bluuebunny/crossref_metadata_2025 huggingface dataset:
Model-Based Simulation Framework for FlexRay Communication Systems
Authors: Muller Candice , Valle Maurizio , Buzas Roman , Brtan Filip
Published: June 2016

Automotive communication systems are complex distributed systems. The design of the electrical physical layer (EPL) is a challenging task. Many parameters affect the signal integrity on the analog bus and the combination of parameter variations can lead to effects (e.g., signal reflections) which degrade the signal and compromise the system reliability. Model-based simulations have been widely proposed as the solution for the design, testing and verification of FlexRay networks. This paper proposes a model-based framework for the design and evaluation of FlexRay communication systems. The framework includes the development of FlexRay system components, the design of different network topologies and the simulation and analysis of EPL. The proposed framework has been developed and possible applications have been figured out. Furthermore, the validation of the proposed approach has been addressed. The validation focuses on the accuracy of the simulations in representing the analog signal on the bus, as well as the accuracy in representing the network timing characteristics. The validation exhaustively explores the system design space, achieving a rigorous analysis of the approach reliability: simulations of 40 different network topologies and 1,264 frames have been evaluated, by comparing simulation results with hardware measurements. The results demonstrate that the proposed framework accurately represents the hardware behavior, and it can be an useful toll during the design and early verification of FlexRay communication networks. Due to the lack of a formal validation approach for the validation of the electrical physical layer, the validation is valuable for the FlexRay community.
Assessment of the Bootstrap Technique in Single-Phase Current-Fed Full-Bridge Resonant Inverters with Reactive Energy
Authors: Aqui-Tapia Juan Antonio , Ponce-Silva Mario , Olivares-Peregrino Víctor Hugo , Oliver-Salazar Marco Antonio , Cortés-García Claudia
Published: June 2016

This paper is aimed to report the consequences in the use of the well-known bootstrap technique in single-phase current-fed full-bridge resonant inverters (SPCFFBRIs) operating with and without reactive energy. Based on both simulations (using the PSPICE[Formula: see text] software) and experiments it is shown that this technique is not feasible for this type of inverters when the load is predominantly reactive. The bootstrap technique conveniently operates when the load is purely resistive or resonant. The unfeasibility in the use of the bootstrap technique with reactive or nonresonant loads comes from the fact that the load voltage is applied to the bootstrap capacitor and, consequently, to the gate of the floating MOSFET, producing an imminent damage both in the control circuit and in the floating MOSFET. Therefore, other alternatives for feeding the floated MOSFETs must be considered.
Multi-Path Class AB Operational Amplifier with High Performance for SC Circuits
Authors: Akbari Meysam , Hashemipour Omid
Published: June 2016

In this paper, a single-stage multi-path operational transconductance amplifier (OTA) with fast-settling response for high performance applications is designed. The produced amplifier uses current-shunt technique, double recycling structure, cross-coupled positive feedback configuration and all idle devices in the signal path to enhance transconductance of the conventional folded cascode (FC) amplifier. These transconductance boosting techniques lead to higher DC gain, gain bandwidth (GBW), slew rate and lower settling time compared to the previous FC structures while phase margin is degraded. Simulation results are presented using 90 nm CMOS technology which show 1,800% increment in GBW and a 33.2 dB DC gain improvement in the approximately same power consumption compared to the conventional FC amplifier.
Editorial — Environmental Assessment in South Asia: Underrepresented in the International Academic Literature?
Authors: Jha-Thakur Urmila
Published: June 2016

Welcome to this special Journal of Environmental Assessment Policy and Management (JEAPM) issue on environmental assessment (EA) research in South Asia, which besides this introductory paper includes seven papers contributing to a wider understanding of EA-related practices in the South Asian Region (SAR). Some of the papers are country-specific while others provide useful overviews of a region and/or parts of a region. The collection of papers is a result of a targeted call to researchers taking a special interest on EA issues within SAR. This special issue is timely considering the challenges and rapid growth this part of the world is currently facing. Furthermore, there is a perception that EA-related research in the region is less reported in the academic literature than others. Although this special issue cannot claim to represent all countries in South Asia, it is a step towards narrowing this perceived gap in the literature and in reporting on the emerging trends of EA within the region. It is hoped that this initiative will encourage further SAR EA-related research and publications in the future.
Elastic Percolation in Nanocomposites with Impenetrable Ellipsoidal Inclusion (Comprehensive Study of Geometry and Interphase Thickness)
Authors: Gharehnazifam Ziba , Baniassadi Majid , Abrinia Karen , Karimpour Morad , Baghani Mostafa
Published: June 2016

In this paper, effects of percolation, shape, and interphase thickness of inclusions have been studied on the effective elastic modulus of polymer nanocomposites. Inclusion distribution within the RVE has been prescribed using the Monte Carlo method, and existence of a relationship between percolation and effective Young’s modulus has been investigated. Further studies were carried out to determine the effect of increased spherical, oblate, and prolate particles in conjunction with different interphase thicknesses. Results suggest that the elastic modulus increases with the interphase thickness, and the maximum strength is associated with prolate inclusions. It has been concluded that percolation has a significant effect on the strength of polymer nanocomposites, and that it results in a spike in the value of Young’s modulus.
The US-China Evolving Relationship: Implications of China’s One Belt, One Road Initiative
Authors: LEE Sun-Jin , LYE Liang Fook
Published: June 2016

The United States has become extremely wary of China in recent years due to reasons such as China’s aspiration to become a maritime power, campaign to strengthen ties with other major powers, efforts to secure a presence in Central Asia and an ambitious economic and industrial outreach. Together with China’s One Belt, One Road initiative, they conjure an image of a China bent on challenging the United States on the world stage.
The United States and the Lower Mekong Initiative
Authors: LE Van My
Published: June 2016

The US Lower Mekong Initiative is a mechanism to support the Mekong countries in their struggle against hunger and poverty. The initiative is also a part of the “US Pivot to Southeast Asia” strategy to rebalance the influence and strategic competition among big countries in the subregion, especially between the United States and China.
CLIMATE CHANGE AND LAND USE IN SOUTHEASTERN U.S.: DID THE “DUMB FARMER” GET IT WRONG?
Authors: TSVETANOV TSVETAN , QI LINGQIAO , MUKHERJEE DEEP , SHAH FARHED , BRAVO-URETA BORIS
Published: June 2016

The assumption of a fixed amount of land remaining in agriculture regardless of changing climate conditions — one of the features of the “dumb farmer scenario” — is likely to bias the estimated social welfare impacts of climate change. In order to quantify this bias, we employ a demand-supply framework to determine both the amount of land allocated to agricultural and nonagricultural uses as well as the social welfare associated with this allocation choice when no market distortions exist. We present an application of our model to the Southeastern United States and simulate the effects of changing climate conditions on land allocation in the region between 2007 and 2040. We find a very modest welfare bias when maintaining current farmland preservation policies and a more substantial bias if we assume that additional land policies are instituted which have spillover welfare effects in other land-using sectors.
Free charge localization and effective dielectric permittivity in oxides
Authors: Maglione Mario
Published: June 2016

This review will deal with several types of free charge localization in oxides and their consequences on the effective dielectric spectra of such materials. The first one is the polaronic localization at the unit cell scale on residual impurities in ferroelectric networks. The second one is the collective localization of free charge at macroscopic interfaces like surfaces, electrodes and grain boundaries in ceramics. Polarons have been observed in many oxide perovskites mostly when cations having several stable electronic configurations are present. In manganites, the density of such polarons is so high as to drive a net lattice of interacting polarons. On the other hand, in ferroelectric materials like BaTiO3 and LiNbO3, the density of polarons is usually very small but they can influence strongly the macroscopic conductivity. The contribution of such polarons to the dielectric spectra of ferroelectric materials is described. Even residual impurities as for example Iron can induce well-defined anomalies at very low temperatures. This is mostly resulting from the interaction between localized polarons and the highly polarizable ferroelectric network in which they are embedded. The case of such residual polarons in SrTiO3 will be described in more detail, emphasizing the quantum polaron state at liquid helium temperatures. Recently, several nonferroelectric oxides have been shown to display giant effective dielectric permittivity. It is first shown that the frequency/temperature behavior of such parameters is very similar in very different compounds (donor-doped BaTiO3, CaCu3Ti4O12, LuFe2O4, Li-doped NiO, etc.). This similarity calls for a common origin of the giant dielectric permittivity in these compounds. A space charge localization at macroscopic interfaces can be the key for such extremely high dielectric permittivity.
Dielectric response of BaZrO3/BaTiO3 superlattice
Authors: Wang D. , Jiang Z.
Published: June 2016

We use the first-principles-based molecular dynamic approach to simulate dipolar dynamics of BaZrO3/BaTiO3 superlattice, and obtain its dielectric response. The dielectric response is decomposed into its compositional, as well as the in-plane and out-of-plane parts, which are then discussed in the context of chemical ordering of Zr/Ti ions. We reveal that, while the in-plane dielectric response of BaZrO3/BaTiO3 superlattice also shows dispersion over probing frequency, it shall not be categorized as relaxor.
Time–space variability of paralic strata deposited in a high accommodation, high sediment supply setting: example from the Cretaceous of Utah
Authors: Mulhern Julia S. , Johnson Cari L.
Published: June 2016

A previously unstudied section of the John Henry Member (Upper Cretaceous, Straight Cliffs Formation) preserves four stacked regressive–transgressive cycles of paralic strata from the Kaiparowits Plateau in south-central Utah. Meso-scale (10–100 s m thick) shoreface, wave-dominated delta and estuarine depositional environments stack vertically and show the complexity of paralic facies in a single location through time. Correlations with nearby exposures show the palaeogeographical variability updip and along-strike over
c.
6.5 myr. Such variability highlights the importance of high accommodation settings in preserving transgressive deposits, including landwards-stepping barrier island and lagoon systems. The Buck Hollow section is expanded two to three times compared with correlative successions only 15–40 km away. Tectonics, eustasy and climate contributed to relative shifts in base level, but these regional controls do not explain the dramatic local thickening observed. Local controls on accommodation were quantified through decompaction analysis. The results showed that the expanded thickness of the John Henry Member in Buck Hollow can be explained by differences in decompaction (
c.
9%), local erosion by fluvial incision (
c.
5%), early compaction (
c.
30%) and local structures such as faults (
c.
100–150%). This outcrop-based study illustrates facies variability within a thick paralic succession and investigates accommodation controls on the preservation of these strata with the goal of improving predictive models for analogous deposits.

Supplementary material:
40
Ar/
39
Ar age data methods and sample location available at
https://doi.org/10.6084/m9.figshare.c.3277436.v1
Astrophysics with Extraterrestrial Materials
Authors: Nittler Larry R. , Ciesla Fred
Published: June 2016

Extraterrestrial materials, including meteorites, interplanetary dust, and spacecraft-returned asteroidal and cometary samples, provide a record of the starting materials and early evolution of the Solar System. We review how laboratory analyses of these materials provide unique information, complementary to astronomical observations, about a wide variety of stellar, interstellar and protoplanetary processes. Presolar stardust grains retain the isotopic compositions of their stellar sources, mainly asymptotic giant branch stars and Type II supernovae. They serve as direct probes of nucleosynthetic and dust formation processes in stars, galactic chemical evolution, and interstellar dust processing. Extinct radioactivities suggest that the Sun's birth environment was decoupled from average galactic nucleosynthesis for some tens to hundreds of Myr but was enriched in short-lived isotopes from massive stellar winds or explosions shortly before or during formation of the Solar System. Radiometric dating of meteorite components tells us about the timing and duration over which solar nebula solids were assembled into the building blocks of the planets. Components of the most primitive meteoritical materials provide further detailed constraints on the formation, processing, and transport of material and associated timescales in the Sun's protoplanetary disk as well as in other forming planetary systems.
The Cytoophidium and Its Kind: Filamentation and Compartmentation of Metabolic Enzymes
Authors: Liu Ji-Long
Published: June 2016

Compartmentation is essential for the localization of biological processes within a cell. In 2010, three groups independently reported that cytidine triphosphate synthase (CTPS), a metabolic enzyme for de novo synthesis of the nucleotide CTP, is compartmentalized in cytoophidia (Greek for “cellular snakes”) in bacteria, yeast, and fruit flies. Subsequent studies demonstrate that CTPS can also form filaments in human cells. Thus, the cytoophidium represents a new type of intracellular compartment that is strikingly conserved across prokaryotes and eukaryotes. Multiple lines of evidence have recently suggested that polymerization of metabolic enzymes such as CTPS and inosine monophosphate dehydrogenase into filamentous cytoophidia modulates enzymatic activity. With many more metabolic enzymes found to form the cytoophidium and its kind, compartmentation via filamentation may serve as a general mechanism for the regulation of metabolism.
Emergence and Evolution of Secondary Lymphoid Organs
Authors: Neely Harold R. , Flajnik Martin F.
Published: June 2016

For effective adaptive immunity to foreign antigens (Ag), secondary lymphoid organs (SLO) provide the confined environment in which Ag-restricted lymphocytes, with very low precursor frequencies, interact with Ag on Ag-presenting cells (APC). The spleen is the primordial SLO, arising in conjunction with adaptive immunity in early jawed vertebrates. The spleen, especially the spleen's lymphoid compartment, the white pulp (WP), has undergone numerous modifications over evolutionary time. We describe the progressive advancement of splenic WP complexity, which evolved in parallel with the increasing functionality of adaptive immunity. The Ag-presenting function of follicular dendritic cells (FDC) also likely emerged at the inception of adaptive immunity, and we propose that a single type of hematopoietically derived APC displayed Ag to both T and B cells. A dedicated FDC, derived from a vascular precursor, is a recent evolutionary innovation that likely permitted the robust affinity maturation found in mammals.
From Tunguska to Chelyabinsk via Jupiter
Authors: Artemieva Natalia A. , Shuvalov Valery V.
Published: June 2016

The Tunguska event remained enigmatic for almost 100 years until the collision of Comet Shoemaker-Levy 9 with Jupiter in 1994 helped to resolve this enigma and allowed us to adequately interpret the more recent Chelyabinsk event. Airbursts typically occur if a meteoroid entering Earth's atmosphere is 10–100 m in diameter, i.e., its energy ranges from 0.5 (Chelyabinsk) to 20 (Tunguska) Mt TNT. All this energy is released in the atmosphere with strong shock waves generated during the entry reaching the surface and causing substantial damage. Atmospheric plumes are capable of dispersing extraterrestrial materials worldwide. Modern civilization is extremely vulnerable to those relatively small disturbances that recur on a decadal timescale and are still difficult to predict.
Sun, Ocean, Nuclear Bombs, and Fossil Fuels: Radiocarbon Variations and Implications for High-Resolution Dating
Authors: Dutta Koushik
Published: June 2016

Radiocarbon, or 14C, is a radiometric dating method ideally suited for providing a chronological framework in archaeology and geosciences for timescales spanning the last 50,000 years. 14C is easily detectable in most common natural organic materials and has a half-life (5,730±40 years) relevant to these timescales. 14C produced from large-scale detonations of nuclear bombs between the 1950s and the early 1960s can be used for dating modern organic materials formed after the 1950s. Often these studies demand high-resolution chronology to resolve ages within a few decades to less than a few years. Despite developments in modern, high-precision 14C analytical methods, the applicability of 14C in high-resolution chronology is limited by short-term variations in atmospheric 14C in the past. This article reviews the roles of the principal natural drivers (e.g., solar magnetic activity and ocean circulation) and the anthropogenic perturbations (e.g., fossil fuel CO2 and 14C from nuclear and thermonuclear bombs) that are responsible for short-term 14C variations in the environment. Methods and challenges of high-resolution 14C dating are discussed.
Triple Oxygen Isotopes: Fundamental Relationships and Applications
Authors: Bao Huiming , Cao Xiaobin , Hayles Justin A.
Published: June 2016

The element oxygen has three stable isotopes: 16O, 17O, and 18O. For a defined process, a change in 18O/16O scales with the corresponding change in 17O/16O, or the fractionation factors 18α and 17α have a relationship of θ = ln17α/ln18α, in which the triple oxygen isotope exponent θ is relatively fixed but does vary with reaction path, temperature, and species involved. When the small variation is of interest, the distinction of three concepts—θ, S (a slope through data points in δ17O–δ18O space), and C (an arbitrary referencing number for the degree of 17O deviation)—becomes important. Triple oxygen isotope variations can be measured by modern instruments and thus offer an additional line of information on the underlying reaction processes and conditions. Analytical methods and Earth science applications have recently been developed for air oxygen, carbon dioxide, water, silicates, oxides, sulfates, carbonates, and phosphates.
The Climate of Titan
Authors: Mitchell Jonathan L. , Lora Juan M.
Published: June 2016

Over the past decade, the Cassini-Huygens mission to the Saturn system has revolutionized our understanding of Titan and its climate. Veiled in a thick organic haze, Titan's visible appearance belies an active, seasonal weather cycle operating in the lower atmosphere. Here we review the climate of Titan, as gleaned from observations and models. Titan's cold surface temperatures (∼90 K) allow methane to form clouds and precipitation analogously to Earth's hydrologic cycle. Because of Titan's slow rotation and small size, its atmospheric circulation falls into a regime resembling Earth's tropics, with weak horizontal temperature gradients. A general overview of how Titan's atmosphere responds to seasonal forcing is provided by estimating a number of climate-related timescales. Titan lacks a global ocean, but methane is cold-trapped at the poles in large seas, and models indicate that weak baroclinic storms form at the boundary of Titan's wet and dry regions. Titan's saturated troposphere is a substantial reservoir of methane, supplied by deep convection from the summer poles. A significant seasonal cycle, first revealed by observations of clouds, causes Titan's convergence zone to migrate deep into the summer hemispheres, but its connection to polar convection remains undetermined. Models suggest that downwelling of air at the winter pole communicates upper-level radiative cooling, reducing the stability of the middle troposphere and priming the atmosphere for spring and summer storms when sunlight returns to Titan's lakes. Despite great gains in our understanding of Titan, many challenges remain. The greatest mystery is how Titan is able to retain an abundance of atmospheric methane with only limited surface liquids, while methane is being irreversibly destroyed by photochemistry. A related mystery is how Titan is able to hide all the ethane that is produced in this process. Future studies will need to consider the interactions between Titan's atmosphere, surface, and subsurface in order to make further progress in understanding Titan's complex climate system.
Protists and the Wild, Wild West of Gene Expression: New Frontiers, Lawlessness, and Misfits
Authors: Smith David Roy , Keeling Patrick J.
Published: June 2016

The DNA double helix has been called one of life's most elegant structures, largely because of its universality, simplicity, and symmetry. The expression of information encoded within DNA, however, can be far from simple or symmetric and is sometimes surprisingly variable, convoluted, and wantonly inefficient. Although exceptions to the rules exist in certain model systems, the true extent to which life has stretched the limits of gene expression is made clear by nonmodel systems, particularly protists (microbial eukaryotes). The nuclear and organelle genomes of protists are subject to the most tangled forms of gene expression yet identified. The complicated and extravagant picture of the underlying genetics of eukaryotic microbial life changes how we think about the flow of genetic information and the evolutionary processes shaping it. Here, we discuss the origins, diversity, and growing interest in noncanonical protist gene expression and its relationship to genomic architecture.
New Nonperturbative Methods in Quantum Field Theory: From Large-NOrbifold Equivalence to Bions and Resurgence
Authors: Dunne Gerald V. , Ünsal Mithat
Published: June 2016

We present a broad conceptual introduction to some new ideas in nonperturbative quantum field theory (QFT) that have led to progress toward an understanding of quark confinement in gauge theories and, more broadly, toward a nonperturbative continuum definition of QFTs. We first present exact orbifold equivalences of supersymmetric and nonsupersymmetric QFTs in the large-N limit and exact equivalences of large-N theories in infinite volume to large-N theories in finite volume, or even at a single point. We discuss principles by which calculable QFTs are continuously connected to strong-coupling QFTs, allowing understanding of the physics of confinement or the absence thereof. We discuss the role of particular saddle solutions, termed bions, in weak-coupling calculable regimes. The properties of bions motivate an extension of semiclassical methods used to evaluate functional integrals to include families of complex saddles (Picard–Lefschetz theory). This analysis leads us to the resurgence program, which may provide a framework for combining divergent perturbation series with semiclassical instanton and bion/renormalon contributions. This program could provide a nonperturbative definition of the path integral.
Developments in Plant Negative-Strand RNA Virus Reverse Genetics
Authors: Jackson Andrew O. , Li Zhenghe
Published: June 2016

Twenty years ago, breakthroughs for reverse genetics analyses of negative-strand RNA (NSR) viruses were achieved by devising conditions for generation of infectious viruses in susceptible cells. Recombinant strategies have subsequently been engineered for members of all vertebrate NSR virus families, and research arising from these advances has profoundly increased understanding of infection cycles, pathogenesis, and complexities of host interactions of animal NSR viruses. These strategies also permitted development of many applications, including attenuated vaccines and delivery vehicles for therapeutic and biotechnology proteins. However, for a variety of reasons, it was difficult to devise procedures for reverse genetics analyses of plant NSR viruses. In this review, we discuss advances that have circumvented these problems and resulted in construction of a recombinant system for Sonchus yellow net nucleorhabdovirus. We also discuss possible extensions to other plant NSR viruses as well as the applications that may emanate from recombinant analyses of these pathogens.
Molecular Soybean-Pathogen Interactions
Authors: Whitham Steven A. , Qi Mingsheng , Innes Roger W. , Ma Wenbo , Lopes-Caitar Valéria , Hewezi Tarek
Published: June 2016

Soybean hosts a wide variety of pathogens that cause significant yield losses. The importance of soybean as a major oilseed crop has led to research focused on its interactions with pathogens, such as Soybean mosaic virus, Pseudomonas syringae, Phytophthora sojae, Phakopsora pachyrhizi, and Heterodera glycines. Pioneering work on soybean's interactions with these organisms, which represent the five major pathogen groups (viruses, bacteria, oomycetes, fungi, and nematodes), has contributed to our understanding of the molecular mechanisms underlying virulence and immunity. These mechanisms involve conserved and unique features that validate the need for research in both soybean and homologous model systems. In this review, we discuss identification of effectors and their functions as well as resistance gene–mediated recognition and signaling. We also point out areas in which model systems and recent advances in resources and tools have provided opportunities to gain deeper insights into soybean-pathogen interactions.
The Evolutionary Ecology of Plant Disease: A Phylogenetic Perspective
Authors: Gilbert Gregory S. , Parker Ingrid M.
Published: June 2016

An explicit phylogenetic perspective provides useful tools for phytopathology and plant disease ecology because the traits of both plants and microbes are shaped by their evolutionary histories. We present brief primers on phylogenetic signal and the analytical tools of phylogenetic ecology. We review the literature and find abundant evidence of phylogenetic signal in pathogens and plants for most traits involved in disease interactions. Plant nonhost resistance mechanisms and pathogen housekeeping functions are conserved at deeper phylogenetic levels, whereas molecular traits associated with rapid coevolutionary dynamics are more labile at branch tips. Horizontal gene transfer disrupts the phylogenetic signal for some microbial traits. Emergent traits, such as host range and disease severity, show clear phylogenetic signals. Therefore pathogen spread and disease impact are influenced by the phylogenetic structure of host assemblages. Phylogenetically rare species escape disease pressure. Phylogenetic tools could be used to develop predictive tools for phytosanitary risk analysis and reduce disease pressure in multispecies cropping systems.
Sustainability and Development
Authors: Barbier Edward B.
Published: June 2016

Sustainable development requires that per capita welfare does not decline over time. The minimum condition is ensuring that any depletion of natural capital is compensated by reproducible and human capital, so that the value of the aggregate stock does not decrease. Meeting this condition is problematic if natural capital includes ecosystems, which not only provide unique goods and services but are also prone to irreversible conversion and abrupt collapse. Net domestic product accounting rules for the depreciation of the total stock of reproducible, human, and natural capital of an economy can be extended to incorporate the direct benefits provided by ecosystems. They also can integrate any capital revaluation that occurs through ecosystem restoration and conversion and the threat of irreversible collapse. These approaches confirm the economic interpretation of sustainability as nondeclining welfare. They can also be used to estimate the changes in the value of ecological capital due to economic activity.
Role of scleraxis in mechanical stretch-mediated regulation of cardiac myofibroblast phenotype
Authors: Roche Patricia L. , Nagalingam Raghu S. , Bagchi Rushita A. , Aroutiounova Nina , Belisle Breanna M. J. , Wigle Jeffrey T. , Czubryt Michael P.
Published: June 2016

The phenotype conversion of fibroblasts to myofibroblasts plays a key role in the pathogenesis of cardiac fibrosis. Numerous triggers of this conversion process have been identified, including plating of cells on solid substrates, cytokines such as transforming growth factor-β, and mechanical stretch; however, the underlying mechanisms remain incompletely defined. Recent studies from our laboratory revealed that the transcription factor scleraxis is a key regulator of cardiac fibroblast phenotype and extracellular matrix expression. Here we report that mechanical stretch induces type I collagen expression and morphological changes indicative of cardiac myofibroblast conversion, as well as scleraxis expression via activation of the scleraxis promoter. Scleraxis causes phenotypic changes similar to stretch, and the effect of stretch is attenuated in scleraxis null cells. Scleraxis was also sufficient to upregulate expression of vinculin and F-actin, to induce stress fiber and focal adhesion formation, and to attenuate both cell migration and proliferation, further evidence of scleraxis-mediated regulation of fibroblast to myofibroblast conversion. Together, these data confirm that scleraxis is sufficient to promote the myofibroblast phenotype and is a required effector of stretch-mediated conversion. Scleraxis may thus represent a potential target for the development of novel antifibrotic therapies aimed at inhibiting myofibroblast formation.
Distribution and trafficking of the μ-opioid receptor in enteric neurons of the guinea pig
Authors: Lay Joslyn , Carbone Simona E. , DiCello Jesse J. , Bunnett Nigel W. , Canals Meritxell , Poole Daniel P.
Published: June 2016

The μ-opioid receptor (MOR) is a major regulator of gastrointestinal motility and secretion and mediates opiate-induced bowel dysfunction. Although MOR is of physiological and therapeutic importance to gut function, the cellular and subcellular distribution and regulation of MOR within the enteric nervous system are largely undefined. Herein, we defined the neurochemical coding of MOR-expressing neurons in the guinea pig gut and examined the effects of opioids on MOR trafficking and regulation. MOR expression was restricted to subsets of enteric neurons. In the stomach MOR was mainly localized to nitrergic neurons (∼88%), with some overlap with neuropeptide Y (NPY) and no expression by cholinergic neurons. These neurons are likely to have inhibitory motor and secretomotor functions. MOR was restricted to noncholinergic secretomotor neurons (VIP-positive) of the ileum and distal colon submucosal plexus. MOR was mainly detected in nitrergic neurons of the colon (nitric oxide synthase positive, 87%), with some overlap with choline acetyltransferase (ChAT). No expression of MOR by intrinsic sensory neurons was detected. [d-Ala2, MePhe4, Gly(ol)5]enkephalin (DAMGO), morphiceptin, and loperamide induced MOR endocytosis in myenteric neurons. After stimulation with DAMGO and morphiceptin, MOR recycled, whereas MOR was retained within endosomes following loperamide treatment. Herkinorin or the δ-opioid receptor agonist [d-Ala2, d-Leu5]enkephalin (DADLE) did not evoke MOR endocytosis. In summary, we have identified the neurochemical coding of MOR-positive enteric neurons and have demonstrated differential trafficking of MOR in these neurons in response to established and putative MOR agonists.
Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running
Authors: Holland Angelia Maleah , Kephart Wesley C. , Mumford Petey W. , Mobley Christopher Brooks , Lowery Ryan P. , Shake Joshua J. , Patel Romil K. , Healy James C. , McCullough Danielle J. , Kluess Heidi A. , Huggins Kevin W. , Kavazis Andreas N. , Wilson Jacob M. , Roberts Michael D.
Published: June 2016

We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9–10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20–60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7–42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8–10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise ( P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats ( P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats ( P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats ( P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats ( P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats ( P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats ( P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss.
A model of calcium homeostasis in the rat
Authors: Granjon David , Bonny Olivier , Edwards Aurélie
Published: June 2016

We developed a model of calcium homeostasis in the rat to better understand the impact of dysfunctions such as primary hyperparathyroidism and vitamin D deficiency on calcium balance. The model accounts for the regulation of calcium intestinal uptake, bone resorption, and renal reabsorption by parathyroid hormone (PTH), vitamin D3, and Ca2+itself. It is the first such model to incorporate recent findings regarding the role of the calcium-sensing receptor (CaSR) in the kidney, the presence of a rapidly exchangeable pool in bone, and the delayed response of vitamin D3synthesis. Accounting for two (fast and slow) calcium storage compartments in bone allows the model to properly predict the effects of bisphophonates on the plasma levels of Ca2+([Ca2+]p), PTH, and vitamin D3. Our model also suggests that Ca2+exchange rates between plasma and the fast pool vary with both sex and age, allowing [Ca2+]pto remain constant in spite of sex- and age-based hormonal and other differences. Our results suggest that the inconstant hypercalciuria that is observed in primary hyperparathyroidism can be attributed in part to counterbalancing effects of PTH and CaSR in the kidney. Our model also correctly predicts that calcimimetic agents such as cinacalcet bring down [Ca2+]pto within its normal range in primary hyperparathyroidism. In addition, the model provides a simulation of CYP24A1 inactivation that leads to a situation reminiscent of infantile hypercalcemia. In summary, our model of calcium handling can be used to decipher the complex regulation of calcium homeostasis.
Functional evidence for a direct excitatory projection from the lateral habenula to the ventral tegmental area in the rat
Authors: Brown P. Leon , Shepard Paul D.
Published: June 2016

The lateral habenula, a phylogenetically conserved epithalamic structure, is activated by aversive stimuli and reward omission. Excitatory efferents from the lateral habenula predominately inhibit midbrain dopamine neuronal firing through a disynaptic, feedforward inhibitory mechanism involving the rostromedial tegmental nucleus. However, the lateral habenula also directly targets dopamine neurons within the ventral tegmental area, suggesting that opposing actions may result from increased lateral habenula activity. In the present study, we tested the effect of habenular efferent stimulation on dopamine and nondopamine neurons in the ventral tegmental area of Sprague-Dawley rats using a parasagittal brain slice preparation. Single pulse stimulation of the fasciculus retroflexus excited 48% of dopamine neurons and 51% of nondopamine neurons in the ventral tegmental area of rat pups. These proportions were not altered by excision of the rostromedial tegmental nucleus and were evident in both cortical- and striatal-projecting dopamine neurons. Glutamate receptor antagonists blocked this excitation, and fasciculus retroflexus stimulation elicited evoked excitatory postsynaptic potentials with a nearly constant onset latency, indicative of a monosynaptic, glutamatergic connection. Comparison of responses in rat pups and young adults showed no significant difference in the proportion of neurons excited by fasciculus retroflexus stimulation. Our data indicate that the well-known, indirect inhibitory effect of lateral habenula activation on midbrain dopamine neurons is complemented by a significant, direct excitatory effect. This pathway may contribute to the role of midbrain dopamine neurons in processing aversive stimuli and salience.
CD3+CD8+CD28−T Lymphocytes in Patients with Lupus Nephritis
Authors: Żabińska Marcelina , Krajewska Magdalena , Kościelska-Kasprzak Katarzyna , Klinger Marian
Published: June 2016

The results of studies on theCD3+CD8+CD28-cells in SLE are inconsistent since several analyses describeCD3+CD8+CD28-as either immunosuppressive or cytotoxic. The aim of this study is to inquire whether the quantitative changes ofCD3+CD8+CD28-T lymphocytes subpopulation are related to the clinical status of patients with lupus nephritis. Evaluation of Foxp3 expression onCD3+CD8+CD28-cells may shed some light on functional properties of these cells. 54 adult SLE patients and 19 sex and age matched healthy volunteers were enrolled in the study. There were 15 patients in inactive (SLEDAI ≤ 5) and 39 in active (SLEDAI > 5) phase of disease. We determined absolute count ofCD3+CD8+CD28-andCD3+CD8+CD28-Foxp3+subpopulations by flow cytometry. We observed a statistically significant increase in absolute count and percentage ofCD3+CD8+CD28-in SLE patients compared to HC (p<0.001). Moreover there was significant positive correlation between increasing absolute count ofCD3+CD8+CD28-cells and disease activity measured by SLEDAI (rs = 0.281,p=0.038). Active LN patients had increased absolute count ofCD3+CD8+CD28-cells compared to HC. Positive correlation ofCD3+CD8+CD28-number with disease activity, and lack of Foxp3 expression on these cells, suggests thatCD3+CD8+CD28-lymphocytes might be responsible for an increased proinflammatory response in the exacerbation of SLE.
Polyetherimide Nanofibres as Sorbents for Organochlorinated Pesticides Determination
Authors: Vojtěch Antoš , Pavel Hrabák , Michal Komárek , Martin Stuchlík
Published: June 2016

Electrospun polyetherimide (PEI) nanofibres were fixed on a steel wire solid phase microextraction (SPME) assembly. The basic properties of the prepared nanofibres were determined by thermogravimetry, differential scanning calorimetry, adsorption, and SEM. The analytical performance of prepared PEI SPME fibres was compared with three commercially available SPME fibres, 7 μm PDMS, 100 μm PDMS, and DVB/Carboxene/PDMS. As model water pollutants, persistent organochlorinated pesticides hexachlorocyclohexanes (HCH) and chlorobenzene (ClB) were chosen as model water pollutants. The fibres were compared in the headspace- (HS-) SPME mode of GC-MS/MS instrumentation. The comparison omitted other method parameters and focused exclusively on the extraction time variability. Lab-made PEI SPME fibres showed significantly better response for the target compounds than the other tested fibres from industrial production. Based on the results, the extraction time could be shortened from 50 to 10 min, if PEI SPME fibres were used as a modification of existing analytical protocol.
Effects of the FCNC Couplings in Production of New Heavy Quarks withinZ′Models at the LHC
Authors: Çetinkaya V. , Arı V. , Çakır O.
Published: June 2016

We study the flavor changing neutral current couplings of new heavy quarks through theZ′models at the LHC. We calculate the cross sections for the signal and the corresponding standard model background processes. Considering the present limits on the mass of new heavy quarks and theZ′boson, we performed an analysis to investigate the parameter space (mixing and mass) through differentZ′models. For FCNC mixing parameterx=0.1and theZ′massMZ′=2000 GeV and new heavy quark massmt′=700 GeV at the LHC withs=13 TeV, we find the cross section for single production of new heavy quarks associated with top quarks as5.8 fb,3.3 fb,1.5 fb, and1.2 fb within theZη′,Zψ′,ZLP′, andZχ′models, respectively. It is shown that the sensitivity would benefit from the flavor tagging.
Amino Acid Starvation Enhances Programmed Ribosomal Frameshift in Metavirus Ty3 ofSaccharomyces cerevisiae
Authors: Türkel Sezai
Published: June 2016

Ty3 is a retroviral-like element and propagates with a retroviral-like mechanism within the yeast cells. Ty3 mRNA contains two coding regions, which are GAG3 and POL3. The coding region POL3 is translated as a GAG3-POL3 fusion protein by a +1 programmed frameshift. In this study, it was shown that the Ty3 frameshift frequency is significantly increased by amino acid starvation in a Gcn2p complex dependent manner. When the yeast cells were subjected to amino acid starvation, the frameshift frequency of Ty3 increased more than 2-fold in the wild-type yeast cells, mostly independent of Gcn4p. However, Ty3 frameshift frequency remained at basal level in thegcn1,gcn20, orgcn2mutant yeast cells in amino acid starved yeasts. Gcn1p forms a complex with Gcn2p and Gcn20p and is involved in the sensing of uncharged tRNAs on the ribosomal A-site during translation. Increases in uncharged tRNA levels due to amino acid depletion lead to ribosomal pauses. These ribosomal pauses are significant actors in the regulation of Ty3 frameshift frequency. Results of this research revealed that frameshift frequency in Ty3 is regulated by the Gcn2p complex in response to amino acid starvation in yeast.
Tissue Kallikrein Alleviates Cerebral Ischemia‐Reperfusion Injury by Activating the B2R‐ERK1/2‐CREB‐Bcl‐2 Signaling Pathway in Diabetic Rats
Authors: Shi Ruifeng , Yuan Kunxiong , Hu Bin , Sang Hongfei , Zhou Lizhi , Xie Yi , Xu Lili , Cao Qinqin , Chen Xin , Zhao Lingling , Xiong Yunyun , Xu Gelin , Liu Xinfeng , Liu Ling , Zhang Renliang
Published: June 2016

Diabetes mellitus (DM) substantially increases the risk of ischemic stroke and reduces the tolerance to ischemic insults. Tissue kallikrein (TK) has been demonstrated to protect neurons from ischemia/reperfusion (I/R) injury in orthoglycemic model by activating the bradykinin B2 receptor (B2R). Considering the differential effects of B2R or bradykinin B1 receptor (B1R) on cardioprotection and neuroprotection in I/R with or without diabetes, this study was designed to investigate the role of TK during cerebral I/R injury in streptozotocin‐induced diabetic rats. Intravenous injection of TK inhibited apoptosis in neurons, alleviated edema and inflammatory reactions after focal cerebral I/R, significantly reduced the infarct volume, and improved functional recovery. These beneficial effects were accompanied by activation of the extracellular signal‐regulated kinase 1/2 (ERK1/2), cAMP response element‐binding (CREB), and Bcl‐2 signal proteins. Inhibition of the B2R or ERK1/2 pathway abated the effects of TK, whereas an antagonist of B1R enhanced the effects. These findings reveal that the neuroprotective effect of TK against cerebral I/R injury in streptozotocin‐induced diabetic rats mainly involves the enhancement of B2R and ERK1/2‐CREB‐Bcl‐2 signaling pathway activity.
Clinician’s Attitudes to the Introduction of Routine Weighing in Pregnancy
Authors: Hasted Tim , Stapleton Helen , Beckmann Michael M. , Wilkinson Shelley A.
Published: June 2016

Background.Excessive gestational weight gain poses significant short- and long-term health risks to both mother and baby. Professional bodies and health services increasingly recommend greater attention be paid to weight gain in pregnancy. A large Australian tertiary maternity hospital plans to facilitate the (re)introduction of routine weighing of all women at every antenatal visit.Objective.To identify clinicians’ perspectives of barriers and enablers to routinely weighing pregnant women and variations in current practice, knowledge, and attitudes between different staff groups.Method.Forty-four maternity staff from three professional groups were interviewed in four focus groups. Staff included midwives; medical staff; and dietitians. Transcripts underwent qualitative content analysis to identify and examine barriers and enablers to the routine weighing of women throughout pregnancy.Results.While most staff supported routine weighing, various concerns were raised. Issues included access to resources and staff; the ability to provide appropriate counselling and evidence-based interventions; and the impact of weighing on patients and the therapeutic relationship.Conclusion. Many clinicians supported the practice of routine weighing in pregnancy, but barriers were also identified. Implementation strategies will be tailored to the discrete professional groups and will address identified gaps in knowledge, resources, and clinician skills and confidence.