bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequency and molecular characteristics of PALB2‐associated cancers in Russian patients
Authors: Preobrazhenskaya Elena V. , Shleykina Alla U. , Gorustovich Olga A. , Martianov Alexandr S. , Bizin Ilya V. , Anisimova Elena I. , Sokolova Tatjana N. , Chuinyshena Svetlana A. , Kuligina Ekatherina Sh. , Togo Alexandr V. , Belyaev Alexey M. , Ivantsov Alexandr O. , Sokolenko Anna P. , Imyanitov Evgeny N. 
Published: September 2020

AbstractPALB2 is а high‐penetrance gene for hereditary breast cancer (BC). Our study aimed to investigate the spectrum of PALB2 mutations in Russian cancer patients. PALB2 sequencing revealed pathogenic variants in 3/190 (1.6%) young‐onset and/or familial and/or bilateral BC cases but none in 96 ovarian cancer (OC) or 172 pancreatic cancer patients. Subsequently, seven recurrent PALB2 pathogenic alleles were selected from this and previous Slavic studies and tested in an extended patient series. PALB2 pathogenic variants were detected in 5/585 (0.9%) “high‐risk” BC, 10/1508 (0.7%) consecutive BC and 5/1802 (0.3%) OC cases. Haplotyping suggested that subjects with Slavic alleles c.509‐510delGA (n = 10) and c.172‐175delTTGT (n = 4) as well as carriers of Finnish c.1592delT mutation (n = 4) originated from a single founder each, while PALB2 p.R414X allele (n = 4) had at least two independent founders. Somatic loss of heterozygosity (LOH) was revealed in 5/10 chemonaive BCs and in 0/2 BC samples obtained after neoadjuvant therapy. Multigene sequencing identified somatic PALB2 inactivating point mutation in one out of two tumors without PALB2 LOH but in none of four BCs with PALB2 LOH. Genomic instability, as determined by NGS, was observed in four out of five tumors with biallelic PALB2 inactivation but not in the BC sample with the preserved wild‐type PALB2 allele. PALB2 germ‐line mutations contribute to a small fraction of cancer cases in Russia. The majority although not all PALB2‐driven BCs have somatic inactivation of the remaining PALB2 allele and therefore potential sensitivity to platinum compounds and PARP inhibitors.
A potential role for aspirin in the prevention and treatment of cholangiocarcinoma
Authors: Shen Xizi , Shen Xingping 
Published: September 2020

AbstractCholangiocarcinoma is the second most common primary hepatic cancer, with a rising incidence worldwide. Owing to late diagnosis and limited treatment options, the prognosis for cholangiocarcinoma remains dismal, compelling a search for new treatments. As aspirin exhibits a well‐supported chemopreventive effect on common cancers, researchers have proposed using aspirin as a potential preventive and adjuvant agent for cholangiocarcinoma. In the present review of the literature, we provide a background on cholangiocarcinoma and potential mechanisms of action underlying the anticancer effect of aspirin. Although the exact mode of action remains unclear, multiple downstream effects of aspirin may interfere with cholangiocarcinogenesis, tumour growth and metastasis—including inhibiting the COX‐2 pathway, preventing platelet aggregation and modulating certain proteins and signalling. This review also summarises evidence to support the chemopreventive effects of aspirin on common cancers, particularly colorectal cancer and discusses studies that report a positive outcome of aspirin in cholangiocarcinoma. Regular use of aspirin is associated with a reduced incidence of colorectal cancers as well as cholangiocarcinomas, and improved survival. Aspirin thus appears to play a role in the primary prevention and treatment of cholangiocarcinoma. However, further studies are needed to confirm these benefits and to establish a cause‐and‐effect relationship.
A generic Systems Engineering process tailoring methodology, based on lessons from MeerKAT
Authors: Küsel Thomas W. 
Published: September 2020

AbstractEach system is unique and requires tailoring of the systems engineering process to ensure that it is applied effectively and efficiently. The concept of tailoring is well recognized, but there is limited literature on generic tailoring methodologies. In this paper, a simple yet effective generic tailoring methodology is proposed. The paper identifies the system characteristics that should be considered during the tailoring process and key performance indicators. The MeerKAT project is used as a case study to derive the methodology and is used to illustrate its application.
Towards a Common Systems Engineering Methodology to Cover a Complete System Development Process
Authors: Morkevicius Aurelijus , Aleksandraviciene Aiste , Armonas Andrius , Fanmuy Gauthier 
Published: September 2020

AbstractModel‐Based System Engineering (MBSE) provides the ability to experience systems early from conceptual phases, and is one of the masterpieces of the Industry Renaissance. We see now in many Industries that we are leaving the world of experimentation to an effective and growing deployment of MBSE. One of the common challenges in industry is to bridge the gap between systems engineering studies and product development in a digital continuity and providing a seamless system experience. This paper presents an end‐to‐end systems engineering methodology, MagicGrid, extending the MBSE Grid methodology, to consider all the viewpoints of engineering of a cyber‐physical system.
Reverse architecting conventional footwear. Towards an A3 Architecture Overview that supports development of alternative footwear architectures.
Authors: Dankers Winnie , Bonnema Gerrit Maarten 
Published: September 2020

AbstractThe architecture of contemporary footwear is the result of a long history of footwear development. In this history, part of the argumentation behind the architecture has been lost, causing footwear developers to make decisions based on habits and badly underpinned assumptions. New insights on the negative influence of most conventional footwear on human (foot) health and the design freedom that arises from modern manufacturing techniques, create the urge to reconsider the common way of developing. By reverse architecting conventional footwear, this paper derives an A3 Architecture Overview of conventional footwear. In the future this overview should provide a tool for enabling product evolution towards healthy footwear, by allowing developers to consciously and purposefully deviate from ‘the standard architecture’ while taking into account the consequences of design decisions they make. The approach that is described in this paper is also applicable to the development of architecture overviews for other product families.
Managing Integration and Verification Risks of the SKA Radio Telescope
Authors: Lord Richard T. , Gammon Donald 
Published: September 2020

AbstractThe Square Kilometre Array (SKA) project is an international effort to build the world's largest radio telescope (SKAO 2020). A brief overview of the SKA project is provided, outlining some of the major challenges that such a project needs to manage. These challenges give rise to risk, which could lead to schedule delays, cost overruns and degraded performance of the final system. This paper describes how the integration and verification (I&V) of this radio telescope has been planned, and how the objective of mitigating risk has been an underlying motivation throughout this planning effort.
Risk and Opportunity Management for Project Selection in the Road Construction Industry
Authors: Stisen Martha , Syverud Elisabet 
Published: September 2020

AbstractRoad Construction projects failing to meet deadlines or budget costs puts burden on the construction company. The consequence may be economically unprofitable projects that significantly weaken the company's financial performance. To avoid unnecessary use of resources, the companies must identify and filter out unprofitable projects as early as possible. This paper lays out a process for use with road construction companies to improve their ability to choose profitable projects. The focus is on active management of risk and opportunity in the pre‐selection phase.The research is based on a case study at a road construction company. We interviewed key personnel to understand their main needs. We validated the proposed solution through a survey of nine employees at the same company.Our research resulted in a new method targeted to guide construction companies through the project selection process. The developed process flow illustrates the sequence and interaction of the different process stages. The risk and opportunity process is complemented with a check list, a risk and opportunity register, and the associated risk and opportunity matrix.
Creating and Applying Total Cost Model: A Case Study at Maritime Company for Last Time Buy Estimation
Authors: Sletaker Lasse Andre , Gonsholt Arild , Muller Gerrit , Kokkula Satyanarayana 
Published: September 2020

AbstractKongsberg Maritime (KM) experiences growth in the number of reactive obsolescence events. Time constraints in the decision‐making process limit options on how to resolve obsolescence. The total cost trajectory of labor and money consumed to resolve obsolescence is not sustainable for KM going forward.Last time buy (LTB) is one of many tools in obsolescence management. LTB is attractive because it does not require reengineering, requalification, or redesign. Despite its benefits, LTB should only be used if the total cost of LTB outweighs other alternatives.In this study a model was created to predict component obsolescence and quantifying the total cost of LTB. The research assumes obsolescence management less effective when dominated by LTBs. By proactively using this model, decision‐makers can evaluate alternatives compared to LTB selecting the most cost‐effective solution. Feedback from decision‐makers confirms a need to have, and willingness to use, the model.
Addressing Cognitive Bias in Systems Engineering Teams
Authors: McDermott Thomas A. , Folds Dennis J. , Hallo Leonie 
Published: September 2020

AbstractCognitive bias is a general issue in human decision making. It is easy to assume there is less bias in engineering, systems engineering, and program management, as these are generally considered rational processes. However, human decision making is almost always affected by bias. In the systems engineering practice as well as training systems engineers, we find directly addressing principles of human cognition, decision‐making, and bias to be an important part of individual and team learning. In the context of systems engineering competencies, these principles are core to mastery of systems and critical thinking, facilitation, and team dynamics. This paper discusses the characteristics of thinking, cognition, and decision‐making; conceptual approaches in psychology that frame these characteristics in the context of human decisions; common biases that affect decisions in the domain of systems engineering; and application of systems thinking tools to help overcome these issues.
Towards an Automated UAF‐based Trade Study Process for System of Systems Architecture
Authors: Bankauskaite Jovita , Morkevicius Aurelijus 
Published: September 2020

AbstractThe major driver for the Model‐based systems engineering adoption in industry is the ability for an engineer to develop systems with traceability to requirements, using one integrated architecture model that enables all types of automated analysis, e.g. impact analysis, gap analysis, trade studies, and simulations. Today, complex real‐life problems require the application of MBSE practices, where evolving systems communicate independently, both operationally and managerially, to achieve a common goal. This is the level of system of systems. At this level the major concern is an architecture assessment and trade study analysis, which can lead to different criteria and techniques for identification and comparison of alternatives to keep architecture in line with budgets and timelines. Although there are multiple process that provide step‐by‐step descriptions of trade study analyses, there are none that detail how trade study analyses could be automated in the model‐based environment in combination with existing architecture frameworks, languages, and tools. The goal of this research is to propose an automated trade study analysis process for the System of systems architecture developed in the Unified Architecture Framework models. It is a part of the larger research of trade study analysis automation, including modeling guidance, model quality checks, and automation scripts.
Patterns for Success in the Adoption and Execution of Feature‐based Product Line Engineering: A Report from Practitioners
Authors: Gregg Susan P. , Hartley David , McAfee Morgan , Pitz Randy , Teaff James , Clements Paul 
Published: September 2020

AbstractSystems and Software Product Line Engineering (PLE) is a general approach to engineer a portfolio of related products in an efficient manner, taking advantage of the products’ similarities while respecting and managing their differences. The approach manages a product portfolio as a single entity, as opposed to a multitude of separate products. Numerous resources describe the organizational benefits associated with incorporating PLE techniques and tools. Feature‐based System and Software Product Line Engineering is a specific form of PLE that is powered by commercial off‐the‐shelf automation, fully defined processes, and a formal language of variation based on features. Many case studies show the efficacy of Feature‐based PLE and the improvements in cost, schedule, and quality that can come with it. In this paper, practitioners from four of world's six largest defense companies highlight their experience with the practices that enable and inhibit success with this powerful engineering discipline.
Pervasive Simulation in a PLM Platform – The key to effective management of ever‐increasing product complexity
Authors: Chądzyński Paweł Z. , Panthaki Malcolm , Nicolich Matteo , Asuri Rama 
Published: September 2020

AbstractCompanies invest in new approaches to manage the ever‐increasing complexities of products and systems being designed today, and more importantly, those that will be designed tomorrow. These involve methodologies, tools, and the underlying platforms that support enterprise‐wide integration of these methodologies, tools, data models, and design flows.Simulation is a critical part of this investment. Unfortunately, simulation remains stubbornly stand‐alone and isolated. For the most part, simulation solution users and tool vendors have focused on automating the simulation process for the individual design phases but not for the entirety of the product's lifecycle that starts with gathering of requirements and ends with deployment of the assets in the field.This paper demonstrates how an appropriate vision for providing simulation as a pervasive tool, available on‐demand within a comprehensive PLM platform (Product Lifecycle Management), allows users to resolve these limitations. This is particularly critical today as PLM platforms are beginning to shift to the cloud.The goal of this paper is not to lay out a scientific theory, but to provide a practical example of a challenge solved through a best practice. The authors have worked and communicated with many OEMs that are all facing a similar set of challenges. These challenges are quite well‐known and hence the authors do not think it is necessary to take up room documenting them in this paper – we think it is more important to document/present a vision for a real‐world, working solution.
Evaluation of Lean Business Process Improvement Methodology
Authors: Måren Niclas , Muller Gerrit , Syverud Elisabet 
Published: September 2020

AbstractIndustry trends such as lean manufacturing have proven to work effectively in removing waste and improving the efficiency and effectiveness of production processes in manufacturing companies. The business processes within some manufacturing companies tend to lack the same attention as the production processes, however. This research explored the value of using the GKN lean business process improvement (BPI) methodology for improving business processes at GKN Aerospace Norway (GAN), an aerospace manufacturing company located in Norway. The method aims to identify and reduce waste by mapping the current state of a selected process, suggest a future state with less waste, generate an action list for changes, and a plan for implementation of the proposals made. During this study, the method showed to be successful at improving the efficiency in 7 out of 8 of the processes adopted. The research also found that employees at GAN respond favorably to BPI initiatives but that better preparation prior to each BPI workshop could further improve the effectiveness of the method.
Addressing the Sustainable Development Goals with a System‐of‐Systems for Monitoring Arctic Coastal Regions
Authors: Honoré‐Livermore Evelyn , Birkeland Roger , Haskins Cecilia 
Published: September 2020

AbstractNorway has a large coastal industry and a strong motivation for developing systems to enable sustainable management of ocean resources. Recent advances in collaborating autonomous systems, Internet‐of‐Things, microsatellites, data fusion, and sensor development have led to initiatives for a more concerted and coordinated effort through the establishment of an ocean studies research project. Applying a System‐of‐Systems perspective on the project highlights the challenges in terms of interoperability and communication interfaces, as well as revealing the use‐cases stakeholders rely on to enable informed decision‐making.
Systems Engineering as a Data‐Driven and Evidence‐Based Discipline
Authors: Kenett Ron S. , Zonnenshain Avigdor , Swarz Robert S. 
Published: September 2020

AbstractData and information are considered today as the “new oil” or the “new gold” in almost all aspects of life and economic domains, such as industry, healthcare, education, entertainment and more. The so‐called 4th Industrial Revolution1 is based on the digital transformation derived from the Big Data revolution, through the capability of storing huge amounts of data and performing very sophisticated analytics.In this paper, we present opportunities for Systems Engineering (SE) to evolve towards a data ‐driven and evidence ‐based discipline, thereby making better systems and engineering decisions. We discuss how systems engineers can apply data‐driven characteristics through systems engineering processes and programs. The classical Model‐Based Systems Engineering (MBSE) approaches are presented here as powerful tools to collect, generate, and analyze data on systems under development. In addition, the “Digital Twin” concept is presented here in the context of system design. We highlight the challenges for systems engineering to become an evidence‐based discipline. Moreover, we empha‐size research and development in systems engineering processes using statistical techniques in the design and analysis of systems testing, and Model‐Based Systems Engineering (SE) as a source for evidence‐based engineering decisions. The success of data driven SE in organizations depends on the information and data analytics infrastructure in these organizations. An information quality frame‐work is proposed for evaluating organizational information infrastructure. In addition, it is proposed to assess the data analytics maturity level in organizations. The level of data analytics is the basis for planning implementation programs of data‐driven and evidence‐based systems engineering. The paper concludes with a case study based on a real‐life complex project, and lessons learned for ef‐fective data analytics implementation.
Top‐down functional composition
Authors: Bredin Johan 
Published: September 2020

AbstractThe functional decomposition methodology forms the basis for how to design system behavior in the systems engineering literature. Unfortunately, this design approach has inherent weaknesses that do not allow for requirement sets to be both complete and design agnostic, both of which are considered necessary characteristics for good requirement sets. In practice, it is also difficult to design the behavior of complicated systems using functional decomposition since a large portion of the design challenge must be handled up‐front.This paper introduces a top‐down functional composition methodology approach to behavioral design. The paper argues that the presented methodology does not have the shortcomings associated with functional decomposition and that it also enables early and continuous‐, integration of design, test of design and validation of design. Therefore, this approach is more beneficial for engineering design of complicated systems, especially when model based systems engineering (MBSE) is applied.
Systems Engineering the Conditions of the Possibility (Towards Systems Engineering v2.0)
Authors: Willett Keith D. 
Published: September 2020

AbstractTraditional systems engineering focus is on cause and effect. When we turn a wheel, pull a lever, or flip a switch we expect a certain outcome. This is a rules‐based approach where stimulus‐response is deterministic in a well‐defined, well‐bounded, finite, and predominantly static system. If there is any deviation from expected, there are simple systemic structures (logic gates) or simple rules (if‐then‐else) to provide optional courses of preplanned action. Human intervention provides the intelligence and action necessary for dynamic adjustment to a negative event (adversity, avoid loss); or, to detect and dynamically adjust to a positive event (opportunity, seek gain). The now and future discipline of systems engineering (SE v2.0) has the tools to transcend cause‐effect and effectively embrace the nondeterministic, flexibly defined, blurred‐boundaries, highly combinatorial if not infinite, and adaptability. Systems engineers can design solutions to adapt to predictable and unpredictable change in order for the system to remain viable in the face of adversity (loss‐driven) and relevant in the face of obsolescence (opportunity‐driven). In addition to cause and effect, SE v2.0 is systems engineering the conditions of the possibility.The intent of this paper is not provide answers, but to provide a framework from which to discern better questions and elicit research in the many technical areas that provide for continual dynamic adaptation of complex socio‐technical systems of systems. Realizing SE v2.0 will come from the hard work of many over years. We are already on the way with this being one more step toward formalizing a new discipline.
Toward a Probabilistic Risk Assessment (PRA) Method for Assessing Mishaps in Legacy Systems Using Mishap Reports
Authors: Dean Joseph , O'Halloran Bryan M. , Van Bossuyt Douglas L. , Mourning Rachel 
Published: September 2020

AbstractThere is a significant delta between the acknowledged probability of potential mishaps under the current safety assessment approach derived from Military Standard 882E (MIL‐STD‐882E), Department of Defense Standard Practice of System Safety, and what is observed from actualized mishaps being reported. When assessing systems safety during the design process, the approaches used that comply with MIL‐STD‐882E simplify the mishap scenario by assuming a single initiating mechanism. By decomposing mishap reports from legacy systems, fault and event trees are used to identify common failure modes that were not adequately assessed under the current process. Each of the mishap reports assessed has identified more than one initiating mechanism. As such, this work suggests a greater mishap probability than was originally acknowledged. To address the current limitation, this work develops (1) an approach for decomposing mishap scenarios for legacy systems to identify mishaps resulting from multiple failure modes, (2) a method for systematically implementing the mishap decomposition on the assessed system or newly designed systems, and (3) a list of characteristics for an improved systems safety method.