bluuebunny/crossref_metadata_2025 huggingface dataset:
Implementation of Open Innovation in The Small and Medium-Size enterprise (SMEs): A Literature Review
Authors: Farid Muhammad , Day Jen-Der
Published: June 2019

This study is a systematic literature review of three academic articles. It aims to investigate and explore the implementation of open innovation in SMEs. The review was conducted in three phases: (i) understanding the concept of innovation and open innovation; (ii) identifying references and (iii) exploring primary study which explains about the implementation of open innovation in SMEs. Finally, this paper examines how the concept of open innovation in SMEs is implemented in different countries. The result shows that open innovation in SMEs focus more on commercialization because marketing channels and global contacts to introduce them effectively to the market. Implementation of open innovation in SMEs has a significant impact to the company in the aspect of 1) motives and perceived challenges, 2) leadership, people, culture, and business improvement; 3) company size on the effectiveness of innovation endures.
Measurement of Level Content of Methane in Household Waste Based on Arduino and Gas Sensor
Authors: Harun Sabran F. , Sokku Saharuddin Ronge
Published: June 2019

Household waste is an alternative energy source that is potential to be developed considering the continuously of production. Nevertheless, it is necessary to measure gas levels of waste as the effort to manage the waste effectively and efficiently. The design and manufacture of methane concentration gauges is the first step for this purpose. The tool is designed using Arduino and gas sensors as the main components. The measurement results are displayed on the LCD screen and picoscope measuring instrument. The sample used as a measuring object are decomposition of vegetables, liquid waste, and mixed waste. The measurement results show that the three types of waste show an increased concentration of methane gas, but the highest concentration of gas in vegetable waste.
Convective heat transfer in the near-wall turbulent gas stratum
Authors: Kuznetsov V A , Trubaev P A
Published: June 2019

In order to diminish the computational cost of heat transfer simulations, some wall functions had been often introduced in numerical algorithms. More universal and robust dimensionless velocity functions that can be employed both in buffer and equilibrium parts of the near-wall turbulent gas stratum are offered here for consideration. They have been obtained on the basis of Prandtl’s semiempirical hypothesis of turbulence. A mode, how to determine the one-sided derivatives of the gas velocity and temperature at the wall surface on a coarse grid, has been substantiated. That allows applying the boundary conditions of Neumann and Robin type for differential equations of the convective heat transfer to the confining walls from the turbulent gas flow. A semiempirical formula for the eddy viscosity in the wall proximity has been deduced, and a valid boundary value has been determined also for the rate of turbulence-energy dissipation. It is demonstrated that the simulation results coincide sufficiently with experimental data.
Parametric model for predicting the reliability of heat power equipment of TPP
Authors: Sultanov M M , Truhanov V M , Gorban Yu A
Published: June 2019

Forecasting and ensuring the required high reliability level of heat power plants (thermal power plants) at a stage of their creation and operation is an important problem of economic value. For the solution of this problem in the present article the task is to develop such mathematical models of forecasting of reliability at all stages of life cycle of a thermal power plant from designing before removal from operation. It would be possible to reduce costs of realization of concrete actions. Parametrical mathematical models of growth of reliability have been developed for the solution of an objective. In particular two-parametrical, three-parametrical and multiple parameter models of growth of reliability have been developed and presented. For calculation of estimates of parameters of distribution standard programs are offered. All developed mathematical models of forecasting of reliability level are based on use of the statistical data obtained in the course of tests or operation of products analogs. Change of reliability level on five stages of life cycle of the power equipment of a thermal power plant is graphically shown in the article.
Mathematical and visual models of asynchronous electric machines energy fields
Authors: Kurillin S P , Denisov V N , Dli M I
Published: June 2019

The research considers the development of topological theory of asynchronous electric machines (AEM). The results of the development of energy aspects of the topological theory are presented in the article. The facts proving the actuality of the research are also given. The central notion giving the topological theory the characteristic of being systematic is the vector space notion. The definition of AEM vector space, its dimension, canonical basis, power and energy field of AEM are presented. Mathematical and visual models of AEM energy fields are analyzed. Energy fields of electric losses and magnetic field dissipation having the spherical symmetry are analyzed in particular. Energy and visual models of the main magnetic field are analyzed using AEM with a short circuited rotor and linear AEM as examples. It is established that this field obtains cylindrical or elliptical symmetry. In general the main magnetic field and the main matrix of winding make AEM vector space fully or partially heterogeneous. Energy efficiency is analyzed and its differences for vector space currents are revealed. The areas of vector spaces with high and low energy currents efficiency are defined. According to this indicator longitudinal and transvers subsets of current having, correspondingly, high and zero energy efficiency are distinguished in the vector space. The description of practical application spheres of AEM topological theory is given.
The thermal and physical aspects of designing facade heat insulation at capital repairs and reconstruction of civic buildings
Authors: Kosukhin M M , Kosukhin A M
Published: June 2019

The brief analysis of civic buildings condition has been presented in this paper. It has been demonstrated that at present the housing stock doesn’t meet the up-to-date heat engineering, energy saving and energy performance requirements. To create the necessary indoor climate of living accommodations and to provide the comfortable living environment, most of civic buildings, built at different times, are in need of large-scale reconstruction. The leading role in solving these problems is assigned to capital repairs. For its satisfactory implementation an integrated approach to repairs and construction works with the use of up-to-date energy-efficient technologies and materials is needed. The efficient heat insulation of en-closing structures should be preceded with professional engineering survey of structures and with providing the scientifically-grounded recommendations, based on present-day scientific achievements in this sphere, for the subsequent making of design specification. It has been pointed out that the economic and processing efficiency of the selection and installation of heat insulation can be achieved only by means of scientific approach and the knowledge of physical and chemical processes and phenomena, taking place in enclosing structures under the influence of internal and external operational environment.
The use of modern highly precise ultrasonic gas flowmeters and etalon stands to enlarge industrial resource efficiency
Authors: Velichko M A , Kostina I B , Gladkikh Yu P
Published: June 2019

In this article we have described our new development that is the ultrasonic flowmeter with high dynamic range of 1 to 2000 for industrial applications. Its high accuracy of measurement can help gas consuming enterprises to save resources. Its software and the software of corresponding computing device is able to avoid gas leakage, to minimize energy consumption and to save human resources while maintaining metrological data. Shown are the new anti-adhesion technologies that can help to increase measurement accuracy and enlarge interval between counters verifications. Described is the low power consumption that makes it possible to use this ultrasonic flowmeter in hard remote environment without direct management for a period of several months. Experiments held in Turkmenistan have shown that device indications didn’t drift and remained stable during the year that is a great advantage in comparison to rotary and turbine flowmeters. Also described is the mobile ultrasonic calibration stand that uses the same physical principles and similar software. Outlined is the usage of modern wireless technologies to collect and transmit metrological data.
Thermotechnical tests of the low power solid fuel heating boilers while incinerating briquetted RDF
Authors: Kornilova N V , Trubaev P A
Published: June 2019

Objective of this paper is an analysis of briquetted waste combustion in the low power boilers. Research was conducted for the 100 kW pyrolysis heating boiler and 200 kW heating boiler with grate stoker. Briquettes were made by compacting milled and crushed materials into cylinders 50 mm in diameter, with a length of 100-200 mm, density of 800 kg/M3. It was established that process of combustion in low power boilers has low thermal efficiency, value of which fluctuated within 60…74% for wood combustion and 50…70% for RDF briquettes combustion. Burning process was stable and characteristics of the RDF combustion were similar to the wood combustion. Incineration of the fuel briquettes had better effectiveness than burning of solid wood. During RDF briquettes combustion high CO content (up to 0,2% or 2000 ppm) in flue gas was observed, which is an indication of insufficient burning time. It may be concluded that waste incineration in low-duty plants is viable, but to secure complete combustion and desired temperatures process of combustion and heat extraction should be separate in terms of design.
Effective ways of molding man-made materials
Authors: Sevostyanov M V , Il’ina T N , Martakov I G
Published: June 2019

The article is devoted to the development of multifunctional technological complexes for obtaining highly dispersed activated materials, including fast-hardening microfibrated composite mixtures. Special attention is paid to the development of conditions for their effective homogenization and the molding technology of various charges. Presented experimental design, aimed at improving the process of forming man-made mixtures. A low-tonnage technological complex for the utilization of technogenic materials with various physical-mechanical properties was developed. The urgency of the development of techniques and technology for the utilization of man-made materials by means of compaction when creating new high-tech industries is shown.
Microstructures and mechanical properties of tungsten-tantalum alloys consolidated by electron beam melting, hot pressing and spark plasma sintering
Authors: Dong F , Chen Y , Bai Z , Wang H , Jiang L
Published: June 2019

The effect of consolidation process conditions and the tungsten concentration on the microstructures and mechanical properties of tantalum–tungsten alloys has been investigated. Ta–10W (in weight percent) and Ta–20W (in weight percent) alloys have been consolidated by electron beam melting (EBM), hot pressing (HP) and spark plasma sintering (SPS) techniques. The results show that the tantalum–tungsten alloys consolidated by EBM exhibit the highest relative density while by HP or SPS exhibit smaller grain-size compared to that by EBM, which may be attributed from the lower process temperature and the existence of oxide on the grain boundary hindering the growth of grain. The alloys with fine grain size (HP or SPS) have a higher microhardness and compression strength than that with coarse grain size (SPS) under the same tungsten concentration. It has been shown that these two alloy systems exhibit a similar general trend of strength increasing and the ductility decreasing when applying different consolidation process, while an enhanced strength-ductility synergy can be achieved for the Ta–10W alloy.
Synthesis and study of high-entropy ceramics based on the carbides of refractory metals
Authors: Sedegov A , Vorotilo S , Tsybulin V , Kuskov K , Moscovskikh D
Published: June 2019

Production of single-phase carbide high entropy ceramic (Hf0.2Ta0.2Ti0.2Nb0.2Mo0.2 or Zr0.2,)C by self-propagating high-temperature synthesis (SHS) from a mechanically activated (MA) reaction mixtures and mechanical synthesized (MS) materials is discussed. The influence of mechanical treatment time at ball mill, on the formation of the phase of a high-entropy material is investigated. Spark plasma sintering and their structure, phase composition, obtained bulk samples and mechanical properties were studied. A self-propagating high-temperature synthesis of high-entropic carbide based on refractory elements was also carried out. The microstructure and mechanical properties of high-entropy ceramics obtained by the methods of mechanical synthesis and SHS were compared.
Design and Fabrication of NiTi Frame Utilizing for Endobronchial Valve
Authors: Amornthitipong Supakit , Sriprasart Thitiwat , Khantachawana Anak
Published: June 2019

This study aims to design and fabricate the NiTi frame for Endobronchial valve (EBV) utilizing shape memory alloy wires. In order to evaluate the transformation and mechanical properties, heat-treatment at 450°C, 500°C and 550°C respectively for 10 minutes are carried out. Results from differential scanning calorimeter (DSC) and load-unloading test by universal tensile testing machine were used to select the heat-treatment condition for NiTi frame fabrication. Moreover, NiTi frames were fabricated by braiding 12 wires together by braiding machine with take up speed of 10, 15, 20 and 25 mm/sec respectively and constant carrier speed at 25 rad/sec. It is confirmed that all specimens show superior superelasticity at body temperature. Radial force of frame was measured by Mylar test at 37°C. Heat-treatment temperature at 500°C was selected since the highest stress for induce Martensite and recovery stress was obtained. The highest radial force was obtained in NiTi frame fabricated with taking up speed of 15 mm/sec. It is able to be concluded that NiTi frame can be illustrated for Endobronchial valve frame in future work.
Reactive Magnetron Sputter Deposition of Copper on TiO2 Support for Photoreduction of CO2 to CH4
Authors: Jantarasorn Nantiya , Mekasuwandumrong Okorn , Kelly Peter , Praserthdam Piyasan
Published: June 2019

In this work, nanocrystalline Cu/TiO2 catalysts have been synthesized by using pulsed direct current (DC) reactive magnetron sputtering of Cu targets in an Ar atmosphere onto P25-TiO2 support. The oscillating bowl was used to make the uniform coating on the substrate. The Cu doping content was varied by adjusting the coating time. The thus-obtained catalysts were characterized by using the X-ray diffraction (XRD), UV-Vis spectroscopy, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). The photocatalytic activities of all catalysts were studied via the photocatalytic reduction of CO2 and H2O to CH4 under UV irradiation, and compared with the pure TiO2 support and conventional-impregnation-made Cu/TiO2. The results showed that the photocatalytic performance of sputtering-made Cu/TiO2 catalyst was much better than the pure TiO2 support. Therefore, reactive magnetron sputtering was a promising technique for deposition of metal onto the support and use as the catalytic process.
Our Town, the MacDowell Colony, and the Art of Civic Mediation
Authors: Roberts Kathryn S
Published: June 2019

Thornton Wilder’s Our Town (1938) has found unusual currency of late. In 2011, the play lent its name to a major funding program launched by the National Endowment for the Arts; in 2017, it appeared in the center of a popular podcast and was revived by a British theater company in the wake of a terrorist attack. These productions recognize what terms like middlebrow obscure: Our Town is a civic mediator, a performance that installs art at the center of community life and community at the center of art. Taking inspiration from Antoine Hennion’s sociology of music, this essay ventures into the archive to trace an unfamiliar origin story for Our Town, involving a turn-of-the-century writers’ colony, a Progressive-Era historical pageant, and Wilder’s self-understanding as both confirmed bachelor and “community man.” Through the trajectory of a single play, civic mediation emerges as a pervasive strategy and ethos of American cultural practice, connecting diverse media through time and space.
Plant speciation in the age of climate change
Authors: Levin Donald A
Published: June 2019

Background

Species diversity is likely to undergo a sharp decline in the next century. Perhaps as many as 33 % of all plant species may expire as a result of climate change. All parts of the globe will be impacted, and all groups of organisms will be affected. Hundreds of species throughout the world have already experienced local extinction

Perspectives

While thousands of species may become extinct in the next century and beyond, species formation will still occur. I consider which modes of plant species formation are likely to prevail in the next 500 years. I argue that speciation primarily will involve mechanisms that produce reproductively isolated lineages within less (often much less) than 100 generations. I will not especially consider the human element in promoting species formation, because it will continue and because the conclusions presented here are unaffected by it. The impact of climate change may be much more severe and widespread.

Conclusions

The most common modes of speciation likely to be operative in the next 500 years ostensibly will be auto- and allopolyploidy. Polyploid species or the antecedents thereof can arise within two generations. Moreover, polyploids often have broader ecological tolerances, and are likely to be more invasive than are their diploid relatives. Polyploid species may themselves spawn additional higher level polyploids either through crosses with diploid species or between pre-existing polyploids. The percentage of polyploid species is likely to exceed 50 % within the next 500 years vs. 35 % today. The stabilized hybrid derivatives (homoploid hybrid speciation) could emerge within a hundred generations after species contact, as could speciation involving chromosomal rearrangements (and perhaps number), but the number of such events is likely to be low. Speciation involving lineage splitting will be infrequent because the formation of substantive pre- and post-zygotic barriers typically takes many thousands of years.
A beginner’s guide for FMDV quasispecies analysis: sub-consensus variant detection and haplotype reconstruction using next-generation sequencing
Authors: Cacciabue Marco , Currá Anabella , Carrillo Elisa , König Guido , Gismondi María Inés
Published: June 2019

Deep sequencing of viral genomes is a powerful tool to study RNA virus complexity. However, the analysis of next-generation sequencing data might be challenging for researchers who have never approached the study of viral quasispecies by this methodology. In this work we present a suitable and affordable guide to explore the sub-consensus variability and to reconstruct viral quasispecies from Illumina sequencing data. The guide includes a complete analysis pipeline along with user-friendly descriptions of software and file formats. In addition, we assessed the feasibility of the workflow proposed by analyzing a set of foot-and-mouth disease viruses (FMDV) with different degrees of variability. This guide introduces the analysis of quasispecies of FMDV and other viruses through this kind of approach.
Increasing the efficiency and accuracy of the ABACUS protein sequence design method
Authors: Xiong Peng , Hu Xiuhong , Huang Bin , Zhang Jiahai , Chen Quan , Liu Haiyan
Published: June 2019

Motivation

The ABACUS (a backbone-based amino acid usage survey) method uses unique statistical energy functions to carry out protein sequence design. Although some of its results have been experimentally verified, its accuracy remains improvable because several important components of the method have not been specifically optimized for sequence design or in contexts of other parts of the method. The computational efficiency also needs to be improved to support interactive online applications or the consideration of a large number of alternative backbone structures.

Results

We derived a model to measure solvent accessibility with larger mutual information with residue types than previous models, optimized a set of rotamers which can approximate the sidechain atomic positions more accurately, and devised an empirical function to treat inter-atomic packing with parameters fitted to native structures and optimized in consistence with the rotamer set. Energy calculations have been accelerated by interpolation between pre-determined representative points in high-dimensional structural feature spaces. Sidechain repacking tests showed that ABACUS2 can accurately reproduce the conformation of native sidechains. In sequence design tests, the native residue type recovery rate reached 37.7%, exceeding the value of 32.7% for ABACUS1. Applying ABACUS2 to designed sequences on three native backbones produced proteins shown to be well-folded by experiments.

Availability and implementation

The ABACUS2 sequence design server can be visited at http://biocomp.ustc.edu.cn/servers/abacus-design.php.

Supplementary information

Supplementary data are available at Bioinformatics online.
HUNER: improving biomedical NER with pretraining
Authors: Weber Leon , Münchmeyer Jannes , Rocktäschel Tim , Habibi Maryam , Leser Ulf
Published: June 2019

Motivation

Several recent studies showed that the application of deep neural networks advanced the state-of-the-art in named entity recognition (NER), including biomedical NER. However, the impact on performance and the robustness of improvements crucially depends on the availability of sufficiently large training corpora, which is a problem in the biomedical domain with its often rather small gold standard corpora.

Results

We evaluate different methods for alleviating the data sparsity problem by pretraining a deep neural network (LSTM-CRF), followed by a rather short fine-tuning phase focusing on a particular corpus. Experiments were performed using 34 different corpora covering five different biomedical entity types, yielding an average increase in F1-score of ∼2 pp compared to learning without pretraining. We experimented both with supervised and semi-supervised pretraining, leading to interesting insights into the precision/recall trade-off. Based on our results, we created the stand-alone NER tool HUNER incorporating fully trained models for five entity types. On the independent CRAFT corpus, which was not used for creating HUNER, it outperforms the state-of-the-art tools GNormPlus and tmChem by 5–13 pp on the entity types chemicals, species and genes.

Availability and implementation

HUNER is freely available at https://hu-ner.github.io. HUNER comes in containers, making it easy to install and use, and it can be applied off-the-shelf to arbitrary texts. We also provide an integrated tool for obtaining and converting all 34 corpora used in our evaluation, including fixed training, development and test splits to enable fair comparisons in the future.

Supplementary information

Supplementary data are available at Bioinformatics online.
Sunken Worlds: The Past and Future of Human-Made Reefs in Marine Conservation
Authors: Tickell Sofia Castelló y , Sáenz-Arroyo Andrea , Milner-Gulland E J
Published: June 2019

Structures submerged in the sea by humans over millennia provide hard and longstanding evidence of anthropogenic influence in the marine environment. Many of these human-made reefs (HMRs) may provide opportunities for conservation despite having been created for different purposes such as fishing or tourism. In the middle of controversy around the costs and benefits of HMRs, a broad analysis of biodiversity and social values is necessary to assess conservation potential. This requires reframing HMRs as social–ecological systems, moving beyond comparisons with natural coral or rocky reefs to consider their roles as ecosystems in their own right; creating frameworks to track their type, number, size, units, location, characteristics, origins, social uses, and associated biodiversity locally and worldwide; and applying systematic assessment of conservation benefits in relation to stated conservation intentions. This integrative approach can catalyze learning, identify conservation opportunities, and inform positive management of HMRs into the future.
Child Protection With Muslim Communities: Considerations For Non-Muslim-Based Orthodoxies/Paradigms in Child Welfare and Social Work
Authors: O’Leary Patrick , Abdalla Mohamad , Hutchinson Aisha , Squire Jason , Young Amy
Published: June 2019

The care and protection of children are a concern that crosses ethnic, religious and national boundaries. How communities act on these concerns are informed by cultural and religious understandings of childhood and protection. Islam has specific teachings that relate to the care and guardianship of children and are interpreted in diverse ways across the Muslim world. Islamic teachings on child-care mostly overlap with Western understandings of child protection, but there can be some contested positions. This creates complexities for social workers intervening in Muslim communities where the basis of their intervention is primarily informed by a non-Muslim paradigm or occurs in secular legal contexts. The purpose of this article is to address at a broad level the issue of how overarching concepts of child protection and Islam influence social work practice with Muslim communities. It addresses a gap in practical applications of the synergy of Islamic thinking with core social work practice in the field of child protection. For effective practice, it is argued that social work practitioners need to consider common ground in Islamic thinking on child protection rather than rely on Western frameworks. This requires further research to build evidence-based practice with Muslim families.
Genetic consequences of long-term isolation for the last French population of Eryngium viviparum (Apiaceae)
Authors: Rascle Pauline , Flaven Elodie , Bioret Frédéric , Magnanon Sylvie , Glemarec Erwan , Gallet Sébastien , Imbert Eric
Published: June 2019

Eryngium viviparum (Apiaceae) is an endangered endemic plant of the Atlantic region of Europe, growing in seasonally flooded sites, and is characterized by a highly disjunct distribution. It occurs in just a few sites in the north-western part of the Iberian Peninsula and in a single locality in France. To improve the conservation status of E. viviparum in France, a conservation programme has been implemented to reintroduce the species. Before considering such an operation, genetic studies were conducted to determine the genetic status of the last French population and to identify the genetic source that should be considered for the best reintroduction strategy. Using microsatellite markers, we documented the genetic structure of the last French population and compared its genetic diversity with that of ten Iberian populations, which cover the three geographical regions where the species occurs. As expected, the French population of E. viviparum shows low genetic diversity due to a bottleneck and geographical isolation. The evolutionary potential appears low, with no private alleles in this population. Furthermore, this population is highly differentiated from the Iberian populations in terms of genetic variation and ecological niche. These results bring new questions regarding the conservation of E. viviparum in France, especially for management and reintroduction aimed at favouring genetic diversity and avoiding extinction.
GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness
Authors: Juarez-Salinas Dina L , Braz Joao M , Etlin Alexander , Gee Steven , Sohal Vikaas , Basbaum Allan I
Published: June 2019

Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.
Sex differences in the genetic predictors of Alzheimer’s pathology
Authors: Dumitrescu Logan , Barnes Lisa L , Thambisetty Madhav , Beecham Gary , Kunkle Brian , Bush William S , Gifford Katherine A , Chibnik Lori B , Mukherjee Shubhabrata , De Jager Philip L , Kukull Walter , Crane Paul K , Resnick Susan M , Keene C Dirk , Montine Thomas J , Schellenberg Gerard D , Deming Yuetiva , Chao Michael J , Huentelman Matt , Martin Eden R , Hamilton-Nelson Kara , Shaw Leslie M , Trojanowski John Q , Peskind Elaine R , Cruchaga Carlos , Pericak-Vance Margaret A , Goate Alison M , Cox Nancy J , Haines Jonathan L , Zetterberg Henrik , Blennow Kaj , Larson Eric B , Johnson Sterling C , Albert Marilyn ,   for the Alzheimer’s Disease Genetics Consortium and the Alzheimer’s Disease Neuroimaging Initiative, Bennett David A , Schneider Julie A , Jefferson Angela L , Hohman Timothy J
Published: June 2019

Autopsy measures of Alzheimer’s disease neuropathology have been leveraged as endophenotypes in previous genome-wide association studies (GWAS). However, despite evidence of sex differences in Alzheimer’s disease risk, sex-stratified models have not been incorporated into previous GWAS analyses. We looked for sex-specific genetic associations with Alzheimer’s disease endophenotypes from six brain bank data repositories. The pooled dataset included 2701 males and 3275 females, the majority of whom were diagnosed with Alzheimer’s disease at autopsy (70%). Sex-stratified GWAS were performed within each dataset and then meta-analysed. Loci that reached genome-wide significance (P < 5 × 10−8) in stratified models were further assessed for sex interactions. Additional analyses were performed in independent datasets leveraging cognitive, neuroimaging and CSF endophenotypes, along with age-at-onset data. Outside of the APOE region, one locus on chromosome 7 (rs34331204) showed a sex-specific association with neurofibrillary tangles among males (P = 2.5 × 10−8) but not females (P = 0.85, sex-interaction P = 2.9 × 10−4). In follow-up analyses, rs34331204 was also associated with hippocampal volume, executive function, and age-at-onset only among males. These results implicate a novel locus that confers male-specific protection from tau pathology and highlight the value of assessing genetic associations in a sex-specific manner.
Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study
Authors: Arabi Yaseen M , Shalhoub Sarah , Mandourah Yasser , Al-Hameed Fahad , Al-Omari Awad , Al Qasim Eman , Jose Jesna , Alraddadi Basem , Almotairi Abdullah , Al Khatib Kasim , Abdulmomen Ahmed , Qushmaq Ismael , Sindi Anees A , Mady Ahmed , Solaiman Othman , Al-Raddadi Rajaa , Maghrabi Khalid , Ragab Ahmed , Al Mekhlafi Ghaleb A , Balkhy Hanan H , Al Harthy Abdulrahman , Kharaba Ayman , Gramish Jawaher A , Al-Aithan Abdulsalam M , Al-Dawood Abdulaziz , Merson Laura , Hayden Frederick G , Fowler Robert
Published: June 2019

Background

The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders.

Methods

This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders.

Results

Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29).

Conclusions

In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.
Immunogenicity of Oral Polio Vaccine and Salk Inactive Polio Vaccine Against Xinjiang Imported Type 1 Wild Poliovirus
Authors: Yan Dongmei , Wang Dongyan , Zhu Shuangli , Zhang Yong , Li Xiaolei , Tang Haishu , Guan Jing , Xu Wenbo
Published: June 2019

Background

An outbreak of an imported Type 1 wild poliovirus from Pakistan occurred in the Xinjiang Uygur Autonomous Region of China in 2011, although the local immunity status of the oral polio vaccine (OPV) was relatively satisfied.

Methods

Neutralizing antibody titers against the Xinjiang strain and Sabin 1 strain were measured in 237 sera from 3 groups of fully OPV-vaccinated persons and 1 group of infants fully vaccinated with the inactive polio vaccine (IPV). Additionally, 17 sera collected from 1 Xinjiang poliomyelitis case and his 16 contacts were also tested. Genomic sequencing was conducted the Xinjiang strain.

Results

The antibody titers against the Xinjiang strain in each of 237 sera were significantly lower than those against the Sabin 1 strain. Notably, 40.0% of children in Group 1 were seronegative against the Xinjiang strain, which indicated that they might play an important role in wild poliovirus transmission, although their antibody titers against the Sabin 1 strain varied between 1:8 and 1:512. Meanwhile, serological results of the Xinjiang poliomyelitis case and his contacts also provided evidence that a proportion of OPV-vaccinated children had indeed been involved in the transmission chain of the Xinjiang outbreak. Genomic sequencing indicated that the Xinjiang strain was greatly distinguishable from the Sabin 1 strain in neutralizing antigenic sites.

Conclusion

The lack of neutralizing antibodies against the Xinjiang strain in persons vaccinated by OPV may be associated with the transmission of Type 1 wild poliovirus in Xinjiang. Using Salk IPV along with OPV might be considered in a wild poliovirus outbreak response, especially in the countries which continued to have persistent wild poliovirus circulation.
High Levels of Circulating Cell-free DNA Are Associated With a Poor Prognosis in Patients With Severe Fever With Thrombocytopenia Syndrome
Authors: Zhang Yue , Song Rui , Shen Yi , Zhao Yongxiang , Zhao Zhenghua , Fan Tianli , Yang Xiaoyu , Wang Lin , Zhang Wei , Chen Chong , Tian Di , Wang Ying , Wen Jing , Ge Ziruo , Yu Xiaoli , Liu Li , Feng Yang , Duan Jianping , Ma Yanli , Li Xingwang , Zeng Hui , Chen Zhihai , Zhu Liuluan
Published: June 2019

Background

The extensive geographical distribution and high mortality rate of severe fever with thrombocytopenia syndrome (SFTS) have made it an important threat to public health. Neutrophil extracellular traps (NETs) can be activated by a variety of pathogens and are associated with thrombocytopenia in viral infections. We aimed to identify NET production and its predictive value for disease progression and prognosis in patients with SFTS.

Methods

A prospective study was performed with a multicenter cohort of patients with SFTS (n = 112) to quantify serum NET levels. Three markers of NETs—namely, cell-free DNA (cfDNA), myeloperoxidase-DNA complexes, and lactoferrin-DNA complexes—were measured with PicoGreen double-stranded DNA assays and enzyme-linked immunosorbent assays. Receiver operating characteristic curves and multivariate regression analyses were performed to calculate the predictive value of cfDNA levels.

Results

SFTS was characterized by pronounced NET formation. The serum levels of NETs changed dynamically during disease progression, with an inverse pattern of the trends of platelet and neutrophil levels. High cfDNA levels were strongly associated with multiple pathological processes, including coagulopathy, myocardial damage, liver dysfunction, and the development of encephalopathy. A high level of cfDNA (>711.7 ng/mL) at the time of the initial diagnosis predicted severe illness in patients with SFTS (odds ratio, 8.285 [95% confidence interval, 2.049–33.503]; P = .003).

Conclusions

This study has a high degree of clinical impact for identification of cfDNA as a useful predictive biomarker of clinical outcomes of SFTS.
Lung Injury on Antiretroviral Therapy in Adults With Human Immunodeficiency Virus/Tuberculosis
Authors: Ravimohan Shruthi , Auld Sara C , Maenetje Pholo , Ratsela Nelly , Mlotshwa Mandla , Ncube Itai , Smith Jonathan P , Vangu Mboyo-Di-Tamba , Sebe Modulakgotla , Kossenkov Andrew , Weissman Drew , Wallis Robert S , Churchyard Gavin , Kornfeld Hardy , Bisson Gregory P
Published: June 2019

Background

Immune restoration on antiretroviral therapy (ART) can drive inflammation in people living with human immunodeficiency virus (HIV) who have pulmonary tuberculosis (TB), but its effects on the lungs have not been assessed. We evaluated associations between pulmonary inflammation, recovery of pathogen-specific CD4 T-cell function, and lung injury prior to and after ART initiation in adults with HIV and pulmonary TB.

Methods

This was a prospective cohort study in South Africa, following adults with HIV and pulmonary TB prior to and up to 48 weeks after ART initiation. Pulmonary-specific inflammation was defined as total glycolytic activity (TGA) on [18]F-fluorodeoxyglucose (FDG) positron emission tomography–computed tomography (PET-CT) at baseline and 4 weeks after ART initiation. Spirometry, respiratory symptom tests, and flow cytometry were performed at the same times to assess lung involvement and the frequency of mycobacteria-specific CD4 T-cells. In addition, we evaluated lung function longitudinally up to 48 weeks after ART initiation.

Results

Greater lung TGA on FDG PET-CT was associated with worse lung function and respiratory symptoms prior to ART initiation, and nearly half of subjects experienced worsening lung inflammation and lung function at Week 4 of ART. Worsening Week 4 lung inflammation and pulmonary function were both associated with greater increases in pathogen-specific functional CD4 T-cell responses on ART, and early decreases in lung function were independently associated with persistently lower lung function months after TB treatment completion.

Conclusions

Increases in pulmonary inflammation and decreases in lung function are common on ART, relate to greater ART-mediated CD4 T-cell restoration, and are associated with the persistent impairment of lung function in individuals with HIV/TB.
TXNIP/Redd1 signalling and excessive autophagy: a novel mechanism of myocardial ischaemia/reperfusion injury in mice
Authors: Gao Chao , Wang Rutao , Li Bing , Guo Yongzhen , Yin Tao , Xia Yunlong , Zhang Fuyang , Lian Kun , Liu Yi , Wang Han , Zhang Ling , Gao Erhe , Yan Wenjun , Tao Ling
Published: June 2019

Aims

Either insufficient or excessive autophagy causes cellular death and contributes to myocardial ischaemia/reperfusion (I/R) injury. However, mechanisms controlling the ‘right-level’ of autophagy in the heart remains unidentified. Thioredoxin-interacting protein (TXNIP) is a pro-oxidative molecule knowing to contribute to I/R injury. However, whether and how TXNIP may further inhibit suppressed autophagy or promote excessive cardiac autophagy in I/R heart has not been previously investigated.

Methods and results

Wild type or gene-manipulated adult male mice were subjected to myocardial I/R. TXNIP was increased in myocardium during I/R. Cardiac-specific TXNIP overexpression increased cardiomyocytes apoptosis and cardiac dysfunction, whereas cardiac-specific TXNIP knock-out significantly mitigated I/R-induced apoptosis and improved cardiac function. Importantly, TXNIP overexpression significantly promoted cardiac autophagy and TXNIP knock-out significantly inhibited cardiac autophagy. In vitro studies demonstrated that TXNIP increased autophagosome formation but inhibited autophagosome clearance during myocardial reperfusion. Atg5 siRNA significantly decreased hypoxia/reoxygenation induced apoptosis in cardiomyocytes with TXNIP overexpression. Mechanistically, TXNIP suppressed autophagosome clearance via increasing reactive oxygen species (ROS) level. However, TXNIP-increased autophagosome formation was not mediated by ROS as a ROS scavenger failed to block increased autophagosome formation in TXNIP overexpression heart. Finally, TXNIP directly interacted and stabilized Redd1 (an autophagy regulator), resulting in mTOR inhibition and autophagy activation. Redd1 knock-down significantly reduced autophagy formation and ameliorated I/R injury in TXNIP overexpression hearts.

Conclusions

Our results demonstrated that increased TXNIP-Redd1 expression is a novel signalling pathway that contributes to I/R injury by exaggerating excessive autophagy during reperfusion. These observations advance our understanding of the mechanisms of myocardial I/R injury.
Adventitial fibroblast-derived vascular endothelial growth factor promotes vasa vasorum-associated neointima formation and macrophage recruitment
Authors: Li Xiao-Dong , Hong Mo-Na , Chen Jing , Lu Yuan-Yuan , Ye Mao-Qing , Ma Yu , Zhu Ding-Liang , Gao Ping-Jin
Published: June 2019

Aims

Adventitial vasa vasorum provides oxygen and nourishment to the vascular wall, but whether it regulates vascular disease remains unclear. We have previously shown that an increased expression of VEGF (vascular endothelial growth factor) is associated with macrophage infiltration. This study aims to determine whether adventitial fibroblast (AF)-derived VEGF increases the number of vasa vasorum contributing to neointima formation through macrophage recruitment.

Methods and results

In rat balloon injury model, vasa vasorum count was increased particularly in the adventitia accompanied by cell proliferation and VEGF expression. Both endogenous and PKH26-labelled exogenous macrophages were mainly distributed in adventitia around vasa vasorum. Interestingly, perivascular delivery of Ranibizumab preferentially concentrated in adventitia resulted in a decrease of neointima formation with concurrent reduction of vasa vasorum count and macrophage infiltration. AFs with adenovirus-mediated VEGF over-expression delivered to the adventitia significantly enhanced these pathological changes after injury. In Tie2-cre/Rosa-LoxP-RFP mice, endothelial cells were increased in the adventitia after wire injury. By using multiphoton laser scanning microscopy, macrophage rolling, adhesion and transmigration were observed in vasa vasorum. Moreover, adoptive transfer of macrophages accelerated injury-induced neointima formation. VEGF-neutralizing antibody administration also attenuated wire injury-induced neointima formation and macrophage infiltration. In primary cultured AFs, exogenous VEGF increased VEGF expression and secretion in a time- and dose-dependent manner. AF-conditioned medium promoted endothelial cell angiogenesis, vascular cell adhesion molecule-1 expression and macrophage adhesion was blocked by VEGF-neutralizing antibody and VEGFR2 inhibitor ZM323881, which also inhibited activation of VEGFR2/ERK1/2 pathway.

Conclusion

These results demonstrate that AF-derived VEGF plays a significant role in the increase of vasa vasorum count which is involved in macrophage recruitment and neointima formation.
Small animal models of heart failure
Authors: Riehle Christian , Bauersachs Johann
Published: June 2019

Heart disease is a major cause of death worldwide with increasing prevalence, which urges the development of new therapeutic strategies. Over the last few decades, numerous small animal models have been generated to mimic various pathomechanisms contributing to heart failure (HF). Despite some limitations, these animal models have greatly advanced our understanding of the pathogenesis of the different aetiologies of HF and paved the way to understanding the underlying mechanisms and development of successful treatments. These models utilize surgical techniques, genetic modifications, and pharmacological approaches. The present review discusses the strengths and limitations of commonly used small animal HF models, which continue to provide crucial insight and facilitate the development of new treatment strategies for patients with HF.
B-cell lymphoma/leukaemia 10 and angiotensin II-induced kidney injury
Authors: Markó Lajos , Park Joon-Keun , Henke Norbert , Rong Song , Balogh András , Klamer Samuel , Bartolomaeus Hendrik , Wilck Nicola , Ruland Jürgen , Forslund Sofia K , Luft Friedrich C , Dechend Ralf , Müller Dominik N
Published: June 2019

Aims

B-cell lymphoma/leukaemia 10 (Bcl10) is a member of the CARMA-Bcl10-MALT1 signalosome, linking angiotensin (Ang) II, and antigen-dependent immune-cell activation to nuclear factor kappa-B signalling. We showed earlier that Bcl10 plays a role in Ang II-induced cardiac fibrosis and remodelling, independent of blood pressure. We now investigated the role of Bcl10 in Ang II-induced renal damage.

Methods and results

Bcl10 knockout mice (Bcl10 KO) and wild-type (WT) controls were given 1% NaCl in the drinking water and Ang II (1.44 mg/kg/day) for 14 days. Additionally, Bcl10 KO or WT kidneys were transplanted onto WT mice that were challenged by the same protocol for 7 days. Kidneys of Ang II-treated Bcl10 KO mice developed less fibrosis and showed fewer infiltrating cells. Nevertheless, neutrophil gelatinase-associated lipocalin (Ngal) and kidney injury molecule (Kim)1 expression was higher in the kidneys of Ang II-treated Bcl10 KO mice, indicating exacerbated tubular damage. Furthermore, albuminuria was significantly higher in Ang II-treated Bcl10 KO mice accompanied by reduced glomerular nephrin expression and podocyte number. Ang II-treated WT mice transplanted with Bcl10 KO kidney showed more albuminuria and renal Ngal, compared to WT- > WT kidney-transplanted mice, as well as lower podocyte number but similar fibrosis and cell infiltration. Interestingly, mice lacking Bcl10 in the kidney exhibited less Ang II-induced cardiac hypertrophy than controls.

Conclusion

Bcl10 has multi-faceted actions in Ang II-induced renal damage. On the one hand, global Bcl10 deficiency ameliorates renal fibrosis and cell infiltration; on the other hand, lack of renal Bcl10 aggravates albuminuria and podocyte damage. These data suggest that Bcl10 maintains podocyte integrity and renal function.