Combining Fine- and Coarse-Grained Classifiers for Diabetic Retinopathy Detection

Visual artefacts of early diabetic retinopathy in retinal fundus images are usually small in size, inconspicuous, and scattered all over retina. Detecting diabetic retinopathy requires physicians to look at the whole image and fixate on some specific regions to locate potential biomarkers of the disease. Therefore, getting inspiration from ophthalmologist, we propose to combine coarse-grained classifiers that detect discriminating features from the whole images, with a recent breed of fine-grained classifiers that discover and pay particular attention to pathologically significant regions. To evaluate the performance of this proposed ensemble, we used publicly available EyePACS and Messidor datasets. Extensive experimentation for binary, ternary and quaternary classification shows that this ensemble largely outperforms individual image classifiers as well as most of the published works in most training setups for diabetic retinopathy detection. Furthermore, the performance of fine-grained classifiers is found notably superior than coarse-grained image classifiers encouraging the development of task-oriented fine-grained classifiers modelled after specialist ophthalmologists.Comment: Pages 12, Figures

Maximal Spontaneous Photon Emission and Energy Loss from Free Electrons

Free electron radiation such as Cerenkov, Smith--Purcell, and transition radiation can be greatly affected by structured optical environments, as has been demonstrated in a variety of polaritonic, photonic-crystal, and metamaterial systems. However, the amount of radiation that can ultimately be extracted from free electrons near an arbitrary material structure has remained elusive. Here we derive a fundamental upper limit to the spontaneous photon emission and energy loss of free electrons, regardless of geometry, which illuminates the effects of material properties and electron velocities. We obtain experimental evidence for our theory with quantitative measurements of Smith--Purcell radiation. Our framework allows us to make two predictions. One is a new regime of radiation operation---at subwavelength separations, slower (nonrelativistic) electrons can achieve stronger radiation than fast (relativistic) electrons. The second is a divergence of the emission probability in the limit of lossless materials. We further reveal that such divergences can be approached by coupling free electrons to photonic bound states in the continuum (BICs). Our findings suggest that compact and efficient free-electron radiation sources from microwaves to the soft X-ray regime may be achievable without requiring ultrahigh accelerating voltages.Comment: 7 pages, 4 figure

Effect of water-to-binder ratio and fly ash content on the mechanical and deformation properties of bendable concrete

To investigate the effect of water-to-binder ratio and fly ash content on the properties of bendable concrete, we prepared four samples of different strength grades with water-to-binder ratios of 0.25 and 0.30 and fly ash contents of 60% and 80%. The effects of water-to-binder ratio and fly ash content on the compressive strength, flexural strength, elastic modulus, fracture toughness, and uniaxial tensile deformation of the samples were investigated. The results show that the strength of bendable concrete can be varied by varying the water-to-binder ratio and fly ash content. Water-to-binder ratio and fly ash content showed almost the same effect on fracture toughness, whereas fly ash content exhibited a greater effect on elastic modulus. With an increase in water-to-binder ratio and fly ash content of concrete, the initial crack stress and tensile strength decreased and the ultimate tensile strain increased, but the change of water-to-binder ratio showed a more significant effect on the ultimate tensile strain

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon

Assessing vegetation response to multi-time-scale drought across inner Mongolia plateau

This study assessed the impacts of climate change in IMP by investigating vegetation responses droughtin multiple timescales. Methods used included the Normalized Difference Vegetation Index (NDVI) andStandardized Precipitation Evapotranspiration Index (SPEI), by annual maximum Pearson correlation(Rmax) and the corresponding month (Rmonth) of drought. Results showed that: (1) It is necessary tozone IMP when analyzing the vegetation responses to drought. (2) Rmax is significantly positive cor-relation in IMP, indicating that vegetation was largely in fl uenced by drought; the most seriously affectedareas are in the north-eastern part of typical steppe, south-western parts of steppe desert and southernpart of desert steppe, while light seriously are distributed in the south-eastern of typical steppe andforest steppe. (3) Vegetation in typical steppe, steppe desert and desert steppe are sensitive to shortertime-scales of droughts, while in the forest, forest steppe and sand desert, vegetation shows a closerelationship with the longer drought time-scales. (4) The effects of drought related climate extremes canalso contr ibute to Rmax and Rmo nth between SPEI and NDVI. Vegetation in forest and sand desert areas,have lower sensitivity to drought under the effect of climate extremes. Adaptation measures, such asbuilding drought resilience vegetation types, applying biochar and monitoring and forecasting drought,must be timely and effectively initiated, especially, in the typical steppe, steppe desert and desert steppein IMP since vegetation in these four areas is affected seriously, once drought occur. The results from thisstudy may provide useful infor mation about appropriate adaptation and mitigation strategies against theinverse effects of drought on vegetation, and even alleviate the losses caused by drought

Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

RNA polymerase II stalling promotes nucleosome occlusion and pTEFb recruitment to drive immortalization by Epstein-Barr virus

Epstein-Barr virus (EBV) immortalizes resting B-cells and is a key etiologic agent in the development of numerous cancers. The essential EBV-encoded protein EBNA 2 activates the viral C promoter (Cp) producing a message of ~120 kb that is differentially spliced to encode all EBNAs required for immortalization. We have previously shown that EBNA 2-activated transcription is dependent on the activity of the RNA polymerase II (pol II) C-terminal domain (CTD) kinase pTEFb (CDK9/cyclin T1). We now demonstrate that Cp, in contrast to two shorter EBNA 2-activated viral genes (LMP 1 and 2A), displays high levels of promoter-proximally stalled pol II despite being constitutively active. Consistent with pol II stalling, we detect considerable pausing complex (NELF/DSIF) association with Cp. Significantly, we observe substantial Cp-specific pTEFb recruitment that stimulates high-level pol II CTD serine 2 phosphorylation at distal regions (up to +75 kb), promoting elongation. We reveal that Cp-specific pol II accumulation is directed by DNA sequences unfavourable for nucleosome assembly that increase TBP access and pol II recruitment. Stalled pol II then maintains Cp nucleosome depletion. Our data indicate that pTEFb is recruited to Cp by the bromodomain protein Brd4, with polymerase stalling facilitating stable association of pTEFb. The Brd4 inhibitor JQ1 and the pTEFb inhibitors DRB and Flavopiridol significantly reduce Cp, but not LMP1 transcript production indicating that Brd4 and pTEFb are required for Cp transcription. Taken together our data indicate that pol II stalling at Cp promotes transcription of essential immortalizing genes during EBV infection by (i) preventing promoter-proximal nucleosome assembly and ii) necessitating the recruitment of pTEFb thereby maintaining serine 2 CTD phosphorylation at distal regions