357 research outputs found
Turbulence in the Solar Atmosphere: Manifestations and Diagnostics via Solar Image Processing
Intermittent magnetohydrodynamical turbulence is most likely at work in the
magnetized solar atmosphere. As a result, an array of scaling and multi-scaling
image-processing techniques can be used to measure the expected
self-organization of solar magnetic fields. While these techniques advance our
understanding of the physical system at work, it is unclear whether they can be
used to predict solar eruptions, thus obtaining a practical significance for
space weather. We address part of this problem by focusing on solar active
regions and by investigating the usefulness of scaling and multi-scaling
image-processing techniques in solar flare prediction. Since solar flares
exhibit spatial and temporal intermittency, we suggest that they are the
products of instabilities subject to a critical threshold in a turbulent
magnetic configuration. The identification of this threshold in scaling and
multi-scaling spectra would then contribute meaningfully to the prediction of
solar flares. We find that the fractal dimension of solar magnetic fields and
their multi-fractal spectrum of generalized correlation dimensions do not have
significant predictive ability. The respective multi-fractal structure
functions and their inertial-range scaling exponents, however, probably provide
some statistical distinguishing features between flaring and non-flaring active
regions. More importantly, the temporal evolution of the above scaling
exponents in flaring active regions probably shows a distinct behavior starting
a few hours prior to a flare and therefore this temporal behavior may be
practically useful in flare prediction. The results of this study need to be
validated by more comprehensive works over a large number of solar active
regions.Comment: 26 pages, 7 figure
Plasmas and Controlled Nuclear Fusion
Contains research objectives and summary of research on six research projects.U.S. Atomic Energy Commission (Contract AT(11-1)-3070
Advances in cholangiocarcinoma research:report from the third Cholangiocarcinoma Foundation Annual Conference
How ligand binds to the type 1 insulin-like growth factor receptor
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the articleâs Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the articleâs Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Intratumor genetic heterogeneity in squamous cell carcinoma of the oral cavity
BackgroundWe sought to evaluate intratumor heterogeneity in squamous cell carcinoma of the oral cavity (OCC) and specifically determine the effect of physical separation and histologic differentiation within the same tumor.MethodsWe performed whole exome sequencing on five biopsy sitesâtwo from wellâdifferentiated, two from poorly differentiated regions, and one from normal parenchymaâfrom five primary OCC specimens.ResultsWe found high levels of intratumor heterogeneity and, in four primary tumors, identified only 0 to 2 identical mutations in all subsites. We found that the heterogeneity inversely correlated with physical separation and that pairs of wellâdifferentiated samples were more similar to each other than analogous poorly differentiated specimens. Only TP53 mutations, but not other purported âdriver mutationsâ in head and neck squamous cell carcinoma, were found in multiple biopsy sites.ConclusionThese data highlight the challenges to characterization of the mutational landscape of OCC with single site biopsy and have implications for personalized medicine.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150549/1/hed25719.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150549/2/hed25719_am.pd
Investigating effects of parasite infection on body condition of the Kafue lechwe (Kobus leche kafuensis) in the Kafue basin
<p>Abstract</p> <p>Background</p> <p>The Kafue lechwe (<it>Kobus leche Kafuensis</it>), a medium-sized semi-aquatic antelope, is endemic to the Kafue basin of Zambia. The population of the Kafue lechwe has significantly dropped in the last decades leading to its subsequent inclusion on the red list of endangered species. In order to save the remaining population from extinction, it has become increasingly important that the impact of parasite infection and infestation on the Kafue lechwe is investigated.</p> <p>Findings</p> <p>Endoparasites accounted for the majority of parasites observed from a study of 40 Kafue lechwe occurring in the the Kafue basin. <it>Amphistoma spp. </it>were present in all animals examined, while <it>Fasciola gigantica </it>had a prevalence rate of 0.525 (95% CI: 0.36 to 0.69) and species of <it>Schistosoma </it>0.3 (95% CI: 0.15 to 0.45). Among the ectoparasites, <it>Strobiloestrous vanzyli</it>, had a prevalence rate of 0.15 (95% CI: 0.03 to 0.27), while <it>Rhipicephalus appendiculatus </it>had a prevalence of 0.075 (3/40). Our findings indicate that body condition was not influenced by the parasitic infestation in Kafue lechwe. There was no association between sex and parasitic burden (odds ratio = 0.3, 95% CI: 0.8-1.3). However, an association between age and parasitic burden was observed as older animals above 15 years were more likely to get parasite infections than those aged between 1-5 years (odds ratio = 1.5, 95% CI: 1.1-2.4).</p> <p>Conclusion</p> <p>Overall, there was no evidence that parasitic infections and infestations adversely affected the lechwe population on the Kafue basin. These findings indicate that ecto- and endo-parasite infestation might not play a significant role in reducing the Kafue lechwe population on the Kafue basin.</p
Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis
Although macrophages are widely recognized to have a profibrotic role in inflammation, we have used a highly tractable CCl(4)-induced model of reversible hepatic fibrosis to identify and characterize the macrophage phenotype responsible for tissue remodeling: the hitherto elusive restorative macrophage. This CD11B(hi) F4/80(int) Ly-6C(lo) macrophage subset was most abundant in livers during maximal fibrosis resolution and represented the principle matrix metalloproteinase (MMP) -expressing subset. Depletion of this population in CD11B promoterâdiphtheria toxin receptor (CD11B-DTR) transgenic mice caused a failure of scar remodeling. Adoptive transfer and in situ labeling experiments showed that these restorative macrophages derive from recruited Ly-6C(hi) monocytes, a common origin with profibrotic Ly-6C(hi) macrophages, indicative of a phenotypic switch in vivo conferring proresolution properties. Microarray profiling of the Ly-6C(lo) subset, compared with Ly-6C(hi) macrophages, showed a phenotype outside the M1/M2 classification, with increased expression of MMPs, growth factors, and phagocytosis-related genes, including Mmp9, Mmp12, insulin-like growth factor 1 (Igf1), and Glycoprotein (transmembrane) nmb (Gpnmb). Confocal microscopy confirmed the postphagocytic nature of restorative macrophages. Furthermore, the restorative macrophage phenotype was recapitulated in vitro by the phagocytosis of cellular debris with associated activation of the ERK signaling cascade. Critically, induced phagocytic behavior in vivo, through administration of liposomes, increased restorative macrophage number and accelerated fibrosis resolution, offering a therapeutic strategy to this orphan pathological process
Exome-wide somatic mutation characterization of small bowel adenocarcinoma
Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.Peer reviewe
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