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Cancer-derived C-terminus-extended p53 mutation confers dominant-negative effect on its wild-type counterpart

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Journal of Molecular Cell Biology 2022年第1期14卷 11-20页

作者： Shibo Huang Bo Cao Jieqiong wang Yiwei Zhang Elisa Ledet oliver Sartor Yuqin Xiong Shelya X.Zeng Hua Lu Institute of Clinical Pharmacology Nanchang UniversityNanchang 330006China Department of Biochemistry&Molecular Biology Tulane University School of MedicineNew OrleansLA 70112USA Tulane Cancer Center Tulane University School of MedicineNew OrleansLA 70112USA College of Pharmacy Xavier University of LouisianaNew OrleansLA 70125USA

The vast majority of p53 missense mutants lose the wild-type (wt) function and/or exert ‘dominant-negative’ effects on their wt counterpart. Here, we identify a novel form of p53 mutation with an extended C-terminus (p53 long C-terminus, p53LC) in a variety of human cancers. Interestingly, the two representative mutants (named ‘p53-374*48’ and ‘p53-393*78’) as tested in this study show both loss-of-function and dominant-negative phenotypes in cell proliferation and colony formation assays. Mechanistically, p53LCs interact with and retain wt p53 in the cytoplasm and prevent it from binding to the promoters of target genes, consequently inhibiting its transcriptional activity. Also, p53LCs are very stable, though not acetylated in cells. Remarkably, the p53LCs can desensitize wt p53-containing cancer cells to p53-activating agents. Together, our results unveil a longer form of p53 mutant that possesses a dominant-negative effect on its wt counterpart, besides losing its wt activity.

关键词： mutant p53-393*78 mutant p53-374*48 p53 longer C-terminus p53 dominant-negative effect drug resistance acetylation

Confucianism in the Perspective of Global Science-A Review of Reconceptualizing Confucian Philosophy in the 21st Century

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Frontiers of Philosophy in China 2018年第1期13卷 150-163页

作者： oliver Davies School of Philosophy Renmin University of China Beijing 100872 China

Today, Confucianism appears as a pre-eminently philosophical approach to the human, which, though deeply rooted in an ancient history in Chinese-speaking lands, now also has the potential to become a global philosophy. In its prescription of a distinctively disciplined way of life, it parallels world religions. However, Confucianism makes no claim to revelation, and so potentially offers a universalist understanding of what it is to be a human being. The fact that the nature or meaning of embodied Confucian life also points to specific social and political structures--even though these may be subject to variation--further suggests that such a universalist anthropology could be one which potentially, though still anchored in philosophy, has concrete content. There are two main challenges to be faced, however. First, there is the need for a reconceptualization of Confucianism in order for it to function as a truly contemporary thought-form. Second, there is the need to discover ways in which the themes and concepts of Confucianism can meaningfully inform our contemporary social and political realities beyond the scope of Chinese language and history. However, these challenges have, in many ways, become less daunting in recent years. Today, there is a new openness for a transcultural, globally-oriented ethical thinking and presence which can foster stability in times of rapid and unpredictable change. And there is a new acceptance that such a practical philosophy, or philosophy of human practice, as a properly global phenomenon could have its origins in China.

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Religion, Politics and Ethics： Towards a Global Theorj of Social Transformation

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Frontiers of Philosophy in China 2012年第4期7卷 572-597页

作者： oliver Davies School of Arts and Humanities King's College London London WC2R 2LS UK

In this paper＇I set out a phenomenology of social transformation, based on an analysis of the distinctively religious form of communication which underlies the trans-generational and trans-cultural transmission of world traditions, taking Confucianism and Christianity as their representatives. A phenomenological analysis of their communicative structure allows the possibility of a better understanding of what can be learnt from them in the context of contemporary debates in both China and the West on the relations between religion, ethics and politics. This analysis suggests that the ethical consistency of belief and act, which is the necessary condition for the engendering of long-term solidarity in religious community, has significant implications for ethics in politics, and especially for the legitimacy of representational leadership as a focal point for change in society. The paper concludes that the historical experience of world religions can offer new insights into the nature of political leadership and representation in today＇s globalised world and that the appropriate locus for this inquiry is the present negotiation and re-negotiation of relations between China and the West.

关键词： social transformation Confucianism and Christianity phenomenology,leadership

The visual analytics of big,open public transport data-a framework and pipeline for monitoring system performance in Greater Sydney

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Big Earth Data 2021年第1期5卷 134-159页

作者： oliver Lock Tomasz Bednarz Christopher Pettit City Analytics Lab Faculty of Built EnvironmentUniversity of New South WalesSydneyAustralia Expanded Perception and Interaction Centre Faculty of Art&DesignUniversity of New South WalesSydneyAustralia

Many cities,countries and transport operators around the world are striving to design intelligent transport *** systems capture the value of multisource and multiform data related to the functionality and use of transportation infrastructure to better support human mobility,interests,economic activity and *** aim to provide services that can enable transportation customers and managers to be better informed and make safer and more efficient use of *** developing principles,guidelines,methods and tools to enable synergistic work between humans and computer-generated information,the science of visual analytics continues to expand our understanding of data through effective and interactive visual *** this paper,we describe an application of visual analytics related to the study of movement and transportation *** application documents the use of rapid,2D and 3D web visualisation and data analytics libraries and explores their potential added value to the analysis of big public transport performance data.A novel approach to displaying such data through a generalisable framework visualisation system is *** framework recalls over a year’sworth of public transport performance data at a highly granular level in a fast,interactive browser-based *** Sydney,Australia forms a case study to highlight potential uses of the visualisation of such large,passively-collected data sets as an applied research *** this paper,we argue that such highly visual systems can add data-driven rigour to service planning and longer-term transport ***,they enable the sharing of quality of service statistics with various stakeholders and citizens and can showcase improvements in services before and after policy *** paper concludes by making recommendations on the value of this approach in embedding these or similar web-based systems in transport planning practice,performance

关键词： WebGL visual analytics public transportation transport performance visualisation open data big data

Boosted Stacking Ensemble Machine Learning Method for Wafer Map Pattern Classification

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Computers, Materials & Continua 2023年第2期74卷 2945-2966页

作者： Jeonghoon Choi Dongjun Suh Marc-oliver Otto Department of Convergence and Fusion System Engineering Kyungpook National UniversitySangju37224Korea Department of Mathematics Natural and Economic SciencesUlm University of Applied SciencesUlm89075Germany

Recently,machine learning-based technologies have been developed to automate the classification of wafer map defect patterns during *** existing approaches used in the wafer map pattern classification include directly learning the image through a convolution neural network and applying the ensemble method after extracting image *** study aims to classify wafer map defects more effectively and derive robust algorithms even for datasets with insufficient defect ***,the number of defects during the actual process may be ***,insufficient data are generated using convolutional auto-encoder(CAE),and the expanded data are verified using the evaluation technique of structural similarity index measure(SSIM).After extracting handcrafted features,a boosted stacking ensemble model that integrates the four base-level classifiers with the extreme gradient boosting classifier as a meta-level classifier is designed and built for training the model based on the expanded data for final *** the proposed algorithm shows better performance than those of existing ensemble classifiers even for insufficient defect patterns,the results of this study will contribute to improving the product quality and yield of the actual semiconductor manufacturing process.

关键词： Wafer map pattern classification machine learning boosted stacking ensemble semiconductor manufacturing processing

Neutrophils in chronic inflammatory diseases

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Cellular & Molecular Immunology 2022年第2期19卷 177-191页

作者： Andrea Herrero-Cervera oliver Soehnlein Ellinor Kenne Institute for Experimental Pathology Center for Molecular Biology of InflammationWestfälische Wilhelms-Universität MünsterMünsterGermany Department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden.

Chronic inflammation is a component of many disease conditions that affect a large group of individuals *** inflammation is characterized by persistent,low-grade inflammation and is increased in the aging *** are normally the first responders to acute inflammation and contribute to the resolution of ***,in chronic inflammation,the role of neutrophils is less well understood and has been described as either beneficial or detrimental,causing tissue damage and enhancing the immune *** evidence suggests that neutrophils are important players in several chronic diseases,such as atherosclerosis,diabetes mellitus,nonalcoholic fatty liver disease and autoimmune *** review will highlight the interaction of neutrophils with other cells in the context of chronic inflammation,the contribution of neutrophils to selected chronic inflammatory diseases,and possible future therapeutic strategies.

关键词： Chronic Inflammation Disease Neutrophil Neutrophil extracellular traps

Increased mutant KRAS gene dosage drives pancreatic cancer progression: evidence for wild-type KRAS as a tumor suppressor?

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Hepatobiliary Surgery and Nutrition 2018年第5期7卷 403-405页

作者： oliver A. Kent Princess Margaret Cancer Centre University Health Network Toronto Medical Discovery Tower Toronto Canada

RAS genes are most commonly associated with gain-of function mutations that promote oncogenic behavior. Activating mutations in KRAS occur in 90–95% cases of pancreatic ductal adenocarcinoma (PDAC) a deadly and highly metastatic disease. Currently the fourth leading cause of cancer death in the United States, PDAC presents with a dismal 5-year survival rate of less than 5% (1).

关键词： KRAS dosage cancer

Neurogenesis within the adult hippocampus under physiological conditions and in depression

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Neural Regeneration Research 2012年第7期7卷 552-559页

作者： Martin Dokter oliver von Bohlen und Halbach Institute of Anatomy and Cell Biology Ernst Moritz Arndt University of GreifswaldGermany

Adult neurogenesis can only be observed in some specific brain regions. One of these areas is the dentate gyrus of the hippocampal formation. The progenitor cells located in the subgranular layer of the dentate gyrus proliferate, differentiate, and give rise to young neurons that can become integrated into existing neuronal circuits. Under physiological conditions, hippocampal neurogenesis is linked to hippocampal-dependent learning, whereas deficits in adult hippocampal neurogenesis have been shown to correlate with disturbances in spatial learning and memory. This review summarizes the phenomenon of adult hippocampal neurogenesis and the use of suitable markers for the investigation of adult hippocampal neurogenesis. In addition, we focused on the disturbances in neurogenesis that can be seen in depression. Interestingly, several antidepressants have been found to be capable of increasing the rate of hippocampal neurogenesis. Based on that, it can be speculated that factors, which directly or indirectly increase the rate of hippocampal neurogenesis, may be helpful in the treatment of depression.

关键词： hippocampus dentate gyrus learning depression aging environment

Lightweight and Secure Mutual Authentication Scheme for IoT Devices Using CoAP Protocol

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Computer Systems Science & Engineering 2022年第5期41卷 767-780页

作者： S.Gladson oliver T.Purusothaman Department of Information Technology Government College of TechnologyCoimbatore641013India Department of Electronics and Communication Engineering Government College of TechnologyCoimbatore641013India

Internet of things enables every real world objects to be seamlessly integrated with traditional *** objects of real world are enhanced with capability to communicate,computing capabilities and standards to interoperate with existing network and these entities are resource constrained and vulnerable to various security *** number of research works are being carried out to analyze various possible attacks and to propose standards for securing communication between devices in internet of things(IoT).In this article,a robust and lightweight authentication scheme for mutual authentication between client and server using constrained application protocol is *** of things enables devices with different characteristics and capabilities to be integrated with *** heterogeneous devices should interoperate with each other to accumulate,process and transmit data for facilitating smart *** growth of IoT applications leads to the rapid growth of IoT devices incorporated to the global network and network traffic over the traditional *** scheme greatly reduces the authentication overhead between the devices by reducing the packet size of messages,number of messages transmitted and processing overhead on communicating *** of this authentication scheme against attacks such as DoS(denial of service),replay attacks and attacks to exhaust the resources are also *** transmission time reduced upto 50%of using proposed techniques.

关键词： IoT CoAP AES encryption message transmisssion