A computational cognition model of perception, memory, and judgment

The mechanism of human cognition and its computability provide an important theoretical foundation to intelligent computation of visual media. This paper focuses on the intelligent processing of massive data of visual media and its corresponding processes of perception, memory, and judgment in cognition. In particular, both the human cognitive mechanism and cognitive computability of visual media are investigated in this paper at the following three levels: neurophysiology, cognitive psychology, and computational modeling. A computational cognition model of Perception, Memory, and Judgment (PMJ model for short) is proposed, which consists of three stages and three pathways by integrating the cognitive mechanism and computability aspects in a unified framework. Finally, this paper illustrates the applications of the proposed PMJ model in five visual media research areas. As demonstrated by these applications, the PMJ model sheds some light on the intelligent processing of visual media, and it would be innovative for researchers to apply human cognitive mechanism to computer science.</p

Wnt2 secreted by tumour fibroblasts promotes tumour progression in oesophageal cancer by activation of the Wnt/β-catenin signalling pathway

Objectives: Interaction between neoplastic and stromal cells plays an important role in tumour progression. It was recently found that WNT2 was frequently overexpressed in fibroblasts isolated from tumour tissue tumour fibroblasts (TF) compared with fibroblasts from non-tumour tissue normal fibroblasts in oesophageal squamous cell carcinoma (OSCC). This study aimed to investigate the effect of TF-secreted Wnt2 in OSCC development via the tumour - stroma interaction. Methods: Quantitative PCR, western blotting, immunohistochemistry and immunofluorescence were used to study the expression pattern of Wnt2 and its effect on the Wnt/β-catenin pathway. A Wnt2-secreting system was established in Chinese hamster ovary cells and its conditioned medium was used to study the role of Wnt2 in cell proliferation and invasion. Results: Expression of Wnt2 could only be detected in TF but not in OSCC cancer cell lines. In OSCC tissues, Wnt2 (+) cells were mainly detected in the boundary between stroma and tumour tissue or scattered within tumour tissue. In this study, Wnt2-positive OSCC was defined when five or more Wnt2(+) cells were observed in 2003X microscopy field. Interestingly, Wnt2-positive OSCC (22/51 cases) was significantly associated with lymph node metastases (p=0.001), advanced TNM stage (p=0.001) and disease-specific survival (p<0.0001). Functional study demonstrated that secreted Wnt2 could promote oesophageal cancer cell growth by activating the Wnt/β-catenin signalling pathway and subsequently upregulated cyclin D1 and c-myc expression. Further study found that Wnt2 could enhance cell motility and invasiveness by inducing epithelial-mesenchymal transition. Conclusions: TF-secreted Wnt2 acts as a growth and invasion-promoting factor through activating the canonical Wnt/β-catenin signalling pathway in oesophageal cancer cells.published_or_final_versio

Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Sequential establishment of stripe patterns in an expanding cell population

Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.published_or_final_versio

Genetic Structure and Demographic History Should Inform Conservation: Chinese Cobras Currently Treated as Homogenous Show Population Divergence

An understanding of population structure and genetic diversity is crucial for wildlife conservation and for determining the integrity of wildlife populations. The vulnerable Chinese cobra (Naja atra) has a distribution from the mouth of the Yangtze River down to northern Vietnam and Laos, within which several large mountain ranges and water bodies may influence population structure. We combined 12 microsatellite loci and 1117 bp of the mitochondrial cytochrome b gene to explore genetic structure and demographic history in this species, using 269 individuals from various localities in Mainland China and Vietnam. High levels of genetic variation were identified for both mtDNA and microsatellites. mtDNA data revealed two main (Vietnam + southern China + southwestern China; eastern + southeastern China) and one minor (comprising only two individuals from the westernmost site) clades. Microsatellite data divided the eastern + southeastern China clade further into two genetic clusters, which include individuals from the eastern and southeastern regions, respectively. The Luoxiao and Nanling Mountains may be important barriers affecting the diversification of lineages. In the haplotype network of cytchrome b, many haplotypes were represented within a “star” cluster and this and other tests suggest recent expansion. However, microsatellite analyses did not yield strong evidence for a recent bottleneck for any population or genetic cluster. The three main clusters identified here should be considered as independent management units for conservation purposes. The release of Chinese cobras into the wild should cease unless their origin can be determined, and this will avoid problems arising from unnatural homogenization

Identifying efficient solutions via simulation: myopic multi-objective budget allocation for the bi-objective case

Simulation optimisation offers great opportunities in the design and optimisation of complex systems. In the presence of multiple objectives, there is usually no single solution that performs best on all objectives. Instead, there are several Pareto-optimal (efficient) solutions with different trade-offs which cannot be improved in any objective without sacrificing performance in another objective. For the case where alternatives are evaluated on multiple stochastic criteria, and the performance of an alternative can only be estimated via simulation, we consider the problem of efficiently identifying the Pareto-optimal designs out of a (small) given set of alternatives. We present a simple myopic budget allocation algorithm for multi-objective problems and propose several variants for different settings. In particular, this myopic method only allocates one simulation sample to one alternative in each iteration. This paper shows how the algorithm works in bi-objective problems under different settings. Empirical tests show that our algorithm can significantly reduce the necessary simulation budget

Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-gamma-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-gamma expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-gamma production, but also the protective function of iNKT cells in arthritis

CRISPR/Cas9-mediated editing of GABRR2 gene in RGC-5 cells induces random exon deletion, exon splicing and new exon recruitment

CRISPR/Cas9 and its variations provide an efficient tool for targeted genome editing. CRISPR/Cas9-based genome editing can induce mutations in genome that has high probability to cause exon truncation or deletion. However, screening mutations in diploid cells is difficult because of two copies of chromosome. It is an important task for determining genotypes in diploid cells subjected to editing before using these cells in gene function study. In this study, we applied CRISPR/Cas9 to edit the GABRR2 gene in mouse retinal ganglion cells to study what exactly happened in two alleles and what real mRNA isoforms formed in diploid cells. A single sgRNA was employed to generate double-strand DNA breaks. PCR sequencing was used for single clone validation in diploid cells subjected to editing. The indels and the corresponding effects at the target locus were further studied at genomic and RNA levels. We observed that CRISPR/Cas9 induces random deletions in the target region of GABRR2 gene, and both big and small indels can lead to unexpected high probability of exon truncation/skipping. In addition, random deletions in genomic region recruited introns to generate new “exon”. It is the first observation of exon recruitment by CRISPR/Cas9-mediated GABRR2 gene editing. The observations may offer a reference for the future gene splicing study

Anti-CTLA4 monoclonal antibodies: the past and the future in clinical application

Recently, two studies using ipilimumab, an anti-CTLA-4 monoclonal antibody (mab) demonstrated improvements in overall survival in the treatment of advanced melanoma. These studies utilized two different schedules of treatment in different patient categories (first and second line of treatment). However, the results were quite similar despite of different dosage used and the combination with dacarbazine in the first line treatment. We reviewed the result of randomized phase II-III clinical studies testing anti-CTLA-4 antibodies (ipilimumab and tremelimumab) for the treatment of melanoma to focus on practical or scientific questions related to the broad utilization of these products in the clinics. These analyses raised some considerations about the future of these compounds, their potential application, dosage, the importance of the schedule (induction/manteinance compared to induction alone) and their role as adjuvants. Anti-CTLA-4 antibody therapy represents the start of a new era in the treatment of advanced melanoma but we are on the steep slope of the learning curve toward the optimization of their utilization either a single agents or in combination