bluuebunny/crossref_metadata_2025 huggingface dataset:
Circularly conformal patch array antenna with omnidirectional or electronically switched directive beam
Authors: Sanchez‐Olivares Pablo , Sanchez‐Dancausa Paula P. , Masa‐Campos Jose Luis
Published: October 2017

A circularly conformal array antenna of double stacked microstrip patches is presented in two radiation versions: omnidirectional and electronically switched directive beam. Every single element is disposed on an eight‐faced regular prism structure built in 3D print technology. The omnidirectional pattern is achieved in the azimuth plane by using a microstrip uniform power divider to equally excite the circular antenna. The switched directive beam coverage is obtained by replacing the uniform power divider with an electronically switched power divider. Four switched beams of 90° angular separation are digitally configured. A fractional matching bandwidth of 17.2% has been measured for both omnidirectional and switched beam prototypes. The conformal antenna was entirely manufactured by using both printed circuit board and 3D printing technologies. Therefore, a very compact, low cost and light weight antenna design has been implemented, suitable to many applications such as Worldwide Interoperability for Microwave Access, wireless local area network, unmanned aerial vehicles or direction finding.
Security in device‐to‐device communications: a survey
Authors: Nait Hamoud Othmane , Kenaza Tayeb , Challal Yacine
Published: October 2017

Device‐to‐device (D2D) communication is a promising technology for the next generation mobile communication networks (5G). Indeed, it is expected to allow high throughput, reduce communication delays and reduce energy consumption and traffic load. D2D technology will enhance the capacity and the performance of traditional cellular networks. Security issues must be considered in all types of communications, especially when it comes to wireless communication between devices involved in controlling critical infrastructures and/or dealing with personal data. The authors propose taxonomy based on the review of recent works which have addressed the security issues in D2D communications. This taxonomy is more practical since it gives, on the one hand, a better readability and a good understanding of all the works that have addressed the security issues in the literature, and on the other hand, a roadmap towards a global security solution that combines the best techniques and security solutions inherent to each layer: physical, MAC, network and application.
Generalised distance partitioning for multiple‐detection tracking filter based on random finite set
Authors: Shen Xinglin , Song Zhiyong , Fan Hongqi , Fu Qiang
Published: October 2017

When a target generates multiple detections, standard tracking algorithms are not applicable. Unlike extended target tracking, which has received considerable attention, studies on generalised multiple‐detection tracking (MDT) are still scarce. MDT algorithms proposed in recent years suffer from high computational complexity. In this work, based on distance partitioning, the authors propose a generalised distance partitioning (GD partitioning) algorithm to reduce the number of partitions, and thus decrease the computational complexity of MDT filters. In the algorithm, after defining a multi‐detection distance and calculating the corresponding distance threshold, the authors calculate the original partition of measurement set by using distance partitioning. Subsequently, on the basis of original partition, they can obtain informative subsets to replace all subsets in a multiple‐detection Bernoulli filter, as well as a collection of partitions to replace all partitions in multiple‐detection probability hypothesis density filter. Simulations show that the algorithm can notably reduce the number of subsets and partitions. Thus, by means of a partitioning algorithm, computational complexity of random finite set‐based MDT filters is decreased successfully, which implies that a GD partitioning algorithm may play an important part in real‐time MDT systems.
Enhanced wear resistance of Stellite 12 by Mo addition and LSM
Authors: Dilawary Shaikh Asad Ali , Motallebzadeh Amir , Akhter Rehan , Atar Erdem , Cimenoglu Huseyin
Published: October 2017

Aiming at additional improvements in the properties of Stellite 12 PTA hardfacing alloy deposited on 4140 steel substrate, the authors have adopted a dual approach. During PTA deposition Stellite 12 hardfacing powder was alloyed with 10 wt-% Mo, followed by laser surface melting (LSM). Addition of 10 wt-% Mo, led to an increase in the volume fraction of Co and W-rich complex carbides. Later on LSM executed on the PTA led to the development of unique microstructure near the surface, characterised by the segregation of hard Cr-rich carbides. The resultant layers were subjected to mechanical characterisation, at room temperature, e.g. hardness and wear resistance. It was concluded that combining both approaches i.e. addition of Mo during the hardfacing process followed by LSM of deposited layer gave additional improvements in mechanical properties owing to evolution of a unique carbide structure.
Brain activation associated with eccentric movement: A narrative review of the literature
Authors: Perrey Stéphane
Published: October 2017

The movement occurring when a muscle exerts tension while lengthening is known as eccentric muscle action. Literature contains limited evidence on how our brain controls eccentric movement. However, how the cortical regions in the motor network are activated during eccentric muscle actions may be critical for understanding the underlying control mechanism of eccentric movements encountered in daily tasks. This is a novel topic that has only recently begun to be investigated through advancements in neuroimaging methods (electroencephalography, EEG; functional magnetic resonance imaging, fMRI). This review summarizes a selection of seven studies indicating mainly: longer time and higher cortical signal amplitude (EEG) for eccentric movement preparation and execution, greater magnitude of cortical signals with wider activated brain area (EEG, fMRI), and weaker brain functional connectivity (fMRI) between primary motor cortex (M1) and other cortical areas involved in the motor network during eccentric muscle actions. Only some differences among studies due to the forms of movement with overload were observed in the contralateral (to the active hand) M1 activity during eccentric movement. Altogether, the findings indicate an important challenge to the brain for controlling the eccentric movement. However, our understanding remains limited regarding the acute effects of eccentric exercise on cortical regions and their cooperation as functional networks that support motor functions. Further analysis and standardized protocols will provide deeper insights into how different cortical regions of the underlying motor network interplay with each other in increasingly demanding muscle exertions in eccentric mode.
Visualization portal for genetic variation (VizGVar): a tool for interactive visualization of SNPs and somatic mutations in exons, genes and protein domains
Authors: Solano-Román Antonio , Alfaro-Arias Verónica , Cruz-Castillo Carlos , Orozco-Solano Allan
Published: October 2017

Motivation

VizGVar was designed to meet the growing need of the research community for improved genomic and proteomic data viewers that benefit from better information visualization.

Results

We implemented a new information architecture and applied user centered design principles to provide a new improved way of visualizing genetic information and protein data related to human disease. VizGVar connects the entire database of Ensembl protein motifs, domains, genes and exons with annotated SNPs and somatic variations from PharmGKB and COSMIC. VizGVar precisely represents genetic variations and their respective location by colored curves to designate different types of variations. The structured hierarchy of biological data is reflected in aggregated patterns through different levels, integrating several layers of information at once. VizGVar provides a new interactive, web-based JavaScript visualization of somatic mutations and protein variation, enabling fast and easy discovery of clinically relevant variation patterns.

Availability and implementation

VizGVar is accessible at http://vizport.io/vizgvar; http://vizport.io/vizgvar/doc/.
Efficient comparative phylogenetics on large trees
Authors: Louca Stilianos , Doebeli Michael
Published: October 2017

Motivation

Biodiversity databases now comprise hundreds of thousands of sequences and trait records. For example, the Open Tree of Life includes over 1 491 000 metazoan and over 300 000 bacterial taxa. These data provide unique opportunities for analysis of phylogenetic trait distribution and reconstruction of ancestral biodiversity. However, existing tools for comparative phylogenetics scale poorly to such large trees, to the point of being almost unusable.

Results

Here we present a new R package, named ‘castor’, for comparative phylogenetics on large trees comprising millions of tips. On large trees castor is often 100–1000 times faster than existing tools.

Availability and implementation

The castor source code, compiled binaries, documentation and usage examples are freely available at the Comprehensive R Archive Network (CRAN).

Supplementary information

Supplementary data are available at Bioinformatics online.
Stable Strata of Geodesics in Outer Space
Authors: Algom-Kfir Yael , Kapovich Ilya , Pfaff Catherine
Published: October 2017

In this article, we propose an Outer space analog for the principal stratum of the unit tangent bundle to the Teichmüller space ${\mathcal{T}}(S)$ of a closed hyperbolic surface $S$. More specifically, we focus on properties of the geodesics in Teichmüller space determined by the principal stratum. We show that the analogous Outer space “principal” periodic geodesics share certain stability properties with the principal stratum geodesics of Teichmüller space. We also show that the stratification of periodic geodesics in Outer space exhibits some new pathological phenomena not present in the Teichmüller space context.
Spectral Multiplicity for Maaß Newforms of Non-Squarefree Level
Authors: Humphries Peter
Published: October 2017

We show that if a positive integer $q$ has $s(q)$ odd prime divisors $p$ for which $p^2$ divides $q$, then a positive proportion of the Laplacian eigenvalues of Maaß newforms of weight $0$, level $q$, and principal character occur with multiplicity at least $2^{s(q)}$. Consequently, the new part of the cuspidal spectrum of the Laplacian on $\Gamma_0(q) \backslash \mathbb{H}$ cannot be simple for any odd non-squarefree integer $q$. This generalises work of Strömberg who proved this for $q = 9$ by different methods.
Immunoglobulin Attenuates Streptokinase-Mediated Virulence inStreptococcus dysgalactiae Subspeciesequisimilis Necrotizing Fasciitis
Authors: Andreoni Federica , Ugolini Fabio , Keller Nadia , Neff Andrina , Nizet Victor , Hollands Andrew , Marques Maggio Ewerton , Zinkernagel Annelies S , Schuepbach Reto A
Published: October 2017

Background

Necrotizing fasciitis (NF) retains a very high mortality rate despite prompt and adequate antibiotic treatment and surgical debridement. Necrotizing fasciitis has recently been associated withStreptococcus dysgalactiae subspeciesequisimilis (SDSE).

Methods

We investigated the causes of a very severe clinical manifestation of SDSE-NF by assessing both host and pathogen factors.

Results

We found a lack of streptokinase-function blocking antibodies in the patient resulting in increased streptokinase-mediated fibrinolysis and bacterial spread. At the same time, the clinical SDSE isolate produced very high levels of streptokinase. Exogenous immunoglobulin Gs (ex-IgGs) efficiently blocked streptokinase-mediated fibrinolysis in vitro, indicating a protective role against the action of streptokinase. In vivo, SDSE infection severity was also attenuated by ex-IgGs in a NF mouse model.

Conclusions

These findings illustrate for the first time that the lack of specific antibodies against streptococcal virulence factors, such as streptokinase, may contribute to NF disease severity. This can be counteracted by ex-IgGs.
Generation of allo-antigen-specific induced Treg stabilized by vitamin C treatment and its application for prevention of acute graft versus host disease model
Authors: Kasahara Hidenori , Kondo Taisuke , Nakatsukasa Hiroko , Chikuma Shunsuke , Ito Minako , Ando Makoto , Kurebayashi Yutaka , Sekiya Takashi , Yamada Taketo , Okamoto Shinichiro , Yoshimura Akihiko
Published: October 2017

Antigen-specific regulatory T cells (Tregs) possess the potential to reduce excess immune responses in autoimmune diseases, allergy, rejection after organ transplantation and graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation. Although in vitro-expanded antigen-specific induced Tregs (iTregs) have been considered to be a promising therapeutic agent against such excessive immune reactions, the instability of iTregs after transfer is a fundamental problem in their clinical application. In this study, we searched for the optimal way to generate stable iTregs for the prevention of the murine GVHD model, in which conventional iTregs are reported to be inefficient. Allo-antigen-specific iTregs were generated by co-culturing naive T cells with allogenic dendritic cells in the presence of TGF-β and retinoic acid. By examining various agents and genes, we found that vitamin C stabilized Foxp3 expression most effectively in adoptively transferred iTregs under a GVHD environment. Vitamin C treatment caused active DNA demethylation specifically on the conserved non-coding sequence 2 (CNS2) enhancer of the Foxp3 gene locus in allo-antigen-specific iTregs and reduced iTreg conversion into pathogenic exFoxp3 cells. Vitamin C-treated iTregs suppressed GVHD symptoms more efficiently than untreated iTregs. Vitamin C also facilitated induction of a FOXP3high iTreg population from human naive T cells, which was very stable even in the presence of IL-6 in vitro. The treatment of vitamin C for iTreg promises innovative clinical application for adoptive Treg immunotherapy.
Planck Sunyaev–Zel’dovich cluster mass calibration using Hyper Suprime-Cam weak lensing
Authors: Medezinski Elinor , Battaglia Nicholas , Umetsu Keiichi , Oguri Masamune , Miyatake Hironao , Nishizawa Atsushi J , Sifón Cristóbal , Spergel David N , Chiu I-Non , Lin Yen-Ting , Bahcall Neta , Komiyama Yutaka
Published: October 2017

Using ∼140 deg2 Subaru Hyper Suprime-Cam (HSC) survey data, we stack the weak lensing (WL) signal around five Planck clusters found within the footprint. This yields a 15σ detection of the mean Planck cluster mass density profile. The five Planck clusters span a relatively wide mass range, MWL,500c = (2–30) × 1014 M⊙ with a mean mass of MWL,500c = (4.15 ± 0.61) × 1014 M⊙ . The ratio of the stacked Planck Sunyaev–Zel’dovich (SZ) mass to the stacked WL mass is 〈MSZ〉/〈MWL〉 = 1 − b = 0.80 ± 0.14. This mass bias is consistent with previous WL mass calibrations of Planck clusters within the errors. We discuss the implications of our findings for the calibration of SZ cluster counts and the much discussed tension between Planck SZ cluster counts and Planck ΛCDM cosmology.
Observational study on the fine structure and dynamics of a solar jet. II. Energy release process revealed by spectral analysis
Authors: Sakaue Takahito , Tei Akiko , Asai Ayumi , Ueno Satoru , Ichimoto Kiyoshi , Shibata Kazunari
Published: October 2017

We report on a solar jet phenomenon associated with the C5.4 class flare on 2014 November 11. The data of the jet was provided by the Solar Dynamics Observatory, the X-Ray Telescope (XRT) aboard Hinode, and the Interface Region Imaging Spectrograph and Domeless Solar Telescope (DST) at Hida Observatory, Kyoto University. These plentiful data enabled us to present this series of papers to discuss all the processes of the observed phenomena, including energy storage, event trigger, and energy release. In this paper, we focus on the energy release process of the observed jet, and mainly describe our spectral analysis on the Hα data of DST to investigate the internal structure of the Hα jet and its temporal evolution. This analysis reveals that in the physical quantity distributions of the Hα jet, such as line-of-sight velocity and optical thickness, there is a significant gradient in the direction crossing the jet. We interpret this internal structure as the consequence of the migration of the energy release site, based on the idea of ubiquitous reconnection. Moreover, by measuring the horizontal flow of the fine structures in the jet, we succeeded in deriving the three-dimensional velocity field and the line-of-sight acceleration field of the Hα jet. The analysis result indicates that part of the ejecta in the Hα jet experienced additional acceleration after it had been ejected from the lower atmosphere. This secondary acceleration was found to occur in the vicinity of the intersection between the trajectories of the Hα jet and the X-ray jet observed by Hinode/XRT. We propose that a fundamental cause of this phenomenon is magnetic reconnection involving the plasmoid in the observed jet.
Longitudinal Relationship Between Knee Pain Status and Incident Frailty: Data from the Osteoarthritis Initiative
Authors: Bindawas Saad M , Vennu Vishal , Stubbs Brendon
Published: October 2017

Objective

Examine the longitudinal association between knee pain and prefrailty/frailty.

Design

Longitudinal study.

Setting

Five clinical centers across the United States.

Subject

Data from 3,053 nonfrail participants aged 45–79 years at baseline from the Osteoarthritis Initiative.

Methods

According to self-reported knee pain at baseline, the participants were placed into three groups: no knee pain (N = 1,600), unilateral knee pain (N = 822), and bilateral knee pain (N = 631). Frailty status was assessed over time using the five frailty indicators (unintentional weight loss, exhaustion, weak energy, slow gait speed, and little physical activity). Based on the number of frailty indicators present, prefrailty (1–2) and frailty (≥3) were diagnosed. Generalized estimating equations logistic regression analyses were conducted to examine the relationship between knee pain status and prefrailty/frailty.

Results

After adjusting for age, sex, race, education, marital status, smoking status, comorbidities, and body mass index, unilateral knee pain at baseline was associated with an increased odds of developing prefrailty (odds ratio [OR] = 1.14, 95% confidence interval [CI] = 1.01–1.27) and frailty (OR = 1.89, 95% CI = 1.38–2.62), and bilateral knee pain at baseline was also associated with an increased risk of prefrailty (OR = 1.41, 95% CI = 1.24–1.62) and frailty (OR = 2.21, 95% CI = 1.63–3.01) over time in comparison with no knee pain. The interaction of knee pain status by time was not significantly associated with either prefrailty or frailty.

Conclusions

Knee pain (particularly bilateral knee pain) is associated with an increased risk of developing prefrailty and frailty over time.
Gene-expression profiling of single cells from archival tissue with laser-capture microdissection and Smart-3SEQ
Authors: Foley Joseph W. , Zhu Chunfang , Jolivet Philippe , Zhu Shirley X. , Lu Peipei , Meaney Michael J. , West Robert B.
Published: October 2017

RNA sequencing (RNA-seq) is a sensitive and accurate method for quantifying gene expression. Small samples or those whose RNA is degraded, such as formalin-fixed, paraffin-embedded (FFPE) tissue, remain challenging to study with nonspecialized RNA-seq protocols. Here we present a new method, Smart-3SEQ, that accurately quantifies transcript abundance even with small amounts of total RNA and effectively characterizes small samples extracted by laser-capture microdissection (LCM) from FFPE tissue. We also obtain distinct biological profiles from FFPE single cells, which have been impossible to study with previous RNA-seq protocols, and we use these data to identify possible new macrophage phenotypes associated with the tumor microenvironment. We propose Smart-3SEQ as a highly cost-effective method to enable large gene-expression profiling experiments unconstrained by sample size and tissue availability. In particular, Smart-3SEQ’s compatibility with FFPE tissue unlocks an enormous number of archived clinical samples, and combined with LCM it allows unprecedented studies of small cell populations and single cells isolated by theirin situcontext.
Genotype fingerprints enable fast and private comparison of genetic testing results for research and direct-to-consumer applications
Authors: Robinson Max , Glusman Gustavo
Published: October 2017

As genetic testing expands out of the research laboratory into medical practice as well as the direct-to-consumer market, the efficiency with which the resulting genotype data can be compared between individuals is of increasing importance.

We present a method for summarizing personal genotypes, yielding ’genotype fingerprints’ that can be derived from any single nucleotide polymorphism (SNP)-based assay and readily compared to estimate relatedness. The resulting fingerprints remain comparable as chip designs evolve to higher marker densities. We demonstrate that they support applications including distinguishing genotypes of closely related individuals by relationship type, distinguishing closely related individuals from individuals from the same background population, identification of individuals in known background populations, and de novo identification of subpopulations within a large cohort in a high-throughput manner.

An important feature of genotype fingerprints is that, while fingerprints do not preserve anonymity, they summarize individual marker data in a way that prevents phenotype prediction. Genotype fingerprints are therefore well-suited to public sharing for ancestry determination purposes, without revealing personal health risk status.
The Multivariate Normal Distribution Framework for Analyzing Association Studies
Authors: Lozano Jose A. , Hormozdiari Farhad , Joo Jong Wha (Joanne) , Han Buhm , Eskin Eleazar
Published: October 2017

Genome-wide association studies (GWAS) have discovered thousands of variants involved in common human diseases. In these studies, frequencies of genetic variants are compared between a cohort of individuals with a disease (cases) and a cohort of healthy individuals (controls). Any variant that has a significantly different frequency between the two cohorts is considered an associated variant. A challenge in the analysis of GWAS studies is the fact that human population history causes nearby genetic variants in the genome to be correlated with each other. In this review, we demonstrate how to utilize the multivariate normal (MVN) distribution to explicitly take into account the correlation between genetic variants in a comprehensive framework for analysis of GWAS. We show how the MVN framework can be applied to perform association testing, correct for multiple hypothesis testing, estimate statistical power, and perform fine mapping and imputation.
Rapid high-resolution measurement of DNA replication timing by droplet digital PCR
Authors: Batrakou Dzmitry G. , Heron Emma D. , Nieduszynski Conrad A.
Published: October 2017

Genomes are replicated in a reproducible temporal pattern. Current methods for assaying allele replication timing are time consuming and/or expensive. These include high-throughput sequencing which can be used to measure DNA copy number as a proxy for allele replication timing. Here, we use droplet digital PCR to study DNA replication timing at multiple loci in budding yeast and human cells. We establish that the method has temporal and spatial resolutions comparable to the high-throughput sequencing approaches, while being faster than alternative locus-specific methods. Furthermore, the approach is capable of allele discrimination. We apply this method to determine relative replication timing across timing transition zones in cultured human cells. Finally, multiple samples can be analysed in parallel, allowing us to rapidly screen kinetochore mutants for perturbation to centromere replication timing. Therefore, this approach is well suited to the study of locus-specific replication and the screening of cis- and trans-acting mutants to identify mechanisms that regulate local genome replication timing.
Dengue modeling in rural Cambodia: statistical performance versus epidemiological relevance
Authors: Champagne Clara , Paul Richard , Ly Sowath , Duong Veasna , Leang Rithea , Cazelles Bernard
Published: October 2017

Dengue dynamics are shaped by the complex interplay between several factors, including vector seasonality, interaction between four virus serotypes, and inapparent infections. However, paucity or quality of data do not allow for all of these to be taken into account in mathematical models. In order to explore separately the importance of these factors in models, we combined surveillance data with a local-scale cluster study in the rural province of Kampong Cham (Cambodia), in which serotypes and asymptomatic infections were documented. We formulate several mechanistic models, each one relying on a different set of hypotheses, such as explicit vector dynamics, transmission via asymptomatic infections and coexistence of several virus serotypes. Models are confronted with the observed time series using Bayesian inference, through Markov chain Monte Carlo. Model selection is then performed using statistical information criteria, but also by studying the coherence of epidemiological characteristics (reproduction numbers, incidence proportion, dynamics of the susceptible class) in each model. Considering the available data, our analyses on transmission dynamics in a rural endemic setting highlight both the importance of using two-strain models with interacting effects and the lack of added value of incorporating vector and explicit asymptomatic components.
A novel domain assembly routine for creating full-length models of membrane proteins from known domain structures
Authors: Leman Julia Koehler , Bonneau Richard
Published: October 2017

Membrane proteins composed of soluble and membrane domains are often studied one domain at a time. However, to understand the biological function of entire protein systems and their interactions with each other and drugs, knowledge of full-length structures or models is required. Although few computational methods exist that could potentially be used to model full-length constructs of membrane proteins, none of these methods are perfectly suited for the problem at hand. Existing methods either require an interface or knowledge of the relative orientations of the domains, are not designed for domain assembly, and none of them are developed for membrane proteins. Here we describe the first domain assembly protocol specifically designed for membrane proteins that assembles intra- and extracellular soluble domains and the transmembrane domain into models of the full-length membrane protein. Our protocol does not require an interface between the domains and samples possible domain orientations based on backbone dihedrals in the flexible linker regions, created via fragment insertion, while keeping the transmembrane domain fixed in the membrane. Our method, mp_domain_assembly, implemented in RosettaMP samples domain orientations close to the native structure and is best used in conjunction with experimental data to reduce the conformational search space.
The Spectral Fingerprint of Sleep Problems in Post-Traumatic Stress Disorder
Authors: de Boer M. , Nijdam M.J. , Jongedijk R.A. , Olff  , M. Hofman W.F. , Talamini L.M.
Published: October 2017

BACKGROUND

Sleep problems are a core feature of post-traumatic stress disorder (PTSD). However, a robust objective measure for the sleep disturbance in patients has yet to be found.

METHODS

The current study assessed EEG power across a wide frequency range and multiple scalp locations, in matched trauma-exposed individuals with and without PTSD, during rapid eye movement (REM) and non-REM (NREM) sleep. In addition, a full polysomnographical evaluation was performed, including sleep staging and assessment of respiratory function, limb movements and heart rate. The occurrence of sleep disorders was also assessed.

RESULTS

In PTSD patients, NREM sleep shows a substantial loss of slow oscillation power and increased higher frequency activity compared to controls. The change is most pronounced in right-frontal brain areas and correlates with insomnia. PTSD REM sleep shows a large power shift in the opposite direction, with increased slow oscillation power in occipital areas, which is strongly related to nightmare activity and to lesser extent with insomnia. These pronounced spectral changes occur in the context of severe subjective sleep problems, increased occurrence of various sleep disorders and modest changes in sleep macrostructure.

CONCLUSIONS

This is the first study to show pronounced changes in EEG spectral topologies during both NREM and REM sleep in PTSD. Importantly, the observed power changes reflect the hallmarks of PTSD sleep problems: insomnia and nightmares and may thus be specific for PTSD. A spectral index derived from these data distinguishes patients from controls with high effect size, bearing promise as a candidate biomarker.
Heritability of hierarchical structural brain network
Authors: Chung Moo K. , Luo Zhan , Adluru Nagesh , Alexander Andrew L. , Richard Davidson J. , Goldsmith H. Hill
Published: October 2017

We present a new structural brain network parcellation scheme that can subdivide existing parcellations into smaller subregions in a hierarchically nested fashion. The hierarchical parcellation was used to build multilayer convolutional structural brain networks that preserve topology across different network scales. As an application, we applied the method to diffusion weighted imaging study of 111 twin pairs. The genetic contribution of the whole brain structural connectivity was determined. We showed that the overall heritability is consistent across different network scales.
miCloud: a plug and play, on-premises bioinformatics cloud, providing seamless integration with Illumina genome sequencers
Authors: Kim Baekdoo , Ali Thahmina , Krampis Konstantinos , Dong Changsu , Laungani Bobby , Wultsch Claudia , Lijeron Carlos
Published: October 2017

Benchtop genome sequencers such as the Illumina MiSeq or MiniSeq [1], [2] are revolutionizing genomics research for smaller, independent laboratories, by enabling access to low-cost Next Generation Sequencing (NGS) technology in-house. These benchtop genome sequencing instruments require only standard laboratory equipment, in addition to minimal time for sample preparation. However, post-sequencing bioinformatics data analysis still presents a significant bottleneck, for research laboratories lacking specialized software and technical data analysis skills on their teams. While bioinformatics computes clouds providing solutions following a Software as a Service (SaaS) are available ([3]–[6], review in [7]), currently, there are only a few options which are user-friendly for non-experts while at the same time are also low-cost or free. One primary example is Illumina BaseSpace [8] that is very easy to access by non-experts, and also offers an integrated solution where data are streamed directly from the MiSeq sequencing instrument to the cloud. Once the data is on the BaseSpace cloud, users can access a range of bioinformatics applications with pre-installed algorithms through an intuitive web interface. Nonetheless, BaseSpace can be a costly solution as a yearly subscription depending on whether the user is associated with an academic or private institution, ranges in price from $999 - $4,999. Additional “iCredits” [9] might need to be purchased for frequent users that exhaust the base credit allowance as part of the subscription. Considering the reduction of computer hardware cost in recent years, a multi-core Intel Xeon server with 64 GigaByte (GB) of memory and multiple TeraByte (TB) of storage is priced less than the yearly subscription to Basespace [10], and similarly when compared to renting compute cycles from providers such as Amazon Web Services (AWS) [11]. Furthermore, the current generation of laptops usually come with 6–10 GigaBytes (GB) of memory and 1 TeraByte (TB) of storage, providing enough computational capacity to analyze data from small NGS experiments [12] that include only a few samples.
Optical excitation and detection of neuronal activity
Authors: Hu Chenfei , Sam Richard , Shan Mingguang , Nastasa Viorel , Wang Minqi , Kim Taewoo , Gillette Martha , Sengupta Parijat , Popescu Gabriel
Published: October 2017

Optogenetics has emerged as an exciting tool for manipulating neural activity, which in turn, can modulate behavior in live organisms. However, detecting the response to the optical stimulation requires electrophysiology with physical contact or fluorescent imaging at target locations, which is often limited by photobleaching and phototoxicity. In this paper, we show that phase imaging can report the intracellular transport induced by optogenetic stimulation. We developed a multimodal instrument that can both stimulate cells with high spatial resolution and detect optical pathlength changes with nanometer scale sensitivity. We found that optical pathlength fluctuations following stimulation are consistent with active organelle transport. Furthermore, the results indicate a broadening in the transport velocity distribution, which is significantly higher in stimulated cells compared to optogenetically inactive cells. It is likely that this label-free, contactless measurement of optogenetic response will provide an enabling approach to neuroscience.
A novel feature selection for RNA-seq analysis
Authors: Han Henry
Published: October 2017

RNA-seq data are challenging existing omics data analytics for its volume and complexity. Although quite a few computational models were proposed from different standing points to conduct differential expression (D.E.) analysis, almost all these methods do not provide a rigorous feature selection for high-dimensional RNA-seq count data. Instead, most or even all genes are invited into differential calls no matter they have real contributions to data variations or not. Thus, it would inevitably affect the robustness of D.E. analysis and lead to the increase of false positive ratios.

In this study, we presented a novel feature selection method: nonnegative singular value approximation (NSVA) to enhance RNA-seq differential expression analysis by taking advantage of RNA-seq count data’s non-negativity. As a variance-based feature selection method, it selects genes according to its contribution to the first singular value direction of input data in a data-driven approach. It demonstrates robustness to depth bias and gene length bias in feature selection in comparison with its five peer methods. Combining with state-of-the-art RNA-seq differential expression analysis, it contributes to enhancing differential expression analysis by lowering false discovery rates caused by the biases. Furthermore, we demonstrated the effectiveness of the proposed feature selection by proposing a data-driven differential expression analysis: NSVA-seq, besides conducting network marker discovery.
Hypoxia in the grape berry linked to mesocarp cell death: the role of seed respiration and lenticels on the berry pedicel
Authors: Xiao Zeyu , Rogiers Suzy , Sadras Victor , Tyerman Stephen D.
Published: October 2017

Mesocarp cell death (CD) during ripening is common in berries of seededVitis viniferaL wine cultivars. We examined if hypoxia within berries is linked to CD. Internal oxygen concentration ([O2]) across the mesocarp was measured in berries from Chardonnay and Shiraz, both seeded, and Ruby Seedless, using an oxygen micro-sensor. Steep [O2] gradients were observed across the skin and [O2] decreased toward the middle of the mesocarp. As ripening progressed the minimum [O2] approached zero in the seeded cultivars and correlated to CD. Seed respiration was a large proportion of total berry respiration early in ripening but did not account for O2deficiency late in ripening. [O2] increased towards the central axis corresponding to the presence of air spaces visualised using x-ray microCT. These connect to lenticels on the pedicel that were critical for berry O2uptake as a function of temperature, and when blocked caused anoxia in the berry, ethanol accumulation and CD. Lenticel area on Chardonnay pedicels was higher than that for Shiraz probably accounting for the lower sensitivity of Chardonnay berry CD to high temperatures. The implications of hypoxia in grape berries are discussed in terms of its role in ripening and berry water relations.

Highlight

Grape berry internal oxygen concentration is dependent upon lenticels on the pedicel and cultivar differences in lenticels may account for temperature sensitivity of cell death in the mesocarp.
Single Molecule Sequencing of Cell-free DNA from Maternal Plasma for Noninvasive Trisomy Detection
Authors: Dong Minyue , Deng Liwei , Jin Huan , Cai Jinsen , Shang Huan , Zhang Shuo , Zhang Yueping , Qin Jinzhou , Zhang Dikai , Long Feng , Zhang Renli , Chen Runsheng , Deem Michael W. , Yu Jun , He Jiankui
Published: October 2017

The demand of non-invasive prenatal testing for autosomal aneuploidy using cell-free fetal DNA (cffDNA) in maternal plasma is a highly sought-after diagnostic, with a rapidly growing market. Current approaches developed by next generation sequencing (NGS) need PCR amplifcation during sample preparation, which results in amplification bias in GC-rich areas of the human genome. With these approaches, the minimum fetal fraction in maternal plasma is 4% for the small differences in circulating cfDNA between trisomic and disomic pregnancies to be detectable. In this paper, we performed single molecule sequencing of cell-free DNA from maternal plasma for noninvasive trisomy 13, 18 and 21 detections using the GenoCare platform. We found that single molecule sequencing is sensitive enough to detect these chromosome abnormalities when the fetal DNA fraction is as low as 2%. Compared to the Hiseq2500 platform, no significant GC bias was observed. The improved sensitivity and unbiased GC readout make GenoCare a promising platform for autosomal aneuploidy detections, even in the very early stage of pregnancy.
Molecular insights into the pathways underlying naked mole-rat eusociality
Authors: Mulugeta Eskeatnaf , Marion-Poll Lucile , Gentien David , Ganswindt Stefanie B. , Ganswindt André , Bennett Nigel C. , Blackburn Elizabeth H. , Faulkes Chris G. , Heard Edith
Published: October 2017

Background

Eusociality is the highest level of social organization and naked mole-rats (NMR)s are amongst the few mammals showing this unique social behavior; nevertheless, little is known about the molecular mechanisms underlying the eusociality of NMRs.

Results

Gene expression profiling of NMR brain and gonads (ovary and testis), from animals belonging to different reproductive castes, revealed robust gene expression differences between reproductive and non-reproductive members of NMR colonies. In the brain, dopaminergic pathways appear to be potential players in NMR eusocial behaviour. Breeding animals (queens and breeding males) showed increased expression of genes involved in dopamine metabolism. Using immunohistochemistry, we notably found these differences to be in dopaminergic hypothalamic areas, which provide inhibitory control over the secretion of prolactin, amongst other regions. Furthermore, plasma prolactin concentrations were elevated in many non-breeders (of both sexes), often reaching levels exceeding that of pregnant or lactating queens, suggesting a role for hyperprolactinaemia in socially-induced reproductive suppression. We also found that the ovaries of non-breeding females are arrested at pre-pubertal stage. They contained fewer supporting stromal cells compared to queens, and had very low expression of the aromatase geneCyp19A1(a key enzyme in estrogen synthesis) compared to non-breeding females. In the testes, genes involved in post meiosis spermatogenesis and sperm maturation (Prm1, Prm2, Odf3andAkap4) were highly expressed in breeding males compared to non-breeders, explaining the low sperm number and impaired sperm motility characteristic of non-breeding males.

Conclusions

Our study suggests that extreme reproductive skew, one of the defining features of eusociality, is associated with changes in expression of key components of dopamine pathways, which could lead to hypogonadism and a lifetime of socially-induced sterility for most NMRs.
A first global phylogeny ofMaize chlorotic mottle virus
Authors: Braidwood Luke A , Quito-Avila Diego F , Cabanas Darlene , Bressan Alberto , Wangai Anne , Baulcombe David C.
Published: October 2017

Maize chlorotic mottle virushas been rapidly spreading around the globe over the past decade. The interactions ofMaize chlorotic mottle viruswith potyviridae viruses causes an aggressive synergistic viral condition - maize lethal necrosis, which can cause total yield loss. Maize production in sub-Saharan Africa, where it is the most important cereal, is threatened by the arrival of maize lethal necrosis. We obtainedMaize chlorotic mottle virusgenome sequences from across East Africa and for the first time from Ecuador and Hawaii, and constructed a phylogeny which highlights the similarity of Chinese to African isolates, and Ecuadorian to Hawaiian isolates. We used a measure of clustering, the adjusted Rand index, to extract region-specific SNPs and coding variation that can be used for diagnostics. The population genetics analysis we performed shows that the majority of sequence diversity is partitioned between populations, with diversity extremely low within China and East Africa.
Automated microuidic cell culture of stem cell derived dopaminergic neurons in Parkinson’s disease
Authors: Kane Khalid I.W. , Moreno Edinson Lucumi , Hachi Siham , Walter Moriz , Jarazo Javier , Hankemeier Thomas , Vulto Paul , Schwamborn Jens , Thoma Martin , Fleming Ronan M.T.
Published: October 2017

Parkinson’s disease is a slowly progressive neurodegenerative disease characterised by dysfunction and death of selectively vulnerable midbrain dopaminergic neurons leading mainly to motor dysfunction, but also other non-motor symptoms. The development of human in vitro cellular models with similar phenotypic characteristics to selectively vulnerable neurons is a major challenge in Parkinson’s disease research. We constructed a fully automated cell culture platform optimised for long-term maintenance and monitoring of induced pluripotent stem cell derived neurons in three dimensional microfluidic cell culture devices. The system can be flexibly adapted to various experimental protocols and features time-lapse imaging microscopy for quality control and electrophysiology monitoring to assess neuronal activity. Using this system, we continuously monitored the differentiation of Parkinson’s disease patient derived human neuroepithelial stem cells into midbrain specific dopaminergic neurons. Calcium imaging confirmed the electrophysiological activity of differentiated neurons and immunostaining confirmed the efficiency of the differentiation protocol. This system is the first example of a fully automated Organ-on-a-Chip culture and enables a versatile array of in vitro experiments for patient-specific disease modelling.
DiscoSnp++: de novo detection of small variants from raw unassembled read set(s)
Authors: Peterlongo Pierre , Riou Chloé , Drezen Erwan , Lemaitre Claire
Published: October 2017

Motivation

Next Generation Sequencing (NGS) data provide an unprecedented access to life mechanisms. In particular, these data enable to detect polymorphisms such as SNPs and indels. As these polymorphisms represent a fundamental source of information in agronomy, environment or medicine, their detection in NGS data is now a routine task. The main methods for their prediction usually need a reference genome. However, non-model organisms and highly divergent genomes such as in cancer studies are extensively investigated.

Results

We propose DiscoSnp++, in which we revisit the DiscoSnp algorithm. DiscoSnp++ is designed for detecting and ranking all kinds of SNPs and small indels from raw read set(s). It outputs files in fasta and VCF formats. In particular, predicted variants can be automatically localized afterwards on a reference genome if available. Its usage is extremely simple and its low resource requirements make it usable on common desktop computers. Results show that DiscoSnp++ performs better than state-of-the-art methods in terms of computational resources and in terms of results quality. An important novelty is the de novo detection of indels, for which we obtained 99% precision when calling indels on simulated human datasets and 90% recall on high confident indels from the Platinum dataset.

License

GNU Affero general public license

Availability

https://github.com/GATB/DiscoSnp

Contact

pierre.peterlongo@inria.fr
Fossilized Microbial Forms in Baltic and Goan Amber-A Comparative Pioneer Study
Authors: Sujata Dabolkar , Nandkumar Kamat
Published: October 2017

This paper is based on surveys, exploration and standardization of techniques to recover rare amber samples from sands in Goa and identify specimens embedded with distinct microbial fossils based on studies on reference samples of imported Baltic amber. We developed techniques to locate, detect and identify amber samples in local sand. In this pioneer study, we report presumptive microbial forms such as actinobacteria and fungi in amber samples of Goa throwing light on microbial paleobiodiversity. Baltic amber (Succinate) is fossilized resin belonging to the Eocene period (44-49 million years old) derived from the Araucariaceae and Leguminoseae families of trees containing up to 8% of Succinic acid and compounds such as terpenoids and phenolic derivatives. Sooty moulds in the amber fossils have been studied (Schmidt et al., 2014). Samples of imported Baltic amber were validated, studied and used as reference for identification and characterization of amber found in sand of Goa. FTIR Spectroscopic tests diagnostic of presence of Succinate proved that both samples meet the criteria as plant derived Succinate containing products. Fossil fungi in Baltic amber were observed, and compared with similar forms in rare amber fragments of Goa. These samples were subjected to microscopic examination. Actinobacterial and fungal forms embedded in local amber were compared with similar forms found in imported Baltic amber and those published in literature. Detection of fossilized actinobacterial and fungal forms has shown us the potential for further studies for comprehensive collection and microscopic examination of such paleomicrobial forms in rare local amber samples.