Developmental differences in myocyte contractile response after cardioplegic arrest

AbstractAlthough developmental differences in left ventricular function after cardioplegic arrest and rewarming have been postulated, whether differences exist at the level of the myocyte remains unexplored. This project tested the hypothesis that there is a differential effect of hypothermic hyperkalemic cardioplegic arrest with subsequent rewarming on contractile function of immature compared with adult ventricular myocytes. Myocytes were isolated from the left ventricular free wall of five immature and five adult rabbits and incubated for 2 hours in hyperkalemic modified Ringer's solution at 4° C (cardioplegia) or for 2 hours in cell culture medium at 37° C (normothermia). Myocytes were resuspended (“rewarmed”) in 37° C cell culture medium after the incubation protocol. Normothermic baseline contractile performance was lower in immature, compared with adult, myocytes. Specifically, myocyte shortening velocity was 62 ± 4 μm/sec in immature and 112 ± 6 μm/sec in adult myocytes (p < 0.01). After cardioplegia and rewarming, immature myocyte contractile function was unchanged, whereas adult myocyte contractile function was significantly diminished. For example, myocyte shortening velocity was 65 ± 4 μm/sec in immature and 58 ± 3 μm/sec in adult myocytes (p < 0.01 versus normothermic). Myocyte surface area, which reflects myocyte volume, was increased after cardioplegia and rewarming in adults (3582 ± 55 versus 3316 ± 46 μm2, p < 0.01), but remained unchanged in immature myocytes (2212 ± 27 versus 2285 ± 28 μm2, p = not significant). These unique findings demonstrate a preservation of myocyte contractile function and volume regulation in immature myocytes after cardioplegic arrest and rewarming. Thus this study directly demonstrates that developmental differences exist in myocyte responses to hypothermic hyperkalemic cardioplegic arrest with subsequent rewarming. (J THORAC CARDIOVASC SURG 1996;111:1257-66

Architectural Analysis of Complex Evolving Systems of Systems

The goal of this collaborative project between FC-MD, APL, and GSFC and supported by NASA IV&V Software Assurance Research Program (SARP), was to develop a tool, Dynamic SAVE, or Dyn-SAVE for short, for analyzing architectures of systems of systems. The project team was comprised of the principal investigator (PI) from FC-MD and four other FC-MD scientists (part time) and several FC-MD students (full time), as well as, two APL software architects (part time), and one NASA POC (part time). The PI and FC-MD scientists together with APL architects were responsible for requirements analysis, and for applying and evaluating the Dyn-SAVE tool and method. The PI and a group of FC-MD scientists were responsible for improving the method and conducting outreach activities, while another group of FC-MD scientists were responsible for development and improvement of the tool. Oversight and reporting was conducted by the PI and NASA POC. The project team produced many results including several prototypes of the Dyn-SAVE tool and method, several case studies documenting how the tool and method was applied to APL s software systems, and several published papers in highly respected conferences and journals. Dyn-SAVE as developed and enhanced throughout this research period, is a software tool intended for software developers and architects, software integration testers, and persons who need to analyze software systems from the point of view of how it communicates with other systems. Using the tool, the user specifies the planned communication behavior of the system modeled as a sequence diagram. The user then captures and imports the actual communication behavior of the system, which is then converted and visualized as a sequence diagram by Dyn-SAVE. After mapping the planned to the actual and specifying parameter and timing constraints, Dyn-SAVE detects and highlights deviations between the planned and the actual behavior. Requirements based on the need to analyze two inter-system communication protocols that are representative of protocols used in the Aerospace industry have been specified. The protocols are related: APL s Common Ground System (CGS) as used in the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) and the Radiation Belt Space Probes (RBSP) missions. The analyzed communications were implementations of the Telemetry protocol and the CCSDS File Delivery Protocol (CFDP) protocol. Based on these requirements, three prototypes of Dyn-SAVE were developed and applied to these protocols. The application of Dyn-SAVE to these protocols resulted in the detection of several issues. Dyn-SAVE was also applied to several Testbeds that have previously been used for experimentation earlier on this project, as well as, to other protocols and logs for testing its broader applicability. For example, Dyn-SAVE was used to analyze 1) the communication pattern between a web browser and a web server, 2) the system log of a computer in order to detect offnominal computer shut-down behavior, and 3) the actual test cases of NASA Goddard s Core Flight System (CFS) and automatically generated test cases in order to determine the overlap between the two sets of test cases. In all cases, Dyn-SAVE assisted in providing insightful conclusions about each of the cases identified above

Using Sequence Diagrams to Detect Communication Problems Between Systems

Many software systems are evolving complex system of systems (SoS) for which inter-system communication is both mission-critical and error-prone. Such communication problems ideally would be detected before deployment. In a NASA-supported Software Assurance Research Program (SARP) project, we are researching a new approach addressing such problems. In this paper, we show that problems in the communication between two systems can be detected by using sequence diagrams to model the planned communication and by comparing the planned sequence to the actual sequence. We identify different kinds of problems that can be addressed by modeling the planned sequence using different level of abstractions

Developing an Approach for Analyzing and Verifying System Communication

This slide presentation reviews a project for developing an approach for analyzing and verifying the inter system communications. The motivation for the study was that software systems in the aerospace domain are inherently complex, and operate under tight constraints for resources, so that systems of systems must communicate with each other to fulfill the tasks. The systems of systems requires reliable communications. The technical approach was to develop a system, DynSAVE, that detects communication problems among the systems. The project enhanced the proven Software Architecture Visualization and Evaluation (SAVE) tool to create Dynamic SAVE (DynSAVE). The approach monitors and records low level network traffic, converting low level traffic into meaningful messages, and displays the messages in a way the issues can be detected

Connecting Research and Practice: An Experience Report on Research Infusion with SAVE

NASA systems need to be highly dependable to avoid catastrophic mission failures. This calls for rigorous engineering processes including meticulous validation and verification. However, NASA systems are often highly distributed and overwhelmingly complex, making the software portion of these systems challenging to understand, maintain, change, reuse, and test. NASA's systems are long-lived and the software maintenance process typically constitutes 60-80% of the total cost of the entire lifecycle. Thus, in addition to the technical challenges of ensuring high life-time quality of NASA's systems, the post-development phase also presents a significant financial burden. Some of NASA's software-related challenges could potentially be addressed by some of the many powerful technologies that are being developed in software research laboratories. Many of these research technologies seek to facilitate maintenance and evolution by for example architecting, designing and modeling for quality, flexibility, and reuse. Other technologies attempt to detect and remove defects and other quality issues by various forms of automated defect detection, architecture analysis, and various forms of sophisticated simulation and testing. However promising, most such research technologies nevertheless do not make the transition from the research lab to the software lab. One reason the transition from research to practice seldom occurs is that research infusion and technology transfer is difficult. For example, factors related to the technology are sometimes overshadowed by other types of factors such as reluctance to change and therefore prohibits the technology from sticking. Successful infusion might also take very long time. One famous study showed that the discrepancy between the conception of the idea and its practical use was 18 years plus or minus three. Nevertheless, infusing new technology is possible. We have found that it takes special circumstances for such research infusion to succeed: 1) there must be evidence that the technology works in the practitioner's particular domain, 2) there must be a potential for great improvements and enhanced competitive edge for the practitioner, 3) the practitioner has to have strong individual curiosity and continuous interest in trying out new technologies, 4) the practitioner has to have support on multiple levels (i.e. from the researchers, from management, from sponsors etc), and 5) to remain infused, the new technology has to be integrated into the practitioner's processes so that it becomes a natural part of the daily work. NASA IV&V's Research Infusion initiative sponsored by NASA's Office of Safety & Mission Assurance (OSMA) through the Software Assurance Research Program (SARP), strives to overcome some of the problems related to research infusion

On the exact electric and magnetic fields of an electric dipole

We derive from Jefimenko's equations a multipole expansion in order to obtain the exact expressions for the electric and magnetic fields of an electric dipole with an arbitrary time dependence. A few comments are also made about the usual expositions found in most common undergraduate and graduate textbooks as well as in the literature on this topic

Architecture Analysis of Evolving Complex Systems of Systems (C107)

This viewgraph presentation reviews the analysis of the architecture of complex systems and the development of a tool to assist in the analysis. The goal of the project was to research and develop a tool for architecture analysis of dynamic and static data. The new tool, Dyn-SAVE, was an extension of an already existing static tool, Software Architecture Visualization and Evaluation (SAVE)

Recurrent mutation of IGF signalling genes and distinct patterns of genomic rearrangement in osteosarcoma

Osteosarcoma is a primary malignancy of bone that affects children and adults. Here, we present the largest sequencing study of osteosarcoma to date, comprising 112 childhood and adult tumours encompassing all major histological subtypes. A key finding of our study is the identification of mutations in insulin-like growth factor (IGF) signalling genes in 8/112 (7%) of cases. We validate this observation using fluorescence in situ hybridization (FISH) in an additional 87 osteosarcomas, with IGF1 receptor (IGF1R) amplification observed in 14% of tumours. These findings may inform patient selection in future trials of IGF1R inhibitors in osteosarcoma. Analysing patterns of mutation, we identify distinct rearrangement profiles including a process characterized by chromothripsis and amplification. This process operates recurrently at discrete genomic regions and generates driver mutations. It may represent an age-independent mutational mechanism that contributes to the development of osteosarcoma in children and adults alike

The New Horizons Spacecraft

The New Horizons spacecraft was launched on 19 January 2006. The spacecraft was designed to provide a platform for seven instruments that will collect and return data from Pluto in 2015. The design drew on heritage from previous missions developed at The Johns Hopkins University Applied Physics Laboratory (APL) and other missions such as Ulysses. The trajectory design imposed constraints on mass and structural strength to meet the high launch acceleration needed to reach the Pluto system prior to the year 2020. The spacecraft subsystems were designed to meet tight mass and power allocations, yet provide the necessary control and data handling finesse to support data collection and return when the one-way light time during the Pluto flyby is 4.5 hours. Missions to the outer solar system require a radioisotope thermoelectric generator (RTG) to supply electrical power, and a single RTG is used by New Horizons. To accommodate this constraint, the spacecraft electronics were designed to operate on less than 200 W. The spacecraft system architecture provides sufficient redundancy to provide a probability of mission success of greater than 0.85, even with a mission duration of over 10 years. The spacecraft is now on its way to Pluto, with an arrival date of 14 July 2015. Initial inflight tests have verified that the spacecraft will meet the design requirements.Comment: 33 pages, 13 figures, 4 tables; To appear in a special volume of Space Science Reviews on the New Horizons missio