bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2, randomized, open‐label study of ramucirumab in combination with first‐line pemetrexed and platinum chemotherapy in patients with nonsquamous, advanced/metastatic non–small cell lung cancer
Authors: Doebele Robert C. , Spigel David , Tehfe Mustapha , Thomas Sachdev , Reck Martin , Verma Sunil , Eakle Janice , Bustin Frederique , Goldschmidt Jerome , Cao Dachuang , Alexandris Ekaterine , Yurasov Sergey , Camidge D. Ross , Bonomi Philip 
Published: November 2014

BACKGROUNDVascular endothelial growth factor (VEGF)–mediated angiogenesis plays an important role in non–small cell lung cancer (NSCLC). Ramucirumab is a human immunoglobulin G1 monoclonal antibody that inhibits VEGF receptor 2. This phase 2 study investigated ramucirumab in combination with first‐line pemetrexed and platinum chemotherapy in advanced/metastatic NSCLC.METHODSEligible stage IV nonsquamous NSCLC patients with no prior chemotherapy for metastatic disease were randomized 1:1 to pemetrexed and carboplatin (or cisplatin) or ramucirumab (10 mg/kg) plus pemetrexed and carboplatin (or cisplatin) once every 3 weeks. Treatment was given for 4 to 6 cycles, and this was followed by a maintenance phase with pemetrexed or ramucirumab and pemetrexed. The primary endpoint was progression‐free survival (PFS) with a sample size of sufficient power to detect an increase from 7 to 10.4 months.RESULTSFrom October 2010 to October 2011, 140 patients were randomized (pemetrexed‐platinum arm, 71; ramucirumab‐pemetrexed‐platinum arm, 69), and most baseline characteristics were similar for the 2 treatment arms. The median PFS was 5.6 months for the pemetrexed‐platinum arm and 7.2 months for the ramucirumab‐pemetrexed‐platinum arm (hazard ratio, 0.75; P = .132). The objective response rates were 38.0% and 49.3% for the pemetrexed‐platinum and ramucirumab‐pemetrexed‐platinum arms, respectively (P = .180). The disease control rate was 70.4% for the pemetrexed‐platinum arm and 85.5% for the ramucirumab‐pemetrexed‐platinum arm (P = .032). The grade 3 or higher adverse events occurring in 10% or more of patients were thrombocytopenia, neutropenia, fatigue, anemia, nausea, back pain, and hypertension.CONCLUSIONSThe primary endpoint of significant prolongation of PFS was not met; however, ramucirumab showed evidence of clinical activity in combination with pemetrexed and platinum in nonsquamous NSCLC patients. The addition of ramucirumab to pemetrexed and platinum did not result in new or unexpected safety findings. Cancer 2015;121:883–892. © 2014 American Cancer Society.
Decomposition of Perfluorinated Compounds in Water by DC Plasma within Oxygen Bubbles
Authors: Hayashi Ryuichi , Obo Hayato , Takeuchi Nozomi , Yasuoka Koichi 
Published: November 2014

SUMMARYComplete decomposition of perfluorooctanoic acid (PFOA) at a concentration of 41.4 mg/L and perfluorooctane sulfonate (PFOS) at a concentration of 60 mg/L in water was successfully completed by DC plasma within oxygen bubbles. PFOA and PFOS were decomposed completely after 3‐h operation and 8‐h operation, respectively. The decomposition efficiency was evaluated by measuring the amounts of fluorine ions that were detached from PFOA and PFOS in the solution. As indicated by the measurement of LC/MS, the main byproducts generated during the plasma treatment turned out to be perfluorocarboxylic acids. For practical application, 2‐parallel operation of DC plasma was also demonstrated as a basic technology for a large capacity reactor. The decomposition efficiency of 2‐parallel operation was at the same level as that of single operation.
The First Late‐Transition‐Metal Cyclopentadienyl Chelate Complexes with Silylphosphane or Secondary Phosphane Tethers
Authors: Werner Irina , Butenschön Holger 
Published: November 2014

AbstractWhile phosphane‐tethered cyclopentadienyl complexes with tertiary phosphane moieties have extensively been investigated for many metals, this is not the case for such complexes with a secondary phosphane tether. Only a few representatives of such complexes with early‐transition‐metals are known. Here, we report the first late‐transition‐metal cyclopentadienyl chelate complexes with silylphosphane or secondary phosphane tethers. The respective ligand system is generated by nucleophilic opening of spiro[2.4]hepta‐4,6‐diene with lithium tert‐butylphosphide. The anionic ligand is trapped with iron(II) chloride with formation of the respective ferrocene derivative. Treatment of lithium tert‐butylphosphide with tert‐butylchlorodimethylsilane or with chlorotriisopropylsilane affords the respective secondary silylphosphanes. Deprotonation, reaction with spiro[2.4]hepta‐4,6‐diene, followed by treatment with nickel dihalide complexes affords the respective nickel cyclopentadienylalkylsilylphosphane chelates as the first representatives of their kind. Their halide ligands can easily be exchanged by methylation with methyllithium or by reaction with trimethylsilyl cyanide to give the respective cyano chelate. Under the chromatographic conditions applied, this complex undergoes a protiodesilylation to give the first secondary cyclopentadienylalkylphosphane chelate of a late‐transition‐metal, which has been characterized by X‐ray crystallographic analysis. Alternatively, deprotonation of the extremely sterically crowded primary (2,4,6‐tri‐tert‐butylphenyl)phosphane followed by nucleophilic ring opening of spiro[2.4]hepta‐4,6‐diene and reaction of the anionic ligand system with NiBr2(thf)2 directly affords the respective cyclopentadienylalkylphosphane nickel chelate with a secondary phosphane ligand.
Amperometric In Vitro Monitoring of Penetration through Skin Membrane
Authors: Gari Hala , Rembiesa Jadwiga , Masilionis Ignas , Vreva Naida , Svensson Birgitta , Sund Torbjörn , Hansson Henri , Morén Anna Karin , Sjöö Malin , Wahlgren Marie , Engblom Johan , Ruzgas Tautgirdas 
Published: November 2014

AbstractThe aim of this study was to demonstrate that penetration of quercetin, hydrogen peroxide and ascorbic acid through skin membranes can be monitored amperometrically. Skin membrane was fixed on the top of chemically modified electrodes and penetration of the appropriate compound was registered as electrode current. The methodology allows the study of penetration from solution as well as from pharmaceutical creams. From real‐time measurements of electrode current, fluxes and diffusion coefficients of mentioned compounds in skin membranes have been estimated.
Natural stressors in uncontaminated sediments of shallow freshwaters: The prevalence of sulfide, ammonia, and reduced iron
Authors: Kinsman-Costello Lauren E. , O'Brien Jonathan M. , Hamilton Stephen K. 
Published: November 2014

Abstract

Potentially toxic levels of 3 naturally occurring chemical stressors (dissolved sulfide, ammonia, and iron) can appear in freshwater sediments, although their roles in shaping ecosystem structure (i.e., plant and animal communities) and function (e.g., biologically mediated elemental cycles) have received little study. The present critical review discusses the prevalence and ecological effects of potentially toxic concentrations of sulfide, ammonia, and iron in uncontaminated freshwater sediments, including a review of the literature as well as a case study presenting previously unpublished data on sediment porewaters from a diverse set of shallow (&lt;2 m) freshwater ecosystems in southwest Michigan, USA. Measured concentrations are compared with surface water quality criteria established by the US Environmental Protection Agency (USEPA) and with acute and chronic toxic thresholds in the published literature, where available. Based on USEPA criteria for aquatic life for these 3 stressors, the benthic environment of almost every freshwater ecosystem sampled was theoretically stressful to some component of aquatic life in some area or at some time (i.e., in at least 1 sample), and 54% of samples exceeded more than 1 criterion simultaneously. Organismal tolerances to chemical stressors vary, so the observed concentrations are likely shaping benthic animal communities and influencing rates of ecosystem processes. Consideration of the role of natural chemical stressors is important in shaping freshwater benthic environments and in developing bioassessments, restoration goals, and remediation plans. Environ Toxicol Chem 2015;34:467–479. © 2014 SETAC
The mirror neuron system and the strange case of Broca's area
Authors: Cerri Gabriella , Cabinio Monia , Blasi Valeria , Borroni Paola , Iadanza Antonella , Fava Enrica , Fornia Luca , Ferpozzi Valentina , Riva Marco , Casarotti Alessandra , Martinelli Boneschi Filippo , Falini Andrea , Bello Lorenzo 
Published: November 2014

AbstractMirror neurons, originally described in the monkey premotor area F5, are embedded in a frontoparietal network for action execution and observation. A similar Mirror Neuron System (MNS) exists in humans, including precentral gyrus, inferior parietal lobule, and superior temporal sulcus. Controversial is the inclusion of Broca's area, as homologous to F5, a relevant issue in light of the mirror hypothesis of language evolution, which postulates a key role of Broca's area in action/speech perception/production. We assess “mirror” properties of this area by combining neuroimaging and intraoperative neurophysiological techniques. Our results show that Broca's area is minimally involved in action observation and has no motor output on hand or phonoarticulatory muscles, challenging its inclusion in the MNS. The presence of these functions in premotor BA6 makes this area the likely homologue of F5 suggesting that the MNS may be involved in the representation of articulatory rather than semantic components of speech. Hum Brain Mapp 36:1010–1027, 2015. © 2014 Wiley Periodicals, Inc.
3.1.4 SOME LESSONS LEARNED IN REQUIREMENTS MANAGEMENT
Authors: Jones David A. 
Published: November 2014

AbstractSome basic lessons learned, some “heresies,” and some causes of requirement denial are presented with the goal of providing information and food for thought for persons interested in designing requirement management systems. These are based upon practical experience of the author and others.One of the major lessons learned is the advantage of the use of a limited number of analysis documents to control derived, implied, or budgeted requirements. A layered schema made up of alternating specification (hardware/software/process/test) layers and analysis layers has proved ideal for handling all types of requirements.The heresies are some challenges to current strongly held beliefs. Sample heresy is “Just because we can't test it doesn't mean it's not a requirement.”Requirement denial is something like, “That's not a requirement that's just an algorithm we're going to use to meet a requirement.” (The other side of the argument is “If you gotta do it, it's a requirement.”)
2.1.1 THE APPLICATION OF SYSTEMS ENGINEERING TECHNIQUES IN A REGULATORY ENVIRONMENT: NRC HIGH‐LEVEL WASTE REGULATORY PROGRAM
Authors: Mackin Patrick C. , DeWispelare Aaron R. , Brient Robert D. , Johnson Robert L. 
Published: November 2014

AbstractThe Nuclear Regulatory Commission (NRC) and its Federally Funded Research and Development Center, the Center for Nuclear Waste Regulatory Analyses (CNWRA) are streamlining the NRC high‐level radioactive waste (HLW) regulatory program by applying systems engineering (SE) techniques. This effort is partially in response to a statutory mandate requiring a licensing decision for construction of a geologic repository for HLW within three years after license application submission. The tailored use of SE presented herein has evolved from experience gained attempting to apply classical SE techniques to evaluating regulatory compliance. This compliance evaluation is made against the criterion of “reasonable assurance.” The resulting subjectivity prevents a clear definition of a requirements hierarchy and development of specifications. Efforts have been made to streamline the HLW program in the following areas: (i) definition of a regulatory structure for program execution, (ii) provision of regulatory guidance to the license applicant, (iii) provision of guidance to the NRC staff in the form of compliance determination strategies and methods, and (iv) establishment of criteria to support prioritization of technical and regulatory work.
4.2.4 THE ROLE OF MODELING IN THE DEVELOPMENT OF LARGE SYSTEMS
Authors: Hodapp Jonathan M. , Hyer Scott A. 
Published: November 2014

AbstractWhen developing a complex system it is becoming less acceptable to build a prototype or first article without first predicting performance, functionality, form, and fit with a set of models. Models are used to reduce risks by identifying problems early and providing means to trade off candidate solutions. With the relatively recent explosion in computer capabilities, modeling has become more efficient and affordable than ever before. This paper discusses the reasons for using models and the value they add throughout the system life cycle, describes the different levels of modeling, and suggests how models should be developed. A case study from work done by the authors is included to support the general statements made and to demonstrate their practical application.
5.2.3 JUSTIFYING THE INVESTMENT IN SYSTEMS ENGINEERING TOOLS
Authors: Sampson Mark E. 
Published: November 2014

Abstract“Automation Tools for Systems Engineers are good and the right thing to do…” has never been a good enough justification in most companies for purchasing tools for Systems Engineers. Arguments such as “Systems Engineering has been successfully done without automation over the last thousands of years” (the pyramid builders were Systems Engineers or we landed a man on the moon with my slide rule) always took the wind out of our justification sails. Of course the basic response to that argument is that computerized tools are needed to handle the complexity, communication, control, and myriad other issues that Systems Engineers are called upon to design/manage; but we could never quite pin it down financially. This article attempts to gather the appropriate cost/benefit financial justification arguments in one place and presents a framework for dealing with management unbelief.
7.2.2 A Systems Engineering Tools Taxonomy
Authors: Oliver David W. , Steiner Rick 
Published: November 2014

AbstractThe goal of this paper is to provide a classification of tools that may be useful to systems engineers in understanding tool choices for the automation of their work. The material here draws upon input from the NCOSE tools committee members and published work.The tools automate the systems engineering process. Each kind of tool performs particular functions and captures particular sets of information. In this paper the tools are classified into several categories that are helpful in making tool selections. The classification of tools by how they are used is considered in detail through several layers of decomposition.The tool classes defined by classification by use can be mapped to the systems engineering process to show exactly how the tools are used, what functions they perform what information they capture, and how they interface with one another. That mapping is considered in a companion paper. In the sections that follow descriptions are given for:
A general classification of tools
A detailed classification of tools by use
PARAMETER‐BASED REPRESENTATION FOR MODELING COMPLEX SYSTEMS
Authors: Friedenthal Sanford A. 
Published: November 2014

AbstractThis paper describes a concept for a parameter‐based representation (PBR) to model complex systems. The representation combines features from both process and object‐oriented representations including IDEF0, data and control flows, entity relationship attribute (ERA) diagrams, and parameter flows.The parameter‐based approach provides enhanced capability over existing representations because it represents the multiple attributes of a system, including the performance, physical, design, and process parameters, and explicitly defines the relationships between them. This approach enables the systems designer to perform critical analysis and better assess the impact of design decisions and changes on the overall system performance, while maintaining design traceability.The systems engineering process provides the framework for applying PBR to construct and analyze the system model and fully describe the system. The application of a systematic approach using PBR to develop a system model will provide improved ability over current representations to capture critical systems information, analyze complex system interrelationships, and communicate the information among the development team.
1.3.3 Training System Risk Management
Authors: Boggs William B. 
Published: November 2014

AbstractThis paper examines the role of risk management within the training system segment of major weapon system development organizations. Too often the risks associated with the training system are overlooked because the same criterion is used to evaluate all program risks. This approach prohibits technical and programmatic problems associated with the training system from being adequately identified and mitigated early in the weapon system life cycle; thus, adding cost and eliminating technical solutions. The intent of this paper is to increase awareness of the Risk Manager, Systems Engineering Manager, Training System Manager and Program Manager as to the typical approach of training system risk management. Risk management solutions that address training system risk management problems are provided within this paper.
2.3.2 PROGRAM RISK THE BALANCING OF PERFORMANCE, SCHEDULE, AND COST RISKS
Authors: May Charles , Olson Robert 
Published: November 2014

AbstractThis paper addresses the need for a risk management program to provide the program level decision makers a quantitative assessment of the level of risk associated with their program. Included are the characteristics of a suitable indicator of program risk, and one approach for obtaining an assessment of program risk and making adjustments to the level of program risk.
2.3.4 FAILURE MODE ANALYSIS IN SYSTEMS ENGINEERING
Authors: Armstrong James R. 
Published: November 2014

AbstractThe concept of failure mode analysis can be more productively applied than as a critique of the completed detail design. In fact, it can be effectively applied in the initial systems engineering analysis of the desired system requirements and functionality. This takes a little thought and may not be well received by failure analysis purists due to lack of hard failure data as is available for hardware components. However, it can be an effective tool in the systems engineer's bag of tricks.
3.3.3 TEAMING TECHNIQUES DERIVED FROM HUMAN SYSTEMS THEORY: NEUTRALITY, HYPOTHESIZING AND CIRCULARITY
Authors: Alessi R. Samuel , Mayhew Michael E. 
Published: November 2014

AbstractSystems engineers who work effectively with teams of engineers and stakeholders can improve the efficiency of the overall engineering process. This paper discusses techniques that are used by human systems analysts to understand, guide and improve human interaction. Three cooperating principles: neutrality, hypothesizing and circularity, enacted through questioning strategies, are used to understand, validate and intervene in any human interaction situation. An example is given which shows how questioning with the aid of neutrality, hypothesizing and circularity can lessen a confrontational situation and improve human dialogue. A drill is also provided to help systems engineers practice and learn these techniques. If team members can learn these techniques, engineering communications problems will be lessened.
4.1.4 System Engineering in an Integrated Product Team Organization
Authors: Thomas L. Dale 
Published: November 2014

AbstractThis paper presents a discussion of the functions of a system engineering organization in an integrated product team (IPT) setting. IPTs are being adapted widely as a more efficient means for accomplishing large product developments. Recent examples include the US Air Force F‐22 fighter program. Additionally, when management difficulties plagued NASA's Space Station Freedom program, NASA responded by implementing an IPT management structure for the program.A brief review of classical system engineering functions as described by government and academic texts and a resultant synopsis are followed by a brief review of the IPT organizational schema. Subsequent discussion presents a paradigm for system engineering within an IPT setting, and describes the similarity in function of the analysis and integration teams (AITs) within an IPT versus classical systems engineering functions. A conclusion is supported that by controlling the scope of the system engineering task, the function of AITs is comparable to that of classical system engineering organizations. Finally, system engineering within NASA's International Space Station Alpha (ISSA) program is presented as example of a system engineering application within an IPT setting.
4.3.4 COMMON ARCHITECTURE THROUGH REQUIREMENTS MANAGEMENT
Authors: Lukaszewski Matthew S. , Manduley Flavio M. 
Published: November 2014

AbstractAn increasingly important corporate goal has been the development of a process for product architecture which will allow businesses to provide compatible and complimentary products to customers, while increasing the efficiency of the product development cycle and reducing operational and component costs. This paper addresses a process and an automated mechanism for achievement of these goals.
2.2.4 On the Diversity of Process Metrics Users: Identification of Metrics Types and Other Attributes
Authors: Martin James N. 
Published: November 2014

AbstractThis paper explores the relationship between process metrics users and their diverse needs. Twenty metrics user classes and nine basic metrics types are identified. Other attributes of metrics are defined. These metrics types are correlated to the different user classes with regard to their degree of usefulness to each user class. Other attributes such as data tempo, data level of detail and data type are identified for each user class. Three categories of correlation factors are identified that can be used by the metrics analyst and users: normalization factors, quality correlation factors, and cost estimating relationship factors. The degree of usefulness of each correlation factor for the user classes is also identified.
6.2.2 Re‐Engineering of the Metrics Collection Process
Authors: Martin James N. , Miller William D. 
Published: November 2014

AbstractThis paper describes the re‐engineered process for metrics collection in the Advanced Technology Systems sector of AT&T. The previous process was cumbersome for both the metrics data collector and the metrics analyst. Much of the data collected was unusable. The collectors of metrics were frustrated since they spent many hours hunting for the data and it was often difficult to obtain. Therefore, much of the data the metrics analyst needed to do his job was not available. Hence, our major criteria for re‐engineering the process was to simplify the metrics data forms, to minimize the amount of work to be done by the data collector.The major advance was to collect existing cost and schedule data directly from the financial management system (FMS) instead of asking the metrics data collector to provide this. To do this, we developed a means to collect data using an “extraction map” to locate the existing cost/schedule data from the FMS. The new metrics data forms are described along with the streamlined collection and analysis process.