bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Chemical Constituents from the Fermented Mycelia of the Medicinal Fungus Xylaria nigripes.
Authors: Xiong Juan , Huang Ya , Wu Xi‐Ying , Liu Xin‐Hua , Fan Hui , Wang Wei , Zhao Yun , Yang Guo‐Xun , Zhang Hai‐Yan , Hu Jin‐Feng
Published: May 2016

Compounds (I), (II), and (III) are isolated from the ethanol extract of the fermented mycelia of Xylaria nigripes.
ChemInform Abstract: Trichiconlides A and B: Two Novel Limonoids from the Fruits of Trichilia connaroides.
Authors: An Fa‐Liang , Luo Jun , Wang Xiao‐Bing , Yang Ming‐Hua , Kong Ling‐Yi
Published: May 2016

In addition to the title trichiconlides A (I) and B (II) a biosynthesis derived derivative, trichiconlide C (III), is isolated.
ChemInform Abstract: Direct Preparation of High Quality Graphene on Dielectric Substrates
Authors: Chen Xin , Wu Bin , Liu Yunqi
Published: May 2016

Review: 50 refs.
ChemInform Abstract: Zr‐Based Metal—Organic Frameworks: Design, Synthesis, Structure, and Applications
Authors: Bai Yan , Dou Yibo , Xie Lin‐Hua , Rutledge William , Li Jian‐Rong , Zhou Hong‐Cai
Published: May 2016

Review: 300 refs.
ChemInform Abstract: Recent Advances in C(sp3)—H Bond Functionalization via Metal—Carbene Insertions
Authors: Wang Bo , Qiu Di , Zhang Yan , Wang Jianbo
Published: May 2016

Review: [45 refs.
ChemInform Abstract: Chemistry of 2‐Aminoimidazoles
Authors: Zula Ales , Kikelj Danijel , Ilas Janez
Published: May 2016

Review: 67 refs.
ChemInform Abstract: Ruthenium‐Catalyzed Direct Arylations with Aryl Chlorides
Authors: Zha Gao‐Feng , Qin Hua‐Li , Kantchev Eric Assen B.
Published: May 2016

Review: [50 refs.
ChemInform Abstract: A Very Peculiar Family of N‐Heterocyclic Phosphines: Unusual Structures and the Unique Reactivity of 1,3,2‐Diazaphospholenes
Authors: Gudat D.
Published: May 2016

Review: 79 refs.
ChemInform Abstract: Control of Biogenic Nanocrystal Formation in Biomineralization
Authors: Addadi Lia , Gal Assaf , Faivre Damien , Scheffel Andre , Weiner Steve
Published: May 2016

Review: 109 refs.
ChemInform Abstract: Thiazolo[4,5‐d]pyrimidines as a Privileged Scaffold in Drug Discovery
Authors: Kuppast Bhimanna , Fahmy Hesham
Published: May 2016

Review: 74 refs.
ChemInform Abstract: Chemical Protein Modification Through Cysteine
Authors: Gunnoo Smita B. , Madder Annemieke
Published: May 2016

Review: 271 refs.
ChemInform Abstract: Nanoparticles and Mesenchymal Stem Cells: A Win‐Win Alliance for Anticancer Drug Delivery
Authors: Li Min , Zhang Fangrong , Chen Kerong , Wang Cheng , Su Yujie , Liu Yuan , Zhou Jianping , Wang Wei
Published: May 2016

Review: 134 refs.
ChemInform Abstract: Computational Catalysis Using the Artificial Force Induced Reaction Method
Authors: Sameera W. M. C. , Maeda Satoshi , Morokuma Keiji
Published: May 2016

Review: 33 refs.
A priori error estimation of upscaled coarse grids for water‐flooding process
Authors: Khoozan Davood , Firoozabadi Bahar
Published: May 2016

Advanced reservoir characterization methods can yield geological models at a very fine resolution, containing 1011–1018 cells, while the common reservoir simulators can only handle much lower numbers of cells due to computer hardware limitations. The process of coarsening a fine‐scale model to a simulation model is known as upscaling. Predicting the accuracy of simulation results over an upscaled grid with respect to the fine grid is highly important, as it can yield the optimum upscaling process. In this paper, permeability‐based and velocity‐based a priori error estimation techniques are proposed by introducing image processing‐based comparison methods in the context of upscaling. The performance of the introduced error estimation techniques as well as the contribution of the employed image processing method are investigated thoroughly over highly heterogeneous cases under various coarsening levels, permeability upscaling methods, boundary conditions, and mobility ratios. The results show the superior performance of the proposed image processing‐based techniques compared to the existing methods in terms of predicting the accuracy of the water‐flooding process over the upscaled model with respect to the original fine grid results.
A spatiotemporal characterization method for the dynamic cytoskeleton
Authors: Alhussein Ghada , Shanti Aya , Farhat Ilyas A. H. , Timraz Sara B. H. , Alwahab Noaf S. A. , Pearson Yanthe E. , Martin Matthew N. , Christoforou Nicolas , Teo Jeremy C. M.
Published: May 2016

The significant gap between quantitative and qualitative understanding of cytoskeletal function is a pressing problem; microscopy and labeling techniques have improved qualitative investigations of localized cytoskeleton behavior, whereas quantitative analyses of whole cell cytoskeleton networks remain challenging. Here we present a method that accurately quantifies cytoskeleton dynamics. Our approach digitally subdivides cytoskeleton images using interrogation windows, within which box‐counting is used to infer a fractal dimension (Df) to characterize spatial arrangement, and gray value intensity (GVI) to determine actin density. A partitioning algorithm further obtains cytoskeleton characteristics from the perinuclear, cytosolic, and periphery cellular regions. We validated our measurement approach on Cytochalasin‐treated cells using transgenically modified dermal fibroblast cells expressing fluorescent actin cytoskeletons. This method differentiates between normal and chemically disrupted actin networks, and quantifies rates of cytoskeletal degradation. Furthermore, GVI distributions were found to be inversely proportional to Df, having several biophysical implications for cytoskeleton formation/degradation. We additionally demonstrated detection sensitivity of differences in Df and GVI for cells seeded on substrates with varying degrees of stiffness, and coated with different attachment proteins. This general approach can be further implemented to gain insights on dynamic growth, disruption, and structure of the cytoskeleton (and other complex biological morphology) due to biological, chemical, or physical stimuli. © 2016 Wiley Periodicals, Inc.
Filopodia formation by crosslinking of F‐actin with fascin in two different binding manners
Authors: Aramaki Shinji , Mayanagi Kouta , Jin Mingyue , Aoyama Kazuhiro , Yasunaga Takuo
Published: May 2016

Filopodia are finger‐like protrusions at the leading edge of migrating cells that play a crucial antennal function during cell motility. It is known that actin filaments are bundled hexagonally and provide rigidity to filopodia by virtue of fascin, which plays a central role in actin filament bundling. However, the molecular mechanisms underlying their formation remain unclear. Here, we observed the filopodia of intact whole cells fixed by rapid freezing and revealed their three‐dimensional structure by cryo‐electron tomography and image processing; the actin filament bundling structure by fascin was clarified at high resolution under physiological conditions. It was found that actin filaments in vivo were more numerous than in bundles reconstructed in vitro, and each filopodial actin filament had limited variability in helical twisting. In addition, statistical analysis of actin filament bundles unveiled their detailed architecture. In filopodia, actin filaments had highly ordered structures, and the shift between cross‐links of each adjacent actin filament was approximately 2.7 nm, similar to the monomer repeat of actin filaments. We then proposed a plausible actin‐fascin cross‐link model at the amino acid level and identified three fascin binding sites on two adjacent actin filaments: one filament bound fascin at two discrete, widely separated regions and the other bound fascin in a single small region. We propose that these two different binding modalities should confer rigid bundles that retain flexibility and dynamic performance. © 2016 Wiley Periodicals, Inc.
Sexual function in male long‐term survivors of childhood acute lymphoblastic leukemia
Authors: Haavisto Anu , Henriksson Markus , Heikkinen Risto , Puukko‐Viertomies Leena‐Riitta , Jahnukainen Kirsi
Published: May 2016

BACKGROUND

Infertility, poor semen quality, and gonadal dysfunction are well recognized long‐term sequelae in male survivors of childhood acute lymphoblastic leukemia (ALL). However, few studies have investigated adult sexual functioning in these survivors.

METHODS

The authors studied 52 male survivors of childhood ALL at a median age of 28.5 years (range, 25‐38 years) ≥ 10 years after diagnosis. In addition, 56 men without a history of cancer were recruited for an age‐matched control group. The participants completed the Derogatis Interview for Sexual Functioning self‐report. To analyze predictive factors for sexual dysfunction, variables assessing sociodemographic background, antileukemia treatment, testicular size, laboratory variables from current serum and semen samples, self‐reported depressive symptoms, and self‐reported physical functioning were included in multiple regression analyses.

RESULTS

ALL survivors had significantly poorer sexual functioning, as measured by the Derogatis Interview for Sexual Functioning self‐report, compared with the control group. Survivors had a similar frequency of sexual fantasies, autoerotic acts, and full erection during these activities as the control group, but they had less frequent sexual activity with a sexual partner, poorer self‐rated orgasms, and lower satisfaction with their sex life. Predictive factors for poorer sexual functioning were depressive symptoms, the absence of a relationship, and, to a lesser extent, testicular size as an indication of gonadal damage from childhood antileukemia therapy. Older survivors experienced a deeper decline in sexual functioning compared with men in the control group.

CONCLUSIONS

Decline in sexual functioning at an early adult age can be regarded as 1 of the late effects of childhood cancer. Monitoring these survivors' sexual health is indicated. Cancer 2016;122:2268–76. © 2016 American Cancer Society.
Monodispersed Li4Ti5O12 with Controlled Morphology as High Power Lithium Ion Battery Anodes
Authors: Li Yunchao , Fu Guoyi , Watson Mark , Harrison Stephen , Paranthaman M. Parans
Published: May 2016

Monodispersed Li4Ti5O12 (LTO) nanoparticles with controlled microstructure were successfully synthesized by a combination of hydrolysis and hydrothermal method followed by a post‐annealing process. The scanning electron microscopy images showed that particles with a size of 30–50 nm were precisely controlled throughout the synthesis process. The electrochemical tests of the as‐prepared LTO electrodes in a half‐cell proved its high rate performance and outstanding cyclability which benefits from the preserved well‐controlled nanoparticle size and morphology. LTO electrodes were also tested in a full cell configuration in pairing with LiFePO4 cathodes, which demonstrated a capacity of 147.3 mA h g−1. In addition, we have also demonstrated that LTO materials prepared using lithium salts separated from geothermal brine solutions had good cyclability. These demonstrations provide a promising way for making low‐cost, large‐scale LTO electrode materials for energy storage applications.
EPIC: A framework to exploit parallelism in irregular codes
Authors: Neves Diogo Telmo
Published: May 2016

To harness the performance potential of current multicore processors, a multitude of algorithms, frameworks and libraries have been developed. Nevertheless, it is still extremely difficult to take advantage of the full potential of multicore processors. Moreover, when using third‐party tools and/or in the presence of asymmetric sets of tasks, this problem would only aggravate. The EPIC framework was developed to ease the exploitation of task parallelism in irregular applications that use third‐party tools and/or generate asymmetric sets of tasks. It is based on a software design and implements two algorithms that, together, allow, in a seamlessly way, the efficient exploitation of coarse‐grained parallelism, fine‐grained parallelism, and the combination of both of these types. Thus, it becomes possible to make a better and transparent usage of the performance potential of current multicore processors on shared‐memory systems. In this paper, we present two refinements to the EPIC framework: one that refines the software design of the EPIC framework and another that refines the scheduling algorithm of the EPIC framework. Together, these refinements allow to cope with a special class of sets of tasks: sets of tasks where asymmetry is insignificant or can be neglected. Thus, these refinements broaden the applicability of the EPIC framework to a large class of irregular applications where task parallelism can be exploited. To assess the feasibility and the benefit of using this new version of the EPIC framework to exploit task parallelism, we used four real‐world irregular applications—three from phylogenetics and another from astrophysics—and several input data sets with different characteristics. Our studies show groundbreaking results in terms of the achieved speedups and that scalability is not impaired, even when using third‐party tools and/or in the presence of (a)symmetric sets of tasks. Copyright © 2016 John Wiley & Sons, Ltd.
WISP: A pattern‐based approach to the interchange of scientific workflow specifications
Authors: Bastos Bruno F. , Braga Regina Maria M. , Gomes Antonio Tadeu A.
Published: May 2016

Scientific workflows are used for dealing with complex problems in different e‐science domains. These workflows are modeled and executed using Scientific Workflow Management Systems (SWfMSs). Generally, SWfMSs provide their own Workflow Specification Language, and this is a challenge considering the possibility of interchanging workflow specifications between different SWfMSs. In this paper, we propose the use of workflow patterns combined with software architecture concepts to capture the key semantics expressed in scientific workflows specified in different Workflow Specification Languages. These concepts are materialized in a novel specification interchange language (and associated tooling) called Workflow Interchange in Science with Patterns (WISP), which is the main contribution of our work. We have evaluated WISP based on real world specifications; in this paper, we present the results of such evaluation (including an assessment of the quality of the research material available), which has eventually led us to reformulate our initial proposal with more stringent assumptions on the input and output specifications. Copyright © 2016 John Wiley & Sons, Ltd.
A social content delivery network for e‐Science
Authors: Chard Kyle , Caton Simon , Kugler Kai , Rana Omer , Katz Daniel S.
Published: May 2016

We are in the midst of a scientific data explosion in which the rate of data growth is rapidly increasing. While large‐scale research projects have developed sophisticated data distribution networks to share their data with researchers globally, there is no such support for the many millions of research projects generating data of interest to much smaller audiences (as exemplified by the long tail scientist). In data‐oriented research, every aspect of the research process is influenced by data access. However, sharing and accessing data efficiently as well as lowering access barriers are difficult. In the absence of dedicated large‐scale storage, many have noted that there is an enormous storage capacity available via connected peers, none more so than the storage resources of many research groups. With widespread usage of the content delivery network model for disseminating web content, we believe a similar model can be applied to distributing, sharing, and accessing long tail research data in an e‐Science context. We describe the vision and architecture of a social content delivery network – a model that leverages the social networks of researchers to automatically share and replicate data on peers' resources based upon shared interests and trust. Using this model, we describe a simulator and investigate how aspects such as user activity, geographic distribution, trust, and replica selection algorithms affect data access and storage performance. From these results, we show that socially informed replication strategies are comparable with more general strategies in terms of availability and outperform them in terms of spatial efficiency. Copyright © 2016 John Wiley & Sons, Ltd.
A dedicated private‐shared cache design for scalable multiprocessors
Authors: Cebrián Juan M. , Fernández‐Pascual Ricardo , Jimborean Alexandra , Acacio Manuel E. , Ros Alberto
Published: May 2016

Most modern architectures are based on a shared‐memory design. Correctness of these architectures is ensured by means of coherence protocols and consistency models. However, performance and scalability of shared‐memory systems is usually constrained by the amount and size of the messages used to keep the memory subsystem coherent. This is not only important in high performance computing, but also in low power embedded systems, specially if coherence is required between different components of the system‐on‐chip. We argue that using the same mechanism to keep coherence for all memory accesses can be counterproductive, because it incurs unnecessary overhead for data addresses that would remain coherent after the access (i.e., private data and read‐only shared data). This paper proposes the use of dedicated caches for two different kinds of data (i) data that can be accessed without contacting other nodes and (ii) modifiable shared data. The private cache (L1P) will be independent for each core and will store private data and read‐only shared data. On the other hand, the shared cache (L1S), will be logically shared but physically distributed for all cores. With this design, we can significantly simplify the coherence protocol, reduce the on‐chip area requirements and reduce invalidation time. However, this dedicated cache design requires a classification mechanism to detect the nature of the data that is being accessed. Results show two drawbacks to this approach: first, the accuracy of the classification mechanism has a huge impact on performance. Second, a traditional interconnection network is not optimal for accessing the L1S, increasing register‐to‐cache latency when accessing shared data. Copyright © 2016 John Wiley & Sons, Ltd.
Production of 3‐D Airway Organoids From Primary Human Airway Basal Cells and Their Use in High‐Throughput Screening
Authors: Hild Marc , Jaffe Aron B.
Published: May 2016

The ability of human airway basal cells to serve as progenitor cells in the conducting airway makes them an attractive target in a number of respiratory diseases associated with epithelial remodeling. This unit describes a protocol for the culture of ‘bronchospheres’, three‐dimensional (3‐D) organoids that are derived from primary human airway basal cells. Mature bronchospheres are composed of functional multi‐ciliated cells, mucin‐producing goblet cells, and airway basal cells. In contrast to existing methods used for the culture of well‐differentiated human airway epithelial cells, bronchospheres do not require growth on a permeable support and can be cultured in 384‐well assay plates. The system provides a mechanism for investigating the regulation of basal cell fate during airway epithelial morphogenesis, as well as a basis for studying the function of the human airway epithelium in high‐throughput assays. © 2016 by John Wiley & Sons, Inc.
European canine lymphoma network consensus recommendations for reporting flow cytometry in canine hematopoietic neoplasms
Authors: Comazzi S. , Avery P. R. , Garden O. A. , Riondato F. , Rütgen B. , Vernau W. ,   on behalf of the European Canine Lymphoma Network
Published: May 2016

Background

Flow cytometry (FC) is assuming increasing importance in diagnosis in veterinary oncology. The European Canine Lymphoma Network (ECLN) is an international cooperation of different institutions working on canine lymphoma diagnosis and therapy. The ECLN panel of experts on FC has defined the issue of reporting FC on canine lymphoma and leukemia as their first hot topic, since a standardized report that includes all the important information is still lacking in veterinary medicine.

Methods

The flow cytometry panel of the ECLN started a consensus initiative using the Delphi approach. Clinicians were considered the main target of FC reports. A panel of experts in FC was interrogated about the important information needed from a report.

Results

Using the feedback from clinicians and subsequent discussion, a list of information to be included in the report was made, with four different levels of recommendation. The final report should include both a quantitative part and a qualitative or descriptive part with interpretation of the salient results. Other items discussed included the necessity of reporting data regarding the quality of samples, use of absolute numbers of positive cells, cutoff values, the intensity of fluorescence, and possible aberrant patterns of antigen expression useful from a clinical point of view.

Conclusion

The consensus initiative is a first step toward standardization of diagnostic approach to canine hematopoietic neoplasms among different institutions and countries. This harmonization will improve communication and patient care and also facilitate the multicenter studies necessary to further our knowledge of canine hematopoietic neoplasms. © 2016 International Clinical Cytometry Society
Isobolographic Analysis of the Interaction Between Tapentadol and Ketorolac in a Mouse Model of Visceral Pain
Authors: Zapata‐Morales Juan R. , Aragon‐Martinez Othoniel H. , Adriana Soto‐Castro Tely , Alonso‐Castro Ángel J. , Castañeda‐Santana Demian I. , Isiordia‐Espinoza Mario A.
Published: May 2016

Preclinical Research

The aim of this experimental assay was to assess the antinociceptive interaction between tapentadol and ketorolac in the acetic acid‐induced writhing model in mice. Tapentadol (5.62–31.6 mg/kg ip) or ketorolac (5.62–31.6 mg/kg ip) were administered 15 min before the acetic acid administration. The ED50 values of the individual drugs were determined and different proportions (tapentadol–ketorolac in 1:1, 3:1, and 1:3) were assayed in combination in the writhing test. Isobolographic analysis and the interaction index demonstrated an antinociceptive synergistic interaction between tapentadol and ketorolac in all combination. Thus, the experimental ED50 values were lower when compared with their theoretical ED50 values. These data suggest that the tapentadol–ketorolac combination produces an antinociceptive synergistic interaction in the mouse acetic acid‐induced writhing model. Drug Dev Res 77 : 187–191, 2016.   © 2016 Wiley Periodicals, Inc.
Dynamic Lightpath Establishment Considering Four‐Wave Mixing for Achieving Low‐Power All‐Optical Networks
Authors: HIRATA KOUJI , MURAGUCHI MASAHIRO
Published: May 2016

This paper proposes a method for dynamically establishing a lightpath that takes into consideration power consumption and four‐wave mixing (FWM) in an all‐optical network. In an all‐optical network, an optical fiber amplifier is used to amplify a group of optical signals of different wavelengths in a fiber without O/E/O conversion. Even if only one optical signal passes through an optical fiber amplifier in a fiber, the optical fiber amplifier operates. Thus, to efficiently use the power of an optical fiber amplifier, multiple optical signals in the fiber should be simultaneously amplified. FWM is one of the most important physical impediments to be resolved an in all‐optical network because FWM degrades the performance of such networks. The FWM power in a fiber increases with the number of wavelengths used in the fiber. Therefore, in order to reduce the FWM power, it is preferable to have optical signals be transmitted on different fibers. The proposed method provides an ingenious path, wavelength, and fiber selection strategy that takes the trade‐off between power consumption and FWM power into account. Furthermore, the proposed method avoids blocking of lightpath establishment due to depletion of wavelength resources. Through simulation experiments, we show that the proposed method can efficiently reduce the blocking probability, power consumption, and FWM power when the number of fibers is fixed.
Estimation of Number of Comparators Required in N‐Bit Stochastic Flash AD Converters
Authors: SUGIMOTO TOSHIKI , TANIMOTO HIROSHI , YOSHIZAWA SHINGO
Published: May 2016

The peak SQNR is theoretically calculated for stochastic flash AD converters (SFADC) composed of n comparators with uniformly distributed threshold voltages. A systematic estimation method is presented to obtain the minimum required number of comparators for realizing specified SFADC resolution by using comparators with uniformly distributed threshold voltages. The proposed method has been supported by numerical simulations.
Preparation of Phosphorescent Polymer Patterns by Spin‐Coating Photoreactive Small Molecules
Authors: MIYAGAWA DAICHI , MUROYAMA MASAKAZU , TANAKA KUNIAKI , USUI HIROAKI
Published: May 2016

Patterned polymer thin films were prepared by spin‐coating a solution consisting of an acryl monomer of 2‐(9H‐carbazol‐9‐yl)ethylmethacrylate, a photoinitiator of 4‐(dimethylamino)benzophenone, and a phosphorescent dopant of iridium(III) bis(2‐phenylpyridinate(4‐vinylphenylpyridine)). The film was exposed to ultraviolet (UV) light through a photomask and rinsed with an organic solvent to develop a patterned polymer thin film. A mixture of tetrahydrofuran and 1,4‐dioxane was used as the spin‐coating solvent, and ethanol was used as the developing solution. The effects of solvent, exposure time, UV intensity, and the phosphorescent dopant were examined to optimize the patterning condition. The patterned film was utilized as an emissive layer to construct an organic light‐emitting diode.
Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double‐blind, randomized comparison of two uptitration regimens
Authors: Senni Michele , McMurray John J.V. , Wachter Rolf , McIntyre Hugh F. , Reyes Antonio , Majercak Ivan , Andreka Peter , Shehova‐Yankova Nina , Anand Inder , Yilmaz Mehmet B. , Gogia Harinder , Martinez‐Selles Manuel , Fischer Steffen , Zilahi Zsolt , Cosmi Franco , Gelev Valeri , Galve Enrique , Gómez‐Doblas Juanjo J. , Nociar Jan , Radomska Maria , Sokolova Beata , Volterrani Maurizio , Sarkar Arnab , Reimund Bernard , Chen Fabian , Charney Alan
Published: May 2016

Aims

To assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%).

Methods and results

A 5‐day open‐label run‐in (sacubitril/valsartan 50 mg twice daily) preceded an 11‐week, double‐blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily (‘condensed’ regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily (‘conservative’ regimen)]. Patients were stratified by pre‐study dose of angiotensin‐converting enzyme inhibitor/angiotensin‐receptor blocker (ACEI/ARB; low‐dose stratum included ACEI/ARB‐naïve patients). Of 540 patients entering run‐in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre‐defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in (‘condensed’ vs. ‘conservative’) 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre‐defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down‐titration over 12 weeks (77.8% vs. 84.3% for ‘condensed’ vs. ‘conservative’; P = 0.078). Rates by ACEI/ARB pre‐study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high‐dose/‘condensed’ vs. high‐dose/‘conservative’ and 84.9% vs. 73.6% (P = 0.030) for low‐dose/‘conservative’ vs. low‐dose/‘condensed’.

Conclusions

Initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low‐dose ACEI/ARB group.
PESERA‐PEAT: a fluvial erosion model for blanket peatlands
Authors: Li Pengfei , Holden Joseph , Irvine Brian , Grayson Richard
Published: May 2016

In peatlands, fluvial erosion can lead to a dramatic decline in hydrological function, major changes in the net carbon balance and loss of biodiversity. Climate and land management change are thought to be important influences on rates of peat erosion. However, sediment production in peatlands is different to that of other soils and no models of erosion specifically for peatlands currently exist. Hence, forecasting the influence of future climate or spatially‐distributed management interventions on peat erosion is difficult. The PESERA‐GRID model was substantially modified in this study to include dominant blanket peat erosion processes. In the resulting fluvial erosion model, PESERA‐PEAT, freeze–thaw and desiccation processes were accounted for by a novel sediment supply index as key features of erosion. Land management practices were parameterized for their influence on vegetation cover, biomass and soil moisture condition. PESERA‐PEAT was numerically evaluated using available field data from four blanket peat‐covered catchments with different erosion conditions and management intensity. PESERA‐PEAT was found to be robust in modelling fluvial erosion in blanket peat. A sensitivity analysis of PESERA‐PEAT showed that modelled sediment yield was more sensitive to vegetation cover than other tested factors such as precipitation, temperature, drainage density and ditch/gully depth. Two versions of PESERA‐PEAT, equilibrium and time‐series, produced similar results under the same environmental conditions, facilitating the use of the model at different scales. The equilibrium model is suitable for assessing the high‐resolution spatial variability of average monthly peat erosion over the study period across large areas (national or global assessments), while the time‐series model is appropriate for investigating continuous monthly peat erosion throughout study periods across smaller areas or large regions using a coarser‐spatial resolution. PESERA‐PEAT will therefore support future investigations into the impact of climate change and management options on blanket peat erosion at various spatial and temporal scales. Copyright © 2016 John Wiley & Sons, Ltd.
Water flow and solute transport model of potentially toxic elements through unsaturated zone at regional wellfield Kosnica
Authors: Ružičić Stanko , Mileusnić Marta , Posavec Kristijan , Nakić Zoran , Durn Goran , Filipović Vilim
Published: May 2016

The objective of this work was to build a prognostic water flow model and potentially toxic elements (lead, cadmium, zinc) transport model in the unsaturated zone. Research was conducted in the catchment area of Kosnica regional wellfield, where the unsaturated zone is characterised by Fluvisol. Lower sorption capacities were determined in the first horizons for all three potentially toxic elements. Correlation coefficient of the measured and simulated values of tracer concentration is 0.58 for the AC horizon and 0.84 for the 2C/C1 horizon. Based on calibrated water flow and transport parameters, a prognostic water flow model and potentially toxic elements (lead, cadmium, zinc) transport model in the unsaturated zone was built. In case of an accidental spill of potentially toxic elements with concentrations of 1000 mg/l, the risk of contamination of the aquifer is present. Copyright © 2016 John Wiley & Sons, Ltd.
Sensitivity of physical lake processes to climate change within a large Precambrian Shield catchment
Authors: Crossman J. , Eimers M. C. , Kerr J. G. , Yao H.
Published: May 2016

Potential future changes in lake physical processes (e.g. stratification and freezing) can be assessed through exploring their sensitivity to climate change, and assessing the current vulnerability of different lake types to plausible changes in meteorological drivers. This study quantifies the impacts of climate change and sensitivity of lake physical processes within a large (5100 km2) Precambrian Shield catchment in south‐central Ontario. Historic regional relationships are established between climate drivers, lake morphology, and lake physical changes through generalized linear modelling (GLM), and are used to quantify likely changes in timing of ice phenology and lake stratification across 72 lakes under a range of future climate models and scenarios.

In response to projections of increased temperature (ensemble mean of +3.3 °C), both earlier ice‐off and onset of summer stratification were projected, with later ice‐on and fall turnover compared to the baseline. Process sensitivity to climate change varied by lake type; shallower lakes with a smaller volume (less than 15 m deep and less than 0.05 km3) were more sensitive to processes associated with lake heating (stratification onset and ice‐off), and deeper lakes with a larger surface area (greater than 30 m deep and greater than 1000 ha) were more sensitive to processes associated with lake cooling (fall turnover and ice‐on). These results indicate that whereas small lakes are vulnerable to climate warming because of changes that occur in spring and summer, larger lakes are particularly sensitive during the fall. The findings suggest that lake morphology and associated sensitivity should be considered in the development of sustainable lake management strategies. Copyright © 2016 John Wiley & Sons, Ltd.
Quantifying aggregation and change in runoff source in accordance with catchment area increase in a forested headwater catchment
Authors: Egusa Tomohiro , Ohte Nobuhito , Oda Tomoki , Suzuki Masakazu
Published: May 2016

There has been a great deal of research interest regarding changes in flow path/runoff source with increases in catchment area. However, there have been very few quantitative studies taking subscale variability and convergence of flow path/runoff source into account, especially in relation to headwater catchments. This study was performed to elucidate how the contributions and discharge rates of subsurface water (water in the soil layer) and groundwater (water in fractured bedrock) aggregate and change with catchment area increase, and to elucidate whether the spatial variability of the discharge rate of groundwater determines the spatial variability of stream discharge or groundwater contribution. The study area was a 5‐km2 forested headwater catchment in Japan. We measured stream discharge at 113 points and water chemistry at 159 points under base flow conditions. End‐member mixing analysis was used to separate stream water into subsurface water and groundwater. The contributions of both subsurface water and groundwater had large variability below 1 km2. The contribution of subsurface water decreased markedly, while that of groundwater increased markedly, with increases in catchment area. The specific discharge of subsurface water showed a large degree of variability and decreased with catchment area below 0.1 km2, becoming almost constant above 0.1 km2. The specific discharge of groundwater showed large variability below 1 km2 and increased with catchment area. These results indicated that the variabilities of stream discharge and groundwater contribution corresponded well with the variability of the discharge rate of groundwater. However, below 0.1 km2, it was necessary to consider variations in the discharge rates of both subsurface water and groundwater. Copyright © 2016 John Wiley & Sons, Ltd.
Constructing Interaction: The Development of Gaze Dynamics
Authors: Nomikou Iris , Leonardi Giuseppe , Rohlfing Karharina J. , Rączaszek‐Leonardi Joanna
Published: May 2016

Gaze is one of the first and most important means of communication and coordination in parent–infant dyads. In the present paper we used a novel method, designed to discover patterns in time‐series, to investigate the dynamics of gaze in dyads and its developmental change. Using a longitudinal corpus of natural interactions, mutual mother–infant gaze was coded when the infants were 3, 6, and 8 months old and subjected to recurrence analysis. The cross‐recurrence profiles obtained for the three time points show systematic differences: While the engagement in mutual gaze decreases with age, the behaviour becomes more tightly coupled as a more regular temporal structure emerges. We suggest that this stronger interdependency of gaze behaviour may indicate the development of a social feedback loop enabling engagement in interaction. Copyright © 2016 John Wiley & Sons, Ltd.
Exosome‐encapsulated microRNAs as circulating biomarkers for breast cancer
Authors: Joyce Doireann P. , Kerin Michael J. , Dwyer Róisín M.
Published: May 2016

Breast cancer is a highly prevalent disease, accounting for 29% of invasive cancers in women. Survival from this disease depends on the stage at diagnosis, with patients who are detected earlier having more favourable outcomes. It is because of this that research groups are focusing on the development of a blood‐based biomarker for breast cancer. Such biomarkers may facilitate the detection of breast cancer in its infancy before it has spread beyond the primary site. MicroRNAs (miRNAs) have shown immense potential in this setting. These short, non‐coding RNA sequences have been shown to be dysregulated in breast cancer. Despite showing immense promise, miRNAs have not been successfully implemented in the clinical setting due to a lack of a standardised approach which has resulted in conflicting results. These challenges may be addressed at least in part through the study of exosomes. The biomarker potential for exosomes holds huge promise and may revolutionise the way in which we diagnose and manage breast cancer. These nanovesicles may be isolated from a variety of bodily fluids, including serum, and their miRNA content has been shown to reflect that of the parent breast cancer cell. This review will highlight the nomenclature and defining characteristics of exosomes, and current methods of isolation of serum‐derived exosomes. Initial promising reports on the potential utility of exosomal miRNAs to be used as breast cancer biomarkers will also be addressed.
Inflammatory bowel disease, cancer and medication: Cancer risk in the Dutch population‐based IBDSL cohort
Authors: van den Heuvel Tim R.A. , Wintjens Dion S.J. , Jeuring Steven F.G. , Wassink Maartje H.H. , Romberg‐Camps Marielle J.L. , Oostenbrug Liekele E. , Sanduleanu Silvia , Hameeteman Wim H. , Zeegers Maurice P. , Masclee Ad A. , Jonkers Daisy M. , Pierik Marie J.
Published: May 2016

The management of inflammatory bowel disease (IBD) has changed since the mid‐1990s (e.g., use of thiopurines/anti‐TNFα agents, improved surveillance programs), possibly affecting cancer risk. To establish current cancer risk in IBD, updates are warranted from cohorts covering this time span, and detailed enough to study associations with phenotype and medication. We studied intestinal‐, extra‐intestinal‐ and overall cancer risk in the Dutch population‐based IBDSL cohort. In total, 1,157 Crohn's disease (CD) and 1,644 ulcerative colitis (UC) patients were diagnosed between 1991 and 2011, and followed until 2013. Standardized incidence ratios (SIRs) were calculated for CD and UC separately, as well as for gender‐, phenotype‐, disease duration‐, diagnosis era‐ and medication groups. We found an increased risk for colorectal cancer in CD patients with colon involvement (SIR 2.97; 95% CI 1.08–6.46), but not in the total CD or UC population. In addition, CD patients were at increased risk for hematologic‐ (2.41; 1.04–4.76), overall skin‐ (1.55; 1.06–2.19), skin squamous cell‐ (SCC; 3.83; 1.83–7.04) and overall cancer (1.28; 1.01–1.60), whereas UC patients had no increased risk for extra‐intestinal‐ and overall cancer. Finally, in a medication analysis on CD and UC together, long‐term immunosuppression exposure (>12 months) was associated with an increased risk for hematologic cancer, non‐Hodgkin lymphoma, SCC and overall cancer, and this increase was mainly attributed to thiopurines. IBD patients with long‐term immunosuppression exposure can be considered as having a higher cancer risk, and our data support the advice in recent IBD guidelines to consider skin cancer screening in these patients.
Full statistical mediation of the relationship between trauma and depressive symptoms
Authors: Place Patricia J. , Ling Shichun , Patihis Lawrence
Published: May 2016

Owing to the potentially devastating effects of trauma‐induced depression, explaining the relationship between trauma and depressive symptoms is important. In this study, we measured lifelong exposure to potentially traumatic events and depressive symptoms in 370‐female undergraduates. We also measured anxiety, past negative time perspective and dissociation as potential mediators. Trauma exposure and depressive symptoms were related with a small but significant effect size (r = .16). Trauma was not associated with dissociation. We found that past negative time perspective and anxiety were full statistical mediators of this trauma‐depressive symptoms relationship. These two mediators combined accounted for all of the variance in that association. Anxiety accounted for more of the variance than past negative time perspective. A proposed explanation is that trauma both affectively elevates anxiety and cognitively creates an enduring focus on the events. Chronic anxiety and a past negative time perspective may lead to depression over time. The clinical implications are possible explanations as to why some treatments work.
Conceptualizing Big Data: Analysis of Case Studies
Authors: Ylijoki Ossi , Porras Jari
Published: May 2016

Digitization and the related datafication produce huge amounts of data. Organizations have started to exploit these new data in order to gain benefits. Exploring this ‘big data jungle’ is a new area for both scholars and practitioners, and the experiences of early adopters are valuable. This paper analyses big data use cases described in the academic literature by using computerized content analysis methods. Based on the analysis results, we have conceptualized themes and guidelines of big data in the context of an organization, thus contributing to the emerging research of big data. In addition to the realized benefits, the case studies reveal issues regarding technology, skills, organizational culture and decision‐making processes. The paper also points out several new research avenues, acts as a reference collection to big data case studies found in academic sources, and bridges theory and practice by pointing out several topics that practitioners should consider. Copyright © 2016 John Wiley & Sons, Ltd.
Subjective Well‐Being and Income: A Re‐Examination of Satiation Using the Regression Kink Model With an Unknown Threshold
Authors: Lien Donald , Hu Yue , Liu Long
Published: May 2016

A methodological challenge in testing Easterlin's paradox, which states that increasing income fails to boost happiness beyond a satiation point, lies in the determination of this threshold if it exists. In the existing literature, various levels of GDP per capita have been chosen based upon visual inspection of the scatter plots of the data. The estimated income–well‐being gradients are sensitive to the choice of such kink points. We first replicate the results in Stevenson and Wolfers (American Economic Review, Papers and Proceedings 2013; 103(3): 598–604), then apply the methods proposed in Hansen (Journal of Business and Economic Statistics 2016), which estimate the regression kink model with an unknown threshold, to the data in Stevenson and Wolfers () to re‐examine the two modified versions of Easterlin's hypothesis. In most cases, we do not find the existence of any kink point. In the few cases where a kink point is detected, the estimated kink point thresholds are different from those chosen in the previous literature. Overall, we find no evidence of a satiation point, which is in support of Stevenson and Wolfers (). Copyright © 2016 John Wiley & Sons, Ltd.
Synthesis of stiffness‐tunable and cell‐responsive Gelatin–poly(ethylene glycol) hydrogel for three‐dimensional cell encapsulation
Authors: Cao Ye , Lee Bae Hoon , Peled Havazelet Bianco , Venkatraman Subbu S.
Published: May 2016

Biosynthetic poly(ethylene glycol) (PEG)‐based hydrogels have been extensively investigated as extracellular matrix (ECM) mimicking gels as they retain the benefits of both ECM (biological cues) and synthetic hydrogels (tunable mechanical properties). In this article, we developed and characterized a new gelatin–PEG (GP) hydrogel that retains the benefits of gelatin and synthetic hydrogels. In this strategy, the thiolation of gelatin was accomplished by reacting with Traut's reagent; the thiolated gelatin was then conjugated to one end of PEG diacrylate (PEGDA) by Michael‐type addition reaction. Two kinds of GP precursors, GP30 and GP60, were synthesized by changing the amount of Traut's reagent, while the weight ratio between thiolated‐gelatin and PEGDA of GP30 and GP60 was 1.451:1 and 0.785:1, respectively. Finally, neonatal human dermal fibroblasts were encapsulated into the hydrogel by cross‐linking the remaining double bonds of precursor under ultraviolet light. These GP hydrogels can encapsulate the fibroblasts in situ with high cell viability. Moreover, the behaviors of cells within the GP hydrogels can be modulated by varying the cross‐linking density of GP hydrogel (storage modulus from 40 to 2000 Pa). In particular, this article showed that a minimum amount of cell‐binding motifs (gelatin >2.30 wt/vol % and 44.0% dry weight percentage) are required for attachment; and appropriate initial rheological and structural properties (storage modulus <∼100 Pa and mesh size >∼150 nm) can accelerate the attachment of cells and improve cell viability. Hence, this mixed‐hydrogel platform allows an easily control hydrogel structure and modulates cell behavior to reconstruct new tissue in the three‐dimensional microenvironments. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2401–2411, 2016.
Validating the Sensitivity of High‐Resolution Melting Analysis for JAK2 V617F Mutation in the Clinical Setting
Authors: Lin Chien‐Yu , Ho Cheng‐Mao , Tamamyan Gevorg , Yang Shu‐Fen , Peng Ching‐Tien , Chang Jan‐Gowth
Published: May 2016

Background

Janus kinase 2 (JAK2) plays an important role in normal hematopoietic growth factor signaling. The detection of the JAK2 V617F mutation (c.1849GNT, GTC → TTC) is crucial for the diagnosis of myeloproliferative neoplasm (MPN) and has become the essential criteria for diagnosis of MPN by the WHO. High‐resolution melt (HRM) curve analysis is a nongel‐based, closed‐tube method, in which PCR amplification and subsequent analysis are sequentially performed in the well, making it more convenient than other scanning methodologies.

Methods

We evaluated JAK2 V617F mutation by HRM. Twenty‐nine patients diagnosed with MPN were examined. We studied the analytical sensitivity of the HRM analysis using real‐time polymerase chain reaction (PCR) for identifying the JAK2 V617F mutation. Additionally, the sensitivity of HRM analysis and allele‐specific PCR (AS‐PCR) assay was compared.

Results

The JAK2 V617F mutation was successfully discriminated at an abundance of 6% or above in HRM analysis. Both HRM analysis and AS‐PCR showed 100% accuracy with detection limits of 6% and 2.5%, respectively.

Conclusion

HRM analysis is a fast, simple, reliable, and nonexpensive method for the detection of the JAK2 V617F mutation. However, more validation of the detection limits of HRM analysis should be performed before declaration of the analytic sensitivity of the method.