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The growth plate (GP) comprising sequentially differentiated cell layers is a critical structure for bone elongation and regeneration. Although several key regulators in GP development have been identified using genetic perturbation, systematic understanding is still limited. Here, we used single-cell RNA-sequencing (RNA-seq) to determine the gene expression profiles of 217 single cells from GPs and developed a bioinformatics pipeline named Sinova to de novo reconstruct physiological GP development in both temporal and spatial high resolution. Our unsupervised model not only confirmed prior knowledge, but also enabled the systematic discovery of genes, potential signal pathways, and surface markers CD9/CD200 to precisely depict development. Sinova further identified the effective combination of transcriptional factors (TFs) that regulates GP maturation, and the result was validated using an in vitro EGFP-Col10a screening system. Our case systematically reconstructed molecular cascades in GP development through single-cell profiling, and the bioinformatics pipeline is applicable to other developmental processes.
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The Ångström-scale transport characteristics of water and six different solutes, methanol, ethanol, 2-propanol, urea, Na+, and Cl-, were studied for a polyamide reverse osmosis (RO) membrane, FT-30, using non-equilibrium molecular dynamics (NEMD) simulations. Results indicate that water transport increases with an increasing fraction of connected percolated free volume, or water-accessible open space, in the membrane polymer structure. This free volume is enhanced by the dynamic structure of the membrane at the molecular level as it swells when hydrated and vibrates due to molecular collisions allowing a continuous path connecting the opposite membrane surfaces. The tortuous paths available for transport of solutes result in Brownian motion of solute molecules and hopping from pore to pore as they pass through the polymer network structure of the membrane. The transport of alcohol solutes decreases for solutes with larger Van der Waals volume, which corresponds to less available percolated free volume, or solute-accessible space, within the membrane polymer structure. However, the Van der Waals size of the dehydrated solutes is generally not a good measure to predict solute transport or rejection. Urea has reduced transport compared to ethanol, most likely due to more complex chemistry, even though urea has a smaller Van der Waals volume than ethanol. Na+ and Cl- experience the lowest transport, likely due to strong ion-water and ion-ion electrostatic interactions.
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Governments and companies around the world collect point clouds (datasets containing elevation points) because these are useful for many applications, e.g. to reconstruct 3D city models, to understand and predict the impact of floods, and to monitor dikes. We address in this paper the visualisation of point clouds, which is perhaps the most essential instrument a practitioner or a scientist has to analyse and understand such datasets. We argue that it is currently hampered by two main problems: (1) point clouds are often massive (several billion points); (2) the viewer's perception of depth and structure is often lost (because of the sparse and unstructured points). We propose solving both problems by using the Medial Axis Transform (MAT) and its properties. This allows us to (1) smartly simplify a point cloud in a geometry-dependent way (to preserve only significant features), and (2) to render splats whose radii are adaptive to the distribution of points (and thus obtain less “holes” in the surface). Our main contribution is a series of heuristics that allows us to compute the MAT robustly for noisy real-world LiDAR point clouds, and to compute the MAT for point clouds that do not fit into the main memory. We have implemented our algorithms, we report on experiments made with point clouds (of more than one billion points), and we demonstrate that we are able to render scenes with much less points than in the original point cloud (we preserve around 10%) while retaining good depth-perception and a sense of structure at close viewing distances.
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This paper presents the first application of the Point-Time-Reversal-Sponge-Layer (PTRSL) damping technique to enhance the focal-resolution of experimental flow-induced dipole sources obtained using the Time-Reversal (TR) source localization method. Experiments were conducted in an Anechoic Wind Tunnel for the case of a full-span cylinder located in a low Mach number cross-flow. The far-field acoustic pressure sampled using two line arrays of microphones located above and below the cylinder exhibited a dominant Aeolian tone. The aeroacoustic TR simulations were implemented using the time-reversed signals whereby the source map revealed the lift-dipole nature at the Aeolian tone frequency. A PTRSL (centred at the predicted dipole location) was shown to reduce the size of dipole focal spots to 7/20th of a wavelength as compared to one wavelength without its use, thereby dramatically enhancing the focal-resolution of the TR technique.
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The use of science to understand its own structure is becoming popular, but understanding the organization of knowledge areas is still limited because some patterns are only discoverable with proper computational treatment of large-scale datasets. In this paper, we introduce a framework to combine network-based methodologies and text analytics to construct the taxonomy of science fields. The methodology is illustrated with application to two topics: complex networks (CN) and photonic crystals (PC). We built citation networks using data from the Web of Science and used a community detection algorithm for partitioning to obtain science maps for the two topics. We also created an importance index for text analytics, which is employed to extract keywords that define the communities and, combined with network topology metrics, to generate dendrograms of relatedness among subtopics. Interesting patterns emerging from the analysis included identification of two well-defined communities in PC area, which is consistent with the known existence of two distinct communities of researchers in the area: telecommunication engineers and physicists. With the methodology, it was also possible to assess the interdisciplinary nature and time evolution of subtopics defined by the keywords. The automatic tools described here are potentially useful not only to provide an overview of scientific areas but also to assist scientists in performing systematic research on a specific topic.
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During amniote embryogenesis the nervous and vascular systems interact in a process that significantly affects the respective morphogenesis of each network by forming a “neurovascular” link. The importance of neurovascular cross-talk in the central nervous system has recently come into focus with the growing awareness that these two systems interact extensively both during development, in the stem-cell niche, and in neurodegenerative conditions such as Alzheimer's Disease and Amyotrophic Lateral Sclerosis. With respect to the peripheral nervous system, however, there have been no live, real-time investigations of the potential relationship between these two developing systems. To address this deficit, we used multispectral 4D time-lapse imaging in a transgenic quail model in which endothelial cells (ECs) express a yellow fluorescent marker, while neural crest cells (NCCs) express an electroporated red fluorescent marker. We monitored EC and NCC migration in real-time during formation of the peripheral nervous system. Our time-lapse recordings indicate that NCCs and ECs are physically juxtaposed and dynamically interact at multiple locations along their trajectories. These interactions are stereotypical and occur at precise anatomical locations along the NCC migratory pathway. NCCs migrate alongside the posterior surface of developing intersomitic vessels, but fail to cross these continuous streams of motile ECs. NCCs change their morphology and migration trajectory when they encounter gaps in the developing vasculature. Within the nascent dorsal root ganglion, proximity to ECs causes filopodial retraction which curtails forward persistence of NCC motility. Overall, our time-lapse recordings support the conclusion that primary vascular networks substantially influence the distribution and migratory behavior of NCCs and the patterned formation of dorsal root and sympathetic ganglia.
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Bradykinesia is associated with reduced quality of life and medication non-compliance, and it may be a prodrome for schizophrenia. Therefore, screening/monitoring for subtle bradykinesia is of clinical and scientific importance. This study investigated the validity and reliability of such an instrument. Included were 70 patients with psychotic disorders. Inertial sensors captured mean cycle duration, amplitude and velocity of four movement tasks: walking, elbow flexion/extension, forearm pronation/supination and leg agility. The concurrent validity with the Unified Parkinson's Disease Rating Scale (UPDRS) bradykinesia subscale was determined using regression analysis. Reliability was investigated with the intra-class correlation coefficient. The duration, amplitude and velocities of the four tasks measured by the instrument explained 67% of the variance on the UPDRS bradykinesia subscale. The instrument test-retest reliability was high. The instrument investigated in this study is a valid and reliable alternative to observer-rated scales. It is an ideal tool for monitoring bradykinesia as it requires little training and experience to achieve reliable results.
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An innovative design of a counter-current two-phase thermosyphon is investigated for the in-plane cooling of flat product structures. The thermosyphon features multiple pools staggered along the entire evaporator section, in which liquid flowing toward the bottom of the thermosyphon can be stored. The pools are used to cascade the working fluid to the evaporator end cap. Liquid accumulates in the pools until they overflow, thereby spreading the working fluid across the entire evaporator length rather than creating one liquid pool at the bottom end cap. Multiple of such thermosyphons operating in parallel can be used for low-gradient planar cooling of vertically oriented surfaces. A numerical model using a control volume approach is developed to predict and to validate the experimental results of this innovative design. The main advantages of the control volume approach are the adaptability of the entire model and the fast computational speed in comparison to elaborate fluid dynamics models. Empirical correlations are used for the modeling of the heat transfer coefficients and friction factors of the counter-current flow. A proof of principle is given by observing a prototype that was milled into a copper bar. Next to logging temperature measurements, the prototype had a glass top plate to visually record the working fluid behavior. The model presented is well suitable for the early stages of thermosyphon design studies and for the impact evaluation of design changes.
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The Wolffian duct, the proximal end of the mesonephric duct, undergoes non-branching morphogenesis to achieve an optimal length and size for sperm maturation. It is important to examine the mechanisms by which the developing mouse Wolffian duct elongates and coils for without proper morphogenesis, male infertility will result. Here we show that highly proliferative epithelial cells divide in a random orientation relative to the elongation axis in the developing Wolffian duct. Convergent extension (CE)-like of cell rearrangements is required for elongating the duct while maintaining a relatively unchanged duct diameter. The Wolffian duct epithelium is planar polarized, which is characterized by oriented cell elongation, oriented cell rearrangements, and polarized activity of regulatory light chain of myosin II. Conditional deletion of protein tyrosine kinase 7 (PTK7), a regulator of planar cell polarity (PCP), from mesoderm results in loss of the PCP characteristics in the Wolffian duct epithelium. Although loss of Ptk7 does not alter cell proliferation or division orientation, it affects CE and leads to the duct with significantly shortened length, increased diameter, and reduced coiling, which eventually results in loss of sperm motility, a key component of sperm maturation. In vitro experiments utilizing inhibitors of myosin II results in reduced elongation and coiling, similar to the phenotype of Ptk7 knockout. This data suggest that PTK7 signaling through myosin II regulates PCP, which in turn ensures CE-like of cell rearrangements to drive elongation and coiling of the Wolffian duct. Therefore, PTK7 is essential for Wolffian duct morphogenesis and male fertility.
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Mental health nursing for adults with intellectual disabilities and mental illness is underresearched. The aim of this review is to summarize empirical mental health nursing studies including adults with intellectual disabilities and additional mental illness. Out of 137 hits, 16 articles were reviewed in full text. Thirteen of the articles presented modified nursing interventions. Three articles discussed training and education. The main finding is that mental health nursing interventions in patients with intellectual disabilities and additional mental illness are in line with mental health nursing for the general population. There are still not many publications on empirical studies concerning mental health nursing for adults with intellectual disabilities. Clinical implications are primarily related to the need for facilitated nurse–patient communication adjusted to the patients' cognitive levels. Insights drawn from this review illuminate the importance of mental health nursing interventions adjusting to the particular patients' symptoms, instead of targeting behavior change. The findings underpin factors found to have a positive impact on patients with mental illness in the general population as relevant topics for future research.
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