bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parkinson disease age of onset GWAS: defining heritability, genetic loci and a-synuclein mechanisms
Authors: Blauwendraat Cornelis , Heilbron Karl , Vallerga Costanza L. , Bandres-Ciga Sara , von Coelln Rainer , Pihlstrøm Lasse , Simón-Sánchez Javier , Schulte Claudia , Sharma Manu , Krohn Lynne , Siitonen Ari , Iwaki Hirotaka , Leonard Hampton , Noyce Alastair J. , Tan Manuela , Gibbs J. Raphael , Hernandez Dena G. , Scholz Sonja W. , Jankovic Joseph , Shulman Lisa M. , Lesage Suzanne , Corvol Jean-Christophe , Brice Alexis , van Hilten Jacobus J. , Marinus Johan ,   The 23andMe Research Team, Tienari Pentti , Majamaa Kari , Toft Mathias , Grosset Donald G. , Gasser Thomas , Heutink Peter , Shulman Joshua M , Wood Nicolas , Hardy John , Morris Huw R , Hinds David A. , Gratten Jacob , Visscher Peter M. , Gan-Or Ziv , Nalls Mike A. , Singleton Andrew B. ,   for the International Parkinson’s Disease Genomics Consortium (IPDGC)
Published: October 2018

AbstractIncreasing evidence supports an extensive and complex genetic contribution to Parkinson’s disease (PD). Previous genome-wide association studies (GWAS) have shed light on the genetic basis of risk for this disease. However, the genetic determinants of PD age of onset are largely unknown. Here we performed an age of onset GWAS based on 28,568 PD cases. We estimated that the heritability of PD age of onset due to common genetic variation was ~0.11, lower than the overall heritability of risk for PD (~0.27) likely in part because of the subjective nature of this measure. We found two genome-wide significant association signals, one at SNCA and the other a protein-coding variant in TMEM175, both of which are known PD risk loci and a Bonferroni corrected significant effect at other known PD risk loci, INPP5F/BAG3, FAM47E/SCARB2, and MCCC1. In addition, we identified that GBA coding variant carriers had an earlier age of onset compared to non-carriers. Notably, SNCA, TMEM175, SCARB2, BAG3 and GBA have all been shown to either directly influence alpha-synuclein aggregation or are implicated in alpha-synuclein aggregation pathways. Remarkably, other well-established PD risk loci such as GCH1, MAPT and RAB7L1/NUCKS1 (PARK16) did not show a significant effect on age of onset of PD. While for some loci, this may be a measure of power, this is clearly not the case for the MAPT locus; thus genetic variability at this locus influences whether but not when an individual develops disease. We believe this is an important mechanistic and therapeutic distinction. Furthermore, these data support a model in which alpha-synuclein and lysosomal mechanisms impact not only PD risk but also age of disease onset and highlights that therapies that target alpha-synuclein aggregation are more likely to be disease-modifying than therapies targeting other pathways.
Host Genetic Background and Gut Microbiota Contribute to Differential Metabolic Responses to Fructose Consumption in Mice
Authors: Ahn In Sook , Lang Jennifer M. , Olson Christine A. , Diamante Graciel , Zhang Guanglin , Ying Zhe , Byun Hyae Ran , Cely Ingrid , Ding Jessica , Cohn Peter , Kurtz Ira , Gomez-Pinilla Fernando , Lusis Aldons J. , Hsiao Elaine Y. , Yang Xia 
Published: October 2018

ABSTRACTBackgroundIt is unclear how high fructose consumption induces disparate metabolic responses in genetically diverse mouse strains.ObjectiveWe aim to investigate whether the gut microbiota contributes to differential metabolic responses to fructose.MethodsEight-week-old male C57BL/6J (B6), DBA/2J (DBA), and FVB/NJ (FVB) mice were given 8% fructose solution or regular water (control) for 12 weeks. The gut microbiota composition in cecum and feces was analyzed using 16S rDNA sequencing, and PERMANOVA was used to compare community across mouse strains, treatments, and time points. Microbiota abundance was correlated with metabolic phenotypes and host gene expression in hypothalamus, liver and adipose tissues using Biweight midcorrelation. To test the causal role of the gut microbiota in determining fructose response, we conducted fecal transplants from B6 to DBA mice and vice versa for 4 weeks, as well as gavaged antibiotic-treated DBA mice with Akkermansia for 9 weeks, accompanied with or without fructose treatment.ResultsCompared to B6 and FVB, DBA mice had significantly higher Firmicutes/Bacteroidetes ratio and lower baseline levels of Akkermansia and S24-7 (P < 0.05), accompanied by metabolic dysregulation after fructose consumption. Fructose altered specific microbial taxa in individual mouse strains, such as a 7.27-fold increase in Akkermansia in B6 and 0.374-fold change in Rikenellaceae in DBA (FDR < 5%), which demonstrated strain-specific correlations with host metabolic and transcriptomic phenotypes. Fecal transplant experiments indicated that B6 microbes conferred resistance to fructose-induced weight gain in DBA mice (F = 43.1, P < 0.001), and Akkermansia colonization abrogated the fructose-induced weight gain (F = 17.8, P <0.001) and glycemic dysfunctions (F = 11.8, P = 0.004) in DBA mice.ConclusionsOur findings support that differential microbiota composition between mouse strains is partially responsible for host metabolic sensitivity to fructose, and that Akkermansia is a key bacterium that confers resistance to fructose-induced metabolic dysregulation.
Cover crop mixture diversity, biomass productivity, weed suppression, and stability
Authors: Florence A. M. , Higley L. G. , Drijber R. A. , Francis C. A. , Lindquist J. L. 
Published: October 2018

AbstractThe diversity-productivity, diversity-invasibility, and diversity-stability hypotheses propose that increasing species diversity should lead, respectively, to increased average biomass productivity, increased invasion resistance, and increased stability. We tested these three hypotheses in the context of cover crop mixtures, evaluating the effects of increasing cover crop mixture diversity on aboveground biomass, weed suppression, and biomass stability. Twenty to forty cover crop treatments were replicated three or four times at eleven sites using eighteen species representing three cover crop species each from six pre-defined functional groups: cool-season grasses, cool-season legumes, cool-season brassicas, warm-season grasses, warm-season legumes, and warm-season broadleaves. Each species was planted in monoculture, and the most diverse treatment contained all eighteen species. Remaining treatments included treatments representing intermediate levels of cover crop species and functional richness and a no cover crop control. Cover crop planting dates ranged from late July to late September with both cover crop and weed aboveground biomass being sampled prior to winterkill. Stability was assessed by evaluating the variability in cover crop biomass for each treatment across plots within each site. While increasing cover crop mixture diversity was associated with increased average aboveground biomass, this was the result of the average biomass of the monocultures being drawn down by low yielding species rather than due to niche complementarity or increased resource use efficiency. At no site did the highest yielding mixture out-yield the highest yielding monoculture. Furthermore, while increases in cover crop mixture diversity were correlated with increases in weed suppression and increases in biomass stability, we argue that this was largely the result of diversity co-varying with aboveground biomass, and that differences in aboveground biomass rather than differences in diversity drove the differences observed in weed suppression and stability. The results of this study contradict popular interpretations of the diversity-productivity, diversity-invasibility, and diversity-stability hypotheses.
Reduced representation sequencing for symbiotic anthozoans: are reference genomes necessary to eliminate endosymbiont contamination and make robust phylogeographic inference?
Authors: Titus Benjamin M. , Daly Marymegan 
Published: October 2018

AbstractAnthozoan cnidarians form the backbone of coral reefs. Their success relies on endosymbiosis with photosynthetic dinoflagellates in the family Symbiodiniaceae. Photosymbionts represent a hurdle for researchers using population genomic techniques to study these highly imperiled and ecologically critical species because sequencing datasets harbor unknown mixtures of anthozoan and photosymbiont loci. Here we use range-wide sampling and a double-digest restriction-site associated DNA sequencing (ddRADseq) of the sea anemoneBartholomea annulatato explore how symbiont loci impact the interpretation of phylogeographic patterns and population genetic parameters. We use the genome of the closely relatedExaiptasia diaphana(previouslyAiptasia pallida)to create an anthozoan-only dataset from a genomic dataset containing bothB. annulataand its symbiodiniacean symbionts and then compare this to the raw, holobiont dataset. For each, we investigate spatial patterns of genetic diversity and use coalescent model-based approaches to estimate demographic history and population parameters. The Florida Straits are the only phylogeographic break we recover forB. annulata, with divergence estimated during the last glacial maximum. BecauseB. annulatahosts multiple members of Symbiodiniaceae, we hypothesize that, under moderate missing data thresholds,de novoclustering algorithms that identify orthologs across datasets will have difficulty identifying shared non-coding loci from the photosymbionts. We infer that, for anthozoans hosting diverse members of Symbiodinaceae, clustering algorithms act asde factofilters of symbiont loci. Thus, while at least some photosymbiont loci remain, these are swamped by orders of magnitude greater numbers of anthozoan loci and thus represent genetic “noise,” rather than contributing genetic signal.
Coupled Reaction Networks for Noise Suppression
Authors: Xiao Fangzhou , Fang Meichen , Yan Jiawei , Doyle John C. 
Published: October 2018

AbstractNoise is intrinsic to many important regulatory processes in living cells, and often forms obstacles to be overcome for reliable biological functions. However, due to stochastic birth and death events of all components in biomolecular systems, suppression of noise of one component by another is fundamentally hard and costly. Quantitatively, a widelycited severe lower bound on noise suppression in biomolecular systems was established by Lestaset. al.in 2010, assuming that the plant and the controller have separate birth and death reactions. This makes the precision observed in several biological phenomena, e.g., cell fate decision making and cell cycle time ordering, seem impossible. We demonstrate that coupling, a mechanism widely observed in biology, could suppress noise lower than the bound of Lestaset. al.with moderate energy cost. Furthermore, we systematically investigate the coupling mechanism in all two-node reaction networks, showing that negative feedback suppresses noise better than incoherent feedforward achitectures, coupled systems have less noise than their decoupled version for a large class of networks, and coupling has its own fundamental limitations in noise suppression. Results in this work have implications for noise suppression in biological control and provide insight for a new efficient mechanism of noise suppression in biology.
Biofilm/Persister/Stationary Phase Bacteria Cause More Severe Disease Than Log Phase Bacteria – I BiofilmBorrelia burgdorferiNot Only Display More Tolerance to Lyme Antibiotics But Also Cause More Severe Pathology In a Mouse Arthritis Model: Implications for Understanding Persistence, PTLDS and Treatment Failure
Authors: Feng Jie , Li Tingting , Yuan Yuting , Yee Rebecca , Zhang Ying 
Published: October 2018

AbstractLyme disease, caused byBorrelia burgdorferi,is the most common tick-borne illness in US and Europe. While most patients can be cured with a 2-4 week antibiotic therapy, about 10%-20% patients continue to suffer persistent symptoms of fatigue, pain or joint and muscle aches, and neurocognitive despite the treatment, a condition called post-treatment Lyme disease syndrome (PTLDS). The cause for PTLDS is unclear but one possibility is persistent infection withB. burgdorferi. B. burgdorferiis known to develop morphological variant forms such as round bodies and aggregated biofilm-like microcolonies as a log phase culture consisting of spirochete form grows into stationary phase. Here we isolated biofilm-like microcolony and planktonic form (spirochetal forms and round body) from stationary phase culture and found that the stationary phase planktonic form (SP) and microcolony form (MC) were much more tolerant to the current antibiotics for Lyme disease, doxycycline, ceftriaxone and cefuroxime than log phase spirochete form (LOG). In addition, we also compared the ability of the variant forms to cause disease in a mouse arthritis model. Surprisingly, the MC in particular and the SP caused a more severe arthritis with an earlier onset of inflammation and joint swelling than LOG. MC-infected mice showed significant joint swelling as early as 9 days post-infection, while the LOG and SP did not cause significant swelling. At 21 days, the joint swelling of the MC group dramatically increased and peaked, while the SP showed significant swelling at this time but less severe than the MC group. The LOG infected mice were just beginning to develop joint swelling at 21-day post-infection, with only slight swelling. At 30-day post infection, the SP group mice also developed similar severity of joint swelling as the MC group, but the LOG group still did not show significant swelling. However, at 35-day post infection, all three infected groups showed similar degree of significant joint swelling. Thereafter, the joint swelling of the three infected groups waxed and waned during the 90-day observation. Thus, we established a new biofilm-inocula mediated visual arthritis model that could facilitate more efficient evaluation of treatment regimens for persistentB. burgdorferiinfections. Our findings provide new insight about disease pathogenesis and may have implications for understanding PTLDS and PTLDS treatment failure, due to possible biofilm inoculation during tick-bite. This biofilm/persister seeding model may be valid for different microbial infections and facilitate developing more effective treatments of persistent infections in general.
Aircraft model for automatic taxi directional control system design
Authors: Krawczyk Mariusz , Szczepanski Cezary Jerzy , Zajdel Albert 
Published: October 2018

Purpose
This paper aims to present a concept of an automatic directional control system of remotely piloted aerial system (RPAS) during the taxiing phase. In particular, it shows the initial stages of the control laws synthesis – mathematical model and simulation of taxiing aircraft. Several reasons have emerged in recent years that make the automation of taxiing an important design challenge including decreased safety, performance and pilot workload.

Design/methodology/approach
The adapted methodology follows the model-based design approach in which the control system and the aircraft are mathematically modelled to allow control laws synthesis. The computer simulations are carried out to analyse the model behaviour.

Findings
Chosen methodology and modelling technique, especially tire-ground contact model, resulted in a taxing aircraft model that can be used for directional control law synthesis. Aerodynamic forces and moments were identified in the wind tunnel tests for the full range of the slip angle. Simulations allowed to compute the critical speeds for different taxiway conditions in a 90° turn.

Practical implications
The results can be used for the taxi directional control law synthesis and simulation of the control system. The computed critical speeds can be treated as safety limits.

Originality/value
The taxi directional control system has not been introduced to the RPAS yet. Therefore, the model of taxiing aircraft including aerodynamic characteristics for the full range of the slip angle has a big value in the process of design and implementation of the future auto taxi systems. Moreover, computed speed safety limits can be used by designers and standard creators.
Investigation on the benefit of formation flight with a focus on the leading and trailing aircraft rotation
Authors: Liu Yaolong , Zhou Yaoming 
Published: October 2018

Purpose
The purpose of this paper is to study the potential advantages of aircraft formation flight (FF) and to exploit further benefits through exchanging the leading positions.

Design/methodology/approach
The detailed and robust methodologies concerning FF mission analysis including the leading aircraft rotation strategies are developed in this paper to study the fuel burn benefit and the additional bonus of formation rotation.

Findings
Switch of FF leading positions can offset the undesired weight ratios between the leading and trailing aircraft within FF missions, which further alleviates the deviations from design flight conditions. The case studies on two long-range civil transport aircraft in FF show that the leading and trailing aircraft can achieve almost equal fuel benefit through rotations. As compared to FF without rotation, the fuel efficiency can be improved by more than 11 per cent.

Research limitations/implications
The work can bring benefit the research communities as a fundamental basis for operational studies of FF, such as FF airspace management in the future, which is significant for a future real-world implementation of FFs.

Practical implications
According to the authors’ study, equal or quasi-equal fuel savings can be achieved if the rotation is properly arranged. For the real-world FF application, fuel consumption (FC) or cost redistribution problem for leading and trailing aircraft belonging to two different operating airlines can therefore be resolved through the concept proposed by the paper.

Originality/value
The methods developed in the paper have the advantage to give more reliable estimations of the achievable fuel burn savings of FF. The concept proposed in the paper has significant meaning with respect to offset the undesired weight ratios between the leading and trailing aircraft within FF missions and redistributing FC or cost redistribution of different operating airlines.
Price transmission, reserve regulation and price volatility
Authors: Tan Yanwen , Zeng Huasheng 
Published: October 2018

Purpose
The purpose of this paper is to examine whether Chinese pork reserve regulation policy fulfills its function in stabilizing market prices and simultaneously to theoretically and empirically analyze the causes leading to the failure of Chinese Government’s intervention in the market, especially in the context of asymmetric pork and hog price information transmission.

Design/methodology/approach
A modified Reserve-Cobweb model based on the competitive storage model developed by Muth in 1961 is employed to examine the transmission effect of hog and pork prices under the setting of Chinese Government’s pork reserve regulation policy, using the data on Chinese hog and pork prices from June 2009 to June 2015.

Findings
While the Reserve-Cobweb model provides theoretical insights, suggesting that the implementation of the government’s reserve policy tool to control price volatility actually leads to increased price volatility, the empirical results indicate that the policy induces hypercorrection and impels greater price volatility, especially in the context of existence of asymmetric price information transmission.

Social implications
The Chinese Government should reduce excessive pork price intervention and instead allow the market to play its role in the hog and pork markets.

Originality/value
This paper develops a modified Reserve-Cobweb model based on the price transmission effect on different links within the agricultural products supply chain, which is used to empirically validate the existence of asymmetric price information transmission between pork and hog price in China.
3D numerical analysis of atmospheric-aerosol/carbon-black nanofluid flow within a solar air heater located in Shiraz, Iran
Authors: Sadripour Soroush 
Published: October 2018

Purpose
In this study, the effects of using corrugated absorber plate (instead of flat plate) and also using aerosol/carbon-black nanofluid (instead of air) on heat transfer and turbulent flow characteristics in solar collectors were numerically investigated.

Design/methodology/approach
The 3D continuity, momentum and energy equation were solved by finite volume and SIMPLE algorithm. As a result, the corrugated absorber plate was inspected in the case of triangle, rectangle and sinuous with the wave length of 1 mm and wave amplitude of 3 mm in turbulent flow regime and Reynolds number between 2,500 and 4,000. Choosing the proper geometry was carried out based on the best performance evaluation criteria (PEC) and increasing the air temperature from collector inlet to outlet.

Findings
The results revealed that for all times of the year the highest PEC was obtained for corrugated Sinusoidal model; however, the highest temperature increase from inlet to outlet was obtained for rectangular corrugated model. In addition, the results indicated that in sinusoidal model, the nanoparticles volume fractions increase leads to heat performance coefficient increase and the best heat performance conditions were attained in volume fraction of 0.1 per cent and Reynolds number of 4,000 for both six months period. In model with rectangular corrugated plate, usage of nanofluid in all range of Reynolds numbers leads to reduction of outlet temperature.

Originality/value
The effect of some nanoparticles on heat transfer using thermal– hydraulic performances in heat exchangers has been assessed, but the effects of atmospheric aerosol-based nanofluid using carbon-black nanoparticles (CBNPs) on the heat transfer in corrugated heat sink solar collectors by 3D numerical modeling has not been yet investigated. In present study, usage of CBNPs with different volume fractions in range of 0 to 0.1 per cent in turbulent regime of fluid flow is analyzed. Furthermore, in this paper, besides the effects of using CBNPs, a solar absorber located in Shiraz, as one of the best solar irradiation receiver cities in Iran is evaluated.
Can UGITs promote liquidity management and sustainable development?
Authors: Aassouli Dalal , Ebrahim Muhammed-Shahid , Basiruddin Rohaida 
Published: October 2018

Purpose
This paper aims to propose a liquidity management solution for Islamic financial institutions (IFIs) that concurs with sustainable development and financial stability.

Design/methodology/approach
The study is a qualitative research. It uses the exploratory research methodology, specifically the content analysis approach, to gather primary data and identify and interpret relevant secondary data and Sharīʿah concepts. The purpose is to develop a liquidity management solution for IFIs. The proposal is based on the Unleveraged Green Investment Trust (UGIT) model, which is consistent with Basel III regulatory requirements. In developing the UGIT model, the exploratory research was complemented by a case study to examine the UGIT solution for the particular case of renewable energy.

Findings
The model demonstrates how financial innovation can meet both financial stability and sustainable development objectives, thereby achieving the spirit of Islamic finance. The structure further highlights the importance of regulatory and fiscal frameworks to enhance liquidity management and investor appeal for green financial instruments.

Originality/value
This study suggests a structure of UGIT to enable IFIs to meet their liquidity management needs while promoting sustainable development.