A Decision Fusion Framework for Treatment Recommendation Systems.

PubMed

Mei, Jing; Liu, Haifeng; Li, Xiang; Xie, Guotong; Yu, Yiqin

2015-01-01

Treatment recommendation is a nontrivial task--it requires not only domain knowledge from evidence-based medicine, but also data insights from descriptive, predictive and prescriptive analysis. A single treatment recommendation system is usually trained or modeled with a limited (size or quality) source. This paper proposes a decision fusion framework, combining both knowledge-driven and data-driven decision engines for treatment recommendation. End users (e.g. using the clinician workstation or mobile apps) could have a comprehensive view of various engines' opinions, as well as the final decision after fusion. For implementation, we leverage several well-known fusion algorithms, such as decision templates and meta classifiers (of logistic and SVM, etc.). Using an outcome-driven evaluation metric, we compare the fusion engine with base engines, and our experimental results show that decision fusion is a promising way towards a more valuable treatment recommendation.

Combinatorial Fusion Analysis for Meta Search Information Retrieval

NASA Astrophysics Data System (ADS)

Hsu, D. Frank; Taksa, Isak

Leading commercial search engines are built as single event systems. In response to a particular search query, the search engine returns a single list of ranked search results. To find more relevant results the user must frequently try several other search engines. A meta search engine was developed to enhance the process of multi-engine querying. The meta search engine queries several engines at the same time and fuses individual engine results into a single search results list. The fusion of multiple search results has been shown (mostly experimentally) to be highly effective. However, the question of why and how the fusion should be done still remains largely unanswered. In this chapter, we utilize the combinatorial fusion analysis proposed by Hsu et al. to analyze combination and fusion of multiple sources of information. A rank/score function is used in the design and analysis of our framework. The framework provides a better understanding of the fusion phenomenon in information retrieval. For example, to improve the performance of the combined multiple scoring systems, it is necessary that each of the individual scoring systems has relatively high performance and the individual scoring systems are diverse. Additionally, we illustrate various applications of the framework using two examples from the information retrieval domain.

Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer. | Office of Cancer Genomics

Cancer.gov

Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in TCGA datasets.

Emerging drugs for hemophilia B.

PubMed

Mannucci, Pier Mannuccio; Franchini, Massimo

2014-09-01

Hemophilia B is a rare congenital bleeding disorder characterized by a deficiency of coagulation factor IX (FIX). Hemophilia B patients experience mild-to-severe bleeding complications according to the degree of FIX defect. Prophylaxis, with regular infusion of FIX concentrates, is nowadays, the mainstay of hemophilia care. However, because the relatively short half-life of such products necessitates frequent infusions and thus makes patients' adherence difficult, a number of strategies have been implemented to improve the pharmacokinetics of FIX clotting factors. This review summarizes the main results of Phase I/II and III studies on new FIX molecules engineered to have a longer half-life. Several technologies are being applied to extend FIX half-life, including Fc fusion, recombinant (r) albumin fusion and the addition of PEG polymers. By prolonging the FIX half-life up to 5 times, long-acting FIX products are expected to substantially improve the management of hemophilia B patients, allowing less frequent infusions and improving patients' adherence to prophylactic regimens and individualized treatments. Some of them are at an advanced stage of development, such as the rFIX-Fc which has been launched in March 2014. Along with the ongoing Phase III trials, long-term post-marketing surveillance studies are needed to assess their safety and effectiveness and their impact on patients' quality of life.

Scalloped Hibachi and Vacuum-Pressure Foil for Electra: Electron Beam Pumped KrF Laser

DTIC Science & Technology

2007-06-01

confinement fusion energy (IFE) applications [1-8]. The foils are a critical part of this durability and efficiency. The electron beam, generated in a high...and A. W. Maschke, “Design descriptions of the Prometheus- L and -H inertial fusion energy drivers,” Fusion Engineering and Design, vol. 25, pp...inertial fusion energy ,” Fusion Engineering and Design, vol. 44, pp. 371-375, March 1999. [4] I. Okuda, e. Takahashi, and Y. Owadano, “A

Demonstration Project for a Multi-Material Lightweight Prototype Vehicle as Part of the Clean Energy Dialogue with Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Skszek, Tim

2015-12-29

The intent of the Multi-Material Lightweight Vehicle (“MMLV”) was to assess the feasibility of achieving a significant level of vehicle mass reduction, enabling engine downsizing resulting in a tangible fuel reduction and environmental benefit. The MMLV project included the development of two (2) lightweight vehicle designs, referred to as Mach-I and Mach-II MMLV variants, based on a 2013 Ford production C/D segment production vehicle (Fusion). Weight comparison, life cycle assessment and limited full vehicle testing are included in the project scope. The Mach-I vehicle variant was comprised of materials and processes that are commercially available or previously demonstrated. The 363more » kg mass reduction associated with the Mach-I design enabled use of a one-liter, three-cylinder, gasoline turbocharged direct injection engine, maintaining the performance and utility of the baseline vehicle. The full MMLV project produced seven (7) MMLV Mach-I “concept vehicles” which were used for testing and evaluation. The full vehicle tests confirmed that MMLV Mach-I concept vehicle performed approximately equivalent to the baseline 2013 Ford Fusion vehicle thereby validating the design of the multi material lightweight vehicle design. The results of the Life Cycle Assessment, conducted by third party consultant, indicated that if the MMLV Mach-I design was built and operated in North America for 250,000 km (155,343 miles) it would produce significant environmental and fuel economy benefits including a 16% reduction in Global Warming Potential (GWP) and 16% reduction in Total Primary Energy (TPE). The LCA calculations estimated the combined fuel economy of 34 mpg (6.9 l/100 km) associated with the MMLV Mach-I Design compared to 28 mpg (8.4 l/100 km) for the 2013 Ford Fusion.« less

Direct Fusion Drive for a Human Mars Orbital Mission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paluszek, Michael; Pajer, Gary; Razin, Yosef

2014-08-01

The Direct Fusion Drive (DFD) is a nuclear fusion engine that produces both thrust and electric power. It employs a field reversed configuration with an odd-parity rotating magnetic field heating system to heat the plasma to fusion temperatures. The engine uses deuterium and helium-3 as fuel and additional deuterium that is heated in the scrape-off layer for thrust augmentation. In this way variable exhaust velocity and thrust is obtained.

Gasdynamic Mirror (GDM) Fusion Propulsion Engine Experiment

NASA Technical Reports Server (NTRS)

1999-01-01

The Gasdynamic Mirror, or GDM, is an example of a magnetic mirror-based fusion propulsion system. Its design is primarily consisting of a long slender solenoid surrounding a vacuum chamber that contains plasma. The bulk of the fusion plasma is confined by magnetic field generated by a series of toroidal-shaped magnets in the center section of the device. the purpose of the GDM Fusion Propulsion Experiment is to confirm the feasibility of the concept and to demonstrate many of the operational characteristics of a full-size plasma can be confined within the desired physical configuration and still reman stable. This image shows an engineer from Propulsion Research Technologies Division at Marshall Space Flight Center inspecting solenoid magnets-A, an integrate part of the Gasdynamic Mirror Fusion Propulsion Engine Experiment.

Inertial Fusion Power Plant Concept of Operations and Maintenance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anklam, T.; Knutson, B.; Dunne, A. M.

2015-01-15

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oilmore » refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.« less

Inertial fusion power plant concept of operations and maintenance

NASA Astrophysics Data System (ADS)

Knutson, Brad; Dunne, Mike; Kasper, Jack; Sheehan, Timothy; Lang, Dwight; Anklam, Tom; Roberts, Valerie; Mau, Derek

2015-02-01

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oil refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.

Life is 3D: Boosting Spheroid Function for Tissue Engineering.

PubMed

Laschke, Matthias W; Menger, Michael D

2017-02-01

Spheroids provide a 3D environment with intensive cell-cell contacts. As a result of their excellent regenerative properties and rapid progress in their high-throughput production, spheroids are increasingly suggested as building blocks for tissue engineering. In this review, we focus on innovative biotechnological approaches that increase the quality of spheroids for this specific type of application. These include in particular the fabrication of coculture spheroids, mimicking the complex morphology and physiological tasks of natural tissues. In vitro preconditioning under different culture conditions and incorporation of biomaterials improve the function of spheroids and their directed fusion into macrotissues of desired shapes. The continuous development of these sophisticated approaches may markedly contribute to a broad implementation of spheroid-based tissue engineering in future regenerative medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

The NASA-JPL advanced propulsion program

NASA Technical Reports Server (NTRS)

Frisbee, Robert H.

1994-01-01

The NASA Advanced Propulsion Concepts (APC) program at the Jet Propulsion Laboratory (JPL) consists of two main areas: The first involves cooperative modeling and research activities between JPL and various universities and industry; the second involves research at universities and industry that is directly supported by JPL. The cooperative research program consists of mission studies, research and development of ion engine technology using C-60 (Buckminsterfullerene) propellant, and research and development of lithium-propellant Lorentz-force accelerator (LFA) engine technology. The university/industry- supported research includes research (modeling and proof-of-concept experiments) in advanced, long-life electric propulsion, and in fusion propulsion. These propulsion concepts were selected primarily to cover a range of applications from near-term to far-term missions. For example, the long-lived pulsed-xenon thruster research that JPL is supporting at Princeton University addresses the near-term need for efficient, long-life attitude control and station-keeping propulsion for Earth-orbiting spacecraft. The C-60-propellant ion engine has the potential for good efficiency in a relatively low specific impulse (Isp) range (10,000 - 30,000 m/s) that is optimum for relatively fast (less than 100 day) cis-lunar (LEO/GEO/Lunar) missions employing near-term, high-specific mass electric propulsion vehicles. Research and modeling on the C-60-ion engine are currently being performed by JPL (engine demonstration), Caltech (C-60 properties), MIT (plume modeling), and USC (diagnostics). The Li-propellant LFA engine also has good efficiency in the modest Isp range (40,000 - 50,000 m/s) that is optimum for near-to-mid-term megawatt-class solar- and nuclear-electric propulsion vehicles used for Mars missions transporting cargo (in support of a piloted mission). Research and modeling on the Li-LFA engine are currently being performed by JPL (cathode development), Moscow Aviation Institute (engine testing), Thermacore (electrode development), as well as at MIT (plume modeling), and USC (diagnostics). Also, the mission performance of a nuclear-electric propulsion (NEP) Li-LFA Mars cargo vehicle is being modeled by JPL (mission analysis; thruster and power processor modeling) and the Rocketdyne Energy Technology and Engineering Center (ETEC) (power system modeling). Finally, the fusion propulsion research activities that JPL is supporting at Pennsylvania State University (PSU) and at Lawrenceville Plasma Physics (LPP) are aimed at far-term fast (less than 100 day round trip) piloted Mars missions and, in the very far term, interstellar missions.

The first IEC fusion industrial neutron generator and developments

NASA Astrophysics Data System (ADS)

Sved, John

1999-06-01

Inertial Electrostatic Confinement fusion grade plasma containment has been sporadically researched since the early 1960's. In the 1990's the work of G. H. Miley and his team at the University of Illinios, Fusion Studies Laboratory, Champaign-Urbana has stimulated a collaboration with industry. The development and test program for the first industrial IEC neutron generator has progressed to the point where an endurance test is under way to demonstrate at least 10,000 hours of operational life of the sealed chamber device without servicing. The market entry goals of steady 107 D-D n/s CW output with an air-cooled system have been achieved. DASA has invested in the development of the industrial product and the continuing basic research at the UI-FSL. The complete DASA FusionStar IEC-PS1 point source neutron generator set is described with emphasis on the interfaces to user NAA systems. The next product developments are pulsed neutron operations and higher fusion reaction rates of up to 1010 by means of affordable add-ons to the basic IEC-PS system. The production engineering experience gained will next be applied to a more challenging line source variant of the IEC. Beyond neutron and proton sources, several other IEC applications are being developed.

Fusion interfaces for tactical environments: An application of virtual reality technology

NASA Technical Reports Server (NTRS)

Haas, Michael W.

1994-01-01

The term Fusion Interface is defined as a class of interface which integrally incorporates both virtual and nonvirtual concepts and devices across the visual, auditory, and haptic sensory modalities. A fusion interface is a multisensory virtually-augmented synthetic environment. A new facility has been developed within the Human Engineering Division of the Armstrong Laboratory dedicated to exploratory development of fusion interface concepts. This new facility, the Fusion Interfaces for Tactical Environments (FITE) Facility is a specialized flight simulator enabling efficient concept development through rapid prototyping and direct experience of new fusion concepts. The FITE Facility also supports evaluation of fusion concepts by operation fighter pilots in an air combat environment. The facility is utilized by a multidisciplinary design team composed of human factors engineers, electronics engineers, computer scientists, experimental psychologists, and oeprational pilots. The FITE computational architecture is composed of twenty-five 80486-based microcomputers operating in real-time. The microcomputers generate out-the-window visuals, in-cockpit and head-mounted visuals, localized auditory presentations, haptic displays on the stick and rudder pedals, as well as executing weapons models, aerodynamic models, and threat models.

Modeling the Removal of Xenon from Lithium Hydrate with Aspen HYSYS

NASA Astrophysics Data System (ADS)

Efthimion, Phillip; Gentile, Charles

2011-10-01

The Laser Inertial Fusion Engine (LIFE) project mission is to provide a long-term, carbon-free source of sustainable energy, in the form of electricity. A conceptual xenon removal system has been modeled with the aid of Aspen HYSYS, a chemical process simulator. Aspen HYSYS provides excellent capability to model chemical flow processes, which generates outputs which includes specific variables such as temperature, pressure, and molar flow. The system is designed to strip out hydrogen isotopes deuterium and tritium. The base design bubbles plasma exhaust laden with x filled with liquid helium. The system separates the xenon from the hydrogen, deuterium, and tritium with a lithium hydrate and a lithium bubbler. After the removal of the hydrogen and its isotopes, the xenon is then purified by way of the process of cryogenic distillation. The pure hydrogen, deuterium, and tritium are then sent to the isotope separation system (ISS). The removal of xenon is an integral part of the laser inertial fusion engine and Aspen HYSYS is an excellent tool to calculate how to create pure xenon.

Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody.

PubMed

Pardridge, William M

2015-02-01

Biologic drugs are large molecules that do not cross the blood- brain barrier (BBB). Brain penetration is possible following the re-engineering of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the fused biologic drug into the brain via receptor-mediated transport on the endogenous BBB TfR. This review discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG-neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG-avidin fusion proteins, as well as BBB transport of bispecific antibodies formed by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also discussed are quantitative aspects of the plasma pharmacokinetics and brain uptake of TfRMAb fusion proteins, as compared to the brain uptake of small molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin fusion proteins for BBB targeted delivery of biotinylated peptide radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety pharmacology of chronic administration of TfRMAb fusion proteins. The BBB delivery of biologic drugs is possible following re-engineering as a fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of this technology will be determined by the outcome of future clinical trials.

Design Considerations for Clean QED Fusion Propulsion Systems

NASA Astrophysics Data System (ADS)

Bussard, Robert W.; Jameson, Lorin W.

1994-07-01

The direct production of electric power appears possible from fusion reactions between fuels whose products consist solely of charged particles and thus do not present radiation hazards from energetic neutron production, as do reactions involving deuteron-bearing fuels. Among these are the fuels p, 11B, 3He, and 6Li. All of these can be ``burned'' in inertial-electrostatic-fusion (IEF) devices to power QED fusion-electric rocket engines. These IEF sources provide direct-converted electrical power at high voltage (MeV) to drive e-beams for efficient propellant heating to extreme temperatures, with resulting high specific impulse performance capabilities. IEF/QED engine systems using p11B can outperform all other advanced concepts for controlled fusion propulsion by 2-3 orders of magnitude, while 6Li6Li fusion yields one order of magnitude less advance. Either of these fusion rocket propulsion systems can provide very rapid transit for solar system missions, with high payload fractions in single-stage vehicles. The 3He3He reaction can not be used practically for direct electric conversion because of the wide spread in energy of its fusion products. However, it may eventually prove useful for thermal/electrical power generation in central station power plants, or for direct-fusion-product (DFP) propellant heatingin advanced deep-space rocket engines.

Department of Defense Instrumentation Award.

DTIC Science & Technology

1985-07-01

Office of Scientific Research Prepared by The Electrical Engineering Department and The Laboratory for Plasma and Fusion Energy Studies University of...Electrical Engineering Department Laboratory for Plasma and Fusion Energy Studies University of Maryland College Park, Maryland 20742 Principal Investigator

Fusion Power—A Chemical Engineering View of the Integrated Enterprise

NASA Astrophysics Data System (ADS)

Manganaro, James L.

2003-03-01

The purpose of this article was to achieve the beginning of an understanding of the integrated fusion enterprise from raw materials through power generation to decommissioning and waste disposal. The particular view point is that of a technically trained person who is only casually acquainted with the field. Emphasis is given to the chemical engineering aspects of controlled fusion power. It is concluded that there are indeed many areas in which the discipline of chemical engineering may contribute to the fusion effort. These areas include separation technology by physical and chemical means, heat and mass transfer in a packed bed blanket, tritium removal from molten coolants, distillation technology for isotope separation, and preparation of deuterium and lithium feed materials.

Revitalizing Fusion via Fission Fusion

NASA Astrophysics Data System (ADS)

Manheimer, Wallace

2001-10-01

Existing tokamaks could generate significant nuclear fuel. TFTR, operating steady state with DT might generate enough fuel for a 300 MW nuclear reactor. The immediate goals of the magnetic fusion program would necessarily shift from a study of advanced plasma regimes in larger sized devices, to mostly known plasmas regimes, but at steady state or high duty cycle operation in DT plasmas. The science and engineering of breeding blankets would be equally important. Follow on projects could possibly produce nuclear fuel in large quantity at low price. Although today there is strong opposition to nuclear power in the United States, in a 21st century world of 10 billion people, all of whom will demand a middle class life style, nuclear energy will be important. Concern over greenhouse gases will also drive the world toward nuclear power. There are studies indicating that the world will need 10 TW of carbon free energy by 2050. It is difficult to see how this can be achieved without the breeding of nuclear fuel. By using the thorium cycle, proliferation risks are minimized. [1], [2]. 1 W. Manheimer, Fusion Technology, 36, 1, 1999, 2.W. Manheimer, Physics and Society, v 29, #3, p5, July, 2000

Engineering and Functional Characterization of Fusion Genes Identifies Novel Oncogenic Drivers of Cancer.

PubMed

Lu, Hengyu; Villafane, Nicole; Dogruluk, Turgut; Grzeskowiak, Caitlin L; Kong, Kathleen; Tsang, Yiu Huen; Zagorodna, Oksana; Pantazi, Angeliki; Yang, Lixing; Neill, Nicholas J; Kim, Young Won; Creighton, Chad J; Verhaak, Roel G; Mills, Gordon B; Park, Peter J; Kucherlapati, Raju; Scott, Kenneth L

2017-07-01

Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK , and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in The Cancer Genome Atlas datasets. In addition to confirming oncogenic activity of the known fusion oncogenes engineered by our construction strategy, we validated five novel fusion genes involving MET, NTRK2 , and BRAF kinases that exhibited potent transforming activity and conferred sensitivity to FDA-approved kinase inhibitors. Our fusion construction strategy also enabled domain-function studies of BRAF fusion genes. Our results confirmed other reports that the transforming activity of BRAF fusions results from truncation-mediated loss of inhibitory domains within the N-terminus of the BRAF protein. BRAF mutations residing within this inhibitory region may provide a means for BRAF activation in cancer, therefore we leveraged the modular design of our fusion gene construction methodology to screen N-terminal domain mutations discovered in tumors that are wild-type at the BRAF mutation hotspot, V600. We identified an oncogenic mutation, F247L, whose expression robustly activated the MAPK pathway and sensitized cells to BRAF and MEK inhibitors. When applied broadly, these tools will facilitate rapid fusion gene construction for subsequent functional characterization and translation into personalized treatment strategies. Cancer Res; 77(13); 3502-12. ©2017 AACR . ©2017 American Association for Cancer Research.

Women's experiences of daily life after anterior cervical decompression and fusion surgery: A qualitative interview study.

PubMed

Hermansen, Anna; Peolsson, Anneli; Kammerlind, Ann-Sofi; Hjelm, Katarina

2016-04-01

To explore and describe women's experiences of daily life after anterior cervical decompression and fusion surgery. Qualitative explorative design. Fourteen women aged 39-62 years (median 52 years) were included 1.5-3 years after anterior cervical decompression and fusion for cervical disc disease. Individual semi-structured interviews were analysed by qualitative content analysis with an inductive approach. The women described their experiences of daily life in 5 different ways: being recovered to various extents; impact of remaining symptoms on thoughts and feelings; making daily life work; receiving support from social and occupational networks; and physical and behavioural changes due to interventions and encounters with healthcare professionals. This interview study provides insight into women's daily life after anterior cervical decompression and fusion. Whilst the subjects improved after surgery, they also experienced remaining symptoms and limitations in daily life. A variety of mostly active coping strategies were used to manage daily life. Social support from family, friends, occupational networks and healthcare professionals positively influenced daily life. These findings provide knowledge about aspects of daily life that should be considered in individualized postoperative care and rehabilitation in an attempt to provide better outcomes in women after anterior cervical decompression and fusion.

Self-recognition in corals facilitates deep-sea habitat engineering

USGS Publications Warehouse

Hennige, Sebastian J; Morrison, Cheryl L.; Form, Armin U.; Buscher, Janina; Kamenos, Nicholas A.; Roberts, J. Murray

2014-01-01

The ability of coral reefs to engineer complex three-dimensional habitats is central to their success and the rich biodiversity they support. In tropical reefs, encrusting coralline algae bind together substrates and dead coral framework to make continuous reef structures, but beyond the photic zone, the cold-water coral Lophelia pertusa also forms large biogenic reefs, facilitated by skeletal fusion. Skeletal fusion in tropical corals can occur in closely related or juvenile individuals as a result of non-aggressive skeletal overgrowth or allogeneic tissue fusion, but contact reactions in many species result in mortality if there is no ‘self-recognition’ on a broad species level. This study reveals areas of ‘flawless’ skeletal fusion in Lophelia pertusa, potentially facilitated by allogeneic tissue fusion, are identified as having small aragonitic crystals or low levels of crystal organisation, and strong molecular bonding. Regardless of the mechanism, the recognition of ‘self’ between adjacent L. pertusa colonies leads to no observable mortality, facilitates ecosystem engineering and reduces aggression-related energetic expenditure in an environment where energy conservation is crucial. The potential for self-recognition at a species level, and subsequent skeletal fusion in framework-forming cold-water corals is an important first step in understanding their significance as ecological engineers in deep-seas worldwide.

Adjoint-Based Implicit Uncertainty Analysis for Figures of Merit in a Laser Inertial Fusion Engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seifried, J E; Fratoni, M; Kramer, K J

A primary purpose of computational models is to inform design decisions and, in order to make those decisions reliably, the confidence in the results of such models must be estimated. Monte Carlo neutron transport models are common tools for reactor designers. These types of models contain several sources of uncertainty that propagate onto the model predictions. Two uncertainties worthy of note are (1) experimental and evaluation uncertainties of nuclear data that inform all neutron transport models and (2) statistical counting precision, which all results of a Monte Carlo codes contain. Adjoint-based implicit uncertainty analyses allow for the consideration of anymore » number of uncertain input quantities and their effects upon the confidence of figures of merit with only a handful of forward and adjoint transport calculations. When considering a rich set of uncertain inputs, adjoint-based methods remain hundreds of times more computationally efficient than Direct Monte-Carlo methods. The LIFE (Laser Inertial Fusion Energy) engine is a concept being developed at Lawrence Livermore National Laboratory. Various options exist for the LIFE blanket, depending on the mission of the design. The depleted uranium hybrid LIFE blanket design strives to close the fission fuel cycle without enrichment or reprocessing, while simultaneously achieving high discharge burnups with reduced proliferation concerns. Neutron transport results that are central to the operation of the design are tritium production for fusion fuel, fission of fissile isotopes for energy multiplication, and production of fissile isotopes for sustained power. In previous work, explicit cross-sectional uncertainty analyses were performed for reaction rates related to the figures of merit for the depleted uranium hybrid LIFE blanket. Counting precision was also quantified for both the figures of merit themselves and the cross-sectional uncertainty estimates to gauge the validity of the analysis. All cross-sectional uncertainties were small (0.1-0.8%), bounded counting uncertainties, and were precise with regard to counting precision. Adjoint/importance distributions were generated for the same reaction rates. The current work leverages those adjoint distributions to transition from explicit sensitivities, in which the neutron flux is constrained, to implicit sensitivities, in which the neutron flux responds to input perturbations. This treatment vastly expands the set of data that contribute to uncertainties to produce larger, more physically accurate uncertainty estimates.« less

We have AN Increasing Need to Model Ourselves

NASA Astrophysics Data System (ADS)

Farmer, J. Doyne

Pierre Teilhard de Chardin referred to the fusion of biological life, human culture, and technology as the noosphere. Technological improvement is causing the noosphere to evolve rapidly, driving the enormous increase in human population over the last 10,000 years and the transformation (and devastation) of the biosphere. The rapid proliferation of the internet is changing human culture, including everything from the way we find mates to the way democracy functions, or fails to function. The emergence of the BINC (Bio, Info, Nano, Cogno) technologies promises to further accelerate this change. We are acquiring an ever-increasing ability to engineer devices at a molecular level, to control the genome, and to create new forms of life and intelligence...

Energy Logic (EL): a novel fusion engine of multi-modality multi-agent data/information fusion for intelligent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2009-04-01

The rapidly advancing hardware technology, smart sensors and sensor networks are advancing environment sensing. One major potential of this technology is Large-Scale Surveillance Systems (LS3) especially for, homeland security, battlefield intelligence, facility guarding and other civilian applications. The efficient and effective deployment of LS3 requires addressing number of aspects impacting the scalability of such systems. The scalability factors are related to: computation and memory utilization efficiency, communication bandwidth utilization, network topology (e.g., centralized, ad-hoc, hierarchical or hybrid), network communication protocol and data routing schemes; and local and global data/information fusion scheme for situational awareness. Although, many models have been proposed to address one aspect or another of these issues but, few have addressed the need for a multi-modality multi-agent data/information fusion that has characteristics satisfying the requirements of current and future intelligent sensors and sensor networks. In this paper, we have presented a novel scalable fusion engine for multi-modality multi-agent information fusion for LS3. The new fusion engine is based on a concept we call: Energy Logic. Experimental results of this work as compared to a Fuzzy logic model strongly supported the validity of the new model and inspired future directions for different levels of fusion and different applications.

The life cycle of platelet granules.

PubMed

Sharda, Anish; Flaumenhaft, Robert

2018-01-01

Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans -Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

Engineered three-dimensional multicellular culture model to recapitulate morphogenetic fusion using human cells

EPA Science Inventory

Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in...

A direct fusion drive for rocket propulsion

NASA Astrophysics Data System (ADS)

Razin, Yosef S.; Pajer, Gary; Breton, Mary; Ham, Eric; Mueller, Joseph; Paluszek, Michael; Glasser, Alan H.; Cohen, Samuel A.

2014-12-01

The Direct Fusion Drive (DFD), a compact, anuetronic fusion engine, will enable more challenging exploration missions in the solar system. The engine proposed here uses a deuterium-helium-3 reaction to produce fusion energy by employing a novel field-reversed configuration (FRC) for magnetic confinement. The FRC has a simple linear solenoid coil geometry yet generates higher plasma pressure, hence higher fusion power density, for a given magnetic field strength than other magnetic-confinement plasma devices. Waste heat generated from the plasma's Bremsstrahlung and synchrotron radiation is recycled to maintain the fusion temperature. The charged reaction products, augmented by additional propellant, are exhausted through a magnetic nozzle. A 1 MW DFD is presented in the context of a mission to deploy the James Webb Space Telescope (6200 kg) from GPS orbit to a Sun-Earth L2 halo orbit in 37 days using just 353 kg of propellant and about half a kilogram of 3He. The engine is designed to produce 40 N of thrust with an exhaust velocity of 56.5 km/s and has a specific power of 0.18 kW/kg.

A new vision for fusion energy research: Fusion rocket engines for planetary defense

DOE PAGES

Wurden, G. A.; Weber, T. E.; Turchi, P. J.; ...

2015-11-16

Here, we argue that it is essential for the fusion energy program to identify an imagination-capturing critical mission by developing a unique product which could command the marketplace. We lay out the logic that this product is a fusion rocket engine, to enable a rapid response capable of deflecting an incoming comet, to prevent its impact on the planet Earth, in defense of our population, infrastructure, and civilization. As a side benefit, deep space solar system exploration, with greater speed and orders-of-magnitude greater payload mass would also be possible.

A new vision for fusion energy research: Fusion rocket engines for planetary defense

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wurden, G. A.; Weber, T. E.; Turchi, P. J.

Here, we argue that it is essential for the fusion energy program to identify an imagination-capturing critical mission by developing a unique product which could command the marketplace. We lay out the logic that this product is a fusion rocket engine, to enable a rapid response capable of deflecting an incoming comet, to prevent its impact on the planet Earth, in defense of our population, infrastructure, and civilization. As a side benefit, deep space solar system exploration, with greater speed and orders-of-magnitude greater payload mass would also be possible.

In vitro assay using engineered yeast vacuoles for neuronal SNARE-mediated membrane fusion

PubMed Central

Ko, Young-Joon; Lee, Miriam; Kang, KyeongJin; Song, Woo Keun; Jun, Youngsoo

2014-01-01

Intracellular membrane fusion requires not only SNARE proteins but also other regulatory proteins such as the Rab and Sec1/Munc18 (SM) family proteins. Although neuronal SNARE proteins alone can drive the fusion between synthetic liposomes, it remains unclear whether they are also sufficient to induce the fusion of biological membranes. Here, through the use of engineered yeast vacuoles bearing neuronal SNARE proteins, we show that neuronal SNAREs can induce membrane fusion between yeast vacuoles and that this fusion does not require the function of the Rab protein Ypt7p or the SM family protein Vps33p, both of which are essential for normal yeast vacuole fusion. Although excess vacuolar SNARE proteins were also shown to mediate Rab-bypass fusion, this fusion required homotypic fusion and vacuole protein sorting complex, which bears Vps33p and was accompanied by extensive membrane lysis. We also show that this neuronal SNARE-driven vacuole fusion can be stimulated by the neuronal SM protein Munc18 and blocked by botulinum neurotoxin serotype E, a well-known inhibitor of synaptic vesicle fusion. Taken together, our results suggest that neuronal SNARE proteins are sufficient to induce biological membrane fusion, and that this new assay can be used as a simple and complementary method for investigating synaptic vesicle fusion mechanisms. PMID:24821814

External Heat Transfer Coefficient Measurements on a Surrogate Indirect Inertial Confinement Fusion Target

DOE PAGES

Miles, Robin; Havstad, Mark; LeBlanc, Mary; ...

2015-09-15

External heat transfer coefficients were measured around a surrogate Indirect inertial confinement fusion (ICF) based on the Laser Inertial Fusion Energy (LIFE) design target to validate thermal models of the LIFE target during flight through a fusion chamber. Results indicate that heat transfer coefficients for this target 25-50 W/m 2∙K are consistent with theoretically derived heat transfer coefficients and valid for use in calculation of target heating during flight through a fusion chamber.

The ring of life provides evidence for a genome fusion origin of eukaryotes.

PubMed

Rivera, Maria C; Lake, James A

2004-09-09

Genomes hold within them the record of the evolution of life on Earth. But genome fusions and horizontal gene transfer seem to have obscured sufficiently the gene sequence record such that it is difficult to reconstruct the phylogenetic tree of life. Here we determine the general outline of the tree using complete genome data from representative prokaryotes and eukaryotes and a new genome analysis method that makes it possible to reconstruct ancient genome fusions and phylogenetic trees. Our analyses indicate that the eukaryotic genome resulted from a fusion of two diverse prokaryotic genomes, and therefore at the deepest levels linking prokaryotes and eukaryotes, the tree of life is actually a ring of life. One fusion partner branches from deep within an ancient photosynthetic clade, and the other is related to the archaeal prokaryotes. The eubacterial organism is either a proteobacterium, or a member of a larger photosynthetic clade that includes the Cyanobacteria and the Proteobacteria.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Chapman, J.; Fincher, S.; Philips, A.; Polsgrove, T.

2003-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Basic operation of an MTF propulsion system is introduced. Structural, thermal, radiation-management and electrical design details are presented. The propellant storage and supply system design is also presented. A propulsion system mass estimate and associated performance figures are given. The advantages of helium-3 as a fusion fuel for an advanced MTF system are discussed.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Fincher, S.; Polsgrove, T.; Chapman, J.; Philips, A.

2002-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Structural, thermal and radiation-management design details are presented. Propellant storage and supply options are also discussed and a propulsion system mass estimate is given.

Computer-aided endovascular aortic repair using fully automated two- and three-dimensional fusion imaging.

PubMed

Panuccio, Giuseppe; Torsello, Giovanni Federico; Pfister, Markus; Bisdas, Theodosios; Bosiers, Michel J; Torsello, Giovanni; Austermann, Martin

2016-12-01

To assess the usability of a fully automated fusion imaging engine prototype, matching preinterventional computed tomography with intraoperative fluoroscopic angiography during endovascular aortic repair. From June 2014 to February 2015, all patients treated electively for abdominal and thoracoabdominal aneurysms were enrolled prospectively. Before each procedure, preoperative planning was performed with a fully automated fusion engine prototype based on computed tomography angiography, creating a mesh model of the aorta. In a second step, this three-dimensional dataset was registered with the two-dimensional intraoperative fluoroscopy. The main outcome measure was the applicability of the fully automated fusion engine. Secondary outcomes were freedom from failure of automatic segmentation or of the automatic registration as well as accuracy of the mesh model, measuring deviations from intraoperative angiography in millimeters, if applicable. Twenty-five patients were enrolled in this study. The fusion imaging engine could be used in successfully 92% of the cases (n = 23). Freedom from failure of automatic segmentation was 44% (n = 11). The freedom from failure of the automatic registration was 76% (n = 19), the median error of the automatic registration process was 0 mm (interquartile range, 0-5 mm). The fully automated fusion imaging engine was found to be applicable in most cases, albeit in several cases a fully automated data processing was not possible, requiring manual intervention. The accuracy of the automatic registration yielded excellent results and promises a useful and simple to use technology. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The VISTA spacecraft: Advantages of ICF (Inertial Confinement Fusion) for interplanetary fusions propulsion applications

NASA Technical Reports Server (NTRS)

Orth, Charles D.; Klein, Gail; Sercel, Joel; Hoffman, Nate; Murray, Kathy; Chang-Diaz, Franklin

1987-01-01

Inertial Confinement Fusion (ICF) is an attractive engine power source for interplanetary manned spacecraft, especially for near-term missions requiring minimum flight duration, because ICF has inherent high power-to-mass ratios and high specific impulses. We have developed a new vehicle concept called VISTA that uses ICF and is capable of round-trip manned missions to Mars in 100 days using A.D. 2020 technology. We describe VISTA's engine operation, discuss associated plasma issues, and describe the advantages of DT fuel for near-term applications. Although ICF is potentially superior to non-fusion technologies for near-term interplanetary transport, the performance capabilities of VISTA cannot be meaningfully compared with those of magnetic-fusion systems because of the lack of a comparable study of the magnetic-fusion systems. We urge that such a study be conducted.

Engineering Considerations for the Self-Energizing Magnetoplasmadynamic (MPD)-Type Fusion Plasma Thruster

DTIC Science & Technology

1992-02-01

Feasibility studies Of dense plasma focus (DPF) device as a fusion propulsion thruster have been performed. Both conventional and spin-polarized D...uncertainties remain in the validity of scaling laws on capacitor mass at high current beyond 1 MA. Fusion Propulsion, Dense Plasma Focus , Magnetoplasmadynamic Thruster, Advanced Fuel, D-3He Fusion, Spin-Polarized Fusion.

Fragmentation, Fusion, and Genetic Homogeneity in a Calcareous Sponge (Porifera, Calcarea).

PubMed

Padua, André; Leocorny, Pedro; Custódio, Márcio Reis; Klautau, Michelle

2016-06-01

Sessile marine invertebrates living on hard substrata usually present strategies such as size variations, longer life spans, fragmentation and fusion to occupy and compete for space. Calcareous sponges are usually small and short-lived, and some species are known to undergo frequent fragmentation and fusion events. However, whether fusion occurs only between genetically identical individuals remains unclear. We investigated the occurrence of chimaeras in the calcareous sponge Clathrina aurea by following the dynamics of fragmentation and fusion of 66 individuals in the field for up to 18 months and determined size variations and the life span of each individual. Microsatellites were used to determine whether fusion events occur among genetically different individuals. Growth and shrinkage of individuals were frequently observed, showing that size cannot be associated with age in C. aurea. The life span of the species ranged from 1 to 16 months (mean: 4.7 months). Short life spans and variable growth rates have been observed in other species of the class Calcarea. Fragmentation and fusion events were observed, but fusion events always occurred between genetically identical individuals, as has been suggested by graft experiments in adult Demospongiae and other Calcarea. These results suggest that at least C. aurea adults may have some mechanism to avoid chimaerism. © 2016 Wiley Periodicals, Inc.

Newly Engineered Magnetic Erythrocytes for Sustained and Targeted Delivery of Anti-Cancer Therapeutic Compounds

PubMed Central

Taranta, Monia; Naldi, Ilaria

2011-01-01

Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the target cells and to efficiently release therapeutic compounds inside the cells. The efficacy of the anti-cancer drug employed is increased and the dose required is 10 time less than that needed with conventional therapy. PMID:21373641

Engineering Globular Protein Vesicles through Tunable Self-Assembly of Recombinant Fusion Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, Yeongseon; Choi, Won Tae; Heller, William T.

Vesicles assembled from folded, globular proteins have potential for functions different from traditional lipid or polymeric vesicles. However, they also present challenges in understanding the assembly process and controlling vesicle properties. From detailed investigation of the assembly behavior of recombinant fusion proteins, this work reports a simple strategy to engineer protein vesicles containing functional, globular domains. This is achieved through tunable self-assembly of recombinant globular fusion proteins containing leucine zippers and elastin-like polypeptides. The fusion proteins form complexes in solution via high affinity binding of the zippers, and transition through dynamic coacervates to stable hollow vesicles upon warming. The thermalmore » driving force, which can be tuned by protein concentration or temperature, controls both vesicle size and whether vesicles are single or bi-layered. Lastly, these results provide critical information to engineer globular protein vesicles via self-assembly with desired size and membrane structure.« less

Engineering Globular Protein Vesicles through Tunable Self-Assembly of Recombinant Fusion Proteins

DOE PAGES

Jang, Yeongseon; Choi, Won Tae; Heller, William T.; ...

2017-07-27

Vesicles assembled from folded, globular proteins have potential for functions different from traditional lipid or polymeric vesicles. However, they also present challenges in understanding the assembly process and controlling vesicle properties. From detailed investigation of the assembly behavior of recombinant fusion proteins, this work reports a simple strategy to engineer protein vesicles containing functional, globular domains. This is achieved through tunable self-assembly of recombinant globular fusion proteins containing leucine zippers and elastin-like polypeptides. The fusion proteins form complexes in solution via high affinity binding of the zippers, and transition through dynamic coacervates to stable hollow vesicles upon warming. The thermalmore » driving force, which can be tuned by protein concentration or temperature, controls both vesicle size and whether vesicles are single or bi-layered. Lastly, these results provide critical information to engineer globular protein vesicles via self-assembly with desired size and membrane structure.« less

Advanced Fusion Reactors for Space Propulsion and Power Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, John J.

In recent years the methodology proposed for conversion of light elements into energy via fusion has made steady progress. Scientific studies and engineering efforts in advanced fusion systems designs have introduced some new concepts with unique aspects including consideration of Aneutronic fuels. The plant parameters for harnessing aneutronic fusion appear more exigent than those required for the conventional fusion fuel cycle. However aneutronic fusion propulsion plants for Space deployment will ultimately offer the possibility of enhanced performance from nuclear gain as compared to existing ionic engines as well as providing a clean solution to Planetary Protection considerations and requirements. Protonmore » triggered 11Boron fuel (p- 11B) will produce abundant ion kinetic energy for In-Space vectored thrust. Thus energetic alpha particles' exhaust momentum can be used directly to produce high Isp thrust and also offer possibility of power conversion into electricity. p-11B is an advanced fusion plant fuel with well understood reaction kinematics but will require some new conceptual thinking as to the most effective implementation.« less

Advanced Fusion Reactors for Space Propulsion and Power Systems

NASA Technical Reports Server (NTRS)

Chapman, John J.

2011-01-01

In recent years the methodology proposed for conversion of light elements into energy via fusion has made steady progress. Scientific studies and engineering efforts in advanced fusion systems designs have introduced some new concepts with unique aspects including consideration of Aneutronic fuels. The plant parameters for harnessing aneutronic fusion appear more exigent than those required for the conventional fusion fuel cycle. However aneutronic fusion propulsion plants for Space deployment will ultimately offer the possibility of enhanced performance from nuclear gain as compared to existing ionic engines as well as providing a clean solution to Planetary Protection considerations and requirements. Proton triggered 11Boron fuel (p- 11B) will produce abundant ion kinetic energy for In-Space vectored thrust. Thus energetic alpha particles "exhaust" momentum can be used directly to produce high ISP thrust and also offer possibility of power conversion into electricity. p- 11B is an advanced fusion plant fuel with well understood reaction kinematics but will require some new conceptual thinking as to the most effective implementation.

A Foreign Object Damage Event Detector Data Fusion System for Turbofan Engines

NASA Technical Reports Server (NTRS)

Turso, James A.; Litt, Jonathan S.

2004-01-01

A Data Fusion System designed to provide a reliable assessment of the occurrence of Foreign Object Damage (FOD) in a turbofan engine is presented. The FOD-event feature level fusion scheme combines knowledge of shifts in engine gas path performance obtained using a Kalman filter, with bearing accelerometer signal features extracted via wavelet analysis, to positively identify a FOD event. A fuzzy inference system provides basic probability assignments (bpa) based on features extracted from the gas path analysis and bearing accelerometers to a fusion algorithm based on the Dempster-Shafer-Yager Theory of Evidence. Details are provided on the wavelet transforms used to extract the foreign object strike features from the noisy data and on the Kalman filter-based gas path analysis. The system is demonstrated using a turbofan engine combined-effects model (CEM), providing both gas path and rotor dynamic structural response, and is suitable for rapid-prototyping of control and diagnostic systems. The fusion of the disparate data can provide significantly more reliable detection of a FOD event than the use of either method alone. The use of fuzzy inference techniques combined with Dempster-Shafer-Yager Theory of Evidence provides a theoretical justification for drawing conclusions based on imprecise or incomplete data.

Field-Reversed Configuration Power Plant Critical-Issue Scoping Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santarius, J. F.; Mogahed, E. A.; Emmert, G. A.

A team from the Universities of Wisconsin, Washington, and Illinois performed an engineering scoping study of critical issues for field-reversed configuration (FRC) power plants. The key tasks for this research were (1) systems analysis for deuterium-tritium (D-T) FRC fusion power plants, and (2) conceptual design of the blanket and shield module for an FRC fusion core. For the engineering conceptual design of the fusion core, the project team focused on intermediate-term technology. For example, one decision was to use steele structure. The FRC systems analysis led to a fusion power plant with attractive features including modest size, cylindrical symmetry, goodmore » thermal efficiency (52%), relatively easy maintenance, and a high ratio of electric power to fusion core mass, indicating that it would have favorable economics.« less

The fusion of biology, computer science, and engineering: towards efficient and successful synthetic biology.

PubMed

Linshiz, Gregory; Goldberg, Alex; Konry, Tania; Hillson, Nathan J

2012-01-01

Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.

Simulation and Analysis of Isotope Separation System for Fusion Fuel Recovery System

NASA Astrophysics Data System (ADS)

Senevirathna, Bathiya; Gentile, Charles

2011-10-01

This paper presents results of a simulation of the Fuel Recovery System (FRS) for the Laser Inertial Fusion Engine (LIFE) reactor. The LIFE reaction will produce exhaust gases that will need to be recycled in the FRS along with xenon, the chamber's intervention gas. Solids and liquids will first be removed and then vapor traps are used to remove large gas molecules such as lead. The gas will be reacted with lithium at high temperatures to extract the hydrogen isotopes, protium, deuterium, and tritium in hydride form. The hydrogen isotopes will be recovered using a lithium blanket processing system already in place and this product will be sent to the Isotope Separation System (ISS). The ISS will be modeled in software to analyze its effectiveness. Aspen HYSYS was chosen for this purpose for its widespread use industrial gas processing systems. Reactants and corresponding chemical reactions had to be initialized in the software. The ISS primarily consists of four cryogenic distillation columns and these were modeled in HYSYS based on design requirements. Fractional compositions of the distillate and liquid products were analyzed and used to optimize the overall system.

Comparison of the Recently proposed Super Marx Generator Approach to Thermonuclear Ignition with the DT Laser Fusion-Fission Hybrid Concept (LIFE) by the Lawrence Livermore National Laboratory.

NASA Astrophysics Data System (ADS)

Winterberg, Friedwardt

2009-05-01

The recently proposed Super Marx pure deuterium micro-detonation ignition concept [1] is compared to the Lawrence Livermore National Ignition Facility (NIF) laser DT fusion-fission hybrid concept (LIFE) [2]. A typical example of the LIFE concept is a fusion gain 30, and a fission gain of 10, making up for a total gain of 300, with about 10 times more energy released into fission as compared to fusion. This means a substantial release of fission products, as in fusion-less pure fission reactors. In the Super Marx approach for the ignition of a pure deuterium micro-detonation gains of the same magnitude can in theory be reached. If the theoretical prediction can be supported by more elaborate calculations, the Super Marx approach is likely to make lasers obsolete as a means for the ignition of thermonuclear micro-explosions. [1] ``Ignition of a Deuterium Micro-Detonation with a Gigavolt Super Marx Generator,'' Winterberg, F., Journal of Fusion Energy, Springer, 2008. http://www.springerlink.com/content/r2j046177j331241/fulltext.pdf. [2] ``LIFE: Clean Energy from Nuclear Waste,'' https://lasers.llnl.gov/missions/energy&_slash;for&_slash;the&_slash;future/life/

Optimization of the SHX Fusion Powered Transatmospheric Propulsion Concept

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Landrum, D. Brian

2001-01-01

Existing propulsion technology has not achieved cost effective payload delivery rates to low earth orbit. A fusion based propulsion system, denoted as the Simultaneous Heating and eXpansion (SHX) engine, has been proposed in earlier papers. The SHX couples energy generated by a fusion reactor to the engine flowpath by use of coherent beam emitters. A quasi-one-dimensional flow model was used to quantify the effects of area expansion and energy input on propulsive efficiency for several beam models. Entropy calculations were included to evaluate the lost work in the system.

Finding Patterns of Emergence in Science and Technology

DTIC Science & Technology

2012-09-24

formal evaluation scheduled – Case Studies, Eight Examples: Tissue Engineering, Cold Fusion, RF Metamaterials, DNA Microarrays, Genetic Algorithms, RNAi...emerging capabilities Case Studies, Eight Examples: • Tissue Engineering, Cold Fusion, RF Metamaterials, DNA Microarrays, Genetic Algorithms...Evidence Quality (i.e., the rubric ) and deliver comprehensible evidential support for nomination • Demonstrate proof-of-concept nomination for Chinese

LIFE: a sustainable solution for developing safe, clean fusion power.

PubMed

Reyes, Susana; Dunne, Mike; Kramer, Kevin; Anklam, Tom; Havstad, Mark; Mazuecos, Antonio Lafuente; Miles, Robin; Martinez-Frias, Joel; Deri, Bob

2013-06-01

The National Ignition Facility (NIF) at the Lawrence Livermore National Laboratory (LLNL) in California is currently in operation with the goal to demonstrate fusion energy gain for the first time in the laboratory-also referred to as "ignition." Based on these demonstration experiments, the Laser Inertial Fusion Energy (LIFE) power plant is being designed at LLNL in partnership with other institutions with the goal to deliver baseload electricity from safe, secure, sustainable fusion power in a time scale that is consistent with the energy market needs. For this purpose, the LIFE design takes advantage of recent advances in diode-pumped, solid-state laser technology and adopts the paradigm of Line Replaceable Units used on the NIF to provide high levels of availability and maintainability and mitigate the need for advanced materials development. The LIFE market entry plant will demonstrate the feasibility of a closed fusion fuel cycle, including tritium breeding, extraction, processing, refueling, accountability, and safety, in a steady-state power-producing device. While many fusion plant designs require large quantities of tritium for startup and operations, a range of design choices made for the LIFE fuel cycle act to reduce the in-process tritium inventory. This paper presents an overview of the delivery plan and the preconceptual design of the LIFE facility with emphasis on the key safety design principles being adopted. In order to illustrate the favorable safety characteristics of the LIFE design, some initial accident analysis results are presented that indicate potential for a more attractive licensing regime than that of current fission reactors.

Method and apparatus to produce high specific impulse and moderate thrust from a fusion-powered rocket engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, Samuel A.; Pajer, Gary A.; Paluszek, Michael A.

A system and method for producing and controlling high thrust and desirable specific impulse from a continuous fusion reaction is disclosed. The resultant relatively small rocket engine will have lower cost to develop, test, and operate that the prior art, allowing spacecraft missions throughout the planetary system and beyond. The rocket engine method and system includes a reactor chamber and a heating system for heating a stable plasma to produce fusion reactions in the stable plasma. Magnets produce a magnetic field that confines the stable plasma. A fuel injection system and a propellant injection system are included. The propellant injectionmore » system injects cold propellant into a gas box at one end of the reactor chamber, where the propellant is ionized into a plasma. The propellant and fusion products are directed out of the reactor chamber through a magnetic nozzle and are detached from the magnetic field lines producing thrust.« less

Tau Zero: In the cockpit of a Bussard ramjet

NASA Astrophysics Data System (ADS)

Blatter, Heinz; Greber, Thomas

2017-12-01

A Bussard ramjet is a relativistic spacecraft, fueled by fusion energy of cosmic matter that is collected during the flight. We derive the equation of motion of such a spaceship for a given mass density in space and the fusion mass defect. Two ramjet engine scenarios, where the thrust for propulsion is generated by emission of photons or acceleration of matter, are outlined. As long as not all collected matter is transformed into fusion energy, mass engines are superior to photon engines. If the collected matter is stopped by the spacecraft before fusion it may not reach relativistic terminal velocities. For an ideal ramjet, where no matter is stopped for the generation of energy for propulsion, endless acceleration and relativistic velocities may be obtained such that crossing the universe in a human lifespan would be possible. A journey along one space coordinate and the smallest possible radii of curves were evaluated. The results are compared to the plots in the novel "Tau Zero" by Poul Anderson.

Z-Pinch Fusion for Energy Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

SPIELMAN,RICK B.

2000-01-01

Z pinches, the oldest fusion concept, have recently been revisited in light of significant advances in the fields of plasma physics and pulsed power engineering. The possibility exists for z-pinch fusion to play a role in commercial energy applications. We report on work to develop z-pinch fusion concepts, the result of an extensive literature search, and the output for a congressionally-mandated workshop on fusion energy held in Snowmass, Co July 11-23,1999.

Research Technology

NASA Image and Video Library

1999-05-12

The Gasdynamic Mirror, or GDM, is an example of a magnetic mirror-based fusion propulsion system. Its design is primarily consisting of a long slender solenoid surrounding a vacuum chamber that contains plasma. The bulk of the fusion plasma is confined by magnetic field generated by a series of toroidal-shaped magnets in the center section of the device. the purpose of the GDM Fusion Propulsion Experiment is to confirm the feasibility of the concept and to demonstrate many of the operational characteristics of a full-size plasma can be confined within the desired physical configuration and still reman stable. This image shows an engineer from Propulsion Research Technologies Division at Marshall Space Flight Center inspecting solenoid magnets-A, an integrate part of the Gasdynamic Mirror Fusion Propulsion Engine Experiment.

Convective Heating of the LIFE Engine Target During Injection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holdener, D S; Tillack, M S; Wang, X R

2011-10-24

Target survival in the hostile, high temperature xenon environment of the proposed Laser Inertial Fusion Energy (LIFE) engine is critical. This work focuses on the flow properties and convective heat load imposed upon the surface of the indirect drive target while traveling through the xenon gas. While this rarefied flow is traditionally characterized as being within the continuum regime, it is approaching transition where conventional CFD codes reach their bounds of operation. Thus ANSYS, specifically the Navier-Stokes module CFX, will be used in parallel with direct simulation Monte Carlo code DS2V and analytically and empirically derived expressions for heat transfermore » to the hohlraum for validation. Comparison of the viscous and thermal boundary layers of ANSYS and DS2V were shown to be nearly identical, with the surface heat flux varying less than 8% on average. From the results herein, external baffles have been shown to reduce this heat transfer to the sensitive laser entrance hole (LEH) windows and optimize target survival independent of other reactor parameters.« less

Kinetic advantage of controlled intermediate nuclear fusion

NASA Astrophysics Data System (ADS)

Guo, Xiaoming

2012-09-01

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion very difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.

Fusion energy division annual progress report, period ending December 31, 1980

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1981-11-01

The ORNL Program encompasses most aspects of magnetic fusion research including research on two magnetic confinement programs (tokamaks and ELMO bumpy tori); the development of the essential technologies for plasma heating, fueling, superconducting magnets, and materials; the development of diagnostics; the development of atomic physics and radiation effect data bases; the assessment of the environmental impact of magnetic fusion; the physics and engineering of present-generation devices; and the design of future devices. The integration of all of these activities into one program is a major factor in the success of each activity. An excellent example of this integration is themore » extremely successful application of neutral injection heating systems developed at ORNL to tokamaks both in the Fusion Energy Division and at Princeton Plasma Physics Laboratory (PPPL). The goal of the ORNL Fusion Program is to maintain this balance between plasma confinement, technology, and engineering activities.« less

Thermo-mechanical and neutron lifetime modelling and design of Be pebbles in the neutron multiplier for the LIFE engine

NASA Astrophysics Data System (ADS)

DeMange, P.; Marian, J.; Caro, M.; Caro, A.

2009-11-01

Concept designs for the laser inertial fusion/fission energy (LIFE) engine include a neutron multiplication blanket containing Be pebbles flowing in a molten salt coolant. These pebbles must be designed to withstand the extreme irradiation and temperature conditions in the blanket to enable a reliable and cost-effective operation of LIFE. In this work, we develop design criteria for spherical Be pebbles on the basis of their thermo-mechanical behaviour under continued neutron exposure. We consider the effects of high fluence and fast fluxes on the elastic, thermal and mechanical properties of nuclear-grade Be. Our results suggest a maximum pebble diameter of 30 mm to avoid tensile failure, coated with an anti-corrosive, high-strength metallic shell to avoid failure by pebble contact. Moreover, we find that the operation temperature must always be kept above 450 °C to enable creep to relax the stresses induced by swelling. Under these circumstances, we estimate the pebble lifetime to be at least 16 months if uncoated, and up to six years when coated. We identify the sources of uncertainty on the properties used and discuss the advantages of new intermetallic beryllides and their use in LIFE's neutron multiplier. To establish Be-pebble lifetimes with improved confidence, reliable experiments to measure irradiation creep must be performed.

Preface to the Special Issue: Strategic Opportunities for Fusion Energy

DOE PAGES

Mauel, M. E.; Greenwald, Martin; Ryutov, Dmitri D.; ...

2016-01-23

Here, the Journal of Fusion Energy provides a forum for discussion of broader policy and planning issues that play a crucial role in energy fusion programs. In keeping with this purpose and in response to several recent strategic planning efforts worldwide, this Special Issue on Strategic Opportunities was launched with the goal to invite fusion scientists and engineers to record viewpoints of the scientific opportunities and policy issues that can drive continued advancements in fusion energy research.

Virtually-augmented interfaces for tactical aircraft.

PubMed

Haas, M W

1995-05-01

The term Fusion Interface is defined as a class of interface which integrally incorporates both virtual and non-virtual concepts and devices across the visual, auditory and haptic sensory modalities. A fusion interface is a multi-sensory virtually-augmented synthetic environment. A new facility has been developed within the Human Engineering Division of the Armstrong Laboratory dedicated to exploratory development of fusion-interface concepts. One of the virtual concepts to be investigated in the Fusion Interfaces for Tactical Environments facility (FITE) is the application of EEG and other physiological measures for virtual control of functions within the flight environment. FITE is a specialized flight simulator which allows efficient concept development through the use of rapid prototyping followed by direct experience of new fusion concepts. The FITE facility also supports evaluation of fusion concepts by operational fighter pilots in a high fidelity simulated air combat environment. The facility was utilized by a multi-disciplinary team composed of operational pilots, human-factors engineers, electronics engineers, computer scientists, and experimental psychologists to prototype and evaluate the first multi-sensory, virtually-augmented cockpit. The cockpit employed LCD-based head-down displays, a helmet-mounted display, three-dimensionally localized audio displays, and a haptic display. This paper will endeavor to describe the FITE facility architecture, some of the characteristics of the FITE virtual display and control devices, and the potential application of EEG and other physiological measures within the FITE facility.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Xiaoming

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion verymore » difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.« less

Development scenario for laser fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maniscalco, J.A.; Hovingh, J.; Buntzen, R.R.

1976-03-30

This scenario proposes establishment of test and engineering facilities to (1) investigate the technological problems associated with laser fusion, (2) demonstrate fissile fuel production, and (3) demonstrate competitive electrical power production. Such facilities would be major milestones along the road to a laser-fusion power economy. The relevant engineering and economic aspects of each of these research and development facilities are discussed. Pellet design and gain predictions corresponding to the most promising laser systems are presented for each plant. The results show that laser fusion has the potential to make a significant contribution to our energy needs. Beginning in the earlymore » 1990's, this new technology could be used to produce fissile fuel, and after the turn of the century it could be used to generate electrical power.« less

Developing the Pulsed Fission-Fusion (PuFF) Engine

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Cassibry, Jason; Bradley, David; Fabisinski, Leo; Statham, Geoffrey

2014-01-01

In September 2013 the NASA Innovative Advanced Concept (NIAC) organization awarded a phase I contract to the PuFF team. Our phase 1 proposal researched a pulsed fission-fusion propulsion system that compressed a target of deuterium (D) and tritium (T) as a mixture in a column, surrounded concentrically by Uranium. The target is surrounded by liquid lithium. A high power current would flow down the liquid lithium and the resulting Lorentz force would compress the column by roughly a factor of 10. The compressed column would reach criticality and a combination of fission and fusion reactions would occur. Our Phase I results, summarized herein, review our estimates of engine and vehicle performance, our work to date to model the fission-fusion reaction, and our initial efforts in experimental analysis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mauel, M. E.; Greenwald, Martin; Ryutov, Dmitri D.

Here, the Journal of Fusion Energy provides a forum for discussion of broader policy and planning issues that play a crucial role in energy fusion programs. In keeping with this purpose and in response to several recent strategic planning efforts worldwide, this Special Issue on Strategic Opportunities was launched with the goal to invite fusion scientists and engineers to record viewpoints of the scientific opportunities and policy issues that can drive continued advancements in fusion energy research.

Fusion Propulsion Z-Pinch Engine Concept

NASA Technical Reports Server (NTRS)

Miernik, J.; Statham, G.; Fabisinski, L.; Maples, C. D.; Adams, R.; Polsgrove, T.; Fincher, S.; Cassibry, J.; Cortez, R.; Turner, M.;

Efficient replication of a paramyxovirus independent of full zippering of the fusion protein six-helix bundle domain

PubMed Central

Brindley, Melinda A.; Plattet, Philippe; Plemper, Richard Karl

2014-01-01

Enveloped viruses such as HIV and members of the paramyxovirus family use metastable, proteinaceous fusion machineries to merge the viral envelope with cellular membranes for infection. A hallmark of the fusogenic glycoproteins of these pathogens is refolding into a thermodynamically highly stable fusion core structure composed of six antiparallel α-helices, and this structure is considered instrumental for pore opening and/or enlargement. Using a paramyxovirus fusion (F) protein, we tested this paradigm by engineering covalently restricted F proteins that are predicted to be unable to close the six-helix bundle core structure fully. Several candidate bonds formed efficiently, resulting in F trimers and higher-order complexes containing covalently linked dimers. The engineered F complexes were incorporated into recombinant virions efficiently and were capable of refolding into a postfusion conformation without temporary or permanent disruption of the disulfide bonds. They efficiently formed fusion pores based on virus replication and quantitative cell-to-cell and virus-to-cell fusion assays. Complementation of these F mutants with a monomeric, fusion-inactive F variant enriched the F oligomers for heterotrimers containing a single disulfide bond, without affecting fusion complementation profiles compared with standard F protein. Our demonstration that complete closure of the fusion core does not drive paramyxovirus entry may aid the design of strategies for inhibiting virus entry. PMID:25157143

Efficient replication of a paramyxovirus independent of full zippering of the fusion protein six-helix bundle domain.

PubMed

Brindley, Melinda A; Plattet, Philippe; Plemper, Richard Karl

2014-09-09

Enveloped viruses such as HIV and members of the paramyxovirus family use metastable, proteinaceous fusion machineries to merge the viral envelope with cellular membranes for infection. A hallmark of the fusogenic glycoproteins of these pathogens is refolding into a thermodynamically highly stable fusion core structure composed of six antiparallel α-helices, and this structure is considered instrumental for pore opening and/or enlargement. Using a paramyxovirus fusion (F) protein, we tested this paradigm by engineering covalently restricted F proteins that are predicted to be unable to close the six-helix bundle core structure fully. Several candidate bonds formed efficiently, resulting in F trimers and higher-order complexes containing covalently linked dimers. The engineered F complexes were incorporated into recombinant virions efficiently and were capable of refolding into a postfusion conformation without temporary or permanent disruption of the disulfide bonds. They efficiently formed fusion pores based on virus replication and quantitative cell-to-cell and virus-to-cell fusion assays. Complementation of these F mutants with a monomeric, fusion-inactive F variant enriched the F oligomers for heterotrimers containing a single disulfide bond, without affecting fusion complementation profiles compared with standard F protein. Our demonstration that complete closure of the fusion core does not drive paramyxovirus entry may aid the design of strategies for inhibiting virus entry.

Assembly of tissue engineered blood vessels with spatially-controlled heterogeneities.

PubMed

Strobel, Hannah A; Hookway, Tracy; Piola, Marco; Fiore, Gianfranco Beniamino; Soncini, Monica; Alsberg, Eben; Rolle, Marsha

2018-05-04

Tissue-engineered human blood vessels may enable in vitro disease modeling and drug screening to accelerate advances in vascular medicine. Existing methods for tissue engineered blood vessel (TEBV) fabrication create homogenous tubes not conducive to modeling the focal pathologies characteristic of vascular disease. We developed a system for generating self-assembled human smooth muscle cell ring-units, which were fused together into TEBVs. The goal of this study was to assess the feasibility of modular assembly and fusion of ring building units to fabricate spatially-controlled, heterogeneous tissue tubes. We first aimed to enhance fusion and reduce total culture time, and determined that reducing ring pre-culture duration improved tube fusion. Next, we incorporated electrospun polymer ring units onto tube ends as reinforced extensions, which allowed us to cannulate tubes after only 7 days of fusion, and culture tubes with luminal flow in a custom bioreactor. To create focal heterogeneities, we incorporated gelatin microspheres into select ring units during self-assembly, and fused these rings between ring units without microspheres. Cells within rings maintained their spatial position within tissue tubes after fusion. This work describes a platform approach for creating modular TEBVs with spatially-defined structural heterogeneities, which may ultimately be applied to mimic focal diseases such as intimal hyperplasia or aneurysm.

Combining MHD Airbreathing and Fusion Rocket Propulsion for Earth-to-Orbit Flight

NASA Astrophysics Data System (ADS)

Froning, H. D.; Miley, G. H.; Luo, Nie; Yang, Yang; Momota, H.; Burton, E.

2005-02-01

Previous studies have shown that Single-State-to-Orbit (SSTO) vehicle propellant can be reduced by Magnets-Hydro-Dynamic (MHD) processes that minimize airbreathing propulsion losses and propellant consumption during atmospheric flight. Similarly additional reduction in SSTO propellant is enabled by Inertial Electrostatic Confinement (IEC) fusion, whose more energetic reactions reduce rocket propellant needs. MHD airbreathing propulsion during an SSTO vehicle's initial atmospheric flight phase and IEC fusion propulsion during its final exo-atmospheric flight phase is therefore being explored. Accomplished work is not yet sufficient for claiming such a vehicle's feasibility. But takeoff and propellant mass for an MHD airbreathing and IEC fusion vehicle could be as much as 25 and 40 percent less than one with ordinary airbreathing and IEC fusion; and as much as 50 and 70 percent less than SSTO takeoff and propellant mass with MHD airbreathing and chemical rocket propulsion. Thus this unusual combined cycle engine shows great promise for performance gains beyond contemporary combined-cycle airbreathing engines.

Construction of a multi-functional extracellular matrix protein that increases number of N1E-115 neuroblast cells having neurites.

PubMed

Nakamura, Makiko; Mie, Masayasu; Mihara, Hisakazu; Nakamura, Makoto; Kobatake, Eiry

2009-10-01

An artificially designed fusion protein, which was designed to have strong cell adhesive activity and an active functional unit that enhances neuronal differentiation of mouse N1E-115 neuroblast cells, was developed. In this study, a laminin-1-derived IKVAV sequence, which stimulates neurite outgrowth in conditions of serum deprivation, was engineered and incorporated into an elastin-derived structural unit. The designed fusion protein also had a cell-adhesive RGD sequence derived from fibronectin. The resultant fusion protein could adsorb efficiently onto hydrophobic culture surfaces and showed cell adhesion activity similar to laminin. N1E-115 cells grown on the fusion protein exhibited more cells with neurites than cells grown on laminin-1. These results indicated that the constructed protein could retain properties of incorporated functional peptides and could provide effective signal transport. The strategy of designing multi-functional fusion proteins has the possibility for supporting current tissue engineering techniques. (c) 2009 Wiley Periodicals, Inc.

Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics

PubMed Central

Rath, Timo; Baker, Kristi; Dumont, Jennifer A.; Peters, Robert T.; Jiang, Haiyan; Qiao, Shuo-Wang; Lencer, Wayne I.; Pierce, Glenn F.; Blumberg, Richard S.

2016-01-01

Nearly 350 IgG-based therapeutics are approved for clinical use or are under development for many diseases lacking adequate treatment options. These include molecularly engineered biologicals comprising the IgG Fc-domain fused to various effector molecules (so-called Fc-fusion proteins) that confer the advantages of IgG, including binding to the neonatal Fc receptor (FcRn) to facilitate in vivo stability, and the therapeutic benefit of the specific effector functions. Advances in IgG structure-function relationships and an understanding of FcRn biology have provided therapeutic opportunities for previously unapproachable diseases. This article discusses approved Fc-fusion therapeutics, novel Fc-fusion proteins and FcRn-dependent delivery approaches in development, and how engineering of the FcRn–Fc interaction can generate longer-lasting and more effective therapeutics. PMID:24156398

NASA C-17 Usage Overview

NASA Technical Reports Server (NTRS)

Miller, Christopher R.

2008-01-01

The usage and integrated vehicle health management of the NASA C-17. Propulsion health management flight objectives for the aircraft include mapping of the High Pressure Compressor in order to calibrate a Pratt and Whitney engine model and the fusion of data collected from existing sensors and signals to develop models, analysis methods and information fusion algorithms. An additional health manage flight objective is to demonstrate that the Commercial Modular Aero-Propulsion Systems Simulation engine model can successfully execute in real time onboard the C-17 T-1 aircraft using engine and aircraft flight data as inputs. Future work will address aircraft durability and aging, airframe health management, and propulsion health management research in the areas of gas path and engine vibration.

High-Energy Space Propulsion Based on Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Thio, Y. C. F.; Freeze, B.; Kirkpatrick, R. C.; Landrum, B.; Gerrish, H.; Schmidt, G. R.

1999-01-01

A conceptual study is made to explore the feasibility of applying magnetized target fusion (MTF) to space propulsion for omniplanetary travel. Plasma-jet driven MTF not only is highly amenable to space propulsion, but also has a number of very attractive features for this application: 1) The pulsed fusion scheme provides in situ a very dense hydrogenous liner capable of moderating the neutrons, converting more than 97% of the neutron energy into charged particle energy of the fusion plasma available for propulsion. 2) The fusion yield per pulse can be maintained at an attractively low level (< 1 GJ) despite a respectable gain in excess of 70. A compact, low-weight engine is the result. An engine with a jet power of 25 GW, a thrust of 66 kN, and a specific impulse of 77,000 s, can be achieved with an overall engine mass of about 41 metric tons, with a specific power density of 605 kW/kg, and a specific thrust density of 1.6 N/kg. The engine is rep-rated at 40 Hz to provide this power and thrust level. At a practical rep-rate limit of 200 Hz, the engine can deliver 128 GW jet power and 340 kN of thrust, at specific power and thrust density of 1,141 kW/kg and 3 N/kg respectively. 3) It is possible to operate the magnetic nozzle as a magnetic flux compression generator in this scheme, while attaining a high nozzle efficiency of 80% in converting the spherically radial momentum of the fusion plasma to an axial impulse. 4) A small fraction of the electrical energy generated from the flux compression is used directly to recharge the capacitor bank and other energy storage equipment, without the use of a highvoltage DC power supply. A separate electrical generator is not necessary. 5) Due to the simplicity of the electrical circuit and the components, involving mainly inductors, capacitors, and plasma guns, which are connected directly to each other without any intermediate equipment, a high rep-rate (with a maximum of 200 Hz) appears practicable. 6) All fusion related components are within the current state of the art for pulsed power technology. Experimental facilities with the required pulsed power capabilities already exist. 7) The scheme does not require prefabricated fuel target and liner hardware in any esoteric form or state. All necessary fuel and liner material are introduced into the engine in the form of ordinary matter in gaseous state at room temperature, greatly simplifying their handling on board. They are delivered into the fusion reaction chamber in a completely standoff manner.

Performance Optimization of the Gasdynamic Mirror Propulsion System

NASA Technical Reports Server (NTRS)

Emrich, William J., Jr.; Kammash, Terry

1999-01-01

Nuclear fusion appears to be a most promising concept for producing extremely high specific impulse rocket engines. Engines such as these would effectively open up the solar system to human exploration and would virtually eliminate launch window restrictions. A preliminary vehicle sizing and mission study was performed based on the conceptual design of a Gasdynamic Mirror (GDM) fusion propulsion system. This study indicated that the potential specific impulse for this engine is approximately 142,000 sec. with about 22,100 N of thrust using a deuterium-tritium fuel cycle. The engine weight inclusive of the power conversion system was optimized around an allowable engine mass of 1500 Mg assuming advanced superconducting magnets and a Field Reversed Configuration (FRC) end plug at the mirrors. The vehicle habitat, lander, and structural weights are based on a NASA Mars mission study which assumes the use of nuclear thermal propulsion' Several manned missions to various planets were analyzed to determine fuel requirements and launch windows. For all fusion propulsion cases studied, the fuel weight remained a minor component of the total system weight regardless of when the missions commenced. In other words, the use of fusion propulsion virtually eliminates all mission window constraints and effectively allows unlimited manned exploration of the entire solar system. It also mitigates the need to have a large space infrastructure which would be required to support the transfer of massive amounts of fuel and supplies to lower a performing spacecraft.

Current status and recent research achievements in SiC/SiC composites

NASA Astrophysics Data System (ADS)

Katoh, Y.; Snead, L. L.; Henager, C. H.; Nozawa, T.; Hinoki, T.; Iveković, A.; Novak, S.; Gonzalez de Vicente, S. M.

2014-12-01

The silicon carbide fiber-reinforced silicon carbide matrix (SiC/SiC) composite system for fusion applications has seen a continual evolution from development a fundamental understanding of the material system and its behavior in a hostile irradiation environment to the current effort which is directed at a broad-based program of technology maturation program. In essence, over the past few decades this material system has steadily moved from a laboratory curiosity to an engineering material, both for fusion structural applications and other high performance application such as aerospace. This paper outlines the recent international scientific and technological achievements towards the development of SiC/SiC composite material technologies for fusion application and discusses future research directions. It also reviews the materials system in the larger context of progress to maturity as an engineering material for both the larger nuclear community and broader engineering applications.

Data Fusion for Enhanced Aircraft Engine Prognostics and Health Management

NASA Technical Reports Server (NTRS)

Volponi, Al

2005-01-01

Aircraft gas-turbine engine data is available from a variety of sources, including on-board sensor measurements, maintenance histories, and component models. An ultimate goal of Propulsion Health Management (PHM) is to maximize the amount of meaningful information that can be extracted from disparate data sources to obtain comprehensive diagnostic and prognostic knowledge regarding the health of the engine. Data fusion is the integration of data or information from multiple sources for the achievement of improved accuracy and more specific inferences than can be obtained from the use of a single sensor alone. The basic tenet underlying the data/ information fusion concept is to leverage all available information to enhance diagnostic visibility, increase diagnostic reliability and reduce the number of diagnostic false alarms. This report describes a basic PHM data fusion architecture being developed in alignment with the NASA C-17 PHM Flight Test program. The challenge of how to maximize the meaningful information extracted from disparate data sources to obtain enhanced diagnostic and prognostic information regarding the health and condition of the engine is the primary goal of this endeavor. To address this challenge, NASA Glenn Research Center, NASA Dryden Flight Research Center, and Pratt & Whitney have formed a team with several small innovative technology companies to plan and conduct a research project in the area of data fusion, as it applies to PHM. Methodologies being developed and evaluated have been drawn from a wide range of areas including artificial intelligence, pattern recognition, statistical estimation, and fuzzy logic. This report will provide a chronology and summary of the work accomplished under this research contract.

Elastin-like-polypeptide based fusion proteins for osteogenic factor delivery in bone healing.

PubMed

McCarthy, Bryce; Yuan, Yuan; Koria, Piyush

2016-07-08

Modern treatments of bone injuries and diseases are becoming increasingly dependent on the usage of growth factors to stimulate bone growth. Bone morphogenetic protein-2 (BMP-2), a potent osteogenic inductive protein, exhibits promising results in treatment models, but recently has had its practical efficacy questioned due to the lack of local retention, ectopic bone formation, and potentially lethal inflammation. Where a new delivery technique of the BMP-2 is necessary, here we demonstrate the viability of an elastin-like peptide (ELP) fusion protein containing BMP-2 for delivery of the BMP-2. This fusion protein retains the performance characteristics of both the BMP-2 and ELP. The fusion protein was found to induce osteogenic differentiation of mesenchymal stem cells as evidenced by the production of alkaline phosphatase and extracellular calcium deposits in response to treatment by the fusion protein. Retention of the ELPs inverse phase transition property has allowed for expression of the fusion protein within a bacterial host (such as Escherichia coli) and easy and rapid purification using inverse transition cycling. The fusion protein formed self-aggregating nanoparticles at human-body temperature. The data collected suggests the viability of these fusion protein nanoparticles as a dosage-efficient and location-precise noncytotoxic delivery vehicle for BMP-2 in bone treatment. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1029-1037, 2016. © 2016 American Institute of Chemical Engineers.

Clinical utility and patient perspectives on the use of extended half-life rFIXFc in the management of hemophilia B

PubMed Central

Miguelino, Maricel G; Powell, Jerry S

2014-01-01

Hemophilia B is an X-linked genetic disease caused by mutation of the gene for coagulation protein factor IX (FIX), with an incidence of approximately once every 30,000 male births in all populations and ethnic groups. When severe, the disease leads to spontaneous life threatening bleeding episodes. When untreated, most patients die from bleeding complications before 25 years of age. Current therapy requires frequent intravenous infusions of therapeutic recombinant or plasma-derived protein concentrates containing FIX. Most patients administer the infusions at home every few days, and must limit their physical activities to avoid abnormal bleeding when the FIX activity levels are below normal. After completing the pivotal Phase III clinical trial, a new therapeutic FIX preparation that has been engineered for an extended half-life in circulation, received regulatory approval in March 2014 in Canada and the US. This new FIX represents a major therapeutic advance for patients with hemophilia B. The half-life is prolonged due to fusion of the native FIX molecule with the normal constant region of immunoglobulin G. This fusion molecule then follows the normal immunoglobulin recirculation pathways through endothelial cells, resulting in prolonged times in circulation. In the clinical trials, over 150 patients successfully used eftrenonacog alfa regularly for more than 1 year to prevent spontaneous bleeding, to successfully treat any bleeding episodes, and to provide effective coagulation for major surgery. All infusions were well tolerated and effective, with no inhibitors detected and no safety concerns. This promising therapy should allow patients to use fewer infusions to maintain appropriate FIX activity levels in all clinical settings. PMID:25143713

Fusion characteristics of volcanic ash relevant to aviation hazards

NASA Astrophysics Data System (ADS)

Song, Wenjia; Hess, Kai-Uwe; Damby, David E.; Wadsworth, Fabian B.; Lavallée, Yan; Cimarelli, Corrado; Dingwell, Donald B.

2014-04-01

The fusion dynamics of volcanic ash strongly impacts deposition in hot parts of jet engines. In this study, we investigate the sintering behavior of volcanic ash using natural ash of intermediate composition, erupted in 2012 at Santiaguito Volcano, Guatemala. A material science procedure was followed in which we monitored the geometrical evolution of cylindrical-shaped volcanic ash compact upon heating from 50 to 1400°C in a heating microscope. Combined morphological, mineralogical, and rheological analyses helped define the evolution of volcanic ash during fusion and sintering and constrain their sticking potential as well as their ability to flow at characteristic temperatures. For the ash investigated, 1240°C marks the onset of adhesion and flowability. The much higher fusibility of ash compared to that of typical test sands demonstrates for the need of a more extensive fusion characterization of volcanic ash in order to mitigate the risk posed on jet engine operation.

Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein.

PubMed

Boado, Ruben J; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Zhou, Qing-Hui; Pardridge, William M

2010-03-01

Decoy receptors, such as the human tumor necrosis factor receptor (TNFR), are potential new therapies for brain disorders. However, decoy receptors are large molecule drugs that are not transported across the blood-brain barrier (BBB). To enable BBB transport of a TNFR decoy receptor, the human TNFR-II extracellular domain was re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan horse to ferry the TNFR therapeutic decoy receptor across the BBB. The HIRMAb-TNFR fusion protein was expressed in stably transfected CHO cells, and was analyzed with electrophoresis, Western blotting, size exclusion chromatography, and binding assays for the HIR and TNFalpha. The HIRMAb-TNFR fusion protein was radio-labeled by trititation, in parallel with the radio-iodination of recombinant TNFR:Fc fusion protein, and the proteins were co-injected in the adult Rhesus monkey. The TNFR:Fc fusion protein did not cross the primate BBB in vivo, but the uptake of the HIRMAb-TNFR fusion protein was high and 3% of the injected dose was taken up by the primate brain. The TNFR was selectively targeted to brain, relative to peripheral organs, following fusion to the HIRMAb. This study demonstrates that decoy receptors may be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse that selectively targets the brain, and enables penetration of the BBB in vivo. IgG-decoy receptor fusion proteins represent a new class of human neurotherapeutics. Copyright 2010 Elsevier B.V. All rights reserved.

Biochemical and functional characterization of a recombinant monomeric factor VIII-Fc fusion protein.

PubMed

Peters, R T; Toby, G; Lu, Q; Liu, T; Kulman, J D; Low, S C; Bitonti, A J; Pierce, G F

2013-01-01

Hemophilia A results from a deficiency in factor VIII activity. Current treatment regimens require frequent dosing, owing to the short half-life of FVIII. A recombinant FVIII-Fc fusion protein (rFVIIIFc) was molecularly engineered to increase the half-life of FVIII, by 1.5-2-fold, in several preclinical animal models and humans. To perform a biochemical and functional in vitro characterization of rFVIIIFc, with existing FVIII products as comparators.  rFVIIIFc was examined by utilizing a series of structural and analytic assays, including mass spectrometry following lysyl endopeptidase or thrombin digestion. rFVIIIFc activity was determined in both one-stage clotting (activated partial thromboplastin time) and chromogenic activity assays, in the context of the FXase complex with purified components, and in both in vitro and ex vivo rotational thromboelastometry (ROTEM) assays performed in whole blood.  rFVIIIFc contained the predicted primary structure and post-translational modifications, with an FVIII moiety that was similar to other recombinant FVIII products. The von Willebrand factor-binding and specific activity of rFVIIIFc were also found to be similar to those of other recombinant FVIII molecules. Both chromogenic and one-stage assays of rFVIIIFc gave similar results. Ex vivo ROTEM studies demonstrated that circulating rFVIIIFc activity was prolonged in mice with hemophilia A in comparison with B-domain-deleted or full-length FVIII. Clot parameters at early time points were similar to those for FVIII, whereas rFVIIIFc showed prolonged improvement of clot formation.  rFVIIIFc maintains normal FVIII interactions with other proteins necessary for its activity, with prolonged in vivo activity, owing to fusion with the Fc region of IgG(1) . © 2012 International Society on Thrombosis and Haemostasis.

Structural and kinetic analysis of the unnatural fusion protein 4-coumaroyl-CoA ligase::stilbene synthase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yechun; Yi, Hankuil; Wang, Melissa

2012-10-24

To increase the biochemical efficiency of biosynthetic systems, metabolic engineers have explored different approaches for organizing enzymes, including the generation of unnatural fusion proteins. Previous work aimed at improving the biosynthesis of resveratrol, a stilbene associated a range of health-promoting activities, in yeast used an unnatural engineered fusion protein of Arabidopsis thaliana (thale cress) 4-coumaroyl-CoA ligase (At4CL1) and Vitis vinifera (grape) stilbene synthase (VvSTS) to increase resveratrol levels 15-fold relative to yeast expressing the individual enzymes. Here we present the crystallographic and biochemical analysis of the 4CL::STS fusion protein. Determination of the X-ray crystal structure of 4CL::STS provides the firstmore » molecular view of an artificial didomain adenylation/ketosynthase fusion protein. Comparison of the steady-state kinetic properties of At4CL1, VvSTS, and 4CL::STS demonstrates that the fusion protein improves catalytic efficiency of either reaction less than 3-fold. Structural and kinetic analysis suggests that colocalization of the two enzyme active sites within 70 {angstrom} of each other provides the basis for enhanced in vivo synthesis of resveratrol.« less

Superior serum half life of albumin tagged TNF ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus

2010-06-11

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined bymore » ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.« less

Creating a Star: The Science of Fusion--Fusion Power Would Not Contribute to Global Warming, Acid Rain, or Other Forms of Air Pollution, nor Would It Create Long-Lived Radioactive Waste

ERIC Educational Resources Information Center

Baird, Stephen L.

2005-01-01

Fusion is the process that powers the sun and the stars. Since the 1950s, scientists and engineers in the United States and around the world have been conducting fusion research in pursuit of the creation of a new energy source for our planet and to further our understanding and control of plasma, the fourth state of matter that dominates the…

Engineering of living cells for the expression of holo-phycobiliprotein-based constructs

DOEpatents

Glazer, Alexander N.; Tooley, Aaron J.; Cai, Yuping

2004-05-25

Recombinant cells which express a fluorescent holo-phycobiliprotein fusion protein and methods of use are described. The cells comprises a bilin, a recombinant bilin reductase, an apo-phycobiliprotein fusion protein precursor of the fusion protein comprising a corresponding apo-phycobiliprotein domain, and a recombinant phycobiliprotein domain-bilin lyase, which components react to form the holo-phycobiliprotein fusion protein. Also described are holo-phycobiliprotein based transcription reporter cells and assays, which cells conditionally express a heterologous-to-the-cell, fluorescent, first holo-phycobiliprotein domain.

Development of an Information Fusion System for Engine Diagnostics and Health Management

NASA Technical Reports Server (NTRS)

Volponi, Allan J.; Brotherton, Tom; Luppold, Robert; Simon, Donald L.

2004-01-01

Aircraft gas-turbine engine data are available from a variety of sources including on-board sensor measurements, maintenance histories, and component models. An ultimate goal of Propulsion Health Management (PHM) is to maximize the amount of meaningful information that can be extracted from disparate data sources to obtain comprehensive diagnostic and prognostic knowledge regarding the health of the engine. Data Fusion is the integration of data or information from multiple sources, to achieve improved accuracy and more specific inferences than can be obtained from the use of a single sensor alone. The basic tenet underlying the data/information fusion concept is to leverage all available information to enhance diagnostic visibility, increase diagnostic reliability and reduce the number of diagnostic false alarms. This paper describes a basic PHM Data Fusion architecture being developed in alignment with the NASA C17 Propulsion Health Management (PHM) Flight Test program. The challenge of how to maximize the meaningful information extracted from disparate data sources to obtain enhanced diagnostic and prognostic information regarding the health and condition of the engine is the primary goal of this endeavor. To address this challenge, NASA Glenn Research Center (GRC), NASA Dryden Flight Research Center (DFRC) and Pratt & Whitney (P&W) have formed a team with several small innovative technology companies to plan and conduct a research project in the area of data fusion as applied to PHM. Methodologies being developed and evaluated have been drawn from a wide range of areas including artificial intelligence, pattern recognition, statistical estimation, and fuzzy logic. This paper will provide a broad overview of this work, discuss some of the methodologies employed and give some illustrative examples.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

PubMed

Hoshi, K; Fujihara, Y; Mori, Y; Asawa, Y; Kanazawa, S; Nishizawa, S; Misawa, M; Numano, T; Inoue, H; Sakamoto, T; Watanabe, M; Komura, M; Takato, T

2016-09-01

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds. Copyright © 2016. Published by Elsevier Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morgan, O.B. Jr.; Berry, L.A.; Sheffield, J.

This annual report on fusion energy discusses the progress on work in the following main topics: toroidal confinement experiments; atomic physics and plasma diagnostics development; plasma theory and computing; plasma-materials interactions; plasma technology; superconducting magnet development; fusion engineering design center; materials research and development; and neutron transport. (LSP)

The Ancient Gamete Fusogen HAP2 Is a Eukaryotic Class II Fusion Protein.

PubMed

Fédry, Juliette; Liu, Yanjie; Péhau-Arnaudet, Gérard; Pei, Jimin; Li, Wenhao; Tortorici, M Alejandra; Traincard, François; Meola, Annalisa; Bricogne, Gérard; Grishin, Nick V; Snell, William J; Rey, Félix A; Krey, Thomas

2017-02-23

Sexual reproduction is almost universal in eukaryotic life and involves the fusion of male and female haploid gametes into a diploid cell. The sperm-restricted single-pass transmembrane protein HAP2-GCS1 has been postulated to function in membrane merger. Its presence in the major eukaryotic taxa-animals, plants, and protists (including important human pathogens like Plasmodium)-suggests that many eukaryotic organisms share a common gamete fusion mechanism. Here, we report combined bioinformatic, biochemical, mutational, and X-ray crystallographic studies on the unicellular alga Chlamydomonas reinhardtii HAP2 that reveal homology to class II viral membrane fusion proteins. We further show that targeting the segment corresponding to the fusion loop by mutagenesis or by antibodies blocks gamete fusion. These results demonstrate that HAP2 is the gamete fusogen and suggest a mechanism of action akin to viral fusion, indicating a way to block Plasmodium transmission and highlighting the impact of virus-cell genetic exchanges on the evolution of eukaryotic life. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

[Rumination and cognitive fusion in dementia family caregivers].

PubMed

Romero-Moreno, Rosa; Márquez-González, María; Losada, Andrés; Fernández-Fernández, Virginia; Nogales-González, Celia

2015-01-01

Rumination has been described as a dysfunctional coping strategy related to emotional distress. Recently, it has been highlighted from the Acceptance and Commitment Therapy therapeutic approach, the negative role that cognitive fusion (the extent to which we are psychologically tangled with and dominated by the form or content of our thoughts) has on the explanation of distress. The aim of this study is to simultaneously analyze the role of rumination and cognitive fusion in the caregiving stress process. The sample of 176 dementia caregivers was divided in four groups, taking into account their levels of rumination and cognitive fusion: HRHF=high rumination+high cognitive fusion; HRLF=high rumination+low cognitive fusion; LRHF= low rumination+high cognitive fusion; and LRLC=low rumination and low cognitive fusion. Caregiver stress factors, frequency of pleasant events, experiential avoidance, coherence and satisfaction with personal values, depression, anxiety and satisfaction with life, were measured. The HRHF group showed higher levels of depression, anxiety, experiential avoidance and lower levels of satisfaction with life, frequency of pleasant events, coherence and satisfaction with personal values, than the other three groups. Considering simultaneously rumination and cognitive fusion may contribute to a better understanding of caregiver coping and distress. Copyright © 2014 SEGG. Published by Elsevier Espana. All rights reserved.

First AC loss test and analysis of a Bi2212 cable-in-conduit conductor for fusion application

NASA Astrophysics Data System (ADS)

Qin, Jinggang; Shi, Yi; Wu, Yu; Li, Jiangang; Wang, Qiuliang; He, Yuxiang; Dai, Chao; Liu, Fang; Liu, Huajun; Mao, Zhehua; Nijhuis, Arend; Zhou, Chao; Devred, Arnaud

2018-01-01

The main goal of the Chinese fusion engineering test reactor (CFETR) is to build a fusion engineering tokamak reactor with a fusion power of 50-200 MW, and plan to test the breeding tritium during the fusion reaction. This may require a maximum magnetic field of the central solenoid and toroidal field coils up to 15 T. New magnet technologies should be developed for the next generation of fusion reactors with higher requirements. Bi2Sr2CaCu2Ox (Bi2212) is considered as a potential and promising superconductor for the magnets in the CFETR. R&D activities are ongoing at the Institute of Plasma Physics, Chinese Academy of Sciences for demonstration of the feasibility of a CICC based on Bi2212 round wire. One sub-size conductor cabled with 42 wires was designed, manufactured and tested with limited strand indentation during cabling and good transport performance. In this paper, the first test results and analysis on the AC loss of Bi2212 round wires and cabled conductor samples are presented. Furthermore, the impact of mechanical load on the AC loss of the sub-size conductor is investigated to represent the operation conditions with electromagnetic loads. The first tests provide an essential basis for the validation of Bi2212 CICC and its application in fusion magnets.

FusionHub: A unified web platform for annotation and visualization of gene fusion events in human cancer.

PubMed

Panigrahi, Priyabrata; Jere, Abhay; Anamika, Krishanpal

2018-01-01

Gene fusion is a chromosomal rearrangement event which plays a significant role in cancer due to the oncogenic potential of the chimeric protein generated through fusions. At present many databases are available in public domain which provides detailed information about known gene fusion events and their functional role. Existing gene fusion detection tools, based on analysis of transcriptomics data usually report a large number of fusion genes as potential candidates, which could be either known or novel or false positives. Manual annotation of these putative genes is indeed time-consuming. We have developed a web platform FusionHub, which acts as integrated search engine interfacing various fusion gene databases and simplifies large scale annotation of fusion genes in a seamless way. In addition, FusionHub provides three ways of visualizing fusion events: circular view, domain architecture view and network view. Design of potential siRNA molecules through ensemble method is another utility integrated in FusionHub that could aid in siRNA-based targeted therapy. FusionHub is freely available at https://fusionhub.persistent.co.in.

Engineering human cell spheroids to model embryonic tissue fusion in vitro.

EPA Science Inventory

Epithelial-mesenchymal interactions drive embryonic fusion events during development and upon perturbation can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known abo...

The path to fusion power†

PubMed Central

Smith, Chris Llewellyn; Cowley, Steve

2010-01-01

The promise, status and challenges of developing fusion power are outlined. The key physics and engineering principles are described and recent progress quantified. As the successful demonstration of 16 MW of fusion in 1997 in the Joint European Torus showed, fusion works. The central issue is therefore to make it work reliably and economically on the scale of a power station. We argue that to meet this challenge in 30 years we must follow the aggressive programme known as the ‘Fast Track to Fusion’. This programme is described in some detail. PMID:20123748

Engineering human cell spheroids to model embryonic tissue fusion in vitro

PubMed Central

Wolf, Cynthia J.; Wood, Carmen; Ren, Hongzu; Grindstaff, Rachel; Padgett, William; Swank, Adam; MacMillan, Denise; Fisher, Anna; Winnik, Witold; Abbott, Barbara D.

2017-01-01

Epithelial-mesenchymal interactions drive embryonic fusion events during development, and perturbations of these interactions can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known about the effect of chemical exposures on fusion events during human development because of a lack of relevant and robust human in vitro assays of developmental fusion behavior. Given the etiology and prevalence of cleft palate and the relatively simple architecture and composition of the embryonic palate, we sought to develop a three-dimensional culture system that mimics the embryonic palate and could be used to study fusion behavior in vitro using human cells. We engineered size-controlled human Wharton’s Jelly stromal cell (HWJSC) spheroids and established that 7 days of culture in osteogenesis differentiation medium was sufficient to promote an osteogenic phenotype consistent with embryonic palatal mesenchyme. HWJSC spheroids supported the attachment of human epidermal keratinocyte progenitor cells (HPEKp) on the outer spheroid surface likely through deposition of collagens I and IV, fibronectin, and laminin by mesenchymal spheroids. HWJSC spheroids coated in HPEKp cells exhibited fusion behavior in culture, as indicated by the removal of epithelial cells from the seams between spheroids, that was dependent on epidermal growth factor signaling and fibroblast growth factor signaling in agreement with palate fusion literature. The method described here may broadly apply to the generation of three-dimensional epithelial-mesenchymal co-cultures to study developmental fusion events in a format that is amenable to predictive toxicology applications. PMID:28898253

Importance of neonatal FcR in regulating the serum half-life of therapeutic proteins containing the Fc domain of human IgG1: a comparative study of the affinity of monoclonal antibodies and Fc-fusion proteins to human neonatal FcR.

PubMed

Suzuki, Takuo; Ishii-Watabe, Akiko; Tada, Minoru; Kobayashi, Tetsu; Kanayasu-Toyoda, Toshie; Kawanishi, Toru; Yamaguchi, Teruhide

2010-02-15

The neonatal FcR (FcRn) binds to the Fc domain of IgG at acidic pH in the endosome and protects IgG from degradation, thereby contributing to the long serum half-life of IgG. To date, more than 20 mAb products and 5 Fc-fusion protein products have received marketing authorization approval in the United States, the European Union, or Japan. Many of these therapeutic proteins have the Fc domain of human IgG1; however, the serum half-lives differ in each protein. To elucidate the role of FcRn in the pharmacokinetics of Fc domain-containing therapeutic proteins, we evaluated the affinity of the clinically used human, humanized, chimeric, or mouse mAbs and Fc-fusion proteins to recombinant human FcRn by surface plasmon resonance analysis. The affinities of these therapeutic proteins to FcRn were found to be closely correlated with the serum half-lives reported from clinical studies, suggesting the important role of FcRn in regulating their serum half-lives. The relatively short serum half-life of Fc-fusion proteins was thought to arise from the low affinity to FcRn. The existence of some mAbs having high affinity to FcRn and a short serum half-life, however, suggested the involvement of other critical factor(s) in determining the serum half-life of such Abs. We further investigated the reason for the relatively low affinity of Fc-fusion proteins to FcRn and suggested the possibility that the receptor domain of Fc-fusion protein influences the structural environment of the FcRn binding region but not of the FcgammaRI binding region of the Fc domain.

Overview of the IFMIF/EVEDA project

NASA Astrophysics Data System (ADS)

Knaster, J.; Garin, P.; Matsumoto, H.; Okumura, Y.; Sugimoto, M.; Arbeiter, F.; Cara, P.; Chel, S.; Facco, A.; Favuzza, P.; Furukawa, T.; Heidinger, R.; Ibarra, A.; Kanemura, T.; Kasugai, A.; Kondo, H.; Massaut, V.; Molla, J.; Micciche, G.; O'hira, S.; Sakamoto, K.; Yokomine, T.; Wakai, E.; the IFMIF/EVEDA Integrated Project Team

2017-10-01

IFMIF, the International Fusion Materials Irradiation Facility, is presently in its engineering validation and engineering design activities (EVEDA) phase under the Broader Approach Agreement. The engineering design activity (EDA) phase was successfully accomplished within the allocated time. The engineering validation activity (EVA) phase has focused on validating the Accelerator Facility (AF), the Target Facility and the Test Facility (TF) by constructing prototypes. The ELTL at JAEAc, Oarai successfully demonstrated the long-term stability of a Li flow under the IFMIF’s nominal operational conditions keeping the specified free-surface fluctuations below  ±1 mm in a continuous manner for 25 d. A full-scale prototype of the high flux test module (HFTM) was successfully tested in the HELOKA loop (KIT, Karlsruhe), where it was demonstrated that the irradiation temperature can be set individually and kept uniform. LIPAc, designed and constructed in European labs under the coordination of F4E, presently under installation and commissioning in the Rokkasho Fusion Institute, aims at validating the concept of IFMIF accelerators with a D+ beam of 125 mA continuous wave (CW) and 9 MeV. The commissioning phases of the H+/D+ beams at 100 keV are progressing and should be concluded in 2017; in turn, the commissioning of the 5 MeV beam is due to start during 2017. The D+ beam through the superconducting cavities is expected to be achieved within the Broader Approach Agreement time frame with the superconducting cryomodule being assembled in Rokkasho. The realisation of a fusion-relevant neutron source is a necessary step for the successful development of fusion. The ongoing success of the IFMIF/EVEDA involves ruling out concerns about potential technical showstoppers which were raised in the past. Thus, a situation has emerged where soon steps towards constructing a Li(d,xn) fusion-relevant neutron source could be taken, which is also justified in the light of costs which are marginal to those of a fusion plant. In Memoriam Yoshikazu Okumura who passed away on 6 March 2017.

Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 3: assessment of economic outcome.

PubMed

Ghogawala, Zoher; Whitmore, Robert G; Watters, William C; Sharan, Alok; Mummaneni, Praveen V; Dailey, Andrew T; Choudhri, Tanvir F; Eck, Jason C; Groff, Michael W; Wang, Jeffrey C; Resnick, Daniel K; Dhall, Sanjay S; Kaiser, Michael G

2014-07-01

A comprehensive economic analysis generally involves the calculation of indirect and direct health costs from a societal perspective as opposed to simply reporting costs from a hospital or payer perspective. Hospital charges for a surgical procedure must be converted to cost data when performing a cost-effectiveness analysis. Once cost data has been calculated, quality-adjusted life year data from a surgical treatment are calculated by using a preference-based health-related quality-of-life instrument such as the EQ-5D. A recent cost-utility analysis from a single study has demonstrated the long-term (over an 8-year time period) benefits of circumferential fusions over stand-alone posterolateral fusions. In addition, economic analysis from a single study has found that lumbar fusion for selected patients with low-back pain can be recommended from an economic perspective. Recent economic analysis, from a single study, finds that femoral ring allograft might be more cost-effective compared with a specific titanium cage when performing an anterior lumbar interbody fusion plus posterolateral fusion.

Interdisciplinary multisensory fusion: design lessons from professional architects

NASA Astrophysics Data System (ADS)

Geiger, Ray W.; Snell, J. T.

1992-11-01

Psychocybernetic systems engineering design conceptualization is mimicking the evolutionary path of habitable environmental design and the professional practice of building architecture, construction, and facilities management. Human efficacy for innovation in architectural design has always reflected more the projected perceptual vision of the designer visa vis the hierarchical spirit of the design process. In pursuing better ways to build and/or design things, we have found surprising success in exploring certain more esoteric applications. One of those applications is the vision of an artistic approach in/and around creative problem solving. Our evaluation in research into vision and visual systems associated with environmental design and human factors has led us to discover very specific connections between the human spirit and quality design. We would like to share those very qualitative and quantitative parameters of engineering design, particularly as it relates to multi-faceted and interdisciplinary design practice. Discussion will cover areas of cognitive ergonomics, natural modeling sources, and an open architectural process of means and goal satisfaction, qualified by natural repetition, gradation, rhythm, contrast, balance, and integrity of process. One hypothesis is that the kinematic simulation of perceived connections between hard and soft sciences, centering on the life sciences and life in general, has become a very effective foundation for design theory and application.

Prolonged activity of a recombinant factor VIII-Fc fusion protein in hemophilia A mice and dogs

PubMed Central

Dumont, Jennifer A.; Liu, Tongyao; Low, Susan C.; Zhang, Xin; Kamphaus, George; Sakorafas, Paul; Fraley, Cara; Drager, Douglas; Reidy, Thomas; McCue, Justin; Franck, Helen W. G.; Merricks, Elizabeth P.; Nichols, Timothy C.; Bitonti, Alan J.; Pierce, Glenn F.

2012-01-01

Despite proven benefits, prophylactic treatment for hemophilia A is hampered by the short half-life of factor VIII. A recombinant factor VIII-Fc fusion protein (rFVIIIFc) was constructed to determine the potential for reduced frequency of dosing. rFVIIIFc has an ∼ 2-fold longer half-life than rFVIII in hemophilia A (HemA) mice and dogs. The extension of rFVIIIFc half-life requires interaction of Fc with the neonatal Fc receptor (FcRn). In FcRn knockout mice, the extension of rFVIIIFc half-life is abrogated, and is restored in human FcRn transgenic mice. The Fc fusion has no impact on FVIII-specific activity. rFVIIIFc has comparable acute efficacy as rFVIII in treating tail clip injury in HemA mice, and fully corrects whole blood clotting time (WBCT) in HemA dogs immediately after dosing. Furthermore, consistent with prolonged half-life, rFVIIIFc shows 2-fold longer prophylactic efficacy in protecting HemA mice from tail vein transection bleeding induced 24-48 hours after dosing. In HemA dogs, rFVIIIFc also sustains partial correction of WBCT 1.5- to 2-fold longer than rFVIII. rFVIIIFc was well tolerated in both species. Thus, the rescue of FVIII by Fc fusion to provide prolonged protection presents a novel pathway for FVIII catabolism, and warrants further investigation. PMID:22246033

An Engineered Organoid Culture Model That Incorporates Human Mesenchymal and Epithelial Cells to Model Palatal Fusion.

EPA Science Inventory

During embryonic development, fusion events are critical to morphogenesis of organs and tissues, including the iris, urethra, heart, neural tube, and secondary palate. Modeling this process in vitro is challenging as the interactions of mesenchymal and epithelial cells can be cr...

A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance

PubMed Central

Watterson, Daniel; Robinson, Jodie; Chappell, Keith J.; Butler, Mark S.; Edwards, David J.; Fry, Scott R.; Bermingham, Imogen M.; Cooper, Matthew A.; Young, Paul R.

2016-01-01

Fusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus. PMID:26976324

Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.

PubMed

Dauvillée, David; Delhaye, Stéphane; Gruyer, Sébastien; Slomianny, Christian; Moretz, Samuel E; d'Hulst, Christophe; Long, Carole A; Ball, Steven G; Tomavo, Stanislas

2010-12-15

Malaria, an Anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. Despite the incidence of malaria, which remains one of the most severe infections of human populations, there is no licensed vaccine against this life-threatening disease. In this context, we decided to explore the expression of Plasmodium vaccine antigens fused to the granule bound starch synthase (GBSS), the major protein associated to the starch matrix in all starch-accumulating plants and algae such as Chlamydomonas reinhardtii. We describe the development of genetically engineered starch granules containing plasmodial vaccine candidate antigens produced in the unicellular green algae Chlamydomonas reinhardtii. We show that the C-terminal domains of proteins from the rodent Plasmodium species, Plasmodium berghei Apical Major Antigen AMA1, or Major Surface Protein MSP1 fused to the algal granule bound starch synthase (GBSS) are efficiently expressed and bound to the polysaccharide matrix. Mice were either immunized intraperitoneally with the engineered starch particles and Freund adjuvant, or fed with the engineered particles co-delivered with the mucosal adjuvant, and challenged intraperitoneally with a lethal inoculum of P. Berghei. Both experimental strategies led to a significantly reduced parasitemia with an extension of life span including complete cure for intraperitoneal delivery as assessed by negative blood thin smears. In the case of the starch bound P. falciparum GBSS-MSP1 fusion protein, the immune sera or purified immunoglobulin G of mice immunized with the corresponding starch strongly inhibited in vitro the intra-erythrocytic asexual development of the most human deadly plasmodial species. This novel system paves the way for the production of clinically relevant plasmodial antigens as algal starch-based particles designated herein as amylosomes, demonstrating that efficient production of edible vaccines can be genetically produced in Chlamydomonas.

Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases

PubMed Central

Lambert, Abigail R.; Kuhar, Ryan; Jarjour, Jordan; Kulshina, Nadia; Parmeggiani, Fabio; Danaher, Patrick; Gano, Jacob; Baker, David; Stoddard, Barry L.; Scharenberg, Andrew M.

2012-01-01

Although engineered LAGLIDADG homing endonucleases (LHEs) are finding increasing applications in biotechnology, their generation remains a challenging, industrial-scale process. As new single-chain LAGLIDADG nuclease scaffolds are identified, however, an alternative paradigm is emerging: identification of an LHE scaffold whose native cleavage site is a close match to a desired target sequence, followed by small-scale engineering to modestly refine recognition specificity. The application of this paradigm could be accelerated if methods were available for fusing N- and C-terminal domains from newly identified LHEs into chimeric enzymes with hybrid cleavage sites. Here we have analyzed the structural requirements for fusion of domains extracted from six single-chain I-OnuI family LHEs, spanning 40–70% amino acid identity. Our analyses demonstrate that both the LAGLIDADG helical interface residues and the linker peptide composition have important effects on the stability and activity of chimeric enzymes. Using a simple domain fusion method in which linker peptide residues predicted to contact their respective domains are retained, and in which limited variation is introduced into the LAGLIDADG helix and nearby interface residues, catalytically active enzymes were recoverable for ∼70% of domain chimeras. This method will be useful for creating large numbers of chimeric LHEs for genome engineering applications. PMID:22684507

Performance potential of gas-core and fusion rockets - A mission applications survey.

NASA Technical Reports Server (NTRS)

Fishbach, L. H.; Willis, E. A., Jr.

1971-01-01

This paper reports an evaluation of the performance potential of five nuclear rocket engines for four mission classes. These engines are: the regeneratively cooled gas-core nuclear rocket; the light bulb gas-core nuclear rocket; the space-radiator cooled gas-core nuclear rocket; the fusion rocket; and an advanced solid-core nuclear rocket which is included for comparison. The missions considered are: earth-to-orbit launch; near-earth space missions; close interplanetary missions; and distant interplanetary missions. For each of these missions, the capabilities of each rocket engine type are compared in terms of payload ratio for the earth launch mission or by the initial vehicle mass in earth orbit for space missions (a measure of initial cost). Other factors which might determine the engine choice are discussed. It is shown that a 60 day manned round trip to Mars is conceivable.-

Design of multivalent complexes using the barnase*barstar module.

PubMed

Deyev, Sergey M; Waibel, Robert; Lebedenko, Ekaterina N; Schubiger, August P; Plückthun, Andreas

2003-12-01

The ribonuclease barnase (12 kDa) and its inhibitor barstar (10 kDa) form a very tight complex in which all N and C termini are accessible for fusion. Here we exploit this system to create modular targeting molecules based on antibody scFv fragment fusions to barnase, to two barnase molecules in series and to barstar. We describe the construction, production and purification of defined dimeric and trimeric complexes. Immobilized barnase fusions are used to capture barstar fusions from crude extracts to yield homogeneous, heterodimeric fusion proteins. These proteins are stable, soluble and resistant to proteolysis. Using fusions with anti-p185(HER2-ECD) 4D5 scFv, we show that the anticipated gain in avidity from monomer to dimer to trimer is obtained and that favorable tumor targeting properties are achieved. Many permutations of engineered multispecific fusion proteins become accessible with this technology of quasi-covalent heterodimers.

Enhanced NIF neutron activation diagnostics.

PubMed

Yeamans, C B; Bleuel, D L; Bernstein, L A

2012-10-01

The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

Z-Pinch Magneto-Inertial Fusion Propulsion Engine Design Concept

NASA Technical Reports Server (NTRS)

Miernik, Janie H.; Statham, Geoffrey; Adams, Robert B.; Polsgrove, Tara; Fincher, Sharon; Fabisinski, Leo; Maples, C. Dauphne; Percy, Thomas K.; Cortez, Ross J.; Cassibry, Jason

2011-01-01

Fusion-based nuclear propulsion has the potential to enable fast interplanetary transportation. Due to the great distances between the planets of our solar system and the harmful radiation environment of interplanetary space, high specific impulse (Isp) propulsion in vehicles with high payload mass fractions must be developed to provide practical and safe vehicles for human spaceflight missions. Magneto-Inertial Fusion (MIF) is an approach which has been shown to potentially lead to a low cost, small fusion reactor/engine assembly (1). The Z-Pinch dense plasma focus method is an MIF concept in which a column of gas is compressed to thermonuclear conditions by an estimated axial current of approximately 100 MA. Recent advancements in experiments and the theoretical understanding of this concept suggest favorable scaling of fusion power output yield as I(sup 4) (2). The magnetic field resulting from the large current compresses the plasma to fusion conditions, and this is repeated over short timescales (10(exp -6) sec). This plasma formation is widely used in the field of Nuclear Weapons Effects (NWE) testing in the defense industry, as well as in fusion energy research. There is a wealth of literature characterizing Z-Pinch physics and existing models (3-5). In order to be useful in engineering analysis, a simplified Z-Pinch fusion thermodynamic model was developed to determine the quantity of plasma, plasma temperature, rate of expansion, energy production, etc. to calculate the parameters that characterize a propulsion system. The amount of nuclear fuel per pulse, mixture ratio of the D-T and nozzle liner propellant, and assumptions about the efficiency of the engine, enabled the sizing of the propulsion system and resulted in an estimate of the thrust and Isp of a Z-Pinch fusion propulsion system for the concept vehicle. MIF requires a magnetic nozzle to contain and direct the nuclear pulses, as well as a robust structure and radiation shielding. The structure, configuration, and materials of the nozzle must meet many severe requirements. The configuration would focus, in a conical manner, the Deuterium-Tritium (D-T) fuel and Lithium-6/7 liner fluid to meet at a specific point that acts as a cathode so the Li-6 can serve as a current return path to complete the circuit. In addition to serving as a current return path, the Li liner also serves as a radiation shield. The advantage to this configuration is the reaction between neutrons and Li-6 results in the production of additional Tritium, thus adding further fuel to the fusion reaction and boosting the energy output. To understand the applicability of Z-Pinch propulsion to interplanetary travel, it is necessary to design a concept vehicle that uses it. The propulsion system significantly impacts the design of the electrical, thermal control, avionics, radiation shielding, and structural subsystems of a vehicle. The design reference mission is the transport of crew and cargo to Mars and back, with the intention that the vehicle be reused for other missions. Several aspects of this vehicle are based on a previous crewed fusion vehicle study called Human Outer Planet Exploration (HOPE), which employed a Magnetized Target Fusion (MTF) propulsion concept. Analysis of this propulsion system concludes that a 40-fold increase of Isp over chemical propulsion is predicted. This along with a greater than 30% predicted payload mass fraction certainly warrants further development of enabling technologies. The vehicle is designed for multiple interplanetary missions and conceivably may be suited for an automated one-way interstellar voyage.

Purification of CD47-streptavidin fusion protein from bacterial lysate using biotin-agarose affinity chromatography.

PubMed

Salehi, Nasrin; Peng, Ching-An

2016-07-08

CD47 is a widely expressed transmembrane glycoprotein that modulates the activity of a plethora of immune cells via its extracellular domain. Therefore, CD47 plays important roles in the regulation of immune responses and may serve as targets for the development of immunotherapeutic agents. To make sure CD47 functionality is intact under the process of protein conjugation, CD47-streptavidin fusion protein was expressed and purified because it can easily bind to biotin-tagged materials via the unique biotin-streptavidin affinity. In this study, gene sequences of CD47 extracellular domain (CD47ECD) and core streptavidin (coreSA) with a total 834 bp were inserted into pET20b plasmid to construct recombinant plasmid encoding CD47-SA fusion gene. After bacteria transformation, the CD47-SA fusion protein was expressed by isopropyl-β-d-thiogalactopyranoside (IPTG) induction. The collected bacteria lysate was loaded on biotinylated agarose to proceed the purification of CD47-SA fusion protein. Due to the unexpected high affinity between biotin and coreSA, standard washing and elution approaches (e.g., varying pH, using biotin, and applying guanidine hydrochloride) reported for biotin-streptavidin affinity chromatography were not able to separate the target fusion protein. Instead, using low concentration of the non-ionic detergent Triton X-100 followed with alkaline buffer could efficiently weaken the binding between biotin and coreSA, thereby eluting out CD47-SA fusion protein from the biotin agarose column. The purified CD47-SA fusion protein was further characterized by molecular biology methods and its antiphagocytic functionality was confirmed by the phagocytosis assay. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:949-958, 2016. © 2016 American Institute of Chemical Engineers.

Statistical algorithms improve accuracy of gene fusion detection

PubMed Central

Hsieh, Gillian; Bierman, Rob; Szabo, Linda; Lee, Alex Gia; Freeman, Donald E.; Watson, Nathaniel; Sweet-Cordero, E. Alejandro

2017-01-01

Abstract Gene fusions are known to play critical roles in tumor pathogenesis. Yet, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. In this paper, we present a new statistical algorithm, MACHETE (Mismatched Alignment CHimEra Tracking Engine), which achieves highly sensitive and specific detection of gene fusions from RNA-Seq data, including the highest Positive Predictive Value (PPV) compared to the current state-of-the-art, as assessed in simulated data. We show that the best performing published algorithms either find large numbers of fusions in negative control data or suffer from low sensitivity detecting known driving fusions in gold standard settings, such as EWSR1-FLI1. As proof of principle that MACHETE discovers novel gene fusions with high accuracy in vivo, we mined public data to discover and subsequently PCR validate novel gene fusions missed by other algorithms in the ovarian cancer cell line OVCAR3. These results highlight the gains in accuracy achieved by introducing statistical models into fusion detection, and pave the way for unbiased discovery of potentially driving and druggable gene fusions in primary tumors. PMID:28541529

TAT-MTS-MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM-deficient cells.

PubMed

Erlich-Hadad, Tal; Hadad, Rita; Feldman, Anat; Greif, Hagar; Lictenstein, Michal; Lorberboum-Galski, Haya

2018-03-01

Methylmalonic aciduria (MMA) is a disorder of organic acid metabolism resulting from a functional defect of the mitochondrial enzyme, methylmalonyl-CoA mutase (MCM). The main treatments for MMA patients are dietary restriction of propiogenic amino acids and carnitine supplementation. Liver or combined liver/kidney transplantation has been used to treat those with the most severe clinical manifestations. Thus, therapies are necessary to help improve quality of life and prevent liver, renal and neurological complications. Previously, we successfully used the TAT-MTS-Protein approach for replacing a number of mitochondrial-mutated proteins. In this targeted system, TAT, an 11 a.a peptide, which rapidly and efficiently can cross biological membranes, is fused to a mitochondrial targeting sequence (MTS), followed by the mitochondrial mature protein which sends the protein into the mitochondria. In the mitochondria, the TAT-MTS is cleaved off and the native protein integrates into its natural complexes and is fully functional. In this study, we used heterologous MTSs of human, nuclear-encoded mitochondrial proteins, to target the human MCM protein into the mitochondria. All fusion proteins reached the mitochondria and successfully underwent processing. Treatment of MMA patient fibroblasts with these fusion proteins restored mitochondrial activity such as ATP production, mitochondrial membrane potential and oxygen consumption, indicating the importance of mitochondrial function in this disease. Treatment with the fusion proteins enhanced cell viability and most importantly reduced MMA levels. Treatment also enhanced albumin and urea secretion in a CRISPR/Cas9-engineered HepG2 MUT (-/-) liver cell line. Therefore, we suggest using this TAT-MTS-Protein approach for the treatment of MMA. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Visiting Scholars Program

DTIC Science & Technology

2016-09-01

other associated grants. 15. SUBJECT TERMS SUNY Poly, STEM, Artificial Intelligence , Command and Control 16. SECURITY CLASSIFICATION OF: 17...neuromorphic system has the potential to be widely used in a high-efficiency artificial intelligence system. Simulation results have indicated that the...novel multiresolution fusion and advanced fusion performance evaluation tool for an Artificial Intelligence based natural language annotation engine for

Materials handbook for fusion energy systems

NASA Astrophysics Data System (ADS)

Davis, J. W.; Marchbanks, M. F.

A materials data book for use in the design and analysis of components and systems in near term experimental and commercial reactor concepts has been created by the Office of Fusion Energy. The handbook is known as the Materials Handbook for Fusion Energy Systems (MHFES) and is available to all organizations actively involved in fusion related research or system designs. Distribution of the MHFES and its data pages is handled by the Hanford Engineering Development Laboratory (HEDL), while its direction and content is handled by McDonnell Douglas Astronautics Company — St. Louis (MDAC-STL). The MHFES differs from other handbooks in that its format is geared more to the designer and structural analyst than to the materials scientist or materials engineer. The format that is used organizes the handbook by subsystems or components rather than material. Within each subsystem is information pertaining to material selection, specific material properties, and comments or recommendations on treatment of data. Since its inception a little more than a year ago, over 80 copies have been distributed to over 28 organizations consisting of national laboratories, universities, and private industries.

Review of Fusion Systems and Contributing Technologies for SIHS-TD (Examen des Systemes de Fusion et des Technologies d’Appui pour la DT SIHS)

DTIC Science & Technology

2007-03-31

Unlimited, Nivisys, Insight technology, Elcan, FLIR Systems, Stanford photonics Hardware Sensor fusion processors Video processing boards Image, video...Engineering The SPIE Digital Library is a resource for optics and photonics information. It contains more than 70,000 full-text papers from SPIE...conditions Top row: Stanford Photonics XR-Mega-10 Extreme 1400 x 1024 pixels ICCD detector, 33 msec exposure, no binning. Middle row: Andor EEV iXon

Status of DEMO-FNS development

NASA Astrophysics Data System (ADS)

Kuteev, B. V.; Shpanskiy, Yu. S.; DEMO-FNS Team

2017-07-01

Fusion-fission hybrid facility based on superconducting tokamak DEMO-FNS is developed in Russia for integrated commissioning of steady-state and nuclear fusion technologies at the power level up to 40 MW for fusion and 400 MW for fission reactions. The project status corresponds to the transition from a conceptual design to an engineering one. This facility is considered, in RF, as the main source of technological and nuclear science information, which should complement the ITER research results in the fields of burning plasma physics and control.

Antibody engineering--a valuable asset in preventing closed environment epidemics.

PubMed

Fjallman, Ted; Hall, J Christopher

2005-01-01

Investigations of Mir, Space Shuttle, Skylab and Apollo missions report extensive colonisation of the spacecraft by bacteria and fungi, which can lead to degradative effects on spacecraft equipment and devastating effects on space-grown crops. More than 80% of terrestrial greenhouse epidemics are due to the fungal genera Phytophthora, Pythium and Fusarium, which have been found in life support system test-beds. The advent of recombinant antibody technologies, including ribosome display and phage display, has made it possible to develop antibodies against virtually any toxin or organism and allows for maturation of antibodies by in vitro molecular evolution. These antibodies may play an important role in an integrated pest management regime for life support systems. Efficacy of existing fungal countermeasures could be increased by chemical linkage to antibodies, which target the site of action of the biocide or trap the pathogen in a biofilter. Novel recombinant antibody-biocide fusions can be expressed in situ by plants or symbiotic microbes to create direct disease resistance. c2005 Elsevier Ltd. All rights reserved.

Fusion Studies in Japan

NASA Astrophysics Data System (ADS)

Ogawa, Yuichi

2016-05-01

A new strategic energy plan decided by the Japanese Cabinet in 2014 strongly supports the steady promotion of nuclear fusion development activities, including the ITER project and the Broader Approach activities from the long-term viewpoint. Atomic Energy Commission (AEC) in Japan formulated the Third Phase Basic Program so as to promote an experimental fusion reactor project. In 2005 AEC has reviewed this Program, and discussed on selection and concentration among many projects of fusion reactor development. In addition to the promotion of ITER project, advanced tokamak research by JT-60SA, helical plasma experiment by LHD, FIREX project in laser fusion research and fusion engineering by IFMIF were highly prioritized. Although the basic concept is quite different between tokamak, helical and laser fusion researches, there exist a lot of common features such as plasma physics on 3-D magnetic geometry, high power heat load on plasma facing component and so on. Therefore, a synergetic scenario on fusion reactor development among various plasma confinement concepts would be important.

An Overview of INEL Fusion Safety R&D Facilities

NASA Astrophysics Data System (ADS)

McCarthy, K. A.; Smolik, G. R.; Anderl, R. A.; Carmack, W. J.; Longhurst, G. R.

1997-06-01

The Fusion Safety Program at the Idaho National Engineering Laboratory has the lead for fusion safety work in the United States. Over the years, we have developed several experimental facilities to provide data for fusion reactor safety analyses. We now have four major experimental facilities that provide data for use in safety assessments. The Steam-Reactivity Measurement System measures hydrogen generation rates and tritium mobilization rates in high-temperature (up to 1200°C) fusion relevant materials exposed to steam. The Volatilization of Activation Product Oxides Reactor Facility provides information on mobilization and transport and chemical reactivity of fusion relevant materials at high temperature (up to 1200°C) in an oxidizing environment (air or steam). The Fusion Aerosol Source Test Facility is a scaled-up version of VAPOR. The ion-implanta-tion/thermal-desorption system is dedicated to research into processes and phenomena associated with the interaction of hydrogen isotopes with fusion materials. In this paper we describe the capabilities of these facilities.

Engineered three-dimensional multicellular culture model to ...

EPA Pesticide Factsheets

Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in developmental processes including heart development, neural tube closure, and palatal fusion are dependent on epithelial-mesenchymal interactions (EMIs) and specific signaling pathways that have been elucidated largely using gene knockout mouse models. A broad analysis of literature using ToxRefDB identified 63 ToxCast chemicals associated with cleft palate in animal models. However, the influence of these and other putative teratogens on human palatal fusion has not been examined in depth due to the lack of in vitro models incorporating EMIs between human cell types. We sought to engineer the stratified mesenchymal and epithelial structure of the developing palate in vitro using spheroid culture of human Wharton’s Jelly mesenchymal stem cells (hMSC). hMSC spheroids exhibited uniform size over time (175 ± 21 µm mean diameter) that was proportional to starting cell density. Further, hMSCs in spheroid culture exhibited increased alkaline phosphatase activity and increased expression of bglap and runx2 after 7 days of culture in osteo-induction medium, which suggests that spheroid culture together with osteo-induction medium supports osteogenic differentiation. We developed a novel pro

Extension of an iterative closest point algorithm for simultaneous localization and mapping in corridor environments

NASA Astrophysics Data System (ADS)

Yue, Haosong; Chen, Weihai; Wu, Xingming; Wang, Jianhua

2016-03-01

Three-dimensional (3-D) simultaneous localization and mapping (SLAM) is a crucial technique for intelligent robots to navigate autonomously and execute complex tasks. It can also be applied to shape measurement, reverse engineering, and many other scientific or engineering fields. A widespread SLAM algorithm, named KinectFusion, performs well in environments with complex shapes. However, it cannot handle translation uncertainties well in highly structured scenes. This paper improves the KinectFusion algorithm and makes it competent in both structured and unstructured environments. 3-D line features are first extracted according to both color and depth data captured by Kinect sensor. Then the lines in the current data frame are matched with the lines extracted from the entire constructed world model. Finally, we fuse the distance errors of these line-pairs into the standard KinectFusion framework and estimate sensor poses using an iterative closest point-based algorithm. Comparative experiments with the KinectFusion algorithm and one state-of-the-art method in a corridor scene have been done. The experimental results demonstrate that after our improvement, the KinectFusion algorithm can also be applied to structured environments and has higher accuracy. Experiments on two open access datasets further validated our improvements.

Model-based diagnostics of gas turbine engine lubrication systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byington, C.S.

1998-09-01

The objective of the current research was to develop improved methodology for diagnosing anomalies and maintaining oil lubrication systems for gas turbine engines. The effort focused on the development of reasoning modules that utilize the existing, inexpensive sensors and are applicable to on-line monitoring within the full-authority digital engine controller (FADEC) of the engine. The target application is the Enhanced TF-40B gas turbine engine that powers the Landing Craft Air Cushion (LCAC) platform. To accomplish the development of the requisite data fusion algorithms and automated reasoning for the diagnostic modules, Penn State ARL produced a generic Turbine Engine Lubrication Systemmore » Simulator (TELSS) and Data Fusion Workbench (DFW). TELSS is a portable simulator code that calculates lubrication system parameters based upon one-dimensional fluid flow resistance network equations. Validation of the TF- 40B modules was performed using engineering and limited test data. The simulation model was used to analyze operational data from the LCAC fleet. The TELSS, as an integral portion of the DFW, provides the capability to experiment with combinations of variables and feature vectors that characterize normal and abnormal operation of the engine lubrication system. The model-based diagnostics approach is applicable to all gas turbine engines and mechanical transmissions with similar pressure-fed lubrication systems.« less

Development of a Tightly Controlled Off Switch for Saccharomyces cerevisiae Regulated by Camphor, a Low-Cost Natural Product

PubMed Central

Ikushima, Shigehito; Zhao, Yu; Boeke, Jef D.

2015-01-01

Here we describe the engineering of a distant homolog of the Tet repressor, CamR, isolated from Pseudomonas putida, that is regulated by camphor, a very inexpensive small molecule (at micromolar concentrations) for use in Saccharomyces cerevisiae. The repressor was engineered by expression from a constitutive yeast promoter, fusion to a viral activator protein cassette, and codon optimization. A suitable promoter responsive to the CamR fusion protein was engineered by embedding a P. putida operator binding sequence within an upstream activating sequence (UAS)-less CYC1 promoter from S. cerevisiae. The switch, named the Camphor-Off switch, activates expression of a reporter gene in camphor-free media and represses it with micromolar concentrations of camphor. PMID:26206350

Fiber Laser Welded AZ31 Magnesium Alloy: The Effect of Welding Speed on Microstructure and Mechanical Properties

NASA Astrophysics Data System (ADS)

Chowdhury, S. H.; Chen, D. L.; Bhole, S. D.; Powidajko, E.; Weckman, D. C.; Zhou, Y.

2012-06-01

This study was aimed at characterizing microstructural change and evaluating tensile and fatigue properties of fiber laser welded AZ31B-H24 Mg alloy with special attention to the effect of welding speed. Laser welding led to the formation of equiaxed dendrites in the fusion zone and columnar dendrites near the fusion zone boundary along with divorced eutectic Mg17Al12 particles and recrystallized grains in the heat-affected zone. The lowest hardness across the weld appeared in the fusion zone. Although the yield strength, ductility, and fatigue life decreased, the hardening capacity increased after laser welding, with a joint efficiency reaching about 90 pct. A higher welding speed resulted in a narrower fusion zone, smaller grain size, higher yield strength, and longer fatigue life, as well as a slightly lower strain-hardening capacity mainly because of the smaller grain sizes. Tensile fracture occurred in the fusion zone, whereas fatigue failure appeared essentially in between the heat-affected zone and the fusion zone. Fatigue cracks initiated from the near-surface welding defects and propagated by the formation of fatigue striations together with secondary cracks.

Lead (Pb) Hohlraum: Target for Inertial Fusion Energy

PubMed Central

Ross, J. S.; Amendt, P.; Atherton, L. J.; Dunne, M.; Glenzer, S. H.; Lindl, J. D.; Meeker, D.; Moses, E. I.; Nikroo, A.; Wallace, R.

2013-01-01

Recent progress towards demonstrating inertial confinement fusion (ICF) ignition at the National Ignition Facility (NIF) has sparked wide interest in Laser Inertial Fusion Energy (LIFE) for carbon-free large-scale power generation. A LIFE-based fleet of power plants promises clean energy generation with no greenhouse gas emissions and a virtually limitless, widely available thermonuclear fuel source. For the LIFE concept to be viable, target costs must be minimized while the target material efficiency or x-ray albedo is optimized. Current ICF targets on the NIF utilize a gold or depleted uranium cylindrical radiation cavity (hohlraum) with a plastic capsule at the center that contains the deuterium and tritium fuel. Here we show a direct comparison of gold and lead hohlraums in efficiently ablating deuterium-filled plastic capsules with soft x rays. We report on lead hohlraum performance that is indistinguishable from gold, yet costing only a small fraction. PMID:23486285

Lead (Pb) hohlraum: target for inertial fusion energy.

PubMed

Ross, J S; Amendt, P; Atherton, L J; Dunne, M; Glenzer, S H; Lindl, J D; Meeker, D; Moses, E I; Nikroo, A; Wallace, R

2013-01-01

Recent progress towards demonstrating inertial confinement fusion (ICF) ignition at the National Ignition Facility (NIF) has sparked wide interest in Laser Inertial Fusion Energy (LIFE) for carbon-free large-scale power generation. A LIFE-based fleet of power plants promises clean energy generation with no greenhouse gas emissions and a virtually limitless, widely available thermonuclear fuel source. For the LIFE concept to be viable, target costs must be minimized while the target material efficiency or x-ray albedo is optimized. Current ICF targets on the NIF utilize a gold or depleted uranium cylindrical radiation cavity (hohlraum) with a plastic capsule at the center that contains the deuterium and tritium fuel. Here we show a direct comparison of gold and lead hohlraums in efficiently ablating deuterium-filled plastic capsules with soft x rays. We report on lead hohlraum performance that is indistinguishable from gold, yet costing only a small fraction.

Fusion-Enabled Pluto Orbiter and Lander

NASA Technical Reports Server (NTRS)

Thomas, Stephanie

2017-01-01

The Pluto orbiter mission proposed here is credible and exciting. The benefits to this and all outer-planet and interstellar-probe missions are difficult to overstate. The enabling technology, Direct Fusion Drive, is a unique fusion engine concept based on the Princeton Field-Reversed Configuration (PFRC) fusion reactor under development at the Princeton Plasma Physics Laboratory. The truly game-changing levels of thrust and power in a modestly sized package could integrate with our current launch infrastructure while radically expanding the science capability of these missions. During this Phase I effort, we made great strides in modeling the engine efficiency, thrust, and specific impulse and analyzing feasible trajectories. Based on 2D fluid modeling of the fusion reactors outer stratum, its scrape-off-layer (SOL), we estimate achieving 2.5 to 5 N of thrust for each megawatt of fusion power, reaching a specific impulse, Isp, of about 10,000 s. Supporting this model are particle-in-cell calculations of energy transfer from the fusion products to the SOL electrons. Subsequently, this energy is transferred to the ions as they expand through the magnetic nozzle and beyond. Our point solution for the Pluto mission now delivers 1000 kg of payload to Pluto orbit in 3.75 years using 7.5 N constant thrust. This could potentially be achieved with a single 1 MW engine. The departure spiral from Earth orbit and insertion spiral to Pluto orbit require only a small portion of the total delta-V. Departing from low Earth orbit reduces mission cost while increasing available mission mass. The payload includes a lander, which utilizes a standard green propellant engine for the landing sequence. The lander has about 4 square meters of solar panels mounted on a gimbal that allows it to track the orbiter, which beams 30 to 50 kW of power using a 1080 nm laser. Optical communication provides dramatically high data rates back to Earth. Our mass modeling investigations revealed that if current high-temperature superconductors are utilized at liquid nitrogen temperatures, they drive the mass of the engine, partly because of the shielding required to maintain their critical temperature. Second generation materials are thinner but the superconductor is a very thin layer deposited on a substrate with additional layers of metallic classing. Tremendous research is being performed on a variety of these superconducting materials, and new irradiation data is now available. This raises the possibility of operating nearfuture high-temperature superconductors at a moderately low temperature to dramatically reduce the amount of shielding required. At the same time, a first generation space engine may require low-temperature superconductors, which are higher TRL and have been designed for space coils before (AMS-02 experiment for the ISS). We performed detailed analysis of the startup system and thermal conversion system components. The ideal working fluid was determined to be a blend of Helium and Xenon. No significant problems were identified with these subsystems. For the RF system, we conceived of a new, more efficient design using state-of-the-art switch amplifiers, which have the potential for 100% efficiency. This report presents details of our engine and trajectory analyses, mass modeling efforts, and updated vehicle designs.

Integrated Display and Simulation for Automatic Dependent Surveillance-Broadcast and Traffic Collision Avoidance System Data Fusion.

PubMed

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-11-13

Automatic Dependent Surveillance-Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications.

Fusion Safety Program annual report, fiscal year 1994

NASA Astrophysics Data System (ADS)

Longhurst, Glen R.; Cadwallader, Lee C.; Dolan, Thomas J.; Herring, J. Stephen; McCarthy, Kathryn A.; Merrill, Brad J.; Motloch, Chester C.; Petti, David A.

1995-03-01

This report summarizes the major activities of the Fusion Safety Program in fiscal year 1994. The Idaho National Engineering Laboratory (INEL) is the designated lead laboratory and Lockheed Idaho Technologies Company is the prime contractor for this program. The Fusion Safety Program was initiated in 1979. Activities are conducted at the INEL, at other DOE laboratories, and at other institutions, including the University of Wisconsin. The technical areas covered in this report include tritium safety, beryllium safety, chemical reactions and activation product release, safety aspects of fusion magnet systems, plasma disruptions, risk assessment failure rate data base development, and thermalhydraulics code development and their application to fusion safety issues. Much of this work has been done in support of the International Thermonuclear Experimental Reactor (ITER). Also included in the report are summaries of the safety and environmental studies performed by the Fusion Safety Program for the Tokamak Physics Experiment and the Tokamak Fusion Test Reactor and of the technical support for commercial fusion facility conceptual design studies. A major activity this year has been work to develop a DOE Technical Standard for the safety of fusion test facilities.

Task toward a Realization of Commercial Tokamak Fusion Plants in 2050 -The Role of ITER and the Succeeding Developments- 4.Technology and Material Research in Fusion Power Plant Development

NASA Astrophysics Data System (ADS)

Akiba, Masato; Matsui, Hideki; Takatsu, Hideyuki; Konishi, Satoshi

Technical issues regarding the fusion power plant that are required to be developed in the period of ITER construction and operation, both with ITER and with other facilities that complement ITER are described in this section. Three major fields are considered to be important in fusion technology. Section 4.1 summarizes blanket study, and ITER Test Blanket Module (TBM) development that focuses its effort on the first generation power blanket to be installed in DEMO. ITER will be equipped with 6 TBMs which are developed under each party's fusion program. In Japan, the solid breeder using water as a coolant is the primary candidate, and He-cooled pebble bed is the alternative. Other liquid options such as LiPb, Li or molten salt are developed by other parties' initiatives. The Test Blanket Working Group (TBWG) is coordinating these efforts. Japanese universities are investigating advanced concepts and fundamental crosscutting technologies. Section 4.2 introduces material development and particularly, the international irradiation facility, IFMIF. Reduced activation ferritic/martensitic steels are identified as promising candidates for the structural material of the first generation fusion blanket, while and vanadium alloy and SiC/SiC composite are pursued as advanced options. The IFMIF is currently planning the next phase of joint activity, EVEDA (Engineering Validation and Engineering Design Activity) that encompasses construction. Material studies together with the ITER TBM will provide essential technical information for development of the fusion power plant. Other technical issues to be addressed regarding the first generation fusion power plant are summarized in section 4.3. Development of components for ITER made remarkable progress for the major essential technology also necessary for future fusion plants, however many still need further improvements toward power plant. Such areas includes; the divertor, plasma heating/current drive, magnets, tritium, and remote handling. There remain many other technical issues for power plant which require integrated efforts.

Developing the IVIG biomimetic, Hexa-Fc, for drug and vaccine applications

PubMed Central

Czajkowsky, Daniel M.; Andersen, Jan Terje; Fuchs, Anja; Wilson, Timothy J.; Mekhaiel, David; Colonna, Marco; He, Jianfeng; Shao, Zhifeng; Mitchell, Daniel A.; Wu, Gang; Dell, Anne; Haslam, Stuart; Lloyd, Katy A.; Moore, Shona C.; Sandlie, Inger; Blundell, Patricia A.; Pleass, Richard J.

2015-01-01

The remarkable clinical success of Fc-fusion proteins has driven intense investigation for even more potent replacements. Using quality-by-design (QbD) approaches, we generated hexameric-Fc (hexa-Fc), a ~20 nm oligomeric Fc-based scaffold that we here show binds low-affinity inhibitory receptors (FcRL5, FcγRIIb, and DC-SIGN) with high avidity and specificity, whilst eliminating significant clinical limitations of monomeric Fc-fusions for vaccine and/or cancer therapies, in particular their poor ability to activate complement. Mass spectroscopy of hexa-Fc reveals high-mannose, low-sialic acid content, suggesting that interactions with these receptors are influenced by the mannose-containing Fc. Molecular dynamics (MD) simulations provides insight into the mechanisms of hexa-Fc interaction with these receptors and reveals an unexpected orientation of high-mannose glycans on the human Fc that provides greater accessibility to potential binding partners. Finally, we show that this biosynthetic nanoparticle can be engineered to enhance interactions with the human neonatal Fc receptor (FcRn) without loss of the oligomeric structure, a crucial modification for these molecules in therapy and/or vaccine strategies where a long plasma half-life is critical. PMID:25912958

Ignition and Inertial Confinement Fusion at The National Ignition Facility

NASA Astrophysics Data System (ADS)

Moses, Edward I.

2016-10-01

The National Ignition Facility (NIF), the world's largest and most powerful laser system for inertial confinement fusion (ICF) and for studying high-energy-density (HED) science, is now operational at Lawrence Livermore National Laboratory (LLNL). The NIF is now conducting experiments to commission the laser drive, the hohlraum and the capsule and to develop the infrastructure needed to begin the first ignition experiments in FY 2010. Demonstration of ignition and thermonuclear bum in the laboratory is a major NIF goal. NIF will achieve this by concentrating the energy from the 192 beams into a mm3-sized target and igniting a deuterium-tritium mix, liberating more energy than is required to initiate the fusion reaction. NIP's ignition program is a national effort managed via the National Ignition Campaign (NIC). The NIC has two major goals: execution of DT ignition experiments starting in FY20l0 with the goal of demonstrating ignition and a reliable, repeatable ignition platform by the conclusion of the NIC at the end of FY2012. The NIC will also develop the infrastructure and the processes required to operate NIF as a national user facility. The achievement of ignition at NIF will demonstrate the scientific feasibility of ICF and focus worldwide attention on laser fusion as a viable energy option. A laser fusion-based energy concept that builds on NIF, known as LIFE (Laser Inertial Fusion Energy), is currently under development. LIFE is inherently safe and can provide a global carbon-free energy generation solution in the 21st century. This paper describes recent progress on NIF, NIC, and the LIFE concept.

Prion extraction methods: comparison of bead beating, ultrasonic disruption and repeated freeze-thaw methodologies for the recovery of functional renilla-prion fusion protein from bacteria

USDA-ARS?s Scientific Manuscript database

Molecular DNA technology allows for production of mammalian proteins in bacteria at sufficient quantities for downstream use and analysis. Variation in design and engineering of DNA expression vectors imparts selective alterations resulting in the generation of fusion proteins with intrinsic report...

Regulation of skeletal myotube formation and alignment by nanotopographically controlled cell-secreted extracellular matrix.

PubMed

Jiao, Alex; Moerk, Charles T; Penland, Nisa; Perla, Mikael; Kim, Jinsung; Smith, Alec S T; Murry, Charles E; Kim, Deok-Ho

2018-06-01

Skeletal muscle has a well-organized tissue structure comprised of aligned myofibers and an encasing extracellular matrix (ECM) sheath or lamina, within which reside satellite cells. We hypothesize that the organization of skeletal muscle tissues in culture can affect both the structure of the deposited ECM and the differentiation potential of developing myotubes. Furthermore, we posit that cellular and ECM cues can be a strong determinant of myoblast fusion and morphology in 3D tissue culture environments. To test these, we utilized a thermoresponsive nanofabricated substratum to engineer anisotropic sheets of myoblasts which could then be transferred and stacked into multilayered tissues. Within such engineered tissues, we found that myoblasts rapidly sense topography and deposit structurally organized ECM proteins. Furthermore, the initial tissue structure was found to exert significant control over myoblast fusion and eventual myotube organization. These results highlight the importance of ECM structure on myoblast fusion and organization, and provide insights into substrate-mediated control of myotube formation in the development of novel, more effective, engineered skeletal muscle tissues. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1543-1551, 2018. © 2018 Wiley Periodicals, Inc.

Tapered Roller Bearing Damage Detection Using Decision Fusion Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Kreider, Gary; Fichter, Thomas

2006-01-01

A diagnostic tool was developed for detecting fatigue damage of tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. A diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests conducted using health monitoring hardware. Failure progression tests were performed with tapered roller bearings under simulated engine load conditions. Tests were performed on one healthy bearing and three pre-damaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor and three accelerometers were monitored and recorded for the occurrence of bearing failure. The bearing was removed and inspected periodically for damage progression throughout testing. Using data fusion techniques, two different monitoring technologies, oil debris analysis and vibration, were integrated into a health monitoring system for detecting bearing surface fatigue pitting damage. The data fusion diagnostic tool was evaluated during bearing failure progression tests under simulated engine load conditions. This integrated system showed improved detection of fatigue damage and health assessment of the tapered roller bearings as compared to using individual health monitoring technologies.

Advantages of Production of New Fissionable Nuclides for the Nuclear Power Industry in Hybrid Fusion-Fission Reactors

NASA Astrophysics Data System (ADS)

Tsibulskiy, V. F.; Andrianova, E. A.; Davidenko, V. D.; Rodionova, E. V.; Tsibulskiy, S. V.

2017-12-01

A concept of a large-scale nuclear power engineering system equipped with fusion and fission reactors is presented. The reactors have a joint fuel cycle, which imposes the lowest risk of the radiation impact on the environment. The formation of such a system is considered within the framework of the evolution of the current nuclear power industry with the dominance of thermal reactors, gradual transition to the thorium fuel cycle, and integration into the system of the hybrid fusion-fission reactors for breeding nuclear fuel for fission reactors. Such evolution of the nuclear power engineering system will allow preservation of the existing structure with the dominance of thermal reactors, enable the reprocessing of the spent nuclear fuel (SNF) with low burnup, and prevent the dangerous accumulation of minor actinides. The proposed structure of the nuclear power engineering system minimizes the risk of radioactive contamination of the environment and the SNF reprocessing facilities, decreasing it by more than one order of magnitude in comparison with the proposed scheme of closing the uranium-plutonium fuel cycle based on the reprocessing of SNF with high burnup from fast reactors.

Engineering naturally occurring trans-acting non-coding RNAs to sense molecular signals

PubMed Central

Qi, Lei; Lucks, Julius B.; Liu, Chang C.; Mutalik, Vivek K.; Arkin, Adam P.

2012-01-01

Non-coding RNAs (ncRNAs) are versatile regulators in cellular networks. While most trans-acting ncRNAs possess well-defined mechanisms that can regulate transcription or translation, they generally lack the ability to directly sense cellular signals. In this work, we describe a set of design principles for fusing ncRNAs to RNA aptamers to engineer allosteric RNA fusion molecules that modulate the activity of ncRNAs in a ligand-inducible way in Escherichia coli. We apply these principles to ncRNA regulators that can regulate translation (IS10 ncRNA) and transcription (pT181 ncRNA), and demonstrate that our design strategy exhibits high modularity between the aptamer ligand-sensing motif and the ncRNA target-recognition motif, which allows us to reconfigure these two motifs to engineer orthogonally acting fusion molecules that respond to different ligands and regulate different targets in the same cell. Finally, we show that the same ncRNA fused with different sensing domains results in a sensory-level NOR gate that integrates multiple input signals to perform genetic logic. These ligand-sensing ncRNA regulators provide useful tools to modulate the activity of structurally related families of ncRNAs, and building upon the growing body of RNA synthetic biology, our ability to design aptamer–ncRNA fusion molecules offers new ways to engineer ligand-sensing regulatory circuits. PMID:22383579

Spinal fusion surgery: From relief to insecurity.

PubMed

Damsgaard, Janne B; Jørgensen, Lene B; Norlyk, Annelise; Birkelund, Regner

2017-02-01

During their decision-making process patients perceive surgery as a voluntary yet necessary choice. Surgery initiates hope for a life with less pain but also creates a feeling of existential insecurity in terms of fear, isolation and uncertainty. The aim of this study was to explore how patients experience their situation from the point of making the decision to undergo spinal fusion surgery to living their everyday life after surgery. A phenomenological-hermeneutic study design was applied based on the French philosopher Paul Ricoeur's theory of interpretation. Data were collected through observations and semi-structured interviews. The recommendation and decision to undergo spinal fusion surgery felt like a turning point for the patients and brought hope of regaining their normal lives, of being a more resourceful parent, partner, friend and colleague with no or less pain. Thus, deciding to undergo surgery created a brief feeling of relief. However, life with back pain had changed the patients' understanding of themselves. Consequently, some patients postoperatively experienced insecurity and a weakened self-image with difficulties creating meaning in their lives. Being recommended and undergoing spinal fusion surgery initiates hope for a life with less pain and altered life conditions. At the same time, paradoxically, this creates a feeling of existential insecurity in terms of facing the surgery and the future to come. It is, therefore, important to recognise and include the patients' everyday life experiences concerning how they give (or may not give) meaning to their illness, i.e. their understanding of how it is affecting them. These aspects are essential for the patients' definition and re-definition of themselves and thus crucial to draw upon in the relationship and communication between patient and healthcare professional. Copyright © 2016 Elsevier Ltd. All rights reserved.

Current Status and Recent Research Achievements in SiC/SiC Composites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katoh, Yutai; Snead, Lance L.; Henager, Charles H.

2014-12-01

The development and maturation of the silicon carbide fiber-reinforced silicon carbide matrix (SiC/SiC) composite system for fusion applications has seen the evolution from fundamental development and understanding of the material system and its behavior in a hostile irradiation environment to the current effort which essentially is a broad-based program of technology, directed at moving this material class from a laboratory curiosity to an engineering material. This paper lays out the recent international scientific and technological achievements in the development of SiC/SiC composite material technologies for fusion application and will discuss future research directions. It also reviews the materials system inmore » the larger context of progress to maturity as an engineering material for both the larger nuclear community and for general engineering applications.« less

Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor.

PubMed

Boado, Ruben J; Lu, Jeff Zhiqiang; Hui, Eric K-W; Sumbria, Rachita K; Pardridge, William M

2013-05-01

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, and acts as a molecular Trojan horse to ferry the ASA into brain from blood. The HIRMAb-ASA is expressed in stably transfected Chinese hamster ovary cells grown in serum free medium, and purified by protein A affinity chromatography. The fusion protein retains high affinity binding to the HIR, EC50 = 0.34 ± 0.11 nM, and retains high ASA enzyme activity, 20 ± 1 units/mg. The HIRMAb-ASA fusion protein is endocytosed and triaged to the lysosomal compartment in MLD fibroblasts. The fusion protein was radio-labeled with the Bolton-Hunter reagent, and the [(125) I]-HIRMAb-ASA rapidly penetrates the brain in the Rhesus monkey following intravenous administration. Film and emulsion autoradiography of primate brain shows global distribution of the fusion protein throughout the monkey brain. These studies describe a new biological entity that is designed to treat the brain of humans with MLD following non-invasive, intravenous infusion of an IgG-ASA fusion protein. Copyright © 2012 Wiley Periodicals, Inc.

IgG-Paraoxonase-1 Fusion Protein for Targeted Drug Delivery Across the Human Blood-Brain Barrier

PubMed Central

Boado, Ruben J.; Zhang, Yun; Zhang, Yufeng; Wang, Yuntao; Pardridge, William M.

2009-01-01

Paraoxonase (PON)-1 is the most potent human protein with organophosphatase activity against organophosphate (OP) toxins. OP compounds readily cross the blood-brain barrier (BBB), and have lethal mechanisms of action within the brain. The production of a brain penetrating form of human PON1, which crosses the BBB, is possible with the re-engineering of the enzyme as a fusion protein with a monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via the endogenous insulin receptor, and acts as a molecular Trojan horse to ferry the PON1 into brain. The human PON1 was fused to the carboxyl terminus of the heavy chain of the chimeric HIRMAb. COS cells were dual transfected with the heavy chain gene and the light chain gene, and the HIRMAb-PON1 fusion protein was affinity purified with protein A chromatography. Western blotting with antibodies to human IgG or human PON1 showed the heavy chain of the HIRMAb-PON1 fusion protein was 40 kDa larger than the heavy chain of the chimeric HIRMAb. The ED50 of binding to the HIR extracellular domain was 0.55 ± 0.07 nM and 1.1 ±0.1 nM, respectively, for the chimeric HIRMAb and the HIRMAb-PON1 fusion protein. The PON1 enzyme activity of the fusion protein was approximately 25% of the enzyme activity in human plasma, based on a fluorometric enzymatic assay. In conclusion, human PON1 has been re-engineered as an IgG-organophosphatase fusion protein that penetrates the human BBB. PMID:19434854

Application of Laser Treatment for Hardening Parts of Gas Turbine Engines from Titanium Alloys

NASA Astrophysics Data System (ADS)

Girzhon, V. V.; Ovchinnikov, A. V.

2017-03-01

X-ray diffraction analysis and light microscopy are used to study the structure of surface layers of helically extruded specimens of titanium alloy VT25U after laser fusion of the surface. It is shown that the rates of cooling of the melt promote formation of a martensitic α″-phase in the zone of laser fusion and of a submicrocrystalline microstructure. The microhardness in the zone of fusion of the initial specimens exceeds the microhardness of the specimens after the extrusion.

Fusion Propulson System Requirements for an Interstellar Probe

NASA Technical Reports Server (NTRS)

Spencer, D. F.

1963-01-01

An examination of the engine constraints for a fusion-propelled vehicle indicates that minimum flight times for a probe to a 5 light-year star will be approximately 50 years. The principal restraint on the vehicle is the radiator weight and size necessary to dissipate the heat which enters the chamber walls from the fusion plasma. However, it is interesting, at least theoretically, that the confining magnetic field strength is of reasonable magnitude, 2 to 3 x 10(exp5) gauss, and the confinement time is approximately 0.1 sec.

Latent cytokines for targeted therapy of inflammatory disorders.

PubMed

Mullen, Lisa; Adams, Gill; Layward, Lorna; Vessillier, Sandrine; Annenkov, Alex; Mittal, Gayatri; Rigby, Anne; Sclanders, Michelle; Baker, David; Gould, David; Chernajovsky, Yuti

2014-01-01

The use of cytokines as therapeutic agents is important, given their potent biological effects. However, this very potency, coupled with the pleiotropic nature and short half-life of these molecules, has limited their therapeutic use. Strategies to increase the half-life and to decrease toxicity are necessary to allow effective treatment with these molecules. A number of strategies are used to overcome the natural limitations of cytokines, including PEGylation, encapsulation in liposomes, fusion to targeting peptides or antibodies and latent cytokines. Latent cytokines are engineered using the latency-associated peptide of transforming growth factor-β to produce therapeutic cytokines/peptides that are released only at the site of disease by cleavage with disease-induced matrix metalloproteinases. The principles underlying the latent cytokine technology are described and are compared to other methods of cytokine delivery. The potential of this technology for developing novel therapeutic strategies for the treatment of diseases with an inflammatory-mediated component is discussed. Methods of therapeutic cytokine delivery are addressed. The latent cytokine technology holds significant advantages over other methods of drug delivery by providing simultaneously increased half-life and localised drug delivery without systemic effects. Cytokines that failed clinical trials should be reassessed using this delivery system.

Beyond ITER: neutral beams for a demonstration fusion reactor (DEMO) (invited).

PubMed

McAdams, R

2014-02-01

In the development of magnetically confined fusion as an economically sustainable power source, International Tokamak Experimental Reactor (ITER) is currently under construction. Beyond ITER is the demonstration fusion reactor (DEMO) programme in which the physics and engineering aspects of a future fusion power plant will be demonstrated. DEMO will produce net electrical power. The DEMO programme will be outlined and the role of neutral beams for heating and current drive will be described. In particular, the importance of the efficiency of neutral beam systems in terms of injected neutral beam power compared to wallplug power will be discussed. Options for improving this efficiency including advanced neutralisers and energy recovery are discussed.

Active inclusion bodies of acid phosphatase PhoC: aggregation induced by GFP fusion and activities modulated by linker flexibility

PubMed Central

2013-01-01

Background Biologically active inclusion bodies (IBs) have gained much attention in recent years. Fusion with IB-inducing partner has been shown to be an efficient strategy for generating active IBs. To make full use of the advantages of active IBs, one of the key issues will be to improve the activity yield of IBs when expressed in cells, which would need more choices on IB-inducing fusion partners and approaches for engineering IBs. Green fluorescent protein (GFP) has been reported to aggregate when overexpressed, but GFP fusion has not been considered as an IB-inducing approach for these fusion proteins so far. In addition, the role of linker in fusion proteins has been shown to be important for protein characteristics, yet impact of linker on active IBs has never been reported. Results Here we report that by fusing GFP and acid phosphatase PhoC via a linker region, the resultant PhoC-GFPs were expressed largely as IBs. These IBs show high levels of specific fluorescence and specific PhoC activities (phosphatase and phosphotransferase), and can account for up to over 80% of the total PhoC activities in the cells. We further demonstrated that the aggregation of GFP moiety in the fusion protein plays an essential role in the formation of PhoC-GFP IBs. In addition, PhoC-GFP IBs with linkers of different flexibility were found to exhibit different levels of activities and ratios in the cells, suggesting that the linker region can be utilized to manipulate the characteristics of active IBs. Conclusions Our results show that active IBs of PhoC can be generated by GFP fusion, demonstrating for the first time the potential of GFP fusion to induce active IB formation of another soluble protein. We also show that the linker sequence in PhoC-GFP fusion proteins plays an important role on the regulation of IB characteristics, providing an alternative and important approach for engineering of active IBs with the goal of obtaining high activity yield of IBs. PMID:23497261

Paramyxovirus Glycoproteins and the Membrane Fusion Process.

PubMed

Aguilar, Hector C; Henderson, Bryce A; Zamora, J Lizbeth; Johnston, Gunner P

2016-09-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development.

Paramyxovirus Glycoproteins and the Membrane Fusion Process

PubMed Central

Aguilar, Hector C.; Henderson, Bryce A.; Zamora, J. Lizbeth; Johnston, Gunner P.

2016-01-01

The family Paramyxoviridae includes many viruses that significantly affect human and animal health. An essential step in the paramyxovirus life cycle is viral entry into host cells, mediated by virus-cell membrane fusion. Upon viral entry, infection results in expression of the paramyxoviral glycoproteins on the infected cell surface. This can lead to cell-cell fusion (syncytia formation), often linked to pathogenesis. Thus membrane fusion is essential for both viral entry and cell-cell fusion and an attractive target for therapeutic development. While there are important differences between viral-cell and cell-cell membrane fusion, many aspects are conserved. The paramyxoviruses generally utilize two envelope glycoproteins to orchestrate membrane fusion. Here, we discuss the roles of these glycoproteins in distinct steps of the membrane fusion process. These findings can offer insights into evolutionary relationships among Paramyxoviridae genera and offer future targets for prophylactic and therapeutic development. PMID:28138419

Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

PubMed

Young, Patricia A; Morrison, Sherie L; Timmerman, John M

2014-10-01

The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

Situational awareness of a coordinated cyber attack

NASA Astrophysics Data System (ADS)

Sudit, Moises; Stotz, Adam; Holender, Michael

2005-03-01

As technology continues to advance, services and capabilities become computerized, and an ever increasing amount of business is conducted electronically the threat of cyber attacks gets compounded by the complexity of such attacks and the criticality of the information which must be secured. A new age of virtual warfare has dawned in which seconds can differentiate between the protection of vital information and/or services and a malicious attacker attaining their goal. In this paper we present a novel approach in the real-time detection of multistage coordinated cyber attacks and the promising initial testing results we have obtained. We introduce INFERD (INformation Fusion Engine for Real-time Decision-making), an adaptable information fusion engine which performs fusion at levels zero, one, and two to provide real-time situational assessment and its application to the cyber domain in the ECCARS (Event Correlation for Cyber Attack Recognition System) system. The advantages to our approach are fourfold: (1) The complexity of the attacks which we consider, (2) the level of abstraction in which the analyst interacts with the attack scenarios, (3) the speed at which the information fusion is presented and performed, and (4) our disregard for ad-hoc rules or a priori parameters.

Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen.

PubMed

Klose, Diana; Saunders, Ute; Barth, Stefan; Fischer, Rainer; Jacobi, Annett Marita; Nachreiner, Thomas

2016-02-17

In an earlier study we developed a unique strategy allowing us to specifically eliminate antigen-specific murine B cells via their distinct B cell receptors using a new class of fusion proteins. In the present work we elaborated our idea to demonstrate the feasibility of specifically addressing and eliminating human memory B cells. The present study reveals efficient adaptation of the general approach to selectively target and eradicate human memory B cells. In order to demonstrate the feasibility we engineered a fusion protein following the principle of recombinant immunotoxins by combining a model antigen (tetanus toxoid fragment C, TTC) for B cell receptor targeting and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA') to induce apoptosis after cellular uptake. The TTC-ETA' fusion protein not only selectively bound to a TTC-reactive murine B cell hybridoma cell line in vitro but also to freshly isolated human memory B cells from immunized donors ex vivo. Specific toxicity was confirmed on an antigen-specific population of human CD27(+) memory B cells. This protein engineering strategy can be used as a generalized platform approach for the construction of therapeutic fusion proteins with disease-relevant antigens as B cell receptor-binding domains, offering a promising approach for the specific depletion of autoreactive B-lymphocytes in B cell-driven autoimmune diseases.

A Roadmap for Aircraft Engine Life Extending Control

NASA Technical Reports Server (NTRS)

Guo, Ten-Huei

2001-01-01

The concept of Aircraft Engine Life Extending Control is introduced. A brief description of the tradeoffs between performance and engine life are first explained. The overall goal of the life extending controller is to reduce the engine operating cost by extending the on-wing engine life while improving operational safety. The research results for NASA's Rocket Engine life extending control program are also briefly described. Major building blocks of the Engine Life Extending Control architecture are examined. These blocks include: life prediction models, engine operation models, stress and thermal analysis tools, control schemes, and intelligent control systems. The technology areas that would likely impact the successful implementation of an aircraft engine life extending control are also briefly described. Near, intermediate, and long term goals of NASA's activities are also presented.

Effect of Individual Component Life Distribution on Engine Life Prediction

NASA Technical Reports Server (NTRS)

Zaretsky, Erwin V.; Hendricks, Robert C.; Soditus, Sherry M.

2003-01-01

The effect of individual engine component life distributions on engine life prediction was determined. A Weibull-based life and reliability analysis of the NASA Energy Efficient Engine was conducted. The engine s life at a 95 and 99.9 percent probability of survival was determined based upon the engine manufacturer s original life calculations and assumed values of each of the component s cumulative life distributions as represented by a Weibull slope. The lives of the high-pressure turbine (HPT) disks and blades were also evaluated individually and as a system in a similar manner. Knowing the statistical cumulative distribution of each engine component with reasonable engineering certainty is a condition precedent to predicting the life and reliability of an entire engine. The life of a system at a given reliability will be less than the lowest-lived component in the system at the same reliability (probability of survival). Where Weibull slopes of all the engine components are equal, the Weibull slope had a minimal effect on engine L(sub 0.1) life prediction. However, at a probability of survival of 95 percent (L(sub 5) life), life decreased with increasing Weibull slope.

Neutron transport-burnup code MCORGS and its application in fusion fission hybrid blanket conceptual research

NASA Astrophysics Data System (ADS)

Shi, Xue-Ming; Peng, Xian-Jue

2016-09-01

Fusion science and technology has made progress in the last decades. However, commercialization of fusion reactors still faces challenges relating to higher fusion energy gain, irradiation-resistant material, and tritium self-sufficiency. Fusion Fission Hybrid Reactors (FFHR) can be introduced to accelerate the early application of fusion energy. Traditionally, FFHRs have been classified as either breeders or transmuters. Both need partition of plutonium from spent fuel, which will pose nuclear proliferation risks. A conceptual design of a Fusion Fission Hybrid Reactor for Energy (FFHR-E), which can make full use of natural uranium with lower nuclear proliferation risk, is presented. The fusion core parameters are similar to those of the International Thermonuclear Experimental Reactor. An alloy of natural uranium and zirconium is adopted in the fission blanket, which is cooled by light water. In order to model blanket burnup problems, a linkage code MCORGS, which couples MCNP4B and ORIGEN-S, is developed and validated through several typical benchmarks. The average blanket energy Multiplication and Tritium Breeding Ratio can be maintained at 10 and 1.15 respectively over tens of years of continuous irradiation. If simple reprocessing without separation of plutonium from uranium is adopted every few years, FFHR-E can achieve better neutronic performance. MCORGS has also been used to analyze the ultra-deep burnup model of Laser Inertial Confinement Fusion Fission Energy (LIFE) from LLNL, and a new blanket design that uses Pb instead of Be as the neutron multiplier is proposed. In addition, MCORGS has been used to simulate the fluid transmuter model of the In-Zinerater from Sandia. A brief comparison of LIFE, In-Zinerater, and FFHR-E will be given.

A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity.

PubMed

York, Joanne; Nunberg, Jack H

2018-01-01

For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase. These effector cells are mixed with target cells infected with the vCB21R-lacZ vaccinia virus encoding a β-galactosidase reporter under the control of the T7 promoter. Cell-cell fusion is induced upon exposure to low-pH medium (pH 5.0), and the resultant expression of the β-galactosidase reporter is quantitated using a chemiluminescent substrate. We have utilized this robust microplate cell-cell fusion assay extensively to study arenavirus entry and its inhibition by small-molecule fusion inhibitors.

Information fusion based optimal control for large civil aircraft system.

PubMed

Zhen, Ziyang; Jiang, Ju; Wang, Xinhua; Gao, Chen

2015-03-01

Wind disturbance has a great influence on landing security of Large Civil Aircraft. Through simulation research and engineering experience, it can be found that PID control is not good enough to solve the problem of restraining the wind disturbance. This paper focuses on anti-wind attitude control for Large Civil Aircraft in landing phase. In order to improve the riding comfort and the flight security, an information fusion based optimal control strategy is presented to restrain the wind in landing phase for maintaining attitudes and airspeed. Data of Boeing707 is used to establish a nonlinear mode with total variables of Large Civil Aircraft, and then two linear models are obtained which are divided into longitudinal and lateral equations. Based on engineering experience, the longitudinal channel adopts PID control and C inner control to keep longitudinal attitude constant, and applies autothrottle system for keeping airspeed constant, while an information fusion based optimal regulator in the lateral control channel is designed to achieve lateral attitude holding. According to information fusion estimation, by fusing hard constraint information of system dynamic equations and the soft constraint information of performance index function, optimal estimation of the control sequence is derived. Based on this, an information fusion state regulator is deduced for discrete time linear system with disturbance. The simulation results of nonlinear model of aircraft indicate that the information fusion optimal control is better than traditional PID control, LQR control and LQR control with integral action, in anti-wind disturbance performance in the landing phase. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

The attitudes of science policy, environmental, and utility leaders on US energy issues and fusion

NASA Astrophysics Data System (ADS)

Miller, J. D.

1986-11-01

One example of basic and applied research at LLNL that has produced major, highly visible scientific and engineering advances has been the research related to controlled fusion energy. Continuing experimentation at LLNL and elsewhere is likely to demonstrate that fusion is a viable, inexhaustible alternative source of energy. Having conducted major fusion energy experiments for over 30 years at LLNL, it scientists and engineers recognized the enormous challenges that lay ahead in this important endeavor. To be successful, it was clear that collaborative efforts with universities, private industry, and other national laboratories would need to be greatly expanded. Along with invention and scientific discovery would come the challenge of transferring the myriad of new technologies from the laboratories to the private sector for commercialization of the fusion energy process and the application of related technologies to yet unimagined new industries and products. Therefore, using fusion energy research as the focus, the Laboratory's Technology Transfer Initiatives Program contracted with the Public Opinion Laboratory to conduct a survey designed to promote a better understanding of effective technology transfer. As one of the recognized authorities on scientific surveys, Dr. Jon Miller of the POL worked with Laboratory scientists to understand the objectives of the survey. He then formulated the questions, designed the survey, and derived his survey sample from a qualified list developed at the POL, which has formed the basis for other survey panels. This report, prepared by Dr. Miller, describes the basis and methodology of this survey process and then presents the survey findings and some conclusions.

Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement.

PubMed

Yari, Maryam; Ghoshoon, Mohammad B; Vakili, Bahareh; Ghasemi, Younes

2017-01-01

Among therapeutic proteins, enzymes represent small and of course profitable market. They can be used to treat important, rare, and deadly diseases. Enzyme therapy is the only available treatment for certain disorders. Here, pharmaceutical enzymes are reviewed. They are categorized in four main groups, enzymes in replacement therapy, enzymes in cancer treatment, enzymes for fibrinolysis, and finally enzymes that are used topically for various treatments. Furthermore, enzyme gene therapy and future perspective of therapeutic enzymes are mentioned in brief. There are many important approved enzymes in pharmaceutical market. Several approaches such as point mutation, fusion protein designing, glycoengineering, and PEGylation were used to achieve improved enzymes. Although sometimes enzymes were engineered to facilitate production and purification process, appropriate delivery to target sites, extending half-life, and reducing immunogenicity are among the main goals of engineering approaches. Overall, enzymes play a critical role in treatment of common and rare diseases. Evaluation of new enzymes as well as improvement of approved enzymes are of the most important challenges in biotechnology. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Data fusion strategies for hazard detection and safe site selection for planetary and small body landings

NASA Astrophysics Data System (ADS)

Câmara, F.; Oliveira, J.; Hormigo, T.; Araújo, J.; Ribeiro, R.; Falcão, A.; Gomes, M.; Dubois-Matra, O.; Vijendran, S.

2015-06-01

This paper discusses the design and evaluation of data fusion strategies to perform tiered fusion of several heterogeneous sensors and a priori data. The aim is to increase robustness and performance of hazard detection and avoidance systems, while enabling safe planetary and small body landings anytime, anywhere. The focus is on Mars and asteroid landing mission scenarios and three distinct data fusion algorithms are introduced and compared. The first algorithm consists of a hybrid camera-LIDAR hazard detection and avoidance system, the H2DAS, in which data fusion is performed at both sensor-level data (reconstruction of the point cloud obtained with a scanning LIDAR using the navigation motion states and correcting the image for motion compensation using IMU data), feature-level data (concatenation of multiple digital elevation maps, obtained from consecutive LIDAR images, to achieve higher accuracy and resolution maps while enabling relative positioning) as well as decision-level data (fusing hazard maps from multiple sensors onto a single image space, with a single grid orientation and spacing). The second method presented is a hybrid reasoning fusion, the HRF, in which innovative algorithms replace the decision-level functions of the previous method, by combining three different reasoning engines—a fuzzy reasoning engine, a probabilistic reasoning engine and an evidential reasoning engine—to produce safety maps. Finally, the third method presented is called Intelligent Planetary Site Selection, the IPSIS, an innovative multi-criteria, dynamic decision-level data fusion algorithm that takes into account historical information for the selection of landing sites and a piloting function with a non-exhaustive landing site search capability, i.e., capable of finding local optima by searching a reduced set of global maps. All the discussed data fusion strategies and algorithms have been integrated, verified and validated in a closed-loop simulation environment. Monte Carlo simulation campaigns were performed for the algorithms performance assessment and benchmarking. The simulations results comprise the landing phases of Mars and Phobos landing mission scenarios.

Bone Morphogenetic Proteins in Anterior Cervical Fusion: A Systematic Review and Meta-Analysis.

PubMed

Zadegan, Shayan Abdollah; Abedi, Aidin; Jazayeri, Seyed Behnam; Nasiri Bonaki, Hirbod; Jazayeri, Seyed Behzad; Vaccaro, Alexander R; Rahimi-Movaghar, Vafa

2017-08-01

Bone morphogenetic proteins (BMPs) have been commonly used as a graft substitute in spinal fusion. Although the U.S. Food and Drug Administration issued a warning on life-threatening complications of recombinant human BMPs (rhBMPs) in cervical spine fusion in 2008, their off-label use has been continued. This investigation aimed to review the evidence for the use of rhBMP-2 and rhBMP-7 in anterior cervical spine fusions. A comprehensive search was performed through Ovid (MEDLINE), PubMed, and Embase. The risk of bias assessment was according to the recommended criteria by the Cochrane Back and Neck group and MINORS (Methodological Index for Non-Randomized Studies). A wide array of radiographic and clinical outcomes including the adverse events were collated. Eighteen articles (1 randomized and 17 nonrandomized) were eligible for inclusion. The fusion rate was higher with use of rhBMP in most studies and our meta-analysis of the pooled data from 4782 patients confirmed this finding (odds ratio, 5.45; P < 0.00001). Altogether, the rhBMP and control groups were comparable in patient-reported outcomes. However, most studies tended to show a significantly higher incidence of overall complication rate, dysphagia/dysphonia, cervical swelling, readmission, wound complications, neurologic complications, and ossification. Application of rhBMPs in cervical spine fusion yields a significantly higher fusion rate with similar patient-reported outcomes, yet increased risk of life-threatening complications. Thus, we do not recommend the use of rhBMP in anterior cervical fusions. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of data fusion in predictive maintenance using digital twin

NASA Astrophysics Data System (ADS)

Liu, Zheng; Meyendorf, Norbert; Mrad, Nezih

2018-04-01

Modern aerospace industry is migrating from reactive to proactive and predictive maintenance to increase platform operational availability and efficiency, extend its useful life cycle and reduce its life cycle cost. Multiphysics modeling together with data-driven analytics generate a new paradigm called "Digital Twin." The digital twin is actually a living model of the physical asset or system, which continually adapts to operational changes based on the collected online data and information, and can forecast the future of the corresponding physical counterpart. This paper reviews the overall framework to develop a digital twin coupled with the industrial Internet of Things technology to advance aerospace platforms autonomy. Data fusion techniques particularly play a significant role in the digital twin framework. The flow of information from raw data to high-level decision making is propelled by sensor-to-sensor, sensor-to-model, and model-to-model fusion. This paper further discusses and identifies the role of data fusion in the digital twin framework for aircraft predictive maintenance.

Turbulent Transport at High Reynolds Numbers in an Inertial Confinement Fusion Context

DTIC Science & Technology

2014-09-01

Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794 P . Rao1 Department of Applied Mathematics and Statistics...scales, 1Corresponding author. Contributed by the Fluids Engineering Division of ASME for publication in the JOURNAL OF FLUIDS ENGINEERING...Engineering SEPTEMBER 2014, Vol. 136 / 091206-1Copyright VC 2014 by ASME Downloaded From: http://fluidsengineering.asmedigitalcollection.asme.org/ on

ITER-FEAT operation

NASA Astrophysics Data System (ADS)

Shimomura, Y.; Aymar, R.; Chuyanov, V. A.; Huguet, M.; Matsumoto, H.; Mizoguchi, T.; Murakami, Y.; Polevoi, A. R.; Shimada, M.; ITER Joint Central Team; ITER Home Teams

2001-03-01

ITER is planned to be the first fusion experimental reactor in the world operating for research in physics and engineering. The first ten years of operation will be devoted primarily to physics issues at low neutron fluence and the following ten years of operation to engineering testing at higher fluence. ITER can accommodate various plasma configurations and plasma operation modes, such as inductive high Q modes, long pulse hybrid modes and non-inductive steady state modes, with large ranges of plasma current, density, beta and fusion power, and with various heating and current drive methods. This flexibility will provide an advantage for coping with uncertainties in the physics database, in studying burning plasmas, in introducing advanced features and in optimizing the plasma performance for the different programme objectives. Remote sites will be able to participate in the ITER experiment. This concept will provide an advantage not only in operating ITER for 24 hours a day but also in involving the worldwide fusion community and in promoting scientific competition among the ITER Parties.

Integrated Display and Simulation for Automatic Dependent Surveillance–Broadcast and Traffic Collision Avoidance System Data Fusion

PubMed Central

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-01-01

Automatic Dependent Surveillance–Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications. PMID:29137194

Establishment and characterization of an open mini-thoracotomy surgical approach to an ovine thoracic spine fusion model.

PubMed

Yong, Mostyn R N O; Saifzadeh, Siamak; Askin, Geoffrey N; Labrom, Robert D; Hutmacher, Dietmar W; Adam, Clayton J

2014-01-01

A large animal model is required for the assessment of minimally invasive, tissue-engineering-based approaches to thoracic spine fusion, with relevance to deformity correction surgery for human adolescent idiopathic scoliosis. Here, we develop a novel open mini-thoracotomy approach in an ovine model of thoracic interbody fusion that allows the assessment of various fusion constructs, with a focus on novel, tissue-engineering-based interventions. The open mini-thoracotomy surgical approach was developed through a series of mock surgeries, and then applied in a live sheep study. Customized scaffolds were manufactured to conform with intervertebral disc space clearances that were required of the study. Six male Merino sheep aged 4-6 years and weighing 35-45 kg underwent the procedure mentioned earlier and were alloted a survival timeline of 6 months. Each sheep underwent a three-level discectomy (T6/7, T8/9, and T10/11) with a randomly allocated implantation of a different graft substitute at each of the following three levels: (1) polycaprolactone (PCL)-based scaffold plus 0.54 μg recombinant human bone morphogenetic protein-2 (rhBMP-2); (2) PCL-based scaffold alone; or (3) autograft. The sheep were closely monitored postoperatively for signs of pain (i.e., gait abnormalities/teeth gnawing/social isolation). Fusion assessments were conducted postsacrifice using computed tomography and hard-tissue histology. All scientific work was undertaken in accordance with the study protocol that was approved by the Institute's committee on animal research. All six sheep were successfully operated on and reached the allotted survival timeline, thereby demonstrating the feasibility of the surgical procedure and postoperative care. There were no significant complications and during the postoperative period, the animals did not exhibit marked signs of distress according to the previously described assessment criteria. Computed tomographic scanning demonstrated higher fusion grades in the rhBMP-2 plus PCL-based scaffold group in comparison to either PCL-based scaffold alone or autograft. These results were supported by a histological evaluation of the respective groups. This novel open mini-thoracotomy surgical approach to the ovine thoracic spine represents a safe surgical method that can reproducibly form the platform for research into various spine-tissue-engineered constructs and their fusion-promoting properties.

Real-time sensor validation and fusion for distributed autonomous sensors

NASA Astrophysics Data System (ADS)

Yuan, Xiaojing; Li, Xiangshang; Buckles, Bill P.

2004-04-01

Multi-sensor data fusion has found widespread applications in industrial and research sectors. The purpose of real time multi-sensor data fusion is to dynamically estimate an improved system model from a set of different data sources, i.e., sensors. This paper presented a systematic and unified real time sensor validation and fusion framework (RTSVFF) based on distributed autonomous sensors. The RTSVFF is an open architecture which consists of four layers - the transaction layer, the process fusion layer, the control layer, and the planning layer. This paradigm facilitates distribution of intelligence to the sensor level and sharing of information among sensors, controllers, and other devices in the system. The openness of the architecture also provides a platform to test different sensor validation and fusion algorithms and thus facilitates the selection of near optimal algorithms for specific sensor fusion application. In the version of the model presented in this paper, confidence weighted averaging is employed to address the dynamic system state issue noted above. The state is computed using an adaptive estimator and dynamic validation curve for numeric data fusion and a robust diagnostic map for decision level qualitative fusion. The framework is then applied to automatic monitoring of a gas-turbine engine, including a performance comparison of the proposed real-time sensor fusion algorithms and a traditional numerical weighted average.

Development of the Scale for "Convergence Thinking" in Engineering

ERIC Educational Resources Information Center

Park, Sungmi

2016-01-01

Purpose: The purpose of this paper is to define the concept of "convergence thinking" as a trading zone for knowledge fusion in the engineering field, and develops its measuring scale. Design/ Methodology/Approach: Based on results from literature review, this study clarifies a theoretical ground for "convergence thinking."…

The Light Ion Pulsed Power Induction Accelerator for ETF

DTIC Science & Technology

1995-07-01

the technical development necessary to demonstrate scientific and engineering feasibility for fusion energy production with a reprated driver. In...order for ETF to be cost effective, the accelerator system must be able to drive several target chambers which will test various Inertial Fusion ... Energy (IFE) reactor technologies. We envision an elevator system positioning and removing multiple target chambers from the center area of the ion beam

Fusion Propulsion and Power for Future Flight

NASA Technical Reports Server (NTRS)

Froning, H. D., Jr.

1996-01-01

There are innovative magnetic and electric confinement fusion power and propulsion system designs with potential for: vacuum specific impulses of 1500-2000 seconds with rocket engine thrust/mass ratios of 5-10 g's; environmentally favorable exhaust emissions if aneutronic fusion propellants can be used; a 2 to 3-fold reduction in the mass of hypersonic airliners and SSTO aerospace planes; a 10 to 20 fold reduction in Mars expedition mass and cost (if propellant from planetary atmospheres is used); and feasibility or in-feasibility of these systems could be confirmed with a modest applied research and exploratory development cost.

The National Ignition Facility: The Path to a Carbon-Free Energy Future

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stolz, C J

2011-03-16

The National Ignition Facility (NIF), the world's largest and most energetic laser system, is now operational at Lawrence Livermore National Laboratory (LLNL). The NIF will enable exploration of scientific problems in national strategic security, basic science and fusion energy. One of the early NIF goals centers on achieving laboratory-scale thermonuclear ignition and energy gain, demonstrating the feasibility of laser fusion as a viable source of clean, carbon-free energy. This talk will discuss the precision technology and engineering challenges of building the NIF and those we must overcome to make fusion energy a commercial reality.

The National Ignition Facility: the path to a carbon-free energy future.

PubMed

Stolz, Christopher J

2012-08-28

The National Ignition Facility (NIF), the world's largest and most energetic laser system, is now operational at Lawrence Livermore National Laboratory. The NIF will enable exploration of scientific problems in national strategic security, basic science and fusion energy. One of the early NIF goals centres on achieving laboratory-scale thermonuclear ignition and energy gain, demonstrating the feasibility of laser fusion as a viable source of clean, carbon-free energy. This talk will discuss the precision technology and engineering challenges of building the NIF and those we must overcome to make fusion energy a commercial reality.

Fusion Energy Division progress report, 1 January 1990--31 December 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sheffield, J.; Baker, C.C.; Saltmarsh, M.J.

1994-03-01

The Fusion Program of the Oak Ridge National Laboratory (ORNL), a major part of the national fusion program, encompasses nearly all areas of magnetic fusion research. The program is directed toward the development of fusion as an economical and environmentally attractive energy source for the future. The program involves staff from ORNL, Martin Marietta Energy systems, Inc., private industry, the academic community, and other fusion laboratories, in the US and abroad. Achievements resulting from this collaboration are documented in this report, which is issued as the progress report of the ORNL Fusion Energy Division; it also contains information from componentsmore » for the Fusion Program that are external to the division (about 15% of the program effort). The areas addressed by the Fusion Program include the following: experimental and theoretical research on magnetic confinement concepts; engineering and physics of existing and planned devices, including remote handling; development and testing of diagnostic tools and techniques in support of experiments; assembly and distribution to the fusion community of databases on atomic physics and radiation effects; development and testing of technologies for heating and fueling fusion plasmas; development and testing of superconducting magnets for containing fusion plasmas; development and testing of materials for fusion devices; and exploration of opportunities to apply the unique skills, technology, and techniques developed in the course of this work to other areas (about 15% of the Division`s activities). Highlights from program activities during 1990 and 1991 are presented.« less

Lunar Helium-3 and Fusion Power

NASA Technical Reports Server (NTRS)

1988-01-01

The NASA Office of Exploration sponsored the NASA Lunar Helium-3 and Fusion Power Workshop. The meeting was held to understand the potential of using He-3 from the moon for terrestrial fusion power production. It provided an overview, two parallel working sessions, a review of sessions, and discussions. The lunar mining session concluded that mining, beneficiation, separation, and return of He-3 from the moon would be possible but that a large scale operation and improved technology is required. The fusion power session concluded that: (1) that He-3 offers significant, possibly compelling, advantages over fusion of tritium, principally increased reactor life, reduced radioactive wastes, and high efficiency conversion, (2) that detailed assessment of the potential of the D/He-3 fuel cycle requires more information, and (3) D/He-3 fusion may be best for commercial purposes, although D/T fusion is more near term.

Real-Time Aircraft Engine-Life Monitoring

NASA Technical Reports Server (NTRS)

Klein, Richard

2014-01-01

This project developed an inservice life-monitoring system capable of predicting the remaining component and system life of aircraft engines. The embedded system provides real-time, inflight monitoring of the engine's thrust, exhaust gas temperature, efficiency, and the speed and time of operation. Based upon this data, the life-estimation algorithm calculates the remaining life of the engine components and uses this data to predict the remaining life of the engine. The calculations are based on the statistical life distribution of the engine components and their relationship to load, speed, temperature, and time.

Investigation of the Possibility of Using Nuclear Magnetic Spin Alignment

NASA Technical Reports Server (NTRS)

Dent, William V., Jr.

1998-01-01

The goal of the program to investigate a "Gasdynamic fusion propulsion system for space exploration" is to develop a fusion propulsion system for a manned mission to the planet mars. A study using Deuterium and Tritium atoms are currently in progress. When these atoms under-go fusion, the resulting neutrons and alpha particles are emitted in random directions (isotropically). The probable direction of emission is equal for all directions, thus resulting in wasted energy, massive shielding and cooling requirements, and serious problems with the physics of achieving fusion. If the nuclear magnetic spin moments of the deuterium and tritium nuclei could be precisely aligned at the moment of fusion, the stream of emitted neutrons could be directed out the rear of the spacecraft for thrust and the alpha particles directed forward into an electromagnet ot produce electricity to continue operating the fusion engine. The following supporting topics are discussed: nuclear magnetic moments and spin precession in magnetic field, nuclear spin quantum mechanics, kinematics of nuclear reactions, and angular distribution of particles.

Effect of Heat Input on the Tensile Damage Evolution in Pulsed Laser Welded Ti6Al4V Titanium Sheets

NASA Astrophysics Data System (ADS)

Liu, Jing; Gao, Xiaolong; Zhang, Jianxun

2016-11-01

The present paper is focused on studying the effect of heat input on the tensile damage evolution of pulsed Nd:YAG laser welding of Ti6Al4V alloy under monotonic loading. To analyze the reasons that the tensile fracture site of the pulsed-laser-welded Ti6Al4V sheet joints changes with the heat input under monotonic loading, the microstructure of the sample with different nominal strain values was investigated by in situ observation. Experiment results show that the tensile ductility and fatigue life of welded joints with low heat input are higher than that of welded joints with high heat input. Under tensile loads, the critical engineering strain for crack initiation is much lower in the welded joint with high heat input than in the welded joints with low and medium heat input. And the microstructural damage accumulation is much faster in the fusion zone than in the base metal for the welded joints with high input, whereas the microstructural damage accumulation is much faster in the base metal than in the fusion zone for the welded joints with low input. Consequently, the welded joints fractured in the fusion zone for the welds with high heat input, whereas the welded joints ruptured in the base metal for the welds with low heat input. It is proved that the fine grain microstructure produced by low heat input can improve the critical nominal strain for crack initiation and the resistance ability of microstructural damage.

Dynamics simulations for engineering macromolecular interactions

NASA Astrophysics Data System (ADS)

Robinson-Mosher, Avi; Shinar, Tamar; Silver, Pamela A.; Way, Jeffrey

2013-06-01

The predictable engineering of well-behaved transcriptional circuits is a central goal of synthetic biology. The artificial attachment of promoters to transcription factor genes usually results in noisy or chaotic behaviors, and such systems are unlikely to be useful in practical applications. Natural transcriptional regulation relies extensively on protein-protein interactions to insure tightly controlled behavior, but such tight control has been elusive in engineered systems. To help engineer protein-protein interactions, we have developed a molecular dynamics simulation framework that simplifies features of proteins moving by constrained Brownian motion, with the goal of performing long simulations. The behavior of a simulated protein system is determined by summation of forces that include a Brownian force, a drag force, excluded volume constraints, relative position constraints, and binding constraints that relate to experimentally determined on-rates and off-rates for chosen protein elements in a system. Proteins are abstracted as spheres. Binding surfaces are defined radially within a protein. Peptide linkers are abstracted as small protein-like spheres with rigid connections. To address whether our framework could generate useful predictions, we simulated the behavior of an engineered fusion protein consisting of two 20 000 Da proteins attached by flexible glycine/serine-type linkers. The two protein elements remained closely associated, as if constrained by a random walk in three dimensions of the peptide linker, as opposed to showing a distribution of distances expected if movement were dominated by Brownian motion of the protein domains only. We also simulated the behavior of fluorescent proteins tethered by a linker of varying length, compared the predicted Förster resonance energy transfer with previous experimental observations, and obtained a good correspondence. Finally, we simulated the binding behavior of a fusion of two ligands that could simultaneously bind to distinct cell-surface receptors, and explored the landscape of linker lengths and stiffnesses that could enhance receptor binding of one ligand when the other ligand has already bound to its receptor, thus, addressing potential mechanisms for improving targeted signal transduction proteins. These specific results have implications for the design of targeted fusion proteins and artificial transcription factors involving fusion of natural domains. More broadly, the simulation framework described here could be extended to include more detailed system features such as non-spherical protein shapes and electrostatics, without requiring detailed, computationally expensive specifications. This framework should be useful in predicting behavior of engineered protein systems including binding and dissociation reactions.

Dynamics simulations for engineering macromolecular interactions.

PubMed

Robinson-Mosher, Avi; Shinar, Tamar; Silver, Pamela A; Way, Jeffrey

2013-06-01

The predictable engineering of well-behaved transcriptional circuits is a central goal of synthetic biology. The artificial attachment of promoters to transcription factor genes usually results in noisy or chaotic behaviors, and such systems are unlikely to be useful in practical applications. Natural transcriptional regulation relies extensively on protein-protein interactions to insure tightly controlled behavior, but such tight control has been elusive in engineered systems. To help engineer protein-protein interactions, we have developed a molecular dynamics simulation framework that simplifies features of proteins moving by constrained Brownian motion, with the goal of performing long simulations. The behavior of a simulated protein system is determined by summation of forces that include a Brownian force, a drag force, excluded volume constraints, relative position constraints, and binding constraints that relate to experimentally determined on-rates and off-rates for chosen protein elements in a system. Proteins are abstracted as spheres. Binding surfaces are defined radially within a protein. Peptide linkers are abstracted as small protein-like spheres with rigid connections. To address whether our framework could generate useful predictions, we simulated the behavior of an engineered fusion protein consisting of two 20,000 Da proteins attached by flexible glycine/serine-type linkers. The two protein elements remained closely associated, as if constrained by a random walk in three dimensions of the peptide linker, as opposed to showing a distribution of distances expected if movement were dominated by Brownian motion of the protein domains only. We also simulated the behavior of fluorescent proteins tethered by a linker of varying length, compared the predicted Förster resonance energy transfer with previous experimental observations, and obtained a good correspondence. Finally, we simulated the binding behavior of a fusion of two ligands that could simultaneously bind to distinct cell-surface receptors, and explored the landscape of linker lengths and stiffnesses that could enhance receptor binding of one ligand when the other ligand has already bound to its receptor, thus, addressing potential mechanisms for improving targeted signal transduction proteins. These specific results have implications for the design of targeted fusion proteins and artificial transcription factors involving fusion of natural domains. More broadly, the simulation framework described here could be extended to include more detailed system features such as non-spherical protein shapes and electrostatics, without requiring detailed, computationally expensive specifications. This framework should be useful in predicting behavior of engineered protein systems including binding and dissociation reactions.

Distributed Multisensor Data Fusion under Unknown Correlation and Data Inconsistency

PubMed Central

Abu Bakr, Muhammad; Lee, Sukhan

2017-01-01

The paradigm of multisensor data fusion has been evolved from a centralized architecture to a decentralized or distributed architecture along with the advancement in sensor and communication technologies. These days, distributed state estimation and data fusion has been widely explored in diverse fields of engineering and control due to its superior performance over the centralized one in terms of flexibility, robustness to failure and cost effectiveness in infrastructure and communication. However, distributed multisensor data fusion is not without technical challenges to overcome: namely, dealing with cross-correlation and inconsistency among state estimates and sensor data. In this paper, we review the key theories and methodologies of distributed multisensor data fusion available to date with a specific focus on handling unknown correlation and data inconsistency. We aim at providing readers with a unifying view out of individual theories and methodologies by presenting a formal analysis of their implications. Finally, several directions of future research are highlighted. PMID:29077035

Fusion of uniluminal vascular spheroids: a model for assembly of blood vessels

PubMed Central

Fleming, Paul A.; Argraves, W. Scott; Gentile, Carmine; Neagu, Adrian; Forgacs, Gabor; Drake, Christopher J.

2010-01-01

Here, we evaluated the self-assembly properties of uniluminal vascular spheroids having outer layers of vascular smooth muscle cells and a contiguous inner layer of endothelial cells lining a central lumen. We showed that while pairs of uniluminal vascular spheroids suspended in culture medium fused to form a larger diameter spheroidal structure, spheroids in collagen hydrogels formed elongated structures. These findings highlight the potential use of uniluminal vascular spheroids as modules to engineer blood vessels. We also demonstrate that uniluminal vascular spheroid fusion conforms to models describing the coalescence of liquid drops. Furthermore, the fusion of uniluminal vascular spheroids in vitro closely resembled the in vivo process by which the descending aorta forms from the fusion of the paired dorsal aortae during embryonic development. Together, the findings indicate that tissue liquidity underlies uniluminal vascular spheroid fusion and that in vivo anastomosis of blood vessels may involve a similar mechanism. PMID:19918756

Overview of the present progress and activities on the CFETR

NASA Astrophysics Data System (ADS)

Wan, Yuanxi; Li, Jiangang; Liu, Yong; Wang, Xiaolin; Chan, Vincent; Chen, Changan; Duan, Xuru; Fu, Peng; Gao, Xiang; Feng, Kaiming; Liu, Songlin; Song, Yuntao; Weng, Peide; Wan, Baonian; Wan, Farong; Wang, Heyi; Wu, Songtao; Ye, Minyou; Yang, Qingwei; Zheng, Guoyao; Zhuang, Ge; Li, Qiang; CFETR Team

2017-10-01

The China Fusion Engineering Test Reactor (CFETR) is the next device in the roadmap for the realization of fusion energy in China, which aims to bridge the gaps between the fusion experimental reactor ITER and the demonstration reactor (DEMO). CFETR will be operated in two phases. Steady-state operation and self-sufficiency will be the two key issues for Phase I with a modest fusion power of up to 200 MW. Phase II aims for DEMO validation with a fusion power over 1 GW. Advanced H-mode physics, high magnetic fields up to 7 T, high frequency electron cyclotron resonance heating and lower hybrid current drive together with off-axis negative-ion neutral beam injection will be developed for achieving steady-state advanced operation. The recent detailed design, research and development (R&D) activities including integrated modeling of operation scenarios, high field magnet, material, tritium plant, remote handling and future plans are introduced in this paper.

Micro-engineered first wall tungsten armor for high average power laser fusion energy systems

NASA Astrophysics Data System (ADS)

Sharafat, Shahram; Ghoniem, Nasr M.; Anderson, Michael; Williams, Brian; Blanchard, Jake; Snead, Lance; HAPL Team

2005-12-01

The high average power laser program is developing an inertial fusion energy demonstration power reactor with a solid first wall chamber. The first wall (FW) will be subject to high energy density radiation and high doses of high energy helium implantation. Tungsten has been identified as the candidate material for a FW armor. The fundamental concern is long term thermo-mechanical survivability of the armor against the effects of high temperature pulsed operation and exfoliation due to the retention of implanted helium. Even if a solid tungsten armor coating would survive the high temperature cyclic operation with minimal failure, the high helium implantation and retention would result in unacceptable material loss rates. Micro-engineered materials, such as castellated structures, plasma sprayed nano-porous coatings and refractory foams are suggested as a first wall armor material to address these fundamental concerns. A micro-engineered FW armor would have to be designed with specific geometric features that tolerate high cyclic heating loads and recycle most of the implanted helium without any significant failure. Micro-engineered materials are briefly reviewed. In particular, plasma-sprayed nano-porous tungsten and tungsten foams are assessed for their potential to accommodate inertial fusion specific loads. Tests show that nano-porous plasma spray coatings can be manufactured with high permeability to helium gas, while retaining relatively high thermal conductivities. Tungsten foams where shown to be able to overcome thermo-mechanical loads by cell rotation and deformation. Helium implantation tests have shown, that pulsed implantation and heating releases significant levels of implanted helium. Helium implantation and release from tungsten was modeled using an expanded kinetic rate theory, to include the effects of pulsed implantations and thermal cycles. Although, significant challenges remain micro-engineered materials are shown to constitute potential candidate FW armor materials.

A methodology for hard/soft information fusion in the condition monitoring of aircraft

NASA Astrophysics Data System (ADS)

Bernardo, Joseph T.

2013-05-01

Condition-based maintenance (CBM) refers to the philosophy of performing maintenance when the need arises, based upon indicators of deterioration in the condition of the machinery. Traditionally, CBM involves equipping machinery with electronic sensors that continuously monitor components and collect data for analysis. The addition of the multisensory capability of human cognitive functions (i.e., sensemaking, problem detection, planning, adaptation, coordination, naturalistic decision making) to traditional CBM may create a fuller picture of machinery condition. Cognitive systems engineering techniques provide an opportunity to utilize a dynamic resource—people acting as soft sensors. The literature is extensive on techniques to fuse data from electronic sensors, but little work exists on fusing data from humans with that from electronic sensors (i.e., hard/soft fusion). The purpose of my research is to explore, observe, investigate, analyze, and evaluate the fusion of pilot and maintainer knowledge, experiences, and sensory perceptions with digital maintenance resources. Hard/soft information fusion has the potential to increase problem detection capability, improve flight safety, and increase mission readiness. This proposed project consists the creation of a methodology that is based upon the Living Laboratories framework, a research methodology that is built upon cognitive engineering principles1. This study performs a critical assessment of concept, which will support development of activities to demonstrate hard/soft information fusion in operationally relevant scenarios of aircraft maintenance. It consists of fieldwork, knowledge elicitation to inform a simulation and a prototype.

Ohmic ignition with high engineering beta based on the RFP

NASA Astrophysics Data System (ADS)

Sarff, J. S.; Anderson, J. K.; Chapman, B. E.; McCollam, K. J.

2017-10-01

The RFP configuration allows the possibility of ohmic ignition for fusion energy, eliminating the need for auxiliary heating by rf or neutral beam injection. Complex plasma-facing antennas and NBI sources are therefore not required, simplifying the difficult fusion materials challenge. While all toroidal configurations require a volume-average 〈 B 〉 >= 5 T, the field strength at the magnet in the RFP is only Bcoil 3T since plasma current generates almost all of the field. Engineering beta is therefore maximized. We summarize access to ohmic ignition by examining a Lawson-like power balance for an RFP fusion plasma comparable to the ARIES-AT advanced tokamak, which generates neutron wall loading Pn / A 5 MW/m2. The required energy confinement for ohmic ignition in an RFP is similar to that for a tokamak. Confinement in MST is comparable to a same-size, same-field tokamak plasma, but 〈 B 〉 in MST is only 1/20th that required for fusion. While transport could ultimately be dominated by micro turbulence, extrapolation of stochastic transport using Lundquist number scaling for MHD tearing indicates standard RFP confinement (not enhanced by current profile control) could be sufficient to access ohmic ignition. This bolsters the possibility for steady-state inductive sustainment using oscillating field current drive. The high beta and classical energetic ion confinement measured in MST also bolster the RFP's fusion potential. Work supported by U.S. DoE.

Hemi-fused structure mediates and controls fusion and fission in live cells

PubMed Central

Zhao, Wei-Dong; Hamid, Edaeni; Shin, Wonchul; Wen, Peter J.; Krystofiak, Evan S.; Villarreal, Seth A.; Chiang, Hsueh-Cheng; Kachar, Bechara; Wu, Ling-Gang

2016-01-01

Membrane fusion and fission are vital to eukaryotes’ life1–5. For three decades, it has been proposed that fusion is mediated by fusion between proximal leaflets of two bilayers (hemi-fusion) that produces a hemi-fused structure, followed by fusion between distal leaflets, whereas fission is via hemi-fission, which also produces a hemi-fused structure, followed by full fission1, 4, 6–10. This hypothesis remained unsupported owing to the lack of observation of hemi-fusion/hemi-fission in live cells. A competing fusion hypothesis involving protein-lined pore formation has also been proposed2, 11–15. Using confocal and super-resolution STED microscopy, we observed the hemi-fused Ω-shaped structure for the first time in live cells, neuroendocrine chromaffin cells and pancreatic β-cells. This structure was generated from fusion pore opening or closure (fission) at the plasma membrane. Unexpectedly, its transition to full fusion or fission was determined by competition between fusion and calcium/dynamin-dependent fission mechanisms, and was surprisingly slow (seconds to tens of seconds) in a significant fraction of the events. These results provide key missing evidence over the past three decades proving the hemi-fusion and hemi-fission hypothesis in live cells, and reveal the hemi-fused intermediate as a key structure controlling fusion/fission, as fusion and fission mechanisms compete to determine its transition to fusion or fission. PMID:27309816

Revisions to the JDL data fusion model

NASA Astrophysics Data System (ADS)

Steinberg, Alan N.; Bowman, Christopher L.; White, Franklin E.

1999-03-01

The Data Fusion Model maintained by the Joint Directors of Laboratories (JDL) Data Fusion Group is the most widely-used method for categorizing data fusion-related functions. This paper discusses the current effort to revise the expand this model to facilitate the cost-effective development, acquisition, integration and operation of multi- sensor/multi-source systems. Data fusion involves combining information - in the broadest sense - to estimate or predict the state of some aspect of the universe. These may be represented in terms of attributive and relational states. If the job is to estimate the state of a people, it can be useful to include consideration of informational and perceptual states in addition to the physical state. Developing cost-effective multi-source information systems requires a method for specifying data fusion processing and control functions, interfaces, and associate databases. The lack of common engineering standards for data fusion systems has been a major impediment to integration and re-use of available technology: current developments do not lend themselves to objective evaluation, comparison or re-use. This paper reports on proposed revisions and expansions of the JDL Data FUsion model to remedy some of these deficiencies. This involves broadening the functional model and related taxonomy beyond the original military focus, and integrating the Data Fusion Tree Architecture model for system description, design and development.

Tritium

DTIC Science & Technology

2011-11-01

fusion energy -production processes of the particular type of reactor using a lithium (Li) blanket or related alloys such as the Pb-17Li eutectic. As such, tritium breeding is intimately connected with energy production, thermal management, radioactivity management, materials properties, and mechanical structures of any plausible future large-scale fusion power reactor. JASON is asked to examine the current state of scientific knowledge and engineering practice on the physical and chemical bases for large-scale tritium

Optimization of a bundle divertor for FED

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hively, L.M.; Rothe, K.E.; Minkoff, M.

1982-01-01

Optimal double-T bundle divertor configurations have been obtained for the Fusion Engineering Device (FED). On-axis ripple is minimized, while satisfying a series of engineering constraints. The ensuing non-linear optimization problem is solved via a sequence of quadratic programming subproblems, using the VMCON algorithm. The resulting divertor designs are substantially improved over previous configurations.

Remote Control of Tissue Interactions via Engineered Photo-switchable Cell Surfaces

NASA Astrophysics Data System (ADS)

Luo, Wei; Pulsipher, Abigail; Dutta, Debjit; Lamb, Brian M.; Yousaf, Muhammad N.

2014-09-01

We report a general cell surface molecular engineering strategy via liposome fusion delivery to create a dual photo-active and bio-orthogonal cell surface for remote controlled spatial and temporal manipulation of microtissue assembly and disassembly. Cell surface tailoring of chemoselective functional groups was achieved by a liposome fusion delivery method and quantified by flow cytometry and characterized by a new cell surface lipid pull down mass spectrometry strategy. Dynamic co-culture spheroid tissue assembly in solution and co-culture tissue multilayer assembly on materials was demonstrated by an intercellular photo-oxime ligation that could be remotely cleaved and disassembled on demand. Spatial and temporal control of microtissue structures containing multiple cell types was demonstrated by the generation of patterned multilayers for controlling stem cell differentiation. Remote control of cell interactions via cell surface engineering that allows for real-time manipulation of tissue dynamics may provide tools with the scope to answer fundamental questions of cell communication and initiate new biotechnologies ranging from imaging probes to drug delivery vehicles to regenerative medicine, inexpensive bioreactor technology and tissue engineering therapies.

Chimeric TALE recombinases with programmable DNA sequence specificity.

PubMed

Mercer, Andrew C; Gaj, Thomas; Fuller, Roberta P; Barbas, Carlos F

2012-11-01

Site-specific recombinases are powerful tools for genome engineering. Hyperactivated variants of the resolvase/invertase family of serine recombinases function without accessory factors, and thus can be re-targeted to sequences of interest by replacing native DNA-binding domains (DBDs) with engineered zinc-finger proteins (ZFPs). However, imperfect modularity with particular domains, lack of high-affinity binding to all DNA triplets, and difficulty in construction has hindered the widespread adoption of ZFPs in unspecialized laboratories. The discovery of a novel type of DBD in transcription activator-like effector (TALE) proteins from Xanthomonas provides an alternative to ZFPs. Here we describe chimeric TALE recombinases (TALERs): engineered fusions between a hyperactivated catalytic domain from the DNA invertase Gin and an optimized TALE architecture. We use a library of incrementally truncated TALE variants to identify TALER fusions that modify DNA with efficiency and specificity comparable to zinc-finger recombinases in bacterial cells. We also show that TALERs recombine DNA in mammalian cells. The TALER architecture described herein provides a platform for insertion of customized TALE domains, thus significantly expanding the targeting capacity of engineered recombinases and their potential applications in biotechnology and medicine.

Circumferential fusion is dominant over posterolateral fusion in a long-term perspective: cost-utility evaluation of a randomized controlled trial in severe, chronic low back pain.

PubMed

Soegaard, Rikke; Bünger, Cody E; Christiansen, Terkel; Høy, Kristian; Eiskjaer, Søren P; Christensen, Finn B

2007-10-15

Cost-utility evaluation of a randomized, controlled trial with a 4- to 8-year follow-up. To investigate the incremental cost per quality-adjusted-life-year (QALY) when comparing circumferential fusion to posterolateral fusion in a long-term, societal perspective. The cost-effectiveness of circumferential fusion in a long-term perspective is uncertain but nonetheless highly relevant as the ISSLS prize winner 2006 in clinical studies reported the effect of circumferential fusion superior to the effect of posterolateral fusion. A recent trial found no significant difference between posterolateral and circumferential fusion reporting cost-effectiveness from a 2-year viewpoint. A total of 146 patients were randomized to posterolateral or circumferential fusion and followed 4 to 8 years after surgery. The mean age of the cohort was 46 years (range, 20-65 years); 61% were females, 49% were smokers, 30% had primary diagnosis of isthmic spondylolisthesis, 35% had disc degeneration and no previous surgery, and 35% had disc degeneration and previous surgery. Eighty-two percent of patients have had symptoms for more than 2 years and 50% were out of the labor market due to sickness. The EQ-5D instrument was applied for the measurement of health-related quality of life and costs (2004 U.S. dollars) were measured in a full-scale societal perspective. Productivity costs were valued by the Friction Cost method, and both costs and effects were discounted. Arithmetic means and 95% bias-corrected, bootstrapped confidence intervals were reported. Nonparametric statistics were used for tests of statistical significance. Comprehensive sensitivity analysis was conducted and reported using cost-effectiveness acceptability curves. The circumferential group demonstrated clinical superiority over the posterolateral fusion group in functional outcome (P < 0.01), fusion rate (P < 0.04), and number of reoperations (P < 0.01) among others. Cost-utility analysis demonstrated circumferential fusion dominant over posterolateral fusion, that is, for each QALY gained performing circumferential fusion, the incremental saving was estimated at U.S. $49,306 (95% confidence interval, $27,183-$2,735,712). Results proved to be strong to various sensitivity analyses; only a differentiated underestimation of patients' need for postoperative household help against the circumferential approach could alter the dominance; however, still the probability of cost-effectiveness was >0.85 given a threshold for willingness to pay of U.S. $50,000 per QALY. Circumferential fusion is dominant over instrumented posterolateral fusion, that is, both being significantly cheaper and significantly better in a long-term, societal perspective.

Applications of Fusion Energy Sciences Research - Scientific Discoveries and New Technologies Beyond Fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wendt, Amy; Callis, Richard; Efthimion, Philip

Since the 1950s, scientists and engineers in the U.S. and around the world have worked hard to make an elusive goal to be achieved on Earth: harnessing the reaction that fuels the stars, namely fusion. Practical fusion would be a source of energy that is unlimited, safe, environmentally benign, available to all nations and not dependent on climate or the whims of the weather. Significant resources, most notably from the U.S. Department of Energy (DOE) Office of Fusion Energy Sciences (FES), have been devoted to pursuing that dream, and significant progress is being made in turning it into a reality.more » However, that is only part of the story. The process of creating a fusion-based energy supply on Earth has led to technological and scientific achievements of far-reaching impact that touch every aspect of our lives. Those largely unanticipated advances, spanning a wide variety of fields in science and technology, are the focus of this report. There are many synergies between research in plasma physics (the study of charged particles and fluids interacting with self-consistent electric and magnetic fields), high-energy physics, and condensed matter physics dating back many decades. For instance, the formulation of a mathematical theory of solitons, solitary waves which are seen in everything from plasmas to water waves to Bose-Einstein Condensates, has led to an equal span of applications, including the fields of optics, fluid mechanics and biophysics. Another example, the development of a precise criterion for transition to chaos in Hamiltonian systems, has offered insights into a range of phenomena including planetary orbits, two-person games and changes in the weather. Seven distinct areas of fusion energy sciences were identified and reviewed which have had a recent impact on fields of science, technology and engineering not directly associated with fusion energy: Basic plasma science; Low temperature plasmas; Space and astrophysical plasmas; High energy density laboratory plasmas and inertial fusion energy; Particle accelerator technology; Fusion nuclear science; and Magnetically confined plasmas. Individual sections within the report summarize applications associated with each of these areas. These sections were also informed by a survey that went out to the community, and the subcommittee wishes to thank those who responded, as well as to the national labs and universities that contributed photographs.« less

Improved two-point model for limiter scrape-off layer

NASA Astrophysics Data System (ADS)

Tokar, M. Z.; Kobayashi, M.; Feng, Y.

2004-10-01

An analytical model for a limiter scrape-off layer (SOL) is proposed, which takes self-consistently into account both conductive and convective contributions to the heat transport in SOL. The particle flows in the SOL main part are determined by considering the recycling of neutrals. The model allows us to interpret the results of numerical simulation by the code EMC3-EIRENE [Y. Feng, F. Sardei, P. Grigull, K. McCormick, J. Kisslinger, D. Reiter, and Y. Igitkhanov, Plasma Phys. Controlled Fusion 44, 611 (2002)] for the edge region of Tokamak Experiment for Technology Oriented Research (TEXTOR) [Proceedings of the 16th IEEE Symposium on Fusion Engineering, 1995 (Institute for Electrical and Electronics Engineers, Piscataway, NJ, 1995), p. 470].

A tethering complex drives the terminal stage of SNARE-dependent membrane fusion

NASA Astrophysics Data System (ADS)

D'Agostino, Massimo; Risselada, Herre Jelger; Lürick, Anna; Ungermann, Christian; Mayer, Andreas

2017-11-01

Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.

Extending the Serum Half-Life of G-CSF via Fusion with the Domain III of Human Serum Albumin

PubMed Central

Zhao, Shuqiang; Zhang, Yu; Tian, Hong; Chen, Xiaofei; Cai, Di; Yao, Wenbing; Gao, Xiangdong

2013-01-01

Protein fusion technology is one of the most commonly used methods to extend the half-life of therapeutic proteins. In this study, in order to prolong the half-life of Granulocyte colony stimulating factor (G-CSF), the domain III of human serum albumin (3DHSA) was genetically fused to the N-terminal of G-CSF. The 3DHSA-G-CSF fusion gene was cloned into pPICZαA along with the open reading frame of the α-factor signal under the control of the AOX1 promoter. The recombinant expression vector was transformed into Pichia pastoris GS115, and the recombinant strains were screened by SDS-PAGE. As expected, the 3DHSA-G-CSF showed high binding affinity with HSA antibody and G-CSF antibody, and the natural N-terminal of 3DHSA was detected by N-terminal sequencing. The bioactivity and pharmacokinetic studies of 3DHSA-G-CSF were respectively determined using neutropenia model mice and human G-CSF ELISA kit. The results demonstrated that 3DHSA-G-CSF has the ability to increase the peripheral white blood cell (WBC) counts of neutropenia model mice, and the half-life of 3DHSA-G-CSF is longer than that of native G-CSF. In conclusion, 3DHSA can be used to extend the half-life of G-CSF. PMID:24151579

Critical Science Issues for Direct Drive Inertial Fusion Energy

NASA Astrophysics Data System (ADS)

Dahlburg, Jill P.; Gardner, John H.; Schmitt, Andrew J.; Obenschain, S. P.

1998-09-01

There are several topics that require resolution prior to the construction of an Inertial Fusion Energy [IFE] laboratory Engineering Test Facility [ETF]: a pellet that produces high gain; a pellet fabrication system that cost-effectively and rapidly manufactures these pellets; a sufficiently uniform and durable high repetition-rate laser pellet driver; a practical target injection system that provides accurate pellet aiming; and, a target chamber that will survive the debris and radiation of repeated high-gain pellet implosions. In this summary we describe the science issues and opportunities that are involved in the design of a successful high gain direct drive Inertial Confinement Fusion [ICF] pellet.

Expression, isolation, and purification of soluble and insoluble biotinylated proteins for nerve tissue regeneration.

PubMed

McCormick, Aleesha M; Jarmusik, Natalie A; Endrizzi, Elizabeth J; Leipzig, Nic D

2014-01-22

Recombinant protein engineering has utilized Escherichia coli (E. coli) expression systems for nearly 4 decades, and today E. coli is still the most widely used host organism. The flexibility of the system allows for the addition of moieties such as a biotin tag (for streptavidin interactions) and larger functional proteins like green fluorescent protein or cherry red protein. Also, the integration of unnatural amino acids like metal ion chelators, uniquely reactive functional groups, spectroscopic probes, and molecules imparting post-translational modifications has enabled better manipulation of protein properties and functionalities. As a result this technique creates customizable fusion proteins that offer significant utility for various fields of research. More specifically, the biotinylatable protein sequence has been incorporated into many target proteins because of the high affinity interaction between biotin with avidin and streptavidin. This addition has aided in enhancing detection and purification of tagged proteins as well as opening the way for secondary applications such as cell sorting. Thus, biotin-labeled molecules show an increasing and widespread influence in bioindustrial and biomedical fields. For the purpose of our research we have engineered recombinant biotinylated fusion proteins containing nerve growth factor (NGF) and semaphorin3A (Sema3A) functional regions. We have reported previously how these biotinylated fusion proteins, along with other active protein sequences, can be tethered to biomaterials for tissue engineering and regenerative purposes. This protocol outlines the basics of engineering biotinylatable proteins at the milligram scale, utilizing  a T7 lac inducible vector and E. coli expression hosts, starting from transformation to scale-up and purification.

Expression, Isolation, and Purification of Soluble and Insoluble Biotinylated Proteins for Nerve Tissue Regeneration

PubMed Central

McCormick, Aleesha M.; Jarmusik, Natalie A.; Endrizzi, Elizabeth J.; Leipzig, Nic D.

2014-01-01

Recombinant protein engineering has utilized Escherichia coli (E. coli) expression systems for nearly 4 decades, and today E. coli is still the most widely used host organism. The flexibility of the system allows for the addition of moieties such as a biotin tag (for streptavidin interactions) and larger functional proteins like green fluorescent protein or cherry red protein. Also, the integration of unnatural amino acids like metal ion chelators, uniquely reactive functional groups, spectroscopic probes, and molecules imparting post-translational modifications has enabled better manipulation of protein properties and functionalities. As a result this technique creates customizable fusion proteins that offer significant utility for various fields of research. More specifically, the biotinylatable protein sequence has been incorporated into many target proteins because of the high affinity interaction between biotin with avidin and streptavidin. This addition has aided in enhancing detection and purification of tagged proteins as well as opening the way for secondary applications such as cell sorting. Thus, biotin-labeled molecules show an increasing and widespread influence in bioindustrial and biomedical fields. For the purpose of our research we have engineered recombinant biotinylated fusion proteins containing nerve growth factor (NGF) and semaphorin3A (Sema3A) functional regions. We have reported previously how these biotinylated fusion proteins, along with other active protein sequences, can be tethered to biomaterials for tissue engineering and regenerative purposes. This protocol outlines the basics of engineering biotinylatable proteins at the milligram scale, utilizing  a T7 lac inducible vector and E. coli expression hosts, starting from transformation to scale-up and purification. PMID:24513608

The relationships between stressful life events during childhood and differentiation of self and intergenerational triangulation in adulthood.

PubMed

Peleg, Ora

2014-12-01

This study examined the relationships between stressful life events in childhood and differentiation of self and intergenerational triangulation in adulthood. The sample included 217 students (173 females and 44 males) from a college in northern Israel. Participants completed the Hebrew versions of Life Events Checklist (LEC), Differentiation of Self Inventory-Revised (DSI-R) and intergenerational triangulation (INTRI). The main findings were that levels of stressful life events during childhood and adolescence among both genders were positively correlated with the levels of fusion with others and intergenerational triangulation. The levels of positive life events were negatively related to levels of emotional reactivity, emotional cut-off and intergenerational triangulation. Levels of stressful life events in females were positively correlated with emotional reactivity. Intergenerational triangulation was correlated with emotional reactivity, emotional cut-off, fusion with others and I-position. Findings suggest that families that experience higher levels of stressful life events may be at risk for higher levels of intergenerational triangulation and lower levels of differentiation of self. © 2014 International Union of Psychological Science.

Patient-reported outcomes of occipitocervical and atlantoaxial fusions in children.

PubMed

Vedantam, Aditya; Hansen, Daniel; Briceño, Valentina; Brayton, Alison; Jea, Andrew

2017-01-01

OBJECTIVE There is limited literature on patient-reported outcomes (PROs) and health-related quality of life (HRQOL) outcomes in pediatric patients undergoing surgery for craniovertebral junction pathology. The aim of the present study was to assess surgical and quality of life outcomes in children who had undergone occipitocervical or atlantoaxial fusion. METHODS The authors retrospectively reviewed the demographics, procedural data, and outcomes of 77 consecutive pediatric patients who underwent posterior occipitocervical or atlantoaxial fusion between 2008 and 2015 at Texas Children's Hospital. Outcome measures (collected at last follow-up) included mortality, neurological improvement, complications, Scoliosis Research Society Outcomes Measure-22 (SRS-22) score, SF-36 score, Neck Disability Index (NDI), and Pediatric Quality of Life Inventory (PedsQL). Multivariate linear regression analysis was performed to identify factors affecting PROs and HRQOL scores at follow-up. RESULTS The average age in this series was 10.6 ± 4.5 years. The median follow-up was 13.9 months (range 0.5-121.5 months). Sixty-three patients (81.8%) were treated with occipitocervical fusion, and 14 patients (18.1%) were treated with atlantoaxial fusion. The American Spinal Injury Association (ASIA) grade at discharge was unchanged in 73 patients (94.8%). The average PRO metrics at the time of last follow-up were as follows: SRS-22 score, 4.2 ± 0.8; NDI, 3.0 ± 2.6; the parent's PedsQL (ParentPedsQL) score, 69.6 ± 22.7, and child's PedsQL score, 75.5 ± 18.7. Multivariate linear regression analysis revealed that older age at surgery was significantly associated with lower SRS-22 scores at follow-up (B = -0.06, p = 0.03), and the presence of comorbidities was associated with poorer ParentPedsQL scores at follow-up (B = -19.68, p = 0.03). CONCLUSIONS This study indicates that occipitocervical and atlantoaxial fusions in children preserve neurological function and are associated with acceptable PROs and ParentPedsQL scores, considering the serious nature and potential for morbidity in this patient population. However, longer follow-up and disease-specific scales are necessary to fully elucidate the impact of occipitocervical and atlantoaxial fusions on children.

Membranes linked by trans-SNARE complexes require lipids prone to non-bilayer structure for progression to fusion.

PubMed

Zick, Michael; Stroupe, Christopher; Orr, Amy; Douville, Deborah; Wickner, William T

2014-01-01

Like other intracellular fusion events, the homotypic fusion of yeast vacuoles requires a Rab GTPase, a large Rab effector complex, SNARE proteins which can form a 4-helical bundle, and the SNARE disassembly chaperones Sec17p and Sec18p. In addition to these proteins, specific vacuole lipids are required for efficient fusion in vivo and with the purified organelle. Reconstitution of vacuole fusion with all purified components reveals that high SNARE levels can mask the requirement for a complex mixture of vacuole lipids. At lower, more physiological SNARE levels, neutral lipids with small headgroups that tend to form non-bilayer structures (phosphatidylethanolamine, diacylglycerol, and ergosterol) are essential. Membranes without these three lipids can dock and complete trans-SNARE pairing but cannot rearrange their lipids for fusion. DOI: http://dx.doi.org/10.7554/eLife.01879.001.

Molecular engineering of industrial enzymes: recent advances and future prospects.

PubMed

Yang, Haiquan; Li, Jianghua; Shin, Hyun-Dong; Du, Guocheng; Liu, Long; Chen, Jian

2014-01-01

Many enzymes are efficiently produced by microbes. However, the use of natural enzymes as biocatalysts has limitations such as low catalytic efficiency, low activity, and low stability, especially under industrial conditions. Many protein engineering technologies have been developed to modify natural enzymes and eliminate these limitations. Commonly used protein engineering strategies include directed evolution, site-directed mutagenesis, truncation, and terminal fusion. This review summarizes recent advances in the molecular engineering of industrial enzymes and discusses future prospects in this field. We expect this review to increase interest in and advance the molecular engineering of industrial enzymes.

WaterlooClarke: TREC 2015 Clinical Decision Support Track

DTIC Science & Technology

2015-11-20

questions (diagnosis, test and treatment articles). The two different full-text search engines we adopted in order to search over the collection of articles...two different search engines using reciprocal rank fusion. The evaluation of the submitted runs using partially marked results of Text Retrieval Conference (TREC) from the previous year shows that the methodologies are promising.

Bionic Manufacturing: Towards Cyborg Cells and Sentient Microbots.

PubMed

Srivastava, Sarvesh Kumar; Yadav, Vikramaditya G

2018-05-01

Bio-inspired engineering applies biological design principles towards developing engineering solutions but is not practical as a manufacturing paradigm. We advocate 'bionic manufacturing', a synergistic fusion of biotic and abiotic components, to transition away from bio-inspiration toward bio-augmentation to address current limitations in bio-inspired manufacturing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Efficient killing of CD22{sup +} tumor cells by a humanized diabody-RNase fusion protein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Krauss, Juergen; Arndt, Michaela A.E.; Vu, Bang K.

2005-06-03

We report on the generation of a dimeric immunoenzyme capable of simultaneously delivering two ribonuclease (RNase) effector domains on one molecule to CD22{sup +} tumor cells. As targeting moiety a diabody derived from the previously humanized scFv SGIII with grafted specificity of the murine anti-CD22 mAb RFB4 was constructed. Further engineering the interface of this construct (V{sub L}36{sub Leu{yields}}{sub Tyr}) resulted in a highly robust bivalent molecule that retained the same high affinity as the murine mAb RFB4 (K{sub D} 0.2 nM). A dimeric immunoenzyme comprising this diabody and Rana pipiens liver ribonuclease I (rapLRI) was generated, expressed as solublemore » protein in bacteria, and purified to homogeneity. The dimeric fusion protein killed several CD22{sup +} tumor cell lines with high efficacy (IC{sub 50} = 3-20 nM) and exhibited 9- to 48-fold stronger cytotoxicity than a monovalent rapLRI-scFv counterpart. Our results demonstrate that engineering of dimeric antibody-ribonuclease fusion proteins can markedly enhance their biological efficacy.« less

Hairpin Folding of HIV gp41 Abrogates Lipid Mixing Function at Physiologic pH and Inhibits Lipid Mixing by Exposed gp41 Constructs†

PubMed Central

Sackett, Kelly; Nethercott, Matthew J.; Shai, Yechiel; Weliky, David P.

2009-01-01

Conformational changes in the HIV gp41 protein are directly correlated with fusion between the HIV and target cell plasma membranes which is the initial step of infection. Key gp41 fusion conformations include an early extended conformation termed pre-hairpin which contains exposed regions and a final low energy conformation termed hairpin which has compact six-helix bundle structure. Current fusion models debate the roles of hairpin and pre-hairpin conformations in the process of membrane merger. In the present work, gp41 constructs have been engineered which correspond to fusion relevant parts of both pre-hairpin and hairpin conformations, and have been analyzed for their ability to induce lipid mixing between membrane vesicles. The data correlate membrane fusion function with the pre-hairpin conformation and suggest that one of the roles of the final hairpin conformation is sequestration of membrane perturbing gp41 regions with consequent loss of the membrane disruption induced earlier by the pre-hairpin structure. To our knowledge, this is the first biophysical study to delineate the membrane fusion potential of gp41 constructs modeling key fusion conformations. PMID:19222185

Liquid Metals as Plasma-facing Materials for Fusion Energy Systems: From Atoms to Tokamaks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stone, Howard A.; Koel, Bruce E.; Bernasek, Steven L.

The objective of our studies was to advance our fundamental understanding of liquid metals as plasma-facing materials for fusion energy systems, with a broad scope: from atoms to tokamaks. The flow of liquid metals offers solutions to significant problems of the plasma-facing materials for fusion energy systems. Candidate metals include lithium, tin, gallium, and their eutectic combinations. However, such liquid metal solutions can only be designed efficiently if a range of scientific and engineering issues are resolved that require advances in fundamental fluid dynamics, materials science and surface science. In our research we investigated a range of significant and timelymore » problems relevant to current and proposed engineering designs for fusion reactors, including high-heat flux configurations that are being considered by leading fusion energy groups world-wide. Using experimental and theoretical tools spanning atomistic to continuum descriptions of liquid metals, and bridging surface chemistry, wetting/dewetting and flow, our research has advanced the science and engineering of fusion energy materials and systems. Specifically, we developed a combined experimental and theoretical program to investigate flows of liquid metals in fusion-relevant geometries, including equilibrium and stability of thin-film flows, e.g. wetting and dewetting, effects of electromagnetic and thermocapillary fields on liquid metal thin-film flows, and how chemical interactions and the properties of the surface are influenced by impurities and in turn affect the surface wetting characteristics, the surface tension, and its gradients. Because high-heat flux configurations produce evaporation and sputtering, which forces rearrangement of the liquid, and any dewetting exposes the substrate to damage from the plasma, our studies addressed such evaporatively driven liquid flows and measured and simulated properties of the different bulk phases and material interfaces. The range of our studies included (i) quantum mechanical calculations that allow inclusion of many thousands of atoms for the characterization of the interface of liquid metals exposed to continuous bombardment by deuterium and tritium as expected in fusion, (ii) molecular dynamics studies of the phase behavior of liquid metals, which (a) utilize thermodynamic properties computed using our quantum mechanical calculations and (b) establish material and wetting properties of the liquid metals, including relevant eutectics, (iii) experimental investigations of the surface science of liquid metals, interacting both with the solid substrate as well as gaseous species, and (iv) fluid dynamical studies that incorporate the material and surface science results of (ii) and (iii) in order to characterize flow in capillary porous materials and the thin-film flow along curved boundaries, both of which are potentially major components of plasma-facing materials. The outcome of these integrated studies was new understanding that enables developing design rules useful for future developments of the plasma-facing components critical to the success of fusion energy systems.« less

High Energy Plasma Space Propulsion

NASA Technical Reports Server (NTRS)

Wu, S. T.

2000-01-01

In order to meet NASA's challenge on advanced concept activity in the propulsion area, we initiated a new program entitled "High Energy Plasma Space Propulsion Studies" within the current cooperative agreement in 1998. The goals of this work are to gain further understanding of the engine of the AIMStar spacecraft, a concept which was developed at Penn State University, and to develop a prototype concept for the engine. The AIMStar engine concept was developed at Penn State University several years ago as a hybrid between antimatter and fusion technologies. Because of limited amounts of antimatter available, and concurrently the demonstrated ability for antiprotons to efficiently ignite nuclear fusion reactions, it was felt that this was a very good match. Investigations have been made concerning the performance of the reaction trap. This is a small Penning-like electromagnetic trap, which is used to simultaneously confine antiprotons and fusion fuels. Small DHe3 or DT droplets, containing a few percent molar of a fissile material, are injected into the trap, filled with antiprotons. We have found that it is important to separate the antiprotons into two adjacent wells, to inject he droplet between them and to simultaneously bring the antiprotons to the center of the trap, surrounding the droplet. Our previous concept had the droplet falling onto one cloud of antiprotons. This proved to be inefficient, as the droplet tended to evaporate away from the cloud as it interacted on its surface.

Project Icarus: Analysis of Plasma jet driven Magneto-Inertial Fusion as potential primary propulsion driver for the Icarus probe

NASA Astrophysics Data System (ADS)

Stanic, M.; Cassibry, J. T.; Adams, R. B.

2013-05-01

Hopes of sending probes to another star other than the Sun are currently limited by the maturity of advanced propulsion technologies. One of the few candidate propulsion systems for providing interstellar flight capabilities is nuclear fusion. In the past many fusion propulsion concepts have been proposed and some of them have even been explored in detail, Project Daedalus for example. However, as scientific progress in this field has advanced, new fusion concepts have emerged that merit evaluation as potential drivers for interstellar missions. Plasma jet driven Magneto-Inertial Fusion (PJMIF) is one of those concepts. PJMIF involves a salvo of converging plasma jets that form a uniform liner, which compresses a magnetized target to fusion conditions. It is an Inertial Confinement Fusion (ICF)-Magnetic Confinement Fusion (MCF) hybrid approach that has the potential for a multitude of benefits over both ICF and MCF, such as lower system mass and significantly lower cost. This paper concentrates on a thermodynamic assessment of basic performance parameters necessary for utilization of PJMIF as a candidate propulsion system for the Project Icarus mission. These parameters include: specific impulse, thrust, exhaust velocity, mass of the engine system, mass of the fuel required etc. This is a submission of the Project Icarus Study Group.

Designing proteins for therapeutic applications.

PubMed

Lazar, Greg A; Marshall, Shannon A; Plecs, Joseph J; Mayo, Stephen L; Desjarlais, John R

2003-08-01

Protein design is becoming an increasingly useful tool for optimizing protein drugs and creating novel biotherapeutics. Recent progress includes the engineering of monoclonal antibodies, cytokines, enzymes and viral fusion inhibitors.

Fast retrieval and autonomous regulation of single spontaneously recycling synaptic vesicles

PubMed Central

Leitz, Jeremy; Kavalali, Ege T

2014-01-01

Presynaptic terminals release neurotransmitters spontaneously in a manner that can be regulated by Ca2+. However, the mechanisms underlying this regulation are poorly understood because the inherent stochasticity and low probability of spontaneous fusion events has curtailed their visualization at individual release sites. Here, using pH-sensitive optical probes targeted to synaptic vesicles, we visualized single spontaneous fusion events and found that they are retrieved extremely rapidly with faster re-acidification kinetics than their action potential-evoked counterparts. These fusion events were coupled to postsynaptic NMDA receptor-driven Ca2+ signals, and at elevated Ca2+ concentrations there was an increase in the number of vesicles that would undergo fusion. Furthermore, spontaneous vesicle fusion propensity in a synapse was Ca2+-dependent but regulated autonomously: independent of evoked fusion probability at the same synapse. Taken together, these results expand classical quantal analysis to incorporate endocytic and exocytic phases of single fusion events and uncover autonomous regulation of spontaneous fusion. DOI: http://dx.doi.org/10.7554/eLife.03658.001 PMID:25415052

Central Sensitization Inventory as a Predictor of Worse Quality of Life Measures and Increased Length of Stay Following Spinal Fusion.

PubMed

Bennett, E Emily; Walsh, Kevin M; Thompson, Nicolas R; Krishnaney, Ajit A

2017-08-01

Central sensitization is abnormal and intense enhancement of pain mechanism by the central nervous system. Patients with central sensitization may be at higher risk of poor outcomes after spinal fusion. The Central Sensitivity Inventory (CSI) was developed to identify and quantify key symptoms related to central sensitization. In 664 patients who underwent thoracic and/or lumbar fusion, we evaluated retrospectively pretreatment CSI as a predictor of postoperative quality of life measures, length of stay, and discharge status. Preoperative Pain Disability Questionnaire scores, Patient Health Questionnaire-9 scores, and EuroQol-5 Dimensions index scores were significantly worse in patients with preoperative CSI ≥40 compared with patients with preoperative CSI <40 (P < 0.0001 for all). After adjusting for demographic variables, operation duration, and preoperative health status, preoperative CSI was significantly associated with higher postoperative Pain Disability Questionnaire total score (unadjusted P < 0.001, adjusted P = 0.009), higher postoperative Patient Health Questionnaire-9 score (unadjusted P < 0.001, adjusted P = 0.001), and lower postoperative EuroQol-5 Dimensions index (unadjusted P < 0.001, adjusted P = 0.001). For each 10-unit increase in CSI, average length of stay increased by 6.4% (95% confidence interval 0.4%-12.6%, P = 0.035). The odds of being discharged home after adjusting for confounders was not statistically related to preoperative CSI (P = 0.0709). Preoperative CSI was associated with worse quality of life outcomes and increased length of stay after spinal fusions. CSI may be an additional measure in evaluating patients preoperatively to better predict successful spinal fusion outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Cost-Effectiveness Comparison of Imaging-Guided Prostate Biopsy Techniques: Systematic Transrectal Ultrasound, Direct In-Bore MRI, and Image Fusion.

PubMed

Venderink, Wulphert; Govers, Tim M; de Rooij, Maarten; Fütterer, Jurgen J; Sedelaar, J P Michiel

2017-05-01

Three commonly used prostate biopsy approaches are systematic transrectal ultrasound guided, direct in-bore MRI guided, and image fusion guided. The aim of this study was to calculate which strategy is most cost-effective. A decision tree and Markov model were developed to compare cost-effectiveness. Literature review and expert opinion were used as input. A strategy was deemed cost-effective if the costs of gaining one quality-adjusted life year (incremental cost-effectiveness ratio) did not exceed the willingness-to-pay threshold of €80,000 (≈$85,000 in January 2017). A base case analysis was performed to compare systematic transrectal ultrasound- and image fusion-guided biopsies. Because of a lack of appropriate literature regarding the accuracy of direct in-bore MRI-guided biopsy, a threshold analysis was performed. The incremental cost-effectiveness ratio for fusion-guided biopsy compared with systematic transrectal ultrasound-guided biopsy was €1386 ($1470) per quality-adjusted life year gained, which was below the willingness-to-pay threshold and thus assumed cost-effective. If MRI findings are normal in a patient with clinically significant prostate cancer, the sensitivity of direct in-bore MRI-guided biopsy has to be at least 88.8%. If that is the case, the incremental cost-effectiveness ratio is €80,000 per quality-adjusted life year gained and thus cost-effective. Fusion-guided biopsy seems to be cost-effective compared with systematic transrectal ultrasound-guided biopsy. Future research is needed to determine whether direct in-bore MRI-guided biopsy is the best pathway; in this study a threshold was calculated at which it would be cost-effective.

Near Earth Asteroids- Prospection, Orbit Modification and Mining

NASA Astrophysics Data System (ADS)

Grandl, W.; Bazso, A.

2014-04-01

The number of known Near Earth Asteroids (NEAs) has increased continuously during the last decades. Now we understand the role of asteroid impacts for the evolution of life on Earth. To ensure that mankind will survive in the long run, we have to face the "asteroid threat" seriously. On one hand we will have to develop methods of detection and deflection for Hazardous Asteroids, on the other hand we can use these methods to modify their orbits and exploit their resources. Rare-earth elements, rare metals like platinum group elements, etc. may be extracted more easily from NEAs than from terrestrial soil, without environmental pollution or political and social problems. In a first step NEAs, which are expected to contain resources like nickel-iron, platinum group metals or rare-earth elements, will be prospected by robotic probes. Then a number of asteroids with a minimum bulk density of 2 g/cm^3 and a diameter of 150 to 500 m will be selected for mining. Given the long duration of an individual mission time of 10-20 years, the authors propose a "pipeline" concept. While the observation of NEAs can be done in parallel, the precursor missions of the the next phase can be launched in short intervals, giving time for technical corrections and upgrades. In this way a continuous data flow is established and there are no idle times. For our purpose Potentially Hazardous Asteroids (PHAs) seem to be a favorable choice for the following reasons: They have frequent closeencounters to Earth, their minimum orbit intersection distance is less than 0.05 AU (Astronomic Units) and they have diameters exceeding 150 meters. The necessary velocity change (delta V) for a spaceship is below 12 km/s to reach the PHA. The authors propose to modify the orbits of the chosen PHAs by orbital maneuvers from solar orbits to stable Earth orbits beyond the Moon. To change the orbits of these celestial bodies it is necessary to develop advanced propulsion systems. They must be able to deliver high thrust and specific impulse to move the huge masses of the asteroids. Such a propulsion system could be the Bussard Fusion System, also known as the quiet-electricdischarge (QED) engine. It uses electrostatic fusion devices to generate electrical power. The fuel consists of Deuterium and Helium3 that are fusing to Helium4 plus protons releasing 18.3 MeV of energy per reaction. The charged protons escape from the confinement; their kinetic energy can be converted to electricity or be used directly as a plasma beam for generating thrust. For the reaction a specific energy of 3.5x1014 Joule/kg can be computed, i.e. orders-ofmagnitude higher than for any existing propulsion system. As an example we take the Asteroid with the designation 2008 EV5. It is classified as an Aten group asteroid with a mean diameter of 450 meters and belongs to spectral type S (stony asteroids). Our mass estimate (using a bulk density of 3 g/cm^3) is 1.4x1011 kg. To transfer 2008 EV5 to an Earth-like orbit the energy required is estimated to be in the order of 2.8x1018 Joule. This is the difference in Kepler energy between the NEA's current orbit and the Earth's orbit around the sun. Using the Bussard Fusion System the amount of fuel would be approx. 8000 kg of Helium3. To move an asteroid by remote control the authors propose to design unmanned space tugs which are propelled by Bussard Fusion Engines. A pair of space tugs is docked to each asteroid using drilling anchors. The fusion engines of the tugs then apply the thrust forces for the maneuvers. The first tug, which carries the main fuel quantity, applies the primary force for the orbital maneuvers. The second one adjust the flight track by short engine thrusts.

Rheological behavior and cryogenic properties of cyanate ester/epoxy insulation material for fusion superconducting magnet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Z. X.; Huang, C. J.; Li, L. F.

2014-01-27

In a Tokamak fusion reactor device like ITER, insulation materials for superconducting magnets are usually fabricated by a vacuum pressure impregnation (VPI) process. Thus these insulation materials must exhibit low viscosity, long working life as well as good radiation resistance. Previous studies have indicated that cyanate ester (CE) blended with epoxy has an excellent resistance against neutron irradiation which is expected to be a candidate insulation material for a fusion magnet. In this work, the rheological behavior of a CE/epoxy (CE/EP) blend containing 40% CE was investigated with non-isothermal and isothermal viscosity experiments. Furthermore, the cryogenic mechanical and electrical propertiesmore » of the composite were evaluated in terms of interlaminar shear strength and electrical breakdown strength. The results showed that CE/epoxy blend had a very low viscosity and an exceptionally long processing life of about 4 days at 60 °C.« less

A Review on the Potential Use of Austenitic Stainless Steels in Nuclear Fusion Reactors

NASA Astrophysics Data System (ADS)

Şahin, Sümer; Übeyli, Mustafa

2008-12-01

Various engineering materials; austenitic stainless steels, ferritic/martensitic steels, vanadium alloys, refractory metals and composites have been suggested as candidate structural materials for nuclear fusion reactors. Among these structural materials, austenitic steels have an advantage of extensive technological database and lower cost compared to other non-ferrous candidates. Furthermore, they have also advantages of very good mechanical properties and fission operation experience. Moreover, modified austenitic stainless (Ni and Mo free) have relatively low residual radioactivity. Nevertheless, they can't withstand high neutron wall load which is required to get high power density in fusion reactors. On the other hand, a protective flowing liquid wall between plasma and solid first wall in these reactors can eliminate this restriction. This study presents an overview of austenitic stainless steels considered to be used in fusion reactors.

Efficient growth inhibition of ErbB2-overexpressing tumor cells by anti-ErbB2 ScFv-Fc-IL-2 fusion protein in vitro and in vivo.

PubMed

Shi, Ming; Zhang, Ling; Gu, Hong-Tao; Jiang, Feng-Qin; Qian, Lu; Yu, Ming; Chen, Guo-Jiang; Luo, Qun; Shen, Bei-Fen; Guo, Ning

2007-10-01

To investigate the antitumor activities of an anti-ErbB2 scFv-Fc-interleukin 2 (IL-2) fusion protein (HFI) in vitro and in vivo. Fusion protein HFI was constructed. The efficacy of HFI in mediating tumor cell lysis was determined by colorimetric lactate dehydrogenase release assays. The antitumor activity of HFI was evaluated in tumor xenograft models. The fusion protein was folded as a homodimer formed by covalently linking Fc portions and it retained ErbB2 specificity and IL-2 biological activity. HFI mediated antibody-dependent cell-mediated cytotoxicity (ADCC) at low effector-to-target ratios in vitro and improved the therapeutic efficacy of IL-2 in experiments in vivo. The genetically-engineered anti-ErbB2 scFv-Fc-IL-2 fusion protein exhibited high efficiency both in mediating ADCC in vitro and significant antitumor activity in tumor xenograft models.

BMP9 induces osteogenesis and adipogenesis in the immortalized human cranial suture progenitors from the patent sutures of craniosynostosis patients.

PubMed

Song, Dongzhe; Zhang, Fugui; Reid, Russell R; Ye, Jixing; Wei, Qiang; Liao, Junyi; Zou, Yulong; Fan, Jiaming; Ma, Chao; Hu, Xue; Qu, Xiangyang; Chen, Liqun; Li, Li; Yu, Yichun; Yu, Xinyi; Zhang, Zhicai; Zhao, Chen; Zeng, Zongyue; Zhang, Ruyi; Yan, Shujuan; Wu, Tingting; Wu, Xingye; Shu, Yi; Lei, Jiayan; Li, Yasha; Zhang, Wenwen; Wang, Jia; Lee, Michael J; Wolf, Jennifer Moriatis; Huang, Dingming; He, Tong-Chuan

2017-11-01

The cranial suture complex is a heterogeneous tissue consisting of osteogenic progenitor cells and mesenchymal stem cells (MSCs) from bone marrow and suture mesenchyme. The fusion of cranial sutures is a highly coordinated and tightly regulated process during development. Craniosynostosis is a congenital malformation caused by premature fusion of cranial sutures. While the progenitor cells derived from the cranial suture complex should prove valuable for studying the molecular mechanisms underlying suture development and pathogenic premature suture fusion, primary human cranial suture progenitors (SuPs) have limited life span and gradually lose osteoblastic ability over passages. To overcome technical challenges in maintaining sufficient and long-term culture of SuPs for suture biology studies, we establish and characterize the reversibly immortalized human cranial suture progenitors (iSuPs). Using a reversible immortalization system expressing SV40 T flanked with FRT sites, we demonstrate that primary human suture progenitor cells derived from the patent sutures of craniosynostosis patients can be efficiently immortalized. The iSuPs maintain long-term proliferative activity, express most of the consensus MSC markers and can differentiate into osteogenic and adipogenic lineages upon BMP9 stimulation in vitro and in vivo. The removal of SV40 T antigen by FLP recombinase results in a decrease in cell proliferation and an increase in the endogenous osteogenic and adipogenic capability in the iSuPs. Therefore, the iSuPs should be a valuable resource to study suture development, intramembranous ossification and the pathogenesis of craniosynostosis, as well as to explore cranial bone tissue engineering. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Randomized Controlled Trial of Minimally Invasive Sacroiliac Joint Fusion Using Triangular Titanium Implants vs Nonsurgical Management for Sacroiliac Joint Dysfunction: 12-Month Outcomes.

PubMed

Polly, David W; Cher, Daniel J; Wine, Kathryn D; Whang, Peter G; Frank, Clay J; Harvey, Charles F; Lockstadt, Harry; Glaser, John A; Limoni, Robert P; Sembrano, Jonathan N

2015-11-01

Sacroiliac joint (SIJ) dysfunction is a prevalent cause of chronic, unremitting lower back pain. To concurrently compare outcomes after surgical and nonsurgical treatment for chronic SIJ dysfunction. A total of 148 subjects with SIJ dysfunction were randomly assigned to minimally invasive SIJ fusion with triangular titanium implants (n = 102) or nonsurgical management (n = 46). Pain, disability, and quality-of-life scores were collected at baseline and at 1, 3, 6, and 12 months. Success rates were compared using Bayesian methods. Crossover from nonsurgical to surgical care was allowed after the 6-month study visit was complete. Six-month success rates were higher in the surgical group (81.4% vs 26.1%; posterior probability of superiority > 0.9999). Clinically important (≥ 15 point) Oswestry Disability Index improvement at 6 months occurred in 73.3% of the SIJ fusion group vs 13.6% of the nonsurgical management group (P < .001). At 12 months, improvements in SIJ pain and Oswestry Disability Index were sustained in the surgical group. Subjects who crossed over had improvements in pain, disability, and quality of life similar to those in the original surgical group. Adverse events were slightly more common in the surgical group (1.3 vs 1.1 events per subject; P = .31). This Level 1 study showed that minimally invasive SIJ fusion using triangular titanium implants was more effective than nonsurgical management at 1 year in relieving pain, improving function, and improving quality of life in patients with SIJ dysfunction caused by degenerative sacroiliitis or SIJ disruptions. Pain, disability, and quality of life also improved after crossover from nonsurgical to surgical treatment.

Biotechnological Production of Dimethoxyflavonoids Using a Fusion Flavonoid O-Methyltransferase Possessing Both 3'- and 7-O-Methyltransferase Activities.

PubMed

Lee, Danbi; Park, Hye Lin; Lee, Sang-Won; Bhoo, Seong Hee; Cho, Man-Ho

2017-05-26

Although they are less abundant in nature, methoxyflavonoids have distinct physicochemical and pharmacological properties compared to common nonmethylated flavonoids. Thus, enzymatic conversion and biotransformation using genetically engineered microorganisms of flavonoids have been attempted for the efficient production of methoxyflavonoids. Because of their regiospecificity, more than two flavonoid O-methyltransferases (FOMTs) and enzyme reactions are required to biosynthesize di(or poly)-methoxyflavonoids. For the one-step biotechnological production of bioactive di-O-methylflavonoids, we generated a multifunctional FOMT fusing a 3'-OMT (SlOMT3) and a 7-OMT (OsNOMT). The SlOMT3/OsNOMT fusion enzyme possessed both 3'- and 7-OMT activities to diverse flavonoid substrates, which were comparable to those of individual SlOMT3 and OsNOMT. The SlOMT3/OsNOMT enzyme also showed 3'- and 7-OMT activity for 7- or 3'-O-methylflavonoids, respectively, suggesting that the fusion enzyme can sequentially methylate flavonoids into di-O-methylflavonoids. The biotransformation of the flavonoids quercetin, luteolin, eriodictyol, and taxifolin using SlOMT3/OsNOMT-transformed Escherichia coli generated corresponding di-O-methylflavonoids, rhamnazin, velutin, 3',7-di-O-methyleriodictyol, and 3',7-di-O-methyltaxifolin, respectively. These results indicate that dimethoxyflavonoids may be efficiently produced from nonmethylated flavonoid precursors through a one-step biotransformation using the engineered E. coli harboring the SlOMT3/OsNOMT fusion gene.

Engineering Styrene Monooxygenase for Biocatalysis: Reductase-Epoxidase Fusion Proteins.

PubMed

Heine, Thomas; Tucker, Kathryn; Okonkwo, Nonye; Assefa, Berhanegebriel; Conrad, Catleen; Scholtissek, Anika; Schlömann, Michael; Gassner, George; Tischler, Dirk

2017-04-01

The enantioselective epoxidation of styrene and related compounds by two-component styrene monooxygenases (SMOs) has targeted these enzymes for development as biocatalysts. In the present work, we prepare genetically engineered fusion proteins that join the C-terminus of the epoxidase (StyA) to the N-terminus of the reductase (StyB) through a linker peptide and demonstrate their utility as biocatalysts in the synthesis of Tyrain purple and other indigoid dyes. A single-vector expression system offers a simplified platform for transformation and expansion of the catalytic function of styrene monooxygenases, and the resulting fusion proteins are self-regulated and couple efficiently NADH oxidation to styrene epoxidation. We find that the reductase domain proceeds through a sequential ternary-complex mechanism at low FAD concentration and a double-displacement mechanism at higher concentrations of FAD. Single-turnover studies indicate an observed rate constant for FAD-to-FAD hydride transfer of ~8 s -1 . This step is rate limiting in the styrene epoxidation reaction and helps to ensure that flavin reduction and styrene epoxidation reactions proceed without wasteful side reactions. Comparison of the reductase activity of the fusion proteins with the naturally occurring reductase, SMOB, and N-terminally histidine-tagged reductase, NSMOB, suggests that the observed changes in catalytic mechanism are due in part to an increase in flavin-binding affinity associated with the N-terminal extension of the reductase.

Dynamics simulations for engineering macromolecular interactions

PubMed Central

Robinson-Mosher, Avi; Shinar, Tamar; Silver, Pamela A.; Way, Jeffrey

2013-01-01

The predictable engineering of well-behaved transcriptional circuits is a central goal of synthetic biology. The artificial attachment of promoters to transcription factor genes usually results in noisy or chaotic behaviors, and such systems are unlikely to be useful in practical applications. Natural transcriptional regulation relies extensively on protein-protein interactions to insure tightly controlled behavior, but such tight control has been elusive in engineered systems. To help engineer protein-protein interactions, we have developed a molecular dynamics simulation framework that simplifies features of proteins moving by constrained Brownian motion, with the goal of performing long simulations. The behavior of a simulated protein system is determined by summation of forces that include a Brownian force, a drag force, excluded volume constraints, relative position constraints, and binding constraints that relate to experimentally determined on-rates and off-rates for chosen protein elements in a system. Proteins are abstracted as spheres. Binding surfaces are defined radially within a protein. Peptide linkers are abstracted as small protein-like spheres with rigid connections. To address whether our framework could generate useful predictions, we simulated the behavior of an engineered fusion protein consisting of two 20 000 Da proteins attached by flexible glycine/serine-type linkers. The two protein elements remained closely associated, as if constrained by a random walk in three dimensions of the peptide linker, as opposed to showing a distribution of distances expected if movement were dominated by Brownian motion of the protein domains only. We also simulated the behavior of fluorescent proteins tethered by a linker of varying length, compared the predicted Förster resonance energy transfer with previous experimental observations, and obtained a good correspondence. Finally, we simulated the binding behavior of a fusion of two ligands that could simultaneously bind to distinct cell-surface receptors, and explored the landscape of linker lengths and stiffnesses that could enhance receptor binding of one ligand when the other ligand has already bound to its receptor, thus, addressing potential mechanisms for improving targeted signal transduction proteins. These specific results have implications for the design of targeted fusion proteins and artificial transcription factors involving fusion of natural domains. More broadly, the simulation framework described here could be extended to include more detailed system features such as non-spherical protein shapes and electrostatics, without requiring detailed, computationally expensive specifications. This framework should be useful in predicting behavior of engineered protein systems including binding and dissociation reactions. PMID:23822508

14 CFR 33.70 - Engine life-limited parts.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Engine life-limited parts. 33.70 Section 33.70 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.70 Engine life...

14 CFR 33.70 - Engine life-limited parts.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Engine life-limited parts. 33.70 Section 33.70 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.70 Engine life...

Importance of lifetime effects in breakup and suppression of complete fusion in reactions of weakly bound nuclei

NASA Astrophysics Data System (ADS)

Cook, K. J.; Simpson, E. C.; Luong, D. H.; Kalkal, Sunil; Dasgupta, M.; Hinde, D. J.

2016-06-01

Background: Complete fusion cross sections in collisions of light weakly bound nuclei and high-Z targets show suppression of complete fusion at above-barrier energies. This has been interpreted as resulting from the breakup of the weakly bound nucleus prior to reaching the fusion barrier, reducing the probability of complete charge capture. Below-barrier studies of reactions of 9Be have found that the breakup of 8Be formed by neutron stripping dominates over direct breakup and that transfer-triggered breakup may account for the observed suppression of complete fusion. Purpose: This paper investigates how the above conclusions are affected by lifetimes of the resonant states that are populated prior to breakup. If the mean life of a populated resonance (above the breakup threshold) is much longer than the fusion time scale, then its breakup (decay) cannot suppress complete fusion. For short-lived resonances, the situation is more complex. This work explicitly includes the mean life of the short-lived 2+ resonance in 8Be in classical dynamical model calculations to determine its effect on energy and angular correlations of the breakup fragments and on model predictions of suppression of cross sections for complete fusion at above-barrier energies. Method: Previously performed coincidence measurements of breakup fragments produced in reactions of 9Be with 144Sm, 168Er, 186W, 196Pt, 208Pb, and 209Bi at energies below the barrier have been reanalyzed using an improved efficiency determination of the BALiN detector array. Predictions of breakup observables and of complete and incomplete fusion at energies above the fusion barrier are then made using the classical dynamical simulation code platypus, modified to include the effect of lifetimes of resonant states. Results: The agreement of the breakup observables is much improved when lifetime effects are included explicitly. Sensitivity to subzeptosecond lifetime is observed. The predicted suppression of complete fusion owing to breakup is nearly independent of Z and has an average value of ˜9 % . This is below the experimentally determined fusion suppression, which is typically ˜30 % in these systems. Conclusions: Inclusion of resonance lifetimes is essential to correctly reproduce breakup observables. This results in a larger fraction of nuclei remaining intact at the fusion-barrier radius compared with calculations that do not explicitly include lifetime effects. The more realistic treatment of breakup followed in this work leads to the conclusion that the suppression of complete fusion cannot be fully explained by breakup prior to reaching the fusion barrier. Only one-third of the observed fusion suppression can be attributed to the competing process of breakup. Other mechanisms that can suppress complete fusion must therefore be investigated. One of the possible candidates is cluster transfer that produces the same heavy targetlike nuclei as those formed by incomplete fusion.

40 CFR 90.105 - Useful life periods for Phase 2 engines.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Useful life periods for Phase 2 engines... Emission Standards and Certification Provisions § 90.105 Useful life periods for Phase 2 engines. (a) Manufacturers shall declare the applicable useful life category for each engine family at the time of...

Strategies for enhancing bioluminescent bacterial sensor performance by promoter region manipulation

PubMed Central

Bilic, Benny; Belkin, Shimshon

2010-01-01

Genetically engineered microbial reporter strains are based upon the fusion of an inducible sensing element upstream of a reporting element, so that the construct emits a dose-dependent signal when exposed to the inducing compound(s) or stress factor(s). In this communication1 we described several general approaches undertaken in order to enhance the sensing performance of such promoter::reporter fusions. Significant improvements in detection sensitivity, response kinetics and signal intensity were achieved by modi fication of the length of the promoter-containing DNA fragment, by random or site-directed mutagenesis and by promoter duplication. The general nature of these genetics manipulations makes them applicable to other types of promoter::reporter fusions. PMID:21326942

Dynamic Creation of Social Networks for Syndromic Surveillance Using Information Fusion

NASA Astrophysics Data System (ADS)

Holsopple, Jared; Yang, Shanchieh; Sudit, Moises; Stotz, Adam

To enhance the effectiveness of health care, many medical institutions have started transitioning to electronic health and medical records and sharing these records between institutions. The large amount of complex and diverse data makes it difficult to identify and track relationships and trends, such as disease outbreaks, from the data points. INFERD: Information Fusion Engine for Real-Time Decision-Making is an information fusion tool that dynamically correlates and tracks event progressions. This paper presents a methodology that utilizes the efficient and flexible structure of INFERD to create social networks representing progressions of disease outbreaks. Individual symptoms are treated as features allowing multiple hypothesis being tracked and analyzed for effective and comprehensive syndromic surveillance.

Interplanetary propulsion using inertial fusion

NASA Technical Reports Server (NTRS)

Orth, C. D.; Hogan, W. J.; Hoffman, N.; Murray, K.; Klein, G.; Diaz, F. C.

1987-01-01

Inertial fusion can be used to power spacecraft within the solar system and beyond. Such spacecraft have the potential for short-duration manned-mission performance exceeding other technologies. We are conducting a study to assess the systems aspects of inertial fusion as applied to such missions, based on the conceptual engine design of Hyde (1983) we describe the required systems for an entirely new spacecraft design called VISTA that is based on the use of DT fuel. We give preliminary design details for the power conversion and power conditioning systems for manned missions to Mars of total duration of about 100 days. Specific mission performance results will be published elsewhere, after the study has been completed.

Sensor Based Engine Life Calculation: A Probabilistic Perspective

NASA Technical Reports Server (NTRS)

Guo, Ten-Huei; Chen, Philip

2003-01-01

It is generally known that an engine component will accumulate damage (life usage) during its lifetime of use in a harsh operating environment. The commonly used cycle count for engine component usage monitoring has an inherent range of uncertainty which can be overly costly or potentially less safe from an operational standpoint. With the advance of computer technology, engine operation modeling, and the understanding of damage accumulation physics, it is possible (and desirable) to use the available sensor information to make a more accurate assessment of engine component usage. This paper describes a probabilistic approach to quantify the effects of engine operating parameter uncertainties on the thermomechanical fatigue (TMF) life of a selected engine part. A closed-loop engine simulation with a TMF life model is used to calculate the life consumption of different mission cycles. A Monte Carlo simulation approach is used to generate the statistical life usage profile for different operating assumptions. The probabilities of failure of different operating conditions are compared to illustrate the importance of the engine component life calculation using sensor information. The results of this study clearly show that a sensor-based life cycle calculation can greatly reduce the risk of component failure as well as extend on-wing component life by avoiding unnecessary maintenance actions.

Balancing Efficiency and Effectiveness for Fusion-Based Search Engines in the "Big Data" Environment

ERIC Educational Resources Information Center

Li, Jieyu; Huang, Chunlan; Wang, Xiuhong; Wu, Shengli

2016-01-01

Introduction: In the big data age, we have to deal with a tremendous amount of information, which can be collected from various types of sources. For information search systems such as Web search engines or online digital libraries, the collection of documents becomes larger and larger. For some queries, an information search system needs to…

The knowledge instinct, cognitive algorithms, modeling of language and cultural evolution

NASA Astrophysics Data System (ADS)

Perlovsky, Leonid I.

2008-04-01

The talk discusses mechanisms of the mind and their engineering applications. The past attempts at designing "intelligent systems" encountered mathematical difficulties related to algorithmic complexity. The culprit turned out to be logic, which in one way or another was used not only in logic rule systems, but also in statistical, neural, and fuzzy systems. Algorithmic complexity is related to Godel's theory, a most fundamental mathematical result. These difficulties were overcome by replacing logic with a dynamic process "from vague to crisp," dynamic logic. It leads to algorithms overcoming combinatorial complexity, and resulting in orders of magnitude improvement in classical problems of detection, tracking, fusion, and prediction in noise. I present engineering applications to pattern recognition, detection, tracking, fusion, financial predictions, and Internet search engines. Mathematical and engineering efficiency of dynamic logic can also be understood as cognitive algorithm, which describes fundamental property of the mind, the knowledge instinct responsible for all our higher cognitive functions: concepts, perception, cognition, instincts, imaginations, intuitions, emotions, including emotions of the beautiful. I present our latest results in modeling evolution of languages and cultures, their interactions in these processes, and role of music in cultural evolution. Experimental data is presented that support the theory. Future directions are outlined.

Development of a biodegradable scaffold with interconnected pores by heat fusion and its application to bone tissue engineering.

PubMed

Shin, Michael; Abukawa, Harutsugi; Troulis, Maria J; Vacanti, Joseph P

2008-03-01

Tissue engineering has been proposed as an approach to alleviate the shortage of donor tissue and organs by combining cells and a biodegradable scaffold as a temporary extracellular matrix. While numerous scaffold fabrication methods have been proposed, tissue formation is typically limited to the surface of the scaffolds in bone tissue engineering applications due to early calcification on the surface. To improve tissue formation, a novel scaffold with a hierarchical interconnected pore structure on two distinct length scales has been developed. Here we present the fabrication process and the application of the scaffold to bone tissue engineering. Porous poly(lactide-co-glycolide) (PLGA) scaffolds were made by combining solvent casting/particulate leaching with heat fusion. Porcine bone marrow-derived mesenchymal stem cells (MSCs) were differentiated into osteoblasts and cultured on these scaffolds in vitro for 2, 4, and 6 weeks. Subsequently, the constructs were assessed using histology and scanning electron microscopy. The bone marrow-derived osteoblasts attached well on these scaffolds. Cells were observed throughout the scaffolds. These initial results show promise for this scaffold to aid in the regeneration of bone. (c) 2007 Wiley Periodicals, Inc.

Z-Pinch Pulsed Plasma Propulsion Technology Development

NASA Technical Reports Server (NTRS)

Polsgrove, Tara; Adams, Robert B.; Fabisinski, Leo; Fincher, Sharon; Maples, C. Dauphne; Miernik, Janie; Percy, Tom; Statham, Geoff; Turner, Matt; Cassibry, Jason;

Intelligent Life-Extending Controls for Aircraft Engines

NASA Technical Reports Server (NTRS)

Guo, Ten-Huei; Chen, Philip; Jaw, Link

2005-01-01

Aircraft engine controllers are designed and operated to provide desired performance and stability margins. The purpose of life-extending-control (LEC) is to study the relationship between control action and engine component life usage, and to design an intelligent control algorithm to provide proper trade-offs between performance and engine life usage. The benefit of this approach is that it is expected to maintain safety while minimizing the overall operating costs. With the advances of computer technology, engine operation models, and damage physics, it is necessary to reevaluate the control strategy fro overall operating cost consideration. This paper uses the thermo-mechanical fatigue (TMF) of a critical component to demonstrate how an intelligent engine control algorithm can drastically reduce the engine life usage with minimum sacrifice in performance. A Monte Carlo simulation is also performed to evaluate the likely engine damage accumulation under various operating conditions. The simulation results show that an optimized acceleration schedule can provide a significant life saving in selected engine components.

A local approach for focussed Bayesian fusion

NASA Astrophysics Data System (ADS)

Sander, Jennifer; Heizmann, Michael; Goussev, Igor; Beyerer, Jürgen

2009-04-01

Local Bayesian fusion approaches aim to reduce high storage and computational costs of Bayesian fusion which is separated from fixed modeling assumptions. Using the small world formalism, we argue why this proceeding is conform with Bayesian theory. Then, we concentrate on the realization of local Bayesian fusion by focussing the fusion process solely on local regions that are task relevant with a high probability. The resulting local models correspond then to restricted versions of the original one. In a previous publication, we used bounds for the probability of misleading evidence to show the validity of the pre-evaluation of task specific knowledge and prior information which we perform to build local models. In this paper, we prove the validity of this proceeding using information theoretic arguments. For additional efficiency, local Bayesian fusion can be realized in a distributed manner. Here, several local Bayesian fusion tasks are evaluated and unified after the actual fusion process. For the practical realization of distributed local Bayesian fusion, software agents are predestinated. There is a natural analogy between the resulting agent based architecture and criminal investigations in real life. We show how this analogy can be used to improve the efficiency of distributed local Bayesian fusion additionally. Using a landscape model, we present an experimental study of distributed local Bayesian fusion in the field of reconnaissance, which highlights its high potential.

Comparison of the recently proposed super-Marx generator approach to thermonuclear ignition with the deuterium-tritium laser fusion-fission hybrid concept by the Lawrence Livermore National Laboratory

DOE PAGES

Winterberg, F.

2009-01-01

The recently proposed super-Marx generator pure deuterium microdetonation ignition concept is compared to the Lawrence Livermore National Ignition Facility (NIF) Laser deuterium-tritium fusion-fission hybrid concept (LIFE). In a super-Marx generator, a large number of ordinary Marx generators charge up a much larger second stage ultrahigh voltage Marx generator from which for the ignition of a pure deuterium microexplosion an intense GeV ion beam can be extracted. Typical examples of the LIFE concept are a fusion gain of 30 and a fission gain of 10, making up a total gain of 300, with about ten times more energy released into fissionmore » as compared to fusion. This means the substantial release of fission products, as in fissionless pure fission reactors. In the super-Marx approach for the ignition of pure deuterium microdetonation, a gain of the same magnitude can, in theory, be reached. If feasible, the super-Marx generator deuterium ignition approach would make lasers obsolete as a means for the ignition of thermonuclear microexplosions.« less

Cost-effectiveness analysis of total ankle arthroplasty.

PubMed

SooHoo, Nelson F; Kominski, Gerald

2004-11-01

There is renewed interest in total ankle arthroplasty as an alternative to ankle fusion in the treatment of end-stage ankle arthritis. Despite a lack of long-term data on the clinical outcomes associated with these implants, the use of ankle arthroplasty is expanding. The purpose of this cost-effectiveness analysis was to evaluate whether the currently available literature justifies the emerging use of total ankle arthroplasty. This study also identifies thresholds for the durability and function of ankle prostheses that, if met, would support more widespread dissemination of this new technology. A decision model was created for the treatment of ankle arthritis. The literature was reviewed to identify possible outcomes and their probabilities following ankle fusion and ankle arthroplasty. Each outcome was weighted for quality of life with use of a utility factor, and effectiveness was expressed in units of quality-adjusted life years. Gross costs were estimated from Medicare charge and reimbursement data for the relevant codes. The effect of the uncertainty of estimates of costs and effectiveness was assessed with sensitivity analysis. The reference case of our model assumed a ten-year duration of survival of the prosthesis, resulting in an incremental cost-effectiveness ratio for ankle arthroplasty of $18,419 per quality-adjusted life year gained. This reflects a gain of 0.52 quality-adjusted life years at a cost of $9578 when ankle arthroplasty is chosen over fusion. This ratio compares favorably with the cost-effectiveness of other medical and surgical interventions. Sensitivity analysis determined that the cost per quality-adjusted life year gained with ankle arthroplasty rises above $50,000 if the prosthesis is assumed to fail before seven years. Treatment options with ratios above $50,000 per quality-adjusted life year are commonly considered to have limited cost-effectiveness. This threshold is also crossed when the theoretical functional advantages of ankle arthroplasty are eliminated in sensitivity analysis. The currently available literature has not yet shown that total ankle arthroplasty predictably results in levels of durability and function that make it cost-effective at this time. However, the reference case of this analysis does demonstrate that total ankle arthroplasty has the potential to be a cost-effective alternative to ankle fusion. This reference case assumes that the theoretical functional advantages of ankle arthroplasty over ankle fusion will be borne out in future clinical studies. Performance of total ankle replacement will be better justified if these thresholds are met in published long-term clinical trials.

The accomplishment of the Engineering Design Activities of IFMIF/EVEDA: The European-Japanese project towards a Li(d,xn) fusion relevant neutron source

NASA Astrophysics Data System (ADS)

Knaster, J.; Ibarra, A.; Abal, J.; Abou-Sena, A.; Arbeiter, F.; Arranz, F.; Arroyo, J. M.; Bargallo, E.; Beauvais, P.-Y.; Bernardi, D.; Casal, N.; Carmona, J. M.; Chauvin, N.; Comunian, M.; Delferriere, O.; Delgado, A.; Diaz-Arocas, P.; Fischer, U.; Frisoni, M.; Garcia, A.; Garin, P.; Gobin, R.; Gouat, P.; Groeschel, F.; Heidinger, R.; Ida, M.; Kondo, K.; Kikuchi, T.; Kubo, T.; Le Tonqueze, Y.; Leysen, W.; Mas, A.; Massaut, V.; Matsumoto, H.; Micciche, G.; Mittwollen, M.; Mora, J. C.; Mota, F.; Nghiem, P. A. P.; Nitti, F.; Nishiyama, K.; Ogando, F.; O'hira, S.; Oliver, C.; Orsini, F.; Perez, D.; Perez, M.; Pinna, T.; Pisent, A.; Podadera, I.; Porfiri, M.; Pruneri, G.; Queral, V.; Rapisarda, D.; Roman, R.; Shingala, M.; Soldaini, M.; Sugimoto, M.; Theile, J.; Tian, K.; Umeno, H.; Uriot, D.; Wakai, E.; Watanabe, K.; Weber, M.; Yamamoto, M.; Yokomine, T.

2015-08-01

The International Fusion Materials Irradiation Facility (IFMIF), presently in its Engineering Validation and Engineering Design Activities (EVEDA) phase under the frame of the Broader Approach Agreement between Europe and Japan, accomplished in summer 2013, on schedule, its EDA phase with the release of the engineering design report of the IFMIF plant, which is here described. Many improvements of the design from former phases are implemented, particularly a reduction of beam losses and operational costs thanks to the superconducting accelerator concept, the re-location of the quench tank outside the test cell (TC) with a reduction of tritium inventory and a simplification on its replacement in case of failure, the separation of the irradiation modules from the shielding block gaining irradiation flexibility and enhancement of the remote handling equipment reliability and cost reduction, and the water cooling of the liner and biological shielding of the TC, enhancing the efficiency and economy of the related sub-systems. In addition, the maintenance strategy has been modified to allow a shorter yearly stop of the irradiation operations and a more careful management of the irradiated samples. The design of the IFMIF plant is intimately linked with the EVA phase carried out since the entry into force of IFMIF/EVEDA in June 2007. These last activities and their on-going accomplishment have been thoroughly described elsewhere (Knaster J et al [19]), which, combined with the present paper, allows a clear understanding of the maturity of the European-Japanese international efforts. This released IFMIF Intermediate Engineering Design Report (IIEDR), which could be complemented if required concurrently with the outcome of the on-going EVA, will allow decision making on its construction and/or serve as the basis for the definition of the next step, aligned with the evolving needs of our fusion community.

AAAIC '88 - Aerospace Applications of Artificial Intelligence; Proceedings of the Fourth Annual Conference, Dayton, OH, Oct. 25-27, 1988. Volumes 1 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, J.R.; Netrologic, Inc., San Diego, CA)

1988-01-01

Topics presented include integrating neural networks and expert systems, neural networks and signal processing, machine learning, cognition and avionics applications, artificial intelligence and man-machine interface issues, real time expert systems, artificial intelligence, and engineering applications. Also considered are advanced problem solving techniques, combinational optimization for scheduling and resource control, data fusion/sensor fusion, back propagation with momentum, shared weights and recurrency, automatic target recognition, cybernetics, optical neural networks.

Multiple-source spatial data fusion and integration research in the region unified planning management information system

NASA Astrophysics Data System (ADS)

Liu, Zhijun; Zhang, Liangpei; Liu, Zhenmin; Jiao, Hongbo; Chen, Liqun

2008-12-01

In order to manage the internal resources of Gulf of Tonkin and integrate multiple-source spatial data, the establishment of region unified plan management system is needed. The data fusion and the integrated research should be carried on because there are some difficulties in the course of the system's establishment. For example, kinds of planning and the project data format are different, and data criterion is not unified. Besides, the time state property is strong, and spatial reference is inconsistent, etc. In this article the ARCGIS ENGINE is introduced as the developing platform, key technologies are researched, such as multiple-source data transformation and fusion, remote sensing data and DEM fusion and integrated, plan and project data integration, and so on. Practice shows that the system improves the working efficiency of Guangxi Gulf of Tonkin Economic Zone Management Committee significantly and promotes planning construction work of the economic zone remarkably.

Plasma facing materials and components for future fusion devices—development, characterization and performance under fusion specific loading conditions

NASA Astrophysics Data System (ADS)

Linke, J.

2006-04-01

The plasma exposed components in existing and future fusion devices are strongly affected by the plasma material interaction processes. These mechanisms have a strong influence on the plasma performance; in addition they have major impact on the lifetime of the plasma facing armour and the joining interface between the plasma facing material (PFM) and the heat sink. Besides physical and chemical sputtering processes, high heat quasi-stationary fluxes during normal and intense thermal transients are of serious concern for the engineers who develop reliable wall components. In addition, the material and component degradation due to intense fluxes of energetic neutrons is another critical issue in D-T-burning fusion devices which requires extensive R&D. This paper presents an overview on the materials development and joining, the testing of PFMs and components, and the analysis of the neutron irradiation induced degradation.

Realizing "2001: A Space Odyssey": Piloted Spherical Torus Nuclear Fusion Propulsion

NASA Technical Reports Server (NTRS)

Williams, Craig H.; Dudzinski, Leonard A.; Borowski, Stanley K.; Juhasz, Albert J.

2005-01-01

A conceptual vehicle design enabling fast, piloted outer solar system travel was created predicated on a small aspect ratio spherical torus nuclear fusion reactor. The initial requirements were satisfied by the vehicle concept, which could deliver a 172 mt crew payload from Earth to Jupiter rendezvous in 118 days, with an initial mass in low Earth orbit of 1,690 mt. Engineering conceptual design, analysis, and assessment was performed on all major systems including artificial gravity payload, central truss, nuclear fusion reactor, power conversion, magnetic nozzle, fast wave plasma heating, tankage, fuel pellet injector, startup/re-start fission reactor and battery bank, refrigeration, reaction control, communications, mission design, and space operations. Detailed fusion reactor design included analysis of plasma characteristics, power balance/utilization, first wall, toroidal field coils, heat transfer, and neutron/x-ray radiation. Technical comparisons are made between the vehicle concept and the interplanetary spacecraft depicted in the motion picture 2001: A Space Odyssey.

Measles virus fusion machinery activated by sialic acid binding globular domain.

PubMed

Talekar, Aparna; Moscona, Anne; Porotto, Matteo

2013-12-01

Paramyxoviruses, including the human pathogen measles virus (MV) and the avian Newcastle disease virus (NDV), enter host cells through fusion of the viral envelope with the target cell membrane. This fusion is driven by the concerted action of two viral envelope glycoproteins: the receptor binding protein and the fusion protein (F). The MV receptor binding protein (hemagglutinin [H]) attaches to proteinaceous receptors on host cells, while the receptor binding protein of NDV (hemagglutinin-neuraminidase [HN]) interacts with sialic acid-containing receptors. The receptor-bound HN/H triggers F to undergo conformational changes that render it competent to mediate fusion of the viral and cellular membranes. The mechanism of fusion activation has been proposed to be different for sialic acid-binding viruses and proteinaceous receptor-binding viruses. We report that a chimeric protein containing the NDV HN receptor binding region and the MV H stalk domain can activate MV F to fuse, suggesting that the signal to the stalk of a protein-binding receptor binding molecule can be transmitted from a sialic acid binding domain. By engineering the NDV HN globular domain to interact with a proteinaceous receptor, the fusion activation signal was preserved. Our findings are consistent with a unified mechanism of fusion activation, at least for the Paramyxovirinae subfamily, in which the receptor binding domains of the receptor binding proteins are interchangeable and the stalk determines the specificity of F activation.

Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

PubMed Central

Schotten, Sebastiaan; Meijer, Marieke; Walter, Alexander Matthias; Huson, Vincent; Mamer, Lauren; Kalogreades, Lawrence; ter Veer, Mirelle; Ruiter, Marvin; Brose, Nils; Rosenmund, Christian

2015-01-01

The energy required to fuse synaptic vesicles with the plasma membrane (‘activation energy’) is considered a major determinant in synaptic efficacy. From reaction rate theory, we predict that a class of modulations exists, which utilize linear modulation of the energy barrier for fusion to achieve supralinear effects on the fusion rate. To test this prediction experimentally, we developed a method to assess the number of releasable vesicles, rate constants for vesicle priming, unpriming, and fusion, and the activation energy for fusion by fitting a vesicle state model to synaptic responses induced by hypertonic solutions. We show that complexinI/II deficiency or phorbol ester stimulation indeed affects responses to hypertonic solution in a supralinear manner. An additive vs multiplicative relationship between activation energy and fusion rate provides a novel explanation for previously observed non-linear effects of genetic/pharmacological perturbations on synaptic transmission and a novel interpretation of the cooperative nature of Ca2+-dependent release. DOI: http://dx.doi.org/10.7554/eLife.05531.001 PMID:25871846

Pharmacokinetics and safety in rhesus monkeys of a monoclonal antibody-GDNF fusion protein for targeted blood-brain barrier delivery.

PubMed

Pardridge, William M; Boado, Ruben J

2009-10-01

Glial-derived neurotrophic factor (GDNF) is a potential therapy for stroke, Parkinson's disease, or drug addiction. However, GDNF does not cross the blood-brain barrier (BBB). GDNF is re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR), which acts as a molecular Trojan horse to deliver the GDNF across the BBB. The pharmacokinetics (PK), toxicology, and safety pharmacology of the HIRMAb-GDNF fusion protein were investigated in Rhesus monkeys. The fusion protein was administered as an intravenous injection at doses up to 50 mg/kg over a 60 h period to 56 Rhesus monkeys. The plasma concentration of the HIRMAb-GDNF fusion protein was measured with a 2-site sandwich ELISA. No adverse events were observed in a 2-week terminal toxicology study, and no neuropathologic changes were observed. The PK analysis showed a linear relationship between plasma AUC and dose, a large systemic volume of distribution, as well as high clearance rates of 8-10 mL/kg/min. A no-observable-adverse-effect level is established in the Rhesus monkey for the acute administration of the HIRMAb-GDNF fusion protein. The fusion protein targeting the insulin receptor has a PK profile similar to a classical small molecule.

A genetically encoded fluorescent tRNA is active in live-cell protein synthesis

PubMed Central

Masuda, Isao; Igarashi, Takao; Sakaguchi, Reiko; Nitharwal, Ram G.; Takase, Ryuichi; Han, Kyu Young; Leslie, Benjamin J.; Liu, Cuiping; Gamper, Howard; Ha, Taekjip; Sanyal, Suparna

2017-01-01

Abstract Transfer RNAs (tRNAs) perform essential tasks for all living cells. They are major components of the ribosomal machinery for protein synthesis and they also serve in non-ribosomal pathways for regulation and signaling metabolism. We describe the development of a genetically encoded fluorescent tRNA fusion with the potential for imaging in live Escherichia coli cells. This tRNA fusion carries a Spinach aptamer that becomes fluorescent upon binding of a cell-permeable and non-toxic fluorophore. We show that, despite having a structural framework significantly larger than any natural tRNA species, this fusion is a viable probe for monitoring tRNA stability in a cellular quality control mechanism that degrades structurally damaged tRNA. Importantly, this fusion is active in E. coli live-cell protein synthesis allowing peptidyl transfer at a rate sufficient to support cell growth, indicating that it is accommodated by translating ribosomes. Imaging analysis shows that this fusion and ribosomes are both excluded from the nucleoid, indicating that the fusion and ribosomes are in the cytosol together possibly engaged in protein synthesis. This fusion methodology has the potential for developing new tools for live-cell imaging of tRNA with the unique advantage of both stoichiometric labeling and broader application to all cells amenable to genetic engineering. PMID:27956502

Modeling for free surface flow with phase change and its application to fusion technology

NASA Astrophysics Data System (ADS)

Luo, Xiaoyong

The development of predictive capabilities for free surface flow with phase change is essential to evaluate liquid wall protection schemes for various fusion chambers. With inertial fusion energy (IFE) concepts such as HYLIFE-II, rapid condensation into cold liquid surfaces is required when using liquid curtains for protecting reactor walls from blasts and intense neutron radiation. With magnetic fusion energy (MFE) concepts, droplets are injected onto the free surface of the liquid to minimize evaporation by minimizing the surface temperature. This dissertation presents a numerical methodology for free surface flow with phase change to help resolve feasibility issues encountered in the aforementioned fusion engineering fields, especially spray droplet condensation efficiency in IFE and droplet heat transfer enhancement on free surface liquid divertors in MFE. The numerical methodology is being conducted within the framework of the incompressible flow with the phase change model. A new second-order projection method is presented in conjunction with Approximate-Factorization techniques (AF method) for incompressible Navier-Stokes equations. A sub-cell conception is introduced and the Ghost Fluid Method in extended in a modified mass transfer model to accurately calculate the mass transfer across the interface. The Crank-Nicholson method is used for the diffusion term to eliminate the numerical viscous stability restriction. The third-order ENO scheme is used for the convective term to guarantee the accuracy of the method. The level set method is used to capture accurately the free surface of the flow and the deformation of the droplets. This numerical investigation identifies the physics characterizing transient heat and mass transfer of the droplet and the free surface flow. The results show that the numerical methodology is quite successful in modeling the free surface with phase change even though some severe deformations such as breaking and merging occur. The versatility of the numerical methodology shows that the work can easily handle complex physical conditions that occur in the fusion science and engineering.

A novel protocol for the production of recombinant LL-37 expressed as a thioredoxin fusion protein.

PubMed

Li, Yifeng

2012-02-01

LL-37 is the only cathelicidin-derived antimicrobial peptide found in humans and it has a multifunctional role in host defense. The peptide has been shown to possess immunomodulatory functions in addition to antimicrobial activity. To provide sufficient material for biological and structural characterization of this important peptide, various systems were developed to produce recombinant LL-37 in Escherichia coli. In one previous approach, LL-37 coding sequence was cloned into vector pET-32a, allowing the peptide to be expressed as a thioredoxin fusion. The fusion protein contains two thrombin cleavage sites: a vector-encoded one that is 30-residue upstream of the insert and an engineered one that is immediately adjacent to LL-37. Cleavage at these two sites shall generate three fragments, one of which is the target peptide. However, when the fusion protein was treated with thrombin, cleavage only occurred at the remote upstream site. A plausible explanation is that the thrombin site adjacent to LL-37 is less accessible due to the peptide's aggregation tendency and cleavage at the remote site generates a fragment, which forms a large aggregate that buries the intended site. In this study, I deleted the vector-encoded thrombin site and S tag in pET-32a, and then inserted the coding sequence for LL-37 plus a thrombin site into the modified vector. Although removing the S tag did not change the oligomeric state of the fusion protein, deletion of the vector-encoded thrombin site allowed the fusion to be cleaved at the engineered site to release LL-37. The released peptide was separated from the carrier and cleavage enzyme by size-exclusion chromatography. This new approach enables a quick production of high quality active LL-37 with a decent amount. Copyright © 2011 Elsevier Inc. All rights reserved.

Z-Pinch fusion-based nuclear propulsion

NASA Astrophysics Data System (ADS)

Miernik, J.; Statham, G.; Fabisinski, L.; Maples, C. D.; Adams, R.; Polsgrove, T.; Fincher, S.; Cassibry, J.; Cortez, R.; Turner, M.; Percy, T.

2013-02-01

Fusion-based nuclear propulsion has the potential to enable fast interplanetary transportation. Due to the great distances between the planets of our solar system and the harmful radiation environment of interplanetary space, high specific impulse (Isp) propulsion in vehicles with high payload mass fractions must be developed to provide practical and safe vehicles for human space flight missions. The Z-Pinch dense plasma focus method is a Magneto-Inertial Fusion (MIF) approach that may potentially lead to a small, low cost fusion reactor/engine assembly [1]. Recent advancements in experimental and theoretical understanding of this concept suggest favorable scaling of fusion power output yield [2]. The magnetic field resulting from the large current compresses the plasma to fusion conditions, and this process can be pulsed over short timescales (10-6 s). This type of plasma formation is widely used in the field of Nuclear Weapons Effects testing in the defense industry, as well as in fusion energy research. A Z-Pinch propulsion concept was designed for a vehicle based on a previous fusion vehicle study called "Human Outer Planet Exploration" (HOPE), which used Magnetized Target Fusion (MTF) [3] propulsion. The reference mission is the transport of crew and cargo to Mars and back, with a reusable vehicle. The analysis of the Z-Pinch MIF propulsion system concludes that a 40-fold increase of Isp over chemical propulsion is predicted. An Isp of 19,436 s and thrust of 3812 N s/pulse, along with nearly doubling the predicted payload mass fraction, warrants further development of enabling technologies.

A stabilized headless measles virus attachment protein stalk efficiently triggers membrane fusion.

PubMed

Brindley, Melinda A; Suter, Rolf; Schestak, Isabel; Kiss, Gabriella; Wright, Elizabeth R; Plemper, Richard K

2013-11-01

Paramyxovirus attachment and fusion (F) envelope glycoprotein complexes mediate membrane fusion required for viral entry. The measles virus (MeV) attachment (H) protein stalk domain is thought to directly engage F for fusion promotion. However, past attempts to generate truncated, fusion-triggering-competent H-stem constructs remained fruitless. In this study, we addressed the problem by testing the hypothesis that truncated MeV H stalks may require stabilizing oligomerization tags to maintain intracellular transport competence and F-triggering activity. We engineered H-stems of different lengths with added 4-helix bundle tetramerization domains and demonstrate restored cell surface expression, efficient interaction with F, and fusion promotion activity of these constructs. The stability of the 4-helix bundle tags and the relative orientations of the helical wheels of H-stems and oligomerization tags govern the kinetics of fusion promotion, revealing a balance between H stalk conformational stability and F-triggering activity. Recombinant MeV particles expressing a bioactive H-stem construct in the place of full-length H are viable, albeit severely growth impaired. Overall, we demonstrate that the MeV H stalk represents the effector domain for MeV F triggering. Fusion promotion appears linked to the conformational flexibility of the stalk, which must be tightly regulated in viral particles to ensure efficient virus entry. While the pathways toward assembly of functional fusion complexes may differ among diverse members of the paramyxovirus family, central elements of the triggering machinery emerge as highly conserved.

Correlative Microscopy Combining Secondary Ion Mass Spectrometry and Electron Microscopy: Comparison of Intensity-Hue-Saturation and Laplacian Pyramid Methods for Image Fusion.

PubMed

Vollnhals, Florian; Audinot, Jean-Nicolas; Wirtz, Tom; Mercier-Bonin, Muriel; Fourquaux, Isabelle; Schroeppel, Birgit; Kraushaar, Udo; Lev-Ram, Varda; Ellisman, Mark H; Eswara, Santhana

2017-10-17

Correlative microscopy combining various imaging modalities offers powerful insights into obtaining a comprehensive understanding of physical, chemical, and biological phenomena. In this article, we investigate two approaches for image fusion in the context of combining the inherently lower-resolution chemical images obtained using secondary ion mass spectrometry (SIMS) with the high-resolution ultrastructural images obtained using electron microscopy (EM). We evaluate the image fusion methods with three different case studies selected to broadly represent the typical samples in life science research: (i) histology (unlabeled tissue), (ii) nanotoxicology, and (iii) metabolism (isotopically labeled tissue). We show that the intensity-hue-saturation fusion method often applied for EM-sharpening can result in serious image artifacts, especially in cases where different contrast mechanisms interplay. Here, we introduce and demonstrate Laplacian pyramid fusion as a powerful and more robust alternative method for image fusion. Both physical and technical aspects of correlative image overlay and image fusion specific to SIMS-based correlative microscopy are discussed in detail alongside the advantages, limitations, and the potential artifacts. Quantitative metrics to evaluate the results of image fusion are also discussed.

Weibull-Based Design Methodology for Rotating Aircraft Engine Structures

NASA Technical Reports Server (NTRS)

Zaretsky, Erwin; Hendricks, Robert C.; Soditus, Sherry

2002-01-01

The NASA Energy Efficient Engine (E(sup 3)-Engine) is used as the basis of a Weibull-based life and reliability analysis. Each component's life and thus the engine's life is defined by high-cycle fatigue (HCF) or low-cycle fatigue (LCF). Knowing the cumulative life distribution of each of the components making up the engine as represented by a Weibull slope is a prerequisite to predicting the life and reliability of the entire engine. As the engine Weibull slope increases, the predicted lives decrease. The predicted engine lives L(sub 5) (95 % probability of survival) of approximately 17,000 and 32,000 hr do correlate with current engine maintenance practices without and with refurbishment. respectively. The individual high pressure turbine (HPT) blade lives necessary to obtain a blade system life L(sub 0.1) (99.9 % probability of survival) of 9000 hr for Weibull slopes of 3, 6 and 9, are 47,391 and 20,652 and 15,658 hr, respectively. For a design life of the HPT disks having probable points of failure equal to or greater than 36,000 hr at a probability of survival of 99.9 %, the predicted disk system life L(sub 0.1) can vary from 9,408 to 24,911 hr.

Randomized Controlled Trial of Minimally Invasive Sacroiliac Joint Fusion Using Triangular Titanium Implants vs Nonsurgical Management for Sacroiliac Joint Dysfunction: 12-Month Outcomes

PubMed Central

Polly, David W.; Wine, Kathryn D.; Whang, Peter G.; Frank, Clay J.; Harvey, Charles F.; Lockstadt, Harry; Glaser, John A.; Limoni, Robert P.; Sembrano, Jonathan N.

2015-01-01

BACKGROUND: Sacroiliac joint (SIJ) dysfunction is a prevalent cause of chronic, unremitting lower back pain. OBJECTIVE: To concurrently compare outcomes after surgical and nonsurgical treatment for chronic SIJ dysfunction. METHODS: A total of 148 subjects with SIJ dysfunction were randomly assigned to minimally invasive SIJ fusion with triangular titanium implants (n = 102) or nonsurgical management (n = 46). Pain, disability, and quality-of-life scores were collected at baseline and at 1, 3, 6, and 12 months. Success rates were compared using Bayesian methods. Crossover from nonsurgical to surgical care was allowed after the 6-month study visit was complete. RESULTS: Six-month success rates were higher in the surgical group (81.4% vs 26.1%; posterior probability of superiority > 0.9999). Clinically important (≥ 15 point) Oswestry Disability Index improvement at 6 months occurred in 73.3% of the SIJ fusion group vs 13.6% of the nonsurgical management group (P < .001). At 12 months, improvements in SIJ pain and Oswestry Disability Index were sustained in the surgical group. Subjects who crossed over had improvements in pain, disability, and quality of life similar to those in the original surgical group. Adverse events were slightly more common in the surgical group (1.3 vs 1.1 events per subject; P = .31). CONCLUSION: This Level 1 study showed that minimally invasive SIJ fusion using triangular titanium implants was more effective than nonsurgical management at 1 year in relieving pain, improving function, and improving quality of life in patients with SIJ dysfunction caused by degenerative sacroiliitis or SIJ disruptions. Pain, disability, and quality of life also improved after crossover from nonsurgical to surgical treatment. ABBREVIATIONS: EQ-5D, EuroQoL-5D INSITE, Investigation of Sacroiliac Fusion Treatment MCS, mental component summary NSM, nonsurgical management ODI, Oswestry Disability Index PCS, physical component summary RFA, radiofrequency ablation SF-36, Short Form-36 SIJ, sacroiliac joint TTO, time trade-off VAS, visual analog scale PMID:26291338

A general approach for chemical labeling and rapid, spatially controlled protein inactivation

PubMed Central

Marks, Kevin M.; Braun, Patrick D.; Nolan, Garry P.

2004-01-01

Chemical labeling of proteins inside of living cells can enable studies of the location, movement, and function of proteins in vivo. Here we demonstrate an approach for chemical labeling of proteins that uses the high-affinity interaction between an FKBP12 mutant (F36V) and a synthetic, engineered ligand (SLF′). A fluorescein conjugate to the engineered ligand (FL-SLF′) retained binding to FKBP12(F36V) and possessed similar fluorescence properties as parental fluorescein. FL-SLF′ labeled FKBP12(F36V) fusion proteins in live mammalian cells, and was used to monitor the subcellular localization of a membrane targeted FKBP12(F36V) construct. Chemical labeling of FKBP12(F36V) fusion proteins with FL-SLF′ was readily detectable at low expression levels of the FKBP12(F36V) fusion, and the level of fluorescent staining with FL-SLF′ was proportional to the FKBP12(F36V) expression level. This FL-SLF′-FKBP12(F36V) labeling technique was tested in fluorophore assisted laser inactivation (FALI), a light-mediated technique to rapidly inactivate fluorophore-labeled target proteins. FL-SLF′ mediated FALI of a β-galactosidase-FKBP12(F36V) fusion protein, causing rapid inactivation of >90% of enzyme activity upon irradiation in vitro. FL-SLF′ also mediated FALI of a β-galactosidase fusion expressed in living NIH 3T3 cells, where β-galactosidase activity was reduced in 15 s. Thus, FL-SLF′ can be used to monitor proteins in vivo and to target rapid, spatially and temporally defined inactivation of target proteins in living cells in a process that we call FK-FALI. PMID:15218100

Establishment of a canine model of human type 2 diabetes mellitus by overexpressing phosphoenolypyruvate carboxykinase.

PubMed

Jeong, Yeon Woo; Lee, Geun-Shik; Kim, Joung Joo; Park, Sun Woo; Ko, Kyeong Hee; Kang, Mina; Kim, Yu Kyung; Jung, Eui-Man; Hyun, Sang Hwan; Shin, Taeyoung; Jeung, Eui-Bae; Hwang, Woo Suk

2012-08-01

Dogs are useful models for studying human metabolic diseases such as type 2 diabetes mellitus due to similarities in physiology, anatomy and life styles with humans. Somatic cell nuclear transfer (SCNT) facilitates the production of transgenic dogs. In this study, we generated transgenic dogs expressing the phosphoenolpyruvate carboxykinase (PEPCK) gene, which is closely involved in the pathogenesis of type 2 diabetes mellitus. In addition, we assessed the cloning efficiency associated with adult or fetal (cloned or natural mating) fibroblasts as a nuclear source. Cloning efficiency was determined by the fusion, pregnancy and cloning rates. The fusion rates were significantly high for fibroblasts from cloned fetuses, but the pregnancy and cloning rates were relatively high for cells from normal fetuses. Based on these data, fetal fibroblasts were selected as the nuclear donor for SCNT and genetically engineered to overexpress the PEPCK gene and dual selection marker genes controlled by the PEPCK promoter. The transgenic cells were introduced into oocytes and transferred into five recipient dogs, resulting in two pregnancies. Finally, three puppies were born and confirmed by microsatellite analysis to be genetically identical to the donor. One puppy successfully overexpressed PEPCK mRNA and protein in the liver. This canine disease model may be useful for studying the pathogenesis and/or therapeutic targets of type 2 diabetes mellitus.

Accumulation and processing of a recombinant protein designed as a cleavable fusion to the endogenous Rubisco LSU protein in Chlamydomonas chloroplast

PubMed Central

Muto, Machiko; Henry, Ryan E; Mayfield, Stephen P

2009-01-01

Background Expression of recombinant proteins in green algal chloroplast holds substantial promise as a platform for the production of human therapeutic proteins. A number of proteins have been expressed in the chloroplast of Chlamydomonas reinhardtii, including complex mammalian proteins, but many of these proteins accumulate to significantly lower levels than do endogenous chloroplast proteins. We examined if recombinant protein accumulation could be enhanced by genetically fusing the recombinant reporter protein, luciferase, to the carboxy-terminal end of an abundant endogenous protein, the large subunit of ribulose bisphosphate carboxylase (Rubisco LSU). Additionally, as recombinant proteins fused to endogenous proteins are of little clinical or commercial value, we explored the possibility of engineering our recombinant protein to be cleavable from the endogenous protein in vivo. This strategy would obviate the need for further in vitro processing steps in order to produce the desired recombinant protein. To achieve this, a native protein-processing site from preferredoxin (preFd) was placed between the Rubisco LSU and luciferase coding regions in the fusion protein construct. Results The luciferase from the fusion protein accumulated to significantly higher levels than luciferase expressed alone. By eliminating the endogenous Rubisco large subunit gene (rbcL), we achieved a further increase in luciferase accumulation with respect to luciferase expression in the WT background. Importantly, near-wild type levels of functional Rubisco holoenzyme were generated following the proteolytic removal of the fused luciferase, while luciferase activity for the fusion protein was almost ~33 times greater than luciferase expressed alone. These data demonstrate the utility of using fusion proteins to enhance recombinant protein accumulation in algal chloroplasts, and also show that engineered proteolytic processing sites can be used to liberate the exogenous protein from the endogenous fusion partner, allowing for the purification of the intended mature protein. Conclusion These results demonstrate the utility of fusion proteins in algal chloroplast as a method to increase accumulation of recombinant proteins that are difficult to express. Since Rubisco is ubiquitous to land plants and green algae, this strategy may also be applied to higher plant transgenic expression systems. PMID:19323825

[Prokaryotic expression of trigeminy artificial fusion gene of Leptospira interrogans and the immunogenicity of its products].

PubMed

Luo, Dong-jiao; Qiu, Xiao-feng; Wang, Jiang; Yan, Jin; Wang, Hai-bin; Zhou, Jin-cheng; Yan, Jie

2008-11-01

To construct lipL32/1-lipL21-OmpL1/2 fusion gene of Leptospira interrogans and its prokaryotic expression system, and to identify the immunogenicity of its products. PCR using linking primers was applied to construct lipL32/1-lipL21-OmpL1/2 fusion gene and a prokaryotic expression system of the fusion gene was then established using routine genetic engineering technique. SDS-PAGE was used to examine output of the target recombinant protein rLipL32/1-LipL21-OmpL1/2. Double immunodiffusion and Western Blot assay were applied to identify immunogenicity of rLipL32/1-LipL21-OmpL1/2. lipL32/1-lipL21-OmpL1/2 fusion gene with correct sequence and its prokaryotic expression system E.coli BL21DE3pET42a-lipL32/1-lipL21-ompL1/2 was obtained in this study. The output of rLipL32/1-LipL21- OmpL1/2 after optimisation was 37.78 mg/L. The immunodiffusion titer of rabbit antiserum against rLipL32/1-LipL21-OmpL1/2 was 1:4. The rLipL32/1-LipL21-OmpL1/2 antiserum was able to recognize rLipL32/1-LipL21-OmpL1/2, rLipL32/1, rLipL21 and rOmpL1/2. Positive Western hybridization signals were found among rLipL32/1-LipL21-OmpL1/2 and rabbit antiserum against whole cell of strain 56601 and serum from patients infected with L.interrogans serogroups Icterohaemorrhagiae, Grippotyphosa, Autumnalis and Pomona. The fusion gene lipL32/1-lipL21-OmpL1/2 and its prokaryotic expression system were successfully constructed in this study. The expressed fusion protein can be used as the antigen for developing universal genetic engineering vaccine and universal serological tests of leptospirosis.

NRG1-Fc improves metabolic health via dual hepatic and central action.

PubMed

Zhang, Peng; Kuang, Henry; He, Yanlin; Idiga, Sharon O; Li, Siming; Chen, Zhimin; Yang, Zhao; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J; Xu, Yong; Lin, Jiandie D

2018-03-08

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat-enriched secreted factor NRG4 protects mice from high-fat diet-induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake.

NRG1-Fc improves metabolic health via dual hepatic and central action

PubMed Central

Kuang, Henry; Idiga, Sharon O.; Li, Siming; Chen, Zhimin; Cai, Xing; Zhang, Kezhong; Potthoff, Matthew J.; Xu, Yong; Lin, Jiandie D.

2018-01-01

Neuregulins (NRGs) are emerging as an important family of signaling ligands that regulate glucose and lipid homeostasis. NRG1 lowers blood glucose levels in obese mice, whereas the brown fat–enriched secreted factor NRG4 protects mice from high-fat diet–induced insulin resistance and hepatic steatosis. However, the therapeutic potential of NRGs remains elusive, given the poor plasma half-life of the native ligands. Here, we engineered a fusion protein using human NRG1 and the Fc domain of human IgG1 (NRG1-Fc) that exhibited extended half-life in circulation and improved potency in receptor signaling. We evaluated its efficacy in improving metabolic parameters and dissected the mechanisms of action. NRG1-Fc treatment triggered potent AKT activation in the liver, lowered blood glucose, improved insulin sensitivity, and suppressed food intake in obese mice. NRG1-Fc acted as a potent secretagogue for the metabolic hormone FGF21; however, the latter was largely dispensable for its metabolic effects. NRG1-Fc directly targeted the hypothalamic POMC neurons to promote membrane depolarization and increase firing rate. Together, NRG1-Fc exhibits improved pharmacokinetic properties and exerts metabolic benefits through dual inhibition of hepatic gluconeogenesis and caloric intake. PMID:29515030

High-Speed Photography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paisley, D.L.; Schelev, M.Y.

1998-08-01

The applications of high-speed photography to a diverse set of subjects including inertial confinement fusion, laser surgical procedures, communications, automotive airbags, lightning etc. are briefly discussed. (AIP) {copyright} {ital 1998 Society of Photo-Optical Instrumentation Engineers.}

Adaptation of Decoy Fusion Strategy for Existing Multi-Stage Search Workflows

NASA Astrophysics Data System (ADS)

Ivanov, Mark V.; Levitsky, Lev I.; Gorshkov, Mikhail V.

2016-09-01

A number of proteomic database search engines implement multi-stage strategies aiming at increasing the sensitivity of proteome analysis. These approaches often employ a subset of the original database for the secondary stage of analysis. However, if target-decoy approach (TDA) is used for false discovery rate (FDR) estimation, the multi-stage strategies may violate the underlying assumption of TDA that false matches are distributed uniformly across the target and decoy databases. This violation occurs if the numbers of target and decoy proteins selected for the second search are not equal. Here, we propose a method of decoy database generation based on the previously reported decoy fusion strategy. This method allows unbiased TDA-based FDR estimation in multi-stage searches and can be easily integrated into existing workflows utilizing popular search engines and post-search algorithms.

Tracking and Control of Gas Turbine Engine Component Damage/Life

NASA Technical Reports Server (NTRS)

Jaw, Link C.; Wu, Dong N.; Bryg, David J.

2003-01-01

This paper describes damage mechanisms and the methods of controlling damages to extend the on-wing life of critical gas turbine engine components. Particularly, two types of damage mechanisms are discussed: creep/rupture and thermo-mechanical fatigue. To control these damages and extend the life of engine hot-section components, we have investigated two methodologies to be implemented as additional control logic for the on-board electronic control unit. This new logic, the life-extending control (LEC), interacts with the engine control and monitoring unit and modifies the fuel flow to reduce component damages in a flight mission. The LEC methodologies were demonstrated in a real-time, hardware-in-the-loop simulation. The results show that LEC is not only a new paradigm for engine control design, but also a promising technology for extending the service life of engine components, hence reducing the life cycle cost of the engine.

Fusion energy for space: Feasibility demonstration. A proposal to NASA

NASA Technical Reports Server (NTRS)

Schulze, Norman R.

1992-01-01

This proposed program is to initiate a space flight research and development program to develop fusion energy for the space applications of direct space propulsion and direct space power, that is, a Space Fusion Energy (SFE) program. 'Direct propulsion' refers to the use of plasma energy directly for thrust without requiring other energy conversion systems. Further, to provide space missions with large electrical power, 'direct space power' is proposed whereby the direct conversion of charged particles into electricity is used, thereby avoiding thermal conversion system losses. The energy release from nuclear fusion reactions makes these highly efficient, high power space systems possible. The program as presented conducts in an orderly, hierarchical manner the necessary planning, analyses, and testing to demonstrate the practical use of fusion energy for space. There is nothing discussed that is known to be theoretically impossible. Validation of the engineering principles is sought in this program which uses a cost-benefit approach. Upon successful program completion, space will become more accessible and space missions more safely conducted. The country will have taken a giant step toward the commercialization of space. The mission enabling capability provided by fusion energy is well beyond mission planners' current dreams.

A Testbed for Data Fusion for Engine Diagnostics and Prognostics1

DTIC Science & Technology

2002-03-01

detected ; too late to be useful for prognostics development. Table 1. Table of acronyms ACRONYM MEANING AD Anomaly detector...strictly defined points. Determining where we are on the engine health curve is the first step in prognostics . Fault detection / diagnostic reasoning... Detection As described above the ability of the monitoring system to detect an anomaly is especially important for knowledge-based systems, i.e.,

Yeast Surface Display Approaches for Engineering Stabilized Viral Fusion Protein Subunit Vaccines

DTIC Science & Technology

This research proposal focuses on the development of a novel library screening approach to engineering highly stabilized subunit vaccine candidates...for major pathogens within the paramyxovirus family. The research addresses the PRMRP topic areas related to vaccine development for infectious...proposal focuses on four viruses that fall into two subclasses within the broader family, respiratory syncytial virus (RSV), human metapneumovirus (HMPV

A Computer Code for Gas Turbine Engine Weight And Disk Life Estimation

NASA Technical Reports Server (NTRS)

Tong, Michael T.; Ghosn, Louis J.; Halliwell, Ian; Wickenheiser, Tim (Technical Monitor)

2002-01-01

Reliable engine-weight estimation at the conceptual design stage is critical to the development of new aircraft engines. It helps to identify the best engine concept amongst several candidates. In this paper, the major enhancements to NASA's engine-weight estimate computer code (WATE) are described. These enhancements include the incorporation of improved weight-calculation routines for the compressor and turbine disks using the finite-difference technique. Furthermore, the stress distribution for various disk geometries was also incorporated, for a life-prediction module to calculate disk life. A material database, consisting of the material data of most of the commonly-used aerospace materials, has also been incorporated into WATE. Collectively, these enhancements provide a more realistic and systematic way to calculate the engine weight. They also provide additional insight into the design trade-off between engine life and engine weight. To demonstrate the new capabilities, the enhanced WATE code is used to perform an engine weight/life trade-off assessment on a production aircraft engine.

Identification of novel target sites and an inhibitor of the dengue virus E protein.

PubMed

Yennamalli, Ragothaman; Subbarao, Naidu; Kampmann, Thorsten; McGeary, Ross P; Young, Paul R; Kobe, Bostjan

2009-06-01

Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus life cycle. In this study, we analyzed the pre-fusion and post-fusion structures of the dengue virus E protein to identify potential novel sites that could bind small molecules, which could interfere with the conformational transitions that mediate the fusion process. We used an in silico virtual screening approach combining three different docking algorithms (DOCK, GOLD and FlexX) to identify compounds that are likely to bind to these sites. Seven structurally diverse molecules were selected to test experimentally for inhibition of dengue virus propagation. The best compound showed an IC(50) in the micromolar range against dengue virus type 2.

Identification of novel target sites and an inhibitor of the dengue virus E protein

NASA Astrophysics Data System (ADS)

Yennamalli, Ragothaman; Subbarao, Naidu; Kampmann, Thorsten; McGeary, Ross P.; Young, Paul R.; Kobe, Bostjan

2009-06-01

Dengue and related flaviviruses represent a significant global health threat. The envelope glycoprotein E mediates virus attachment to a host cell and the subsequent fusion of viral and host cell membranes. The fusion process is driven by conformational changes in the E protein and is an essential step in the virus life cycle. In this study, we analyzed the pre-fusion and post-fusion structures of the dengue virus E protein to identify potential novel sites that could bind small molecules, which could interfere with the conformational transitions that mediate the fusion process. We used an in silico virtual screening approach combining three different docking algorithms (DOCK, GOLD and FlexX) to identify compounds that are likely to bind to these sites. Seven structurally diverse molecules were selected to test experimentally for inhibition of dengue virus propagation. The best compound showed an IC50 in the micromolar range against dengue virus type 2.

From Data Acquisition to Data Fusion: A Comprehensive Review and a Roadmap for the Identification of Activities of Daily Living Using Mobile Devices

PubMed Central

Pires, Ivan Miguel; Garcia, Nuno M.; Pombo, Nuno; Flórez-Revuelta, Francisco

2016-01-01

This paper focuses on the research on the state of the art for sensor fusion techniques, applied to the sensors embedded in mobile devices, as a means to help identify the mobile device user’s daily activities. Sensor data fusion techniques are used to consolidate the data collected from several sensors, increasing the reliability of the algorithms for the identification of the different activities. However, mobile devices have several constraints, e.g., low memory, low battery life and low processing power, and some data fusion techniques are not suited to this scenario. The main purpose of this paper is to present an overview of the state of the art to identify examples of sensor data fusion techniques that can be applied to the sensors available in mobile devices aiming to identify activities of daily living (ADLs). PMID:26848664

The role of syncytins in human reproduction and reproductive organ cancers.

PubMed

Soygur, Bikem; Sati, Leyla

2016-11-01

Human life begins with sperm and oocyte fusion. After fertilization, various fusion events occur during human embryogenesis and morphogenesis. For example, the fusion of trophoblastic cells constitutes a key process for normal placental development. Fusion in the placenta is facilitated by syncytin 1 and syncytin 2. These syncytins arose from retroviral sequences that entered the primate genome 25 million and more than 40 million years ago respectively. About 8% of the human genome consists of similar human endogenous retroviral (HERVs) sequences. Many are inactive because of mutations or deletions. However, the role of the few that remain transcriptionally active has not been fully elucidated. Syncytin proteins maintain cell-cell fusogenic activity based on ENV: gene-mediated viral cell entry. In this review, we summarize how syncytins and their receptors are involved in fusion events during human reproduction. The significance of syncytins in tumorigenesis is also discussed. © 2016 Society for Reproduction and Fertility.

Accelerators for Fusion Materials Testing

NASA Astrophysics Data System (ADS)

Knaster, Juan; Okumura, Yoshikazu

Fusion materials research is a worldwide endeavor as old as the parallel one working toward the long term stable confinement of ignited plasma. In a fusion reactor, the preservation of the required minimum thermomechanical properties of the in-vessel components exposed to the severe irradiation and heat flux conditions is an indispensable factor for safe operation; it is also an essential goal for the economic viability of fusion. Energy from fusion power will be extracted from the 14 MeV neutron freed as a product of the deuterium-tritium fusion reactions; thus, this kinetic energy must be absorbed and efficiently evacuated and electricity eventually generated by the conventional methods of a thermal power plant. Worldwide technological efforts to understand the degradation of materials exposed to 14 MeV neutron fluxes >1018 m-2s-1, as expected in future fusion power plants, have been intense over the last four decades. Existing neutron sources can reach suitable dpa (“displacement-per-atom”, the figure of merit to assess materials degradation from being exposed to neutron irradiation), but the differences in the neutron spectrum of fission reactors and spallation sources do not allow one to unravel the physics and to anticipate the degradation of materials exposed to fusion neutrons. Fusion irradiation conditions can be achieved through Li (d, xn) nuclear reactions with suitable deuteron beam current and energy, and an adequate flowing lithium screen. This idea triggered in the late 1970s at Los Alamos National Laboratory (LANL) a campaign working toward the feasibility of continuous wave (CW) high current linacs framed by the Fusion Materials Irradiation Test (FMIT) project. These efforts continued with the Low Energy Demonstrating Accelerator (LEDA) (a validating prototype of the canceled Accelerator Production of Tritium (APT) project), which was proposed in 2002 to the fusion community as a 6.7MeV, 100mA CW beam injector for a Li (d, xn) source to bridge with the International Fusion Materials Irradiation Facility (IFMIF) under discussion at the time. Worldwide technological efforts are maturing soundly and the time for a fusion-relevant neutron source has arrived according to world fusion roadmaps; if decisions are taken we could count the next decade with a powerful source of 14 MeV neutrons thanks to the expected significant results of the Engineering Validation and Engineering Design Activity (EVEDA) phase of the IFMIF project. The accelerator know-how has matured in all possible aspects since the times of FMIT conception in the 1970s; today, operating 125 mA deuteron beam at 40 MeV in CW with high availabilities seems feasible thanks to the understanding of the beam halo physics and the three main technological breakthroughs in accelerator technology: (1) the ECR ion source for light ions developed at Chalk River Laboratories in the early 1990s, (2) the RFQ operation of H+ in CW with 100 mA demonstrated by LEDA in LANL in the late 1990s, and (3) the growing maturity of superconducting resonators for light hadrons and low β beams achieved in recent years.

Accelerators for Fusion Materials Testing

NASA Astrophysics Data System (ADS)

Knaster, Juan; Okumura, Yoshikazu

Fusion materials research is a worldwide endeavor as old as the parallel one working toward the long term stable confinement of ignited plasma. In a fusion reactor, the preservation of the required minimum thermomechanical properties of the in-vessel components exposed to the severe irradiation and heat flux conditions is an indispensable factor for safe operation; it is also an essential goal for the economic viability of fusion. Energy from fusion power will be extracted from the 14 MeV neutron freed as a product of the deuterium-tritium fusion reactions; thus, this kinetic energy must be absorbed and efficiently evacuated and electricity eventually generated by the conventional methods of a thermal power plant. Worldwide technological efforts to understand the degradation of materials exposed to 14 MeV neutron fluxes > 1018 m-2s-1, as expected in future fusion power plants, have been intense over the last four decades. Existing neutron sources can reach suitable dpa ("displacement-per-atom", the figure of merit to assess materials degradation from being exposed to neutron irradiation), but the differences in the neutron spectrum of fission reactors and spallation sources do not allow one to unravel the physics and to anticipate the degradation of materials exposed to fusion neutrons. Fusion irradiation conditions can be achieved through Li (d, xn) nuclear reactions with suitable deuteron beam current and energy, and an adequate flowing lithium screen. This idea triggered in the late 1970s at Los Alamos National Laboratory (LANL) a campaign working toward the feasibility of continuous wave (CW) high current linacs framed by the Fusion Materials Irradiation Test (FMIT) project. These efforts continued with the Low Energy Demonstrating Accelerator (LEDA) (a validating prototype of the canceled Accelerator Production of Tritium (APT) project), which was proposed in 2002 to the fusion community as a 6.7MeV, 100mA CW beam injector for a Li (d, xn) source to bridge with the International Fusion Materials Irradiation Facility (IFMIF) under discussion at the time. Worldwide technological efforts are maturing soundly and the time for a fusion-relevant neutron source has arrived according to world fusion roadmaps; if decisions are taken we could count the next decade with a powerful source of 14 MeV neutrons thanks to the expected significant results of the Engineering Validation and Engineering Design Activity (EVEDA) phase of the IFMIF project. The accelerator know-how has matured in all possible aspects since the times of FMIT conception in the 1970s; today, operating 125 mA deuteron beam at 40 MeV in CW with high availabilities seems feasible thanks to the understanding of the beam halo physics and the three main technological breakthroughs in accelerator technology: (1) the ECR ion source for light ions developed at Chalk River Laboratories in the early 1990s, (2) the RFQ operation of H+ in CW with 100 mA demonstrated by LEDA in LANL in the late 1990s, and (3) the growing maturity of superconducting resonators for light hadrons and low β beams achieved in recent years.

Pharmacokinetics and brain uptake of an IgG-TNF decoy receptor fusion protein following intravenous, intraperitoneal, and subcutaneous administration in mice.

PubMed

Sumbria, Rachita K; Zhou, Qing-Hui; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Boado, Ruben J; Pardridge, William M

2013-04-01

Tumor necrosis factor (TNF)-α is a proinflammatory cytokine active in the brain. Etanercept, the TNF decoy receptor (TNFR), does not cross the blood-brain barrier (BBB). The TNFR was re-engineered for BBB penetration as a fusion protein with a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), and this fusion protein is designated cTfRMAb-TNFR. The cTfRMAb domain of the fusion protein acts as a molecular Trojan horse and mediates transport via the endogenous BBB TfR. To support future chronic treatment of mouse models of neural disease with daily administration of the cTfRMAb-TNFR fusion protein, a series of pharmacokinetics and brain uptake studies in the mouse was performed. The cTfRMAb-TNFR fusion protein was radiolabeled and injected into mice via the intravenous, intraperitoneal (IP), or subcutaneous (SQ) routes of administration at doses ranging from 0.35 to 10 mg/kg. The distribution of the fusion protein into plasma following the IP or SQ routes was enhanced by increasing the injection dose from 3 to 10 mg/kg. The fusion protein demonstrated long circulation times with high metabolic stability following the IP or SQ routes of injection. The IP or SQ routes produced concentrations of the cTfRMAb-TNFR fusion protein in the brain that exceed by 20- to 50-fold the concentration of TNFα in pathologic conditions of the brain. The SQ injection is the preferred route of administration, as the level of cTfRMAb fusion protein produced in the brain is comparable to that generated with intravenous injection, and at a much lower plasma area under the concentration curve of the fusion protein as compared to IP administration.

Antigen Binding and Site-Directed Labeling of Biosilica-Immobilized Fusion Proteins Expressed in Diatoms.

PubMed

Ford, Nicole R; Hecht, Karen A; Hu, DeHong; Orr, Galya; Xiong, Yijia; Squier, Thomas C; Rorrer, Gregory L; Roesijadi, Guritno

2016-03-18

The diatom Thalassiosira pseudonana was genetically modified to express biosilica-targeted fusion proteins comprising either enhanced green fluorescent protein (EGFP) or single chain antibodies engineered with a tetracysteine tagging sequence. Of interest were the site-specific binding of (1) the fluorescent biarsenical probe AsCy3 and AsCy3e to the tetracysteine tagged fusion proteins and (2) high and low molecular mass antigens, the Bacillus anthracis surface layer protein EA1 or small molecule explosive trinitrotoluene (TNT), to biosilica-immobilized single chain antibodies. Analysis of biarsenical probe binding using fluorescence and structured illumination microscopy indicated differential colocalization with EGFP in nascent and mature biosilica, supporting the use of either EGFP or bound AsCy3 and AsCy3e in studying biosilica maturation. Large increases in the lifetime of a fluorescent analogue of TNT upon binding single chain antibodies provided a robust signal capable of discriminating binding to immobilized antibodies in the transformed frustule from nonspecific binding to the biosilica matrix. In conclusion, our results demonstrate an ability to engineer diatoms to create antibody-functionalized mesoporous silica able to selectively bind chemical and biological agents for the development of sensing platforms.

MFTF-. cap alpha. + T progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, W.D.

1985-04-01

Early in FY 1983, several upgrades of the Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) were proposed to the fusion community. The one most favorably received was designated MFTF-..cap alpha..+T. The engineering design of this device, guided by LLNL, has been a principal activity of the Fusion Engineering Design Center during FY 1983. This interim progress report represents a snapshot of the device design, which was begun in FY 1983 and will continue for several years. The report is organized as a complete design description. Because it is an interim report, some parts are incomplete; theymore » will be supplied as the design study proceeds. As described in this report, MFTF-..cap alpha..+T uses existing facilities, many MFTF-B components, and a number of innovations to improve on the physics parameters of MFTF-B. It burns deuterium-tritium and has a central-cell Q of 2, a wall loading GAMMA/sub n/ of 2 MW/m/sup 2/ (with a central-cell insert module), and an availability of 10%. The machine is fully shielded, allows hands-on maintenance of components outside the vacuum vessel 24 h after shutdown, and has provisions for repair of all operating components.« less

Fusion antibody for Alzheimer's disease with bidirectional transport across the blood-brain barrier and abeta fibril disaggregation.

PubMed

Boado, Ruben J; Zhang, Yufeng; Zhang, Yun; Xia, Chun-Fang; Pardridge, William M

2007-01-01

Delivery of monoclonal antibody therapeutics across the blood-brain barrier is an obstacle to the diagnosis or therapy of CNS disease with antibody drugs. The immune therapy of Alzheimer's disease attempts to disaggregate the amyloid plaque of Alzheimer's disease with an anti-Abeta monoclonal antibody. The present work is based on a three-step model of immune therapy of Alzheimer's disease: (1) influx of the anti-Abeta monoclonal antibody across the blood-brain barrier in the blood to brain direction, (2) binding and disaggregation of Abeta fibrils in brain, and (3) efflux of the anti-Abeta monoclonal antibody across the blood-brain barrier in the brain to blood direction. This is accomplished with the genetic engineering of a trifunctional fusion antibody that binds (1) the human insulin receptor, which mediates the influx from blood to brain across the blood-brain barrier, (2) the Abeta fibril to disaggregate amyloid plaque, and (3) the Fc receptor, which mediates the efflux from brain to blood across the blood-brain barrier. This fusion protein is a new antibody-based therapeutic for Alzheimer's disease that is specifically engineered to cross the human blood-brain barrier in both directions.

Autonomous Propulsion System Technology Being Developed to Optimize Engine Performance Throughout the Lifecycle

NASA Technical Reports Server (NTRS)

Litt, Jonathan S.

2004-01-01

The goal of the Autonomous Propulsion System Technology (APST) project is to reduce pilot workload under both normal and anomalous conditions. Ongoing work under APST develops and leverages technologies that provide autonomous engine monitoring, diagnosing, and controller adaptation functions, resulting in an integrated suite of algorithms that maintain the propulsion system's performance and safety throughout its life. Engine-to-engine performance variation occurs among new engines because of manufacturing tolerances and assembly practices. As an engine wears, the performance changes as operability limits are reached. In addition to these normal phenomena, other unanticipated events such as sensor failures, bird ingestion, or component faults may occur, affecting pilot workload as well as compromising safety. APST will adapt the controller as necessary to achieve optimal performance for a normal aging engine, and the safety net of APST algorithms will examine and interpret data from a variety of onboard sources to detect, isolate, and if possible, accommodate faults. Situations that cannot be accommodated within the faulted engine itself will be referred to a higher level vehicle management system. This system will have the authority to redistribute the faulted engine's functionality among other engines, or to replan the mission based on this new engine health information. Work is currently underway in the areas of adaptive control to compensate for engine degradation due to aging, data fusion for diagnostics and prognostics of specific sensor and component faults, and foreign object ingestion detection. In addition, a framework is being defined for integrating all the components of APST into a unified system. A multivariable, adaptive, multimode control algorithm has been developed that accommodates degradation-induced thrust disturbances during throttle transients. The baseline controller of the engine model currently being investigated has multiple control modes that are selected according to some performance or operational criteria. As the engine degrades, parameters shift from their nominal values. Thus, when a new control mode is swapped in, a variable that is being brought under control might have an excessive initial error. The new adaptive algorithm adjusts the controller gains on the basis of the level of degradation to minimize the disruptive influence of the large error on other variables and to recover the desired thrust response.

Status and improvement of CLAM for nuclear application

NASA Astrophysics Data System (ADS)

Huang, Qunying

2017-08-01

A program for China low activation martensitic steel (CLAM) development has been underway since 2001 to satisfy the material requirements of the test blanket module (TBM) for ITER, China fusion engineering test reactor and China fusion demonstration reactor. It has been undertaken by the Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences under wide domestic and international collaborations. Extensive work and efforts are being devoted to the R&D of CLAM, such as mechanical property evaluation before and after neutron irradiation, fabrication of scaled TBM by welding and additive manufacturing, improvement of its irradiation resistance as well as high temperature properties by precipitate strengthening to achieve its final successful application in fusion systems. The status and improvement of CLAM are introduced in this paper.

Space fusion energy conversion using a field reversed configuration reactor: A new technical approach for space propulsion and power

NASA Technical Reports Server (NTRS)

Schulze, Norman R.; Miley, George H.; Santarius, John F.

1991-01-01

The fusion energy conversion design approach, the Field Reversed Configuration (FRC) - when burning deuterium and helium-3, offers a new method and concept for space transportation with high energy demanding programs, like the Manned Mars Mission and planetary science outpost missions require. FRC's will increase safety, reduce costs, and enable new missions by providing a high specific power propulsion system from a high performance fusion engine system that can be optimally designed. By using spacecraft powered by FRC's the space program can fulfill High Energy Space Missions (HESM) in a manner not otherwise possible. FRC's can potentially enable the attainment of high payload mass fractions while doing so within shorter flight times.

Protein- protein interaction detection system using fluorescent protein microdomains

DOEpatents

Waldo, Geoffrey S.; Cabantous, Stephanie

2010-02-23

The invention provides a protein labeling and interaction detection system based on engineered fragments of fluorescent and chromophoric proteins that require fused interacting polypeptides to drive the association of the fragments, and further are soluble and stable, and do not change the solubility of polypeptides to which they are fused. In one embodiment, a test protein X is fused to a sixteen amino acid fragment of GFP (.beta.-strand 10, amino acids 198-214), engineered to not perturb fusion protein solubility. A second test protein Y is fused to a sixteen amino acid fragment of GFP (.beta.-strand 11, amino acids 215-230), engineered to not perturb fusion protein solubility. When X and Y interact, they bring the GFP strands into proximity, and are detected by complementation with a third GFP fragment consisting of GFP amino acids 1-198 (strands 1-9). When GFP strands 10 and 11 are held together by interaction of protein X and Y, they spontaneous association with GFP strands 1-9, resulting in structural complementation, folding, and concomitant GFP fluorescence.

A bi-functional antibody-receptor domain fusion protein simultaneously targeting IGF-IR and VEGF for degradation

PubMed Central

Shen, Yang; Zeng, Lin; Novosyadlyy, Ruslan; Forest, Amelie; Zhu, Aiping; Korytko, Andrew; Zhang, Haifan; Eastman, Scott W; Topper, Michael; Hindi, Sagit; Covino, Nicole; Persaud, Kris; Kang, Yun; Burtrum, Douglas; Surguladze, David; Prewett, Marie; Chintharlapalli, Sudhakar; Wroblewski, Victor J; Shen, Juqun; Balderes, Paul; Zhu, Zhenping; Snavely, Marshall; Ludwig, Dale L

2015-01-01

Bi-specific antibodies (BsAbs), which can simultaneously block 2 tumor targets, have emerged as promising therapeutic alternatives to combinations of individual monoclonal antibodies. Here, we describe the engineering and development of a novel, human bi-functional antibody-receptor domain fusion molecule with ligand capture (bi-AbCap) through the fusion of the domain 2 of human vascular endothelial growth factor receptor 1 (VEGFR1) to an antibody directed against insulin-like growth factor – type I receptor (IGF-IR). The bi-AbCap possesses excellent stability and developability, and is the result of minimal engineering. Beyond potent neutralizing activities against IGF-IR and VEGF, the bi-AbCap is capable of cross-linking VEGF to IGF-IR, leading to co-internalization and degradation of both targets by tumor cells. In multiple mouse xenograft tumor models, the bi-AbCap improves anti-tumor activity over individual monotherapies. More importantly, it exhibits superior inhibition of tumor growth, compared with the combination of anti-IGF-IR and anti-VEGF therapies, via powerful blockade of both direct tumor cell growth and tumor angiogenesis. The unique “capture-for-degradation” mechanism of the bi-AbCap is informative for the design of next-generation bi-functional anti-cancer therapies directed against independent signaling pathways. The bi-AbCap design represents an alternative approach to the creation of dual-targeting antibody fusion molecules by taking advantage of natural receptor-ligand interactions. PMID:26073904

Intelligent Life-Extending Controls for Aircraft Engines Studied

NASA Technical Reports Server (NTRS)

Guo, Ten-Huei

2005-01-01

Current aircraft engine controllers are designed and operated to provide desired performance and stability margins. Except for the hard limits for extreme conditions, engine controllers do not usually take engine component life into consideration during the controller design and operation. The end result is that aircraft pilots regularly operate engines under unnecessarily harsh conditions to strive for optimum performance. The NASA Glenn Research Center and its industrial and academic partners have been working together toward an intelligent control concept that will include engine life as part of the controller design criteria. This research includes the study of the relationship between control action and engine component life as well as the design of an intelligent control algorithm to provide proper tradeoffs between performance and engine life. This approach is expected to maintain operating safety while minimizing overall operating costs. In this study, the thermomechanical fatigue (TMF) of a critical component was selected to demonstrate how an intelligent engine control algorithm can significantly extend engine life with only a very small sacrifice in performance. An intelligent engine control scheme based on modifying the high-pressure spool speed (NH) was proposed to reduce TMF damage from ground idle to takeoff. The NH acceleration schedule was optimized to minimize the TMF damage for a given rise-time constraint, which represents the performance requirement. The intelligent engine control scheme was used to simulate a commercial short-haul aircraft engine.

Investigational drugs for coagulation disorders.

PubMed

Mannucci, Pier Mannuccio; Mancuso, Maria Elisa

2013-08-01

The current standard treatment in persons with hemophilia (PWH) is prophylaxis, given intravenously twice or thrice weekly, which is associated with a non negligible burden on patients' quality of life. Therefore the main attempts aiming to improve the management of PWH are targeted towards the development of a new generation of coagulation factors endowed with properties facilitating prophylaxis and/or a better control of bleeding. This article summarizes the main results obtained so far in the development of new antihemophilic products, and emphasizes the formidable requirements imposed upon by regulatory agencies to get marketing authorization for new drugs, which make progress in this field difficult. Published literature on new molecules for replacement treatment in hemophilia A and B has been retrieved by using PubMed search and all ongoing clinical trials have been looked for online. New molecules are usually engineered to have a longer plasma half-life but also in some instances a higher potency. The prolongation of half-life may be obtained by using sustained release delivery vehicles, by chemical modification or by creating fusion proteins. Factors VIII, IX and VII have been variably modified in order to obtain improved coagulation products and results from Phase I/II studies are encouraging, particularly for factor IX. However, Phase III studies that should provide evidence on efficacy and effectiveness more cogent for clinical use are still ongoing and results are not yet available.

Engineering Consideration for the Self-Energizing Magnetoplasmadynamic (MPD) - Type Fusion Plasma Thruster

DTIC Science & Technology

1993-02-01

currents can be reached by optimizing the electrode geometry and the charging circuit voltage and that the equivalent circuit modelling provides a realistic basis for analyzing plasma focus pinch dynamics.

Dealing with Altruism

ERIC Educational Resources Information Center

Kennedy, Donald

2013-01-01

At a time when schools are focusing heavily on high tech and engineering, general education is more important than ever. Wilson's book furnishes good ideas on how to bring about a curricular fusion between human studies and the sciences.

Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butrapet, Siritorn; Childers, Thomas; Moss, Kelley J.

Fifteen mutant dengue viruses were engineered and used to identify AAs in the molecular hinge of the envelope protein that are critical to viral infection. Substitutions at Q52, A54, or E133 reduced infectivity in mammalian cells and altered the pH threshold of fusion. Mutations at F193, G266, I270, or G281 affected viral replication in mammalian and mosquito cells, but only I270W had reduced fusion activity. T280Y affected the pH threshold for fusion and reduced replication in C6/36 cells. Three different mutations at L135 were lethal in mammalian cells. Among them, L135G abrogated fusion and reduced replication in C6/36 cells, butmore » only slightly reduced the mosquito infection rate. Conversely, L135W replicated well in C6/36 cells, but had the lowest mosquito infection rate. Possible interactions between hinge residues 52 and 277, or among 53, 135, 170, 186, 265, and 276 required for hinge function were discovered by sequence analysis to identify compensatory mutations.« less

Presentation Stations of the General Atomics Fusion Educational Program

NASA Astrophysics Data System (ADS)

Lee, R. L.; Fusion Group Education Outreach Team

1996-11-01

The General Atomics Fusion Group's Educational Program has been actively promoting fusion science and applications throughout San Diego County's secondary school systems for over three years. The educational program allows many students to learn more about nuclear fusion science, its applications, and what it takes to become an active participant in an important field of study. It also helps educators to better understand how to teach fusion science in their classroom. Tours of the DIII--D facility are a centerpiece of the program. Over 1000 students visited the DIII--D research facility during the 1995--1996 school year for a half-day of presentations, discussions, and hands-on learning. Interactive presentations are provided at six different stations by GA scientists and engineers to small groups of students during the tours. Stations include topics on energy, plasma science, the electromagnetic spectrum, radiation and risk assessment, and data acquisition. Included also is a tour of the DIII--D machine hall and model where students can see and discuss many aspects of the tokamak. Portions of each station will be presented and discussed.

The High Field Path to Practical Fusion Energy

NASA Astrophysics Data System (ADS)

Mumgaard, Robert; Whyte, D.; Greenwald, M.; Hartwig, Z.; Brunner, D.; Sorbom, B.; Marmar, E.; Minervini, J.; Bonoli, P.; Irby, J.; Labombard, B.; Terry, J.; Vieira, R.; Wukitch, S.

2017-10-01

We propose a faster, lower cost development path for fusion energy enabled by high temperature superconductors, devices at high magnetic field, innovative technologies and modern approaches to technology development. Timeliness, scale, and economic-viability are the drivers for fusion energy to combat climate change and aid economic development. The opportunities provided by high-temperature superconductors, innovative engineering and physics, and new organizational structures identified over the last few years open new possibilities for realizing practical fusion energy that could meet mid-century de-carbonization needs. We discuss re-factoring the fusion energy development path with an emphasis on concrete risk retirement strategies utilizing a modular approach based on the high-field tokamak that leverages the broader tokamak physics understanding of confinement, stability, and operational limits. Elements of this plan include development of high-temperature superconductor magnets, simplified immersion blankets, advanced long-leg divertors, a compact divertor test tokamak, efficient current drive, modular construction, and demountable magnet joints. An R&D plan culminating in the construction of an integrated pilot plant and test facility modeled on the ARC concept is presented.

The cost-effectiveness of interbody fusions versus posterolateral fusions in 137 patients with lumbar spondylolisthesis.

PubMed

Bydon, Mohamad; Macki, Mohamed; Abt, Nicholas B; Witham, Timothy F; Wolinsky, Jean-Paul; Gokaslan, Ziya L; Bydon, Ali; Sciubba, Daniel M

2015-03-01

Reimbursements for interbody fusions have declined recently because of their questionable cost-effectiveness. A Markov model was adopted to compare the cost-effectiveness of posterior lumbar interbody fusion (PLIF) or transforaminal lumbar interbody fusion (/TLIF) versus noninterbody fusion and posterolateral fusion (PLF) in patients with lumbar spondylolisthesis. Decision model analysis based on retrospective data from a single institutional series. One hundred thirty-seven patients underwent first-time instrumented lumbar fusions for degenerative or isthmic spondylolisthesis. Quality of life adjustments and expenditures were assigned to each short-term complication (durotomy, surgical site infection, and medical complication) and long-term outcome (bowel/bladder dysfunction and paraplegia, neurologic deficit, and chronic back pain). Patients were divided into a PLF cohort and a PLF plus PLIF/TLIF cohort. Anterior techniques and multilevel interbody fusions were excluded. Each short-term complication and long-term outcome was assigned a numerical quality-adjusted life-year (QALY), based on time trade-off values in the Beaver Dam Health Outcomes Study. The cost data for short-term complications were calculated from charges accrued by the institution's finance sector, and the cost data for long-term outcomes were estimated from the literature. The difference in cost of PLF plus PLIF/TLIF from the cost of PLF alone divided by the difference in QALY equals the cost-effectiveness ratio (CER). We do not report any study funding sources or any study-specific appraisal of potential conflict of interest-associated biases in this article. Of 137 first-time lumbar fusions for spondylolisthesis, 83 patients underwent PLF and 54 underwent PLIF/TLIF. The average time to reoperation was 3.5 years. The mean QALY over 3.5 years was 2.81 in the PLF cohort versus 2.66 in the PLIFo/TLIF cohort (p=.110). The mean 3.5-year costs of $54,827.05 after index interbody fusion were statistically higher than that of the $48,822.76 after PLF (p=.042). The CER of interbody fusion to PLF after the first operation was -$46,699.40 per QALY; however, of the 27 patients requiring reoperation, the incident (reoperation) rate ratio was 7.89 times higher after PLF (2.91, 26.67). The CER after the first reoperation was -$24,429.04 per QALY (relative to PLF). Two patients in the PLF cohort required a second reoperation, whereas none required a second reoperation in the PLIF/TLIF cohort. Taken collectively, the total CER for the interbody fusion is $9,883.97 per QALY. The reoperation rate was statistically higher for PLF, whereas the negative CER for the initial operation and first reoperation favors PLF. However, when second reoperations were included, the CER for the interbody fusion became $9,883.97 per QALY, suggesting moderate long-term cost savings and better functional outcomes with the interbody fusion. Copyright © 2015 Elsevier Inc. All rights reserved.

Solar Thermal Propulsion

NASA Technical Reports Server (NTRS)

Gerrish, Harold P., Jr.

2003-01-01

This paper presents viewgraphs on Solar Thermal Propulsion (STP). Some of the topics include: 1) Ways to use Solar Energy for Propulsion; 2) Solar (fusion) Energy; 3) Operation in Orbit; 4) Propulsion Concepts; 5) Critical Equations; 6) Power Efficiency; 7) Major STP Projects; 8) Types of STP Engines; 9) Solar Thermal Propulsion Direct Gain Assembly; 10) Specific Impulse; 11) Thrust; 12) Temperature Distribution; 13) Pressure Loss; 14) Transient Startup; 15) Axial Heat Input; 16) Direct Gain Engine Design; 17) Direct Gain Engine Fabrication; 18) Solar Thermal Propulsion Direct Gain Components; 19) Solar Thermal Test Facility; and 20) Checkout Results.

Methods for high yield production of terpenes

DOEpatents

Kutchan, Toni; Higashi, Yasuhiro; Feng, Xiaohong

2017-01-03

Provided are enhanced high yield production systems for producing terpenes in plants via the expression of fusion proteins comprising various combinations of geranyl diphosphate synthase large and small subunits and limonene synthases. Also provided are engineered oilseed plants that accumulate monoterpene and sesquiterpene hydrocarbons in their seeds, as well as methods for producing such plants, providing a system for rapidly engineering oilseed crop production platforms for terpene-based biofuels.

IFMIF: overview of the validation activities

NASA Astrophysics Data System (ADS)

Knaster, J.; Arbeiter, F.; Cara, P.; Favuzza, P.; Furukawa, T.; Groeschel, F.; Heidinger, R.; Ibarra, A.; Matsumoto, H.; Mosnier, A.; Serizawa, H.; Sugimoto, M.; Suzuki, H.; Wakai, E.

2013-11-01

The Engineering Validation and Engineering Design Activities (EVEDA) for the International Fusion Materials Irradiation Facility (IFMIF), an international collaboration under the Broader Approach Agreement between Japan Government and EURATOM, aims at allowing a rapid construction phase of IFMIF in due time with an understanding of the cost involved. The three main facilities of IFMIF (1) the Accelerator Facility, (2) the Target Facility and (3) the Test Facility are the subject of validation activities that include the construction of either full scale prototypes or smartly devised scaled down facilities that will allow a straightforward extrapolation to IFMIF needs. By July 2013, the engineering design activities of IFMIF matured with the delivery of an Intermediate IFMIF Engineering Design Report (IIEDR) supported by experimental results. The installation of a Linac of 1.125 MW (125 mA and 9 MeV) of deuterons started in March 2013 in Rokkasho (Japan). The world's largest liquid Li test loop is running in Oarai (Japan) with an ambitious experimental programme for the years ahead. A full scale high flux test module that will house ∼1000 small specimens developed jointly in Europe and Japan for the Fusion programme has been constructed by KIT (Karlsruhe) together with its He gas cooling loop. A full scale medium flux test module to carry out on-line creep measurement has been validated by CRPP (Villigen).

A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug.

PubMed

de Graaf, M; Boven, E; Oosterhoff, D; van der Meulen-Muileman, I H; Huls, G A; Gerritsen, W R; Haisma, H J; Pinedo, H M

2002-03-04

Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme beta-glucuronidase. The sequences encoding C28 and human enzyme beta-glucuronidase were joined by a sequence encoding a flexible linker, and were preceded by the IgGkappa signal sequence for secretion of the fusion protein. A CHO cell line was engineered to secrete C28-beta-glucuronidase fusion protein. Antibody specificity and enzyme activity were retained in the secreted fusion protein that had an apparent molecular mass of 100 kDa under denaturing conditions. The fusion protein was able to convert a non-toxic prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-beta-glucuronyl carbamate to doxorubicin, resulting in cytotoxicity. A bystander effect was demonstrated, as doxorubicin was detected in all cells after N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-beta-glucuronyl carbamate administration when only 10% of the cells expressed the fusion protein. This is the first fully human and functional fusion protein consisting of an scFv against epithelial cell adhesion molecule and human enzyme beta-glucuronidase for future use in tumour-specific activation of a non-toxic glucuronide prodrug. Copyright 2002 Cancer Research UK

Tritium Breeding Blanket for a Commercial Fusion Power Plant - A System Engineering Assessment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meier, Wayne R.

The goal of developing a new source of electric power based on fusion has been pursued for decades. If successful, future fusion power plants will help meet growing world-wide demand for electric power. A key feature and selling point for fusion is that its fuel supply is widely distributed globally and virtually inexhaustible. Current world-wide research on fusion energy is focused on the deuterium-tritium (DT for short) fusion reaction since it will be the easiest to achieve in terms of the conditions (e.g., temperature, density and confinement time of the DT fuel) required to produce net energy. Over the pastmore » decades countless studies have examined various concepts for TBBs for both magnetic fusion energy (MFE) and inertial fusion energy (IFE). At this time, the key organizations involved are government sponsored research organizations world-wide. The near-term focus of the MFE community is on the development of TBB mock-ups to be tested on the ITER tokamak currently under construction in Caderache France. TBB concepts for IFE tend to be different from MFE primarily due to significantly different operating conditions and constraints. This report focuses on longer-term commercial power plants where the key stakeholders include: electric utilities, plant owner and operator, manufacturer, regulators, utility customers, and in-plant subsystems including the heat transfer and conversion systems, fuel processing system, plant safety systems, and the monitoring control systems.« less

Brief Report: A mass spectrometry assay to simultaneously analyze ROS1 and RET fusion gene expression in non-small cell lung cancer

PubMed Central

Wijesinghe, Priyanga; Bepler, Gerold

2014-01-01

Introduction ROS1 and RET gene fusions were recently discovered in non-small cell lung cancer (NSCLC) as potential therapeutic targets with small molecule kinase inhibitors. The conventional screening methods of these fusions are time consuming and require samples of high quality and quantity. Here, we describe a novel and efficient method by coupling the power of multiplexing PCR and the sensitivity of mass spectrometry. Methods The multiplex mass spectrometry platform simultaneously tests samples for the expression of nine ROS1 and six RET fusion genes. The assay incorporates detection of wild-type exon junctions immediately upstream and downstream of the fusion junction to exclude false negative results. To flag false positives, the system also comprises two independent assays for each fusion gene junction. Results The characteristic mass spectrometric peaks of the gene fusions were obtained using engineered plasmid constructs. Specific assays targeting the wild-type gene exon junctions were validated using cDNA from lung tissue of healthy individuals. The system was further validated using cDNA derived from NSCLC cell lines that express endogenous fusion genes. The expressed ROS1-SLC34A2 and CCDC6-RET gene fusions from the NSCLC cell lines HCC78 and LC-2/ad, respectively, were accurately detected by the novel assay. The assay is extremely sensitive, capable of detecting an event in test specimens containing 0.5% positive tumors. Conclusion The novel multiplexed assay is robustly capable of detecting 15 different clinically relevant RET and ROS1 fusion variants. The benefits of this detection method include exceptionally low sample input, high cost efficiency, flexibility, and rapid turnover. PMID:25384172

Crop improvement and conservation through tissue culture techniques

USDA-ARS?s Scientific Manuscript database

Crop improvement through classic breeding and/or genetic engineering methods is possible in the majority of cultivated crops. However, gene manipulations, chromosome duplication, protoplast fusion, bioassays, interspecific cross recovery involve tissue culture techniques. For vegetatively propagated...

Sensor data validation and reconstruction. Phase 1: System architecture study

NASA Technical Reports Server (NTRS)

1991-01-01

The sensor validation and data reconstruction task reviewed relevant literature and selected applicable validation and reconstruction techniques for further study; analyzed the selected techniques and emphasized those which could be used for both validation and reconstruction; analyzed Space Shuttle Main Engine (SSME) hot fire test data to determine statistical and physical relationships between various parameters; developed statistical and empirical correlations between parameters to perform validation and reconstruction tasks, using a computer aided engineering (CAE) package; and conceptually designed an expert system based knowledge fusion tool, which allows the user to relate diverse types of information when validating sensor data. The host hardware for the system is intended to be a Sun SPARCstation, but could be any RISC workstation with a UNIX operating system and a windowing/graphics system such as Motif or Dataviews. The information fusion tool is intended to be developed using the NEXPERT Object expert system shell, and the C programming language.

Construction and evaluation of an exopolysaccharide-producing engineered bacterial strain by protoplast fusion for microbial enhanced oil recovery.

PubMed

Sun, Shanshan; Luo, Yijing; Cao, Siyuan; Li, Wenhong; Zhang, Zhongzhi; Jiang, Lingxi; Dong, Hanping; Yu, Li; Wu, Wei-Min

2013-09-01

Enterobacter cloacae strain JD, which produces water-insoluble biopolymers at optimal temperature of 30°C, and a thermophilic Geobacillus strain were used to construct an engineered strain for exopolysaccharide production at high temperatures by protoplast fusion. The obtained fusant strain ZR3 produced exopolysaccharides at up to 45°C with optimal growth temperature at 35°C. The fusant produced exopolysaccharides of approximately 7.5 g/L or more at pH between 7.0 and 9.0. The feasibility of the enhancement of crude oil recovery with the fusant was tested in a sand-packed column at 40°C. The results demonstrated that bioaugmentation of the fusant was promising approach for MEOR. Mass growth of the fusant was confirmed in fermentor tests. Copyright © 2013 Elsevier Ltd. All rights reserved.

Proteolytic enzyme engineering: a tool for wool.

PubMed

Araújo, Rita; Silva, Carla; Machado, Raul; Casal, Margarida; Cunha, António M; Rodriguez-Cabello, José Carlos; Cavaco-Paulo, Artur

2009-06-08

One of the goals of protein engineering is to tailor the structure of enzymes to optimize industrial bioprocesses. In the present work, we present the construction of a novel high molecular weight subtilisin, based on the fusion of the DNA sequences coding for Bacillus subtilis prosubtilisin E and for an elastin-like polymer (ELP). The resulting fusion protein was biologically produced in Escherichia coli , purified and used for wool finishing assays. When compared to the commercial protease Esperase, the recombinant subtilisinE-VPAVG(220) activity was restricted to the cuticle of wool, allowing a significant reduction of pilling, weight loss and tensile strength loss of wool fibers. Here we report, for the first time, the microbial production of a functionalized high molecular weight protease for controlled enzymatic hydrolysis of wool surface. This original process overcomes the unrestrained diffusion and extended fiber damage which are the major obstacles for the use of proteases for wool finishing applications.

Fusion to Human Serum Albumin Extends the Circulatory Half-Life and Duration of Antithrombotic Action of the Kunitz Protease Inhibitor Domain of Protease Nexin 2.

PubMed

Sheffield, William P; Eltringham-Smith, Louise J; Bhakta, Varsha

2018-01-01

The Kunitz Protease Inhibitor (KPI) domain of protease nexin 2 (PN2) potently inhibits coagulation factor XIa. Recombinant KPI has been shown to inhibit thrombosis in mouse models, but its clearance from the murine circulation remains uncharacterized. The present study explored the pharmacokinetic and pharmacodynamic effects of fusing KPI to human serum albumin (HSA) in fusion protein KPIHSA. Hexahistidine-tagged KPI (63 amino acids) and KPIHSA (656 amino acids) were expressed in Pichia pastoris yeast and purified by nickel-chelate chromatography. Clearance profiles in mice were determined, as well as the effects of KPI or KPIHSA administration on FeCl3-induced vena cava thrombus size or carotid artery time to occlusion, respectively. Fusion to HSA increased the mean terminal half-life of KPI by 8-fold and eliminated its interaction with the low density lipoprotein receptor-related protein. KPI and KPIHSA similarly reduced thrombus size and occlusion in both venous and arterial thrombosis models when administered at the time of injury, but only KPI was effective when administered one hour before injury. Albumin fusion deflects KPI from rapid in vivo clearance without impairing its antithrombotic properties and widens its potential therapeutic window. © 2018 The Author(s). Published by S. Karger AG, Basel.

40 CFR 90.105 - Useful life periods for Phase 2 engines.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Useful life periods for Phase 2... Emission Standards and Certification Provisions § 90.105 Useful life periods for Phase 2 engines. (a) Manufacturers shall declare the applicable useful life category for each engine family at the time of...

40 CFR 90.105 - Useful life periods for Phase 2 engines.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Useful life periods for Phase 2... Emission Standards and Certification Provisions § 90.105 Useful life periods for Phase 2 engines. (a) Manufacturers shall declare the applicable useful life category for each engine family at the time of...

Preliminary Investigation on Life Cycle Inventory of Powder Bed Fusion of Stainless Steel

NASA Astrophysics Data System (ADS)

Nyamekye, Patricia; Piili, Heidi; Leino, Maija; Salminen, Antti

Manufacturing of work pieces from stainless steel with laser additive manufacturing, known also as laser sintering or 3D printing may increase energy and material efficiency. The use of powder bed fusion offers advantages to make parts for dynamic applications of light weight and near-net-shape products. Due to these advantages among others, PBF may also reduce emissions and operational cost in various applications. However, there are only few life cycle assessment studies examining this subject despite its prospect to business opportunity. The application of Life Cycle Inventory (LCI) in Powder Bed Fusion (PBF) provides a distinct evaluation of material and energy consumption. LCI offers a possibility to improve knowledge of process efficiency. This study investigates effect of process sustainability in terms of raw material, energy and time consumption with PBF and CNC machining. The results of the experimental study indicated lower energy efficiency in the production process with PBF. This study revealed that specific energy consumption in PBF decreased when several components are built simultaneously than if they would be built individually. This is due to fact that energy consumption per part is lower. On the contrary, amount of energy needed to machine on part in case of CNC machining is lower when parts are done separately.

An Overview of Research and Design Activities at CTFusion

NASA Astrophysics Data System (ADS)

Sutherland, D. A.; Jarboe, T. R.; Hossack, A. C.

2016-10-01

CTFusion, a newly formed company dedicated to the development of compact, toroidal fusion energy, is a spin-off from the University of Washington that will build upon the successes of the HIT-SI research program. The mission of the company to develop net-gain fusion power cores that will serve as the heart of economical fusion power plants or radioactive-waste destroying burner reactors. The overarching vision and development plan of the company will be presented, along with a detailed justification and design for our next device, the HIT-TD (Technology Demonstration) prototype. By externally driving the edge current and imposing non-axisymmetric magnetic perturbations, HIT-TD should demonstrate the sustainment of stable spheromak configurations with Imposed-Dynamo Current Drive (IDCD), as was accomplished in the HIT-SI device, with higher current gains and temperatures than previously possible. HIT-TD, if successful, will be an instrumental step along this path to economical fusion energy, and will serve as the stepping stone to our Proof-Of-Principle device (HIT-PoP). Beyond the implications of higher performance, sustained spheromaks for fusion applications, the HIT-TD platform will provide a unique system to observe plasma self-organizational phenomena of interest for other fusion devices, and astrophysical systems as well. Lastly, preliminary nuclear engineering design simulations with the MCNP6 code of the HIT-FNSF (Fusion Nuclear Science Facility) device will be presented.

Increases thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase by fusion of cellulose binding domain derived from Trichoderma reesei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thongekkaew, Jantaporn, E-mail: jantaporn_25@yahoo.com; Ikeda, Hiroko; Iefuji, Haruyuki

Highlights: Black-Right-Pointing-Pointer The CSLP and fusion enzyme were successfully expressed in the Pichia pastoris. Black-Right-Pointing-Pointer The fusion enzyme was stable at 80 Degree-Sign C for 120-min. Black-Right-Pointing-Pointer The fusion enzyme was responsible for cellulose-binding capacity. Black-Right-Pointing-Pointer The fusion enzyme has an attractive applicant for enzyme immobilization. -- Abstract: To improve the thermal stability and cellulose-binding capacity of Cryptococcus sp. S-2 lipase (CSLP), the cellulose-binding domain originates from Trichoderma reesei cellobiohydrolase I was engineered into C-terminal region of the CSLP (CSLP-CBD). The CSLP and CSLP-CBD were successfully expressed in the Pichia pastoris using the strong methanol inducible alcohol oxidase 1 (AOX1)more » promoter and the secretion signal sequence from Saccharomyces cerevisiae ({alpha} factor). The recombinant CSLP and CSLP-CBD were secreted into culture medium and estimated by SDS-PAGE to be 22 and 27 kDa, respectively. The fusion enzyme was stable at 80 Degree-Sign C and retained more than 80% of its activity after 120-min incubation at this temperature. Our results also found that the fusion of fungal exoglucanase cellulose-binding domain to CSLP is responsible for cellulose-binding capacity. This attribute should make it an attractive applicant for enzyme immobilization.« less

Combined Engineering Education Based on Regional Needs Aiming for Design Education

NASA Astrophysics Data System (ADS)

Hama, Katsumi; Yaegashi, Kosuke; Kobayashi, Junya

The importance of design education that cultivates integrated competences has been suggested in higher educational institutions in fields of engineering in relation to quality assurance of engineering education. However, it is also pointed out to lay stress on cooperative education in collaboration with the community because there is a limit to correspond to the design education only by a group of educational institutions. This paper reports the outline of the practical engineering education, which is executing in the project learning of Hakodate National College of Technology, based on regional needs and the result of the activity as a model of education program for fusion and combination.

Applications of yeast surface display for protein engineering

PubMed Central

Cherf, Gerald M.; Cochran, Jennifer R.

2015-01-01

The method of displaying recombinant proteins on the surface of Saccharomyces cerevisiae via genetic fusion to an abundant cell wall protein, a technology known as yeast surface display, or simply, yeast display, has become a valuable protein engineering tool for a broad spectrum of biotechnology and biomedical applications. This review focuses on the use of yeast display for engineering protein affinity, stability, and enzymatic activity. Strategies and examples for each protein engineering goal are discussed. Additional applications of yeast display are also briefly presented, including protein epitope mapping, identification of protein-protein interactions, and uses of displayed proteins in industry and medicine. PMID:26060074

Phosphatidylcholine Membrane Fusion Is pH-Dependent.

PubMed

Akimov, Sergey A; Polynkin, Michael A; Jiménez-Munguía, Irene; Pavlov, Konstantin V; Batishchev, Oleg V

2018-05-03

Membrane fusion mediates multiple vital processes in cell life. Specialized proteins mediate the fusion process, and a substantial part of their energy is used for topological rearrangement of the membrane lipid matrix. Therefore, the elastic parameters of lipid bilayers are of crucial importance for fusion processes and for determination of the energy barriers that have to be crossed for the process to take place. In the case of fusion of enveloped viruses (e.g., influenza) with endosomal membrane, the interacting membranes are in an acidic environment, which can affect the membrane's mechanical properties. This factor is often neglected in the analysis of virus-induced membrane fusion. In the present work, we demonstrate that even for membranes composed of zwitterionic lipids, changes of the environmental pH in the physiologically relevant range of 4.0 to 7.5 can affect the rate of the membrane fusion notably. Using a continual model, we demonstrated that the key factor defining the height of the energy barrier is the spontaneous curvature of the lipid monolayer. Changes of this parameter are likely to be caused by rearrangements of the polar part of lipid molecules in response to changes of the pH of the aqueous solution bathing the membrane.

Immunoglobulin Fc Heterodimer Platform Technology: From Design to Applications in Therapeutic Antibodies and Proteins.

PubMed

Ha, Ji-Hee; Kim, Jung-Eun; Kim, Yong-Sung

2016-01-01

The monospecific and bivalent characteristics of naturally occurring immunoglobulin G (IgG) antibodies depend on homodimerization of the fragment crystallizable (Fc) regions of two identical heavy chains (HCs) and the subsequent assembly of two identical light chains (LCs) via disulfide linkages between each HC and LC. Immunoglobulin Fc heterodimers have been engineered through modifications to the CH3 domain interface, with different mutations on each domain such that the engineered Fc fragments, carrying the CH3 variant pair, preferentially form heterodimers rather than homodimers. Many research groups have adopted different strategies to generate Fc heterodimers, with the goal of high heterodimerization yield, while retaining biophysical and biological properties of the wild-type Fc. Based on their ability to enforce heterodimerization between the two different HCs, the established Fc heterodimers have been extensively exploited as a scaffold to generate bispecific antibodies (bsAbs) in full-length IgG and IgG-like formats. These have many of the favorable properties of natural IgG antibodies, such as high stability, long serum half-life, low immunogenicity, and immune effector functions. As of July 2016, more than seven heterodimeric Fc-based IgG-format bsAbs are being evaluated in clinical trials. In addition to bsAbs, heterodimeric Fc technology is very promising for the generation of Fc-fused proteins and peptides, as well as cytokines (immunocytokines), which can present the fusion partners in the natural monomeric or heterodimeric form rather than the artificial homodimeric form with wild-type Fc. Here, we present relevant concepts and strategies for the generation of heterodimeric Fc proteins, and their application in the development of bsAbs in diverse formats for optimal biological activity. In addition, we describe wild-type Fc-fused monomeric and heterodimeric proteins, along with the difficulties associated with their preparations, and discuss the use of heterodimeric Fc as an alternative scaffold of wild-type Fc for naturally monomeric or heterodimeric proteins, to create Fc-fusion proteins with novel therapeutic modality.

The QED engine spectrum - Fusion-electric propulsion for air-breathing to interstellar flight

NASA Technical Reports Server (NTRS)

Bussard, Robert W.; Jameson, Lorin W.

1993-01-01

A new inertial-electrostatic-fusion direct electric power source can be used to drive a relativistic e-beam to heat propellant. The resulting system is shown to yield specific impulse and thrust/mass ratio 2-3 orders of magnitude larger than from other advanced propulsion concepts. This QED system can be applied to aerospace vehicles from air-breathing to near-interstellar flight. Examples are given for Earth/Mars flight missions, that show transit times of 40 d with 20 percent payload in single-stage vehicles.

Creep Deformation and Rupture Behavior of Single- and Dual-Pass 316LN Stainless-Steel-Activated TIG Weld Joints

NASA Astrophysics Data System (ADS)

Vijayanand, V. D.; Vasudevan, M.; Ganesan, V.; Parameswaran, P.; Laha, K.; Bhaduri, A. K.

2016-06-01

Creep deformation and rupture behavior of single-pass and dual-pass 316LN stainless steel (SS) weld joints fabricated by an autogenous activated tungsten inert gas welding process have been assessed by performing metallography, hardness, and conventional and impression creep tests. The fusion zone of the single-pass joint consisted of columnar zones adjacent to base metals with a central equiaxed zone, which have been modified extensively by the thermal cycle of the second pass in the dual-pass joint. The equiaxed zone in the single-pass joint, as well as in the second pass of the dual-pass joint, displayed the lowest hardness in the joints. In the dual-pass joint, the equiaxed zone of the first pass had hardness comparable to the columnar zone. The hardness variations in the joints influenced the creep deformation. The equiaxed and columnar zone in the first pass of the dual-pass joint was more creep resistant than that of the second pass. Both joints possessed lower creep rupture life than the base metal. However, the creep rupture life of the dual-pass joint was about twofolds more than that of the single-pass joint. Creep failure in the single-pass joint occurred in the central equiaxed fusion zone, whereas creep cavitation that originated in the second pass was blocked at the weld pass interface. The additional interface and strength variation between two passes in the dual-pass joint provides more restraint to creep deformation and crack propagation in the fusion zone, resulting in an increase in the creep rupture life of the dual-pass joint over the single-pass joint. Furthermore, the differences in content, morphology, and distribution of delta ferrite in the fusion zone of the joints favors more creep cavitation resistance in the dual-pass joint over the single-pass joint with the enhancement of creep rupture life.

Requirement of myomaker-mediated stem cell fusion for skeletal muscle hypertrophy

PubMed Central

Goh, Qingnian; Millay, Douglas P

2017-01-01

Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy. This blunted hypertrophic response was associated with a reduction in Akt and p70s6k signaling and protein synthesis, suggesting a link between myonuclear accretion and activation of pro-hypertrophic pathways. Furthermore, fusion-incompetent muscle exhibited increased fibrosis after muscle overload, indicating a protective role for normal stem cell activity in reducing myofiber strain associated with hypertrophy. These findings reveal an essential contribution of myomaker-mediated stem cell fusion during physiological adult muscle hypertrophy. DOI: http://dx.doi.org/10.7554/eLife.20007.001 PMID:28186492

Fusion for Space Propulsion

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Schafer, Charles (Technical Monitor)

2001-01-01

There is little doubt that humans will attempt to explore and develop the solar system in this century. A large amount of energy will be required for accomplishing this. The need for fusion propulsion is discussed. For a propulsion system, there are three important thermodynamical attributes: (1) The absolute amount of energy available, (2) the propellant exhaust velocity, and (3) the jet power per unit mass of the propulsion system (specific power). For human exploration and development of the solar system, propellant exhaust velocity in excess of 100 km/s and specific power in excess of 10 kW/kg are required. Chemical combustion can produce exhaust velocity up to about 5 km/s. Nuclear fission processes typically result in producing energy in the form of heat that needs to be manipulated at temperatures limited by materials to about 2,800 K. Using the energy to heat a hydrogen propellant increases the exhaust velocity by only a factor of about two. Alternatively the energy can be converted into electricity which is then used to accelerate particles to high exhaust velocity. The necessary power conversion and conditioning equipment, however, increases the mass of the propulsion system for the same jet power by more than two orders of magnitude over chemical system, thus greatly limits the thrust-to-weight ratio attainable. The principal advantage of the fission process is that its development is relatively mature and is available right now. If fusion can be developed, fusion appears to have the best of all worlds in terms of propulsion - it can provide the absolute amount, the propellant exhaust velocity, and the high specific jet power. An intermediate step towards pure fusion propulsion is a bimodal system in which a fission reactor is used to provide some of the energy to drive a fusion propulsion unit. The technical issues related to fusion for space propulsion are discussed. The technical priorities for developing and applying fusion for propulsion are somewhat different from those for terrestrial electrical power generation. Thus fusion schemes that are initially attractive for electrical power generation might not necessarily be attractive also for propulsion and vice versa, though the underlying fusion science and engineering enjoy much overlap. Parallel efforts to develop these qualitatively differently fusion schemes for the two applications could benefit greatly from each other due to the synergy in the underlying physics and engineering. Pulsed approaches to fusion have not been explored to the same degree as steady-state or long-pulse approaches to fusion in the fusion power research program. The concerns early on were several. One was that the pulsed power components might not have the service lifetimes meeting the requirements of a practical power generating plant. Another was that, for many pulsed fusion schemes, it was not clear whether the destruction of hardware per pulse could be minimized or eliminated or recycled to such an extent as to make economical electrical power generation feasible, Significant development of the underlying pulsed power component technologies have occurred in the last two decades because of defense and other energy requirements. The state of development of the pulsed power technologies are sufficiently advanced now to make it compelling to visit or re-visit pulsed fusion approaches for application to propulsion where the cost of energy is not so demanding a factor as in the case of terrestrial power application. For propulsion application, the overall mass of the fusion system is the critical factor. Producing fusion reactions require extreme states of matter. Conceptually, these extreme states of matter are more readily realizable in the pulsed states, at least within appropriate bounds, than in the steady states. Significant saving in system mass may result in such systems. Magnetic fields are effective in confining plasma energy, whereas inertial compression is an effective way of heating and containing the plasma. Intensive research in developing magnetic energy containment and inertial plasma compression are being pursued in distinctively different fusion experiments in the terrestrial fusion power program. Fusion schemes that attempt to combine the favorable attributes of these two aspects into one single integrated fusion scheme appear to have benefits that are worth exploring for propulsion application.

Flight evaluation of an extended engine life mode on an F-15 airplane

NASA Technical Reports Server (NTRS)

Myers, Lawrence P.; Conners, Timothy R.

1992-01-01

An integrated flight and propulsion control system designed to reduce the rate of engine deterioration was developed and evaluated in flight on the NASA Dryden F-15 research aircraft. The extended engine life mode increases engine pressure ratio while reducing engine airflow to lower the turbine temperature at constant thrust. The engine pressure ratio uptrim is modulated in real time based on airplane maneuver requirements, flight conditions, and engine information. The extended engine life mode logic performed well, significantly reducing turbine operating temperature. Reductions in fan turbine inlet temperature of up to 80 F were obtained at intermediate power and up to 170 F at maximum augmented power with no appreciable loss in thrust. A secondary benefit was the considerable reduction in thrust-specific fuel consumption. The success of the extended engine life mode is one example of the advantages gained from integrating aircraft flight and propulsion control systems.

Engineering workstation: Sensor modeling

NASA Technical Reports Server (NTRS)

Pavel, M; Sweet, B.

1993-01-01

The purpose of the engineering workstation is to provide an environment for rapid prototyping and evaluation of fusion and image processing algorithms. Ideally, the algorithms are designed to optimize the extraction of information that is useful to a pilot for all phases of flight operations. Successful design of effective fusion algorithms depends on the ability to characterize both the information available from the sensors and the information useful to a pilot. The workstation is comprised of subsystems for simulation of sensor-generated images, image processing, image enhancement, and fusion algorithms. As such, the workstation can be used to implement and evaluate both short-term solutions and long-term solutions. The short-term solutions are being developed to enhance a pilot's situational awareness by providing information in addition to his direct vision. The long term solutions are aimed at the development of complete synthetic vision systems. One of the important functions of the engineering workstation is to simulate the images that would be generated by the sensors. The simulation system is designed to use the graphics modeling and rendering capabilities of various workstations manufactured by Silicon Graphics Inc. The workstation simulates various aspects of the sensor-generated images arising from phenomenology of the sensors. In addition, the workstation can be used to simulate a variety of impairments due to mechanical limitations of the sensor placement and due to the motion of the airplane. Although the simulation is currently not performed in real-time, sequences of individual frames can be processed, stored, and recorded in a video format. In that way, it is possible to examine the appearance of different dynamic sensor-generated and fused images.

Application of Recommended Design Practices for Conceptual Nuclear Fusion Space Propulsion Systems

NASA Technical Reports Server (NTRS)

Williams, Craig H.

2004-01-01

An AIAA Special Project Report was recently produced by AIAA's Nuclear and Future Flight Propulsion Technical Committee and is currently in peer review. The Report provides recommended design practices for conceptual engineering studies of nuclear fusion space propulsion systems. Discussion and recommendations are made on key topics including design reference missions, degree of technological extrapolation and concomitant risk, thoroughness in calculating mass properties (nominal mass properties, weight-growth contingency and propellant margins, and specific impulse), and thoroughness in calculating power generation and usage (power-flow, power contingencies, specific power). The report represents a general consensus of the nuclear fusion space propulsion system conceptual design community and proposes 15 recommendations. This paper expands on the Report by providing specific examples illustrating how to apply each of the recommendations.

Gasdynamic Mirror Fusion Propulsion Experiment

NASA Technical Reports Server (NTRS)

Emrich, William J., Jr.; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

Nuclear fusion appears to be the most promising concept for producing extremely high specific impulse rocket engines. One particular fusion concept which seems to be particularly well suited for fusion propulsion applications is the gasdynamic mirror (GDM). This device would operate at much higher plasma densities and with much larger LD ratios than previous mirror machines. Several advantages accrue from such a design. First, the high LA:) ratio minimizes to a large extent certain magnetic curvature effects which lead to plasma instabilities causing a loss of plasma confinement. Second, the high plasma density will result in the plasma behaving much more Re a conventional fluid with a mean free path shorter than the length of the device. This characteristic helps reduce problems associated with "loss cone" microinstabilities. An experimental GDM device is currently being constructed at the NASA Marshall Space Flight Center to provide an initial assessment of the feasibility of this type of propulsion system. Initial experiments are expected to commence in the late fall of 2000.

Hybrid fusion reactor for production of nuclear fuel with minimum radioactive contamination of the fuel cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Velikhov, E. P.; Kovalchuk, M. V.; Azizov, E. A., E-mail: Azizov-EA@nrcki.ru

2015-12-15

The paper presents the results of the system research on the coordinated development of nuclear and fusion power engineering in the current century. Considering the increasing problems of resource procurement, including limited natural uranium resources, it seems reasonable to use fusion reactors as high-power neutron sources for production of nuclear fuel in a blanket. It is shown that the share of fusion sources in this structural configuration of the energy system can be relatively small. A fundamentally important aspect of this solution to the problem of closure of the fuel cycle is that recycling of highly active spent fuel canmore » be abandoned. Radioactivity released during the recycling of the spent fuel from the hybrid reactor blanket is at least two orders of magnitude lower than during the production of the same number of fissile isotopes after the recycling of the spent fuel from a fast reactor.« less

Conceptual design of the cryogenic system and estimation of the recirculated power for CFETR

NASA Astrophysics Data System (ADS)

Liu, Xiaogang; Qiu, Lilong; Li, Junjun; Wang, Zhaoliang; Ren, Yong; Wang, Xianwei; Li, Guoqiang; Gao, Xiang; Bi, Yanfang

2017-01-01

The China Fusion Engineering Test Reactor (CFETR) is the next tokamak in China’s roadmap for realizing commercial fusion energy. The CFETR cryogenic system is crucial to creating and maintaining operational conditions for its superconducting magnet system and thermal shields. The preliminary conceptual design of the CFETR cryogenic system has been carried out with reference to that of ITER. It will provide an average capacity of 75 to 80 kW at 4.5 K and a peak capacity of 1300 kW at 80 K. The electric power consumption of the cryogenic system is estimated to be 24 MW, and the gross building area is about 7000 m2. The relationships among the auxiliary power consumed by the cryogenic system, the fusion power gain and the recirculated power of CFETR are discussed, with the suggestion that about 52% of the electric power produced by CFETR in phase II must be recirculated to run the fusion test reactor.

Optical design and Initial Results from The National Institute of Standards and Technology’s AMMT/TEMPS Facility

PubMed Central

Grantham, Steven; Lane, Brandon; Neira, Jorge; Mekhontsev, Sergey; Vlasea, Mihaela; Hanssen, Leonard

2017-01-01

The National Institute of Standards and Technology’s (NIST) Physical Measurement and Engineering Laboratories are jointly developing the Additive Manufacturing Measurement Testbed (AMMT)/ Temperature and Emittance of Melts, Powders and Solids (TEMPS) facilities. These facilities will be co-located on an open architecture laser-based powder bed fusion system allowing users full access to the system’s operation parameters. This will provide users with access to machine-independent monitoring and control of the powder bed fusion process. In this paper there will be emphasis on the AMMT, which incorporates in-line visible light collection optics for monitoring and feedback control of the powder bed fusion process. We shall present an overview of the AMMT/TEMPS program and its goals. The optical and mechanical design of the open architecture powder-bed fusion system and the AMMT will also be described. In addition, preliminary measurement results from the system along with the current status of the system will be described. PMID:28579666

High-Energy Space Propulsion Based on Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Thio, Y. C. F.; Landrum, D. B.; Freeze, B.; Kirkpatrick, R. C.; Gerrish, H.; Schmidt, G. R.

1999-01-01

Magnetized target fusion is an approach in which a magnetized target plasma is compressed inertially by an imploding material wall. A high energy plasma liner may be used to produce the required implosion. The plasma liner is formed by the merging of a number of high momentum plasma jets converging towards the center of a sphere where two compact toroids have been introduced. Preliminary 3-D hydrodynamics modeling results using the SPHINX code of Los Alamos National Laboratory have been very encouraging and confirm earlier theoretical expectations. The concept appears ready for experimental exploration and plans for doing so are being pursued. In this talk, we explore conceptually how this innovative fusion approach could be packaged for space propulsion for interplanetary travel. We discuss the generally generic components of a baseline propulsion concept including the fusion engine, high velocity plasma accelerators, generators of compact toroids using conical theta pinches, magnetic nozzle, neutron absorption blanket, tritium reprocessing system, shock absorber, magnetohydrodynamic generator, capacitor pulsed power system, thermal management system, and micrometeorite shields.

Comparison of instrumented anterior interbody fusion with instrumented circumferential lumbar fusion.

PubMed

Madan, S S; Boeree, N R

2003-12-01

Posterior lumbar interbody fusion (PLIF) restores disc height, the load bearing ability of anterior ligaments and muscles, root canal dimensions, and spinal balance. It immobilizes the painful degenerate spinal segment and decompresses the nerve roots. Anterior lumbar interbody fusion (ALIF) does the same, but could have complications of graft extrusion, compression and instability contributing to pseudarthrosis in the absence of instrumentation. The purpose of this study was to assess and compare the outcome of instrumented circumferential fusion through a posterior approach [PLIF and posterolateral fusion (PLF)] with instrumented ALIF using the Hartshill horseshoe cage, for comparable degrees of internal disc disruption and clinical disability. It was designed as a prospective study, comparing the outcome of two methods of instrumented interbody fusion for internal disc disruption. Between April 1994 and June 1998, the senior author (N.R.B.) performed 39 instrumented ALIF procedures and 35 instrumented circumferential fusion with PLIF procedures. The second author, an independent assessor (S.M.), performed the entire review. Preoperative radiographic assessment included plain radiographs, magnetic resonance imaging (MRI) and provocative discography in all the patients. The outcome in the two groups was compared in terms of radiological improvement and clinical improvement, measured on the basis of improvement of back pain and work capacity. Preoperatively, patients were asked to fill out a questionnaire giving their demographic details, maximum walking distance and current employment status in order to establish the comparability of the two groups. Patient assessment was with the Oswestry Disability Index, quality of life questionnaire (subjective), pain drawing, visual analogue scale, disability benefit, compensation status, and psychological profile. The results of the study showed a satisfactory outcome (score< or =30) on the subjective (quality of life questionnaire) score of 71.8% (28 patients) in the ALIF group and 74.3% (26 patients) in the PLIF group (P>0.05). On categorising Oswestry Index scores into "excellent", "better", "same", and "worse", we found no difference in outcome between the two groups: 79.5% (n=31) had satisfactory outcome with ALIF and 80% (n=28) had satisfactory outcome with PLIF. The rate of return to work was no different in the two groups. On radiological assessment, we found two nonunions in the circumferential fusion (PLIF) group (94.3% fusion rate) and indirect evidence of no nonunions in the ALIF group. There was no significant difference between the compensation rate and disability benefit rate between the two groups. There were three complications in ALIF group and four in the PLIF (circumferential) group. On the basis of these results, we conclude that it is possible to treat discogenic back pain by anterior interbody fusion with Hartshill horseshoe cage or with circumferential fusion using instrumented PLIF.

First Breakthrough for Future Air-Breathing Magneto-Plasma Propulsion Systems

NASA Astrophysics Data System (ADS)

Göksel, B.; Mashek, I. Ch

2017-04-01

A new breakthrough in jet propulsion technology since the invention of the jet engine is achieved. The first critical tests for future air-breathing magneto-plasma propulsion systems have been successfully completed. In this regard, it is also the first time that a pinching dense plasma focus discharge could be ignited at one atmosphere and driven in pulse mode using very fast, nanosecond electrostatic excitations to induce self-organized plasma channels for ignition of the propulsive main discharge. Depending on the capacitor voltage (200-600 V) the energy input at one atmosphere varies from 52-320 J/pulse corresponding to impulse bits from 1.2-8.0 mNs. Such a new pulsed plasma propulsion system driven with one thousand pulses per second would already have thrust-to-area ratios (50-150 kN/m²) of modern jet engines. An array of thrusters could enable future aircrafts and airships to start from ground and reach altitudes up to 50km and beyond. The needed high power could be provided by future compact plasma fusion reactors already in development by aerospace companies. The magneto-plasma compressor itself was originally developed by Russian scientists as plasma fusion device and was later miniaturized for supersonic flow control applications. So the first breakthrough is based on a spin-off plasma fusion technology.

Construction and Cloning of Reporter-Tagged Replicon cDNA for an In Vitro Replication Study of Murine Norovirus-1 (MNV-1).

PubMed

Ahmad, Muhammad Khairi; Tabana, Yasser M; Ahmed, Mowaffaq Adam; Sandai, Doblin Anak; Mohamed, Rafeezul; Ismail, Ida Shazrina; Zulkiflie, Nurulisa; Yunus, Muhammad Amir

2017-12-01

A norovirus maintains its viability, infectivity and virulence by its ability to replicate. However, the biological mechanisms of the process remain to be explored. In this work, the NanoLuc™ Luciferase gene was used to develop a reporter-tagged replicon system to study norovirus replication. The NanoLuc™ Luciferase reporter protein was engineered to be expressed as a fusion protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A (FMDV2A) sequence was inserted between the 3'end of the reporter gene and the VP2 start sequence to allow co-translational 'cleavage' of fusion proteins during intracellular transcript expression. Amplification of the fusion gene was performed using a series of standard and overlapping polymerase chain reactions. The resulting amplicon was then cloned into three readily available backbones of MNV-1 cDNA clones. Restriction enzyme analysis indicated that the NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA clone. The insertion was further confirmed by using DNA sequencing. NanoLuc™ Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such clones can be exploited to develop robust experimental assays for in vitro assessments of viral RNA replication.

Combining elements of information fusion and knowledge-based systems to support situation analysis

NASA Astrophysics Data System (ADS)

Roy, Jean

2006-04-01

Situation awareness has emerged as an important concept in military and public security environments. Situation analysis is defined as a process, the examination of a situation, its elements, and their relations, to provide and maintain a product, i.e., a state of situation awareness for the decision maker(s). It is well established that information fusion, defined as the process of utilizing one or more information sources over time to assemble a representation of aspects of interest in an environment, is a key enabler to meeting the demanding requirements of situation analysis. However, although information fusion is important, developing and adopting a knowledge-centric view of situation analysis should provide a more holistic perspective of this process. This is based on the notion that awareness ultimately has to do with having knowledge of something. Moreover, not all of the situation elements and relationships of interest are directly observable. Those aspects of interest that cannot be observed must be inferred, i.e., derived as a conclusion from facts or premises, or by reasoning from evidence. This paper discusses aspects of knowledge, and how it can be acquired from experts, formally represented and stored in knowledge bases to be exploited by computer programs, and validated. Knowledge engineering is reviewed, with emphasis given to cognitive and ontological engineering. Facets of reasoning are discussed, along with inferencing methods that can be used in computer applications. Finally, combining elements of information fusion and knowledge-based systems, an overall approach and framework for the building of situation analysis support systems is presented.

Experimental study of heating scheme effect on the inner divertor power footprint widths in EAST lower single null discharges

NASA Astrophysics Data System (ADS)

Deng, G. Z.; Xu, J. C.; Liu, X.; Liu, X. J.; Liu, J. B.; Zhang, H.; Liu, S. C.; Chen, L.; Yan, N.; Feng, W.; Liu, H.; Xia, T. Y.; Zhang, B.; Shao, L. M.; Ming, T. F.; Xu, G. S.; Guo, H. Y.; Xu, X. Q.; Gao, X.; Wang, L.

2018-04-01

A comprehensive work of the effects of plasma current and heating schemes on divertor power footprint widths is carried out in the experimental advanced superconducting tokamak (EAST). The divertor power footprint widths, i.e., the scrape-off layer heat flux decay length λ q and the heat spreading S, are crucial physical and engineering parameters for fusion reactors. Strong inverse scaling of λ q and S with plasma current have been demonstrated for both neutral beam (NB) and lower hybrid wave (LHW) heated L-mode and H-mode plasmas at the inner divertor target. For plasmas heated by the combination of the two kinds of auxiliary heating schemes (NB and LHW), the divertor power widths tend to be larger in plasmas with higher ratio of LHW power. Comparison between experimental heat flux profiles at outer mid-plane (OMP) and divertor target for NB heated and LHW heated L-mode plasmas reveals that the magnetic topology changes induced by LHW may be the main reason to the wider divertor power widths in LHW heated discharges. The effect of heating schemes on divertor peak heat flux has also been investigated, and it is found that LHW heated discharges tend to have a lower divertor peak heat flux compared with NB heated discharges under similar input power. All these findings seem to suggest that plasmas with LHW auxiliary heating scheme are better heat exhaust scenarios for fusion reactors and should be the priorities for the design of next-step fusion reactors like China Fusion Engineering Test Reactor.

Reduction in Brain Heparan Sulfate with Systemic Administration of an IgG Trojan Horse-Sulfamidase Fusion Protein in the Mucopolysaccharidosis Type IIIA Mouse.

PubMed

Boado, Ruben J; Lu, Jeff Zhiqiang; Hui, Eric Ka-Wai; Pardridge, William M

2018-02-05

Mucopolysaccharidosis Type IIIA (MPSIIIA), also known as Sanfilippo A syndrome, is an inherited neurodegenerative disease caused by mutations in the lysosomal enzyme, N-sulfoglucosamine sulfohydrolase (SGSH), also known as sulfamidase. Mutations in the SGSH enzyme, the only mammalian heparan N-sulfatase, cause accumulation of lysosomal inclusion bodies in brain cells comprising heparan sulfate (HS) glycosaminoglycans (GAGs). Treatment of MPSIIIA with intravenous recombinant SGSH is not possible because this large molecule does not cross the blood-brain barrier (BBB). BBB penetration by SGSH was enabled in the present study by re-engineering this enzyme as an IgG-SGSH fusion protein, where the IgG domain is a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), designated the cTfRMAb. The IgG domain of the fusion protein acts as a molecular Trojan horse to deliver the enzyme into brain via transport on the endogenous BBB TfR. The cTfRMAb-SGSH fusion protein bound to the mouse TfR with high affinity, ED 50 = 0.74 ± 0.07 nM, and retained high SGSH enzyme activity, 10 043 ± 1003 units/mg protein, which is comparable to recombinant human SGSH. Male and female MPSIIIA mice, null for the SGSH enzyme, were treated for 6 weeks with thrice-weekly intraperitoneal injections of vehicle, 5 mg/kg of the cTfRMAb alone, or 5 mg/kg of the cTfRMAb-SGSH fusion protein, starting at the age of 2 weeks, and were euthanized 1 week after the last injection. Brain and liver HS, as determined by liquid chromatography-mass spectrometry, were elevated 30-fold and 36-fold, respectively, in the MPSIIIA mouse. Treatment of the mice with the cTfRMAb-SGSH fusion protein caused a 70% and 85% reduction in brain and liver HS, respectively. The reduction in brain HS was associated with a 28% increase in latency on the rotarod test of motor activity in male mice. The mice exhibited no injection related reactions, and only a low titer end of study antidrug antibody response was observed. In conclusion, substantial reductions in brain pathologic GAGs in a murine model of MPSIIIA are produced by chronic systemic administration of an IgG-SGSH fusion protein engineered to penetrate the BBB via receptor-mediated transport.

Evaluation of a UCMK/dCK fusion enzyme for gemcitabine-mediated cytotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Adam J.; Brown, Melissa N.; Black, Margaret E., E-mail: blackm@vetmed.wsu.edu

2011-12-09

Highlights: Black-Right-Pointing-Pointer Goal was to enhance dFdC cytotoxicity by the creation of a UCMK/dCK fusion enzyme. Black-Right-Pointing-Pointer The UCMK/dCK fusion enzyme possesses both native activities. Black-Right-Pointing-Pointer The fusion renders cells equally sensitive to dFdC relative to dCK expression alone. Black-Right-Pointing-Pointer Dual activities of fusion not sufficient to augment cell dFdC sensitivity in vitro. Black-Right-Pointing-Pointer Data may warrant the implementation of UCMK mutagenesis studies. -- Abstract: While gemcitabine (2 Prime -2 Prime -difluoro-2 Prime -deoxycytidine, dFdC) displays wide-ranging antineoplastic activity as a single agent, variable response rates and poor intracellular metabolism often limit its clinical efficacy. In an effort to enhancemore » dFdC cytotoxicity and help normalize response rates, we created a bifunctional fusion enzyme that combines the enzymatic activities of deoxycytidine kinase (dCK) and uridine/cytidine monophosphate kinase (UCMK) in a single polypeptide. Our goal was to evaluate whether the created fusion could induce beneficial, functional changes toward dFdC, expedite dFdC conversion to its active antimetabolites and consequently amplify cell dFdC sensitivity. While kinetic analyses revealed the UCMK/dCK fusion enzyme to possess both native activities, the fusion rendered cells sensitive to the cytotoxic effects of dFdC at the same level as dCK expression alone. These results suggest that increased wild-type UCMK expression does not provide a significant enhancement in dFdC-mediated cytotoxicity and may warrant the implementation of studies aimed at engineering UCMK variants with improved activity toward gemcitabine monophosphate.« less

A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug

PubMed Central

de Graaf, M; Boven, E; Oosterhoff, D; van der Meulen-Muileman, I H; Huls, G A; Gerritsen, W R; Haisma, H J; Pinedo, H M

2002-01-01

Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme β-glucuronidase. The sequences encoding C28 and human enzyme β-glucuronidase were joined by a sequence encoding a flexible linker, and were preceded by the IgGκ signal sequence for secretion of the fusion protein. A CHO cell line was engineered to secrete C28-β-glucuronidase fusion protein. Antibody specificity and enzyme activity were retained in the secreted fusion protein that had an apparent molecular mass of 100 kDa under denaturing conditions. The fusion protein was able to convert a non-toxic prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate to doxorubicin, resulting in cytotoxicity. A bystander effect was demonstrated, as doxorubicin was detected in all cells after N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate administration when only 10% of the cells expressed the fusion protein. This is the first fully human and functional fusion protein consisting of an scFv against epithelial cell adhesion molecule and human enzyme β-glucuronidase for future use in tumour-specific activation of a non-toxic glucuronide prodrug. British Journal of Cancer (2002) 86, 811–818. DOI: 10.1038/sj/bjc/6600143 www.bjcancer.com © 2002 Cancer Research UK PMID:11875747

Perspectives on Lunar Helium-3

NASA Astrophysics Data System (ADS)

Schmitt, Harrison H.

1999-01-01

Global demand for energy will likely increase by a factor of six or eight by the mid-point of the 21st Century due to a combination of population increase, new energy intensive technologies, and aspirations for improved standards of living in the less-developed world (1). Lunar helium-3 (3He), with a resource base in the Tranquillitatis titanium-rich lunar maria (2,3) of at least 10,000 tonnes (4), represents one potential energy source to meet this rapidly escalating demand. The energy equivalent value of 3He delivered to operating fusion power plants on Earth would be about 3 billion per tonne relative to today's coal which supplies most of the approximately 90 billion domestic electrical power market (5). These numbers illustrate the magnitude of the business opportunity. The results from the Lunar Prospector neutron spectrometer (6) suggests that 3He also may be concentrated at the lunar poles along with solar wind hydrogen (7). Mining, extraction, processing, and transportation of helium to Earth requires new innovations in engineering but no known new engineering concepts (1). By-products of lunar 3He extraction, largely hydrogen, oxygen, and water, have large potential markets in space and ultimately will add to the economic attractiveness of this business opportunity (5). Inertial electrostatic confinement (IEC) fusion technology appears to be the most attractive and least capital intensive approach to terrestrial fusion power plants (8). Heavy lift launch costs comprise the largest cost uncertainty facing initial business planning, however, many factors, particularly long term production contracts, promise to lower these costs into the range of 1-2000 per kilogram versus about 70,000 per kilogram fully burdened for the Apollo Saturn V rocket (1). A private enterprise approach to developing lunar 3He and terrestrial IEC fusion power would be the most expeditious means of realizing this unique opportunity (9). In spite of the large, long-term potential return on investment, access to capital markets for a lunar 3He and terrestrial fusion power business will require a near-term return on investment, based on early applications of IEC fusion technology (10).

A Burning Plasma Experiment: the role of international collaboration

NASA Astrophysics Data System (ADS)

Prager, Stewart

2003-04-01

The world effort to develop fusion energy is at the threshold of a new stage in its research: the investigation of burning plasmas. A burning plasma is self-heated. The 100 million degree temperature of the plasma is maintained by the heat generated by the fusion reactions themselves, as occurs in burning stars. The fusion-generated alpha particles produce new physical phenomena that are strongly coupled together as a nonlinear complex system, posing a major plasma physics challenge. Two attractive options are being considered by the US fusion community as burning plasma facilities: the international ITER experiment and the US-based FIRE experiment. ITER (the International Thermonuclear Experimental Reactor) is a large, power-plant scale facility. It was conceived and designed by a partnership of the European Union, Japan, the Soviet Union, and the United States. At the completion of the first engineering design in 1998, the US discontinued its participation. FIRE (the Fusion Ignition Research Experiment) is a smaller, domestic facility that is at an advanced pre-conceptual design stage. Each facility has different scientific, programmatic and political implications. Selecting the optimal path for burning plasma science is itself a challenge. Recently, the Fusion Energy Sciences Advisory Committee recommended a dual path strategy in which the US seek to rejoin ITER, but be prepared to move forward with FIRE if the ITER negotiations do not reach fruition by July, 2004. Either the ITER or FIRE experiment would reveal the behavior of burning plasmas, generate large amounts of fusion power, and be a huge step in establishing the potential of fusion energy to contribute to the world's energy security.

Targeted diphtheria toxin to treat BPDCN.

PubMed

FitzGerald, David J

2014-07-17

In this issue of Blood, Frankel et al describe a novel treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) using an engineered version of diphtheria toxin that is targeted to malignant cells via a fusion with interleukin (IL)3 (see panel A).

TRISO Fuel Performance: Modeling, Integration into Mainstream Design Studies, and Application to a Thorium-fueled Fusion-Fission Hybrid Blanket

NASA Astrophysics Data System (ADS)

Powers, Jeffrey J.

2011-12-01

This study focused on creating a new tristructural isotropic (TRISO) coated particle fuel performance model and demonstrating the integration of this model into an existing system of neutronics and heat transfer codes, creating a user-friendly option for including fuel performance analysis within system design optimization and system-level trade-off studies. The end product enables both a deeper understanding and better overall system performance of nuclear energy systems limited or greatly impacted by TRISO fuel performance. A thorium-fueled hybrid fusion-fission Laser Inertial Fusion Energy (LIFE) blanket design was used for illustrating the application of this new capability and demonstrated both the importance of integrating fuel performance calculations into mainstream design studies and the impact that this new integrated analysis had on system-level design decisions. A new TRISO fuel performance model named TRIUNE was developed and verified and validated during this work with a novel methodology established for simulating the actual lifetime of a TRISO particle during repeated passes through a pebble bed. In addition, integrated self-consistent calculations were performed for neutronics depletion analysis, heat transfer calculations, and then fuel performance modeling for a full parametric study that encompassed over 80 different design options that went through all three phases of analysis. Lastly, side studies were performed that included a comparison of thorium and depleted uranium (DU) LIFE blankets as well as some uncertainty quantification work to help guide future experimental work by assessing what material properties in TRISO fuel performance modeling are most in need of improvement. A recommended thorium-fueled hybrid LIFE engine design was identified with an initial fuel load of 20MT of thorium, 15% TRISO packing within the graphite fuel pebbles, and a 20cm neutron multiplier layer with beryllium pebbles in flibe molten salt coolant. It operated at a system power level of 2000 MWth, took about 3.5 years to reach full plateau power, and was capable of an End of Plateau burnup of 38.7 %FIMA if considering just the neutronic constraints in the system design; however, fuel performance constraints led to a maximum credible burnup of 12.1 %FIMA due to a combination of internal gas pressure and irradiation effects on the TRISO materials (especially PyC) leading to SiC pressure vessel failures. The optimal neutron spectrum for the thorium-fueled blanket options evaluated seemed to favor a hard spectrum (low but non-zero neutron multiplier thicknesses and high TRISO packing fractions) in terms of neutronic performance but the fuel performance constraints demonstrated that a significantly softer spectrum would be needed to decrease the rate of accumulation of fast neutron fluence in order to improve the maximum credible burnup the system could achieve.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schulze, N.R.

This proposed program is to initiate a space flight research and development program to develop fusion energy for the space applications of direct space propulsion and direct space power, that is, a Space Fusion Energy (SFE) program. 'Direct propulsion' refers to the use of plasma energy directly for thrust without requiring other energy conversion systems. Further, to provide space missions with large electrical power, 'direct space power' is proposed whereby the direct conversion of charged particles into electricity is used, thereby avoiding thermal conversion system losses. The energy release from nuclear fusion reactions makes these highly efficient, high power spacemore » systems possible. The program as presented conducts in an orderly, hierarchical manner the necessary planning, analyses, and testing to demonstrate the practical use of fusion energy for space. There is nothing discussed that is known to be theoretically impossible. Validation of the engineering principles is sought in this program which uses a cost-benefit approach. Upon successful program completion, space will become more accessible and space missions more safely conducted. The country will have taken a giant step toward the commercialization of space. The mission enabling capability provided by fusion energy is well beyond mission planners' current dreams.« less

T-cell immunotherapy for human MK-1-expressing tumors using a fusion protein of the superantigen SEA and anti-MK-1 scFv antibody.

PubMed

Ueno, Aruto; Arakawa, Fumiko; Abe, Hironori; Matsumoto, Hisanobu; Kudo, Toshio; Asano, Ryutaro; Tsumoto, Kohei; Kumagai, Izumi; Kuroki, Motomu; Kuroki, Masahide

2002-01-01

The bacterial superantigen staphylococcal enterotoxin A (SEA) is an extremely potent activator of T lymphocytes when presented on major histocompatibility complex (MHC) class II molecules. To develop a tumor-specific superantigen for cancer therapy, we constructed a recombinant fusion protein of SEA and the single-chain variable fragment (scFv) of the FU-MK-1 antibody, which recognizes a glycoprotein antigen (termed MK-1 antigen) present on most carcinomas. We employed recombinant DNA techniques to fuse recombinant mutant SEA to an scFv antibody derived from FU-MK-1 and the resulting fusion protein (SEA/FUscFv) was produced by a bacterial expression system, purified with a metal-affinity column, and characterized for its MK-1-binding specificity and its antitumor activity. The SEA/FUscFv fusion protein retained the reactivity with MK-1-expressing tumor cells, introduced a specific cytotoxicity of lymphokine-activated killer T-cells to the tumor cells, and consequently suppressed the tumor growth in a SCID mouse xenograft model. This genetically engineered SEA/FUscFv fusion protein may serve as a potentially useful immunotherapeutic reagent for human MK-1-expressing tumors.

Assessing the Mirror Fusion Propulsion System (MFPS) Concept as Applied to Outer-Solar-System (OSS) Missions

NASA Astrophysics Data System (ADS)

Carpenter, Scott A.; Deveny, Marc E.; Schulze, Norman R.; Gatti, Raymond C.; Peters, Micheal B.

1994-07-01

In this paper, we strive to achieve three goals: (1) to describe a continuous-thrusting space-fusion-propulsion engine called the Mirror Fusion Propulsion System (MFPS), (2) to describe MFPS' ability to accomplish two candidate outer-solar-system (OSS) missions using various levels of advanced technology identified in the laboratory, and (3) to describe some interesting safety features of MFPS that include continuous mission-abort capability, magnetic-field-shielding against solar particle events (SPE), and performance of in-orbit characterization of the target body's natural resources (prior to human landings) using fusion-neutrons, x-rays, and possibly the neutralized thrust beam. The first OSS mission discussed is a mission to the Saturnian system, primarily exploration and resource- characterization driven, with emphasis on minimizing the Earth-to-Saturn and return-trip flight times. The other OSS mission discussed is an economically-driven mission to Uranus, stopping first to perform in-orbit resource characterization of the major moons of Uranus prior to human landing, and then returning to earth with a payload consisting of 3He (removed from the Uranian atmosphere or extracted from the Uranian moons) to be used in a future earth-based fusion-power industry.

Nuclear Fusion Blast and Electrode Lifetimes in a PJMIF Reactor

NASA Astrophysics Data System (ADS)

Thio, Y. C. Francis; Witherspoon, F. D.; Case, A.; Brockington, S.; Cruz, E.; Luna, M.; Hsu, S. C.

2017-10-01

We present an analysis and numerical simulation of the nuclear blast from the micro-explosion following the completion of the fusion burn for a baseline design of a PJMIF fusion reactor with a fusion gain of 20. The stagnation pressure from the blast against the chamber wall defines the engineering requirement for the structural design of the first wall and the plasma guns. We also present an analysis of the lifetimes of the electrodes of the plasma guns which are exposed to (1) the high current, and (2) the neutron produced by the fusion reactions. We anticipate that the gun electrodes are made of tungsten alloys as plasma facing components reinforced structurally by appropriate steel alloys. Making reasonable assumptions about the electrode erosion rate (100 ng/C transfer), the electrode lifetime limited by the erosion rate is estimated to be between 19 and 24 million pulses before replacement. Based on known neutron radiation effects on structural materials such as steel alloys and plasma facing component materials such as tungsten alloys, the plasma guns are expected to survive some 22 million shots. At 1 Hz, this equal to about 6 months of continuous operation before they need to be replaced. Work supported by Strong Atomics, LLC.

Fusion Building: New Trend with Some Old Roots

ERIC Educational Resources Information Center

Hamilton, Craig

2009-01-01

The focus on the quality of a student's entire academic experience has led to a greater emphasis on student life activities and facilities. In response, many campuses are renovating, expanding, or creating new buildings that support student life. While many of these are traditional stand-alone student dormitories, dining facilities, unions, and…

Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain

PubMed Central

Müller, Mischa R.; Saunders, Kenneth; Grace, Christopher; Jin, Macy; Piche-Nicholas, Nicole; Steven, John; O’Dwyer, Ronan; Wu, Leeying; Khetemenee, Lam; Vugmeyster, Yulia; Hickling, Timothy P.; Tchistiakova, Lioudmila; Olland, Stephane; Gill, Davinder; Jensen, Allan; Barelle, Caroline J.

2012-01-01

Advances in recombinant antibody technology and protein engineering have provided the opportunity to reduce antibodies to their smallest binding domain components and have concomitantly driven the requirement for devising strategies to increase serum half-life to optimise drug exposure, thereby increasing therapeutic efficacy. In this study, we adopted an immunization route to raise picomolar affinity shark immunoglobulin new antigen receptors (IgNARs) to target human serum albumin (HSA). From our model shark species, Squalus acanthias, a phage display library encompassing the variable binding domain of IgNAR (VNAR) was constructed, screened against target, and positive clones were characterized for affinity and specificity. N-terminal and C-terminal molecular fusions of our lead hit in complex with a naïve VNAR domain were expressed, purified and exhibited the retention of high affinity binding to HSA, but also cross-selectivity to mouse, rat and monkey serum albumin both in vitro and in vivo. Furthermore, the naïve VNAR had enhanced pharmacokinetic (PK) characteristics in both N- and C-terminal orientations and when tested as a three domain construct with naïve VNAR flanking the HSA binding domain at both the N and C termini. Molecules derived from this platform technology also demonstrated the potential for clinical utility by being available via the subcutaneous route of delivery. This study thus demonstrates the first in vivo functional efficacy of a VNAR binding domain with the ability to enhance PK properties and support delivery of multifunctional therapies. PMID:23676205

Improving the pharmacokinetic properties of biologics by fusion to an anti-HSA shark VNAR domain.

PubMed

Müller, Mischa R; Saunders, Kenneth; Grace, Christopher; Jin, Macy; Piche-Nicholas, Nicole; Steven, John; O'Dwyer, Ronan; Wu, Leeying; Khetemenee, Lam; Vugmeyster, Yulia; Hickling, Timothy P; Tchistiakova, Lioudmila; Olland, Stephane; Gill, Davinder; Jensen, Allan; Barelle, Caroline J

2012-01-01

Advances in recombinant antibody technology and protein engineering have provided the opportunity to reduce antibodies to their smallest binding domain components and have concomitantly driven the requirement for devising strategies to increase serum half-life to optimise drug exposure, thereby increasing therapeutic efficacy. In this study, we adopted an immunization route to raise picomolar affinity shark immunoglobulin new antigen receptors (IgNARs) to target human serum albumin (HSA). From our model shark species, Squalus acanthias, a phage display library encompassing the variable binding domain of IgNAR (VNAR) was constructed, screened against target, and positive clones were characterized for affinity and specificity. N-terminal and C-terminal molecular fusions of our lead hit in complex with a naïve VNAR domain were expressed, purified and exhibited the retention of high affinity binding to HSA, but also cross-selectivity to mouse, rat and monkey serum albumin both in vitro and in vivo. Furthermore, the naïve VNAR had enhanced pharmacokinetic (PK) characteristics in both N- and C-terminal orientations and when tested as a three domain construct with naïve VNAR flanking the HSA binding domain at both the N and C termini. Molecules derived from this platform technology also demonstrated the potential for clinical utility by being available via the subcutaneous route of delivery. This study thus demonstrates the first in vivo functional efficacy of a VNAR binding domain with the ability to enhance PK properties and support delivery of multifunctional therapies.

Potential of derived lunar volatiles for life support

NASA Technical Reports Server (NTRS)

Bula, R. J.; Wittenberg, L. J.; Tibbitts, T. W.; Kulcinski, G. L.

1992-01-01

The lunar regolith contains small quantities of solar wind implanted volatile compounds that have vital, basic uses for maintaining life support systems of lunar or space settlements. Recent proposals to utilize the helium-3 isotope (He-3) derived from the lunar regolith as a fuel for fusion reactors would result in the availability of large quantities of other lunar volatile compounds. The quantities obtained would provide the annual life support replacement requirements of 1150 to 23,000 inhabitants per ton of He-3 recovered, depending on the volatile compound. Utilization of the lunar volatile compounds for life support depends on the costs, in terms of materials and energy, associated with their extraction from the lunar regolith as compared to the delivery costs of these compounds from Earth resources. Considering today's conservative estimated transportation costs ($10,000 dollars per kilogram) and regolith mining costs ($5 dollars per ton), the life support replacement requirements could be more economically supplied by recovering the lunar volatile compounds than transporting these materials from Earth resources, even before He-3 will be utilized as a fusion fuel. In addition, availability of lunar volatile compounds could have a significant cost impact on maintaining the life support systems of the space station and a Mars base.

A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints.

PubMed

Mullen, Lisa; Adams, Gill; Foster, Julie; Vessillier, Sandrine; Köster, Mario; Hauser, Hansjörg; Layward, Lorna; Gould, David; Chernajovsky, Yuti

2014-09-01

Latent cytokines are engineered by fusing the latency associated peptide (LAP) derived from transforming growth factor-β (TGF-β) with the therapeutic cytokine, in this case interferon-β (IFN-β), via an inflammation-specific matrix metalloproteinase (MMP) cleavage site. To demonstrate latency and specific delivery in vivo and to compare therapeutic efficacy of aggrecanase-mediated release of latent IFN-β in arthritic joints to the original MMP-specific release. Recombinant fusion proteins with MMP, aggrecanase or devoid of cleavage site were expressed in CHO cells, purified and characterised in vitro by Western blotting and anti-viral protection assays. Therapeutic efficacy and half-life were assessed in vivo using the mouse collagen-induced arthritis model (CIA) of rheumatoid arthritis and a model of acute paw inflammation, respectively. Transgenic mice with an IFN-regulated luciferase gene were used to assess latency in vivo and targeted delivery to sites of disease. Efficient localised delivery of IFN-β to inflamed paws, with low levels of systemic delivery, was demonstrated in transgenic mice using latent IFN-β. Engineering of latent IFN-β with an aggrecanase-sensitive cleavage site resulted in efficient cleavage by ADAMTS-4, ADAMTS-5 and synovial fluid from arthritic patients, with an extended half-life similar to the MMP-specific molecule and greater therapeutic efficacy in the CIA model. Latent cytokines require cleavage in vivo for therapeutic efficacy, and they are delivered in a dose dependent fashion only to arthritic joints. The aggrecanase-specific cleavage site is a viable alternative to the MMP cleavage site for the targeting of latent cytokines to arthritic joints. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

CRISPR/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion Is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma.

PubMed

Engelholm, Lars H; Riaz, Anjum; Serra, Denise; Dagnæs-Hansen, Frederik; Johansen, Jens V; Santoni-Rugiu, Eric; Hansen, Steen H; Niola, Francesco; Frödin, Morten

2017-12-01

Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects children and young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis. We used the CRISPR/Cas9 technique to delete in mice the syntenic region on chromosome 8 to create a Dnajb1-Prkaca fusion and monitored the mice for liver tumor development. We delivered CRISPR/Cas9 vectors designed to juxtapose exon 1 of Dnajb1 with exon 2 of Prkaca to create the Dnajb1-Prkaca gene fusion associated with FL-HCC, or control Cas9 vector, via hydrodynamic tail vein injection to livers of 8-week-old female FVB/N mice. These mice did not have any other engineered genetic alterations and were not exposed to liver toxins or carcinogens. Liver tissues were collected 14 months after delivery; genomic DNA was analyzed by PCR to detect the Dnajb1-Prkaca fusion, and tissues were characterized by histology, immunohistochemistry, RNA sequencing, and whole-exome sequencing. Livers from 12 of the 15 mice given the vectors to induce the Dnajb1-Prkaca gene fusion, but none of the 11 mice given the control vector, developed neoplasms. The tumors contained the Dnajb1-Prkaca gene fusion and had histologic and cytologic features of human FL-HCCs: large polygonal cells with granular, eosinophilic, and mitochondria-rich cytoplasm, prominent nucleoli, and markers of hepatocytes and cholangiocytes. In comparing expression levels of genes between the mouse tumor and non-tumor liver cells, we identified changes similar to those detected in human FL-HCC, which included genes that affect cell cycle and mitosis regulation. Genomic analysis of mouse neoplasms induced by the Dnajb1-Prkaca fusion revealed a lack of mutations in genes commonly associated with liver cancers, as observed in human FL-HCC. Using CRISPR/Cas9 technology, we found generation of the Dnajb1-Prkaca fusion gene in wild-type mice to be sufficient to initiate formation of tumors that have many features of human FL-HCC. Strategies to block DNAJB1-PRKACA might be developed as therapeutics for this form of liver cancer. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

On-Board Real-Time Optimization Control for Turbo-Fan Engine Life Extending

NASA Astrophysics Data System (ADS)

Zheng, Qiangang; Zhang, Haibo; Miao, Lizhen; Sun, Fengyong

2017-11-01

A real-time optimization control method is proposed to extend turbo-fan engine service life. This real-time optimization control is based on an on-board engine mode, which is devised by a MRR-LSSVR (multi-input multi-output recursive reduced least squares support vector regression method). To solve the optimization problem, a FSQP (feasible sequential quadratic programming) algorithm is utilized. The thermal mechanical fatigue is taken into account during the optimization process. Furthermore, to describe the engine life decaying, a thermal mechanical fatigue model of engine acceleration process is established. The optimization objective function not only contains the sub-item which can get fast response of the engine, but also concludes the sub-item of the total mechanical strain range which has positive relationship to engine fatigue life. Finally, the simulations of the conventional optimization control which just consider engine acceleration performance or the proposed optimization method have been conducted. The simulations demonstrate that the time of the two control methods from idle to 99.5 % of the maximum power are equal. However, the engine life using the proposed optimization method could be surprisingly increased by 36.17 % compared with that using conventional optimization control.

Mechanical Engineering Department engineering research: Annual report, FY 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denney, R.M.; Essary, K.L.; Genin, M.S.

1986-12-01

This report provides information on the five areas of research interest in LLNL's Mechanical Engineering Department. In Computer Code Development, a solid geometric modeling program is described. In Dynamic Systems and Control, structure control and structure dynamics are discussed. Fabrication technology involves machine cutting, interferometry, and automated optical component manufacturing. Materials engineering reports on composite material research and measurement of molten metal surface properties. In Nondestructive Evaluation, NMR, CAT, and ultrasound machines are applied to manufacturing processes. A model for underground collapse is developed. Finally, an alternative heat exchanger is investigated for use in a fusion power plant. Separate abstractsmore » were prepared for each of the 13 reports in this publication. (JDH)« less

Probabilistic/Fracture-Mechanics Model For Service Life

NASA Technical Reports Server (NTRS)

Watkins, T., Jr.; Annis, C. G., Jr.

1991-01-01

Computer program makes probabilistic estimates of lifetime of engine and components thereof. Developed to fill need for more accurate life-assessment technique that avoids errors in estimated lives and provides for statistical assessment of levels of risk created by engineering decisions in designing system. Implements mathematical model combining techniques of statistics, fatigue, fracture mechanics, nondestructive analysis, life-cycle cost analysis, and management of engine parts. Used to investigate effects of such engine-component life-controlling parameters as return-to-service intervals, stresses, capabilities for nondestructive evaluation, and qualities of materials.

Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Griffin, Steven T.

2002-01-01

Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

A general strategy to construct small molecule biosensors in eukaryotes

PubMed Central

Feng, Justin; Jester, Benjamin W; Tinberg, Christine E; Mandell, Daniel J; Antunes, Mauricio S; Chari, Raj; Morey, Kevin J; Rios, Xavier; Medford, June I; Church, George M; Fields, Stanley; Baker, David

2015-01-01

Biosensors for small molecules can be used in applications that range from metabolic engineering to orthogonal control of transcription. Here, we produce biosensors based on a ligand-binding domain (LBD) by using a method that, in principle, can be applied to any target molecule. The LBD is fused to either a fluorescent protein or a transcriptional activator and is destabilized by mutation such that the fusion accumulates only in cells containing the target ligand. We illustrate the power of this method by developing biosensors for digoxin and progesterone. Addition of ligand to yeast, mammalian, or plant cells expressing a biosensor activates transcription with a dynamic range of up to ~100-fold. We use the biosensors to improve the biotransformation of pregnenolone to progesterone in yeast and to regulate CRISPR activity in mammalian cells. This work provides a general methodology to develop biosensors for a broad range of molecules in eukaryotes. DOI: http://dx.doi.org/10.7554/eLife.10606.001 PMID:26714111

Genetic therapies against HIV

PubMed Central

Rossi, John J; June, Carl H; Kohn, Donald B

2015-01-01

Highly active antiretroviral therapy prolongs the life of HIV-infected individuals, but it requires lifelong treatment and results in cumulative toxicities and viral-escape mutants. Gene therapy offers the promise of preventing progressive HIV infection by sustained interference with viral replication in the absence of chronic chemotherapy. Gene-targeting strategies are being developed with RNA-based agents, such as ribozymes, antisense, RNA aptamers and small interfering RNA, and protein-based agents, such as the mutant HIV Rev protein M10, fusion inhibitors and zinc-finger nucleases. Recent advances in T-cell–based strategies include gene-modified HIV-resistant T cells, lentiviral gene delivery, CD8+ T cells, T bodies and engineered T-cell receptors. HIV-resistant hematopoietic stem cells have the potential to protect all cell types susceptible to HIV infection. The emergence of viral resistance can be addressed by therapies that use combinations of genetic agents and that inhibit both viral and host targets. Many of these strategies are being tested in ongoing and planned clinical trials. PMID:18066041

New design of cable-in-conduit conductor for application in future fusion reactors

NASA Astrophysics Data System (ADS)

Qin, Jinggang; Wu, Yu; Li, Jiangang; Liu, Fang; Dai, Chao; Shi, Yi; Liu, Huajun; Mao, Zhehua; Nijhuis, Arend; Zhou, Chao; Yagotintsev, Konstantin A.; Lubkemann, Ruben; Anvar, V. A.; Devred, Arnaud

2017-11-01

The China Fusion Engineering Test Reactor (CFETR) is a new tokamak device whose magnet system includes toroidal field, central solenoid (CS) and poloidal field coils. The main goal is to build a fusion engineering tokamak reactor with about 1 GW fusion power and self-sufficiency by blanket. In order to reach this high performance, the magnet field target is 15 T. However, the huge electromagnetic load caused by high field and current is a threat for conductor degradation under cycling. The conductor with a short-twist-pitch (STP) design has large stiffness, which enables a significant performance improvement in view of load and thermal cycling. But the conductor with STP design has a remarkable disadvantage: it can easily cause severe strand indentation during cabling. The indentation can reduce the strand performance, especially under high load cycling. In order to overcome this disadvantage, a new design is proposed. The main characteristic of this new design is an updated layout in the triplet. The triplet is made of two Nb3Sn strands and one soft copper strand. The twist pitch of the two Nb3Sn strands is large and cabled first. The copper strand is then wound around the two superconducting strands (CWS) with a shorter twist pitch. The following cable stages layout and twist pitches are similar to the ITER CS conductor with STP design. One short conductor sample with a similar scale to the ITER CS was manufactured and tested with the Twente Cable Press to investigate the mechanical properties, AC loss and internal inspection by destructive examination. The results are compared to the STP conductor (ITER CS and CFETR CSMC) tests. The results show that the new conductor design has similar stiffness, but much lower strand indentation than the STP design. The new design shows potential for application in future fusion reactors.

Crystal Structures of Beta- and Gammaretrovirus Fusion Proteins Reveal a Role for Electrostatic Stapling in Viral Entry

PubMed Central

Aydin, Halil; Cook, Jonathan D.

2014-01-01

Membrane fusion is a key step in the life cycle of all envelope viruses, but this process is energetically unfavorable; the transmembrane fusion subunit (TM) of the virion-attached glycoprotein actively catalyzes the membrane merger process. Retroviral glycoproteins are the prototypical system to study pH-independent viral entry. In this study, we determined crystal structures of extramembrane regions of the TMs from Mason-Pfizer monkey virus (MPMV) and xenotropic murine leukemia virus-related virus (XMRV) at 1.7-Å and 2.2-Å resolution, respectively. The structures are comprised of a trimer of hairpins that is characteristic of class I viral fusion proteins and now completes a structural library of retroviral fusion proteins. Our results allowed us to identify a series of intra- and interchain electrostatic interactions in the heptad repeat and chain reversal regions. Mutagenesis reveals that charge-neutralizing salt bridge mutations significantly destabilize the postfusion six-helix bundle and abrogate retroviral infection, demonstrating that electrostatic stapling of the fusion subunit is essential for viral entry. Our data indicate that salt bridges are a major stabilizing force on the MPMV and XMRV retroviral TMs and likely provide the key energetics for viral and host membrane fusion. PMID:24131724

Safety of engineered allergen-specific immunotherapy vaccines

PubMed Central

Focke-Tejkl, Margarete; Valenta, Rudolf

2015-01-01

Purpose of review The purpose of the review is to summarize and comment on recent developments regarding the safety of engineered immunotherapy vaccines. Recent findings In the last 2 years, several studies were published in which allergy vaccines were developed on the basis of chemical modification of natural allergen extracts, the engineering of allergen molecules by recombinant DNA technology and synthetic peptide chemistry, allergen genes, new application routes and conjugation with immune modulatory molecules. Several studies exemplified the general applicability of hypoallergenic vaccines on the basis of recombinant fusion proteins consisting of nonallergenic allergen-derived peptides fused to allergen-unrelated carrier molecules. These vaccines are engineered to reduce both, immunoglobulin E (IgE) as well as allergen-specific T cell epitopes in the vaccines, and thus should provoke less IgE and T-cell-mediated side-effects. They are made to induce allergen-specific IgG antibodies against the IgE-binding sites of allergens with the T-cell help of the carrier molecule. Summary Several interesting examples of allergy vaccines with potentially increased safety profiles have been published. The concept of fusion proteins consisting of allergen-derived hypoallergenic peptides fused to allergen-unrelated proteins that seems to be broadly applicable for a variety of allergens appears to be of particular interest because it promises not only to reduce side-effects but also to increase efficacy and convenience of allergy vaccines. PMID:22885888

Summary of sensor evaluation for the Fusion Electromagnetic Induction Experiment (FELIX)

NASA Astrophysics Data System (ADS)

Knott, M. J.

1982-08-01

As part of the First Wall/Blanket/Shield Engineering Test Program, a test bed called FELIX (fusion electromagnetic induction experiment) is under construction. Its purpose is to test, evaluate, and develop computer codes for the prediction of electromagnetically induced phenomenon in a magnetic environment modeling that of a fusion reaction. Crucial to this process is the sensing and recording of the various induced effects. Sensor evaluation for FELIX reached the point where most sensor types were evaluated and preliminary decisions are being made as to type and quantity for the initial FELIX experiments. These early experiments, the first, flat plate experiment in particular, will be aimed at testing the sensors as well as the pertinent theories involved. The reason for these evaluations, decisions, and proof tests is the harsh electrical and magnetic environment that FELIX presents.

Mitigation of X-ray shadow seeding of hydrodynamic instabilities on inertial confinement fusion capsules using a reduced diameter fuel fill-tube

NASA Astrophysics Data System (ADS)

MacPhee, A. G.; Smalyuk, V. A.; Landen, O. L.; Weber, C. R.; Robey, H. F.; Alfonso, E. L.; Biener, J.; Bunn, T.; Crippen, J. W.; Farrell, M.; Felker, S.; Field, J. E.; Hsing, W. W.; Kong, C.; Milovich, J.; Moore, A.; Nikroo, A.; Rice, N.; Stadermann, M.; Wild, C.

2018-05-01

We report a reduced X-ray shadow imprint of hydrodynamic instabilities on the high-density carbon ablator surface of inertial confinement fusion (ICF) capsules using a reduced diameter fuel fill tube on the National Ignition Facility (NIF). The perturbation seed mass from hydrodynamic instabilities was reduced by approximately an order of magnitude by reducing both the diameter and wall thickness of the fill tube by ˜2×, consistent with analytical estimates. This work demonstrates a successful mitigation strategy for engineered features for ICF implosions on the NIF.

Scientist to appeal misconduct charge

NASA Astrophysics Data System (ADS)

Gwynne, Peter

2008-08-01

Lawyers for the "bubble-fusion" researcher Rusi Taleyarkhan have told Physics World that he will appeal over the findings of a panel that last month found him guilty of two charges of scientific misconduct. Taleyarkhan, a nuclear engineer at Purdue University in the US, was charged by a sixmember internal committee, which concluded that he had cited a paper by researchers in his own lab as if it were an independent confirmation of his alleged discovery of bubble fusion in 2002. The committee also found him guilty of adding the name of a student who had not contributed to that paper as an author.

Interplanetary propulsion using inertial fusion

NASA Technical Reports Server (NTRS)

Orth, Charles D.; Hoffman, Nate; Murray, Kathy; Klein, Gail; Diaz, Franklin Chang

1987-01-01

Inertial fusion can be used to power spacecraft within the solar system and beyond. Such spacecraft have the potential for short duration manned mission performance exceeding other technologies. A study was conducted to assess the systems aspects of inertial as applied to such missions, based on the conceptual engine design of Hyde (1983). The required systems for an entirely new spacecraft design called VISTA that is based on the use of DT fuel is described. Preliminary design details are given for the power conversion and power conditioning systems for manned missions to Mars of total duration of about 100 days.

Fusion of approaches to the treatment of organ failure.

PubMed

Ogle, Brenda; Cascalho, Marilia; Platt, Jeffrey L

2004-01-01

Because organ transplantation is the preferred treatment for organ failure, the demand for human organs for transplantation is large and growing. From this demand, several fields based on new technologies for the replacement or repair of damaged tissues and organs have emerged. These fields include stem cell biology, cloning, tissue engineering and xenotransplantation. Here we evaluate the potential contribution of these to the devising of alternative approaches to organ replacement. We present our vision for the development of two structurally complex organs - the lung and the kidney - based on a 'fusion' of new and established technologies.

Project-oriented teaching model about specialized courses in the information age

NASA Astrophysics Data System (ADS)

Chen, Xiaodong; Wang, Jinjiang; Tian, Qingguo; Wang, Yi; Cai, Huaiyu

2017-08-01

Specialized courses play a significant role in the usage of basic knowledge in the practical application for engineering college students. The engineering data available has sharply increased since the beginning of the information age in the 20th century, providing much more approaches to study and practice. Therefore, how to guide students to make full use of resources for active engineering practice learning has become one of the key problems for specialized courses. This paper took the digital image processing course for opto-electronic information science and technology major as an example, discussed the teaching model of specialized course in the information age, put forward the "engineering resource oriented model", and fostered the ability of engineering students to use the basic knowledge to innovate and deal with specific project objectives. The fusion of engineering examples into practical training and teaching encourages students to practice independent engineering thinking.

10 CFR 1045.15 - Classification and declassification presumptions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Classification and declassification presumptions. (a) The Director of Classification and the Chief Health, Safety... presumption as a starting point. (d) The Director of Classification and the Chief Health, Safety and Security... experimental physics, engineering, materials science, biology and medicine; (2) Magnetic confinement fusion...

10 CFR 1045.15 - Classification and declassification presumptions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... experimental physics, engineering, materials science, biology and medicine; (2) Magnetic confinement fusion... the application of the criteria in § 1045.16 indicates otherwise: (1) Detailed designs, specifications... design and analysis of nuclear weapons; (3) Vulnerabilities of U.S. nuclear weapons to sabotage...

10 CFR 1045.15 - Classification and declassification presumptions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... experimental physics, engineering, materials science, biology and medicine; (2) Magnetic confinement fusion... the application of the criteria in § 1045.16 indicates otherwise: (1) Detailed designs, specifications... design and analysis of nuclear weapons; (3) Vulnerabilities of U.S. nuclear weapons to sabotage...

10 CFR 1045.15 - Classification and declassification presumptions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... criteria in § 1045.16 indicates otherwise: (1) Basic science: mathematics, chemistry, theoretical and experimental physics, engineering, materials science, biology and medicine; (2) Magnetic confinement fusion...); (5) Fact of use of safety features (e.g., insensitive high explosives, fire resistant pits) to lower...

10 CFR 1045.15 - Classification and declassification presumptions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... criteria in § 1045.16 indicates otherwise: (1) Basic science: mathematics, chemistry, theoretical and experimental physics, engineering, materials science, biology and medicine; (2) Magnetic confinement fusion...); (5) Fact of use of safety features (e.g., insensitive high explosives, fire resistant pits) to lower...

Engineering Antimicrobials Refractory to Resistance

USDA-ARS?s Scientific Manuscript database

Multi-drug resistant superbugs are a persistent problem in modern health care, demonstrating the need for a new class of antimicrobials that can address this concern. Triple-acting peptidoglycan hydrolase fusions are a novel class of antimicrobials which have qualities well suited to avoiding resis...

14 CFR 33.70 - Engine life-limited parts.

Code of Federal Regulations, 2014 CFR

2014-01-01

... parts are rotor and major static structural parts whose primary failure is likely to result in a....70 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: AIRCRAFT ENGINES Design and Construction; Turbine Aircraft Engines § 33.70 Engine life...

Lumbar interbody fusion: techniques, indications and comparison of interbody fusion options including PLIF, TLIF, MI-TLIF, OLIF/ATP, LLIF and ALIF

PubMed Central

Phan, Kevin; Malham, Greg; Seex, Kevin; Rao, Prashanth J.

2015-01-01

Degenerative disc and facet joint disease of the lumbar spine is common in the ageing population, and is one of the most frequent causes of disability. Lumbar spondylosis may result in mechanical back pain, radicular and claudicant symptoms, reduced mobility and poor quality of life. Surgical interbody fusion of degenerative levels is an effective treatment option to stabilize the painful motion segment, and may provide indirect decompression of the neural elements, restore lordosis and correct deformity. The surgical options for interbody fusion of the lumbar spine include: posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), minimally invasive transforaminal lumbar interbody fusion (MI-TLIF), oblique lumbar interbody fusion/anterior to psoas (OLIF/ATP), lateral lumbar interbody fusion (LLIF) and anterior lumbar interbody fusion (ALIF). The indications may include: discogenic/facetogenic low back pain, neurogenic claudication, radiculopathy due to foraminal stenosis, lumbar degenerative spinal deformity including symptomatic spondylolisthesis and degenerative scoliosis. In general, traditional posterior approaches are frequently used with acceptable fusion rates and low complication rates, however they are limited by thecal sac and nerve root retraction, along with iatrogenic injury to the paraspinal musculature and disruption of the posterior tension band. Minimally invasive (MIS) posterior approaches have evolved in an attempt to reduce approach related complications. Anterior approaches avoid the spinal canal, cauda equina and nerve roots, however have issues with approach related abdominal and vascular complications. In addition, lateral and OLIF techniques have potential risks to the lumbar plexus and psoas muscle. The present study aims firstly to comprehensively review the available literature and evidence for different lumbar interbody fusion (LIF) techniques. Secondly, we propose a set of recommendations and guidelines for the indications for interbody fusion options. Thirdly, this article provides a description of each approach, and illustrates the potential benefits and disadvantages of each technique with reference to indication and spine level performed. PMID:27683674

SUPPORT FOR HU CFRT SUMMER HIGH SCHOOL FUSION WORKSHOP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Punjabi, Alkesh

Nine summer fusion science research workshops for minority and female high school students were conducted at the Hampton University Center for Fusion Research and Training from 1996 to 2005. Each workshop was of the duration of eight weeks. In all 35 high school students were mentored. The students presented 28 contributed papers at the annual meetings of the American Physical Society Division of Plasma Physics. These contributed papers were very well received by the plasma physics and fusion science research community. The students won a number of prestigious local, state, and national honors, awards, prizes, and scholarships. The notable amongmore » these are the two regional finalist positions in the 1999 Siemens-Westinghouse Science and Technology Competitions; 1st Place U.S. Army Award, 2006; 1st Place U.S. Naval Science Award, 2006; Yale Science and Engineering Association Best 11th Grade Project, 2006; Society of Physics Students Book Award, 2006; APS Corporate Minority Scholarship and others. This workshop program conducted by the HU CFRT has been an exemplary success, and served the minority and female students exceptionally fruitfully. The Summer High School Fusion Science Workshop is an immensely successful outreach activity conducted by the HU CFRT. In this workshop, we train, motivate, and provide high quality research experiences to young and talented high school scholars with emphasis on under-represented minorities and female students in fusion science and related areas. The purpose of this workshop is to expose minority and female students to the excitement of research in science at an early stage in their academic lives. It is our hope that this may lead the high school students to pursue higher education and careers in physical sciences, mathematics, and perhaps in fusion science. To our knowledge, this workshop is the first and only one to date, of fusion science for under-represented minorities and female high school students at an HBCU. The faculty researchers in the HU CFRT mentor the students during summers. Mentors spend a considerable amount of time and efforts in training, teaching, guiding and supervising research projects. The HU CFRT has so far conducted nine workshops during the summers of 1996-2000 and 2002-2005. The first workshop was conducted in summer 1996. Students for the workshop are chosen from a national pool of exceptionally talented high school rising seniors/juniors. To our knowledge, most of these students have gone on to prestigious universities such as Duke University, John Hopkins University, CalTech, UCLA, Hampton University, etc. after completing their high school. For instance, Tiffany Fisher, participant of the 1996 summer workshop completed her BS in Mathematics at Hampton University in May 2001. She then went on to Wake Forest University at Winston-Salem, North Carolina to pursue graduate studies. Anshul Haldipur, participant of the 1999 summer workshop, began his undergraduate studies at Duke University in 2000. Christina Nguyen and Ilissa Martinez, participants of the 2000 summer workshop, are pursuing their undergraduate degrees at the UCLA and Florida State University respectively. The organizing committee of the APS DPP annual meeting invited Dr. Punjabi to deliver an invited talk on training the next generation of fusion scientists and engineers at the 2005 APS DPP meeting in Denver, CO. The organizing committee distributed a special flier with the Bulletin to highlight this invited talk and another talk on education as well the expo. This has given wide publicity and recognition to our workshops and Hampton University. Prof. Punjabi's talk: 'LI2 2: Training the next generation of fusion scientists and engineers: summer high school fusion science workshop, Bull. Amer. Phys. Soc. 50, 221 (2005)' was very well-received. He talked about HU education and outreach initiative and the HU CFRT Summer High School Workshop. The audience had a considerable number of questions about our workshops and the High School to PhD Pipeline in fusion science. Professor William Mathews of University of Delaware offered to give the HU Team MHD codes to use, and Professor Birdsall of University of California, Berkeley, plasma theory and simulation group, offered to give the team simple simulation codes to use. We are very happy and proud and very gratified by this, and we thank the US DOE OFES, Dr. Sam Barish and Dr. Michael Crisp for their support and encouragement.« less

Antibody-cytokine fusion proteins for improving efficacy and safety of cancer therapy.

PubMed

Valedkarimi, Zahra; Nasiri, Hadi; Aghebati-Maleki, Leili; Majidi, Jafar

2017-11-01

Cytokines are key players in the regulation of immune responses both in physiological and pathological states. A number of cytokines have been evaluated in clinical trials and shown promising results in the treatment of different malignancies. Despite this, the clinical application of these molecules may be plagued by undesirable side effects The development of recombinant antibody-cytokine fusion proteins, which offer a means for target delivery of cytokines toward the tumor site, has significantly improved the therapeutic index of these immunomodulatory molecules. Selective tumor localization is provided by the monoclonal antibody component of the fusion protein that binds to the molecules present on the surface of tumor cells or accumulated preferentially in the diseased site. In this manner, the cytokine element is specifically located at the tumor site and can stimulate immune cells with appropriate cytokine receptors. Over the recent years, several antibody-cytokine fusion proteins have been developed with the capacity to target a wide variety of cancers whose application, in some cases, has led to complete rejection of the tumor. These findings support the notion that antibody-cytokine fusion proteins represent huge potential for cancer therapy. This review presents an overview of the advances made in the field of targeted cytokine delivery, which is made possible by genetically engineering antibody-cytokine fusion proteins. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Facility Monitoring: A Qualitative Theory for Sensor Fusion

NASA Technical Reports Server (NTRS)

Figueroa, Fernando

2001-01-01

Data fusion and sensor management approaches have largely been implemented with centralized and hierarchical architectures. Numerical and statistical methods are the most common data fusion methods found in these systems. Given the proliferation and low cost of processing power, there is now an emphasis on designing distributed and decentralized systems. These systems use analytical/quantitative techniques or qualitative reasoning methods for date fusion.Based on other work by the author, a sensor may be treated as a highly autonomous (decentralized) unit. Each highly autonomous sensor (HAS) is capable of extracting qualitative behaviours from its data. For example, it detects spikes, disturbances, noise levels, off-limit excursions, step changes, drift, and other typical measured trends. In this context, this paper describes a distributed sensor fusion paradigm and theory where each sensor in the system is a HAS. Hence, given the reach qualitative information from each HAS, a paradigm and formal definitions are given so that sensors and processes can reason and make decisions at the qualitative level. This approach to sensor fusion makes it possible the implementation of intuitive (effective) methods to monitor, diagnose, and compensate processes/systems and their sensors. This paradigm facilitates a balanced distribution of intelligence (code and/or hardware) to the sensor level, the process/system level, and a higher controller level. The primary application of interest is in intelligent health management of rocket engine test stands.

Analysis of Internet Information on Lateral Lumbar Interbody Fusion.

PubMed

Belayneh, Rebekah; Mesfin, Addisu

2016-07-01

Lateral lumbar interbody fusion (LLIF) is a surgical technique that is being increasingly used. The authors' objective was to examine information on the Internet pertaining to the LLIF technique. An analysis was conducted of publicly accessible websites pertaining to LLIF. The following search engines were used: Google (www.google.com), Bing (www.bing.com), and Yahoo (www.yahoo.com). DuckDuckGo (www.duckduckgo.com) was an additional search engine used due to its emphasis on generating accurate and consistent results while protecting searchers' privacy and reducing advertisements. The top 35 websites providing information on LLIF from the 4 search engines were identified. A total of 140 websites were evaluated. Each web-site was categorized based on authorship (academic, private, medical industry, insurance company, other) and content of information. Using the search term lateral lumbar interbody fusion, 174,000 Google results, 112,000 Yahoo results, and 112,000 Bing results were obtained. DuckDuckGo does not display the number of results found for a search. From the top 140 websites collected from each website, 78 unique websites were identified. Websites were authored by a private medical group in 46.2% of the cases, an academic medical group in 26.9% of the cases, and the biomedical industry in 5.1% of the cases. Sixty-eight percent of websites reported indications, and 24.4% reported contraindications. Benefits of LLIF were reported by 69.2% of websites. Thirty-six percent of websites reported complications of LLIF. Overall, the quality of information regarding LLIF on the Internet is poor. Spine surgeons and spine societies can assist in improving the quality of the information on the Internet regarding LLIF. [Orthopedics. 2016; 39(4):e701-e707.]. Copyright 2016, SLACK Incorporated.

Cost-Utility Analysis of Pedicle Screw Removal After Successful Posterior Instrumented Fusion in Thoracolumbar Burst Fractures.

PubMed

Lee, Han-Dong; Jeon, Chang-Hoon; Chung, Nam-Su; Seo, Young-Wook

2017-08-01

A cost-utility analysis (CUA). The aim of this study was to determine the cost-effectiveness of pedicle screw removal after posterior fusion in thoracolumbar burst fractures. Pedicle screw instrumentation is a standard fixation method for unstable thoracolumbar burst fracture. However, removal of the pedicle screw after successful fusion remains controversial because the clinical benefits remain unclear. CUA can help clinicians make appropriate decisions about optimal health care for pedicle screw removal after successful fusion in thoracolumbar burst fractures. We conducted a single-center, retrospective, longitudinal matched-cohort study of prospectively collected outcomes. In total, 88 consecutive patients who had undergone pedicle screw instrumentation for thoracolumbar burst fracture with successful fusion confirmed by computed tomography (CT) were used in this study. In total, 45 patients wanted to undergo implant removal surgery (R group), and 43 decided not to remove the implant (NR group). A CUA was conducted from the health care perspective. The direct costs of health care were obtained from the medical bill of each patient. Changes in health-related quality of life (HRQoL) scores, validated by Short Form 6D, were used to calculate quality-adjusted life-years (QALYs). Total costs and gained QALY were calculated at 1 year (1 year) and 2 years (2 years) compared with baseline. Results are expressed as an incremental cost-effectiveness ratio (ICER). Different discount rates (0%, 3%, and 5%) were applied to both cost and QALY for sensitivity analysis. Baseline patient variables were similar between the two groups (all P > 0.05). The additional benefits of implant removal (0.201 QALY at 2 years) were achieved with additional costs ($2541 at 2 years), equating to an ICER of $12,641/QALY. On the basis of the different discount rates, the robustness of our study's results was also determined. Implant removal after successful fusion in a thoracolumbar burst fracture is cost-effective until postoperative year 2. 3.

Flexibility of the Head-Stalk Linker Domain of Paramyxovirus HN Glycoprotein Is Essential for Triggering Virus Fusion.

PubMed

Adu-Gyamfi, Emmanuel; Kim, Lori S; Jardetzky, Theodore S; Lamb, Robert A

2016-10-15

The Paramyxoviridae comprise a large family of enveloped, negative-sense, single-stranded RNA viruses with significant economic and public health implications. For nearly all paramyxoviruses, infection is initiated by fusion of the viral and host cell plasma membranes in a pH-independent fashion. Fusion is orchestrated by the receptor binding protein hemagglutinin-neuraminidase (HN; also called H or G depending on the virus type) protein and a fusion (F) protein, the latter undergoing a major refolding process to merge the two membranes. Mechanistic details regarding the coupling of receptor binding to F activation are not fully understood. Here, we have identified the flexible loop region connecting the bulky enzymatically active head and the four-helix bundle stalk to be essential for fusion promotion. Proline substitution in this region of HN of parainfluenza virus 5 (PIV5) and Newcastle disease virus HN abolishes cell-cell fusion, whereas HN retains receptor binding and neuraminidase activity. By using reverse genetics, we engineered recombinant PIV5-EGFP viruses with mutations in the head-stalk linker region of HN. Mutations in this region abolished virus recovery and infectivity. In sum, our data suggest that the loop region acts as a "hinge" around which the bulky head of HN swings to-and-fro to facilitate timely HN-mediate F-triggering, a notion consistent with the stalk-mediated activation model of paramyxovirus fusion. Paramyxovirus fusion with the host cell plasma membrane is essential for virus infection. Membrane fusion is orchestrated via interaction of the receptor binding protein (HN, H, or G) with the viral fusion glycoprotein (F). Two distinct models have been suggested to describe the mechanism of fusion: these include "the clamp" and the "provocateur" model of activation. By using biochemical and reverse genetics tools, we have obtained strong evidence in favor of the HN stalk-mediated activation of paramyxovirus fusion. Specifically, our data strongly support the notion that the short linker between the head and stalk plays a role in "conformational switching" of the head group to facilitate F-HN interaction and triggering. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Flexibility of the Head-Stalk Linker Domain of Paramyxovirus HN Glycoprotein Is Essential for Triggering Virus Fusion

PubMed Central

Adu-Gyamfi, Emmanuel; Kim, Lori S.; Jardetzky, Theodore S.

2016-01-01

ABSTRACT The Paramyxoviridae comprise a large family of enveloped, negative-sense, single-stranded RNA viruses with significant economic and public health implications. For nearly all paramyxoviruses, infection is initiated by fusion of the viral and host cell plasma membranes in a pH-independent fashion. Fusion is orchestrated by the receptor binding protein hemagglutinin-neuraminidase (HN; also called H or G depending on the virus type) protein and a fusion (F) protein, the latter undergoing a major refolding process to merge the two membranes. Mechanistic details regarding the coupling of receptor binding to F activation are not fully understood. Here, we have identified the flexible loop region connecting the bulky enzymatically active head and the four-helix bundle stalk to be essential for fusion promotion. Proline substitution in this region of HN of parainfluenza virus 5 (PIV5) and Newcastle disease virus HN abolishes cell-cell fusion, whereas HN retains receptor binding and neuraminidase activity. By using reverse genetics, we engineered recombinant PIV5-EGFP viruses with mutations in the head-stalk linker region of HN. Mutations in this region abolished virus recovery and infectivity. In sum, our data suggest that the loop region acts as a “hinge” around which the bulky head of HN swings to-and-fro to facilitate timely HN-mediate F-triggering, a notion consistent with the stalk-mediated activation model of paramyxovirus fusion. IMPORTANCE Paramyxovirus fusion with the host cell plasma membrane is essential for virus infection. Membrane fusion is orchestrated via interaction of the receptor binding protein (HN, H, or G) with the viral fusion glycoprotein (F). Two distinct models have been suggested to describe the mechanism of fusion: these include “the clamp” and the “provocateur” model of activation. By using biochemical and reverse genetics tools, we have obtained strong evidence in favor of the HN stalk-mediated activation of paramyxovirus fusion. Specifically, our data strongly support the notion that the short linker between the head and stalk plays a role in “conformational switching” of the head group to facilitate F-HN interaction and triggering. PMID:27489276

Feasibility study of a magnetic fusion production reactor

NASA Astrophysics Data System (ADS)

Moir, R. W.

1986-12-01

A magnetic fusion reactor can produce 10.8 kg of tritium at a fusion power of only 400 MW —an order of magnitude lower power than that of a fission production reactor. Alternatively, the same fusion reactor can produce 995 kg of plutonium. Either a tokamak or a tandem mirror production plant can be used for this purpose; the cost is estimated at about 1.4 billion (1982 dollars) in either case. (The direct costs are estimated at 1.1 billion.) The production cost is calculated to be 22,000/g for tritium and 260/g for plutonium of quite high purity (1%240Pu). Because of the lack of demonstrated technology, such a plant could not be constructed today without significant risk. However, good progress is being made in fusion technology and, although success in magnetic fusion science and engineering is hard to predict with assurance, it seems possible that the physics basis and much of the needed technology could be demonstrated in facilities now under construction. Most of the remaining technology could be demonstrated in the early 1990s in a fusion test reactor of a few tens of megawatts. If the Magnetic Fusion Energy Program constructs a fusion test reactor of approximately 400 MW of fusion power as a next step in fusion power development, such a facility could be used later as a production reactor in a spinoff application. A construction decision in the late 1980s could result in an operating production reactor in the late 1990s. A magnetic fusion production reactor (MFPR) has four potential advantages over a fission production reactor: (1) no fissile material input is needed; (2) no fissioning exists in the tritium mode and very low fissioning exists in the plutonium mode thus avoiding the meltdown hazard; (3) the cost will probably be lower because of the smaller thermal power required; (4) and no reprocessing plant is needed in the tritium mode. The MFPR also has two disadvantages: (1) it will be more costly to operate because it consumes rather than sells electricity, and (2) there is a risk of not meeting the design goals.

Energy and technology review, July--August, 1990

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burnham, A.K.

1990-01-01

This report highlights various research programs conducted at the Lab to include: defense systems, laser research, fusion energy, biomedical and environmental sciences, engineering, physics, chemistry, materials science, and computational analysis. It also contains a statement on the state of the Lab and Laboratory Administration. (JEF)

Constructive Ontology Engineering

ERIC Educational Resources Information Center

Sousan, William L.

2010-01-01

The proliferation of the Semantic Web depends on ontologies for knowledge sharing, semantic annotation, data fusion, and descriptions of data for machine interpretation. However, ontologies are difficult to create and maintain. In addition, their structure and content may vary depending on the application and domain. Several methods described in…

Somatic chromosomal engineering identifies BCAN-NTRK1 as a potent glioma driver and therapeutic target.

PubMed

Cook, Peter J; Thomas, Rozario; Kannan, Ram; de Leon, Esther Sanchez; Drilon, Alexander; Rosenblum, Marc K; Scaltriti, Maurizio; Benezra, Robert; Ventura, Andrea

2017-07-11

The widespread application of high-throughput sequencing methods is resulting in the identification of a rapidly growing number of novel gene fusions caused by tumour-specific chromosomal rearrangements, whose oncogenic potential remains unknown. Here we describe a strategy that builds upon recent advances in genome editing and combines ex vivo and in vivo chromosomal engineering to rapidly and effectively interrogate the oncogenic potential of genomic rearrangements identified in human brain cancers. We show that one such rearrangement, an microdeletion resulting in a fusion between Brevican (BCAN) and Neurotrophic Receptor Tyrosine Kinase 1 (NTRK1), is a potent oncogenic driver of high-grade gliomas and confers sensitivity to the experimental TRK inhibitor entrectinib. This work demonstrates that BCAN-NTRK1 is a bona fide human glioma driver and describes a general strategy to define the oncogenic potential of novel glioma-associated genomic rearrangements and to generate accurate preclinical models of this lethal human cancer.

How much does a tokamak reactor cost?

NASA Astrophysics Data System (ADS)

Freidberg, J.; Cerfon, A.; Ballinger, S.; Barber, J.; Dogra, A.; McCarthy, W.; Milanese, L.; Mouratidis, T.; Redman, W.; Sandberg, A.; Segal, D.; Simpson, R.; Sorensen, C.; Zhou, M.

2017-10-01

The cost of a fusion reactor is of critical importance to its ultimate acceptability as a commercial source of electricity. While there are general rules of thumb for scaling both overnight cost and levelized cost of electricity the corresponding relations are not very accurate or universally agreed upon. We have carried out a series of scaling studies of tokamak reactor costs based on reasonably sophisticated plasma and engineering models. The analysis is largely analytic, requiring only a simple numerical code, thus allowing a very large number of designs. Importantly, the studies are aimed at plasma physicists rather than fusion engineers. The goals are to assess the pros and cons of steady state burning plasma experiments and reactors. One specific set of results discusses the benefits of higher magnetic fields, now possible because of the recent development of high T rare earth superconductors (REBCO); with this goal in mind, we calculate quantitative expressions, including both scaling and multiplicative constants, for cost and major radius as a function of central magnetic field.

High Efficiency push-pull class E amplifiers for fusion rocket engines

NASA Astrophysics Data System (ADS)

Gaitan, Gabriel; Ham, Eric; Cohen, S. A.; Swanson, Charles; Chen, Minjie; Brunkhorst, Christopher

2017-10-01

In a Field Reversed Configuration fusion reactor, ions in the plasma are heated by an antenna operating at RF frequencies. This paper presents how push-pull class E amplifiers can be used to efficiently drive this antenna in the MHz range, from 0.5MHz to 4 MHz, while maintaining low harmonic content in the output signal. We offer four different configurations that present a trade-off between efficiency and low harmonic content. The paper presents theoretical values and breadboard results from these configurations, which operate at a power of around 100W. For a practical design, multiple amplifiers would be linked in parallel and would power the RF antenna at around 1MW. These designs provide multiple different options for reactor systems that could be used in a variety of applications, from power plants on the ground to rocket engines in space. This work was supported, in part, by DOE Contract Number DE-AC02-09CH11466 and Princeton Environmental Institute.

Engineering Technical Review Planning Briefing

NASA Technical Reports Server (NTRS)

Gardner, Terrie

2012-01-01

The general topics covered in the engineering technical planning briefing are 1) overviews of NASA, Marshall Space Flight Center (MSFC), and Engineering, 2) the NASA Systems Engineering(SE) Engine and its implementation , 3) the NASA Project Life Cycle, 4) MSFC Technical Management Branch Services in relation to the SE Engine and the Project Life Cycle , 5) Technical Reviews, 6) NASA Human Factor Design Guidance , and 7) the MSFC Human Factors Team. The engineering technical review portion of the presentation is the primary focus of the overall presentation and will address the definition of a design review, execution guidance, the essential stages of a technical review, and the overall review planning life cycle. Examples of a technical review plan content, review approaches, review schedules, and the review process will be provided and discussed. The human factors portion of the presentation will focus on the NASA guidance for human factors. Human factors definition, categories, design guidance, and human factor specialist roles will be addressed. In addition, the NASA Systems Engineering Engine description, definition, and application will be reviewed as background leading into the NASA Project Life Cycle Overview and technical review planning discussion.

Fusion tags for protein solubility, purification and immunogenicity in Escherichia coli: the novel Fh8 system

PubMed Central

Costa, Sofia; Almeida, André; Castro, António; Domingues, Lucília

2014-01-01

Proteins are now widely produced in diverse microbial cell factories. The Escherichia coli is still the dominant host for recombinant protein production but, as a bacterial cell, it also has its issues: the aggregation of foreign proteins into insoluble inclusion bodies is perhaps the main limiting factor of the E. coli expression system. Conversely, E. coli benefits of cost, ease of use and scale make it essential to design new approaches directed for improved recombinant protein production in this host cell. With the aid of genetic and protein engineering novel tailored-made strategies can be designed to suit user or process requirements. Gene fusion technology has been widely used for the improvement of soluble protein production and/or purification in E. coli, and for increasing peptide’s immunogenicity as well. New fusion partners are constantly emerging and complementing the traditional solutions, as for instance, the Fh8 fusion tag that has been recently studied and ranked among the best solubility enhancer partners. In this review, we provide an overview of current strategies to improve recombinant protein production in E. coli, including the key factors for successful protein production, highlighting soluble protein production, and a comprehensive summary of the latest available and traditionally used gene fusion technologies. A special emphasis is given to the recently discovered Fh8 fusion system that can be used for soluble protein production, purification, and immunogenicity in E. coli. The number of existing fusion tags will probably increase in the next few years, and efforts should be taken to better understand how fusion tags act in E. coli. This knowledge will undoubtedly drive the development of new tailored-made tools for protein production in this bacterial system. PMID:24600443

Production and characterization of active recombinant interleukin-12/eGFP fusion protein in stably-transfected DF1 chicken cells.

PubMed

Wu, Hsing Chieh; Chen, Yu San; Shen, Pin Chun; Shien, Jui Hung; Lee, Long Huw; Chiu, Hua Hsien

2015-01-01

The adjuvant activity of chicken interleukin-12 (chIL-12) protein has been described as similar to that of mammalian IL-12. Recombinant chIL-12 can be produced using several methods, but chIL-12 production in eukaryotic cells is lower than that in prokaryotic cells. Stimulating compounds, such as dimethyl sulfoxide (DMSO), can be added to animal cell cultures to overcome this drawback. In this study, we constructed a cell line, DF1/chIL-12 which stably expressed a fusion protein, chIL-12 and enhanced green fluorescent protein (eGFP) connected by a (G4 S)3 linker sequence. Fusion protein production was increased when cells were cultured in the presence of DMSO. When 1 × 10(6) DF1/chIL-12 cells were inoculated in a T-175 flask containing 30 mL of media, incubated for 15 h, and further cultivated in the presence of 4% DMSO for 48 h, the production of total fusion protein was mostly enhanced compared with the production of total fusion protein by using cell lysates induced with DMSO at other concentrations. The concentrations of the unpurified and purified total fusion proteins in cell lysates were 2,781 ± 2.72 ng mL(-1) and 2,207 ± 3.28 ng mL(-1) , respectively. The recovery rate was 79%. The fusion protein stimulated chicken splenocytes to produce IFN-γ, which was measured using an enzyme-linked immunosorbent assay, in the culture supernatant, indicating that treating DF1/chIL-12 cells with DMSO or producing chIL-12 in a fusion protein form does not have adverse effects on the bioactivity of chIL-12. © 2015 American Institute of Chemical Engineers.

Conservation of Life as a Unifying Theme for Process Safety in Chemical Engineering Education

ERIC Educational Resources Information Center

Klein, James A.; Davis, Richard A.

2011-01-01

This paper explores the use of "conservation of life" as a concept and unifying theme for increasing awareness, application, and integration of process safety in chemical engineering education. Students need to think of conservation of mass, conservation of energy, and conservation of life as equally important in engineering design and analysis.…

Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

PubMed Central

Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

2018-01-01

Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

Combining cognitive engineering and information fusion architectures to build effective joint systems

NASA Astrophysics Data System (ADS)

Sliva, Amy L.; Gorman, Joe; Voshell, Martin; Tittle, James; Bowman, Christopher

2016-05-01

The Dual Node Decision Wheels (DNDW) architecture concept was previously described as a novel approach toward integrating analytic and decision-making processes in joint human/automation systems in highly complex sociotechnical settings. In this paper, we extend the DNDW construct with a description of components in this framework, combining structures of the Dual Node Network (DNN) for Information Fusion and Resource Management with extensions on Rasmussen's Decision Ladder (DL) to provide guidance on constructing information systems that better serve decision-making support requirements. The DNN takes a component-centered approach to system design, decomposing each asset in terms of data inputs and outputs according to their roles and interactions in a fusion network. However, to ensure relevancy to and organizational fitment within command and control (C2) processes, principles from cognitive systems engineering emphasize that system design must take a human-centered systems view, integrating information needs and decision making requirements to drive the architecture design and capabilities of network assets. In the current work, we present an approach for structuring and assessing DNDW systems that uses a unique hybrid DNN top-down system design with a human-centered process design, combining DNN node decomposition with artifacts from cognitive analysis (i.e., system abstraction decomposition models, decision ladders) to provide work domain and task-level insights at different levels in an example intelligence, surveillance, and reconnaissance (ISR) system setting. This DNDW structure will ensure not only that the information fusion technologies and processes are structured effectively, but that the resulting information products will align with the requirements of human decision makers and be adaptable to different work settings .

Overproduction of Geranylgeraniol by Metabolically Engineered Saccharomyces cerevisiae▿

PubMed Central

Tokuhiro, Kenro; Muramatsu, Masayoshi; Ohto, Chikara; Kawaguchi, Toshiya; Obata, Shusei; Muramoto, Nobuhiko; Hirai, Masana; Takahashi, Haruo; Kondo, Akihiko; Sakuradani, Eiji; Shimizu, Sakayu

2009-01-01

(E, E, E)-Geranylgeraniol (GGOH) is a valuable starting material for perfumes and pharmaceutical products. In the yeast Saccharomyces cerevisiae, GGOH is synthesized from the end products of the mevalonate pathway through the sequential reactions of farnesyl diphosphate synthetase (encoded by the ERG20 gene), geranylgeranyl diphosphate synthase (the BTS1 gene), and some endogenous phosphatases. We demonstrated that overexpression of the diacylglycerol diphosphate phosphatase (DPP1) gene could promote GGOH production. We also found that overexpression of a BTS1-DPP1 fusion gene was more efficient for producing GGOH than coexpression of these genes separately. Overexpression of the hydroxymethylglutaryl-coenzyme A reductase (HMG1) gene, which encodes the major rate-limiting enzyme of the mevalonate pathway, resulted in overproduction of squalene (191.9 mg liter−1) rather than GGOH (0.2 mg liter−1) in test tube cultures. Coexpression of the BTS1-DPP1 fusion gene along with the HMG1 gene partially redirected the metabolic flux from squalene to GGOH. Additional expression of a BTS1-ERG20 fusion gene resulted in an almost complete shift of the flux to GGOH production (228.8 mg liter−1 GGOH and 6.5 mg liter−1 squalene). Finally, we constructed a diploid prototrophic strain coexpressing the HMG1, BTS1-DPP1, and BTS1-ERG20 genes from multicopy integration vectors. This strain attained 3.31 g liter−1 GGOH production in a 10-liter jar fermentor with gradual feeding of a mixed glucose and ethanol solution. The use of bifunctional fusion genes such as the BTS1-DPP1 and ERG20-BTS1 genes that code sequential enzymes in the metabolic pathway was an effective method for metabolic engineering. PMID:19592534

Evaluation of CFETR as a Fusion Nuclear Science Facility using multiple system codes

NASA Astrophysics Data System (ADS)

Chan, V. S.; Costley, A. E.; Wan, B. N.; Garofalo, A. M.; Leuer, J. A.

2015-02-01

This paper presents the results of a multi-system codes benchmarking study of the recently published China Fusion Engineering Test Reactor (CFETR) pre-conceptual design (Wan et al 2014 IEEE Trans. Plasma Sci. 42 495). Two system codes, General Atomics System Code (GASC) and Tokamak Energy System Code (TESC), using different methodologies to arrive at CFETR performance parameters under the same CFETR constraints show that the correlation between the physics performance and the fusion performance is consistent, and the computed parameters are in good agreement. Optimization of the first wall surface for tritium breeding and the minimization of the machine size are highly compatible. Variations of the plasma currents and profiles lead to changes in the required normalized physics performance, however, they do not significantly affect the optimized size of the machine. GASC and TESC have also been used to explore a lower aspect ratio, larger volume plasma taking advantage of the engineering flexibility in the CFETR design. Assuming the ITER steady-state scenario physics, the larger plasma together with a moderately higher BT and Ip can result in a high gain Qfus ˜ 12, Pfus ˜ 1 GW machine approaching DEMO-like performance. It is concluded that the CFETR baseline mode can meet the minimum goal of the Fusion Nuclear Science Facility (FNSF) mission and advanced physics will enable it to address comprehensively the outstanding critical technology gaps on the path to a demonstration reactor (DEMO). Before proceeding with CFETR construction steady-state operation has to be demonstrated, further development is needed to solve the divertor heat load issue, and blankets have to be designed with tritium breeding ratio (TBR) >1 as a target.

Advancing Pre-college Science and Mathematics Education

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Rick

With support from the US Department of Energy, Office of Science, Fusion Energy Sciences, and General Atomics, an educational and outreach program primarily for grades G6-G13 was developed using the basic science of plasma and fusion as the content foundation. The program period was 1994 - 2015 and provided many students and teachers unique experiences such as a visit to the DIII-D National Fusion Facility to tour the nation’s premiere tokamak facility or to interact with interesting and informative demonstration equipment and have the opportunity to increase their understanding of a wide range of scientific content, including states of matter,more » the electromagnetic spectrum, radiation & radioactivity, and much more. Engaging activities were developed for classroom-size audiences, many made by teachers in Build-it Day workshops. Scientist and engineer team members visited classrooms, participated in science expositions, held workshops, produced informational handouts in paper, video, online, and gaming-CD format. Participants could interact with team members from different institutions and countries and gain a wider view of the world of science and engineering educational and career possibilities. In addition, multiple science stage shows were presented to audiences of up to 700 persons in a formal theatre setting over a several day period at Science & Technology Education Partnership (STEP) Conferences. Annually repeated participation by team members in various classroom and public venue events allowed for the development of excellent interactive skills when working with students, teachers, and educational administrative staff members. We believe this program has had a positive impact in science understanding and the role of the Department of Energy in fusion research on thousands of students, teachers, and members of the general public through various interactive venues.« less

Fusion of Tracks with Road Constraints

DTIC Science & Technology

2008-06-12

of orthogonality, the projec- tion error vector »¡ »D is orthogonal to D, i.e., each and every basis of it: h»¡ »D, dii = h»¡DTc, dii = dTi (»¡DTc) = 0, i... Electrical Engineers, 2004. [13] M. Ulmke and W. Koch Multi hypothesis track extraction and maintenance of GMTI sensor data. In Proceedings of the 8th...in Annapolis, MD (2000) and in Philadelphia, PA (2005), respectively. Dr. Yang is also an Adjunct Professor of Electrical and Computer Engineering at

Case report: 122° kyphosis secondary to C5-L3 laminectomy and quadriplegia, surgical correction and 30-year follow-up.

PubMed

Winter, R B; Akbarnia, B A

2011-09-01

The study design was a case report with 30-year follow-up. In 1980, there were no pedicle screws available, so it was a great challenge to achieve correction and fusion in a patient with no laminae, and who was quadriplegic. Such a case with such a long follow-up has not been previously reported. This is a single case report with an ultra-long follow-up. The patient underwent an anterior fusion from T3 to L4 via two incisions, and at a second stage, a posterior fusion from T3 to S1 using Luque rods and wires passed through the foramenae. After 2 years he underwent repair of two pseudarthroses with both anterior and posterior procedures. He achieved solid fusion following the pseudarthrosis repair. Although being a C7 quadriplegic all his life, he is totally independent in his activities of daily living, and is fully employed. Correction and fusion can be achieved even in the absence of laminae and pedicle screws.

Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells.

PubMed Central

Gillies, S D; Reilly, E B; Lo, K M; Reisfeld, R A

1992-01-01

A genetically engineered fusion protein consisting of a chimeric anti-ganglioside GD2 antibody (ch14.18) and interleukin 2 (IL2) was tested for its ability to enhance the killing of autologous GD2-expressing melanoma target cells by a tumor-infiltrating lymphocyte line (660 TIL). The fusion of IL2 to the carboxyl terminus of the immunoglobulin heavy chain did not reduce IL2 activity as measured in a standard proliferation assay using either mouse or human T-cell lines. Antigen-binding activity was greater than that of the native chimeric antibody. The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein. This stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2. Such antibody-cytokine fusion proteins may prove useful in targeting the biological effect of IL2 and other cytokines to tumor cells and in this way stimulate their immune destruction. Images PMID:1741398

Visualizing and quantifying protein secretion using a Renilla luciferase-GFP fusion protein.

PubMed

Liu, J; Wang, Y; Szalay, A A; Escher, A

2000-01-01

We have shown previously that an engineered form of Renilla luciferase (SRUC) can be secreted as a functional enzyme by mammalian cells, and that fusing wild-type Renilla luciferase with the green fluorescent protein from Aequorea victoria (GFP) yields a chimeric protein retaining light-emission properties similar to that of unfused Renilla luciferase and GFP. In the work presented here, SRUC was fused with GFP to determine whether it could be used to both visualize and quantify protein secretion in mammalian cells. Simian COS-7 and Chinese hamster ovary (CHO) cells were transiently transfected with gene constructs encoding a secreted or an intracellular version of a Renilla luciferase-GFP fusion protein. Renilla luciferase activity was measured from COS-7 cell lysates and culture media, and GFP activity was detected in CHO cells using fluorescence microscopy. Data indicated that the SRUC-GFP fusion protein was secreted as a chimeric protein that had both Renilla luciferase and GFP activity. This fusion protein could be a useful marker for the study of protein secretion in mammalian cells. Copyright 2000 John Wiley & Sons, Ltd.

A New Method to Measure Temperature and Burner Pattern Factor Sensing for Active Engine Control

NASA Technical Reports Server (NTRS)

Ng, Daniel

1999-01-01

The determination of the temperatures of extended surfaces which exhibit non-uniform temperature variation is very important for a number of applications including the "Burner Pattern Factor" (BPF) of turbine engines. Exploratory work has shown that use of BPF to control engine functions can result in many benefits, among them reduction in engine weight, reduction in operating cost, increase in engine life, while attaining maximum engine efficiency. Advanced engines are expected to operate at very high temperature to achieve high efficiency. Brief exposure of engine components to higher than design temperatures due to non-uniformity in engine burner pattern can reduce engine life. The engine BPF is a measure of engine temperature uniformity. Attainment of maximum temperature uniformity and high temperatures is key to maximum efficiency and long life. A new approach to determine through the measurement of just one radiation spectrum by a multiwavelength pyrometer is possible. This paper discusses a new temperature sensing approach and its application to determine the BPF.

In planta expression of HIV-1 p24 protein using an RNA plant virus-based expression vector.

PubMed

Zhang, G; Leung, C; Murdin, L; Rovinski, B; White, K A

2000-02-01

Plant viruses show significant potential as expression vectors for the production of foreign proteins (e.g., antigens) in plants. The HIV-1 p24 nucleocapsid protein is an important early marker of HIV infection and has been used as an antigen in the development of HIV vaccines. Toward developing a plant-based expression system for the production of p24, we have investigated the use of a (positive)-strand RNA plant virus, tomato bushy stunt virus (TBSV), as an expression vector. The HIV p24 open reading frame (ORF) was introduced into a cloned cDNA copy of the TBSV genome as an in-frame fusion with a 5'-terminal portion of the TBSV coat protein ORF. In vitro-generated RNA transcripts corresponding to the engineered virus vector were infectious when inoculated into plant protoplasts; Northern and Western blot analyses verified the accumulation of a predicted p24-encoding viral subgenomic mRNA and the production of p24 fusion product. Whole-plant infections with the viral vector led to the accumulation of p24 fusion protein in inoculated leaves, which cross-reacted with p24-specific antibodies, thus confirming the maintenance of key antigenic determinants. This study is the first to demonstrate that TBSV can be engineered to express a complete foreign protein of clinical importance. Strategies for optimizing protein yield from this viral vector are discussed.

Neutronics Comparison Analysis of the Water Cooled Ceramics Breeding Blanket for CFETR

NASA Astrophysics Data System (ADS)

Li, Jia; Zhang, Xiaokang; Gao, Fangfang; Pu, Yong

2016-02-01

China Fusion Engineering Test Reactor (CFETR) is an ITER-like fusion engineering test reactor that is intended to fill the scientific and technical gaps between ITER and DEMO. One of the main missions of CFETR is to achieve a tritium breeding ratio that is no less than 1.2 to ensure tritium self-sufficiency. A concept design for a water cooled ceramics breeding blanket (WCCB) is presented based on a scheme with the breeder and the multiplier located in separate panels for CFETR. Based on this concept, a one-dimensional (1D) radial built breeding blanket was first designed, and then several three-dimensional models were developed with various neutron source definitions and breeding blanket module arrangements based on the 1D radial build. A set of nuclear analyses have been carried out to compare the differences in neutronics characteristics given by different calculation models, addressing neutron wall loading (NWL), tritium breeding ratio (TBR), fast neutron flux on inboard side and nuclear heating deposition on main in-vessel components. The impact of differences in modeling on the nuclear performance has been analyzed and summarized regarding the WCCB concept design. supported by the National Special Project for Magnetic Confined Nuclear Fusion Energy (Nos. 2013GB108004, 2014GB122000, and 2014GB119000), and National Natural Science Foundation of China (No. 11175207)

Construction and Cloning of Reporter-Tagged Replicon cDNA for an In Vitro Replication Study of Murine Norovirus-1 (MNV-1)

PubMed Central

Ahmad, Muhammad Khairi; Tabana, Yasser M; Ahmed, Mowaffaq Adam; Sandai, Doblin Anak; Mohamed, Rafeezul; Ismail, Ida Shazrina; Zulkiflie, Nurulisa; Yunus, Muhammad Amir

2017-01-01

Background A norovirus maintains its viability, infectivity and virulence by its ability to replicate. However, the biological mechanisms of the process remain to be explored. In this work, the NanoLuc™ Luciferase gene was used to develop a reporter-tagged replicon system to study norovirus replication. Methods The NanoLuc™ Luciferase reporter protein was engineered to be expressed as a fusion protein for MNV-1 minor capsid protein, VP2. The foot-and-mouth disease virus 2A (FMDV2A) sequence was inserted between the 3′end of the reporter gene and the VP2 start sequence to allow co-translational ‘cleavage’ of fusion proteins during intracellular transcript expression. Amplification of the fusion gene was performed using a series of standard and overlapping polymerase chain reactions. The resulting amplicon was then cloned into three readily available backbones of MNV-1 cDNA clones. Results Restriction enzyme analysis indicated that the NanoLucTM Luciferase gene was successfully inserted into the parental MNV-1 cDNA clone. The insertion was further confirmed by using DNA sequencing. Conclusion NanoLuc™ Luciferase-tagged MNV-1 cDNA clones were successfully engineered. Such clones can be exploited to develop robust experimental assays for in vitro assessments of viral RNA replication. PMID:29379384

Factors associated with health-related quality of life among operating engineers.

PubMed

Choi, Seung Hee; Redman, Richard W; Terrell, Jeffrey E; Pohl, Joanne M; Duffy, Sonia A

2012-11-01

Because health-related quality of life among blue-collar workers has not been well studied, the purpose of this study was to determine factors associated with health-related quality of life among Operating Engineers. With cross-sectional data from a convenience sample of 498 Operating Engineers, personal and health behavioral factors associated with health-related quality of life were examined. Multivariate linear regression analysis revealed that personal factors (older age, being married, more medical comorbidities, and depression) and behavioral factors (smoking, low fruit and vegetable intake, low physical activity, high body mass index, and low sleep quality) were associated with poor health-related quality of life. Operating Engineers are at risk for poor health-related quality of life. Underlying medical comorbidities and depression should be well managed. Worksite wellness programs addressing poor health behaviors may be beneficial.

Direct heating of a laser-imploded core using ultraintense laser LFEX

NASA Astrophysics Data System (ADS)

Kitagawa, Y.; Mori, Y.; Ishii, K.; Hanayama, R.; Nishimura, Y.; Okihara, S.; Nakayama, S.; Sekine, T.; Takagi, M.; Watari, T.; Satoh, N.; Kawashima, T.; Komeda, O.; Hioki, T.; Motohiro, T.; Azuma, H.; Sunahara, A.; Sentoku, Y.; Arikawa, Y.; Abe, Y.; Miura, E.; Ozaki, T.

2017-07-01

A CD shell was preimploded by two counter-propagating green beams from the GEKKO laser system GXII (based at the Institute of Laser Engineering, Osaka University), forming a dense core. The core was predominantly heated by energetic ions driven by the laser for fast-ignition-fusion experiment, an extremely energetic ultrashort pulse laser, that is illuminated perpendicularly to the GXII axis. Consequently, we observed the D(d, n)3 He-reacted neutrons (DD beam-fusion neutrons) at a yield of 5× {{10}8} n/4π sr. The beam-fusion neutrons verified that the ions directly collided with the core plasma. Whereas the hot electrons heated the whole core volume, the energetic ions deposited their energies locally in the core. As evidenced in the spectrum, the process simultaneously excited thermal neutrons with a yield of 6× {{10}7} n/4π sr, raising the local core temperature from 0.8 to 1.8 keV. The shell-implosion dynamics (including the beam fusion and thermal fusion initiated by fast deuterons and carbon ions) can be explained by the one-dimensional hydrocode STAR 1D. Meanwhile, the core heating due to resistive processes driven by hot electrons, and also the generation of fast ions were well-predicted by the two-dimensional collisional particle-in-cell code. Together with hot electrons, the ion contribution to fast ignition is indispensable for realizing high-gain fusion. By virtue of its core heating and ignition, the proposed scheme can potentially achieve high-gain fusion.

The Quality and Readability of Information Available on the Internet Regarding Lumbar Fusion

PubMed Central

Zhang, Dafang; Schumacher, Charles; Harris, Mitchel B.; Bono, Christopher M.

2015-01-01

Study Design An Internet-based evaluation of Web sites regarding lumbar fusion. Objective The Internet has become a major resource for patients; however, the quality and readability of Internet information regarding lumbar fusion is unclear. The objective of this study is to evaluate the quality and readability of Internet information regarding lumbar fusion and to determine whether these measures changed with Web site modality, complexity of the search term, or Health on the Net Code of Conduct certification. Methods Using five search engines and three different search terms of varying complexity (“low back fusion,” “lumbar fusion,” and “lumbar arthrodesis”), we identified and reviewed 153 unique Web site hits for information quality and readability. Web sites were specifically analyzed by search term and Web site modality. Information quality was evaluated on a 5-point scale. Information readability was assessed using the Flesch-Kincaid score for reading grade level. Results The average quality score was low. The average reading grade level was nearly six grade levels above that recommended by National Work Group on Literacy and Health. The quality and readability of Internet information was significantly dependent on Web site modality. The use of more complex search terms yielded information of higher reading grade level but not higher quality. Conclusions Higher-quality information about lumbar fusion conveyed using language that is more readable by the general public is needed on the Internet. It is important for health care providers to be aware of the information accessible to patients, as it likely influences their decision making regarding care. PMID:26933614

The Quality and Readability of Information Available on the Internet Regarding Lumbar Fusion.

PubMed

Zhang, Dafang; Schumacher, Charles; Harris, Mitchel B; Bono, Christopher M

2016-03-01

Study Design An Internet-based evaluation of Web sites regarding lumbar fusion. Objective The Internet has become a major resource for patients; however, the quality and readability of Internet information regarding lumbar fusion is unclear. The objective of this study is to evaluate the quality and readability of Internet information regarding lumbar fusion and to determine whether these measures changed with Web site modality, complexity of the search term, or Health on the Net Code of Conduct certification. Methods Using five search engines and three different search terms of varying complexity ("low back fusion," "lumbar fusion," and "lumbar arthrodesis"), we identified and reviewed 153 unique Web site hits for information quality and readability. Web sites were specifically analyzed by search term and Web site modality. Information quality was evaluated on a 5-point scale. Information readability was assessed using the Flesch-Kincaid score for reading grade level. Results The average quality score was low. The average reading grade level was nearly six grade levels above that recommended by National Work Group on Literacy and Health. The quality and readability of Internet information was significantly dependent on Web site modality. The use of more complex search terms yielded information of higher reading grade level but not higher quality. Conclusions Higher-quality information about lumbar fusion conveyed using language that is more readable by the general public is needed on the Internet. It is important for health care providers to be aware of the information accessible to patients, as it likely influences their decision making regarding care.

[Construction and prokaryotic expression of recombinant gene EGFRvIII HBcAg and immunogenicity analysis of the fusion protein].

PubMed

Duan, Xiao-yi; Wang, Jian-sheng; Guo, You-min; Han, Jun-li; Wang, Quan-ying; Yang, Guang-xiao

2007-01-01

To construct recombinant prokaryotic expression plasmid pET28a(+)/c-PEP-3-c and evaluate the immunogenicity of the fusion protein. cDNA fragment encoding PEP-3 was obtained from pGEM-T Easy/PEP-3 and inserted into recombinant plasmid pGEMEX/HBcAg. Then it was subcloned in prokaryotic expression vector and transformed into E.coli BL21(DE3). The fusion protein was expressed by inducing IPTG and purified by Ni(2+)-NTA affinity chromatography. BALB/c mice were immunized with fusion protein and the antibody titre was determined by indirect ELISA. The recombinant gene was confirmed to be correct by restriction enzyme digestion and DNA sequencing. After prokaryotic expression, fusion protein existed in sediment and accounted for 56% of all bacterial lysate. The purified product accounted for 92% of all protein and its concentration was 8 g/L. The antibody titre in blood serum reached 1:16 000 after the fourth immunization and reached 1:2.56x10(5) after the sixth immunization. The titre of anti-PEP-3 antibody reached 1:1.28x10(5) and the titre of anti-HBcAg antibody was less than 1:4x10(3). Fusion gene PEP-3-HBcAg is highly expressed in E.coli BL21. The expressed fusion protein can induce neutralizing antibody with high titer and specificity, which lays a foundation for the study of genetically engineering vaccine for malignant tumors with the high expression of EGFRvIII.

A real-time monitoring platform of myogenesis regulators using double fluorescent labeling

PubMed Central

Sapoznik, Etai; Niu, Guoguang; Zhou, Yu; Prim, Peter M.; Criswell, Tracy L.

2018-01-01

Real-time, quantitative measurement of muscle progenitor cell (myoblast) differentiation is an important tool for skeletal muscle research and identification of drugs that support skeletal muscle regeneration. While most quantitative tools rely on sacrificial approach, we developed a double fluorescent tagging approach, which allows for dynamic monitoring of myoblast differentiation through assessment of fusion index and nuclei count. Fluorescent tagging of both the cell cytoplasm and nucleus enables monitoring of cell fusion and the formation of new myotube fibers, similar to immunostaining results. This labeling approach allowed monitoring the effects of Myf5 overexpression, TNFα, and Wnt agonist on myoblast differentiation. It also enabled testing the effects of surface coating on the fusion levels of scaffold-seeded myoblasts. The double fluorescent labeling of myoblasts is a promising technique to visualize even minor changes in myogenesis of myoblasts in order to support applications such as tissue engineering and drug screening. PMID:29444187

Educational Outreach at the M.I.T. Plasma Fusion Center

NASA Astrophysics Data System (ADS)

Censabella, V.

1996-11-01

Educational outreach at the MIT Plasma Fusion Center consists of volunteers working together to increase the public's knowledge of fusion and plasma-related experiments. Seeking to generate excitement about science, engineering and mathematics, the PFC holds a number of outreach activities throughout the year, such as Middle and High School Outreach Days. Outreach also includes the Mr. Magnet Program, which uses an interactive strategy to engage elementary school children. Included in this year's presentation will be a new and improved C-MOD Jr, a confinement video game which helps students to discover how computers manipulate magnetic pulses to keep a plasma confined for as long as possible. Also on display will be an educational toy created by the Cambridge Physics Outlet, a PFC spin-off company. The PFC maintains a Home Page on the World Wide Web, which can be reached at http://cmod2.pfc.mit.edu/.

Designing Radiation Resistance in Materials for Fusion Energy

NASA Astrophysics Data System (ADS)

Zinkle, S. J.; Snead, L. L.

2014-07-01

Proposed fusion and advanced (Generation IV) fission energy systems require high-performance materials capable of satisfactory operation up to neutron damage levels approaching 200 atomic displacements per atom with large amounts of transmutant hydrogen and helium isotopes. After a brief overview of fusion reactor concepts and radiation effects phenomena in structural and functional (nonstructural) materials, three fundamental options for designing radiation resistance are outlined: Utilize matrix phases with inherent radiation tolerance, select materials in which vacancies are immobile at the design operating temperatures, or engineer materials with high sink densities for point defect recombination. Environmental and safety considerations impose several additional restrictions on potential materials systems, but reduced-activation ferritic/martensitic steels (including thermomechanically treated and oxide dispersion-strengthened options) and silicon carbide ceramic composites emerge as robust structural materials options. Materials modeling (including computational thermodynamics) and advanced manufacturing methods are poised to exert a major impact in the next ten years.

Realizing steady-state tokamak operation for fusion energy

NASA Astrophysics Data System (ADS)

Luce, T. C.

2011-03-01

Continuous operation of a tokamak for fusion energy has clear engineering advantages but requires conditions beyond those sufficient for a burning plasma. The fusion reactions and external sources must support both the pressure and the current equilibrium without inductive current drive, leading to demands on stability, confinement, current drive, and plasma-wall interactions that exceed those for pulsed tokamaks. These conditions have been met individually, and significant progress has been made in the past decade to realize scenarios where the required conditions are obtained simultaneously. Tokamaks are operated routinely without disruptions near pressure limits, as needed for steady-state operation. Fully noninductive sustainment with more than half of the current from intrinsic currents has been obtained for a resistive time with normalized pressure and confinement approaching those needed for steady-state conditions. One remaining challenge is handling the heat and particle fluxes expected in a steady-state tokamak without compromising the core plasma performance.

Interstellar Travel without 'Magic'

NASA Astrophysics Data System (ADS)

Woodcock, G.

The possibility of interstellar space travel has become a popular subject. Distances of light years are an entirely new realm for human space travel. New means of propulsion are needed. Speculation about propulsion has included "magic", space warps, faster-than-light travel, known physics such as antimatter for which no practical implementation is known and also physics for which current research offers at least a hint of implementation, i.e. fusion. Performance estimates are presented for the latter and used to create vehicle concepts. Fusion propulsion will mean travel times of hundreds of years, so we adopt the "space colony" concepts of O'Neill as a ship design that could support a small civilization indefinitely; this provides the technical means. Economic reasoning is presented, arguing that development and production of "space colony" habitats for relief of Earth's population, with addition of fusion engines, will lead to vessels that can go interstellar. Scenarios are presented and a speculative estimate of a timetable is given.

Inducible model for β-six-mediated site-specific recombination in mammalian cells

PubMed Central

Servert, Pilar; Garcia-Castro, Javier; Díaz, Vicente; Lucas, Daniel; Gonzalez, Manuel A.; Martínez-A, Carlos; Bernad, Antonio

2006-01-01

The prokaryotic β recombinase catalyzes site-specific recombination between two directly oriented minimal six sites in chromatin-integrated substrates. Here, we demonstrate that an enhanced green fluorescent protein (EGFP)-fused version of β recombinase (β-EGFP) is fully active, retaining most specific activity. It is used to develop a recombination-dependent activatable gene expression (RAGE) system based on the androgen receptor (AR) ligand-binding domain (LBD). Two hybrid molecules, a direct fusion of the LBD-AR to the C-terminus of β recombinase (β-AR) and a triple fusion of β-EGFP to the same ligand-binding domain (β-EGFP-AR), were engineered and their subcellular behavior, stability and catalytic activity were evaluated. Both chimeric β recombinase proteins showed in vivo inducible recombinogenic activity dependent on addition of an androgen receptor agonist, although the β-AR fusion protein demonstrated more accurate ligand-dependent translocation from cytoplasm to nucleus. PMID:16394020

Identifying transposon insertions and their effects from RNA-sequencing data.

PubMed

de Ruiter, Julian R; Kas, Sjors M; Schut, Eva; Adams, David J; Koudijs, Marco J; Wessels, Lodewyk F A; Jonkers, Jos

2017-07-07

Insertional mutagenesis using engineered transposons is a potent forward genetic screening technique used to identify cancer genes in mouse model systems. In the analysis of these screens, transposon insertion sites are typically identified by targeted DNA-sequencing and subsequently assigned to predicted target genes using heuristics. As such, these approaches provide no direct evidence that insertions actually affect their predicted targets or how transcripts of these genes are affected. To address this, we developed IM-Fusion, an approach that identifies insertion sites from gene-transposon fusions in standard single- and paired-end RNA-sequencing data. We demonstrate IM-Fusion on two separate transposon screens of 123 mammary tumors and 20 B-cell acute lymphoblastic leukemias, respectively. We show that IM-Fusion accurately identifies transposon insertions and their true target genes. Furthermore, by combining the identified insertion sites with expression quantification, we show that we can determine the effect of a transposon insertion on its target gene(s) and prioritize insertions that have a significant effect on expression. We expect that IM-Fusion will significantly enhance the accuracy of cancer gene discovery in forward genetic screens and provide initial insight into the biological effects of insertions on candidate cancer genes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Femtosecond laser surgery of two-cell mouse embryos: effect on viability, development, and tetraploidization.

PubMed

Osychenko, Alina A; Zalessky, Alexandr D; Kostrov, Andrey N; Ryabova, Anastasia V; Krivokharchenko, Alexander S; Nadtochenko, Viktor A

2017-12-01

The effect of the laser pulse energy and total expose of the energy incident on the embryo blastomere fusion probability was investigated. The probability of the four different events after laser pulse was determined: the fusion of two blastomeres with the following formation of tetraploid embryo, the destruction of the first blastomere occurs, the second blastomere conservation remains intact, the destruction and the death of both cells; two blastomeres were not fused, and no morphological changes occurred. We report on viability and quality of the embryo after laser surgery as a function of the laser energy incident. To characterize embryo quality, the probability of the blastocyst stage achievement was estimated and the blastocyst cells number was calculated. Blastocoel formation is the only event of morphogenesis in the preimplantation development of mammals, so we assumed it as an indicator of the time of embryonic "clocks" and observed it among fused and control embryos. The blastocoel formation time is the same for fused and control embryos. It indicates that embryo clocks were not affected due to blastomere fusion. Thus, the analysis of the fluorescence microscopic images of nuclei in the fused embryo revealed that nuclei fusion does not occur after blastomere fusion. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Prospects for Attractive Fusion Power

NASA Astrophysics Data System (ADS)

Najmabadi, Farrokh

2006-10-01

During the past ten years, the ARIES Team, a national team involving universities, national laboratories, and industry, has studied a variety of magnetic fusion power plants (tokamaks, stellarators, ST, and RFP). In this paper, we present the top-level requirements and goals for commercial fusion power plants developed with consultation with US utilities and industry. We will review several ARIES designs and discuss the candidate options for physics operation regime as well engineering design of various components (e.g., choice of structural material, coolant, breeder). For each option, we will discuss (1) the potential to satisfy the requirements and goals, and (2) the critical R&D needs. In particular, we will discuss fusion R&D issues which are similar to those of advanced fission systems. For tokamaks, our results indicate that dramatic improvement over first-stability operation can be obtained through either utilization of high-field magnets (e.g., high-temperature superconductors) or operation in advanced-tokamak modes (e.g., reversed-shear). In particular, if full benefits of reversed-shear operation are realized, as is assumed in ARIES-AT, tokamak power plants will have a cost of electricity competitive with other sources of electricity. Emerging technologies such as advanced Baryon cycle, high-temperature superconductor, and advanced manufacturing techniques can improve the cost and attractiveness of fusion plants.

The Effect of Differentially Designed Fusion Proteins to Elicit Efficient Anti-human Thyroid Stimulating Hormone Immune Responses.

PubMed

Mard-Soltani, Maysam; Rasaee, Mohamad Javad; Khalili, Saeed; Sheikhi, Abdol-Karim; Hedayati, Mehdi; Ghaderi-Zefrehi, Hossein; Alasvand, Milad

2018-04-01

The production of human thyroid stimulating hormone (hTSH) immunoassays requires specific antibodies against hTSH which is a cumbersome process. Therefore, producing specific polyclonal antibodies against engineered recombinant fusion hTSH antigens would be of great significance. The best immunogenic region of the hTSH was selected based on in silico analyses and equipped with two different fusions. Standard methods were used for protein expression, purification, verification, structural evaluation, and immunizations of the white New Zealand rabbits. Ultimately, immunized serums were used for antibody titration, purification and characterization (specificity, sensitivity and cross reactivity). The desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. Structural analyses indicated that only the bigger antigen has showed changed 2 dimensional (2D) and 3D structural properties in comparison to the smaller antigen. The raised polyclonal antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum and negligible. The fusion which was solely composed of the tetanus toxin epitopes led to better protein folding and was capable of immunizing the host animals resulting into high titer antibody. Therefore, the minimal fusion sequences seem to be more effective in eliciting specific antibody responses.

Fusion powered human transport to Mars (UWFR94)

NASA Technical Reports Server (NTRS)

Cappellari, John; Grota, Susan; Hagedorn, David; Hirai, Yoshi; Remmel, Mark; Schmidt, Deanna; Sveum, Matt; Wandow, Helena

1994-01-01

In the future, two important technological dreams will have become reality: fusion will be a viable power source, and human settlement on Mars will be feasible, desirable, and even necessary. Merging these two concepts is especially attractive for the aerospace engineer because of the high specific power that will be possible with fusion (on the order 10 kW/kg). The UWFR94, a large, fusion-powered, human-transport ship, is designed to transport 100 passengers between earth and Mars in approximately thirty days. This relatively short transit time, which mitigates the need for artificial gravity, is made possible by a Polywell inertial electrostatic fusion reactor capable of 20 kW/kg. The mass of each reactor is 37 metric tons and the fuel used is (3)He-(3)He. The electricity generated drives the propulsion system, composed of nine ion thrusters and 780 tons of xenon propellant. The payload consists of three independent, identical cylinders housing the crew, and has a mass of approximately 400 tons. The aluminum cylinders' radius and length are 3 and 12 meters, respectively, with a thickness of 6 cm (15 cm in the solar flare safe rooms). Atmospheric reentry is avoided by constructing and repairing the UWFR94 in space, and by transferring crew and cargo to shuttle-like vehicles for transportation to the planet upon arrival.

Review of Two-Stage FEL Research at KMS Fusion.

DTIC Science & Technology

1983-01-21

vi ty Research and Engineering Technical Library (3 copies) NST. Station, MS 39529 Information Office Library Branch The Pentagon Naval Explosive ...Shafer Associates, Inc. Office of Naval Research 10 Lakeside Office Park Arlington, VA 22217 Wakefield, MA 01880 Dr. Don Prosnitz Dr. T. C. Marshall

Engineering Information Infrastructure for Product Lifecycle Managment

NASA Astrophysics Data System (ADS)

Kimura, Fumihiko

For proper management of total product life cycle, it is fundamentally important to systematize design and engineering information about product systems. For example, maintenance operation could be more efficiently performed, if appropriate parts design information is available at the maintenance site. Such information shall be available as an information infrastructure for various kinds of engineering operations, and it should be easily accessible during the whole product life cycle, such as transportation, marketing, usage, repair/upgrade, take-back and recycling/disposal. Different from the traditional engineering database, life cycle support information has several characteristic requirements, such as flexible extensibility, distributed architecture, multiple viewpoints, long-time archiving, and product usage information, etc. Basic approaches for managing engineering information infrastructure are investigated, and various information contents and associated life cycle applications are discussed.

[Research progress in hirudin fusion protein--review].

PubMed

Zhang, Chuan-Ling; Yu, Ai-Ping; Jin, Ji-De; Wu, Chu-Tse

2007-02-01

Natural hirudin extracted from the secretion of medical leech salivary gland is a single-chain peptide containing 65 aminoacid residues with molecular weight of 7000 D, and exists in three isomers of HV1, HV2 and HV3. Hirudin possesses three disulfide bridges forming the structure of core cyclic peptides, which binds to the catalytic site of thrombin so as to inhibit the catalysis of thrombin. Its c-terminus rich in acidic aminoacid residues possesses hydrophilicity, and is free on the molecular surface, and can bind with fibrin recognition site of hirudin. The minimal segment of 12 - 16 C-terminal acidic residues keeps the minimal activity of anti-thrombosis. Thus, hirudin, as a potent and specific inhibitor of thrombin, can be used to protect from and to treat clinically thrombosis. As it has some disadvantages such as short half-life, bleeding side-effect and mono-function, and so on, hirudin has been fused with some other functional proteins in recent years. The obtained fusion proteins can prolong the half life of hirudin, or relieve it bleeding side effect, or bring new functions, such as thrombolysis, inhibiting the platelet aggregation, targeting specifically. The research progress in hirudin fusion protein was summarized in this review.

Preface: Twenty-First Target Fabrication Specialists Meeting

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nikroo, Abbas; Czechowicz, Don

The Twenty First Target Fabrication Meeting held in Las Vegas, Nevada, from June xx-yy 2015, was attended by more than 100 scientists, engineers, and technicians from the United States, the United Kingdom, France, and Japan, bringing together international experts on the design, development, and fabrication of inertial confinement fusion (ICF) and high-energy-density (HED) experimental targets fielded on laser and pulsed-power facilities around the world. We were delighted to have such exceptional international representation. The program included 4 invited papers, 53 contributed papers, and 55 posters. A selection of these is presented in this dedicated issue of Fusion Science and Technologymore » (FST).« less

Preface: Twenty-First Target Fabrication Specialists Meeting

DOE PAGES

Nikroo, Abbas; Czechowicz, Don

2017-04-21

The Twenty First Target Fabrication Meeting held in Las Vegas, Nevada, from June xx-yy 2015, was attended by more than 100 scientists, engineers, and technicians from the United States, the United Kingdom, France, and Japan, bringing together international experts on the design, development, and fabrication of inertial confinement fusion (ICF) and high-energy-density (HED) experimental targets fielded on laser and pulsed-power facilities around the world. We were delighted to have such exceptional international representation. The program included 4 invited papers, 53 contributed papers, and 55 posters. A selection of these is presented in this dedicated issue of Fusion Science and Technologymore » (FST).« less

The Na+ /H+ antiporter Nhx1 controls vacuolar fusion indispensible for life cycles in vitro and in vivo in a fungal insect pathogen.

PubMed

Zhu, Jing; Ying, Sheng-Hua; Feng, Ming-Guang

2016-11-01

The sole Na + /H + antiporter Nhx1 has been generally unexplored in filamentous fungi. We characterized Nhx1 in the entomopathogenic fungus Beauveria bassiana. An eGFP-tagged Nhx1 fusion accumulated in small punctuate structures, presumably endosomal and trans-Golgi network compartments, between septum and tubular vacuole of each wild-type cell stained with a vacuole-specific dye. Deletion of nhx1 resulted in significant acidification and severe fusion defect in vacuoles, which were fragmented and distinct from large or tubular wild-type vacuoles. The deletion also caused a drastic reduction in aerial conidiation or submerged blastospore production and more severe defect in vegetative growth than in conidial germination. The Δnhx1 mutant became more sensitive to high osmolarity, heat shock and several metal ions during growth but its conidia showed increased UV-B tolerance. Intriguingly, Δnhx1 was unable to infect a model insect through cuticle penetration or intrahaemocoel injection because it produced much less biomass and cuticle-degrading enzymes in a minimal broth and failed to form blastospores in the insect haemolymph. All changes were completely or largely restored by targeted nhx1 complementation. Our results provide novel insight into an indispensability of Nhx1 for not only vacuolar fusion but also life cycles in vitro and in vivo in B. bassiana. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP 3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy

DOE PAGES

Zhu, Xiaojie; Zhu, Yun; Ye, Sheng; ...

2015-08-19

Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP 3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neithermore » recognized AP 3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP 3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP 3 form a hook-like structure to stabilize interaction between AP 3 and NHR helices. Therefore, AP 3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.« less

Clinical comparison of Zero-profile interbody fusion device and anterior cervical plate interbody fusion in treating cervical spondylosis.

PubMed

Yan, Bin; Nie, Lin

2015-01-01

the aim of the study was to compare the clinical effect of Zero-profile interbody fusion device (Zero-P) with anterior cervical plate interbody fusion system (PCB) in treating cervical spondylosis. a total of 98 patients with cervical spondylosis (110 segments) in February 2011 to January 2013 were included in our hospital. All participants were randomly divided into observation group and control group with 49 cases in each group. The observation group was treated with Zero-P, while the control group received PCB treatment. Comparison of the two groups in neurological function score (JOA), pain visual analogue scale (VAS), the neck disability index (NDI), quality of life score (SF-36) and cervical curvature (Cobb angle) change were recorded and analyzed before and after treatment. The observation group was found with 90% excellent and good rate, which was higher than that of the control group (80%). Dysphagia rate in observational group was 16.33% (8/49), which was significantly less than that in control group (46.94%). Operation time and bleeding volume in the observation group was less than those in control group. Postoperative improvements of JOA score, VAS score, and NDI in observational group were also significantly better than that in control group (P<0.05). The clinical effect of Zero-P and PCB for the treatment of cervical spondylosis was quite fair, but Zero-P showed a better therapeutic effect with improvement of life quality.

Improved Pharmacological and Structural Properties of HIV Fusion Inhibitor AP 3 over Enfuvirtide: Highlighting Advantages of Artificial Peptide Strategy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Xiaojie; Zhu, Yun; Ye, Sheng

Enfuvirtide (T20), is the first HIV fusion inhibitor approved for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, its clinical application is limited because of short half-life, drug resistance and cross-reactivity with the preexisting antibodies in HIV-infected patients. Using an artificial peptide strategy, we designed a peptide with non-native protein sequence, AP 3, which exhibited potent antiviral activity against a broad spectrum of HIV-1 strains, including those resistant to T20, and had remarkably longer in vivo half-life than T20. While the preexisting antibodies in HIV-infected patients significantly suppressed T20’s antiviral activity, these antibodies neithermore » recognized AP 3, nor attenuated its anti-HIV-1 activity. Structurally different from T20, AP 3 could fold into single-helix and interact with gp41 NHR. The two residues, Met and Thr, at the N-terminus of AP 3 form a hook-like structure to stabilize interaction between AP 3 and NHR helices. Therefore, AP 3 has potential for further development as a new HIV fusion inhibitor with improved antiviral efficacy, resistance profile and pharmacological properties over enfuvirtide. Meanwhile, this study highlighted the advantages of artificially designed peptides, and confirmed that this strategy could be used in developing artificial peptide-based viral fusion inhibitors against HIV and other enveloped viruses.« less

Exploring the engineering limit of heat flux of a W/RAFM divertor target for fusion reactors

NASA Astrophysics Data System (ADS)

Mao, X.; Fursdon, M.; Chang, X. B.; Zhang, J. W.; Liu, P.; Ellwood, G.; Qian, X. Y.; Qin, S. J.; Peng, X. B.; Barrett, T. R.; Liu, P.

2018-06-01

The design and development of a fusion reactor divertor plasma facing component (PFC) is one of the many challenging issues on the road to commercial use of fusion energy. The divertor PFC is expected to exhaust steady state heat loads in the region of 10 MW m‑2 while keeping temperatures and thermo-mechanical stresses in its structure within the allowable limits. For ITER (International Thermo-Nuclear Experimental Reactor) a water cooled W/CuCrZr divertor PFC concept has been developed. However, this concept is not necessarily assured for use in future fusion reactors mainly because the neutron radiation dose would be at least an order magnitude higher, resulting in limited thermo-mechanical performance and considerably more activated waste products. In the present study, a water cooled divertor PFC using reduced activation ferritic-martensitic (RAFM) steel as the heat sink pipe has been designed with pressurised water reactor-like cooling conditions (pressure of 15.5 MPa, velocity of 10–20 m s‑1 and temperature of 300 °C). The PFC is made up of a number of rectangular tungsten tiles, each with an inner circular hole (so-called monoblocks), joined onto a RAFM steel pipe with copper interlayers. The thermo-mechanical performance of the PFC has been studied in detail. The heat transfer coefficient between the RAFM pipe inner surface and the water was calculated using published correlations. Geometric parameters and water velocity were optimized with finite element (FE) thermal analysis, to achieve acceptable temperatures in the structure given the target exhaust heat load of 10 MW m‑2. Under this heat load and the optimised thermal design parameters, the structure of the PFC was further assessed by mechanical analysis. We find that under these conditions the RAFM steel pipe experiences cyclic plasticity, and fails the common linear elastic ratchetting (3 Sm) rule. Nevertheless, the designed W/RAFM divertor PFU can withstand 10 MW m‑2 heat load, albeit with a fatigue life of approximately 0.55 years based on the expected operation scenario of a prototype or test reactor. This study extends the state of knowledge of the technological limit of a divertor based on a RAFM steel pipe structure.

NASA's Robotics Mining Competition Provides Undergraduates Full Life Cycle Systems Engineering Experience

NASA Technical Reports Server (NTRS)

Stecklein, Jonette

2017-01-01

NASA has held an annual robotic mining competition for teams of university/college students since 2010. This competition is yearlong, suitable for a senior university engineering capstone project. It encompasses the full project life cycle from ideation of a robot design to actual tele-operation of the robot in simulated Mars conditions mining and collecting simulated regolith. A major required element for this competition is a Systems Engineering Paper in which each team describes the systems engineering approaches used on their project. The score for the Systems Engineering Paper contributes 25% towards the team's score for the competition's grand prize. The required use of systems engineering on the project by this competition introduces the students to an intense practical application of systems engineering throughout a full project life cycle.

Life-Extending Control for Aircraft Engines Studied

NASA Technical Reports Server (NTRS)

Guo, Te-Huei

2002-01-01

Current aircraft engine controllers are designed and operated to provide both performance and stability margins. However, the standard method of operation results in significant wear and tear on the engine and negatively affects the on-wing life--the time between cycles when the engine must be physically removed from the aircraft for maintenance. The NASA Glenn Research Center and its industrial and academic partners have been working together toward a new control concept that will include engine life usage as part of the control function. The resulting controller will be able to significantly extend the engine's on-wing life with little or no impact on engine performance and operability. The new controller design will utilize damage models to estimate and mitigate the rate and overall accumulation of damage to critical engine parts. The control methods will also provide a means to assess tradeoffs between performance and structural durability on the basis of mission requirements and remaining engine life. Two life-extending control methodologies were studied to reduce the overall life-cycle cost of aircraft engines. The first methodology is to modify the baseline control logic to reduce the thermomechanical fatigue (TMF) damage of cooled stators during acceleration. To accomplish this, an innovative algorithm limits the low-speed rotor acceleration command when the engine has reached a threshold close to the requested thrust. This algorithm allows a significant reduction in TMF damage with only a very small increase in the rise time to reach the commanded rotor speed. The second methodology is to reduce stress rupture/creep damage to turbine blades and uncooled stators by incorporating an engine damage model into the flight mission. Overall operation cost is reduced by an optimization among the flight time, fuel consumption, and component damages. Recent efforts have focused on applying life-extending control technology to an existing commercial turbine engine, and doing so without modifying the hardware or adding sensors. This approach makes it possible to retrofit existing engines with life-extending control technology by changing only the control software in the full-authority digital engine controller (FADEC). The significant results include demonstrating a 20- to 30-percent reduction in TMF damage to the hot section by developing and implementing smart acceleration logic during takeoff. The tradeoff is an increase, from 5.0 to 5.2 sec, in the time required to reach maximum power from ground idle. On a typical flight profile of a cruise at Mach 0.8 at an altitude of 41,000 ft, and cruise time of 104 min, the optimized system showed that a reduction in cruise speed from Mach 0.8 to 0.79 can achieve an estimated 25-to 35-percent creep/rupture damage reduction in the engine's hot section and a fuel savings of 2.1 percent. The tradeoff is an increase in flight time of 1.3 percent (1.4 min).

A plasmid toolkit for cloning chimeric cDNAs encoding customized fusion proteins into any Gateway destination expression vector

PubMed Central

2013-01-01

Background Valuable clone collections encoding the complete ORFeomes for some model organisms have been constructed following the completion of their genome sequencing projects. These libraries are based on Gateway cloning technology, which facilitates the study of protein function by simplifying the subcloning of open reading frames (ORF) into any suitable destination vector. The expression of proteins of interest as fusions with functional modules is a frequent approach in their initial functional characterization. A limited number of Gateway destination expression vectors allow the construction of fusion proteins from ORFeome-derived sequences, but they are restricted to the possibilities offered by their inbuilt functional modules and their pre-defined model organism-specificity. Thus, the availability of cloning systems that overcome these limitations would be highly advantageous. Results We present a versatile cloning toolkit for constructing fully-customizable three-part fusion proteins based on the MultiSite Gateway cloning system. The fusion protein components are encoded in the three plasmids integral to the kit. These can recombine with any purposely-engineered destination vector that uses a heterologous promoter external to the Gateway cassette, leading to the in-frame cloning of an ORF of interest flanked by two functional modules. In contrast to previous systems, a third part becomes available for peptide-encoding as it no longer needs to contain a promoter, resulting in an increased number of possible fusion combinations. We have constructed the kit’s component plasmids and demonstrate its functionality by providing proof-of-principle data on the expression of prototype fluorescent fusions in transiently-transfected cells. Conclusions We have developed a toolkit for creating fusion proteins with customized N- and C-term modules from Gateway entry clones encoding ORFs of interest. Importantly, our method allows entry clones obtained from ORFeome collections to be used without prior modifications. Using this technology, any existing Gateway destination expression vector with its model-specific properties could be easily adapted for expressing fusion proteins. PMID:23957834

A plasmid toolkit for cloning chimeric cDNAs encoding customized fusion proteins into any Gateway destination expression vector.

PubMed

Buj, Raquel; Iglesias, Noa; Planas, Anna M; Santalucía, Tomàs

2013-08-20

Valuable clone collections encoding the complete ORFeomes for some model organisms have been constructed following the completion of their genome sequencing projects. These libraries are based on Gateway cloning technology, which facilitates the study of protein function by simplifying the subcloning of open reading frames (ORF) into any suitable destination vector. The expression of proteins of interest as fusions with functional modules is a frequent approach in their initial functional characterization. A limited number of Gateway destination expression vectors allow the construction of fusion proteins from ORFeome-derived sequences, but they are restricted to the possibilities offered by their inbuilt functional modules and their pre-defined model organism-specificity. Thus, the availability of cloning systems that overcome these limitations would be highly advantageous. We present a versatile cloning toolkit for constructing fully-customizable three-part fusion proteins based on the MultiSite Gateway cloning system. The fusion protein components are encoded in the three plasmids integral to the kit. These can recombine with any purposely-engineered destination vector that uses a heterologous promoter external to the Gateway cassette, leading to the in-frame cloning of an ORF of interest flanked by two functional modules. In contrast to previous systems, a third part becomes available for peptide-encoding as it no longer needs to contain a promoter, resulting in an increased number of possible fusion combinations. We have constructed the kit's component plasmids and demonstrate its functionality by providing proof-of-principle data on the expression of prototype fluorescent fusions in transiently-transfected cells. We have developed a toolkit for creating fusion proteins with customized N- and C-term modules from Gateway entry clones encoding ORFs of interest. Importantly, our method allows entry clones obtained from ORFeome collections to be used without prior modifications. Using this technology, any existing Gateway destination expression vector with its model-specific properties could be easily adapted for expressing fusion proteins.

Planetary engineering

NASA Technical Reports Server (NTRS)

Pollack, James B.; Sagan, Carl

1991-01-01

Assuming commercial fusion power, heavy lift vehicles and major advances in genetic engineering, the authors survey possible late-21st century methods of working major transformations in planetary environments. Much more Earthlike climates may be produced on Mars by generating low freezing point greenhouse gases from indigenous materials; on Venus by biological conversion of CO2 to graphite, by canceling the greenhouse effect with high-altitude absorbing fine particles, or by a sunshield at the first Lagrangian point; and on Titan by greenhouses and/or fusion warming. However, in our present state of ignorance we cannot guarantee a stable endstate or exclude unanticipated climatic feedbacks or other unintended consequences. Moreover, as the authors illustrate by several examples, many conceivable modes of planetary engineering are so wasteful of scarce solar system resources and so destructive of important scientific information as to raise profound ethical issues, even if they were economically feasible, which they are not. Global warming on Earth may lead to calls for mitigation by planetary engineering, e.g., emplacement and replenishment of anti-greenhouse layers at high altitudes, or sunshields in space. But here especially we must be concerned about precision, stability, and inadvertent side-effects. The safest and most cost-effective means of countering global warming - beyond, e.g., improved energy efficiency, CFC bans and alternative energy sources - is the continuing reforestation of approximately 2 times 107 sq km of the Earth's surface. This can be accomplished with present technology and probably at the least cost.

The LIFE Laser Design in Context: A Comparison to the State-of-the-Art

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deri, R J; Bayramian, A J; Erlandson, A C

2011-03-21

The current point design for the LIFE laser leverages decades of solid-state laser development in order to achieve the performance and attributes required for inertial fusion energy. This document provides a brief comparison of the LIFE laser point design to other state-of-the-art solid-state lasers. Table I compares the attributes of the current LIFE laser point design to other systems. the state-of-the-art for single-shot performance at fusion-relevant beamline energies is exemplified by performance observed on the National Ignition Facility. The state-of-the-art for high average power is exemplified by the Northrup Grumman JHPSSL laser. Several items in Table I deal with themore » laser efficiency; a more detailed discussion of efficiency can be found in reference 5. The electrical-to-optical efficiency of the LIFE design exceeds that of reference 4 due to the availability of higher efficiency laser diode pumps (70% vs. {approx}50% used in reference 4). LIFE diode pumps are discussed in greater detail in reference 6. The 'beam steering' state of the art is represented by the deflection device that will be used in the LIFE laser, not a laser system. Inspection of Table I shows that most LIFE laser attributes have already been experimentally demonstrated. The two cases where the LIFE design is somewhat better than prior experimental work do not involve the development of new concepts: beamline power is increased simply by increasing aperture (as demonstrated by the power/aperture comparison in Table I), and efficiency increases are achieved by employing state-of-the-art diode pumps. In conclusion, the attributes anticipated for the LIFE laser are consistent with the demonstrated performance of existing solid-state lasers.« less

Protection of calves by a prefusion-stabilized bovine RSV F vaccine.

PubMed

Zhang, Baoshan; Chen, Lei; Silacci, Chiara; Thom, Michelle; Boyington, Jeffrey C; Druz, Aliaksandr; Joyce, M Gordon; Guzman, Efrain; Kong, Wing-Pui; Lai, Yen-Ting; Stewart-Jones, Guillaume B E; Tsybovsky, Yaroslav; Yang, Yongping; Zhou, Tongqing; Baxa, Ulrich; Mascola, John R; Corti, Davide; Lanzavecchia, Antonio; Taylor, Geraldine; Kwong, Peter D

2017-03-08

Bovine respiratory syncytial virus, a major cause of respiratory disease in calves, is closely related to human RSV, a leading cause of respiratory disease in infants. Recently, promising human RSV-vaccine candidates have been engineered that stabilize the metastable fusion (F) glycoprotein in its prefusion state; however, the absence of a relevant animal model for human RSV has complicated assessment of these vaccine candidates. Here, we use a combination of structure-based design, antigenic characterization, and X-ray crystallography to translate human RSV F stabilization into the bovine context. A "DS2" version of bovine respiratory syncytial virus F with subunits covalently fused, fusion peptide removed, and pre-fusion conformation stabilized by cavity-filling mutations and intra- and inter-protomer disulfides was recognized by pre-fusion-specific antibodies, AM14, D25, and MPE8, and elicited bovine respiratory syncytial virus-neutralizing titers in calves >100-fold higher than those elicited by post-fusion F. When challenged with a heterologous bovine respiratory syncytial virus, virus was not detected in nasal secretions nor in respiratory tract samples of DS2-immunized calves; by contrast bovine respiratory syncytial virus was detected in all post-fusion- and placebo-immunized calves. Our results demonstrate proof-of-concept that DS2-stabilized RSV F immunogens can induce highly protective immunity from RSV in a native host with implications for the efficacy of prefusion-stabilized F vaccines in humans and for the prevention of bovine respiratory syncytial virus in calves.

Traditional engineering in the biological century: the biotraditional engineer.

PubMed

Friedman, M H

2001-12-01

The increasing importance of life science in all engineering is prompting departments in the traditional engineering disciplines to offer life science as part of their curricula. Students who take advantage of this opportunity--"biotraditional engineers"--will be well positioned for careers in their discipline and in related areas of bioengineering. The founder engineering societies, such as the Bioengineering Division of ASME, are responding to this trend by broadening their scope and working increasingly across interdisciplinary borders.

Overproduction, purification and characterization of human interferon alpha2a-human serum albumin fusion protein produced in methilotropic yeast Pichia pastoris

NASA Astrophysics Data System (ADS)

Ningrum, R. A.; Santoso, A.; Herawati, N.

2017-05-01

Human interferon alpha2a (hIFNα2a) is a therapeutic protein that used in cancer and hepatitis B/C therapy. The main problem of using hIFNα-2a is its short elimination half life due to its low molecular weight. Development of higher molecular weight protein by albumin fusion technology is a rational strategy to solve the problem. In our previous research we constructed an open reading frame (ORF) encoding hIFNα2a-human serum albumin (HSA) fusion protein that expressed in Pichia pastoris (P. pastoris) protease deficient strain SMD1168. This research was performed to overproduce, purify and characterize the fusion protein. To overproduce the protein, cultivation was performed in buffered complex medium containing glyserol (BMGY) for 24 h and protein overproduction was applied in buffered complex medium containing methanol (BMMY) for 48 hours at 30°C. The fusion protein was purified by blue sepharose affinity chromatography. Molecular weight characterization by SDS PAGE corresponds with its theoretical size, 85 kDa. Western blot analysis demonstrated that the fusion protein was recognized by anti hIFNα2 and anti HSA monoclonal antibody as well. Amino acid sequence of the fusion protein was determined by LC MS/MS2 mass spectrometry with trypsin as proteolitic enzyme. There were three fragments that identified as hIFNα2a and seven fragments that identified as HSA. Total identified amino acids were 150 residues with 20% coverage from total residues. To conclude, hIFNα2a-HSA fusion protein was overproduced, purified and characterized. Characterization based on molecular weight, antibody recognition and amino acid sequence confirmed that the fusion protein has correct identity as theoretically thought.

[Research advances in the role of sphingolipids in HCV and HBV life cycles].

PubMed

Zhang, J Y; Duan, Z P; Zhang, J L; Zheng, S J

2016-12-20

Sphingolipids and their metabolites are not only important structural molecules of the cell membrane, but also involved in all phases of viral life cycle, including cell adhesion, membrane fusion, viral replication, viral assembly, intracellular transport, protein sorting, and exocytosis. In recent years, sphingolipids have become one of the focuses of lipid research. This article reviews the role of sphingolipids in the life cycles of hepatitis C virus and hepatitis B virus with reference to recent research achievements in China and foreign countries.

Endosomal protein sorting and autophagy genes contribute to the regulation of yeast life span.

PubMed

Longo, Valter D; Nislow, Corey; Fabrizio, Paola

2010-11-01

Accumulating evidence from various organisms points to a role for autophagy in the regulation of life span. By performing a genome-wide screen to identify novel life span determinants in Saccharomyces cerevisiae, we have obtained further insights into the autophagy-related and -unrelated degradation processes that may be important for preventing cellular senescence. The generation of multivesicular bodies and their fusion with the vacuole in the endosomal pathway emerged as novel cell functions involved in yeast chronological survival and longevity extension.

40 CFR 1045.103 - What exhaust emission standards must my outboard and personal watercraft engines meet?

Code of Federal Regulations, 2011 CFR

2011-07-01

... emission standards must my outboard and personal watercraft engines meet? (a) Duty-cycle emission standards.... (3) Other engines: THC emissions. (e) Useful life. Your engines must meet the exhaust emission standards in paragraphs (a) through (c) of this section over the full useful life as follows: (1) For...

Evaluation of quality of life in adolescent idiopathic scoliosis with different distal fusion level: a comparison of L3 versus L4.

PubMed

Ding, Ran; Liang, Jinqian; Qiu, Guixing; Shen, Jianxiong; Li, Zheng

2014-07-01

Retrospective case-control study. The aim of this study was to assess patients' quality of life with different fusion levels in posterior pedicle screw correction of idiopathic scoliosis. No previous study has demonstrated differences in health-related quality of life (HRQoL) between patients fused to L3 versus L4. A retrospective study was conducted on 30 scoliotic patients fused to L3 using complete pedicle screw instruments. Thirty age-matched and sex-matched scoliotic patients fused to L4 were in the control group. Radiologic parameters were assessed before surgery and at latest follow-up between the 2 groups. These 2 groups were compared for the Scoliosis Research Society 22 questionnaire (SRS-22), Oswestry Disability Index (ODI), visual analogue scale (VAS), and Short Form-36 (SF-36) questionnaires, which were administered preoperatively and at final follow-up. There were no significant differences in sex, age, follow-up duration, the distribution of curve patterns, the postoperative residual Cobb angle of the main curve, complications, or surgical method between the L3 and L4 groups (P>0.05). Preoperative scores were statistically similar in the L3 and L4 groups for all domains of all questionnaires. There was no difference between the L3 and L4 groups for ODI (P=0.527) and VAS (P=0.518). There were no significant differences in the scores on function/activity, self-image/appearance, pain, mental health, or satisfaction with treatment domains between the 2 groups. No significant differences between the 2 groups were found at the final follow-up in the SF-36 subscales/domain scores. This study attempted to elucidate the correlation between the length of fusion and functional outcome; however, it could not identify any difference between different fusion levels. On the basis of short-term results, there were no significant differences in the questionnaire scores between the 2 groups.

Artificial Life Art, Creativity, and Techno-hybridization (editor's introduction).

PubMed

Dorin, Alan

2015-01-01

Artists and engineers have devised lifelike technology for millennia. Their ingenious devices have often prompted inquiry into our preferences, prejudices, and beliefs about living systems, especially regarding their origins, status, constitution, and behavior. A recurring fabrication technique is shared across artificial life art, science, and engineering. This involves aggregating representations or re-creations of familiar biological parts-techno-hybridization-but the motives of practitioners may differ markedly. This article, and the special issue it introduces, explores how ground familiar to contemporary artificial life science and engineering has been assessed and interpreted in parallel by (a) artists and (b) theorists studying creativity explicitly. This activity offers thoughtful, alternative perspectives on artificial life science and engineering, highlighting and sometimes undermining the fields' underlying assumptions, or exposing avenues that are yet to be explored outside of art. Additionally, art has the potential to engage the general public, supporting and exploring the findings of scientific research and engineering. This adds considerably to the maturity of a culture tackling the issues the discipline of artificial life raises.

Engineering Molecular Immunity Against Plant Viruses.

PubMed

Zaidi, Syed Shan-E-Ali; Tashkandi, Manal; Mahfouz, Magdy M

2017-01-01

Genomic engineering has been used to precisely alter eukaryotic genomes at the single-base level for targeted gene editing, replacement, fusion, and mutagenesis, and plant viruses such as Tobacco rattle virus have been developed into efficient vectors for delivering genome-engineering reagents. In addition to altering the host genome, these methods can target pathogens to engineer molecular immunity. Indeed, recent studies have shown that clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) systems that target the genomes of DNA viruses can interfere with viral activity and limit viral symptoms in planta, demonstrating the utility of this system for engineering molecular immunity in plants. CRISPR/Cas9 can efficiently target single and multiple viral infections and confer plant immunity. Here, we discuss the use of site-specific nucleases to engineer molecular immunity against DNA and RNA viruses in plants. We also explore how to address the potential challenges encountered when producing plants with engineered resistance to single and mixed viral infections. © 2017 Elsevier Inc. All rights reserved.

Nuclear power in the 21st century: Challenges and possibilities.

PubMed

Horvath, Akos; Rachlew, Elisabeth

2016-01-01

The current situation and possible future developments for nuclear power--including fission and fusion processes--is presented. The fission nuclear power continues to be an essential part of the low-carbon electricity generation in the world for decades to come. There are breakthrough possibilities in the development of new generation nuclear reactors where the life-time of the nuclear waste can be reduced to some hundreds of years instead of the present time-scales of hundred thousand of years. Research on the fourth generation reactors is needed for the realisation of this development. For the fast nuclear reactors, a substantial research and development effort is required in many fields--from material sciences to safety demonstration--to attain the envisaged goals. Fusion provides a long-term vision for an efficient energy production. The fusion option for a nuclear reactor for efficient production of electricity has been set out in a focussed European programme including the international project of ITER after which a fusion electricity DEMO reactor is envisaged.

Regulation of cell protrusions by small GTPases during fusion of the neural folds

PubMed Central

Rolo, Ana; Savery, Dawn; Escuin, Sarah; de Castro, Sandra C; Armer, Hannah EJ; Munro, Peter MG; Molè, Matteo A; Greene, Nicholas DE; Copp, Andrew J

2016-01-01

Epithelial fusion is a crucial process in embryonic development, and its failure underlies several clinically important birth defects. For example, failure of neural fold fusion during neurulation leads to open neural tube defects including spina bifida. Using mouse embryos, we show that cell protrusions emanating from the apposed neural fold tips, at the interface between the neuroepithelium and the surface ectoderm, are required for completion of neural tube closure. By genetically ablating the cytoskeletal regulators Rac1 or Cdc42 in the dorsal neuroepithelium, or in the surface ectoderm, we show that these protrusions originate from surface ectodermal cells and that Rac1 is necessary for the formation of membrane ruffles which typify late closure stages, whereas Cdc42 is required for the predominance of filopodia in early neurulation. This study provides evidence for the essential role and molecular regulation of membrane protrusions prior to fusion of a key organ primordium in mammalian development. DOI: http://dx.doi.org/10.7554/eLife.13273.001 PMID:27114066

NASA's Robotic Mining Competition Provides Undergraduates Full Life Cycle Systems Engineering Experience

NASA Technical Reports Server (NTRS)

Stecklein, Jonette

2017-01-01

NASA has held an annual robotic mining competition for teams of university/college students since 2010. This competition is yearlong, suitable for a senior university engineering capstone project. It encompasses the full project life cycle from ideation of a robot design, through tele-operation of the robot collecting regolith in simulated Mars conditions, to disposal of the robot systems after the competition. A major required element for this competition is a Systems Engineering Paper in which each team describes the systems engineering approaches used on their project. The score for the Systems Engineering Paper contributes 25% towards the team’s score for the competition’s grand prize. The required use of systems engineering on the project by this competition introduces the students to an intense practical application of systems engineering throughout a full project life cycle.

Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes.

PubMed

Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian; Kielian, Margaret

2016-07-15

The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium binding by the membrane fusion protein. Here we addressed the mechanism of the calcium requirement and the required location of calcium during virus entry. Both calcium and low pH were essential during the virus fusion reaction, which was shown to occur in the early endosome compartment. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Calcium-Dependent Rubella Virus Fusion Occurs in Early Endosomes

PubMed Central

Dubé, Mathieu; Etienne, Loïc; Fels, Maximilian

2016-01-01

ABSTRACT The E1 membrane protein of rubella virus (RuV) is a class II membrane fusion protein structurally related to the fusion proteins of the alphaviruses, flaviviruses, and phleboviruses. Virus entry is mediated by a low pH-dependent fusion reaction through E1's insertion into the cell membrane and refolding to a stable homotrimer. Unlike the other described class II proteins, RuV E1 contains 2 fusion loops, which complex a metal ion between them by interactions with residues N88 and D136. Insertion of the E1 protein into the target membrane, fusion, and infection require calcium and are blocked by alanine substitution of N88 or D136. Here we addressed the requirements of E1 for calcium binding and the intracellular location of the calcium requirement during virus entry. Our results demonstrated that N88 and D136 are optimally configured to support RuV fusion and are strongly selected for during the virus life cycle. While E1 has some similarities with cellular proteins that bind calcium and anionic lipids, RuV binding to the membrane was independent of anionic lipids. Virus fusion occurred within early endosomes, and chelation of intracellular calcium showed that calcium within the early endosome was required for virus fusion and infection. Calcium triggered the reversible insertion of E1 into the target membrane at neutral pH, but E1 homotrimer formation and fusion required a low pH. Thus, RuV E1, unlike other known class II fusion proteins, has distinct triggers for membrane insertion and fusion protein refolding mediated, respectively, by endosomal calcium and low pH. IMPORTANCE Rubella virus causes a mild disease of childhood, but infection of pregnant women frequently results in miscarriage or severe birth defects. In spite of an effective vaccine, RuV disease remains a serious problem in many developing countries. RuV infection of host cells involves endocytic uptake and low pH-triggered membrane fusion and is unusual in its requirement for calcium binding by the membrane fusion protein. Here we addressed the mechanism of the calcium requirement and the required location of calcium during virus entry. Both calcium and low pH were essential during the virus fusion reaction, which was shown to occur in the early endosome compartment. PMID:27122589

Tissue-engineered human bioartificial muscles expressing a foreign recombinant protein for gene therapy

NASA Technical Reports Server (NTRS)

Powell, C.; Shansky, J.; Del Tatto, M.; Forman, D. E.; Hennessey, J.; Sullivan, K.; Zielinski, B. A.; Vandenburgh, H. H.

1999-01-01

Murine skeletal muscle cells transduced with foreign genes and tissue engineered in vitro into bioartificial muscles (BAMs) are capable of long-term delivery of soluble growth factors when implanted into syngeneic mice (Vandenburgh et al., 1996b). With the goal of developing a therapeutic cell-based protein delivery system for humans, similar genetic tissue-engineering techniques were designed for human skeletal muscle stem cells. Stem cell myoblasts were isolated, cloned, and expanded in vitro from biopsied healthy adult (mean age, 42 +/- 2 years), and elderly congestive heart failure patient (mean age, 76 +/- 1 years) skeletal muscle. Total cell yield varied widely between biopsies (50 to 672 per 100 mg of tissue, N = 10), but was not significantly different between the two patient groups. Percent myoblasts per biopsy (73 +/- 6%), number of myoblast doublings prior to senescence in vitro (37 +/- 2), and myoblast doubling time (27 +/- 1 hr) were also not significantly different between the two patient groups. Fusion kinetics of the myoblasts were similar for the two groups after 20-22 doublings (74 +/- 2% myoblast fusion) when the biopsy samples had been expanded to 1 to 2 billion muscle cells, a number acceptable for human gene therapy use. The myoblasts from the two groups could be equally transduced ex vivo with replication-deficient retroviral expression vectors to secrete 0.5 to 2 microg of a foreign protein (recombinant human growth hormone, rhGH)/10(6) cells/day, and tissue engineered into human BAMs containing parallel arrays of differentiated, postmitotic myofibers. This work suggests that autologous human skeletal myoblasts from a potential patient population can be isolated, genetically modified to secrete foreign proteins, and tissue engineered into implantable living protein secretory devices for therapeutic use.

Data-Mining Toolset Developed for Determining Turbine Engine Part Life Consumption

NASA Technical Reports Server (NTRS)

Litt, Jonathan S.

2003-01-01

The current practice in aerospace turbine engine maintenance is to remove components defined as life-limited parts after a fixed time, on the basis of a predetermined number of flight cycles. Under this schedule-based maintenance practice, the worst-case usage scenario is used to determine the usable life of the component. As shown, this practice often requires removing a part before its useful life is fully consumed, thus leading to higher maintenance cost. To address this issue, the NASA Glenn Research Center, in a collaborative effort with Pratt & Whitney, has developed a generic modular toolset that uses data-mining technology to parameterize life usage models for maintenance purposes. The toolset enables a "condition-based" maintenance approach, where parts are removed on the basis of the cumulative history of the severity of operation they have experienced. The toolset uses data-mining technology to tune life-consumption models on the basis of operating and maintenance histories. The flight operating conditions, represented by measured variables within the engine, are correlated with repair records for the engines, generating a relationship between the operating condition of the part and its service life. As shown, with the condition-based maintenance approach, the lifelimited part is in service until its usable life is fully consumed. This approach will lower maintenance costs while maintaining the safety of the propulsion system. The toolset is a modular program that is easily customizable by users. First, appropriate parametric damage accumulation models, which will be functions of engine variables, must be defined. The tool then optimizes the models to match the historical data by computing an effective-cycle metric that reduces the unexplained variability in component life due to each damage mode by accounting for the variability in operational severity. The damage increment due to operating conditions experienced during each flight is used to compute the effective cycles and ultimately the replacement time. Utilities to handle data problems, such as gaps in the flight data records, are included in the toolset. The tool was demonstrated using the first stage, high-pressure turbine blade of the PW4077 engine (Pratt & Whitney, East Hartford, CT). The damage modes considered were thermomechanical fatigue and oxidation/erosion. Each PW4077 engine contains 82 first-stage, high-pressure turbine blades, and data from a fleet of engines were used to tune the life-consumption models. The models took into account not only measured variables within the engine, but also unmeasured variables such as engine health parameters that are affected by degradation of the engine due to aging. The tool proved effective at predicting the average number of blades scrapped over time due to each damage mode, per engine, given the operating history of the engine. The customizable tools are available to interested parties within the aerospace community.

Stress and fatigue in sound engineers: the effect of broadcasting in a life show and shift work.

PubMed

Vangelova, Katia K

2008-06-01

The aim was to study the time-of-day variations of cortisol, fatigue and sleep disturbances in sound engineers in relation to job task and shift work. The concentration of saliva cortisol and feeling of stress, sleepiness and fatigue were followed at three hour intervals in 21 sound engineers: 13 sound engineers, aged 45.1 +/- 7.3 years, broadcasting in a life show during fast forward rotating shifts and 8 sound engineers, aged 47.1 +/- 9.8 years, making records in a studio during fast rotating day shifts. Cortisol concentration was assessed in saliva with radioimmunological kits. The participants reported for stress symptoms during the shifts and filled sleep diary. The data were analyzed by tests of between-subjects effects (SPSS). A trend for higher cortisol was found with the group broadcasting in a life show. The sound engineers broadcasting in a life show reported higher scores of stress, sleepiness and fatigue, but no significant differences concerning the sleep disturbances between the groups were found. In conclusion our data show moderate level of stress and fatigue with the studied sound engineers, higher with the subjects broadcasting in a life show. The quality of sleep showed no significant differences between the studied groups, an indication that the sound engineers were able to tolerate the fast forward rotating shifts.

TRISO Fuel Performance: Modeling, Integration into Mainstream Design Studies, and Application to a Thorium-fueled Fusion-Fission Hybrid Blanket

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powers, Jeffrey James

2011-11-30

This study focused on creating a new tristructural isotropic (TRISO) coated particle fuel performance model and demonstrating the integration of this model into an existing system of neutronics and heat transfer codes, creating a user-friendly option for including fuel performance analysis within system design optimization and system-level trade-off studies. The end product enables both a deeper understanding and better overall system performance of nuclear energy systems limited or greatly impacted by TRISO fuel performance. A thorium-fueled hybrid fusion-fission Laser Inertial Fusion Energy (LIFE) blanket design was used for illustrating the application of this new capability and demonstrated both the importancemore » of integrating fuel performance calculations into mainstream design studies and the impact that this new integrated analysis had on system-level design decisions. A new TRISO fuel performance model named TRIUNE was developed and verified and validated during this work with a novel methodology established for simulating the actual lifetime of a TRISO particle during repeated passes through a pebble bed. In addition, integrated self-consistent calculations were performed for neutronics depletion analysis, heat transfer calculations, and then fuel performance modeling for a full parametric study that encompassed over 80 different design options that went through all three phases of analysis. Lastly, side studies were performed that included a comparison of thorium and depleted uranium (DU) LIFE blankets as well as some uncertainty quantification work to help guide future experimental work by assessing what material properties in TRISO fuel performance modeling are most in need of improvement. A recommended thorium-fueled hybrid LIFE engine design was identified with an initial fuel load of 20MT of thorium, 15% TRISO packing within the graphite fuel pebbles, and a 20cm neutron multiplier layer with beryllium pebbles in flibe molten salt coolant. It operated at a system power level of 2000 MW th, took about 3.5 years to reach full plateau power, and was capable of an End of Plateau burnup of 38.7 %FIMA if considering just the neutronic constraints in the system design; however, fuel performance constraints led to a maximum credible burnup of 12.1 %FIMA due to a combination of internal gas pressure and irradiation effects on the TRISO materials (especially PyC) leading to SiC pressure vessel failures. The optimal neutron spectrum for the thorium-fueled blanket options evaluated seemed to favor a hard spectrum (low but non-zero neutron multiplier thicknesses and high TRISO packing fractions) in terms of neutronic performance but the fuel performance constraints demonstrated that a significantly softer spectrum would be needed to decrease the rate of accumulation of fast neutron fluence in order to improve the maximum credible burnup the system could achieve.« less

Improving Echo-Guided Procedures Using an Ultrasound-CT Image Fusion System.

PubMed

Diana, Michele; Halvax, Peter; Mertz, Damien; Legner, Andras; Brulé, Jean-Marcel; Robinet, Eric; Mutter, Didier; Pessaux, Patrick; Marescaux, Jacques

2015-06-01

Image fusion between ultrasound (US) and computed tomography (CT) scan or magnetic resonance can increase operator accuracy in targeting liver lesions, particularly when those are undetectable with US alone. We have developed a modular gel to simulate hepatic solid lesions for educational purposes in imaging and minimally invasive ablation techniques. We aimed to assess the impact of image fusion in targeting artificial hepatic lesions during the hands-on part of 2 courses (basic and advanced) in hepatobiliary surgery. Under US guidance, 10 fake tumors of various sizes were created in the livers of 2 pigs, by percutaneous injection of a biocompatible gel engineered to be hyperdense on CT scanning and barely detectable on US. A CT scan was obtained and a CT-US image fusion was performed using the ACUSON S3000 US system (Siemens Healthcare, Germany). A total of 12 blinded course attendants, were asked in turn to perform a 10-minute liver scan with US alone followed by a 10-minute scan using image fusion. Using US alone, the expert managed to identify all lesions successfully. The true positive rate for course attendants with US alone was 14/36 and 2/24 in the advanced and basic courses, respectively. The total number of false positives identified was 26. With image fusion, the rate of true positives significantly increased to 31/36 (P < .001) in the advanced group and 16/24 in the basic group (P < .001). The total number of false positives, considering all participants, decreased to 4 (P < .001). Image fusion significantly increases accuracy in targeting hepatic lesions and might improve echo-guided procedures. © The Author(s) 2015.

Chemical heterogeneity as a result of hydroxylamine cleavage of a fusion protein of human insulin-like growth factor I.

PubMed Central

Canova-Davis, E; Eng, M; Mukku, V; Reifsnyder, D H; Olson, C V; Ling, V T

1992-01-01

Recombinant DNA techniques were used to biosynthesize human insulin-like growth factor I (hIGF-I) as a fusion protein wherein the fusion polypeptide is an IgG-binding moiety derived from staphylococcal protein A. This fusion protein is produced in Escherichia coli and secreted into the fermentation broth. In order to release mature recombinant-derived hIGF-I (rhIGF-I), the fusion protein is treated with hydroxylamine, which cleaves a susceptible Asn-Gly bond that has been engineered into the fusion protein gene. Reversed-phase h.p.l.c. was used to estimate the purity of the rhIGF-I preparations, especially for the quantification of the methionine sulphoxide-containing variant. It was determined that hydroxylamine cleavage of the fusion protein produced, as a side reaction, hydroxamates of the asparagine and glutamine residues in rhIGF-I. Although isoelectric focusing was effective in detecting, and reversed-phase h.p.l.c. for producing enriched fractions of the hydroxamate variants, ion-exchange chromatography was a more definitive procedure, as it allowed quantification and facile removal of these variants. The identity of the variants as hydroxamates was established by Staphylococcus aureus V8 proteinase digestion, followed by m.s., as the modification was transparent to amino acid and N-terminal sequence analyses. The biological activity of rhIGF-I was established by its ability to incorporate [3H]thymidine into the DNA of BALB/c373 cells and by a radioreceptor assay utilizing human placental membranes. Both assays demonstrate that the native, recombinant and methionine sulphoxide and hydroxamate IGF-I variants are essentially equipotent. Images Fig. 2. PMID:1637301

Enhanced transport of plant-produced rabies single-chain antibody-RVG peptide fusion protein across an in cellulo blood-brain barrier device.

PubMed

Phoolcharoen, Waranyoo; Prehaud, Christophe; van Dolleweerd, Craig J; Both, Leonard; da Costa, Anaelle; Lafon, Monique; Ma, Julian K-C

2017-10-01

The biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. In this study, we have generated a novel antibody molecule in planta for targeted delivery across the blood-brain barrier (BBB). Rabies virus (RABV) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system. This study investigated the use of a RABV glycoprotein peptide sequence to assist delivery of a rabies neutralizing single-chain antibody (ScFv) across an in cellulo model of human BBB. The 29 amino acid rabies virus peptide (RVG) recognizes the nicotinic acetylcholine receptor (nAchR) at neuromuscular junctions and the BBB. ScFv and ScFv-RVG fusion proteins were produced in Nicotiana benthamiana by transient expression. Both molecules were successfully expressed and purified, but the ScFv expression level was significantly higher than that of ScFv-RVG fusion. Both ScFv and ScFv-RVG fusion molecules had potent neutralization activity against RABVin cellulo. The ScFv-RVG fusion demonstrated increased binding to nAchR and entry into neuronal cells, compared to ScFv alone. Additionally, a human brain endothelial cell line BBB model was used to demonstrate that plant-produced ScFv-RVG P fusion could translocate across the cells. This study indicates that the plant-produced ScFv-RVG P fusion protein was able to cross the in celluloBBB and neutralize RABV. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Information technology security system engineering methodology

NASA Technical Reports Server (NTRS)

Childs, D.

2003-01-01

A methodology is described for system engineering security into large information technology systems under development. The methodology is an integration of a risk management process and a generic system development life cycle process. The methodology is to be used by Security System Engineers to effectively engineer and integrate information technology security into a target system as it progresses through the development life cycle. The methodology can also be used to re-engineer security into a legacy system.

Software engineering and the role of Ada: Executive seminar

NASA Technical Reports Server (NTRS)

Freedman, Glenn B.

1987-01-01

The objective was to introduce the basic terminology and concepts of software engineering and Ada. The life cycle model is reviewed. The application of the goals and principles of software engineering is applied. An introductory understanding of the features of the Ada language is gained. Topics addressed include: the software crises; the mandate of the Space Station Program; software life cycle model; software engineering; and Ada under the software engineering umbrella.

Advanced General Aviation Turbine Engine (GATE) concepts

NASA Technical Reports Server (NTRS)

Lays, E. J.; Murray, G. L.

1979-01-01

Concepts are discussed that project turbine engine cost savings through use of geometrically constrained components designed for low rotational speeds and low stress to permit manufacturing economies. Aerodynamic development of geometrically constrained components is recommended to maximize component efficiency. Conceptual engines, airplane applications, airplane performance, engine cost, and engine-related life cycle costs are presented. The powerplants proposed offer encouragement with respect to fuel efficiency and life cycle costs, and make possible remarkable airplane performance gains.

Cost-effectiveness of minimally invasive sacroiliac joint fusion.

PubMed

Cher, Daniel J; Frasco, Melissa A; Arnold, Renée Jg; Polly, David W

2016-01-01

Sacroiliac joint (SIJ) disorders are common in patients with chronic lower back pain. Minimally invasive surgical options have been shown to be effective for the treatment of chronic SIJ dysfunction. To determine the cost-effectiveness of minimally invasive SIJ fusion. Data from two prospective, multicenter, clinical trials were used to inform a Markov process cost-utility model to evaluate cumulative 5-year health quality and costs after minimally invasive SIJ fusion using triangular titanium implants or non-surgical treatment. The analysis was performed from a third-party perspective. The model specifically incorporated variation in resource utilization observed in the randomized trial. Multiple one-way and probabilistic sensitivity analyses were performed. SIJ fusion was associated with a gain of approximately 0.74 quality-adjusted life years (QALYs) at a cost of US$13,313 per QALY gained. In multiple one-way sensitivity analyses all scenarios resulted in an incremental cost-effectiveness ratio (ICER) <$26,000/QALY. Probabilistic analyses showed a high degree of certainty that the maximum ICER for SIJ fusion was less than commonly selected thresholds for acceptability (mean ICER =$13,687, 95% confidence interval $5,162-$28,085). SIJ fusion provided potential cost savings per QALY gained compared to non-surgical treatment after a treatment horizon of greater than 13 years. Compared to traditional non-surgical treatments, SIJ fusion is a cost-effective, and, in the long term, cost-saving strategy for the treatment of SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption.

Cost-effectiveness of minimally invasive sacroiliac joint fusion

PubMed Central

Cher, Daniel J; Frasco, Melissa A; Arnold, Renée JG; Polly, David W

2016-01-01

Background Sacroiliac joint (SIJ) disorders are common in patients with chronic lower back pain. Minimally invasive surgical options have been shown to be effective for the treatment of chronic SIJ dysfunction. Objective To determine the cost-effectiveness of minimally invasive SIJ fusion. Methods Data from two prospective, multicenter, clinical trials were used to inform a Markov process cost-utility model to evaluate cumulative 5-year health quality and costs after minimally invasive SIJ fusion using triangular titanium implants or non-surgical treatment. The analysis was performed from a third-party perspective. The model specifically incorporated variation in resource utilization observed in the randomized trial. Multiple one-way and probabilistic sensitivity analyses were performed. Results SIJ fusion was associated with a gain of approximately 0.74 quality-adjusted life years (QALYs) at a cost of US$13,313 per QALY gained. In multiple one-way sensitivity analyses all scenarios resulted in an incremental cost-effectiveness ratio (ICER) <$26,000/QALY. Probabilistic analyses showed a high degree of certainty that the maximum ICER for SIJ fusion was less than commonly selected thresholds for acceptability (mean ICER =$13,687, 95% confidence interval $5,162–$28,085). SIJ fusion provided potential cost savings per QALY gained compared to non-surgical treatment after a treatment horizon of greater than 13 years. Conclusion Compared to traditional non-surgical treatments, SIJ fusion is a cost-effective, and, in the long term, cost-saving strategy for the treatment of SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption. PMID:26719717

Productivity benefits of minimally invasive surgery in patients with chronic sacroiliac joint dysfunction.

PubMed

Saavoss, Josh D; Koenig, Lane; Cher, Daniel J

2016-01-01

Sacroiliac joint (SIJ) dysfunction is associated with a marked decrease in quality of life. Increasing evidence supports minimally invasive SIJ fusion as a safe and effective procedure for the treatment of chronic SIJ dysfunction. The impact of SIJ fusion on worker productivity is not known. Regression modeling using data from the National Health Interview Survey was applied to determine the relationship between responses to selected interview questions related to function and economic outcomes. Regression coefficients were then applied to prospectively collected, individual patient data in a randomized trial of SIJ fusion (INSITE, NCT01681004) to estimate expected differences in economic outcomes across treatments. Patients who receive SIJ fusion using iFuse Implant System(®) have an expected increase in the probability of working of 16% (95% confidence interval [CI] 11%-21%) relative to nonsurgical patients. The expected change in earnings across groups was US $3,128 (not statistically significant). Combining the two metrics, the annual increase in worker productivity given surgical vs nonsurgical care was $6,924 (95% CI $1,890-$11,945). For employees with chronic, severe SIJ dysfunction, minimally invasive SIJ fusion may improve worker productivity compared to nonsurgical treatment.

Dilation of fusion pores by crowding of SNARE proteins

PubMed Central

Wu, Zhenyong; Bello, Oscar D; Thiyagarajan, Sathish; Auclair, Sarah Marie; Vennekate, Wensi; Krishnakumar, Shyam S; O'Shaughnessy, Ben; Karatekin, Erdem

2017-01-01

Hormones and neurotransmitters are released through fluctuating exocytotic fusion pores that can flicker open and shut multiple times. Cargo release and vesicle recycling depend on the fate of the pore, which may reseal or dilate irreversibly. Pore nucleation requires zippering between vesicle-associated v-SNAREs and target membrane t-SNAREs, but the mechanisms governing the subsequent pore dilation are not understood. Here, we probed the dilation of single fusion pores using v-SNARE-reconstituted ~23-nm-diameter discoidal nanolipoprotein particles (vNLPs) as fusion partners with cells ectopically expressing cognate, 'flipped' t-SNAREs. Pore nucleation required a minimum of two v-SNAREs per NLP face, and further increases in v-SNARE copy numbers did not affect nucleation rate. By contrast, the probability of pore dilation increased with increasing v-SNARE copies and was far from saturating at 15 v-SNARE copies per face, the NLP capacity. Our experimental and computational results suggest that SNARE availability may be pivotal in determining whether neurotransmitters or hormones are released through a transient ('kiss and run') or an irreversibly dilating pore (full fusion). DOI: http://dx.doi.org/10.7554/eLife.22964.001 PMID:28346138

A Software Tool for Integrated Optical Design Analysis

NASA Technical Reports Server (NTRS)

Moore, Jim; Troy, Ed; DePlachett, Charles; Montgomery, Edward (Technical Monitor)

2001-01-01

Design of large precision optical systems requires multi-disciplinary analysis, modeling, and design. Thermal, structural and optical characteristics of the hardware must be accurately understood in order to design a system capable of accomplishing the performance requirements. The interactions between each of the disciplines become stronger as systems are designed lighter weight for space applications. This coupling dictates a concurrent engineering design approach. In the past, integrated modeling tools have been developed that attempt to integrate all of the complex analysis within the framework of a single model. This often results in modeling simplifications and it requires engineering specialist to learn new applications. The software described in this presentation addresses the concurrent engineering task using a different approach. The software tool, Integrated Optical Design Analysis (IODA), uses data fusion technology to enable a cross discipline team of engineering experts to concurrently design an optical system using their standard validated engineering design tools.

Analysis of prevertebral soft-tissue swelling and dysphagia in multilevel anterior cervical discectomy and fusion with recombinant human bone morphogenetic protein-2 in patients at risk for pseudarthrosis.

PubMed

Stachniak, Joseph B; Diebner, Jeffrey D; Brunk, Estee S; Speed, Shelley M

2011-02-01

The goal of this study was to demonstrate the incidence of fusion and soft-tissue swelling in multilevel anterior cervical discectomies and fusions (ACDFs) using polyetheretherketone (PEEK) spacers with recombinant human bone morphogenetic protein-2 (rhBMP-2) impregnated in a Type I collagen sponge and titanium plates. A single surgeon performed 30 multilevel ACDFs using PEEK spacers with an rhBMP-2 impregnated collagen sponge (0.4 ml, or the equivalent of 0.6 mg rhBMP-2). Soft-tissue swelling was assessed using cervical spine radiographs on postoperative Day 1 and at 2, 6, and 10 weeks and 6 months after surgery. Incidence of dysphagia was assessed with the Cervical Spine Research Society Swallowing-Quality of Life tool. Clinical success was evaluated with the Neck Disability Index, neck pain scores, and arm pain scores. Final fusion was assessed with CT by an independent neuroradiologist. Patients were followed for 6 months unless they had an incomplete fusion; those patients were reassessed at 9 months. Twenty-four patients underwent 2-level ACDFs and 6 underwent 3-level ACDFs were performed on patients with the following risk factors for pseudarthrosis: smoking (33%), diabetes (13%), and obesity (body mass index ≥ 30 [43%]). Seventeen percent of the patients had multiple risk factors. Soft-tissue swelling peaked at 2 weeks regardless of level of surgery or number of levels treated surgically and decreased to near preoperative levels by 6 months. At 2 weeks, Swallowing-Quality of Life evaluation showed 19% of patients frequently choking on food, 4.8% frequently choking when drinking, and 47.6% with frequent food sticking in the throat. Scores continued to improve, and at 6 months, 0% had frequent choking on food, 6.7% had frequent difficulty drinking, and 6.7% had frequent food sticking in the throat. The Neck Disability Index, neck pain, and arm pain scores all improved progressively over 6 months. Incidence of fusion was 95% at 6 months and 100% at 9 months. There were no rehospitalizations or reoperations for soft-tissue swelling or dysphagia. Multilevel ACDF procedures using PEEK grafts and rhBMP-2 can be performed safely in patients with multiple risk factors for pseudarthrosis with excellent fusion outcomes.

TALYS/TENDL verification and validation processes: Outcomes and recommendations

NASA Astrophysics Data System (ADS)

Fleming, Michael; Sublet, Jean-Christophe; Gilbert, Mark R.; Koning, Arjan; Rochman, Dimitri

2017-09-01

The TALYS-generated Evaluated Nuclear Data Libraries (TENDL) provide truly general-purpose nuclear data files assembled from the outputs of the T6 nuclear model codes system for direct use in both basic physics and engineering applications. The most recent TENDL-2015 version is based on both default and adjusted parameters of the most recent TALYS, TAFIS, TANES, TARES, TEFAL, TASMAN codes wrapped into a Total Monte Carlo loop for uncertainty quantification. TENDL-2015 contains complete neutron-incident evaluations for all target nuclides with Z ≤116 with half-life longer than 1 second (2809 isotopes with 544 isomeric states), up to 200 MeV, with covariances and all reaction daughter products including isomers of half-life greater than 100 milliseconds. With the added High Fidelity Resonance (HFR) approach, all resonances are unique, following statistical rules. The validation of the TENDL-2014/2015 libraries against standard, evaluated, microscopic and integral cross sections has been performed against a newly compiled UKAEA database of thermal, resonance integral, Maxwellian averages, 14 MeV and various accelerator-driven neutron source spectra. This has been assembled using the most up-to-date, internationally-recognised data sources including the Atlas of Resonances, CRC, evaluated EXFOR, activation databases, fusion, fission and MACS. Excellent agreement was found with a small set of errors within the reference databases and TENDL-2014 predictions.

40 CFR 89.104 - Useful life, recall, and warranty periods.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Useful life, recall, and warranty... Standards and Certification Provisions § 89.104 Useful life, recall, and warranty periods. (a) The useful life is based on the rated power and rated speed of the engine. (1) For all engines rated under 19 kW...

40 CFR 89.104 - Useful life, recall, and warranty periods.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Useful life, recall, and warranty... Standards and Certification Provisions § 89.104 Useful life, recall, and warranty periods. (a) The useful life is based on the rated power and rated speed of the engine. (1) For all engines rated under 19 kW...

40 CFR 89.104 - Useful life, recall, and warranty periods.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Useful life, recall, and warranty... Standards and Certification Provisions § 89.104 Useful life, recall, and warranty periods. (a) The useful life is based on the rated power and rated speed of the engine. (1) For all engines rated under 19 kW...

40 CFR 1051.107 - What are the exhaust emission standards for all-terrain vehicles (ATVs) and offroad utility...

Code of Federal Regulations, 2010 CFR

2010-07-01

... Phase 1 2006 50 1.5 35 20.0 2007 and later 100 1.5 35 20.0 (2) You may certify ATVs with engines that... life. For ATVs with engines that have total displacement of 100 cc or greater, the minimum useful life... with engines that have total displacement of less than 100 cc, the minimum useful life is 5,000...

40 CFR 1051.107 - What are the exhaust emission standards for all-terrain vehicles (ATVs) and offroad utility...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Phase 1 2006 50 1.5 35 20.0 2007 and later 100 1.5 35 20.0 (2) You may certify ATVs with engines that... life. For ATVs with engines that have total displacement of 100 cc or greater, the minimum useful life... with engines that have total displacement of less than 100 cc, the minimum useful life is 5,000...

Determination of Turbine Blade Life from Engine Field Data

NASA Technical Reports Server (NTRS)

Zaretsky, Erwin V.; Litt, Jonathan S.; Hendricks, Robert C.; Soditus, Sherry M.

2013-01-01

It is probable that no two engine companies determine the life of their engines or their components in the same way or apply the same experience and safety factors to their designs. Knowing the failure mode that is most likely to occur minimizes the amount of uncertainty and simplifies failure and life analysis. Available data regarding failure mode for aircraft engine blades, while favoring low-cycle, thermal-mechanical fatigue (TMF) as the controlling mode of failure, are not definitive. Sixteen high-pressure turbine (HPT) T-1 blade sets were removed from commercial aircraft engines that had been commercially flown by a single airline and inspected for damage. Each set contained 82 blades. The damage was cataloged into three categories related to their mode of failure: (1) TMF, (2) Oxidation/erosion (O/E), and (3) Other. From these field data, the turbine blade life was determined as well as the lives related to individual blade failure modes using Johnson-Weibull analysis. A simplified formula for calculating turbine blade life and reliability was formulated. The L10 blade life was calculated to be 2427 cycles (11 077 hr). The resulting blade life attributed to O/E equaled that attributed to TMF. The category that contributed most to blade failure was Other. If there were no blade failures attributed to O/E and TMF, the overall blade L(sub 10) life would increase approximately 11 to 17 percent.

Mixing and electronic entropy contributions to thermal energy storage in low melting point alloys

NASA Astrophysics Data System (ADS)

Shamberger, Patrick J.; Mizuno, Yasushi; Talapatra, Anjana A.

2017-07-01

Melting of crystalline solids is associated with an increase in entropy due to an increase in configurational, rotational, and other degrees of freedom of a system. However, the magnitude of chemical mixing and electronic degrees of freedom, two significant contributions to the entropy of fusion, remain poorly constrained, even in simple 2 and 3 component systems. Here, we present experimentally measured entropies of fusion in the Sn-Pb-Bi and In-Sn-Bi ternary systems, and decouple mixing and electronic contributions. We demonstrate that electronic effects remain the dominant contribution to the entropy of fusion in multi-component post-transition metal and metalloid systems, and that excess entropy of mixing terms can be equal in magnitude to ideal mixing terms, causing regular solution approximations to be inadequate in the general case. Finally, we explore binary eutectic systems using mature thermodynamic databases, identifying eutectics containing at least one semiconducting intermetallic phase as promising candidates to exceed the entropy of fusion of monatomic endmembers, while simultaneously maintaining low melting points. These results have significant implications for engineering high-thermal conductivity metallic phase change materials to store thermal energy.

Development of a Dehalogenase-Based Protein Fusion Tag Capable of Rapid, Selective and Covalent Attachment to Customizable Ligands

PubMed Central

Encell, Lance P; Friedman Ohana, Rachel; Zimmerman, Kris; Otto, Paul; Vidugiris, Gediminas; Wood, Monika G; Los, Georgyi V; McDougall, Mark G; Zimprich, Chad; Karassina, Natasha; Learish, Randall D; Hurst, Robin; Hartnett, James; Wheeler, Sarah; Stecha, Pete; English, Jami; Zhao, Kate; Mendez, Jacqui; Benink, Hélène A; Murphy, Nancy; Daniels, Danette L; Slater, Michael R; Urh, Marjeta; Darzins, Aldis; Klaubert, Dieter H; Bulleit, Robert F; Wood, Keith V

2012-01-01

Our fundamental understanding of proteins and their biological significance has been enhanced by genetic fusion tags, as they provide a convenient method for introducing unique properties to proteins so that they can be examinedin isolation. Commonly used tags satisfy many of the requirements for applications relating to the detection and isolation of proteins from complex samples. However, their utility at low concentration becomes compromised if the binding affinity for a detection or capture reagent is not adequate to produce a stable interaction. Here, we describe HaloTag® (HT7), a genetic fusion tag based on a modified haloalkane dehalogenase designed and engineered to overcome the limitation of affinity tags by forming a high affinity, covalent attachment to a binding ligand. HT7 and its ligand have additional desirable features. The tag is relatively small, monomeric, and structurally compatible with fusion partners, while the ligand is specific, chemically simple, and amenable to modular synthetic design. Taken together, the design features and molecular evolution of HT7 have resulted in a superior alternative to common tags for the overexpression, detection, and isolation of target proteins. PMID:23248739

Current Status of the Gasdynamic Mirror Fusion Propulsion Experiment

NASA Technical Reports Server (NTRS)

Emrich, William J., Jr.

2002-01-01

Nuclear fusion appears to be the most promising concept for producing extremely high specific impulse rocket engines. One particular fusion concept which seems to be particularly well suited for fusion propulsion applications is the gasdynamic mirror (GDM). An experimental GDM device has been constructed at the NASA Marshall Space Flight Center to provide an initial assessment of the feasibility of this type of propulsion system. An initial shakedown of the device is currently underway with initial experiments slated to occur in late 2001. This device would operate at much higher plasma densities and with much larger L/D ratios than previous mirror machines. The high L/D ratio minimizes to a large extent certain magnetic curvature effects which lead to plasma instabilities causing a loss of plasma confinement. The high plasma density results in the plasma behaving much more like a conventional fluid with a mean free path shorter than the length of the device. This characteristic helps reduce problems associated with 'loss cone' microinstabilities. The device has been constructed to allow a considerable degree of flexibility in its configuration thus permitting the experiment to grow over time without necessitating a great deal of additional fabrication.

The characterization of copper alloys for the application of fusion reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ishiyama, S.; Fukaya, K.; Eto, M.

Three kinds of candidate copper alloys for divertor structural materials of fusion experimental reactors, that is, Oxygen Free High thermal conductivity Copper (OFHC), alumina disperse reinforced copper (DSC) and the composite of W and Cu (W/Cu), were prepared for strength and fatigue tests at temperatures ranging from R.T. to 500 C in a vacuum. High temperature strength of DSC and W/Cu with rapid fracture after peak loading at the temperatures is higher than that of OFHC by factor of 2, but fracture strains of DFC and W/Cu are smaller than that of OFHC. Fatigue life of DSC, which shows themore » same fatigue behavior of OFHC at room temperature, is longer than other materials at 400 C. Remarkable fatigue life reduction of OFHC found in this experiment is to be due to recrystallization of OFHC yielded above 400 C.« less

Performance Investigation of Proteomic Identification by HCD/CID Fragmentations in Combination with High/Low-Resolution Detectors on a Tribrid, High-Field Orbitrap Instrument

PubMed Central

Shen, Shichen; Sheng, Quanhu; Shyr, Yu; Qu, Jun

2016-01-01

The recently-introduced Orbitrap Fusion mass spectrometry permits various types of MS2 acquisition methods. To date, these different MS2 strategies and the optimal data interpretation approach for each have not been adequately evaluated. This study comprehensively investigated the four MS2 strategies: HCD-OT (higher-energy-collisional-dissociation with Orbitrap detection), HCD-IT (HCD with ion trap, IT), CID-IT (collision-induced-dissociation with IT) and CID-OT on Orbitrap Fusion. To achieve extensive comparison and identify the optimal data interpretation method for each technique, several search engines (SEQUEST and Mascot) and post-processing methods (score-based, PeptideProphet, and Percolator) were assessed for all techniques for the analysis of a human cell proteome. It was found that divergent conclusions could be made from the same dataset when different data interpretation approaches were used and therefore requiring a relatively fair comparison among techniques. Percolator was chosen for comparison of techniques because it performs the best among all search engines and MS2 strategies. For the analysis of human cell proteome using individual MS2 strategies, the highest number of identifications was achieved by HCD-OT, followed by HCD-IT and CID-IT. Based on these results, we concluded that a relatively fair platform for data interpretation is necessary to avoid divergent conclusions from the same dataset, and HCD-OT and HCD-IT may be preferable for protein/peptide identification using Orbitrap Fusion. PMID:27472422

Cancer translocations in human cells induced by zinc finger and TALE nucleases

PubMed Central

Piganeau, Marion; Ghezraoui, Hind; De Cian, Anne; Guittat, Lionel; Tomishima, Mark; Perrouault, Loic; René, Oliver; Katibah, George E.; Zhang, Lei; Holmes, Michael C.; Doyon, Yannick; Concordet, Jean-Paul; Giovannangeli, Carine; Jasin, Maria; Brunet, Erika

2013-01-01

Chromosomal translocations are signatures of numerous cancers and lead to expression of fusion genes that act as oncogenes. The wealth of genomic aberrations found in cancer, however, makes it challenging to assign a specific phenotypic change to a specific aberration. In this study, we set out to use genome editing with zinc finger (ZFN) and transcription activator-like effector (TALEN) nucleases to engineer, de novo, translocation-associated oncogenes at cognate endogenous loci in human cells. Using ZFNs and TALENs designed to cut precisely at relevant translocation breakpoints, we induced cancer-relevant t(11;22)(q24;q12) and t(2;5)(p23;q35) translocations found in Ewing sarcoma and anaplastic large cell lymphoma (ALCL), respectively. We recovered both translocations with high efficiency, resulting in the expression of the EWSR1–FLI1 and NPM1–ALK fusions. Breakpoint junctions recovered after ZFN cleavage in human embryonic stem (ES) cell–derived mesenchymal precursor cells fully recapitulated the genomic characteristics found in tumor cells from Ewing sarcoma patients. This approach with tailored nucleases demonstrates that expression of fusion genes found in cancer cells can be induced from the native promoter, allowing interrogation of both the underlying mechanisms and oncogenic consequences of tumor-related translocations in human cells. With an analogous strategy, the ALCL translocation was reverted in a patient cell line to restore the integrity of the two participating chromosomes, further expanding the repertoire of genomic rearrangements that can be engineered by tailored nucleases. PMID:23568838

A novel antibody-drug conjugate anti-CD19(Fab)-LDM in the treatment of B-cell non-Hodgkin lymphoma xenografts with enhanced anticancer activity.

PubMed

Jiang, Linlin; Yang, Ming; Zhang, Xiaoyun; Bao, Shiqi; Ma, Li; Fan, Dongmei; Zhou, Yuan; Xiong, Dongsheng; Zhen, Yongsu

2016-01-01

Rituximab is widely used in clinical setting for the treatment of B malignant lymphoma and has achieved remarkable success. However, in most patients, the disease ultimately relapses and become resistant to rituximab. To overcome the limitation, there is still a need to find novel strategy for improving therapeutic efficacy. To construct genetically engineered antibody anti-CD19(Fab)-LDM, and verify the anticancer activity targeted toward B-lymphoma. The anticancer activity of anti-CD19(Fab)-LDM in vitro and in vivo was examined. In vitro, the binding activity and internalization of anti-CD19(Fab)-LDP were measured. Using comet assay and apoptosis, the cytotoxicity of energized fusion proteins was observed. From in vivo experiments, targeting of therapeutic effect and anticancer efficacy bythe fusion protein was verified. Data showed that anti-CD19(Fab)-LDM does not only binding the cell surface but is also internalized into the cell. The energized fusion proteins anti-CD19(Fab)-LDM can induce DNA damage. Furthermore, significant in vivo therapeutic efficacy was observed. The present study demonstrated that the genetically engineered antibody anti-CD19(Fab)-LDM exhibited enhanced cytotoxicity compared to LDM alone. One of the most powerful advantages of anti-CD19(Fab)-LDM, however, is that it can be internalized within the cells and carry out cytotoxic effects. Therefore, anti-CD19(Fab)-LDM may be as a useful targeted therapy for B-cell lymphoma.

The Human Metapneumovirus Small Hydrophobic Protein Has Properties Consistent with Those of a Viroporin and Can Modulate Viral Fusogenic Activity

PubMed Central

Masante, Cyril; El Najjar, Farah; Chang, Andres; Jones, Angela; Moncman, Carole L.

2014-01-01

ABSTRACT Human metapneumovirus (HMPV) encodes three glycoproteins: the glycoprotein, which plays a role in glycosaminoglycan binding, the fusion (F) protein, which is necessary and sufficient for both viral binding to the target cell and fusion between the cellular plasma membrane and the viral membrane, and the small hydrophobic (SH) protein, whose function is unclear. The SH protein of the closely related respiratory syncytial virus has been suggested to function as a viroporin, as it forms oligomeric structures consistent with a pore and alters membrane permeability. Our analysis indicates that both the full-length HMPV SH protein and the isolated SH protein transmembrane domain can associate into higher-order oligomers. In addition, HMPV SH expression resulted in increases in permeability to hygromycin B and alteration of subcellular localization of a fluorescent dye, indicating that SH affects membrane permeability. These results suggest that the HMPV SH protein has several characteristics consistent with a putative viroporin. Interestingly, we also report that expression of the HMPV SH protein can significantly decrease HMPV F protein-promoted membrane fusion activity, with the SH extracellular domain and transmembrane domain playing a key role in this inhibition. These results suggest that the HMPV SH protein could regulate both membrane permeability and fusion protein function during viral infection. IMPORTANCE Human metapneumovirus (HMPV), first identified in 2001, is a causative agent of severe respiratory tract disease worldwide. The small hydrophobic (SH) protein is one of three glycoproteins encoded by all strains of HMPV, but the function of the HMPV SH protein is unknown. We have determined that the HMPV SH protein can alter the permeability of cellular membranes, suggesting that HMPV SH is a member of a class of proteins termed viroporins, which modulate membrane permeability to facilitate critical steps in a viral life cycle. We also demonstrated that HMPV SH can inhibit the membrane fusion function of the HMPV fusion protein. This work suggests that the HMPV SH protein has several functions, though the steps in the HMPV life cycle impacted by these functions remain to be clarified. PMID:24672047

Study of impurity effects on CFETR steady-state scenario by self-consistent integrated modeling

NASA Astrophysics Data System (ADS)

Shi, Nan; Chan, Vincent S.; Jian, Xiang; Li, Guoqiang; Chen, Jiale; Gao, Xiang; Shi, Shengyu; Kong, Defeng; Liu, Xiaoju; Mao, Shifeng; Xu, Guoliang

2017-12-01

Impurity effects on fusion performance of China fusion engineering test reactor (CFETR) due to extrinsic seeding are investigated. An integrated 1.5D modeling workflow evolves plasma equilibrium and all transport channels to steady state. The one modeling framework for integrated tasks framework is used to couple the transport solver, MHD equilibrium solver, and source and sink calculations. A self-consistent impurity profile constructed using a steady-state background plasma, which satisfies quasi-neutrality and true steady state, is presented for the first time. Studies are performed based on an optimized fully non-inductive scenario with varying concentrations of Argon (Ar) seeding. It is found that fusion performance improves before dropping off with increasing {{Z}\\text{eff}} , while the confinement remains at high level. Further analysis of transport for these plasmas shows that low-k ion temperature gradient modes dominate the turbulence. The decrease in linear growth rate and resultant fluxes of all channels with increasing {{Z}\\text{eff}} can be traced to impurity profile change by transport. The improvement in confinement levels off at higher {{Z}\\text{eff}} . Over the regime of study there is a competition between the suppressed transport and increasing radiation that leads to a peak in the fusion performance at {{Z}\\text{eff}} (~2.78 for CFETR). Extrinsic impurity seeding to control divertor heat load will need to be optimized around this value for best fusion performance.

Sensor and information fusion for improved hostile fire situational awareness

NASA Astrophysics Data System (ADS)

Scanlon, Michael V.; Ludwig, William D.

2010-04-01

A research-oriented Army Technology Objective (ATO) named Sensor and Information Fusion for Improved Hostile Fire Situational Awareness uniquely focuses on the underpinning technologies to detect and defeat any hostile threat; before, during, and after its occurrence. This is a joint effort led by the Army Research Laboratory, with the Armaments and the Communications and Electronics Research, Development, and Engineering Centers (CERDEC and ARDEC) partners. It addresses distributed sensor fusion and collaborative situational awareness enhancements, focusing on the underpinning technologies to detect/identify potential hostile shooters prior to firing a shot and to detect/classify/locate the firing point of hostile small arms, mortars, rockets, RPGs, and missiles after the first shot. A field experiment conducted addressed not only diverse modality sensor performance and sensor fusion benefits, but gathered useful data to develop and demonstrate the ad hoc networking and dissemination of relevant data and actionable intelligence. Represented at this field experiment were various sensor platforms such as UGS, soldier-worn, manned ground vehicles, UGVs, UAVs, and helicopters. This ATO continues to evaluate applicable technologies to include retro-reflection, UV, IR, visible, glint, LADAR, radar, acoustic, seismic, E-field, narrow-band emission and image processing techniques to detect the threats with very high confidence. Networked fusion of multi-modal data will reduce false alarms and improve actionable intelligence by distributing grid coordinates, detection report features, and imagery of threats.

Thermonuclear Power Engineering: 60 Years of Research. What Comes Next?

NASA Astrophysics Data System (ADS)

Strelkov, V. S.

2017-12-01

This paper summarizes results of more than half a century of research of high-temperature plasmas heated to a temperature of more than 100 million degrees (104 eV) and magnetically insulated from the walls. The energy of light-element fusion can be used for electric power generation or as a source of fissionable fuel production (development of a fusion neutron source—FNS). The main results of studies of tokamak plasmas which were obtained in the Soviet Union with the greatest degree of thermal plasma isolation among all other types of devices are presented. As a result, research programs of other countries were redirected to tokamaks. Later, on the basis of the analysis of numerous experiments, the international fusion community gradually came to an opinion that it is possible to build a tokamak (ITER) with Q > 1 (where Q is the ratio of the fusion power to the external power injected into the plasma). The ITER program objective is to achieve Q = 1-10 for a discharge time of up to 1000 s. The implementation of this goal does not solve the problem of a steadystate operation. The solution to this problem is a reliable first wall and current generation. This is a task of the next fusion power plant construction stage, called DEMO. Comparison of DEMO and FNS parameters shows that, at this development stage, the operating parameters and conditions of these devices are identical.

5 CFR 532.313 - Private sector industries.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the physical, engineering, and life sciences (except biotechnology). 56172 Janitorial services. 62191... Research and development in the physical, engineering, and life sciences (except biotechnology). Heavy Duty...