347 research outputs found

    The escaping set of a quasiregular mapping

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    We show that if the maximum modulus of a quasiregular mapping f grows sufficiently rapidly then there exists a non-empty escaping set I(f) consisting of points whose forward orbits under iteration tend to infinity. This set I(f) has an unbounded component but, in contrast to the case of entire functions on the complex plane, the closure of I(f) may have a bounded component.Comment: 10 page

    Amelioration of Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice by Photobiomodulation Induced by 670 nm Light

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    The approved immunomodulatory agents for the treatment of multiple sclerosis (MS) are only partially effective. It is thought that the combination of immunomodulatory and neuroprotective strategies is necessary to prevent or reverse disease progression. Irradiation with far red/near infrared light, termed photobiomodulation, is a therapeutic approach for inflammatory and neurodegenerative diseases. Data suggests that near-infrared light functions through neuroprotective and anti-inflammatory mechanisms. We sought to investigate the clinical effect of photobiomodulation in the Experimental Autoimmune Encephalomyelitis (EAE) model of multiple sclerosis.The clinical effect of photobiomodulation induced by 670 nm light was investigated in the C57BL/6 mouse model of EAE. Disease was induced with myelin oligodendrocyte glycoprotein (MOG) according to standard laboratory protocol. Mice received 670 nm light or no light treatment (sham) administered as suppression and treatment protocols. 670 nm light reduced disease severity with both protocols compared to sham treated mice. Disease amelioration was associated with down-regulation of proinflammatory cytokines (interferon-γ, tumor necrosis factor-α) and up-regulation of anti-inflammatory cytokines (IL-4, IL-10) in vitro and in vivo.These studies document the therapeutic potential of photobiomodulation with 670 nm light in the EAE model, in part through modulation of the immune response

    DNA choreography: correlating mobility and organization of DNA across different resolutions from loops to chromosomes

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    The dynamics of DNA in the cell nucleus plays a role in cellular processes and fates but the interplay of DNA mobility with the hierarchical levels of DNA organization is still underexplored. Here, we made use of DNA replication to directly label genomic DNA in an unbiased genome-wide manner. This was followed by live-cell time-lapse microscopy of the labeled DNA combining imaging at different resolutions levels simultaneously and allowing one to trace DNA motion across organization levels within the same cells. Quantification of the labeled DNA segments at different microscopic resolution levels revealed sizes comparable to the ones reported for DNA loops using 3D super-resolution microscopy, topologically associated domains (TAD) using 3D widefield microscopy, and also entire chromosomes. By employing advanced chromatin tracking and image registration, we discovered that DNA exhibited higher mobility at the individual loop level compared to the TAD level and even less at the chromosome level. Additionally, our findings indicate that chromatin movement, regardless of the resolution, slowed down during the S phase of the cell cycle compared to the G1/G2 phases. Furthermore, we found that a fraction of DNA loops and TADs exhibited directed movement with the majority depicting constrained movement. Our data also indicated spatial mobility differences with DNA loops and TADs at the nuclear periphery and the nuclear interior exhibiting lower velocity and radius of gyration than the intermediate locations. On the basis of these insights, we propose that there is a link between DNA mobility and its organizational structure including spatial distribution, which impacts cellular processes

    Strong-coupling scenario of a metamagnetic transition

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    We investigate the periodic Anderson model in the presence of an external magnetic field, using dynamical mean-field theory in combination with the modified perturbation theory. A metamagnetic transition is observed which exhibits a massive change in the electronic properties. These are discussed in terms of the quasiparticle weight and densities of states. The results are compared with the experimental results of the metamagnetic transition in CeRu_2Si_2.Comment: 5 pages, 3 figures, to appear in PR

    Constant intraperitoneal 5‐fluorouracil infusion through a totally implanted system

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109794/1/cptclpt198412.pd

    Alterations of immune response of non-small lung cancer with azacytidine

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    Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

    Long-Dose Intensive Therapy Is Necessary for Strong, Clinically Significant, Upper Limb Functional Gains and Retained Gains in Severe/Moderate Chronic Stroke

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    Background. Effective treatment methods are needed for moderate/severely impairment chronic stroke. Objective. The questions were the following: (1) Is there need for long-dose therapy or is there a mid-treatment plateau? (2) Are the observed gains from the prior-studied protocol retained after treatment? Methods. Single-blind, stratified/randomized design, with 3 applied technology treatment groups, combined with motor learning, for long-duration treatment (300 hours of treatment). Measures were Arm Motor Ability Test time and coordination-function (AMAT-T, AMAT-F, respectively), acquired pre-/posttreatment and 3-month follow-up (3moF/U); Fugl-Meyer (FM), acquired similarly with addition of mid-treatment. Findings. There was no group difference in treatment response (P ≥ .16), therefore data were combined for remaining analyses (n = 31; except for FM pre/mid/post, n = 36). Pre-to-Mid-treatment and Mid-to-Posttreatment gains of FM were statistically and clinically significant (P \u3c .0001; 4.7 points and P \u3c .001; 5.1 points, respectively), indicating no plateau at 150 hours and benefit of second half of treatment. From baseline to 3moF/U: (1) FM gains were twice the clinically significant benchmark, (2) AMAT-F gains were greater than clinically significant benchmark, and (3) there was statistically significant improvement in FM (P \u3c .0001); AMAT-F (P \u3c .0001); AMAT-T (P \u3c .0001). These gains indicate retained clinically and statistically significant gains at 3moFU. From posttreatment to 3moF/U, gains on FM were maintained. There were statistically significant gains in AMAT-F (P = .0379) and AMAT-T P = .003

    BEAST detection of a brown dwarf and a low-mass stellar companion around the young bright B star HIP 81208

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    Recent observations from B-star Exoplanet Abundance Study (BEAST) have illustrated the existence of sub-stellar companions around very massive stars. In this paper, we present the detection of two lower mass companions to a relatively nearby (148.71.3+1.5148.7^{+1.5}_{-1.3} pc), young (174+317^{+3}_{-4} Myr), bright (V=6.632±0.0066.632\pm0.006 mag), 2.58±0.06 M2.58\pm0.06~ M_{\odot} B9V star HIP 81208 residing in the Sco-Cen association, using the Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE) instrument at the Very Large Telescope (VLT) in Chile. Analysis of the photometry obtained gives mass estimates of 677+6 MJ67^{+6}_{-7}~M_J for the inner companion and 0.1350.013+0.010 M0.135^{+0.010}_{-0.013}~M_{\odot} for the outer companion, indicating the former to be most likely a brown dwarf and the latter to be a low-mass star. The system is compact but unusual, as the orbital planes of the two companions are likely close to orthogonal. The preliminary orbital solutions we derived for the system indicate that the star and the two companions are likely in a Kozai resonance, rendering the system dynamically very interesting for future studies.Comment: 18 pages, 14 figures, 5 tables Accepted for publication in the 10. Planets and planetary systems section of A&

    Ontology-Based Multiplatform Identification Method

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    This paper puts forward a multiplatform identification method to overcome the limitations of a single platform strategy when mass customization is required. The method is applied to redesign or consolidate an existing product family. The method consists of four steps: (1) the determination of component values, (2) the estimation of component redesign efforts, (3) the platform component identification, and (4) the formation of multiple platform instances. An ontology-based framework is also provided to facilitate the information representation and the data integration in the identification of multiplatform structure. Once the platforms are identified, an ontology reasoning mechanism verifies the platform sharing among products and determines the possible multiplatform coalition. A water cooler product family is used to illustrate the ontology-based multiplatform identification method
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