192 research outputs found
Wavefront Sensing and Control Architecture for the Spherical Primary Optical Telescope (SPOT)
Testbed results are presented demonstrating high-speed image-based wavefront sensing and control for a spherical primary optical telescope (SPOT). The testbed incorporates a phase retrieval camera coupled to a 3-Mirror Vertex testbed (3MV) at the NASA Goddard Space Flight Center. Actuator calibration based on the Hough transform is discussed as well as several supercomputing archtectures for image-based wavefront sensing. Timing results are also presented based on various algorithm implementations using a cluster of 64 TigerShare TSlOl DSP's (digital-signal processors)
Rapid model-guided design of organ-scale synthetic vasculature for biomanufacturing
Our ability to produce human-scale bio-manufactured organs is critically
limited by the need for vascularization and perfusion. For tissues of variable
size and shape, including arbitrarily complex geometries, designing and
printing vasculature capable of adequate perfusion has posed a major hurdle.
Here, we introduce a model-driven design pipeline combining accelerated
optimization methods for fast synthetic vascular tree generation and
computational hemodynamics models. We demonstrate rapid generation, simulation,
and 3D printing of synthetic vasculature in complex geometries, from small
tissue constructs to organ scale networks. We introduce key algorithmic
advances that all together accelerate synthetic vascular generation by more
than 230-fold compared to standard methods and enable their use in arbitrarily
complex shapes through localized implicit functions. Furthermore, we provide
techniques for joining vascular trees into watertight networks suitable for
hemodynamic CFD and 3D fabrication. We demonstrate that organ-scale vascular
network models can be generated in silico within minutes and can be used to
perfuse engineered and anatomic models including a bioreactor, annulus,
bi-ventricular heart, and gyrus. We further show that this flexible pipeline
can be applied to two common modes of bioprinting with free-form reversible
embedding of suspended hydrogels and writing into soft matter. Our synthetic
vascular tree generation pipeline enables rapid, scalable vascular model
generation and fluid analysis for bio-manufactured tissues necessary for future
scale up and production.Comment: 58 pages (19 main and 39 supplement pages), 4 main figures, 9
supplement figure
TNFα Contributes to Diabetes Impaired Angiogenesis in Fracture Healing
Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10 days after induction of fractures. Diabetes decreased both angiogenesis and VEGFA expression by chondrocytes. The reduced angiogenesis and VEGFA expression in diabetic fractures was rescued by specific inhibition of TNF in vivo. In addition, the TNF inhibitor rescued the negative effect of diabetes on endothelial cell proliferation and endothelial cell apoptosis. The effect of TNFα in vitro was enhanced by high glucose and an advanced glycation endproduct to impair microvascular endothelial cell proliferation and tube formation and to stimulate apoptosis. The effect of TNF, high glucose and an AGE was mediated by the transcription factor FOXO1, which increased expression of p21 and caspase-3. These studies indicate that inflammation plays a major role in diabetes-impaired angiogenesis in endochondral bone formation through its effect on microvascular endothelial cells and FOXO1
The Large UV/Optical/Infrared Surveyor (LUVOIR): Decadal Mission Concept Design Update
In preparation for the 2020 Astrophysics Decadal Survey, NASA has commissioned the study of four large mission concepts, including the Large Ultraviolet / Optical / Infrared (LUVOIR) Surveyor. The LUVOIR Science and Technology Definition Team (STDT) has identified a broad range of science objectives including the direct imaging and spectral characterization of habitable exoplanets around sun-like stars, the study of galaxy formation and evolution, the epoch of reionization, star and planet formation, and the remote sensing of Solar System bodies. NASAs Goddard Space Flight Center (GSFC) is providing the design and engineering support to develop executable and feasible mission concepts that are capable of the identified science objectives. We present an update on the first of two architectures being studied: a 15-meter-diameter segmented-aperture telescope with a suite of serviceable instruments operating over a range of wavelengths between 100 nm to 2.5 microns. Four instruments are being developed for this architecture: an optical / near-infrared coronagraph capable of 10(exp -10) contrast at inner working angles as small as 2 lambda/D; the LUVOIR UV Multi-object Spectrograph (LUMOS), which will provide low- and medium-resolution UV (100 400 nm) multi-object imaging spectroscopy in addition to far-UV imaging; the High Definition Imager (HDI), a high-resolution wide-field-of-view NUV-Optical-IR imager; and a UV spectro-polarimeter being contributed by Centre National dEtudes Spatiales (CNES). A fifth instrument, a multi-resolution optical-NIR spectrograph, is planned as part of a second architecture to be studied in late 2017
Cingulum bundle integrity associated with delusions of control in schizophrenia: Preliminary evidence from diffusion-tensor tractography
High-specificity bioinformatics framework for epigenomic profiling of discordant twins reveals specific and shared markers for ACPA and ACPA-positive rheumatoid arthritis
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A meta-analysis of two high-risk prospective cohort studies reveals autism-specific transcriptional changes to chromatin, autoimmune, and environmental response genes in umbilical cord blood
Abstract
Background
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects more than 1% of children in the USA. ASD risk is thought to arise from both genetic and environmental factors, with the perinatal period as a critical window. Understanding early transcriptional changes in ASD would assist in clarifying disease pathogenesis and identifying biomarkers. However, little is known about umbilical cord blood gene expression profiles in babies later diagnosed with ASD compared to non-typically developing and non-ASD (Non-TD) or typically developing (TD) children.
Methods
Genome-wide transcript levels were measured by Affymetrix Human Gene 2.0 array in RNA from cord blood samples from both the Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) and the Early Autism Risk Longitudinal Investigation (EARLI) high-risk pregnancy cohorts that enroll younger siblings of a child previously diagnosed with ASD. Younger siblings were diagnosed based on assessments at 36 months, and 59 ASD, 92 Non-TD, and 120 TD subjects were included. Using both differential expression analysis and weighted gene correlation network analysis, gene expression between ASD and TD, and between Non-TD and TD, was compared within each study and via meta-analysis.
Results
While cord blood gene expression differences comparing either ASD or Non-TD to TD did not reach genome-wide significance, 172 genes were nominally differentially expressed between ASD and TD cord blood (log2(fold change) > 0.1, p < 0.01). These genes were significantly enriched for functions in xenobiotic metabolism, chromatin regulation, and systemic lupus erythematosus (FDR q < 0.05). In contrast, 66 genes were nominally differentially expressed between Non-TD and TD, including 8 genes that were also differentially expressed in ASD. Gene coexpression modules were significantly correlated with demographic factors and cell type proportions.
Limitations
ASD-associated gene expression differences identified in this study are subtle, as cord blood is not the main affected tissue, it is composed of many cell types, and ASD is a heterogeneous disorder.
Conclusions
This is the first study to identify gene expression differences in cord blood specific to ASD through a meta-analysis across two prospective pregnancy cohorts. The enriched gene pathways support involvement of environmental, immune, and epigenetic mechanisms in ASD etiology.https://deepblue.lib.umich.edu/bitstream/2027.42/152245/1/13229_2019_Article_287.pd
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