bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating operation modes for the individual wheel electric drive of the all-wheel drive vehicle with the use of the driving simulator
Authors: Kotiev G O , Miroshnichenko A V , Stadukhin A A , Kositsyn B B
Published: June 2019

With the development of the electric drive systems and vehicle on-board power sources the electric transport is becoming more popular, in particular wheeled vehicles with individually driven wheels, while the question of choosing power plants for this type of transport remains unresolved. In the presented article, the authors illustrate an approach to determining the requirements for power plants of such vehicles by an example of a four-wheel drive car equipped with an individual electric wheel drive. The approach is based on the use of the real-time driving simulator allowing the operator to drive the vehicle along typical routes. The typical routes for the driving simulator are generated from the known statistical data on the excitation inputs during the vehicle motion. Thus, the developed driving simulator provides analysis of the vehicle traction motors operation in the conditions most close to the actual ones and collection of the necessary statistical data which can be used for statement of the requirements for new electric machines which would provide their most effective use on the vehicle.
Creation concept of objective control systems for traffic safety of vehicles
Authors: Saikin A M , Buznikov S E
Published: June 2019

Traffic safety is one of the most important problems for modern society. The relevance of research aimed at creating effective means for monitoring the vehicle technical condition and driver condition is determined by the importance of improving traffic safety. The study aims to propose the scientific substantiation of the creation concept of objective control systems for traffic safety of vehicles. To conduct the study system analysis methods and modern control theory were used. The safe driving task is formulated as collision prevention with moving and stationary obstacles. A structured set of collisions contains all typical collisions and overturns caused by technical malfunctions, pavement condition and driving errors. The system creation concept assumes both the measurement and recording of the state vector, its dynamic boundaries and warning signals demonstration to the driver about approaching dangerous boundaries or exceeding them. Modern foreign and domestic objective control automotive systems were compared. System acquires intellectual properties by using mathematical models and algorithms for indirect measurements performed with a minimal quantity of primary information sensors. The research novelty consists in the scientific substantiation of building automobile systems for objective control based on virtual information sensors providing the solution of the dynamic stabilization problem in its most fully algorithmically resolved form.
Reliability Analysis of Certain Rocket Engine Based on Fault Tree
Authors: Wang Wensheng , Jin Liying , Sun Xi , Liu Jing
Published: June 2019

In this paper, a fault tree model of certain rocket engine is established according to its structure and working principle. Through qualitative analysis and quantitative calculation, the factors affecting the reliability of a certain type of rocket engine are obtained, and the corresponding improvement measures are put forward to improve the reliability and safety of a certain type of rocket engine.
Research on Vulnerability and Damage Assessment of Tactical Ballistic Missile
Authors: Gu Hongping , Cheng Chun , Sun Aixi , Lei Xiaoyun , Shi Yijian , Huang Fenghua
Published: June 2019

The threat of TBM (Tactical Ballistic Missile) on the battlefield makes it an important intercept target of anti missile system. In order to effectively evaluate the damage degree of TBM when intercepted, the system and function characteristics of TBM were analyzed with "Iskander" TBM as an example, the missile vulnerability model was constructed, the vulnerability and damage assessment program was developed, and the damage assessment test methods of TBM were summarized. The research results will help to carry out real-time evaluation of the damage effect of antimissile system towards TBM.
Fatigue Analysis of Suspension Control Arm Based on Road Spectrum
Authors: Yuan-chun Kang
Published: June 2019

Aiming at precisely predicting fatigue life for suspension control arm, a fatigue life analysis method is presented. First of all, 2D road spectrum is structured using Sayers. Then, a rigid-flexible coupling multi-body model is built for vehicle dynamics simulation based on ADAMS software. Automobile test is simulated and the time-load histories of each connecting point of the suspension control arm are obtained. By means of the rain flow counting method, fatigue analysis load spectrums are obtained. Finally, the fatigue life of the control arm is analyzed. The result of fatigue life analysis shows that the control arm is designed to meet the requirements of durability.
Analysis of fraction distribution of the water drops stream generated by the spraying nozzles of new KOMAG design
Authors: Bałaga D , Kalita M , Siegmund M
Published: June 2019

Theoretical backgrounds of airborne dust control with use of atomized stream of liquid are presented. Testing procedure, with a special attention paid to analysis of drops fraction distribution, is presented on the example of new nozzle design developed at KOMAG. The method for calculation of absorption surface is discussed. The test results are used to analyse operational parameters of the nozzle which are important for the dust control systems.
Hard rock mining – cutting or disk tools
Authors: Kotwica K
Published: June 2019

The article presents problems related to the mining of compact and very hard rocks with cutting tools, mainly with tangential-rotary picks. The currently used disc tools, their parameters and the way of working are described. The disadvantages of selected solutions and related obstacles to their wider use in mining have been presented. The directions of further development of disk tools were presented, allowing their use, for example, in mining heads of longwall shearers and roadheaders.
The global expansion of climate mitigation policy interventions, the Talanoa Dialogue and the role of behavioural insights
Authors: Mundaca Luis , Sonnenschein Jonas , Steg Linda , Höhne Niklas , Ürge-Vorsatz Diana
Published: June 2019

Increasing attention is being paid to the Paris Climate Agreement and the impacts of Nationally Determined Contributions (NDCs) intended to limit global warming to 1.5 °C. However, the nature and evolution of existing policy mixes that underlie NDCs remain poorly understood. This critical issue has emerged from the outcomes of the Talanoa Dialogue for Climate Ambition, where little progress was made in building a comprehensive, evidence-based foundation for effective climate policy. To a large extent, this is due to the nature of the process, and a lack of data related to policy interventions in the pre-2020 period, notably their composition, coverage, and orientation. We seek to address these shortcomings by applying a directed content analysis to a dataset of national and city-level policy interventions. The aim is to quantify the nature and evolution of policy efforts that promote the adoption of low-carbon energy technologies (LCETs) globally. Fifteen databases, containing more than 10,000 policies and measures were reviewed. Our findings highlight the rapid spread of policy portfolios and an international convergence towards economic incentives (notably subsidies). At the city level, technology and infrastructure policies dominate. However, it is unclear to what extent behavioural factors (i.e., cognitive, motivational and contextual aspects) that affect the choice and use of LCETs are taken into account in policy design. This is particularly important because studies that model the feasibility of the 1.5 °C target reveal behavioural changes and the rapid adoption of low-carbon lifestyles as critical enabling factors. In response to the outcomes from the Talanoa Dialogue, we argue that policymakers need to go beyond stringent policy mixes and rapidly re-think their traditional economic-driven policymaking approach. Far more attention needs to be given to behavioural factors when designing, evaluating and implementing LCET policies.
Rho-dependent control of the Citron kinase, Sticky, drives midbody ring maturation
Authors: El-amine Nour , Carim Sabrya C. , Wernike Denise , Hickson Gilles R. X.
Published: June 2019

Rho-dependent proteins control assembly of the cytokinetic contractile ring, yet it remains unclear how those proteins guide ring closure and how they promote subsequent formation of a stable midbody ring. Citron kinase is one important component required for midbody ring formation but its mechanisms of action and relationship with Rho are controversial. Here, we conduct a structure–function analysis of the Drosophila Citron kinase, Sticky, in Schneider’s S2 cells. We define two separable and redundant RhoGEF/Pebble-dependent inputs into Sticky recruitment to the nascent midbody ring and show that each input is subsequently required for retention at, and for the integrity of, the mature midbody ring. The first input is via an actomyosin-independent interaction between Sticky and Anillin, a key scaffold also required for midbody ring formation. The second input requires the Rho-binding domain of Sticky, whose boundaries we have defined. Collectively, these results show how midbody ring biogenesis depends on the coordinated actions of Sticky, Anillin, and Rho.
Estimating the True Burden of Legionnaires’ Disease
Authors: Cassell Kelsie , Gacek Paul , Rabatsky-Ehr Therese , Petit Susan , Cartter Matthew , Weinberger Daniel M
Published: June 2019

Over the past decade, the reported incidence of Legionnaires’ disease (LD) in the northeastern United States has increased, reaching 1–3 cases per 100,000 population. There is reason to suspect that this is an underestimate of the true burden, since LD cases may be underdiagnosed. In this analysis of pneumonia and influenza (P&I) hospitalizations, we estimated the percentages of cases due to Legionella, influenza, and respiratory syncytial virus (RSV) by age group. We fitted mixed-effects models to estimate attributable percents using weekly time series data on P&I hospitalizations in Connecticut from 2000 to 2014. Model-fitted values were used to calculate estimates of numbers of P&I hospitalizations attributable to Legionella (and influenza and RSV) by age group, season, and year. Our models estimated that 1.9%, 8.8%, and 5.1% of total (all-ages) inpatient P&I hospitalizations could be attributed to Legionella, influenza, and RSV, respectively. Only 10.6% of total predicted LD cases had been clinically diagnosed as LD during the study period. The observed incidence rate of 1.2 cases per 100,000 population was substantially lower than our estimated rate of 11.6 cases per 100,000 population. Our estimates of numbers of P&I hospitalizations attributable to Legionella are comparable to those provided by etiological studies of community-acquired pneumonia and emphasize the potential for underdiagnosis of LD in clinical settings.
Bioinoculant capability enhancement through metabolomics and systems biology approaches
Authors: Chaudhary Twinkle , Shukla Pratyoosh
Published: June 2019

Bioinoculants are eco-friendly microorganisms, and their products are utilized for improving the potential of soil and fulfill the nutrients requirement for the host plant. The agricultural yield has increased due to the use of bioinoculants over chemical-based fertilizers, and thus it generates interest in understanding the innovation process by various methods. By gene-editing tool, the desired gene product can be changed for engineered microbial inoculants. We have also described various modern biotechnological tools like constraint-based modeling, OptKnock, flux balance analysis and modeling of the biological network for enhancing the bioinoculant capability. These fluxes give the fascinating perception of the metabolic network in the absence of comprehensive kinetic information. These tools also help in the stimulation of the metabolic networks by incorporation of enzyme-encoding genes. The present review explains the use of systems biology and gene-editing tools for improving the capability of bioinoculants. Moreover, this review also emphasizes on the challenges and future perspective of systems biology and its multidisciplinary facets.
Protein contact prediction using metagenome sequence data and residual neural networks
Authors: Wu Qi , Peng Zhenling , Anishchenko Ivan , Cong Qian , Baker David , Yang Jianyi
Published: June 2019

Motivation

Almost all protein residue contact prediction methods rely on the availability of deep multiple sequence alignments (MSAs). However, many proteins from the poorly populated families do not have sufficient number of homologs in the conventional UniProt database. Here we aim to solve this issue by exploring the rich sequence data from the metagenome sequencing projects.

Results

Based on the improved MSA constructed from the metagenome sequence data, we developed MapPred, a new deep learning-based contact prediction method. MapPred consists of two component methods, DeepMSA and DeepMeta, both trained with the residual neural networks. DeepMSA was inspired by the recent method DeepCov, which was trained on 441 matrices of covariance features. By considering the symmetry of contact map, we reduced the number of matrices to 231, which makes the training more efficient in DeepMSA. Experiments show that DeepMSA outperforms DeepCov by 10–13% in precision. DeepMeta works by combining predicted contacts and other sequence profile features. Experiments on three benchmark datasets suggest that the contribution from the metagenome sequence data is significant with P-values less than 4.04E-17. MapPred is shown to be complementary and comparable the state-of-the-art methods. The success of MapPred is attributed to three factors: the deeper MSA from the metagenome sequence data, improved feature design in DeepMSA and optimized training by the residual neural networks.

Availability and implementation

http://yanglab.nankai.edu.cn/mappred/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Pediatric Bacterial Meningitis Surveillance in the World Health Organization African Region Using the Invasive Bacterial Vaccine-Preventable Disease Surveillance Network, 2011–2016
Authors: Mwenda Jason M , Soda Elizabeth , Weldegebriel Goitom , Katsande Regis , Biey Joseph Nsiari-Muzeyi , Traore Tieble , de Gouveia Linda , du Plessis Mignon , von Gottberg Anne , Antonio Martin , Kwambana-Adams Brenda , Worwui Archibald , Gierke Ryan , Schwartz Stephanie , van Beneden Chris , Cohen Adam , Serhan Fatima , Lessa Fernanda C
Published: June 2019

Background

Bacterial meningitis is a major cause of morbidity and mortality in sub-Saharan Africa. We analyzed data from the World Health Organization’s (WHO) Invasive Bacterial Vaccine-preventable Diseases Surveillance Network (2011–2016) to describe the epidemiology of laboratory-confirmed Streptococcus pneumoniae (Spn), Neisseria meningitidis, and Haemophilus influenzae meningitis within the WHO African Region. We also evaluated declines in vaccine-type pneumococcal meningitis following pneumococcal conjugate vaccine (PCV) introduction.

Methods

Reports of meningitis in children <5 years old from sentinel surveillance hospitals in 26 countries were classified as suspected, probable, or confirmed. Confirmed meningitis cases were analyzed by age group and subregion (South-East and West-Central). We described case fatality ratios (CFRs), pathogen distribution, and annual changes in serotype and serogroup, including changes in vaccine-type Spn meningitis following PCV introduction.

Results

Among 49 844 reported meningitis cases, 1670 (3.3%) were laboratory-confirmed. Spn (1007/1670 [60.3%]) was the most commonly detected pathogen; vaccine-type Spn meningitis cases declined over time. CFR was the highest for Spn meningitis: 12.9% (46/357) in the South-East subregion and 30.9% (89/288) in the West-Central subregion. Meningitis caused by N. meningitidis was more common in West-Central than South-East Africa (321/954 [33.6%] vs 110/716 [15.4%]; P < .0001). Haemophilus influenzae (232/1670 [13.9%]) was the least prevalent organism.

Conclusions

Spn was the most common cause of pediatric bacterial meningitis in the African region even after reported cases declined following PCV introduction. Sustaining robust surveillance is essential to monitor changes in pathogen distribution and to inform and guide vaccination policies.
Pediatric Bacterial Meningitis Surveillance in Nigeria From 2010 to 2016, Prior to and During the Phased Introduction of the 10-Valent Pneumococcal Conjugate Vaccine
Authors: Tagbo Beckie N , Bancroft Rowan E , Fajolu Iretiola , Abdulkadir Mohammed B , Bashir Muhammad F , Okunola Olusola P , Isiaka Ayodeji H , Lawal Namadi M , Edelu Benedict O , Onyejiaka Ngozi , Ihuoma Chinonyerem J , Ndu Florence , Ozumba Uchenna C , Udeinya Frances , Ogunsola Folasade , Saka Aishat O , Fadeyi Abayomi , Aderibigbe Sunday A , Abdulraheem Jimoh , Yusuf Adamu G , Sylvanus Ndow Peter , Ogbogu Philomena , Kanu Chinomnso , Emina Velly , Makinwa Olajumoke J , Gehre Florian , Yusuf Kabir , Braka Fiona , Mwenda Jason M , Ticha Johnson M , Nwodo Dorothy , Worwui Archibald , Biey Joseph N , Kwambana-Adams Brenda A , Antonio Martin
Published: June 2019

Background

Historically, Nigeria has experienced large bacterial meningitis outbreaks with high mortality in children. Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae are major causes of this invasive disease. In collaboration with the World Health Organization, we conducted longitudinal surveillance in sentinel hospitals within Nigeria to establish the burden of pediatric bacterial meningitis (PBM).

Methods

From 2010 to 2016, cerebrospinal fluid was collected from children <5 years of age, admitted to 5 sentinel hospitals in 5 Nigerian states. Microbiological and latex agglutination techniques were performed to detect the presence of pneumococcus, meningococcus, and H. influenzae. Species-specific polymerase chain reaction and serotyping/grouping were conducted to determine specific causative agents of PBM.

Results

A total of 5134 children with suspected meningitis were enrolled at the participating hospitals; of these 153 (2.9%) were confirmed PBM cases. The mortality rate for those infected was 15.0% (23/153). The dominant pathogen was pneumococcus (46.4%: 71/153) followed by meningococcus (34.6%: 53/153) and H. influenzae (19.0%: 29/153). Nearly half the pneumococcal meningitis cases successfully serotyped (46.4%: 13/28) were caused by serotypes that are included in the 10-valent pneumococcal conjugate vaccine. The most prevalent meningococcal and H. influenzae strains were serogroup W and serotype b, respectively.

Conclusions

Vaccine-type bacterial meningitis continues to be common among children <5 years in Nigeria. Challenges with vaccine introduction and coverage may explain some of these finding. Continued surveillance is needed to determine the distribution of serotypes/groups of meningeal pathogens across Nigeria and help inform and sustain vaccination policies in the country.
Global regurgitant volume: approaching the critical mass in valvular-driven heart failure
Authors: Bartko Philipp E , Arfsten Henrike , Heitzinger Gregor , Pavo Noemi , Spinka Georg , Kastl Stefan , Prausmüller Suriya , Strunk Guido , Mascherbauer Julia , Hengstenberg Christian , Hülsmann Martin , Goliasch Georg
Published: June 2019

Aims

Recent progress in the diagnosis of functional valve regurgitation forms a coherent perception of severity thresholds by quantitative assessment. However, thresholds focused on either valve in isolation—not accounting for the global haemodynamic burden arising from concomitant functional regurgitation of the mitral and tricuspid valves. We sought to determine whether the global regurgitant volume is associated with adverse cardiac remodelling and mortality.

Methods and results

This long-term observational study included 414 patients on guideline-directed medical therapy. Baseline global regurgitant load defined as the sum of mitral and tricuspid regurgitant volume was assessed by the proximal flow convergence method. All-cause mortality during 5 years follow-up served as the primary endpoint. The median global regurgitant load was 30 mL (interquartile range 15–49) with 67% accounting for mitral and 33% accounting for tricuspid regurgitant volume. The global regurgitant load had significant impact on outcome with a crude hazard ratio of 1.46 (1.28–1.66; P < 0.001) for a 1-SD increase in global regurgitant volume, results that remained virtually unchanged after bootstrap or clinical confounder-based adjustment (P < 0.001 for adjusted models). Spline curve analysis showed a linearly increasing risk with a threshold of 50 mL and sustained increasing risk thereafter.

Conclusions

The present study demonstrates the detrimental effect of the global regurgitant load in patients with heart failure with reduced ejection fraction. The threshold where heart failure is driven by the valve lesions is a global regurgitant volume of 50 mL with continuously increasing risk beyond that threshold. Future studies need to address whether an attempt to reduce the global regurgitant volume can improve outcome.
Whole-Genome Analysis of Halomonas sp. Soap Lake #7 Reveals It Possesses Putative Mrp Antiporter Operon Groups 1 and 2
Authors: Mormile Melanie R , Edwards Tiffany , Frank Ron , Geurin Zachery , Haendiges Julie , Hoffmann Maria , Miller Jesse
Published: June 2019

The genus Halomonas possesses bacteria that are halophilic or halotolerant and exhibit a wide range of pH tolerance. The genome of Halomonas sp. Soap Lake #7 was sequenced to provide a better understanding of the mechanisms for salt and pH tolerance in this genus. The bacterium’s genome was found to possess two complete multiple resistance and pH antiporter systems, Group 1 and Group 2. This is the first report of both multiple resistance and pH antiporter Groups 1 and 2 in the genome of a haloalkaliphilic bacterium.
Psychometric Evaluation of the Social Isolation Scale in Older Adults
Authors: Nicholson Nicholas R , Feinn Richard , Casey E A , Dixon Jane
Published: June 2019

Background and Objectives

Social isolation is known to be detrimental to the health of older adults, yet there is no brief instrument to measure it. The objective was to describe the psychometric testing of a brief instrument constructed from theoretical underpinnings to measure social isolation in older adults.

Research Design and Methods

A sample of 9,245 participants, all aged 60 years and older, was obtained from 44 states in the United States. Summary descriptive statistics were calculated, followed by exploratory factor analysis using Geomin rotation and subsequently confirmatory factor analysis (CFA). After finding the best model, differential item functioning (DIF) was conducted using a multiple indicator multiple cause structural equation model to determine if item responses differed by gender or race after controlling for level of social isolation. Internal consistency was calculated and validity was assessed by correlating factor scores with 2 external measures.

Results

Exploratory factor analysis resulted in all items having statistically significant loadings. CFA showed the 2-factor model demonstrated excellent fit (CFI = 0.997, RMSEA = .038). The 2 factors were labeled connectedness and belongingness. After adjusting for demographic variables, no evidence suggested DIF. Internal consistency was good (alpha = .77) and the scale moderately correlated with the Social Network Index (r = .47).

Discussion and Implications

The Social Isolation Scale has been shown to be an effective measure of social isolation in older adults. Using this concise instrument to quickly measure social isolation in a fast-paced health care environment would be beneficial to health care providers and patients.
A demographic model for the conservation and management of the European eel: an application to a Mediterranean coastal lagoon
Authors: Bevacqua Daniele , Melià Paco , Schiavina Marcello , Crivelli Alain J , De Leo Giulio A , Gatto Marino
Published: June 2019

We present a general size- and age-structured demographic model of the continental phase of catadromous eels’ life cycle, allowing for the incorporation of (i) fluctuations of juvenile recruitment, (ii) density-dependent settlement and sex determination, (iii) plastic body growth and sexual dimorphism, and (iv) vital rates driven by body size rather than age. The model can be used to assess (i) standing stock, (ii) fishing yield, and (iii) spawner production under different recruitment and management scenarios. We demonstrate the model by applying it to a European eel stock (Camargue lagoons, southern France) that was continuously monitored for 17 years (1993–2009). Results indicate that the upper limit to settlement in the Camargue water system is ∼419 eels ha−1 per year. A balanced sex ratio occurs for a settlement of ∼94 eels ha−1, shifting towards males at higher densities. Catchability is higher in adult silver eels than in sub-adult yellow eels, possibly due to behavioural differences. Estimated standing stock ranged between 7 and 19 kg ha−1. Fishing yield was 5–7 kg ha−1 per year, while spawner escapement ranged between 0 and 13 kg ha−1 per year (<30% of what would occur in the absence of fishing and obstacles to migration).
Analysis of survival after coronary endarterectomy combined with coronary artery bypass grafting compared with isolated coronary artery bypass grafting: a meta-analysis
Authors: Wang Chuan , Chen Jun , Gu Chengxiong , Li Jingxing
Published: June 2019

OBJECTIVES

The aim of this analysis was to compare survival outcomes of coronary endarterectomy (CE) combined with coronary artery bypass grafting (CABG) with those of conventional CABG.

METHODS

Eight observational studies were included in this analysis, including 10 529 different patients in Asia, Europe and North America, from 1985 to 2012, among whom 1925 underwent CE + CAGB and 8604 underwent conventional CAGB. The follow-up period ranged from 4 to 14 years. This meta-analysis was performed with the fixed-effects model.

RESULTS

After rigorous assessment of the quality of the studies included, this analysis showed that CE + CABG had a statistically significant weaker short-term outcome, with a higher risk of mortality [odds ratio (OR)] 1.61; P = 0.002]. Further, this phenomenon was exacerbated in the midterm. One-year and 2-year results indicated that death was, respectively, 163% (OR 2.63; P < 0.001) and 133% (OR 2.60; P < 0.001) more likely to occur in the CE + CABG group. However, the long-term results indicated no difference between the 2 groups. The 4-year hazard ratio (1.13; P = 0.10) did not show significant differences between the groups, and the Kaplan–Meier survival curves had the same level and pattern.

CONCLUSIONS

CE + CABG had a significantly weaker short-term outcome than conventional CABG, and this trend continued in the midterm. The survival rate had the largest gap in the midterm. However, there was no significant difference between these 2 groups in the long run.
One Thicket in Fraud on a Power
Authors: Hudson Jessica
Published: June 2019

This article considers the effect of fraud on a power as it applies to private powers arising across a range of institutions, such as express trusts, agency and companies. The article makes two main arguments. First, the effect of fraud on a power is determined by the equitable nature of the doctrine and its interaction with a particular type of power. The significance is that the effect of fraud on a power cannot be described as either voidness or voidability. There is a more important question as to the priority of equity’s response to fraud on a power. The second argument is that equity calibrates its response to fraud on a power depending on the method by which the power is devolved. The article goes on to consider the justification for this calibration, including the risk profiles that inhere in the different ways that institutions devolve power.
Scintillation balloon for neutrinoless double-beta decay search with liquid scintillator detectors
Authors: Obara S , Gando Y , Ishidoshiro K
Published: June 2019

Environmental radioactivity is a dominant background for rare decay search experiments, and it is difficult to completely remove such an impurity from detector vessels. We propose a scintillation balloon as the active vessel of a liquid scintillator in order to identify this undesirable radioactivity. According to our feasibility studies, the scintillation balloon enables the bismuth–polonium sequential decay to be tagged with a 99.7% efficiency, assuming a KamLAND-type (KamLAND = Kamioka Liquid scintillator AntiNeutrino Detector) liquid scintillator detector. This tagging of sequential decay using alpha rays from the polonium improves the sensitivity to neutrinoless double-beta decay while rejecting beta ray background from the bismuth.
Recent Debates on Public-Private Cost Sharing for Higher Education in Japan
Authors: TANAKA Ryuichi
Published: June 2019

This essay reviews three books and one article about recent debates on public-private cost sharing for higher education in Japan. To mitigate the problems related to low fertility and a rapidly aging population, the Japanese government plans to implement a free tuition policy for higher education for students from less affluent households. These books and the article reveal the historical, political, and economic factors behind why Japan’s current level of public spending on higher education is lower than that of other OECD countries. They also reveal that household income remains one of the most important determinants of college advancement, and that a free tuition policy has the potential to increase enrollment in higher education. However, this essay argues that a deeper understanding of the demand for higher education based on empirical studies is needed to make the policy successful.
Blood and Ice: Intimacy and Factionalism at Fort Defiance Indian Agency, 1887–1888
Authors: Wallace Adams David
Published: June 2019

On a bitterly cold morning on November 19, 1887, six Navajo boys were walking across the school grounds at Fort Defiance Indian Agency when they came across a clot of blood containing a human fetus. A brief investigation by the agent pointed to the unmarried school matron as being the mother of the fetus, a finding that provoked a deep factional dispute among agency employees. Given the explosiveness of the situation, the commissioner of Indian affairs found cause to send an inspector to the remote agency to collect evidence and render a judgement as to whether any individuals were guilty of “undue intimacy.” More than a detective story, this essay utilizes the Fort Defiance story as a window for exploring the problems of agency factionalism and the challenges facing the Office of Indian Affairs in its efforts to monitor and regulate employee behavior in its colonial outposts.
Comparison of EOSQ-24 and SRS-22 Scores in Congenital Scoliosis: A Preliminary Study
Authors: Li Ying , Burke Michelle C. , Gagnier Joel , Caird Michelle S. , Farley Frances A.
Published: June 2019

Background:

The 24-item Early-Onset Scoliosis Questionnaire (EOSQ-24) and 22-item Scoliosis Research Society (SRS-22) questionnaire measure health-related quality of life in patients with scoliosis. The EOSQ-24 has been recently validated in early-onset scoliosis (EOS), including congenital scoliosis (CS). The SRS-22 has been validated in idiopathic scoliosis. The EOSQ-24 is completed by the caregiver and the SRS-22 is completed by the patient. The primary purpose of this study was to compare the EOSQ-24 and SRS-22 in patients with CS. The secondary purpose was to compare scores by age and also in developmentally delayed patients. We hypothesized that the SRS-22 is appropriate for children with EOS from CS who do not have a diagnosis of developmental delay.

Methods:

This was a prospective comparative study. A prospective institutional CS database was queried to identify patients who had the EOSQ-24 and SRS-22 completed at the same time point. Children without a diagnosis of developmental delay completed both questionnaires if they understood the questions, regardless of age. Otherwise, the caregiver completed both questionnaires. For the analysis, similar questions were matched so that the EOSQ-24 questions fit into the SRS-22 domains of Function, Pain, Mental Health, and Satisfaction. Pearson correlation coefficients (r) were used to compare domain scores, with r≥0.70 indicating a strong relationship.

Results:

The final study group included 98 patients. The average age at completion of the questionnaires was 9.5 years. A strong correlation was found for all domains except Satisfaction when the patient or caregiver completed both questionnaires. Subanalysis demonstrated the strongest relationship between domains in the age group 0 to 5 years. In developmentally delayed patients, a weak correlation was noted for all domain scores except Pain, which showed a strong correlation. There was a strong correlation for Pain and a weak correlation for Satisfaction domains across all subgroups.

Conclusions:

The SRS-22 may be appropriate for children with EOS from CS who do not have a diagnosis of developmental delay. Our findings suggest that the results of previous studies that collected the SRS-22 and future studies that collect the EOSQ-24 can be correlated. It remains unclear which questionnaire is more suitable for developmentally delayed patients.

Level of Evidence:

Level I—diagnostic.
A RANDOMIZED PAIRED-EYE TRIAL OF INTRAVITREAL DEXAMETHASONE IMPLANT FOR CYSTOID MACULAR EDEMA IN RETINITIS PIGMENTOSA
Authors: Park Un Chul , Park Jung Hyun , Ma Dae Joong , Cho In Hwan , Oh Baek-Lok , Yu Hyeong Gon
Published: June 2019

Purpose:

To evaluate the efficacy and safety of intravitreal dexamethasone (DEX) implant in retinitis pigmentosa patients with cystoid macular edema (CME).

Methods:

In this randomized, noncontrolled, paired-eye, single crossover clinical trial, one eye of retinitis pigmentosa patients with bilateral CME with central macular thickness of >250 µm was randomized to intravitreal DEX implant while the fellow eye was observed. Both eyes were started on topical dorzolamide. At Month 6, DEX implant was eligible for both eyes when CME was >250 µm. Patients were followed up until Month 12. Primary outcome measures were the central macular thickness and best-corrected visual acuity changes from baseline at Month 2.

Results:

Fourteen patients with bilateral RP-CME were included. Study eyes showed significant central macular thickness decrease (median, −147.5 µm; P = 0.001) and best-corrected visual acuity improvement (median, +6 letters; P = 0.001) at Month 2, but not at Month 6. Intravitreal DEX implant at Month 6 produced comparable efficacy to baseline treatment in 11 fellow eyes and 12 study eyes. Topical dorzolamide did not show significant therapeutic efficacy. During 12 months, elevated intraocular pressure of >21 mmHg and cataract progression were observed in 14.3% and 40.0% of study eyes.

Conclusion:

Intravitreal DEX implant can both reduce macular thickness and improve vision in RP-CME, while repeated injection is required.
Initial development of an attention-deficit/hyperactivity disorder visual analog scale for rapid assessment of medication effects
Authors: Woolsey Colleen , Smoldon Jeremy , Devney Robert
Published: June 2019

Attention-deficit/hyperactivity disorder (ADHD) is a commonly occurring neurodevelopmental disorder in children and young adults. If under or inadequately treated, long-term morbidity, mortality, increased social, and health care costs may follow. Standardized assessment tools aid in accurate diagnosis and ongoing treatment modifications; however, they are underused by providers at follow-up visits. This article discusses the development of an assessment tool, presents initial data on the use of a nonstandardized visual analog scale (VAS), and re-emphasizes the importance of regular inclusion of standardized rating scales during periodic reassessments. A targeted literature search of PubMed, Articles+, ERIC, CINAHL, and Google Scholar was performed and findings were reported. An interview with the developer was conducted along with a chart review comparing those using and not using the VAS. The use of the VAS may improve appointment efficiency and result in more thorough symptom assessment. Introduction of the VAS may remind providers of the importance of using standardized tools to reassess all ADHD symptoms regularly. Furthermore, the need for practice efficiency highlights the value of standardization of this VAS.
Minimal descriptions of cyclic memories
Authors: Paulsen Joseph D. , Keim Nathan C.
Published: June 2019

Many materials that are out of equilibrium can ‘learn’ one or more inputs that are repeatedly applied. Yet, a common framework for understanding such memories is lacking. Here, we construct minimal representations of cyclic memory behaviours as directed graphs, and we construct simple physically motivated models that produce the same graph structures. We show how a model of worn grass between park benches can produce multiple transient memories—a behaviour previously observed in dilute suspensions of particles and charge-density-wave conductors—and the Mullins effect. Isolating these behaviours in our simple model allows us to assess the necessary ingredients for these kinds of memory, and to quantify memory capacity. We contrast these behaviours with a simple Preisach model that produces return-point memory. Our analysis provides a unified method for comparing and diagnosing cyclic memory behaviours across different materials.
BigTop: A Three-Dimensional Virtual Reality tool for GWAS Visualization
Authors: Westreich Samuel T. , Nattestad Maria , Meyer Christopher
Published: June 2019

Background

Genome-wide association studies (GWAS) are typically visualized using a two-dimensional Manhattan plot, displaying chromosomal location of SNPs along the x-axis and the negative log-10 of their p-value on the y-axis. This traditional plot provides a broad overview of the results, but offers little opportunity for interaction or expansion of specific regions, and is unable to show additional dimensions of the dataset.

Results

We created BigTop, a visualization framework in virtual reality (VR), designed to render a Manhattan plot in three dimensions, wrapping the graph around the user in a simulated cylindrical room. BigTop uses the z-axis to display minor allele frequency of each SNP, allowing for the identification of allelic variants of genes. BigTop also offers additional interactivity, allowing users to select any individual SNP and receive expanded information, including SNP name, exact values, and gene location, if applicable. BigTop is built in JavaScript using the React and A-Frame frameworks, and can be rendered using commercially available VR headsets or in a two-dimensional web browser such as Google Chrome. Data is read into BigTop in JSON format, and can be provided as either JSON or a tab-separated text file.

Conclusions

Using additional dimensions and interactivity options offered through VR, we provide a new, interactive, three-dimensional representation of the traditional Manhattan plot for displaying and exploring GWAS data.
Protein expression of prenyltransferase subunits in postmortem schizophrenia dorsolateral prefrontal cortex
Authors: Pinner Anita L. , Mueller Toni M. , Alganem Khaled , McCullumsmith Robert , Meador-Woodruff James H.
Published: June 2019

The pathophysiology of schizophrenia includes altered neurotransmission, dysregulated intracellular signaling pathway activity, and abnormal dendritic morphology that contribute to deficits of synaptic plasticity in the disorder. These processes all require dynamic protein-protein interactions at cell membranes. Lipid modifications target proteins to membranes by increasing substrate hydrophobicity by the addition of a fatty acid or isoprenyl moiety, and recent evidence suggests that dysregulated post-translational lipid modifications may play a role in multiple neuropsychiatric disorders including schizophrenia. Consistent with these emerging findings, we have recently reported decreased protein S-palmitoylation in schizophrenia. Protein prenylation is a lipid modification that occurs upstream of S-palmitoylation on many protein substrates, facilitating membrane localization and activity of key intracellular signaling proteins. Accordingly, we hypothesized that in addition to palmitoylation, protein prenylation may be abnormal in schizophrenia. To test this, we assayed protein expression of the five prenyltransferase subunits (FNTA, FNTB, PGGT1B, RABGGTA, and RABGGTB) in postmortem dorsolateral prefrontal cortex from patients with schizophrenia and paired comparison subjects (N = 13 pairs). We found decreased levels of FNTA (14%), PGGT1B (13%), and RABGGTB (8%) in schizophrenia. To determine if upstream or downstream factors may be driving these changes, we also assayed protein expression of the isoprenoid synthases FDPS and GGPS1, and prenylation-dependent processing enzymes REC and ICMT. We found these upstream and downstream enzymes to have normal protein expression. To rule out effects from chronic antipsychotic treatment, we assayed FNTA, PGGT1B and RABGGTB in cortex from rats treated long-term with haloperidol decanoate, and found no change in the expression of these proteins. Given the role prenylation plays in localization of key signaling proteins found at the synapse, these data offer a potential mechanism underlying abnormal protein-protein interactions and protein localization in schizophrenia.
Layer 6 ensembles can selectively regulate the behavioral impact and layer-specific representation of sensory deviants
Authors: Voigts Jakob , Deister Christopher A , Moore Christopher I
Published: June 2019

Predictive models can enhance the salience of unanticipated input, and the neocortical laminar architecture is believed to be central to this computation. Here, we examined the role of a key potential node in model formation, layer (L) 6, using behavioral, electrophysiological and imaging methods in mouse somatosensory cortex. To test the contribution of L6, we applied weak optogenetic drive that changed which L6 neurons were sensory-responsive, without affecting overall firing rates in L6 or L2/3. This stimulation suppressed L2/3 deviance encoding, but maintained other stimulus encoding. The stimulation also selectively suppressed behavioral sensitivity to deviant stimuli without impacting baseline performance. In contrast, stronger L6 drive inhibited firing and suppressed overall sensory function. These findings indicate that, despite their sparse activity, specific ensembles of stimulus-driven L6 neurons are required to form neocortical predictions, and for their behavioral benefit.
Selective Activation of TASK-3-containing K+ Channels Reveals Their Therapeutic Potentials in Analgesia
Authors: Liao Ping , Qiu Yunguang , Mo Yiqing , Fu Jie , Song Zhenpeng , Huang Lu , Bai Suwen , Wang Yang , Zhu Jia-Jie , Tian Fuyun , Chen Zhuo , Pan Nanfang , Sun Er-Yi , Yang Linghui , Lan Xi , Chen Yinbin , Huang Dongping , Sun Peihua , Zhao Lifen , Yang Dehua , Lu Weiqiang , Yang Tingting , Xiao Junjie , Li Wei-Guang , Gao Zhaobing , Shen Bing , Zhang Qiansen , Liu Jin , Jiang Hualiang , Jiang Ruotian , Yang Huaiyu
Published: June 2019

The paucity of selective agonists for TASK-3, a member of two-pore domain K+ (K2P) channels, has contributed to our limited understanding of its biological functions. By targeting a novel druggable transmembrane cavity using a structure-based drug design approach, we discovered a biguanide compound, CHET3, as a highly selective allosteric activator for TASK-3-containing K2P channels, including TASK-3 homomer and TASK-3/TASK-1 heteromer. CHET3 displayed unexpectedly potent analgesic effects in vivo in a variety of acute and chronic pain models in rodents that could be abolished by pharmacology or genetic ablation of TASK-3. We further found that TASK-3-containing channels anatomically define a unique subset population of small-sized, TRPM8, TRPV1 or tyrosine hydroxylase-positive nociceptive sensory neurons and functionally regulate their membrane excitability, supporting CHET3 analgesia in thermal hyperalgesia and mechanical allodynia under chronic pain. Overall, our proof-of-concept study reveals TASK-3-containing K2P channels as a novel druggable target for treating pain.

One Sentence Summary

Identification of a novel drug target and its new hit compounds for developing new-generation non-opioid analgesics.
On the emergence ofCandida auris: climate change, azoles, swamps and birds
Authors: Casadevall Arturo , Kontoyiannis Dimitrios P. , Robert Vincent
Published: June 2019

The most enigmatic aspect of the rise ofCandida aurisas a human pathogen is that it emerged simultaneously in three continents with each clade being genetically distinct. Although new pathogenic fungal species are described regularly, these are mostly species associated with single cases in individuals who are immunosuppressed. In this study, we used phylogenetic analysis to compare C.auriswith temperature susceptibility of close relatives and use these results to argue that it may be the first example of a new fungal disease emerging from climate change with the caveat that many other factors could have contributed.
NADH dehydrogenases contribute to extracellular electron transfer byShewanella oneidensisMR-1 in bioelectrochemical systems
Authors: Madsen Cody S. , TerAvest Michaela A.
Published: June 2019

Shewanella oneidensisMR-1 is quickly becoming a synthetic biology workhorse for bioelectrochemical technologies due to a high level of understanding of its interaction with electrodes. Transmembrane electron transfer via the Mtr pathway has been well characterized, however, the role of NADH dehydrogenases in feeding electrons to Mtr has been only minimally studied inS. oneidensisMR-1. Four NADH dehydrogenases are encoded in the genome, suggesting significant metabolic flexibility in oxidizing NADH under a variety of conditions. Strains containing in-frame deletions of each of these dehydrogenases were grown in anodic bioelectrochemical systems with N-acetylglucosamine or D,L-lactate as the carbon source to determine impact on extracellular electron transfer. A strain lacking the two dehydrogenases essential for aerobic growth exhibited a severe growth defect with an anode (+0.4 VSHE) or Fe(III)-NTA as the terminal electron acceptor. Our study reveals that the same NADH dehydrogenase complexes are utilized under oxic conditions or with a high potential anode. Understanding the role of NADH in extracellular electron transfer may help improve biosensors and give insight into other applications for bioelectrochemical systems.

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