bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographic and socioeconomic factors affecting delivery of bariatric surgery across high- and low-utilization healthcare systems
Authors: Doumouras A G , Saleh F , Sharma A M , Anvari S , Gmora S , Anvari M , Hong D
Published: April 2017

Background

In countries with universal health coverage, the delivery of care should be driven by need. However, other factors, such as proximity to local facilities or neighbourhood socioeconomic status, may be more important. The objective of this study was to evaluate which geographic and socioeconomic factors affect the delivery of bariatric care in Canada.

Methods

This was a national retrospective cohort study of all adult patients undergoing bariatric surgery between April 2008 and March 2015 in Canada (excluding Quebec). The main outcome was neighbourhood rate of bariatric surgery per 1000 obese individuals (BMI over 30 kg/m2). Geographic cluster analysis and multilevel ordinal logistic regression were used to identify high-use clusters, and to evaluate the effect of geographic and socioeconomic factors on care delivery.

Results

Having a bariatric facility within the same public health unit as the neighbourhood was associated with a 6·6 times higher odds of being in a bariatric high-use cluster (odds ratio (OR) 6·60, 95 per cent c.i. 1·90 to 22·88; P = 0·003). This finding was consistent across provinces after adjusting for utilization rates. Neighbourhoods with higher obesity rates were also more likely to be within high-use clusters (OR per 5 per cent increase: 2·95, 1·54 to 5·66; P = 0·001), whereas neighbourhoods closer to bariatric centres were less likely to be (OR per 50 km: 0·91, 0·82 to 1·00; P = 0·048).

Conclusion

In this study, across provincial healthcare systems with high and low utilization, the delivery of care was driven by the presence of local facilities and neighbourhood obesity rates. Increasing distance to bariatric centres substantially influenced care delivery.
The Impact of Carbon Performance on Climate Change Disclosure
Authors: Giannarakis Grigoris , Zafeiriou Eleni , Sariannidis Nikolaos
Published: April 2017

In the light of the significant role of environmental accounting in sustainable development, this study examines whether climate change disclosure reflects a firm's environmental performance. The novelty of the study stands on the approaches adopted to describe environmental performance. The first approach concerns performance in terms of output, direct and indirect greenhouse gas emissions, while the second one is based on environmental intention of mitigating climate change, including climate change policy and emission reduction initiatives. The Climate Performance Leadership Index is employed as a measure for climate change disclosure level, incorporating initiatives contributing to climate change mitigation, adaptation and transparency. Ordered logit regression is the appropriate methodology for the data employed concerning firms listed on FTSE 350. According to our findings, environmental performance for both adopted approaches entails a positive effect on climate change disclosure, a result that is consistent with voluntary disclosure theory. It is inferred that firms cannot manipulate their information reflecting their actual environmental performance and adopting a forthright and factual attitude towards sustainable development. Finally, findings provide an insight into managers' strategic behavior towards climate change issues. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Fatty acid‐binding protein 5 function in hepatocellular carcinoma through induction of epithelial–mesenchymal transition
Authors: Ohata Takanori , Yokoo Hideki , Kamiyama Toshiya , Fukai Moto , Aiyama Takeshi , Hatanaka Yutaka , Hatanaka Kanako , Wakayama Kenji , Orimo Tatsuya , Kakisaka Tatsuhiko , Kobayashi Nozomi , Matsuno Yoshihiro , Taketomi Akinobu
Published: April 2017

Hepatocellular carcinoma (HCC) is a highly prevalent cancer with poor prognosis. The correlation between overexpression of fatty acid‐binding protein 5 (FABP5) and malignant potential of tumor growth and metastasis in several cancers has been previously reported. However, the correlation between FABP5 expression and HCC malignant behavior remains unknown. We compared FABP5 expression and patient characteristics in paired HCC and adjacent noncancerous liver tissues from 243 patients who underwent surgical resection of primary HCC. Cell proliferation, invasion, and migration assays were performed in HCC cell lines overexpressing FABP5 or downregulated for FABP5. Tumor growths were monitored in xenograft model, and liver and lung metastasis models were established. In the 243 HCC patients, FABP5‐positive staining (n = 139/243, 57.2%) was associated with poor prognosis and recurrence (P < 0.0001) and showed positive correlation with distant metastasis, tumor size and vascular invasion (P < 0.05). Cell proliferation, invasion, and migration in vitro were enhanced by upregulation of FABP5 and decreased by downregulation of FABP5 in HCC cell lines. Similar results in tumor formation and metastasis were obtained through in vivo analyses. PCR array results revealed upregulation of SNAI1 in FABP5‐overexpressing HepG2 cells. Western blot analysis showed significantly increased expression of E‐cadherin and ZO‐1 and decreased SNAI1 expression and nuclear translocation of β‐catenin by knockdown of FABP5. We revealed a significant role for FABP5 in HCC progression and metastasis through the induction of epithelial‐to‐mesenchymal transition. FABP5 may be a potential novel prognostic biomarker and new therapeutic target for HCC.
Near‐Infrared Electrochemiluminescence from Au Nanoclusters Enhanced by EDTA and Modulated by Ions
Authors: Wang Tanyu , Padelford Jonathan W. , Ma Hedi , Gubitosi‐Raspino Maria F. , Wang Gangli
Published: April 2017

Near‐infrared electrochemiluminescence (ECL) from Au‐thiolate nanoclusters is activated by electrode reactions and enhanced by ethylenediamine tetraacetic acid (EDTA). The enhancement effect is higher at pH 7.4 than at more basic or acidic pHs. Magnesium ions are found to modulate the ECL signals through complexation with EDTA and the interaction with the Au nanoclusters. The chemical system and the signal modulation mechanism are believed to be generalizable and advantageous for future sensing and analysis applications with the following merits: 1) Ambient ECL without oxygen removal, 2) high enhancement at physiological pH values, 3) in the near‐IR spectrum window with low interference, 4) rich and tunable redox activity of the Au nanoclusters, and 5) EDTA representing other ionophores or chelaters as versatile coreactants.
High Capacitance and Cycle‐Life Performance of a Binder‐Free Supercapacitor Nanocomposite Electrode by Direct Growth of Manganese Oxide Nanostructures on Carbon Nanotubes
Authors: Ataherian Fatemeh , Wang Youling , Tabet‐Aoul Amel , Mohamedi Mohamed
Published: April 2017

MnOx thin films with various oxidation states (MnO, Mn2O3, MnO2 and mixed MnO/Mn3O4) were directly grown onto carbon nanotubes by pulsed laser deposition under vacuum and at different oxygen partial pressures. The microstructural features of the as‐deposited thin films are characterized by scanning electron microscopy and X‐ray photoelectron spectroscopy. The electrochemical behavior of the CNT/MnOx nanocomposites in 1 M Na2SO4 electrolyte is discussed with regards to specific capacitance, and cycle‐life, by means of cyclic voltammetry and electrochemical impedance measurements. First, at slow potential scan rate of 1 mV s−1, MnOx prepared under vacuum and 10 mTorr of O2 delivered specific capacitance as high as 738 and 653 F g−1, respectively. Second, the rate capability of these two nanocomposites over a wide range of scan rates showed that at 500 mV s−1, the former retained 93 % whereas the later displayed an increase of 1.2 % with regards to their respective initial specific capacitance values at 1 mV s−1. They also maintained 90 % and 95 % of their specific capacitance after 10 000 continuous cycles with a 100 mV s−1 scan rate. The binder‐free nature of the CNT/MnOx nanocomposites and remarkable electrochemical properties suggest that these materials could find application as excellent electrodes for supercapacitors.
From NAD+ to Nickel Pincer Complex: A Significant Cofactor Evolution Presented by Lactate Racemase
Authors: Yu Ming‐Jia , Chen Shi‐Lu
Published: April 2017

Lactate racemase (LarA), a new nickel enzyme discovered recently, catalyzes the racemization between d‐ and l‐lactates with a novel nickel pincer cofactor (Ni‐PTTMN) derived from nicotinic acid. In this study, by using DFT and a 200‐atom active‐site model, LarA is revealed to employ a modified proton‐coupled hydride‐transfer mechanism in which a hydride is transferred to a cofactor pyridine carbon from the substrate α‐carbon along with proton transfer from the substrate hydroxy group to a histidine, and then moved back from the opposite side. Tyr294 and Lys298 provide significant acceleration effects by orientating substrates and stabilizing the negative charge developing at the substrate hydroxy oxygen. The barrier was determined to be 12.0 kcal mol−1, which reveals enhanced racemase activity relative to the LarA reaction using NAD+‐like cofactors. Compared with NAD+, Ni‐PTTMN has a stronger hydride‐addition reactivity in moderate and high environmental polarity and may fit perfectly the moderately polar active site of LarA.
In Situ Formation of Co9S8/N‐C Hollow Nanospheres by Pyrolysis and Sulfurization of ZIF‐67 for High‐Performance Lithium‐Ion Batteries
Authors: Zeng Peiyuan , Li Jianwen , Ye Ming , Zhuo Kaifeng , Fang Zhen
Published: April 2017

Co9S8 is considered a promising candidate as the anode material in lithium‐ion batteries (LIBs) because of its remarkable electrical conductivity, high theoretical capacity, and low cost. However, the practical application of Co9S8 is greatly restricted because of its poor cycling stability and rate performance, which result mainly from the large volume expansion and dissolution of the polysulfide intermediates during the charge/discharge process. In this report, Co9S8 embedded in N‐rich carbon hollow spheres are successfully designed and synthesized through an in situ pyrolysis and sulfurization process, employing the well‐known ZIF‐67 as the precursor and ethanethiol as the sulfur source. Co9S8 nanoparticles embedded in the N‐rich hollow carbon shell exhibit excellent lithium storage properties at a high charge/discharge rate. A discharge capacity of 784 mAh g−1 is obtained upon battery testing at a current density of 1 C (544 mA g−1). Even upon cycling at a current density of 4 C, the as‐prepared Co9S8/N‐C can still deliver a discharge capacity of 518 mAh g−1. The excellent battery performance can be attributed to the hollow structure as well as the N‐rich carbon encapsulation. Moreover, this metal–organic framework sulfurization route also shows good generality for the synthesis of other metal sulfide–carbon composites such as ZnS/N‐C and Cu2S/C.
Intramolecular Pancake Bonding in Helical Structures
Authors: Takamuku Shota , Nakano Masayoshi , Kertesz Miklos
Published: April 2017

We show that diradicaloid helical conjugated molecules can display strong through‐space bonding interactions. These interactions are analogous to π‐stacking pancake bonding widely observed for dimers and other aggregates of stable π‐conjugated radicals. We show that these multicenter interactions can have a significant stabilizing effect, but they depend in subtle ways on the specific overlap and relative orientations of the radical carrying subunits. The specific through‐space interactions between the radicaloid units occur at specific size ranges of the helical molecules.
Hydration of Cyclohexene into Cyclohexanol using H‐ZSM5 as Catalyst
Authors: Spod Hendrik , Lucas Martin , Claus Peter
Published: April 2017

Um die Wettbewerbsfähigkeit aufrecht zu erhalten gilt es Prozesse stetig zu optimieren. Polyamide gehören zu den verbreitetsten Kunststoffen weltweit und finden vor allem als Synthesefasern ihre Anwendung. Untersucht wird eine alternative Teilreaktion in der Produktion von Adipinsäure, die Flüssigphasenhydratisierung von Cyclohexen zu Cyclohexanol, unter Verwendung des Zeolithen H‐ZSM5 als Katalysator. Mit einem Si/Al‐Verhältnis von 28 weist er im optimalen Reaktionsfenster die beste Performance hinsichtlich der Selektivität und Aktivität zu Cyclohexanol auf, wodurch eine maximale Ausbeute von 13 % erreicht wird.
Improvement of Growth, Yield, and Pigmentation of Mung Bean Plants UsingOchrobactrum intermediumCP‐2 as Bioinoculant
Authors: Saini Amita , Nain Lata , Garg Veena , Saxena Jyoti
Published: April 2017

The selection of strains for production of biofertilizers is of primary importance. A strain with diverse growth promoting activities, especially the nitrogen fixation and phosphate solubilization, has highest preference over those with just one activity. In the present study, a symbiotic nitrogen fixing bacterium was isolated from the root nodules of chickpea and characterized asOchrobactrum intermediumCP‐2 on the basis of biochemical tests and partial 16S rRNA gene sequencing and blast analysis. Besides fixing nitrogen, the CP‐2 strain also showed the ability of phosphate solubilization and indole acetic acid production. It was also found positive for ammonia and siderophore production. A significant increase in the lengths of radical and plumule and percent germination was observed when the rhizobacterial strain selected for the study was inoculated in vitro for seed assay.O. intermediumCP‐2 significantly (p < 0.05) increased shoot and root lengths, fresh and dry weights, and yield of mung bean plants both in pot trials and under field conditions. The nutrient uptake and microbial count also increased significantly with inoculation of the strain during the experiment. This study revealed the positive effect ofO. intermediumCP‐2 on mung bean crop.
Prognostic disclosures over time: Parental preferences and physician practices
Authors: Sisk Bryan A. , Kang Tammy I. , Mack Jennifer W.
Published: April 2017

BACKGROUND

Although the majority of parents of children with cancer say they want prognostic information, to the authors’ knowledge little is known regarding how their desire for and experiences with prognosis communication change over time.

METHODS

A longitudinal, prospective questionnaire‐based cohort study of 156 parents of children with cancer treated at 2 academic pediatric hospitals was performed. Previously published scales were administered at the time of diagnosis and at 4 months and 12 months later.

RESULTS

The majority of parents preferred to hear about prognosis in as much detail as possible throughout the first year after a diagnosis of cancer (87%, 85%, and 84%, respectively, at the time of diagnosis, 4 months, and 12 months). Although nearly no parents reported wanting less information (<5% at any time point), a significant percentage reported wanting more information at each time point (25%, 28%, and 24%, respectively, at the time of diagnosis, 4 months, and 12 months). The majority of parents reported having had new prognostic discussions with the physician at each time point (93%, 74%, and 81%, respectively, at the time of diagnosis, 4 months, and 12 months). Irrespective of prognosis, parents were more likely to be satisfied with prognostic communication when physicians provided more extensive disclosure at the time of diagnosis (odds ratio, 1.85 per element of disclosure; 95% confidence interval, 1.25‐2.74 [P = .002]) and when physicians discussed prognosis again before 4 months (odds ratio, 8.71; 95% confidence interval, 2.64‐28.72 [P = .0004]).

CONCLUSIONS

The majority of parents wanted detailed, longitudinal prognostic conversations; nearly none of the parents preferred less prognostic information. A return to these conversations over time can help rather than hurt parents. Future studies should assess the ideal contents of these longitudinal discussions, and the communication preferences of pediatric patients. Cancer 2017;123:4031‐8. © 2017 American Cancer Society.
Anatomy and spatial organization of Müller glia in mouse retina
Authors: Wang Jingjing , O’Sullivan Matthew L. , Mukherjee Dibyendu , Puñal Vanessa M. , Farsiu Sina , Kay Jeremy N.
Published: April 2017

Müller glia, the most abundant glia of vertebrate retina, have an elaborate morphology characterized by a vertical stalk that spans the retina and branches in each retinal layer. Müller glia play diverse, critical roles in retinal homeostasis, which are presumably enabled by their complex anatomy. However, much remains unknown, particularly in mouse, about the anatomical arrangement of Müller cells and their arbors, and how these features arise in development. Here we use membrane‐targeted fluorescent proteins to reveal the fine structure of mouse Müller arbors. We find sublayer‐specific arbor specializations within the inner plexiform layer (IPL) that occur consistently at defined laminar locations. We then characterize Müller glia spatial patterning, revealing how individual cells collaborate to form a pan‐retinal network. Müller cells, unlike neurons, are spread across the retina with homogenous density, and their arbor sizes change little with eccentricity. Using Brainbow methods to label neighboring cells in different colors, we find that Müller glia tile retinal space with minimal overlap. The shape of their arbors is irregular but nonrandom, suggesting that local interactions between neighboring cells determine their territories. Finally, we identify a developmental window at postnatal Days 6 to 9 when Müller arbors first colonize the synaptic layers beginning in stereotyped inner plexiform layer sublaminae. Together, our study defines the anatomical arrangement of mouse Müller glia and their network in the radial and tangential planes of the retina, in development and adulthood. The local precision of Müller glia organization suggests that their morphology is sculpted by specific cell to cell interactions with neurons and each other.
Diaphragm‐Regulated Growth of Nanosheet Arrays of α‐Phase Ni–Co Layered Double Hydroxides on Arbitrary Substrates for Wettability Control and Rechargeable Alkaline Batteries
Authors: Meng Xinghua , Deng Da
Published: April 2017

Room‐temperature synthesis of α‐phase bimetallic nickel–cobalt layered double hydroxides (Ni–Co LDHs) nanosheets in the forms of arrays grown on arbitrary substrates is still a challenging task. We demonstrate a facile diaphragm‐assisted approach to grow α‐phase Ni–Co LDHs nanosheet arrays on various substrates at room temperature. The as‐synthesized nanosheet arrays can induce high surface roughness at the microscale, achieving both superoleophobicity underwater and superhydrophobicity in air, with contact angles measured for oil at 160° and for water at 154°, respectively. The nanosheet arrays of Ni–Co LDHs formed directly on 3D nickel foam substrates can be used as binder‐free electrodes for rechargeable batteries, achieving a specific capacity of 177 mA h g−1 when tested at 2000 mA g−1. In contrast to literature reports, in which LDHs are often considered for pseudocapacitors, we suggest our electrodes are good for rechargeable alkaline secondary batteries or as battery electrodes in hybrid supercapacitors, based on battery behavior observed in our electrochemical tests. Other substrates, including titanium wires and carbon fiber papers, can be used as substrates. The as‐prepared α‐phase Ni–Co LDHs nanosheet arrays coated substrates and their derivatives (e.g., oxides, sulfides) can find many potential applications, including wastewater treatment, separation, electrochromic devices, catalysis and electrocatalysis, as well as energy storage.
Correlative Fluorescence and Electron Microscopy in 3D—Scanning Electron Microscope Perspective
Authors: Franks Jonathan , Wallace Callen T. , Shibata Masateru , Suga Mitsuo , Erdman Natasha , Stolz Donna B. , Watkins Simon C.
Published: April 2017

The ability to correlate fluorescence microscopy (FM) and electron microscopy (EM) data obtained on biological (cell and tissue) specimens is essential to bridge the resolution gap between the data obtained by these different imaging techniques. In the past such correlations were limited to either EM navigation in two dimensions to the locations previously highlighted by fluorescence markers, or subsequent high‐resolution acquisition of tomographic information using a TEM. We present a novel approach whereby a sample previously investigated by FM is embedded and subjected to sequential mechanical polishing and backscatter imaging by scanning electron microscope. The resulting three dimensional EM tomogram of the sample can be directly correlated to the FM data. © 2017 by John Wiley & Sons, Inc.
Surfactant‐Free Polar‐to‐Nonpolar Phase Transfer of Exfoliated MoS2 Two‐Dimensional Colloids
Authors: Giovanelli Emerson , Castellanos‐Gomez Andres , Pérez Emilio M.
Published: April 2017

Exfoliation of lamellar materials into their corresponding layers represented a breakthrough, owing to the outstanding properties arising from the nanometric thickness confinement. Among the cleavage techniques, liquid‐phase exfoliation is now on the rise because it is scalable and leads to easy‐to‐manipulate colloids. However, all appropriate exfoliating solvents exhibit strong polarity, which greatly restricts the scope of feasible functionalization or processing of the resulting flakes. Here, this scope is extended: nanosheets exfoliated in a polar medium are demonstrated to properly disperse in a nonpolar solvent. To that purpose, suspensions of molybdenum disulfide flakes were prepared in isopropanol/water and a phase transfer of the nanosheets to chloroform was developed by flocculation and redispersion/centrifugation sequences, without any assisting surfactant. The colloidal stability of the nanosheets in chloroform was found to be governed by their lateral dimensions and, although lower than in polar media, proved to be high enough to open the way to subsequent functionalization or processing of the flakes in nonpolar media.
Computational Prediction of Intrinsic Disorder in Proteins
Authors: Meng Fanchi , Uversky Vladimir , Kurgan Lukasz
Published: April 2017

Computational prediction of intrinsically disordered proteins (IDPs) is a mature research field. These methods predict disordered residues and regions in an input protein chain. More than 60 predictors of IDPs have been developed. This unit defines computational prediction of intrinsic disorder, summarizes major types of predictors of disorder, and provides details about three accurate and recently released methods. We demonstrate the use of these methods to predict intrinsic disorder for several illustrative proteins, provide insights into how predictions should be interpreted, and quantify and discuss predictive performance. Predictions can be freely and conveniently obtained using webservers. We point to the availability of databases that provide access to annotations of intrinsic disorder determined by structural studies and putative intrinsic disorder pre‐computed by computational methods. Lastly, we also summarize experimental methods that can be used to validate computational predictions. © 2017 by John Wiley & Sons, Inc.
N‐Terminal Methionine Processing
Authors: Wingfield Paul T.
Published: April 2017

Protein synthesis is initiated by methionine in eukaryotes and by formylmethionine in prokaryotes. N‐terminal methionine can be co‐translationally cleaved by the enzyme methionine aminopeptidase (MAP). When recombinant proteins are expressed in bacterial and mammalian expression systems, there is a simple universal rule that predicts whether the initiating methionine will be processed by MAP based on the size of the residue adjacent (penultimate) to the N‐methionine. In general, if the side chains of the penultimate residues have a radius of gyration of 1.29 Å or less, methionine is cleaved. © 2017 by John Wiley & Sons, Inc.
Worldwide Distribution of Cytochrome P450 Alleles: A Meta‐analysis of Population‐scale Sequencing Projects
Authors: Zhou Y , Ingelman‐Sundberg M , Lauschke VM
Published: April 2017

Genetic polymorphisms in cytochrome P450 (CYP) genes can result in altered metabolic activity toward a plethora of clinically important medications. Thus, single nucleotide variants and copy number variations in CYP genes are major determinants of drug pharmacokinetics and toxicity and constitute pharmacogenetic biomarkers for drug dosing, efficacy, and safety. Strikingly, the distribution of CYP alleles differs considerably between populations with important implications for personalized drug therapy and healthcare programs. To provide a global distribution map of CYP alleles with clinical importance, we integrated whole‐genome and exome sequencing data from 56,945 unrelated individuals of five major human populations. By combining this dataset with population‐specific linkage information, we derive the frequencies of 176 CYP haplotypes, providing an extensive resource for major genetic determinants of drug metabolism. Furthermore, we aggregated this dataset into spectra of predicted functional variability in the respective populations and discuss the implications for population‐adjusted pharmacological treatment strategies.
Occlusion in the Flow of New Drugs for Cardiovascular Disease
Authors: Ringel MS , Shah NA , Baedeker M , Lim CT , Lamichhane A , Schulze U
Published: April 2017

There is a large misalignment between unmet need and both private and public investment activity in cardiovascular disease. In this paper, we quantify the magnitude of the gap, analyze a range of potential root causes in two main categories (issues of feasibility and valuation), and propose steps toward solutions to close the gap.
Building Capability for Clinical Pharmacology Research in Sub‐Saharan Africa
Authors: Gutierrez MM , Pillai G , Felix S , Romero F , Onyango KO , Owusu‐Agyei S , Asante KP , Barnes KI , Sinxadi P , Allen E , Abdulla S , Masimirembwa C , Munyoro M , Yimer G , Gebre‐Mariam T , Spector J , Ogutu B
Published: April 2017

A strong scientific rationale exists for conducting clinical pharmacology studies in target populations because local factors such as genetics, environment, comorbidities, and diet can affect variability in drug responses. However, clinical pharmacology studies are not widely conducted in sub‐Saharan Africa, in part due to limitations in technical expertise and infrastructure. Since 2012, a novel public‐private partnership model involving research institutions and a pharmaceutical company has been applied to developing increased capability for clinical pharmacology research in multiple African countries.
Chronic Administration of Anacetrapib Is Associated With Accumulation in Adipose and Slow Elimination
Authors: Krishna R , Gheyas F , Liu Y , Hagen DR , Walker B , Chawla A , Cote J , Blaustein RO , Gutstein DE
Published: April 2017

Anacetrapib is a novel cholesteryl‐ester transfer protein (CETP) inhibitor in late‐stage clinical development, shown in preceding clinical trials to have residual pharmacological activity after prolonged washout after chronic dosing. Preclinical findings suggest that white adipose tissue is a potential depot and that accumulation into adipose tissue governs the long‐term kinetics of anacetrapib in mice. A phase I study performed to test this hypothesis in humans revealed that plasma exposure was correlated with fat content in food administered with the drug. Plasma concentrations of anacetrapib seemed to reach plateau faster than adipose concentrations. Anacetrapib continued to accumulate in adipose during the treatment period despite apparent plateau in plasma with only minimal decline in adipose levels up to 1 year postdose. Because of its high lipophilicity, anacetrapib partitions into adipose tissue, this likely forms a drug reservoir that, in turn, contributes to the long residence time of the drug in plasma.
Comparative study on heterophase structures in ferroelectric solid solutions based on barium titanate
Authors: Topolov VitalyYu. , Kalyani Ajay Kumar , Brajesh Kumar , Ranjan Rajeev , Panich Anatoly E.
Published: April 2017

Heterophase structures are first compared for related perovskite‐type ferroelectric solid solutions that are tin‐modified barium titanate and hafnium‐modified barium titanate with compositions near the morphotropic phase boundary. The studied heterophase structures are interpreted in terms of two models wherein two polydomain phases and a single‐domain interlayer or polydomain and single‐domain phases and a polydomain interlayer coexist at the complete stress relief. The role of the non‐180° domain types and unit‐cell parameters of the coexisting phases is highlighted to show the important link between the phase contents and unit‐cell parameters near the morphotropic phase boundary. A link between the heterophase/polydomain regions and piezoelectric activity of the ferroelectric solid solutions is discussed. Results on the phase contents in the morphotropic region are consistent with experimental data on the aforementioned solid solutions based on barium titanate.
Monitoring CD49d Receptor Occupancy: A Method to Optimize and Personalize Natalizumab Therapy in Multiple Sclerosis Patients
Authors: Puñet‐Ortiz Joan , Hervás‐García José Vicente , Teniente‐Serra Aina , Cano‐Orgaz Antonio , Mansilla Maria José , Quirant‐Sánchez Bibiana , Navarro‐Barriuso Juan , Fernández‐Sanmartín Marco A. , Presas‐Rodríguez Silvia , Ramo‐Tello Cristina , Martínez‐Cáceres Eva María
Published: April 2017

Background

In natalizumab‐treated relapsing‐remitting MS (RRMS) patients, various extended interval dosing strategies are under evaluation to minimize severe treatment‐associated side effects, mainly progressive multifocal leukoencephalopathy development. Up to now, it has not been presented any approach, even in form of assay design, to determine the optimal percentage of CD49d receptor occupancy (RO) associated with a favorable clinical, radiological, and immunological response.

Methods

A multiparametric quantitative flow cytometry method was settled to measure CD49d RO on peripheral blood lymphocytes. The analytical protocol was tested in a 6‐month follow‐up from 19 RRMS patients treated with the natalizumab standard dosing of every 4 weeks or an extended‐interval dosing of every 6 weeks.

Results

Extended natalizumab dose schedule promoted an increase of CD49d molecules per cell surface and a reduction of CD49d RO levels. The reduction observed on CD49d RO was not only depending on dose schedule but also on individual parameters such as body mass. Interestingly, individual clinical outcome was apparently the same between the different dose schedules or even better with the extended interval dosing.

Conclusions

Following up CD49d RO levels with a well‐regulated monitoring work scheme is crucial to further identify over‐/under‐treated patients and to define a safe, personalized natalizumab regimen. © 2017 International Clinical Cytometry Society
An MRI study of the corpus callosum in monkeys: Developmental trajectories and effects of neonatal hippocampal and amygdala lesions
Authors: Payne Christa , Cirilli Laetitia , Bachevalier Jocelyne
Published: April 2017

This study provides the first characterization of early developmental trajectories of corpus callosum (CC) segments in rhesus macaques using noninvasive MRI techniques and assesses long‐term effects of neonatal amygdala or hippocampal lesions on CC morphometry. In Experiment 1, 10 monkeys (5 males) were scanned at 1 week—2 years of age; eight additional infants (4 males) were scanned once at 1–4 weeks of age. The first 8 months showed marked growth across all segments, with sustained, albeit slower, growth through 24 months. Males and females had comparable patterns of CC maturation overall, but exhibited slight differences in the anterior and posterior segments, with greater increases in the isthmus for males and greater increases in the rostrum for females. The developmental changes are likely a consequence of varying degrees of axonal myelination, redirection, and pruning. In Experiment 2, animals with neonatal lesions of the amygdala (n = 6; 3 males) or hippocampus (n = 6; 4 males) were scanned at 1.5 years post‐surgery and compared to scans of six control animals from Experiment 1. Whereas amygdala damage yielded larger rostral and posterior body segments, hippocampal damage yielded larger rostrum and isthmus. These differences demonstrate that early perturbations to one medial temporal lobe structure may produce extensive and long‐lasting repercussions in other brain areas. The current findings emphasize the complexity of neural circuitry putatively subserving neurodevelopmental disorders such as autism spectrum disorder and Williams syndrome, which are each characterized by malformations and dysfunction of complex neural networks that include regions of the medial temporal lobe.
Sexual signals reflect telomere dynamics in a wild bird
Authors: Taff Conor Claverie , Freeman‐Gallant Corey R.
Published: April 2017

Telomere dynamics in natural populations have been linked to survival, reproduction, and energetic investment. Given their putative role in mediating life‐history trade‐offs, telomeres are also a likely candidate for maintaining honesty in sexually selected signals; few studies to date, however, have demonstrated a correlation between sexual signals and telomere dynamics. Here, we show that plumage coloration in male common yellowthroats (Geothlypis trichas) is correlated with both relative telomere length and with the rate of telomere loss between years. Elevated antioxidant capacity is also associated with reduced telomere loss, but only among older males. Previous work in this population has demonstrated that males with brighter plumage are in better condition, have higher reproductive success, and are more likely to survive over winter. Thus, the signal attribute associated with mate choice in this system also conveys reliable information about telomere dynamics. At present, it is unclear whether telomere maintenance plays a causal role in maintaining signal honesty or whether the correlation arises due to underlying variation in individual resources or genotypes. We suggest that subsequent work should consider the possibility that fundamental trade‐offs between signal investment and cell‐level processes that influence aging and reproductive senescence may provide a foundation for understanding the maintenance of sexual signal honesty.
Effects of light intensity on litter decomposition in a subtropical region
Authors: Ma Zhiliang , Yang Wanqin , Wu Fuzhong , Tan Bo
Published: April 2017

Sunlight, as a main driver of terrestrial ecosystem process, not only runs the synthesis, but also the decomposition. In nature, soil surface might be exposed to different light intensities, but the decomposition as affected by light intensity remains unknown. A shading experiment was conducted to simulate the effects of different light intensities on decomposition of foliar litter in a subtropical region of western China. Over two‐year incubation, foliar litter mass lost 54.46–100% depending on tree species and light intensities, and 37.21–80.58% of mass losses occurred in rainy seasons. Light intensity gave strong effects on litter mass loss, but the effects varied with tree species and season. Shading treatments promoted the litter decomposition in the dry seasons, but inhibited the decomposition in the rainy seasons. Light intensity, tree species, and their interactions are the main factors regulating litter decomposition in subtropical regions.
Benthic primary producers are key to sustain the Wadden Sea food web: stable carbon isotope analysis at landscape scale
Authors: Christianen M. J. A. , Middelburg J. J. , Holthuijsen S. J. , Jouta J. , Compton T. J. , van der Heide T. , Piersma T. , Sinninghe Damsté J. S. , van der Veer H. W. , Schouten S. , Olff H.
Published: April 2017

Coastal food webs can be supported by local benthic or pelagic primary producers and by the import of organic matter. Distinguishing between these energy sources is essential for our understanding of ecosystem functioning. However, the relative contribution of these components to the food web at the landscape scale is often unclear, as many studies lack good taxonomic and spatial resolution across large areas. Here, using stable carbon isotopes, we report on the primary carbon sources for consumers and their spatial variability across one of the world's largest intertidal ecosystems (Dutch Wadden Sea; 1460 km2 intertidal surface area), at an exceptionally high taxonomic (178 species) and spatial resolution (9,165 samples from 839 locations). The absence of overlap in δ13C values between consumers and terrestrial organic matter suggests that benthic and pelagic producers dominate carbon input into this food web. In combination with the consistent enrichment of benthic primary producers (δ13C −16.3‰) relative to pelagic primary producers (δ13C −18.8) across the landscape, this allowed the use of a two‐food‐source isotope‐mixing model. This spatially resolved modelling revealed that benthic primary producers (microphytobenthos) are the most important energy source for the majority of consumers at higher trophic levels (worms, molluscs, crustaceans, fish, and birds), and thus to the whole food web. In addition, we found large spatial heterogeneity in the δ13C values of benthic primary producers (δ13C −19.2 to −11.5‰) and primary consumers (δ13C −25.5 to −9.9‰), emphasizing the need for spatially explicit sampling of benthic and pelagic primary producers in coastal ecosystems. Our findings have important implications for our understanding of the functioning of ecological networks and for the management of coastal ecosystems.
Keystone predation and molecules of keystone significance
Authors: Zimmer Richard K. , Ferrier Graham A. , Kim Steven J. , Ogorzalek Loo Rachel R. , Zimmer Cheryl Ann , Loo Joseph A.
Published: April 2017

Keystone species structure ecological communities and are major determinants of biodiversity. A synthesis of research on keystone species is nonetheless missing a critical component – the sensory mechanisms for behavioral interactions that determine population‐ and community‐wide attributes. Here, we establish the chemosensory basis for keystone predation by sea stars (Pisaster ochraceus) on mussels. This consumer‐resource interaction is prototypic of top‐down driven trophic cascades. Each mussel species (Mytilus californianus and M. galloprovincialis) secretes a glycoprotein orthologue (29.6 and 28.1 kDa, respectively) that acts, singularly, to evoke the sea star predatory response. The orthologues (named “KEYSTONEin”) are localized in the epidermis, extrapallial fluid, and organic shell coating (periostracum) of live, intact mussels. Thus, KEYSTONEin contacts chemosensory receptors on tube feet as sea stars crawl over rocky surfaces in search of prey. The complete nucleotide sequences reveal that KEYSTONEin shares 87% (M. californianus) or 98% (M. galloprovincialis) homology with a calcium‐binding protein in the shell matrix of a closely related congener, M. edulis. All three molecules cluster tightly within the Complement Component 1 Domain Containing (C1qDC) protein family; each exhibits a large globular domain, low complexity region(s), coiled coil, and at least four of five histidine‐aspartic acid tandem motifs. Collective results support the hypothesis that KEYSTONEin evolved ancestrally in immunological, and later, in biomineralization roles. More recently, the substance has become exploited by sea stars as a contact cue for prey recognition. As the first identified compound to evoke keystone predation, KEYSTONEin provides valuable sensory information, promotes biodiversity, and shapes community structure and function. Without this molecule, there would be no predation by sea stars on mussels.
Design of a multicentre randomized controlled trial to assess the safety and efficacy of dose titration by specialized nurses in patients with heart failure. ETIFIC study protocol
Authors: Oyanguren Juana , García‐Garrido LLuisa , Nebot Margalef Magdalena , Lekuona Iñaki , Comin‐Colet Josep , Manito Nicolás , Roure Julia , Ruiz Rodriguez Pilar , Enjuanes Cristina , Latorre Pedro , Torcal Laguna Jesús , García‐Gutiérrez Susana ,   on behalf of the ETIFIC research group
Published: April 2017

Aims

Heart failure (HF) is associated with many hospital admissions and relatively high mortality, rates decreasing with administration of beta‐blockers (BBs), angiotensin‐converting‐enzyme inhibitors, angiotensin II receptor blockers, and mineralocorticoid receptor antagonists. The effect is dose dependent, suboptimal doses being common in clinical practice. The 2012 European guidelines recommend close monitoring and dose titration by HF nurses. Our main aim is to compare BB doses achieved by patients after 4 months in intervention (HF nurse‐managed) and control (cardiologist‐managed) groups. Secondary aims include comparing doses of the other aforementioned drugs achieved after 4 months, adverse events, and outcomes at 6 months in the two groups.

Methods

We have designed a multicentre (20 hospitals) non‐inferiority randomized controlled trial, including patients with new‐onset HF, left ventricular ejection fraction ≤40%, and New York Heart Association class II–III, with no contraindications to BBs. We will also conduct qualitative analysis to explore potential barriers to and facilitators of dose titration by HF nurses. In the intervention group, HF nurses will implement titration as prescribed by cardiologists, following a protocol. In controls, cardiologists will both prescribe and titrate doses. The study variables are doses of each of the drugs after 4 months relative to the target dose (%), New York Heart Association class, left ventricular ejection fraction, N‐terminal pro B‐type natriuretic peptide levels, 6 min walk distance, comorbidities, renal function, readmissions, mortality, quality of life, and psychosocial characteristics.

Conclusions

The trial seeks to assess whether titration by HF nurses of drugs recommended in practice guidelines is safe and not inferior to direct management by cardiologists. The results could have an impact on clinical practice.
Electrospray‐Ionisation Mass‐Spectrometric (ESI‐MS) Investigation of Beryllium Hydrolysis in Acidic Solutions of Beryllium Sulfate
Authors: Raymond Onyekachi , Henderson William , Brothers Penelope J. , Plieger Paul G.
Published: April 2017

The speciation and hydrolysis of beryllium ions in an aqueous solution of its sulfate salt have been studied over a pH range of 2.5–6.0 by using electrospray ionisation mass spectrometry (ESI‐MS). Ions observed by ESI‐MS revealed that the highly charged beryllium hydroxido species in solution were preserved into the gas phase by pairing with the sulfate ion. The pH‐dependent hydrolytic tendencies of the Be2+ cation presented as an ESI‐MS speciation diagram were in good agreement with previous speciation data, suggesting the ability of ESI‐MS to be developed as a quick, sensitive and safe screening technique to observe beryllium speciation with ligands of interest at low concentrations. Collision‐induced dissociation patterns further supported the trimer [Be3(OH)3]3+ as the most stable beryllium hydroxide species arrangement while the pronounced association of the beryllium cation and sulfato ligand yielded additional beryllium cluster arrangements such as {Be3(µ3‐O)} clusters and mixed sulfato/hydroxido species such as [Be3O(HSO4)3]+.
Photochemical C–H Activation: Generation of Indole and Carbazole Libraries, and First Total Synthesis of Clausenawalline D
Authors: Alimi Isak , Remy Richard , Bochet Christian G.
Published: April 2017

The photolysis of N‐aryltriazoles and N‐arylbenzotriazoles leads to indoles and carbazoles, respectively. Because libraries of triazoles can be accessed rapidly, for example by the copper‐catalyzed [3+2] cycloaddition reaction between alkynes and azides, this reaction allows the preparation of indoles in a single operation, by the simultaneous photolysis of the precursor library. As an example of such a synthesis of carbazoles, we prepared for the first time clausenawalline D, an antimalarial alkaloid that was recently isolated.
A Novel Biomimetic Hydrogen Peroxide Biosensor Based on Pt Flowers‐decorated Fe3O4/Graphene Nanocomposite
Authors: Zhao Xueling , Li Zhanhong , Chen Cheng , Wu Yihua , Zhu Zhigang , Zhao Hongli , Lan Minbo
Published: April 2017

A sensitive and selective amperometric H2O2 biosensor was obtained by utilizing the electrodeposition of Pt flowers on iron oxide‐reduced graphene oxide (Fe3O4/rGO) nanocomposite modified glassy carbon electrode (GCE). The morphology of Fe3O4/rGO and Pt/Fe3O4/rGO was characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM), respectively. The step‐wise modification and the electrochemical characteristics of the resulting biosensor were characterized by cyclic voltammetry (CV) and chronoamperometry methods. Thanks to the fast electron transfer at the Pt/Fe3O4/rGO electrode interface, the developed biosensor exhibits a fast and linear amperometric response upon H2O2. The linear range of Pt/Fe3O4/rGO is 0.1∼2.4 mM (R2=0.998), with a sensitivity of 6.875 μA/mM and a detection limit of 1.58 μM (S/N=3). In addition, the prepared biosensor also provides good anti‐interferent ability and long‐term stability due to the favorable biocompatibility of the electrode interface. The proposed sensor will become a reliable and effective tool for monitoring and sensing the H2O2 in complicate environment.
An Electrochemical Sensor Based on Gold Nanoparticles Incorporated in Mesoporous MFI Zeolite for Determination of Purine Bases in DNA
Authors: Song Huixian , Huo Shijie , Dong Junping , Xu Jiaqiang
Published: April 2017

An electrochemical sensor was developed based on gold nanoparticles incorporated in mesoporous MFI zeolite for the determination of purine bases. Au nanoparticles (AuNPs) were incorporated into the mesoporous MFI zeolite (AuNPs/m‐MFI) by post‐grafting reaction. The composite materials were characterized by transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS) and electrochemical methods. Au nanoparticles with a size of 5‐20 nm are uniformly dispersed in the pores of mesoporous MFI zeolite. And the morphology of MFI zeolite can be perfectly kept after pore expansion and Au nanoparticles incorporation. The electrocatalytic oxidation of purine bases (guanine and adenine in DNA) is investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The surface‐confined Au nanoparticles provide the good catalytic activity for oxidation of purine bases. The simultaneous detection of guanine and adenine can be achieved at AuNPs/m‐MFI composites modified glassy carbon electrode (GCE). The electrochemical sensor based on AuNPs/m‐MFI exhibits wide linear range of 0.5–500 μM and 0.8–500 μM with detection limit of 0.25 and 0.29 μM for guanine and adenine, respectively. Moreover, the electrochemical sensor is applied to evaluation of guanine and adenine in herring sperm DNA samples with satisfactory results.