775 research outputs found
Nuclear burst plasma injection into the magnetosphere and resulting spacecraft charging
The passage of debris from a high altitude ( 400 km) nuclear burst over the ionospheric plasma is found to be capable of exciting large amplitude whistler waves which can act to structure a collisionless shock. This instability will occur in the loss cone exits of the nuclear debris bubble, and the accelerated ambient ions will freestream along the magnetic field lines into the magnetosphere. Using Starfish-like parameters and accounting for plasma diffusion and thermalization of the propagating plasma mass, it is found that synchronous orbit plasma fluxes of high temperature electrons (near 10 keV) will be significantly greater than those encountered during magnetospheric substorms. These fluxes will last for sufficiently long periods of time so as to charge immersed bodies to high potentials and arc discharges to take place
Potential Mechanisms Underlying TGF-β-mediated Complement Activation in Lung Fibrosis
While our previous studies suggest that limiting bleomycin-induced complement activation suppresses TGF-β signaling, the specific hierarchical interactions between TGF-β and complement in lung fibrosis are unclear. Herein, we investigated the mechanisms underlying TGF-β-induced complement activation in the pathogenesis of lung fibrosis. C57-BL6 mice were given intratracheal instillations of adenoviral vectors overexpressing TGF-β (Ad-TGFβ) or the firefly gene-luciferase (Ad-Luc; control). Two weeks later, mice with fibrotic lungs were instilled RNAi specific to receptors for C3a or C5a-C3ar or C5ar, and sacrificed at day 28. Histopathological analyses revealed that genetic silencing of C3ar or C5ar arrested the progression of TGF-β-induced lung fibrosis, collagen deposition and content (hydroxyproline, col1a1/2); and significantly suppressed local complement activation. With genetic silencing of either C3ar or C5ar, in Ad-TGFβ-injured lungs: we detected the recovery of Smad7 (TGF-β inhibitor) and diminished local release of DAF (membrane-bound complement inhibitor); in vitro: TGF-β-mediated loss of DAF was prevented. Conversely, blockade of the TGF-β receptor prevented C3a-mediated loss of DAF in both normal primary human alveolar and small airway epithelial cells. Of the 52 miRNAs analyzed as part of the Affymetrix array, normal primary human SAECs exposed to C3a, C5a or TGF-β caused discrete and overlapping miRNA regulation related to epithelial proliferation or apoptosis (miR-891A, miR-4442, miR-548, miR-4633), cellular contractility (miR-1197) and lung fibrosis (miR-21, miR-200C, miR-31HG, miR-503). Our studies present potential mechanisms by which TGF-β activates complement and promotes lung fibrosis
Training CNNs with Low-Rank Filters for Efficient Image Classification.
We propose a new method for creating computationally efficient convolutional neural networks (CNNs) by using low-rank representations of convolutional filters. Rather than approximating filters in previously-trained networks with more efficient versions, we learn a set of small basis filters from scratch; during training, the network learns to combine these basis filters into more complex filters that are discriminative for image classification. To train such networks, a novel weight initialization scheme is used. This allows effective initialization of connection weights in convolutional layers composed of groups of differently-shaped filters. We validate our approach by applying it to several existing CNN architectures and training these networks from scratch using the CIFAR, ILSVRC and MIT Places datasets. Our results show similar or higher accuracy than conventional CNNs with much less compute. Applying our method to an improved version of VGG-11 network using global max-pooling, we achieve comparable validation accuracy using 41% less compute and only 24% of the original VGG-11 model parameters; another variant of our method gives a 1 percentage point increase in accuracy over our improved VGG-11 model, giving a top-5 center-crop validation accuracy of 89.7% while reducing computation by 16% relative to the original VGG-11 model. Applying our method to the GoogLeNet architecture for ILSVRC, we achieved comparable accuracy with 26% less compute and 41% fewer model parameters. Applying our method to a near state-of-the-art network for CIFAR, we achieved comparable accuracy with 46% less compute and 55% fewer parameters.Microsoft Research PhD Scholarshi
ILâ17A deficiency mitigates bleomycinâinduced complement activation during lung fibrosis
Interleukin 17A (ILâ17A) and complement (Câ˛) activation have each been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). We have reported that ILâ17A induces epithelial injury via TGFâβ in murine bronchiolitis obliterans; that TGFâβ and the CⲠcascade present signaling interactions in mediating epithelial injury; and that the blockade of CⲠreceptors mitigates lung fibrosis. In the present study, we investigated the role of ILâ17A in regulating CⲠin lung fibrosis. Microarray analyses of mRNA isolated from primary normal human small airway epithelial cells indicated that ILâ17A (100 ng/ml; 24 h; n = 5 donor lungs) induces CⲠcomponents (CⲠfactor B, C3, and GPCR kinase isoform 5), cytokines (IL8, â6, and â1B), and cytokine ligands (CXCL1, â2, â3, â5, â6, and â16). ILâ17A induces protein and mRNA regulation of CⲠcomponents and the synthesis of active CⲠ3a (C3a) in normal primary human alveolar type II epithelial cells (AECs). Wildâtype mice subjected to ILâ17A neutralization and ILâ17A knockout (i717aâ/â) mice were protected against bleomycin (BLEO)âinduced fibrosis and collagen deposition. Further, BLEOâinjured i17aâ/â mice had diminished levels of circulating Krebs Von Den Lungen 6 (alveolar epithelial injury marker), local caspaseâ3/7, and local endoplasmic reticular stressârelated genes. BLEOâinduced local CⲠactivation [C3a, C5a, and terminal CⲠcomplex (C5bâ9)] was attenuated in il17aâ/â mice, and ILâ17A neutralization prevented the loss of epithelial CⲠinhibitors (CⲠreceptorâ1 related isoform Y and decay accelerating factor), and an increase in local TUNEL levels. RNAiâmediated gene silencing of il17a in fibrotic mice arrested the progression of lung fibrosis, attenuated cellular apoptosis (caspaseâ3/7) and lung deposition of collagen and CⲠ(C5bâ9). Compared to normals, plasma from IPF patients showed significantly higher hemolytic activity. Our findings demonstrate that limiting complement activation by neutralizing ILâ17A is a potential mechanism in ameliorating lung fibrosis.âCipolla, E., Fisher, A. J., Gu, H., Mickler, E. A., Agarwal, M., Wilke, C. A., Kim, K. K., Moore, B. B., Vittal, R. ILâ17A deficiency mitigates bleomycinâinduced complement activation during lung fibrosis. FASEB J. 31, 5543â5556 (2017). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154482/1/fsb2fj201700289r-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154482/2/fsb2fj201700289r.pd
Molecular chaperones and thyroid cancer
Thyroid cancers are the most common of the endocrine system malignancies and progress must be made in the areas of differential diagnosis and treatment to improve patient management. Advances in the understanding of carcinogenic mechanisms have occurred in various fronts, including studies of the chaperone system (CS). Components of the CS are found to be quantitatively increased or decreased, and some correlations have been established between the quantitative changes and tumor type, prognosis, and response to treatment. These correlations provide the basis for identi-fying distinctive patterns useful in differential diagnosis and for planning experiments aiming at elucidating the role of the CS in tumorigenesis. Here, we discuss studies of the CS components in various thyroid cancers (TC). The chaperones belonging to the families of the small heat-shock proteins Hsp70 and Hsp90 and the chaperonin of Group I, Hsp60, have been quantified mostly by immunohistochemistry and Western blot in tumor and normal control tissues and in extracellular vesicles. Distinctive differences were revealed between the various thyroid tumor types. The most frequent finding was an increase in the chaperones, which can be attributed to the augmented need for chaperones the tumor cells have because of their accelerated metabolism, growth, and division rate. Thus, chaperones help the tumor cell rather than protect the patient, exemplifying chaperonopathies by mistake or collaborationism. This highlights the need for research on chaperonotherapy, namely the development of means to eliminate/inhibit pathogenic chaperones
Immunomorphological Patterns of Chaperone System Components in Rare Thyroid Tumors with Promise as Biomarkers for Differential Diagnosis and Providing Clues on Molecular Mechanisms of Carcinogenesis
Hurthle cell (HC), anaplastic (AC), and medullary (MC) carcinomas are low frequency
thyroid tumors that pose several challenges for physicians and pathologists due to the scarcity of
cases, information, and histopathological images, especially in the many areas around the world
in which sophisticated molecular and genetic diagnostic facilities are unavailable. It is, therefore,
cogent to provide tools for microscopists to achieve accurate diagnosis, such as histopathological
images with reliable biomarkers, which can help them to reach a differential diagnosis. We are
investigating whether components of the chaperone system (CS), such as the molecular chaperones,
can be considered dependable biomarkers, whose levels and distribution inside and outside cells in
the tumor tissue could present a distinctive histopathological pattern for each tumor type. Here, we
report data on the chaperones Hsp27, Hsp60, and Hsp90. They presented quantitative levels and
distribution patterns that were different for each tumor and differed from those of a benign thyroid
pathology, goiter (BG). Therefore, the reported methodology can be beneficial when the microscopist
must differentiate between HC, AC, MC, and BG
Quantitative immunomorphological analysis of heat shock proteins in thyroid follicular adenoma and carcinoma tissues reveals their potential for differential diagnosis and points to a role in carcinogenesis
Hsp27, Hsp60, Hsp70, and Hsp90 are chaperones that play a crucial role in cellular
homeostasis and differentiation, but they may be implicated in carcinogenesis. Follicular neoplasms
of the thyroid include follicular adenoma and follicular carcinoma. The former is a very frequent benign
encapsulated nodule, whereas the other is a nodule that infiltrates the capsule, blood vessels and the
adjacent parenchyma, with a tendency to metastasize. The main objective was to assess the potential
of the Hsps in differential diagnosis and carcinogenesis. We quantified by immunohistochemistry
Hsp27, Hsp60, Hsp70, and Hsp90 on thin sections of human thyroid tissue with follicular adenoma or
follicular carcinoma, comparing the tumor with the adjacent peritumoral tissue. Hsp60, Hsp70, and
Hsp90 were increased in follicular carcinoma compared to follicular adenoma, while Hsp27 showed
no difference. Histochemical quantification of Hsp60, Hsp70, and Hsp90 allows diagnostic distinction
between follicular adenoma and carcinoma, and between tumor and adjacent non-tumoral tissue.
The quantitative variations of these chaperones in follicular carcinoma suggest their involvement in
tumorigenesis, for instance in processes such as invasion of thyroid parenchyma and metastasization
From Multiview Image Curves to 3D Drawings
Reconstructing 3D scenes from multiple views has made impressive strides in
recent years, chiefly by correlating isolated feature points, intensity
patterns, or curvilinear structures. In the general setting - without
controlled acquisition, abundant texture, curves and surfaces following
specific models or limiting scene complexity - most methods produce unorganized
point clouds, meshes, or voxel representations, with some exceptions producing
unorganized clouds of 3D curve fragments. Ideally, many applications require
structured representations of curves, surfaces and their spatial relationships.
This paper presents a step in this direction by formulating an approach that
combines 2D image curves into a collection of 3D curves, with topological
connectivity between them represented as a 3D graph. This results in a 3D
drawing, which is complementary to surface representations in the same sense as
a 3D scaffold complements a tent taut over it. We evaluate our results against
truth on synthetic and real datasets.Comment: Expanded ECCV 2016 version with tweaked figures and including an
overview of the supplementary material available at
multiview-3d-drawing.sourceforge.ne
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