bluuebunny/crossref_metadata_2025 huggingface dataset:
Augmenting Bowen Family of Origin Work: Using the Genogram and Therapeutic Art‐based Activity
Authors: Gatfield Emma
Published: June 2017

This article explores the use of creative artistic activity and metaphor to augment Bowen family of origin work. It draws on the case study of a couple engaging in premarital counselling to illustrate several ways that art making can be used to enhance Bowen systemic processes. It illustrates the value of collaborative genograms and related creative products to offer a supplementary voice for salient, verbally inexpressible content while supporting clients in externalising and processing difficult emotions with reduced reactivity.
Sometimes Words Just Ain't Enough – Enhancing the Contribution of Children in Therapy through Creative Expression
Authors: Klop Saskia
Published: June 2017

The meaningful inclusion of children in family therapy is an ideal that therapists readily align with and yet struggle to implement effectively. Within a practice that relies heavily on verbal expression, young children provide a unique challenge for therapists, who require developmentally appropriate opportunities for the child to express, document, and share his or her experience in all its richness and colour. In this paper the author utilises art therapy to support greater inclusion of children in family therapy by capitalising on their creative talents and facilitating the child's visual story within the family dialogue. This can assist in the formulation and treatment of systemic issues.
Cost‐effective teaching of radiology with preclinical anatomy
Authors: Wilson James S. , Alvarez Jacqueline , Davis Bonnie C. , Duerinckx Andre J.
Published: June 2017

Graduating physicians in all subspecialties have an increased need for competency in radiology, particularly since the use of diagnostic imaging continues to grow. To integrate the teaching of radiology with anatomy during the first year of medical school at Howard University, a novel approach was developed to overcome the limitations of resources including funding, faculty, and curricular time. The resulting program relies on self‐study and peer‐to‐peer interactions to develop proficiency at manipulating free versions of medical image viewer software (using the DICOM standard), identifying normal anatomy in medical images, and applying critical thinking skills to understand common clinical conditions. An effective collaborative relationship between a radiologist and anatomist was necessary to develop and implement the program of anatomic–radiographic instruction which consists of five tiers: (1) initial exposure to anatomy through dissection which provides a foundation of knowledge; (2) study of annotated radiographs from atlases; (3) a radiology quiz open to group discussions; (4) small group study of clinical cases with diagnostic images; and (5) radiographic tests. Students took all quizzes and tests by working from image datasets preloaded on their personal computers, mimicking the approach by which radiologists analyze medical images. In addition to stimulating student support of a new teaching initiative, the strengths of Howard's program are that it can be introduced into an existing preclinical curriculum in almost any medical school with minimal disruption, it requires few additional resources to implement and run, and its design is consistent with the principles of modern education theory. Anat Sci Educ 11: 196–206. © 2017 American Association of Anatomists.
Bifunctional Boron Phosphate as an Efficient Catalyst for Epoxide Activation to Synthesize Cyclic Carbonates with CO2
Authors: Xue Zhimin , Zhao Xinhui , Wang Jinfang , Mu Tiancheng
Published: June 2017

Development of inexpensive, easily prepared, non‐toxic, and efficient catalysts for the cycloaddition of CO2 with epoxides to synthesize five‐membered cyclic carbonates is a very attractive topic in the field of CO2 transformation. In this work, we conducted the first work on the cycloaddition of CO2 with epoxides to produce cyclic carbonates catalyzed by a binary catalyst system consisting of KI and boron phosphate (BPO4), which are both inexpensive and non‐toxic, and various corresponding cyclic carbonates could be produced with high yields (93–99 %) at 110 °C with a CO2 pressure of 4 MPa under solvent‐free conditions. In the BPO4/KI catalyst system, BPO4, a Brønsted and Lewis acid hybrid, played the role of activating the epoxy ring through the formation of hydrogen bonds with Brønsted acidic sites and the interaction with Lewis acidic sites simultaneously, and thus enhanced the activity of KI for the cycloaddition of CO2 with epoxides significantly. Additionally, the activity of the BPO4/KI catalyst system showed no noticeable decrease after being reused five times, indicating that the BPO4 was stable under the reaction conditions.
Some closed form robust moment‐based estimators for the MEM(1,1)
Authors: Lu Wanbo , Ke Rui
Published: June 2017

In this paper, we extend the closed form moment estimator (ordinary MCFE) for the autoregressive conditional duration model given by Lu et al (2016) and propose some closed form robust moment‐based estimators for the multiplicative error model to deal with the additive and innovational outliers. The robustification of the closed form estimator is done by replacing the sample mean and sample autocorrelation with some robust estimators. These estimators are more robust than the quasi‐maximum likelihood estimator (QMLE) often used to estimate this model, and they are easy to implement and do not require the use of any numerical optimization procedure and the choice of initial value. The performance of our proposal in estimating the parameters and forecasting conditional meanμtof the MEM(1,1) process is compared with the proposals existing in the literature via Monte Carlo experiments, and the results of these experiments show that our proposal outperforms the ordinary MCFE, QMLE, and least absolute deviation estimator in the presence of outliers in general. Finally, we fit the price durations of IBM stock with the robust closed form estimators and the benchmarks and analyze their performances in estimating model parameters and forecasting the irregularly spaced intraday Value at Risk.
Cell migration analysis: A low‐cost laboratory experiment for cell and developmental biology courses using keratocytes from fish scales
Authors: Prieto Daniel , Aparicio Gonzalo , Sotelo‐Silveira Jose R.
Published: June 2017

Cell and developmental processes are complex, and profoundly dependent on spatial relationships that change over time. Innovative educational or teaching strategies are always needed to foster deep comprehension of these processes and their dynamic features. However, laboratory exercises in cell and developmental biology at the undergraduate level do not often take into account the time dimension. In this article, we provide a laboratory exercise focused in cell migration, aiming to stimulate thinking in time and space dimensions through a simplification of more complex processes occurring in cell or developmental biology. The use of open‐source tools for the analysis, as well as the whole package of raw results (available at http://github.com/danielprieto/keratocyte) make it suitable for its implementation in courses with very diverse budgets.

Aiming to facilitate the student's transition from science‐students to science‐practitioners we propose an exercise of scientific thinking, and an evaluation method. This in turn is communicated here to facilitate the finding of common caveats and weaknesses in the process of producing simple scientific communications describing the results achieved. © 2017 by The International Union of Biochemistry and Molecular Biology, 45(6):475–482, 2017.
Iatrogenic right coronary artery dissection caused by diagnostic transradial cardiac catheterization
Authors: Baghdasaryan David , Nazaryan Aram
Published: June 2017

Key Clinical Message

We are presenting rare, but life‐threatening complication of diagnostic coronary catheterization. To overcome the problem requires operator's experience and appropriate actions. We want to share our experience to interventionalists to be aware and ready to recognize and overcome such complication.
Acute suppurative thyroiditis caused by Streptococcus agalactiae infection: a case report
Authors: Akuzawa Nobuhiro , Yokota Toru , Suzuki Tsukasa , Kurabayashi Masahiko
Published: June 2017

Key Clinical Message

Acute suppurative thyroiditis is a serious disease; therefore, its diagnosis in the acute phase is important. Fine needle aspiration biopsy of the thyroid gland plays a pivotal role in the diagnosis of acute suppurative thyroiditis. Appropriate culture technique and optimal imaging modalities are also important for its diagnosis.
Selective One‐Pot Two‐Step C−C Bond Formation using Metal–Organic Frameworks with Mild Basicity as Heterogeneous Catalysts
Authors: Cirujano Francisco G. , López‐Maya Elena , Rodríguez‐Albelo Marleny , Barea Elisa , Navarro Jorge A. R. , De Vos Dirk E.
Published: June 2017

Copper‐ion‐exchanged nickel pyrazolate frameworks behave as selective heterogeneous catalysts for the one‐pot, two‐step (Henry reaction/Michael type addition) synthesis of neuroactive pharmaceutical intermediates starting from nitromethane and benzaldehyde. Tuning the basicity of multifunctional metal–organic framework catalysts through ion exchange with copper(II) cations allows the tandem C−C bond‐forming process to be selectively directed towards the desired pharmaceutical intermediate.
A Dumbbell CaBi2O4 Photoelectrode for Photoelectrochemical Water Splitting
Authors: Wang Xuan , Liu Zhihua , Liu Zhifeng
Published: June 2017

This paper describes a promising film based on the dumbbell‐shaped CaBi2O4 nanostructure that is applied in photoelectrochemical (PEC) water splitting as a photoelectrode for the first time. The morphology and microstructure of CaBi2O4 were characterized in detail. PEC measurements showed that the dumbbell‐shaped CaBi2O4 nanostructure film, on the basis of the optimal hydrothermal time, exhibited higher photoelectrochemical activity, as the photocurrent density reached up to 1.19 mA cm−2. The remarkable PEC performance may stem from excellent light absorbance and efficient charge–hole pair separation and collection. This research indicates that the dumbbell‐like CaBi2O4 nanostructure film has enormous potential in PEC water splitting.
Cinchona alkaloid derivatives catalyzed asymmetric aza‐Friedel–crafts reaction of α‐naphthols with aryl aldimines
Authors: Li Ya Wei , Wang Li Ming , Jin Ying , Chang Sheng
Published: June 2017

Cinchona alkaloid derivatives as organocatalysts were applied in the asymmetric aza‐Friedel–Crafts reaction of α‐naphthol with aryl aldimines. The desired chiral aminoarylnaphthols were obtained in 85% enantiomeric excess.
A Multifunctional Radiotheranostic Agent for Dual Targeting of Breast Cancer Cells
Authors: Vultos Filipe , Fernandes Célia , Mendes Filipa , Marques Fernanda , Correia João D. G. , Santos Isabel , Gano Lurdes
Published: June 2017

A straightforward synthetic route for a new multifunctional 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) derivative is described. To demonstrate the versatility of this pro‐chelator for the preparation of radiolabeled hybrid compounds containing two different biological targeting moieties, an antitumor agent (e.g., a DNA‐intercalating agent) and an estrogen receptor (ER) ligand (e.g., LXXLL‐based peptide) were regiospecifically conjugated to the DOTA derivative. The bifunctional probe was radiolabeled with the auger electron emitter indium‐111, and the resulting radioconjugate was demonstrated to induce DNA damage in vitro, which, along with the nuclear internalization exhibited in breast cancer cells, might enhance its therapeutic activity. This favorable in vitro performance suggests that these hybrid compounds could be attractive probes for theranostic applications.
Koi Fish‐Scale Iridophore Cells Orient Guanine Crystals to Maximize Light Reflection
Authors: Funt Nir , Palmer Benjamin A. , Weiner Steve , Addadi Lia
Published: June 2017

Fish‐scale iridophore cells deposit guanine crystals and assemble them into multilayer reflectors to produce silvery reflectance. The crystal orientation controls the reflective properties of the fish scales, but little is known about the degree of orientation of the guanine crystals and whether this orientation is pre‐determined at the level of an individual cell. Koi fish‐scale‐attached iridophores, iridophores on regenerated scales, and cultured iridophores were examined by using light microscopy and synchrotron micro‐X‐ray diffraction. More than 95 % of the thin {100} guanine crystal plates in the iridophores of the mature and regenerated scales are oriented parallel to the scale surface and perpendicular to the direction of the incoming light. More than 70 % of the crystals in cultured iridophore cells are also in this orientation. The crystals are elongated and within each cell on the mature scale and in the cultured cells the long morphological axes are well aligned with the long axis of the iridophore. In contrast to the cultured iridophores, in the mature scale the iridophore cells are co‐aligned with each other. Cultured iridophores are flexible and motile, and azimuthal crystal orientations vary as the cells move. We conclude that iridophore cells function as independent units and that the control over crystal orientation is pre‐determined at the individual cell level in the direction that is essential for function, namely, exposing the large reflecting crystal surface to light.
The Ussing Chamber Assay to Study Drug Metabolism and Transport in the Human Intestine
Authors: Kisser Beatrice , Mangelsen Eva , Wingolf Caroline , Partecke Lars Ivo , Heidecke Claus‐Dieter , Tannergren Christer , Oswald Stefan , Keiser Markus
Published: June 2017

The Ussing chamber is an old but still powerful technique originally designed to study the vectorial transport of ions through frog skin. This technique is also used to investigate the transport of chemical agents through the intestinal barrier as well as drug metabolism in enterocytes, both of which are key determinants for the bioavailability of orally administered drugs. More contemporary model systems, such as Caco‐2 cell monolayers or stably transfected cells, are more limited in their use compared to the Ussing chamber because of differences in expression rates of transporter proteins and/or metabolizing enzymes. While there are limitations to the Ussing chamber assay, the use of human intestinal tissue remains the best laboratory test for characterizing the transport and metabolism of compounds following oral administration. Detailed in this unit is a step‐by‐step protocol for preparing human intestinal tissue, for designing Ussing chamber experiments, and for analyzing and interpreting the findings. © 2017 by John Wiley & Sons, Inc.
Cobalt‐Based Active Species Molecularly Immobilized on Carbon Nanotubes for the Oxygen Reduction Reaction
Authors: Kim Sujin , Jang Dawoon , Lim Joonwon , Oh Junghoon , Kim Sang Ouk , Park Sungjin
Published: June 2017

Hybrid systems in which molecule‐based active species are combined with nanoscale materials may offer valuable routes to enhance catalytic performances for electrocatalytic reactions. The development of rationally designed, cost‐effective, efficient catalysts for the oxygen reduction reaction (ORR) is a crucial challenge for applications in fuel cells and metal–air batteries. A new hybrid ORR catalyst has been synthesized through a well‐defined reaction between Co‐based organometallic molecules and N‐doped multiwalled carbon nanotubes (MWCNTs) at room temperature. The hybrid ORR catalyst shows excellent catalytic performance with an onset potential of 0.95 V [vs. the reversible hydrogen electrode (RHE)], superior durability, and good methanol tolerance. Chemical and structural characterization after many reaction cycles reveals that the Co‐based organometallic species maintained the original structure of cobalt(II) acetylacetonate with coordination to the heteroatoms of the MWCNTs. A thorough electrochemical investigation indicates that the major catalytically active site is Co−O4−NCNT.
A Method for Analyzing and Visualizing Intermodule Relations to Support the Reuse‐Based Embedded Software Development
Authors: KAMBE HIDETOSHI , KITAGAMI SHINJI , SAWAMOTO JUN , MITSUI HIROYASU , KOIZUMI HISAO
Published: June 2017

The number of lines of code in embedded software has been growing. In reuse‐based embedded software development, there are more and more cases in which software from two or more products is combined. The reuse of existing software has thus become inevitable. However, if the existing software to be reused is not well managed or organized, there is no way to know which modules will be affected when some parts of the reused software are modified. In this paper, we propose a method to accomplish the effective reuse of software modules by managing dependency information among modules and adding development management property data to each module. We have developed a configuration management tool that visualizes the mutual relations among existing software modules and visually presents not only the dependencies among modules but also the development management property data of the modules based on the developer's demand for the reuse of modules. We evaluated the method by applying it to some actual development projects.
Predation risk: a potential mechanism for effects of a wind energy facility on Greater Prairie‐Chicken survival
Authors: Smith J. A. , Brown M. B. , Harrison J. O. , Powell L. A.
Published: June 2017

Recent expansion of the wind energy industry has raised concerns about the potential effects of wind energy facilities on prairie grouse. For example, efforts have been made to evaluate indirect effects on prairie grouse survival, but it is also critical to investigate the underlying mechanisms to direct conservation strategies. The objective of this study was to investigate the indirect effects of a wind energy facility on the survival of female Greater Prairie‐Chickens (Tympanuchus cupido pinnatus) and on the occupancy of avian and mammalian predators. Between March and July of 2013 and 2014, we investigated spatial variation in predation risk by sampling occupancy of mammalian and avian predators within 10 km of a wind energy facility constructed in 2005 in Brown County, Nebraska, USA. During the same period, we assessed spatial variation in daily survival of radio‐marked females within the same area. We found little evidence that probability of site occupancy (Ψ) of avian predators was lower near the wind energy facility (within 2 km: Ψ = 0.70, 95% CI = 0.22–0.95; beyond 2 km: Ψ = 0.93, 95% CI = 0.02–1.00), suggesting that avian predators did not display local‐scale avoidance behavior around wind turbines. Mammalian predators were documented at all of our sample locations, but the capture index for all mammals was lower at sample sites near the wind turbines (P = 0.004). Occupancy of coyotes (Canis latrans), the likely main mammalian predator of adult prairie‐chickens in the area, did not vary significantly throughout our study site (within 0.5 km of wind energy facility: Ψ = 0.65, 95% CI = 0.07–0.98; beyond 0.5 km: Ψ = 0.96, 95% CI = 0.04–1.00), although trends were in the direction expected if coyotes were avoiding the wind energy facility. Distance to wind turbine had no effect on daily survival (SD) of female prairie‐chickens (SD = 0.9948, SE = 0.0015). The potential for predators to avoid wind energy facilities, and thus affect predation risk, underscores the complexity of planning to address potential impacts of wind energy as variation in predation risk may have consequences for the population viability of a wide range of species at risk from wind energy development.
Nanostructured Platinum‐iridium Alloy Microelectrode for Ammonia Determination
Authors: Jiang Junhua , Zhang Lei
Published: June 2017

Nanostructured platinum‐iridium alloy microelectrode with high surface area was successfully prepared by applying successive potential cycles to a conventional PtIr microdisc in ionic liquid electrolyte containing ZnCl2at elevated temperature. Scanning‐electron microscope studies show that a very thin nanostructured film was created on the electrode upon 20 potential cycles between −2.0 and 0.75 V versus a Ag pseudo‐reference electrode. The film nanostructures are characteristic of regular hill‐like nano‐spacings separated by valley‐like nano‐cracks, and a roughness factor of approximately 40. The nanostructured electrode is highly active towards electrochemical oxidation of ammonia, and generates a linear relation between voltammetric peak currents (or chronoamperometric currents), and logarithm of ammonia concentration in a range of approximately 1 ppm to 10000 ppm. It has been proposed that theTemkinadsorption of ammonia from the bulk solution onto the electrode surfaces was involved in its electrochemical oxidation and could be responsible for the linear current‐logarithmic concentration relation.
One‐on‐one contract game–based dynamic virtual machine migration scheme for Mobile Edge Computing
Authors: Kim Sungwook
Published: June 2017

In the evolution toward fifth‐generation networks, Mobile Edge Computing (MEC) is an emerging paradigm, conceived to meet the ever‐increasing computational demands of mobile applications. Within the access range of mobile devices, the MEC technique promises the enablement of efficient Mobile Cloud Computing services. In an MEC system, virtual machine (VM) migration is a key issue; VM migration is the process of moving a VM from an edge node to another edge node. To improve service quality and system performance, the VM migration method has a dual focus on the MEC system's computation and communication resources. In this study, we formulate the VM migration problem as a one‐on‐one contract game model and develop a learning‐based price control mechanism to effectively handle the MEC's resource. By using the game methodology and learning process, our approach is able to capture the dynamics of MEC systems, and it interacts continually with an unknown system environment. Finally, extensive simulation results are provided to demonstrate the capability of the proposed approach in achieving, with respect to existing MEC schemes, both higher resource utilization and system throughput, as well as reduced service drop ratio and reduced service delay.
Toward the network of the future: From enabling technologies to 5G concepts
Authors: Bega Dario , Gramaglia Marco , Bernardos Cano Carlos Jesus , Banchs Albert , Costa‐Perez Xavier
Published: June 2017

There is a wide consensus by the research community and the industry that it will not be possible to satisfy future mobile traffic demand and application requirements by simply evolving the current fourth‐generation architecture. Instead, there is a need for a considerable revision of the mobile network system: such an effort is commonly referred to as the future fifth‐generation (5G) architecture, and large‐scale initiatives all around the globe have been launched worldwide to address this challenge. While these initiatives have not yet defined the future 5G architecture, the research community has already invested a very substantial effort on the definition of new individual technologies. The fact that all new proposals are tagged as 5G has created a lot of confusion on what 5G really is. The aim of this article is to shed some light on the current status of the 5G architecture definition and the trends on the required technologies. Our key contributions are the following: (1) we review the requirements for 5G identified by the different worldwide initiatives, highlighting similarities and differences; (2) we discuss current trends in technologies, showing that there is a wide consensus on the key enablers for 5G; and (3) we make an effort to understand the new concepts that need to be devised, building on the enablers, to satisfy the desired requirements.
Species, genera, and phylogenetic structure in the human fossil record: a modest proposal
Authors: Tattersall Ian
Published: June 2017

Because of the greater morphological distances among them, genera should be more robustly recognizable in the fossil record than species are. But there are clearly upper as well as lower bounds to their species inclusivity. Currently, the vast majority of fossils composing the large and rapidly expanding paleoanthropological record are crammed into one of two genera (Australopithecus vs Homo), expanding the latter, especially, far beyond any reasonable morphological or phylogenetic limits. This excessive inclusivity obscures both diversity and the complexities of phylogenetic structure within the hominid family.
The North African Middle Stone Age and its place in recent human evolution
Authors: Scerri Eleanor M. L.
Published: June 2017

The North African Middle Stone Age (NAMSA, ∼300‐24 thousand years ago, or ka) features what may be the oldest fossils of our species as well as extremely early examples of technological regionalization and ‘symbolic’ material culture (d'Errico, Vanhaeren, Barton, Bouzouggar, Mienis, Richter, Hublin, McPherron, Louzouet, & Klein, ; Scerri, ; Richter, Grün, Joannes‐Boyau, Steele, Amani, Rué, Fernandes, Raynal, Geraads, Ben‐Ncer Hublin, McPherron, ). The geographic situation of North Africa and an increased understanding of the wet‐dry climatic pulses of the Sahara Desert also show that North Africa played a strategic role in continental‐scale evolutionary processes by modulating human dispersal and demographic structure (Drake, Blench, Armitage, Bristow, & White, ; Blome, Cohen, Tryon, Brooks, & Russell, ). However, current understanding of the NAMSA remains patchy and subject to a bewildering array of industrial nomenclatures that mask underlying variability. These issues are compounded by a geographic research bias skewed toward non‐desert regions. As a result, it has been difficult to test long‐established narratives of behavioral and evolutionary change in North Africa and to resolve debates on their wider significance. In order to evaluate existing data and identify future research directions, this paper provides a critical overview of the component elements of the NAMSA and shows that the timing of many key behaviors has close parallels with others in sub‐Saharan Africa and Southwest Asia.
Sky‐High Promise (and Potential Pitfalls) of Drones
Authors: Turner Joshua S. , Ross Katy M. , Lin John T.
Published: June 2017

Few technologies today raise as many interesting legal issues as the use of unmanned aircraft systems, known as UASs or (less formally) “drones.”
The new‐generation pan‐peroxisome proliferator‐activated receptor agonist IVA337 protects the liver from metabolic disorders and fibrosis
Authors: Wettstein Guillaume , Luccarini Jean‐Michel , Poekes Laurence , Faye Patrick , Kupkowski Francine , Adarbes Vanessa , Defrêne Evelyne , Estivalet Céline , Gawronski Xavier , Jantzen Ingrid , Philippot Alain , Tessier Julien , Tuyaa‐Boustugue Pascale , Oakley Fiona , Mann Derek A. , Leclercq Isabelle , Francque Sven , Konstantinova Irena , Broqua Pierre , Junien Jean‐Louis
Published: June 2017

IVA337 is a pan‐peroxisome proliferator‐activated receptor (PPAR) agonist with moderate and well‐balanced activity on the three PPAR isoforms (α, γ, δ). PPARs are regulators of lipid metabolism, inflammation, insulin resistance, and fibrogenesis. Different single or dual PPAR agonists have been investigated for their therapeutic potential in nonalcoholic steatohepatitis (NASH), a chronic liver condition in which steatosis coexists with necroinflammation, potentially leading to liver fibrosis and cirrhosis. Clinical results have demonstrated variable improvements of histologically assessed hepatic lesions depending on the profile of the tested drug, suggesting that concomitant activation of the three PPAR isoforms would translate into a more substantial therapeutic outcome in patients with NASH. We investigated the effects of IVA337 on several preclinical models reproducing the main metabolic and hepatic features associated with NASH. These models comprised a diet‐induced obesity model (high‐fat/high‐sucrose diet); a methionine‐ and choline‐deficient diet; the foz/foz model; the CCl4‐induced liver fibrosis model (prophylactic and therapeutic) and human primary hepatic stellate cells. IVA337 normalized insulin sensitivity while controlling body weight gain, adiposity index, and serum triglyceride increases; it decreased liver steatosis, inflammation, and ballooning. IVA337 demonstrated preventive and curative effects on fibrosis in the CCl4 model and inhibited proliferation and activation of human hepatic stellate cells, the key cells driving liver fibrogenesis in NASH. Moreover, IVA337 inhibited the expression of (pro)fibrotic and inflammasome genes while increasing the expression of β‐oxidation‐related and fatty acid desaturation‐related genes in both the methionine‐ and choline‐deficient diet and the foz/foz model. For all models, IVA337 displayed an antifibrotic efficacy superior to selective PPARα, PPARδ, or PPARγ agonists. Conclusion: The therapeutic potential of IVA337 for the treatment of patients with NASH is supported by our data. (Hepatology Communications 2017;1:524–537)
Mn‐[4‐Chlorophenyl‐Salicylaldimine‐Methylpyranopyrazole]Cl2 as a Novel Nanostructured Schiff Base Complex and Catalyst
Authors: Moosavi‐Zare Ahmad Reza , Goudarziafshar Hamid , Dastbaz Sharmin
Published: June 2017

Mn‐[4‐chlorophenyl‐salicylaldimine‐methylpyranopyrazole]Cl2 ([Mn‐4CSMP]Cl2) as nano‐Schiff base complex was prepared and fully characterized by Fourier transform infrared spectroscopy, X‐ray diffraction, thermal gravimetric analysis, derivative thermogravimetry, scanning electron microscopy, energy‐dispersive X‐ray analysis, and UV–vis spectroscopy. The reactivity of nano‐[Mn‐4CSMP]Cl2 as a catalyst was tested on the tandem cyclocondensation–Knoevenagel condensation–Michael reaction between phenylhydrazine and ethyl acetoacetate with various aromatic aldehydes to give 4,4′‐(arylmethylene)‐bis‐(3‐methyl‐1‐phenyl‐1H
‐pyrazol‐5‐ol)s derivatives.
Utilization of the Bridging Strategy for the Development of New Drugs in Oncology to Avoid Drug Lag
Authors: Kogure Seiji , Koyama Nobuyuki , Hidaka Shinji
Published: June 2017

Global trial (GT) strategy and bridging (BG) strategy are currently the main clinical development strategies of oncology drugs in Japan, but the relationship between development style and drug lag and how the bridging strategy has contributed to the solution of drug lag have not been clear. We investigated the potential factors that influenced submission lag (SL), and also compared the differences in SL among early‐initiation BG strategy, late‐initiation BG strategy, and GT strategy. A stepwise linear regression analysis identified the potential factors that shorten SL: development start lag and development style. Comparison of the differences in SL among the strategies also indicated that the SL in the GT strategy and that in the early‐initiation BG strategy were significantly shorter than that in the late‐initiation BG strategy. The findings in our study suggest that the late‐initiation BG strategy may not contribute to shortening drug lag. Because the number of late‐initiation BG studies has not decreased, we propose first that pharmaceutical companies should initiate clinical development as early as possible in Japan so that they can choose the GT strategy as a first option at the next step, and second when they cannot choose the GT strategy after investigating differences in exposure between Japanese and non‐Japanese in a phase 1 study, they should select the early BG strategy to avoid future drug lag. It is also important for the regulatory authorities to provide reasonable guidance to have a positive impact on strategic decisions, even for foreign‐capital companies.
Vortex‐ultrasound‐assisted dispersive liquid–liquid microextraction coupled with gas chromatography–mass spectrometry for the analysis of volatile bioactive components and comparative pharmacokinetic study of the herb–herb interactions in Guanxin Shutong Capsule
Authors: Mu Jingqing , Gao Xun , Li Qing , Yang Xiaomei , Yang Wenling , Sun Xu , Bi Kaishun , Zhang Huifen
Published: June 2017

Guanxin Shutong Capsule, an effective traditional Chinese medicine, is widely used for coronary heart disease clinically. Volatile components are one of its important bioactive constituents. To better understand the material basis for the therapeutic effects, the components of Guanxin Shutong Capsule absorbed into the blood and their metabolites were identified based on gas chromatography with mass spectrometry coupled with vortex‐ultrasound‐assisted dispersive liquid–liquid microextraction. As a result, three prototypes and 15 metabolites were identified or tentatively characterized in rat plasma. Subsequently, a pharmacokinetic study was carried out to monitor the concentrations of the main bioactive constituents and metabolites (isoborneol, borneol, eugenol, and camphor) by gas chromatography with mass spectrometry in rat plasma following oral administration of single herb extract and different combinations of herbs in this prescription. Compared to other groups, a statistically significant difference of the pharmacokinetic properties was obtained when the total complex prescription was administered, indicating possible drug–drug interactions among the complex ingredients of Guanxin Shutong Capsule. These findings provided an experimental basis concerning the clinical application and medicinal efficacy of Guanxin Shutong Capsule in the treatment of coronary heart disease.
Common Findings in Late‐Gestation Fetal Echocardiography
Authors: Tague Lauren , Donofrio Mary T. , Fulgium Amanda , McCarter Robert , Limperopoulos Catherine , Schidlow David N.
Published: June 2017

Objectives

Fetal echocardiography provides detailed information about cardiac structure and function in utero. Limited information is available regarding normal findings late in pregnancy. We therefore sought to identify and describe common cardiac findings in late gestation.

Methods

Fetuses with structurally normal hearts were identified in mid gestation within a subset of pregnant women in a prospective study. The atrioventricular valves, right and left atria, aortic isthmus and ductus arteriosus dimensions and flow abnormalities, aneurysm of the septum primum, and presence and grade of tricuspid regurgitation were assessed throughout pregnancy. Linear and logistic regression analyses were used to characterize changes in quantitative and qualitative fetal echocardiographic parameters by gestational age (GA).

Results

Forty fetuses between 24 and 38 weeks' GA were studied. Each had a fetal echocardiographic study completed before and after 34 weeks' gestation, which were compared. Tricuspid‐to‐mitral valve and right‐to‐left atrium ratios increased with GA (P < .001). More frequently noted after 34 weeks were tapering of the ductus arteriosus (2.5% versus 32%), prominent aortic isthmus diastolic flow (5% versus 67%), prominent ductus arteriosus diastolic flow (2.5% versus 25%), trivial or mild tricuspid regurgitation (35% versus 80%), and aneurysms of the septum primum (37.5% versus 80%). These findings all increased linearly with GA (P < .001).

Conclusions

Atrioventricular valve and right/left atrium disproportion, mild ductus arteriosus tapering, prominent aortic isthmus and ductus arteriosus diastolic flow, trivial or mild tricuspid regurgitation, and aneurysms of the septum primum are frequently identified after 34 weeks' GA. Their identification suggests that these fetal echocardiographic findings in isolation are likely normal and are results of the physiologic alterations that occur late in the third trimester.
Spatially explicit population estimates for black bears based on cluster sampling
Authors: Humm Jacob M. , McCown J. Walter , Scheick Brian K. , Clark Joseph D.
Published: June 2017

We estimated abundance and density of the 5 major black bear (Ursus americanus) subpopulations (i.e., Eglin, Apalachicola, Osceola, Ocala‐St. Johns, Big Cypress) in Florida, USA with spatially explicit capture‐mark‐recapture (SCR) by extracting DNA from hair samples collected at barbed‐wire hair sampling sites. We employed a clustered sampling configuration with sampling sites arranged in 3 × 3 clusters spaced 2 km apart within each cluster and cluster centers spaced 16 km apart (center to center). We surveyed all 5 subpopulations encompassing 38,960 km2during 2014 and 2015. Several landscape variables, most associated with forest cover, helped refine density estimates for the 5 subpopulations we sampled. Detection probabilities were affected by site‐specific behavioral responses coupled with individual capture heterogeneity associated with sex. Model‐averaged bear population estimates ranged from 120 (95% CI = 59–276) bears or a mean 0.025 bears/km2(95% CI = 0.011–0.44) for the Eglin subpopulation to 1,198 bears (95% CI = 949–1,537) or 0.127 bears/km2(95% CI = 0.101–0.163) for the Ocala‐St. Johns subpopulation. The total population estimate for our 5 study areas was 3,916 bears (95% CI = 2,914–5,451). The clustered sampling method coupled with information on land cover was efficient and allowed us to estimate abundance across extensive areas that would not have been possible otherwise. Clustered sampling combined with spatially explicit capture‐recapture methods has the potential to provide rigorous population estimates for a wide array of species that are extensive and heterogeneous in their distribution. © 2017 The Wildlife Society.
Multiple solutions for Kirchhoff‐type problems with variable exponent and nonhomogeneous Neumann conditions
Authors: Heidarkhani Shapour , De Araujo Anderson L. A. , Afrouzi Ghasem A. , Moradi Shahin
Published: June 2017

The existence of at least three weak solutions for a class of differential equations with ‐Kirchhoff‐type and subject to small perturbations of nonhomogeneous Neumann conditions is established under suitable assumptions. Our technical approach is based on variational methods. In addition, an example to illustrate our results is given.
Abrasive wear behavior of various reinforced AA6061 matrix composites produced with hot pressing process: A comparative study
Authors: Ismail O.
Published: June 2017

The effects of various reinforcements (boron carbide ‐silicon carbide‐alumina) with constant volume fraction (20 %) on the abrasive wear properties of AA6061 matrix composites produced with hot pressing process were investigated. The wear tests were carried out using a pin‐on‐disk wear tester by sliding at sliding speeds of 1.2 m/s against silicon carbide paper. Applied normal loads have 5, 10 and 15 N magnitude at room temperature. The wear morphologies of the worn surfaces were analyzed using a scanning electron microscope in order to examine the wear characteristics and to investigate the wear mechanisms. The effects of reinforcement type on the wear behavior of AA6061 matrix composites were observed. Results exhibited that the optimum wear resistance obtained with the boron carbide reinforced composite parts. All reinforced samples showed better wear resistance compared to as‐received samples in all the studied conditions. Scanning electron microscope characterization showed that test specimens have complex combination of wear mechanisms on the worn surface.
Effect of the structural reinforcement of composite adherends on the mechanical strength of adhesive joints
Authors: Hunter R. , Vizán A. , Peréz J. , Möller J. , Leyrer J. , Silva L.F.M. da
Published: June 2017

This study proposes a novel method to strengthen fiber reinforced plastic (FRP) adherends in a single lap joint (SLJ) by using Kevlar threads. The adherend reinforcement procedure consists of applying a zigzag thread in the fiber glass layers that comprise the adherend in order to subsequently manufacture the adherends using the vacuum infusion method. For this study, three single lap joint configurations were used: Adherends without Kevlar reinforcement (SLJ1), adherends with Kevlar reinforcement with a medium step zigzag (SLJ2) and adherends with Kevlar reinforcement with a small step zigzag (SLJ3). Mechanical tensile tests were carried out to determine the ultimate strength and displacement of the single lap joint configurations studied. Adherends reinforced by Kevlar threads increase the strength and displacement of the single lap joint. However, the influence of the step size of zigzag threads on the adherend does not significantly influence the strength, but significantly affects the maximum displacement of the single lap joint.
Mesocorticolimbic hemodynamic response in Parkinson's disease patients with compulsive behaviors
Authors: Claassen Daniel O. , Stark Adam J. , Spears Charis A. , Petersen Kalen J. , van Wouwe Nelleke C. , Kessler Robert M. , Zald David H. , Donahue Manus J.
Published: June 2017

Background

PD patients treated with dopamine therapy can develop maladaptive impulsive and compulsive behaviors, manifesting as repetitive participation in reward‐driven activities. This behavioral phenotype implicates aberrant mesocorticolimbic network function, a concept supported by past literature. However, no study has investigated the acute hemodynamic response to dopamine agonists in this subpopulation.

Objectives

We tested the hypothesis that dopamine agonists differentially alter mesocortical and mesolimbic network activity in patients with impulsive‐compulsive behaviors.

Methods

Dopamine agonist effects on neuronal metabolism were quantified using arterial‐spin‐labeling MRI measures of cerebral blood flow in the on‐dopamine agonist and off‐dopamine states. The within‐subject design included 34 PD patients, 17 with active impulsive compulsive behavior symptoms, matched for age, sex, disease duration, and PD severity.

Results

Patients with impulsive‐compulsive behaviors have a significant increase in ventral striatal cerebral blood flow in response to dopamine agonists. Across all patients, ventral striatal cerebral blood flow on‐dopamine agonist is significantly correlated with impulsive‐compulsive behavior severity (Questionnaire for Impulsive Compulsive Disorders in Parkinson's Disease‐ Rating Scale). Voxel‐wise analysis of dopamine agonist–induced cerebral blood flow revealed group differences in mesocortical (ventromedial prefrontal cortex; insular cortex), mesolimbic (ventral striatum), and midbrain (SN; periaqueductal gray) regions.

Conclusions

These results indicate that dopamine agonist therapy can augment mesocorticolimbic and striato‐nigro‐striatal network activity in patients susceptible to impulsive‐compulsive behaviors. Our findings reinforce a wider literature linking studies of maladaptive behaviors to mesocorticolimbic networks and extend our understanding of biological mechanisms of impulsive compulsive behaviors in PD. © 2017 International Parkinson and Movement Disorder Society
Sonographic screening for Wilms tumor in children with CLOVES syndrome
Authors: Peterman Caitlin M. , Fevurly R. Dawn , Alomari Ahmad I. , Trenor Cameron C. , Adams Denise M. , Vadeboncoeur Sophie , Liang Marilyn G. , Greene Arin K. , Mulliken John B. , Fishman Steven J.
Published: June 2017

Background

CLOVES syndrome is associated with somatic mosaic PIK3CA mutations and characterized by congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and skeletal anomalies. Wilms tumor (WT) is a malignant embryonal renal neoplasm associated with hemihypertrophy and certain overgrowth disorders. After identifying WT in a child with CLOVES, we questioned whether ultrasonographic screening was necessary in these patients.

Methods

We retrospectively reviewed patients with CLOVES syndrome in our Vascular Anomalies Center at Boston Children's Hospital between 1998 and 2016 to identify those who developed WT. A PubMed literature search was also conducted to find other patients with both conditions.

Results

A total of 122 patients with CLOVES syndrome were found in our database (mean age 7.7 years, range 0–53 years). Four patients developed WT; all were diagnosed by 2 years of age. The incidence of WT in our CLOVES patient population (3.3%) was significantly greater than the incidence of WT in the general population (1/10,000) (P < 0.001). Four additional patients with WT and CLOVES syndrome were identified in our literature review.

Conclusion

Patients with CLOVES syndrome have an increased risk of WT. Given the benefits of early detection and treatment, children with CLOVES syndrome should be considered for quarterly abdominal ultrasonography until age 7 years. Screening may be most beneficial for patients under 3 years of age.
Spectral library‐based glycopeptide analysis–detection of circulating galectin‐3 binding protein in pancreatic cancer
Authors: Nigjeh Eslam N. , Chen Ru , Allen‐Tamura Yasuko , Brand Randall E. , Brentnall Teresa A. , Pan Sheng
Published: June 2017

Purpose

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease characterized by its late diagnosis, poor prognosis and rapid development of drug resistance. Using the data‐independent acquisition (DIA) technique, the authors applied a spectral library‐based proteomic approach to analyze N‐glycosylated peptides in human plasma, in the context of pancreatic cancer study.

Experimental design

The authors extended the application of DIA to the quantification of N‐glycosylated peptides enriched from plasma specimens from a clinically well‐defined cohort that consists of patients with early stage PDAC, chronic pancreatitis and healthy subjects.

Results

The analytical platform was evaluated in light of its robustness for quantitative analysis of large‐scale clinical specimens. The authors analysis indicated that the level of N‐glycosylated peptides derived from galectin‐3 binding proteins (LGALS3BP) were frequently elevated in plasma from PDAC patients, concurrent with the altered N‐glycosylation of LGALS3BP observed in the tumor tissue.

Conclusion and clinical relevance

The glycosylation form of LGALS3BP influences its function in the galectin network, which profoundly involves in cancer progression, immune response and drug resistance. As one of the major binding ligands of galectin network, discovery of site specific N‐glycosylation changes of LGALS3BP in association of PDAC may provide useful clues to facilitate cancer detection or phenotype stratification.
Cross‐resistance to purified Bt proteins, Bt corn and Bt cotton in a Cry2Ab2‐corn resistant strain of Spodoptera frugiperda
Authors: Yang Fei , Kerns David L , Head Graham P , Price Paula , Huang Fangneng
Published: June 2017

BACKGROUND

Gene‐pyramiding by combining two or more dissimilar Bacillus thuringiensis (Bt) proteins into a crop has been used to delay insect resistance. The durability of gene‐pyramiding can be reduced by cross‐resistance. Fall armyworm, Spodoptera frugiperda, is a major target pest of the Cry2Ab2 protein used in pyramided Bt corn and cotton. Here, we provide the first experimental evaluation of cross‐resistance in S. frugiperda selected with Cry2Ab2 corn to multiple Bt sources including purified Bt proteins, Bt corn and Bt cotton.

RESULTS

Concentration − response bioassays showed that resistance ratios for Cry2Ab2‐resistant (RR) relative to Cry2Ab2‐susceptible (SS)
S. frugiperda
were −1.4 for Cry1F, 1.2 for Cry1A.105, >26.7 for Cry2Ab2, >10.0 for Cry2Ae and −1.1 for Vip3A. Larvae of Cry2Ab2‐heterozygous (RS), SS and RR
S. frugiperda
were all susceptible to Bt corn and Bt cotton containing Cry1 (Cry1F or Cry1A.105) and/or Vip3A proteins. Pyramided Bt cotton containing Cry1Ac + Cry2Ab2 or Cry1Ab + Cry2Ae were also effective against SS and RS, but not RR.

CONCLUSION

These findings suggest that Cry2Ab2‐corn‐selected
S. frugiperda
is not cross‐resistant to Cry1F, Cry1A.105 or Vip3A protein, or corn and cotton plants containing these Bt proteins, but it can cause strong cross‐resistance to Cry2Ae and Bt crops expressing similar Bt proteins. © 2017 Society of Chemical Industry