Augmentation is AUtO-Net: Augmentation-Driven Contrastive Multiview Learning for Medical Image Segmentation

The utilisation of deep learning segmentation algorithms that learn complex organs and tissue patterns and extract essential regions of interest from the noisy background to improve the visual ability for medical image diagnosis has achieved impressive results in Medical Image Computing (MIC). This thesis focuses on retinal blood vessel segmentation tasks, providing an extensive literature review of deep learning-based medical image segmentation approaches while comparing the methodologies and empirical performances. The work also examines the limitations of current state-of-the-art methods by pointing out the two significant existing limitations: data size constraints and the dependency on high computational resources. To address such problems, this work proposes a novel efficient, simple multiview learning framework that contrastively learns invariant vessel feature representation by comparing with multiple augmented views by various transformations to overcome data shortage and improve generalisation ability. Moreover, the hybrid network architecture integrates the attention mechanism into a Convolutional Neural Network to further capture complex continuous curvilinear vessel structures. The result demonstrates the proposed method validated on the CHASE-DB1 dataset, attaining the highest F1 score of 83.46% and the highest Intersection over Union (IOU) score of 71.62% with UNet structure, surpassing existing benchmark UNet-based methods by 1.95% and 2.8%, respectively. The combination of the metrics indicates the model detects the vessel object accurately with a highly coincidental location with the ground truth. Moreover, the proposed approach could be trained within 30 minutes by consuming less than 3 GB GPU RAM, and such characteristics support the efficient implementation for real-world applications and deployments

Comparative study of discretization methods of microarray data for inferring transcriptional regulatory networks

<p>Abstract</p> <p>Background</p> <p>Microarray data discretization is a basic preprocess for many algorithms of gene regulatory network inference. Some common discretization methods in informatics are used to discretize microarray data. Selection of the discretization method is often arbitrary and no systematic comparison of different discretization has been conducted, in the context of gene regulatory network inference from time series gene expression data.</p> <p>Results</p> <p>In this study, we propose a new discretization method "bikmeans", and compare its performance with four other widely-used discretization methods using different datasets, modeling algorithms and number of intervals. Sensitivities, specificities and total accuracies were calculated and statistical analysis was carried out. Bikmeans method always gave high total accuracies.</p> <p>Conclusions</p> <p>Our results indicate that proper discretization methods can consistently improve gene regulatory network inference independent of network modeling algorithms and datasets. Our new method, bikmeans, resulted in significant better total accuracies than other methods.</p

A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein

Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past 2 decades, which highlights the pressing need for antiviral therapeutics. In a high-throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV-infected cultures with 2 MBDAA reduced the virion production by greater than 2 logs, the compound was not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug-resistant viruses revealed that replacement of the proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine, or alanine conferred YFV with resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, replacement of P219 with glycine conferred BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 amino acid is localized at the endoplasmic reticulum lumen side of the fifth putative transmembrane domain of NS4B, and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed an important role and the structural basis for the NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs, and attenuated virus infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever

Establishment and Characterization of an Immortalized Porcine Oral Mucosal Epithelial Cell Line as a Cytopathogenic Model for Porcine Circovirus 2 Infection

Porcine circovirus 2 (PCV2) is a major etiological agent for porcine circovirus-associated diseases and causes enormous economic losses in domestic and overseas swine production. However, there are currently no suitable cell models to study the cytopathic effects (CPE) of PCV2 in vitro, which severely restricts the study of PCV2 pathogenesis. In the present study, we established an immortalized porcine oral mucosal epithelial cell line (hTERT-POMEC) by introducing the hTERT gene into primary porcine oral mucosal epithelial cells (POMECs) derived from a neonatal, unsuckled piglet. The hTERT-POMEC cells have a homogeneous cobblestone-like morphology and retain the basic physiological properties of primary POMECs. No chromosome abnormality and tumorigenicity transformation was observed in immortalized hTERT-POMECs. Viral infection assays demonstrated that PCV2 propagated and caused CPE in hTERT-POMECs. We conclude that the immortalized cell line hTERT-POMEC is a crucial tool for further research into the pathogenesis of PCV2

Cloning and sequence analysis of Wild Argali short palate, lung and nasal epithelium clone 1 cDNA

Objective Experiments were conducted to clone the sequence of Wild Argali short palate, lung and nasal epithelium clone 1 (SPLUNC1) cDNA, and to lay the foundation for further study the biological function of Wild Argali SPLUNC1. Methods The complete sequence of Wild Argali SPLUNC1 cDNA was generated by rapid amplification of cDNA ends. The entire coding sequence was inserted into the pPIC9K vector and expressed in Pichia pastoris (P. pastoris) GS115. The recombinant SPLUNC1 protein was detected by Western blot and purified by Ni2+ chelate affinity chromatography. The test of effect of the protein on Mycoplasma ovipneumoniae (MO) was performed with real-time polymerase chain reaction. Results The Wild Argali SPLUNC1 cDNA was 1,076 bp with an open reading frame of 768 bp, which encoded a 26.49 kDa protein composed of 255 amino acids. Its amino acid sequence shared 98.4%, 96.9%, 94.5%, 90.2%, 80.8%, 78.4%, 78.3%, 72.5%, 72.3%, 68.8% identity with those of SPLUNC1 cDNA from Ovis aries (accession no. NP_001288334.1), Capra hircus (accession no. XP_005688516.1), Pantholops hodgsonii (accession no. XP_005979709.1), Bos taurus (accession no. NP_776851.1), Felis catus (accession no. XP_006929910.1), Homo sapiens (accession no. NP_001230122.1), Sus scrofa (accession no. NP_001005727.1), Chinchilla lanigera (accession no. NP_001269294.1), Mus musculus (accession no. NP_035256.2), and Rattus norvegicus (accession no. NP_742028.1), respectively. The recombinant protein corresponded to the expected molecular mass of 25.47 kDa as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it was detected in the supernatant of P. pastoris, and it could be purified. The results from the test of inhibition effect of argali recombinant SPLUNC1 protein on MO showed that the product could inhibit MO very well (p<0.01). Conclusion The amino acid sequence of Wild Argali SPLUNC1 was different from other organisms. The recombinant SPLUNC1 protein has good biological activity

Neutral operator with variable parameter and third-order neutral differential equation

Additional file 1. The TRS sequences of structural genes in the HP-PRRSV/SD16 genome (GenBank: JX087437)

Environmental Stress Responses of DnaJA1, DnaJB12 and DnaJC8 in Apis cerana cerana

DnaJ, also known as Hsp40, plays important roles in maintaining the normal physiological state of an organism under stress conditions by mediating essential processes, such as protein synthesis, degradation, folding and metabolism. However, the exact functions of most DnaJ members are not fully understood in insects. Here, we identified three genes, AccDnaJA1, AccDnaJB12, and AccDnaJC8, in Apis cerana cerana and explored their connection with the environmental stress response. Quantitative real-time PCR results showed that the mRNA levels of AccDnaJA1, AccDnaJB12, and AccDnaJC8 were all induced under cold, UV, H2O2 and different pesticides treatment. The expression patterns of AccDnaJB12 and AccDnaJC8 were upregulated by CdCl2 and HgCl2 stress, while the transcriptional levels of AccDnaJA1 were downregulated by CdCl2 and HgCl2 stress. Western blot findings further indicated that AccDnaJB12 protein levels were increased by some stress conditions. Knockdown of each of these three genes downregulated the transcriptional patterns of several stress response-related genes at different levels. Functional analysis further demonstrated that the resistance of A. cerana cerana to lambda-cyhalothrin stress was reduced with knockdown of AccDnaJA1, AccDnaJB12, or AccDnaJC8, indicating that these three genes may be involved in the tolerance to this pesticide. Taken together, these findings indicate that AccDnaJA1, AccDnaJB12, and AccDnaJC8 may play pivotal roles in the stress response by facilitating honeybee survival under some adverse circumstances. To our knowledge, this is the first report that reveals the roles of DnaJ family proteins under different adverse circumstances in A. cerana cerana

1,25-Dihydroxyvitamin D3 Ameliorates Collagen-Induced Arthritis via Suppression of Th17 Cells Through miR-124 Mediated Inhibition of IL-6 Signaling

Objectives: To explore the molecular mechanisms in which vitamin D (VD) regulates T cells, especially Th17 cells in collagen-induced arthritis (CIA).Methods: DBA1/J mice induced for CIA were intraperitoneally treated with VD. CIA clinical symptoms and inflammatory responses including Th1/Th17/Tregs percentages were determined and compared. Mouse naïve CD4+ T cells transduced with miR-124 inhibitor or not were polarized to Th17 cells with or without VD. Subsequently, cellular differentiation and IL-6 signaling moleculars were analyzed.Results: VD treatment significantly delayed CIA onset, decreased incidence and clinical scores of arthritis, downregulated serum IgG levels and ameliorated bone erosion. VD downregulated IL-17A production in CD4+ T cells while increased CD4+Foxp3+Nrp-1+ cells both in draining lymph nodes and synovial fluid in arthritic mice. VD inhibited Th17 cells differentiation in vivo and in vitro and potentially functioning directly on T cells to restrain Th17 cells through limiting IL-6R expression and its downstream signaling including STAT3 phosphorylation, while these effects were blocked when naïve CD4+ T cells were transduced with miR-124 inhibitor.Conclusions: VD treatment ameliorates CIA via suppression of Th17 cells and enhancement of Tregs. miR-124-mediated inhibition of IL-6 signaling, provides a novel explanation for VD's role on T cells in CIA mice or RA patients and suggests that VD may have treatment implications in rheumatoid arthritis