bluuebunny/crossref_metadata_2025_split huggingface dataset:
dtangle: accurate and fast cell-type deconvolution
Authors: Hunt Gregory J. , Freytag Saskia , Bahlo Melanie , Gagnon-Bartsch Johann A. 
Published: March 2018

AbstractMotivationUnderstanding cell type composition is important to understanding many biological processes. Furthermore, in gene expression studies cell type composition can confound differential expression analysis (DEA). To aid understanding cell type composition, methods of estimating (deconvolving) cell type proportions from gene expression data have been developed.ResultsWe propose dtangle, a new cell-type deconvolution method. dtangle works on a range of DNA microarray and bulk RNA-seq platforms. It estimates cell-type proportions using publicly available, often cross-platform, reference data. To comprehensively evaluate dtangle, we assemble ten benchmark data sets. Here, dtangle is competitive with published deconvolution methods, is robust to selection of tuning parameters and is quicker than other methods. As a case study, we investigate the human immune response to Lyme disease. dtangle’s estimates reveal a temporal trend consistent with previous findings and are important covariates for DEA across disease status.Availabilitydtangle is on CRAN (cran.r-project.org/package=dtangle) or github (dtangle.github.io).Contactgjhunt@umich.edu
The functional brain organization of an individual predicts measures of social abilities in autism spectrum disorder: Predicting symptoms in autism with brain imaging
Authors: Lake Evelyn MR , Finn Emily S , Noble Stephanie M , Vanderwal Tamara , Shen Xilin , Rosenberg Monica D , Spann Marisa N , Chun Marvin M , Scheinost Dustin , Todd Constable R 
Published: March 2018

ABSTRACTAutism Spectrum Disorder (ASD) is associated with multiple complex abnormalities in functional brain connectivity measured with functional magnetic resonance imaging (fMRI). Despite much research in this area, to date, neuroimaging-based models are not able to characterize individuals with ASD with sufficient sensitivity and specificity; this is likely due to the heterogeneity and complexity of this disorder. Here we apply a data-driven subject-level approach, connectome-based predictive modeling, to resting-state fMRI data from a set of individuals from the Autism Brain Imaging Data Exchange. Using leave-one-subject-out and split-half analyses, we define two functional connectivity networks that predict continuous scores on the Social Responsiveness Scale (SRS) and Autism Diagnostic Observation Schedule (ADOS) and confirm that these networks generalize to novel subjects. Notably, these networks were found to share minimal anatomical overlap. Further, our results generalize to individuals for whom SRS/ADOS scores are unavailable, predicting worse scores for ASD than typically developing individuals. In addition, predicted SRS scores for individuals with attention-deficit/hyperactivity disorder (ADHD) from the ADHD-200 Consortium are linked to ADHD symptoms, supporting the hypothesis that the functional brain organization changes relevant to ASD severity share a component associated with attention. Finally, we explore the membership of predictive connections within conventional (atlas-based) functional networks. In summary, our results suggest that an individual’s functional connectivity profile contains information that supports dimensional, non-binary classification in ASD, aligning with the goals of precision medicine and individual-level diagnosis.
Quantification of Phase-Amplitude Coupling in Neuronal Oscillations: Comparison of Phase-Locking Value, Mean Vector Length, and Modulation Index
Authors: Hülsemann Mareike J. , Dr. rer. nat  , Naumann Ewald , Dr. rer. nat  , Rasch Björn 
Published: March 2018

AbstractPhase-amplitude coupling is a promising construct to study cognitive processes in electroencephalography (EEG) and magnetencephalography (MEG). Due to the novelty of the concept, various measures are used in the literature to calculate phase-amplitude coupling. Here, performance of the three most widely used phase-amplitude coupling measures – phase-locking value (PLV), mean vector length (MVL), and modulation index (MI) – is thoroughly compared with the help of simulated data. We combine advantages of previous reviews and use a realistic data simulation, examine moderators and provide inferential statistics for the comparison of all three indices of phase-amplitude coupling. Our analyses show that all three indices successfully differentiate coupling strength and coupling width when monophasic coupling is present. While the mean vector length was most sensitive to modulations in coupling strengths and width, biphasic coupling can solely be detected by the modulation index. Coupling values of all three indices were influenced by moderators including data length, signal-to-noise-ratio, and sampling rate when approaching Nyquist frequencies. The modulation index was most robust against confounding influences of these moderators. Based on our analyses, we recommend the modulation index for noisy and short data epochs with unknown forms of coupling. For high quality and long data epochs with monophasic coupling and a high signal-to-noise ratio, the use of the mean vector length is recommended. Ideally, both indices are reported simultaneously for one data set.Highlightsmean vector length is most sensitive for differentiating coupling strengthmodulation index is most robust to differences in data length, sampling rate and SNRphase-locking value and mean vector length cannot detect biphasic phase-amplitude coupling
Cell membranes resist flow
Authors: Shi Zheng , Graber Zachary T. , Baumgart Tobias , Stone Howard A. , Cohen Adam E. 
Published: March 2018

SUMMARYThe fluid-mosaic model posits a liquid-like plasma membrane, which can flow in response to tension gradients. It is widely assumed that membrane flow transmits local changes in membrane tension across the cell in milliseconds. This conjectured signaling mechanism has been invoked to explain how cells coordinate changes in shape, motility, and vesicle fusion, but the underlying propagation has never been observed. Here we show that propagation of membrane tension occurs quickly in cell-attached blebs, but is largely suppressed in intact cells. The failure of tension to propagate in cells is explained by a fluid dynamical model that incorporates the flow resistance from cytoskeleton-bound transmembrane proteins. In primary endothelial cells, local increases in membrane tension lead only to local activation of mechanosensitive ion channels and to local vesicle fusion. Thus membrane tension is not a mediator of long-range intra-cellular signaling, but local variations in tension mediate distinct processes in sub-cellular domains.
Fast calcium transients in neuronal spines driven by extreme statistics
Authors: Basnayake Kanishka , Korkotian Eduard , Holcman David 
Published: March 2018

AbstractExtreme statistics describe the distribution of rare events that can define the timescales of transduction within cellular microdomains. We combine biophysical modeling and analysis of live-cell calcium imaging to explain the fast calcium transient in spines. We show that in the presence of a spine apparatus (SA), which is an extension of the smooth endoplasmic reticulum (ER), calcium transients during synaptic inputs rely on rare and extreme calcium ion trajectories. Using numerical simulations, we predicted the asymmetrical distributions of Ryanodine receptors and SERCA pumps that we confirmed experimentally. When calcium ions are released in the spine head, the fastest ions arriving at the base determine the transient timescale through a calcium-induced calcium release mechanism. In general, the fastest particles arriving at a small target are likely to be a generic mechanism that determines the timescale of molecular transduction in cellular neuroscience.Significance statementIntrigued by fast calcium transients of few milliseconds in dendritic spines, we investigated its underlying biophysical mechanism. We show here that it is generated by the diffusion of the fastest calcium ions when the spine contains a Spine Apparatus, an extension of the endoplasmic reticulum. This timescale is modulated by the initial number of released calcium ions and the asymmetric distribution of its associated calcium release associated Ryanodyne receptors, present only at the base of a spine. This novel mechanism of calcium signaling that we have unraveled here is driven by the fastest particles. To conclude, the rate of arrival of the fastest particles (ions) to a small target receptor defines the timescale of activation instead of the classical forward rate of chemical reactions introduced by von Smoluchowski in 1916. Applying this new rate theory to transduction should refine our understanding of the biophysical mechanisms underlying molecular signaling.
Towards a bioelectronic computer: A theoretical study of a multi-layer biomolecular computing system that can process electronic inputs
Authors: Dunn Katherine E. , Trefzer Martin A. , Johnson Steven , Tyrrell Andy M. 
Published: March 2018

ABSTRACTDNA molecular machines have great potential for use in computing systems. Since Adleman originally introduced the concept of DNA computing through his use of DNA strands to solve a Hamiltonian path problem, a range of DNA-based computing elements have been developed, including logic gates, neural networks, finite state machines (FSMs) and non-deterministic universal Turing machines. It has also been established that DNA molecular machines can be controlled using electrical signals and that the state of DNA nanodevices can be measured using an electrochemical readout. However, to the best of our knowledge there has as yet been no demonstration of a fully integrated biomolecular computing system that has multiple levels of information processing capacity, can accept electronic inputs and is capable of independent operation. In this paper we address the question of how such a system could work. We present simulation results showing that such an integrated hybrid system could convert electrical impulses into biomolecular signals, perform logical operations and take a decision, storing its history. We also illustrate theoretically how such a system could potentially be used to perform a task such as controlling an autonomous robot navigating through a maze.
Does deterministic coexistence theory matter in a finite world?
Authors: Schreiber Sebastian J. , Levine Jonathan M. , Godoy Oscar , Kraft Nathan J.B. , Hart Simon P. 
Published: March 2018

AbstractContemporary studies of species coexistence are underpinned by deterministic models that assume that competing species have continuous (i.e. non-integer) densities, live in infinitely large landscapes, and coexist over infinite time horizons. By contrast, in nature species are composed of discrete individuals subject to demographic stochasticity, and occur in habitats of finite size where extinctions occur in finite time. One consequence of these discrepancies is that metrics of species coexistence derived from deterministic theory may be unreliable predictors of the duration of species coexistence in nature. These coexistence metrics include invasion growth rates and niche and fitness differences, which are now commonly applied in theoretical and empirical studies of species coexistence. Here we test the efficacy of deterministic coexistence metrics on the duration of species coexistence in a finite world. We introduce new theoretical and computational methods to estimate coexistence times in stochastic counterparts of classic deterministic models of competition. Importantly, we parameterized this model using experimental field data for 90 pairwise combinations of 18 species of annual plants, allowing us to derive biologically-informed estimates of coexistence times for a natural system. Strikingly, we find that for species expected to deterministically coexist, habitat sizes containing only tens of individuals have predicted coexistence times of greater than 1, 000 years. We also find that invasion growth rates explain 60% of the variation in intrinsic coexistence times, reinforcing their general usefulness in studies of coexistence. However, only by integrating information on both invasion growth rates and species’ equilibrium population sizes could most (> 99%) of the variation in species coexistence times be explained. This integration is achieved with demographically uncoupled single species models solely determined by the invasion growth rates and equilibrium population sizes. Moreover, because of a complex relationship between niche overlap/fitness differences and equilibrium population sizes, increasing niche overlap and increasing fitness differences did not always result in decreasing coexistence times as deterministic theory would predict. Nevertheless, our results tend to support the informed use of deterministic theory for understanding the duration of species coexistence, while highlighting the need to incorporate information on species’ equilibrium population sizes in addition to invasion growth rates.
The Impact Of Thigh And Shank Marker Quantity On Lower Extremity Kinematics Using A Constrained Model
Authors: Slater Annelise A , Hullfish Todd J. , Baxter Josh R. 
Published: March 2018

AbstractMusculoskeletal models are commonly used to quantify joint motions and loads during human motion. Constraining joint kinematics simplifies these models but the implications of the number of markers used during data acquisition remains unclear. The purpose of this study was to establish the effects of marker placement and quantity on kinematic fidelity when using a constrained-kinematic model. We hypothesized that a constrained-kinematic model would faithfully reproduce lower extremity kinematics regardless of the number of tracking markers removed from the thigh and shank. Healthy-young adults (N = 10) walked on a treadmill at slow, moderate, and fast speeds while skin-mounted markers were tracked using motion capture. Lower extremity kinematics were calculated for 256 combinations of leg and shank markers to establish the implications of marker placement and quantity on joint kinematics. Sagittal joint and hip coronal kinematics errors were smaller than documented errors caused by soft-tissue artifact, which tends to be approximately 5 degrees, when excluding thigh and shank markers. Joint angle and center kinematic errors negatively correlated with the number of markers included in the analyses (R2 > 0.97) and typically showed the greatest error reductions when two markers were included. Further, we demonstrated that a simplified marker set that included markers on the pelvis, lateral knee condyle, lateral malleolus, and shoes produced kinematics that strongly agreed with the traditional marker set. In conclusion, constrained-kinematic models are resilient to marker placement and quantity, which has implications on study design and post-processing workflows.Ethics Approval and Consent to Participate this study was approved by the Institutional Review Board at the University of Pennsylvania (#824466). Subjects provided written-informed consentConsent to Publish this submission does not contain any individual dataAvailability of Data and Materials the datasets analyzed in this study are available from the corresponding author on reasonable request.Competing Interests one author (JB) is an associate editor for BMC Musculoskeletal Disorders. None of the other authors have any competing interests.Funding no funding has been provided for this researchAuthors’ ContributionsAS, TH, and JB designed the experiment; AS and TH collected the data; AS and JB analyzed and interpreted the data; AS and JB drafted the manuscript; AS, TH, and JB revised the intellectual content of the manuscript; AS, TH, and JB approved the final version of the manuscript; and AS, TH, and JB agreed to be accountable for all aspects of the study.
A gate-and-switch model for head orientation behaviors in C. elegans
Authors: Ouellette Marie-Hélène , Desrochers Melanie J. , Gheta Ioana , Ramos Ryan , Hendricks Michael 
Published: March 2018

SummaryThe nervous system seamlessly integrates perception and action. This ability is essential for stable representation of and appropriate responses to the external environment. How the sensorimotor integration underlying this ability occurs at the level of individual neurons is of keen interest. In Caenorhabditis elegans, RIA interneurons receive input from sensory pathways and have reciprocal connections with head motor neurons. Through separate physiological mechanisms, RIA simultaneously encodes both head orientation and sensory stimuli. Based on these observations, we proposed a model for how RIA may integrate these two signals to detect the spatial distribution of stimuli across head sweeps and generate directional head responses. Here, we show that blocking synaptic release from RIA disrupts head orientation behaviors in response to unilaterally presented stimuli. We found that sensory encoding in RIA is gated according to head orientation. This dependence on head orientation is independent of motor encoding in RIA, suggesting a second, posture-dependent pathway upstream of RIA. This gating mechanism may allow RIA to selectively attend to stimuli that are asymmetric across head sweeps. Attractive odor removal during head bends triggers rapid head withdrawal in the opposite direction. Unlike sensory encoding, this directional response is dependent on motor inputs to and synaptic output from RIA. Together, these results suggest that RIA is part of a sensorimotor pathway that is dynamically regulated according to head orientation at two levels: the first is a gate that filters sensory representations in RIA, and the second is a switch that routes RIA synaptic output to dorsal or ventral head motor neurons.
A generalized VECM/VAR-DCC/ADCC framework and its application in the Black-Litterman model
Authors: Deng Qi 
Published: March 2018

PurposeThe existing literature on the Black-Litterman (BL) model does not offer adequate guidance on how to generate investors’ views in an objective manner. Therefore, the purpose of this paper is to establish a generalized multivariate Vector Error Correction Model (VECM)/Vector Auto-Regressive (VAR)-Dynamic Conditional Correlation (DCC)/Asymmetric DCC (ADCC) framework, and applies it to generate objective views to improve the practicality of the BL model.Design/methodology/approachThis paper establishes a generalized VECM/VAR-DCC/ADCC framework that can be utilized to model multivariate financial time series in general, and produce objective views as inputs to the BL model in particular. To test the VECM/VAR-DCC/ADCC preconditioned BL model’s practical utility, it is applied to a six-asset China portfolio (including one risk-free asset).FindingsWith dynamically optimized view confidence parameters, the VECM/VAR-DCC/ADCC preconditioned BL model offers clear advantage over the standard mean-variance method, and provides an automated portfolio optimization alternative to the classic BL approach.Originality/valueThe VECM/VAR-DCC/ADCC framework and its application in the BL model proposed by this paper provide an alternative approach to the classic BL method. Since all the view parameters, including estimated mean return vectors, conditional covariance matrices and pick matrices, are generated in the VECM/VAR and DCC/ADCC preconditioning stage, the model improves the objectiveness of the inputs to the BL stage. In conclusion, the proposed model offers a practical choice for automated portfolio balancing and optimization in a China context.
Perceived organizational support and employee well-being
Authors: Wattoo Mashal Ahmed , Zhao Shuming , Xi Meng 
Published: March 2018

PurposeConsidering work and family responsibility has become an important issue due to changes in the lives of people, understanding work and family responsibilities is essential for organizations in assisting employees to increase their well-being. Therefore, the purpose of this paper is to find the impact of perceived organizational support (POS) on work–family facilitation (WFF) and work–family conflict (WFC) and eventually on employee well-being.Design/methodology/approachA survey questionnaire is administered to 1,340 employees of Chinese enterprises. Structural equation modeling is used to test the model fit.FindingsResults of this study indicate a significant positive relationship between POS and WFF and significant negative relation between POS and WFC. Results of this paper also indicate that WFF and WFC partially mediate the relationship between POS and employee well-being.Originality/valueOver the past two decades, the extent of research on work–family literature has been increased. Most of the work–family research works have been conducted in the Western countries. Very little is known about whether these results are applicable to Eastern societies. This study is extended to focus on work–family literature by drawing a sample from different regions of China. The findings of this study may provide a good understanding of WFC and WFF for Chinese employees. This study stresses the importance of providing organizational support to increase the well-being of employees.
The strategic national infrastructure assessment of digital communications
Authors: Oughton Edward J. , Frias Zoraida , Dohler Mischa , Whalley Jason , Sicker Douglas , Hall Jim W. , Crowcroft Jon , Cleevely David D. 
Published: March 2018

Purpose
Public policy requires effective identification of the current and emerging issues being faced in industry and beyond. This paper aims to identify a set of key issues currently facing digital communications and reviews their relevance for the strategic provision of infrastructure, particularly within the UK context.

Design/methodology/approach
The methodology focusses on taking a horizon-scanning approach to obtaining current information from a range of authoritative decision makers across industry, government and academia. After structuring the issues identified, these areas are explored by a multi-disciplinary research team covering engineering, economics and computer science.

Findings
Five key categories were identified including future demand; coverage and capacity; policy and regulation; economics and business models; and technology. The results are reported for both fixed and wireless networks. Shared issues affecting the wider digital ecosystem are also identified including Brexit, connecting remote areas and the degree to which the economics of infrastructure allows for building multiple overlapping infrastructures. The authors find that future demand uncertainty is one of the major issues affecting the digital communications sector driven by rigid willingness-to-pay, weak revenue and an increasing shift from fixed to wireless technologies. Policy must create the market conditions that encourage the entry of new competitors with innovative thinking and disruptive business models.

Research limitations/implications
A limitation of the analysis is that it is quite UK-focussed; hence, further research could broaden this analysis to assessing issues at a continental or global scale.

Originality/value
The value of this paper originates from the breadth of the expert elicitation exercise carried out to gather the initial set of issues, followed by the analysis of this data by a multi-disciplinary team of researchers. The results direct a future research agenda, as many issues are indicative of a lack of existing evidence to support effective decision-making.