bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable Strata of Geodesics in Outer Space
Authors: Algom-Kfir Yael , Kapovich Ilya , Pfaff Catherine 
Published: October 2017

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

AbstractRNA 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

AbstractAs 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

AbstractGenome-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

ABSTRACTGenomes 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

AbstractDengue 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

AbstractMembrane 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

AbstractBACKGROUNDSleep 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.METHODSThe 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.RESULTSIn 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.CONCLUSIONSThis 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

ABSTRACTWe 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.
A novel feature selection for RNA-seq analysis
Authors: Han Henry 
Published: October 2017

AbstractRNA-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

AbstractMesocarp 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.HighlightGrape 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.