Yanjing Wang

Contactin-Associated protein-like 2 is a large multidomain neuronal adhesion molecule implicated in a number of neurological disorders, including epilepsy, schizophrenia, autism spectrum disorder, intellectual disability, and language delay. We reveal here by electron microscopy that the architecture of CNTNAP2 is composed of a large, medium, and small lobe that flex with respect to each other. Using epitope labeling and fragments, we assign the F58C, L1, and L2 domains to the large lobe, the FBG and L3 domains to the middle lobe, and the L4 domain to the small lobe of the CNTNAP2 molecular envelope. Our data reveal that CNTNAP2 has a very different architecture compared with neurexin 1α, a fellow member of the neurexin superfamily and a prototype, suggesting that CNTNAP2 uses a different strategy to integrate into the synaptic protein network. We show that the ectodomains of CNTNAP2 and contactin 2 bind directly and specifically, with low nanomolar affinity. We show further that mutations in CNTNAP2 implicated in autism spectrum disorder arenot segregated but are distributed over the whole ectodomain. The molecular shape and dimensions of CNTNAP2 place constraints on how CNTNAP2 integrates in the cleft of axo-glial and neuronal contact sites and how it functions as an organizing and adhesive molecule.

Analysis of gene expression patterns in gastric cancer can help to identify a comprehensive panel of gene biomarkers for predicting clinical outcomes and to discover potential new therapeutic targets. Here, a multi-step bioinformatics analytic approach was developed to establish a novel prognostic scoring system for GC. We first identified 276 genes that were robustly differentially expressed between normal and GC tissues, of which, 249 were found to be significantly associated with overall survival by univariate Cox regression analysis. The biological functions of 249 genes are related to cell cycle, RNA/ncRNA process, acetylation and extracellular matrix organization. A network was generated for view of the gene expression architecture of 249 genes in 265 GCs. Finally, we applied a canonical discriminant analysis approach to identify a 53-gene signature and a prognostic scoring system was established based on a canonical discriminant function of 53 genes. The prognostic scores strongly predicted patients with GC to have either a poor or good OS. Our study raises the prospect that the practicality of GC patient prognosis can be assessed by this prognostic scoring system.

Selective photothermolysis is the basic principle for laser treatment of vascular malformations such as port wine stain birthmarks. During cutaneous laser surgery, blood inside blood vessels is heated due to selective absorption of laser energy, while the surrounding normal tissue is spared. As a result, the blood and the surrounding tissue experience a local thermodynamic non-equilibrium condition. Traditionally, the PWS laser treatment process was simulated by a discrete-blood-vessel model that simplifies blood vessels into parallel cylinders buried in a multi-layer skin model. In this paper, PWS skin is treated as a porous medium made of tissue matrix and blood in the dermis. A two-temperature model is constructed following the local thermal non-equilibrium theory of porous media. Both transient and steady heat conduction problems are solved in a unit cell for the interfacial heat transfer between blood vessels and the surrounding tissue to close the present two-temperature model. The present two-temperature model is validated by good agreement with those from the discrete-blood-vessel model. The characteristics of the present two-temperature model are further illustrated through a comparison with the previously-used homogenous model, in which a local thermodynamic equilibrium assumption between the blood and the surrounding tissue is employed. © 2013 Published by Elsevier Inc.

Background: PPM1G is a nuclear localized serine/threonine phosphatase implicated to be a regulator of chromatin remodeling, mRNA splicing, and DNA damage. However, its in vivo function is unknown. Results: Here we show that ppm1g expression is highly enriched in the central nervous system during mouse and zebrafish development. ppm1g-/- mice were embryonic lethal with incomplete penetrance after E12.5. Rostral defects, including neural tube and craniofacial defects were observed in ppm1g-/- embryos associated with increased cell death in the neural epithelium. In zebrafish, loss of ppm1g also led to neural defects with aberrant neural marker gene expression. Primary fibroblasts from ppm1g-/- embryos failed to grow without immortalization while immortalized ppm1g-/- fibroblasts had increased cell death upon oxidative and genotoxic stress when compared to wild type fibroblasts. Conclusions: Our in vivo and in vitro studies revealed a critical role for PPM1G in normal development and cell survival. © 2013 Wiley Periodicals, Inc.

© 2015 IEEE. Over 50% of HIV+ individuals exhibit neurocognitive impairment and subcortical atrophy, but the pattern of brain abnormalities associated with HIV is still poorly understood. Using parametric surface-based shape analyses, we mapped the 3D profile of subcortical morphometry in 63 HIV+ participants and 31 uninfected controls. The thalamus, corpus striatum, hippocampus, amygdala, brainstem, callosum and ventricles were segmented from brain MRIs. To investigate subcortical shape, we analyzed the Jacobian determinant and radial distances for structure surfaces. We also investigated effects of nadir CD4+ T-cell counts, viral load, and illness duration on subcortical morphology. Our results characterize subcortical morphometry in older HIV+ people, where participants showed significant volumetric enlargements in the thalamus, left pallidum and the ventricles while showing a reduction in the callosum. Further, RD maps revealed atrophy of the left thalamus and expansion of the brainstem in HIV. RD and JD maps of the right pallidum identified tissue expansion associated with illness duration while the left pallidum showed anterior atrophy and posterior expansion associated with viral load.

Background: Malaria around the China-Myanmar border is a serious health problem in the countries of South-East Asia. An. minimus is a principle malaria vector with a wide geographic distribution in this area. Malaria is endemic along the boundary between Yunnan province in China and the Kachin State of Myanmar where the local Anopheles community and the malaria transmission vectors have never been clarified. Methods. Adult Anopheles specimens were collected using CDC light traps in four villages along the border of China and Myanmar from May 2012 to April 2013. Morphological and molecular identification of mosquito adults confirmed the species of Anopheles. Blood-meal identification using the female abdomens was conducted using multiplex PCR. For sporozoite detection in An. minimus, sets of 10 female salivary glands were pooled and identified with SSU rDNA using nested PCR. Monthly abundance of An. minimus populations during the year was documented. The diversity of Anopheles and the role of An. minimus on malaria transmission in this border area were analyzed. Results: 4,833 adult mosquitoes in the genus Anopheles were collected and morphologically identified to species or species complex. The Anopheles community is comprised of 13 species, and 78.83% of our total specimens belonged to An. minimus s.l., followed by An. maculatus and the An. culicifacies complex. The quantity of trapped An. minimus in the rainy season of malaria transmission was greater than during the non-malarial dry season, and a peak was found in May 2012. An. minimus fed on the blood of four animals: humans, cattle, pigs and dogs. 1,500 females of An. minimus were pooled into 150 samples and tested for sporozoites: only 1 pooled sample was found to have sporozoites of Plasmodium vivax. Conclusion: Anopheles is abundant with An. minimus being the dominant species and having a high human blood index along the China-Myanmar border. The sporozoites in An. minimus were determined to be Plasmodium vivax with a 0.07-0.7% infection rate. © 2013Yu et al.; licensee BioMed Central Ltd.

This paper connects the following four topics: a class of generalized graphs whose relations do not have fixed arities called hypergraphs, a family of non-normal modal logics rejecting the aggregative axiom, an epistemic framework fighting logical omniscience, and the classical group knowledge modality of ‘someone knows’. Through neighborhood frames as their meeting point, we show that, among many completeness results obtained in this paper, the limit of a family of weakly aggregative logics is both exactly the modal logic of hypergraphs and also the epistemic logic of local reasoning with veracity and positive introspection, and upon adding a single combinatorial axiom, it is also the logic of ‘someone knows’ for a fixed finite number of positively introspective agents. At the core of all these completeness results is a new canonical neighborhood model construction for monotone modal logics that is capable of dealing with all these diverse cases. We also provide an axiomatization for the logic of all non-n-colorable hypergraphs based on a filtration argument that also shows the decidability of the logics of hypergraphs we study.

Weakly Aggregative Modal Logic ) is a collection of disguised polyadic modal logics with n-ary modalities whose arguments are all the same. \ has interesting applications on epistemic logic, deontic logic, and the logic of belief. In this paper, we study some basic model theoretical aspects of \. Specifically, we first give a van Benthem–Rosen characterization theorem of \ based on an intuitive notion of bisimulation. Then, in contrast to many well known normal or non-normal modal logics, we show that each basic \ system \ lacks Craig interpolation. Finally, by model theoretical techniques, we show that an extension of \ does have Craig interpolation, as an example of amending the interpolation problem of \.

In this paper, using a propositional modal language extended with the window modality, we capture the first-order properties of various mereological theories. In this setting, $\Box \varphi $ reads all the parts (of the current object) are $\varphi $, interpreted on the models with a whole-part binary relation under various constraints. We show that all the usual mereological theories can be captured by modal formulas in our language via frame correspondence. We also correct a mistake in the existing completeness proof for a basic system of mereology by providing a new construction of the canonical model.

This paper connects the following three apparently unrelated topics: an epistemic framework fighting logical omniscience, a class of generalized graphs without the arities of relations, and a family of non-normal modal logics rejecting the aggregative axiom. Through neighborhood frames as their meeting point, we show that, among many completeness results obtained in this paper, the limit of a family of weakly aggregative logics is both exactly the modal logic of hypergraphs and also the epistemic logic of local reasoning with veracity and positive introspection. The logics studied are shown to be decidable based on a filtration construction.

In this paper, we give an alternative semantics to the non-normal logic of knowing how proposed by Fervari et al., based on a class of Kripke neighborhood models with both the epistemic relations and neighborhood structures. This alternative semantics is inspired by the same quantifier alternation pattern of ∃∀\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\exists \forall $$\end{document} in the semantics of the know-how modality and the neighborhood semantics for the standard modality. We show that this new semantics is equivalent to the original Kripke semantics in terms of the validities. A key result is a representation theorem showing that the more abstract Kripke neighborhood models can be represented by the concrete Kripke models with action transitions modulo the valid formulas. We prove the completeness of the logic for the neighborhood semantics. The neighborhood semantics can be adapted to other variants of logics of knowing how. It provides us a powerful technical tool to study these logics while preserving the basic semantic intuition.

As a new type of epistemic logics, the logics of knowing how capture the high-level epistemic reasoning about the knowledge of various plans to achieve certain goals. Existing work on these logics focuses on axiomatizations; this paper makes the first study of their model theoretical properties. It does so by introducing suitable notions of bisimulation for a family of five knowing how logics based on different notions of plans. As an application, we study and compare the expressive power of these logics.

When we say “I know why he was late”, we know not only the fact that he was late, but also an explanation of this fact. We propose a logical framework of “knowing why” inspired by the existing formal studies on why-questions, scientific explanation, and justification logic. We introduce the Kyi\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${{\mathcal {K}}{}\textit{y}}_i$$\end{document} operator into the language of epistemic logic to express “agent i knows why φ\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\varphi $$\end{document}” and propose a Kripke-style semantics of such expressions in terms of knowing an explanation of φ\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\varphi $$\end{document}. We obtain two sound and complete axiomatizations w.r.t. two different model classes depending on different assumptions about introspection. Finally we connect our logic with justification logic technically by providing an alternative semantics and an in-depth comparison on various design choices.

© Springer-Verlag Berlin Heidelberg 2015. When reasoning about knowledge of procedures under imperfect information, the explicit representation of epistemic possibilities blows up the S5like models of standard epistemic logic. To overcome this drawback, in this paper, we propose a new logical framework based on compact models without epistemic accessibility relations for reasoning about knowledge of procedures. Inspired by the 3-valued abstraction method in model checking, we introduce hyper models which encode the imperfect procedural information. We give a highly non-trivial 2-valued semantics of epistemic dynamic logic on such models while validating all the usual S5 axioms. Our approach is suitable for applications where procedural information is ‘learned’ incrementally, as demonstrated by various examples.

When agents know a protocol, this leads them to have expectations about future observations. Agents can update their knowledge by matching their actual observations with the expected ones. They eliminate states where they do not match. In this paper, we study how agents perceive protocols that are not commonly known, and propose a semantics-driven logical framework to reason about knowledge in such scenarios. In particular, we introduce the notion of epistemic expectation models and a propositional dynamic logic-style epistemic logic for reasoning about knowledge via matching agentsÊ expectations to their observations. It is shown how epistemic expectation models can be obtained from epistemic protocols. Furthermore, a characterization is presented of the effective equivalence of epistemic protocols. We introduce a new logic that incorporates updates of protocols and that can model reasoning about knowledge and observations. Finally, the framework is extended to incorporate fact-changing actions, and a worked-out example is given. © 2013 Elsevier B.V.

Epistemic protocols are communication protocols aiming at transfer of knowledge in a controlled way. Typically, the preconditions or goals for protocol actions depend on the knowledge of agents, often in nested form. Informal epistemic protocol descriptions for muddy children, coordinated attack, dining cryptographers, Russian cards, secret key exchange are well known. The contribution of this paper is a formal study of a natural requirement on epistemic protocols, that the contents of the protocol can be assumed to be common knowledge. By formalizing this requirement we can prove that there can be no unbiased deterministic protocol for the Russian cards problem. For purposes of our formal analysis we introduce an epistemic protocol language, and we show that its model checking problem is decidable.

© The Author, 2017. Published by Oxford University Press. All rights reserved. In this article, we introduce a lightweight dynamic epistemic logical framework for automated planning under initial uncertainty. We generalize the standard conformant planning problem in AI in two crucial aspects: first, the planning goal can be any formula expressed in an epistemic propositional dynamic logic ; second, procedural constraints of the desired plan specified by regular expressions can be imposed. We then reduce the problem of generalized conformant planning to the model checking problem of our logic. Although our conformant planning problem is much more general than the standard one with Boolean goals and no procedural constraints, the complexity is still PSPACE-complete which is equally hard as standard conformant planning over explicit transition systems.

Recent years witnessed a growing interest in non-standard epistemic logics of knowing whether, knowing how, knowing what, knowing why and so on. The new epistemic modalities introduced in those logics all share, in their semantics, the general schema of ∃x◻φ, e.g., knowing how to achieve φ roughly means that there exists a way such that you know that it is a way to ensure that φ. Moreover, the resulting logics are decidable. Inspired by those particular logics, in this work, we propose a very general and powerful framework based on quantifier-free predicate language extended by a new modality, which packs exactly ∃x◻ together. We show that the resulting language, though much more expressive, shares many good properties of the basic propositional modal logic over arbitrary models, such as finite-tree-model property and van Benthem-like characterization w.r.t.\ first-order modal logic. We axiomatize the logic over S5 frames with intuitive axioms to capture the interaction between the new modality and know-that operator in an epistemic setting.

Epistemic logic has become a major field of philosophical logic ever since the groundbreaking work by Hintikka [58]. Despite its various successful applications in theoretical computer science, AI, and game theory, the technical development of the field has been mainly focusing on the propositional part, i.e., the propositional modal logics of “knowing that”. However, knowledge is expressed in everyday life by using various other locutions such as “knowing whether”, “knowing what”, “knowing how” and so on (knowing-wh hereafter). Such knowledge expressions are better captured in quantified epistemic logic, as was already discussed by Hintikka [58] and his sequel works at length. This paper aims to draw the attention back again to such a fascinating but largely neglected topic. We first survey what Hintikka and others did in the literature of quantified epistemic logic, and then advocate a new quantifier-free approach to study the epistemic logics of knowing-wh, which we believe can balance expressivity and complexity, and capture the essential reasoning patterns about knowing-wh. We survey our recent line of work on the epistemic logics of ‘knowing whether”, “knowing what” and “knowing how” to demonstrate the use of this new approach.