Zeitschriftenartikel: „Complex engineered system“

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Mehrpouyan, Hoda, Brandon Haley, Andy Dong, Irem Y. Tumer und Christopher Hoyle. „Resiliency analysis for complex engineered system design“. Artificial Intelligence for Engineering Design, Analysis and Manufacturing 29, Nr. 1 (19.01.2015): 93–108. http://dx.doi.org/10.1017/s0890060414000663.

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AbstractResilience is a key driver in the design of systems that must operate in an uncertain operating environment, and it is a key metric to assess the capacity for systems to perform within the specified performance envelop despite disturbances to their operating environment. This paper describes a graph spectral approach to calculate the resilience of complex engineered systems. The resilience of the design architecture of complex engineered systems is deduced from graph spectra. This is calculated from adjacency matrix representations of the physical connections between components in complex engineered systems. Furthermore, we propose a new method to identify the most vulnerable components in the design and design architectures that are robust to transmission of failures. Nonlinear dynamical system and epidemic spreading models are used to compare the failure propagation mean time transformation. Using these metrics, we present a case study based on the Advanced Diagnostics and Prognostics Testbed, which is an electrical power system developed at NASA Ames as a subsystem for the ramp system of an infantry fighting vehicle.

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Liu, Boyuan, Shuangxi Huang, Wenhui Fan, Tianyuan Xiao, James Humann, Yuyang Lai und Yan Jin. „Data driven uncertainty evaluation for complex engineered system design“. Chinese Journal of Mechanical Engineering 29, Nr. 5 (16.05.2016): 889–900. http://dx.doi.org/10.3901/cjme.2016.0422.058.

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McIntire, Matthew G., Christopher Hoyle, Irem Y. Tumer und David C. Jensen. „Safety-informed design: Using subgraph analysis to elicit hazardous emergent failure behavior in complex systems“. Artificial Intelligence for Engineering Design, Analysis and Manufacturing 30, Nr. 4 (04.10.2016): 466–73. http://dx.doi.org/10.1017/s089006041600041x.

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AbstractIdentifying failure paths and potentially hazardous scenarios resulting from component faults and interactions is a challenge in the early design process. The inherent complexity present in large engineered systems leads to nonobvious emergent behavior, which may result in unforeseen hazards. Current hazard analysis techniques focus on single hazards (fault trees), single faults (event trees), or lists of known hazards in the domain (hazard identification). Early in the design of a complex system, engineers may represent their system as a functional model. A function failure reasoning tool can then exhaustively simulate qualitative failure scenarios. Some scenarios can be identified as hazardous by hazard rules specified by the engineer, but the goal is to identify scenarios representing unknown hazards. The incidences of specific subgraphs in graph representations of known hazardous scenarios are used to train a classifier to distinguish hazard from nonhazard. The algorithm identifies the scenario most likely to be hazardous, and presents it to the engineer. After viewing the scenario and judging its safety, the engineer may have insight to produce additional hazard rules. The collaborative process of strategic presentation of scenarios by the computer and human judgment will identify previously unknown hazards. The feasibility of this methodology has been tested on a relatively simple functional model of an electrical power system with positive results. Related work applying function failure reasoning to a team of robotic rovers will provide data from a more complex system.

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Basole, Rahul C., Ahsan Qamar, Hyunwoo Park, Christiaan J. J. Paredis und Leon F. McGinnis. „Visual Analytics for Early-Phase Complex Engineered System Design Support“. IEEE Computer Graphics and Applications 35, Nr. 2 (März 2015): 41–51. http://dx.doi.org/10.1109/mcg.2015.3.

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Dimauro, G., S. Impedovo, G. Pirlo und A. Salzo. „Automatic Bankcheck Processing: A New Engineered System“. International Journal of Pattern Recognition and Artificial Intelligence 11, Nr. 04 (Juni 1997): 467–504. http://dx.doi.org/10.1142/s0218001497000214.

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A new bankcheck processing system is presented in this paper. A full exploitation of the contextual knowledge, together with a multi-expert approach, have been used both to analyze the complex shape of handwritten text and to design the system. Several processing modules have been integrated in the system. Some of the most relevant are those for data acquisition, preprocessing, machine-printed numeral recognition, layout analysis, courtesy amount recognition, legal amount recognition, amount validation, and signature verification. Some combination techniques have also been used in the system. Reuse and maintenance of the system were two of the main goals of the designing process and the Khoros software tool was used for this purpose.

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Sun, Eric D., Thomas C. T. Michaels und L. Mahadevan. „Optimal control of aging in complex networks“. Proceedings of the National Academy of Sciences 117, Nr. 34 (12.08.2020): 20404–10. http://dx.doi.org/10.1073/pnas.2006375117.

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Many complex systems experience damage accumulation, which leads to aging, manifest as an increasing probability of system collapse with time. This naturally raises the question of how to maximize health and longevity in an aging system at minimal cost of maintenance and intervention. Here, we pose this question in the context of a simple interdependent network model of aging in complex systems and show that it exhibits cascading failures. We then use both optimal control theory and reinforcement learning alongside a combination of analysis and simulation to determine optimal maintenance protocols. These protocols may motivate the rational design of strategies for promoting longevity in aging complex systems with potential applications in therapeutic schedules and engineered system maintenance.

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Burg, Timothy, Cheryl A. P. Cass, Richard Groff, Matthew Pepper und Karen J. L. Burg. „Building off-the-shelf tissue-engineered composites“. Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences 368, Nr. 1917 (28.04.2010): 1839–62. http://dx.doi.org/10.1098/rsta.2010.0002.

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Rapid advances in technology have created the realistic possibility of personalized medicine. In 2000, Time magazine listed tissue engineering as one of the ‘hottest 10 career choices’. However, in the past decade, only a handful of tissue-engineered products were translated to the clinical market and none were financially viable. The reality of complex business planning and the high-investment, high-technology environment was not apparent, and the promise of tissue engineering was overstated. In the meantime, biologists were steadily applying three-dimensional benchtop tissue-culture systems for cellular research, but the systems were gelatinous and thus limited in their ability to facilitate the development of complex tissues. Now, the bioengineering literature has seen an emergence of literature describing biofabrication of tissues and organs. However, if one looks closely, again, the viable products appear distant. ‘Rapid’ prototyping to reproduce the intricate patterns of whole organs using large volumes of cellular components faces daunting challenges. Homogenous forms are being labelled ‘tissues’, but, in fact, do not represent the heterogeneous structure of the native biological system. In 2003, we disclosed the concept of combining rapid prototyping techniques with tissue engineering technologies to facilitate precision development of heterogeneous complex tissue-test systems, i.e. systems to be used for drug discovery and the study of cellular behaviour, biomedical devices and progression of disease. The focus of this paper is on the challenges we have faced since that time, moving this concept towards reality, using the case of breast tissue as an example.

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Noor, Ahmed K. „The World is More Than Complicated“. Mechanical Engineering 133, Nr. 11 (01.11.2011): 30–35. http://dx.doi.org/10.1115/1.2011-nov-1.

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This article discusses the need of complex systems to be adaptive, and various innovative technologies that are required to engineer these systems. Complex adaptive systems consist of several simultaneously interacting parts or components, which are expected to function in an uncertain, complex environment, and to adapt to unforeseeable contingencies. The defining characteristics of complex adaptive systems are that the components are continually changing, the systems involve many interactions among components, and configurations cannot be fully determined in advance. Studies have shown that complex systems of the future will require a multidisciplinary framework—an approach that has been called emergent (complexity) engineering. Emergent engineering designs a system from the bottom-up by designing the individual components and their interactions that can lead to a desired global response. Although significant effort has been devoted to understanding complexity in natural and engineered systems, the research into complex adaptive systems is fragmented and is largely focused on specific examples. In order to accelerate the development of future diverse complex systems, there is a profound need for developing the new multidisciplinary framework of emergent engineering, along with associated systematic approaches, and generally valid methods and tools for high-fidelity simulations of the collective emergent behavior of these systems.

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Christensen, G., Y. Wang und K. R. Chien. „Physiological assessment of complex cardiac phenotypes in genetically engineered mice“. American Journal of Physiology-Heart and Circulatory Physiology 272, Nr. 6 (01.06.1997): H2513—H2524. http://dx.doi.org/10.1152/ajpheart.1997.272.6.h2513.

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The recent development of techniques for surgical manipulation and for the assessment of cardiac physiology in genetically engineered mice has allowed scientists to address some of the most fundamental questions related to congenital and acquired forms of human heart disease. This review discusses recent advances in the techniques for studying cardiac disease using the mouse as a model system. Because cardiac overload is one of the most important stimuli for development of hypertrophy and heart failure in humans, various models of cardiac pressure and volume overload, as well as myocardial ischemia, have been developed and characterized. Moreover, it is possible to reliably examine murine cardiac physiology in vivo with microtransducers, echocardiography, and other miniaturized techniques. Sophisticated methods have also been developed to enable an examination of single-cell phenotypes of isolated cardiomyocytes derived from genetically engineered mice. These physiological assessments, coupled with conventional histology and molecular markers, have allowed the characterization of several gene-targeted and transgenic mouse models of hypertrophy and dilated cardiomyopathy, as well as mouse models of cardiac developmental defects. Such mouse models of heart disease will ultimately allow the molecular dissection of the interplay between the various factors leading to heart disease, and they may serve as a guide to appropriate therapeutic strategies for human heart disease.

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Nossa, Roberta, Joana Costa, Ludovica Cacopardo und Arti Ahluwalia. „Breathing in vitro: Designs and applications of engineered lung models“. Journal of Tissue Engineering 12 (Januar 2021): 204173142110086. http://dx.doi.org/10.1177/20417314211008696.

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The aim of this review is to provide a systematic design guideline to users, particularly engineers interested in developing and deploying lung models, and biologists seeking to identify a suitable platform for conducting in vitro experiments involving pulmonary cells or tissues. We first discuss the state of the art on lung in vitro models, describing the most simplistic and traditional ones. Then, we analyze in further detail the more complex dynamic engineered systems that either provide mechanical cues, or allow for more predictive exposure studies, or in some cases even both. This is followed by a dedicated section on microchips of the lung. Lastly, we present a critical discussion of the different characteristics of each type of system and the criteria which may help researchers select the most appropriate technology according to their specific requirements. Readers are encouraged to refer to the tables accompanying the different sections where comprehensive and quantitative information on the operating parameters and performance of the different systems reported in the literature is provided.

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Katina, Polinpapilinho F., Charles B. Keating, James A. Bobo und Tyrone S. Toland. „A Governance Perspective for System-of-Systems“. Systems 7, Nr. 4 (09.12.2019): 54. http://dx.doi.org/10.3390/systems7040054.

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The operating landscape of 21st century systems is characteristically ambiguous, emergent, and uncertain. These characteristics affect the capacity and performance of engineered systems/enterprises. In response, there are increasing calls for multidisciplinary approaches capable of confronting increasingly ambiguous, emergent, and uncertain systems. System of Systems Engineering (SoSE) is an example of such an approach. A key aspect of SoSE is the coordination and the integration of systems to enable ‘system-of-systems’ capabilities greater than the sum of the capabilities of the constituent systems. However, there is a lack of qualitative studies exploring how coordination and integration are achieved. The objective of this research is to revisit SoSE utility as a potential multidisciplinary approach and to suggest ‘governance’ as the basis for enabling ‘system-of-systems’ coordination and integration. In this case, ‘governance’ is concerned with direction, oversight, and accountability of ‘system-of-systems.’ ‘Complex System Governance’ is a new and novel basis for improving ‘system-of-system’ performance through purposeful design, execution, and evolution of essential metasystem functions.’

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Camenen, B., G. Naudet, G. Dramais, J. Le Coz und A. Paquier. „A multi-technique approach for evaluating sand dynamics in a complex engineered piedmont river system“. Science of The Total Environment 657 (März 2019): 485–97. http://dx.doi.org/10.1016/j.scitotenv.2018.11.394.

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Zhang, He, Junming Sun, Ding Ma, Gisela Weinberg, Dang Sheng Su und Xinhe Bao. „Engineered Complex Emulsion System: Toward Modulating the Pore Length and Morphological Architecture of Mesoporous Silicas“. Journal of Physical Chemistry B 110, Nr. 51 (Dezember 2006): 25908–15. http://dx.doi.org/10.1021/jp065760w.

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Hori, Tetsuya, Wei-Hao Shang, Kozo Takeuchi und Tatsuo Fukagawa. „The CCAN recruits CENP-A to the centromere and forms the structural core for kinetochore assembly“. Journal of Cell Biology 200, Nr. 1 (31.12.2012): 45–60. http://dx.doi.org/10.1083/jcb.201210106.

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CENP-A acts as an important epigenetic marker for kinetochore specification. However, the mechanisms by which CENP-A is incorporated into centromeres and the structural basis for kinetochore formation downstream of CENP-A remain unclear. Here, we used a unique chromosome-engineering system in which kinetochore proteins are targeted to a noncentromeric site after the endogenous centromere is conditionally removed. Using this system, we created two distinct types of engineered kinetochores, both of which were stably maintained in chicken DT40 cells. Ectopic targeting of full-length HJURP, CENP-C, CENP-I, or the CENP-C C terminus generated engineered kinetochores containing major kinetochore components, including CENP-A. In contrast, ectopic targeting of the CENP-T or CENP-C N terminus generated functional kinetochores that recruit the microtubule-binding Ndc80 complex and chromosome passenger complex (CPC), but lack CENP-A and most constitutive centromere-associated network (CCAN) proteins. Based on the analysis of these different engineered kinetochores, we conclude that the CCAN has two distinct roles: recruiting CENP-A to establish the kinetochore and serving as a structural core to directly recruit kinetochore proteins.

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Shegogue, Daniel, und W. Jim Zheng. „Object-oriented biological system integration: a SARS coronavirus example“. Bioinformatics 21, Nr. 10 (24.02.2005): 2502–9. http://dx.doi.org/10.1093/bioinformatics/bti344.

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Abstract Motivation The importance of studying biology at the system level has been well recognized, yet there is no well-defined process or consistent methodology to integrate and represent biological information at this level. To overcome this hurdle, a blending of disciplines such as computer science and biology is necessary. Results By applying an adapted, sequential software engineering process, a complex biological system (severe acquired respiratory syndrome-coronavirus viral infection) has been reverse-engineered and represented as an object-oriented software system. The scalability of this object-oriented software engineering approach indicates that we can apply this technology for the integration of large complex biological systems. Availability A navigable web-based version of the system is freely available at http://people.musc.edu/~zhengw/SARS/Software-Process.htm Contact zhengw@musc.edu Supplementary information Supplemental data: Table 1 and Figures 1–16.

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Chavez, Alejandro, Benjamin W. Pruitt, Marcelle Tuttle, Rebecca S. Shapiro, Ryan J. Cecchi, Jordan Winston, Brian M. Turczyk, Michael Tung, James J. Collins und George M. Church. „Precise Cas9 targeting enables genomic mutation prevention“. Proceedings of the National Academy of Sciences 115, Nr. 14 (19.03.2018): 3669–73. http://dx.doi.org/10.1073/pnas.1718148115.

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Here, we present a generalized method of guide RNA “tuning” that enables Cas9 to discriminate between two target sites that differ by a single-nucleotide polymorphism. We employ our methodology to generate an in vivo mutation prevention system in which Cas9 actively restricts the occurrence of undesired gain-of-function mutations within a population of engineered organisms. We further demonstrate that the system is scalable to a multitude of targets and that the general tuning and prevention concepts are portable across engineered Cas9 variants and Cas9 orthologs. Finally, we show that the mutation prevention system maintains robust activity even when placed within the complex environment of the mouse gastrointestinal tract.

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Sattarova, Kseniya T., Victoria V. Kokareva und Nikolay D. Pronichev. „The Ratio-Delay Method of the Manufacturing System Analysis“. Applied Mechanics and Materials 770 (Juni 2015): 641–44. http://dx.doi.org/10.4028/www.scientific.net/amm.770.641.

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This paper describes the application of a ratio-delay to a study of operations of mechanical Job-Shop production in Samara factory. To analyze the operations efficiency it may be necessary to obtain organizational and technical data in each job stages. In fact, ratio-delay is an effective tool to determine direct labor productivity for shop floor activities. In the context of manufacturing operations, ratio-delay can determine productivity levels as a baseline that provides focus for new “industrial engineered” improvement measures of complex re-engineering project or lean management.

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Yasar, Ozlem, und Binil Starly. „Fabrication of Lindenmayer System-Based Designed Engineered Scaffolds Using UV-Maskless Photolithography“. MRS Advances 1, Nr. 11 (2016): 749–54. http://dx.doi.org/10.1557/adv.2016.223.

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ABSTRACTIn the field of tissue engineering, design and fabrication of precisely and spatially patterned, highly porous scaffolds/matrixes are required to guide overall shape of tissue growth and replacement. Although rapid prototyping fabrication techniques have been used to fabricate the scaffolds with desired design characteristics, controlling the interior architecture of the scaffolds has been a challenge due to Computer-aided Design (CAD) constrains. Moreover, thick engineered tissue scaffolds show inadequate success due to the limited diffusion of oxygen and nutrients to the interior part of the scaffolds. These limitations lead to improper tissue regeneration. In this work, in order to overcome these design and fabrication limitations, research has been expanded to generation of scaffolds which have inbuilt micro and nanoscale fluidic channels. Branching channels serve as material delivery paths to provide oxygen and nutrients for the cells. These channels are designed and controlled with Lindenmayer Systems (L-Systems) which is an influential way to create the complex branching networks by rewriting process. In this research, through the computational modeling process, to control the thickness, length, number and the position of the channels/branches, main attributes of L-Systems algorithms are characterized and effects of algorithm parameters are investigated. After the L-System based branching design is completed, 3D tissue scaffolds were fabricated by “UV-Maskless Photolithography”. In this fabrication technique, Polyethylene (glycol) Diacrylate (PEGDA), which is biodegradable and biocompatible polymer, was used as a fabrication material. Our results show that L-System parameters can be successfully controlled to design of 3D tissue engineered scaffolds. Our fabrication results also show that L-System based designed scaffolds with internal branch structures can be fabricated layer-by-layer fashion by Maskless Photolithography. This technology can be easily applied to engineering living systems.

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Forsythe, Chris, und Caren Wenner. „Surety of Human Elements of High Consequence Systems: An Organic Model“. Proceedings of the Human Factors and Ergonomics Society Annual Meeting 44, Nr. 22 (Juli 2000): 839–42. http://dx.doi.org/10.1177/154193120004402289.

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Despite extensive safety analysis and application of safety measures, there is a frequent lament, “Why do we continue to have accidents?” Two breakdowns are prevalent in risk management and prevention. First, accidents result from human actions that engineers, analysts and management never envisioned and second, controls, intended to preclude/mitigate accident sequences, prove inadequate. This paper addresses the first breakdown, the inability to anticipate scenarios involving human action/inaction. The failure of controls has been addressed in a previous publication (Forsythe and Grose, 1998). Specifically, this paper presents an approach referred to as “surety.” The objective of this approach is to provide high levels of assurance in situations where potential system failure paths cannot be fully characterized. With regard to human elements of complex systems, traditional approaches to human reliability are not sufficient to attain surety. Consequently, an Organic Model has been developed to account for the organic properties exhibited by engineered systems that result from human involvement in those systems.

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An, Shun, Wen Shang, Modi Jiang, Yini Luo, Benwei Fu, Chengyi Song, Peng Tao und Tao Deng. „Human hand as a powerless and multiplexed infrared light source for information decryption and complex signal generation“. Proceedings of the National Academy of Sciences 118, Nr. 15 (05.04.2021): e2021077118. http://dx.doi.org/10.1073/pnas.2021077118.

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With the increasing pursuit of intelligent systems, the integration of human components into functional systems provides a promising route to the ultimate human-compatible intelligent systems. In this work, we explored the integration of the human hand as the powerless and multiplexed infrared (IR) light source in different functional systems. With the spontaneous IR radiation, the human hand provides a different option as an IR light source. Compared to engineered IR light sources, the human hand brings sustainability with no need of external power and also additional level of controllability to the functional systems. Besides the whole hand, each finger of the hand can also independently provide IR radiation, and the IR radiation from each finger can be selectively diffracted by specific gratings, which helps the hand serve as a multiplexed IR light source. Considering these advantages, we show that the human hand can be integrated into various engineered functional systems. The integration of hand in an encryption/decryption system enables both unclonable and multilevel information encryption/decryption. We also demonstrate the use of the hand in complex signal generation systems and its potential application in sign language recognition, which shows a simplified recognition process with a high level of accuracy and robustness. The use of the human hand as the IR light source provides an alternative sustainable solution that will not only reduce the power used but also help move forward the effort in the integration of human components into functional systems to increase the level of intelligence and achieve ultimate control of these systems.

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Kim, Hyobin, Omar K. Pineda und Carlos Gershenson. „A Multilayer Structure Facilitates the Production of Antifragile Systems in Boolean Network Models“. Complexity 2019 (09.12.2019): 1–11. http://dx.doi.org/10.1155/2019/2783217.

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Antifragility is a property from which systems are able to resist stress and furthermore benefit from it. Even though antifragile dynamics is found in various real-world complex systems where multiple subsystems interact with each other, the attribute has not been quantitatively explored yet in those complex systems which can be regarded as multilayer networks. Here we study how the multilayer structure affects the antifragility of the whole system. By comparing single-layer and multilayer Boolean networks based on our recently proposed antifragility measure, we found that the multilayer structure facilitated the production of antifragile systems. Our measure and findings will be useful for various applications such as exploring properties of biological systems with multilayer structures and creating more antifragile engineered systems.

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Ng´ang´a, Peter Njenga, Julia K. Ebner, Matthias Plessner, Klaus Aktories und Gudula Schmidt. „Engineering Photorhabdus luminescens toxin complex (PTC) into a recombinant injection nanomachine“. Life Science Alliance 2, Nr. 5 (20.09.2019): e201900485. http://dx.doi.org/10.26508/lsa.201900485.

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Engineering delivery systems for proteins and peptides into mammalian cells is an ongoing challenge for cell biological studies as well as for therapeutic approaches. Photorhabdus luminescens toxin complex (PTC) is a heterotrimeric protein complex able to deliver diverse protein toxins into mammalian cells. We engineered the syringe-like nanomachine for delivery of protein toxins from different species. In addition, we loaded the highly active copepod luciferase Metridia longa M-Luc7 for accurate quantification of injected molecules. We suggest that besides the probable size limitation, the charge of the cargo also influences the efficiency of packing and transport into mammalian cells. Our data show that the PTC constitutes a powerful system to inject recombinant proteins, peptides, and potentially, other molecules into mammalian cells. In addition, in contrast to other protein transporters based on pore formation, the closed, compact structure of the PTC may protect cargo from degradation.

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Jabeur, Nafaâ, Nabil Sahli und Sherali Zeadally. „Enabling Cyber Physical Systems with Wireless Sensor Networking Technologies, Multiagent System Paradigm, and Natural Ecosystems“. Mobile Information Systems 2015 (2015): 1–15. http://dx.doi.org/10.1155/2015/908315.

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Wireless sensor networks (WSNs) are key components in the emergent cyber physical systems (CPSs). They may include hundreds of spatially distributed sensors which interact to solve complex tasks going beyond their individual capabilities. Due to the limited capabilities of sensors, sensor actions cannot meet CPS requirements while controlling and coordinating the operations of physical and engineered systems. To overcome these constraints, we explore the ecosystem metaphor for WSNs with the aim of taking advantage of the efficient adaptation behavior and communication mechanisms of living organisms. By mapping these organisms onto sensors and ecosystems onto WSNs, we highlight shortcomings that prevent WSNs from delivering the capabilities of ecosystems at several levels, including structure, topology, goals, communications, and functions. We then propose an agent-based architecture that migrates complex processing tasks outside the physical sensor network while incorporating missing characteristics of autonomy, intelligence, and context awareness to the WSN. Unlike existing works, we use software agents to map WSNs to natural ecosystems and enhance WSN capabilities to take advantage of bioinspired algorithms. We extend our architecture and propose a new intelligent CPS framework where several control levels are embedded in the physical system, thereby allowing agents to support WSNs technologies in enabling CPSs.

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Lee, I., J. S. Tabb, C. Chase, T. Kuritz, E. T. Owens und E. Greenbaum. „Characterization of Photosystem I/Bio-Engineered Nanoparticle Complex System by Atomic Force Microscopy and Scanning Surface Potential Microscopy“. Microscopy and Microanalysis 9, S02 (August 2003): 194–95. http://dx.doi.org/10.1017/s1431927603440439.

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Liu, Cui, Jianzhong Sun, He Liu, Shiying Lei und Xinhua Hu. „Complex engineered system health indexes extraction using low frequency raw time-series data based on deep learning methods“. Measurement 161 (September 2020): 107890. http://dx.doi.org/10.1016/j.measurement.2020.107890.

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Wolfe, Darren, April M. Craft, Justus B. Cohen und Joseph C. Glorioso. „A Herpes Simplex Virus Vector System for Expression of Complex Cellular cDNA Libraries“. Journal of Virology 84, Nr. 14 (12.05.2010): 7360–68. http://dx.doi.org/10.1128/jvi.02388-09.

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ABSTRACT Viral vector-based gene expression libraries from normal or diseased tissues offer opportunities to interrogate cellular functions that influence or participate directly in specific biological processes. Here we report the creation and characterization of a herpes simplex virus (HSV)-based expression library consisting of cDNAs derived from PC12 pheochromocytoma cells. A replication-defective HSV vector backbone was engineered to contain both a bacterial artificial chromosome (BAC) and the Invitrogen in vitro Gateway recombination system, creating DBAC-GW. A cDNA library was produced and transferred into the DBAC-GW genome by in vitro recombination and selection in bacteria to produce DBAC-L. DBAC-L contained at least 15,000 unique cDNAs, as shown by DNA array analysis of PCR-amplified cDNA inserts, representing a wide range of cancer- and neuron-related cellular functions. Transfection of the recombinant DBAC-L DNA into complementing animal cells produced more than 1 million DBAC-L virus particles representing the library genes. By microarray analysis of vector-infected cells, we observed that individual members of this vector population expressed unique PC12 cDNA-derived mRNA, demonstrating the power of this system to transfer and express a variety of gene activities. We discuss the potential utility of this and similarly derived expression libraries for genome-wide approaches to identify cellular functions that participate in complex host-pathogen interactions or processes related to disease and to cell growth and development.

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Han, Shuo, Boxuan Simen Zhao, Samuel A. Myers, Steven A. Carr, Chuan He und Alice Y. Ting. „RNA–protein interaction mapping via MS2- or Cas13-based APEX targeting“. Proceedings of the National Academy of Sciences 117, Nr. 36 (24.08.2020): 22068–79. http://dx.doi.org/10.1073/pnas.2006617117.

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RNA–protein interactions underlie a wide range of cellular processes. Improved methods are needed to systematically map RNA–protein interactions in living cells in an unbiased manner. We used two approaches to target the engineered peroxidase APEX2 to specific cellular RNAs for RNA-centered proximity biotinylation of protein interaction partners. Both an MS2-MCP system and an engineered CRISPR-Cas13 system were used to deliver APEX2 to the human telomerase RNA hTR with high specificity. One-minute proximity biotinylation captured candidate binding partners for hTR, including more than a dozen proteins not previously linked to hTR. We validated the interaction between hTR and theN6-methyladenosine (m6A) demethylase ALKBH5 and showed that ALKBH5 is able to erase the m6A modification on endogenous hTR. ALKBH5 also modulates telomerase complex assembly and activity. MS2- and Cas13-targeted APEX2 may facilitate the discovery of novel RNA–protein interactions in living cells.

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Bondoc, Andrew, Brian Golbourn, Christian Smith, Annie Huang und James Rutka. „ATRT-16. MODELLING ATRT THROUGH SWI/SNF COMPLEX DEFICIENCY IN GENETICALLY-ENGINEERED MOUSE MODELS“. Neuro-Oncology 22, Supplement_3 (01.12.2020): iii278—iii279. http://dx.doi.org/10.1093/neuonc/noaa222.015.

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Abstract Atypical Teratoid/Rhabdoid Tumours (ATRT) are highly malignant neoplasms arising primarily in the CNS of children. They are defined by loss of function mutations in smarcb1, a gene serving a vital role in neurogenesis and differentiation. In order to recapitulate ATRT in the mouse, we used a Cre-Lox recombination system to conditionally knockout smarcb1 in specific cell compartments. Loss of smarcb1 in BLBP-expressing cells of the developing brain led to severe neurologic defects. Mice exhibited seizures, ataxia, and median 12-day survival. Histological analysis revealed severe thinning of the cerebral cortex and cerebellum. Temporally-targeted smarcb1 loss in BLBP/Nestin-expressing embryonic compartments did not result in tumour formation. Similarly, BLBP-expressing, smarcb1-deficient neural stem/progenitor cells (NSC/NPCs) were isolated and allografted but did not form tumours. These cells demonstrated decreased proliferation, higher apoptosis, and upregulation of p53, CDKN1A, and CDKN2A. In contrast, ubiquitous smarcb1 loss at the earlier embryonic day 6.5 produced widespread tumorigenicity in the forebrain, hindbrain, skullbase, and spine; each with unique phenotypes, survival, and morphology. We employed a clinically-relevant Nanostring gene-panel screen to stratify tumours into genetically distinct subgroups. Our findings indicate that smarcb1 plays an important role in CNS development. Loss of smarcb1 in NSC/NPCs is lethal, and its developmental context influences cell fate. Targeted smarcb1 loss likely plays a tumorigenic role at an earlier developmental stage than previously determined, in a diverse array of primitive stem cells. These data support the generation of a murine ATRT model capable of producing distinct tumour entities that recapitulate the human disease.

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Wang, Xinyu, Jiahua Pu, Yi Liu, Fang Ba, Mengkui Cui, Ke Li, Yu Xie et al. „Immobilization of functional nano-objects in living engineered bacterial biofilms for catalytic applications“. National Science Review 6, Nr. 5 (30.07.2019): 929–43. http://dx.doi.org/10.1093/nsr/nwz104.

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Abstract Nanoscale objects feature very large surface-area-to-volume ratios and are now understood as powerful tools for catalysis, but their nature as nanomaterials brings challenges including toxicity and nanomaterial pollution. Immobilization is considered a feasible strategy for addressing these limitations. Here, as a proof-of-concept for the immobilization of nanoscale catalysts in the extracellular matrix of bacterial biofilms, we genetically engineered amyloid monomers of the Escherichia coli curli nanofiber system that are secreted and can self-assemble and anchor nano-objects in a spatially precise manner. We demonstrated three scalable, tunable and reusable catalysis systems: biofilm-anchored gold nanoparticles to reduce nitro aromatic compounds such as the pollutant p-nitrophenol, biofilm-anchored hybrid Cd0.9Zn0.1S quantum dots and gold nanoparticles to degrade organic dyes and biofilm-anchored CdSeS@ZnS quantum dots in a semi-artificial photosynthesis system for hydrogen production. Our work demonstrates how the ability of biofilms to grow in scalable and complex spatial arrangements can be exploited for catalytic applications and clearly illustrates the design utility of segregating high-energy nano-objects from injury-prone cellular components by engineering anchoring points in an extracellular matrix.

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Kaplan, Jonathan. „Hydraulics, Cacao, and Complex Developments at Preclassic Chocolá, Guatemala: Evidence and Implications“. Latin American Antiquity 19, Nr. 4 (Dezember 2008): 399–413. http://dx.doi.org/10.1017/s1045663500004351.

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Investigations begun in 2003 and continued through 2005 at Chocolá, in Southwestern Guatemala, have determined the existence of an extensive Preclassic network of well-engineered subterranean canals. The hydraulics discovered at the site, as well as other findings, add to long-standing evidence of Preclassic developments in the site's immediate region. While I consider an impressive Preclassic hydraulic system proven for Chocolá, a similarly early industry of cacao—a high-water demand plant of pan-Mesoamerican importance and native to the region—is discussed here admittedly only as a plausible hypothesis, based on copious ethnohistoric attestation but also on the long-known but disparate evidence of a temporal priority to many developments considered key to later Classic Maya civilization that are found in the Southern Maya area.

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Sun, Huiyan, Limin Zhang, Wei Cheng, Fengxia Hao, Liyan Zhou und Qiang Li. „Injectable Hydrogels in Repairing Central Nervous System Injuries“. Advances in Materials Science and Engineering 2021 (18.09.2021): 1–11. http://dx.doi.org/10.1155/2021/7381980.

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The injured central nervous system (CNS) can hardly regenerate. In vitro engineering of brain tissue hits technical bottlenecks. Also, the compaction and complexity of anatomical structure defy the accurate positioning for lesion sites in intracranial injuries. Therefore, repairing injured CNS remains a significant clinical challenge. Various recent in vivo and in vitro experiments have demonstrated the excellent effect of tissue engineering on repairing central nerve cells and tissues through implanting new materials and engineered cells. Except for porous three-dimensional structures able to pad lesions in various shapes and simulate the natural extracellular matrix with nutrients for cell proliferation, hydrogels incorporate high biocompatibility. Injectable hydrogels with the merits of avoiding complex surgery on large wounds, filling irregular gaps, delivering drugs, and others, are of growing interest. This review focuses on the experimental studies regarding injectable hydrogels, especially applying various injectable hydrogels to repair brain damage.

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Hingorani, Kastoori, Brendon Conlan, Warwick Hillier und Tom Wydrzynski. „Elucidating Photochemical Pathways of Tyrosine Oxidation in an Engineered Bacterioferritin 'Reaction Centre'“. Australian Journal of Chemistry 62, Nr. 10 (2009): 1351. http://dx.doi.org/10.1071/ch09264.

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Photosystem II (PSII) is the chlorophyll/protein complex in green plants that catalyzes the oxidation of water to molecular oxygen. We have utilized bacterioferritin (BFR), an iron storage protein found in Escherichia coli, as a protein scaffold to build in PSII cofactors in a simpler in vitro model system. Previously, we have shown that the native heme in BFR can be replaced with the chlorophyll analog zinc-chlorin (ZnCe6) and that the intrinsic di-iron site can bind two manganese ions. Upon flash excitation of the ZnCe6 modified BFR, not only is the dinuclear manganese complex oxidized but also a tyrosine residue. There are seven tyrosine residues in each BFR monomeric subunit. We mutated the three tyrosine residues within electron tunnelling distance of the ZnCe6. Here we present evidence based on electron paramagnetic resonance and fluorescence spectroscopy that one is not oxidized while the other two seem to be oxidized in parallel. Localization of this photoactive tyrosine is the first step in creating a linear electron flow in BFR like in PSII.

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Astor, J. C., und C. Adami. „A Developmental Model for the Evolution of Artificial Neural Networks“. Artificial Life 6, Nr. 3 (Juli 2000): 189–218. http://dx.doi.org/10.1162/106454600568834.

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We present a model of decentralized growth and development for artificial neural networks (ANNs), inspired by developmental biology and the physiology of nervous systems. In this model, each individual artificial neuron is an autonomous unit whose behavior is determined only by the genetic information it harbors and local concentrations of substrates. The chemicals and substrates, in turn, are modeled by a simple artificial chemistry. While the system is designed to allow for the evolution of complex networks, we demonstrate the power of the artificial chemistry by analyzing engineered (handwritten) genomes that lead to the growth of simple networks with behaviors known from physiology. To evolve more complex structures, a Java-based, platform-independent, asynchronous, distributed genetic algorithm (GA) has been implemented that allows users to participate in evolutionary experiments via the World Wide Web.

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Ramachandran, Gayetri, und David Bikard. „Editing the microbiome the CRISPR way“. Philosophical Transactions of the Royal Society B: Biological Sciences 374, Nr. 1772 (25.03.2019): 20180103. http://dx.doi.org/10.1098/rstb.2018.0103.

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Our bodies are colonized by a complex ecosystem of bacteria, unicellular eukaryotes and their viruses that together play a major role in our health. Over the past few years tools derived from the prokaryotic immune system known as CRISPR-Cas have empowered researchers to modify and study organisms with unprecedented ease and efficiency. Here we discuss how various types of CRISPR-Cas systems can be used to modify the genome of gut microorganisms and bacteriophages. CRISPR-Cas systems can also be delivered to bacterial population and programmed to specifically eliminate members of the microbiome. Finally, engineered CRISPR-Cas systems can be used to control gene expression and modulate the production of metabolites and proteins. Together these tools provide exciting opportunities to investigate the complex interplay between members of the microbiome and our bodies, and present new avenues for the development of drugs that target the microbiome. This article is part of a discussion meeting issue ‘The ecology and evolution of prokaryotic CRISPR-Cas adaptive immune systems’.

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Dispenza, Clelia, Daniela Giacomazza und Mats Jonsson. „Micro- to Nanoscale Bio-Hybrid Hydrogels Engineered by Ionizing Radiation“. Biomolecules 11, Nr. 1 (31.12.2020): 47. http://dx.doi.org/10.3390/biom11010047.

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Bio-hybrid hydrogels consist of a water-swollen hydrophilic polymer network encapsulating or conjugating single biomolecules, or larger and more complex biological constructs like whole cells. By modulating at least one dimension of the hydrogel system at the micro- or nanoscale, the activity of the biological component can be extremely upgraded with clear advantages for the development of therapeutic or diagnostic micro- and nano-devices. Gamma or e-beam irradiation of polymers allow a good control of the chemistry at the micro-/nanoscale with minimal recourse to toxic reactants and solvents. Another potential advantage is to obtain simultaneous sterilization when the absorbed doses are within the sterilization dose range. This short review will highlight opportunities and challenges of the radiation technologies to produce bio-hybrid nanogels as delivery devices of therapeutic biomolecules to the target cells, tissues, and organs, and to create hydrogel patterns at the nano-length and micro-length scales on surfaces.

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García-García, Andrés, Thibaut Klein, Gordian Born, Morgane Hilpert, Arnaud Scherberich, Claudia Lengerke, Radek C. Skoda, Paul E. Bourgine und Ivan Martin. „Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches“. Proceedings of the National Academy of Sciences 118, Nr. 40 (27.09.2021): e2114227118. http://dx.doi.org/10.1073/pnas.2114227118.

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Human malignant hematopoietic stem and progenitor cells (HSPCs) reside in bone marrow (BM) niches, which remain challenging to explore due to limited in vivo accessibility and constraints with humanized animal models. Several in vitro systems have been established to culture patient-derived HSPCs in specific microenvironments, but they do not fully recapitulate the complex features of native bone marrow. Our group previously reported that human osteoblastic BM niches (O-N), engineered by culturing mesenchymal stromal cells within three-dimensional (3D) porous scaffolds under perfusion flow in a bioreactor system, are capable of maintaining, expanding, and functionally regulating healthy human cord blood-derived HSPCs. Here, we first demonstrate that this 3D O-N can sustain malignant CD34+ cells from acute myeloid leukemia (AML) and myeloproliferative neoplasm patients for up to 3 wk. Human malignant cells distributed in the bioreactor system mimicking the spatial distribution found in native BM tissue, where most HSPCs remain linked to the niches and mature cells are released to the circulation. Using human adipose tissue-derived stromal vascular fraction cells, we then generated a stromal-vascular niche and demonstrated that O-N and stromal-vascular niche differentially regulate leukemic UCSD-AML1 cell expansion, immunophenotype, and response to chemotherapy. The developed system offers a unique platform to investigate human leukemogenesis and response to drugs in customized environments, mimicking defined features of native hematopoietic niches and compatible with the establishment of personalized settings.

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Rippa, Massimo, Riccardo Castagna, Domenico Sagnelli, Ambra Vestri, Giorgia Borriello, Giovanna Fusco, Jun Zhou und Lucia Petti. „SERS Biosensor Based on Engineered 2D-Aperiodic Nanostructure for In-Situ Detection of Viable Brucella Bacterium in Complex Matrix“. Nanomaterials 11, Nr. 4 (31.03.2021): 886. http://dx.doi.org/10.3390/nano11040886.

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Brucella is a foodborne pathogen globally affecting both the economy and healthcare. Surface Enhanced Raman Spectroscopy (SERS) nano-biosensing can be a promising strategy for its detection. We combined high-performance quasi-crystal patterned nanocavities for Raman enhancement with the use of covalently immobilized Tbilisi bacteriophages as high-performing bio-receptors. We coupled our efficient SERS nano-biosensor to a Raman system to develop an on-field phage-based bio-sensing platform capable of monitoring the target bacteria. The developed biosensor allowed us to identify Brucella abortus in milk by our portable SERS device. Upon bacterial capture from samples (104 cells), a signal related to the pathogen recognition was observed, proving the concrete applicability of our system for on-site and in-food detection.

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MacCalman, Alex D., und Simon R. Goerger. „Leveraging a design of experiments methodology to enhance impacts of modeling and simulations for engineered resilient systems“. Journal of Defense Modeling and Simulation: Applications, Methodology, Technology 15, Nr. 4 (04.05.2018): 383–97. http://dx.doi.org/10.1177/1548512918765701.

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System engineers rely on a variety of models and simulations to help understand multiple perspectives in several domains throughout a system’s life-cycle. These domain models include operational simulations, life-cycle cost models, physics-based computational models, and many more. Currently, there is a technical gap with regard to our ability to untangle system design drivers within system life-cycle domains. This article provides a procedural workflow that addresses this technical gap by leveraging the methods of experimental design in order to clearly identify tradable variables and narrow the search for viable system variants. Our purpose is to illuminate trade decisions across several different viewpoints by integrating metamodels that approximate the behavior of multiple domain models; a metamodel is a statistical function that acts as a surrogate to a model. Model inputs often represent value properties that define a system alternative configuration or environmental conditions that represent uncertain factors within the system boundary. Model outputs represent measures of performance or effectiveness that allow us to compare alternatives and understand the tradeoffs among several objectives. In order to illuminate the tradeoffs that exist in a complex system design problem we propose an approach that approximates model input and output behavior using the functional form of statistical metamodels. After performing an experimental design, we can fit a metamodel with a functional form known as a response surface. We utilize contour profilers that show horizontal cross sections of multiple response surfaces to visualize where key trade decisions exist. Our research supports the tradespace analytics pillar for the development of the engineered resilient system (ERS) architecture. The article concludes with instructions on how to perform simulation experiments to construct a dynamic dashboard that illuminates system tradeoffs.

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Kariolis, Mihalis S., Robert C. Wells, Jennifer A. Getz, Wanda Kwan, Cathal S. Mahon, Raymond Tong, Do Jin Kim et al. „Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys“. Science Translational Medicine 12, Nr. 545 (27.05.2020): eaay1359. http://dx.doi.org/10.1126/scitranslmed.aay1359.

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Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB). We describe the development of a BBB transport vehicle (TV) comprising an engineered Fc fragment that exploits receptor-mediated transcytosis for CNS delivery of biotherapeutics by binding a highly expressed brain endothelial cell target. TVs were engineered using directed evolution to bind the apical domain of the human transferrin receptor (hTfR) without the use of amino acid insertions, deletions, or unnatural appendages. A crystal structure of the TV-TfR complex revealed the TV binding site to be away from transferrin and FcRn binding sites, which was further confirmed experimentally in vitro and in vivo. Recombinant expression of TVs fused to anti–β-secretase (BACE1) Fabs yielded antibody transport vehicle (ATV) molecules with native immunoglobulin G (IgG) structure and stability. Peripheral administration of anti-BACE1 ATVs to hTfR-engineered mice and cynomolgus monkeys resulted in substantially improved CNS uptake and sustained pharmacodynamic responses. The TV platform readily accommodates numerous additional configurations, including bispecific antibodies and protein fusions, yielding a highly modular CNS delivery platform.

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Xu, Mingen, Yongnian Van, Haixia Liu, Rui Yag und Xiaohong Wang. „Controlled Adipose-derived Stromal Cells Differentiation into Adipose and Endothelial Cells in a 3D Structure Established by Cell-assembly Technique“. Journal of Bioactive and Compatible Polymers 24, Nr. 1_suppl (Mai 2009): 31–47. http://dx.doi.org/10.1177/0883911509102794.

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One of the major obstacles in engineering thick and complex tissues while vascularizing tissues in vitro is to maintain cell viability during tissue growth and structural organization. Adipose-derived stromal (ADS) cells were used to establish a multicellular system through a cell-assembly technique. Attempts were made to control ADS cells differentiation into different targeted cell types according to their positions within an orderly 3D structure. Oil red 0 staining confirmed that the ADS cells in the structure differentiated into adipocytes with a spherical shape while immunostaining tests confirmed that the endothelial growth factor induced ADS cells on the walls of channels differentiated into mature endothelial cells and then organized into tubular structures throughout the engineered 3D structure. The endothelin-1 and nitric oxide release rules of the endothelial cells were coincidental with those in vivo. This study provides a new approach to engineer orderly endothelial vessel networks in vitro and has potential applications in adipose-tissue engineering.

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Lucas, Andrew T., Amber Moody, Allison N. Schorzman und William C. Zamboni. „Importance and Considerations of Antibody Engineering in Antibody-Drug Conjugates Development from a Clinical Pharmacologist’s Perspective“. Antibodies 10, Nr. 3 (26.07.2021): 30. http://dx.doi.org/10.3390/antib10030030.

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Antibody-drug conjugates (ADCs) appear to be in a developmental boom, with five FDA approvals in the last two years and a projected market value of over $4 billion by 2024. Major advancements in the engineering of these novel cytotoxic drug carriers have provided a few early success stories. Although the use of these immunoconjugate agents are still in their infancy, valuable lessons in the engineering of these agents have been learned from both preclinical and clinical failures. It is essential to appreciate how the various mechanisms used to engineer changes in ADCs can alter the complex pharmacology of these agents and allow the ADCs to navigate the modern-day therapeutic challenges within oncology. This review provides a global overview of ADC characteristics which can be engineered to alter the interaction with the immune system, pharmacokinetic and pharmacodynamic profiles, and therapeutic index of ADCs. In addition, this review will highlight some of the engineering approaches being explored in the creation of the next generation of ADCs.

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Meshcheryakova, A., und A. Vorobyova. „CHRONIC DEMYELINIZING POLYNEUROPATHY: ETIOPATHOGENETIC, CLINICAL ASPECTS, MODERN DIRECTIONS OF MEDICAL THERAPY“. National Association of Scientists 1, Nr. 67 (15.06.2021): 23–25. http://dx.doi.org/10.31618/nas.2413-5291.2021.1.67.423.

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Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system. The article discusses the practical experience of using off label therapy with rituximab in the complex treatment of a patient with a progressive course of chronic inflammatory demyelinating polyneuropathy. Due to the ineffectiveness of standard therapy, the option of treatment with genetically engineered drugs (rituximab) was considered. The use of rituximab contributed to the achievement of positive dynamics and an improvement in the patient's quality of life.

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Hulse, Daniel, Kagan Tumer, Christopher Hoyle und Irem Tumer. „Modeling multidisciplinary design with multiagent learning“. Artificial Intelligence for Engineering Design, Analysis and Manufacturing 33, Nr. 1 (28.08.2018): 85–99. http://dx.doi.org/10.1017/s0890060418000161.

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AbstractComplex engineered systems design is a collaborative activity. To design a system, experts from the relevant disciplines must work together to create the best overall system from their individual components. This situation is analogous to a multiagent system in which agents solve individual parts of a larger problem in a coordinated way. Current multiagent models of design teams, however, do not capture this distributed aspect of design teams – instead either representing designers as agents which control all variables, measuring organizational outcomes instead of design outcomes, or representing different aspects of distributed design, such as negotiation. This paper presents a new model which captures the distributed nature of complex systems design by decomposing the ability to control design variables to individual computational designers acting on a problem with shared constraints. These designers are represented as a multiagent learning system which is shown to perform similarly to a centralized optimization algorithm on the same domain. When used as a model, this multiagent system is shown to perform better when the level of designer exploration is not decayed but is instead controlled based on the increase of design knowledge, suggesting that designers in multidisciplinary teams should not simply reduce the scope of design exploration over time, but should adapt based on changes in their collective knowledge of the design space. This multiagent system is further shown to produce better-performing designs when computational designers design collaboratively as opposed to independently, confirming the importance of collaboration in complex systems design.

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Cusano, Angela Maria, Filippo Causa, Raffaella Della Moglie, Nunzia Falco, Pasqualina Liana Scognamiglio, Anna Aliberti, Raffaele Vecchione et al. „Integration of binding peptide selection and multifunctional particles as tool-box for capture of soluble proteins in serum“. Journal of The Royal Society Interface 11, Nr. 99 (06.10.2014): 20140718. http://dx.doi.org/10.1098/rsif.2014.0718.

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In this paper, we report on a general approach for the detection of a specific tumoural biomarker directly in serum. Such detection is made possible using a protein-binding peptide selected through an improved phage display technique and then conjugated to engineered microparticles (MPs). Protein biomarkers represent an unlimited source of information for non-invasive diagnostic and prognostic tests; MP-based assays are becoming largely used in manipulation of soluble biomarkers, but their direct use in serum is hampered by the complex biomolecular environment. Our technique overcomes the current limitations as it produces a selective MP—engineered with an antifouling layer—that ‘captures’ the relevant protein staying impervious to the background. Our system succeeds in fishing-out the human tumour necrosis factor alpha directly in serum with a high selectivity degree. Our method could have great impact in soluble protein manipulation and detection for a wide variety of diagnostic applications.

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Yoon, Jim, Christian Klassert, Philip Selby, Thibaut Lachaut, Stephen Knox, Nicolas Avisse, Julien Harou et al. „A coupled human–natural system analysis of freshwater security under climate and population change“. Proceedings of the National Academy of Sciences 118, Nr. 14 (29.03.2021): e2020431118. http://dx.doi.org/10.1073/pnas.2020431118.

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Limited water availability, population growth, and climate change have resulted in freshwater crises in many countries. Jordan’s situation is emblematic, compounded by conflict-induced population shocks. Integrating knowledge across hydrology, climatology, agriculture, political science, geography, and economics, we present the Jordan Water Model, a nationwide coupled human–natural-engineered systems model that is used to evaluate Jordan’s freshwater security under climate and socioeconomic changes. The complex systems model simulates the trajectory of Jordan’s water system, representing dynamic interactions between a hierarchy of actors and the natural and engineered water environment. A multiagent modeling approach enables the quantification of impacts at the level of thousands of representative agents across sectors, allowing for the evaluation of both systemwide and distributional outcomes translated into a suite of water-security metrics (vulnerability, equity, shortage duration, and economic well-being). Model results indicate severe, potentially destabilizing, declines in freshwater security. Per capita water availability decreases by approximately 50% by the end of the century. Without intervening measures, >90% of the low-income household population experiences critical insecurity by the end of the century, receiving <40 L per capita per day. Widening disparity in freshwater use, lengthening shortage durations, and declining economic welfare are prevalent across narratives. To gain a foothold on its freshwater future, Jordan must enact a sweeping portfolio of ambitious interventions that include large-scale desalinization and comprehensive water sector reform, with model results revealing exponential improvements in water security through the coordination of supply- and demand-side measures.

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Cowling, James Austin, und Wendy K. Ivins. „Assessing the Potential Improvement an Open Systems Development Perspective Could Offer to the Software Evolution Paradigm“. International Journal of Information Technologies and Systems Approach 9, Nr. 2 (Juli 2016): 68–87. http://dx.doi.org/10.4018/ijitsa.2016070105.

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Emerging stakeholder needs and a changing environment drive increasing demands for the constant adaption of software through maintenance and new capability development. A more evolutionary software engineering approach is sought to improve engineering responsiveness; Open System Development appears to offer a partial contribution but presents many challenges. This exploratory research proposes a new definition of the evolution of complex engineered systems, building on the essential features of ‘openness' described by Cowling et al (2014) and Lehman's (1980) ideas of evolutionary software. Using Checkland's (1999) Soft System Methodology enabled a structured literature review and analysis of the relative contributions of three divergent methodologies to the success of systems outcomes. These methodologies are: Plan-Driven, Agile, and Open Source Software Development. The analysis reveals several opportunities and highlights the critical issue of determining return on investment which needs to be overcome if an open approach is to contribute to evolutionary software engineering.

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Busby, J. S., und E. J. Hughes. „How plan delegation contributes to systemic failure“. Human Systems Management 22, Nr. 1 (01.03.2003): 13–22. http://dx.doi.org/10.3233/hsm-2003-22102.

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Complex, engineered systems often require extensively planned behaviour on the part of operators and maintenance staff if such systems are to maintain their integrity. A study was undertaken to determine how the absence of planning on the part of operators imperilled such systems. The aim was to help future designers understand how, in effect, operators delegate planning to the system, and to help designers make systems robust to this delegation. An analysis was undertaken of 59 incidents in the offshore industry in an attempt to characterise both the aspect of system activity that operators failed to plan (for example its completeness) and the general processes they were engaged in at the time (for example system start-up). All the processes that were implicated in the failures were either changes in the state of the system, such as start-up and shut-down, or operations that could not be said to take place in a steady state: there were no cases involving routine, continual activity. This suggests that designers' risk analyses should concentrate on non steady-state behaviour in systems, and that these risk analyses would benefit from some kind of characterisation of how systems are vulnerable to plan delegation.

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Keshavarzi, Elham, Matthew McIntire und Christopher Hoyle. „A dynamic design approach using the Kalman filter for uncertainty management“. Artificial Intelligence for Engineering Design, Analysis and Manufacturing 31, Nr. 2 (Mai 2017): 161–72. http://dx.doi.org/10.1017/s0890060417000051.

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AbstractIt is desirable for complex engineered systems to be resilient to various sources of uncertainty throughout their life cycle. Such systems are high in cost and complexity, and often incorporate highly sophisticated materials, components, design, and other technologies. There are many uncertainties such systems will face throughout their life cycles due to changes in internal and external conditions, or states of interest, to the designer, such as technology readiness, market conditions, or system health. These states of interest affect the success of the system design with respect to the main objectives and application of the system, and are generally uncertain over the life cycle of the system. To address such uncertainties, we propose a resilient design approach for engineering systems. We utilize a Kalman filter approach to model the uncertain future states of interest. Then, based upon the modeled states, the optimal change in the design of the system is achieved to respond to the new states. This resilient method is applicable in systems when the ability to change is embedded in the system design. A design framework is proposed encompassing a set of definitions, metrics, and methodologies. A case study of a communication satellite system is presented to illustrate the features of the approach.

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Witherden, Deborah, Nicolai van Oers, Caroline Waltzinger, Arthur Weiss, Christophe Benoist und Diane Mathis. „Tetracycline-controllable Selection of CD4+ T Cells: Half-Life and Survival Signals in the Absence of Major Histocompatibility Complex Class II Molecules“. Journal of Experimental Medicine 191, Nr. 2 (17.01.2000): 355–64. http://dx.doi.org/10.1084/jem.191.2.355.

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A system that allows the study, in a gentle fashion, of the role of MHC molecules in naive T cell survival is described. Major histocompatibility complex class II–deficient mice were engineered to express Eα chains only in thymic epithelial cells in a tetracycline (tet)-controllable manner. This resulted in tet-responsive display of cell surface E complexes, positive selection of CD4+8– thymocytes, and generation of a CD4+ T cell compartment in a class II–barren periphery. Using this system, we have addressed two unresolved issues: the half-life of naive CD4+ T cells in the absence of class II molecules (3–4 wk) and the early signaling events associated with class II molecule engagement by naive CD4+ T cells (partial CD3 ζ chain phosphorylation and ZAP-70 association).

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Georgakakos, Christine B., Paul L. Richards und M. Todd Walter. „Tracing Septic Pollution Sources Using Synthetic DNA Tracers: Proof of Concept“. Air, Soil and Water Research 12 (Januar 2019): 117862211986379. http://dx.doi.org/10.1177/1178622119863794.

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Contamination from septic systems is one of the most difficult sources of nonpoint source (NPS) pollution to quantify. Quantification is difficult in part because locating malfunctioning septic systems within a watershed is challenging. This study used synthetic-DNA-based tracers to track flows from 2 septic systems. Sample DNA was quantified using quantitative polymerase chain reaction (qPCR). This technology could be especially useful for simultaneously assessing multiple septic systems because there are essentially infinite unique combinations of DNA bases such that unique tracers could be engineered for each septic system. Two studies were conducted: the first, to determine whether the tracers move through septic systems (experiment 1), and the second, to determine whether the tracers were detectable at watershed scales (experiment 2). In both cases, clear, although complex, breakthrough curves were detected. Experiment 1 revealed possible preferential flow paths that might not have been otherwise obvious, indicative of short circuiting systems. This proof of concept suggests that these tracers could be applied to watersheds suspected of experiencing NPS septic system pollution.

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