bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between the electric field integral value and vacuum breakdown characteristics in small electrode with multi‐apertures
Authors: Okura Tetsuya , Nishiyama Masashi , Yamano Yasushi , Kojima Atsushi , Kashiwagi Mieko
Published: October 2019

For a critical plasma test equipment JT‐60SA, vacuum electric breakdown around apertures is a serious problem for developing a high‐energy and high‐power negative ion source accelerator. To improve the high voltage performance of the accelerator, we investigated the relation of a breakdown electric field in a vacuum with the electric field integral value of electrode's surface for multi‐apertures electrode. The results of breakdown tests for various types of multi‐aperture electrode show that the electric field integration ES had a relation with the vacuum breakdown field and field emission current characteristics. The reduction in the ES with the relaxation of electric fields improved the breakdown performance. Moreover, the low value of ES decreased the field enhancement factor ‘β’ and the emission area ‘A’ of field electron emission from the electrode. Therefore, we found that the breakdown electric field can be improved by reducing the prebreakdown current that flows before the occurrence of breakdown by reducing the ES. © 2019 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Northern Ireland's longstanding record wind gust is almost certainly incorrect
Authors: Aylott Lucy , Burt Stephen , Saunders Mark
Published: October 2019

Abstract Online only

Accurate assessment of record extreme wind gusts is important for building design standards and for industries such as insurance and forestry. Here, we show that the current record wind gust for Northern Ireland – 108kn (56ms−1) recorded at Kilkeel on 12 January 1974 – is almost certainly incorrect and may have arisen from an instrumental error or a power surge. We deduce this from direct anemograph inspection and from a variety of indirect supporting evidence. We recommend that other longstanding UK record wind gusts should also be independently re‐examined to assess their veracity.
Envelope methods
Authors: Cook R. Dennis
Published: October 2019

An envelope is a relatively new construct for decreasing estimative and predictive variation relative to standard methods in multivariate statistics, sometimes by amounts equivalent to increasing the sample size many times over. Essentially a form of targeted dimension reduction that is descendent from sufficient dimension reduction, an envelope inherits its underlying philosophy from Fisher's notion of sufficient statistics. The initial development of envelope methods took place largely in the context of the multivariate linear model, resulting in response envelopes for response reduction, predictor envelopes for predictor reduction, simultaneous envelopes for response and predictor reduction and partial envelopes for specialized considerations, each demonstrating a potential for substantial reduction in estimative variation. These advances demonstrated that there are close connections between envelopes and some standard multivariate methods like partial least squares regression and canonical correlations. Subsequently, envelope methodology has been adapted and extended to diverse areas, including envelopes for regressions with matrix and tensor‐valued responses, envelopes for spatial statistics, quantile envelopes for quantile regression, Bayesian response envelopes. Sparse versions of response and predictor envelopes have also been developed. More generally, there is also envelope methodology for reducing the variation in any asymptotically normal vector‐valued estimator. These advances have opened a new chapter in multivariate statistics, allowing variation that is material to the goals of an analysis to be separated effectively from immaterial variation that serves only to confound estimation and prediction.

This article is categorized under:

Statistical Models > Multivariate Models

Statistical and Graphical Methods of Data Analysis > Multivariate Analysis

Statistical and Graphical Methods of Data Analysis > Dimension Reduction
A Faster Tree-Decomposition Based Algorithm for Counting Linear Extensions
Authors: Kangas Kustaa , Koivisto Mikko , Salonen Sami
Published: October 2019

We investigate the problem of computing the number of linear extensions of a givenn-element poset whose cover graph has treewidtht. We present an algorithm that runs in time$${\tilde{O}}(n^{t+3})$$O~(nt+3)for any constantt; the notation$${\tilde{O}}$$O~hides polylogarithmic factors. Our algorithm applies dynamic programming along a tree decomposition of the cover graph; the join nodes of the tree decomposition are handled by fast multiplication of multivariate polynomials. We also investigate the algorithm from a practical point of view. We observe that the running time is not well characterized by the parametersnandtalone: fixing these parameters leaves large variance in running times due to uncontrolled features of the selected optimal-width tree decomposition. We compare two approaches to select an efficient tree decomposition: one is to include additional features of the tree decomposition to build a more accurate, heuristic cost function; the other approach is to fit a statistical regression model to collected running time data. Both approaches are shown to yield a tree decomposition that typically is significantly more efficient than a random optimal-width tree decomposition.
Finding events in temporal networks: segmentation meets densest subgraph discovery
Authors: Rozenshtein Polina , Bonchi Francesco , Gionis Aristides , Sozio Mauro , Tatti Nikolaj
Published: October 2019

In this paper, we study the problem of discovering a timeline of events in a temporal network. We model events as dense subgraphs that occur within intervals of network activity. We formulate the event discovery task as an optimization problem, where we search for a partition of the network timeline into k non-overlapping intervals, such that the intervals span subgraphs with maximum total density. The output is a sequence of dense subgraphs along with corresponding time intervals, capturing the most interesting events during the network lifetime. A naïve solution to our optimization problem has polynomial but prohibitively high running time. We adapt existing recent work on dynamic densest subgraph discovery and approximate dynamic programming to design a fast approximation algorithm. Next, to ensure richer structure, we adjust the problem formulation to encourage coverage of a larger set of nodes. This problem is NP-hard; however, we show that on static graphs a simple greedy algorithm leads to approximate solution due to submodularity. We extend this greedy approach for temporal networks, but we lose the approximation guarantee in the process. Finally, we demonstrate empirically that our algorithms recover solutions with good quality.
Impact of certification status of the institute and surgeon on short-term outcomes after surgery for thoracic esophageal cancer: evaluation using data on 16,752 patients from the National Clinical Database in Japan
Authors: Motoyama Satoru , Yamamoto Hiroyuki , Miyata Hiroaki , Yano Masahiko , Yasuda Takushi , Ohira Masaichi , Kajiyama Yoshiaki , Toh Yasushi , Watanabe Masayuki , Kakeji Yoshihiro , Seto Yasuyuki , Doki Yuichiro , Matsubara Hisahiro
Published: October 2019

Background

In 2009, the Japan Esophageal Society (JES) established a system for certification of qualified surgeons as “Board Certified Esophageal Surgeons” (BCESs) or institutes as “Authorized Institutes for Board Certified Esophageal Surgeons” (AIBCESs). We examined the short-term outcomes after esophagectomy, taking into consideration the certifications statuses of the institutes and surgeons.

Methods

This study investigated patients who underwent esophagectomy for thoracic esophageal cancer and who were registered in the Japanese National Clinical Database (NCD) between 2015 and 2017. Using hierarchical multivariable logistic regression analysis adjusted for patient-level risk factors, we determined whether the institute’s or surgeon’s certification status had greater influence on surgery-related mortality or postoperative complications.

Results

Enrolled were 16,752 patients operated on at 854 institutes by 1879 surgeons. There were significant differences in the backgrounds and incidences of postoperative complications and surgery-related mortality rates between the 11,162 patients treated at AIBCESs and the 5590 treated at Non–AIBCESs (surgery-related mortality rates: 1.6% vs 2.8%). There were also differences between the 6854 patients operated on by a BCES and the 9898 treated by a Non-BCES (1.7% vs 2.2%). Hierarchical logistic regression analysis revealed that surgery-related mortality was significantly lower among patients treated at AIBCESs. The institute’s certification had greater influence on short-term surgical outcomes than the operating surgeon’s certification.

Conclusions

The certification system for surgeons and institutes established by the JES appears to be appropriate, as indicated by the improved surgery-related mortality rate. It also appears that the JES certification system contributes to a more appropriate medical delivery system for thoracic esophageal cancer in Japan.
Quality of Life and Meeting 24-h WHO Guidelines Among Preschool Children in Singapore
Authors: Chia Michael Yong Hwa , Tay Lee Yong , Chua Terence Buan Kiong
Published: October 2019

The objective of the study was to determine the proportion of preschool children under 5 years old meeting the 24-h World Health Organisation guidelines on physical activity, sedentary behaviour and sleep. Another objective was to examine the association between the health-related quality of life and meeting these guidelines among preschool children in Singapore. Parents completed an online and anonymous SMALLQ® (Surveillance of digital Media hAbits in earLy chiLdhood Questionnaire) on children’s physical activity, sedentary behaviour and sleep. Meeting the 24-h WHO guidelines meant, within a 24-h period, (i) having at least 180 min of physical activity (ii) engaging in less than 60 min of screen media and (iii) having 10–13 h of good quality sleep. Parent-reported health-related quality of life of the children was determined using the Pediatric Quality of Life Inventory™, collected online at the same time. Parent-reported data showed that 12.6% met none while 9.6% of preschool children met all the WHO guidelines. 70.7%, 56.9% and 26.5%, of preschool children respectively, achieved the sleep, physical activity and screen media use guidelines within a 24-h period. 40.5% met two guidelines while 37.4% met one guideline. Significant differences were detected in the health-related quality of life among preschool children who met all, none, or met 1–2 of the WHO guidelines (i.e. total health score: 82.9 ± 12.4 vs. 76.4 ± 15.1 vs. 78.6 ± 14.5%, p < 0.05; ƞ2 = 0.008–0.11). Our results show that the health-related quality of life of preschool children increased with the number of WHO guidelines accomplished.
Sensory Abnormality and Quantitative Autism Traits in Children With and Without Autism Spectrum Disorder in an Epidemiological Population
Authors: Jussila K. , Junttila M. , Kielinen M. , Ebeling H. , Joskitt L. , Moilanen I. , Mattila M.-L.
Published: October 2019

Sensory abnormalities (SAs) are recognized features in Autism Spectrum Disorder (ASD), and a relationship between SAs and ASD traits is also suggested in general population. Our aims were to estimate the prevalence of SAs in three different settings, and to study the association between SAs and quantitative autism traits (QAT) using the Autism Spectrum Screening Questionnaire (ASSQ) and a parental questionnaire. In an epidemiological population of 8-year-old children (n = 4397), the prevalence of SAs was 8.3%, in an ASD sample (n = 28), 53.6%, and in a non-ASD sample (n = 4369), 8.0%, respectively. Tactile and auditory hypersensitivity predicted an ASD diagnosis. The ASSQ was able to differentiate children with and without SA. In conclusion, QAT level and SAs were associated in all study samples.
Row-crop planter performance to support variable-rate seeding of maize
Authors: Virk S. S. , Fulton J. P. , Porter W. M. , Pate G. L.
Published: October 2019

Current planting technology possesses the ability to increase crop productivity and improve field efficiency by precisely metering and placing crop seeds. Planter performance depends on determining and utilizing optimal settings for different planting variables such as seed depth, down pressure, and seed metering unit. The evolution of “Big Data” in agriculture today brings focus on the need for quality as-planted and yield mapping data. Therefore, an investigation was conducted to evaluate the performance of current planting technology for accurate placement of seeds while understanding the accuracy of as-planted data. Two studies consisting of two different setups on a 6-row, John Deere planter for seeding of maize (Zea mays L.) were conducted. The first study aimed at assessing planter performance at 2 depth settings (25 and 51 mm) and four different down pressure settings (varying from none to high), while the second study focused on evaluating planter performance during variable-rate seeding with treatments consisting of two seed metering units (John Deere Standard and Precision Planting’s eSet setups) with five different seeding rates and four ground speed treatments which provided a combination of 20 different meter speeds. Field data collection consisted of measuring plant emergence, plant population and seed depth whereas plant spacing, plant population after emergence along with distance and location for rate changes within the field were also recorded for the variable-rate seeding study. Results indicated that both depth setting and downforce affected final seeding depth. Measured seed depth was significantly different from the target depth even though time was spent adjusting the units to achieve the desired prior to planting. Crop emergence did not vary significantly for the different depth and downforce settings except for target depth in Field 1. Results from the variable-rate study indicated that seeding rate changes were accomplished within a quick response time (< 1 s) at all ground speeds regardless of magnitude of rate change. Data showed that planter performance in terms of emergence and plant spacing CV was comparable for most of the meter speeds (17.4–33.5 rpm) among the two seed meters utilized in the study. Plant spacing CV increased with an increase in meter speed, however no significant differences existed among meter speeds in the range of 17.4–33.5 rpm. Results implied that correct seed metering unit setup is very critical to obtain expected performance of today’s planting technology. A concerning find was that the quality of as-applied maps from the commercial variable-rate display was not reflective of the actual planter performance in the field. The study recommended that operators need to ensure the correct planter and display setups in order to achieve needed seed placement performance to support variable-rate seeding.
Quality Differences of Public, For-Profit and Nonprofit Providers in Scandinavian Welfare? User Satisfaction in Kindergartens
Authors: Trætteberg Håkon Solbu , Fladmoe Audun
Published: October 2019

Research on differences between public, for-profit, and nonprofit providers of welfare services has provided mixed findings, depending on welfare state arrangement, regulation, and service area. This paper’s objective is to study the differences between public, nonprofit (cooperatives and other nonprofits), and for-profit welfare providers from the perspective of the users in the tightly regulated Scandinavian context. We ask how the users perceive the providers from different sectors differently and how this variation can be explained. The study relies on a large-scale survey carried out in 2015 in the city of Oslo, Norway. From the survey, we identify the two main results. First, despite limited differences, users of nonprofit kindergartens are generally more satisfied than users of for-profit and public kindergartens. Second, an important explanation for variations in user satisfaction among kindergartens is identified in a pocket of regulatory leniency: the quality of food service. This is the only expense that varies among kindergartens in Norway. These results indicate that more lenient regulations could potentially increase provider distinctiveness. Based on the existing literature, we discuss why nonprofit providers seem to fare better in the minds of users than public and for-profit providers.
Correction to: Combination Treatment with an Antibody–Drug Conjugate (A1mcMMAF) Targeting the Oncofetal Glycoprotein 5T4 and Carboplatin Improves Survival in a Xenograft Model of Ovarian Cancer
Authors: Wan Y. Louise , Sapra Puja , Bolton James , Chua Jia Xin , Durrant Lindy G. , Stern Peter L.
Published: October 2019

The article Combination Treatment with an Antibody–Drug Conjugate (A1mcMMAF) Targeting the Oncofetal Glycoprotein 5T4 and Carboplatin Improves Survival in a Xenograft Model of Ovarian Cancer, written by Y. Louise Wan, Puja Sapra, James Bolton, Jia Xin Chua, Lindy G. Durrant and Peter L. Stern, was originally published under a CC BY-NC 4.0 license, but has now been made available under a CC BY 4.0 license.
Genetic diversity and differentiation of pedunculate (Quercus robur) and sessile (Q. petraea) oaks
Authors: Jurkšienė Girmantė , Baranov Oleg Yu. , Kagan Dmitry I. , Kovalevič-Razumova Olja A. , Baliuckas Virgilijus
Published: October 2019

This study was conducted to determine the parent–offspring genetic structure of the pedunculate oak (Quercus roburL.), sessile oak (Q. petraea[Matt.] Liebl.) and their hybrids. Forty half-sibQuercusfamilies and their maternal trees originating from one tree stand in southern Lithuania were analyzed using SSR and RAPD markers. Based on a preliminary study of leaf morphological traits, the individuals separated into six groups. The studied half-sib oak families were also compared for allelic diversity, including group variations; genotypic structure; genetic diversity; and the degree of genetic subdivision and differentiation. The level of genetic variation and subdivision was lower in the hybrid families than in the families of the parental species. Genotypic analysis of the half-sibling offspring showed the asymmetric nature of interspecific hybridization processes of pedunculate and sessile oaks in mixed stands.
Effects of n-butanol presence, inlet loading, empty bed residence time and starvation periods on the performance of a biotrickling filter removing cyclohexane vapors from air
Authors: Rybarczyk Piotr , Szulczyński Bartosz , Gospodarek Milena , Gębicki Jacek
Published: October 2019

This paper presents the results of investigations on the removal of cyclohexane vapors from air using a peat-perlite packed biotrickling filter. Effects of basic process parameters i.e. inlet loading and empty bed residence time as well as introduction of n-butanol to the treated air stream and starvation periods on the process performance were evaluated. The results show that the introduction of hydrophilic n-butanol results in an enhanced removal of hydrophobic cyclohexane comparing to the experiments where only cyclohexane was treated. Additionally, the biotrickling filter performance after the starvation events is regained to more extent for mixed system than for the single cyclohexane. A novel and interesting element of the paper is the application of an electronic nose for the process monitoring. Obtained results are discussed in the perspective of an influence of the presence of a compound with different affinity to aqueous phase on the removal efficiency of the compound with opposite chemical properties.
Sex‐specific composite scales for longitudinal studies of incipient Alzheimer's disease
Authors: Banks Sarah J. , Shifflett Benjamin , Berg Jody‐Lynn , Sundermann Erin , Peavy Guerry , Bondi Mark W. , Edland Steven D. ,   Alzheimer's Disease Neuroimaging Initiative
Published: October 2019

Introduction

The impact of Alzheimer's disease (AD) on cognitive decline differs by sex. Composite scores are useful as singular outcomes in clinical trials, yet to date these have not been developed to measure sex‐specific change.

Method

We derived optimal composites from component scales available in the AD Neuroimaging Initiative (ADNI) database among cognitively normal and mild cognitively impaired subjects who are cerebrospinal fluid amyloid‐β positive for early AD. Maximally sensitive composites were constructed separately for men and women using standard formulas. We compared the statistical power of the composites with the ADNI Prodromal Alzheimer's Cognitive Composite.

Results

Among 9 cognitive measures and clinical dementia rating sum of boxes, the optimal sex‐specific composites included 5 measures, including the clinical dementia rating and 4 distinct cognitive measures. The sex‐specific composites consistently outperformed sex‐agnostic composites and the ADNI Prodromal Alzheimer's Cognitive Composite.

Discussion

Sex‐specific composite scales may improve the power of longitudinal studies of early AD and clinical trials.
Student-Managed Commodity Fund—A New Frontier in Experiential Learning
Authors: Massa Olga Isengildina , Ramsey A. Ford
Published: October 2019

This study provides a road map for creating and operating a student-managed investment fund (SMIF) as an experiential learning opportunity in commodity market analysis. We describe the reasons for implementing a SMIF and the benefits it offers relative to traditional simulation approaches. We outline the necessary steps for starting a SMIF and explain its organizational structure. We discuss a SMIF’s operation and main activities, which include recruitment, training, trading, and interaction with the client and alumni. The implications of participating in a SMIF are reviewed within a cost-benefit framework.
The electronic exhibition space as a catalyst for engagement and inquiry
Authors: Hibben Yuki
Published: October 2019

The Cabell Screen, a 400 square foot media display installed on the façade of James Branch Cabell Library is a recent venue for artistic and scholarly expression at Virginia Commonwealth University Libraries. Spanning two floors of the main academic library building, the Cabell Screen displays curated electronic exhibitions of still and moving images to thousands of people who walk by the building each day. With no additional budget or staffing, a committee of librarians developed a mission statement, content strategy, and workflows to program and promote content. While the Cabell Screen uses a specific type of technology, the practices established at VCU Libraries can be applied to a range of budgets and media, including projections and monitors, to create a dedicated electronic exhibition space.
Digital and tangible: The accessibility of sketchbooks in the UK's memory institutions
Authors: Hobbs James
Published: October 2019

How are sketchbooks collected, organized, indexed and made accessible in the UK's memory institutions? My research is outlined, describing how, through interviews and a questionnaire sent to sketchbook-holding institutions, they are acquired, who they are accessed by, problems faced by those accessing them, the extent to which sketchbooks can be handled and examined physically, and the benefits and consequences of digitization and online access of sketchbooks. Finally, institutions offer ideas on how access to sketchbooks can be improved.
The American Sufis: Self-Help, Sufism, and Metaphysical Religion in Postcolonial Egypt
Authors: Zárate Arthur Shiwa
Published: October 2019

This article examines an Arabic commentary on the American self-help pioneer Dale Carnegie's How to Stop Worrying and Start Living, written by a one-time leading intellectual of the Egyptian Muslim Brotherhood, Muḥammad al-Ghazālī. Ghazālī’s 1956 commentary was perhaps the earliest manifestation of an influential genre of literature within the Islamic world today: “Islamic self-help.” Although scholars treat Islamic self-help as an effect of neoliberalism, this article reorients the study of Islamic self-help beyond neoliberalism by showing first, that Ghazālī’s early version of it emerged through a critical engagement with several ideological forms that relate in complex ways to neoliberalism's antecedent, liberalism; and second, that his Islamic self-help is best understood in terms of an Islamic encounter with American metaphysical religion made possible by Carnegie's text. It argues that Ghazālī’s Islamic self-help constituted a radical reconfiguration of Western self-help, one that replaced the ethics of self-reliance and autonomy with Islamic ethical sensibilities clustered around the notions of human insufficiency and dependence upon God. In doing so, it highlights how scholars of contemporary Islam might fruitfully pose the question of how novel intellectual trends and cultural forms, like self-help, become Islamic, instead of limiting their analysis to how Islam is reshaped by modern Euro-American thought, institutions, and practices.
To Kill or Not to Kill? The Challenge of Restraining Violence in a Balkan Community
Authors: Bergholz Max
Published: October 2019

Explaining why restraint of violence becomes a strategy for armed groups has recently attracted the attention of researchers, especially political scientists. The emergent literature generally argues by way of macro-level statistical correlation, in which a single factor, such as the desire of armed groups to adhere to international norms about human rights or the existence of high levels of political education among fighters, is believed to explain the presence of restraint. Missing in this approach are close analyses of actual historical episodes of restraint. We thus lack comprehension of how those with ideas about restraining violence translate their thoughts into actions, especially in contexts such as civil wars. This article addresses this weakness by examining the history of a Balkan community wracked by intercommunal violence during 1941 to explain the puzzling practice of restraint in the midst of waves of retaliatory violence. Rather than identify a single factor, this micro-comparative case study reveals that a cluster of mostly endogenous factors, shaped significantly by ongoing violence, explains the successful practice of restraint. Methodologically, this article stresses the need for researchers of restraint to employ microhistorical and comparative methods. They hold the greatest potential to illuminate what remains insufficiently explained in the extant political science literature: the contingent local processes whereby a desire for restraint or escalation of violence—the existence of which may be conditioned by longer-term historical developments—becomes a reality in certain moments.
Slowing rates of regional exhumation in the western Himalaya: fission track evidence from the Indus Fan
Authors: Zhou Peng , Carter Andrew , Li Yuting , Clift Peter D.
Published: October 2019

We use apatite fission track ages from sediments recovered by the International Ocean Discovery Program in the Laxmi Basin, Arabian Sea, to constrain exhumation rates in the western Himalaya and Karakoram since 15.5 Ma. With the exception of a Triassic population in the youngest 0.93 Ma samples supplied from western Peninsular India, apatite fission track ages are overwhelmingly Cenozoic, largely <25 Ma, consistent with both a Himalaya–Karakoram source and rapid erosion. Comparison of the minimum cooling age of each sample with depositional age (lag time) indicates an acceleration in exhumation between 7.8 and 7.0 Ma, with lag times shortening from ∼6.0 Myr at 8.5–7.8 Ma to being within error of zero between 7.0 and 5.7 Ma. Sediment supply at 7.0–5.7 Ma was largely from the Karakoram, and to a lesser extent the Himalaya, based on U–Pb zircon ages from the same samples. This time coincides with a period of drying in the Himalayan foreland caused by weaker summer monsoons and Westerly winds. It also correlates with a shift of erosion away from the Karakoram, Kohistan and the Tethyan Himalaya towards more erosion of the Lesser and Greater Himalaya and Nanga Parbat, as shown by zircon U–Pb provenance data, and especially after 5.7 Ma based on Nd isotope data. Samples younger than 5.7 Ma have lag times of ∼4.5 Myr, similar to Holocene Indus delta sediments.
Don Mauro's Letters:The Marquis of Villagarcía and the Imperial Networks of Patronage in Spain
Authors: Polo y La Borda Adolfo
Published: October 2019

In 1657, the marquis of Villagarcía was appointed as president of the Audiencia of Charcas. Although, he eventually declined the post, his nomination generated an unusual trail of private documents. Using my study of this correspondence as a base, I will discuss how the networks of patronage were built and sustained, how they operated, and how they impacted the global mobility of imperial officials. Patronage networks were indispensable to itinerant officials who relied on their clients, patrons, and brokers to help them govern distant regions by gathering resources and information, and implementing their objectives. Moreover, this particular case gives us a glimpse into the relationship between Villagarcía as husband and his wife, and the private assessments and negotiations surrounding the transatlantic journey.
IL-6-driven FasL promotes NF-κBp65/PUMA-mediated apoptosis in portal hypertensive gastropathy
Authors: Tan Siwei , Xu Minyi , Ke Bilun , Lu Yu , Liu Huiling , Jiang Jie , Wu Bin
Published: October 2019

Mucosal epithelial apoptosis with non-specific inflammation is an essential pathological characteristic in portal hypertensive gastropathy (PHG). However, whether a coordinated crosstalk between myeloid cells and epithelial cells involved in PHG remains unclear. IL-6, which is induced in the mucosa of PHG patients and mice, promotes FasL production via enhancing NF-κBp65 activation in myeloid cells, while blockage of IL-6 signaling by Tocilizumab or deletion of NF-κBp65 in myeloid cells attenuates the inflammatory response and Fas/FasL-mediated epithelial apoptosis in PHG. IL-6-driven FasL from myeloid cells combines with epithelial Fas receptor to encourage NF-κBp65/PUMA-mediated epithelial apoptosis in PHG, and inhibition of NF-κBp65 or knockout of PUMA alleviates Fas/FasL-mediated epithelial apoptosis in PHG. These results indicate that IL-6 drives FasL generation via NF-κBp65 in myeloid cells to promote Fas/NF-κBp65/PUMA-mediated epithelial apoptosis in PHG, and this coordinated crosstalk between myeloid cells and epithelial cells may provide a potential therapeutic target for PHG.
CircCDR1as upregulates autophagy under hypoxia to promote tumor cell survival via AKT/ERK½/mTOR signaling pathways in oral squamous cell carcinomas
Authors: Gao Ling , Dou Zhi-Chao , Ren Wen-Hao , Li Shao-Ming , Liang Xiao , Zhi Ke-Qian
Published: October 2019

Autophagy, as an important non-selective degradation mechanism, could promote tumor initiation and progression by maintaining cellular homeostasis and the cell metabolism as well as cell viability. CircCDR1as has been shown to function as an oncogene in cancer progression, however, it remains largely unknown as to how autophagy is regulated by circCDR1as in oral squamous cell carcinoma (OSCC). In this study, we validated the functional roles of circCDR1as in regulation of autophagy in OSCC cells and further investigated how circCDR1as contributed to cell survival via up-regulating autophagy under a hypoxic microenvironment by using combination of human tissue model, in vitro cell experiments and in vivo mice model. We found that hypoxia promoted the expression level of circCDR1as in OSCC cells and elevated autophagy. In addition, circCDR1as further increased hypoxia-mediated autophagy by targeting multiple key regulators of autophagy. We revealed that circCDR1as enhanced autophagy in OSCC cells via inhibition of rapamycin (mTOR) activity and upregulation of AKT and ERK½ pathways. Overexpression of circCDR1as enhanced OSCC cells viability, endoplasmic reticulum (ER) stress, and inhibited cell apoptosis under a hypoxic microenvironment. Moreover, circCDR1as promoted autophagy in OSCC cells by sponging miR-671-5p. Collectively, these results revealed that high expression of circCDR1as enhanced the viability of OSCC cells under a hypoxic microenvironment by promoting autophagy, suggesting a novel treatment strategy involving circCDR1as and the inhibition of autophagy in OSCC cells.
Double knock-out of Hmga1 and Hipk2 genes causes perinatal death associated to respiratory distress and thyroid abnormalities in mice
Authors: Gerlini Raffaele , Amendola Elena , Conte Andrea , Valente Valeria , Tornincasa Mara , Credendino Sara Carmela , Cammarota Francesca , Gentile Chiara , Di Guida Luigi , Paladino Simona , De Vita Gabriella , Fusco Alfredo , Pierantoni Giovanna Maria
Published: October 2019

The serine–threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) modulates important cellular functions during development, acting as a signal integrator of a wide variety of stress signals, and as a regulator of transcription factors and cofactors. We have previously demonstrated that HIPK2 binds and phosphorylates High-Mobility Group A1 (HMGA1), an architectural chromatinic protein ubiquitously expressed in embryonic tissues, decreasing its binding affinity to DNA. To better define the functional role of HIPK2 and HMGA1 interaction in vivo, we generated mice in which both genes are disrupted. About 50% of these Hmga1/Hipk2 double knock-out (DKO) mice die within 12 h of life (P1) for respiratory failure. The DKO mice present an altered lung morphology, likely owing to a drastic reduction in the expression of surfactant proteins, that are required for lung development. Consistently, we report that both HMGA1 and HIPK2 proteins positively regulate the transcriptional activity of the genes encoding the surfactant proteins. Moreover, these mice display an altered expression of thyroid differentiation markers, reasonably because of a drastic reduction in the expression of the thyroid-specific transcription factors PAX8 and FOXE1, which we demonstrate here to be positively regulated by HMGA1 and HIPK2. Therefore, these data indicate a critical role of HIPK2/HMGA1 cooperation in lung and thyroid development and function, suggesting the potential involvement of their impairment in the pathogenesis of human lung and thyroid diseases.
C9-ALS/FTD-linked proline–arginine dipeptide repeat protein associates with paraspeckle components and increases paraspeckle formation
Authors: Suzuki Hiroaki , Shibagaki Yoshio , Hattori Seisuke , Matsuoka Masaaki
Published: October 2019

A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene has been identified as the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. The repeat expansion undergoes unconventional translation to produce five dipeptide repeat proteins (DPRs). Although DPRs are thought to be neurotoxic, the molecular mechanism underlying the DPR-caused neurotoxicity has not been fully elucidated. The current study shows that poly-proline-arginine (poly-PR), the most toxic DPR in vitro, binds to and up-regulates nuclear paraspeckle assembly transcript 1 (NEAT1) that plays an essential role as a scaffold non-coding RNA during the paraspeckle formation. The CRISPR-assisted up-regulation of endogenous NEAT1 causes neurotoxicity. We also show that the poly-PR modulates the function of several paraspeckle-localizing heterogeneous nuclear ribonucleoproteins. Furthermore, dysregulated expression of TAR DNA-binding protein 43 (TDP-43) up-regulates NEAT1 expression and induces neurotoxicity. These results suggest that the increase in the paraspeckle formation may be involved in the poly-PR- and TDP-43-mediated neurotoxicity.
Impaired Wnt/β-catenin pathway leads to dysfunction of intestinal regeneration during necrotizing enterocolitis
Authors: Li Bo , Lee Carol , Cadete Marissa , Zhu Haitao , Koike Yuhki , Hock Alison , Wu Richard Y. , Botts Steven R. , Minich Adam , Alganabi Mashriq , Chi Lijun , Zani-Ruttenstock Elke , Miyake Hiromu , Chen Yong , Mutanen Annika , Ngan Bo , Johnson-Henry Kathene C. , De Coppi Paolo , Eaton Simon , Määttänen Pekka , Delgado-Olguin Paul , Sherman Philip M. , Zani Augusto , Pierro Agostino
Published: October 2019

Necrotizing enterocolitis (NEC) is a devastating neonatal disease characterized by acute intestinal injury. Intestinal stem cell (ISC) renewal is required for gut regeneration in response to acute injury. The Wnt/β-catenin pathway is essential for intestinal renewal and ISC maintenance. We found that ISC expression, Wnt activity and intestinal regeneration were all decreased in both mice with experimental NEC and in infants with acute active NEC. Moreover, intestinal organoids derived from NEC-injured intestine of both mice and humans failed to maintain proliferation and presented more differentiation. Administration of Wnt7b reversed these changes and promoted growth of intestinal organoids. Additionally, administration of exogenous Wnt7b rescued intestinal injury, restored ISC, and reestablished intestinal epithelial homeostasis in mice with NEC. Our findings demonstrate that during NEC, Wnt/β-catenin signaling is decreased, ISC activity is impaired, and intestinal regeneration is defective. Administration of Wnt resulted in the maintenance of intestinal epithelial homeostasis and avoidance of NEC intestinal injury.
A tri-ionic anchor mechanism drives Ube2N-specific recruitment and K63-chain ubiquitination in TRIM ligases
Authors: Kiss Leo , Zeng Jingwei , Dickson Claire F. , Mallery Donna L. , Yang Ji-Chun , McLaughlin Stephen H. , Boland Andreas , Neuhaus David , James Leo C.
Published: October 2019

The cytosolic antibody receptor TRIM21 possesses unique ubiquitination activity that drives broad-spectrum anti-pathogen targeting and underpins the protein depletion technology Trim-Away. This activity is dependent on formation of self-anchored, K63-linked ubiquitin chains by the heterodimeric E2 enzyme Ube2N/Ube2V2. Here we reveal how TRIM21 facilitates ubiquitin transfer and differentiates this E2 from other closely related enzymes. A tri-ionic motif provides optimally distributed anchor points that allow TRIM21 to wrap an Ube2N~Ub complex around its RING domain, locking the closed conformation and promoting ubiquitin discharge. Mutation of these anchor points inhibits ubiquitination with Ube2N/Ube2V2, viral neutralization and immune signalling. We show that the same mechanism is employed by the anti-HIV restriction factor TRIM5 and identify spatially conserved ionic anchor points in other Ube2N-recruiting RING E3s. The tri-ionic motif is exclusively required for Ube2N but not Ube2D1 activity and provides a generic E2-specific catalysis mechanism for RING E3s.
Polariton nanophotonics using phase-change materials
Authors: Chaudhary Kundan , Tamagnone Michele , Yin Xinghui , Spägele Christina M. , Oscurato Stefano L. , Li Jiahan , Persch Christoph , Li Ruoping , Rubin Noah A. , Jauregui Luis A. , Watanabe Kenji , Taniguchi Takashi , Kim Philip , Wuttig Matthias , Edgar James H. , Ambrosio Antonio , Capasso Federico
Published: October 2019

Polaritons formed by the coupling of light and material excitations enable light-matter interactions at the nanoscale beyond what is currently possible with conventional optics. However, novel techniques are required to control the propagation of polaritons at the nanoscale and to implement the first practical devices. Here we report the experimental realization of polariton refractive and meta-optics in the mid-infrared by exploiting the properties of low-loss phonon polaritons in isotopically pure hexagonal boron nitride interacting with the surrounding dielectric environment comprising the low-loss phase change material Ge3Sb2Te6. We demonstrate rewritable waveguides, refractive optical elements such as lenses, prisms, and metalenses, which allow for polariton wavefront engineering and sub-wavelength focusing. This method will enable the realization of programmable miniaturized integrated optoelectronic devices and on-demand biosensors based on high quality phonon resonators.
Exact exchange-correlation potentials from ground-state electron densities
Authors: Kanungo Bikash , Zimmerman Paul M. , Gavini Vikram
Published: October 2019

The quest for accurate exchange-correlation functionals has long remained a grand challenge in density functional theory (DFT), as it describes the many-electron quantum mechanical behavior through a computationally tractable quantity—the electron density—without resorting to multi-electron wave functions. The inverse DFT problem of mapping the ground-state density to its exchange-correlation potential is instrumental in aiding functional development in DFT. However, the lack of an accurate and systematically convergent approach has left the problem unresolved, heretofore. This work presents a numerically robust and accurate scheme to evaluate the exact exchange-correlation potentials from correlated ab-initio densities. We cast the inverse DFT problem as a constrained optimization problem and employ a finite-element basis—a systematically convergent and complete basis—to discretize the problem. We demonstrate the accuracy and efficacy of our approach for both weakly and strongly correlated molecular systems, including up to 58 electrons, showing relevance to realistic polyatomic molecules.
Evaporative electron cooling in asymmetric double barrier semiconductor heterostructures
Authors: Yangui Aymen , Bescond Marc , Yan Tifei , Nagai Naomi , Hirakawa Kazuhiko
Published: October 2019

Rapid progress in high-speed, densely packed electronic/photonic devices has brought unprecedented benefits to our society. However, this technology trend has in reverse led to a tremendous increase in heat dissipation, which degrades device performance and lifetimes. The scientific and technological challenge henceforth lies in efficient cooling of such high-performance devices. Here, we report on evaporative electron cooling in asymmetric Aluminum Gallium Arsenide/Gallium Arsenide (AlGaAs/GaAs) double barrier heterostructures. Electron temperature, Te, in the quantum well (QW) and that in the electrodes are determined from photoluminescence measurements. At 300 K, Te in the QW is gradually decreased down to 250 K as the bias voltage is increased up to the maximum resonant tunneling condition, whereas Te in the electrode remains unchanged. This behavior is explained in term of the evaporative cooling process and is quantitatively described by the quantum transport theory.
Gingival solitary chemosensory cells are immune sentinels for periodontitis
Authors: Zheng Xin , Tizzano Marco , Redding Kevin , He Jinzhi , Peng Xian , Jiang Peihua , Xu Xin , Zhou Xuedong , Margolskee Robert F.
Published: October 2019

Solitary chemosensory cells (SCCs) are epithelial sentinels that utilize bitter Tas2r receptors and coupled taste transduction elements to detect pathogenic bacterial metabolites, triggering host defenses to control the infection. Here we report that SCCs are present in mouse gingival junctional epithelium, where they express several Tas2rs and the taste signaling components α-gustducin (Gnat3), TrpM5, and Plcβ2. Gnat3−/− mice have altered commensal oral microbiota and accelerated naturally occurring alveolar bone loss. In ligature-induced periodontitis, knockout of taste signaling molecules or genetic absence of gingival SCCs (gSCCs) increases the bacterial load, reduces bacterial diversity, and renders the microbiota more pathogenic, leading to greater alveolar bone loss. Topical treatment with bitter denatonium to activate gSCCs upregulates the expression of antimicrobial peptides and ameliorates ligature-induced periodontitis in wild-type but not in Gnat3−/− mice. We conclude that gSCCs may provide a promising target for treating periodontitis by harnessing innate immunity to regulate the oral microbiome.
Atrial Fibrillation Is Associated with Increased Mortality in Patients Presenting with Ventricular Tachyarrhythmias
Authors: Behnes Michael , Rusnak Jonas , Taton Gabriel , Schupp Tobias , Reiser Linda , Bollow Armin , Reichelt Thomas , Engelke Niko , Ellguth Dominik , Kuche Philipp , Ibrahim El-Battrawy  , Lang Siegfried , Nienaber Christoph A. , Mashayekhi Kambis , Akin Muharrem , Bertsch Thomas , Ferdinand Dennis , Weiss Christel , Borggrefe Martin , Akin Ibrahim
Published: October 2019

Heterogenous data about the prognostic impact of atrial fibrillation (AF) in patients with ventricular tachyarrhythmias exist. Therefore, this study evaluates this impact of AF in patients presenting with ventricular tachyarrhythmias. 1,993 consecutive patients presenting with ventricular tachyarrhythmias (i.e. ventricular tachycardia and fibrillation (VT, VF)) on admission at one institution were included (from 2002 until 2016). All medical data of index and follow-up hospitalizations were collected during the complete follow-up period for each patient. Statistics comprised univariable Kaplan-Meier and multivariable Cox regression analyses in the unmatched consecutive cohort and after propensity-score matching for harmonization. The primary prognostic endpoint was long-term all-cause mortality at 2.5 years. AF was present in 31% of patients presenting with index ventricular tachyarrhythmias on admission (70% paroxysmal, 9% persistent, 21% permanent). VT was more common (67% versus 59%; p = 0.001) than VF (33% versus 41%; p = 0.001) in AF compared to non-AF patients. Long-term all-cause mortality at 2.5 years occurred more often in AF compared to non-AF patients (mortality rates 40% versus 24%, log rank p = 0.001; HR = 1.825; 95% CI 1.548–2.153; p = 0.001), which may be attributed to higher rates of all-cause mortality at 30 days, in-hospital mortality and mortality after discharge (p < 0.05) (secondary endpoints). Mortality differences were observed irrespective of index ventricular tachyarrhythmia (VT or VF), LV dysfunction or presence of an ICD. In conclusion, this study identifies AF as an independent predictor of death in patients presenting consecutively with ventricular tachyarrhythmias.
Odf2 haploinsufficiency causes a new type of decapitated and decaudated spermatozoa, Odf2-DDS, in mice
Authors: Ito Chizuru , Akutsu Hidenori , Yao Ryoji , Yoshida Keiichi , Yamatoya Kenji , Mutoh Tohru , Makino Tsukasa , Aoyama Kazuhiro , Ishikawa Hiroaki , Kunimoto Koshi , Tsukita Sachiko , Noda Tetsuo , Kikkawa Masahide , Toshimori Kiyotaka
Published: October 2019

Outer dense fibre 2 (Odf2 or ODF2) is a cytoskeletal protein required for flagella (tail)-beating and stability to transport sperm cells from testes to the eggs. There are infertile males, including human patients, who have a high percentage of decapitated and decaudated spermatozoa (DDS), whose semen contains abnormal spermatozoa with tailless heads and headless tails due to head-neck separation. DDS is untreatable in reproductive medicine. We report for the first time a new type of Odf2-DDS in heterozygous mutant Odf2+/− mice. Odf2+/− males were infertile due to haploinsufficiency caused by heterozygous deletion of the Odf2 gene, encoding the Odf2 proteins. Odf2 haploinsufficiency induced sperm neck-midpiece separation, a new type of head-tail separation, leading to the generation of headneck sperm cells or headnecks composed of heads with necks and neckless tails composed of only the main parts of tails. The headnecks were immotile but alive and capable of producing offspring by intracytoplasmic headneck sperm injection (ICSI). The neckless tails were motile and could induce capacitation but had no significant forward motility. Further studies are necessary to show that ICSI in humans, using headneck sperm cells, is viable and could be an alternative for infertile patients suffering from Odf2-DDS.