Lin Zhang

© 2016 Elsevier B.V.The evaporative-cooling roof is a popular passive energy conservation technique. This article presents a novel approach for modelling and analysing the influence of evaporation on roof thermal performance. A multivariate nonlinear model was developed for the prediction of the evaporation rate from porous tile. A computer program was then developed based on the one-dimensional roof unsteady heat transfer theory. Finally, the computer program and hourly weather data of Guangzhou, China, were used to analyse the impacts of evaporation and slope orientation on roof thermal performance. Evaporation beginning at 11:00 can reduce the external surface temperatures of a horizontal roof and 30°-inclined east-sloping and west-sloping roofs by up to 11.3, 10.7, and 9.8 °C, respectively, from those of a non-evaporative roof. This, in turn, can reduce the peak-hour internal surface heat flux. Additionally, with the horizontal roof, the reduction in the peak-hour heat flux can be doubled if the evaporative layer is frequently replenished with water.

© 2015 Elsevier Ltd.Age-related macular degeneration is the leading cause of blindness among the elderly in developed countries. AMD is classified as either neovascular or non-neovascular. Cumulative damage to the retinal pigment epithelium, Bruch's membrane, and choriocapillaris leads to dysfunction and loss of RPE cells. This causes degeneration of the overlying photoreceptors and consequential vision loss in advanced NNV-AMD. In NV-AMD, abnormal growth of capillaries under the retina and RPE, which leads to hemorrhage and fluid leakage, is the main cause of photoreceptor damage. Although a number of drugs are in use for NV-AMD, there is currently no treatment for advanced NNV-AMD. However, replacing dead or dysfunctional RPE with healthy RPE has been shown to rescue dying photoreceptors and improve vision in animal models of retinal degeneration and possibly in AMD patients. Differentiation of RPE from human embryonic stem cells and from induced pluripotent stem cells has created a potentially unlimited source for replacing dead or dying RPE. Such cells have been shown to incorporate into the degenerating retina and result in anatomic and functional improvement. However, major ethical, regulatory, safety, and technical challenges have yet to be overcome before stem cell-based therapies can be used in standard treatments. This review outlines the current knowledge surrounding the application of hESC-RPE and iPSC-RPE in AMD. Following an introduction on the pathogenesis and available treatments of AMD, methods to generate stem cell-derived RPE, immune reaction against such cells, and approaches to deliver desired cells into the eye will be explored along with broader issues of efficacy and safety. Lastly, strategies to improve these stem cell-based treatments will be discussed.

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.

Knowledge of three-dimensional structures of each individual particles of asymmetric and flexible proteins is essential in understanding those proteins' functions; but their structures are difficult to determine. Electron tomography provides a tool for imaging a single and unique biological object from a series of tilted angles, but it is challenging to image a single protein for three-dimensional reconstruction due to the imperfect mechanical control capability of the specimen goniometer under both a medium to high magnification and an optimized beam coherence condition. Here, we report a fully mechanical control method for automating ET data acquisition without using beam tilt/shift processes. This method could reduce the accumulation of beam tilt/shift that used to compensate the error from the mechanical control, but downgraded the beam coherence. Our method was developed by minimizing the error of the target object center during the tilting process through a closed-loop proportional-integral control algorithm. The validations by both negative staining and cryo-electron microscopy suggest that this method has a comparable capability to other ET methods in tracking target proteins while maintaining optimized beam coherence conditions for imaging.

DNA base pairing has been used for many years to direct the arrangement of inorganic nanocrystals into small groupings and arrays with tailored optical and electrical properties. The control of DNA-mediated assembly depends crucially on a better understanding of three-dimensional structure of DNA-nanocrystal-hybridized building blocks. Existing techniques do not allow for structural determination of these flexible and heterogeneous samples. Here we report cryo-electron microscopy and negative-staining electron tomography approaches to image, and three-dimensionally reconstruct a single DNA-nanogold conjugate, an 84-bp double-stranded DNA with two 5-nm nanogold particles for potential substrates in plasmon-coupling experiments. By individual-particle electron tomography reconstruction, we obtain 14 density maps at ~ 2-nm resolution. Using these maps as constraints, we derive 14 conformations of dsDNA by molecular dynamics simulations. The conformational variation is consistent with that from liquid solution, suggesting that individual-particle electron tomography could be an expected approach to study DNA-assembling and flexible protein structure and dynamics.

Cholesteryl ester transfer protein mediates cholesteryl ester transfer from the atheroprotective high density lipoprotein cholesterol to the atherogenic low density lipoprotein cholesterol. In the past decade, this property has driven the development of CETP inhibitors, which have been evaluated in large scale clinical trials for treating cardiovascular diseases. Despite the pharmacological interest, little is known about the fundamental mechanism of CETP in CE transfer. Recent electron microscopy experiments have suggested a tunnel mechanism, and molecular dynamics simulations have shown that the flexible N-terminal distal end of CETP penetrates into the HDL surface and takes up a CE molecule through an open pore. However, it is not known whether a CE molecule can completely transfer through an entire CETP molecule. Here, we used all-atom molecular dynamics simulations to evaluate this possibility. The results showed that a hydrophobic tunnel inside CETP is sufficient to allow a CE molecule to completely transfer through the entire CETP within a predicted transfer time and at a rate comparable with those obtained through physiological measurements. Analyses of the detailed interactions revealed several residues that might be critical for CETP function, which may provide important clues for the effective development of CETP inhibitors and treatment of cardiovascular diseases.

Commonly used methods for determining protein structure, including X-ray crystallography and single-particle reconstruction, often provide a single and unique three-dimensional structure. However, in these methods, the protein dynamics and flexibility/fluctuation remain mostly unknown. Here, we utilized advances in electron tomography to study the antibody flexibility and fluctuation through structural determination of individual antibody particles rather than averaging multiple antibody particles together. Through individual-particle electron tomography 3D reconstruction from negatively-stained ET images, we obtained 120 ab-initio 3D density maps at an intermediate resolution from 120 individual IgG1 antibody particles. Using these maps as a constraint, we derived 120 conformations of the antibody via structural flexible docking of the crystal structure to these maps by targeted molecular dynamics simulations. Statistical analysis of the various conformations disclosed the antibody 3D conformational flexibility through the distribution of its domain distances and orientations. This blueprint approach, if extended to other flexible proteins, may serve as a useful methodology towards understanding protein dynamics and functions.

Cholesteryl ester transfer protein mediates the transfer of cholesterol esters from atheroprotective high-density lipoproteins to atherogenic low-density lipoproteins. CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases. Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

Peptides show much promise as potent and selective drug candidates. Fusing peptides to a scaffold monoclonal antibody produces a conjugated antibody which has the advantages of peptide activity yet also has the pharmacokinetics determined by the scaffold antibody. However, the conjugated antibody often has poor binding affinity to antigens that may be related to unknown structural changes. The study of the conformational change is difficult by conventional techniques because structural fluctuation under equilibrium results in multiple structures co-existing. Here, we employed our two recently developed electron microscopy techniques: optimized negative-staining EM and individual-particle electron tomography. Two-dimensional image analyses and three-dimensional maps have shown that the domains of antibodies present an elongated peptide-conjugated conformational change, suggesting that our EM techniques may be novel tools to monitor the structural conformation changes in heterogeneous and dynamic macromolecules, such as drug delivery vehicles after pharmacological synthesis and development.

Since the discovery and implication of N-ethylmaleimide-sensitive factor -attachment protein receptor proteins in membrane fusion almost two decades ago, there have been significant efforts to understand their involvement at the molecular level. In the current study, we report for the first time the molecular interaction between full-length recombinant t-SNAREs and v-SNARE present in opposing liposomes, leading to the assembly of a t-/v-SNARE ring complex. Using high-resolution electron microscopy, the electron density maps and 3D topography of the membrane-directed SNARE ring complex was determined at nanometre resolution. Similar to the t-/v-SNARE ring complex formed when 50 nm v-SNARE liposomes meet a t-SNARE-reconstituted planer membrane, SNARE rings are also formed when 50 nm diameter isolated synaptic vesicles meet a t-SNARE-reconstituted planer lipid membrane. Furthermore, the mathematical prediction of the SNARE ring complex size with reasonable accuracy, and the possible mechanism of membrane-directed t-/v-SNARE ring complex assembly, was determined from the study. Therefore in the present study, using both lipososome-reconstituted recombinant t-/v-SNARE proteins, and native v-SNARE present in isolated SV membrane, the membrane-directed molecular assembly of the neuronal SNARE complex was determined for the first time and its size mathematically predicted. These results provide a new molecular understanding of the universal machinery and mechanism of membrane fusion in cells, having fundamental implications in human health and disease. © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Immune cells, including natural killer cells, recognize transformed cells and eliminate them in a process termed immunosurveillance. It is thought that tumor cells evade immunosurveillance by shedding membrane ligands that bind to the NKG2D-activating receptor on NK cells and/or Tcells, and desensitize these cells. In contrast, we show that in mice, a shed form of MULT1, a high-affinity NKG2D ligand, causes NK cell activation and tumor rejection. Recombinant soluble MULT1 stimulated tumor rejection in mice. Soluble MULT1 functions, at least in part, by competitively reversing a global desensitization of NK cells imposed by engagement of membrane NKG2D ligands on tumor-associated cells, such as myeloid cells. The results overturn conventional wisdom that soluble ligands are always inhibitory and suggest a new approach for cancer immunotherapy.

Various cytokines have been evaluated as potential anticancer drugs; however, most cytokine trials have shown relatively low efficacy. Here, we found that treatments with IL-12 and IL-18 or with a mutant form of IL-2 provided substantial therapeutic benefit for mice specifically bearing MHC class I-deficient tumors, but these treatments were ineffective for mice with matched MHC class I+ tumors. Cytokine efficacy was linked to the reversal of the anergic state of NK cells that specifically occurred in MHC class I-deficient tumors, but not MHC class I+ tumors. NK cell anergy was accompanied by impaired early signal transduction and was locally imparted by the presence of MHC class I-deficient tumor cells, even when such cells were a minor population in a tumor mixture. These results demonstrate that MHC class I-deficient tumor cells can escape from the immune response by functionally inactivating NK cells, and suggest cytokine-based immunotherapy as a potential strategy for MHC class I-deficient tumors. These results suggest that such cytokine therapies would be optimized by stratification of patients. Moreover, our results suggest that such treatments may be highly beneficial in the context of therapies to enhance NK cell functions in cancer patients.

The production of distinct sets of T cell receptor γδ+ T cells occurs in an ordered fashion in thymic development. The Vγ3 and Vγ4 genes, located downstream in the TCRγ Cγ1 gene cluster, are expressed by the earliest waves of developing TCRγδ+ T cells in the fetal thymus, destined for intraepithelial locations. Upstream Vγ2 and Vγ5 genes are expressed in later waves in the adult and constitute most TCRγδ + T cells in secondary lymphoid tissue. This developmental pattern is caused in part by a preference for rearrangements of the downstream Vγ3 and Vγ4 genes in the early fetal stage, which switches to a preference for rearrangements of the upstream Vγ2 and Vγ5 gene rearrangements in the adult. Our gene targeting studies show that the downstream Vγ genes rearrange preferentially in the early fetal thymus because of their downstream location, independent of promoter or recombination signal sequences and unrelated to the extent of germline transcription. Remarkably, gene deletion studies show that the downstream Vγ genes competitively inhibit upstream Vγ rearrangements at the fetal stage. These data provide a mechanism for specialization of the fetal thymus for the production of T cells expressing specific Vγ genes. JEM © The Rockefeller University Press.

Copyright © 2014, Lin et al.Circadian clocks serve as internal pacemakers that influence many basic homeostatic processes; consequently, the expression and function of their components are tightly regulated by intricate networks of feedback loops that fine-tune circadian processes. Our knowledge of these components and pathways is far from exhaustive. In recent decades, the nuclear envelope has emerged as a global gene regulatory machine, although its role in circadian regulation has not been explored. We report that transcription of the core clock component BMAL1 is positively modulated by the inner nuclear membrane protein MAN1, which directly binds the BMAL1 promoter and enhances its transcription. Our results establish a novel connection between the nuclear periphery and circadian rhythmicity, therefore bridging two global regulatory systems that modulate all aspects of bodily functions.

Both thinkings on Dao in Chinese philosophy and metaphysics in Western philosophy investigate things on a spiritual level that transcends experience, but there are incommensurable differences between them. The objective of "metaphysics" is ontological knowledge about nature from the perspective of epistemological "truth-pursuing". Western metaphysics is thus a "metaphysics of nature". Dao in Chinese philosophy, on the other hand, more often manifests itself in "good-pursuing" by means of the internal, experiential pursuit of moral stature and spiritual security. Philosophy of Dao is thus a "metaphysics of ethics". The cause of this difference can be traced back to the differences between the rational tradition of the West, characterized by the dualism of the subject and the object, and the moral tradition of China, characterized by the integration of man and nature. /// 中国哲学的"形上之道"与西方哲学的"形而上学"都是对超经验的形上事 物的研究，但是两者存在着根本的不可通约的区别"形而上学"是着眼于从认识 论求"真"的角度来研究的关于自然本体论的"知识"即"自然形而上学"而 "形上之道"更多地表现为求"善"的内心体验式的对道德境界的追求和精神寄 托，即"道德形而上学"。产生区别的内在原因是传统西方以"主客两分"为特征 的理性传统与传统中国以"天人合一"为特征的德性传统的不同。.

This study explored the global cyberspace security issues, with the purpose of breaking the stereotype of people’s cognition of cyberspace problems, which reflects the relationship between interdependence and association. Based on the Apriori algorithm in association rules, a total of 181 strong rules were mined from 40 target websites and 56,096 web pages were associated with global cyberspace security. Moreover, this study analyzed support, confidence, promotion, leverage, and reliability to achieve comprehensive coverage of data. A total of 15,661 sites mentioned cyberspace security-related words from the total sample of 22,493 professional websites, accounting for 69.6%, while only 735 sites mentioned cyberspace security-related words from the total sample of 33,603 non-professional sites, accounting for 2%. Due to restrictions of language, the number of samples of target professional websites and non-target websites is limited. Meanwhile, the number of selections of strong rules is not satisfactory. Nowadays, the cores of global cyberspace security issues include internet sovereignty, cyberspace security, cyber attack, cyber crime, data leakage, and data protection.

Early in Aristotle's terminology, and ever since, "essence" has been conceived as having two meanings, namely "universality" and "individuality". According to the tradition of thought that has dominated throughout the history of Western philosophy, "essence" unequivocally refers to "universality". As a matter of fact, however, "universality" cannot cover Aristotle's definition and formulation of "essence": Essence is what makes a thing "happen to be this thing." "Individuality" should be the deep meaning of "essence". By means of an analysis of some relevant Western thoughts and a review of cultural realities, it can be concluded that the difference between the attitudes toward things of the natural sciences and the humane sciences mainly lies in the fact that the former focus on the pursuit of universal regularity, whereas the latter go after the value and significance of human life. The movement from natural things to cultural things is a process in which essence shifts from universality to individuality. It is the author's contention that what should be stressed in the fields of human culture and society is the construction of an ideal society that is "harmonious yet not identical", on the basis of respecting and developing individual peculiarity and otherness. /// "本质" 最早在亚里士多德的用语中包含有两重含义: 是指 "普遍的东 西" ("共相")，一是指 "个体的东西" ("这个")。在西方哲学史上民期占统治 地位的思想片面地认为: "本质" 就是指 "普遍的东西"。但实际上"普遍的东 西" 并不能涵盖亚里士多德对 "本质" 的界定和表述t 本质是使一事物 "恰恰地是 这个事物"的东西。"本质" 的深层含义应是 "个体性"。通过对西方一些相关思 想观点的分析和文化现实的考察，可以得出结论z 自然科学与人文科学对待事物的 态度的区别在于z 前者重普遍性规律的追求，后者重个体性的人生价值意义的追求。 从自然物到文化物是一个由以普遍性为本质到以个体性为本质的转化过程。在人文 社会领域应该强调的是z 在尊重和发扬个人的独特性和差异性的基础上，建立 "和而 不同"的理想社会。.

While past studies have enriched our understanding of the impact of returnee executives on firm market strategy and outcomes, we know relatively little about the relationship between returnee executives and firm nonmarket strategies. Grounded in upper echelons theory, this study explores the relationship between returnee executives and corporate philanthropy, the latter of which is an important nonmarket strategy in emerging economies such as China. Using data on publicly listed Chinese companies from 2010 to 2017, we find that the proportion of returnee executives is negative related to corporate philanthropy. We also find that this negative relationship is strengthened by executive ownership, but weakened by corporate prominence and political connections. Our study makes important theoretical contributions to strategic leadership research, upper echelons theory, and the literature of corporate philanthropy. The managerial implications are also discussed.

The COVID-19 pandemic spread catastrophically over the world since the spring of 2020. In this paper, a heterogeneous branching process with immigration is established to quantify the human-to-human transmission of COVID-19 in local communities, based on the temporal and structural transmission patterns extracted from public case disclosures by four provincial Health Commissions in China. With proper parameter settings, our branching model matches the actual transmission chains satisfactorily and, therefore, sheds light on the underlying COVID-19 spreading mechanism. Moreover, based on our branching model, the efficacy of home quarantine and social distancing are explored, providing a reference for the effective prevention of COVID-19 worldwide.

With the rapid development of the Internet information age, social networks, mobile Internet, and e-commerce have expanded the scope of Internet applications. The “big data” era is a challenge and chance for companies and has a great impact on social economy, politics, culture, and people’s lives. An accurate marketing system is developed based on J2EE, and the architecture is selected from the user layer, business logic layer, and data layer and the B/S3 layer application, including three layers of crip-dm and semma. And, other process methods are used. Data-mining-based marketing system information solutions consist of several parts, such as requirement analysis, design, implementation, and testing. This paper introduces data mining technology to the marketing business based on the practical use and design IT solutions for precision marketing, attribute selection tools, attribute analysis tools, modeling prediction tools, and others. This paper introduces a precision marketing system based on data mining technology. The system passes the actual test and the deployment and the operation of this system are confirmed. The system, which can improve marketing activity, is tested, and the development and operation of this system markedly increase the company’s earnings.

As of the end of October 2020, the cumulative number of confirmed cases of COVID-19 has exceeded 45 million and the cumulative number of deaths has exceeded 1.1 million all over the world. Faced with the fatal pandemic, countries around the world have taken various prevention and control measures. One of the important issues in epidemic prevention and control is the assessment of the prevention and control effectiveness. Changes in the time series of daily new confirmed cases can reflect the impact of policies in certain regions. In this paper, a smooth transition autoregressive model is applied to investigate the intrinsic changes during the epidemic in certain countries and regions. In order to quantitatively evaluate the influence of the epidemic control measures, the sequence is fitted to the STAR model; then, comparisons between the dates of transition points and those of releasing certain policies are applied. Our model well fits the data. Moreover, the nonlinear smooth function within the STAR model reveals that the implementation of prevention and control policies is effective in some regions with different speeds. However, the ineffectiveness is also revealed and the threat of a second wave had already emerged.

This study aimed to explore the association between self-oriented empathy and compassion fatigue, and examine the potential mediating roles of dispositional mindfulness and the counselor’s self-efficacy. A total of 712 hotline psychological counselors were recruited from the Mental Health Service Platform at Central China Normal University, Ministry of Education during the outbreak of Corona Virus Disease 2019, then were asked to complete the questionnaires measuring self-oriented empathy, compassion fatigue, dispositional mindfulness, and counselor’s self-efficacy. Structural equation modeling was utilized to analyze the possible associations and explore potential mediations. In addition to reporting confidence intervals, we employed a new method named model-based constrained optimization procedure to test hypotheses of indirect effects. Results showed that self-oriented empathy was positively associated with compassion fatigue. Dispositional mindfulness and counselor’s self-efficacy independently and serially mediated the associations between self-oriented empathy and compassion fatigue. The findings of this study confirmed and complemented the etiological and the multi-factor model of compassion fatigue. Moreover, the results indicate that it is useful and necessary to add some training for increasing counselor’s self-efficacy in mindfulness-based interventions in order to decrease compassion fatigue.

Interdisciplinary research depends on research traditions and fields originating from different research teams, different countries and regions. Its essence is knowledge integration. As a dynamic and interactive process it continuously pushes the structure of science to become a complex diverse system.In this chapter, we provide a systematic review of interdisciplinary research. Starting from a definition of interdisciplinary research, its elements, and its role for scientific progress, we particularly focus on how to identify the activity of interdisciplinary research, how to measure it and point out the limitations of existing approaches. Stating that one can measure knowledge integration implies that this notion refers to a continuum, beginning from no integration to a large degree of integration.Following Stirling, Rafols and Meyer we show that knowledge integration can be measured by two main factors: a diversity factor and a network coherence factor. The diversity factor itself consists of three aspects: variety, evenness and similarity between categories. In accordance with the Jost–Leinster–Cobbold approach we prefer a so-called true diversity measure.As an illustration, we provide a simple example of a study on interdisciplinarity in the field of synthetic biology, using the true diversity measure derived from the Rao–Stirling measure. Finally, we include some suggestions for future research.