen‐activated protein kinases (MAPKs) in rat cardiac H9c2 cells exposed to PM2.5. H9c2 cells were incubated with PM2.5 at 100–800 µg ml–1 to evaluate the effects of PM2.5 on cell viability, cell apoptosis, intracellular levels of ROS and expression of apoptosis‐related proteins as well as activation of MAPKs. PM2.5 decreased cell viability, increased the cell apoptosis rate and intracellular ROS production in a concentration‐dependent manner. PM2.5 decreased the Bcl‐2/Bax ratio and increased cleaved caspase‐3 levels. A Western blots study showed up‐regulation of phosphorylated MAPKs including extracellular signal‐regulated protein kinases (ERKs), c‐Jun NH2‐terminal kinases (JNKs) and p38 MAPK in the PM2.5‐treated cells. The p38 MAPK inhibitor SB239063 attenuated whereas the ERKs inhibitor PD98059 augmented the effects of PM2.5 on apoptosis and the expression of related proteins. In conclusion, PM2.5 decreases cell viability and increases apoptosis by enhancing intracellular ROS production and activating the MAPKs signaling pathway in H9c2 cells. The MAPKs signaling pathway could be a new promising target for clinical therapeutic strategies against PM2.5‐induced cardiac injury. Copyright © 2015 John Wiley & Sons, Ltd.