bluuebunny/crossref_metadata_2025 huggingface dataset:
Slope-Hunter: A robust method for index-event bias correction in genome-wide association studies of subsequent traits
Authors: Mahmoud Osama , Dudbridge Frank , Smith George Davey , Munafo Marcus , Tilling Kate
Published: February 2020

Background

Studying genetic associations with prognosis (e.g. survival, disability, subsequent disease events) is problematic due to selection bias - also termed index event bias or collider bias - whereby selection on disease status can induce associations between causes of incidence with prognosis. A current method for adjusting genetic associations for this bias assumes there is no genetic correlation between incidence and prognosis, which may not be a plausible assumption.

Methods

We propose an alternative, the ‘Slope-Hunter’ approach, which is unbiased even when there is genetic correlation between incidence and prognosis. Our approach has two stages. First, we use cluster-based techniques to identify: variants affecting neither incidence nor prognosis (these should not suffer bias and only a random sub-sample of them are retained in the analysis); variants affecting prognosis only (excluded from the analysis). Second, we fit a cluster-based model to identify the class of variants only affecting incidence, and use this class to estimate the adjustment factor.

Results

Simulation studies showed that the Slope-Hunter method reduces type-1 error by between 49%-85%, increases power by 1%-36%, reduces bias by 17%-47% compared to other methods in the presence of genetic correlation and performs as well as previous methods when there is no genetic correlation. Slope-Hunter and the previous methods perform less well as the proportion of variation in incidence explained by genetic variants affecting only incidence decreases.

Conclusions

The key assumption of Slope-Hunter is that the contribution of the set of genetic variants affecting incidence only to the heritability of incidence is at least as large as the contribution of those affecting both incidence and prognosis. When this assumption holds, our approach is unbiased in the presence of genetic correlation between incidence and progression, and performs no worse than alternative approaches even when there is no correlation. Bias-adjusting methods should be used to carry out causal analyses when conditioning on incidence.
An evolutionary trade-off between parasite virulence and dispersal at experimental invasion fronts
Authors: Nørgaard Louise Solveig , Zilio Giacomo , Saade Camille , Gougat-Barbera Claire , Hall Matthew D. , Fronhofer Emanuel A. , Kaltz Oliver
Published: February 2020

Eco-evolutionary processes may play an important role in the spatial spread of infectious disease. Current theory predicts more exploitative parasites to evolve in highly connected populations or at the front of spreading epidemics. However, many parasites rely on host dispersal to reach new populations. This may lead to conflict between local transmission and global spread, possibly counteracting selection for higher virulence. Here, we used the freshwater hostParamecium caudatumand its bacterial parasiteHolospora undulatato investigate parasite evolution under an experimental range expansion scenario with natural host dispersal. We find that parasites evolving at experimental range fronts favoured higher dispersal rates of infected hosts than did parasites evolving in core populations. Front parasites further showed lower levels of virulence (host division and survival) and delayed development of infection, consistent with parameter estimates from an epidemiological model that we fitted on experimental time-series data. This combined evidence suggests an evolutionary trade-off between virulence and host-mediated dispersal, with a concomitant reduction in the investment into horizontal transmission. Our experiment illustrates how parasite evolution can be shaped by divergent selection encountered in different segments of an epidemic wave. Such an interplay between demography and spatial selection has important implications for the understanding and management of emerging diseases, and, more generally, for biological invasions and other non-equilibrium scenarios of spreading populations.

SIGNIFICANCE STATEMENT

What drives parasite evolution in spatially expanding epidemics? Many parasites require dispersal of infected hosts to reach new patches, and this may produce specific adaptations enhancing spatial spread. We performed experimental range expansions in an aquatic model system, with natural dispersal of infected hosts. Parasites from experimental range fronts were less virulent and interfered less with host dispersal, but also invested less in horizontal transmission than parasites from the range core. Thus, dispersal adaptation at the front may come at a cost of reduced horizontal transmission, a trade-off rarely considered in theoretical models on parasite virulence evolution. These results have important implications in the context of emerging diseases, and for parasite evolution during biological invasions or other spatial non-equilibrium scenarios.
An adaptable analysis workflow for characterization of platelet spreading and morphology
Authors: Pike Jeremy A. , Simms Victoria A. , Smith Christopher W. , Morgan Neil V. , Khan Abdullah O. , Poulter Natalie S. , Styles Iain B. , Thomas Steven G.
Published: February 2020

The assessment of platelet spreading through light microscopy, and the subsequent quantification of parameters such as surface area and circularity, is a key assay for many platelet biologists. Here we present an analysis workflow which robustly segments individual platelets to facilitate the analysis of large numbers of cells while minimising user bias. Image segmentation is performed by interactive learning and touching platelets are separated with an efficient semi-automated protocol. We also use machine learning methods to robustly automate the classification of platelets into different subtypes. These adaptable and reproducible workflows are made freely available and are implemented using the open source software KNIME and ilastik.
Characterisation of factors contributing to the performance of nonwoven fibrous matrices as substrates for adenovirus vectored vaccine stabilisation
Authors: Dulal Pawan , Walters Adam A , Hawkins Nicholas , Claridge Tim DW , Kowal Katarzyna , Neill Steven , Russell Stephen J , Ritchie Adam , Ashfield Rebecca , Hill Adrian VS , Douglas Alexander D
Published: February 2020

The global network of fridges and freezers known as the “cold chain” can account for a significant proportion of the total cost of vaccination and is susceptible to failure. Cost-efficient techniques to enhance stability of vaccines could prevent such losses and improve vaccination coverage, particularly in low income countries. We have previously reported a novel, potentially less expensive thermostabilisation approach using a combination of simple sugars and glass micro-fibrous matrix, achieving an excellent recovery of vaccines after storage at supraphysiological temperatures. This matrix is, however, prone to fragmentation and currently not suitable for clinical translation.

Here, we report an investigation of alternative, potentially GMP compatible, fibrous matrices. A number of commercially-available matrices permitted good protein recovery, quality of sugar glass and moisture content of the dried product but did not achieve the thermostabilisation performance of the original glass fibre matrix. We therefore further investigated physical and chemical characteristics of the glass fibre matrix and its components. Our investigation shows that the polyvinyl alcohol present in the glass fibre matrix assists vaccine stability. This finding enabled us to develop a custom-produced matrix with encouraging performance, as an initial step towards a biocompatible matrix for clinical translation. We discuss the path to transfer of the technology into clinical use, including potential obstacles.
Detecting sex-linked genes using genotyped individuals sampled in natural populations
Authors: Käfer Jos , Lartillot Nicolas , Marais Gabriel A.B. , Picard Franck
Published: February 2020

We propose a method, SDpop, able to infer sex-linkage caused by recombination suppression typical of sex chromosomes. The method is based on the modeling of the allele and genotype frequencies of individuals of known sex in natural populations. It is implemented in a hierarchical probabilistic framework, accounting for different sources of error. It allows to statistically test for the presence or absence of sex chromosomes, and to infer sex-linked genes based on the posterior probabilities in the model. Furthermore, for gametologous sequences, the haplotype and level of nucleotide polymorphism of each copy can be inferred, as well as the divergence between both. We test the method using simulated and human sequencing data, and show that, for most cases, robust predictions are obtained with 5 to 10 individuals per sex.
Less physical activity and more varied and disrupted sleep is associated with a less favorable metabolic profile in adolescents
Authors: Rognvaldsdottir Vaka , Brychta Robert J. , Hrafnkelsdottir Soffia M. , Chen Kong Y. , Arngrimsson Sigurbjorn A. , Johannsson Erlingur , Guðmundsdottir Sigridur L.
Published: February 2020

Background

Sleep and physical activity are modifiable behaviors that play an important role in preventing overweight, obesity, and metabolic health problems. Studies of the association between concurrent objective measures of sleep, physical activity, and metabolic risk factors among adolescents are limited.

Objective

The aim of the study was to examine the association between metabolic risk factors and objectively measured school day physical activity and sleep duration, quality, onset, and variability in adolescents.

Materials and Methods

We measured one school week of free-living sleep and physical activity with wrist actigraphy in 252 adolescents (146 girls), aged 15.8±0.3 years. Metabolic risk factors included body mass index, waist circumference, total body and trunk fat percentage, resting blood pressure, and fasting glucose and insulin levels. Multiple linear regression adjusted for sex, parental education, and day length was used to assess associations between metabolic risk factors and sleep and activity parameters.

Results

On average, participants went to bed at 00:22±0.88 hours and slept 6.2±0.7 hours/night, with 0.83±0.36 hours of awakenings/night. However, night-to-night variability in sleep duration (0.87±0.57 hours) and bedtime (0.79±0.58 hours) was considerable. Neither average sleep duration nor mean bedtime was associated with any metabolic risk factors. However, greater night-to-night variability in sleep duration was associated with higher total body (β=1.9±0.9 %/h, p=0.03) and trunk fat percentage (β=1.6±0.7 %/h, p=0.02), poorer sleep quality (more hours of awakening) was associated with higher systolic blood pressure (β=4.9±2.2 mmHg/h, p=0.03), and less physical activity was associated with higher trunk fat percentage (p=0.04) and insulin levels (p=0.01).

Conclusion

Greater nightly variation in sleep, lower sleep quality, and less physical activity was associated with a less favorable metabolic profile in adolescents. These findings support the idea that, along with an adequate amount of sleep and physical activity, a regular sleep schedule is important to the metabolic health of adolescents.
Utilization of a cell-penetrating peptide-adaptor for delivery of HPV protein E2 into cervical cancer cells to arrest cell growth and promote cell death
Authors: LeCher Julia C. , Didier Hope L. , Dickson Robert L. , Slaughter Lauren R. , Bejarano Juana C. , Ho Steven , Nowak Scott J. , Chrestensen Carol A. , McMurry Jonathan L.
Published: February 2020

Cervical cancer is the second leading cause of cancer deaths in women worldwide. Human papillomavirus (HPV) is the causative agent of nearly all forms of cervical cancer, which arises upon viral integration into the host genome and concurrent loss of regulatory gene E2. E2 protein regulates viral oncoproteins E6 and E7. Loss of E2 upon viral integration results in unregulated expression and activity of E6 and E7, which promotes carcinogenesis. Previous studies using gene-based delivery show that reintroduction of E2 into cervical cancer cell lines can reduce proliferative capacity and promote apoptosis. However, owing in part to limitations on transfectionin vivo, E2 reintroduction has yet to achieve therapeutic usefulness. A promising new approach is protein-based delivery systems utilizing cell-penetrating peptides (CPPs). CPPs readily traverse the plasma membrane and are able to carry with them biomolecular ‘cargos’ to which they are attached. Though more than two decades of research have been dedicated to their development for delivery of biomolecular therapeutics, the full potential of CPPs has yet to be realized as the field is hindered by the tendency of CPP-linked cargos to be trapped in endosomes as well as having significant off-target potentialin vivo. Using a CPP-adaptor system that reversibly binds cargo thereby overcoming the endosomal entrapment that hampers other CPP methods, bioactive E2 protein was delivered into living cervical cancer cells, resulting in inhibition of cellular proliferation and promotion of cell death in a time- and dose-dependent manner. The results suggest that this nucleic acid- and virus-free delivery method could be harnessed to develop novel, effective protein therapeutics for treatment of cervical cancer.
Effort-based decision-making and gross motor performance: Are they linked?
Authors: Gill Simone V. , Abplanalp Samuel J. , Keegan Laura , Fulford Daniel
Published: February 2020

The purpose of this study was to investigate the relationship between effort-based decision making and gross motor performance. Effort-based decision making was measured using a modified version of the Effort Expenditure for Rewards Task in which participants pressed a button on a keyboard to fill a bar on a screen for a monetary reward. Gross motor performance was measured with a walking task in which participants matched their steps to the beat of an audio metronome. We hypothesized that increased effort during the effort-based decision making task would be paired with an increase in steps taken per minute during the gross motor task. However, the results of this study indicated no relationship between the effort-based decision making task and the gross motor task. Planning rather than decision-making may have been the cognitive construct that governed our gross motor task. These findings can be beneficial when thinking about potential interventions for populations who experience deficits in motor performance and cognition as well as for understanding the relationship between both cognitive and motor performance in healthy adults.
Autophagy promotes cell and organismal survival by maintaining NAD(H) pools
Authors: Sedlackova Lucia , Otten Elsje G. , Scialo Filippo , Shapira David , Kataura Tetsushi , Carroll Bernadette , Seranova Elena , Rabanal-Ruiz Yoana , Kelly George , Stefanatos Rhoda , Nelson Glyn , Urselli Francesca , Acharjee Animesh , Kenneth Niall , Trushin Sergey , Zhang Tong , Bascom Charles C. , Tasseff Ryan , Isfort Robert J. , Oblong John E. , Trushina Eugenia , Imoto Masaya , Saiki Shinji , Lazarou Michael , Papamichos Chronakis Manolis , Maddocks Oliver D.K. , Sarkar Sovan , Sanz Alberto , Korolchuk Viktor I.
Published: February 2020

Autophagy is an essential catabolic process that promotes clearance of surplus or damaged intracellular components1. As a recycling process, autophagy is also important for the maintenance of cellular metabolites during periods of starvation2. Loss of autophagy is sufficient to cause cell death in animal models and is likely to contribute to tissue degeneration in a number of human diseases including neurodegenerative and lysosomal storage disorders3–7. However, it remains unclear which of the many cellular functions of autophagy primarily underlies its role in cell survival. Here we have identified a critical role of autophagy in the maintenance of nicotinamide adenine dinucleotide (NAD+/NADH) levels. In respiring cells, loss of autophagy caused NAD(H) depletion resulting in mitochondrial membrane depolarisation and cell death. We also found that maintenance of NAD(H) is an evolutionary conserved function of autophagy from yeast to human cells. Importantly, cell death and reduced viability of autophagy-deficient animal models can be partially reversed by supplementation with an NAD(H) precursor. Our study provides a mechanistic link between autophagy and NAD(H) metabolism and suggests that boosting NAD(H) levels may be an effective intervention strategy to prevent cell death and tissue degeneration in human diseases associated with autophagy dysfunction.
Telomere relocalization to the nuclear pore complex in response to replication stress
Authors: Pinzaru Alexandra M , Lamm Noa , al-Kareh Mike , Lazzerini-Denchi Eros , Cesare Anthony J , Sfeir Agnel
Published: February 2020

Mutations in the telomere binding protein, POT1 are associated with solid tumors and leukemias. POT1 alterations cause rapid telomere elongation, ATR kinase activation, telomere fragility, and accelerated tumor development. Here, we investigated the impact of mutant POT1 alleles through complementary genetic and proteomic approaches based on CRISPR-interference and biotin-based proximity labelling, respectively. These screens revealed that replication stress is a major vulnerability in cells expressing mutant POT1 and manifest in increased mitotic DNA synthesis (MiDAS) at telomeres. Our study also unveiled a role for the nuclear pore complex (NPC) in resolving replication defects at telomeres. Depletion of NPC subunits in the context of POT1 dysfunction increased DNA damage signaling and telomere fragility. Furthermore, we observed telomere repositioning to the nuclear periphery driven by nuclear F-actin polymerization in cells with POT1 mutations. In conclusion, our study establishes that relocalization of dysfunctional telomeres to the nuclear periphery is critical to preserve telomere repeat integrity.
Genomic novelty and process-level convergence in adaptation to whole genome duplication
Authors: Bohutínská Magdalena , Alston Mark , Monnahan Patrick , Mandáková Terezie , Bray Sian , Paajanen Pirita , Kolář Filip , Yant Levi
Published: February 2020

Whole genome duplication (WGD) occurs across kingdoms and can promote adaptation. However, a sudden increase in chromosome number, as well as changes in physiology, are traumatic to conserved processes. Previous work in Arabidopsis arenosa revealed a coordinated genomic response to WGD, involving physically interacting meiosis proteins, as well as changes related to cell cycle and ion homeostasis. Here we ask: is this coordinated shift in the same processes repeated in another species following WGD? To answer this, we resequenced and cytologically assessed replicated populations from a diploid/autotetraploid system, Cardamine amara, and test the hypothesis that gene and process-level convergence will be prevalent between these two WGDs adaptation events. Interestingly, we find that gene-level convergence is negligible, with no more in common than would be expected by chance. This was most clear at meiosis-related genes, consistent with our cytological assessment of somewhat lower meiotic stability in C. amara, despite establishment and broad occurrence of the autotetraploid in nature. In contrast, obvious convergence at the level of functional processes, including meiotic cell cycle, chromosome organisation and stress signalling was evident. This indicates that the two autotetraploids survived challenges attendant to WGD via contrasting solutions, modifying different players from similar processes. Overall, this work gives the first insight into the salient adaptations required to cope with a genome-doubled state and brings the first genomic evidence that autopolyploids can utilize multiple trajectories to achieve adaptation to WGD. We speculate that this flexibility increases the likelihood a nascent polyploid overcomes early stringent challenges to later access the spectrum of evolutionary opportunities of polyploidy.

Significance statement

Whole genome duplication (WGD) is a tremendous mutation and an important evolutionary force. It also presents immediate changes to meiosis and cell physiology that nascent polyploids must overcome to survive. Given the dual facts that WGD adaptation is difficult, but many lineages nevertheless survive WGD, we ask: how constrained are the evolutionary responses to a genome-doubled state? We previously identified candidate genes for WGD adaptation in Arabidopsis arenosa, which has natural diploid and tetraploid variants. Here we test for evolutionary convergence in adaptation to WGD in a species 17 million years distant, Cardamine amara. This work gives the first genomic insight into of how autopolyploids utilize multiple adaptive trajectories to manage a genome-doubled state.
Influences of age and pubertal status on number of perineuronal nets in the rat medial prefrontal cortex
Authors: Drzewiecki Carly M. , Willing Jari , Juraska Janice M.
Published: February 2020

The prefrontal cortex (PFC) is a late developing region of the cortex, and its protracted maturation during adolescence may confer a period of plasticity. Closure of critical, or sensitive, periods in sensory cortices coincides with perineuronal net (PNN) expression, leading to enhanced inhibitory function and synaptic stabilization. PNN density is known to increase across adolescence in the male rodent medial PFC (mPFC). However, the trajectory of female PNN development has not been explored nor has the potential role of pubertal onset in PNN expression. Here, we examined rats at four time points spanning adolescent development to quantify the number of PNNs in the mPFC, as well as the total volume of the prefrontal white matter. Additionally, because puberty coincides with broad behavioral and neuroanatomical changes, we collected tissue from age-matched pre- and post- pubertal siblings within a litter. Results indicate that both males and females show an increase the total number of mPFC PNNs and in white matter under the mPFC between postnatal day (P) 30 and P60. Male puberty did not affect PNNs, while female pubertal onset led to an abrupt decrease in the total number of PNNs that persisted through mid-adolescence before increasing at P60. This decrease in female rats may indicate a difference in timing of maximal plasticity between the sexes during adolescence.
Using genetic algorithms for estimating Weibull parameters with application to wind speed
Authors: Koca Melih Burak , Kilic Muhammet Burak , Şahin Yusuf
Published: February 2020

Renewable energy has become a prominent subject for researchers since fossil fuel reserves have been decreasing and are not promising to meet the energy demand of the future. Wind takes an important place in renewable energy resources and there is extensive research on wind speed modeling. Herein, one of the most commonly used distributions for wind speed modeling is the Weibull distribution with its simplicity and flexibility. Maximum likelihood (ML) method is the most frequently used technique in Weibull parameter estimation. Iterative techniques such as Newton-Raphson (NR) use random initial values to obtain the ML estimators of the parameters of the Weibull distribution. Therefore, the success of the iterative techniques highly depends on the initial value selection. In order to deliver a solution to the initial value problem, genetic algorithm (GA) is considered to obtain the estimators of the model parameters. The ML estimators obtained using the GA and NR techniques are compared with the method of moments (MoM) estimators via Monte Carlo simulation and wind speed applications. The results show that the ML estimators obtained using GA present superiority over MoM and the ML estimators obtained using NR.
Numerical Investigation on the Effect of Different Physiological Cancerous Breast Parameters on the Output of Microwave Ablation
Authors: Kumar Jatin , Repaka Ramjee
Published: February 2020

Microwave ablation (MWA) is a newly developed minimally invasive tumor therapy which possesses several advantages over the existing thermal therapies. Despite the several advantages, MWA also suffers same disadvantages similar to other thermal therapies like poor control over ablation volume. Sensitivity of different tissue parameters is the key factor to design a MWA protocol. In this work, sensitivity analysis has been conducted to quantify the effect of three cancerous breast parameters, viz., breast composition, tumor location, and tumor size, on the efficacy of MWA of breast cancer. Ablation volume has been taken as the indicator of the ablation efficacy during MWA procedure. A Taguchi's design of experimental approach has been utilized to optimize the number of simulations required for the analysis and then analysis of variance (ANOVA) has been performed to predict the most sensitive parameter along with their individual contribution. Finite element approach-based simulations have been performed in a multiphysics software. First, a grid-independent study has been established to optimize the number of mesh elements and to reduce the computational cost. Then, after finding the most optimum grid size, all the simulations have been performed in accordance with the protocol obtained from Taguchi's design of experiment approach and finally statistical analysis software has been used for analyzing Taguchi's design. It has been found that, the breast composition to be the most significant factor, with maximum contribution in ablation volume, among three considered factors followed by tumor location and tumor size, respectively.
A Simple Analytical Model for Head Estimation of Noncavitating Inducers With Arbitrary Shape
Authors: Mohr Matthias , Gwiasda Björn , Böhle Martin
Published: February 2020

Although the increase of suction performance is the primary objective when applying inducers to centrifugal pumps and the combined head of inducer and main impeller is finally to be judged, it is helpful for the designer to estimate the head and flow characteristics provided by the inducer alone in the early design stage. With this knowledge, the matching of inducer and pump impeller can possibly be improved and the limiting of operational range that is essentially due to the application of the inducer can be detected in the initial design phase. An already published method (Li, W.-G., 2011, “Head Curve of Noncavitating Inducer,” ASME J. Fluids Eng., 133(2), p. 024501.), which was limited to the application on inducers with cylindrical hub and shroud, is extended to work with arbitrary-shaped inducer geometries. This article discusses the method of performance estimation and its implementation in detail. Four different designs based on common guidelines available in the open literature are analyzed with the help of the method described. The predicted head curves are compared to experimental and computational results obtained as part of an earlier study by the authors. Despite the simplicity of the method, good agreement of the head estimations with the experimental and numerical data can be observed. This indicates that the loss model seems to be applicable not only to cylindrical inducers but also to arbitrary-shaped inducers. Investigations of the exit conditions show that the analytical flow model only roughly represents the simulated flow distribution at the inducer outlet.
Electrical Conductivity and Structural Evolution of Polymer-Derived SiC Ceramics Pyrolyzed From 1200 °C to 1800 °C
Authors: Chowdhury Md Atiqur Rahman , Wang Kewei , Jia Yujun , Xu Chengying
Published: February 2020

Room temperature (RT) electrical conductivity and microstructure of polymer-derived SiC pyrolyzed at temperatures ranging from 1200 °C to 1800 °C were studied. We have shown that both free carbon content and pyrolysis temperature have significant effects on the DC conductivity of polymer derived ceramic (PDC) SiC. The RT DC conductivity of the PDC SiC increased gradually with increasing pyrolysis temperature, and it drastically increases 3 orders of magnitude after 1500 °C. This high electrical conductivity occurs due to the formation of a network of turbostratic carbon (percolative network). Below the percolation regime, hopping enables the electron movement from one carbon cluster site to another. Microstructural investigation with X-ray diffraction (XRD), Raman, and transmission electron microscopy (TEM) analysis showed that the crystal size of SiC increases with increasing pyrolysis temperature, and carbon clusters act as an inhibitor for grain growth at lower pyrolysis temperature. Upon dissociation of clusters, accelerated grain growth occurs and graphitization of carbon occurs along the grains.
Organ Dose Calculations Using ICRP Adult Voxel Phantoms and TRIPOLI-4 Monte Carlo Code
Authors: Lee Yi-Kang
Published: February 2020

The ICRP 110 adult male and female voxel phantoms are the official computational models representing the ICRP (International Commission on Radiological Protection) Reference Male and Reference Female. In 2018, the Working Group 6 (WG6) of European Radiation Dosimetry Group (EURADOS) organized a study on the usage of the ICRP voxel reference phantoms. Organ dose calculation tasks with radiation transport codes were proposed in occupational, environmental, and medical dosimetry. The TRIPOLI-4 Monte Carlo radiation transport code has been widely used in radiation shielding, criticality safety, and reactor physics fields for supporting French nuclear energy research and industrial applications. To enhance the application fields of TRIPOLI-4, the 2018 EURADOS-WG6 tasks are being taken into account by using different features of the TRIPOLI-4 code. In this work, the ICRP reference voxel phantoms were first adapted into TRIPOLI-4. More than 14 × 106 voxels were represented in a mixed lattice geometry including 140 organs-tissues and 52 tissue media. Diverse exposure scenarios were then investigated by using 60Co and 241Am gamma-ray sources, 16N beta source, and 10 keV neutron source. The TRIPOLI-4 standard nuclear data library was utilized on these neutron, photon, electron, and positron-coupled transport calculations. Energy deposition estimators for electron, positron, neutron, and photon coupled with mesh tally options were used to calculate the organ absorbed dose DT and the effective dose E. TRIPOLI-4 calculation methods and primary results for the EURADOS-WG6 voxel phantom exercise on organ dose study tasks are reported here.
Study on Fatigue of Tubing Joint Thread Induced by Vibration in HTHP Ultradeep Wells
Authors: Mou Yisheng , Lian Zhanghua , Lin Tiejun , Zhang Qiang , Liu Yang
Published: February 2020

According to the tubing string failure statistics in the oilfield, fatigue crack of tubing joint thread in high temperature high pressure (HTHP) ultradeep gas wells remains a problem because it can cause tubing strength degradation, tubing fracture failure, well workover, and even well abandonment. In order to obtain a better understanding of tubing thread fatigue and quantify the fatigue life of tubing joint thread in HTHP ultradeep wells, experimental study, elastic–plastic mechanical simulation, and multi-axial fatigue calculation are carried out in this paper. Based on the similarity theory, the vibration mechanical testing device of the tubing string is designed, and the multi-axial load of the tubing joint thread in the actual working condition is obtained. Meanwhile, tubing joint BX1 thread model is established with ansys software, and the stress distribution of tubing joint thread is analyzed on the boundary condition acquired from experiments of vibration test of tubing string. Finally, according to the multi-axial fatigue theory, the fatigue life prediction value of the tubing thread made of Super 13Cr110 and Super 15Cr125 is compared and analyzed. The work presented in this paper can provide theoretical method and technological basis for the study on the frequent failure mechanism of tubing joint thread in HTHP ultradeep gas wells.
Technical comment on “Synovial fibroblast-neutrophil interactions promote pathogenic adaptive immunity in rheumatoid arthritis”
Authors: Salinger A. J. , Dubuke M. L. , Carmona-Rivera C. , Maurais A. J. , Shaffer S. A. , Weerapana E. , Thompson P. R. , Kaplan M. J.
Published: February 2020

Reassessment of citrullinome cargo in neutrophil extracellular traps confirms the presence of citrullinated peptides.
The Central Iapetus magmatic province: An updated review and link with the ca. 580 Ma Gaskiers glaciation
Authors: Youbi Nasrrddine , Ernst Richard E. , Söderlund Ulf , Boumehdi Moulay Ahmed , Lahna Abdelhak Ait , Tassinari Colombo Celso Gaeta , Moume Warda El , Bensalah Mohamed Khalil
Published: February 2020

Large igneous provinces and associated silicic magmatism can have a significant global climatic effect, so we explored the relationship between the large igneous province record and the ca. 580 Ma Gaskiers glaciation. The late Ediacaran glaciation exists on at least 14 different paleocontinental blocks, and assuming synchroneity, this Gaskiers glaciation was likely of short duration, with estimates ranging from 1.6 m.y. to 340 k.y. The Central Iapetus magmatic province event found in Laurentia, Baltica, and West Africa consists of multiple pulses in the range 620–520 Ma, with the ca. 580 Ma pulse particularly well developed in North Africa. Based on the age matches of 580–570 Ma Central Iapetus magmatic province pulses and the Gaskiers glaciation, and taking into consideration that there is no robust evidence for a major meteorite impact at the time of the Gaskiers onset, we propose that: (1) the initial silicic ca. 580 Ma pulse of the Ouarzazate event (Anti-Atlas of Morocco) helped to trigger the Gaskiers glaciation, and (2) global warming associated with the subsequent ca. 579–570 Ma continental flood basalts, marking the second stage of the Ouarzazate event, helped to end the ice age.
Amplifying factors leading to the collapse of primary producers during the Chicxulub impact and Deccan Traps eruptions
Authors: Le Hir Guillaume , Fluteau Frédéric , Suchéras-Marx Baptiste , Goddéris Yves
Published: February 2020

The latest Cretaceous (Maastrichtian) through earliest Paleogene (Danian) interval was a time marked by one of the five major mass extinctions in Earth’s history. The synthesis of published data permits the temporal correlation of the Cretaceous-Paleogene boundary crisis with two major geological events: (1) the Chicxulub impact, discovered in the Yucatán Peninsula (Mexico), and (2) eruption of the Deccan Traps large igneous province, located on the west-central Indian plateau. In this study, environmental and biological consequences from the Chicxulub impact and emplacement of the Deccan continental flood basalts were explored using a climate-carbon-biodiversity coupled model called the ECO-GEOCLIM model. The novelty of this study was investigation into the ways in which abiotic factors (temperature, pH, and calcite saturation state) acted on various marine organisms to determine the primary productivity and biodiversity changes in response to a drastic environmental change. Results showed that the combination of Deccan volcanism with a 10-km-diameter impactor would lead to global warming (3.5 °C) caused by rising carbon dioxide (CO2) concentration (+470 ppmv), interrupted by a succession of short-term cooling events, provided by a “shielding effect” due to the formation of sulfate aerosols. The consequences related to these climate changes were the decrease of the surface ocean pH by 0.2 (from 8.0 to 7.8), while the deep ocean pH dropped by 0.4 (from 7.8 to 7.4). Without requiring any additional perturbations, these environmental disturbances led to a drastic decrease of the biomass of calcifying species and their biodiversity by ~80%, while the biodiversity of noncalcifying species was reduced by ~60%. We also suggest that the short-lived acidification caused by the Chicxulub impact, when combined with eruption of the Deccan Traps, may explain the severity of the extinction among pelagic calcifying species.
Spin correlations in parton shower simulations
Authors: Richardson Peter , Webster Stephen
Published: February 2020

Spin correlations are an important, but often neglected, effect in modern Monte Carlo event generators. We show that they can be fully incorporated in Herwig7 using the algorithm originally proposed by Collins and Knowles in all stages of the event generation process and between the different stages of the event generation. In this paper we present the final missing ingredient, correlations in both the angular-ordered and dipole shower algorithms and between the parton shower and hard production and decay processes.
Quantum steering for continuous variable in de Sitter space
Authors: Wen Cuihong , Wang Jieci , Jing Jiliang
Published: February 2020

We study the distribution of quantum steerability for continuous variables between two causally disconnected open charts in de Sitter space. It is shown that quantum steerability suffers from “sudden death” in de Sitter space, which is quite different from the behaviors of entanglement and discord because the latter always survives and the former vanishes only in the limit of infinite curvature. It is found that the attainment of maximal steerability asymmetry indicates a transition between unidirectional steerable and bidirectional steerable. Unlike in the flat space, the asymmetry of quantum steerability can be completely destroyed in the limit of infinite curvature for the conformal and massless scalar fields in de Sitter space.
Drug Abuse Research Trend Investigation with Text Mining
Authors: Chou Li-Wei , Chang Kang-Ming , Puspitasari Ira
Published: February 2020

Drug abuse poses great physical and psychological harm to humans, thereby attracting scholarly attention. It often requires experience and time for a researcher, just entering this field, to find an appropriate method to study drug abuse issue. It is crucial for researchers to rapidly understand the existing research on a particular topic and be able to propose an effective new research method. Text mining analysis has been widely applied in recent years, and this study integrated the text mining method into a review of drug abuse research. Through searches for keywords related to the drug abuse, all related publications were identified and downloaded from PubMed. After removing the duplicate and incomplete literature, the retained data were imported for analysis through text mining. A total of 19,843 papers were analyzed, and the text mining technique was used to search for keyword and questionnaire types. The results showed the associations between these questionnaires, with the top five being the Addiction Severity Index (16.44%), the Quality of Life survey (5.01%), the Beck Depression Inventory (3.24%), the Addiction Research Center Inventory (2.81%), and the Profile of Mood States (1.10%). Specifically, the Addiction Severity Index was most commonly used in combination with Quality of Life scales. In conclusion, association analysis is useful to extract core knowledge. Researchers can learn and visualize the latest research trend.
Mathematical Formulation of Feedback Linearizing Control of Doubly Fed Induction Generator Including Magnetic Saturation Effects
Authors: Jose Julia Tholath , Chattopadhyay Adhir Baran
Published: February 2020

This paper proposes a control methodology based on feedback linearization for a doubly fed induction generator (DFIG) incorporating the magnetic saturation. The feedback linearization algebraically converts a nonlinear system model into a linear model, allowing the use of linear control techniques. Feedback linearization control depends on the model of the system and is therefore sensitive to parameter variations. The doubly fed induction generator (DFIG) operating under the magnetic saturation conditions results in the nonlinear variation of magnetizing inductance, which affects the performance of the control algorithm. From this stand point, on the basis of the dynamic model of the doubly fed induction generator considering magnetic saturation, the feedback linearizing control technique has been formulated. The mathematical model of the doubly fed induction generator, integrating the magnetic saturation has been formulated in the stator flux-oriented reference frame with rotor current and stator magnetizing current as state variables. Simulation studies demonstrate that the inclusion of magnetic saturation in the feedback linearization control of the doubly fed induction generator model increases its accuracy and results in a more efficient and reliable synthesis of the control algorithm.
Lipoprotein(a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein(a) Molecule
Authors: Jawi Motasim M. , Frohlich Jiri , Chan Sammy Y.
Published: February 2020

Lipoprotein(a) [Lp(a)], aka “Lp little a”, was discovered in the 1960s in the lab of the Norwegian physician Kåre Berg. Since then, we have greatly improved our knowledge of lipids and cardiovascular disease (CVD). Lp(a) is an enigmatic class of lipoprotein that is exclusively formed in the liver and comprises two main components, a single copy of apolipoprotein (apo) B-100 (apo-B100) tethered to a single copy of a protein denoted as apolipoprotein(a) apo(a). Plasma levels of Lp(a) increase soon after birth to a steady concentration within a few months of life. In adults, Lp(a) levels range widely from <2 to 2500 mg/L. Evidence that elevated Lp(a) levels >300 mg/L contribute to CVD is significant. The improvement of isoform-independent assays, together with the insight from epidemiologic studies, meta-analyses, genome-wide association studies, and Mendelian randomization studies, has established Lp(a) as the single most common independent genetically inherited causal risk factor for CVD. This breakthrough elevated Lp(a) from a biomarker of atherosclerotic risk to a target of therapy. With the emergence of promising second-generation antisense therapy, we hope that we can answer the question of whether Lp(a) is ready for prime-time clinic use. In this review, we present an update on the metabolism, pathophysiology, and current/future medical interventions for high levels of Lp(a).
Acetazolamide Intoxication in an Elderly Patient with Diabetes and Chronic Renal Failure after Cataract Surgery
Authors: Kerber Juliana Maria , de Mello Juliana Dias , Moura Karolinny Borinelli de Aquino , da Silva Gustavo Cardoso , Wawrzeniak Iuri Christmann , Rech Tatiana Helena
Published: February 2020

Carbonic anhydrase inhibitors, such as acetazolamide, are widely used in the treatment of open-angle glaucoma. Severe metabolic acidosis is a rare complication of acetazolamide use, and life-threatening acidosis occurs most commonly in elderly patients, in patients with advanced renal failure, and in patients with diabetes. We describe an unusual case of an elderly patient with diabetic nephropathy and chronic renal failure who presented to the emergency department with severe metabolic acidosis and coma after exposure to high doses of acetazolamide in the postoperative period of ophthalmic surgery. As symptoms of acetazolamide intoxication and uremia are similar, high suspicion is required to detect excessive plasma drug concentrations and intoxication in patients presenting with concomitant uremia. Clinical symptoms are potentially reversible with prompt diagnosis and treatment, including supportive treatment, bicarbonate therapy, and renal replacement therapy. Hemodialysis is particularly helpful in the management of acetazolamide overdose as the medication is dialyzable.
Automated Emergency Vehicle Control Strategy Based on Automated Driving Controls
Authors: So Jaehyun (Jason) , Kang Jiwon , Park Sangmin , Park Inseon , Lee Jongdeok
Published: February 2020

This study proposes an integrated driving control strategy by taking advantage of the automated driving technology at the individual vehicle level and the traffic signal preemption strategy at the traffic infrastructure level. This aims to facilitate an automated driving-based emergency vehicle control and ultimately to achieve efficient and safe control of emergency vehicles. To this end, this study developed the integrated emergency vehicle control logic, implemented the logic in the microscopic traffic simulation environment using the simulation software’s application programming interface capability, and evaluated the impacts of the proposed emergency vehicle control logic in the aspects of mobility and safety with different driving aggressiveness and preemption initiation settings. The study’s results show that the proposed emergency vehicle control logic achieved benefits on mobility and safety and the benefits of emergency vehicle control strategy can be maximized when the signal preemption and the automated driving control operate in collaboration. Therefore, the proposed integrated approach of automated driving controls and signal preemption will be a great reference for enhancing automated driving technologies supporting a safe and fast mobility solution.
CD14 and ALPK1 Affect Expression of Tight Junction Components and Proinflammatory Mediators upon Bacterial Stimulation in a Colonic 3D Organoid Model
Authors: Brooks Pascal , zur Bruegge Talke , Boyle Erin C. , Kalies Stefan , Villarreal Santiago Nahuel , Liese Andrea , Bleich André , Buettner Manuela
Published: February 2020

Cd14 and Alpk1 both encode pathogen recognition receptors and are known candidate genes for affecting severity in inflammatory bowel diseases. CD14 acts as a coreceptor for bacterial lipopolysaccharide (LPS), while ALPK1 senses ADP-D-glycero-beta-D-manno-heptose, a metabolic intermediate of LPS biosynthesis. Intestinal barrier integrity can be influenced by CD14, whereas to date, the role of ALPK1 in maintaining barrier function remains unknown. We used colon-derived 3D organoids, first characterised for growth, proliferation, stem cell markers, and expression of tight junction (TJ) components using qPCR and immunohistochemistry. They showed characteristic crypt stem cells, apical shedding of dead cells, and TJ formation. Afterwards, organoids of different genotypes (WT, Il10-/-, Cd14-/-, and Alpk1-/-) were then stimulated with either LPS or Escherichia coli Nissle 1917 (EcN). Gene expression and protein levels of cytokines and TJ components were analysed. WT organoids increased expression of Tnfα and tight junction components. Cd14-/- organoids expressed significantly less Tnfα and Ocln after LPS stimulation than WT organoids but reacted similarly to WT organoids after EcN stimulation. In contrast, compared to WT, Alpk1-/- organoids showed decreased expression of different TJ and cytokine genes in response to EcN but not LPS. However, Western blotting revealed an effect of ALPK1 on TJ protein levels. These findings demonstrate that Cd14, but not Alpk1, alters the response to LPS stimulation in colonic epithelial cells, whereas Alpk1 is involved in the response upon bacterial challenge.