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To have a coherent picture of Wang Chong’s Lunheng is difficult. Some of Lunheng’s chapters obviously show Wang’s hostility to a large part of the folklore (including the social institutions based ...

The term “epistemic shifts” refers to a widely recognized phenomenon that knowledge ascribers would ascribe different epistemic statuses to the same belief under different internal/external conditions. Mainstream theories explaining shifts (including contextualism, contrastivism, and intellectual invariantism) can all be assimilated into a probabilistic framework, according to which the epistemic status of a belief P can be at least partially evaluated in terms of the strength of the link between this belief and its normal truth-maker, namely, a P-corresponding fact, and the strength of this link can be further probabilistically measured in terms of the knowledge-undermining force of an “abnormal” truth-maker of P, namely, a P-inducing fact which itself is not a P-corresponding fact simpliciter. I will further claim that by accepting my framework, a theorist of shifts has to tolerate a pluralist view of the etiology of shifts on the philosophical level, and mainstream theories explaining shifts are flawed in the sense that they all attempt to exaggerate one single and particular factor underpinning shifts by ignoring others.

“Epistemic safety” refers to an epistemic status in which the subject acquires true beliefs without involving epistemic luck. There is a tradition of cashing out safety-defining modality in terms of possible world semantics (as put forward by Duncan Pritchard), and even Julian Dutant's and Martin Smith's normalcy-based notions of safety also take this semantics as a significant component of them. However, such an approach has to largely depend on epistemologists’ ad hoc intuitions on how to individuate possible worlds and how to pick out “close” worlds. In contrast, I propose a probabilistic approach to safety to maximally preclude the preceding type of ad hoc-ness. The main idea is as follows: Each epistemic vignette wherein a subject S holds a true belief p has to be evaluated by a safety-ascriber, hence, S holds a true belief p safely iff according to the safety-ascriber's evaluation (which is based on her background knowledge), the probability of the occurrence of the truth-maker of p is above a pre-fixed “safety threshold”. My theory will be applied to Lottery Cases, Gettierized Cases and Skeptical Cases to test the scope of its applicability.

Wittgenstein’s criticism of the notion of ‘private language’ is related to the putative centrality of “being“ and the ‘subject-predicate’ distinction . However, his efforts would prove to be more f...

According to the standard interpretation of Gettier cases, they can be used to form significant challenges to the tradition of defining knowledge as justified true beliefs (hereafter “JTB”). This position naturally assumes that varieties of target beliefs involved in typical Gettier cases are all JTBs, namely, unified beliefs which are simultaneously justified and true. But I do not think this is true. Conversely, every target belief in typical Gettier cases should be cashed out as one or more beliefs, none of which is a genuine JTB. In short, there is no JTB in Gettier’s JTB-hostile vignettes at all. Hence, no matter whether the JTB account of knowledge is correct or not, Gettier cases are not really relevant to it. In addition, although I agree to Mizrahi’s (Logos Episteme 7(1):31–44, 2016) general observation that face-values of target beliefs cannot be taken for granted in all Gettier cases, I have made a further claim that there is no cross-board methodology to disambiguate the target beliefs in all Gettier cases.

Iki is the key word of Shūzō Kuki’s The Structure of Iki, and it became one of the most widely recognized Japanese aesthetic categories mainly due to this work. However, in The Problems of Contingency, which is Kuki’s most important philosophical work, there is no discussion of iki again, and consequently, most commentators of Kuki fail to see the correlation between his theories of iki and contingency. This article, by contrast, intends to provide a new interpretation of iki in the light of Kuki’s theory of contingency. The specific thesis of this paper is that aesthetic phenomena categorized as subject to the principles of iki are positively evaluated in Japanese culture just because the consciousness of iki is just one form of the consciousness of contingency, in which the awareness of alternatives to the actual situation could produce considerable spiritual entertainment for aesthetic subjects.

X-ray computed tomography (CT) is one of the most useful imaging technologies in the clinic. To increase the sensitivity of CT, iodinated compounds are used as injectable contrast agents. Unfortunately, the rapid renal clearance results in a narrow imaging window for diagnosis. In addition, the non-specific distributions and high osmolality of small molecules may induce serious adverse effects. However, nanoparticles can substantially overcome these limitations. As a result, developing new iodinated nanoparticles with high feasibility and availability as contrast agents is highly demanded for CT diagnosis. Herein, we reported fundamental research with a one-pot strategy for the synthesis of iohexol nanoparticles (INPs) on a large scale via polymerization-induced self-assembly (PISA) for CT imaging. The crosslinked core of INPs can increase the loading efficiency of iohexol to 36.5%, yielding sufficient contrast in CT imaging. Moreover, the stability of INPs was enhanced significantly via the core-crosslinking, allowing a good dispersion even in an extremely high concentration (120 mg mL−1). Compared to iohexol, the INPs showed a longer circulation time, negligible toxicity, analogous imaging capability and prominent accumulation in tumors. With these advantages, INPs could become better alternative contrast agents for cancer diagnosis and angiography in vivo.

Recently, zwitterionic materials have been developed as alternatives to PEG for prolonging the circulation time of nanoparticles without triggering immune responses. However, zwitterionic coatings also hindered the interactions between nanoparticles and tumor cells, leading to less efficient uptake of nanoparticles by cancer cells. Such effect significantly limited the applications of zwitterionic materials for the purposes of drug delivery and the development to novel therapeutic agents. To overcome these issues, surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces were constructed. Owing to the synergistic effect of zwitterionic coatings and micro-phase-separated surfaces, PMPC mixed-shell micelles exhibited the improved blood circulation time compared to single-PEG-shell micelles (PEGSMs) and single-PMPC-shell micelles (PMPCSMs). Moreover, such MSMs can convert their surface to positively charged ones in response to the acidic tumor microenvironment, leading to a significant enhancement in cellular uptake of MSMs by tumor cells. This strategy demonstrated a general approach to enhance the cellular uptake of zwitterionic nanoparticles without compromising their long circulating capability, providing a practical method for improving the tumor-targeting efficiency of particulate drug delivery systems. Statement of Significance Herein we demonstrate a general strategy to integrate non-fouling zwitterionic surface on the nanoparticles without compromising their capability of tumor accumulation, by constructing a surface-adaptive mixed-shell micelles (MSMs) with poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)/poly(β-amino ester) (PAE) heterogeneous surfaces. At the blood pH (7.4), PAE chains collapsed to the inner of the shell due to the deprotonation, and the forming micro-phase separation structure was synergistic with zwitterionic surface to prolong the circulation time of MSMs in the blood. While at the tumor sites, PAE was protonated, and the positively charged surface of MSMs enhanced cellular uptake. This self-assembly-based strategy is compatible to other zwitterionic materials, endowing a great flexibility for the construction of responsive drug delivery systems particularly to the novel chemotherapeutic agents.

Although the literature devoted to the naturalization of mainstream phenomenology has been blooming recently, not so many efforts have been made to make the intellectual legacy from Wittgenstein, who could also be viewed as a “linguistic phenomenologist,” accessible to cognitive science. The reluctance of making Wittgenstein naturalized is sometimes backed by the worry that Wittgenstein’s criticism of the notion of “thinking” as some “internal process” is also potentially threatening the computational theory of cognition. But this worry itself is based on some serious misunderstandings of the internal/external dichotomies, the clarifications of which would greatly relieve the tension between Wittgenstein and cognitive science. Moreover, cognitive linguistics could also be viewed as the intermediate theory between Wittgenstein and cognitive science due to the affinities it bears with both Wittgenstein’s later philosophy and cognitive science.

The enhanced permeability and retention (EPR) effect in human solid tumors is being increasingly questioned due to the failure of many nanomedicines in their clinical translation. Herein, we developed an ex vivo perfusion model for real-time investigation of the EPR effect in human renal tumors via X-ray computed tomography (CT), proving the EPR in human solid tumors and correlating the EPR effect in human tumors with that in animal models. Unexpectedly, more than 87 % of human renal tumors displayed a considerable EPR effect, which yet showed significant diversity and heterogeneity in different patients. For the first time, we unraveled that the EPR effect in renal tumors was positively correlated with the tumor size, and tumors from male patients exhibited a significantly higher EPR effect. This ex vivo model provides an efficient strategy for investigating the EPR effect in human tumors. Our results may provide a theoretical basis for the development of anticancer nanomedicines in the future.

Although atherosclerosis has been widely investigated at carotid artery bifurcation, there is a lack of morphometric and hemodynamic data at different stages of the disease. The purpose of this study was to determine the lesion difference in patients with carotid artery disease compared with healthy control subjects. The three-dimensional (3D) geometry of carotid artery bifurcation was reconstructed from computed tomography angiography (CTA) images of Chinese control subjects ( n = 30) and patients with carotid artery disease ( n = 30). We defined two novel vector angles (i.e., angles 1 and 2) that were tangential to the reconstructed contour of the 3D vessel. The best-fit diameter was computed along the internal carotid artery (ICA) center line. Hemodynamic analysis was performed at various bifurcations. Patients with stenotic vessels have larger angles 1 and 2 (151 ± 11° and 42 ± 20°) and smaller diameters of the external carotid artery (ECA) (4.6 ± 0.85 mm) compared with control subjects (144 ± 13° and 36 ± 16°, 5.2 ± 0.57 mm) although there is no significant difference in the common carotid artery (CCA) (7.1 ± 1.2 vs. 7.5 ± 1.0 mm, P = 0.18). In particular, all patients with carotid artery disease have a stenosis at the proximal ICA (including both sinus and carina regions), while 20% of patients have stenosis at the middle ICA and 20% have stenosis expansion to the entire cervical ICA. Morphometric and hemodynamic analyses suggest that atherosclerotic plaques initiate at both sinus and carina regions of ICA and progress downstream.

There is higher long‐term failure of the saphenous vein graft (SVG) compared with the left internal mammary artery (LIMA) graft, which is affected by the hemodynamic environment. A comprehensive analysis of postoperative structure‐function changes is important to study the atherogenesis in the SVG. A comparison of morphometric and hemodynamic parameters was carried out between LIMA grafts and SVGs and between different time points postoperatively. Various parameters were obtained from the image reconstruction and flow simulation in patients, who underwent CT exams for ~1 year, 5 and 10 years after revascularization. Morphometric data showed a decrease in lumen size in the entire SVG and anastomosis of different patients in a sequence of ~1 year, 5 and 10 years postoperatively despite negligible changes of LIMA size. Computational results indicated the fourfold increased surface area ratio (SAR) of low time‐averaged wall shear stress (TAWSS) in the SVG and anastomosis at postoperative 10 years than that at postoperative ~1 year. The SAR of high TAWSS gradient (TAWSSG) at the distal anastomosis between SVG and coronary arteries was significantly higher (14 ± 9% vs. 6 ± 8%) than that in the LIMA group at postoperative ~1 year. There were strong correlations between morphometric and hemodynamic parameters in the SVG and distal anastomosis at various time points postoperatively, which showed deterioration relevant to persistent diffuse diseases at postoperative ~10 years.

As many philosophers agree, the frame problem is concerned with how an agent may efficiently filter out irrelevant information in the process of problem-solving. Hence, how to solve this problem hinges on how to properly handle semantic relevance in cognitive modeling, which is an area of cognitive science that deals with simulating human’s cognitive processes in a computerized model. By “semantic relevance”, we mean certain inferential relations among acquired beliefs which may facilitate information retrieval and practical reasoning under certain epistemic constraints, e.g., the insufficiency of knowledge, the limitation of time budget, etc. However, traditional approaches to relevance—as for example, relevance logic, the Bayesian approach, as well as Description Logic—have failed to do justice to the foregoing constraints, and in this sense, they are not proper tools for solving the frame problem/relevance problem. As we will argue in this paper, Non-Axiomatic Reasoning System (NARS) can handle the frame problem in a more proper manner, because the resulting solution seriously takes epistemic constraints on cognition as a fundamental theoretical principle.

Intending to have a constructive dialogue with the combination of evolutionary theory (E) and metaphysical naturalism (N), Alvin Plantinga’s “evolutionary argument against naturalism” (EAAN) takes the reliability of human cognition (in normal environments) as a purported explanandum and E&N as a purported explanans. Then, he considers whether E&N can offer a good explanans for this explanandum, and his answer is negative (an answer employed by him to produce a defeater for N). But I will argue that the whole EAAN goes wrong by assuming that R is a qualified explanandum crying out for scientific explanations, since it cannot meet either of the two criteria for any scientifically qualified explanandum: Realizability Criterion and Informativeness Criterion. Hence, EAAN is simply setting a task that E&N, as a scientific theory, will not care at all. Therefore, EAAN cannot substantially shake E&N.

In this paper, we introduce a system that synthesizes the emotional audio-visual speech for a 3-D talking agent by adopting the PAD (Pleasure-Arousal-Dominance) emotional model. A GMM-based method is introduced to predict variation of acoustic features for emotional speech by PAD values, and a parametric framework of PAD-driven emotional facial expression synthesis is built. As the focus of this paper, we performed a series of perceptual evaluations to understand the reinforcement effect of vocal and facial expression of emotion, and investigated the usefulness and effectiveness of the emotional talking agent in human computer speech communications. Three questions are addressed: 1) To what extent do different interfaces affect human's comprehension of emotion? 2) How accurate the emotional information is conveyed by the talking agent? 3) Is the multimodal (audio-visual) interface helpful to human's emotion comprehension? An evaluation involving 19 participants was conducted to compare the effect of different interfaces (speech, mute agent and talking agent) on improving human's comprehension of emotion. The experimental results unveil the significant mutually reinforcing relationship between audio and video modality in emotion perception, and show that the users have a strong preference to multimodal interface for better comprehension of emotion. The results also prove the effectiveness of our PAD based emotional talking agent synthesis system.