bluuebunny/crossref_metadata_2025 huggingface dataset:
8.5.2 Structural Modeling in Biomedical and Product Engineering
Authors: Graves Henson
Published: November 2014

Structural modeling is common for biomedical systems as well as manufactured products. Examples and experience from both fields clarify modeling issues applicable to each field. Modeling in both fields shares the commonality that a model describes one or more physical, or virtual, structures in terms of their components and connections between components. Modeling effectiveness depends on the relationship between the model and the systems which realize or conform to the model. The logic based approaches used for biomedical modeling can be adapted for engineering with the promise that automated reasoning can be integrated into product development and maintenance. Modeling languages such as SysML provide good graphical syntax and the concepts needed for representing product decompositions and interconnections in multiple domains. This paper illustrates the benefits of working within a logic‐based framework which incorporates the concepts of part decompositions and interconnections found in SysML. The concept of a model as an axiom set used in conceptual modeling languages such as OWL 2 is applied to SysML models. This discussion is intended for model practitioners in both fields.
7.2.1 Bricks for a Lean Systems Engineering Yellow Brick Road
Authors: Hodges Ann
Published: November 2014

A Yellow Brick Road can be thought of as the fabled path to a “promised land” where achievement of hopes and dreams is highly probable. Yellow bricks highlight the appropriate road, and destination mileage and speed limit signs support progress assessment to the chosen objective. Similarly, a common systems engineering (SE) framework, properly implemented at the approproate level of rigor, facilitates monitoring and achievement of a quality product that supports the intended mission. Bricks for a lean SE Yellow Brick Road are described. The bricks include a) using a common framework that integrates SE, project management and quality management; b) right sizing project implementation of this framework using a graded approach; c) applying the framework as early as possible; d) tailoring and waiving as needed; e) using project archetypes; and f) providing a repository that contains reuseable processes, plans, templates, examples, training and associated subject matter experts.
11.4.2 Assessing the Impacts of Uncertainty Propagation to System Requirements by Evaluating Requirement Connectivity
Authors: Salado Alejandro , Nilchiani Roshanak
Published: November 2014

Although theoretically independent, requirements within a decomposition level of a system architecture are not isolated elements. For an existing design, a change of a requirement may endanger or facilitate fulfillment of other requirements within the same level of the decomposition. The present research suggests a requirement connectivity metric to evaluate the potential consequences that changing a requirement may have on a system with respect to fulfillment of other requirements. A particular aspect of the present research is the assumption that connectivity accounts only for requirements within the same decomposition level of an architecture, not for those flowing up or down the decomposition. The metric is used to evaluate different cases in which requirements are changed due to triggering of uncertain events during a project life‐cycle.
4.6.2 Specifying Affordability
Authors: Tuttle Paul , Bobinis Joseph
Published: November 2014

Improving design methods for affordability has become a necessity in the DOD. The concept of affordability can seem straightforward. The difficulty arises when an attempt is made to specify and quantify the affordability of a system. This is significant when writing a specification or when comparing two affordable solutions to conduct an affordability trade study or award a contract based on affordability. This paper examines affordability, its contextual dependence and suggests a method for specifying affordability.

We start from a Department of Defense (DoD) perspective because of the large amount of effort expended by DoD and its support contractors in trying to resolve these problems. All of the DoD affordability activities performed during system development have direct analogues in non‐DoD environments. The foundation for this paper is the DoD and commercial definitions of affordability, as well as, the Dr. Ashton Carter's, Undersecretary of Defense for Acquisition, Technology, and Logistics (ATL), affordability directives which formed the basis for the DoD thrust into this area. Using this as a basis, it is shown that: 1) affordability is dependent on the context in which it is evaluated with a distinction being made between Program and System affordability; and 2) affordability must be evaluated over the entire life cycle of the System of Interest (i.e., both the Primary System and the Enabling System). From this foundation a method of specifying affordability is derived and a specification resulting from this method is shown to: 1) support affordability comparisons between two systems; and 2) fit affordability trades into the standard trade study framework. Thus, it is demonstrated that affordability is not just an abstract concept but has real applicability in the development and life of systems and must be incorporated into Systems Engineering.
6.3.2 Value‐oriented concept selection in aero‐engine sub‐systems design: the EVOKE approach
Authors: Bertoni Marco , Bertoni Alessandro , Isaksson Ola , Amnell Henrik , Johansson Christian
Published: November 2014

Value Driven Design methodologies extend the Requirements Management and Systems Engineering processes to reduce time and costs needed to identify the right solution direction to be pursued in detailed design. Emerging from the findings of an EU FP7 research project, the paper describes an approach, named EVOKE, that uses value as a basis for preliminary concept selection in the design of system components. EVOKE takes as input a list of value dimensions and drivers communicated by the system integrators, together with information about the high‐level engineering characteristics of a candidate design, to enable early stage value analysis to be executed the by sub‐system manufacturers. The approach and its technological enablers are described in detail through the use of a case study related to the design of new intermediate compressor case for turbofan engines.
6.1.2 Portfolio Management Overview
Authors: Schellenberg Thomas , Weghorst Kristen , Cahill Phil
Published: November 2014

This paper describes a holistic systems engineering perspective of Portfolio Management engagements. These perspectives are derived from leveraging insights of The SI Organization, Inc.'s (the SI) 40+ year heritage providing systems engineering support to customer enterprises which consist of complex, tightly coupled web of information systems and information collection platforms. The six step Portfolio Management (PfM) process described in this paper provides a rational, repeatable approach to make programmatic and technical decisions justified by solid systems engineering discipline. The SI's approach to PfM involves partitioning complex problems into workable solutions by applying decision governance and Commercial Off‐the‐Shelf (COTS) based information infrastructure that are both tailored to a customer's unique cultural environment. This customized decision and information environment can then be used to ingest programmatic and technical data needed to inform and justify PfM decisions.
Getting students hooked on systems engineering!
Authors: Haskins Cecilia , Dahl Hans Jørgen
Published: November 2014

During IS2012 a report was made about initiatives in the Norwegian University of Science and Technology to help students learn about systems engineering by doing systems engineering. In this paper, the authors address the question, “lacking a degree program in the university dedicated to systems engineering, what is the best way to give students a taste that makes them want more?” The success of the efforts to date has been indicated by the rapid employment in Norway of students who demonstrate an awareness of and willingness to learn more about systems engineering.

The paper describes three initiatives: results from two courses – a PhD level course that has run for 12 years and a master level course on Industrial Design‐Systems Engineering that is in its fourth year – and a university project that has experienced recent success attributed to the inclusion of a systems engineer on the project team since 2011.

The conclusion is that letting students ‘try out’ systems engineering practices in a laboratory/project classroom environment offers them learning experiences that clearly demonstrate the value of systems engineering practices and theory to both the students and potential employers.
Taking Advantage of the Model: Application of the Quantity, Units, Dimension, and Values Standard in Concurrent Spacecraft Engineering
Authors: Schaus Volker , Fischer Philipp M. , Gerndt Andreas
Published: November 2014

Designing a spacecraft involves many experts from different domains. In the early design phases they are brought together to discuss the spacecraft in a short period of time. The elements and building blocks the individual engineers want to use are stored and described in a shared system model provided by a software framework. A lot of features like the masses or dimensions are described using parameters. Due to the various domains and individual preference, many different units are used, leading to mistakes, distraction and misunderstandings caused by unit conversions. Our paper describes a pragmatic approach how the QUDV is integrated into an existing system model. This allows taking advantage of it by automatically analyzing the unit consistency as well as performing automatic conversions. The presented work shows that with a profound integration into the existing software framework, the engineers can overcome the error‐prone task of unit checks and conversion problems.
10.2.2 Mathematical Models of Emergence in Complex Systems‐of‐systems
Authors: Baldwin W. Clifton , Hostetler Stephanie , Felder Wilson N.
Published: November 2014

This paper presents an analysis of five mathematical models of systems‐of‐systems (SoS) illustrating the potential for emergent behavior. Each case is examined to determine whether or not the resulting system behavior meets the challenge of “essential unpredictability” which would serve as a critical factor in defining the SoS as complex. We conclude that three of the cases provide examples of systems which meet all the criteria for System‐of‐system definition, but do not exhibit emergent behavior, while at least one, and perhaps two, of the cases lead to emergent behavior meeting the “essential unpredictability” test, thereby demonstrating the difference between complicated systems‐of‐systems and complex ones. Further examination of this relationship is proposed, and further questions for study are defined.
5.1.2 A Framework for Visualizing Systems Engineering Research Coverage
Authors: Cook Stephen C. , Ferris Timothy L.J. , Nowakowski Stan
Published: November 2014

This paper describes the evolution of a framework suitable for categorizing and displaying systems engineering (SE) research topics. The paper follows the journey traversed in the evolution of the framework and its progressive evaluation. It also provides the key influences and the rationale for each iteration. The framework was synthesised and refined in three stages. Firstly, the research team gathered a number of research‐oriented SE taxonomies and compared and contrasted these with a SoSE capabilities framework that was an outcome from earlier research. This resulted in a new synthesis that was then evaluated for coverage against a set of SE research agendas. The evaluation informed further refinements that reorganised some of the categories and broadened the elements of SE capability somewhat. The final step was to validate and hone the framework though a process of mapping a representative sample of papers from the Systems Engineering journal onto the framework. The resulting mapping gave confidence that the framework is sufficiently comprehensive for its intended purpose.
A Model‐Based Approach to Unifying Disparate Project Management Tools for Project Classification and Customized Management
Authors: Orhof Ori , Shenhar Aaron , Dori Dov
Published: November 2014

Modern project managers are aware that different types of projects need different styles of project management. A construction project is very different from a high‐tech research program in several ways, including how each is managed. The NTCP “Diamond” framework (Novelty‐Technology‐Complexity‐Pace) suggests classifying complex projects according to four dimensions such that the values attributed to each of these dimensions indicate a recommended style of management for increasing the likelihood of the project's success. It may be difficult to attribute values to these four dimensions in a large and complex project, which calls for systematic analysis of the project as part of its planning phase. The object‐process methodology (OPM) caters to such systematic step‐by‐step analysis by decomposing a project into its fundamental building blocks – objects, possibly with states, and processes that transform the objects. This paper suggests that the confluence of OPM and NTCP can improve the project planning phase and improve the project's overall chances of success.
Agent‐Based Modeling for Systems of Systems
Authors: Mour Ankur , Kenley C. Robert , Davendralingam Navindran , DeLaurentis Daniel
Published: November 2014

Agent‐based modeling is an important tool for the engineering of systems of systems. This paper briefly reviews the historical development of agent‐based modeling and system of systems concepts, compares agent‐based modeling to other approaches, and describes the Purdue Discrete Agent Framework for agent‐based modeling. An application of the Discrete Agent Framework to a system of systems is described and illustrates the ability of agent‐based modeling to capture non‐intuitive behaviors that may arise due to the complex dynamics that occur in interconnected systems of agents that follow a behavioral set of rules. The paper concludes by looking back to the past to understand the potential for applying agent‐based modeling to support the ongoing engineering and operations of an evolving system of systems.
The Agile Enterprise: Systems Engineering Agility at the Enterprise Level
Authors: Brown Don E.
Published: November 2014

Agility is all the rage. Across the landscape, businesses request agility as a deliverable, make claims that they are agile, and (some) go so far as to assert they can provide agility to other corporate entities outside of their own sphere of influence. The challenge before us as a Systems Engineering Community is that (Enterprise) Agility, although well documented throughout engineering literature since the early 1990s, is often misinterpreted. Agility means many things to many people, and heretofore, has been used as a synonym for rapid development and delivery. Although speed is a byproduct of agility, speed in and of itself is not robust enough to encompass all that agility provides an organization, its customers, and partners. The goals of this paper are to shed light on agility in context to businesses, especially with Enterprises engaged in Systems Engineering, and provide guidance as to how agility is best achieved regardless of the Enterprise's business or mission objectives.
8.2.2 Cloud Effectiveness Model
Authors: Feehs Richard J.
Published: November 2014

Cloud computing is a model for enabling convenient, on‐demand network access to a shared pool of configurable computing resources (e.g., networks, servers, storage, applications and services) that can be rapidly provisioned and released with minimal management effort or service provider interaction. This cloud model promotes availability and is composed of five essential characteristics: On‐Demand Self‐Service, Broad Network Access, Resource Pooling, Rapid Elasticity and Measured Service. Although deemed “essential,” not all cloud provider solutions exhibit these characteristics to the same level. This white paper describes a new framework, the Cloud Effectiveness Model (CLEF‐M), which can be used to evaluate:

How effectively a cloud provider's offering meets the “essential characteristics”

The levels to which consumers need and/or value these same characteristics, and

The maturity of a cloud offering and its progress toward a desired end‐state
5.5.2 Efficient and Effective Systems Integration and Verification Planning Using a Model‐Centric Environment
Authors: Salado Alejandro
Published: November 2014

There is an increasing interest in Model‐Based Systems Engineering (MBSE) practices in academia and industry. The majority of research and adoption in industry is relevant to the early phases of the system life‐cycle, where model‐based design is expected to provide improved results during system development. However, little attention has been paid to the application of such methodology to later phases of the development, and in particular to system integration and verification of the actual manufactured system, which continues to be done in the traditional document‐centric environment. This paper proposes a model‐centric environment for system integration and verification activities at the end of the development cycle and presents benefits in effectiveness and efficiency in planning system integration and verification activities for a system under a model‐centric environment.
2.1.1 Defining a System of Systems Engineering and Integration Approach to Address the Navy's Information Technology Technical Authority
Authors: Vaneman Warren K. , Budka Richard
Published: November 2014

The United States Navy's focus on Information Dominance as a warfare enabler requires an integrated and coordinated System of Systems (SoS) for mission success. The Space and Naval Warfare Systems Command (SPAWAR) has been designated the Information Technology Technical Authority (IT TA) to address the challenges posed by this unprecedented interoperability among Navy systems. To address these engineering and planning challenges, SPAWAR has adopted a System of Systems Engineering and Integration (SoSE&I) methodology. SoSE&I is the planning, analyzing, and integrating constituent systems into an SoS capability greater than the sum of those systems. This paper defines the SoSE&I “Vee” process model, and discusses how it is used to engineer the SoS throughout its life‐cycle, and how it can be used by decision‐makers to increase systems integration and interoperability to directly impact the operational effectiveness of the Navy's networks and weapons.
6.5.1 I5: A Model‐Based Framework for Architecting System‐of‐Systems Interoperability, Interconnectivity, Interfacing, Integration, and Interaction
Authors: Mordecai Yaniv , Dori Dov
Published: November 2014

We present I5 — Interoperability, Interconnectivity, Interfacing, Integration, and Interaction — a Model‐Based Framework for Architecting Systems‐of‐Systems. Interoperability programs deliver end‐to‐end cooperation and collaboration capabilities and services among organizations, users, systems, and infrastructures, on top of a set of existing systems. Each system has its own programmatic and technical constraints and issues. System‐level stakeholders usually prefer core functionality over integration, and expect the interconnectivity infrastructure to be transparent and simple, regardless of its actual cost, complexity, or criticality. Hence, coordinating and aligning the multiple system and team efforts in order to reach a synergetic effect is a challenge that many integration professionals in the cyber, energy, manufacturing, and traffic domains are familiar with. Traditional system‐centered design methods fail to capture interconnectivity and collaboration aspects and issues, and they are of little interest to the individual systems' stakeholders. The framework we propose is based on Object–Process Methodology, an emerging ISO standard (ISO 19450) for modeling and design of complex, dynamic, and multidisciplinary systems. Our framework facilitates a smooth transition from a set of disparate system‐centered views to a consolidated, integrated model, which accounts for integration aspects, interface and payload structure and behavior, interconnectivity processes and services, and eventually emergent interoperability capabilities.
8.4.1 A Systems Perspective to Commuter Cycling in Urban Mobility
Authors: Kumar Ashwani , Teo Kwong Meng
Published: November 2014

Taking a systems perspective is essential in solving complex problems such as urban mobility. Hence this paper adopts a systems approach to address the issue of commuter cycling in urban mobility. Applying systems thinking, we develop a new, simple approach to assess the potential of commuter cycling in different urban contexts. Furthermore, we use causal loop based reasoning to figure out the key policy levers. Using this knowledge we suggest effective policy interventions requiring minimal resources. We also evaluate and classify these policies based on the common constraints of budget and implementation difficulty. This paper demonstrates practical use of systems thinking to a complex ***policymaking situation. Apart from addressing the commuter cycling policies, this paper also showcases an interesting methodology for introducing systems thinking in making public policies.
5.5.1 System Design Selection Guidance through Model Execution
Authors: Scott William , Do Quoc
Published: November 2014

The use of modeling languages as the primary means to capture and convey system information presents opportunities to improve the project outcomes. At present, however, such models are constrained by the static and textual nature of the formal requirements capture and model representation. This paper describes research into how such requirements and behavioral models captured in SysML may be executed. This allows quantitative and comparative assessment of the behavior of the designed system options against a set of informal requirements, thereby informing design decisions. The simulation exercises the behavior model of the proposed system in a simulated environment to ascertain how the system will perform against the formal requirements. The activity simulation is captured and displayed as a 3D animation to aid understanding of the system's expected performance.
4.6.3 Affordable Systems: Balancing the Capability, Schedule, Flexibility, and Technical Debt Tradespace
Authors: Lane Jo Ann , Koolmanojwong Supannika , Boehm Barry
Published: November 2014

With the increasing demands for affordable system capabilities that can be provided quickly to the user community, developers must explore a variety of options for identifying “satisficing” solutions. The system capability affordability tradespace must balance expedited systems engineering to reduce schedule and cost, encourage flexibility in architecture decisions to support future evolution of the system, and minimize technical debt that either results in later rework or adversely impacts future options. This paper shows how the University of Southern California (USC) Center for Systems and Software Engineering (CSSE) software and systems engineering cost models can be used in the analysis of this tradespace to show the range of options and the resulting consequences.
5.4.2 Applying Systems Engineering to Transit Facilities: Advancing Beyond “Building Commissioning”
Authors: Gleckler William , O'Neil Anne
Published: November 2014

The demand for increased energy efficiency and sustainable facility designs is significantly increasing the complexity of buildings. With the evolution of higher yielding energy efficient performance for heating, ventilation, and air conditioning (HVAC) systems, integration of new sustainable energy technologies and other sustainable green building systems, there is a growing need to ensure that proper systems techniques are implemented across the lifecycle of new transit facility projects.

Today there continues to be advances in building automation, energy management and fire alarm/control systems for the monitoring and control of the facility subsystems and systems, which correspondingly adds to the complexity for defining the subsystems interfaces, the required level of integration, and how these interfaces and systems are verified during the construction phase of the project. As a result of this advancing complexity for many facility systems the Building industry developed the “Commissioning process”.

This paper describes the evolution of the Commissioning process currently used to deploy facility systems, with a focus on the process application and its deficiencies when compared to a systems engineering approach. Case studies will be provided from New York City Transit's (NYCT) tailored implementation experience and efforts to attain more successful results by further tailoring this Commissioning process to apply systems engineering principles and activities.
7.2.2 Design Reviews: A Process Perspective for Improved Efficiency and Effectiveness
Authors: Young Madalein
Published: November 2014

This paper documents and analyzes a typical design review process in the South African defense industry with the aim of improving the effectiveness and efficiency associated with design reviews. Process steps are scrutinized to identify behavioral and procedural actions that negatively impact on concluding successful design reviews. Poor design review culture and a few bad design review habits are highlighted with the aim that the lessons learnt will be of value to any organization in any environment conducting design reviews. The paper then goes on to suggest enhancements to ensure an improved design review process, as well as initiatives to foster a culture conducive to constructive reviews.
Identification of Lanes of Acquisition from Military Rapid Development Programs
Authors: Lepore Debra Facktor , Colombi John , Wade Jon
Published: November 2014

Research conducted in the Systems Engineering Research Center (SERC) examined military rapid capability and urgent needs programs and identified a framework for rapid development. Discussions with organizations engaged in rapid development indicated a number of different definitions of “rapid”, a wide range of specific practices that were implemented to achieve rapid development, and various domains of product categories that aligned to what the rapid organization aimed to achieve. It was observed that various organizations appeared to focus and operate within lanes of acquisition, which could be analogous to lines of business in the commercial sector and also analogous to other taxonomies of acquisition used in other U.S. government organizations. This paper outlines these observations.
A Lean Engineering Journey
Authors: Terrien Olivier
Published: November 2014

During the three last INCOSE symposiums, Thales Systèmes Aéroportés proposed papers and presented concrete illustrations to implement a Lean approach in Systems Engineering and Product Development. Lean methodology stands on several pillars: ‘obsession of the customers and satisfaction of their needs’, ‘attention to problems and elimination of wastes’ and ‘involvement and development of employees through the resolution of problems’. This tutorial is based on our real experiences and describes achieved examples to address many Lean Enablers for Systems Engineering developed by the INCOSE Lean Working Group such as: “have cross functional stakeholders worked together to build the agreed value stream” and “use formal value stream mapping methods to identify and eliminate Systems Engineering and Product Development waste, and to tailor and scale tasks” This tutorial is divided into four major topics:1. A Lean approach adapted to Systems Engineering: historical and technical Lean fundamentals;2. A Lean approach illustrated by concrete examples: a transformation workshop (up to Obeya), a systematic workshop (up to VSM‐PERT) and a recurrent workshop (up to Waste Diagnosis);3. A Lean approach through pragmatic exercises: a case study about Rework in R&D (model & metrics);4. A Lean approach deployed in Systems Engineering: key success factors, roles, risks, agile vision, Lean Enablers, etc.
Presentation Secrets of Comedians and Stage Performers: The Advanced Presentation Workshop
Authors: Brown Barclay
Published: November 2014

Being a successful systems engineering often means being able to communicate your ideas in a clear, compelling way. This tutorial is designed to start you on the road from being a competent presenter to being a great presenter. Borrowing from great speakers, presenters and performers in the political, entertainment, motivation and inspiration domains, the tutorial will demonstrate and apply concrete new ways of developing yourself as a speaker. This session goes beyond the “imagine your audience in their underwear” and “talk to a spot on the back wall” kind of advice to present advanced techniques that can take you from being a good presenter to being a great one. Once over the universal fear of public speaking and able to speak and present competently, a presenter often slides into a rut, using the same presentation style and the same range of skills year after year. This session provides a kick‐start into a new level of presenting and speaking. Twenty‐five specific, workable techniques are offered for using humor, timing, movement, adding interest, commanding attention, being natural, dealing with presentation challenges and more. Techniques based in psychology, personality and philosophy are boiled down into practical methods you can use right away—no theater skills required! The speaker is a systems engineering, and has master's degrees in psychology and business.
Systems Engineering requirements Analysis and Trade‐off for Trusted Systems and Networks
Authors: Popick Paul , Miller John
Published: November 2014

This tutorial walks through a case study of a requirements analysis pattern to integrate system security for supply chain and cyber into systems engineering (SE) stakeholder requirements, requirements analysis and architectural design. This tutorial emphasizes the need to more tightly integrate security with the overall systems engineering activities and the systems engineering role. The tutorial illustrates the iterative nature of the analysis and also shows how the analysis feeds the RFP. The tutorial uses the DoD trusted systems and networks analysis pattern as the basis of the tutorial. This analysis pattern has broad applicability across industries and aligns well with the Systems Engineering technical processes in ISO 15288–2008. The analysis pattern consists of a mission / business criticality analysis, a vulnerability analysis, a threat assessment and an information assurance assessment as inputs to a risk based cost‐benefit trade‐off analysis. Students will gain hands on experience applying the analysis pattern to an Unmanned Aerial Vehicle (UAV) case study. The UAV case study covers the system engineering analysis of a solution in the early lifecycle phases. The interrelationship with the SE technical processes, system specification and the system technical reviews is described. Relationships to other specialty engineering disciplines will be briefly discussed. Participants are expected to have a systems engineering or program management background and experience. They will work in small teams to develop solutions and alternatives to the case study. The tutorial is presented by experienced systems engineers that have worked on major systems engineering efforts for government, communications and retail sectors solutions.
Endoscopic ultrasound‐guided intravascular therapy
Authors: Binmoeller Kenneth F. , Sendino Oriol , Kane Steven D.
Published: November 2014

The gastrointestinal tract provides a unique “window” to access vascular structures in the mediastinum and abdomen. The advent of interventional endoscopic ultrasound (EUS) has enabled access to these structures with a standard fine‐needle aspiration (FNA) needle. Sclerosants, cyanoacrylate, and coils can be delivered through the lumen of the FNA needle. EUS‐guided treatment of gastric varices has theoretical advantages over conventional endoscopy‐guided treatment. Controlled studies are needed to determine the role of EUS‐guided treatment for primary and secondary prevention of variceal bleeding. There is a growing list of novel indications for EUS‐guided vascular therapy that include portal vein angiography and pressure measurements, intrahepatic portosystemic shunt placement, and micro coil embolization of vascular structures. Additionally, access and therapy of the heart and surrounding structures appears feasible.
The Tosontsengel Mongolia world record sea‐level pressure extreme: spatial analysis of elevation bias in adjustment‐to‐sea‐level pressures
Authors: Purevjav Gomboluudev , Balling Robert C. , Cerveny Randall S. , Allan Rob , Compo Gilbert P. , Jones Philip , Peterson Thomas C. , Brunet Manola , Driouech Fatima , Stella José Luis , Svoma Bohumil M. , Krahenbuhl Daniel , Vose Russell S. , Yin Xungang
Published: November 2014

A World Meteorological Organization (WMO) committee evaluated the record sea‐level pressure (SLP) measurement of 1089.4 hPa on 30 December 2004 in Tosontsengel, Mongolia (1724.6 m). Although instrumentation and data collection procedures were properly followed according to the assessment of the committee, concern was raised regarding the reliability of SLP adjustment from such a high‐elevation station. This paper addresses this concern with a number of analyses that look at relationships between SLP extremes and corresponding station elevation and temperature. First, we selected data from stations extracted from the Integrated Surface Database (ISD‐Lite) of NOAA's National Climate Data Center. A spatial analysis indicates that elevation shows little to no association (R2 values essentially zero) to extreme SLP. However, a second analysis between extreme SLP and air temperature indicates that high regionalism exists in spatial correlations (local R2) between those two variables. This relationship to temperature is likely the result of differences in SLP adjustment formulae used around the world. Based on this analysis, on the need to differentiate the SLP values adjusted using extremely cold temperatures (and generally high elevation), and following past WMO SLP guidelines, the WMO Rapporteurs for Climate and Weather Extremes therefore have created two distinct SLP records: (a) highest adjusted SLP (below 750 m), currently 1083.3 hPa recorded on 31 December 1968 at Agata, Evenhiyskiy, Russia; and (b) highest adjusted SLP (above 750 m), currently 1089.4 hPa (by Russian method; 1089.1 hPa by WMO formula) on 30 December 2004 in Tosontsengel, Mongolia. Future WMO guidance regarding SLP adjustment may lead to re‐evaluation of this and other SLP records.
Short‐ and long‐term outcomes of laryngeal cancer care in the elderly
Authors: Gourin Christine G. , Starmer Heather M. , Herbert Robert J. , Frick Kevin D. , Forastiere Arlene A. , Eisele David W. , Quon Harry
Published: November 2014

Objectives/Hypothesis

To examine associations between pretreatment variables, short‐term and long‐term swallowing and airway impairment, and survival in elderly patients treated for laryngeal squamous cell cancer (SCCA).

Study Design

Retrospective analysis of Surveillance, Epidemiology, and End Results‐Medicare data.

Methods

Longitudinal data from 2,370 patients diagnosed with laryngeal SCCA from 2004 to 2007 were evaluated using cross‐tabulations, multivariate logistic regression, and survival analysis.

Results

Dysphagia (odds ratio [OR] = 1.5 [1.2–1.7]), weight loss (OR = 1.3 [1.1–1.6]), esophageal stricture (OR = 3.8 [2.5–5.9]), airway obstruction (OR = 1.9, [1.6–2.3]), tracheostomy (OR = 1.5 [1.2–1.9]), and pneumonia (OR = 1.8 [1.4–2.2]) increased 1 year after treatment. The odds of airway obstruction, esophageal stricture, and pneumonia increased over subsequent years, with significantly increased risk at 5 years for airway obstruction (OR = 3.3 [1.8–5.8]) and pneumonia (OR = 5.2 [2.5–10.7]). Pretreatment dysphagia, chemoradiation, and salvage surgery were significant predictors of long‐term dysphagia, weight loss, tracheostomy, and gastrostomy, with pretreatment dysphagia and salvage surgery also associated with pneumonia. Surgery and postoperative radiation was associated with long‐term dysphagia (OR = 1.4 [1.0–1.9]) but reduced odds of long‐term pneumonia (OR = 0.7 [0.5–0.9]). Long‐term dysphagia, gastrostomy or tracheostomy dependence, weight loss, airway obstruction, and pneumonia were associated with poorer survival, with pneumonia associated with the greatest risk of death at 5 years (hazard ratio = 2.6 [2.4–2.9]).

Conclusions

Airway and swallowing impairment is common after laryngeal SCCA treatment in elderly patients, increases over time, and is associated with poorer survival—with pneumonia associated with the highest risk of long‐term mortality. Patients with pretreatment dysphagia, initial treatment with chemoradiation, and salvage surgery represent a high‐risk group with an increased risk of disability and death.

Level of Evidence

2c.Laryngoscope, 125:924–933, 2015
The human embryonic stem cell proteome revealed by multidimensional fractionation followed by tandem mass spectrometry
Authors: Zhao Peng , Schulz Thomas C. , Sherrer Eric S. , Weatherly D. Brent , Robins Allan J. , Wells Lance
Published: November 2014

Human embryonic stem cells (hESCs) have received considerable attention due to their therapeutic potential and usefulness in understanding early development and cell fate commitment. In order to appreciate the unique properties of these pluripotent, self‐renewing cells, we have performed an in‐depth multidimensional fractionation followed by LC‐MS/MS analysis of the hESCs harvested from defined media to elucidate expressed, phosphorylated, O‐linked β‐N‐acetylglucosamine (O‐GlcNAc) modified, and secreted proteins. From the triplicate analysis, we were able to assign more than 3000 proteins with less than 1% false‐discovery rate. This analysis also allowed us to identify nearly 500 phosphorylation sites and 68 sites of O‐GlcNAc modification with the same high confidence. Investigation of the phosphorylation sites allowed us to deduce the set of kinases that are likely active in these cells. We also identified more than 100 secreted proteins of hESCs that likely play a role in extracellular matrix formation and remodeling, as well as autocrine signaling for self‐renewal and maintenance of the undifferentiated state. Finally, by performing in‐depth analysis in triplicate, spectral counts were obtained for these proteins and posttranslationally modified peptides, which will allow us to perform relative quantitative analysis between these cells and any derived cell type in the future.
A phosphoproteomic screen demonstrates differential dependence on HER3 for MAP kinase pathway activation by distinct PIK3CA mutations
Authors: Blair Brian G. , Wu Xinyan , Zahari Muhammad Saddiq , Mohseni Morassa , Cidado Justin , Wong Hong Yuen , Beaver Julia A. , Cochran Rory L. , Zabransky Daniel J. , Croessmann Sarah , Chu David , Toro Patricia Valda , Cravero Karen , Pandey Akhilesh , Park Ben Ho
Published: November 2014

The PIK3CA gene encodes for the p110 alpha isoform of PI3 kinase and is one of the most frequently mutated oncogenes in human cancers. However, the mechanisms by which PIK3CA mutations activate cell signaling are not fully understood. Here we used a phosphoproteomic approach to compare differential phosphorylation patterns between human breast epithelial cells and two isogenic somatic cell knock in derivatives, each harboring a distinct PIK3CA mutation. We demonstrated differential phosphorylation patterns between isogenic cell lines containing a PIK3CA helical domain mutation (E545K) compared to cells with a PIK3CA kinase domain mutation (H1047R). In particular, the receptor tyrosine kinase, HER3, showed increased phosphorylation at tyrosine 1328 in H1047R cells versus E545K cells. Genetic studies using shRNA demonstrated that H1047R cells have a profound decrease in growth factor independent proliferation upon HER3 knock down, but this effect was attenuated in E545K cells. In addition, HER3 knock down led to reductions in both PI3 kinase and MAP kinase pathway activation in H1047R cells, but in E545K cells only PI3 kinase pathway diminution was observed. These studies demonstrate the power of using paired isogenic cell lines for proteomic analysis to gain new insights into oncogenic signal transduction pathways.
Ligand binding to a high‐energy partially unfolded protein
Authors: Kasper Joseph R. , Park Chiwook
Published: November 2014

The conformational energy landscape of a protein determines populations of all possible conformations of the protein and also determines the kinetics of the conversion between the conformations. Interaction with ligands influences the conformational energy landscapes of proteins and shifts populations of proteins in different conformational states. To investigate the effect of ligand binding on partial unfolding of a protein, we use Escherichia coli dihydrofolate reductase (DHFR) and its functional ligand NADP+ as a model system. We previously identified a partially unfolded form of DHFR that is populated under native conditions. In this report, we determined the free energy for partial unfolding of DHFR at varying concentrations of NADP+ and found that NADP+ binds to the partially unfolded form as well as the native form. DHFR unfolds partially without releasing the ligand, though the binding affinity for NADP+ is diminished upon partial unfolding. Based on known crystallographic structures of NADP+‐bound DHFR and the model of the partially unfolded protein we previously determined, we propose that the adenosine‐binding domain of DHFR remains folded in the partially unfolded form and interacts with the adenosine moiety of NADP+. Our result demonstrates that ligand binding may affect the conformational free energy of not only native forms but also high‐energy non‐native forms.
Random forest classification of etiologies for an orphan disease
Authors: Speiser Jaime Lynn , Durkalski Valerie L. , Lee William M.
Published: November 2014

Classification of objects into pre‐defined groups based on known information is a fundamental problem in the field of statistics. Although approaches for solving this problem exist, finding an accurate classification method can be challenging in an orphan disease setting, where data are minimal and often not normally distributed. The purpose of this paper is to illustrate the application of the random forest (RF) classification procedure in a real clinical setting and discuss typical questions that arise in the general classification framework as well as offer interpretations of RF results. This paper includes methods for assessing predictive performance, importance of predictor variables, and observation‐specific information. Copyright © 2014 John Wiley & Sons, Ltd.
Synthesis of starch vernolate in 1‐butyl‐3‐methylimidazolium chloride ionic liquid
Authors: Desalegn Tegene , Garcia Ignacio J. Villar , Titman Jeremy , Licence Peter , Chebude Yonas
Published: November 2014

A new method for the preparation of epoxy fatty acid esters of cassava starch (starch vernolates) is presented based on the reaction of cassava starch with vernonia oil methyl ester (epoxy ester) using only 1‐butyl‐3‐methylimidazolium chloride, [C4C1im]Cl, ionic liquid as a reaction medium and a cheap inexpensive base such as pyridine as a catalyst. Under the reported reaction conditions, a high degree of substitution of 1.03 was achieved, at a reaction temperature of 110°C and 24 h reaction time. The new starch vernolates were characterized by infrared spectroscopy (FTIR) and solid state NMR (CP/MAS 13C NMR). Scanning electron microscopy (SEM) and X‐ray diffraction (XRD) showed that the new product is an amorphous material with a continuous and shapeless morphology. The melting point measured by differential scanning calorimetry (DSC) is 111.4°C. The new synthetic method makes the synthesis of starch vernolates less time consuming and more inexpensive. The differences in melting point and degree of substitution with previously synthesized starch vernolates using enzymatic catalysis suggest a difference in reaction selectivity via this new reaction path.
Chromosomale Mosaike in der klinischen Zytogenetik
Authors: Weise Anja , Klein Elisabeth , Mrasek Kristin
Published: November 2014

In der Zytogenetik werden Zellen im Gegensatz zu molekulargenetischen Untersuchungen individuell analysiert. Dadurch können Zellen mit verschiedenen Karyotypen (Zellmosaike) aufgedeckt werden. Dieser Beitrag gibt einen Überblick über die verschiedenen Probleme der diagnostischen Befunderhebung und -interpretation chromosomaler Mosaike. Eine besondere Herausforderung liegt darin, dass zwischen echten Mosaiken einerseits und Kulturartefakten, Pseudomosaiken, Alterseffekten, mütterlicher Kontamination oder Chimärismus andererseits unterschieden werden muss. Die Wahrscheinlichkeit, ein chromosomales Mosaik in der zytogenetischen Routinediagnostik zu übersehen, ist sehr hoch, da hier nur ca. 15 von 1012 Körperzellen und dazu in der Regel nur ein einziger Gewebetyp untersucht werden. Einige zytogenetische Mosaike sind typisch für bestimmte Syndrome, wie z. B. das Pallister-Killian-, das Katzenaugen oder das Ullrich-Turner-Syndrom; andere sind charakteristisch für bestimmte Krankheitsbilder, einschließlich hämatologischer maligner Erkrankungen.
Wilms’ tumor 1 enhances Cisplatin‐resistance of advanced NSCLC
Authors: Wu Chen , Wang Yonggong , Xia Yang , He Shaohua , Wang Zhiqiang , Chen Yijiang , Wu Changping , Shu Yongqian , Jiang Jingting
Published: November 2014

Wilms’ tumor 1 (WT1) is an oncogene that has been correlated with tumor progression, bad prognosis and chemo‐resistance in Non‐Small‐Cell lung cancer (NSCLC). Here, we found that WT1 expression is significantly higher in NSCLCs than in benign controls, and that Cisplatin‐resistant patients display a notable increase in WT1 expression following relapse. In vitro, WT1 levels were associated with the IC50 of NSCLC cells and increased along with treatment time and dose of Cisplatin. Furthermore, WT1 enhanced Major Vault Protein (MVP) transcription via binding to its promoter. Therefore, WT1 may be a potential therapeutic target for solving resistance.
Molecular cloning and characterization of drimenol synthase from valerian plant (Valeriana officinalis)
Authors: Kwon Moonhyuk , Cochrane Stephen A. , Vederas John C. , Ro Dae-Kyun
Published: November 2014

Drimenol, a sesquiterpene alcohol, and its derivatives display diverse bio‐activities in nature. However, a drimenol synthase gene has yet to be identified. We identified a new sesquiterpene synthase cDNA (VoTPS3) in valerian plant (Valeriana officinalis). Purification and NMR analyses of the VoTPS3‐produced terpene, and characterization of the VoTPS3 enzyme confirmed that VoTPS3 synthesizes (−)‐drimenol. In feeding assays, possible reaction intermediates, farnesol and drimenyl diphosphate, could not be converted to drimenol, suggesting that the intermediate remains tightly bound to VoTPS3 during catalysis. A mechanistic consideration of (−)‐drimenol synthesis suggests that drimenol synthase is likely to use a protonation‐initiated cyclization, which is rare for sesquiterpene synthases. VoTPS3 can be used to produce (−)‐drimenol, from which useful drimane‐type terpenes can be synthesized.