The landscape of tumors-infiltrate immune cells in papillary thyroid carcinoma and its prognostic value

Introduction Thyroid cancer is a very common malignant tumor in the endocrine system, while the incidence of papillary thyroid carcinoma (PTC) throughout the world also shows a trend of increase year by year. In this study, we constructed two models: ICIscore and Riskscore. Combined with these two models, we can make more accurate and reasonable inferences about the prognosis of PTC patients. Methods We selected 481 PTC samples from TCGA and 147 PTC samples from GEO (49 samples in GSE33630, 65 samples in GSE35570 and 33 samples in GSE60542). We performed consistent clustering for them and divided them into three subgroups and screened differentially expressed genes from these three subgroups. Then we divided the differential genes into three subtypes. We also distinguished the up-regulated and down-regulated genes and calculated ICIscore for each PTC sample. ICIscore consists of two parts: (1) the PCAu was calculated from up-regulated genes. (2) the PCAd was calculated from down-regulated genes. The PCAu and PCAd of each sample were the first principal component of the relevant gene. What’s more, we divided the patients into two groups and constructed mRNA prognostic signatures. Additionally we also verified the independent prognostic value of the signature. Results Though ICIscore, we were able to observe the relationship between immune infiltration and prognosis. The result suggests that the activation of the immune system may have both positive and negative consequences. Though Riskscore, we could make more accurate predictions about the prognosis of patients with PTC. Meanwhile, we also generated and validated the ICIscore group and Riskscore group respectively. Conclusion All the research results show that by combining the two models constructed, ICIscore and Riskscore, we can make a more accurate and reasonable inference about the prognosis of patients with clinical PTC patients. This suggests that we can provide more effective and reasonable treatment plan for clinical PTC patients.

Consequences of Stability-Induced Epistasis for Substitution Rates

Do interactions between residues in a protein (i.e., epistasis) significantly alter evolutionary dynamics? If so, what consequences might they have on inference from traditional codon substitution models which assume site-independence for the sake of computational tractability? To investigate the effects of epistasis on substitution rates, we employed a mechanistic mutation-selection model in conjunction with a fitness framework derived from protein stability. We refer to this as the stability-informed site-dependent (S-SD) model and developed a new stability-informed site-independent (S-SI) model that captures the average effect of stability constraints on individual sites of a protein. Comparison of S-SI and S-SD offers a novel and direct method for investigating the consequences of stability-induced epistasis on protein evolution. We developed S-SI and S-SD models for three natural proteins and showed that they generate sequences consistent with real alignments. Our analyses revealed that epistasis tends to increase substitution rates compared with the rates under site-independent evolution. We then assessed the epistatic sensitivity of individual site and discovered a counterintuitive effect: Highly connected sites were less influenced by epistasis relative to exposed sites. Lastly, we show that, despite the unrealistic assumptions, traditional models perform comparably well in the presence and absence of epistasis and provide reasonable summaries of average selection intensities. We conclude that epistatic models are critical to understanding protein evolutionary dynamics, but epistasis might not be required for reasonable inference of selection pressure when averaging over time and sites.

Dynamic Graph Representation for Occlusion Handling in Biometrics

The generalization ability of Convolutional neural networks (CNNs) for biometrics drops greatly due to the adverse effects of various occlusions. To this end, we propose a novel unified framework integrated the merits of both CNNs and graphical models to learn dynamic graph representations for occlusion problems in biometrics, called Dynamic Graph Representation (DGR). Convolutional features onto certain regions are re-crafted by a graph generator to establish the connections among the spatial parts of biometrics and build Feature Graphs based on these node representations. Each node of Feature Graphs corresponds to a specific part of the input image and the edges express the spatial relationships between parts. By analyzing the similarities between the nodes, the framework is able to adaptively remove the nodes representing the occluded parts. During dynamic graph matching, we propose a novel strategy to measure the distances of both nodes and adjacent matrixes. In this way, the proposed method is more convincing than CNNs-based methods because the dynamic graph method implies a more illustrative and reasonable inference of the biometrics decision. Experiments conducted on iris and face demonstrate the superiority of the proposed framework, which boosts the accuracy of occluded biometrics recognition by a large margin comparing with baseline methods.

Flow directionality of pristine meandering rivers is embedded in the skewing of high-amplitude bends and neck cutoffs

Information concerning the dynamics of river meandering is embedded in their planforms. Here, we focus on how bend skewing varies with increasing sinuosity, and how flow direction is embedded in bend skewing. It has often been thought that upstream-skewed bends are dominant within a sufficiently long reach. These bends may allow a reasonable inference as to the direction of flow. Here we consider this issue using 20 reaches of freely meandering alluvial rivers that are in remote locations, generally far from human influence. We find that low-amplitude bends tend to be downstream-, rather than upstream-skewed. Bends with sinuosity greater than 2.6, however, are predominantly upstream-skewed. Of particular interest are the neck cutoffs, all chosen to be relatively recent according to their position related to the main channel: 84% of these are upstream-skewed. Neck cutoffs, which have likely evolved directly from bends of the highest sinuosity, represent the planform feature most likely to have flow direction embedded in them. The field data suggest that meander bends without external forcing such as engineering works tend to evolve from downstream-skewed low-sinuosity bends to upstream-skewed high-sinuosity bends before cutoff. This process can be reproduced, to some extent, using models coupling sedimentary dynamics with flow dynamics.

Semantic Health Knowledge Graph: Semantic Integration of Heterogeneous Medical Knowledge and Services

With the explosion of healthcare information, there has been a tremendous amount of heterogeneous textual medical knowledge (TMK), which plays an essential role in healthcare information systems. Existing works for integrating and utilizing the TMK mainly focus on straightforward connections establishment and pay less attention to make computers interpret and retrieve knowledge correctly and quickly. In this paper, we explore a novel model to organize and integrate the TMK into conceptual graphs. We then employ a framework to automatically retrieve knowledge in knowledge graphs with a high precision. In order to perform reasonable inference on knowledge graphs, we propose a contextual inference pruning algorithm to achieve efficient chain inference. Our algorithm achieves a better inference result with precision and recall of 92% and 96%, respectively, which can avoid most of the meaningless inferences. In addition, we implement two prototypes and provide services, and the results show our approach is practical and effective.

Three paradoxes and a reasonable inference

In a previous paper of mine I offered solutions to three paradoxes, two of which were solved in Stalnaker?s famous paper ?Indicative Conditionals? in terms of his distinction between valid and reasonable inference. In a sense my solutions to the two paradoxes are very similar. In this paper I explain why, despite the similarity, I looked for a different solution and new distinctions. After explaining the similarity, I argue that my distinctions point to a more basic phenomenon, which I try to show by applying the distinctions to problems that cannot be solved in terms of Stalnaker?s distinction. The third paradox is one such problem. Beside that, each of the paradoxes, originally formulated in terms of indicative conditionals, can be formulated in terms of counterfactual conditionals. I solve these cases in exactly the same way, while Stalnaker?s distinction is not applicable to them.

Luther and the Sacramentality of Penance

At the beginning of his De captivitate Babylonica ecclesiae praeludium of early October 1520, Luther announced that there, were not seven sacraments of the Church, but only three – baptism, penance, and the Lord’s Supper. By the end of the treatise, the three had been reduced to two. His reasoning was starkly logical. A sacrament, to be a sacrament, must contain the promise of forgiveness of sins, and have attached to it a visible sign instituted by Jesus Christ. Because no such visible sign is associated with the rite, penance cannot be a sacrament. A reasonable inference to draw is that Luther must have come to reject the sacramentality of penance by the time he composed De captivitate Babylonica, in perhaps August 1520.

The Genesis of the Only Diagram in the General Theory

It is well known that the General Theory contains only one diagram, this occurring in chapter 14 criticising the orthodox theory of the rate of interest. Attached to the diagram is a footnote containing an acknowledgement: “This diagram was suggested to me by Mr. R.F. Harrod” (CW VII, p. 180). The impression conveyed by this remark is that Harrod drew the diagram and offered it to Keynes, who then accepted and used it. Further enquiry into the diagram's origins reveals the existence of an initial version which grew out of correspondence between Keynes and Harrod in August-September 1935 (CW XIII, pp. 526-63). Two of Harrod's writings–his (1951) Keynes biography and a letter to Hawtrey in 1951–imply that he was the author of the initial version, and that this was essentially the same as the published version. And, in seeming corroboration of Harrod's comments, there is the virtual equivalence of the initial version given in The Collected Writings of John Maynard Keynes (CW XIII, p. 557) and the final version printed in the General Theory (CW VII, p. 180J. Taken individually and collectively, these items of evidence all point in the same direction. They support the reasonable inference that, apart from trivial changes in lettering, Harrod was the sole author and creator of the initial and final versions of the diagram, and that Keynes was merely the recipient.