Multi-Scale Attention-based Multiple Instance Learning for Classification of Multi-Gigapixel Histology Images

Histology images with multi-gigapixel of resolution yield rich information for cancer diagnosis and prognosis. Most of the time, only slide-level label is available because pixel-wise annotation is labour intensive task. In this paper, we propose a deep learning pipeline for classification in histology images. Using multiple instance learning, we attempt to predict the latent membrane protein 1 (LMP1) status of nasopharyngeal carcinoma (NPC) based on haematoxylin and eosin-stain (H&E) histology images. We utilised attention mechanism with residual connection for our aggregation layers. In our 3-fold cross-validation experiment, we achieved average accuracy, AUC and F1-score 0.936, 0.995 and 0.862, respectively. This method also allows us to examine the model interpretability by visualising attention scores. To the best of our knowledge, this is the first attempt to predict LMP1 status on NPC using deep learning

Delivery of high solubility polyols by vibrating mesh nebuliser to enhance mucociliary clearance

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Comprehensive Analysis of Human Subtelomeres by Whole Genome Mapping

Detailed comprehensive knowledge of the structures of individual long-range telomere-terminal haplotypes are needed to understand their impact on telomere function, and to delineate the population structure and evolution of subtelomere regions. However, the abundance of large evolutionarily recent segmental duplications and high levels of large structural variations have complicated both the mapping and sequence characterization of human subtelomere regions. Here, we use high throughput optical mapping of large single DNA molecules in nanochannel arrays for 154 human genomes from 26 populations to present a comprehensive look at human subtelomere structure and variation. The results catalog many novel long-range subtelomere haplotypes and determine the frequencies and contexts of specific subtelomeric duplicons on each chromosome arm, helping to clarify the currently ambiguous nature of many specific subtelomere structures as represented in the current reference sequence (HG38). The organization and content of some duplicons in subtelomeres appear to show both chromosome arm and population-specific trends. Based upon these trends we estimate a timeline for the spread of these duplication blocks

Upregulation of Id1 by Epstein-Barr Virus-encoded LMP1 confers resistance to TGFβ-mediated growth inhibition

BACKGROUND: Epstein-Barr virus (EBV)-encoded LMP1 protein is commonly expressed in nasopharyngeal carcinoma (NPC). LMP1 is a prime candidate for driving tumourigenesis given its ability to activate multiple signalling pathways and to alter the expression and activity of variety of downstream targets. Resistance to TGFβ-mediated cytostasis is one of the growth transforming effects of LMP1. Of the downstream targets manipulated by LMP1, the induction of Id1 and inactivation of Foxo3a appear particularly relevant to LMP1-mediated effects. Id1, a HLH protein is implicated in cell transformation and plays a role in cell proliferation, whilst Foxo3a, a transcription factor controls cell integrity and homeostasis by regulating apoptosis. The mechanism(s) by which LMP1 induces these effects have not been fully characterised. RESULTS: In this study, we demonstrate that the ability of LMP1 to induce the phosphorylation and inactivation of Foxo3a is linked to the upregulation of Id1. Furthermore, we show that the induction of Id1 is essential for the transforming function of LMP1 as over-expression of Id1 increases cell proliferation, attenuates TGFβ-SMAD-mediated transcription and renders cells refractory to TGFβ-mediated cytostasis. Id1 silencing in LMP1-expressing epithelial cells abolishes the inhibitory effect of LMP1 on TGFβ-mediated cell growth arrest and reduces the ability of LMP1 to attenuate SMAD transcriptional activity. In response to TGFβ stimulation, LMP1 does not abolish SMAD phosphorylation but inhibits p21 protein expression. In addition, we found the induction of Id1 in LMP1-expressing cells upon stimulation by TGFβ. We provide evidence that LMP1 suppresses the transcriptional repressor ATF3, possibly leading to the TGFβ-induced Id1 upregulation. CONCLUSION: The current data provide novel information regarding the mechanisms by which LMP1 suppresses TGFβ-induced cytostasis, highlighting the importance of Id1 in LMP1 mediated cell transformatio

Status update on White-eared Night Heron Gorsachius magnificus in South China

White-eared Night Heron Gorsachius magnificus is probably the most threatened heron species in the world, and the highest priority for heron species conservation. From 1990 to 1998, there were sightings from only six localities in the wild. There are none in captivity. In 1998 a caged bird was found in a wildlife market in the city of Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China. This finding prompted a 12-month survey in 1998-1999 of both markets and potential habitats in Guangxi. Several captured birds provided direct evidence of the existence of small populations in Guangxi and Guangdong Provinces. The respective habitats were surveyed in spring 2000, with emphasis on observations at dusk. The species was seen at two locations. Although some of the captured birds came from highly degraded habitat, the best sites seemed to be in areas near extensive primary forests, with streams, rice fields and marshes. The information obtained will be used to compile a detailed Action Plan designed to prevent the extinction of the species.published_or_final_versio

The symbiotic system AG Draconis. Soft X-ray bremsstrahlung from the nebulae

The modeling of UV and optical spectra emitted from the symbiotic system AG Draconis, adopting collision of the winds, predicts soft X-ray bremsstrahlung from nebulae downstream of the reverse shock with velocities > 150 km/s and intensities comparable to those of the white dwarf black body flux. At outbursts, the envelop of debris, which corresponds to the nebula downstream of the high velocity shocks (700-1000 km/s) accompanying the blast wave, absorbs the black body soft X-ray flux from the white dwarf, explains the broad component of the H and He lines, and leads to low optical-UV-X-ray continuum fluxes. The high optical-UV flux observed at the outbursts is explained by bremsstrahlung downstream of the reverse shock between the stars. The depletion of C, N, O, and Mg relative to H indicates that they are trapped into dust grains and/or into diatomic molecules, suggesting that the collision of the wind from the white dwarf with the dusty shells, ejected from the red giant with about 1 year periodicity, leads to the U-band fluctuations during the major bursts.Comment: 12 pages, 5 figures, 2 tables. New Astronomy, in pres

Submillimeter Array Observation of the Proto-Planetary Nebula CRL 618 in the CO J=6-5 Line

We report on the results of a Submillimeter Array interferometric observation of the proto-planetary nebula CRL 618 in the 12CO J=6-5 line. With the new capability of SMA enabling us to use two receivers at a time, we also observed simultaneously in the 12CO J=2-1 and 13CO J=2-1 lines. The 12CO J=6-5 and 13CO J=2-1 lines were first interferometrically observed toward CRL 618. The flux of the high velocity component of the 12CO J=6-5 line is almost fully recovered, while roughly 80% of the flux of the low velocity component is resolved out. The low recovery rate suggests that the emission region of the low velocity component of the 12CO J=6-5 line is largely extended. Continuum emission is detected both at 230 and 690 GHz. The flux of the 690 GHz continuum emission seems to be partially resolved out, suggesting dust emission partly contaminates the 690 GHz continuum flux. The cavity structure, which has been confirmed in a previous observation in the 12CO J=2-1 line, is not clearly detected in the 12CO J=6-5 line, and only the south wall of the cavity is detected. This result suggests that the physical condition of the molecular envelope of CRL 618 is not exactly axial symmetric.Comment: 24 pages, 9 figures, 1 table, accepted for publication in AJ. Full resolution version available at http://www.asiaa.sinica.edu.tw/~junichi/paper