bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambient Temperature–Corrected Mechanical Stress Mapping of Gallium Nitride and Aluminum Indium Gallium Phosphide Films by Raman Scattering Spectroscopy for Characterization of Light‐Emitting Diodes
Authors: Guo Xiaoru , Mughal Asad , Dunphy Darren , Stone Gregory , Miller David , Huh Sungwook
Published: January 2020

Raman spectroscopy can provide a detailed analysis of mechanical stress in crystalline materials through the measurement of shifts in vibrational frequency. However, the ambient temperature drift during measurements can lead to inaccurate mechanical stress values. Herein, the 2D Raman mapping analysis of gallium nitride (GaN) and aluminum indium gallium phosphide (AlInGaP) epitaxial films within packaged light‐emitting diode (LED) devices reveals micrometer‐scale localized stress distributions. A temperature‐corrected measurement method is developed to evaluate the mechanical stress of InGaN LED dies at various LED operating conditions. The impact of die design on mechanical stress is studied for both GaN on Al2O3 (chip scale package, CSP) and GaN thin‐film flip chip (TFFC) designs. Raman mapping of AlInGaP LEDs is also demonstrated and shows comparable resolution with the GaN LED results.
Investigation of the Structural and Optical Properties of Compositionally V‐Graded Strained InxGa1–xN Layers
Authors: Ghosh Pijush K. , Stanchu Hryhorii V. , Maidaniuk Yurii , Sarollahi Mirsaeid , Aldawsari Manal , Kuchuk Andrian V. , Mazur Yuriy I. , Salamo Gregory J. , Ware Morgan E.
Published: January 2020

Compositionally graded InxGa1–xN‐based materials have been receiving more attention recently due to both their novel structure and intrinsic properties. However, high‐quality material with a well‐controlled and optimized grade to high In composition remains challenging to grow. Herein, the growth and characterization of continuous 2D films of compositionally graded InxGa1–xN are investigated using molecular beam epitaxy (MBE) on (0001) GaN templates at 575 °C. Each film is formed by compositionally grading the growth from GaN to InxGa1–xN and back to GaN, symmetrically, such that the bandgap and the composition of Ga follow a V‐shaped pattern. Here x has been chosen to be ≈0.20 and 0.22. These compositions are confirmed through high‐resolution X‐ray diffraction simulations. Furthermore, asymmetric reciprocal space mapping reveals complete coherence with the GaN substrate. Finally, photoluminescence is measured at low temperature to demonstrate the luminescent properties of the films.
Thickness‐Dependent Ru Exchange Spring at La0.7Sr0.3MnO3–SrRuO3 Interface
Authors: Koch Martin M. , Bergmann Lukas , Agrestini Stefano , Maznichenko Igor , Mertig Ingrid , Herklotz Andreas , Das Sujit , Rata Diana A. , Dörr Kathrin
Published: January 2020

The conducting oxide ferromagnets SrRuO3 (SRO) and La0.7Sr0.3MnO3 (LSMO) form a Ru exchange spring at a coherent low‐interdiffusion interface grown on TiO2‐terminated SrTiO3(STO)(001) substrates as SRO(d)/LSMO/STO(001) bilayers. Field‐ and temperature‐dependent magnetization data with systematically varied thickness d of SRO from 7 to 18 unit cells (uc) indicate a thickness of 10–14 uc of the exchange spring which governs magnetic switching and causes thickness‐dependent field‐cooling effects. Mn L3 edge X‐ray magnetic circular dichroism (XMCD) data reveal the dominating in‐plane orientation of interfacial spins. In low magnetic fields, noncoplanar, topologically nontrivial spin textures arise and can be switched, driven by the Zeeman energy of the LSMO layer.
Magnetic and Electronic Properties of Complex Oxides from First‐Principles
Authors: Hoffmann Martin , Ernst Arthur , Hergert Wolfram , Antonov Victor N. , Adeagbo Waheed A. , Geilhufe R. Matthias , Ben Hamed Hichem
Published: January 2020

The theoretical treatment of complex oxide structures requires a combination of efficient methods to calculate structural, electronic, and magnetic properties, due to special challenges such as strong correlations and disorder. In terms of a multicode approach, this study combines various complementary first‐principles methods based on density functional theory to exploit their specific strengths. Pseudopotential methods, known for giving reliable forces and total energies, are used for structural optimization. The optimized structure serves as input for the Green's function and linear muffin‐tin orbital methods. Those methods are powerful for the calculation of magnetic ground states and spectroscopic properties. Within the multicode approach, disorder is investigated by means of the coherent potential approximation within a Green's function method or by construction of special quasirandom structures in the framework of the pseudopotential methods. Magnetic ground states and phase transitions are studied using an effective Heisenberg model treated in terms of a Monte Carlo method, where the magnetic exchange parameters are calculated from first‐principles. The performance of the multicode approach is demonstrated with different examples, including defect formation, strained films, and surface properties.
Anticancer activity and molecular mechanisms of α‐conidendrin, a polyphenolic compound present in Taxus yunnanensis, on human breast cancer cell lines
Authors: Hafezi Katayoon , Hemmati Ali Asghar , Abbaszadeh Hassan , Valizadeh Armita , Makvandi Manoochehr
Published: January 2020

α‐Conidendrin is a polyphenolic compound found mainly in Taxus yunnanensis, as the source of chemotherapy drug paclitaxel, which has been used in traditional medicine for treatment of cancer. This study aimed to investigate the anticancer activity and molecular mechanisms of α‐conidendrin on breast cancer cell lines. The results of the present study show that α‐conidendrin possesses potent antiproliferative effects on breast cancer cell lines MCF‐7 and MDA‐MB‐231. α‐Conidendrin significantly induced apoptosis in breast cancer cells via reactive oxygen species generation, upregulation of p53 and Bax, downregulation of Bcl‐2, depolarization of mitochondrial membrane potential (MMP), release of cytochrome c from mitochondria, and activation of caspases‐3 and ‐9. α‐Conidendrin remarkably inhibited the proliferation of breast cancer cells through induction of cell cycle arrest by upregulating p53 and p21 and downregulating cyclin D1 and CDK4. Unlike breast cancer cells, the antiproliferative effect of α‐conidendrin on human foreskin fibroblast cells (normal cells) was very small. In normal cells, reactive oxygen species levels, loss of MMP, release of cytochrome c, mRNA expression of p53, p21, cyclin D1, CDK4, Bax, and Bcl‐2 as well as mRNA expression and activity of caspases‐3 and ‐9 were significantly less affected by α‐conidendrin compared with cancer cells. These results suggest that α‐conidendrin can be a promising agent for treatment of breast cancer with little or no toxicity against normal cells.
A comprehensive, self‐contained derivation of the one‐body density matrices from single‐reference excited‐state calculation methods using the equation‐of‐motion formalism
Authors: Etienne Thibaud
Published: January 2020

In this contribution, we review in a rigorous, yet comprehensive fashion the assessment of the one‐body reduced density matrices derived from the most used single‐reference excited‐state calculation methods in the framework of the equation‐of‐motion formalism. Those methods are separated into two types: those which involve the coupling of a deexcitation operator to a single‐excitation transition operator, and those which do not involve such a coupling. The case of many‐body auxiliary wave functions for excited states is also addressed. For each of these approaches we were interested in deriving the elements of the one‐body transition and difference density matrices, and to highlight their particular structure. This has been accomplished by applying a decomposition of integrals involving one‐determinant quantum electronic states on which two or three pairs of second quantization operators can act. Such a decomposition has been done according to a corollary to Wick's theorem, which is brought in a comprehensive and detailed manner. A comment is also given about the consequences of using the equation‐of‐motion formulation in this context, and the two types of excited‐state calculation methods (with and without coupling excitations to deexcitations) are finally compared from the point of view of the structure of their transition and difference density matrices.
Repeatability and agreement between methods for determining the Atterberg limits of fine‐grained soils
Authors: Rehman Hafeez Ur , Pouladi Nastaran , Pulido‐Moncada Mansonia , Arthur Emmanuel
Published: January 2020

The Atterberg limits (plastic limit [PL] and liquid limit [LL]) of fine‐grained soils are important for civil engineering and agronomic applications. Several methodologies exist to determine the PL and LL, each with associated merits and shortcomings. The reproducibility and uncertainties associated with the various methods have not been evaluated for different samples that differ in terms of clay mineralogy and geologic origin. The objectives were to (i) assess the repeatability of two methods each for determining the PL (thread rolling and rolling device) and LL (Casagrande cup and drop cone penetrometer), and compare the subsequent plasticity indexes for 30 samples from 10 countries; and (ii) evaluate the effect of particle size (2 mm and 425 µm) on the plastic and liquid limits for 28 Venezuelan samples. For the PL, the repeatability (estimated as the repeatability coefficient, RC, among replications) for the thread rolling and rolling device methods was similar (2.28 and 2.39%, respectively). For the LL, the drop cone method was 16% more repeatable than the Casagrande cup method. There was a strong correlation between the two respective methods for PL (r2 = 0.98) and LL (r2 = 0.99). For samples that have LL < 45, the LL from the Casagrande cup was slightly higher than LL from the drop cone, and vice versa for samples with LL > 45%. No significant differences were observed between PL measured on <2‐mm or <425‐µm samples; for samples with LL < 35% the two particle sizes gave similar values. There were however larger discrepancies between the two particle sizes for samples with LL > 36%.
Nitrogen fertilization changes the molecular composition of soil organic matter in a subtropical plantation forest
Authors: Geng Jing , Cheng Shulan , Fang Huajun , Pei Jie , Xu Meng , Lu Mingzhu , Yang Yan , Cao Zicheng
Published: January 2020

The biochemical mechanisms responsible for soil organic C (SOC) accumulation under N enrichment are not well understood. By examining two N types (NH4Cl and NaNO3) and three rates (0, 40, and 120 kg N ha−1 yr−1), we investigated the concentration and distribution of SOC by using soil aggregate separation and physical fractionation of soil organic matter (SOM). The molecular composition of SOM within bulk soil and each physical fraction was determined by pyrolysis–gas chromatography‐mass spectrometry. Nitrogen fertilization led to soil NO3−–N accumulation and intensified soil acidification. Four years of N fertilization did not change total SOC concentrations in the 0‐ to 20‐cm depth but a high rate of NaNO3 addition increased the concentrations of fine particulate organic C and microaggregate‐associated organic C by 133 and 83.4%, respectively. The change in SOC concentration was positively correlated with the change in fine particulate organic C and mineral‐associated organic C concentrations. Four years of N fertilization significantly changed the molecular composition of SOM, with an increase in the relative abundance of furfural and acetic acid and a decrease in pyrrole in the mineral‐associated organic matter (MAOM) fraction. Fertilization increased the furfural/pyrrole and aliphatic/aromatic ratios in the SOM and MAOM fractions, suggesting decreased stability of the passive SOM fraction. The SOC concentration was negatively correlated with the benzene/toluene ratio in both bulk soil and the MAOM fraction. Overall, exogenous N input to this subtropical plantation forest decreased the mineralization and humification of SOM, which could be detrimental to soil C accumulation.
Fabrication of BaTaO2N Thin Films by Interfacial Reactions of BaCO3/Ta3N5 Layers on a Ta Substrate and Resulting High Photoanode Efficiencies During Water Splitting
Authors: Nishimae Shinji , Mishima Yuji , Nishiyama Hiroshi , Sasaki Yutaka , Nakabayashi Mamiko , Inoue Yasunobu , Katayama Masao , Domen Kazunari
Published: January 2020

Thin films of barium tantalum oxynitride (BaTaO2N) with thicknesses of 150–680 nm are grown on TaN/Ta substrates via the interfacial reaction of BaCO3/Ta3N5 layers in a N2 atmosphere. A TaN thin film is first deposited on a Ta substrate by the Ar/N2 ion sputtering of a Ta target, and then covered with a TaOx layer by Ar/O2 sputtering. The TaOx layer is subsequently nitrided in an NH3 flow to a Ta3N5 layer. Finally, Ba metal is deposited on the Ta3N5/TaN/Ta substrate under vacuum, oxidized, and carbonized to produce BaCO3. The interfacial reaction between the BaCO3 and Ta3N5 layers is conducted in a N2 atmosphere at high temperatures. X‐ray diffraction patterns confirm BaTaO2N and Ta2N phases on the Ta substrates, while cross‐sectional scanning electron microscopy images show a three‐layer BaTaO2N/Ta2N/Ta structure. Cobalt oxide (CoOx)‐deposited BaTaO2N/Ta2N/Ta photoanodes for water oxidation provide a high photocurrent of 4.6 mA cm−2 at 1.23 V (vs RHE) and an incident photon‐to‐current conversion efficiency of 9% at 600 nm under simulated AM1.5G irradiation. The efficiency of this photoanode is remarkably improved compared with previously reported photoanode thin films. Interestingly, a BaTaO2N/Ta2N/Ta electrode with similar photoanode performance is also obtained via the interfacial reaction between TaN and BaCO3 layers.
Barriers, potentialities, and actions for implementation of sustainable energy procedures in Brazilian federal universities
Authors: Avila Lucas Veiga , da Silveira João Serafim Tusi , Neto Emitério da Rosa , Baggio Daniel Knebel
Published: January 2020

Many universities around the world have served as active centers for research on climate change. However, there are several barriers to their activities, stemming from the nature of research, resources, and the structure of institutions. This document provides an overview of barriers, potential factors, and activities to develop and implement sustainable energy processes in public higher education institutions (HEIs) in Brazil. The research was conducted from March to April of 2018 with representatives of HEIs (rectors or prorectors of research). A total of 63 invitations to respond to the Survey‐monkey survey were emailed, and responses were received from 32 universities. The research concludes by proposing measures that can be taken to make the issue of climate change more present and effective in university research and teaching activities. This includes changes in research, information dissemination, and teaching approaches to better support actions to address climate change. In Brazil, there are many potentialities in terms of natural resources, but actions for implementation are still incipient. Further efforts and investment in research and development will be required.
Inference of Ancestral Recombination Graphs Using ARGweaver
Authors: Hubisz Melissa , Siepel Adam
Published: January 2020

This chapter describes the usage of the program ARGweaver, which estimates the ancestral recombination graph for as many as about 100 genome sequences. The ancestral recombination graph is a detailed description of the coalescence and recombination events that define the relationships among the sampled sequences. This rich description is useful for a wide variety of population genetic analyses. We describe the preparation of data and major considerations for running ARGweaver, as well as the interpretation of results. We then demonstrate an analysis using theDARC(Duffy) gene as an example, and show how ARGweaver can be used to detect signatures of natural selection and Neandertal introgression, as well as to estimate the dates of mutation events. This chapter provides sufficient detail to get a new user up and running with this complex but powerful analysis tool.
Genomics of Long- and Short-Term Adaptation in Maize and Teosintes
Authors: Lorant Anne , Ross-Ibarra Jeffrey , Tenaillon Maud
Published: January 2020

Maize is an excellent model for the study of plant adaptation. Indeed, post domestication maize quickly adapted to a host of new environments across the globe. And work over the last decade has begun to highlight the role of the wild relatives of maize—the teosintes Zea mays ssp. parviglumis and ssp. mexicana—as excellent models for dissecting long-term local adaptation.

Although human-driven selection associated with maize domestication has been extensively studied, the genetic basis of natural variation is still poorly understood. Here we review studies on the genetic basis of adaptation and plasticity in maize and its wild relatives. We highlight a range of different processes that contribute to adaptation and discuss evidence from natural, cultivated, and experimental populations. From an applied perspective, understanding the genetic bases of adaptation and the contribution of plasticity will provide us with new tools to both better understand and mitigate the effect of climate changes on natural and cultivated populations.
Population Genomics in the Great Apes
Authors: Castellano David , Munch Kasper
Published: January 2020

The great apes play an important role as model organisms. They are our closest living relatives, allowing us to identify the genetic basis of phenotypic traits that we think of as characteristically human. However, the most significant asset of great apes as model organisms is that they share with humans most of their genetic makeup. This means that we can extend our vast knowledge of the human genome, its genes, and the associated phenotypes to these species. Comparative genomic studies of humans and apes thus reveal how very similar genomes react when exposed to different population genetic regimes. In this way, each species represents a natural experiment, where a genome highly similar to the human one, is differently exposed to the evolutionary forces of demography, population structure, selection, recombination, and admixture/hybridization. The initial sequencing of reference genomes for chimpanzee, orangutan, gorilla, the bonobo, each provided new insights and a second generation of sequencing projects has provided diversity data for all the great apes. In this chapter, we will outline some of the findings that population genomic analysis of great apes has provided, and how comparative studies have helped us understand how the fundamental forces in evolution have contributed to shaping the genomes and the genetic diversity of the great apes.
Small RNA In Situ Hybridizations on Sections of Arabidopsis Embryos
Authors: Páldi Katalin , Mosiolek Magdalena , Nodine Michael D.
Published: January 2020

Small RNAs mediate posttranscriptional gene silencing in plants and animals. This often occurs in specific cell or tissue types and can be necessary for their differentiation. Determining small RNA (sRNA) localization patterns at cellular resolution can therefore provide information on the corresponding gene regulatory processes they are involved in. Recent improvements with in situ hybridization methods have allowed them to be applied to sRNAs. Here we describe an in situ hybridization protocol to detect sRNAs from sections of early staged Arabidopsis thaliana (Arabidopsis) embryos.
Prolegomena to the Study of Early Modern Commentators on Johannes de Sacrobosco’s Tractatus de sphaera
Authors: Valleriani Matteo
Published: January 2020

By way of introduction to the present volume, a corpus of 359 treatises is described that was used in early modern educational institutions for introductory classes on cosmology and that is referenced by the following contributions. Following a taxonomy of early modern commentaries, central characteristics are analyzed in detail such as the rate of production of the treatises, the places where they were produced, and their various languages and formats. The focus then turns to the balance between the temporal dynamics of production of the treatises and the lifespans of their commentators. This reveals how the early modern textbooks first amplified medieval scientific knowledge and only slowly began to support and spread the echoes of scientific debate among contemporary scholars. The institutional and intellectual profiles of the commentary authors are then described on the basis of the results presented in the contributions to this volume. The commentators are described by referring on one hand to their relations to the universities, religious orders, and commercial institutions, and on the other to their engagement with disciplines both inside and outside the conceptual framework of the quadrivium. Finally, a quantitative summary of the results achieved by this volume is presented along with outlines for future research endeavors that will focus, consequently, on the role of the printers and publishers of the same commentaries.
The Use of Molecular Oxygen for Liquid Phase Aerobic Oxidations in Continuous Flow
Authors: Hone Christopher A. , Kappe C. Oliver
Published: January 2020

Molecular oxygen (O2) is the ultimate “green” oxidant for organic synthesis. There has been recent intensive research within the synthetic community to develop new selective liquid phase aerobic oxidation methodologies as a response to the necessity to reduce the environmental impact of chemical synthesis and manufacture. Green and sustainable chemical processes rely not only on effective chemistry but also on the implementation of reactor technologies that enhance reaction performance and overall safety. Continuous flow reactors have facilitated safer and more efficient utilization of O2, whilst enabling protocols to be scalable. In this article, we discuss recent advancements in the utilization of continuous processing for aerobic oxidations. The translation of aerobic oxidation from batch protocols to continuous flow processes, including process intensification (high T/p), is examined. The use of “synthetic air”, typically consisting of less than 10% O2 in N2, is compared to pure O2 (100% O2) as an oxidant source in terms of process efficiency and safety. Examples of homogeneous catalysis and heterogeneous (packed bed) catalysis are provided. The application of flow photoreactors for the in situ formation of singlet oxygen (1O2) for use in organic reactions, as well as the implementation of membrane technologies, green solvents and recent reactor solutions for handling O2 are covered.
Affektive Epistemologien des Feldes
Authors: Shah Mira
Published: January 2020

Bevor mit Sherwood Washburn und Louis Leakey zwei Leitfiguren der Anthropologie in den 1950er bzw. 1960er Jahren auf die Idee kamen, junge Forscher/innen ‚ins Feld‘ zu schicken, wurde Wissen über Tiere überwiegend aus der Beobachtung gefangener oder der Autopsie toter Exemplare generiert.
UV-finite “old” conformal bootstrap on AdS: scalar case
Authors: Altshuler Boris L.
Published: January 2020

Abstract

The double-trace from UV to IR flow subtraction of infinities used earlier for the UV-convergent calculations of the Witten tadpole diagrams being applied to the bubble self-energy diagrams gives for them the amazingly simple expressions in case of the four- dimensional boundary space. For every N = 1 … 4 in the O(N) symmetric scalar fields model with the conformal Hubbard-Stratonovich field there are three roots of the “old” conformal bootstrap spectral equations that obey unitarity bound demand.
Relating quantum mechanics and kinetics of neutrino oscillations
Authors: Kartavtsev A.
Published: January 2020

Abstract

Simultaneous treatment of neutrino oscillations and collisions in astrophysical environments requires the use of (quantum) kinetic equations. Despite major advances in the field of quantum kinetics, the structure of the kinetic equations and their consistency with the uncertainty principle are still debated. The goals of the present work are threefold. First, it clarifies the structure of the Liouville term in the presence of mixing. Second, we derive evolution equation for neutrinos propagating in vacuum or matter from the Schrödinger equation and show that in the relativistic limit its form matches the form of the (collisionless part of the) kinetic equation derived by Sigl and Raffelt. Third, by constructing solutions of the evolution equation from the known solutions of the Schrödinger equation, we show that the former also admits solutions consistent with the uncertainty principle and accounts for neutrino wave packet separation. The obtained results speak in favor of a (quantum) kinetic approach to the analysis of neutrino propagation in exploding supernovae where neutrino oscillations and collisions, as well as the effect of wave packet separation, might be equally important.
On the geometric concomitant equation
Authors: Moszner Zenon
Published: January 2020

We solve in some cases the equation in the definition of the concomitant of a geometric object for each of the four functions in this equation. Remarks and examples are given, too.
The effect of fornix deep brain stimulation in brain diseases
Authors: Liu Huajie , Temel Yasin , Boonstra Jackson , Hescham Sarah
Published: January 2020

Deep brain stimulation is used to alleviate symptoms of neurological and psychiatric disorders including Parkinson’s disease, epilepsy, and obsessive–compulsive-disorder. Electrically stimulating limbic structures has been of great interest, and in particular, the region of the fornix. We conducted a systematic search for studies that reported clinical and preclinical outcomes of deep brain stimulation within the fornix up to July 2019. We identified 13 studies (7 clinical, 6 preclinical) that examined the effects of fornix stimulation in Alzheimer’s disease (n = 9), traumatic brain injury (n = 2), Rett syndrome (n = 1), and temporal lobe epilepsy (n = 1). Overall, fornix stimulation can lead to decreased rates of cognitive decline (in humans), enhanced memory (in humans and animals), visuo-spatial memorization (in humans and animals), and improving verbal recollection (in humans). While the exact mechanisms of action are not completely understood, studies suggest fornix DBS to be involved with increased functional connectivity and neurotransmitter levels, as well as enhanced neuroplasticity.
P38 MAPK and glucocorticoid receptor crosstalk in bronchial epithelial cells
Authors: Lea Simon , Li Jian , Plumb Jonathan , Gaffey Kate , Mason Sarah , Gaskell Rosie , Harbron Chris , Singh Dave
Published: January 2020

p38 MAPK inhibition may have additive and synergistic anti-inflammatory effects when used with corticosteroids. We investigated crosstalk between p38 MAPK inhibitors and corticosteroids in bronchial epithelial cells to investigate synergistic effects on cytokine production and the molecular mechanisms involved. Effects of the p38 MAPK inhibitor BIRB-796 and dexamethasone alone and in combination on LPS, polyI:C or TNFα -induced IL-6, CXCL8 and RANTES were assessed in 16HBEs (human epithelial cell line) and on TNFα-induced IL-6 and CXCL8 in primary human epithelial cells from asthma patients and healthy controls. 16HBEs were used to assess effects of BIRB-796 alone and in combination with dexamethasone on glucocorticoid receptor (GR) activity by reporter gene assay, expression of GR target genes and nuclear localisation using Western blot. The effects of BIRB-796 on TNFα stimulated phosphorylation of p38 MAPK and GR at serine (S) 226 by Western blot. Epithelial levels of phosphorylated p38 MAPK and GR S226 were determined by immunohistochemistry in bronchial biopsies from asthma patients and healthy controls. BIRB-796 in combination with dexamethasone increased inhibition of cytokine production in a synergistic manner. Combination treatment significantly increased GR nuclear localisation compared to dexamethasone alone. BIRB-796 inhibited TNFα-induced p38 MAPK and GR S226 phosphorylation. Phosphorylated GR S226 and p38 MAPK levels were increased in bronchial epithelium of more severe asthma patients. Molecular crosstalk exists between p38 MAPK activation and GR function in human bronchial epithelial cells, which alters GR activity. Combining a p38 MAPK inhibitor and a corticosteroid may demonstrate therapeutic potential in severe asthma.

Key messages

• Combination of corticosteroid and p38 inhibitor in human bronchial epithelial cells

• Combination increased cytokine inhibition synergistically and nuclear GR

• p38 MAPK inhibition reduced TNFα-induced phosphorylation of GR at S226 but not S211

• Phosphorylated GRS226 and p38 is increased in bronchial epithelium in severe asthma

• Combining a p38 inhibitor and a corticosteroid may be effective in asthma treatment
The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI): Incidence and First-Episode Case–Control Programme
Authors:   EU-GEI WP2 Group, Gayer-Anderson Charlotte , Jongsma Hannah E. , Di Forti Marta , Quattrone Diego , Velthorst Eva , de Haan Lieuwe , Selten Jean-Paul , Szöke Andrei , Llorca Pierre-Michel , Tortelli Andrea , Arango Celso , Bobes Julio , Bernardo Miguel , Sanjuán Julio , Santos José Luis , Arrojo Manuel , Parellada Mara , Tarricone Ilaria , Berardi Domenico , Ruggeri Mirella , Lasalvia Antonio , Ferraro Laura , La Cascia Caterina , La Barbera Daniele , Menezes Paulo Rossi , Del-Ben Cristina Marta , Rutten Bart P. , van Os Jim , Jones Peter B. , Murray Robin M. , Kirkbride James B. , Morgan Craig
Published: January 2020

Purpose

The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders.

Methods

Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case–control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort.

Conclusions

This resource constitutes the largest and most extensive incidence and case–control study of psychosis ever conducted.
The neutrophil–lymphocyte ratio and locoregional melanoma: a multicentre cohort study
Authors: Robinson Alyss V. , Keeble Claire , Lo Michelle C. I. , Thornton Owen , Peach Howard , Moncrieff Marc D. S. , Dewar Donald J. , Wade Ryckie G.
Published: January 2020

Objectives

The neutrophil–lymphocyte ratio (NLR) is an inflammatory biomarker which is useful in cancer prognostication. We aimed to investigate the differences in baseline NLR between patients with localised and metastatic cutaneous melanoma and how this biomarker changed over time with the recurrence of disease.

Methods

This multicentre cohort study describes patients treated for Stage I–III cutaneous melanoma over 10 years. The baseline NLR was measured immediately prior to surgery and again at the time of discharge or disease recurrence. The odds ratios (OR) for sentinel node involvement are estimated using mixed-effects logistic regression. The risk of recurrence is estimated using multivariable Cox regression.

Results

Overall 1489 individuals were included. The mean baseline NLR was higher in patients with palpable nodal disease compared to those with microscopic nodal or localised disease (2.8 versus 2.4 and 2.3, respectively; p < 0.001). A baseline NLR ≥ 2.3 was associated with 30% higher odds of microscopic metastatic melanoma in the sentinel lymph node [adjusted OR 1.3 (95% CI 1.3, 1.3)]. Following surgery, 253 patients (18.7%) developed recurrent melanoma during surveillance although there was no statistically significant association between the baseline NLR and the risk of recurrence [adjusted HR 0.9 (0.7, 1.1)].

Conclusion

The NLR is associated with the volume of melanoma at presentation and may predict occult sentinel lymph metastases. Further prospective work is required to investigate how NLR may be modelled against other clinicopathological variables to predict outcomes and to understand the temporal changes in NLR following surgery for melanoma.
Improvement in Hyperglycemia Prevents Surgical Site Infection Irrespective of Insulin Therapy in Non‐diabetic Patients Undergoing Gastrointestinal Surgery
Authors: Yoneda Ayami , Takesue Yoshio , Takahashi Yoshiko , Ichiki Kaoru , Tsuchida Toshie , Ikeuchi Hiroki , Uchino Motoi , Hatano Etsuro , Shinohara Hisashi , Tomita Naohiro
Published: January 2020

Background

Intensive glycemic control is recommended to prevent surgical site infections (SSI). Our aim was to evaluate retrospectively the effect of improvement in hyperglycemia irrespective of insulin use on the incidence of SSI in non‐diabetic patients.

Methods

The highest blood glucose (BG) concentration within 12 h (early peak BG) and the final BG from 12 to 24 h after surgery were evaluated in patients who underwent gastrointestinal surgery. Patients with an early peak BG of ≥150 mg/dL were divided into those with persistent (final BG of ≥150 mg/dL) and improved hyperglycemia (final BG of <150 mg/dL). Patients without hyperglycemia and those with late‐onset hyperglycemia were also assessed for SSI risk.

Results

Overall, 1612 patients were studied (diabetes, n = 293). Although hyperglycemia increased the SSI rates in non‐diabetic patients, no correlation was demonstrated in patients with diabetes at any cutoff final BG defining htperglycemia except for 180 mg/dL. Hyperglycemia improved without insulin therapy in 283 of 512 non‐diabetic patients who had early hyperglycemia. The adjusted standardized residual for those with SSI and persistent hyperglycemia was 5.2 (P < 0.05). In contrast, the absence of hyperglycemia was a significant preventive factor for SSI. In the multivariate analyses, persistent hyperglycemia was an independent risk factor for SSI (odds ratio 1.54; 95% confidence interval 1.03–2.31).

Conclusions

Remission of hyperglycemia within 24 h after surgery prevented SSI in non‐diabetic patients. Considering that hyperglycemia improved in approximately half of patients without insulin therapy, commencement of insulin dosing after two consecutive BGs of ≥150 mg/dL might be reasonable, especially in general wards.
Fibroepithelial Lesions (FELs) of the Breast: Is Routine Excision Always Necessary?
Authors: Limberg Jessica , Barker Kelly , Hoda Syed , Simmons Rache , Michaels Aya , Marti Jennifer L.
Published: January 2020

Background

When needle core biopsies (NCBs) of the breast reveal fibroepithelial lesions (FELs), excision is often performed to rule out a phyllodes tumor (PT), despite low malignancy rates. Consequently, the natural history of observed FELs is not well described. We analyzed the malignancy risk in excised FELs and the natural history of FELs undergoing active surveillance (AS).

Methods

We retrospectively studied the pathology and imaging records of 215 patients with FELs (n = 252) diagnosed on NCB. Incidence of growth was determined by Kaplan–Meier method.

Results

Of 252 FELs, 80% were immediately excised and 20% underwent AS. Of the excised FELs, 198 (98%) were benign: fibroadenoma (FA) or benign breast tissue in 137 (68%), benign PT in 59 (29%), or LCIS in 2 (1%). Borderline PT or malignant lesions were found in 4 (2%). On ultrasound, malignant and borderline PTs were larger than benign lesions [median 3.9 vs 1.3 cm, p = 0.006]. Fifty FELs underwent AS, with a median follow‐up of 17 (range 2–79) months. The majority remained stable or decreased in size: at 2 years, only 35% increased in volume by ≥ 50%. Of those tumors undergoing AS that were later excised (n = 4), all were benign.

Conclusions

Almost all FELs (98%) were benign on surgical excision, and the majority undergoing AS remained stable, with benign pathology if later excised. Most FELs on NCB can be safely followed with US, with surgery reserved for patients with FELs that are large, symptomatic, or growing. This could spare most women with FELs unnecessary surgery.
Fundamental utilitarianism and intergenerational equity with extinction discounting
Authors: Chichilnisky Graciela , Hammond Peter J. , Stern Nicholas
Published: January 2020

Ramsey famously condemned discounting “future enjoyments” as “ethically indefensible”. Suppes enunciated an equity criterion which, when social choice is utilitarian, implies giving equal weight to all individuals’ utilities. By contrast, Arrow (Contemporary economic issues. International Economic Association Series. Palgrave Macmillan, London, 1999a; Discounting and Intergenerational Effects, Resources for the Future Press, Washington DC, 1999b) accepted, perhaps reluctantly, what he called Koopmans’ (Econometrica 28(2):287–309, 1960) “strong argument” implying that no equitable preference ordering exists for a sufficiently unrestricted domain of infinite utility streams. Here we derive an equitable utilitarian objective for a finite population based on a version of the Vickrey–Harsanyi original position, where there is an equal probability of becoming each person. For a potentially infinite population facing an exogenous stochastic process of extinction, an equitableextinction biasedoriginal position requires equalconditionalprobabilities, given that the individual’s generation survives the extinction process. Such a position is well-defined if and only if survival probabilities decline fast enough for the expected total number of individuals who can ever live to be finite. Then, provided that each individual’s utility is bounded both above and below, maximizing expected “extinction discounted” total utility—as advocated,inter alia, by theStern Reviewon climate change—provides a coherent and dynamically consistent equitable objective, even when the population size of each generation can be chosen.
Middle-ear cholesteatoma co-existing with labyrinthine fistula and vestibular schwannoma
Authors: Zwierz Aleksander , Masna K. , Burduk P.
Published: January 2020

Background

Many conditions, among them vestibular schwannoma and middle ear cholesteatoma with lateral semicircular canal destruction, may be associated with asymmetrical sensorineural hearing loss (SNHL) and vertigo. However, the probability that these two distinct disease entities causing the same symptoms occur in a single patient is very low, approximately 1 per 28 billion per 1 year.

Methods

We present the case of a 40-year-old male admitted to our clinic because of chronic middle ear inflammation with concomitant tinnitus vertigo, and deafness in the right ear. The patient was diagnosed with lateral semicircular canal fistula caused by middle-ear cholesteatoma and concomitant vestibular schwannoma. Canal wall-down surgery was carried out to remove the cholesteatoma, followed by gamma knife radiosurgery for the vestibular schwannoma.

Results

Vertigo and tinnitus resolved within 3 days after the ear surgery, and gamma knife treatment resulted in the complete involution of the vestibular schwannoma. The patient presented with completely dry middle-ear cavity and no recurrence of the cholesteatoma was observed during a 3-year follow-up.

Conclusion

As the hereby reported condition is very rare, the results cannot be compared with any similar report published previously. Nevertheless, based on the outcome, the treatment strategy seems to be both reasonable and effective.
Pancreaticojejunostomy—a review of modern techniques
Authors: Olakowski Marek , Grudzińska Ewa , Mrowiec Sławomir
Published: January 2020

Background

Pancreaticojejunal anastomosis is one of the most demanding procedures in surgery. Up to now, no technique has been proven to reduce the incidence of POPF when compared to the other methods.

Purpose

The aim of this review was to provide a concise and illustrated description of the most recent methods of pancreaticojejunostomy. Their development was directly related to the still ongoing search by surgeons for such a technique of anastomosis that would eliminate the problem of POPF.

Conclusions

Knowledge of various techniques of anastomosis may help the surgeon to find the most suitable and optimal method of pancreatic-intestinal anastomosis for the patient.
A standardized postmortem protocol to assess the real burden of sudden infant death syndrome
Authors: Rizzo Stefania , De Gaspari Monica , Carturan Elisa , Paradiso Beatrice , Favretto Donata , Thiene Gaetano , Basso Cristina
Published: January 2020

Sudden unexpected infant death (SUID) is a major cause of death in infants < 1 year of age. Sudden infant death syndrome (SIDS) is a SUID still unexplained after post-mortem examination. In 2014, a protocol of post-mortem investigation was introduced to assess both the prevalence and the etiopathogenesis of SUID. Our aim was to compare SUID data before and after the application of a standardized autopsy protocol of investigation. In the time interval 2004–2018, SUID cases occurring in the Veneto Region, North-East Italy, were referred to our Core Lab. Since 2014, a complete autopsy was performed, including gross and histological study with toxicologic and molecular analysis carried out at the referral center. A total of 36 SUIDs (22 M, mean age 95.5 ± 80 days), 17 before (group A) and 19 after (group B) 2014, were collected. In group A, only 1 (6%) resulted as explained SUID, due to lymphocytic myocarditis and 16 (94%) were SIDS. In group B, 8 were SIDS (42%) and 11 (58%) explained SUID cases (p < 0.01), consisting of interstitial pneumonia and bronchiolitis in 9 and lymphocytic myocarditis in 2 cases. Molecular analysis was positive for viruses in 8 of them (73%). In conclusion, since the application of a standardized protocol of post-mortem investigation, inflammatory, mostly infective, cardio-pulmonary diseases have been identified as the most common cause of SUID, with SIDS falling from 94 to 42% of SUID. Efforts must be made to implement a uniform autopsy protocol to provide reliable epidemiological data on SIDS.
FAIR data for prehistoric mining archaeology
Authors: Hiebel Gerald , Goldenberg Gert , Grutsch Caroline , Hanke Klaus , Staudt Markus
Published: January 2020

This paper presents an approach how to create FAIR data for prehistoric mining archaeology, based on the CIDOC CRM ontology and semantic web standards. The interdisciplinary Research Centre HiMAT (History of mining activities in the Tyrol and adjacent areas, University of Innsbruck) investigates mining history from prehistoric to modern times with an interdisciplinary approach. One of the projects carried out at the research centre is the multinational DACH project “Prehistoric copper production in the eastern and central Alps”. For a specific geographical region of the project, the data transformation to open and re-usable data is investigated in a separate Open Research Data pilot project. The methodological approach will use the FAIR principles to make data Findable, Accessible, Interoperable and Re-usable. Every archaeological investigation in Austria has to be documented according to the requirements of the Austrian Federal Monuments Office. This documentation is deposited in the CERN-based EU supported research data repository ZENODO. For each deposited file, metadata are created through the application of the conceptual metadata schema CIDOC CRM, an ISO standard for Cultural Heritage Information, which was adopted by ARIADNE, the European Union Research Infrastructure for archaeological resources. Concepts specific to mining archaeology research are organized with the DARIAH Back Bone Thesaurus, a model for sustainable interoperable thesauri maintenance, developed in the European Union Digital Research Infrastructure for the Arts and Humanities. Metadata are created through the extraction of information from the documentation and the transformation to a knowledge graph using semantic web standards. To facilitate usage, graph data are exported to hierarchical and tabular formats representing sites and objects with their geographic locations, temporal and typological assignments and links to the research activities and documents. Metadata are deposited together with the documentation into the repository.
Linking Combinatorial and Classical Dynamics: Conley Index and Morse Decompositions
Authors: Batko Bogdan , Kaczynski Tomasz , Mrozek Marian , Wanner Thomas
Published: January 2020

We prove that every combinatorial dynamical system in the sense of Forman, defined on a family of simplices of a simplicial complex, gives rise to a multivalued dynamical system F on the geometric realization of the simplicial complex. Moreover, F may be chosen in such a way that the isolated invariant sets, Conley indices, Morse decompositions and Conley–Morse graphs of the combinatorial vector field give rise to isomorphic objects in the multivalued map case.
Stability of Low-Rank Tensor Representations and Structured Multilevel Preconditioning for Elliptic PDEs
Authors: Bachmayr Markus , Kazeev Vladimir
Published: January 2020

Folding grid value vectors of size $$2^L$$

2
L

into Lth-order tensors of mode size $$2\times \cdots \times 2$$

2
×
⋯
×
2

, combined with low-rank representation in the tensor train format, has been shown to result in highly efficient approximations for various classes of functions. These include solutions of elliptic PDEs on nonsmooth domains or with oscillatory data. This tensor-structured approach is attractive because it leads to highly compressed, adaptive approximations based on simple discretizations. Standard choices of the underlying bases, such as piecewise multilinear finite elements on uniform tensor product grids, entail the well-known matrix ill-conditioning of discrete operators. We demonstrate that, for low-rank representations, the use of tensor structure itself additionally introduces representation ill-conditioning, a new effect specific to computations in tensor networks. We analyze the tensor structure of a BPX preconditioner for a second-order linear elliptic operator and construct an explicit tensor-structured representation of the preconditioner, with ranks independent of the number L of discretization levels. The straightforward application of the preconditioner yields discrete operators whose matrix conditioning is uniform with respect to the discretization parameter, but in decompositions that suffer from representation ill-conditioning. By additionally eliminating certain redundancies in the representations of the preconditioned discrete operators, we obtain reduced-rank decompositions that are free of both matrix and representation ill-conditioning. For an iterative solver based on soft thresholding of low-rank tensors, we obtain convergence and complexity estimates and demonstrate its reliability and efficiency for discretizations with up to $$2^{50}$$

2
50

nodes in each dimension.