bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Complete Set of Systems Thinking Skills
Authors: Arnold Ross D. , Wade Jon P. 
Published: August 2017

AbstractThis paper proposes a complete set of systems thinking skills for use across many different disciplines. The paper places particular emphasis on the ability to assess each of the skills quantitatively, a comprehensible description of the skills, and the completeness of the set. The proposed skills were derived from a review of the literature, the application of systems thinking experience, and the application of systems thinking to itself. Several different sets of systems thinking skills can be found throughout the systems community, but common key concepts can be distilled from these sets. When combinations of these concepts are considered separately, holistically, and together as a system, a single, cohesive set of skills emerges.Systems thinking is widely believed to be of critical importance across many different fields; it has been said that skillful use of systems thinking skills could have prevented such disasters as World War II, the Great Depression, and the Challenger space shuttle disaster, as well as lessened or avoided the effects of many major environmental disasters. At the opposite send of the spectrum, systems thinking can be used to enhance health care, improve the economy, improve technology, laws, international and interpersonal relationships, schools, organizations, and so much more. However, this very useful skill set still lingers outside mainstream education. To address this problem, a set of assessable, comprehensible systems thinking skills is required. Such skills are defined, described, and detailed in this paper.
Integrated Data as the Foundation of Systems Engineering
Authors: Wheatcraft Louis S. , Ryan Michael J. , Svensson Carl 
Published: August 2017

AbstractThis paper was written from the perspective that requirements, along with all work products, models, designs, documents, diagrams, drawings, etc.) generated during the performance of System Engineering (SE) lifecycle process activities are represented by underlying data and information that must be linked together and integrated into a common, integrated dataset. Using this perspective, the common, integrated dataset can be viewed as the foundation of Systems Engineering.The authors feel this data‐centric perspective of SE provides a better lens through which to acquire a complete understanding of the SE lifecycle process activities and resulting work products and underlying data and information needed to manage the development of increasingly complex systems of the future. This perspective aids in acquiring a practical understanding of the SE lifecycle processes from the perspective of not only models, but all work products that are generated from activities conducted during each of the SE lifecycle processes and the underlying data and information used to represent these work products.Expanding on the concept of SE from a data‐centric perspective, the goal of this paper is to present a broader data‐centric perspective of SE that meets that will aid readers in successfully meeting the challenges associated with today's ever increasingly complex systems, meeting the intent of the MBSE Initiative, and helping organizations move toward INCOSE's Vision 2025.
Developing A Systems Engineering Capability That Meets the Needs of Your Organization
Authors: Wheatcraft Louis S. , Svensson Carl , Ryan Michael J. 
Published: August 2017

AbstractThis paper was written from the perspective that requirements, along with all work products (models, designs, documents, diagrams, drawings, etc.) generated during the performance of System Engineering (SE) lifecycle process activities are represented by underlying data and information that must be integrated into a common, integrated dataset. From this data‐centric perspective, the common, integrated dataset can be viewed as the foundation of Systems Engineering. Based on this perspective, this paper discusses what it means to practice SE from a data‐centric perspective and provides the reader guidance that can be used to understand and successfully create and manage an integrated dataset within their organization.
Trains, Planes and Endoscopes: Using Capability Systems Engineering to reduce hospital‐acquired infections
Authors: O'Neil Meaghan , Kemp Duncan 
Published: August 2017

AbstractCapability Systems Engineering can be used to reduce healthcare‐acquired infections caused by contaminated medical devices. We use examples from rail and defence systems to illustrate how this approach can include operational capabilities and systems of systems. We also provide a demonstration of techniques used to create improvements in the development, regulation and reprocessing of reusable medical devices, and provide a case study of preventing infections associated with endoscopes. This work reflects an ongoing collaboration between INCOSE and the Association for the Advancement for Medical Instrumentation (AAMI). It has been undertaken in support of the AAMI initiative to use a systems approach to reduce healthcare‐acquired infections.
Applying Bayesian Networks to TRL Assessments – Innovation in Systems Engineering
Authors: Austin Marc F. , Homberger Cheyne , Ahalt Virginia , Doolittle Erin , Polacek George A. , York Donald M. 
Published: August 2017

AbstractCurrently, Technology Readiness Assessments (TRAs) are used in determining the maturity of the Critical Technology Elements (CTEs) of a system as it moves forward in the system development life cycle. The TRA method uses Technology Readiness Levels (TRLs) as the decision metric. TRL values are assessed and determined by Subject Matter Experts (SMEs). Since expert evaluators often differ in their judgment when scoring a system element against the TRL scale criteria, this paper argues for the use of a Bayesian network model to provide a mathematical method to consistently combine and validate the judgment of these SMEs and increase the confidence in the determination of the readiness of system components and their technologies.
Breaking Out: Systems Engineering To Go
Authors: Scott Zane 
Published: August 2017

AbstractSystems engineering grew up in the mil‐aero market space. This shaped the discipline in a number of ways. For several decades, the practice developed and grew in a space with plenty of opportunity and revenue for practitioners. But the market space is changing. Funding is shrinking and the nature of warfare is swinging away from the need for large, complex physical systems. This is pressuring the traditional systems engineering market space.This paper explores some of the possible response to this pressure and the obstacles to those responses. Systems engineers are faced with the need to think differently about their discipline. Meeting the challenges of breaking out of the traditional space is no insignificant undertaking. Some suggestions regarding how to approach this situation are the main thrust of the paper.The purpose here is to help practitioners see opportunities in non‐traditional markets and enable communication with potential customers. There has already been excellent work in leveraging communication between systems practitioners in different areas (Martin et al, 2013) It is not the object to repeat or expand on those but to focus on the practitioners themselves and how they see and interact with their new markets.
A Graph Theory Approach to Functional Failure Propagation in Early Complex Cyber‐Physical Systems (CCPSs)
Authors: O'Halloran Bryan M. , Papakonstantinou Nikolaos , Giammarco Kristin , Van Bossuyt Douglas L. 
Published: August 2017

AbstractThis paper presents a framework to quantify failure propagation potential for complex, cyber‐physical systems (CCPSs) during the conceptual stages of design. This method is referred to as the Function Failure Propagation Potential Methodology (FFPPM). This research is motivated by recent trends in engineering design. As systems become increasingly connected, an open area of research for CCPSs is to move reliability and failure assessments earlier in the engineering design process. This allows practitioners to make decisions at a point in the design process where the decision has a high impact and a low cost. Standard methods are limited by the availability of data and often rely on detailed representations of the system. As such, they have not addressed failure propagation in the functional design prior to selecting candidate architectures. To develop the metrics, graph theory is used to model and quantify the connectedness of the functional block diagram (FBD). These metrics quantify (1) the summation of the reachability matrix and (2) the summation of the number of paths between nodes (functions within system models) i and j for all i and j. From a practical standpoint, these metrics quantify the reachability between functions in the graph and the number of paths between functions defines the failure propagation potential of that failure. The unique contribution of this research is to quantify failure propagation potential during conceptual design prior to selecting candidate architectures. The goal of these metrics is to produce derived system requirements, based on an analysis, that focus on minimizing the impact of failures.
Reading the World: Toward a Praxis of Inquiry, Critical Literacy, and Cultural Knowledge
Authors: Kazembe Lasana 
Published: August 2017

AbstractMost people have struggled with reading in one situation or another, depending on their appreciation for the content, their prior experiences, and the texts. This department column shares ways for educators to help literacy learners unlock their potential with instruction anchored in their skills, knowledge, ways of learning, interests, and attitudes.
High Bone Turnover in Mice Carrying a Pathogenic Notch2 Mutation Causing Hajdu-Cheney Syndrome
Authors: Vollersen Nele , Hermans-Borgmeyer Irm , Cornils Kerstin , Fehse Boris , Rolvien Tim , Triviai Ioanna , Jeschke Anke , Oheim Ralf , Amling Michael , Schinke Thorsten , Yorgan Timur Alexander 
Published: August 2017

ABSTRACT

Hajdu-Cheney syndrome (HCS) is a rare autosomal-dominant disorder primarily characterized by acro-osteolysis and early-onset osteoporosis. Genetically, HCS is caused by nonsense or deletion mutations within exon 34 of the NOTCH2 gene, resulting in premature translational termination and production of C-terminally truncated NOTCH2 proteins that are predicted to activate NOTCH2-dependent signaling. To understand the role of Notch2 in bone remodeling, we developed a mouse model of HCS by introducing a pathogenic mutation (6272delT) into the murine Notch2 gene. By μCT and undecalcified histology, we observed generalized osteopenia in two independent mouse lines derived by injection of different targeted embryonic stem (ES) cell clones, yet acro-osteolysis did not occur until the age of 52 weeks. Cellular and dynamic histomorphometry revealed a high bone turnover situation in Notch2+/HCS mice, since osteoblast and osteoclast indices were significantly increased compared with wild-type littermates. Whereas ex vivo cultures failed to uncover cell-autonomous gain-of-functions within the osteoclast or osteoblast lineage, an unbiased RNA sequencing approach identified Tnfsf11 and Il6 as Notch-signaling target genes in bone marrow cells cultured under osteogenic conditions. Because we further observed that the high-turnover pathology of Notch2+/HCS mice was fully normalized by alendronate treatment, our results demonstrate that mutational activation of Notch2 does not directly control osteoblast activity but favors a pro-osteoclastic gene expression pattern, which in turn triggers high bone turnover. © 2017 American Society for Bone and Mineral Research.
Increased Risk of Breast Cancer at a Young Age in Women with Fibrous Dysplasia
Authors: Majoor Bas CJ , Boyce Alison M , Bovée Judith VMG , Smit Vincent THBM , Collins Michael T , Cleton-Jansen Anne-Marie , Dekkers Olaf M , Hamdy Neveen AT , Dijkstra PD Sander , Appelman-Dijkstra Natasha M 
Published: August 2017

ABSTRACT

Fibrous dysplasia (FD) is a rare bone disorder caused by mutations of the GNAS gene, which are also identified in malignancies. We explored the potential relationship between breast cancer and fibrous dysplasia in two fibrous dysplasia cohorts from the Netherlands and the United States. Data on fibrous dysplasia and breast cancer diagnosis were retrieved from hospital records of 134 (Netherlands) and 121 (US) female patients. Results were validated with breast cancer data of 645 female fibrous dysplasia patients from the Dutch Pathology Registry (PALGA). Standardized morbidity ratios for breast cancer were estimated with data from Dutch and US general population registries. GNAS mutation was analyzed in 9 available breast cancer specimens. A combined total of 15 patients (6 polyostotic, 9 McCune-Albright Syndrome) had breast cancer (87% thoracic localizations). In the Netherlands, a breast cancer incidence rate of 7.5% at median age of 46 years was validated in PALGA (6.5% at age 51 years). Breast cancer risk was 3.4-fold increased (95% confidence interval [CI] 1.6–5.9) compared with the Dutch general population; OR 13.2-fold (95% CI 6.2–22.8) in thoracic disease. In the US cohort, breast cancer incidence rate was 4.5% at a median age of 36 years. Breast cancer risk was 3.9-fold increased (95% CI 1.2–8.2) compared with the general population; 5.7-fold (95% CI 1.4–13.0) in thoracic disease. GNAS mutation was positive in 4 breast cancer specimens (44%). Risk of breast cancer is increased at a younger age, particularly in polyostotic FD, suggesting that screening for breast cancer should be considered in this particular group at a younger age than currently advocated by national guidelines. © 2017 American Society for Bone and Mineral Research.
Leucine supplementation after mechanical stimulation activates protein synthesis via L‐type amino acid transporter 1 in vitro
Authors: Nakai Naoya , Kawano Fuminori , Murakami Taro , Nakata Ken , Higashida Kazuhiko 
Published: August 2017

AbstractBranched‐chain amino acid supplements consumed following exercise are widely used to increase muscle mass. Although both exercise (ie, mechanical stimulation) and branched‐chain amino acid leucine supplementation have been reported to stimulate muscle protein synthesis by activating the mammalian target of rapamycin (mTOR) signaling pathway independently, the mechanisms underlying their synergistic effects are largely unknown. Utilizing cultured differentiated C2C12 myotubes, we established a combination treatment model in which the cells were subjected to cyclic uniaxial mechanical stretching (4 h, 15%, 1 Hz) followed by stimulation with 2 mM leucine for 45 min. Phosphorylation of p70 S6 kinase (p70S6K), an mTOR‐regulated marker of protein translation initiation, was significantly increased following mechanical stretching alone but returned to the baseline after 4 h. Leucine supplementation further increased p70S6K phosphorylation, with a greater increase observed in the stretched cells than in the non‐stretched cells. Notably, the expression of L‐type amino acid transporter 1 (LAT1), a stimulator of the mTOR pathway, was also increased by mechanical stretching, and siRNA‐mediated knockdown partially attenuated leucine‐induced p70S6K phosphorylation. These results suggest that mechanical stretching promotes LAT1 expression and, consequently, amino acid uptake, leading to enhanced leucine‐induced activation of protein synthesis. LAT1 has been demonstrated to be a point of crosstalk between exercise‐ and nutrition‐induced skeletal muscle growth.
Co‐expression analysis reveals key gene modules and pathway of human coronary heart disease
Authors: Tang Yu , Ke Zun‐Ping , Peng Yi‐Gen , Cai Ping‐Tai 
Published: August 2017

AbstractCoronary heart disease is a kind of disease which causes great injury to people world‐widely. Although gene expression analyses had been performed previously, to our best knowledge, systemic co‐expression analysis for this disease is still lacking to date. Microarray data of coronary heart disease was downloaded from NCBI with the accession number of GSE20681. Co‐expression modules were constructed by WGCNA. Besides, the connectivity degree of eigengenes was analyzed. Furthermore, GO and KEGG enrichment analysis was performed on these eigengenes in these constructed modules. A total of 11 co‐expression modules were constructed by the 3000 up‐regulated genes from the 99 samples with coronary heart disease. The average number of genes in these modules was 270. The interaction analysis indicated the relative independence of gene expression in these modules. The functional enrichment analysis showed that there was a significant difference in the enriched terms and degree among these 11 modules. The results showed that modules 9 and 10 played critical roles in the occurrence of coronary disease. Pathways of hsa00190 (oxidative phosphorylation) and (hsa01130: biosynthesis of antibiotics) were thought to be closely related to the occurrence and development of coronary heart disease. Our result demonstrated that modules 9 and 10 were the most critical modules in the occurrence of coronary heart disease. Pathways as hsa00190 (oxidative phosphorylation) and (hsa01130: biosynthesis of antibiotics) had the potential to serve as the prognostic and predictive marker of coronary heart disease.
A novel splicing isoform of protein arginine methyltransferase 1 (PRMT1) that lacks the dimerization arm and correlates with cellular malignancy
Authors: Patounas Odysseas , Papacharalampous Ioanna , Eckerich Carmen , Markopoulos Georgios S. , Kolettas Evangelos , Fackelmayer Frank O. 
Published: August 2017

AbstractMethylation of arginine residues is an important modulator of protein function that is involved in epigenetic gene regulation, DNA damage response and RNA maturation, as well as in cellular signaling. The enzymes that catalyze this post‐translational modification are called protein arginine methyltransferases (PRMTs), of which PRMT1 is the predominant enzyme. Human PRMT1 has previously been shown to occur in seven splicing isoforms, which are differentially abundant in different tissues, and have distinct substrate specificity and intracellular localization. Here we characterize a novel splicing isoform which does not affect the amino‐terminus of the protein like the seven known isoforms, but rather lacks exons 8 and 9 which encode the dimerization arm of the enzyme that is essential for enzymatic activity. Consequently, the isoform does not form catalytically active oligomers with the other endogenous PRMT1 isoforms. Photobleaching experiments reveal an immobile fraction of the enzyme in the nucleus, in accordance with earlier results from our laboratory that had shown a tight association of inhibited or inactivated PRMT1 with chromatin and the nuclear scaffold. Thus, it apparently is able to bind to the same substrates as catalytically active PRMT1. This isoform is found in a variety of cell lines, but is increased in those of cancer origin or after expression of the EMT‐inducing transcriptional repressor Snail1. We discuss that the novel isoform could act as a modulator of PRMT1 activity in cancer cells by acting as a competitive inhibitor that shields substrates from access to active PRMT1 oligomers.
Autophagy‐dependent crosstalk between GILT and PAX‐3 influences radiation sensitivity of human melanoma cells
Authors: Hathaway‐Schrader Jessica D. , Doonan Bently P. , Hossain Azim , Radwan Faisal F.Y. , Zhang Lixia , Haque Azizul 
Published: August 2017

AbstractMelanoma represents an ever‐increasing problem in the western world as incidence rates continue to climb. Though manageable during early stages, late stage metastatic disease is highly resistant to current intervention. We have previously shown that gamma‐interferon‐inducible lysosomal thiol‐reductase (GILT) enhances HLA class II antigen processing and immune detection of human melanoma cells. Here we report that GILT expression inhibits a potential target, paired box‐3 (PAX‐3) protein, in late stage human metastatic melanoma. We also show that GILT transfection or induction by IFN‐γ, decreases PAX‐3 protein expression while upregulating the expression of Daxx, which is also a repressor of PAX‐3. Confocal microscopic analysis demonstrated that GILT co‐localizes with PAX‐3 protein, but not with Daxx within melanoma cells. Immunoprecipitation and immunoblotting studies suggest that GILT expression negatively regulates PAX‐3 through the autophagy pathway, potentially resulting in increased susceptibility to conventional treatment in the form of chemotherapy or radiotherapy. While high‐dose radiation is a common treatment for melanoma patients, our data suggest that GILT expression significantly increased the susceptibility of melanoma cells to low‐dose radiation therapy via upregulation of tumor suppressor protein p53. Overall, these data suggest that GILT has multiple roles in inducing human melanoma cells as better targets for radiation and immunotherapy.
Retracted: ZIC2 promotes viability and invasion of human osteosarcoma cells by suppressing SHIP2 expression and activating PI3K/AKT pathways
Authors: Huang Shuaihao , Jin Anmin 
Published: August 2017

AbstractOsteosarcoma is a malignant tumor of the skeletal system. The zinc finger transcription factor ZIC2 has been reported to be highly expressed in human cancers. The present study evaluated the effects of ZIC2 and the possible underlying mechanisms in the human osteosarcoma cells. The expression levels of ZIC2 in human fetal osteoblastic cell line (hFOB1.19), osteosarcoma cell lines (U‐2OS, SaoS2, and MG63), normal bone tissue, and osteosarcoma tumor were analyzed by Western blot, and real‐time quantitative RT‐PCR (qRT‐PCR). Osteosarcoma cells with either overexpressed ZIC2 or suppressed ZIC2 were analyzed to determine cell viability, colony formation, and cell invasion. The expressions of SHIP2 and PI3K/AKT signal pathway‐related proteins were analyzed by Western blot and qRT‐PCR. We first showed that ZIC2 is highly expressed in osteosarcoma cells and tissues. Then we demonstrated that overexpression of ZIC2 promoted viability, migration, and invasion of osteosarcoma cells, whereas suppression of ZIC2 showed opposite effects. Furthermore, SHIP2 expression was negatively regulated by ZIC2. Importantly, ZIC2 overexpression activated the PI3K/AKT signal pathway; however, overexpressed SHIP2 inhibited these effects. Lastly, we showed that activation of the PI3K/AKT signal pathway is essential for the effects of ZIC2 on osteosarcoma cells, as the effects of ZIC2 on the osteosarcoma cells were reversed by a PI3K/AKT inhibitor. Overall, ZIC2 is highly expressed in osteosarcoma cells and tissues, and its overexpression promotes viability, invasion of osteosarcoma cells via SHIP2 suppression, and PI3K/AKT activation. Thus, ZIC2 can be considered as a novel drug target for osteosarcoma management.