bluuebunny/crossref_metadata_2025 huggingface dataset:
Automated Sentiment Analysis of Text Data with NLTK
Authors: Yao Jiawei
Published: May 2019

At present, most of researches in natural language processing primarily are focused on deep learning way to solve accuracy problems. This paper discusses a branch of natural language processing, sentiment analysis. In order to implement the function of sentiment analysis efficiently, we built an algorithm by calling the NLTK library firstly. As a result, this method can roughly obtain the emotional scores of different sentences and compare them with the scores given by human being who create these sentences. The results are presented by correlation calculation and images such as boxplot. The analysis of the images demonstrates the deficiency of the method. In addition, for the results, we found the direction of learning to solve the accuracy problems and made reasonable arrangements and planning.
On the fundamental group of complete manifolds with almost Euclidean volume growth
Authors: Wan Jianming
Published: May 2019

It is proved that the fundamental group of a complete Riemannian manifold with nonnegative Ricci curvature and certain volume growth conditions is trivial or finite.
Astral microtubule forces alter nuclear organization and inhibit DNA repair in budding yeast
Authors: Estrem Cassi , Moore Jeffrey K.
Published: May 2019

Dividing cells must balance the maintenance of genome integrity with the generation of cytoskeletal forces that control chromosome position. In this study, we investigate how forces on astral microtubules impact the genome during cell division by using live-cell imaging of the cytoskeleton, chromatin, and DNA damage repair in budding yeast. Our results demonstrate that dynein-dependent forces on astral microtubules are propagated through the spindle during nuclear migration and when in excess can increase the frequency of double-stranded breaks (DSBs). Under these conditions, we find that homology-directed repair of DSBs is delayed, indicating antagonism between nuclear migration and the mechanism of homology-directed repair. These effects are partially rescued by mutants that weaken pericentric cohesion or mutants that decrease constriction on the nucleus as it moves through the bud neck. We propose that minimizing nuclear movement aids in finding a donor strand for homologous recombination.
Retrograde trafficking and quality control of yeast synaptobrevin, Snc1, are conferred by its transmembrane domain
Authors: Ma Mengxiao , Burd Christopher G.
Published: May 2019

Synaptobrevin/vesicle-associated membrane protein 2 (VAMP2) is an essential soluble N-ethyl maleimide–sensitive factor attachment protein receptor (SNARE) protein that has been extensively studied in its role in synaptic vesicle fusion. However, sorting and trafficking of VAMP2 within the endosomal system is not well understood. Here, we use the yeast VAMP2 homologue Snc1 to investigate the pathways and signals required for endocytic trafficking. We identify two genetically distinct retrieval pathways from the endosomal system: a plasma membrane recycling pathway that requires the Rcy1 F-box protein and a retrograde pathway originating from the multivesicular/prevacuole endosome dependent on the Snx4-Atg20 sorting nexin complex. Lysine residues within the transmembrane domain of Snc1 are necessary for presentation of a Snx4-Atg20–dependent sorting signal located within its juxtamembrane region. Mutations of the transmembrane lysine residues ablate retrograde sorting and subject Snc1 to quality control via sorting into the degradative multivesicular endosome pathway. Degradative sorting requires lysine residues in the juxtamembrane region of Snc1 and is mediated by the Rsp5 ubiquitin ligase and its transmembrane adapters, Ear1 and Ssh4, which localize to endosome and vacuole membranes. This study shows that Snc1 is trafficked between the endosomal system and the Golgi apparatus via multiple pathways and provides evidence for protein quality control surveillance of a SNARE protein in the endo-vacuolar system.
Plural grounding and the principle of sufficient reason
Authors: Werner Jonas
Published: May 2019

In a recent article published in this journal, Kris McDaniel (2019) proposes a variant of Peter van Inwagen’s (1983: 202–4) argument against the principle of sufficient reason that makes crucial use of plural grounding. In this response paper I object to McDaniel’s argument. I argue that there is no notion of plural grounding available that is both irreflexive in the sense required for the argument to go through and general enough to formulate the principle of sufficient reason as proposed by McDaniel.
Providing carbon skeletons to sustain amide synthesis in roots underlines the suitability of Brachypodium distachyon for the study of ammonium stress in cereals
Authors: de la Peña Marlon , González-Moro María Begoña , Marino Daniel
Published: May 2019

Plants mainly acquire N from the soil in the form of nitrate (NO3−) or ammonium (NH4+). Ammonium-based nutrition is gaining interest because it helps to avoid the environmental pollution associated with nitrate fertilization. However, in general, plants prefer NO3− and indeed, when growing only with NH4+ they can encounter so-called ammonium stress. Since Brachypodium distachyon is a useful model species for the study of monocot physiology and genetics, we chose it to characterize performance under ammonium nutrition. Brachypodium distachyon Bd21 plants were grown hydroponically in 1 or 2.5 mM NO3− or NH4+. Nitrogen and carbon metabolism associated with NH4+ assimilation was evaluated in terms of tissue contents of NO3−, NH4+, K, Mg, Ca, amino acids and organic acids together with tricarboxylic acid (TCA) cycle and NH4+-assimilating enzyme activities and RNA transcript levels. The roots behaved as a physiological barrier preventing NH4+ translocation to aerial parts, as indicated by a sizeable accumulation of NH4+, Asn and Gln in the roots. A continuing high NH4+ assimilation rate was made possible by a tuning of the TCA cycle and its associated anaplerotic pathways to match 2-oxoglutarate and oxaloacetate demand for Gln and Asn synthesis. These results show B. distachyon to be a highly suitable tool for the study of the physiological, molecular and genetic basis of ammonium nutrition in cereals.
Iterative feature representations improve N4-methylcytosine site prediction
Authors: Wei Leyi , Su Ran , Luan Shasha , Liao Zhijun , Manavalan Balachandran , Zou Quan , Shi Xiaolong
Published: May 2019

Motivation

Accurate identification of N4-methylcytosine (4mC) modifications in a genome wide can provide insights into their biological functions and mechanisms. Machine learning recently have become effective approaches for computational identification of 4mC sites in genome. Unfortunately, existing methods cannot achieve satisfactory performance, owing to the lack of effective DNA feature representations that are capable to capture the characteristics of 4mC modifications.

Results

In this work, we developed a new predictor named 4mcPred-IFL, aiming to identify 4mC sites. To represent and capture discriminative features, we proposed an iterative feature representation algorithm that enables to learn informative features from several sequential models in a supervised iterative mode. Our analysis results showed that the feature representations learnt by our algorithm can capture the discriminative distribution characteristics between 4mC sites and non-4mC sites, enlarging the decision margin between the positives and negatives in feature space. Additionally, by evaluating and comparing our predictor with the state-of-the-art predictors on benchmark datasets, we demonstrate that our predictor can identify 4mC sites more accurately.

Availability and implementation

The user-friendly webserver that implements the proposed 4mcPred-IFL is well established, and is freely accessible at http://server.malab.cn/4mcPred-IFL.

Supplementary information

Supplementary data are available at Bioinformatics online.
The new marker YKL-40, a molecule related to inflammation, is associated with cardiovascular events in stable haemodialysis patients
Authors: Vega Almudena , Sanchez-Niño Maria Dolores , Ortiz Alberto , Abad Soraya , Macías Nicolás , Aragoncillo Inés , Santos Alba , García-Prieto Ana , Torres Esther , Hernández Andrés , Sánchez-Cámara Luis , Hurtado Esther , Valiño-Rivas Lara , Luño José
Published: May 2019

Background

YKL-40 is a glycoprotein associated with inflammatory conditions, including atherosclerosis and endothelial dysfunction. The objective was to analyse serum YKL-40 levels in a haemodialysis population and explore their association with dialysis dosing measures, inflammation, body composition and development of cardiovascular (CV) events.

Methods

We performed a prospective study of 78 chronic haemodialysis patients enrolled in 2013 and followed up until 2018. At baseline, serum YKL-40, inflammatory and nutrition markers and body composition were assessed. During a median follow-up of 43 (interquartile range 24–66) months, CV events were recorded.

Results

The mean age of patients was 62 ± 16 years and 66% were men. The mean YKL-40 was 207 ± 106 ng/dL. Higher YKL-40 levels were associated with lower Kt/Vurea, convective volume, serum albumin and prealbumin and with higher troponin T. During follow-up, 50% developed CV events. Cox analysis showed an association between CV events and YKL-40, diabetes, hypertension, C-reactive protein, lower prealbumin, β2-microglobulin, glycosylated haemoglobin and troponin T values. The multivariate Cox analysis confirmed an independent association between CV events and YKL-40 {hazard ratio [HR] 1.067 [95% confidence interval (CI) 1.009–1.211]; P: 0.042}, troponin T [HR 1.037 (95% CI 1.009–1.683); P: 0.007], lower prealbumin [HR 0.827 (95% CI 0.224–0.988); P: 0.009] and diabetes [HR 2.103 (95% CI 1.554–3.172); P: 0.008]. Kaplan–Meier confirmed the association between CV events and YKL-40 (log rank 7.28; P = 0.007).

Conclusions

YKL-40 is associated with CV events in haemodialysis patients. Higher dialysis dose and convective volume are associated with lower serum YKL-40 levels.
Development of coupling controlled polymerizations by adapter-ligation in mate-pair sequencing for detection of various genomic variants in one single assay
Authors: Dong Zirui , Zhao Xia , Li Qiaoling , Yang Zhenjun , Xi Yang , Alexeev Andrei , Shen Hanjie , Wang Ou , Ruan Jie , Ren Han , Wei Hanmin , Qi Xiaojuan , Li Jiguang , Zhu Xiaofan , Zhang Yanyan , Dai Peng , Kong Xiangdong , Kirkconnell Killeen , Alferov Oleg , Giles Shane , Yamtich Jennifer , Kermani Bahram G , Dong Chao , Liu Pengjuan , Mi Zilan , Zhang Wenwei , Xu Xun , Drmanac Radoje , Choy Kwong Wai , Jiang Yuan
Published: May 2019

The diversity of disease presentations warrants one single assay for detection and delineation of various genomic disorders. Herein, we describe a gel-free and biotin-capture-free mate-pair method through coupling Controlled Polymerizations by Adapter-Ligation (CP-AL). We first demonstrated the feasibility and ease-of-use in monitoring DNA nick translation and primer extension by limiting the nucleotide input. By coupling these two controlled polymerizations by a reported non-conventional adapter-ligation reaction 3′ branch ligation, we evidenced that CP-AL significantly increased DNA circularization efficiency (by 4-fold) and was applicable for different sequencing methods but at a faction of current cost. Its advantages were further demonstrated by fully elimination of small-insert-contaminated (by 39.3-fold) with a ∼50% increment of physical coverage, and producing uniform genome/exome coverage and the lowest chimeric rate. It achieved single-nucleotide variants detection with sensitivity and specificity up to 97.3 and 99.7%, respectively, compared with data from small-insert libraries. In addition, this method can provide a comprehensive delineation of structural rearrangements, evidenced by a potential diagnosis in a patient with oligo-atheno-terato-spermia. Moreover, it enables accurate mutation identification by integration of genomic variants from different aberration types. Overall, it provides a potential single-integrated solution for detecting various genomic variants, facilitating a genetic diagnosis in human diseases.
Differences in Orientation Behavior and Female Attraction by Rhyzopertha dominica (Coleoptera: Bostrichidae) in a Homogeneous Resource Patch
Authors: Cordeiro Erick M G , Campbell James F , Phillips Thomas
Published: May 2019

The objectives of the study are to understand how naïve beetles disperse after emerging as an adult in a homogeneous resource patch. We compared the movement of adult male and female Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) using a laboratory and a field-collected strain during the first 2 d after their emergence from the wheat kernel in which they developed. We first asked if naïve male and female beetles show any innate orientation pattern. Males showed an upward orientation bias during the first day, but not in the second, whereas females had a random pattern of orientation in both days of evaluation. No significant differences were observed between the two strains. Given that males release an aggregation pheromone, we next asked if the upward movement of males improved their ability to be found by a naïve female. The presence of a male, whether above or below a newly emerged female, changed the females’ movement direction from random to bias towards the male. In contrast, free-walking males exhibited the same upward movement bias on the first day regardless of the position of the caged male. Only on the second day did male movement change to the opposite direction of the caged male. Here, we report differences between males and females’ movement orientation strategies and their response to males producing aggregation pheromone within the grain mass. Our data may improve our understanding of pheromone attraction and help us to develop better monitoring and control tools.
The Effect of Regional Gender-Role Attitudes on Female Labour Supply: A Longitudinal Test Using the BHPS, 1991–2007
Authors: Uunk Wilfred , Lersch Philipp M
Published: May 2019

Despite considerable variation in gender-role attitudes across contexts and its claimed influence on female labour supply, studies provide little support for a contextual gender-role attitude effect. In this study, we reassess the contextual gender-role attitude effect on female labour supply because earlier studies are hampered by two shortcomings: (a) they are cross-nationally comparative, which makes it difficult to distinguish contextual attitude from institutional effects; (b) they are cross-sectional, which may bias the contextual attitude effect. We aim to overcome these shortcomings by performing longitudinal panel analyses on data from the British Household Panel Survey 1991–2007, comparing 138 counties within the United Kingdom. Our fixed-effects regressions report no significant and substantial association of regional, egalitarian gender-role attitudes with individual women’s labour supply, a finding which both holds for women’s probability to be active in the labour market and employed women’s working hours, and for women with and without (young) children. Female labour supply appears to be much stronger associated with women’s own and partners’ gender-role attitudes, in particular for women with (young) children.
A systems perspective on the importance of global health strategy developments for accomplishing today’s Sustainable Development Goals
Authors: Byskov Jens , Maluka Stephen , Marchal Bruno , Shayo Elizabeth H , Blystad Astrid , Bukachi Salome , Zulu Joseph M , Michelo Charles , Hurtig Anna-Karin , Bloch Paul
Published: May 2019

Priority setting within health systems has not led to accountable, fair and sustainable solutions to improving population health. Providers, users and other stakeholders each have their own health and service priorities based on selected evidence, own values, expertise and preferences. Based on a historical account, this article analyses if contemporary health systems are appropriate to optimize population health within the framework of cross cutting targets of the Sustainable Development Goals (SDGs). We applied a scoping review approach to identify and review literature of scientific databases and other programmatic web and library-based documents on historical and contemporary health systems policies and strategies at the global level. Early literature supported the 1977 launching of the global target of Health for All by the year 2000. Reviewed literature was used to provide a historical overview of systems components of global health strategies through describing the conceptualizations of health determinants, user involvement and mechanisms of priority setting over time, and analysing the importance of historical developments on barriers and opportunities to accomplish the SDGs. Definitions, scope and application of health systems-associated priority setting fluctuated and main health determinants and user influence on global health systems and priority setting remained limited. In exploring reasons for the identified lack of SDG-associated health systems and priority setting processes, we discuss issues of accountability, vested interests, ethics and democratic legitimacy as conditional for future sustainability of population health. To accomplish the SDGs health systems must engage beyond their own sector boundary. New approaches to Health in All Policies and One Health may be conducive for scaling up more democratic and inclusive priority setting processes based on proper process guidelines from successful pilots. Sustainable development depends on population preferences supported by technical and managerial expertise.
Age-Related Survival Differences in Patients With Inflammatory Bowel Disease–Associated Colorectal Cancer: A Population-Based Cohort Study
Authors: Bogach Jessica , Pond Gregory , Eskicioglu Cagla , Seow Hsien
Published: May 2019

Despite similar stage at presentation and rates of cancer treatment, patients under 65 with inflammatory bowel disease associated colorectal cancer have worse survival outcomes than patients under 65 with sporadic colorectal cancer. This difference diminishes over age 65.
Vaccine-Preventable Diseases in Hospitalized Patients With Inflammatory Bowel Disease: A Nationwide Cohort Analysis
Authors: Vinsard Daniela Guerrero , Wakefield Dorothy , Vaziri Haleh , Karagozian Raffi
Published: May 2019

The aim of this study is to investigate the most frequent vaccine-preventable diseases for which IBD patients are hospitalized and thereby, contribute with evidence for vaccination guidelines. This study reports important data regarding the burden of HZV in patients with IBD.
Plant Evolutionary Ecology in the Age of the Extended Evolutionary Synthesis
Authors: Olson Mark E
Published: May 2019

Plant ecology is increasingly turning to evolutionary questions, just as evolutionary biology pushes out of the strictures of the Modern Synthesis into what some regard as an “Extended Evolutionary Synthesis.” As plant ecology becomes increasingly evolutionary, it is essential to ask how aspects of the Extended Synthesis might impinge on plant ecological theory and practice. I examine the contribution of plant evolutionary ecology to niche construction theory, as well as the potential for developmental systems theory and genes-as-followers adaptive evolution, all important post-Modern Synthesis themes, in providing novel perspectives for plant evolutionary ecology. I also examine ways that overcoming dichotomies such as “genetic vs. plastic” and “constraint vs. adaptation” provide fertile opportunities for plant evolutionary ecologists. Along the same lines, outgrowing vague concepts such as “stress” and replacing them with more precise terminology in all cases provides vastly increased causal clarity. As a result, the synthetic path that plant ecologists are blazing, becoming more evolutionary every year, bodes extremely well for the field, with vast potential for expansion into important scientific territory.
Integrated Pest Management of Longan (Sapindales: Sapindaceae) in Vietnam
Authors: Tran Hanh , Van Hoa Nguyen , Muniappan Rangaswamy , Amrine James , Naidu Rayapati , Gilbertson Robert , Sidhu Jaspreet
Published: May 2019

This paper describes the current state of pests and diseases of longan (Dimocarpus longan Lour.) and their management in Vietnam. Longan is the third most cultivated fruit crop and second major fruit crop exported from Vietnam. Brief descriptions of arthropod pests Eriophyes dimocarpi Kuang (Acari: Eriophyidae), Conogethes punctiferalis Guenée (Lepidoptera: Crambidae), Conopomorpha sinensis Bradley (Lepidoptera: Gracillariidae), Conopomorpha litchiella Bradley (Lepidoptera: Gracillariidae), Tessaratoma papillosa Drury (Hemiptera: Tessaratomidae), Eudocima phalonia L. comb. (Lepidoptera: Erebidae), oriental fruit fly Bactrocera dorsalis Hendel (Diptera: Tephretidae), Planococcus lilacinus Cockerell (Hemiptera: Pseudococcidae), Drepanococcus chiton Green (Hemiptera: Coccidae), and Cornegenapsylla sinica Yang & Li (Hemiptera: Psyllidae) and fungal diseases Phytophthora palmivora Butler (Peronosporales: Peronosporaceae), Colletotrichum gloeosporioides (Penz.) Penz. & Sacc. (Incertaesedis: Glomerellaceae), and Ceratocystis fimbriata Ellis & Halsted (Microascales: Ceratocystidaceae) affecting longan are given. The longan witches’ broom syndrome is a major factor causing 50–86% annual crop loss in Vietnam and it has been considered the primary constraint in production. The causative agent of this syndrome has been identified as the eriophyid mite E. dimocarpi. Deployment of Integrated Pest Management strategies for longan production in Vietnam is outlined.
TRIM14 promotes endothelial activation via activating NF-κB signaling pathway
Authors: Huang Xuan , Li Yong , Li Xiuzhen , Fan Daping , Xin Hong-Bo , Fu Mingui
Published: May 2019

Endothelial activation by proinflammatory cytokines is closely associated to the pathogenesis of atherosclerosis and other vascular diseases; however, the molecular mechanisms controlling endothelial activation are not fully understood. Here we identify TRIM14 as a new positive regulator of endothelial activation via activating NF-κB signal pathway. TRIM14 is highly expressed in human vascular endothelial cells (ECs) and markedly induced by inflammatory stimuli such as TNF-α, IL-1β, and LPS. Overexpression of TRIM14 significantly increased the expression of adhesion molecules such as VCAM-1, ICAM-1, E-selectin, and cytokines such as CCL2, IL-8, CXCL-1, and TNF-α in activated ECs and by which it facilitated monocyte adhesion to ECs. Conversely, knockdown of TRIM14 has opposite effect on endothelial activation. Upon TNF-α stimulation, TRIM14 is recruited to IKK complex via directly binding to NEMO and promotes the phosphorylation of IκBα and p65, which is dependent on its K63-linked ubiquitination. Meanwhile, p65 can directly bind to the promoter regions of human TRIM14 gene and control its mRNA transcription. Finally, TRIM14 protein level is significantly upregulated in mouse and human atheroma compared to normal arteries. Taken together, these results indicate that TRIM14–NF-κB forms a positive feedback loop to enhance EC activation and TRIM14 may be a potential therapeutic target for vascular inflammatory diseases such as atherosclerosis.
Effect of atherosclerosis and the protective effect of the antioxidant vitamin E on the rabbit cerebellum
Authors: Elbeltagy Maha Abdel Fatah , Elkholy Wael Badr , Salman Ahmed Said
Published: May 2019

Background

Atherosclerosis is a major cardiovascular disease and one of the commonest causes of mortality in the world. Speech, balance, fine motor control and cognition are affected by atherosclerosis of cerebellar arteries. This study investigated the protective role of vitamin E against induced atherosclerosis in the rabbit cerebellum.

Materials and methods

Forty Rex New Zealand adult male rabbits were randomly divided into four groups (10 rabbits each). Group I was designated as the control and received an ordinary diet. Group II received an ordinary diet, but with vitamin E (12 mg/kg/day) added. Group III were given an ordinary diet along with 1% cholesterol powder for 6 weeks. Finally, group IV received an ordinary diet with both 1% cholesterol powder and vitamin E (12 mg/kg/day). Cerebellum samples were stained with haematoxylin and eosin and examined using light microscopy, along with quantitative immunohistochemical assessments of the expression of caspase-3, glial fibrillary acidic protein (GFAP) and inducible nitric oxide synthase (iNOS).

Results

Cerebellum sections from cholesterol-treated rabbits showed ischaemic changes as fibre density decreased, with vacuolation of the molecular layer, and deformed and shrunken Purkinje cells. A significant increase in caspase-3, GFAP and iNOS immunoreactivity was found. However, vitamin E administration reduced these ischaemic manifestations.

Conclusions

The results demonstrate the neurological protective role of vitamin E therapy in atherosclerosis.
Physical Employment Standards for UK Royal Navy Personnel: A Survey of Tasks That Require Muscle Strength and Endurance
Authors: Brown Piete E H , Fallowfield Joanne L
Published: May 2019

Introduction

Physical Employment Standards (PES) safeguard the requirement to create a suitable job-person fit in military occupations, and in doing so mitigate some operational and musculoskeletal injury risk. The primary purpose of this research was to identify critical – physically demanding tasks performed by UK Royal Navy (RN) seafarers to inform the development of a muscle strength and endurance-based PES. A secondary purpose was to explore possible sex and age-based differences in subjective ratings of occupational task physical demand.

Materials and Methods

In accordance with the Ministry of Defence Research Ethics Committee, 515 Naval personnel (443 males, 72 females; aged 30.2 ± 7.3 years) completed an anonymous survey that rated the physical demand (from no to very high), criticality (from not to critically important), and frequency (from seldom to several times per day) of 25 common sea-going tasks on a one to five scale. An a priori criteria was applied to down-select a shortlist of the most critical and physically demanding tasks (i.e., median task criticality and task physical demand scores of ≥4, and ≥3, respectively). A Mann-Whitney and Kruskal-Wallis test explored sex and age-based differences in subjective physical demand ratings.

Results

Ten (out of 25) tasks met the critical – physical demand criteria, which included the four task categories of fire fighting, damage control, casualty handling, and basic movement/transit tasks. Casualty handling emerged as the single most physically demanding task category performed by seafarers, which was rated to have “high” physical demand (4 on the 1 to 5 scale). Sex and age-based differences in subjective ratings of task physical demand were equivocal, with females rating 3 (out of the 25 tasks), and 40–51 year olds rating 4 (out of 25 tasks) to have a higher physical demand than males and 19–29 year olds, respectively.

Conclusion

Ten criterion tasks were identified and should undergo a further job analysis to inform the development of strength-based PES for the RN.
Efficient, divergence-free, high-order MHD on 3D spherical meshes with optimal geodesic meshing
Authors: Balsara Dinshaw S , Florinski Vladimir , Garain Sudip , Subramanian Sethupathy , Gurski Katharine F
Published: May 2019

There is a great need in several areas of astrophysics and space physics to carry out high order of accuracy, divergence-free MHD simulations on spherical meshes. This requires us to pay careful attention to the interplay between mesh quality and numerical algorithms. Methods have been designed that fundamentally integrate high-order isoparametric mappings with the other high accuracy algorithms that are needed for divergence-free MHD simulations on geodesic meshes. The goal of this paper is to document such algorithms that are implemented in the geodesic mesh version of the RIEMANN code. The fluid variables are reconstructed using a special kind of WENO-AO algorithm that integrates the mesh geometry into the reconstruction process from the ground-up. A novel divergence-free reconstruction strategy for the magnetic field that performs efficiently at all orders, even on isoparametrically mapped meshes, is then presented. The MHD equations are evolved in space and time using a novel ADER predictor algorithm that is efficiently adapted to the isoparametrically mapped geometry. The application of one-dimensional and multidimensional Riemann solvers at suitable locations on the mesh then provides the corrector step. The corrector step for the magnetic field uses a Yee-type staggering of magnetic fields. This results in a scheme with divergence-free update for the magnetic field. The use of ADER enables a one-step update that only requires one messaging operation per complete timestep. This is very beneficial for parallel processing. Several accuracy tests are presented as are stringent test problems. PetaScale performance is also demonstrated on the largest available supercomputers.
QBiC-Pred: quantitative predictions of transcription factor binding changes due to sequence variants
Authors: Martin Vincentius , Zhao Jingkang , Afek Ariel , Mielko Zachery , Gordân Raluca
Published: May 2019

Non-coding genetic variants/mutations can play functional roles in the cell by disrupting regulatory interactions between transcription factors (TFs) and their genomic target sites. For most human TFs, a myriad of DNA-binding models are available and could be used to predict the effects of DNA mutations on TF binding. However, information on the quality of these models is scarce, making it hard to evaluate the statistical significance of predicted binding changes. Here, we present QBiC-Pred, a web server for predicting quantitative TF binding changes due to nucleotide variants. QBiC-Pred uses regression models of TF binding specificity trained on high-throughput in vitro data. The training is done using ordinary least squares (OLS), and we leverage distributional results associated with OLS estimation to compute, for each predicted change in TF binding, a P-value reflecting our confidence in the predicted effect. We show that OLS models are accurate in predicting the effects of mutations on TF binding in vitro and in vivo, outperforming widely-used PWM models as well as recently developed deep learning models of specificity. QBiC-Pred takes as input mutation datasets in several formats, and it allows post-processing of the results through a user-friendly web interface. QBiC-Pred is freely available at http://qbic.genome.duke.edu.
Pattern preferences of DNA nucleotide motifs by polyamines putrescine2+, spermidine3+ and spermine4+
Authors: Perepelytsya Sergiy , Uličný Jozef , Laaksonen Aatto , Mocci Francesca
Published: May 2019

The interactions of natural polyamines (putrescine2+, spermidine3+ and spermine4+) with DNA double helix are studied to characterize their nucleotide sequence pattern preference. Atomistic Molecular Dynamics simulations have been carried out for three systems consisting of the same DNA fragment d(CGCGAATTCGCGAATTCGCG) with different polyamines. The results show that polyamine molecules are localized with well-recognized patterns along the double helix with different residence times. We observed a clear hierarchy in the residence times of the polyamines, with the longest residence time (ca 100ns) in the minor groove. The analysis of the sequence dependence shows that polyamine molecules prefer the A-tract regions of the minor groove – in its narrowest part. The preferable localization of putrescine2+, spermidine3+ and spermine4+ in the minor groove with A-tract motifs is correlated with modulation of the groove width by a specific nucleotide sequences. We did develop a theoretical model pointing to the electrostatic interactions as the main driving force in this phenomenon, making it even more prominent for polyamines with higher charges. The results of the study explain the specificity of polyamine interactions with A-tract region of the DNA double helix which is also observed in experiments.
Identification and Estimation in Non-Fundamental Structural VARMA Models
Authors: Gouriéroux Christian , Monfort Alain , Renne Jean-Paul
Published: May 2019

The basic assumption of a structural vector autoregressive moving average (SVARMA) model is that it is driven by a white noise whose components are uncorrelated or independent and can be interpreted as economic shocks, called “structural” shocks. When the errors are Gaussian, independence is equivalent to non-correlation and these models face two identification issues. The first identification problem is “static” and is due to the fact that there is an infinite number of linear transformations of a given random vector making its components uncorrelated. The second identification problem is “dynamic” and is a consequence of the fact that, even if a SVARMA admits a non-invertible moving average (MA) matrix polynomial, it may feature the same second-order dynamic properties as a VARMA process in which the MA matrix polynomials are invertible (the fundamental representation). The aim of this article is to explain that these difficulties are mainly due to the Gaussian assumption, and that both identification challenges are solved in a non-Gaussian framework if the structural shocks are assumed to be instantaneously and serially independent. We develop new parametric and semi-parametric estimation methods that accommodate non-fundamentalness in the MA dynamics. The functioning and performances of these methods are illustrated by applications conducted on both simulated and real data.
Development and Validation of a Dynamic Risk Prediction Model to Forecast Psychosis Onset in Patients at Clinical High Risk
Authors: Studerus Erich , Beck Katharina , Fusar-Poli Paolo , Riecher-Rössler Anita
Published: May 2019

The prediction of outcomes in patients at Clinical High Risk for Psychosis (CHR-P) almost exclusively relies on static data obtained at a single snapshot in time (ie, baseline data). Although the CHR-P symptoms are intrinsically evolving over time, available prediction models cannot be dynamically updated to reflect these changes. Hence, the aim of this study was to develop and internally validate a dynamic risk prediction model (joint model) and to implement this model in a user-friendly online risk calculator. Furthermore, we aimed to explore the prognostic performance of extended dynamic risk prediction models and to compare static with dynamic prediction. One hundred ninety-six CHR-P patients were recruited as part of the “Basel Früherkennung von Psychosen” (FePsy) study. Psychopathology and transition to psychosis was assessed at regular intervals for up to 5 years using the Brief Psychiatric Rating Scale-Expanded (BPRS-E). Various specifications of joint models were compared with regard to their cross-validated prognostic performance. We developed and internally validated a joint model that predicts psychosis onset from BPRS-E disorganization and years of education at baseline and BPRS-E positive symptoms during the follow-up with good prognostic performance. The model was implemented as online risk calculator (http://www.fepsy.ch/DPRP/). The use of extended joint models slightly increased the prognostic accuracy compared to basic joint models, and dynamic models showed a higher prognostic accuracy than static models. Our results confirm that extended joint modeling could improve the prediction of psychosis in CHR-P patients. We implemented the first online risk calculator that can dynamically update psychosis risk prediction.
Increasing sulfate levels show a differential impact on synthetic communities comprising different methanogens and a sulfate reducer
Authors: Chen Jing , Wade Matthew J. , Dolfing Jan , Soyer Orkun S.
Published: May 2019

Methane-producing microbial communities are of ecological and biotechnological interest. Syntrophic interactions among sulfate reducers and aceto/hydrogenotrophic and obligate hydrogenotrophic methanogens form a key component of these communities, yet, the impact of these different syntrophic routes on methane production and their stability against sulfate availability are not well understood. Here, we construct model synthetic communities using a sulfate reducer and two types of methanogens representing different methanogenesis routes. We find that tri-cultures with both routes increase methane production by almost twofold compared to co-cultures and are stable in the absence of sulfate. With increasing sulfate, system stability and productivity decreases and does so faster in communities with aceto/hydrogenotrophic methanogens despite the continued presence of acetate. We show that this is due to a shift in the metabolism of these methanogens towards co-utilization of hydrogen with acetate. These findings indicate the important role of hydrogen dynamics in the stability and productivity of syntrophic communities.
Correlated evolution of neck length and leg length in birds
Authors: Böhmer Christine , Plateau Olivia , Cornette Raphäel , Abourachid Anick
Published: May 2019

Despite a diversity of about 10 000 extant species, the sophisticated avian ‘body plan’ has not much changed once it was achieved around 160 Ma after the origin of powered flight. All birds are bipedal having wings, a rigid trunk, a short and ossified tail, a three-segmented leg and digitigrade feet. The avian neck, however, has always been regarded as a classic example of high variability ranging from short necks in songbirds to extremely long, serpentine necks in herons. Yet, the wide array of small to very large species makes it difficult to evaluate the actual neck length. Here, we investigate the evolution of the vertebral formulae in the neck of birds and the scaling relationships between skeletal dimensions and body size. Cervical count in birds is strongly related to phylogeny, with only some specialists having an exceptional number of vertebrae in the neck. In contrast with mammals, the length of the cervical vertebral column increases as body size increases and, thus, body size does not constrain neck length in birds. Indeed, neck length scales isometrically with total leg length suggesting a correlated evolution between both modules. The strong integration between the cervical and pelvic module in birds is in contrast with the decoupling of the fore- and hindlimb module and may be the result of the loss of a functionally versatile forelimb due to the evolution of powered flight.
Mie scattering and microparticle-based characterization of heavy metal ions and classification by statistical inference methods
Authors: Klug Katherine E. , Jennings Christian M. , Lytal Nicholas , An Lingling , Yoon Jeong-Yeol
Published: May 2019

A straightforward method for classifying heavy metal ions in water is proposed using statistical classification and clustering techniques from non-specific microparticle scattering data. A set of carboxylated polystyrene microparticles of sizes 0.91, 0.75 and 0.40 µm was mixed with the solutions of nine heavy metal ions and two control cations, and scattering measurements were collected at two angles optimized for scattering from non-aggregated and aggregated particles. Classification of these observations was conducted and compared among several machine learning techniques, including linear discriminant analysis, support vector machine analysis, K-means clustering and K-medians clustering. This study found the highest classification accuracy using the linear discriminant and support vector machine analysis, each reporting high classification rates for heavy metal ions with respect to the model. This may be attributed to moderate correlation between detection angle and particle size. These classification models provide reasonable discrimination between most ion species, with the highest distinction seen for Pb(II), Cd(II), Ni(II) and Co(II), followed by Fe(II) and Fe(III), potentially due to its known sorption with carboxyl groups. The support vector machine analysis was also applied to three different mixture solutions representing leaching from pipes and mine tailings, and showed good correlation with single-species data, specifically with Pb(II) and Ni(II). With more expansive training data and further processing, this method shows promise for low-cost and portable heavy metal identification and sensing.
Drivers of sex ratio bias in the eastern bongo: lower inbreeding increases the probability of being born male
Authors: Malo Aurelio F. , Gilbert Tania C. , Riordan Philip
Published: May 2019

Parent sex ratio allocation has consequences for individual fitness, population dynamics, and conservation. Theory predicts that parents should adjust offspring sex ratio when the fitness returns of producing male or female offspring varies. Previous studies have assumed that only mothers are capable of biasing offspring sex ratios, but have neglected fathers, given the expectation of an equal proportion of X- and Y-chromosome-bearing (CBS) sperm in ejaculates due to sex chromosome segregation at meiosis. This assumption has been recently refuted and both paternal fertility and paternal genetic quality have been shown to bias sex ratios. Here, we simultaneously test the relative contribution of paternal, maternal, and individual genetic quality, as measured by inbreeding, on the probability of being born a son or a daughter, using pedigree and lifelong offspring sex ratio data for the eastern bongo (
Tragelaphus eurycerus isaaci
). Our models showed first, that surprisingly, as individual inbreeding decreases the probability of being born male increases, second, that paternal genetic effects on sex ratio were stronger than maternal genetic effects (which were absent). Furthermore, paternal effects were opposite in sign to those predicted; father inbreeding increases the probability of having sons. Previous paternal effects have been interpreted as adaptive due to sex-specific inbreeding depression for reproductive traits. We argue that in the eastern bongo, the opposite sign of the paternal effect on sex ratios results from a reversed sex-specific inbreeding depression pattern (present for female but not male reproductive traits). We anticipate that this research will help stimulate research on evolutionary constraints to sex ratios. Finally, the results open a new avenue of research to predict sex ratio allocation in an applied conservation context. Future models of sex ratio allocation should also include the predicted inbreeding level of the offspring and paternal inbreeding levels.
Theta-phase dependent neuronal coding during sequence learning in human single neurons
Authors: Reddy Leila , Self Matthew W. , Zoefel Benedikt , Poncet Marlène , Possel Jessy K. , Peters Judith C. , Baayen Johannes C. , Idema Sander , VanRullen Rufin , Roelfsema Pieter R.
Published: May 2019

The ability to maintain a sequence of items in short-term memory (STM) is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human subjects learned sequences of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining their sequential order in STM.
Predicting patient-specific radiotherapy responses in head and neck cancer to personalize radiation dose fractionation
Authors: Enderling Heiko , Sunassee Enakshi , Caudell Jimmy J.
Published: May 2019

Human papillomavirus (HPV) related oropharyngeal cancer (OPC) is one of the few types of cancers increasing in incidence. HPV+ OPC treatment with radiotherapy (RT) provides 75-95% five-year locoregional control (LRC). Why some but not all patients with similar clinical stage and molecular profile are controlled remains unknown. We propose the proliferation saturation index, PSI, as a mathematical modeling biomarker of tumor growth and RT response. The model predicts that patients with PSI<0.75 are likely to be cured by radiation, and that hyperfractionated radiation could improve response rates for patients with higher PSI that are predicted to fail standard of care RT. Prospective evaluation is currently ongoing.
Sir2 non-autonomously controls differentiation of germline cells in the ovary ofDrosophila melanogaster
Authors: Ayyub Champakali , Kolthur-Seetharam Ullas
Published: May 2019

InDrosophilaovary, germline stem cells (GSCs) reside in a somatic cell niche that provides them signals necessary for their survival and development. Escort cells (ECs), one of the constituents of the niche, help in differentiation of GSC daughter cells. Since nutritional state is known to affect oogenesis, we set out to address the role of a metabolic sensor. NAD-dependent Sir2 is known to acts as a regulator of organismal life-span in a diet dependent manner. Our current study reveals that Sir2 in somatic cells is necessary for germline differentiation. Specifically, Sir2 in ECs upregulates Dpp signalling giving rise to tumorous germaria. In addition to this non-autonomous role of Sir2 in regulation of the germline cell homeostasis, we have demonstrated that EC-specific Sir2 has a role in attributing the identity of Cap cells as well as in de-differentiation of germline cells. Our study also shows that a genetic interaction betweenSir2andupd2is important for the development of germline cells. Thus, we provide novel insights into the role of Sir2 in ovary development.