bluuebunny/crossref_metadata_2025 huggingface dataset:
Fast and slow climate responses to CO2 and solar forcing: A linear multivariate regression model characterizing transient climate change
Authors: Cao Long , Bala Govindasamy , Zheng Meidi , Caldeira Ken
Published: November 2015

Climate change in response to a change in external forcing can be understood in terms of fast response to the imposed forcing and slow feedback associated with surface temperature change. Previous studies have investigated the characteristics of fast response and slow feedback for different forcing agents. Here we examine to what extent that fast response and slow feedback derived from time‐mean results of climate model simulations can be used to infer total climate change. To achieve this goal, we develop a multivariate regression model of climate change, in which the change in a climate variable is represented by a linear combination of its sensitivity to CO2 forcing, solar forcing, and change in global mean surface temperature. We derive the parameters of the regression model using time‐mean results from a set of HadCM3L climate model step‐forcing simulations, and then use the regression model to emulate HadCM3L‐simulated transient climate change. Our results show that the regression model emulates well HadCM3L‐simulated temporal evolution and spatial distribution of climate change, including surface temperature, precipitation, runoff, soil moisture, cloudiness, and radiative fluxes under transient CO2 and/or solar forcing scenarios. Our findings suggest that temporal and spatial patterns of total change for the climate variables considered here can be represented well by the sum of fast response and slow feedback. Furthermore, by using a simple 1‐D heat‐diffusion climate model, we show that the temporal and spatial characteristics of climate change under transient forcing scenarios can be emulated well using information from step‐forcing simulations alone.
The Pb isotopic evolution of the Martian mantle constrained by initial Pb in Martian meteorites
Authors: Bellucci J. J. , Nemchin A. A. , Whitehouse M. J. , Snape J. F. , Bland P. , Benedix G. K.
Published: November 2015

The Pb isotopic compositions of maskelynite and pyroxene grains were measured in ALH84001 and three enriched shergottites (Zagami, Roberts Massif 04262, and Larkman Nunatuk 12011) by secondary ion mass spectrometry. A maskelynite‐pyroxene isochron for ALH84001 defines a crystallization age of 4089 ± 73 Ma (2σ). The initial Pb isotopic composition of each meteorite was measured in multiple maskelynite grains. ALH84001 has the least radiogenic initial Pb isotopic composition of any Martian meteorite measured to date (i.e., 206Pb/204Pb = 10.07 ± 0.17, 2σ). Assuming an age of reservoir formation for ALH84001 and the enriched shergottites of 4513 Ma, a two‐stage Pb isotopic model has been constructed. This model links ALH84001 and the enriched shergottites by their similar μ value (238U/204Pb) of 4.1–4.6 from 4.51 Ga to 4.1 Ga and 0.17 Ga, respectively. The model employed here is dependent on a chondritic μ value (~1.2) from 4567 to 4513 Ma, which implies that core segregation had little to no effect on the μ value(s) of the Martian mantle. The proposed Pb isotopic model here can be used to calculate ages that are in agreement with Rb‐Sr, Lu‐Hf, and Sm‐Nd ages previously determined in the meteorites and confirm the young (~170 Ma) ages of the enriched shergottites and ancient, >4 Ga, age of ALH84001.
Talking (or Not Talking) about the Past: The Influence of Parent–Child Conversation about Negative Experiences on Children's Memories
Authors: Salmon Karen , Reese Elaine
Published: November 2015

We review research investigating the influence of conversations between parents and their children about past negative experiences on children's memory and management of their emotional experiences. To do so, we are guided by social cultural developmental theory and a developmental psychopathology framework. In the first section, we first discuss the ‘best case’ scenario, in which parents and child have a close relationship within which the child's negative emotions can be discussed and understood, and the child's ability to remember her experiences in a detailed and coherent narrative form is optimised. In the second section, we turn to the most problematic scenario of child maltreatment, including child sexual abuse, and consider the implications for children's memory when these optimizing factors are not present or are limited. Finally, we discuss exemplar intermediary scenarios. We propose that early problems acquiring critical skills for remembering emotional experiences in the context of parent–child relationships can have negative consequences for children's memory but also for their psychological functioning more broadly, which can extend across development. Copyright © 2015 John Wiley & Sons, Ltd.
Improved Electrochemical Performance of Na‐Ion Batteries in Ether‐Based Electrolytes: A Case Study of ZnS Nanospheres
Authors: Su Dawei , Kretschmer Katja , Wang Guoxiu
Published: November 2015

Sodium‐ion batteries are considered as a promising technology for large‐scale energy storage applications, owing to their low cost. However, there are many challenges for developing sodium‐ion batteries with high capacity, long cycle life, and high‐rate capability. Herein, the development of high‐performance sodium‐ion batteries using ZnS nanospheres as anode material and an ether‐based electrolyte, which exhibit improved electrochemical performance over the pure alkyl carbonate electrolytes, is reported. ZnS nanospheres deliver a high specific capacity of 1000 mA h g−1 and high initial Columbic efficiency of 90%. Electrochemical testing and first‐principle calculations demonstrate that the ether‐based solvent can facilitate charge transport, reduce the energy barrier for sodium‐ion diffusion, and thus enhance electrochemical performances. Ex situ measurements (X‐ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS) mapping) reveal that ZnS nanospheres maintain structural integrity during the charge and discharge processes over 100 cycles. As anode material for sodium‐ion batteries, ZnS nanospheres deliver high reversible sodium storage capacity, high Coulombic efficiencies, and extended cycle life.
Acute myeloid leukemia—Major progress over four decades and glimpses into the future
Authors: Kantarjian Hagop
Published: November 2015

In this Review, the progress in research and therapy of acute myeloid leukemia is detailed. Am. J. Hematol. 91:131–145, 2016. © 2015 Wiley Periodicals, Inc.
Two‐Dimensional Nanoporous Networks Formed by Liquid‐to‐Solid Transfer of Hydrogen‐Bonded Macrocycles Built from DNA Bases
Authors: Bilbao Nerea , Destoop Iris , De Feyter Steven , González‐Rodríguez David
Published: November 2015

We present an approach that makes use of DNA base pairing to produce hydrogen‐bonded macrocycles whose supramolecular structure can be transferred from solution to a solid substrate. A hierarchical assembly process ultimately leads to two‐dimensional nanostructured porous networks that are able to host size‐complementary guests.
A Mechanochromic Single Crystal: Turning Two Color Changes into a Tricolored Switch
Authors: Ma Zhiyong , Wang Zhijian , Meng Xiao , Ma Zhimin , Xu Zejun , Ma Yuguo , Jia Xinru
Published: November 2015

The single crystal of M‐4‐B was obtained by attaching the boron of BH3 to the amine linker between a tetraphenylethylene (TPE) unit and rhodamine B. M‐4‐B showed a novel sequential tricolor switching from dark blue to bluish‐green and to a reddish color upon grinding. The boron atom played a key role in developing the single crystal.
Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide‐mimetic drugs
Authors: Arakawa Hiroshi , Kamioka Hiroki , Kanagawa Masahiko , Hatano Yasuko , Idota Yoko , Yano Kentaro , Morimoto Kaori , Ogihara Takuo
Published: November 2015

The study investigated whether quinolone antibiotics inhibit the PEPT1‐mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine‐Ψ(CN‐S)‐alanine (Phe‐Ψ‐Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (Cmax) of orally administered Phe‐Ψ‐Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration–time curve (AUC) of orally administered Phe‐Ψ‐Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe‐Ψ‐Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug–drug interaction. Copyright © 2016 John Wiley & Sons, Ltd.
Simultaneous quantification of hyperin, reynoutrin and guaijaverin in mice plasma by LC‐MS/MS: application to a pharmacokinetic study
Authors: Li Z. , Meng F. , Zhang Y. , Sun L. , Yu L. , Zhang Z. , Peng S. , Guo J.
Published: November 2015

A specific and sensitive LC‐MS/MS assay was developed to simultaneously quantify three structurally similar flavonoid glycosides – hyperin, reynoutrin and guaijaverin – in mouse plasma. Biosamples were prepared by solid‐phase extraction. Isocratic chromatographic separation was performed on an AichromBond‐AQ C18 column (250 × 2.1 mm, 5 μm) with methanol–acetonitrile–water–formic acid (20:25:55:0.1) as the mobile phase. Detection of hyperin, reynoutrin, guaijaverin and internal standard [luteolin‐7‐O‐β‐d‐apiofuranosyl‐(1 → 6)‐β‐d‐glucopyranoside] was achieved by ESI‐MS/MS in the negative ion mode using m/z 463 → m/z 300, m/z 433 → m/z 300, m/z 433 → m/z 300 and m/z 579 → m/z 285 transitions, respectively. Linear concentration ranges of calibration curves were 4.0–800.0 ng/mL for hyperin and reynoutrin and 8.0–1600.0 ng/mL for guaijaverin when 100 μL of plasma was analyzed. We used this validated method to study the pharmacokinetics of hyperin, reynoutrin and guaijaverin in mice following oral and intravenous administration. All three quercetin‐3‐O‐glycosides showed poor oral absorption in mice, and the absolute bioavailability of hyperin after oral administration of 100 mg/kg was 1.2%. Pretreatment with verapamil increased the peak concentration and area under the concentration–time curve of hyperin, which were significantly higher than the control values. The half‐life of hyperin with verapamil was significantly prolonged compared with that of the control. Copyright © 2016 John Wiley & Sons, Ltd.
Greenwashing Revisited: In Search of a Typology and Accusation‐Based Definition Incorporating Legitimacy Strategies
Authors: Seele Peter , Gatti Lucia
Published: November 2015

Is greenwashing a concept describing companies using misleading communication or is it co‐constructed in the eye of the beholder? By discussing the literature, we find that existing definitions of greenwashing overemphasize the strategic intention to mislead and do not incorporate unjust allegations. Then, by combining signaling theory with legitimacy theory, we frame the communication process of the greenwashing accusation and the emergence of a negative narrative caused by the accusation and its effect on legitimacy. Hence, in this paper we argue that greenwashing epistemologically is constituted in the eye of the beholder, depending on an external accusation. Following this view, the greenwashing accusation is understood as a distortion factor altering the signal reliability of green messages. Based on our conceptual analysis, we provide a conceptual framework introducing a new typology of case‐based greenwashing (greenwashing, false greenwashing, potential greenwashing and no greenwashing) and the effects of these types on corporate legitimacy. Finally, we propose a revised definition of greenwashing as co‐creation of an external accusation toward an organization with regard to presenting a misleading green message. Copyright © 2015 John Wiley & Sons, Ltd and ERP Environment
Epidemiological study of soft‐tissue sarcomas in Ireland
Authors: Bhatt Nikita , Deady Sandra , Gillis Amy , Bertuzzi Alexia , Fabre Aurelie , Heffernan Eric , Gillham Charles , O'Toole Gary , Ridgway Paul F.
Published: November 2015

Soft‐tissue sarcomas (STS) account for 1% of adult and 7% of pediatric malignancies. Histopathology and classification of these rare tumors requires further refinements. The aim of this paper is to describe the current incidence and survival of STS from 1994 to 2012 in Ireland and compare these with comparably coded international published reports. This is a retrospective, population study based on the data from the National Cancer Registry of Ireland (NCRI). Incidence and relative survival rates for STS in Ireland were generated. Incidence of STS based on gender, age and anatomical location was examined. Annual mean incidence rate (European Age Standardized) in Ireland between 1994 and 2012 was 4.48 ± 0.15 per 100,000 person‐years. The overall relative 5‐year survival rate of STS for the period 1994–2011 in Ireland was 56%, which was similar to that reported in the U.K. but lower than in most of Europe and U.S.A. Survival rate fluctuated over the period examined, declining slightly in females but showing an increase in males. STS incidence trends in Ireland were comparable to international reports. Survival trends of STS were significantly different between Ireland and other European countries, requiring further study to understand causation.
Interaction of natural killer cells with neutrophils exerts a significant antitumor immunity in hematopoietic stem cell transplantation recipients
Authors: Ueda Ryosuke , Narumi Kenta , Hashimoto Hisayoshi , Miyakawa Reina , Okusaka Takuji , Aoki Kazunori
Published: November 2015

Autologous hematopoietic stem cell transplantation (HSCT) can induce a strong antitumor immunity by homeostatic proliferation (HP) of T cells and suppression of regulatory T cells following preconditioning‐induced lymphopenia. However, the role of innate immunity including natural killer (NK) cells is still not understood. Here, first, we examined whether NK cells exert an antitumor effect after syngeneic HSCT in a murine colon cancer model. Flow cytometry showed that NK cells as well as T cells rapidly proliferated after HSCT, and the frequency of mature NK cells was increased in tumor during HP. Furthermore, NK cells undergoing HP were highly activated, which contributed to substantial tumor suppression. Then, we found that a large number of neutrophils accumulated in tumor early after syngeneic HSCT. It was recently reported that neutrophil‐derived mediators modulate NK cell effector functions, and so we examined whether the neutrophils infiltrated in tumor are associated with NK cell‐mediated antitumor effect. The depletion of neutrophils significantly impaired an activation of NK cells in tumor and increased the fraction of proliferative NK cells accompanied by a decrease in NK cell survival. The results suggested that neutrophils in tumor prevent NK cells from activation‐induced cell death during HP, thus leading to a significant antitumor effect by NK cells. This study revealed a novel aspect of antitumor immunity induced by HSCT and may contribute to the development of an effective therapeutic strategy for cancer using HSCT.
Racial disparities of pancreatic cancer in Georgia: a county‐wide comparison of incidence and mortality across the state, 2000–2011
Authors: Brotherton Lindsay , Welton Michael , Robb Sara W.
Published: November 2015

Understanding the geographic distribution of pancreatic cancer is important in assessing disease burden and identifying high‐risk populations. This study examined the geographic trends of pancreatic cancer incidence, mortality, and mortality‐to‐incidence ratios (MIRs) in Georgia, with a special focus on racial disparities of disease. Directly age‐adjusted pancreatic cancer incidence and mortality rates for Georgia counties (N = 159) were obtained for 2000–2011. Maps of county age‐adjusted disease rates and MIRs were generated separately for African Americans and Caucasians. Cluster analyses were conducted to identify unusual geographic aggregations of cancer cases or deaths. Pearson correlation coefficients were calculated to examine associations between county health factors (e.g., health behaviors, clinical care, and physical environment) and pancreatic cancer incidence or mortality rates. African Americans displayed a significantly higher age‐adjusted incidence (14.6/100,000) and mortality rate (13.3/100,000), compared to Caucasians. Cluster analyses identified five significant incidence clusters and four significant mortality clusters among Caucasians; one significant incidence cluster and two significant mortality clusters were identified among African Americans. Weak but significant correlations were noted between physical environment and pancreatic cancer incidence (ρ = 0.16, P = 0.04) and mortality (ρ = 0.18, P = 0.02) among African Americans. A disproportion burden of pancreatic cancer incidence and mortality was exhibited among African Americans in Georgia. Disease intervention efforts should be implemented in high‐risk areas, such as the southwest and central region of the state. Future studies should assess health behaviors and physical environment in relationship with the spatial distribution of pancreatic cancer.
CHADS2 scores as a predictor of ischemic stroke after radical prostatectomy
Authors: Yang Yu‐Wan , Lee Shang‐Sen , Chen Chi‐Cheng , Liu Hsin‐Ho , Tsai Tsung‐Hsun , Lin Tien‐Huang , Hsieh Teng‐Fu
Published: November 2015

Patients with prostate cancer have an increased risk of stroke, but their absolute rate of stroke depends on age and comorbid conditions. The Charlson Comorbidity Index Score (CCIS) is a widely accepted measure for risk adjustment in administrative claims data sets. This study assesses the predictive value of CHADS2 scores and CCIS for stroke among patients with prostate cancer. The study was conducted based on data taken from Taiwan's National Health Insurance Research Database (NHIRD). We identified a total of 5414 participants with nonatrial fibrillation (AF) prostate cancer diagnoses who underwent radical prostatectomy between 1997 and 2011. CHADS2 scores and CCIS were used to stratify the 5‐year ischemic stroke risk. All participants were followed from the date of enrollment until ischemic stroke, death, or the end of the 5‐year follow‐up period. The 5‐year risk of ischemic stroke in the present study was 1.7%. Ischemic stroke has a better correlation with CHADS2 (CHADS2 score = 0 to 1: 0.02%, CHADS2 score = 2 to 3: 13.9%, CHADS2 score ≥ 4: 44.4%; AUC = 0.978) than CCIS (CCIS = 0 to 1: 1.6%, CCIS = 2 to 3: 1.7%, CCIS ≥ 4: 3.8%; AUC = 0.520). Our results show that patients with prostate cancer who underwent radical prostatectomy show significantly higher risk of ischemic stroke in high CHADS2 score patients, and the CHADS2 score could be applied for ischemic stroke prediction. Cardiovascular risks evaluation and management are suggested for prostate cancer patients with higher CHADS2 score.
Electrocatalytic Performance of High‐Surface‐Area Platinum Catalysts Synthesized by Chemical Vapor Deposition for Water Splitting
Authors: Klett Joachim , Eva Andreas , Heinz Frederick , Kaiser Bernhard , Jaegermann Wolfram , Schäfer Rolf
Published: November 2015

We present the deposition of Pt particles and films by chemical vapor deposition from platinum(II) acetylacetonate for electrochemical water splitting. High‐surface‐area particles can be obtained at substrate temperatures as low as 150 °C by this technique. Clear differences in morphology were identified, which depended on the type of reactive gas introduced in the process. Although oxygen leads to a crystalline film growth, hydrogen leads to an open structure of stacked Pt spheres. The electrochemically active surface area of these deposits were determined by hydrogen adsorption–desorption measurements in alkaline solution. With respect to water splitting and other catalytic processes, we present a way to synthesize and characterize high‐surface‐area Pt samples easily. To evaluate their electrocatalytic performance, the catalysts were analyzed in terms of the overvoltage for the hydrogen evolution reaction.
Halogen‐Bonding‐Assisted Iodosylbenzene Activation by a Homogenous Iron Catalyst
Authors: de Sousa David P. , Wegeberg Christina , Vad Mads Sørensen , Mørup Steen , Frandsen Cathrine , Donald William A. , McKenzie Christine J.
Published: November 2015

The iron(III) complex of hexadentate N,N,N′‐tris(2‐pyridylmethyl)ethylendiamine‐N′‐acetate (tpena−) is a more effective homogenous catalyst for selective sulfoxidation and epoxidation with insoluble iodosylbenzene, [PhIO]n, compared with soluble methyl‐morpholine‐N‐oxide (NMO). We propose that two molecules of [Fe(tpena)]2+ cooperate to solubilize PhIO, extracting two equivalents to form the halogen‐bonded dimeric {[Fe(tpena)OIPh]2}4+. The closest intradimeric I⋅⋅⋅O distance, 2.56 Å, is nearly 1 Å less than the sum of the van de Waals radii of these atoms. A correlation of the rates of the reaction of {[Fe(tpena)OIPh]2}4+ with para‐substituted thioanisoles indicate that this species is a direct metal‐based oxidant rather than a derived ferryl or perferryl complex. A study of gas‐phase reactions indicate that an ion at m/z=231.06100 originates from solution‐state {[Fe(tpena)OIPh]2}4+ and is ascribed to [FeIII(tpenaO)]2+, derived from an intramolecular O atom insertion into an Fe–tpena donor bond. Proposed ion pairs, {[Fe(tpena)OIPh]Cl}+ and {[Fe(tpena)OIPh]ClO4}+, are more stable than native [Fe(tpena)OIPh]2+ ions, suggesting that halogen‐bonding, as for the solution and solid states, operates also in the gas phase.
Modelling of deactivation of Pd‐Au catalyst in vinyl acetate synthesis from oxidation of ethylene and acetic acid in the gaseous phase
Authors: Motahari Kazem , Rempel Garry , Lashkarara Saba , Ghaseminezhad Keyhan , Borumandnejad Amin , Hatami Babak
Published: November 2015

Vinyl acetate monomer (VAM) is produced from oxidation of ethylene and acetic acid on a Pd‐Au/SiO2 catalyst in the gaseous phase. A progressive loss in activity occurs during the lifetime of a commercial Pd‐Au/SiO2 VAM synthesis catalyst; thus, the efficiency of the reaction decreases and the process is no longer operational and economically feasible. In this study, the effective parameters on Pd‐Au/SiO2 catalyst deactivation were investigated using a fixed‐bed reactor pilot, and a model was proposed to predict the reduction in catalyst activity. The proposed model's output was compared with experimental data and an acceptable agreement was observed. The error was < 10 %.
DFT Methods to Study the Reaction Mechanism of Iridium‐Catalyzed Hydrogenation of Olefins: Which Functional Should be Chosen?
Authors: Sun Yihua , Chen Hui
Published: November 2015

To enable the selection of more accurate computational methods for the future theoretical exploration of the reaction mechanism of Ir‐catalyzed olefin hydrogenation, we compared high‐level ab initio coupled cluster and DFT calculations with a simplified model of Pfaltz's Ir/P,N‐type catalyst for all four previously proposed IrI/IrIII and IrIII/IrV mechanisms. Through the systematic assessment of the DFT performances, the DFT empirical dispersion correction (DFT‐D3) is found to be indispensable for improving the accuracy of relative energies between the IrI/IrIII and IrIII/IrV mechanisms. After including the DFT‐D3 correction, the three best performing density functionals (DFs) are B2‐PLYP, BP86, and TPSSh. In these recommended DFs, the computationally more expensive double‐hybrid functional B2‐PLYP‐D3 has a balanced and outstanding performance for calculations of the reaction barriers, reaction energies, and energy gaps between different mechanisms, whereas the less costly BP86‐D3 and TPSSh‐D3 methods have outstanding, but relatively less uniform performances.
Assessing Attachment in Psychotherapy: Validation of the Patient Attachment Coding System (PACS)
Authors: Talia Alessandro , Miller‐Bottome Madeleine , Daniel Sarah I.F.
Published: November 2015

The authors present and validate the Patient Attachment Coding System (PACS), a transcript‐based instrument that assesses clients' in‐session attachment based on any session of psychotherapy, in multiple treatment modalities. One‐hundred and sixty clients in different types of psychotherapy (cognitive–behavioural, cognitive–behavioural‐enhanced, psychodynamic, relational, supportive) and from three different countries were administered the Adult Attachment Interview (AAI) prior to treatment, and one session for each client was rated with the PACS by independent coders. Results indicate strong inter‐rater reliability, and high convergent validity of the PACS scales and classifications with the AAI. These results present the PACS as a practical alternative to the AAI in psychotherapy research and suggest that clinicians using the PACS can assess clients' attachment status on an ongoing basis by monitoring clients' verbal activity. These results also provide information regarding the ways in which differences in attachment status play out in therapy sessions and further the study of attachment in psychotherapy from a pre‐treatment client factor to a process variable. Copyright © 2015 John Wiley & Sons, Ltd.

Key Practitioner Message

The Patient Attachment Coding System is a valid measure of attachment that can classify clients' attachment based on any single psychotherapy transcript, in many therapeutic modalities

Client differences in attachment manifest in part independently of the therapist's contributions

Client adult attachment patterns are likely to affect psychotherapeutic processes
Multiparameter analysis of stimulated human peripheral blood mononuclear cells: A comparison of mass and fluorescence cytometry
Authors: Nicholas Katherine J. , Greenplate Allison R. , Flaherty David K. , Matlock Brittany K. , Juan Juan San , Smith Rita M. , Irish Jonathan M. , Kalams Spyros A.
Published: November 2015

Mass and fluorescence cytometry are quantitative single cell flow cytometry approaches that are powerful tools for characterizing diverse tissues and cellular systems. Here mass cytometry was directly compared with fluorescence cytometry by studying phenotypes of healthy human peripheral blood mononuclear cells (PBMC) in the context of superantigen stimulation. One mass cytometry panel and five fluorescence cytometry panels were used to measure 20 well‐established lymphocyte markers of memory and activation. Comparable frequencies of both common and rare cell subpopulations were observed with fluorescence and mass cytometry using biaxial gating. The unsupervised high‐dimensional analysis tool viSNE was then used to analyze data sets generated from both mass and fluorescence cytometry. viSNE analysis effectively characterized PBMC using eight features per cell and identified similar frequencies of activated CD4+ T cells with both technologies. These results suggest combinations of unsupervised analysis programs and extended multiparameter cytometry will be indispensable tools for detecting perturbations in protein expression in both health and disease. © 2015 International Society for Advancement of Cytometry
The relationships of irisin with bone mineral density and body composition in PCOS patients
Authors: Gao Shanshan , Cheng Yan , Zhao Lingling , Chen Yuxin , Liu Yu
Published: November 2015

Objective

Our study aims to assay the irisin level and investigate the relationships of irisin level with body mass index (BMI), body composition and bone metabolism in the polycystic ovary syndrome (PCOS) and control women.

Methods

Fifty two PCOS and 39 control women were recruited. Serum sex hormone, fasting insulin and C‐peptide were tested. Fasting serum irisin and adiponectin were measured with enzyme‐linked immunosorbent assay. Body composition and bone mineral density were assayed by dual energy X‐ray absorptiometry.

Results

Polycystic ovary syndrome women showed different body compositions compared with controls. Serum irisin level of PCOS did not show significant difference compared with controls although it was decreased. The level of adiponectin in PCOS patients was significantly reduced. BMI had no correlation with irisin level. It indicated a positive correlation between serum irisin levels and bone mineral density in the control group and a negative correlation in the PCOS group after BMI and age adjusted. Furthermore, total lean mass has a significant effect on irisin concentration in the PCOS group. There are no correlations between adiponection and body compositions and bone mineral density in both groups.

Conclusions

The abnormal body composition in PCOS may contribute to the circulation irisin. The crosstalk of irisin in different organs was found and may be related to disease development in PCOS. Copyright © 2015 John Wiley & Sons, Ltd.
Serum uric acid level as an indicator for CKD regression and progression in patients with type 2 diabetes mellitus—a 4.6‐year cohort study
Authors: Chang Yu‐Hung , Lei Chen‐Chou , Lin Kun‐Chen , Chang Dao‐Ming , Hsieh Chang‐Hsun , Lee Yau‐Jiunn
Published: November 2015

Background

To investigate the association of serum uric acid level with renal function change in patients with type 2 diabetes mellitus (T2DM).

Methods

T2DM patients who had been followed‐up for at least 3 years were included. Participants were categorized into stable, progression, or regression groups according to their change in chronic kidney disease (CKD) stage. During the follow‐up period, all numeric values of metabolic factors, including the uric acid level and the medication possession rate, were calculated in order to investigate their associations with CKD development. Multivariate Cox regression analyses were used to identify independent factors associated with change in CKD.

Results

A total of 2367 T2DM patients were enrolled in this study and followed‐up for a mean of 4.6 years. The numbers of patients in the stable, progression and regression groups were 1133 (47.9%), 487 (20.6%), and 747 (31.5%), respectively. The progression group had the highest serum uric acid level (6.9 ± 1.8 mg/dL), and the regression group had the lowest uric acid level (5.4 ± 1.5 mg/dL). In addition, we found that the serum uric acid level was an independent factor associated with CKD progression when the value exceeded 6.3 mg/dL. A lower uric acid level could be beneficial for CKD improvement in T2DM patients with stage 3–5 CKD.

Conclusions

Our data indicated that the serum uric acid level is associated with CKD regression and progression and suggested that a high normal serum uric acid level should be closely monitored in patients with T2DM. Copyright © 2015 John Wiley & Sons, Ltd.
Cholesterol loading in vivo and in vitro alters extracellular matrix proteins production in smooth muscle cells
Authors: Palomino‐Morales Rogelio , Perales Sonia , Torres Carolina , Linares Ana , Alejandre Maria Jose
Published: November 2015

This study supports the SMC dedifferentiation in vitro model and increases our fundamental knowledge of plaque formation and remodeling. With this purpose, we isolated smooth muscle cells form aortic arch of chicks either fed under control or high cholesterol diets. From the former we obtained control SMCs (SMC−C) that were then loaded with cholesterol using cholesterol:methyl‐β‐cyclodextrin (CS) complexes, thus producing cholesterol loaded SMCs in vitro (SMC−C+CS).tained in vivo cholesterol loaded SMC cell cultures (SMC−Ch). We compared the effect of both cholesterol loading processes on extracellular matrix (ECM) production. The proline incorporation showed that collagen synthesis was higher in SMC−Ch and SMC−C+CS than in SMC−C cultures. Quantitative real‐time PCR revealed that expression of extracellular matrix protein‐related genes increased after in vitro and in vivo cholesterol loading with respect to unloaded cells, demonstrating a regulation at mRNA level. In addition, the expression of col3a1 and fibronectin genes was significantly higher in SMC−Ch than in SMC−Ch+CS cultures. We demonstrated that SMC can switch from contractile to synthetic state not only by cholesterol in vivo but also by cholesterol SMC loading in vitro.

Practical applications: Alteration of the differentiated, contractile phenotype of SMCs is known to play an integral role in the formation of atherosclerotic lesions. Although SMCs have previously been induced to accumulate cholesterol in vitro, for either in vitro or in vivo foam cell like SMC cells, there is little information about phenotypic changes at the protein or RNA level. We have characterized the phenotypic changes associated with chicken aortic cholesterol loaded SMCs formation at the protein and molecular level. The results of the present study support the SMC dedifferentiation in vitro model and increase our fundamental knowledge of plaque formation and remodeling.

Diet cholesterol is a risk factor in the atherosclerotic process. Proliferation, apoptosis, migration and the ECM synthesis in SMC contribute to the development of the disease. Both, a cholesterol‐rich diet and exogenous cholesterol loading in vitro yield the overexpression of ECM genes, specifically collagen types I and II and fibronectin. This leads to the dedifferentiation of the SMC to a synthetic phenotype which is one of the main reasons of the vascular hypertrophy.
Early selection for oil quality components in olive breeding progenies
Authors: de la Rosa Raúl , Arias‐Calderón Rocio , Velasco Leonardo , León Lorenzo
Published: November 2015

Olive oil is highly valued for its nutritional quality mainly determined by its fatty acid composition together with the presence of several biologically active minor components. In olive breeding programs, these oil quality components are normally evaluated in the later stages of selection because oil extraction is not suitable for being performed in large seedling progenies with initial low yield. In the present work, we evaluate the ability of open pollinated progenies of 17 olive cultivars located in a large germplasm bank as a means of generate genetic variability for oil quality components directly measured in fruit. High degree of variability was found for most of the oil quality components analyzed, including some cases of transgressive segregation. Narrow‐sense heritability greatly varies among traits, being particularly high for sterol content. Lack of correlation among fruit traits previously reported and oil quality traits suggest the possibility of simultaneous breeding for most of them. In summary, open pollination of cultivars from a germplasm bank together with early evaluation directly in fruit seems to be a convenient strategy for breeding for oil quality traits on olive.

Practical application: The evaluation of oil quality parameters directly on fruits here presented could be a convenient strategy to speed up olive breeding programs aimed at obtaining new olive varieties with olive oil of enhanced quality.

Box and whisker plots for oil quality components evaluated in progenies from open pollination. Female genitors’ names are abbreviated: “Arbequina” (Arb), “Blanqueta” (Bla), “Canetera” (Can), “Changlot Real” (ChR), “Chorrúo Castro del Río” (CCR), “Empeltre” (Emp), “Hojiblanca” (Hoj), “Lechín de Granada” (LGr), “Lechín de Sevilla” (LSe), “Manzanilla del Piquito” (MPi), “Manzanilla de Sevilla” (MSe), “Morona” (Mor), “Ocal” (Oca), “Picudo” (Pdo), “Picual” (Pic), and two previous selection of our breeding program (Sel1 and Sel2). Progenies are shown in ascending order regarding the values of the Spanish cultivars used as parents (represented by stars).
Development of Disposable Carbon Nanofibers Electrodes Supported on Filters
Authors: Paramo Ana Erica , Palmero Susana , Heras Aranzazu , Colina Alvaro , Ibañez David
Published: November 2015

The purpose of this work is to develop simple and reproducible ways to fabricate carbon nanofibers (CNFs) electrodes. Disposable CNFs electrodes were fabricated after filtering CNFs through polytetrafluoroethylene filters (PTFE), using directly as electrodes these filters with the CNFs film. The electrochemical behaviour of CNFs/PTFE electrodes were tested with ferrocenemethanol and tris(2,2′‐bypyridyl)dichlororuthenium(II) (Ru(bipy)32+). As a proof of concept of the analytical usefulness of the CNFs/PFTE electrodes, the study of vitamin B12 was carried out. Multivariate calibrate has been successfully used to determine vitamin B12 in a complex medium with vitamins B1 and B6 as interferents.
Photo-enhanced toxicity of fluoranthene to Gulf of Mexico marine organisms at different larval ages and ultraviolet light intensities
Authors: Finch Bryson E. , Stubblefield William A.
Published: November 2015

Significant increases in toxicity have been observed as a result of polycyclic aromatic hydrocarbon (PAH) absorption of ultraviolet (UV) radiation in aquatic organisms. Early life stage aquatic organisms are predicted to be more susceptible to PAH photo-enhanced toxicity as a result of their translucence and tendency to inhabit shallow littoral or surface waters. The objective of the present study was to evaluate the sensitivity of varying ages of larval mysid shrimp (Americamysis bahia), inland silverside (Menidia beryllina), sheepshead minnow (Cyprinodon variegatus), and Gulf killifish (Fundulus grandis) to photo-enhanced toxicity and to examine the correlation between photo-enhanced toxicity and organism pigmentation. Organisms were exposed to fluoranthene and artificial UV light at different larval ages and results were compared using median lethal concentrations (LC50s) and the lethal time-to-death (LT50s). In addition, a high UV light intensity, short-duration (4-h) experiment was conducted at approximately 24 W/m2 of ultraviolet radiation A (UV-A) and compared with a low-intensity, long-duration (12-h) experiment at approximately 8 W/m2 of UV-A. The results indicated decreased toxicity with increasing age for all larval organisms. The amount of organism pigmentation was correlated with observed LC50 and LT50 values. High-intensity short-duration exposure resulted in greater toxicity than low-intensity long-duration UV treatments for mysid shrimp, inland silverside, and sheepshead minnow. Data from these experiments suggest that toxicity is dependent on age, pigmentation, UV light intensity, and fluoranthene concentration. Environ Toxicol Chem 2016;35:1113–1122. © 2015 SETAC
The derivation of effects threshold concentrations of lead for European freshwater ecosystems
Authors: Van Sprang Patrick A. , Nys Charlotte , Blust Ronny J.P. , Chowdhury Jasim , Gustafsson Jon P. , Janssen Colin J. , De Schamphelaere Karel A.C.
Published: November 2015

The main objective of the present study was to derive ecologically relevant effect threshold concentrations of (dissolved) Pb for selected European Union (EU) freshwater rivers, using the 2008 EU Voluntary Risk Assessment Report as a starting point and more advanced methodologies than those used in the Voluntary Risk Assessment Report. This included 1) implementing more robust quality criteria for selecting chronic toxicity data; 2) the conversion of total to dissolved Pb concentrations using a combination of an empirical equation relating inorganic Pb solubility and geochemical speciation modeling to account for effects of dissolved organic matter; 3) the use of bioavailability models for chronic toxicity for species belonging to 3 different trophic levels; and 4) the use of robust methods for large data set handling (such as species sensitivity distribution [SSD] analysis). The authors used published bioavailability models for an algal species (Pseudokirchneriella subcapitata) and a daphnid (Ceriodaphnia dubia) and developed a new model for the fathead minnow (Pimephales promelas). The research has shown that these models are also useful for, and reasonably accurate in, predicting chronic toxicity to other species, including a snail, a rotifer, midge larvae, and an aquatic plant (read-across). A comprehensive chronic toxicity data set for Pb was compiled, comprising 159 individual high-quality toxicity data for 25 different species. By applying the total dissolved conversion and the bioavailability models, normalized toxicity values were obtained, which were then entered into a SSD analysis. Based on the parametric best-fitting SSDs, the authors calculated that ecological threshold concentrations of Pb protecting 95% of freshwater species for 7 selected European freshwater scenarios were between 6.3 μg dissolved Pb/L and 31.1 μg dissolved Pb/L. Environ Toxicol Chem 2016;35:1310–1320. © 2015 SETAC
Ustekinumab for patients with primary biliary cholangitis who have an inadequate response to ursodeoxycholic acid: A proof‐of‐concept study
Authors: Hirschfield Gideon M. , Gershwin M. Eric , Strauss Richard , Mayo Marlyn J. , Levy Cynthia , Zou Bin , Johanns Jewel , Nnane Ivo P. , Dasgupta Bidisha , Li Katherine , Selmi Carlo , Marschall Hanns‐Ulrich , Jones David , Lindor Keith ,   ; for the PURIFI Study Group
Published: November 2015

The interleukin (IL)‐12 signaling cascade has been associated with primary biliary cholangitis (PBC). This multicenter, open‐label, proof‐of‐concept study evaluated the anti‐IL12/23 monoclonal antibody, ustekinumab (90 mg subcutaneous at weeks 0 and 4, then every 8 weeks through week 20), in adults with PBC and an inadequate response to ursodeoxycholic acid therapy (i.e., alkaline phosphatase [ALP] >1.67× upper limit of normal [ULN] after ≥6 months). ALP response was defined as a >40% decrease from baseline and ALP remission as ALP normalization (if baseline ALP 1.67×‐2.8× ULN) or <1.67× ULN (if baseline ALP >2.8× ULN). Changes in Enhanced Liver Fibrosis (ELF) scores and serum bile acids were also assessed. At baseline, patients had median disease duration of 3.2 years, median ELF score of 9.8, and highly elevated total bile acid concentration (median, 43.3 μmol/L); 13 of 20 (65%) patients had baseline ALP >3× ULN. Although steady‐state serum ustekinumab concentrations were reached by week 12, no patient achieved ALP response or remission. Median percent ALP reduction from baseline to week 28 was 12.1%. ELF score decreased slightly from baseline to week 28 (median reduction: 0.173), and total serum bile acid concentrations decreased from baseline to week 28 (median reduction: 8.8 μmol/L). No serious infections or discontinuations resulting from adverse events were reported through week 28. One patient had a serious upper gastrointestinal hemorrhage considered unrelated to test agent by the investigator. Conclusion: Open‐label ustekinumab therapy, though associated with a modest decrease in ALP after 28 weeks of therapy, did not otherwise appreciably change ALP and overt proof‐of‐concept was not established as per prespecified primary endpoint of proposed efficacy. No new ustekinumab safety signals were observed. (Hepatology 2016;64:189‐199)
Quantitative, 3D Visualization of the Initiation and Progression of Vertebral Fractures Under Compression and Anterior Flexion
Authors: Jackman Timothy M , Hussein Amira I , Curtiss Cameron , Fein Paul M , Camp Anderson , De Barros Lidia , Morgan Elise F
Published: November 2015

The biomechanical mechanisms leading to vertebral fractures are not well understood. Clinical and laboratory evidence suggests that the vertebral endplate plays a key role in failure of the vertebra as a whole, but how this role differs for different types of vertebral loading is not known. Mechanical testing of human thoracic spine segments, in conjunction with time-lapsed micro–computed tomography, enabled quantitative assessment of deformations occurring throughout the entire vertebral body under axial compression combined with anterior flexion (“combined loading”) and under axial compression only (“compression loading”). The resulting deformation maps indicated that endplate deflection was a principal feature of vertebral failure for both loading modes. Specifically, the onset of endplate deflection was temporally coincident with a pronounced drop in the vertebra's ability to support loads. The location of endplate deflection, and also vertebral strength, were associated with the porosity of the endplate and the microstructure of the underlying trabecular bone. However, the location of endplate deflection and the involvement of the cortex differed between the two types of loading. Under the combined loading, deflection initiated, and remained the largest, at the anterior central endplate or the anterior ring apophysis, depending in part on health of the adjacent intervertebral disc. This deflection was accompanied by outward bulging of the anterior cortex. In contrast, the location of endplate deflection was more varied in compression loading. For both loading types, the earliest progression to a mild fracture according to a quantitative morphometric criterion occurred only after much of the failure process had occurred. The outcomes of this work indicate that for two physiological loading modes, the vertebral endplate and underlying trabecular bone are critically involved in vertebral fracture. These outcomes provide a strong biomechanical rationale for clinical methods, such as algorithm-based qualitative (ABQ) assessment, that diagnose vertebral fracture on the basis of endplate depression. © 2015 American Society for Bone and Mineral Research.
Molecular Mechanisms Associated With Particulate and Soluble Heteroglycan Mediated Immune Response
Authors: Devi K. Sanjana P. , Krishna Dhanesh , Das Joyjyoti , Agarwal Tarun , Kumari Kalpana , Maji Somnath , Ghosh Sudip K. , Maiti Tapas K.
Published: November 2015

Immune responses are outcomes of complex molecular machinery which occur inside the cells. Unravelling the cellular mechanisms induced by immune stimulating molecules such as glycans and determining their structure‐function relationship are therefore important factors to be assessed. With this viewpoint, the present study identifies the functional receptor binding unit of a well characterized heteroglycan and also delineates the cellular and molecular processes that are induced upon heteroglycan binding to specific cell surface receptors in immune cells. The heteroglycan was acid hydrolysed and it was revealed that 10–30 kDa fractions served as the functional receptor binding unit of the molecule. Increasing the size of 10–30 kDa heteroglycan showed prominent immune activity. The whole soluble heteroglycan was also conjugated with hyperbranched dendrimers so as to generate a particulate form of the molecule. Dectin‐1 and TLR2 were identified as the major receptors in macrophages that bind to particulate as well as soluble form of the heteroglycan and subsequently caused downstream signaling molecules such as NF‐κβ and MAPK to get activated. High levels of 1L‐1β and IL‐10 mRNA were observed in particulate heteroglycan treated macrophages, signifying that increasing the size and availability of the heteroglycan to its specific receptors is pertinent to its biological functioning. Upregulated expression of PKC and iNOS were also noted in particulate heteroglycan treated RAW 264.7 cells than the soluble forms. Taken together, our results indicate that biological functions of immunomodulatory heteroglycan are dependent on their size and molecular weight. J. Cell. Biochem. 117: 1580–1593, 2016. © 2015 Wiley Periodicals, Inc.