bluuebunny/crossref_metadata_2025 huggingface dataset:
High-dimensional fitting of sparse datasets of CCSD(T) electronic energies and MP2 dipole moments, illustrated for the formic acid dimer and its complex IR spectrum
Authors: Qu Chen , Bowman Joel M.
Published: March 2018

We present high-level, coupled-mode calculations of the infrared spectrum of the cyclic formic acid dimer. The calculations make use of full-dimensional, ab initio potential energy and dipole moment surfaces. The potential is a linear least-squares fit to 13 475 CCSD(T)-F12a/haTZ (haTZ means aug-cc-pVTZ basis set for O and C, and cc-pVTZ for H) energies, and the dipole moment surface is a fit to the dipole components, calculated at the MP2/haTZ level of theory. The variables of both fits are all (45) internuclear distances (actually Morse variables). The potential, which is fully permutationally invariant, is the one published recently and the dipole moment surface is newly reported here. Details of the fits, especially the dipole moment, and the database of configurations are given. The infrared spectrum of the dimer is calculated by solving the nuclear Schrödinger equation using a vibrational self-consistent field and virtual-state configuration interaction method, with subsets of the 24 normal modes, up to 15 modes. The calculations indicate strong mode-coupling in the C—H and O—H stretching region of the spectrum. Comparisons are made with experiments and the complexity of the experimental spectrum in the C—H and O—H stretching region is successfully reproduced.
Application of chaos theory to the particle dynamics of asymmetry-induced transport
Authors: Eggleston D. L.
Published: March 2018

The techniques of chaos theory are employed in an effort to better understand the complex single-particle dynamics of asymmetry-induced transport in non-neutral plasmas. The dynamical equations are re-conceptualized as describing time-independent trajectories in a four-dimensional space consisting of the radius r, rotating frame angle ψ, axial position z, and axial velocity v. Results include the identification of an integral of the motion, fixed-point analysis of the dynamical equations, the construction and interpretation of Poincaré sections to visualize the dynamics, and, for the case of chaotic motion, numerical calculation of the largest Lyapunov exponent. Chaotic cases are shown to be associated with the overlap of resonance islands formed by the applied asymmetry.
Observations of non-linear plasmon damping in dense plasmas
Authors: Witte B. B. L. , Sperling P. , French M. , Recoules V. , Glenzer S. H. , Redmer R.
Published: March 2018

We present simulations using finite-temperature density-functional-theory molecular-dynamics to calculate dynamic dielectric properties in warm dense aluminum. The comparison between exchange-correlation functionals in the Perdew, Burke, Ernzerhof approximation, Strongly Constrained and Appropriately Normed Semilocal Density Functional, and Heyd, Scuseria, Ernzerhof (HSE) approximation indicates evident differences in the electron transition energies, dc conductivity, and Lorenz number. The HSE calculations show excellent agreement with x-ray scattering data [Witte et al., Phys. Rev. Lett. 118, 225001 (2017)] as well as dc conductivity and absorption measurements. These findings demonstrate non-Drude behavior of the dynamic conductivity above the Cooper minimum that needs to be taken into account to determine optical properties in the warm dense matter regime.
Effect of cubic Dresselhaus interaction on the longitudinal optical conductivity of a spin-orbit coupled system
Authors: Cruz Elmer , López-Bastidas Catalina , Maytorena Jesús A.
Published: March 2018

We investigate the effect of the oft-neglected cubic terms of the Dresselhaus spin-orbit coupling on the longitudinal current response of a two-dimensional electron gas with both Rashba and linear Dresselhaus interactions. For a quantum well grown in the [001] direction, the changes caused by these nonlinear-in-momentum terms on the absorption spectrum become more notable under SU(2) symmetry conditions, when the Rashba and linear Dresselhaus coupling strengths are tuned to be equal. The longitudinal optical response no longer vanishes then and shows a strong dependence on the direction of the externally applied electric field, giving a signature of the relative size of several spin-orbit contributions. This anisotropic response arises from the nonisotropic splitting of the spin states induced by the interplay of Rashba and Dresselhaus couplings. However, the presence of cubic terms introduces characteristic spectral features and can modify the overall shape of the spectra for some values of the relative sizes of the spin-orbit parameters. We compare this behavior to the case of a sample with [110] crystal orientation which, under conditions of spin-preserving symmetry, has a collinear spin-orbit vector field that leads to vanishing conductivity, even in the presence of cubic terms. In addition to the control through the driven frequency or electrical gating, such a directional aspect of the current response suggests new ways of manipulation and supports the use of interband optics as a sensitive probe of spin-orbit mechanisms in semiconductor spintronics.
High speed 2-dimensional temperature measurements of nanothermite composites: Probing thermal vs. Gas generation effects
Authors: Jacob Rohit J. , Kline Dylan J. , Zachariah Michael R.
Published: March 2018

This work investigates the reaction dynamics of metastable intermolecular composites through high speed spectrometry, pressure measurements, and high-speed color camera pyrometry. Eight mixtures including Al/CuO and Al/Fe2O3/xWO3 (x being the oxidizer mol. %) were reacted in a constant volume pressure cell as a means of tuning gas release and adiabatic temperature. A direct correlation between gas release, peak pressure, and pressurization rate was observed, but it did not correlate with temperature. When WO3 was varied as part of the stoichiometric oxidizer content, it was found that Al/Fe2O3/70% WO3 achieved the highest pressures and shortest burn time despite a fairly constant temperature between mixtures, suggesting an interplay between the endothermic Fe2O3 decomposition and the higher adiabatic flame temperature sustained by the Al/WO3 reaction in the composite. It is proposed that the lower ignition temperature of Al/WO3 leads to the initiation of the composite and its higher flame temperature enhances the gasification of Fe2O3, thus improving advection and propagation as part of a feedback loop that drives the reaction. Direct evidence of such gas release promoting reactivity was obtained through high speed pyrometry videos of the reaction. These results set the stage for nanoenergetic materials that can be tuned for specific applications through carefully chosen oxidizer mixtures.
Dynamic behavior of combustion instability in a cylindrical combustor with an off-center installed coaxial injector
Authors: Kasuya Haruki , Gotoda Hiroshi , Yoshida Seiji , Tachibana Shigeru
Published: March 2018

We have intensively studied the dynamic behavior of combustion instability in a cylindrical combustor with an off-center installed coaxial injector. The most interesting discovery in this study is the appearance of a deterministic chaos in a transition from a dynamically stable state to well-developed high-frequency thermoacoustic combustion oscillations with increasing the volume flow rate of nitrogen with which oxygen is diluted. The presence of deterministic chaos is reasonably identified by considering an extended version of the Sugihara-May algorithm [G. Sugihara and R. May, Nature 344, 734 (1990)] as a local predictor and the multiscale complexity-entropy causality plane based on statistical complexity.
Non-uniform dependence on initial data for the periodic Constantin-Lannes equation
Authors: Zhou Shouming , Wang Bin , Chen Rong
Published: March 2018

This paper focuses on the periodic Cauchy problem of a model equation for shallow water waves of moderate amplitude (Constantin-Lannes equation). Two suitable sequences of Constantin-Lannes solutions which are bounded in Hs(T) with s > 3/2 and the interval converge to zero at the initial time are constructed, but the lower-bound of distance between the two sequences is a positive constant at any time t. This implies that the solution map of the Constantin-Lannes equation is not uniformly continuous in Sobolev spaces Hs(T).
A review of low-density porous target materials for laser plasma experiments
Authors: Kim Meeri
Published: March 2018

A new review article takes an in-depth look at different types of low-density porous materials for target fabrication in laser plasma experiments.
Population genetics of Pampus echinogaster along the Pacific coastline of China: insights from the mitochondrial DNA control region and microsatellite molecular markers
Authors: Li Yuan , Lin Longshan , Song Na , Zhang Yan , Gao Tianxiang
Published: March 2018

Genetic variation among seven populations of Pampus echinogaster collected from the coastal waters of China was investigated based on the mitochondrial DNA control region and microsatellite molecular markers. The results revealed a high level of genetic diversity that may be related primarily to the life history traits and diverse habitats of this species. Analysis of the genetic structure and migration of P. echinogaster revealed weak genetic differentiation among populations, with an absence of a phylogeographic structure, indicating relatively high genetic homogeneity that may be associated with a recent population expansion event. The complex migratory and high dispersal ability of ichthyoplankton, as well as China’s offshore circulation, may have played important roles in shaping the current genetic structure of P. echinogaster. Unlike stock division in conventional fisheries, the present study found no significant differences among the P. echinogaster populations, all of which were panmictic. Therefore, in addition to accounting for conventional fishery stocks, a comprehensive assessment should be conducted by considering the phylogenetic structure among different populations.
Coevolution of landesque capital intensive agriculture and sociopolitical hierarchy
Authors: Sheehan Oliver , Watts Joseph , Gray Russell D. , Atkinson Quentin D.
Published: March 2018

Significance

Over the past 10,000 years, human societies have grown vastly more complex. How and why this occurred is still debated. One major point of contention is the relationship between two characteristic features of complex societies: intensive resource use and sociopolitical hierarchy. The “materialist” view is that intensification drives hierarchy, but the reverse view and intermediate views have also been proposed. Here we report the results of a phylogenetic study on the coevolution of landesque capital intensive agriculture and sociopolitical hierarchy in the Austronesian-speaking world. We find support for a reciprocal coevolutionary relationship between the two variables, challenging the materialist view and highlighting the importance of social as well as material factors as drivers of cultural evolution.
Frater Bercaldus – Berealdus – Bertholdus de Maisberch
Authors: Jeck Udo Reinhold
Published: March 2018

In early modernity, church historians initially showed little interest in Berthold of Moosburg. They knew him as a commentator of Proclus,
but they did not recognise his importance for the history of Neoplatonism. The librarians and bibliographers who came across Berthold’s
commentary on Proclus in the Balliol College Library at Oxford showed no interest in the philosophical content of this work. An article on
Berthold in the monumental work Scriptores Ordinis Praedicatorum (1719) summarised the available information. It was Johann
Albert Fabricius (1668–1736) who took notice of it. Fabricius was very interested in Proclus as well as in Neoplatonic theology and its
narration in the Elements of Theology; he had started to collect all available information regarding this issue and had
also come across Berthold’s commentary. However, he did not ignore him, as many had done before, but properly recognised the importance of
Berthold for the history of the reception of Proclus’s philosophy. Fabricius always referred to the Dominican thinker when dealing with
Proclus’s Elements of Theology, in particular in his own Bibliotheca graeca. One of the attentive readers
of this work was the German philologist Friedrich Creuzer. In 1822, within the framework of publishing Neoplatonic writings, Creuzer
reedited Proclus’s Elements of Theology. As a consequence of this new edition, Proclus together with his medieval
commentator came into the focus of leading representatives of classical German philosophy.
Trends in suspended sediment quality in the upper St. Clair River: Assessment of large-scale remediation of contaminated sediments in a dynamic riverine environment
Authors: Richman Lisa , Milani Danielle , Marvin Chris
Published: March 2018

Sediment downstream of industrial sources in the Upper St. Clair River was historically contaminated with mercury, hexachlorobutadiene, hexachlorobenzene and octachlorostyrene. Concentrations of contaminants of concern in suspended sediment collected from traps in 1994/1995 and 2001 suggested bottom sediment was mobile and a source of contamination to downstream areas. Sediment was dredged in 1996 and in 2002–2004 from two contaminated areas (Cole Drain and Dow waterfront, respectively). Post remediation concentrations of contaminants of concern in bottom sediment and suspended sediment throughout downstream areas were high, relative to concentrations measured at the upstream reference sites; however, data from sediment traps deployed in 2006–2011 indicated that concentrations of contaminants of concern were trending downward since the remediation efforts. There was a significant (p ≤ 0.05) decrease in concentrations of mercury, hexachlorobutadiene and octachlorosytrene for suspended sediment in 2006 (post-remediation of the Dow waterfront) compared to 2001 (pre-remediation) and contaminants of concern suspended sediment concentrations have remained consistent between 2006 and 2011. Contaminant down-flux rates for the upper St. Clair River have also decreased since remediation; however, data for hexachlorobenzene were variable with no apparent trend through time. Bottom sediment data for hexachlorobenzene, octachlorostyrene and hexachlorobutadiene collected in 2006 and 2008 downstream of the remediation areas have also shown a downward trend when compared to concentration reported for 1990–2001; however, declines in mercury were not apparent.
Tamas Balla: Leading the way with phosphoinositides
Authors: O’Donnell Marie Anne
Published: March 2018

Balla investigates how phosphoinositides control trafficking and signaling.
Hidden chiral symmetries in BDI multichannel Kitaev chains
Authors: Manesco Antônio L R , Weber Gabrielle , Rodrigues Durval
Published: March 2018

Realistic implementations of the Kitaev chain require, in general, the introduction of extra internal degrees of freedom. In the present work, we discuss the presence of hidden BDI symmetries for free Hamiltonians describing systems with an arbitrary number of internal degrees of freedom. We generalize results of a spinfull Kitaev chain to construct a Hamiltonian with n internal degrees of freedom and obtain the corresponding hidden chiral symmetry. As an explicit application of this generalized result, we exploit by analytical and numerical calculations the case of a spinful two-band Kitaev chain, which can host up to four Majorana bound states. We also observe the appearence of minigap states, when chiral symmetry is broken.
accuMUlate: a mutation caller designed for mutation accumulation experiments
Authors: Winter David J , Wu Steven H , Howell Abigail A , Azevedo Ricardo B R , Zufall Rebecca A , Cartwright Reed A
Published: March 2018

Mutation accumulation (MA) is the most widely used method for directly studying the effects of mutation. By sequencing whole genomes from MA lines, researchers can directly study the rate and molecular spectra of spontaneous mutations and use these results to understand how mutation contributes to biological processes. At present there is no software designed specifically for identifying mutations from MA lines. Here we describe accuMUlate, a probabilistic mutation caller that reflects the design of a typical MA experiment while being flexible enough to accommodate properties unique to any particular experiment.

Availability and implementation accuMUlate is available from https://github.com/dwinter/accuMUlate.

Supplementary information

Supplementary data are available at Bioinformatics online.
ALPHA: a toolkit for Automated Local PHylogenomic Analyses
Authors: Elworth R A Leo , Allen Chabrielle , Benedict Travis , Dulworth Peter , Nakhleh Luay
Published: March 2018

The evolutionary histories of individual regions across a genomic alignment—called ‘local genealogies’—can differ from each other, due to processes such as recombination. Elucidating and analyzing these local genealogies are important for a large number of inference tasks, including those pertaining to species phylogenies, evolutionary processes and trait mapping. In this paper, we present a toolkit for automated local phylogenomic analyses, or ALPHA. The purpose of this toolkit is to provide a wide array of functionalities for automated inference of local genealogies as well as analyses based on these local genealogies. The toolkit uses sliding windows to construct local genealogies and can compute a wide array of local phylogeny based statistics, such as the D-statistic. The toolkit comes with a graphical user interface and several import/export functionalities. Over the last few decades, much emphasis in phylogenomics has been put on developing tools for inferring species phylogenies. This toolkit complements those efforts by emphasizing the ‘local’ aspect of phylogenomics.

Availability and implementation

ALPHA is freely available for installation and use, including source code, at https://github.com/chilleo/ALPHA.
Validity and reliability of the Turkish version of the European Health Literacy Survey Questionnaire
Authors: Abacigil Filiz , Harlak Hacer , Okyay Pınar , Kiraz Didem Evci , Gursoy Turan Selen , Saruhan Gulnur , Karakaya Kagan , Tuzun Hakan , Baran Deniz Emine , Tontus Omer , Beşer Erdal
Published: March 2018

Health literacy is a public health priority which refers to individual’s knowledge, motivation and competence to access, understand, appraise and apply health information to prevent disease and promote health in daily life. This study aimed to adapt European Health Literacy Survey Questionnaire (HLS-EU-Q47) into Turkish and to investigate its psychometric properties. The questionnaire was translated into Turkish by using both group translation and expert opinion methods. Forward translation–back translation method was used for language validity and the final Turkish version (HLS-TR) was formed. HLS-EU-Q47 and Health Awareness Scale (HAS) were administered to 505 respondents. The scale reliability was examined using Crohnbach’s alpha coefficient and the construct validity was assessed by principal axis factoring procedure. The convergent validity was obtained by Pearson correlation coefficients between HLS-TR and HAS scores and discriminant validity was examined comparing the scores of participants who were stratified according to ages, educational status, gender, general health status and social status. Cronbach’s alpha coefficient for the whole scale was 0.95. Principal axis factoring extracted nine factors which eigenvalues were >1 and explained 50.01% of total variance. Factor matrix displayed that all items gave greater load in factor 1, showing that health literacy measured with one factor. Positive and significant correlation was found between HLS-TR and HAS. Significant relations were found between HLS-TR scores and selected determinants of health. This study revealed that the HLS-TR was a valid and reliable measuring instrument with appropriate psychometric characteristics.
Adaptive outer synchronization and topology identification between two complex dynamical networks with time-varying delay and disturbance
Authors: Wang Liangshuang , Zhang Jianbao , Sun Weigang
Published: March 2018

In this paper, we investigate adaptive outer synchronization for identifying unknown network topology and parameters between two coupled complex networks with time-varying delays existing in the node dynamics and coupling forms. By designing adaptive controllers and updating laws, we obtain two theorems on the appearance of outer synchronization using Lyapunov stability theory. In the numerical examples, we provide the detailed identification criteria of network topology and system parameter according to the obtained theorems and give some numerical examples to show the efficiency of the proposed controllers.
Peterson Isomorphism in K-theory and Relativistic Toda Lattice
Authors: Ikeda Takeshi , Iwao Shinsuke , Maeno Toshiaki
Published: March 2018

The K-homology ring of the affine Grassmannian of $SL_{n}(\mathbb{C})$ was studied by Lam, Schilling, and Shimozono. It is realized as a certain concrete Hopf subring of the ring of symmetric functions. On the other hand, for the quantum K-theory of the flag variety $F\,\! l_{n}$, Kirillov and Maeno provided a conjectural presentation based on the results obtained by Givental and Lee. We construct an explicit birational morphism between the spectrums of these two rings. Our method relies on Ruijsenaars’s relativistic Toda lattice with unipotent initial condition. From this result, we obtain a K-theory analogue of the so-called Peterson isomorphism for (co)homology. We provide a conjecture on the detailed relationship between the Schubert bases, and, in particular, we determine the image of Lenart–Maeno’s quantum Grothendieck polynomial associated with a Grassmannian permutation.
Spaces of Suffering: Religious Transit in São Paulo’s Devotion to Souls
Authors: Amoruso Michael
Published: March 2018

This article examines the devotion to souls in São Paulo—a practice that involves lighting candles for and petitioning the souls of the anonymous, suffering dead—by focusing on the particularity of place. To that end, it employs the notion of religious transit (trânsito religioso), used by Brazilian scholars to talk about religious change and movement. But whereas most literature on the subject has focused on switching affiliation, this article explores how affect shapes devotees’ religious transit through urban space. It argues that, in the context of the devotion, mutual suffering underpins a relationship of mutual aid, drawing together the living and departed at places of trauma and death.
Design and implementation of a standardized framework to generate and evaluate patient-level prediction models using observational healthcare data
Authors: Reps Jenna M , Schuemie Martijn J , Suchard Marc A , Ryan Patrick B , Rijnbeek Peter R
Published: March 2018

Objective

To develop a conceptual prediction model framework containing standardized steps and describe the corresponding open-source software developed to consistently implement the framework across computational environments and observational healthcare databases to enable model sharing and reproducibility.

Methods

Based on existing best practices we propose a 5 step standardized framework for: (1) transparently defining the problem; (2) selecting suitable datasets; (3) constructing variables from the observational data; (4) learning the predictive model; and (5) validating the model performance. We implemented this framework as open-source software utilizing the Observational Medical Outcomes Partnership Common Data Model to enable convenient sharing of models and reproduction of model evaluation across multiple observational datasets. The software implementation contains default covariates and classifiers but the framework enables customization and extension.

Results

As a proof-of-concept, demonstrating the transparency and ease of model dissemination using the software, we developed prediction models for 21 different outcomes within a target population of people suffering from depression across 4 observational databases. All 84 models are available in an accessible online repository to be implemented by anyone with access to an observational database in the Common Data Model format.

Conclusions

The proof-of-concept study illustrates the framework’s ability to develop reproducible models that can be readily shared and offers the potential to perform extensive external validation of models, and improve their likelihood of clinical uptake. In future work the framework will be applied to perform an “all-by-all” prediction analysis to assess the observational data prediction domain across numerous target populations, outcomes and time, and risk settings.
Pollution and city size: can cities be too small?
Authors: Borck Rainald , Tabuchi Takatoshi
Published: March 2018

We study optimal and equilibrium sizes of cities in a city system model with pollution. Pollution is a function of population size. If pollution is local or per-capita pollution increases with population, equilibrium cities are too large under symmetry; with asymmetric cities, the largest cities are too large and the smallest too small. When pollution is global and per-capita pollution declines with city size, cities may be too small under symmetry; with asymmetric cities, the largest cities are too small and the smallest too large if the marginal damage of pollution is large enough. We calibrate the model to US cities and find that the largest cities may be undersized by 3–4%.
An E2F7-dependent transcriptional program modulates DNA damage repair and genomic stability
Authors: Mitxelena Jone , Apraiz Aintzane , Vallejo-Rodríguez Jon , García-Santisteban Iraia , Fullaondo Asier , Alvarez-Fernández Mónica , Malumbres Marcos , Zubiaga Ana M
Published: March 2018

The cellular response to DNA damage is essential for maintaining the integrity of the genome. Recent evidence has identified E2F7 as a key player in DNA damage-dependent transcriptional regulation of cell-cycle genes. However, the contribution of E2F7 to cellular responses upon genotoxic damage is still poorly defined. Here we show that E2F7 represses the expression of genes involved in the maintenance of genomic stability, both throughout the cell cycle and upon induction of DNA lesions that interfere with replication fork progression. Knockdown of E2F7 leads to a reduction in 53BP1 and FANCD2 foci and to fewer chromosomal aberrations following treatment with agents that cause interstrand crosslink (ICL) lesions but not upon ionizing radiation. Accordingly, E2F7-depleted cells exhibit enhanced cell-cycle re-entry and clonogenic survival after exposure to ICL-inducing agents. We further report that expression and functional activity of E2F7 are p53-independent in this context. Using a cell-based assay, we show that E2F7 restricts homologous recombination through the transcriptional repression of RAD51. Finally, we present evidence that downregulation of E2F7 confers an increased resistance to chemotherapy in recombination-deficient cells. Taken together, our results reveal an E2F7-dependent transcriptional program that contributes to the regulation of DNA repair and genomic integrity.
Nonverbal Visual Sequential Learning in Children With Cochlear Implants: Preliminary Findings
Authors: Klein Kelsey E. , Walker Elizabeth A. , Tomblin J. Bruce
Published: March 2018

The authors tested the hypothesis that children with cochlear implants (CIs) experience domain-general deficits in sequential learning. Twenty children with CIs and 40 children with normal hearing (NH) participated. Participants completed a serial reaction time task that measured implicit sequential learning. During random sequence phases, the CI group had significantly slower reaction times than the NH group. However, there were no significant differences in the rates of sequential learning between groups. Age at implantation was not significantly associated with learning rate in the CI group. Children with CIs demonstrated nonverbal sequential learning that is comparable to children with NH. Contrary to previous research, early auditory deprivation may not be associated with deficits in domain-general sequential learning, but may affect sequential processing. Further investigation is needed to understand the mechanisms underlying the overall delayed reaction times of children with CIs.
The emerging role of immunotherapy in advanced urothelial cancers
Authors: Tabayoyong William , Gao Jianjun
Published: March 2018

Purpose of review

Recent Food and Drug Administration (FDA) approval of five new immune checkpoint inhibitors for the treatment of metastatic urothelial cancer represents the first major treatment breakthrough for this disease since the introduction of combination chemotherapy over 30 years ago. This review examines the recent clinical trials leading to FDA approval of these agents, the current challenges facing immunotherapy and areas that require further research.

Recent findings

The programmed death 1 receptor (PD-1) and its ligand programmed death ligand-1 (PD-L1) are important negative regulators of immune activity, preventing destruction of normal tissues and autoimmunity. Aggressive bladder cancer cells express aberrantly high levels of PD-L1, hijacking the normal immune-regulatory pathway to evade detection and destruction by the immune system. Blockade of the PD-1/PD-L1 axis with immune checkpoint inhibitors augments the immune system's ability to eradicate bladder cancer with impressive safety and tolerability profiles.

Recent clinical trials demonstrate that patients with metastatic urothelial carcinoma are responsive to immune checkpoint inhibitor therapy. Optimal treatment regimens are still under development, but activity has been demonstrated in both the first and second-line setting for metastatic disease.
Exfoliation Syndrome: A Disease of Autophagy and LOXL1 Proteopathy
Authors: Bernstein Audrey M. , Ritch Robert , Wolosin Jose M.
Published: March 2018

Exfoliation syndrome (XFS) is an age-related disease involving the deposition of aggregated fibrillar material (exfoliation material) at extracellular matrices in tissues that synthesize elastic fibers. Its main morbidity is in the eye, where exfoliation material accumulations form on the surface of the ciliary body, iris, and lens. Exfoliation glaucoma (XFG) occurs in a high proportion of persons with XFS and can be a rapidly progressing disease. Worldwide, XFG accounts for about 25% of open-angle glaucoma cases. XFS and XFG show a sharp age-dependence, similarly to the many age-related diseases classified as aggregopathies. Progress in understanding the cellular bases for XFS/XFG has been slowed by a lack of experimental models. Working with primary human tenon fibroblasts (TF) derived from trabeculectomies of XFG patients and age-matched primary open-glaucoma controls, we found that TF from XFG cells display many of the functional features observed in cells from other protein aggregate diseases, such as Parkinson, Alzheimer, Huntington, and age-related macular degeneration. We have documented defects in lysosomal positioning, microtubule organization, autophagy processing rate, and mitochondrial health. In regard to failure of lysosomal and autophagosome positioning in XFG cells, we have found that XFG TF are unable to establish the transnuclear microtubule organizing center that is required for efficient centripetal vesicular locomotion along microtubules. In regard to potential sources of the autophagy malfunction, we have directed our attention to a potential role of the lysyl oxidase-like 1 protein (LOXL1), the elastic fiber catalyst that displays variant-dependent association with risk for XFG. Our experiments show that (a) in XFG cells, a substantial fraction of LOXL1 is processed for degradation by the autophagic system; (b) most of the LOXL1 N-terminus domain exists in a highly disordered state, a condition known to greatly increase the frequency of polypeptide misfolding; (c) that maximum misfolding occurs at amino acid position 153, the location of the high risk variant G153D; and (d) that replacement of glycine (G) by aspartate (D) there results in a substantial decrease in disorder within the 20 amino acid surrounding domain. Finally, we show that clusterin, a protein that can be induced by the presence of intracellular, or extracellular aggregates, is uniformly overexpressed in XFG TF. The implications of our results for a theory relating XFG to cellular aggregopathy are discussed.
Frontalis Muscle Contraction and the Role of Visual Deprivation and Eyelid Proprioception
Authors: Beaulieu Robert , Andre Kaden , Mancini Ronald
Published: March 2018

Purpose:

To determine if frontalis muscle contraction can be induced by manipulating visual and eyelid proprioceptive inputs through simulating visual deprivation and ptosis.

Methods:

Volunteers without prior eyelid or forehead pathologic study were recruited for this nonrandomized, prospective study. Baseline and study phase brow positions were documented. The first phase was to simulate visual deprivation and the second to simulate ptosis. The dominant eye was used for each phase. As a proxy to simulate visual field deprivation, a black contact lens was placed on the eye, which reduced vision to light perception. As a proxy to simulate ptosis, an external eyelid weight was placed on the upper eyelid. Brow position ratios were calculated at various points along the brow and statistical analysis was performed.

Results:

Fifteen subjects participated. The average brow position ratio was 1.00 ± 0.08 for the visual deprivation group, which was not different from baseline (p = 0.86). The average brow position ratio for the external eyelid weight group was 1.13 ± 0.07, which was statistically significant compared with baseline and the visual deprivation group (p < 0.001).

Conclusions:

Inducing visual deprivation with a black contact lens does not lead to a change in brow position. However, placing an external eyelid weight does lead brow elevation, with an average increase of 13% from baseline. This suggests a likely role for proprioceptive or sensory inputs in frontalis muscle contraction in the setting of eyelid ptosis.
Dermalive Facial Filler Granulomas Masquerading as Neurofibromas
Authors: Wolkow Natalie , Jakobiec Frederick A. , Yoon Michael K.
Published: March 2018

A 56-year-old woman presented with periocular nodules that were clinically suspected to be neurofibromas. Histopathologic examination of excised nodules revealed a pronounced granulomatous reaction to a foreign material that was composed of glossy polygonal palely eosinophilic fragments. These fragments were outlined in red with Masson trichrome, stained gray with the elastic stain, and were uniformly red with Gomori methenamine silver staining. The histopathologic appearance was consistent with a granulomatous reaction to Dermalive facial filler. Postoperatively the patient admitted that she had filler injections many years earlier in another country, and that nodules appeared 1 year after injection. Treatment with steroids, intralesional immunosuppressive agents and surgery had been previously attempted to eradicate the nodules. The literature pertaining to granulomatous reactions to Dermalive and related hybrid facial fillers is reviewed and treatment options are discussed. This report is the first to illustrate the unique histopathologic staining characteristics of Dermalive, which may be useful to ophthalmic pathologists in identifying this uncommon foreign material.
Protease-activated receptor 1 is implicated in irritable bowel syndrome mediators–induced signaling to thoracic human sensory neurons
Authors: Desormeaux Cleo , Bautzova Tereza , Garcia-Caraballo Sonia , Rolland Corinne , Barbaro Maria Raffaella , Brierley Stuart M. , Barbara Giovanni , Vergnolle Nathalie , Cenac Nicolas
Published: March 2018

Proteases and protease-activated receptors (PARs) are major mediators involved in irritable bowel syndrome (IBS). Our objectives were to decipher the expression and functionality (calcium signaling) of PARs in human dorsal root ganglia (DRG) neurons and to define mechanisms involved in human sensory neuron signaling by IBS patient mediators. Human thoracic DRG were obtained from the national disease resource interchange. Expression of PAR1, PAR2, and PAR4 was assessed by immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR) in whole DRG or in primary cultures of isolated neurons. Calcium signaling in response to PAR agonist peptides (PAR-AP), their inactive peptides (PAR-IP), thrombin (10 U/mL), supernatants from colonic biopsies of patients with IBS, or healthy controls, with or without PAR1 or PAR4 antagonist were studied in cultured human DRG neurons. PAR1, PAR2, and PAR4 were all expressed in human DRG, respectively, in 20%, 40%, and 40% of the sensory neurons. PAR1-AP increased intracellular calcium concentration in a dose-dependent manner. This increase was inhibited by PAR1 antagonism. By contrast, PAR2-AP, PAR4-AP, and PAR-IP did not cause calcium mobilization. PAR1-AP–induced calcium flux was significantly reduced by preincubation with PAR4-AP, but not with PAR2-AP. Thrombin increased calcium flux, which was inhibited by a PAR1 antagonist and increased by a PAR4 antagonist. Supernatants from colonic biopsies of patients with IBS induced calcium flux in human sensory neurons compared with healthy controls, and this induction was reversed by a PAR1 antagonist. Taken together, our results highlight that PAR1 antagonism should be investigated as a new therapeutic target for IBS symptoms.
Sun Protective Behavior Use in Organ Transplant Recipients
Authors: Petitt Elizabeth K. , Wingo Nancy P.
Published: March 2018

Skin cancer is a major public health issue due to the impact of skin-cancer-related disease, death, and costs to the healthcare system. Organ transplant recipients (OTRs) have higher rates of nonmelanoma skin cancer occurrence, recurrence, and metastasis than the general population. Ultraviolet exposure remains the primary risk factor in the development of posttransplant nonmelanoma skin cancer. A review of the current literature to examine the use of sun protective behaviors (SPBs) in OTRs and to investigate factors influencing these behaviors was performed. After careful selection, we chose the 10 most relevant articles addressing the use of SPB in OTRs. Two important practice gaps identified were a lack of efficacious OTR skin cancer prevention education and the lack of SPB use reinforcement in OTRs. Strategies to address these gaps include (a) clinician use of risk stratification to identify those patients at the highest risk of skin cancer development, (b) clinician use of targeted educational tools known to promote behavioral change, and (c) reinforcement of SPB at follow-up appointments. Continued evidence-based analysis is needed to discover if improving the use of SPBs in OTRs can actually decrease their long-term skin cancer rate.
Degree of Functional Impairment Associated With Vestibular Hypofunction Among Older Adults With Cognitive Decline
Authors: Micarelli Alessandro , Viziano Andrea , Della-Morte David , Augimeri Ivan , Alessandrini Marco
Published: March 2018

Objective:

Considering the altered multisensory signal compensation during senescence, the aim of the present study was to evaluate the integration rearrangements in unilateral vestibular hypofunction (UVH) during age-related cognitive decline.

Study Design:

Cross-sectional study.

Setting:

Longitudinal cohort study unit and of University tertiary referral center.

Patients:

Older UVH individuals ≥ 55 years with Mild Cognitive Impairment (MCI) or Alzheimer Disease (AD) and matched UVH control group with age-appropriate cognitive function.

Intervention:

Vestibulo-ocular reflex, postural sway examination (respectively performed by means of video head impulse test and static posturography), and dizziness-related and quality of life scores were collected in all three groups of UVH patients cognitively evaluated by means of Mini Mental State Examination and Alzheimer's Disease Assessment Scale (ADAS-cog).

Main Outcome Measures:

Vestibulo-ocular reflex gain, length, surface, and spectral values of body oscillation were measured. Dizziness Handicap Inventory, Activities-specific Balance Confidence scale, and Dynamic Gait Index scores were collected.

Results:

A significant (p < 0.05) increase in surface and length values during both eyes closed and eyes open conditions was found when comparing scores for AD to both MCI and control group patients, respectively. These patients demonstrated significantly (p < 0.05) lower spectral values of body oscillation on posturography platform in both eyes closed and eyes open condition within the low-frequency interval than MCI and AD patients.

Conclusion:

This is the first study reporting an association between cognitive decline and posturography parameters with possible preventive clinical implications in evaluating the risk for falls in high-risk patients, such as older adults with common neuro-otological disorders.
Monitoring peripheral perfusion and microcirculation
Authors: Dubin Arnaldo , Henriquez Elizabeth , Hernández Glenn
Published: March 2018

Purpose of review

Microcirculatory alterations play a major role in the pathogenesis of shock. Monitoring tissue perfusion might be a relevant goal for shock resuscitation. The goal of this review was to revise the evidence supporting the monitoring of peripheral perfusion and microcirculation as goals of resuscitation. For this purpose, we mainly focused on skin perfusion and sublingual microcirculation.

Recent findings

Although there are controversies about the reproducibility of capillary refill time in monitoring peripheral perfusion, it is a sound physiological variable and suitable for the ICU settings. In addition, observational studies showed its strong ability to predict outcome. Moreover, a preliminary study suggested that it might be a valuable goal for resuscitation. These results should be confirmed by the ongoing ANDROMEDA-SHOCK randomized controlled trial. On the other hand, the monitoring of sublingual microcirculation might also provide relevant physiological and prognostic information. On the contrary, methodological drawbacks mainly related to video assessment hamper its clinical implementation at the present time.

Measurements of peripheral perfusion might be useful as goal of resuscitation. The results of the ANDROMEDA-SHOCK will clarify the role of skin perfusion as a guide for the treatment of shock. In contrast, the assessment of sublingual microcirculation mainly remains as a research tool.
New insights in the multiple roles of bile acids and their signaling pathways in metabolic control
Authors: de Boer Jan Freark , Bloks Vincent W. , Verkade Esther , Heiner-Fokkema M. Rebecca , Kuipers Folkert
Published: March 2018

Purpose of review

There is a growing awareness that individual bile acid species exert different physiological functions, beyond their classical roles in bile formation and fat absorption, due to differential stimulatory effects on the bile-acid-activated receptors farnesoid X receptor (FXR) and takeda G receptor 5 (TGR5). This review integrates recent findings on the role of individual bile acids and their receptors in metabolic control, with special emphasis on cholesterol homeostasis.

Recent findings

The consequences of altered bile acid metabolism, for example, in type 2 diabetes and during aging, on metabolic control is increasingly recognized but full impact hereof remains to be elucidated. These effects interact with those of newly developed pharmacological FXR and TGR5 modulators that aim to improve metabolic health. Studies in genetically modified mice have provided important new insights, for example, establishment of the role of intestinal FXR in control of the transintestinal cholesterol excretion pathway. However, translation from mice to men is hampered by the presence of rodent-specific bile acid species with special features.

Specific bile acids and their signaling pathways play important roles in control of (cholesterol) metabolism. Deeper insight into the interactions between endogenous (i.e., bile acids) and pharmacological modulators of FXR and TGR5 is needed to optimize therapeutic benefit of the latter. The recent identification of cytochrome P450 2C70 as key enzyme in the formation of rodent-specific hydrophilic muricholic acids allows for the development of adequate mouse models for this purpose.
Do New Mothers Understand the Risk Factors for Maternal Mortality?
Authors: Logsdon M. Cynthia , Davis Deborah Winders , Myers John A. , Masterson Katlin M. , Rushton Jeffrey A. , Lauf Adrian P.
Published: March 2018

Purpose:

The purpose of this study was to describe new mothers' knowledge related to maternal mortality.

Study Design and Methods:

Using a cross-sectional design, new mothers were recruited from a postpartum unit of an academic health sciences center where the population was predominately low-income women. Before hospital discharge, they answered questions on their knowledge of potential postpartum complications that could lead to maternal mortality. Questions were based on recommendations from an expert nursing panel. Descriptive statistics were used for data analysis.

Results:

One hundred twenty new mothers participated. Results indicated that most new mothers knew that they should watch for heavy bleeding, a severe headache, and swelling after hospital discharge. However, fewer participants knew that a new mother could experience feelings that she could harm herself or her baby, have blood clots larger than a baby's hand, a temperature of 100.4 °F or higher, and odor with vaginal discharge. Courses of action new mothers would take if experiencing any of the warning signs included 18% of mothers would take no action, 76.7% would tell their boyfriend/husband/partner, 72.5% would inform their mother. Only 60% who would call the labor and delivery unit. Only 38% of the sample knew that pregnancy-related complications can occur for up to 1 year after birth, and 13% of mothers reported not knowing that complications can occur for up to 6 weeks postpartum.

Clinical Implications:

Our findings provide a foundation to enhance postpartum education for new mothers and their families and to potentially decrease rates of maternal mortality in the United States.
Effective Communication Strategies for Nurses to Discuss Infant Feeding with New Mothers During Postpartum Hospitalization
Authors: Wood Rainey Banick
Published: March 2018

During prenatal care and postpartum hospitalization, nurses have an important role in assisting new mothers to make informed decisions about feeding their newborn infants. There is overwhelming evidence that breastfeeding is beneficial for most new mothers and babies; therefore, perinatal nurses encourage breastfeeding. Newborn infant feeding conversations with women who have chosen to formula feed may be complicated and may cause tension in the nurse–patient relationship. Despite this potential difficulty, these conversations are essential to establish a feeding plan for the newborn infant and to promote healthy outcomes for mothers and babies. Tools are offered for nurses to guide conversations about infant feeding choices and to help to ensure that all mothers receive support and encouragement on their feeding choice.