bluuebunny/crossref_metadata_2025 huggingface dataset:
Abnormal subsurface hydrogen diffusion behaviors in heterogeneous hydrogenation reactions
Authors: Zhai Feina , Li Yuanjie , Yang Yongpeng , Jiang Sisi , Shen Xiangjian
Published: November 2018

Hydrogen adsorption and diffusion behaviors on noble metal model catalyst surfaces and into the subsurfaces are of paramount significance in the exploration of novel heterogenous catalytic hydrogenation reactions. We present an in-depth study of hydrogen adsorption on and diffusion into the subsurfaces of three typical 5d noble metals from three-dimensional electronically adiabatic potential energy surfaces (PESs) by interpolating plenty of ab initio density functional theory (DFT) configuration-energy points. The surfaces and subsurfaces regions of the relaxed Ir(100) and (111), Pt(100) and (111), and Au(100) and (111) surfaces, are, respectively, taken into account. For hydrogen adsorption on the (100) surfaces, the lowest adsorption energy site is the Bridge site, instead of the traditional Hollow site. Hydrogen prefers to follow the indirect pathway with a lower diffusion barrier, in the competition with the direct pathway with much higher diffusion barrier. For hydrogen diffusion on the (111) surfaces, hydrogen follows the pathway from Top site to fcc site on the surface and prefers an up-down direct pathway into the subsurface. Importantly, the nudged elastic band (NEB) based on the PESs can reproduce those results calculated from the NEB(DFT) very well. The developed highly-accurate and efficient approach based on the PESs helps us to further investigate the more complex reactant diffusion dynamics at surfaces.
Transport of particles driven by the traveling obstacle arrays
Authors: Zhu Wei-jing , Zhong Wei-rong , Xiong Jian-wen , Ai Bao-quan
Published: November 2018

Transport of three types of particles (passive particles, active particles without polar interaction, and active particles with polar interaction) is numerically investigated in the presence of traveling obstacle arrays. The transport behaviors are different for different types of particles. For passive particles, there exists an optimal traveling speed (or the translational diffusion) at which the average velocity of particles takes its maximum value. For active particles without polar interaction, the average velocity of particles is a peaked function of the obstacle traveling speed. The average velocity decreases monotonically with increase of the rotational diffusion for large driving speed, while it is a peaked function of the rotational diffusion for small driving speed. For active particles with polar interaction, interestingly, within particular parameter regimes, active particles can move in the opposite direction to the obstacles. The average velocity of particles can change its direction by changing the system parameters (the obstacles driving speed, the polar interaction strength, and the rotational diffusion).
Hierarchically structured metamaterials with simultaneously negative mass density and Young’s modulus by using dynamic homogenization
Authors: Lee K. Y. , Jeon W.
Published: November 2018

We propose one-dimensional hierarchical metamaterials (HMMs) that have simultaneously negative mass density and Young’s modulus in the sense of effective properties. Frequency-dependent effective properties of the HMMs are evaluated by using a dynamic homogenization theory. By considering three necessary conditions for dynamic homogenizability, we verify that our proposed HMMs can have physically meaningful double negativity, whereas the conventional periodic structures cannot. In addition, HMMs yield the broader ranges of the frequency and the effective properties for double negativity due to the large number of geometrical parameters. By exploring all the possible effective properties of HMMs, we discuss whether we can design metamaterials with the opposite sign of material properties in nature, ultimately aiming at perfect impedance matching.
Emergence of interfacial conduction and ferromagnetism in MnTe/InP
Authors: Watanabe R. , Yoshimi R. , Shirai M. , Tanigaki T. , Kawamura M. , Tsukazaki A. , Takahashi K. S. , Arita R. , Kawasaki M. , Tokura Y.
Published: November 2018

We report on emergence of two-dimensional conduction and ferromagnetism at the interface of MnTe thin films and InP substrates. The MnTe/InP heterostructures grown by molecular-beam epitaxy show thickness-independent sheet conductivity above a critical thickness of about 20 nm, indicating the formation of a conducting layer at the interface. Furthermore, the ferromagnetic behavior is confirmed by both magnetization and anomalous Hall effect measurements below a critical temperature of 270 K. The critical temperature is also independent of the thickness. By the investigation of the atomic structure with transmission electron microscopy, we observe a structural anomaly near the interface which consists of an antiprism-type Mn network unlike a prism-type Mn network of conventional MnTe. The band structure calculation shows that the antiprism-type MnTe can host metallic conduction and ferromagnetism, which is consistent with the present experimental results. The interface engineering based on the chalcogenide compound will develop a new arena for designing the emergent low dimensional conduction and magnetism.
Bond dissociation energies of FeSi, RuSi, OsSi, CoSi, RhSi, IrSi, NiSi, and PtSi
Authors: Sevy Andrew , Tieu Erick , Morse Michael D.
Published: November 2018

Resonant two-photon ionization spectroscopy has been used to investigate the spectra of the diatomic late transition metal silicides, MSi, M = Fe, Ru, Os, Co, Rh, Ir, Ni, and Pt, in the vicinity of the bond dissociation energy. In these molecules, the density of vibronic states is so large that the spectra appear quasicontinuous in this energy range. When the excitation energy exceeds the ground separated atom limit, however, a new decay process becomes available—molecular dissociation. This occurs so rapidly that the molecule falls apart before it can absorb another photon and be ionized. The result is a sharp drop to the baseline in the ion signal, which we identify as occurring at the thermochemical 0 K bond dissociation energy, D0. On this basis, the measured predissociation thresholds provide D0 = 2.402(3), 4.132(3), 4.516(3), 2.862(3), 4.169(3), 4.952(3), 3.324(3), and 5.325(9) eV for FeSi, RuSi, OsSi, CoSi, RhSi, IrSi, NiSi, and PtSi, respectively. Using thermochemical cycles, the enthalpies of formation of the gaseous MSi molecules are derived as 627(8), 700(10), 799(10), 595(8), 599(8), 636(10), 553(12), and 497(8) kJ/mol for FeSi, RuSi, OsSi, CoSi, RhSi, IrSi, NiSi, and PtSi, respectively. Likewise, combining these results with other data provides the ionization energies of CoSi and NiSi as 7.49(7) and 7.62(7) eV, respectively. Chemical bonding trends among the diatomic transition metal silicides are discussed.
Effects of ensembles, ligand, and strain on adsorbate binding to alloy surfaces
Authors: Li Hao , Shin Kihyun , Henkelman Graeme
Published: November 2018

Alloying elements with strong and weak adsorption properties can produce a catalyst with optimally tuned adsorbate binding. A full understanding of this alloying effect, however, is not well-established. Here, we use density functional theory to study the ensemble, ligand, and strain effects of close-packed surfaces alloyed by transition metals with a combination of strong and weak adsorption of H and O. Specifically, we consider PdAu, RhAu, and PtAu bimetallics as ordered and randomly alloyed (111) surfaces, as well as randomly alloyed 140-atom clusters. In these alloys, Au is the weak-binding component and Pd, Rh, and Pt are characteristic strong-binding metals. In order to separate the different effects of alloying on binding, we calculate the tunability of H- and O-binding energies as a function of lattice constant (strain effect), number of alloy-substituted sublayers (ligand effect), and randomly alloyed geometries (ensemble effect). We find that on these alloyed surfaces, the ensemble effect more significantly tunes the adsorbate binding as compared to the ligand and strain effects, with the binding energies predominantly determined by the local adsorption environment provided by the specific triatomic ensemble on the (111) surface. However, we also find that tuning of adsorbate binding from the ligand and strain effects cannot be neglected in a quantitative description. Extending our studies to other bimetallics (PdAg, RhAg, PtAg, PdCu, RhCu, and PtCu), we find similar conclusions that the tunability of adsorbate binding on random alloys is predominately described by the ensemble effect.
Slow photoelectron velocity-map imaging of cold C7− and C9−
Authors: Babin Mark C. , DeVine Jessalyn A. , Weichman Marissa L. , Neumark Daniel M.
Published: November 2018

High-resolution anion photoelectron spectra of cryogenically cooled C7− and C9− clusters obtained using slow photoelectron velocity-map imaging are presented, providing insight into the vibronic structure of neutral C7 and C9. These spectra yield accurate measurements of vibrational frequencies for the neutral clusters as well as electron affinities of 3.3517(4) and 3.6766(14) eV for C7 and C9, respectively. In the C7− spectrum, transitions involving the previously unreported v1 and v2 symmetric stretching modes, as well as the v9, v10, and v11 asymmetric bending modes, are assigned. Spin–orbit splitting is observed for several transitions in this spectrum, giving an energy difference of 28(6) cm−1 between the Π1/2g2 and Π3/2g2 spin–orbit levels of the C7− anion. In the spectrum of C9−, transitions involving the previously unreported symmetric stretch v1 and the asymmetric bend v11 are observed. In both spectra, several features are assigned to Franck-Condon forbidden transitions involving the doubly degenerate v10 and v11 modes of C7 and the v13 and v14 modes of C9. The appearance of these transitions is attributed to Herzberg-Teller coupling between the electronic states of the neutral clusters. Additional FC-forbidden transitions to states previously observed in gas-phase infrared experiments are observed and attributed to vibronic coupling between the electronic states of the anion, resulting in non-totally symmetric character in the anion’s full vibrational ground state. Finally, consideration of the energy dependence of detachment cross sections and Dyson orbital analyses reveal that addition of more carbon atoms to the linear chain results in photodetachment from delocalized molecular orbitals with increasing nodal structure, leading to threshold photodetachment cross sections that differ considerably from simple symmetry considerations.
Slip flow of Eyring-Powell nanoliquid film containing graphene nanoparticles
Authors: Khan Noor Saeed , Zuhra Samina , Shah Zahir , Bonyah Ebenezer , Khan Waris , Islam Saeed
Published: November 2018

The purpose of the present study is to discuss the effects of graphene nanoparticles on two dimensional magnetohydrodynamic unsteady flow and heat transfer in a thin film Eyring Powell nanofluid past a stretching sheet using velocity slip condition. The contents of graphene nanoparticles increase simultaneously the thermal conductivity and stability when incorporated into the dispersion of water based liquid network. The basic governing equations for velocity and temperature of the Eyring Powell nanofluid film with the boundary conditions easily and simply provide the transformed nonlinear coupled differential equations by employing appropriate similarity transformations. The modeled equations have been evaluated by using an efficient approach through homotopy analysis method which lead to detailed expressions for the velocity profile and temperature distribution. The present work discusses the salient features of all the indispensable parameters of velocity and temperature profiles which have been displayed graphically and illustrated. Skin friction and Nusselt number show an excellent agreement with the published work. The results are useful in the analysis, design of coating and cooling/heating processes.
Synthetic Bessel light needle for extended depth-of-field microscopy
Authors: Yang Jiamiao , Gong Lei , Shen Yuecheng , Wang Lihong V.
Published: November 2018

An ultra-long light needle is highly desired in optical microscopy for its ability to improve the lateral resolution over a large depth of field (DOF). However, its use in image acquisition usually relies on mechanical raster scanning, which compromises between imaging speed and stability and thereby restricts imaging performance. Here, we propose a synthetic Bessel light needle (SBLN) that can be generated and scanned digitally by complex field modulation using a digital micromirror device. In particular, the SBLN achieves a 45-fold improvement in DOF over its counterpart Gaussian focus. Further, we apply the SBLN to perform motionless two-dimensional and three-dimensional microscopic imaging, achieving both improved resolution and extended DOF. Our work is expected to open up opportunities for potential biomedical applications.
A novel method for characterizing temperature-dependent elastic modulus and glass transition temperature by processing the images of bending cantilever slender beams at different temperatures
Authors: Amalia Nadya , Yuliza Elfi , Margaretta Desyana O. , Utami Fisca D. , Surtiyeni Neni , Viridi Sparisoma , Abdullah Mikrajuddin
Published: November 2018

We propose a novel method for estimating the elastic modulus of several materials by processing the bending image of cantilever material sheets. The calculated results (tested for five samples) were consistent with data obtained by direct measurement using a tensile strength device. By placing the cantilever sheets in an environment inside of which the temperature could be controlled, we were able to obtain the temperature dependence of elastic modulus. We identified a drastic drop of elastic modulus at a certain temperature and assumed this temperature corresponds to glass transition temperature. We also introduced an equation for describing the elastic modulus around that critical temperature and were able to estimate the glass transition temperature for all tested polymer materials. Surprisingly, the estimated glass transition temperatures conform to data obtained by direct measurement using a DTA device. Since the elastic modulus changes suddenly around the glass transition temperature, the proposed method might be more accurate than measurement using a DTA device where the glass transition temperature corresponds to the location of a weak peak at the DTA curve. This is the first attempt for estimating the glass transition temperature of polymer based on bending of cantilever slender beam, and seems to be the simplest method. The method is very potential for developing new equipment for determining the glass transition temperature of polymeric materials.
New topological tool for multistable dynamical systems
Authors: Godara Prakhar , Dudkowski Dawid , Prasad Awadhesh , Kapitaniak Tomasz
Published: November 2018

We introduce a new method for investigation of dynamical systems which allows us to extract as much information as possible about potential system dynamics, based only on the form of equations describing it. The discussed tool of critical surfaces, defined by the zero velocity (and/or) acceleration field for particular variables of the system is related to the geometry of the attractors. Particularly, the developed method provides a new and simple procedure allowing to localize hidden oscillations. Our approach is based on the dimension reduction of the searched area in the phase space and has an advantage (in terms of complexity) over standard procedures for investigating full–dimensional space. The two approaches have been compared using typical examples of oscillators with hidden states. Our topological tool allows us not only to develop alternate ways of extracting information from the equations of motion of the dynamical system, but also provides a better understanding of attractors geometry and their capturing in complex cases, especially including multistable and hidden attractors. We believe that the introduced method can be widely used in the studies of dynamical systems and their applications in science and engineering.
Rate coefficients of the H + H2O2 → H2 + HO2 reaction on an accurate fundamental invariant-neural network potential energy surface
Authors: Lu Xiaoxiao , Meng Qingyong , Wang Xingan , Fu Bina , Zhang Dong H.
Published: November 2018

The rate coefficients of the H + H2O2 → H2 + HO2 reaction are calculated using the ring polymer molecular dynamics (RPMD), quasi-classical trajectory (QCT), and canonical variational transition state theory (CVT) with small curvature tunneling (SCT) correction, in conjunction with the recently constructed fundamental invariant-neural network (FI-NN) potential energy surface (PES) [X. Lu et al., Phys. Chem. Chem. Phys. 20, 23095 (2018)]. In RPMD calculations, 32, 16, and 8 beads are used for computing the rate coefficients at 200 K ≤ T ≤ 400 K, 500 K ≤ T ≤ 700 K, and 700 K < T ≤ 1000 K, respectively. Given that the previous experimental rate coefficients vary widely, in particular, at low temperatures, the present RPMD rate coefficients agree well with most of the experimental results. In addition, comparing with some experimental values, the present QCT and CVT/SCT calculations on the FI-NN PES also predict accurate results at some temperatures. These results strongly support the accuracy of the present dynamics calculations as well as the full-dimensional FI-NN PES.
Targeting αGal epitopes for multi-species embryo immunosurgery
Authors: Kurome Mayuko , Baehr Andrea , Simmet Kilian , Jemiller Eva-Maria , Egerer Stefanie , Dahlhoff Maik , Zakhartchenko Valeri , Nagashima Hiroshi , Klymiuk Nikolai , Kessler Barbara , Wolf Eckhard
Published: November 2018

Immunosurgical isolation of the inner cell mass (ICM) from blastocysts is based on complement-mediated lysis of antibody-coated trophectoderm (TE) cells. Conventionally, anti-species antisera, containing antibodies against multiple undefined TE-cell epitopes, have been used as the antibody source. We previously generated α-1,3-galactosyltransferase deficient (GTKO) pigs to prevent hyperacute rejection of pig-to-primate xenotransplants. Since GTKO pigs lack galactosyl-α-1,3-galactose (αGal) but are exposed to this antigen (e.g. αGal on gut bacteria), they produce anti-αGal antibodies. In this study, we examined whether serum from GTKO pigs could be used as a novel antibody source for multi-species embryo immunosurgery. Mouse, rabbit, pig and cattle blastocysts were used for the experiment. Expression of αGal epitopes on the surface of TE cells was detected in blastocysts of all species tested. GTKO pig serum contained sufficient anti-αGal antibodies to induce complement-mediated lysis of TE cells in blastocysts from all species investigated. Intact ICMs could be successfully recovered and the majority showed the desired level of purity. Our study demonstrates that GTKO pig serum is a reliable and effective source of antibodies targeting the αGal epitopes of TE cells for multi-species embryo immunosurgery.
Colloquialisation and the evolution of Australian English
Authors: Collins Peter , Yao Xinyue
Published: November 2018

This paper investigates whether colloquialisation – a stylistic shift by which written genres come to be more similar to spoken genres – has played a role in the endonormativisation of the grammar of Australian English, a variety which has long been noted for its penchant for colloquialism. The study tracks changes in grammatical colloquialism from the early 20th century against the historical backdrop of the progressive decline in Britishness in Australia and the pervasive effects of “Americanisation”. The data are derived from a suite of parallel Brown-family corpora representing British, American, and Australian English of the 1930s, 1960s, 1990s and 2006. Multivariate techniques are used to delimit 26 “colloquial” and “anti-colloquial” grammatical features from a set of 83 potentially relevant features, and to examine changes in their frequencies between 1931 and 2006, in the three varieties, and across the three major genres of fiction, learned writing and press reportage.
Variational pragmatics, responses to thanks, and the specificity of English in Namibia
Authors: Schröder Anne , Schneider Klaus P.
Published: November 2018

In the framework of variational pragmatics, the focus so far has been on L1-varieties of English, and the present paper introduces this area of research into the wider field of World Englishes. It presents first results from a larger questionnaire study on a number of pragmatic variables in Namibian English (NamE), a variety of English that only recently has aroused the interest of a number of researchers because of its unique history and complex variety status. The study employs methods successfully applied in variational pragmatics and describes the realization of responses to thanks in NamE in comparison to three L1-varieties of English. As the paper shows, NamE differs from these varieties in various ways. It argues that these differences, although possibly being more in degree than in kind, nevertheless index local Namibian solutions in the complex linguistic ecology of the speech community. The results of the study furthermore show that some of the results reported for the L1-varieties need to be reconsidered in view of the Namibian data.
What is natural in writing?
Authors: Meletis Dimitrios
Published: November 2018

Naturalness Theory (NT)is founded on the notion of naturalness and claims that when a linguistic phenomenon can be processed by humans with little effort, both sensomotorically and cognitively, it is deemed more natural compared to other, more complex phenomena. Drawing on evidence such as language change, language acquisition, and language disorders, various parameters of naturalness (e.g., biuniqueness, constructional iconicity) have been postulated, which focus on the phonological and morphological subsystems of language. This paper offers an outline of how naturalness can be adapted to grapholinguistic phenomena.Comparative graphematics(cf.Weingarten 2011), extended tocomparative grapholinguistics, is assessed as a method that can be used to reveal naturalness parameters which apply to both material (graphetic) and linguistic (graphematic) aspects of writing. The reduction of extrinsic symmetry across various scripts will be discussed as an example. By integrating these preliminary theoretical ideas into the framework of NT, it is demonstrated that so-calledNatural Grapholinguisticscould offer promising new insights as well as atertium comparationismethod for future comparative analyses of scripts and writing systems.
Individual and organizational antecedents of trait mindfulness
Authors: Kalafatoğlu Yaprak , Turgut Tülay
Published: November 2018

Previous research on the antecedents of mindfulness is scarce. This study examines the individual and contextual antecedents, specifically ethical climate and goal orientation, of trait mindfulness. Data for this study came from 302 white-collar employees working in Istanbul who completed
cross-sectional questionnaires on ethical climate, goal orientation, and mindfulness. First, it was found that caring climate, which refers to organizations that consider the wellness of its workforce, positively predicted employees’ trait mindfulness. Second, goal orientation was significantly
associated with trait mindfulness. Mastery and performance-approach orientations both predicted positively to trait mindfulness with mastery orientation the strongest predictor. In contrast, a performance-avoidance orientation predicted negatively to trait mindfulness. As a caring climate
predicts to employees’ mindfulness, it is recommended that organizations create a workplace where employees perceive themselves as family members, with an emphasis on teamwork, participation, and intrinsic motivation.
Electrical coupling and its channels
Authors: Harris Andrew L.
Published: November 2018

As the physiology of synapses began to be explored in the 1950s, it became clear that electrical communication between neurons could not always be explained by chemical transmission. Instead, careful studies pointed to a direct intercellular pathway of current flow and to the anatomical structure that was (eventually) called the gap junction. The mechanism of intercellular current flow was simple compared with chemical transmission, but the consequences of electrical signaling in excitable tissues were not. With the recognition that channels were a means of passive ion movement across membranes, the character and behavior of gap junction channels came under scrutiny. It became evident that these gated channels mediated intercellular transfer of small molecules as well as atomic ions, thereby mediating chemical, as well as electrical, signaling. Members of the responsible protein family in vertebrates—connexins—were cloned and their channels studied by many of the increasingly biophysical techniques that were being applied to other channels. As described here, much of the evolution of the field, from electrical coupling to channel structure–function, has appeared in the pages of the Journal of General Physiology.
Towards non-statistical foundation of thermodynamics
Authors: Yu Zakharov A
Published: November 2018

It is shown that the irreversible behavior exists even in two-body system. It is due to the retardation of the interactions between the particles. It is established that a two-particle oscillator with a delayed interaction between particles has an infinite spectrum of both stationary and non-stationary oscillations, which depends on the equilibrium distance between the particles.
Supervised non-negative matrix factorization methods for MALDI imaging applications
Authors: Leuschner Johannes , Schmidt Maximilian , Fernsel Pascal , Lachmund Delf , Boskamp Tobias , Maass Peter
Published: November 2018

Motivation

Non-negative matrix factorization (NMF) is a common tool for obtaining low-rank approximations of non-negative data matrices and has been widely used in machine learning, e.g. for supporting feature extraction in high-dimensional classification tasks. In its classical form, NMF is an unsupervised method, i.e. the class labels of the training data are not used when computing the NMF. However, incorporating the classification labels into the NMF algorithms allows to specifically guide them toward the extraction of data patterns relevant for discriminating the respective classes. This approach is particularly suited for the analysis of mass spectrometry imaging (MSI) data in clinical applications, such as tumor typing and classification, which are among the most challenging tasks in pathology. Thus, we investigate algorithms for extracting tumor-specific spectral patterns from MSI data by NMF methods.

Results

In this article, we incorporate a priori class labels into the NMF cost functional by adding appropriate supervised penalty terms. Numerical experiments on a MALDI imaging dataset confirm that the novel supervised NMF methods lead to significantly better classification accuracy and stability as compared with other standard approaches.

Availability and implementaton

https://gitlab.informatik.uni-bremen.de/digipath/Supervised_NMF_Methods_for_MALDI.git

Supplementary information

Supplementary data are available at Bioinformatics online.
High-complexity regions in mammalian genomes are enriched for developmental genes
Authors: Pirogov Anton , Pfaffelhuber Peter , Börsch-Haubold Angelika , Haubold Bernhard
Published: November 2018

Motivation

Unique sequence regions are associated with genetic function in vertebrate genomes. However, measuring uniqueness, or absence of long repeats, along a genome is conceptually and computationally difficult. Here we use a variant of the Lempel-Ziv complexity, the match complexity, Cm, and augment it by deriving its null distribution for random sequences. We then apply Cm to the human and mouse genomes to investigate the relationship between sequence complexity and function.

Results

We implemented Cm in the program macle and show through simulation that the newly derived null distribution of Cm is accurate. This allows us to delineate high-complexity regions in the human and mouse genomes. Using our program macle2go, we find that these regions are twofold enriched for genes. Moreover, the genes contained in these regions are more than 10-fold enriched for developmental functions.

Availability and implementation

Source code for macle and macle2go is available from www.github.com/evolbioinf/macle and www.github.com/evolbioinf/macle2go, respectively; Cm browser tracks from guanine.evolbio.mgp.de/complexity.

Supplementary information

Supplementary data are available at Bioinformatics online.
Elucidating the role of Agl in bladder carcinogenesis by generation and characterization of genetically engineered mice
Authors: Sottnik Joseph L , Mallaredy Vandana , Chauca-Diaz Ana , Ritterson Lew Carolyn , Owens Charles , Dancik Garrett M , Pagliarani Serena , Lucchiari Sabrina , Moggio Maurizio , Ripolone Michela , Comi Giacomo P , Frierson Henry F , Clouthier David , Theodorescu Dan
Published: November 2018

Amylo-α-1,6-glucosidase,4-α-glucanotransferase (AGL) is an enzyme primarily responsible for glycogen debranching. Germline mutations lead to glycogen storage disease type III (GSDIII). We recently found AGL to be a tumor suppressor in xenograft models of human bladder cancer (BC) and low levels of AGL expression in BC are associated with poor patient prognosis. However, the impact of low AGL expression on the susceptibility of normal bladder to carcinogenesis is unknown. We address this gap by developing a germline Agl knockout (Agl−/−) mouse that recapitulates biochemical and histological features of GSDIII. Agl−/− mice exposed to N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) had a higher BC incidence compared with wild-type mice (Agl+/+). To determine if the increased BC incidence observed was due to decreased Agl expression in the urothelium specifically, we developed a urothelium-specific conditional Agl knockout (Aglcko) mouse using a Uroplakin II-Cre allele. BBN-induced carcinogenesis experiments repeated in Aglcko mice revealed that Aglcko mice had a higher BC incidence than control (Aglfl/fl) mice. RNA sequencing revealed that tumors from Agl−/− mice had 19 differentially expressed genes compared with control mice. An ‘Agl Loss’ gene signature was developed and found to successfully stratify normal and tumor samples in two BC patient datasets. These results support the role of AGL loss in promoting carcinogenesis and provide a rationale for evaluating Agl expression levels, or Agl Loss gene signature scores, in normal urothelium of populations at risk of BC development such as older male smokers.
Telomeres Increasingly Develop Aberrant Structures in Aging Humans
Authors: Boccardi Virginia , Cari Luigi , Nocentini Giuseppe , Riccardi Carlo , Cecchetti Roberta , Ruggiero Carmelinda , Arosio Beatrice , Paolisso Giuseppe , Herbig Utz , Mecocci Patrizia
Published: November 2018

Telomeres progressively shorten with age, and it has been proposed that critically short and dysfunctional telomeres contribute to aging and aging-associated diseases in humans. For many years it was thought that telomere erosion was strictly a consequence of the “end replication problem,” or the inability of replicative polymerases to completely duplicate linear DNA ends. It is becoming increasingly evident, however, that telomere shortening of cultured human cells is also caused because of other replication defects in telomeric repeats, those that cause fragile telomeres and other aberrant telomeric structures that can be detected on metaphase chromosomes. Whether these replication defects contribute to telomere erosion also in human tissues is currently unknown. By analyzing peripheral blood mononuclear cells from a total of 35 healthy subjects ranging in age from 23 to 101 years, we demonstrated that telomeres increasingly display aberrant structures with advancing donor age. Although the percentages of fragile telomeres increased only until adulthood, the percentages of chromosomes displaying sister telomere loss and sister telomere chromatid fusions increased consistently throughout the entire human life span. Our data, therefore, suggest that telomeric replication defects other than the end replication problem contribute to aging-associated telomere erosion in humans.
In Vivo Imaging With Confirmation by Histopathology for Increased Rigor and Reproducibility in Translational Research: A Review of Examples, Options, and Resources
Authors: Gabrielson Kathleen , Maronpot Robert , Monette Sébastien , Mlynarczyk Coraline , Ramot Yuval , Nyska Abraham , Sysa-Shah Polina
Published: November 2018

Preclinical noninvasive imaging can be an indispensable tool for studying animal models of disease. In vivo imaging to assess anatomical, functional, and molecular features requires verification by a comparison to the macroscopic and microscopic morphological features, since all noninvasive in vivo imaging methods have much lower resolution than standard histopathology. Comprehensive pathological evaluation of the animal model is underutilized; yet, many institutions have veterinary or human pathologists with necessary comparative pathology expertise. By performing a rigorous comparison to gross or histopathology for image interpretation, these trained individuals can assist scientists with the development of the animal model, experimental design, and evaluation of the in vivo imaging data. These imaging and pathology corroboration studies undoubtedly increase scientific rigor and reproducibility in descriptive and hypothesis-driven research. A review of case examples including ultrasound, nuclear, optical, and MRI is provided to illustrate how a wide range of imaging modalities data can be confirmed by gross or microscopic pathology. This image confirmation and authentication will improve characterization of the model and may contribute to decreasing costs and number of animals used and to more rapid translation from preclinical animal model to the clinic.
Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research
Authors: Overgaard Nana H , Fan Timothy M , Schachtschneider Kyle M , Principe Daniel R , Schook Lawrence B , Jungersen Gregers
Published: November 2018

The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E’s, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients.

To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.
Applied Institutional Approaches for the Evaluation and Management of Zoonoses in Contemporary Laboratory Animal Research Facilities
Authors: Colby Lesley A , Zitzow Lois
Published: November 2018

Zoonoses, diseases transmitted between animals and humans, have been a concern in laboratory animal medicine for decades. Exposure to zoonotic organisms not only poses health risks to personnel and research animals but may also affect research integrity. Early laboratory animal programs were ineffective at excluding and preventing transmission of zoonotic diseases: the health status of the animals were often unknown, endemic diseases occurred frequently, housing conditions were less controlled, and veterinary care programs were decentralized. Over time, these conditions improved, but despite this, zoonotic diseases remain a contemporary concern. To reduce the incidence of zoonoses, management should perform an accurate risk assessment that takes into account the type of research performed, animal species used, animal sources, and housing conditions. Specific research practices, such as the use of biological materials, can also affect the risk assessment and should be considered. Once identified, the characteristics of significant zoonotic organisms can be examined. In addition, personnel attitudes and training, facility design and management, equipment availability, personal protective equipment used, standard operating procedures, and the institution’s vermin control program can impact the risk assessment. The effectiveness of the occupational health and safety program at managing risks of zoonoses should also be examined. Risk assessment, in the context of zoonotic disease prevention, is a complex exercise and is most effective when a team approach is used and includes research, husbandry, veterinary, and biosafety personnel.
Vanishing of Symplectic Homology and Obstruction to Flexible Fillability
Authors: Zhou Zhengyi
Published: November 2018

For any asymptotically dynamically convex contact manifold $Y$, we show that $SH_{\ast }(W)=0$ is a property independent of the choice of topologically simple (i.e., $c_1(W)=0$ and $\pi _{1}(Y)\rightarrow \pi _1(W)$ is injective) Liouville filling $W$. In particular, if $Y$ is the boundary of a flexible Weinstein domain, then any topologically simple Liouville filling $W$ has vanishing symplectic homology. As a consequence, we answer a question of Lazarev partially: a contact manifold $Y$ admitting flexible fillings determines the integral cohomology of all the topologically simple Liouville fillings of $Y$. The vanishing result provides an obstruction to flexible fillability. As an application, we show that all Brieskorn manifolds of dimension $\ge 5$ cannot be filled by flexible Weinstein manifolds.
Resilience in Displacement and the Protection of Civilians in South Sudan
Authors: Munive Jairo
Published: November 2018

The United Nations Mission in South Sudan (UNMISS) was established in 2011. As violence erupted in 2013, the peacekeeping mission allowed tens of thousands of civilians into its bases, leading to the establishment of Protection of Civilians (POC) sites that today shelter more than 200,000 people. The argument of this article is that the creation of the POC sites became constitutive of a broader set of controversies surrounding the building or otherwise of resilience among displaced civilians. The UNMISS is pushing to offer as few services as possible and is focusing on the delivery of traditional humanitarian assistance to encourage return. Conversely, the humanitarian community is pushing for the expansion of services beyond life-saving short-term interventions and towards building the capacity of Internally Displaced People (IDPs) to resist adverse shocks in the future. This article concludes that contestations over the politics of resilience have become a driver of tension and friction between the peacekeeping mission and the humanitarians.
Emerging evidence of an effect of salt on innate and adaptive immunity
Authors: Evans Rhys D R , Antonelou Marilina , Henderson Scott , Walsh Stephen B , Salama Alan D
Published: November 2018

Salt intake as part of a western diet currently exceeds recommended limits, and the small amount found in the natural diet enjoyed by our Paleolithic ancestors. Excess salt is associated with the development of hypertension and cardiovascular disease, but other adverse effects of excess salt intake are beginning to be recognized, including the development of autoimmune and inflammatory disease. Over the last decade there has been an increasing body of evidence demonstrating that salt affects multiple components of both the innate and adaptive immune systems. In this review we outline the recent laboratory, animal and human data, highlighting the effect of salt on immunity, with a particular focus on the relevance to inflammatory kidney disease.
Effect of Commonly Used Pediatric Antibiotics on Gut Microbial Diversity in Preschool Children in Burkina Faso: A Randomized Clinical Trial
Authors: Oldenburg Catherine E , Sié Ali , Coulibaly Boubacar , Ouermi Lucienne , Dah Clarisse , Tapsoba Charlemagne , Bärnighausen Till , Ray Kathryn J , Zhong Lina , Cummings Milo E , Lebas Elodie , Lietman Thomas M , Keenan Jeremy D , Doan Thuy
Published: November 2018

Background

Exposure to antibiotics may result in alterations to the composition of intestinal microbiota. However, few trials have been conducted, and observational studies are subject to confounding by indication. We conducted a randomized controlled trial to determine the effect of 3 commonly used pediatric antibiotics on the intestinal microbiome in healthy preschool children.

Methods

Children aged 6–59 months were randomized (1:1:1:1) to a 5-day course of 1 of 3 antibiotics, including amoxicillin (25 mg/kg/d twice-daily doses), azithromycin (10 mg/kg dose on day 1 and then 5 mg/kg once daily for 4 days), cotrimoxazole (240 mg once daily), or placebo. Rectal swabs were obtained at baseline and 5 days after the last dose and were processed using 16S rRNA gene sequencing. The prespecified primary outcome was inverse Simpson’s α-diversity index.

Results

Post-treatment Simpson’s diversity was significantly different across the 4 arms (P = .003). The mean Simpson’s α-diversity among azithromycin-treated children was significantly lower than in placebo-treated children (6.6; 95% confidence interval [CI], 5.5–7.8; vs 9.8; 95% CI, 8.7–10.9; P = .0001). Diversity in children treated with amoxicillin (8.3; 95% CI, 7.0–9.6; P = .09) or cotrimoxazole (8.3; 95% CI, 8.2–9.7; P = .08) was not significantly different than placebo.

Conclusions

Azithromycin affects the composition of the pediatric intestinal microbiome. The effect of amoxicillin and cotrimoxazole on microbiome composition was less clear.

Clinical Trials Registration

clinicaltrials.gov NCT03187834.
A Pilot Randomized Controlled Trial Comparing Mindfulness Meditation, Cognitive Therapy, and Mindfulness-Based Cognitive Therapy for Chronic Low Back Pain
Authors: Day Melissa A , Ward L Charles , Ehde Dawn M , Thorn Beverly E , Burns John , Barnier Amanda , Mattingley Jason B , Jensen Mark P
Published: November 2018

Objective

This pilot trial compared the feasibility, tolerability, acceptability, and effects of group-delivered mindfulness meditation (MM), cognitive therapy (CT), and mindfulness-based cognitive therapy (MBCT) for chronic low back pain (CLBP).

Setting

University of Queensland Psychology Clinic.

Subjects

Participants were N = 69 (intent-to-treat [ITT] sample) adults with CLBP.

Design

A pilot, assessor-blinded randomized controlled trial.

Methods

Participants were randomized to treatments. The primary outcome was pain interference; secondary outcomes were pain intensity, physical function, depression, and opioid medication use. The primary study end point was post-treatment; maintenance of gains was evaluated at three- and six-month follow-up.

Results

Ratings of acceptability, and ratios of dropout and attendance showed that MBCT was acceptable, feasible, and well tolerated, with similar results found across conditions. For the ITT sample, large improvements in post-treatment scores for pain interference, pain intensity, physical function, and depression were found (P < 0.001), with no significant between-group differences. Analysis of the follow-up data (N = 43), however, revealed that MBCT participants improved significantly more than MM participants on pain interference, physical function, and depression. The CT group improved more than MM in physical function. The MBCT and CT groups did not differ significantly on any measures.

Conclusions

This is the first study to examine MBCT for CLBP management. The findings show that MBCT is a feasible, tolerable, acceptable, and potentially efficacious treatment option for CLBP. Further, MBCT, and possibly CT, could have sustained benefits that exceed MM on some important CLBP outcomes. A future definitive randomized controlled trial is needed to evaluate these treatments and their differences.
Using codesign to develop a culturally tailored, behavior change mHealth intervention for indigenous and other priority communities: A case study in New Zealand
Authors: Verbiest Marjolein E A , Corrigan Callie , Dalhousie Sally , Firestone Ridvan , Funaki Tevita , Goodwin Debbie , Grey Jacqui , Henry Akarere , Humphrey Gayl , Jull Andrew , Vano Mereaumate , Pekepo Crystal , Morenga Lisa Te , Whittaker Robyn , Mhurchu Cliona Ni
Published: November 2018

The obesity rate in New Zealand is one of the highest worldwide (31%), with highest rates among Māori (47%) and Pasifika (67%). Codesign was used to develop a culturally tailored, behavior change mHealth intervention for Māori and Pasifika in New Zealand. The purpose of this article is to provide an overview of the codesign methods and processes and describe how these were used to inform and build a theory-driven approach to the selection of behavioral determinants and change techniques. The codesign approach in this study was based on a partnership between Māori and Pasifika partners and an academic research team. This involved working with communities on opportunity identification, elucidation of needs and desires, knowledge generation, envisaging the mHealth tool, and prototype testing. Models of Māori and Pasifika holistic well-being and health promotion were the basis for identifying key content modules and were applied to relevant determinants of behavior change and theoretically based behavior change techniques from the Theoretical Domains Framework and Behavior Change Taxonomy, respectively. Three key content modules were identified: physical activity, family/whānau [extended family], and healthy eating. Other important themes included mental well-being/stress, connecting, motivation/support, and health literacy. Relevant behavioral determinants were selected, and 17 change techniques were mapped to these determinants. Community partners established that a smartphone app was the optimal vehicle for the intervention. Both Māori and Pasifika versions of the app were developed to ensure features and functionalities were culturally tailored and appealing to users. Codesign enabled and empowered users to tailor the intervention to their cultural needs. By using codesign and applying both ethnic-specific and Western theoretical frameworks of health and behavior change, the mHealth intervention is both evidence based and culturally tailored.