bluuebunny/crossref_metadata_2025 huggingface dataset:
Model Based Systems Engineering‐Focus on the Initial Stages; “Get it Right in the First Stage”
Authors: Walker Loren Mark
Published: October 2015

A fundamental premise of this paper is that capturing stakeholder needs and the initial development of Systems Engineering documents and architecture models, with top level of capability needs/requirements, in a well written Operational Concept Document (OCD) during the first stages of a development, is absolutely critical for the entire life cycle of the system development. With this information in the OCD, written substantially in the stakeholder's operational terminology, and with Systems Modeling Language (SysMLTM) architecture views, this set of integrated products provide the foundation for all future stages of a development and the system's operational life. The primary emphasis of this paper is the critical importance of “System” Use Case Diagrams (SysUCD), their associated Scenarios and Sequence Diagrams and how essential it is to develop these with the operational customer in this first stage. The use of “Initial Stages” refers to the activities in the upper left of the Systems Engineering Vee diagram where it is essential to develop and understand Stakeholder Needs. This is accomplished by applying the Stakeholder Needs Analysis process using the recommended Object Oriented Systems Engineering Method (OOSEM) and translating the information into well‐defined stakeholder and systems engineering products and architecture views/models.
Implementing Model Semantics and a (MB)SE Ontology in Civil Engineering & Construction Sector
Authors: Balslev Henrik
Published: October 2015

In the period from 2010 – 2015, the Danish Building Construction Sector has implemented basic parts of Systems Engineering as the new ‘common language’ in the building construction sector. The project is anchored in the public and EU supported “cuneco project”. www.cuneco.dk develops the common basis for digitalized cooperation in construction, operation and maintenance to increase efficiency and productivity through enhanced exchange of information. To allow maximum simplicity yet unlimited flexibility, systems and their constituents are first classified and then identified individually to be used consistently over the lifecycle of the component, suitable for IT support. The system‐of‐systems principle is a fundamental approach to achieve unambiguous identification based on the Reference Designation System principles as defined in ISO/IEC 81346 standard series, which originally is designed for modelling and labeling of any kind of industrial plant. Currently, the Danish result is used to update some parts of the 81346 standard series, and thereby introducing Systems Engineering to the building construction sector.
Effective System Engineering Peer Reviews
Authors: Drewien Celeste A. , Artery Georgia , Eras Ken , Ballard William , Nagel John F.
Published: October 2015

Effective and rigorous technical peer reviews provide quality to a product realization process. This paper proposes a five‐step peer review process based on survey of the literature, experience with peer reviews, and pilot trials. Feedback was collected and integrated as lessons learned, resulting in a process that addresses key attributes of a peer review: roles & responsibilities; requirements; rigor; peer identification, independence, and external engagement; and follow‐up actions. An idea for a tool is provided to assist with rigor level determination and scoping of the peer review. Use of this peer review process can yield consistent peer review practices surrounding peer review practices for product realization teams.
A Systemic Framework to facilitate large and complex IT transformational Programs
Authors: Kummamuru Supriya , Hussaini Syed W
Published: October 2015

This paper presents a systemic framework for addressing the distinct challenges of Program management in the Information Technology (IT) services Industry environment. It was an outcome of the work carried out internally in the organization. The study involved identifying the challenges and defining the framework using a multi modeling approach. It was found Programs were treated with the same lens as projects, thereby missing the big picture and the benefits synthesized in a Program. Programs are a collection of projects, they differ in terms of scope, size, scale & complexity with respect to people involved, requirements, interfaces, time required etc. while programs are large and deliver benefits, projects deliver outcomes. The study also reviewed the existing program management frameworks and models for addressing these challenges and found they were domain agnostic and some areas specific to IT domain were not addressed. The nature of every IT programs is distinct because it belongs to different client domains, technology changes are rapid, and requirements keep changing as a result of changes in the environmental. The study identified several challenges which were then organized under five dimensions, each having similar concerns. Solutions were defined under each of these dimensions, they included new systemic frameworks and positioning existing ones appropriately. Given the enormity of the context not all areas could be addressed, which will be taken up latter. Some of the suggested models have also been validated in client program's contexts. This paper covers the multi modeling methodology used for the study, the findings and the proposed framework for Program Management at a conceptual level, because the solutions are proprietary and are the Intellectual Property (IP) of the organization.
Techniques for Conducting Effective Concept Design and Design‐to‐Cost Trade Studies
Authors: Di Pietro David A.
Published: October 2015

Concept design plays a central role in project success as its product effectively locks the majority of system life cycle cost. Such extraordinary leverage presents a business case for conducting concept design in a credible fashion, particularly for first‐of‐a‐kind systems that advance the state of the art and that have high design uncertainty. A key challenge, however, is to know when credible design convergence has been achieved in such systems. Using a space system example, this paper characterizes the level of convergence needed for concept design in the context of technical and programmatic resource margins available in preliminary design and highlights the importance of design and cost evaluation learning curves in determining credible convergence. It also provides techniques for selecting trade study cases that promote objective concept evaluation, help reveal unknowns, and expedite convergence within the trade space and conveys general practices for conducting effective concept design‐to‐cost studies.
An Innovative Approach to the Development of Project Management Processes for Small‐scale Projects in a large Engineering Company
Authors: Laporte Claude Y. , Chevalier Frédéric
Published: October 2015

A Canadian division of a large American engineering company has developed and implemented project management processes for their small‐scale and medium‐scale projects. The company was already using a robust project management process for their large‐scale projects. The objectives of this process improvement project were to reduce cost overruns and project delays, standardize practices to facilitate the integration of new managers, increase the level of customer satisfaction and to reduce risk‐related planning deviations. For this improvement project, the engineering organization used the new ISO/IEC 29110 standard developed specifically for very small entities. An analysis of the cost and the benefits of the implementation of small and medium scale project management processes was performed using the ISO economic benefits of standard methodology. The engineering enterprise estimated that, over a three‐year timeframe, savings of about 780,000$ would be realized due to the implementation of project management processes using the ISO/IEC 29110 standard.
When two is good company, but more is not a crowd
Authors: Nolan Andy J. , Pickard Andrew C , Russell Jennifer L , Schindel William D
Published: October 2015

This paper summarizes an approach to improve the effectiveness of the review (inspection) process. Effectiveness here is defined as the ability to reduce the number of defects escaping a review activity.

By carefully pairing up developers and reviews, Rolls‐Royce was able to halve the rate of occurrence of defects in software, with no change to the process or tools, and with no changes to the team or the effort required to perform the reviews.

The method hinges on an understanding of the capability of the developers and reviewers and making sure that only select pairings of team members will be allowed.

The paper illustrates an example of the practice when applied to software code review but the principle can be applied to any development process. The code review process is an example of the principle but the philosophy can be applied to many more areas of the system development process. The paper ends by illustrating other ways to benefit from this approach.
A modeling pattern for layered system interfaces
Authors: Shames Peter M. , Sarrel Marc A.
Published: October 2015

Communications between systems is often initially represented at a single, high level of abstraction, a link between components. During design evolution it is usually necessary to elaborate the interface model, defining it from several different, related viewpoints and levels of abstraction. This paper presents a pattern to model such multi‐layered interface architectures simply and efficiently, in a way that supports expression of technical complexity, interfaces and behavior, and analysis of complexity. Each viewpoint and layer of abstraction has its own properties and behaviors. System elements are logically connected both horizontally along the communication path, and vertically across the different layers of protocols. The performance of upper layers depends on the performance of lower layers, yet the implementation of lower layers is intentionally opaque to upper layers. Upper layers are hidden from lower layers except as sources and sinks of data. The system elements may not be linked directly at each horizontal layer but only via a communication path, and end‐to‐end communications may depend on intermediate components that are hidden from them, but may need to be shown in certain views and analyzed for certain purposes.

This architectural model pattern uses methods described in ISO 42010 [1], Recommended Practice for Architectural Description of Software‐intensive Systems and CCSDS 311.0‐M‐1 [2], Reference Architecture for Space Data Systems (RASDS). A set of useful viewpoints and views are presented, along with the associated modeling representations, stakeholders and concerns. These viewpoints, views, and concerns then inform the modeling pattern. This pattern permits viewing the system from several different perspectives and at different layers of abstraction. An external viewpoint treats the systems of interest as black boxes and focuses on the applications view, another view exposes the details of the connections and other components between the black boxes. An internal view focuses on the implementation within the systems of interest, either showing external interface bindings and specific standards that define the communication stack profile or at the level of internal behavior. Orthogonally, a horizontal view isolates a single layer and a vertical viewpoint shows all layers at a single interface point between the systems of interest. Each of these views can in turn be described from both behavioral and structural viewpoints.
Adapting Systems Engineering to the Development of Regional Jets
Authors: de Oliveira Wellington Martins , Jackson Scott
Published: October 2015

Regional jet developers, like those for mainline jets, must strive to meet the needs of their customers while complying with rigid regulatory requirements. To meet these goals, developers face demands that require judicious adaptation of selected core systems engineering processes to this domain. These demands result from a more severe life cycle environment compared to mainline jets. This severe environment is seen to have a more far‐reaching impact on the architecture and requirements than one would expect. This adaptation requires the developer to consider the selection of which systems engineering processes are most critical to the successful development of an aircraft, and need more adaptation. This paper pays special attention to increased adaptation of stakeholder requirements and requirements analysis processes and their interaction with architectural design and tailoring with other systems engineering processes. The treatment of stakeholder requirements and requirement analysis needs to be efficient due the complexity and severity of the operational environment and life‐cycle scenarios. This issue results in new technologies that when incorporated in regional jet architectures result in high levels of complexity to deal with high level of performance. The architectural process must be rigorously traceable to the requirements process to deal with the top level requirements. A second area of focus is the discussion of organizational roles and responsibilities on stakeholder requirements and requirements analysis within an aircraft company, whether technical or not, these organizations may understand their role in these processes of capture the customer value on a severe life cycle and flow down to a complex architecture. The paper complements this analysis with the characteristic that regional jet developers apply an enhanced systems engineering process with focus on lean documentation.
On the Development of a Retirement Concept
Authors: Ryan Michael J.
Published: October 2015

ISO/IEC 15288 describes a number of Technical Processes that are invoked throughout the life‐cycle stages of a system. One of the concepts developed throughout the early technical processes is the Retirement Concept. This paper examines the role of retirement in the system life cycle and then differentiates between the retirement of a system at the end of each of its life cycles and the final disposal of the system at the end of its life. Three broad steps have been proposed to support design for retirement: identify the reasons for retirement, identify the potential retirement methods available, and identify the design issues that arise from the consideration of each retirement method. This paper identifies how that approach can support the development of a Retirement Concept. A simple example is offered by way of illustration.
Integrating Systems Safety into Systems Engineering during Concept Development
Authors: Fleming Cody Harrison , Leveson Nancy
Published: October 2015

Safety should be designed into systems from their very conception, which can be achieved by integrating powerful hazard analysis techniques into the general systems engineering process. The primary barrier to achieving this objective is the lack of effectiveness of the existing analytical tools during early concept development.

This paper introduces a new technique, which is based on a more powerful model of accident causality—called systems‐theoretic accident model and process (STAMP)—that can capture behaviors that are prevalent in these complex, software‐intensive systems. The goals are to (1) develop rigorous, systematic tools for the analysis of future concepts in order to identify potentially hazardous scenarios and undocumented assumptions, and (2) extend these tools to assist stakeholders in the development of concepts using a safety‐driven approach.
Guidance for Working Group Maintenance of the Systems Engineering Body of Knowledge (SEBoK) with Systems Security Engineering Example
Authors: Mailloux Logan O. , Garrison Cheryl , Dove Rick , Biondo Ryan C.
Published: October 2015

Recently the Systems Engineering Body of Knowledge (SEBoK) was established to facilitate the advancement of the systems engineering discipline, the maintenance of which has been accepted by the International Council on Systems Engineering (INCOSE) and others. Within INCOSE the responsibility to update and maintain the SEBoK is assigned to individual working groups with respect to their specialty areas. These working groups are populated with volunteers, each with limited participation timelines, special interests, and individual motivations. While SEBoK Editors have the responsibility to maintain a coherent evolution; they depend heavily on inputs from these maintenance groups and their subject matter experts. However, maintenance teams may have different views of what should be covered by the SEBoK than those in other periods, raising the possibility of cyclical focus‐thrash in topic areas, beyond the normal evolution of relevant topic information. Therefore, it is beneficial, and perhaps even necessary, for working groups to facilitate a cohesive approach for maintaining SEBoK content. In this paper, we provide guidance for working groups to maintain SEBoK materials based on the INCOSE systems security engineering working group's recent experiences.
Finding Common Ground: Shared Benefits of the PMI PMBOK and the INCOSE Systems Engineering Handbook
Authors: Luckay Ryan
Published: October 2015

The evidence for the need to have further collaboration between systems engineering (SE) and project management (PM) is all around us: in the rampant overruns in our technology projects, in the increased internal organizational friction, in the clinging to archaic technologies for fear of what may come next. This paper investigates two leading guides for these organizations: the INCOSE Systems Engineering Handbook (SE) Handbook and the Project Management Body of Knowledge (PMBOK). Research indicates three areas for collaboration that might benefit integrating the two: defining tasks, integrated risk management, and stakeholder management.
Accelerating MBSE Impacts Across the Enterprise: Model‐Based S*Patterns
Authors: Schindel William D. , Lewis Stephen A. , Sherey Jason J. , Sanyal Saumya K.
Published: October 2015

Model‐Based Systems Engineering (MBSE) methods can directly address “silos” problems. This paper reports on work by the INCOSE MBSE Initiative Patterns Challenge Team, focusing on Pattern‐Based Systems Engineering (PBSE) using model‐based system patterns based on the S*Metamodel, speeding and improving multiple SE processes.

Distinctive are (1) the configurable, model‐based nature of the patterns (not all historical patterns work has been model‐based), (2) the technical scope of the models, encompassing requirements, design, failure mode, verification, other aspects, (3) the system scope of the models, encompassing whole systems, configurable product lines, and platforms, not just libraries of components, (4) the diverse and integrating cross‐enterprise domains of the patterns, encompassing products, innovation processes, manufacturing, packaging / distribution, and other domains, and (5) the ability to enable a variety of COTS modeling languages and tools, PLM, and other enterprise information systems to integrate support of management and application of S*Patterns across enterprises.
“Suits you sir! ‐‐ choosing the right style of SE before tailoring to fit”
Authors: Kemp Duncan , Beasley Richard , Williams Samantha
Published: October 2015

Despite significant evidence that Systems Engineering (SE) adds value, take‐up is patchy. There is a growing volume of evidence that the ‘understand‐plan‐do’ paradigm behind conventional Systems Engineering only works in some circumstances.

We have seen situations where SE has either over‐complicated the solution or was unable to deliver quickly enough. Applying SE in these situations leads to both a specific failure and damages the credibility of SE more broadly. This paper:

Proposes a new, two phase, tailoring process. Select an approach suitable for the situation then (if appropriate) decide what SE to do.

Includes a Functional Failure Modes and Effects Analysis (FFMEA), which identifies functional failures modes, effects and mitigation activities applicable to the first stage of the tailoring process.

Illustrates the FFMEA with 7 case studies.

The proposed mitigations provide a high level blueprint for an enterprise that implements conventional SE, when, and only when, appropriate.
Creating Executable Agent‐Based Models Using SysML
Authors: Maheshwari Apoorv , Kenley C. Robert , DeLaurentis Daniel A.
Published: October 2015

Simulation plays an important role in the analysis of alternatives during the early phases of systems engineering activities. This is especially true for endeavors in the system of systems realm where there is even more need for simulation to characterize interdependencies. In this paper, we develop a generic framework to translate a SysML conceptual model to an executable agent‐based simulation model. We demonstrate the translation using a simplified air traffic management problem. Along with the potential advantages, we also identify major challenges and possible mismatches in accomplishing a suitable translation for real‐world systems of systems.
System of Systems Approaches for Mobile Source Transit Security
Authors: Mauss Fredrick , Valencia Juan , Hatchell Brian , Silvers Kurt , Crowell Shannon
Published: October 2015

The petroleum industry uses radioactive isotopes in well‐logging operations to support oil exploration activities. Well‐logging service providers use radiological sources to obtain the most accurate estimate of porosity in geologic formations. The National Nuclear Security Administration (NNSA), through its Global Threat Reduction Initiative (GTRI), has a mission to enhance the security of high‐priority nuclear and radiological materials in civilian use. As part of this mission, GTRI intends to facilitate tracking and security of well‐logging radiological sources both in the United States and around the world. GTRI is sponsoring the Pacific Northwest National Laboratory to develop a Mobile Source Transit Security System that can be used by the well‐logging service providers to track these sources in near real time on a worldwide basis. This paper describes the system capabilities, constraints, and conceptual design. System of systems approaches and challenges that were considered in the development of the system are highlighted.
Using Systems Engineering Practices for Distributed Control and Building Performance Simulation
Authors: Yahiaoui Azzedine , Sahraoui Abd‐El‐Kader
Published: October 2015

A distributed simulation between control systems and building performance applications is becoming more and more an invaluable tool in the analysis of Automated Buildings (ABs) for better operation and design. Instead of costly and time‐consuming experiments, using distributed simulations can simultaneously fulfill the occupants’ needs while reducing energy consumption and greenhouse gas emissions. Distributed simulations are used to investigate the impact of advanced control systems on building performance applications. This paper describes the development and implementation of a framework for distributed simulations involving different software tools over a network. The main role of this framework is to run‐time couple one or more building performance simulation tool(s) with a control systems environment over a network, within a Building Automation and Control Systems (BACS) architecture. Finally, the paper ends with some conclusions and perspectives for future work.
Multi‐Level Product Platform Strategy for a Multi‐Level Corporation
Authors: Bergsjö Dag , Levandowski Christoffer , Stig Daniel Corin
Published: October 2015

Reuse strategies based on product platform thinking can provide important advantages over single‐product development, especially for achieving economy‐of‐scale and cost‐efficient product variety. This paper presents the case of a multi‐national corporation that has many opportunities for identifying commonalities across and within its subsidiaries from which product platforms can be defined. The study focuses on the opportunities of one of these subsidiaries to transfer to platform‐based development for some of their components. A framework is presented that defines different levels in the organization where product platforms can be used, as well as different types of reuse strategies that may be adequate for the studied components. These levels are: (A) within each subsidiary, (B) between subsidiaries, and (C) common throughout the umbrella corporation. The types of reuse are categorized as (1) local component sharing, (2) arms‐length buy‐in of components within the corporation, and (3) platform‐based development. It is argued that a platform strategy for the corporation can include various combinations of reuse types and organizational levels, depending on where reuse potential is identified. The main considerations for making this effective is where ownership lies for the shared assets and how to balance multiple stakeholder requirements from different applications, e.g. during engineering change requests.
An Integrated Model‐Based Approach to System Safety and Aircraft System Architecture Development
Authors: Villhauer Eric , Jenkins Brian
Published: October 2015

Industry standards for aircraft development require consideration of System Safety objectives during all phases of System Architecture development and implementation. However, tools that have enabled Systems Engineers and Software Engineers to create high‐fidelity models of System Architectures currently don't address the concerns of the System Safety Engineering discipline. A strategy is necessary to ensure that safety objectives are considered during System Architecture model development while maintaining the required organizational independence between System Safety and the domains with which they interface. This paper details an approach to include a view in an architectural model that addresses System Safety objectives.
Maps or Itineraries? A Systems Engineering Insight from Ancient Navigators
Authors: Schindel William D.
Published: October 2015

Processes and procedures are the heart of current descriptions of Systems Engineering. The “Vee Diagram”, ISO 15288, the INCOSE SE Handbook, and enterprise‐specific business process models focus attention on process and procedure.

However, there is a non‐procedural way to view systems engineering. This approach is to describe the configuration space “navigated” by systems engineering, and what is meant by system trajectories in that space, traveled during system life cycles.

This sounds abstract because we have lacked explicit maps necessary to describe this configuration space. We understand concrete steps of a procedure, so we focus there. But where do these steps take us? And, what does “where” mean in this context? Clues are found in recent discoveries about ancient navigation, as well as later development of mathematics and physics.

This paper (Part I of a Case for Stronger MBSE Semantics) focuses on the underlying configuration space inherent to systems.
Value Modeling for Enterprise Resilience
Authors: Henderson Dale , Lancaster Mary
Published: October 2015

The idea that resilience is a tangible, measureable, and desirable system attribute has grown rapidly over the last decade beyond is origins in explaining ecological, physiological, psychological, and social systems. Operational enterprise resilience requires two types of measurement. First, the system must monitor various operational conditions in order to respond to disruptions. These measurements are part of one or more observation, orientation, decision, and action (OODA) loops The OODA control processes that implement a resilience strategy use these measurements to provide robustness, rapid recovery and reconstitution. In order to assess the effectiveness of the resilience strategy, a different class of measurements is necessary. This second type consists of measurements about how well the OODA processes cover critical enterprise functions and the hazards to which the enterprise is exposed. They allow assessment of how well enterprise management processes anticipate, mitigate, and adapt to a changing environment and the degree to which the system is fault tolerant.

This paper nominates a theoretical framework, in the form of definitions, a model, and a syntax, that accounts for this important distinction, and in so doing provides a mechanism for bridging resilience management process models and the many proposed cyber‐defense metric enumerations.
Professional Resources
Authors: Haddix Marcelle M.
Published: October 2015

This column provides reviews of adolescent and adult professional resources and is a valuable resource for professional resource selection in and outside the classroom.
Why I Write: Confessions of an Undercover Scientist
Authors: Barnes‐Johnson Joy
Published: October 2015

This column features essays written by current middle school and high school teachers, media specialists, librarians, literacy coaches, curriculum specialists, administrators, preservice teachers, teacher educators, and adolescent and adult learners. They highlight diverse perspectives on teaching and/or learning with literacies to inspire reader reflection.
Visual and Digital Texts
Authors: Botzakis Stergios
Published: October 2015

This column highlights and evaluates apps and websites to assist teachers, students, and other interested parties in learning about social studies, particularly geography, history, and government.
The effect of alendronate on biomineralization at the bone/implant interface
Authors: Karlsson Johan , Martinelli Anna , Fathali Hoda M. , Bielecki Johan , Andersson Martin
Published: October 2015

A recent approach to improve the osseointegration of implants is to utilize local drug administration. The presence of an osteoporosis drug may influence both bone quantity and quality at the bone/implant interface. Despite this, the performance of bone‐anchoring implants is traditionally evaluated only by quantitative measurements. In the present study, the osteoporosis drug alendronate (ALN) was administrated from mesoporous titania thin films that were coated onto titanium implants. The effect that the drug had on biomineralization was explored both in vitro using simulated body fluid (SBF) and in vivo in a rat tibia model. The SBF study showed that the apatite formation was completely hindered at a high concentration of ALN (0.1 mg/mL). However, when ALN was administrated from the mesoporous coating the surface became completely covered with apatite. Ex vivo characterization of the bone/implant interface using Raman spectroscopy demonstrated that the presence of ALN enhanced the bone mineralization, and that the chemical signature of newly formed bone in the presence of ALN had a higher resemblance to the pre‐existing mature bone than to the bone formed without drug. Taken together, this study demonstrates the importance of evaluating the quality of the formed bone to better understand the performance of implants. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A 104A: 620–629, 2016.
Ibuprofen loaded PLA nanofibrous scaffolds increase proliferation of human skin cells in vitro and promote healing of full thickness incision wounds in vivo
Authors: Mohiti‐Asli M. , Saha S. , Murphy S.V. , Gracz H. , Pourdeyhimi B. , Atala A. , Loboa E. G.
Published: October 2015

This article presents successful incorporation of ibuprofen in polylactic acid (PLA) nanofibers to create scaffolds for the treatment of both acute and chronic wounds. Nanofibrous PLA scaffolds containing 10, 20, or 30 wt % ibuprofen were created and ibuprofen release profiles quantified. In vitro cytotoxicity to human epidermal keratinocytes (HEK) and human dermal fibroblasts (HDF) of the three scaffolds with varying ibuprofen concentrations were evaluated and compared to pure PLA nanofibrous scaffolds. Thereafter, scaffolds loaded with ibuprofen at the concentration that promoted human skin cell viability and proliferation (20 wt %) were evaluated in vivo in nude mice using a full thickness skin incision model to determine the ability of these scaffolds to promote skin regeneration and/or assist with scarless healing. Both acellular and HEK and HDF cell‐seeded 20 wt % ibuprofen loaded nanofibrous bandages reduced wound contraction compared with wounds treated with Tegaderm™ and sterile gauze. Newly regenerated skin on wounds treated with cell‐seeded 20 wt % ibuprofen bandages exhibited significantly greater blood vessel formation relative to acellular ibuprofen bandages. We have found that degradable anti‐inflammatory scaffolds containing 20 wt % ibuprofen promote human skin cell viability and proliferation in vitro, reduce wound contraction in vivo, and when seeded with skin cells, also enhance new blood vessel formation. The approaches and results reported here hold promise for multiple skin tissue engineering and wound healing applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 327–339, 2017.
Differential Regulation of Telomerase Reverse Transcriptase Promoter Activation and Protein Degradation by Histone Deacetylase Inhibition
Authors: Qing Hua , Aono Jun , Findeisen Hannes M. , Jones Karrie L. , Heywood Elizabeth B. , Bruemmer Dennis
Published: October 2015

Telomerase reverse transcriptase (TERT) maintains telomeres and is rate limiting for replicative life span. While most somatic tissues silence TERT transcription resulting in telomere shortening, cells derived from cancer or cardiovascular diseases express TERT and activate telomerase. In the present study, we demonstrate that histone deacetylase (HDAC) inhibition induces TERT transcription and promoter activation. At the protein level in contrast, HDAC inhibition decreases TERT protein abundance through enhanced degradation, which decreases telomerase activity and induces senescence. Finally, we demonstrate that HDAC inhibition decreases TERT expression during vascular remodeling in vivo. These data illustrate a differential regulation of TERT transcription and protein stability by HDAC inhibition and suggest that TERT may constitute an important target for the anti‐proliferative efficacy of HDAC inhibitors. J. Cell. Physiol. 231: 1276–1282, 2016. © 2015 Wiley Periodicals, Inc.
Adiponectin resistance in skeletal muscle: pathophysiological implications in chronic heart failure
Authors: Sente Tahnee , Van Berendoncks An M , Hoymans Vicky Y , Vrints Christiaan J
Published: October 2015

Skeletal muscle wasting is a common complication of chronic heart failure (CHF) and linked to poor patient prognosis. In recent years, adiponectin was postulated to be centrally involved in CHF‐associated metabolic failure and muscle wasting. This review discusses current knowledge on the role of adiponectin in CHF. Particular emphasis will be given to the complex interaction mechanisms and the intracellular pathways underlying adiponectin resistance in skeletal muscle of CHF patients. In this review, we propose that the resistance process is multifactorial, integrating abnormalities emanating from insulin signalling, mitochondrial biogenesis, and ceramide metabolism.
Implications of mitogen‐activated protein kinase signaling in glioma
Authors: Pandey Vimal , Bhaskara Vasantha Kumar , Babu Phanithi Prakash
Published: October 2015

Gliomas are the most common primary central nervous system tumors. Gliomas originate from astrocytes, oligodendrocytes, and neural stem cells or their precursors. According to WHO classification, gliomas are classified into four different malignant grades ranging from grade I to grade IV based on histopathological features and related molecular aberrations. The induction and maintenance of these tumors can be attributed largely to aberrant signaling networks. In this regard, the mitogen‐activated protein kinase (MAPK) network has been widely studied and is reported to be severely altered in glial tumors. Mutations in MAPK pathways most frequently affect RAS and B‐RAF in the ERK, c‐Jun N‐terminal kinase (JNK), and p38 pathways leading to malignant transformation. Also, it is linked to both inherited and sequential accumulations of mutations that control receptor tyrosine kinase (RTK)‐activated signal transduction pathways, cell cycle growth arrest pathways, and nonresponsive cell death pathways. Genetic alterations that modulate RTK signaling can also alter several downstream pathways, including RAS‐mediated MAP kinases along with JNK pathways, which ultimately regulate cell proliferation and cell death. The present review focuses on recent literature regarding important deregulations in the RTK‐activated MAPK pathway during gliomagenesis and progression. © 2015 Wiley Periodicals, Inc.
Unusual photoanisotropic alignment in amorphous azobenzene polymers
Authors: Ramanujam P. S.
Published: October 2015

It is well known that irradiation of azobenzene polymer films between 490 and 530 nm results in alignment of molecules perpendicular to the polarization of the incident beam. I have recently found that irradiation of amorphous azobenzene polymers with linearly polarized light at wavelengths between 560 and 630 nm, where the absorption is minimal, results in a possible uniaxial hedgehog arrangement of the molecules. Experiments performed with a dye laser, which can be tuned continuously between 560 and 630 nm, are described. Not only azobenzene but also another photosensitive molecule, bacteriorhodopsin, seems to exhibit this behavior.
A simple adjustment to test reliability of bacterivory rates derived from the dilution method
Authors: Pree Bernadette , Kuhlisch Constanze , Pohnert Georg , Sazhin Andrey F. , Jakobsen Hans Henrik , Lund Paulsen Maria , Frischer Marc E. , Stoecker Diane , Nejstgaard Jens C. , Larsen Aud
Published: October 2015

Quantification of grazing losses of marine heterotrophic bacteria is critical for understanding nutrient and carbon pathways in aquatic systems. The dilution method is a commonly used experimental approach for quantifying bacterivory. However, valid estimates of grazing rates obtained using this method depend on several methodological assumptions including that the method does not influence specific growth rates of bacteria. Here, we hypothesize that filtration during the set‐up of a dilution experiment has the potential to release allelochemicals from phytoplankton cells and thereby stimulate or inhibit bacterial growth with the consequence of biased grazing estimates. We tested this hypothesis during a natural Phaeocystis pouchetii bloom at two different locations within an Arctic fjord. Results from the dilution experiments suggest higher gross growth rate and grazing impact for bacteria in the outer fjord compared with the inner fjord. However, specific growth rates estimated by bacterial production cell−1 were significantly elevated in dilutions of water from the outer fjord but not the inner fjord. The analysis of dissolved metabolites in the seawater from both experiments prior and after filtration revealed altered metabolic profiles after filtration at both stations. As unaffected specific growth of prey on dilution is one of three fundamental assumptions of the dilution method, we conclude that it is important that empirically estimated bacterial specific growth rates be routinely included when using the dilution method to quantify bacterivory.
Sponge‐Type Emissive Chemosensors for the Protein Detection Based on Boron Ketoiminate‐Modifying Hydrogels with Aggregation‐Induced Blueshift Emission Property
Authors: Suenaga Kazumasa , Yoshii Ryousuke , Tanaka Kazuo , Chujo Yoshiki
Published: October 2015

The construction of the sponge‐type chemosensors based on the unique optical properties from the aggregates of the dye‐modifying hydrogels is shown herein. Initially, the modified hydrogels involving boron ketoiminate with poly(γ‐glutamic acid) are prepared, and it is confirmed that the synthesized hydrogels can present the aggregation‐induced emission (AIE) properties. In particular, it is found that the AIE color is changed by exposing the hydrogels to organic solvents for shrinking the hydrogels. Interestingly, after the treatments with organic solvents, the AIE color of the hydrogel is diverse. This unique behavior can be explained as aggregation‐induced blueshift emission. Next, based on this color change in the shrinking, the protein sensing is performed. Finally, it is demonstrated that the color changes of the hydrogels can be significantly induced by the protein solution. This is the first example, to the best of our knowledge, to offer the facile chemosensor for the protein detection based on the unique photophysical process, aggregation‐induced blueshift emission.

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Regularity criteria for harmonic heat flow and related system
Authors: Fan Jishan , Ozawa Tohru
Published: October 2015

We will prove some regularity criteria for harmonic heat flow, biharmonic heat flow and a surface growth model.
A Facile Strategy for Catalyst Separation and Recycling Suitable for ATRP of Hydrophilic Monomers Using a Macroligand
Authors: Jiang Xiaowu , Wu Jian , Zhang Lifen , Cheng Zhenping , Zhu Xiulin
Published: October 2015

How to simply and efficiently separate and recycle catalyst has still been a constraint for the wide application of atom transfer radical polymerization (ATRP), especially for the polymerization systems with hydrophilic monomers because the polar functional groups may coordinate with transition metal salts, resulting in abundant catalyst residual in the resultant water‐soluble polymers. In order to overcome this problem, a latent‐biphasic system is developed, which can be successfully used for ATRP catalyst separation and recycling in situ for various kinds of hydrophilic monomers for the first time, such as poly(ethylene glycol) monomethyl ether methacrylate (PEGMA), 2‐hydroxyethyl methacrylate (HEMA), 2‐(dimethylamino)ethyl methacrylate (DMAEMA), N,N‐dimethyl acrylamide (DMA), and N‐isopropylacrylamide (NIPAM). Herein, random copolymer of octadecyl acrylate (OA), MA‐Ln (2‐(bis(pyridin‐2‐ylmethyl)amino)ethyl acrylate), and POA‐ran‐P(MA‐Ln) is designed as the macroligand, and heptane/ethanol is selected as the biphasic solvent. Copper(II) bromide (CuBr2) is employed as the catalyst, PEG‐bound 2‐bromo‐2‐methylpropanoate (PEG350‐Br) as the water‐soluble ATRP initiator and 2,2′‐azobis(isobutyronitrile) (AIBN) as the azo‐initiator to establish an ICAR (initiators for continuous activator regeneration) ATRP system. Importantly, well‐defined water‐soluble polymers are obtained even though the recyclable catalyst is used for sixth times.

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MARVELD1 modulates cell surface morphology and suppresses epithelial–mesenchymal transition in non‐small cell lung cancer
Authors: Yao Yuanfei , Shi Ming , Liu Shanshan , Li Yiqun , Guo Kexin , Ci Yanpeng , Liu Weizhe , Li Yu
Published: October 2015

Integrins have been known to play pivotal roles in malignant progression and epithelial–mesenchymal transition (EMT) of non‐small cell lung cancer (NSCLC). We previously demonstrated that MARVELD1, a potential tumor suppressor, is epigenetically silenced in multiple cancer cells. In this study, we found MARVELD1 silencing altered cell surface ultrastructure of NSCLC cells and inhibited the formation of punctate integrin β1/β4 cluster in microvillus, whereas MARVELD1 overexpression suppressed TGF‐β1‐induced EMT. Remarkably, the balance of integrin β1 and β4 was modulated by MARVELD1. MARVELD1 silencing led to imbalance of integrin β1/β4 and significantly reduced microvillus length, furthermore affected the localization of β1/β4 at microvilli tips. TGF‐β1‐induced EMT was promoted by MARVELD1 silencing, while rebalance of integrin β1/β4 partly rescued the epithelial phenotype of MARVELD1‐silenced cells. Mechanistically, we demonstrate that MARVELD1‐mediated balance of integrin β1 and β4 regulates cell surface ultrastructure and EMT phenotype of NSCLC cells, suggesting MARVELD1 has a potential to be developed as a therapeutic target for NSCLC. © 2015 Wiley Periodicals, Inc.
ROR1 contributes to melanoma cell growth and migration by regulating N‐cadherin expression via the PI3K/Akt pathway
Authors: Fernández Natalia Brenda , Lorenzo Daniela , Picco María Elisa , Barbero Gastón , Dergan‐Dylon Leonardo Sebastián , Marks María Paula , García‐Rivello Hernán , Gimenez Liliana , Labovsky Vivian , Grumolato Luca , Lopez‐Bergami Pablo
Published: October 2015

The Receptor tyrosine kinase‐like Orphan Receptor 1 (ROR1) is primarily expressed by neural crest cells during embryogenesis. Following a complete downregulation after birth, ROR1 was shown to re‐express in various types of cancers. Little is known about ROR1 expression and function in melanoma. Here we show that ROR1 is aberrantly expressed in both melanoma cell lines and tumors and that its expression associates with poor Post‐Recurrence Survival of melanoma. Using gain‐ and loss‐of‐function approaches we found that ROR1 enhances both anchorage‐dependent and ‐independent growth of melanoma cells. In addition, ROR1 decreases cell adhesion and increases cell motility and migration. Mechanistically, ROR1 was found to induce upregulation of Akt and the mesenquimal markers N‐cadherin and vimentin. The regulation of N‐cadherin by ROR1 relies on both Akt dependent and independent mechanisms. ROR1 does not affect Wnt canonical pathway but was found to be engaged in a positive feedback loop with Wnt5a. In summary, we show that ROR1 contributes to melanoma progression and is a candidate biomarker of poor prognosis. Although further studies are needed to confirm this possibility, the present work indicates that ROR1 is a good prospective target for melanoma cancer therapy. © 2015 Wiley Periodicals, Inc.
No Difference on Adherence Between Immediate‐Release Versus Extended‐Release Dopamine Agonists in Uninsured Subjects with Parkinson's Disease
Authors: Bazán‐Rodríguez Lisette , Cervantes‐Arriaga Amin , Llorens‐Arenas Rodrigo , Calderón‐Fajardo Humberto , Rodríguez‐Violante Mayela
Published: October 2015

Background

Pharmacological management of subjects with Parkinson's disease (PD) is complex. Regardless of drug selection, adherence is one of the main concerns. Nonadherence is associated with poor symptomatic control and low quality of life. In general, adherence to once‐a‐day formulations is thought to be better in comparison to 3‐times‐daily dosing.

Methods

A cross‐sectional study was carried out. Consecutive uninsured subjects diagnosed with PD were treated either with an immediate‐ or extended‐release dopamine agonist formulation. Clinical and demographic data were collected. Subjects were assessed using the International Parkinson and Movement Disorder Society UPDRS. Adherence was evaluated using the Morisky‐Green test (MGT).

Results

A total of 314 (175 males and 139 females) subjects with PD were included. In regard to treatment, 188 (59.9%) were on an immediate‐release dopamine agonist and 126 (40.1%) on an extended‐release dopamine agonist. According to the MGT, 21 (6.7%) subjects were classified as nonadherent, 273 (86.9%) with a low adherence, and only 20 (6.4%) were considered with high adherence. Dopamine agonist levodopa equivalent daily dose was higher in the extended‐release group (296.6 ± 112.4 vs. 231.3 ± 133.4; P = 0.011); also, these subjects had more years of formal education (12.3 ± 5.2 vs. 9.5 ± 5.2; P = 0.630). No difference in adherence levels was found (P = 0.802) between subjects treated with an immediate‐release dopamine agonist and those receiving an extended‐release formulation.

Conclusions

Overall adherence in subjects with PD is low. Use of an extended‐release over an immediate‐release dopamine agonist formulation in this study population is not associated with a better adherence.