Avoiding the pitfalls of gene set enrichment analysis with SetRank.

The purpose of gene set enrichment analysis (GSEA) is to find general trends in the huge lists of genes or proteins generated by many functional genomics techniques and bioinformatics analyses. Here we present SetRank, an advanced GSEA algorithm which is able to eliminate many false positive hits. The key principle of the algorithm is that it discards gene sets that have initially been flagged as significant, if their significance is only due to the overlap with another gene set. The algorithm is explained in detail and its performance is compared to that of other methods using objective benchmarking criteria. Furthermore, we explore how sample source bias can affect the results of a GSEA analysis. The benchmarking results show that SetRank is a highly specific tool for GSEA. Furthermore, we show that the reliability of results can be improved by taking sample source bias into account. SetRank is available as an R package and through an online web interface

Impaired scaling of responses to vestibular stimulation in incomplete SCI

Patients with incomplete spinal cord injury (iSCI) have impaired postural control leading to a high danger of falling. Clinically, it is impossible to assess the extent to which postural instability due to sensorimotor deficit is influenced by a disturbance in the vestibulospinal pathways. Galvanic vestibular stimulation (GVS) was applied to investigate changes in the vestibular spinal responses and their potential influence on postural stability in iSCI patients. Six chronic iSCI patients and age-matched controls were stimulated with a bipolar binaural stimulus. The centre of pressure (CoP) and soleus EMG responses during free standing with closed eyes on firm and compliant ground were measured. The impairment in postural stability was assessed by the mean amplitude of CoP deflections during two minutes undisturbed standing. Although iSCI patients were significantly less stable than controls, direct GVS responses of the soleus EMG and postural sways tended to be increased on firm ground. The GVS responses increased when changing from firm to compliant ground, showing a close correlation between the extent of postural instability and the response amplitudes. Therefore, challenging proprioceptive feedback induced a significant up-modulation of the GVS responses. However, when we took the postural instability in iSCI patients into account, the EMG and CoP responses to GVS were reduced compared to controls. The combined assessment of EMG and CoP responses to GVS complements the clinical examination and permits evaluation of the preservation and modulation of vestibulospinal responses in iSC

Differential EMG Biofeedback for Children with ADHD: A Control Method for Neurofeedback Training with a Case Illustration

The objective of the present paper was to develop a differential electromyographic biofeedback (EMG-BF) training for children with attention-deficit/hyperactivity disorder (ADHD) matching multiple neurofeedback training protocols in order to serve as a valid control training. This differential EMG-BF training method feeds back activity from arm muscles involved in fine motor skills such as writing and grip force control. Tonic EMG-BF training (activation and deactivation blocks, involving bimanual motor tasks) matches the training of EEG frequency bands, while phasic EMG-BF training (short activation and deactivation trials) was developed as an equivalent to the training of slow cortical potentials. A case description of a child who learned to improve motor regulation in most task conditions and showed a clinically relevant reduction of behavioral ADHD symptoms illustrates the training course and outcome. Differential EMG-BF training is feasible and provides well-matched control conditions for neurofeedback training in ADHD research. Future studies should investigate its value as a specific intervention for children diagnosed with ADHD and comorbid sensorimotor problem

Identifying biological mechanisms for favorable cancer prognosis using non-hypothesis-driven iterative survival analysis.

Survival analyses based on the Kaplan-Meier estimate have been pervasively used to support or validate the relevance of biological mechanisms in cancer research. Recently, with the appearance of gene expression high-throughput technologies, this kind of analysis has been applied to tumor transcriptomics data. In a 'bottom-up' approach, gene-expression profiles that are associated with a deregulated pathway hypothetically involved in cancer progression are first identified and then subsequently correlated with a survival effect, which statistically supports or requires the rejection of such a hypothesis. In this work, we propose a 'top-down' approach, in which the clinical outcome (survival) is the starting point that guides the identification of deregulated biological mechanisms in cancer by a non-hypothesis-driven iterative survival analysis. We show that the application of our novel method to a population of ~2,000 breast cancer patients of the METABRIC consortium allows the identification of several well-known cancer mechanisms, such as ERBB4, HNF3A and TGFB pathways, and the investigation of their paradoxical dual effect. In addition, several novel biological mechanisms are proposed as potentially involved in cancer progression. The proposed exploratory methodology can be considered both alternative and complementary to classical 'bottom-up' approaches for validation of biological hypotheses. We propose that our method may be used to better characterize cancer, and may therefore impact the future design of therapies that are truly molecularly tailored to individual patients. The method, named SURCOMED, was implemented as a web-based tool, which is publicly available at http://surcomed.vital-it.ch. R scripts are also available at http://surcomed.sourceforge.net)

Quantifying year-round nocturnal bird migration with a fluid dynamics model.

To understand the influence of biomass flows on ecosystems, we need to characterize and quantify migrations at various spatial and temporal scales. Representing the movements of migrating birds as a fluid, we applied a flow model to bird density and velocity maps retrieved from the European weather radar network, covering almost a year. We quantified how many birds take-off, fly, and land across Western Europe to (1) track bird migration waves between nights, (2) cumulate the number of birds on the ground and (3) quantify the seasonal flow into and out of the study area through several regional transects. Our results identified several migration waves that crossed the study area in 4 days only and included up to 188 million (M) birds that took-off in a single night. In spring, we estimated that 494 M birds entered the study area, 251 M left it, and 243 M birds remained within the study area. In autumn, 314 M birds entered the study area while 858 M left it. In addition to identifying fundamental quantities, our study highlights the potential of combining interdisciplinary data and methods to elucidate the dynamics of avian migration from nightly to yearly time scales and from regional to continental spatial scales

Evidence for a Massive Protocluster in S255N

S255N is a luminous far-infrared source that contains many indications of active star formation but lacks a prominent near-infrared stellar cluster. We present mid-infrared through radio observations aimed at exploring the evolutionary state of this region. Our observations include 1.3mm continuum and spectral line data from the Submillimeter Array, VLA 3.6cm continuum and 1.3cm water maser data, and multicolor IRAC images from the Spitzer Space Telescope. The cometary morphology of the previously-known UCHII region G192.584-0.041 is clearly revealed in our sensitive, multi-configuration 3.6cm images. The 1.3mm continuum emission has been resolved into three compact cores, all of which are dominated by dust emission and have radii < 7000AU. The mass estimates for these cores range from 6 to 35 Msun. The centroid of the brightest dust core (SMA1) is offset by 1.1'' (2800 AU) from the peak of the cometary UCHII region and exhibits the strongest HC3N, CN, and DCN line emission in the region. SMA1 also exhibits compact CH3OH, SiO, and H2CO emission and likely contains a young hot core. We find spatial and kinematic evidence that SMA1 may contain further multiplicity, with one of the components coincident with a newly-detected H2O maser. There are no mid-infrared point source counterparts to any of the dust cores, further suggesting an early evolutionary phase for these objects. The dominant mid-infrared emission is a diffuse, broadband component that traces the surface of the cometary UCHII region but is obscured by foreground material on its southern edge. An additional 4.5 micron linear feature emanating to the northeast of SMA1 is aligned with a cluster of methanol masers and likely traces a outflow from a protostar within SMA1. Our observations provide direct evidence that S255N is forming a cluster of intermediate to high-mass stars.Comment: 34 pages, 11 figures, accepted for publication in The Astronomical Journa

A novel Smg6 mouse model reveals regulation of circadian period and daily CRY2 accumulation through the nonsense-mediated mRNA decay pathway

Nonsense-mediated mRNA decay (NMD) has been intensively studied as a surveillance pathway that degrades erroneous transcripts arising from mutations or RNA processing errors. While additional roles in controlling regular mRNA stability have emerged, possible functions in mammalian physiology in vivo have remained unclear. Here, we report a novel conditional mouse allele that allows converting the NMD effector nuclease SMG6 from wild-type to nuclease domain-mutant protein. We analyzed how NMD downregulation affects the function of the circadian clock, a system known to require rapid mRNA turnover. We uncover strong lengthening of free-running circadian periods for liver and fibroblast clocks, and direct NMD regulation of Cry2 mRNA, encoding a key transcriptional repressor within the rhythm-generating feedback loop. In the entrained livers of Smg6 mutant animals we reveal transcriptome-wide alterations in daily mRNA accumulation patterns, altogether expanding the known scope of NMD regulation in mammalian gene expression and physiology

A Review on Mechanics and Mechanical Properties of 2D Materials - Graphene and Beyond

Since the first successful synthesis of graphene just over a decade ago, a variety of two-dimensional (2D) materials (e.g., transition metal-dichalcogenides, hexagonal boron-nitride, etc.) have been discovered. Among the many unique and attractive properties of 2D materials, mechanical properties play important roles in manufacturing, integration and performance for their potential applications. Mechanics is indispensable in the study of mechanical properties, both experimentally and theoretically. The coupling between the mechanical and other physical properties (thermal, electronic, optical) is also of great interest in exploring novel applications, where mechanics has to be combined with condensed matter physics to establish a scalable theoretical framework. Moreover, mechanical interactions between 2D materials and various substrate materials are essential for integrated device applications of 2D materials, for which the mechanics of interfaces (adhesion and friction) has to be developed for the 2D materials. Here we review recent theoretical and experimental works related to mechanics and mechanical properties of 2D materials. While graphene is the most studied 2D material to date, we expect continual growth of interest in the mechanics of other 2D materials beyond graphene

Waves generated by ship convoy: Comparison of physical and numerical modeling with in-situ measurements

A part of the domestic waste of the city of Geneva (Switzerland) is transported with ship convoys on the Rhone River to the waste incineration station. These convoys generate waves, which partially endangers the stability of the river banks and the riparian fauna. To reduce the dominant wave peaks, a flap was added at the stern of the barge. The efficiency of that flap was tested in physical and numerical model tests, and then compared to in-situ measurements. This case study focuses on a discussion of the appropriateness of the two models, by describing their accuracy for the present case. It indicates that the physical model reproduces the wave heights almost correctly, but does not re-produce adequately the dominant frequencies. In contrast, the numerical model damps the wave heights significantly, but gives correct dominant frequencies

A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030100 and XDB29020000), the Creative Research Group Project of National Natural Science Foundation of China (31821001), the Key Project of the Chinese Academy of Sciences (QYZDB-SSW-SMC047), the National Key Research and Development Program of China (2018YFC2000500), the Chinese Academy of Sciences President's International Fellowship Initiative Postdoctoral Fellowship (to A.M.R.) and the President's International Fellowship Initiative Professorial and Wolfson Merit Award (to J.R.S.).Peer reviewedPublisher PD