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Lorenzo Ochoa, Oswaldo, Björn Claes, Oksana Koryak, and Angel Diaz. "Integration through orchestration." Journal of Enterprise Information Management 30, no. 4 (July 10, 2017): 555–82. http://dx.doi.org/10.1108/jeim-02-2016-0060.
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Purpose The purpose of this paper is to examine the mechanisms through which the use of enterprise systems (ESs) enhances buyer-supplier integration (BSI). More specifically, the authors explain a model where ES enhances BSI indirectly, mediated by inventory management capabilities (IMCs), as the way ES enhances BSI remains under-explored in the literature. Design/methodology/approach Application of the resource orchestration framework to explain how capabilities and mechanisms interplay to enhance BSI. Data were collected by means of a survey instrument. Data collection took place as part of a larger project, sponsored by the Spanish Government, to evaluate logistics competitiveness in Spain. Findings ES enhances BSI by serving as a coordinating mechanism that maintains capability configurations in a value-creating alignment. IMC plays a key, yet under-explored role as a mediating mechanism that supports ES-enabled BSI. Research limitations/implications First, this research does not fully capture the multi-party nature of the supply chain context. Second, data collection was limited to companies that were more likely to have a systematic approach to logistics issues (i.e. large- and medium-sized companies) and companies based in Spain. Originality/value This paper enhances both scholarly and practitioner understanding of the mechanisms through which the implementation and use of ES contributes to BSI. In addition, this paper integrates literature from different fields (e.g. strategy, information systems, and operations) to gain a better understanding of how the implementation and use of ES affects BSI.
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Mantovani, Alberto, and Massimo Locati. "Orchestration of macrophage polarization." Blood 114, no. 15 (October 8, 2009): 3135–36. http://dx.doi.org/10.1182/blood-2009-07-231795.
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Nätti, Satu, Pia Hurmelinna-Laukkanen, and Wesley J. Johnston. "Absorptive capacity and network orchestration in innovation communities – promoting service innovation." Journal of Business & Industrial Marketing 29, no. 2 (January 28, 2014): 173–84. http://dx.doi.org/10.1108/jbim-08-2013-0167.
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Purpose – The purpose of this study is to increase understanding of service innovation in networks. Especially the most loosely coupled forms of innovation networks, innovation communities, can be valuable in service innovation, but may not be manageable in the traditional sense. Rather, they may require orchestration characterized by discreet guidance that also accommodates the specific nature of services. Through informed orchestration, it is possible to deal with several contingencies, and influence the absorptive capacity at the network level to generate new service innovations. Design/methodology/approach – These issues are examined through literature review and a case study. Findings – The findings suggest that individual orchestration mechanisms may be more closely connected to certain contingencies than others, and that both orchestration mechanisms and contingency factors have a role in absorptive capacity development within service innovation networks. Research limitations/implications – While the case study approach limits the possibility to make wide generalizations, the in-depth insights provide valuable knowledge. Practical implications – There has been a shift from inter-firm competition towards competition between networks of organizations, increasing relevance of absorptive capacity at the network level. Originality/value – Despite the recent increase in service innovation literature, research on service innovation taking place in networks is scant. Knowledge on some aspects can be derived from more traditional notions on technological innovation, but both the distinctive features of services and central characteristics of innovation networks make it necessary to reconsider some of the established views. In particular, managing – or rather orchestrating – service innovation is still a challenging area.
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Pan, Mei-Ren, Ming-Chuan Hsu, Li-Tzong Chen, and Wen-Chun Hung. "Orchestration of H3K27 methylation: mechanisms and therapeutic implication." Cellular and Molecular Life Sciences 75, no. 2 (July 17, 2017): 209–23. http://dx.doi.org/10.1007/s00018-017-2596-8.
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Schepis, Daniel, Sharon Purchase, and Bella Butler. "Facilitating open innovation processes through network orchestration mechanisms." Industrial Marketing Management 93 (February 2021): 270–80. http://dx.doi.org/10.1016/j.indmarman.2021.01.015.
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Santos, Juliana Bonomi, Laís Moltene, Vittoria Loviscek, Ely Laureano Paiva, Susana Carla Farias Pereira, and Luiz Carlos Di Serio. "Orchestration coordination in innovation ecosystems: mechanisms and enabling factors." Academy of Management Proceedings 2021, no. 1 (August 2021): 15592. http://dx.doi.org/10.5465/ambpp.2021.15592abstract.
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NANDA, MANGALA GOWRI, and NEERAN KARNIK. "SYNCHRONIZATION ANALYSIS FOR DECENTRALIZING COMPOSITE WEB SERVICES." International Journal of Cooperative Information Systems 13, no. 01 (March 2004): 91–119. http://dx.doi.org/10.1142/s0218843004000900.
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Web Services are emerging as the standard mechanism for making information and software available programmatically via the Internet, and as building blocks for applications. A composite web service may be built using multiple component web services. Once its specification has been developed, the composite service may be orchestrated either using a centralized engine or in a decentralized fashion. Decentralized orchestration brings performance benefits, and improves scalability and concurrency. Dynamic binding coupled with decentralized orchestration adds high availability and fault tolerance to the system. However in such systems, the coordination between components needs to be carefully designed to ensure correct execution of the composite and to limit the synchronization overheads. In this paper, we categorize different forms of concurrency and provide an algorithm to identify these forms in a composite service specification. We explore different mechanisms for transferring data between the components in the presence of different forms of concurrency. Then we experimentally evaluate the efficiency and scalability of each mechanism. We also analyze the coordination requirements of a decentralized orchestration in the presence of dynamic binding and fault propagation.
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Trakadas, Panagiotis, Panagiotis Karkazis, Helen C. Leligou, Theodore Zahariadis, Felipe Vicens, Arturo Zurita, Pol Alemany, et al. "Comparison of Management and Orchestration Solutions for the 5G Era." Journal of Sensor and Actuator Networks 9, no. 1 (January 4, 2020): 4. http://dx.doi.org/10.3390/jsan9010004.
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5G is considered to be the technology that will accommodate the development and management of innovative services with stringent and diverse requirements from end users, calling for new business models from the industry. In this context, the development and efficient management of Network Services (NS) serving specific vertical industries and spanning across multiple administrative domains and heterogeneous infrastructures is challenging. The main challenges regard the efficient provision of NSs considering the Quality of Service (QoS) requirements per vertical industry along with the optimal usage of the allocated resources. Towards addressing these challenges, this paper details an innovative approach that we have developed for managing and orchestrating such NSs, called SONATA, and compare it with OSM and Cloudify, which are two of the most known open-source Management and Orchestration (MANO) frameworks. In addition to examining the supported orchestration mechanisms per MANO framework, an evaluation of main operational and functional KPIs is provided based on experimentation using a real testbed. The final aim is the identification of their strong and weak points, and the assessment of their suitability for serving diverse vertical industry needs, including of course the Internet of Things (IoT) service ecosystem.
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Hu, Jingbo, Taohua Ouyang, William X. Wei, and Jiawei Cai. "How Do Manufacturing Enterprises Construct E-Commerce Platforms for Sustainable Development? A Case Study of Resource Orchestration." Sustainability 12, no. 16 (August 17, 2020): 6640. http://dx.doi.org/10.3390/su12166640.
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The existing literatures mainly focus on the pricing, strategic significance and sustainable development characteristics of the e-commerce platform, and lack deep research on mechanisms in the process of construction like main structure of recourses and driving force. This paper takes Haier as a Chinese example and explores how manufacturing enterprises create and develop the sustainable e-commerce platform. The research findings show that: (1) An e-commerce platform respectively carries the functions of sales channels, service differences and innovation incubation in different stages of the manufacturing enterprises’ sustainable development; (2) For managing e-commerce platform of manufacturing enterprises’ sustainable development, resource orchestration can effectively realize the integration of value creation and resource; (3) Finally, it further reveals that the driving power which resource orchestration continuously promotes for the sustainable e-commerce platforms to construct is from the co-creation value of manufacturers and users. This paper discusses the structure of e-commerce platforms based on the main characteristics of each resource, and systematically explores the mechanism and evolutionary driving force of resource orchestration to promote the construction of e-commerce platforms for the sustainable development. It complements and enriches the innovation ecosystem and resource orchestration theory, providing significant practical guidance to the sustainable development of manufacturing enterprises.
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Kelleher, Carol, Deirdre O’Loughlin, Johanna Gummerus, and Lisa Peñaloza. "Shifting Arrays of a Kaleidoscope: The Orchestration of Relational Value Cocreation in Service Systems." Journal of Service Research 23, no. 2 (November 6, 2019): 211–28. http://dx.doi.org/10.1177/1094670519882495.
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The predominant value discourse among scholars characterizes value cocreation as involving multiple actors at the micro-, meso-, and macrolevels in service systems. This research contributes to the knowledge of the interdependencies among multiple resource-integrating actors and value outcomes by employing a relational perspective on value cocreation within the empirical context of family caregiving. The findings reveal how interdependent actors orchestrate value cocreation in service systems, how this impacts value, and how orchestration precipitates system adjustments, which form the recursive context of value cocreation over time. We differentiate and delineate three multi-actor orchestration mechanisms— assembling, performing, and brokering—through which nonreferent beneficiaries coordinate value cocreation on behalf of dependent referent beneficiaries. We term the mutually generalized oscillating multiform negative and positive well-being outcomes that emerge from orchestration among interdependent actors as relational value. In employing the metaphor of the kaleidoscope to emphasize system dynamism, our discussion of relational value cocreation deepens our understanding of how nonreferent beneficiary-led orchestration, founded on generalized mutuality and on behalf of referent beneficiaries with reduced agency, enhances and balances multiform, oscillating and positive and negative well-being outcomes in service systems. This will help service practitioners facilitate orchestration and optimize value for all.
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Murguzur, Aitor, Karmele Intxausti, Aitor Urbieta, Salvador Trujillo, and Goiuria Sagardui. "Process Flexibility in Service Orchestration: A Systematic Literature Review." International Journal of Cooperative Information Systems 23, no. 03 (August 14, 2014): 1430001. http://dx.doi.org/10.1142/s0218843014300010.
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In dynamic environments, changes are often unpredictable and complex. Process models cannot be fully specified up-front and process flexibility becomes a key issue. Enterprise applications and systems supporting such processes are increasingly being architected in a service-oriented style. In this light, our goal is to analyze service orchestration approaches from a process flexibility perspective. Through a systematic literature review, we evaluate 17 service orchestration approaches and analyze their support for: (i) variability, support for large collections of process variants, (ii) adaptation, need for instance changes during runtime, (iii) evolution, need for schema changes during runtime, and (iv) looseness, need for loosely-specified models. The review findings provide a clearer understanding of process flexibility requirements and service orchestration mechanisms that support them, helping us to understand the limitations and shed light on future research areas.
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Elias, Jocelyne, Fabio Martignon, Stefano Paris, and Jianping Wang. "Efficient Orchestration Mechanisms for Congestion Mitigation in NFV: Models and Algorithms." IEEE Transactions on Services Computing 10, no. 4 (July 1, 2017): 534–46. http://dx.doi.org/10.1109/tsc.2015.2498176.
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RITALA, PAAVO, LEILA ARMILA, and KIRSIMARJA BLOMQVIST. "INNOVATION ORCHESTRATION CAPABILITY — DEFINING THE ORGANIZATIONAL AND INDIVIDUAL LEVEL DETERMINANTS." International Journal of Innovation Management 13, no. 04 (December 2009): 569–91. http://dx.doi.org/10.1142/s136391960900242x.
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This paper explores orchestration capability as a concept defining the firm's ability to purposefully build and manage innovation networks. Due to the lack of empirical research on the subject as well as the focus on the organizational level in earlier studies, we approach the issue from a multi-level perspective. By utilizing expert panel discussions and an in-depth case study in an innovation network, we show that orchestration capability consists of both organizational and individual level determinants. Distinct capabilities and skills are identified and illustrated. Furthermore, we identify mechanisms suggesting that the two levels are interconnected in several ways.
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McCabe Pryor, Meghan, Mara P. Steinkamp, Adam M. Halasz, Ye Chen, Shujie Yang, Marilyn S. Smith, Gergely Zahoransky-Kohalmi, et al. "Orchestration of ErbB3 signaling through heterointeractions and homointeractions." Molecular Biology of the Cell 26, no. 22 (November 5, 2015): 4109–23. http://dx.doi.org/10.1091/mbc.e14-06-1114.
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Members of the ErbB family of receptor tyrosine kinases are capable of both homointeractions and heterointeractions. Because each receptor has a unique set of binding sites for downstream signaling partners and differential catalytic activity, subtle shifts in their combinatorial interplay may have a large effect on signaling outcomes. The overexpression and mutation of ErbB family members are common in numerous human cancers and shift the balance of activation within the signaling network. Here we report the development of a spatial stochastic model that addresses the dynamics of ErbB3 homodimerization and heterodimerization with ErbB2. The model is based on experimental measures for diffusion, dimer off-rates, kinase activity, and dephosphorylation. We also report computational analysis of ErbB3 mutations, generating the prediction that activating mutations in the intracellular and extracellular domains may be subdivided into classes with distinct underlying mechanisms. We show experimental evidence for an ErbB3 gain-of-function point mutation located in the C-lobe asymmetric dimerization interface, which shows enhanced phosphorylation at low ligand dose associated with increased kinase activity.
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Subramanian Vignesh, Kavitha, and George S. Deepe. "Immunological orchestration of zinc homeostasis: The battle between host mechanisms and pathogen defenses." Archives of Biochemistry and Biophysics 611 (December 2016): 66–78. http://dx.doi.org/10.1016/j.abb.2016.02.020.
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Mukhopadhyay, Sandip, and Harry Bouwman. "Orchestration and governance in digital platform ecosystems: a literature review and trends." Digital Policy, Regulation and Governance 21, no. 4 (June 10, 2019): 329–51. http://dx.doi.org/10.1108/dprg-11-2018-0067.
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PurposeBecause of the attention increasingly being focused on digital transformation, interest in business models of platform-enabled ecosystems is rising rapidly. Although there are different theoretical views on the role of ecosystems, a synthesis of research, with a focus on governance and orchestration in dynamic, multi-industry eco-systems, is lacking.Design/methodology/approachA systematic literature review was conducted by following a rigorous search protocol in the scholarly databases covering both journal articles and conference papers These papers were subsequently filtered, and finally, 48 relevant papers were selected for analysis.FindingsThe review identifies five key aspects of platform governance design that need close consideration: the meta-organisation or ecosystem design, coordination mechanisms, mechanisms for value co-creation, value appropriation mechanisms and architectural principles. To achieve balance among a set of competing demands, platform leaders need to devote adequate attention to these aspects.Practical implicationsBased on a literature review, the authors provide an overview of underlying theoretical views, research methods and key trends to develop a sound theoretical grounding for research on platform governance design. The paper also suggests research gaps in the existing literature and sets directions for researchers to strengthen the understanding of effective platform governance design. The paper also provides valuable information to managers in developing or leading a successful platform ecosystem.Originality/valueThe paper uses existing literature published in this topic and original in nature.
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Nguyen, Thanh-Tung, Yu-Jin Yeom, Taehong Kim, Dae-Heon Park, and Sehan Kim. "Horizontal Pod Autoscaling in Kubernetes for Elastic Container Orchestration." Sensors 20, no. 16 (August 17, 2020): 4621. http://dx.doi.org/10.3390/s20164621.
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Kubernetes, an open-source container orchestration platform, enables high availability and scalability through diverse autoscaling mechanisms such as Horizontal Pod Autoscaler (HPA), Vertical Pod Autoscaler and Cluster Autoscaler. Amongst them, HPA helps provide seamless service by dynamically scaling up and down the number of resource units, called pods, without having to restart the whole system. Kubernetes monitors default Resource Metrics including CPU and memory usage of host machines and their pods. On the other hand, Custom Metrics, provided by external software such as Prometheus, are customizable to monitor a wide collection of metrics. In this paper, we investigate HPA through diverse experiments to provide critical knowledge on its operational behaviors. We also discuss the essential difference between Kubernetes Resource Metrics (KRM) and Prometheus Custom Metrics (PCM) and how they affect HPA’s performance. Lastly, we provide deeper insights and lessons on how to optimize the performance of HPA for researchers, developers, and system administrators working with Kubernetes in the future.
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Sarne, Victoria, Sandrina Braunmueller, Lisa Rakob, and Rita Seeboeck. "The Relevance of Gender in Tumor-Influencing Epigenetic Traits." Epigenomes 3, no. 1 (January 28, 2019): 6. http://dx.doi.org/10.3390/epigenomes3010006.
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Tumorigenesis as well as the molecular orchestration of cancer progression are very complex mechanisms that comprise numerous elements of influence and regulation. Today, many of the major concepts are well described and a basic understanding of a tumor’s fine-tuning is given. Throughout the last decade epigenetics has been featured in cancer research and it is now clear that the underlying mechanisms, especially DNA and histone modifications, are important regulators of carcinogenesis and tumor progression. Another key regulator, which is well known but has been neglected in scientific approaches as well as molecular diagnostics and, consequently, treatment conceptualization for a long time, is the subtle influence patient gender has on molecular processes. Naturally, this is greatly based on hormonal differences, but from an epigenetic point of view, the diverse susceptibility to stress and environmental influences is of prime interest. In this review we present the current view on which and how epigenetic modifications, emphasizing DNA methylation, regulate various tumor diseases. It is our aim to elucidate gender and epigenetics and their interconnectedness, which will contribute to understanding of the prospect molecular orchestration of cancer in individual tumors.
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Eberlein, Burkard. "Who Fills the Global Governance Gap? Rethinking the Roles of Business and Government in Global Governance." Organization Studies 40, no. 8 (May 31, 2019): 1125–45. http://dx.doi.org/10.1177/0170840619847720.
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Political CSR has made great strides towards a better appreciation of the political involvement of corporations in global governance. However, its portrayal of the shifting balance between business and government in the globalized economy rests on a central, yet largely uncontested, assumption: that of a zero-sum constellation of substitution in which firms take on public responsibilities to fill governance gaps left by governments. This conceptual paper expands the political CSR perspective and makes three contributions to the debate on the political role of business and the role of government in global governance. First, it deconstructs the problematic assumptions underlying the zero-sum notion of governance gaps filled by corporations. Second, it offers a variable-sum mapping of how private and public authority interact in global governance where substitution is only one of four constellations. The mapping identifies ‘soft steering’ as a prominent mode of governments governing business conduct. Third, the paper theorizes ‘orchestration’, a ‘soft steering’ tool discussed in the global governance literature, from an organizational, corporate perspective. It identifies the mechanisms through which orchestration may address the barriers to corporate engagement with the public good and applies these mechanisms to the case of the Global Reporting Initiative.
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Long, Joshua. "Crisis Capitalism and Climate Finance: The Framing, Monetizing, and Orchestration of Resilience-Amidst-Crisis." Politics and Governance 9, no. 2 (April 28, 2021): 51–63. http://dx.doi.org/10.17645/pag.v9i2.3739.
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Throughout the development sector there has been a pronounced call for new funding mechanisms to address the climate crisis, and much of this is focused on attracting private sources of capital to fund ‘bankable’ projects in climate-vulnerable cities throughout the world. Enacted amidst a 21st century landscape of interlocking financial, epidemiological, and ecological crises, this call features an urgent narrative of ‘resilience-amidst-crisis’ that promotes large-scale, profitable investments as a form of green growth through debt-financing. The political orchestration and administration of new funding mechanisms (particularly green bonds and sustainable bonds) requires a new form of climate governance focused on the channeling of enormous sums of private capital through an assemblage of intermediaries toward profitable climate projects. This article interrogates this trend in climate finance, revealing that the framing, monetization, and orchestration of climate projects is dependent on a narrative of crisis capitalism deeply rooted in a colonial mindset of exploitation and profit. A key aim of this article is to deconstruct the contemporary dominance of crisis-oriented development and suggest the goal of decolonizing and democratizing the climate finance system.
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Bittencourt, Bruno Anicet, Aurora Carneiro Zen, Vitor Schmidt, and Douglas Wegner. "The orchestration process for emergence of clusters of innovation." Journal of Science and Technology Policy Management 11, no. 3 (November 19, 2018): 277–90. http://dx.doi.org/10.1108/jstpm-02-2018-0016.
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Purpose Requalification of neglected areas in urban contexts is considered as one of the main challenges for smart cities. Business clusters stand out as mechanisms of innovation for not only the clustered firms but also the territory in which they are located. However, the cluster emergence process is complex and still unknown. The purpose of this paper is to analyze the orchestration process in the emergence of a cluster of innovation (CoI). Design/methodology/approach This study is a qualitative exploratory research in Porto Alegre, a State capital in Southern Brazil, in the region known as 4th District. Data were collected through documentary research, non-participant observation and face-to-face in-depth interviews. Findings Results indicate the importance of alignment among network members, possible difficulties caused by members’ heterogeneity and the need to disseminate information and interaction for the appropriability of knowledge and innovation in the emergence process of CoI. Coordination of actions and joint agenda as facilitators for the construction of a cluster identity emerge as crucial important. Besides, results also highlight that the entrepreneurial process and the perspective of global strategy are essential to build competitive advantage to the region. Research limitations/implications This paper brings a theoretical and managerial contribution to the application of the concept of orchestration to emergence of a CoI. The framework presents network components, orchestration components and the drivers to emergence of a CoI. Originality/value This study proposes a framework to link the orchestration process to the emergence of a CoI. The proposed framework could help policymakers and other actors to enhance the impact of a cluster on the development of the region.
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Bolat, Elvira, Julie Robson, Kokho Jason Sit, Shannon Birch-Chapman, Samreen Ashraf, Juliet Memery, and Caroline Jackson. "Service brand rehab: diagnosing trust repair mechanisms." Qualitative Market Research: An International Journal 23, no. 4 (January 20, 2020): 725–46. http://dx.doi.org/10.1108/qmr-12-2017-0187.
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Purpose This paper aims to understand consumers’ response to the trust repair mechanisms adopted by corporate brands in a service sector context following prominent trust damaging organizational transgressions. Design/methodology/approach Adopting a qualitative approach, six focus group discussions are used to investigate three high-profile consumer trust erosion cases within the service sector. Findings Consumer trust varies by context. Despite the severity of trust damage, corporate brands can recover trust towards their brands amongst consumers not directly affected by transgressions. Not all trust repair mechanisms are equally applicable to all service contexts, and re-branding could be used as a trust repair mechanism. Corporate brands in the service sector should focus on sense-making, relational approaches and transparency. Orchestration of trust repair mechanisms needs to be integrated within the trust rehabilitation processes. Research limitations/implications This study illustrates it is important to reconsider trust repair processes to accommodate context and integrate post-transgression consumer research. Practical implications Successful corporate brand rehabilitation of consumer trust requires examination of the trustworthiness dimensions consumers express before and after the transgression to select the most appropriate trust repair mechanisms. Findings suggest organizations also have preventative trust repair management programs. Originality/value This research is the first to empirically apply the conceptual framework of Bachmann et al. (2015) to explore consumer responses to the trust repair mechanisms adopted by corporate brands by context.
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Robb, Renee J., and Geoffrey R. Hill. "The interferon-dependent orchestration of innate and adaptive immunity after transplantation." Blood 119, no. 23 (June 7, 2012): 5351–58. http://dx.doi.org/10.1182/blood-2012-02-368076.
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Abstract The therapeutic GVL effect after allogeneic stem cell transplantation is limited by the development of GVHD. The ultimate aim of current research is to separate the 2 processes in a meaningful fashion. The IFNs are a pleiotropic group of cytokines that were originally recognized because of their ability to interfere with viral replication. However, it is now established that these cytokines play an important role in orchestrating both innate and adaptive immunity. Multiple studies have investigated the effects of both types I and II IFN on GVHD and GVL in preclinical transplant models. The results indicate variable effects that are dependent on the period of activity within the developing immune response, the presence and type of pretransplant conditioning and the differential mechanisms, and IFN sensitivity of immune pathology within individual target organs during GVHD. This Perspective discusses the current literature on the IFNs and their potential modulation within clinical transplantation, focusing particularly on enhancing the therapeutic GVL effects.
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Sunappan, D., K. Soong, and B. S. Thompson. "The Elastodynamic Response of a Class of Intelligent Machinery, Part II: Computational and Experimental Results." Journal of Vibration and Acoustics 111, no. 4 (October 1, 1989): 437–42. http://dx.doi.org/10.1115/1.3269880.
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This paper, together with a companion paper [1], describes a comprehensive theoretical and experimental investigation on a methodology proposed for suppressing the elastodynamic response of flexible mechanisms. This methodology involves retrofitting the original mechanism by the introduction of a microprocessor-controlled perturbational motion at one of the normally fixed ground-link joints. The orchestration of this motion will, it is hypothesized, enable the inertial loading on the flexible members to be reduced and consequently the magnitude of the elastodynamic response will also be reduced. In Part I of two companion papers, the theoretical developments are presented. Part II presents an experimental investigation of a four-bar linkage with a flexible rocker link, which was then retrofitted to provide an additional, microprocessor-controlled input. The magnitude of the midspan deflections of the retrofitted mechanism were less than those of the original mechanism over a broad range of operating speeds thereby validating the proposed methodology for this class of mechanism system.
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Amadeo, Marica, Giuseppe Ruggeri, Claudia Campolo, Antonella Molinaro, Valeria Loscrí, and Carlos T. Calafate. "Fog Computing in IoT Smart Environments via Named Data Networking: A Study on Service Orchestration Mechanisms." Future Internet 11, no. 11 (October 24, 2019): 222. http://dx.doi.org/10.3390/fi11110222.
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By offering low-latency and context-aware services, fog computing will have a peculiar role in the deployment of Internet of Things (IoT) applications for smart environments. Unlike the conventional remote cloud, for which consolidated architectures and deployment options exist, many design and implementation aspects remain open when considering the latest fog computing paradigm. In this paper, we focus on the problems of dynamically discovering the processing and storage resources distributed among fog nodes and, accordingly, orchestrating them for the provisioning of IoT services for smart environments. In particular, we show how these functionalities can be effectively supported by the revolutionary Named Data Networking (NDN) paradigm. Originally conceived to support named content delivery, NDN can be extended to request and provide named computation services, with NDN nodes acting as both content routers and in-network service executors. To substantiate our analysis, we present an NDN fog computing framework with focus on a smart campus scenario, where the execution of IoT services is dynamically orchestrated and performed by NDN nodes in a distributed fashion. A simulation campaign in ndnSIM, the reference network simulator of the NDN research community, is also presented to assess the performance of our proposal against state-of-the-art solutions. Results confirm the superiority of the proposal in terms of service provisioning time, paid at the expenses of a slightly higher amount of traffic exchanged among fog nodes.
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Mikkilineni, Rao. "Information Processing, Information Networking, Cognitive Apparatuses and Sentient Software Systems." Proceedings 47, no. 1 (May 13, 2020): 27. http://dx.doi.org/10.3390/proceedings2020047027.
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In the physical world, computing processes, message communication networks and cognitive apparatuses are the building blocks of sentient beings. Genes and neural networks provide complementary information processing models that enable execution of mechanisms dealing with “life” using physical, chemical and biological processes. A cognizing agent architecture (mind) provides the orchestration of body and the brain to manage the “life” processes to deal with fluctuations and maintain survival and sustenance. We present a new information processing architecture that enables “digital genes” and “digital neurons” with cognizing agent architecture to design and implement sentient, resilient and intelligent systems in the digital world.
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Mikkilineni, Rao. "Information Processing, Information Networking, Cognitive Apparatuses and Sentient Software Systems." Proceedings 47, no. 1 (May 13, 2020): 27. http://dx.doi.org/10.3390/proceedings47010027.
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In the physical world, computing processes, message communication networks and cognitive apparatuses are the building blocks of sentient beings. Genes and neural networks provide complementary information processing models that enable execution of mechanisms dealing with “life” using physical, chemical and biological processes. A cognizing agent architecture (mind) provides the orchestration of body and the brain to manage the “life” processes to deal with fluctuations and maintain survival and sustenance. We present a new information processing architecture that enables “digital genes” and “digital neurons” with cognizing agent architecture to design and implement sentient, resilient and intelligent systems in the digital world.
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Aerts, Liesbeth, Bart De Strooper, and Vanessa A. Morais. "PINK1 activation–turning on a promiscuous kinase." Biochemical Society Transactions 43, no. 2 (April 1, 2015): 280–86. http://dx.doi.org/10.1042/bst20150002.
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PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1] is a serine/threonine kinase targeted to mitochondria and implicated in early-onset recessive Parkinson's disease (PD). Through the phosphorylation of its downstream targets, PINK1 regulates multiple mitochondrial processes, including ATP production, stress-response and mitochondrial dynamics and quality control. The orchestration of such a wide array of functions by an individual kinase requires a fine-tuned and versatile regulation of its activity. PINK1 proteolytic processing, trafficking and localization, as well as different post-translational modifications, affect its activity and function. Unravelling the regulatory mechanisms of PINK1 is essential for a full comprehension of its kinase function in health and disease.
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Tran, Damien, Mickael Perrigault, Pierre Ciret, and Laura Payton. "Bivalve mollusc circadian clock genes can run at tidal frequency." Proceedings of the Royal Society B: Biological Sciences 287, no. 1918 (January 8, 2020): 20192440. http://dx.doi.org/10.1098/rspb.2019.2440.
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Marine coastal habitats are complex cyclic environments as a result of sun and moon interactions. In contrast with the well-known circadian orchestration of the terrestrial animal rhythmicity (approx. 24 h), the mechanism responsible for the circatidal rhythm (approx. 12.4 h) remains largely elusive in marine organisms. We revealed in subtidal field conditions that the oyster Crassostrea gigas exhibits tidal rhythmicity of circadian clock genes and clock-associated genes. A free-running (FR) experiment showed an endogenous circatidal rhythm. In parallel, we showed in the field that oysters' valve behaviour exhibited a strong tidal rhythm combined with a daily rhythm. In the FR experiment, all behavioural rhythms were circatidal, and half of them were also circadian. Our results fuel the debate on endogenous circatidal mechanisms. In contrast with the current hypothesis on the existence of an independent tidal clock, we suggest that a single ‘circadian/circatidal’ clock in bivalves is sufficient to entrain behavioural patterns at tidal and daily frequencies.
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Wang, Xiaogang, William J. Eagen, and Jean C. Lee. "Orchestration of human macrophage NLRP3 inflammasome activation by Staphylococcus aureus extracellular vesicles." Proceedings of the National Academy of Sciences 117, no. 6 (January 27, 2020): 3174–84. http://dx.doi.org/10.1073/pnas.1915829117.
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Release of extracellular vesicles (EVs) is a common feature among eukaryotes, archaea, and bacteria. However, the biogenesis and downstream biological effects of EVs released from gram-positive bacteria remain poorly characterized. Here, we report that EVs purified from a community-associated methicillin-resistant Staphylococcus aureus strain were internalized into human macrophages in vitro and that this process was blocked by inhibition of the dynamin-dependent endocytic pathway. Human macrophages responded to S. aureus EVs by TLR2 signaling and activation of NLRP3 inflammasomes through K+ efflux, leading to the recruitment of ASC and activation of caspase-1. Cleavage of pro–interleukin (IL)-1β, pro-IL-18, and gasdermin-D by activated caspase-1 resulted in the cellular release of the mature cytokines IL-1β and IL-18 and induction of pyroptosis. Consistent with this result, a dose-dependent cytokine response was detected in the extracellular fluids of mice challenged intraperitoneally with S. aureus EVs. Pore-forming toxins associated with S. aureus EVs were critical for NLRP3-dependent caspase-1 activation of human macrophages, but not for TLR2 signaling. In contrast, EV-associated lipoproteins not only mediated TLR2 signaling to initiate the priming step of NLRP3 activation but also modulated EV biogenesis and the toxin content of EVs, resulting in alterations in IL-1β, IL-18, and caspase-1 activity. Collectively, our study describes mechanisms by which S. aureus EVs induce inflammasome activation and reveals an unexpected role of staphylococcal lipoproteins in EV biogenesis. EVs may serve as a novel secretory pathway for S. aureus to transport protected cargo in a concentrated form to host cells during infections to modulate cellular functions.
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Alfaras, Miquel, William Primett, Muhammad Umair, Charles Windlin, Pavel Karpashevich, Niaz Chalabianloo, Dionne Bowie, et al. "Biosensing and Actuation—Platforms Coupling Body Input-Output Modalities for Affective Technologies." Sensors 20, no. 21 (October 22, 2020): 5968. http://dx.doi.org/10.3390/s20215968.
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Research in the use of ubiquitous technologies, tracking systems and wearables within mental health domains is on the rise. In recent years, affective technologies have gained traction and garnered the interest of interdisciplinary fields as the research on such technologies matured. However, while the role of movement and bodily experience to affective experience is well-established, how to best address movement and engagement beyond measuring cues and signals in technology-driven interactions has been unclear. In a joint industry-academia effort, we aim to remodel how affective technologies can help address body and emotional self-awareness. We present an overview of biosignals that have become standard in low-cost physiological monitoring and show how these can be matched with methods and engagements used by interaction designers skilled in designing for bodily engagement and aesthetic experiences. Taking both strands of work together offers unprecedented design opportunities that inspire further research. Through first-person soma design, an approach that draws upon the designer’s felt experience and puts the sentient body at the forefront, we outline a comprehensive work for the creation of novel interactions in the form of couplings that combine biosensing and body feedback modalities of relevance to affective health. These couplings lie within the creation of design toolkits that have the potential to render rich embodied interactions to the designer/user. As a result we introduce the concept of “orchestration”. By orchestration, we refer to the design of the overall interaction: coupling sensors to actuation of relevance to the affective experience; initiating and closing the interaction; habituating; helping improve on the users’ body awareness and engagement with emotional experiences; soothing, calming, or energising, depending on the affective health condition and the intentions of the designer. Through the creation of a range of prototypes and couplings we elicited requirements on broader orchestration mechanisms. First-person soma design lets researchers look afresh at biosignals that, when experienced through the body, are called to reshape affective technologies with novel ways to interpret biodata, feel it, understand it and reflect upon our bodies.
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Tong, Hongjuan, Jianhong Zhao, Xiangmin Li, Yajun Zhang, Shengnan Ma, Kaiyan Lou, and Wei Wang. "Orchestration of dual cyclization processes and dual quenching mechanisms for enhanced selectivity and drastic fluorescence turn-on detection of cysteine." Chemical Communications 53, no. 25 (2017): 3583–86. http://dx.doi.org/10.1039/c6cc09336a.
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Huwiler, Andrea, and Josef Pfeilschifter. "Hypoxia and lipid signaling." Biological Chemistry 387, no. 10/11 (October 1, 2006): 1321–28. http://dx.doi.org/10.1515/bc.2006.165.
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AbstractSufficient oxygen supply is crucial for the development and physiology of mammalian cells and tissues. When simple diffusion of oxygen becomes inadequate to provide the necessary flow of substrate, evolution has provided cells with tools to detect and respond to hypoxia by upregulating the expression of specific genes, which allows an adaptation to hypoxia-induced stress conditions. The modulation of cell signaling by hypoxia is an emerging area of research that provides insight into the orchestration of cell adaptation to a changing environment. Cell signaling and adaptation processes are often accompanied by rapid and/or chronic remodeling of membrane lipids by activated lipases. This review highlights the bi-directional relation between hypoxia and lipid signaling mechanisms.
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MacKenzie, Anne M., and Soni Lacefield. "CDK Regulation of Meiosis: Lessons from S. cerevisiae and S. pombe." Genes 11, no. 7 (June 29, 2020): 723. http://dx.doi.org/10.3390/genes11070723.
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Meiotic progression requires precise orchestration, such that one round of DNA replication is followed by two meiotic divisions. The order and timing of meiotic events is controlled through the modulation of the phosphorylation state of proteins. Key components of this phospho-regulatory system include cyclin-dependent kinase (CDK) and its cyclin regulatory subunits. Over the past two decades, studies in budding and fission yeast have greatly informed our understanding of the role of CDK in meiotic regulation. In this review, we provide an overview of how CDK controls meiotic events in both budding and fission yeast. We discuss mechanisms of CDK regulation through post-translational modifications and changes in the levels of cyclins. Finally, we highlight the similarities and differences in CDK regulation between the two yeast species. Since CDK and many meiotic regulators are highly conserved, the findings in budding and fission yeasts have revealed conserved mechanisms of meiotic regulation among eukaryotes.
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Gongol, Brendan, Indah Sari, Tiffany Bryant, Geraldine Rosete, and Traci Marin. "AMPK: An Epigenetic Landscape Modulator." International Journal of Molecular Sciences 19, no. 10 (October 19, 2018): 3238. http://dx.doi.org/10.3390/ijms19103238.
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Activated by AMP-dependent and -independent mechanisms, AMP-activated protein kinase (AMPK) plays a central role in the regulation of cellular bioenergetics and cellular survival. AMPK regulates a diverse set of signaling networks that converge to epigenetically mediate transcriptional events. Reversible histone and DNA modifications, such as acetylation and methylation, result in structural chromatin alterations that influence transcriptional machinery access to genomic regulatory elements. The orchestration of these epigenetic events differentiates physiological from pathophysiological phenotypes. AMPK phosphorylation of histones, DNA methyltransferases and histone post-translational modifiers establish AMPK as a key player in epigenetic regulation. This review focuses on the role of AMPK as a mediator of cellular survival through its regulation of chromatin remodeling and the implications this has for health and disease.
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Das, Jyoti, Guangwen Ren, Liying Zhang, Arthur I. Roberts, Xin Zhao, Alfred L. M. Bothwell, Luc Van Kaer, Yufang Shi, and Gobardhan Das. "Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation." Journal of Experimental Medicine 206, no. 11 (September 28, 2009): 2407–16. http://dx.doi.org/10.1084/jem.20082286.
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Interleukin (IL)-17–producing T helper (Th17) cells play a critical role in the pathophysiology of several autoimmune disorders. The differentiation of Th17 cells requires the simultaneous presence of an unusual combination of cytokines: IL-6, a proinflammatory cytokine, and transforming growth factor (TGF) β, an antiinflammatory cytokine. However, the molecular mechanisms by which TGF-β exerts its effects on Th17 cell differentiation remain elusive. We report that TGF-β does not directly promote Th17 cell differentiation but instead acts indirectly by blocking expression of the transcription factors signal transducer and activator of transcription (STAT) 4 and GATA-3, thus preventing Th1 and Th2 cell differentiation. In contrast, TGF-β had no effect on the expression of retinoic acid receptor–related orphan nuclear receptor γt, a Th17-specific transcription factor. Interestingly, in Stat-6−/−T-bet−/− mice, which are unable to generate Th1 and Th2 cells, IL-6 alone was sufficient to induce robust differentiation of Th17 cells, whereas TGF-β had no effect, suggesting that TGF-β is dispensable for Th17 cell development. Consequently, BALB/c Stat-6−/−T-bet−/− mice, but not wild-type BALB/c mice, were highly susceptible to the development of experimental autoimmune encephalomyelitis, which could be blocked by anti–IL-17 antibodies but not by anti–TGF-β antibodies. Collectively, these data provide evidence that TGF-β is not directly required for the molecular orchestration of Th17 cell differentiation.
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Leong, Huey Sze, Morgan Philp, Martin Simone, Paul Kenneth Witting, and Shanlin Fu. "Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction." International Journal of Molecular Sciences 21, no. 4 (February 18, 2020): 1370. http://dx.doi.org/10.3390/ijms21041370.
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Increasing reports of neurological and psychiatric complications due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the precise mechanism of SC toxicity is unclear. This paucity of understanding highlights the need to investigate the in-vitro toxicity and mechanistic pathways of three SCs: butylone, pentylone, and 3,4-Methylenedioxypyrovalerone (MDPV). Human neuronal cells of SH-SY5Y were cultured in supplemented DMEM/F12 media and differentiated to a neuronal phenotype using retinoic acid (10 μM) and 12-O-tetradecanoylphorbol-13-acetate (81 nM). Trypan blue and lactate dehydrogenase assays were utilized to assess the neurotoxicity potential and potency of these three SCs. To investigate the underlying neurotoxicity mechanisms, measurements included markers of oxidative stress, mitochondrial bioenergetics, and intracellular calcium (Ca2+), and cell death pathways were evaluated at two doses (EC15 and EC40), for each drug tested. Following 24 h of treatment, all three SCs exhibited a dose-dependent neurotoxicity, characterized by a significant (p < 0.0001 vs. control) production of reactive oxygen species, decreased mitochondrial bioenergetics, and increased intracellular Ca2+ concentrations. The activation of caspases 3 and 7 implicated the orchestration of mitochondrial-mediated neurotoxicity mechanisms for these SCs. Identifying novel therapeutic agents to enhance an altered mitochondrial function may help in the treatment of acute-neurological complications arising from the illicit use of these SCs.
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Gong, Yu, Fu Jia, Steve Brown, and Lenny Koh. "Supply chain learning of sustainability in multi-tier supply chains." International Journal of Operations & Production Management 38, no. 4 (April 3, 2018): 1061–90. http://dx.doi.org/10.1108/ijopm-05-2017-0306.
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Purpose The purpose of this paper is to explore how multinational corporations (MNCs) orchestrate internal and external resources to help their multi-tier supply chains learn sustainability-related knowledge. Design/methodology/approach An exploratory multiple case study approach was adopted and three MNCs’ sustainable initiatives in China were examined. The data were primarily collected through 43 semi-structured interviews with managers of focal companies and their multi-tier suppliers. Findings The authors found that in order to facilitate their supply chains to learn sustainability, MNCs tend to orchestrate in breadth by internally setting up new functional departments and externally working with third parties, and orchestrate in depth working directly with their extreme upstream suppliers adopting varied governance mechanisms on lower-tier suppliers along the project lifecycle. The resource orchestration in breadth and depth and along the project lifecycle results in changes of supply chain structure. Practical implications The proposed conceptual model provides an overall framework for companies to design and implement their multi-tier sustainable initiatives. Companies could learn from the suggested learning stages and the best practices of case companies. Originality/value The authors extend and enrich resource orchestration perspective (ROP), which is internally focused, to a supply chain level, and answer a theoretical question of how MNCs orchestrate their internal and external resources to help their supply chains to learn sustainability. The extension of ROP refutes the resource dependence theory, which adopts a passive approach of relying on external suppliers and proposes that MNCs should proactively work with internal and external stakeholders to learn sustainability.
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Gao, Li, Xiao Jun Meng, and Yong Jin Yu. "Study on Enterprise Integration Platform Based on Web Services." Applied Mechanics and Materials 16-19 (October 2009): 633–38. http://dx.doi.org/10.4028/www.scientific.net/amm.16-19.633.
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Logical framework of enterprise integration platform is constructed, which is based on the model of user-process-applications. The application systems and business processes are encapsulated by the neutral and standard web services with the support of enterprise applications and database. By using services publishing and discovering mechanisms, enterprise resources can be located and shared. Services within the enterprise can by dynamically orchestrated as processes, so that the enterprise business process can by dynamically constructed and monitored according to the changing environment. Core of the platform is orchestration and management of web services, which is driver by a process engine. The platform is exhibited as enterprise portal supporting single sing-on. An enterprise –wide Kanban system is also incorporated within the platform, covering the enterprise and workshop information. An example is given at the end.
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Wettinger, Johannes, Tobias Binz, Uwe Breitenbücher, Oliver Kopp, and Frank Leymann. "Streamlining Cloud Management Automation by Unifying the Invocation of Scripts and Services Based on TOSCA." International Journal of Organizational and Collective Intelligence 4, no. 2 (April 2014): 45–63. http://dx.doi.org/10.4018/ijoci.2014040103.
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Today, there is a huge variety of script-centric approaches, APIs, and tools available to implement automated provisioning, deployment, and management of applications in the Cloud. The automation of all these aspects is key for reducing costs. However, most of these approaches are script-centric and provide proprietary solutions employing different invocation mechanisms, interfaces, and state models. Moreover, most Cloud providers offer proprietary APIs to be used for provisioning and management purposes. Consequently, it is hard to create deployment and management plans that integrate multiple of these approaches. The goal of our work is to come up with an approach for unifying the invocation of scripts and services without handling each proprietary interface separately. A prototype realizes the presented approach in a standards-based manner using the Topology and Orchestration Specification for Cloud Applications (TOSCA).
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Negrón-Oyarzo, Ignacio, Francisco Aboitiz, and Pablo Fuentealba. "Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders." Neural Plasticity 2016 (2016): 1–16. http://dx.doi.org/10.1155/2016/7539065.
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Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.
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Vadlamudi, Yellamandayya, Debasish K. Dey, and Sun C. Kang. "Emerging Multi-cancer Regulatory Role of ESRP1: Orchestration of Alternative Splicing to Control EMT." Current Cancer Drug Targets 20, no. 9 (September 28, 2020): 654–65. http://dx.doi.org/10.2174/1568009620666200621153831.
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RNA binding proteins (RBPs) associate with nascent and mature RNAs to perform biological functions such as alternative splicing and RNA stability. Having unique RNA recognition binding motifs, RBPs form complexes with RNA in a sequence- and structure-based manner. Aberrant expressions of several RBPs have been identified in tumorigenesis and cancer progression. These uncontrolled RBPs affect several mechanisms, including cell proliferation, tumor growth, invasion, metastasis and chemoresistance. Epithelial splicing regulatory protein 1 (ESRP1) is a member of the hnRNP family of proteins that play a crucial role in regulating numerous cellular processes, including alternative splicing and translation of multiple genes during organogenesis. Abnormal expression of ESRP1 alters the cell morphology, and leads to cell proliferation and tumor growth during cancer progression. ESRP1 mediated alternative splicing of target genes, including CD44, FGFR, PTBP1, LYN, ENAH, SPAG1 and ZMYND8, results in cancer progression. In addition, ESRP1 also regulates circularization and biogenesis of circular RNAs such as circUHRF1, circNOL10 and circANKS1B, whose expressions have been identified as key factors in various cancers. This multi-functional protein is also involved in imposing stability of target mRNAs such as cyclin A2, and thereby cell cycle regulation. The scope of this review is to examine recent scientific data, outcomes of the up- and down-regulated proteins, and the role of ESRP1 in various cancers. We conclude by summarizing ESRP1 dysregulation and its consequences on target genes in various human cancers. Collectively, the consequences of ESRP1 mediated splicing in cancer cells suggest the role of ESRP1 in cell proliferation and chemoresistance via apoptosis and autophagy modulation, which could, therefore, be potential targets for cancer therapeutics.
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Bateman, Jack, and David Van Vactor. "The Trio family of guanine-nucleotide-exchange factors: regulators of axon guidance." Journal of Cell Science 114, no. 11 (June 1, 2001): 1973–80. http://dx.doi.org/10.1242/jcs.114.11.1973.
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Axon guidance requires the integration of diverse guidance signals presented by numerous extracellular cues and cell-cell interactions. The molecular mechanisms that interpret these signals involve networks of intracellular signaling proteins that coordinate a variety of responses to the environment, including remodeling and assembly of the actin cytoskeleton. Although it has been clear for some time that Rho family GTPases play a central role in the orchestration of cytoskeletal assembly, our understanding of the components that regulate these important molecules is far more primitive. Recent functional studies of the Trio family of guanine-nucleotide-exchange factors reveal that Trio proteins play a vital role in neuronal cell migration and axon guidance. Although the molecular analysis of Trio proteins is still in its infancy, accumulated evidence suggests that Trio proteins function as integrators of multiple upstream inputs and as activators of multiple downstream pathways. Future studies of these mechanisms promise to yield insights not only into neural development but also into the ongoing function and remodeling of the adult nervous system.
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Spataru, Adrian. "Decentralized and Fault Tolerant Cloud Service Orchestration." Scalable Computing: Practice and Experience 21, no. 4 (December 20, 2020): 709–25. http://dx.doi.org/10.12694/scpe.v21i4.1838.
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This paper proposes a decentralized framework for the orchestration of Cloud Services using heterogeneous resources residing in the homes of private individuals or small-scale clusters. The framework makes use of Ethereum Smart Contracts to provide a decentralized mechanism for discovering the different interfaces exposed by Cloud Components. The paper introduces a novel concept of Component Administration Networks, which are peer-to-peer networks that monitor and ensure the availability of the software components. The concept applied for the Orchestration process to ensure that the deployment of an Application continues in the presence of Orchestrator component failure. Checkpoints are used to address the continuity of the Management components, in general, and of the Orchestrator, in particular. In our proposal, checkpoint metadata is stored in a Smart Contract to assess the execution time of a Service to reimburse the participants that ensure its execution.
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Amidfar, Meysam, and Yong-Ku Kim. "Recent Developments on Future Antidepressant-related Serotonin Receptors." Current Pharmaceutical Design 24, no. 22 (October 19, 2018): 2541–48. http://dx.doi.org/10.2174/1381612824666180803111240.
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Conventional serotonin-enhancing antidepressants including selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) have shown effectiveness in the treatment of major depression, but their significant limitations such as slowness of action have led to intensive research efforts to develop new antidepressants. Increased synaptic neurotransmission of serotonin (5-hdroxytryptamine; 5-HT) through orchestration of stimulation and blockade of various subtypes of 5-HT receptors is involved in the mechanisms of action of SSRIs. Agonists at the 5-HT1A, 5-HT1B, 5-HT2C, 5-HT4, and 5-HT6 receptors and antagonists at the 5-HT1A, 5-HT2A, 5-HT2C, 5-HT3, 5- HT6, and 5-HT7 receptors have shown antidepressant properties in clinical and preclinical studies. However, paradoxical antidepressant-like effects of both agonists and antagonists at particular 5-HT receptors suggest the need to consider the neurochemical mechanisms of each 5-HT receptor subtype. Therefore, better knowledge of the involvement of individual 5-HT receptors in the mechanisms of action of currently used antidepressants as well as antidepressant effects of selective ligands of 5- HT receptor subtypes will provide opportunities for the development of future antidepressants with more rapid onset of action, fewer side effects, and better efficacy than SSRIs.
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Pensold, Daniel, Julia Reichard, Karen M. J. Van Loo, Natalja Ciganok, Anne Hahn, Cathrin Bayer, Lutz Liebmann, et al. "DNA Methylation-Mediated Modulation of Endocytosis as Potential Mechanism for Synaptic Function Regulation in Murine Inhibitory Cortical Interneurons." Cerebral Cortex 30, no. 7 (March 7, 2020): 3921–37. http://dx.doi.org/10.1093/cercor/bhaa009.
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Abstract The balance of excitation and inhibition is essential for cortical information processing, relying on the tight orchestration of the underlying subcellular processes. Dynamic transcriptional control by DNA methylation, catalyzed by DNA methyltransferases (DNMTs), and DNA demethylation, achieved by ten–eleven translocation (TET)-dependent mechanisms, is proposed to regulate synaptic function in the adult brain with implications for learning and memory. However, focus so far is laid on excitatory neurons. Given the crucial role of inhibitory cortical interneurons in cortical information processing and in disease, deciphering the cellular and molecular mechanisms of GABAergic transmission is fundamental. The emerging relevance of DNMT and TET-mediated functions for synaptic regulation irrevocably raises the question for the targeted subcellular processes and mechanisms. In this study, we analyzed the role dynamic DNA methylation has in regulating cortical interneuron function. We found that DNMT1 and TET1/TET3 contrarily modulate clathrin-mediated endocytosis. Moreover, we provide evidence that DNMT1 influences synaptic vesicle replenishment and GABAergic transmission, presumably through the DNA methylation-dependent transcriptional control over endocytosis-related genes. The relevance of our findings is supported by human brain sample analysis, pointing to a potential implication of DNA methylation-dependent endocytosis regulation in the pathophysiology of temporal lobe epilepsy, a disease characterized by disturbed synaptic transmission.
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Frankfort, Benjamin J., and Graeme Mardon. "R8 development in theDrosophilaeye: a paradigm for neural selection and differentiation." Development 129, no. 6 (March 15, 2002): 1295–306. http://dx.doi.org/10.1242/dev.129.6.1295.
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The Drosophila eye is an outstanding model with which to decipher mechanisms of neural differentiation. Paramount to normal eye development is the organized selection and differentiation of a patterned array of R8 photoreceptors – the founding photoreceptor of each ommatidium that coordinates the incorporation of all other photoreceptors. R8 development is a complex process that requires the integration of transcription factors and signaling pathways, many of which are highly conserved and perform similar functions in other species. This article discusses the developmental control of the four key elements of R8 development: selection, spacing, differentiation and orchestration of later events. New questions that have surfaced because of recent advances in the field are addressed, and the unique characteristics of R8 development are highlighted through comparisons with neural specification in other Drosophila tissues and with ganglion cell development in the mammalian retina.
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SMN Mydin, Rabiatul Basria, Srimala Sreekantan, Roshasnorlyza Hazan, Mustafa Fadzil Farid Wajidi, and Ishak Mat. "Cellular Homeostasis and Antioxidant Response in Epithelial HT29 Cells on Titania Nanotube Arrays Surface." Oxidative Medicine and Cellular Longevity 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/3708048.
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Cell growth and proliferative activities on titania nanotube arrays (TNA) have raised alerts on genotoxicity risk. Present toxicogenomic approach focused on epithelial HT29 cells with TNA surface. Fledgling cell-TNA interaction has triggered G0/G1 cell cycle arrests and initiates DNA damage surveillance checkpoint, which possibly indicated the cellular stress stimuli. A profound gene regulation was observed to be involved in cellular growth and survival signals such as p53 and AKT expressions. Interestingly, the activation of redox regulator pathways (antioxidant defense) was observed through the cascade interactions of GADD45, MYC, CHECK1, and ATR genes. These mechanisms furnish to protect DNA during cellular division from an oxidative challenge, set in motion with XRRC5 and RAD50 genes for DNA damage and repair activities. The cell fate decision on TNA-nanoenvironment has been reported to possibly regulate proliferative activities via expression of p27 and BCL2 tumor suppressor proteins, cogent with SKP2 and BCL2 oncogenic proteins suppression. Findings suggested that epithelial HT29 cells on the surface of TNA may have a positive regulation via cell-homeostasis mechanisms: a careful circadian orchestration between cell proliferation, survival, and death. This nanomolecular knowledge could be beneficial for advanced medical applications such as in nanomedicine and nanotherapeutics.
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Wainwright, Patricia E. "Dietary essential fatty acids and brain function: a developmental perspective on mechanisms." Proceedings of the Nutrition Society 61, no. 1 (February 2002): 61–69. http://dx.doi.org/10.1079/pns2001130.
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Brain development is a complex interactive process in which early disruptive events can have long-lasting effects on later functional adaptation. It is a process that is dependent on the timely orchestration of external and internal inputs through sophisticated intra- and intercellular signalling pathways. Long-chain polyunsaturated fatty acids (LCPUFA), specifically arachidonic acid and docosahexaenoic acid (DHA), accrue rapidly in the grey matter of the brain during development, and brain fatty acid (FA) composition reflects dietary availability. Membrane lipid components can influence signal transduction cascades in various ways, which in the case of LCPUFA include the important regulatory functions mediated by the eicosanoids, and extend to long-term regulation through effects on gene transcription. Our work indicates that FA imbalance as well as specific FA deficiencies can affect development adversely, including the ability to respond to environmental stimulation. For example, although the impaired water-maze performance of mice fed a saturated-fat diet improved in response to early environmental enrichment, the brains of these animals showed less complex patterns of dendritic branching. Dietaryn-3 FA deficiency influences specific neurotransmitter systems, particularly the dopamine systems of the frontal cortex. We showed that dietary deficiency ofn-3 FA impaired the performance of rats on delayed matching-to-place in the water maze, a task of the type associated with prefrontal dopamine function. We did not, however, find an association over a wider range of brain DHA levels and performance on this task. Some, but not all, studies of human infants suggest that dietary DHA may play a role in cognitive development as well as in some neurodevelopmental disorders; this possibility has important implications for population health.
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Erpapazoglou, Zoi, and Olga Corti. "The endoplasmic reticulum/mitochondria interface: a subcellular platform for the orchestration of the functions of the PINK1–Parkin pathway?" Biochemical Society Transactions 43, no. 2 (April 1, 2015): 297–301. http://dx.doi.org/10.1042/bst20150008.
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Mitochondrial dysfunction is a hallmark of both idiopathic and familial Parkinson's disease (PD). Mutations in the PARK2 and PARK6 genes, coding for the cytosolic E3 ubiquitin protein ligase Parkin and the mitochondrial serine/threonine kinase PINK1 [phosphatase and tensin homologue (PTEN)-induced putative kinase 1], lead to clinically similar early-onset Parkinsonian syndromes. PINK1 and Parkin cooperate within a conserved pathway to preserve mitochondrial quality through the regulation of a variety of processes, including mitochondrial dynamics, transport, bioenergetics, biogenesis and turnover. The molecular mechanisms behind the orchestration of this plethora of functions remain poorly understood. In the present review, we emphasize the functional overlap between the PINK1–Parkin pathway and the endoplasmic reticulum (ER)-mitochondria interface, a subcellular compartment critically involved in neurodegeneration. We discuss how this compartment may constitute a hub for the spatiotemporal organization of the activities of the PINK1–Parkin pathway.