bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of electron optics with an offset cylindrical lens: Application to a monochromator or energy analyzer
Authors: Ogawa Takashi , Takai Yoshizo
Published: May 2018

Electron beam monochromators (MCs) and energy analyzers (EAs), which are equivalent optical units with energy filtering capabilities, are of importance in electron microscopy and surface analysis instruments. The authors report the evaluation results for electron optics with an offset cylindrical lens (CL) and an additional transfer lens (TL) for application to an MC or EA. The offset CL deflects beams and generates energy dispersions, and the TL enhances their performance through collimating and retarding the beams. Following the previous theoretical studies, the authors have designed and manufactured the optics with a high mechanical accuracy at the micrometer level and integrated it with electronics with low noise and high stability. The authors adopt two methods for evaluating the energy-resolving performance. First, the authors treat the optics as an EA and evaluate the resolution through comparing the measured total energy distributions of Schottky emitters with the results from the theory. The energy resolution dE is estimated to be 88 meV at a beam energy E0 of 3.1 keV, and the index of performance dE/E0 reaches 2.7 × 10−5. Second, the authors treat the optics as an MC and evaluate directly the energy resolution or the energy spread of the monochromatic beams with an additional EA on the downstream side. The energy resolution dE is 73 meV. Both methods show similar energy resolutions, which enhance the credibility of the evaluation results. Charged particle simulation confirms the results and reveals that the resolution is limited by the width of the energy selection slit. As a total measurement system, the accuracy and stability are better than 3 meV. The MC with the optics exhibits high potential and a simple structure and is suitable for practical use. Advantages of the EA are band-pass filtering type, linear optics, compact size, and easy integration into analytical systems. The MC or EA using the optics will open new possibilities in the research fields of materials science, biology, and electronic devices, where advanced EMs or surface analytical instruments play essential roles.
Kriging-based spatial interpolation from measurements for sound level mapping in urban areas
Authors: Aumond Pierre , Can Arnaud , Mallet Vivien , De Coensel Bert , Ribeiro Carlos , Botteldooren Dick , Lavandier Catherine
Published: May 2018

Network-based sound monitoring systems are deployed in various cities over the world and mobile applications allowing participatory sensing are now common. Nevertheless, the sparseness of the collected measurements, either in space or in time, complicates the production of sound maps. This paper describes the results of a measurement campaign that has been conducted in order to test different spatial interpolation strategies for producing sound maps. Mobile measurements have been performed while walking multiple times in every street of the XIIIth district of Paris. By adaptively constructing a noise map on the basis of these measurements, the role of the density of observations and the performance of four different interpolation strategies is investigated. Ordinary and universal Kriging methods are assessed, as well as the effect of using an alternative definition of the distance between observation locations, which takes the topology of the road network into account. The results show that a high density of observation points is necessary to obtain an interpolated sound map close to the reference map.
Passive acoustic detection and estimation of the number of sources using compact arrays
Authors: Urazghildiiev Ildar R. , Hannay David E.
Published: May 2018

The problem of estimating the number of sound-producing sources detected using a compact array of hydrophones is addressed. Closed form expressions representing the techniques of automatic detection and estimation of the number of callers are given. Their performance is evaluated on a year-long dataset (1 October 2015–6 October 2016) containing humpback whale and killer whale calls collected in the Strait of Georgia, near Vancouver, British Columbia. Manual verification of the automatic detections produced by the approach required ∼40 h.
High-flux soft x-ray harmonic generation from ionization-shaped few-cycle laser pulses
Authors: Johnson Allan S. , Austin Dane R. , Wood David A. , Brahms Christian , Gregory Andrew , Holzner Konstantin B. , Jarosch Sebastian , Larsen Esben W. , Parker Susan , Strüber Christian S. , Ye Peng , Tisch John W. G. , Marangos Jon P.
Published: May 2018

X-ray harmonics made with long-wavelength lasers reach higher fluxes and photon energies when plasma effects dominate.
Toward tailoring Majorana bound states in artificially constructed magnetic atom chains on elemental superconductors
Authors: Kim Howon , Palacio-Morales Alexandra , Posske Thore , Rózsa Levente , Palotás Krisztián , Szunyogh László , Thorwart Michael , Wiesendanger Roland
Published: May 2018

We demonstrate the artificial construction of magnetic atom chains on a conventional superconductor as a Majorana platform.
Substrate-modulated unwinding of transmembrane helices in the NSS transporter LeuT
Authors: Merkle Patrick S. , Gotfryd Kamil , Cuendet Michel A. , Leth-Espensen Katrine Z. , Gether Ulrik , Loland Claus J. , Rand Kasper D.
Published: May 2018

The substrate-modulated, partial unwinding of transmembrane helices may facilitate the release of Na
+
and substrate in LeuT.
Phase behaviors of colloidal analogs of bent-core liquid crystals
Authors: Yang Yang , Pei Hanwen , Chen Guangdong , Webb Kyle Thomas , Martinez-Miranda Luz J. , Lloyd Isabel K. , Lu Zhongyuan , Liu Kun , Nie Zhihong
Published: May 2018

Bent colloidal rods exhibit fascinating polar ordering and chirality formation despite the achiral nature of the rods.
Artificial 3D hierarchical and isotropic porous polymeric materials
Authors: Chisca Stefan , Musteata Valentina-Elena , Sougrat Rachid , Behzad Ali Reza , Nunes Suzana P.
Published: May 2018

We report a simple method for rapid replication of hierarchical, isotropic porous materials that mimic complex living structures.
Experimental two-dimensional quantum walk on a photonic chip
Authors: Tang Hao , Lin Xiao-Feng , Feng Zhen , Chen Jing-Yuan , Gao Jun , Sun Ke , Wang Chao-Yue , Lai Peng-Cheng , Xu Xiao-Yun , Wang Yao , Qiao Lu-Feng , Yang Ai-Lin , Jin Xian-Min
Published: May 2018

The first spatial 2D quantum walk on a photonic chip with thousands of nodes is realized for future analog quantum computing.
Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis
Authors: Tzelepis Fanny , Blagih Julianna , Khan Nargis , Gillard Joshua , Mendonca Laura , Roy Dominic G. , Ma Eric H. , Joubert Philippe , Jones Russell G. , Divangahi Maziar
Published: May 2018

The regulation of a T cell metabolic program is a critical component of host tolerance to tuberculosis.
Plasmodium falciparum MSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection
Authors: Deshmukh Arunaditya , Chourasia Bishwanath Kumar , Mehrotra Sonali , Kana Ikhlaq Hussain , Paul Gourab , Panda Ashutosh , Kaur Inderjeet , Singh Susheel Kumar , Rathore Sumit , Das Aparup , Gupta Priya , Kalamuddin Md , Gakhar S. K. , Mohmmed Asif , Theisen Michael , Malhotra Pawan
Published: May 2018

Plasmodium falciparummerozoite surface protein 3 (MSP3) is an abundantly expressed secreted merozoite surface protein and a leading malaria vaccine candidate antigen. However, it is unclear how MSP3 is retained on the surface of merozoites without a glycosylphosphatidylinositol (GPI) anchor or a transmembrane domain.
Exploration of methods for lamb carcass yield estimation in Canada
Authors: Juárez M. , López-Campos Ó. , Roberts J.C. , Prieto N. , Larsen I.L. , Uttaro B. , Dugan M.E.R. , Cancino-Baier D. , Hosford S. , Galbraith J. , Aalhus J.L.
Published: May 2018

Different approaches were evaluated to improve the accuracy of carcass yield predictions of Canadian lamb carcasses using manually obtained measurements and dual-energy X-ray absorptiometry (DEXA). Several linear carcass measurements were obtained from a population of commercial lamb carcasses representative of the variability in Canadian slaughter plants (n = 155). Carcass measures were categorized into four sets according to when each measure could be obtained in the slaughter process. Each set of carcass measurements were subjected to stepwise regression and used to develop models for the estimation of lean meat and saleable yield percentages. Tissue depth measures (at the GR site) explained 44% of variation in lean meat yield in hot carcasses and 53% in cold carcasses. When additional parameters were included with cold GR, the regression model explained 61.9% of the variability in lean meat yield. Saleable yield predictions were less accurate (R2 < 0.40); the greatest degree of variability was predicted when the model included ribeye area (R2 = 0.39). The DEXA scans obtained on carcass sides were able to predict about 78% of variability in carcass lean meat yield and 91% of fat content. This information could be used by the lamb meat industry to establish new carcass classification systems based on more accurate lean meat yield values.
Assessing haplotype-based models for genomic evaluation in Holstein cattle
Authors: Karimi Z. , Sargolzaei M. , Robinson J.A.B. , Schenkel F.S.
Published: May 2018

A single-nucleotide polymorphisms-based genomic relationship matrix (GSNP) discriminate less identity by state from identity by descent (IBD) alleles compared with a multi-locus haplotype-based relationship matrix (GHAP), which can better capture IBD alleles and recent relationships. We aimed to compare the prediction reliability and prediction bias of genomic best linear unbiased prediction (GBLUP) using either GSNPor GHAPin Holstein cattle. Therefore, a total of 57 traits with a wide range of heritability values were analyzed. Classical validation tests were done using a validation dataset comprised of 50k genotype records of 561–669 proven bulls born in 2010–2011 with an official estimated breeding value (EBV) in 2016 and a training set of 5314–19 678 bulls born before 2010, depending on the trait. The method for building the genomic relationship matrix (G) had significant, but small effect on observed reliability (r2GEBV) (p < 0.0001) and bias (p < 0.0001). A significant interaction between G and the level of trait heritability on r2GEBVand bias was also observed (p < 0.0001). The small gains in r2GEBVand small reductions in the bias by using GHAPBLUP were increased when predicting moderate to high-heritability traits compared with low-heritability traits.
Cascading failure model for improving the robustness of scale-free networks
Authors: Ju Zhichao , Ma Jinlong , Xie Jianjun , Qi Zhaohui
Published: May 2018

To control the spread of cascading failure on scale-free networks, we propose a new model with the betweenness centrality and the degrees of the nodes which are combined. The effects of the parameters of the edge weight on cascading dynamics are investigated. Five metrics to evaluate the robustness of the network are given: the threshold parameter ([Formula: see text]), the proportion of collapsed edges ([Formula: see text]), the proportion of collapsed nodes ([Formula: see text]), the number of nodes in the largest connected component ([Formula: see text]) and the number of the connected component ([Formula: see text]). Compared with the degrees of nodes’ model and the betweenness of the nodes’ model, the new model could control the spread of cascading failure more significantly. This work might be helpful for preventing and mitigating cascading failure in real life, especially for small load networks.
Resolving controls for exact and approximate controllability of viscous Burgers’ equation: The Green’s function approach
Authors: Khurshudyan Asatur Zh.
Published: May 2018

In this paper, we consider a nonlinear control problem for one-dimensional viscous Burgers’ equation associated with a controlled linear heat equation by means of the Hopf–Cole transformation. The control is carried out by the time-dependent intensity of a distributed heat source influencing the heat equation. The set of admissible controls consists of compactly supported [Formula: see text] functions. Using the Green’s function approach, we analyze the possibilities of exact and approximate establishment of a given terminal state for the associated nonlinear Burgers’ equation within a desired amount of time. It is shown that the exact controllability of the associated Burgers’ equation and the heat equation are equivalent. Furthermore, sufficient conditions for the approximate controllability are derived. The set of resolving controls is constructed in both cases. The determination of the resolving controls providing exact controllability is reduced to an infinite-dimensional system of linear algebraic equations. By means of the heuristic method of resolving control determination, parametric hierarchies of solutions providing approximate controllability are constructed. The results of a numerical simulation supporting the theoretical derivations are discussed.
Renormalized volumes with boundary
Authors: Gover A. Rod , Waldron Andrew
Published: May 2018

We develop a general regulated volume expansion for the volume of a manifold with boundary whose measure is suitably singular along a separating hypersurface. The expansion is shown to have a regulator independent anomaly term and a renormalized volume term given by the primitive of an associated anomaly operator. These results apply to a wide range of structures. We detail applications in the setting of measures derived from a conformally singular metric. In particular, we show that the anomaly generates invariant ([Formula: see text]-curvature, transgression)-type pairs for hypersurfaces with boundary. For the special case of anomalies coming from the volume enclosed by a minimal hypersurface ending on the boundary of a Poincaré–Einstein structure, this result recovers Branson’s [Formula: see text]-curvature and corresponding transgression. When the singular metric solves a boundary version of the constant scalar curvature Yamabe problem, the anomaly gives generalized Willmore energy functionals for hypersurfaces with boundary. Our approach yields computational algorithms for all the above quantities, and we give explicit results for surfaces embedded in 3-manifolds.
A semilinear Schrödinger equation with zero on the boundary of the spectrum and exponential growth in ℝ2
Authors: Cavalcante Marcius Petrúcio , Alves Claudianor O. , Medeiros Everaldo
Published: May 2018

The main purpose of this paper is to establish the existence of solutions for the semilinear Schrödinger equation [Formula: see text] where the potential [Formula: see text] is periodic, [Formula: see text] lies on the boundary of a spectral gap of the Schrödinger operator [Formula: see text] and the nonlinearity [Formula: see text] is periodic and has subquadratic exponential growth. The proofs rely on a linking-type argument and a Trudinger–Moser type inequality proved in this paper.
Adoption of Cloud Computing: A Study with Public and Private Hospitals in a Developing Country
Authors: Mallmann Gabriela Labres , Maçada Antônio Carlos Gastaud
Published: May 2018

This research aims to analyze the factors influencing the adoption of cloud computing (CC) in public and private hospitals in a developing country setting, specifically in Brazil’s hospital industry. We interviewed IT professionals from four hospitals. The study demonstrates that concerns with security and availability matter more to the hospitals than the expected benefits of CC, such as flexibility and cost reduction. In addition, the findings show that there are relevant differences between public and private organizations, such as regulatory issues and cost, which influence the adoption of cloud computing in each context. Cloud-based resources continue to worry companies that deal with sensitive data as healthcare institutions. Knowledge acquired from this study is particularly beneficial to IT executives to guide their decision to create or adjust CC initiatives in healthcare.
Toward a Pragmatic Theory for Managing Nescience
Authors: Weber Charles M. , Hasenauer Rainer P. , Mayande Nitin V.
Published: May 2018

Aristotle’s dictum scio nescio (I know that I don’t know) may serve as a source of enhanced performance for organizations. Awareness of nescience sets the direction for further inquiry, as managers tend to move in the direction that they believe will reduce nescience most. However, nescience is difficult to quantify, so, to date, managers have primarily relied on intuition. This paper introduces a theoretical framework for managing nescience that is based on information theory. This framework is tested in three exploratory empirical studies that take place in highly contrasting settings: semiconductor manufacturing, medical diagnostics and social media analytics. All three studies demonstrate that metrics related to information entropy can be used to quantify nescience. However, practitioners value the framework and its metrics more highly in the settings where the quality of or access to information drives successful product development. The problems encountered in these settings tended to be well-structured, or they were converted from being ill-structured to being well-structured. Further study of more highly contrasting practical settings will be required to determine whether frameworks based on information theory can serve as foundations for a broadly based, pragmatic theory for managing nescience.
Strategic Complexity of Impactful Innovation in Automotive Component Manufacturing in an Emerging Economy
Authors: van den Blink P. Alexander , Steyn Jasper L.
Published: May 2018

This research was directed at the impact of innovation strategy complexity on the breadth of innovation strategy objectives achievement. The context is automotive component manufacturing in developing economies. Given the risk associated with innovation activity, the question is whether firms can improve their success by adopting a complex market access strategy. The methodology was survey based, utilizing data on the innovation activities of some 530 automotive component manufacturing firms obtained by a questionnaire applied in the Pune region in India, Beijing region in China and in South Africa. Path analysis by structural equation modeling was applied to analyze the data for the hypothesized relationships. It was found that strategic complexity in the larger combined country data set is positively and significantly related to a greater breadth of impact of innovation in terms of the market access strategies implemented. It was also observed that diversity of technology and knowledge sources, and innovation types, play a fundamental role in this relationship. The results for individual countries are different from those of all countries combined and yielded varying conclusions. The SA data set was unfortunately too small to meet the requirements for reliable results on its own, but served to support understanding of the influence of its different environment. The findings support the proposition that a diverse innovation strategy should be developed and executed in a business strategy directed at innovation.
Numerical Study of Integrated Solar Photovoltaic–Thermal Module with a Refrigeration System for Air-Conditioning and Hot Water Production under the Tropical Climate Conditions of Singapore
Authors: Dubey Swapnil , Subiantoro Alison
Published: May 2018

Thermal systems of buildings in the tropics are highly energy intensive. In this study, a novel integrated solar photovoltaic–thermal–refrigeration (PVTR) system used to produce hot water and air-conditioning in the tropical climate conditions of Singapore was analyzed. A dynamic simulation model was formulated for the analysis. Mathematical models were developed for the PV sandwich attached with a solar flat plate collector and for the main components of the refrigeration system. Thorough investigation of the electrical and thermal performances of the system were conducted through the analysis of coefficient of performance (COP), cooling capacity, water temperature and heat capacity in water heater, photovoltaic (PV) module temperature and PV efficiency. The results show that attractive electrical and thermal performance can be achieved with a maximum annual cooling COP of 9.8 and a heating COP of 11.3. The PV efficiency and power saving were 14% and 53%, respectively. The annual cooling, heating and PV energy produced were 9.7, 15.6 and 1.6[Formula: see text]MWh, respectively. The financial payback period of the system was 3.2 years and greenhouse gas (GHG) emission reduction annually was 12.6 tons of CO2 equivalents (tCO2e).
Effect of sintering temperature on microstructure and nonlinear electrical characteristics of ZnO varistor
Authors: Bouchekhlal Ahmed , Hobar Farida
Published: May 2018

The nonlinear properties of ZBMCCS-based varistors, which are composed of ZnO–Bi2O3–MnO2–Cr2O3–Sb2O3–Co3O4 and SiO2 are studied inrelation to sintering temperature, in the range of 1280–1350[Formula: see text]C. The samples are investigated for grain morphology by using scanning electron microscope (SEM). These samples were examined by using X-ray diffraction patterns (XRD) and DC electrical measurements. X-ray diffraction analysis of the samples show the presence of ZnO, Zn2SiO4 willemite phase and Co[Formula: see text]Sb[Formula: see text]O4 spinel phases.The average grain size of ZnO increased as the sintering temperature increased from 2.57 to 6.84 [Formula: see text]m. In the examined temperature range, the breakdown field decreased from 2992 to 127[Formula: see text]V/cm with the increase of sintering temperature. This system gives a relatively high nonlinearity coefficient [Formula: see text] (at a sintering temperature of 1280[Formula: see text]C) with a low leakage current of 0.21[Formula: see text]mA/cm2.
A national assessment of landslide hazard from Outside Party Slopes to the rail network of Great Britain
Authors: Freeborough K. , Dashwood C. , Diaz Doce D. , Jessamy G. , Brooks S. , Reeves H. , Abbott S.
Published: May 2018

In recent years, a number of high profile landslide events have caused disruption, derailments or damage to railway infrastructure in Great Britain. A landslide susceptibility model of the entire railway network was created, designed to give a national overview of potential landslide hazard originating from Outside Party Slopes. The current assessment was compiled using Geographic Information System (GIS) techniques and desktop modelling to apply a structured analysis of each buffered Earthwork Inspection 5 Chain (
c
. 100 m; EI5C). Data analysed along the network included the BGS GeoSure instability model and newly updated national models for debris flow, earth flow and rock fall, supported by historical landslide data. In order to further focus the Outside Party Slope zone, a buffer of External Natural Geological Influence (BENGI) was created using a 5 m Digital Terrain Model. Landslide susceptibility for each EI5C was categorized using a ‘Classification of Hazards on Outside Party Slopes’ (CHOPS) score; representing the modelled potential for landslide hazard. The outputs were combined as a series of matrices to present the CHOPS and Network Rail Derailment Criticality Band interactions. This research will allow further focused analysis of the network, in order to prioritize and direct future investigation and policy decisions.
Compositional Synthesis of Piece-Wise Functions by Learning Classifiers
Authors: Neider Daniel , Saha Shambwaditya , Madhusudan P.
Published: May 2018

We present a novel general technique that uses classifier learning to synthesize piece-wise functions (functions that split the domain into regions and apply simpler functions to each region) against logical synthesis specifications. Our framework works by combining a synthesizer of functions for fixed concrete inputs and a synthesizer of predicates that can be used to define regions. We develop a theory of single-point refutable specifications that facilitate generating concrete counterexamples using constraint solvers. We implement the framework for synthesizing piece-wise functions in linear integer arithmetic, combining leaf expression synthesis using constraint-solving with predicate synthesis using enumeration, and tie them together using a decision tree classifier. We demonstrate that this compositional approach is competitive compared to existing synthesis engines on a set of synthesis specifications.
Cluster and Single-Node Analysis of Long-Term Deduplication Patterns
Authors: Sun Zhen “Jason” , Kuenning Geoff , Mandal Sonam , Shilane Philip , Tarasov Vasily , Xiao Nong , Zadok Erez
Published: May 2018

Deduplication has become essential in disk-based backup systems, but there have been few long-term studies of backup workloads. Most past studies either were of a small static snapshot or covered only a short period that was not representative of how a backup system evolves over time. For this article, we first collected 21 months of data from a shared user file system; 33 users and over 4,000 snapshots are covered. We then analyzed the dataset, examining a variety of essential characteristics across two dimensions: single-node deduplication and cluster deduplication. For single-node deduplication analysis, our primary focus was individual-user data. Despite apparently similar roles and behavior among all of our users, we found significant differences in their deduplication ratios. Moreover, the data that some users share with others had a much higher deduplication ratio than average. For cluster deduplication analysis, we implemented seven published data-routing algorithms and created a detailed comparison of their performance with respect to deduplication ratio, load distribution, and communication overhead. We found that per-file routing achieves a higher deduplication ratio than routing by super-chunk (multiple consecutive chunks), but it also leads to high data skew (imbalance of space usage across nodes). We also found that large chunking sizes are better for cluster deduplication, as they significantly reduce data-routing overhead, while their negative impact on deduplication ratios is small and acceptable. We draw interesting conclusions from both single-node and cluster deduplication analysis and make recommendations for future deduplication systems design.
Some Advances in the Design of Survey Experiments
Authors: Sniderman Paul M.
Published: May 2018

This article calls attention to some designs in survey experiments that give new leverage in hypothesis testing and validation. The premise of this review is the modesty of survey experiments—modesty of treatment, modesty of scale, modesty of measurement. The focus of this review, accordingly, is the compensating virtues of modesty. With respect to hypothesis testing, I spotlight ( a) cross-category comparisons, ( b) null-by-design experiments, ( c) explication, ( d) conjoint designs, and ( e) sequential factorials. With respect to validation regimes, I discuss ( a) parallel studies, ( b) paired designs, and ( c) splicing. Throughout, the emphasis is on moving from experiment in the singular to experiments in the plural, learning as you go.
A Taxonomy of Protest Voting
Authors: Alvarez R. Michael , Kiewiet D. Roderick , Núñez Lucas
Published: May 2018

Observers of elections often report that voters have engaged in protest voting. We find that “protest voting” refers to a wide range of behaviors, and we create a taxonomy of these phenomena. Support for fringe or insurgent parties is often labeled as protest voting. Voting theorists have used the term in a completely different way, identifying an unusual type of tactical voting as protest voting. Protest voting also occurs when voters cast blank, null, or spoiled ballots. There are also instances when protest voting is organized and directed by political elites. Finally, several countries provide voters with the option of casting a vote for “None of the Above,” which some see as a form of protest voting. In addition to developing this taxonomy, we discuss the analytical and empirical challenges confronting research on each type of protest voting.
On the Theory of Parties
Authors: McCarty Nolan , Schickler Eric
Published: May 2018

The theory of parties put forward by scholars associated with the University of California at Los Angeles argues that political parties are best viewed as coalitions of intense policy demanders. These policy demanders use their control of nomination processes to select candidates loyal to the groups’ shared policy priorities. By highlighting the role of groups, this theory has made a major contribution to our understanding of party politics, breathing new life into important debates about the limitations of democratic responsiveness in the United States. The theory, however, leaves a number of theoretical and empirical issues unresolved. The “invisible primary” hypothesis has performed poorly in recent presidential elections. More importantly, we argue that the next generation of party theorizing needs to account for the distinctive roles and capacities of officeholders and voters, and to reengage the idea of formal parties as institutional intermediaries between groups, politicians, and voters.
Advanced age results in a diminished endothelial glycocalyx
Authors: Machin Daniel R. , Bloom Samuel I. , Campbell Robert A. , Phuong Tam T. T. , Gates Phillip E. , Lesniewski Lisa A. , Rondina Matthew T. , Donato Anthony J.
Published: May 2018

Age-related microvascular dysfunction is well characterized in rodents and humans, but little is known about the properties of the microvascular endothelial glycocalyx in advanced age. We examined the glycocalyx in microvessels of young and old male C57BL6 mice (young: 6.1 ± 0.1 mo vs. old: 24.6 ± 0.2 mo) using intravital microscopy and transmission electron microscopy and in human participants (young: 29 ± 1 yr vs. old: 60 ± 2 yr) using intravital microscopy. Glycocalyx thickness in mesenteric and skeletal muscle microvessels was 51–54% lower in old compared with young mice. We also observed 33% lower glycocalyx thickness in the sublingual microcirculation of humans in advanced age. The perfused boundary region, a marker of glycocalyx barrier function, was also obtained using an automated capture and analysis system. In advanced age, we observed a 10–22% greater perfused boundary region in mice and humans, indicating a more penetrable glycocalyx. Finally, using this automated analysis system, we examined perfused microvascular density and red blood cell (RBC) fraction. Perfused microvascular density is a marker of microvascular function that reflects the length of perfused microvessel segments in a given area; RBC fraction represents the heterogeneity in RBC presence between microvessel segments. Compared with young, the perfused microvascular density was 16–21% lower and RBC fraction was 5–14% lower in older mice and in older humans. These data provide novel evidence that, across mammalian species, a diminished glycocalyx is present in advanced age and is accompanied by markers of impaired microvascular perfusion. Age-related glycocalyx deterioration may be an important contributor to microvascular dysfunction in older adults and subsequent pathophysiology.

NEW & NOTEWORTHY Advanced age is characterized by microvascular dysfunction that contributes to age-related cardiovascular diseases, but little is known about endothelial glycocalyx properties in advanced age. This study reveals, for the first time, lower glycocalyx thickness and barrier function that is accompanied by impaired microvascular perfusion in both mice and humans in advanced age.
Differential gene expression patterns in vein regions susceptible versus resistant to neointimal hyperplasia
Authors: Kwon Sun Hyung , Li Li , Terry Christi M. , Shiu Yan-Ting , Moos Philip J. , Milash Brett A. , Cheung Alfred K. , Blumenthal Donald K.
Published: May 2018

Arteriovenous hemodialysis graft (AVG) stenosis results in thrombosis and AVG failure, but prevention of stenosis has been unsuccessful due in large part to our limited understanding of the molecular processes involved in neointimal hyperplasia (NH) formation. AVG stenosis develops chiefly as a consequence of highly localized NH formation in the vein-graft anastomosis region. Surprisingly, the vein region just downstream of the vein-graft anastomosis (herein termed proximal vein region) is relatively resistant to NH. We hypothesized that the gene expression profiles of the NH-prone and NH-resistant regions will be different from each other after graft placement, and analysis of their genomic profiles may yield potential therapeutic targets to prevent AVG stenosis. To test this, we evaluated the vein-graft anastomosis (NH-prone) and proximal vein (NH-resistant) regions in a porcine model of AVG stenosis with a porcine microarray. Gene expression changes in these two distinct vein regions, relative to the gene expression in unoperated control veins, were examined at early (5 days) and later (14 days) time points following graft placement. Global genomic changes were much greater in the NH-prone region than in the NH-resistant region at both time points. In the NH-prone region, genes related to regulation of cell proliferation and osteo-/chondrogenic vascular remodeling were most enriched among the significantly upregulated genes, and genes related to smooth muscle phenotype were significantly downregulated. These results provide insights into the spatial and temporal genomic modulation underlying NH formation in AVG and suggest potential therapeutic strategies to prevent and/or limit AVG stenosis.
Mechanisms of allelic and clinical heterogeneity of lamin A/C phenotypes
Authors: Perovanovic Jelena , Hoffman Eric P.
Published: May 2018

Mutations in the lamin A/C ( LMNA) gene cause a broad range of clinical syndromes that show tissue-restricted abnormalities of post mitotic tissues, such as muscle, nerve, heart, and adipose tissue. Mutations in other nuclear envelope proteins cause clinically overlapping disorders. The majority of mutations are dominant single amino acid changes (toxic protein produced by the single mutant gene), and patients are heterozygous with both normal and abnormal proteins. Experimental support has been provided for different models of cellular pathogenesis in nuclear envelope diseases, including changes in heterochromatin formation at the nuclear membrane (epigenomics), changes in the timing of steps during terminal differentiation of cells, and structural abnormalities of the nuclear membrane. These models are not mutually exclusive and may be important in different cells at different times of development. Recent experiments using fusion proteins of normal and mutant lamin A/C proteins fused to a bacterial adenine methyltransferase (DamID) provided compelling evidence of mutation-specific perturbation of epigenomic imprinting during terminal differentiation. These gain-of-function properties include lineage-specific ineffective genomic silencing during exit from the cell cycle (heterochromatinization), as well as promiscuous initiation of silencing at incorrect places in the genome. To date, these findings have been limited to a few muscular dystrophy and lipodystrophy LMNA mutations but seem shared with a distinct nuclear envelope disease, emerin-deficient muscular dystrophy. The dominant-negative structural model and gain-of-function epigenomic models for distinct LMNA mutations are not mutually exclusive, and it is likely that both models contribute to aspects of the many complex clinical phenotypes observed.
Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain
Authors: He Hong , Holl Katie , DeBehnke Sarah , Yeo Chay Teng , Hansen Polly , Gebre Abraham K. , Leone-Kabler Sandra , Ruas Margarida , Parks John S. , Parrington John , Solberg Woods Leah C.
Published: May 2018

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.
Current Status of the Third-LineHelicobacter pyloriEradication
Authors: Choi Jae Ho , Yang Young Joo , Bang Chang Seok , Lee Jae Jun , Baik Gwang Ho
Published: May 2018

Antibiotic resistance is growing worldwide, and patients who have failed consecutive 1st- and 2nd-lineH. pylorieradication regimens are increasing. Therefore, the role of the bacterial culture with antibiotic susceptibility testing and molecular susceptibility testing is important for avoiding the use of ineffective antibiotics. However, antibiotic susceptibility testing-guided treatment does not necessarily guarantee successful eradication, and there have been mixed results for the effectiveness of a 3rd-line rescue therapy. Therefore, providing patients with pretreatment medication instructions and education is important. It is also crucial to determine the reason of the eradication failure, including host-related factors (poor compliance to eradication regimen, smoking, and cytochrome P450 2C19 genetic polymorphism) or treatment-related factors (inadequate dosage or duration of therapy and gastric acidity), as such factors can be modified for a tailored therapy. Although the indications forH. pylorieradication have widened, patients at a high risk of gastric cancer can gain definitive benefits with a 3rd-line or even 4th-line therapy.
CD4+ T-cell–Mediated Rejection of MHC Class II–Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs
Authors: Haabeth Ole Audun W. , Fauskanger Marte , Manzke Melanie , Lundin Katrin U. , Corthay Alexandre , Bogen Bjarne , Tveita Anders A.
Published: May 2018

Tumor-specific CD4+ T cells have been shown to mediate efficient antitumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)–expressing tumor cells, or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4+ T cells reactive against an epitope within the Ig light chain variable region of a murine B-cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II–restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II–expressing tumor cells was essential both for the priming and effector phase of CD4+ T-cell–driven antitumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen–specific CD4+ T cells in vivo. These findings demonstrate that MHC class II expression on tumor cells themselves is not required for CD4+ T-cell–mediated rejection and that indirect display on host APC is sufficient for effective tumor elimination. These results support the importance of tumor-infiltrating APC as mediators of tumor cell killing by CD4+ T cells.

Significance: Elimination of tumors by CD4+ T cells recognizing secreted tumor neoantigens can occur in the absence of tumor cell-intrinsic MHC II expression, highlighting the potential clinical relevance of indirect antigen recognition by tumor-infiltrating APC.

Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4573/F1.large.jpg. Cancer Res; 78(16); 4573–85. ©2018 AACR.
The Highly Metastatic Nature of Uterine Cervical/Endometrial Cancer Displaying Tumor-Related Leukocytosis: Clinical and Preclinical Investigations
Authors: Sasano Tomoyuki , Mabuchi Seiji , Kozasa Katsumi , Kuroda Hiromasa , Kawano Mahiru , Takahashi Ryoko , Komura Naoko , Yokoi Eriko , Matsumoto Yuri , Hashimoto Kae , Sawada Kenjiro , Morii Eiichi , Kimura Tadashi
Published: May 2018

Purpose: The aim of this study was to investigate the metastatic potential of uterine cervical and endometrial cancer displaying tumor-related leukocytosis (TRL).

Experimental Design: Clinical data on uterine cervical (N = 732) and endometrial cancer (N = 900) were collected, and the metastatic potential of TRL-positive cancer was evaluated in univariate and multivariate analyses. Tumor and blood samples obtained from patients with cervical cancer, cervical cancer cell lines, and a mouse model of cervical cancer were used to examine the mechanisms underlying the highly metastatic nature of TRL-positive cancer, focusing on tumor-derived G-CSF and the myeloid-derived suppressor cell (MDSC)-mediated premetastatic niche.

Results: Pretreatment TRL was significantly associated with visceral organ metastasis in patients with uterine cervical or endometrial cancer. The patients with TRL-positive cervical cancer displayed upregulated tumor G-CSF expression, elevated G-CSF levels, and increased MDSC frequencies in the peripheral blood compared with the TRL-negative patients. In vitro and in vivo investigations revealed that MDSCs produced in response to tumor-derived G-CSF are involved in premetastatic niche formation, which promotes visceral organ metastasis of TRL-positive cancer. The depletion of MDSCs attenuated this premetastatic niche formation and effectively inhibited the visceral organ metastasis of TRL-positive cancer.

Conclusions: Uterine cervical/endometrial cancer displaying TRL is a distinct clinical entity with high metastatic potential. Tumor-derived G-CSF and the MDSC-mediated premetastatic niche are responsible for the highly metastatic nature of this type of cancer. MDSC-targeting therapy might represent a potential strategy for combating metastasis derived from TRL-positive uterine cancer. Clin Cancer Res; 24(16); 4018–29. ©2018 AACR.
Parque Industrial, de Patrícia Galvão: cartografia feminista na São Paulo em modernização
Authors: Menezes Ludimila Moreira
Published: May 2018

A contemporaneidade do romance em suas ressonâncias feministas permite pensar as personagens mulheres a partir de um processo múltiplo de interações e insurgências que se contrapõe com a realidade chapada e uniforme de personagens resignadas com o devir de opressão ofertada pelo capitalismo. Com provocações, que confrontam de imediato teleologias e racismos, o romance, margeado pela crítica comunista, se vale de uma memória emocional para romper com o esquema pedagógico pleiteado pelo partido comunista e desferir suas histórias repletas do agora difícil, mas não impossível, de revoluções.
Florbela Espanca e Adília Lopes: A subversão do papel feminino
Authors: Magalhães Clêuma de Carvalho
Published: May 2018

Este trabalho tem como propósito analisar a subversão do papel feminino na obra das escritoras portuguesas Florbela Espanca e Adília Lopes. Cada uma à sua maneira, ambas constroem uma imagem feminina que foge aos padrões impostos pela sociedade portuguesa, negando o seu papel de submissão, assumindo o desejo que habita o seu corpo e afirmando-se como sujeito.
Desmedidas fronteiras na relação Sul-Sul
Authors: Lopes Estefânia Francis
Published: May 2018

O presente artigo se propõe a focalizar os diálogos presentes no livro Desmedida: Luanda, São Paulo, São Francisco e volta, do escritor angolano, Ruy Duarte de Carvalho. Diálogos entre Brasil e Angola estabelecidos por meio da literatura, antropologia, música e relatos de viagens. Apontamos na construção textual como o autor, ao querer conhecer mais de perto o Brasil, que sempre esteve presente em seu imaginário, seja por meio das artes ou notícias, acaba por (re)encontrar Angola.
Lírica e cidade em “Reféns da metrópole”, de Jenyffer Nascimento
Authors: Sena Fernando Reis de
Published: May 2018

Analisa-se, a partir do poema “Reféns da metrópole”, da coletânea Terra fértil (2014), de Jenyffer Nascimento, a relação entre sujeito lírico e cidade. Argumenta-se que o poema – sem escamotear a solidão, a depressão e a deterioração das identidades individuais e coletivas no tempo presente – se desenvolve nas relações entre seres humanos e os meios tecnológicos, revelando a cibercidade, em cujos espaços os sujeitos se (des)encontram e se (des)realizam.
Cadela: um aspecto da submissão de gênero
Authors: Johann Gisela
Published: May 2018

O presente estudo visa identificar a matéria literária imbricada na estrutura do conto Cadela, de Luis Vilela (2006), que revela o espaço ocupado pela mulher dentro do casamento e na sociedade. Com base nos estudos sociológicos de Gilberto Freyre (1951) em Sobrados e Mucambos, destacam-se, assim, resquícios da sociedade patriarcal no que diz respeito ao que se propunha como papel social masculino e feminino.
Letras femininas. Mulheres escritoras em Portugal entre os séculos XVI/XVII e XVIII.
Authors: Machado Alleid Ribeiro
Published: May 2018

O presente artigo empreende uma breve revisão da literatura tradicional portuguesa, trazendo à cena os nomes de três escritoras portuguesas que fizeram parte do período histórico-literário seiscentista/setecentista, denominado Barroco, e do Iluminismo do século XVIII. Dessa forma, alinhado à proposta da crítica literária feminista, que tem se empenhado no resgate e estudo de autoras do passado, o artigo revisita excertos das Cartas portuguesas, de Mariana Alcoforado; alguns sonetos de Leonor de Almeida, a Marquesa de Alorna; e trechos do romance As aventuras de Diófanes, de Teresa Margarida da Silva e Orta, estabelecendo-se, assim, um diálogo analítico de viés comparatista entre essas produções e questões de caráter feminista e de gênero.
Uma, duas, três princesas de Ana Maria Machado: a jornada feminina da torre à rua
Authors: Ramos Samira dos Santos
Published: May 2018

Este artigo pretende problematizar a jornada do herói na literatura infantil contemporânea em que se observa que a figura da princesa deixa seu tradicional movimento de espera para colocar-se em jornada. Com base em Jolles, Coelho e Azevedo, realizamos o estudo da obra Uma, Duas, Três Princesas, de Ana Maria Machado, e suas convergências e divergências com os contos populares tradicionais.