Part 2: Conserving and Planting Trees at Development Sites

Treesearch

Karen Cappiella; Tom Schueler; Tiffany Wright

2006-01-01

This manual presents specific ways to enable developers, engineers or landscape architects to incorporate more trees into a development site. The proposed approach focuses on protecting existing trees, planting trees in storm water treatment practices, and planting trees in other open spaces at the development site. This manual introduces conceptual designs for storm...

SP-100 ground engineering system test site description and progress update

NASA Astrophysics Data System (ADS)

Baxter, William F.; Burchell, Gail P.; Fitzgibbon, Davis G.; Swita, Walter R.

1991-01-01

The SP-100 Ground Engineering System Test Site will provide the facilities for the testing of an SP-100 reactor, which is technically prototypic of the generic design for producing 100 kilowatts of electricity. This effort is part of the program to develop a compact, space-based power system capable of producing several hundred kilowatts of electrical power. The test site is located on the U.S. Department of Energy's Hanford Site near Richland, Washington. The site is minimizing capital equipment costs by utilizing existing facilities and equipment to the maximum extent possible. The test cell is located in a decommissioned reactor containment building, and the secondary sodium cooling loop will use equipment from the Fast Flux Test Facility plant which has never been put into service. Modifications to the facility and special equipment are needed to accommodate the testing of the SP-100 reactor. Definitive design of the Ground Engineering System Test Site facility modifications and systems is in progress. The design of the test facility and the testing equipment will comply with the regulations and specifications of the U.S. Department of Energy and the State of Washington.

MODEST: a web-based design tool for oligonucleotide-mediated genome engineering and recombineering

PubMed Central

Bonde, Mads T.; Klausen, Michael S.; Anderson, Mads V.; Wallin, Annika I.N.; Wang, Harris H.; Sommer, Morten O.A.

2014-01-01

Recombineering and multiplex automated genome engineering (MAGE) offer the possibility to rapidly modify multiple genomic or plasmid sites at high efficiencies. This enables efficient creation of genetic variants including both single mutants with specifically targeted modifications as well as combinatorial cell libraries. Manual design of oligonucleotides for these approaches can be tedious, time-consuming, and may not be practical for larger projects targeting many genomic sites. At present, the change from a desired phenotype (e.g. altered expression of a specific protein) to a designed MAGE oligo, which confers the corresponding genetic change, is performed manually. To address these challenges, we have developed the MAGE Oligo Design Tool (MODEST). This web-based tool allows designing of MAGE oligos for (i) tuning translation rates by modifying the ribosomal binding site, (ii) generating translational gene knockouts and (iii) introducing other coding or non-coding mutations, including amino acid substitutions, insertions, deletions and point mutations. The tool automatically designs oligos based on desired genotypic or phenotypic changes defined by the user, which can be used for high efficiency recombineering and MAGE. MODEST is available for free and is open to all users at http://modest.biosustain.dtu.dk. PMID:24838561

Integrated medical and behavioral laboratory measurement system engineering analysis and laboratory specification

NASA Technical Reports Server (NTRS)

Grave, C.; Margold, D. W.

1973-01-01

Site selection, program planning, cost and design studies for support of the IMBLMS program were investigated. Accomplishments are reported for the following areas: analysis of responses to site selection criteria, space-oriented biotechnology, life sciences payload definition, and program information transfer.

A Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer

DTIC Science & Technology

2016-12-01

the extracellular microenvironment at cancer sites. The objective for this proposal is to use a bio -engineering approach to produce recombinant pro...ominous diagnosis. The objective for this project is to use a bio -engineering approach to produce recombinant pro-toxins designed for specific cleavage

Coupling Protein Side-Chain and Backbone Flexibility Improves the Re-design of Protein-Ligand Specificity.

PubMed

Ollikainen, Noah; de Jong, René M; Kortemme, Tanja

2015-01-01

Interactions between small molecules and proteins play critical roles in regulating and facilitating diverse biological functions, yet our ability to accurately re-engineer the specificity of these interactions using computational approaches has been limited. One main difficulty, in addition to inaccuracies in energy functions, is the exquisite sensitivity of protein-ligand interactions to subtle conformational changes, coupled with the computational problem of sampling the large conformational search space of degrees of freedom of ligands, amino acid side chains, and the protein backbone. Here, we describe two benchmarks for evaluating the accuracy of computational approaches for re-engineering protein-ligand interactions: (i) prediction of enzyme specificity altering mutations and (ii) prediction of sequence tolerance in ligand binding sites. After finding that current state-of-the-art "fixed backbone" design methods perform poorly on these tests, we develop a new "coupled moves" design method in the program Rosetta that couples changes to protein sequence with alterations in both protein side-chain and protein backbone conformations, and allows for changes in ligand rigid-body and torsion degrees of freedom. We show significantly increased accuracy in both predicting ligand specificity altering mutations and binding site sequences. These methodological improvements should be useful for many applications of protein-ligand design. The approach also provides insights into the role of subtle conformational adjustments that enable functional changes not only in engineering applications but also in natural protein evolution.

Airborne remote sensors applied to engineering geology and civil works design investigations

NASA Technical Reports Server (NTRS)

Gelnett, R. H.

1975-01-01

The usefulness of various airborne remote sensing systems in the detection and identification of regional and specific geologic structural features that may affect the design and location of engineering structures on major civil works projects is evaluated. The Butler Valley Dam and Blue Lake Project in northern California was selected as a demonstration site. Findings derived from the interpretation of various kinds of imagery used are given.

Design of an allosterically modulated doxycycline and doxorubicin drug-binding protein.

PubMed

Schmidt, Karin; Gardill, Bernd R; Kern, Alina; Kirchweger, Peter; Börsch, Michael; Muller, Yves A

2018-05-14

The allosteric interplay between distant functional sites present in a single protein provides for one of the most important regulatory mechanisms in biological systems. While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. Here it is shown how computational design algorithms enabled the introduction of doxycycline- and doxorubicin-binding sites into the serine proteinase inhibitor (serpin) family member α1-antichymotrypsin. Further engineering allowed exploitation of the proteinase-triggered serpin-typical S-to-R transition to modulate the ligand affinities. These design variants follow strategies observed in naturally occurring plasma globulins that allow for the targeted delivery of hormones in the blood. By analogy, we propose that the variants described in the present study could be further developed to allow for the delivery of the antibiotic doxycycline and the anticancer compound doxorubicin to tissues/locations that express specific proteinases, such as bacterial infection sites or tumor cells secreting matrix metalloproteinases.

Development studies for a novel wet oxidation process. Phase 2

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

NONE

1994-07-01

DETOX{sup SM} is a catalyzed wet oxidation process which destroys organic materials in an acidic water solution of iron at 373 to 473 K. The solution can be used repeatedly to destroy great amounts of organic materials. Since the process is conducted in a contained vessel, air emissions from the process can be well controlled. The solution is also capable of dissolving and concentrating many heavy and radioactive metals for eventual stabilization and disposal. The Phase 2 effort for this project is site selection and engineering design for a DETOX demonstration unit. Site selection was made using a set ofmore » site selection criteria and evaluation factors. A survey of mixed wastes at DOE sites was conducted using the Interim Mixed Waste Inventory Report. Sites with likely suitable waste types were identified. Potential demonstration sites were ranked based on waste types, interest, regulatory needs, scheduling, ability to provide support, and available facilities. Engineering design for the demonstration unit is in progress and is being performed by Jacobs Applied Technology. The engineering design proceeded through preliminary process flow diagrams (PFDs), calculation of mass and energy balances for representative waste types, process and instrumentation diagrams (P and IDs), preparation of component specifications, and a firm cost estimate for fabrication of the demonstration unit.« less

Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

PubMed Central

Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

2016-01-01

The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

Enabling Geotechnical Data for Broader Use by the Spatial Data Infrastructures

ERIC Educational Resources Information Center

Zand, Amir Ghasem

2011-01-01

Geotechnical data are one of the most prevalent data types in civil engineering projects. The majority of the civil engineering projects that are in use today are designed using site-specific geotechnical data. The usage of geotechnical data is not limited to construction projects. This data is used in a wide range of applications, including…

Missile Defense Information Technology Small Business Conference

DTIC Science & Technology

2009-09-01

NetOps Survivability 4 • Supported User Base • Number of Workstations • Number of Servers • Number of Special Circuits • Number of Sites • Number...Contracts, MDIOC • Ground Test (DTC) • MDSEC (SS) • Infrastructure (IC) • BMDS Support (BCT) • JTAAS – SETA • Mod & Sim ( DES ) • Analysis (GML) • Tenants...AUG 09) 4 MDA DOCE Engineering Functions • Design Engineers – Develop detailed design artifacts based on architectural specifications – Coordinate

Rational approaches for engineering novel functionalities in carbon-carbon bond forming enzymes

PubMed Central

Baker, Perrin; Seah, Stephen Y. K.

2012-01-01

Enzymes that catalyze carbon-carbon bond formation can be exploited as biocatalyst for synthetic organic chemistry. However, natural enzymes frequently do not possess the required properties or specificities to catalyze industrially useful transformations. This mini-review describes recent work using knowledge-guided site-specific mutagenesis of key active site residues to alter substrate specificity, stereospecificity and reaction specificity of these enzymes. In addition, examples of de novo designed enzymes that catalyze C-C bond reactions not found in nature will be discussed. PMID:24688644

Engineered T cells for cancer treatment

PubMed Central

Anurathapan, Usanarat; Leen, Ann M.; Brenner, Malcolm K.; Vera, Juan F.

2014-01-01

Adoptively transferred T cells have the capacity to traffic to distant tumor sites, infiltrate even fibrotic tissue and kill antigen-expressing tumor cells. A variety of groups have investigated different genetic engineering strategies designed to enhance tumor specificity, increase T cell potency, improve proliferation, persistence, or migratory capacity, and increase safety. In this review we focus on recent developments in the T cell engineering arena, discuss the application of these engineered cell products clinically, and outline future prospects for this therapeutic modality. PMID:24239105

Simultaneous non-contiguous deletions using large synthetic DNA and site-specific recombinases

PubMed Central

Krishnakumar, Radha; Grose, Carissa; Haft, Daniel H.; Zaveri, Jayshree; Alperovich, Nina; Gibson, Daniel G.; Merryman, Chuck; Glass, John I.

2014-01-01

Toward achieving rapid and large scale genome modification directly in a target organism, we have developed a new genome engineering strategy that uses a combination of bioinformatics aided design, large synthetic DNA and site-specific recombinases. Using Cre recombinase we swapped a target 126-kb segment of the Escherichia coli genome with a 72-kb synthetic DNA cassette, thereby effectively eliminating over 54 kb of genomic DNA from three non-contiguous regions in a single recombination event. We observed complete replacement of the native sequence with the modified synthetic sequence through the action of the Cre recombinase and no competition from homologous recombination. Because of the versatility and high-efficiency of the Cre-lox system, this method can be used in any organism where this system is functional as well as adapted to use with other highly precise genome engineering systems. Compared to present-day iterative approaches in genome engineering, we anticipate this method will greatly speed up the creation of reduced, modularized and optimized genomes through the integration of deletion analyses data, transcriptomics, synthetic biology and site-specific recombination. PMID:24914053

Computational Design of DNA-Binding Proteins.

PubMed

Thyme, Summer; Song, Yifan

2016-01-01

Predicting the outcome of engineered and naturally occurring sequence perturbations to protein-DNA interfaces requires accurate computational modeling technologies. It has been well established that computational design to accommodate small numbers of DNA target site substitutions is possible. This chapter details the basic method of design used in the Rosetta macromolecular modeling program that has been successfully used to modulate the specificity of DNA-binding proteins. More recently, combining computational design and directed evolution has become a common approach for increasing the success rate of protein engineering projects. The power of such high-throughput screening depends on computational methods producing multiple potential solutions. Therefore, this chapter describes several protocols for increasing the diversity of designed output. Lastly, we describe an approach for building comparative models of protein-DNA complexes in order to utilize information from homologous sequences. These models can be used to explore how nature modulates specificity of protein-DNA interfaces and potentially can even be used as starting templates for further engineering.

Definition of design criteria of mechanical transfer: an interaction between engineering and health areas.

PubMed

Luz, Taciana Ramos; Echternacht, Eliza Helena de Oliveira

2012-01-01

This study aims to analyze the factors that justify the low use of a mechanical transfer in the context of a long-term institution. It is a device intended for internal transportation of individuals who have mobility problems. The analysis involves researchers from the fields of health and engineering in order to generate design criteria that consider the needs of caregivers and patients of this institution. To understand the reality of this site and their specificities, was used Ergonomic Work Analysis.

Mathematics and online learning experiences: a gateway site for engineering students

NASA Astrophysics Data System (ADS)

Masouros, Spyridon D.; Alpay, Esat

2010-03-01

This paper focuses on the preliminary design of a multifaceted computer-based mathematics resource for undergraduate and pre-entry engineering students. Online maths resources, while attractive in their flexibility of delivery, have seen variable interest from students and teachers alike. Through student surveys and wide consultations, guidelines have been developed for effectively collating and integrating learning, support, application and diagnostic tools to produce an Engineer's Mathematics Gateway. Specific recommendations include: the development of a shared database of engineering discipline-specific problems and examples; the identification of, and resource development for, troublesome mathematics topics which encompass ideas of threshold concepts and mastery components; the use of motivational and promotional material to raise student interest in learning mathematics in an engineering context; the use of general and lecture-specific concept maps and matrices to identify the needs and relevance of mathematics to engineering topics; and further exploration of the facilitation of peer-based learning through online resources.

Redesigning the specificity of protein-DNA interactions with Rosetta.

PubMed

Thyme, Summer; Baker, David

2014-01-01

Building protein tools that can selectively bind or cleave specific DNA sequences requires efficient technologies for modifying protein-DNA interactions. Computational design is one method for accomplishing this goal. In this chapter, we present the current state of protein-DNA interface design with the Rosetta macromolecular modeling program. The LAGLIDADG endonuclease family of DNA-cleaving enzymes, under study as potential gene therapy reagents, has been the main testing ground for these in silico protocols. At this time, the computational methods are most useful for designing endonuclease variants that can accommodate small numbers of target site substitutions. Attempts to engineer for more extensive interface changes will likely benefit from an approach that uses the computational design results in conjunction with a high-throughput directed evolution or screening procedure. The family of enzymes presents an engineering challenge because their interfaces are highly integrated and there is significant coordination between the binding and catalysis events. Future developments in the computational algorithms depend on experimental feedback to improve understanding and modeling of these complex enzymatic features. This chapter presents both the basic method of design that has been successfully used to modulate specificity and more advanced procedures that incorporate DNA flexibility and other properties that are likely necessary for reliable modeling of more extensive target site changes.

Using network screening methods to determine locations with specific safety issues: A design consistency case study.

PubMed

Butsick, Andrew J; Wood, Jonathan S; Jovanis, Paul P

2017-09-01

The Highway Safety Manual provides multiple methods that can be used to identify sites with promise (SWiPs) for safety improvement. However, most of these methods cannot be used to identify sites with specific problems. Furthermore, given that infrastructure funding is often specified for use related to specific problems/programs, a method for identifying SWiPs related to those programs would be very useful. This research establishes a method for Identifying SWiPs with specific issues. This is accomplished using two safety performance functions (SPFs). This method is applied to identifying SWiPs with geometric design consistency issues. Mixed effects negative binomial regression was used to develop two SPFs using 5 years of crash data and over 8754km of two-lane rural roadway. The first SPF contained typical roadway elements while the second contained additional geometric design consistency parameters. After empirical Bayes adjustments, sites with promise (SWiPs) were identified. The disparity between SWiPs identified by the two SPFs was evident; 40 unique sites were identified by each model out of the top 220 segments. By comparing sites across the two models, candidate road segments can be identified where a lack design consistency may be contributing to an increase in expected crashes. Practitioners can use this method to more effectively identify roadway segments suffering from reduced safety performance due to geometric design inconsistency, with detailed engineering studies of identified sites required to confirm the initial assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Engineering Translational Activators with CRISPR-Cas System.

PubMed

Du, Pei; Miao, Chensi; Lou, Qiuli; Wang, Zefeng; Lou, Chunbo

2016-01-15

RNA parts often serve as critical components in genetic engineering. Here we report a design of translational activators which is composed of an RNA endoribonuclease (Csy4) and two exchangeable RNA modules. Csy4, a member of Cas endoribonuclease, cleaves at a specific recognition site; this cleavage releases a cis-repressive RNA module (crRNA) from the masked ribosome binding site (RBS), which subsequently allows the downstream translation initiation. Unlike small RNA as a translational activator, the endoribonuclease-based activator is able to efficiently unfold the perfect RBS-crRNA pairing. As an exchangeable module, the crRNA-RBS duplex was forwardly and reversely engineered to modulate the dynamic range of translational activity. We further showed that Csy4 and its recognition site, together as a module, can also be replaced by orthogonal endoribonuclease-recognition site homologues. These modularly structured, high-performance translational activators would endow the programming of gene expression in the translation level with higher feasibility.

NGA-West 2 GMPE average site coefficients for use in earthquake-resistant design

USGS Publications Warehouse

Borcherdt, Roger D.

2015-01-01

Site coefficients corresponding to those in tables 11.4–1 and 11.4–2 of Minimum Design Loads for Buildings and Other Structures published by the American Society of Civil Engineers (Standard ASCE/SEI 7-10) are derived from four of the Next Generation Attenuation West2 (NGA-W2) Ground-Motion Prediction Equations (GMPEs). The resulting coefficients are compared with those derived by other researchers and those derived from the NGA-West1 database. The derivation of the NGA-W2 average site coefficients provides a simple procedure to update site coefficients with each update in the Maximum Considered Earthquake Response MCER maps. The simple procedure yields average site coefficients consistent with those derived for site-specific design purposes. The NGA-W2 GMPEs provide simple scale factors to reduce conservatism in current simplified design procedures.

Metal stabilization of collagen and de novo designed mimetic peptides

PubMed Central

Parmar, Avanish S.; Xu, Fei; Pike, Douglas H.; Belure, Sandeep V.; Hasan, Nida F.; Drzewiecki, Kathryn E.; Shreiber, David I.; Nanda, Vikas

2017-01-01

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix. PMID:26225466

Metal Stabilization of Collagen and de Novo Designed Mimetic Peptides.

PubMed

Parmar, Avanish S; Xu, Fei; Pike, Douglas H; Belure, Sandeep V; Hasan, Nida F; Drzewiecki, Kathryn E; Shreiber, David I; Nanda, Vikas

2015-08-18

We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo- and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal-specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix.

Implications of NGA for NEHRP site coefficients

USGS Publications Warehouse

Borcherdt, Roger D.

2012-01-01

Three proposals are provided to update tables 11.4-1 and 11.4-2 of Minimum Design Loads for Buildings and Other Structures (7-10), by the American Society of Civil Engineers (2010) (ASCE/SEI 7-10), with site coefficients implied directly by NGA (Next Generation Attenuation) ground motion prediction equations (GMPEs). Proposals include a recommendation to use straight-line interpolation to infer site coefficients at intermediate values of ̅vs (average shear velocity). Site coefficients are recommended to ensure consistency with ASCE/SEI 7-10 MCER (Maximum Considered Earthquake) seismic-design maps and simplified site-specific design spectra procedures requiring site classes with associated tabulated site coefficients and a reference site class with unity site coefficients. Recommended site coefficients are confirmed by independent observations of average site amplification coefficients inferred with respect to an average ground condition consistent with that used for the MCER maps. The NGA coefficients recommended for consideration are implied directly by the NGA GMPEs and do not require introduction of additional models.

A rapid, generally applicable method to engineer zinc fingers illustrated by targeting the HIV-1 promoter.

PubMed

Isalan, M; Klug, A; Choo, Y

2001-07-01

DNA-binding domains with predetermined sequence specificity are engineered by selection of zinc finger modules using phage display, allowing the construction of customized transcription factors. Despite remarkable progress in this field, the available protein-engineering methods are deficient in many respects, thus hampering the applicability of the technique. Here we present a rapid and convenient method that can be used to design zinc finger proteins against a variety of DNA-binding sites. This is based on a pair of pre-made zinc finger phage-display libraries, which are used in parallel to select two DNA-binding domains each of which recognizes given 5 base pair sequences, and whose products are recombined to produce a single protein that recognizes a composite (9 base pair) site of predefined sequence. Engineering using this system can be completed in less than two weeks and yields proteins that bind sequence-specifically to DNA with Kd values in the nanomolar range. To illustrate the technique, we have selected seven different proteins to bind various regions of the human immunodeficiency virus 1 (HIV-1) promoter.

Design and evaluation guidelines for Department of Energy facilities subjected to natural phenomena hazards

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

Kennedy, R.P.; Short, S.A.; McDonald, J.R.

1990-06-01

The Department of Energy (DOE) and the DOE Natural Phenomena Hazards Panel have developed uniform design and evaluation guidelines for protection against natural phenomena hazards at DOE sites throughout the United States. The goal of the guidelines is to assure that DOE facilities can withstand the effects of natural phenomena such as earthquakes, extreme winds, tornadoes, and flooding. The guidelines apply to both new facilities (design) and existing facilities (evaluation, modification, and upgrading). The intended audience is primarily the civil/structural or mechanical engineers conducting the design or evaluation of DOE facilities. The likelihood of occurrence of natural phenomena hazards atmore » each DOE site has been evaluated by the DOE Natural Phenomena Hazard Program. Probabilistic hazard models are available for earthquake, extreme wind/tornado, and flood. Alternatively, site organizations are encouraged to develop site-specific hazard models utilizing the most recent information and techniques available. In this document, performance goals and natural hazard levels are expressed in probabilistic terms, and design and evaluation procedures are presented in deterministic terms. Design/evaluation procedures conform closely to common standard practices so that the procedures will be easily understood by most engineers. Performance goals are expressed in terms of structure or equipment damage to the extent that: (1) the facility cannot function; (2) the facility would need to be replaced; or (3) personnel are endangered. 82 refs., 12 figs., 18 tabs.« less

KSC-2012-6405

NASA Image and Video Library

2012-09-20

CAPE CANAVERAL, Fla. -- At NASA’s Kennedy Space Center in Florida, a groundbreaking was held to mark the start of construction on the Antenna Test Bed Array for the Ka-Band Objects Observation and Monitoring, or Ka-BOOM system. Using ceremonial shovels to mark the site, from left are Michael Le, lead design engineer and construction manager Sue Vingris, Cape Design Engineer Co. project manager Kannan Rengarajan, chief executive officer of Cape Design Engineer Co. Lutfi Mized, president of Cape Design Engineer Co. David Roelandt, construction site superintendent with Cape Design Engineer Co. Marc Seibert, NASA project manager Michael Miller, NASA project manager Peter Aragona, KSC’s Electromagnetic Lab manager Stacy Hopper, KSCs master planning supervisor Dr. Bary Geldzabler, NASA chief scientist and KSC’s Chief Technologist Karen Thompson. The construction site is near the former Vertical Processing Facility, which has been demolished. Workers will begin construction on the pile foundations for the 40-foot-diameter dish antenna arrays and their associated utilities, and prepare the site for the operations command center facility. Photo credit: NASA/Charisse Nahser

Site-specific estimation of peak-streamflow frequency using generalized least-squares regression for natural basins in Texas

USGS Publications Warehouse

Asquith, William H.; Slade, R.M.

1999-01-01

The U.S. Geological Survey, in cooperation with the Texas Department of Transportation, has developed a computer program to estimate peak-streamflow frequency for ungaged sites in natural basins in Texas. Peak-streamflow frequency refers to the peak streamflows for recurrence intervals of 2, 5, 10, 25, 50, and 100 years. Peak-streamflow frequency estimates are needed by planners, managers, and design engineers for flood-plain management; for objective assessment of flood risk; for cost-effective design of roads and bridges; and also for the desin of culverts, dams, levees, and other flood-control structures. The program estimates peak-streamflow frequency using a site-specific approach and a multivariate generalized least-squares linear regression. A site-specific approach differs from a traditional regional regression approach by developing unique equations to estimate peak-streamflow frequency specifically for the ungaged site. The stations included in the regression are selected using an informal cluster analysis that compares the basin characteristics of the ungaged site to the basin characteristics of all the stations in the data base. The program provides several choices for selecting the stations. Selecting the stations using cluster analysis ensures that the stations included in the regression will have the most pertinent information about flooding characteristics of the ungaged site and therefore provide the basis for potentially improved peak-streamflow frequency estimation. An evaluation of the site-specific approach in estimating peak-streamflow frequency for gaged sites indicates that the site-specific approach is at least as accurate as a traditional regional regression approach.

A de novo NADPH generation pathway for improving lysine production of Corynebacterium glutamicum by rational design of the coenzyme specificity of glyceraldehyde 3-phosphate dehydrogenase.

PubMed

Bommareddy, Rajesh Reddy; Chen, Zhen; Rappert, Sugima; Zeng, An-Ping

2014-09-01

Engineering the cofactor availability is a common strategy of metabolic engineering to improve the production of many industrially important compounds. In this work, a de novo NADPH generation pathway is proposed by altering the coenzyme specificity of a native NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) to NADP, which consequently has the potential to produce additional NADPH in the glycolytic pathway. Specifically, the coenzyme specificity of GAPDH of Corynebacterium glutamicum is systematically manipulated by rational protein design and the effect of the manipulation for cellular metabolism and lysine production is evaluated. By a combinatorial modification of four key residues within the coenzyme binding sites, different GAPDH mutants with varied coenzyme specificity were constructed. While increasing the catalytic efficiency of GAPDH towards NADP enhanced lysine production in all of the tested mutants, the most significant improvement of lysine production (~60%) was achieved with the mutant showing similar preference towards both NAD and NADP. Metabolic flux analysis with (13)C isotope studies confirmed that there was no significant change of flux towards the pentose phosphate pathway and the increased lysine yield was mainly attributed to the NADPH generated by the mutated GAPDH. The present study highlights the importance of protein engineering as a key strategy in de novo pathway design and overproduction of desired products. Copyright © 2014 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

An Analytical Index to the Internet: Dreams of Utopia.

ERIC Educational Resources Information Center

Casey, Carol

1999-01-01

Explores the need for analytical indexes to access Internet resources. Considers bibliographic control, Web site design, keyword search engines, hierarchical subject indexes, and special indexes and compilations of links, and concludes that the creation of small, focused indexes may be the best solution for accessing specific types of digital…

Deep Borehole Disposal Safety Analysis.

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

Freeze, Geoffrey A.; Stein, Emily; Price, Laura L.

This report presents a preliminary safety analysis for the deep borehole disposal (DBD) concept, using a safety case framework. A safety case is an integrated collection of qualitative and quantitative arguments, evidence, and analyses that substantiate the safety, and the level of confidence in the safety, of a geologic repository. This safety case framework for DBD follows the outline of the elements of a safety case, and identifies the types of information that will be required to satisfy these elements. At this very preliminary phase of development, the DBD safety case focuses on the generic feasibility of the DBD concept.more » It is based on potential system designs, waste forms, engineering, and geologic conditions; however, no specific site or regulatory framework exists. It will progress to a site-specific safety case as the DBD concept advances into a site-specific phase, progressing through consent-based site selection and site investigation and characterization.« less

Human-factors engineering control-room design review/audit: Waterford 3 SES Generating Station, Louisiana Power and Light Company

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

Savage, J.W.

1983-03-10

A human factors engineering design review/audit of the Waterford-3 control room was performed at the site on May 10 through May 13, 1982. The report was prepared on the basis of the HFEB's review of the applicant's Preliminary Human Engineering Discrepancy (PHED) report and the human factors engineering design review performed at the site. This design review was carried out by a team from the Human Factors Engineering Branch, Division of Human Factors Safety. The review team was assisted by consultants from Lawrence Livermore National Laboratory (University of California), Livermore, California.

Earthquake scenario and probabilistic ground-shaking hazard maps for the Albuquerque-Belen-Santa Fe, New Mexico, corridor

USGS Publications Warehouse

Wong, I.; Olig, S.; Dober, M.; Silva, W.; Wright, D.; Thomas, P.; Gregor, N.; Sanford, A.; Lin, K.-W.; Love, D.

2004-01-01

These maps are not intended to be a substitute for site-specific studies for engineering design nor to replace standard maps commonly referenced in building codes. Rather, we hope that these maps will be used as a guide by government agencies; the engineering, urban planning, emergency preparedness, and response communities; and the general public as part of an overall program to reduce earthquake risk and losses in New Mexico.

Finite element strategies to satisfy clinical and engineering requirements in the field of percutaneous valves.

PubMed

Capelli, Claudio; Biglino, Giovanni; Petrini, Lorenza; Migliavacca, Francesco; Cosentino, Daria; Bonhoeffer, Philipp; Taylor, Andrew M; Schievano, Silvia

2012-12-01

Finite element (FE) modelling can be a very resourceful tool in the field of cardiovascular devices. To ensure result reliability, FE models must be validated experimentally against physical data. Their clinical application (e.g., patients' suitability, morphological evaluation) also requires fast simulation process and access to results, while engineering applications need highly accurate results. This study shows how FE models with different mesh discretisations can suit clinical and engineering requirements for studying a novel device designed for percutaneous valve implantation. Following sensitivity analysis and experimental characterisation of the materials, the stent-graft was first studied in a simplified geometry (i.e., compliant cylinder) and validated against in vitro data, and then in a patient-specific implantation site (i.e., distensible right ventricular outflow tract). Different meshing strategies using solid, beam and shell elements were tested. Results showed excellent agreement between computational and experimental data in the simplified implantation site. Beam elements were found to be convenient for clinical applications, providing reliable results in less than one hour in a patient-specific anatomical model. Solid elements remain the FE choice for engineering applications, albeit more computationally expensive (>100 times). This work also showed how information on device mechanical behaviour differs when acquired in a simplified model as opposed to a patient-specific model.

Launch Vehicle Control Center Architectures

NASA Technical Reports Server (NTRS)

Watson, Michael D.; Epps, Amy; Woodruff, Van; Vachon, Michael Jacob; Monreal, Julio; Williams, Randall; McLaughlin, Tom

2014-01-01

This analysis is a survey of control center architectures of the NASA Space Launch System (SLS), United Launch Alliance (ULA) Atlas V and Delta IV, and the European Space Agency (ESA) Ariane 5. Each of these control center architectures have similarities in basic structure, and differences in functional distribution of responsibilities for the phases of operations: (a) Launch vehicles in the international community vary greatly in configuration and process; (b) Each launch site has a unique processing flow based on the specific configurations; (c) Launch and flight operations are managed through a set of control centers associated with each launch site, however the flight operations may be a different control center than the launch center; and (d) The engineering support centers are primarily located at the design center with a small engineering support team at the launch site.

Site Selection for Mars Surveyor Landing Sites: Some Key Factors for 2001 and Relation to Long-Term Exploration of Mars

NASA Astrophysics Data System (ADS)

Head, James W.

1999-01-01

The Site Selection Process: Site selection as a process can be subdivided into several main elements and these can be represented as the corners of a tetrahedron. Successful site selection outcome requires the interactions between these elements or corners, and should also take into account several other external factors or considerations. In principle, elements should be defined in approximately the following order: (1) major scientific and programmatic goals and objectives: What are the major questions that are being asked, goals that should be achieved, and objectives that must be accomplished. Do programmatic goals (e.g., sample return) differ from mission goals (e.g., precursor to sample return)? It is most helpful if these questions can be placed in the context of site characterization and hypothesis testing (e.g., Was Mars warm and wet in the Noachian? Land at a Noachian-aged site that shows evidence of surface water and characterize it specifically to address this question). Goals and objectives, then, help define important engineering factors such as type of payload, landing regions of interest (highlands, lowlands, smooth, rough, etc.), mobility, mission duration, etc. Goals and objectives then lead to: (2) spacecraft design and engineering landing site constraints: the spacecraft is designed to optimize the areas that will meet the goals and objectives, but this in turn introduces constraints that must be met in the selection of a landing site. Scientific and programmatic goals and objectives also help to define (3), the specific lander scientific payload requirements and capabilities. For example, what observations and experiments are required to address the major questions? How do we characterize the site in reference to the specific questions? Is mobility required and if so, how much? Which experiments are on the spacecraft, which on the rover? The results of these deliberations should lead to a surface exploration strategy, in which the goals and objectives can in principle be achieved through the exploration of a site meeting the basic engineering constraints. Armed with all of this important background information, one can then proceed to (4) the selection of optimum sites to address major scientific and programmatic objectives. Following the successful completion of this process and the selection of a site or region, there is a further step of mission optimization, in which a detailed mission profile and surface exploration plan is developed. In practice, the process never works in a linear fashion. Scientific goals are influenced by ongoing discoveries and developments and simple crystallization of thinking. Programmatic goals are influenced by evolving fiscal constraints, perspectives on program duration, and roles of specific missions in the context of the larger program. Engineering constraints are influenced by evolving fiscal constraints, decisions on hardware design that may have little to do with scientific goals (e.g., lander clearance; size of landing ellipse), and evolving understanding (e.g., assessment of engineering constraint space reveals further the degree to which mission duration is severely influenced by available solar energy and thus latitude). Lander scientific payload is influenced by fiscal constraints, total mass, evolving complexity, technological developments, and a payload selection process that may involve very long-term goals (e.g., human exploration) as well as shorter term scientific and programmatic goals. Site selection activities commonly involve scientists who are actively trying to decipher the complex geology of the crust of Mars and to unravel its geologic history through geological mapping. By the nature of the process, they are thinking in terms of broad morphostratigraphic units which may have multiple possible origins, defined using images with resolutions of many tens to hundreds of meters, and whose surfaces at the scale of the lander and rover are virtually unknown; this approach and effort is crucially important but does not necessarily readily lend itself to integration with the other elements.

Coast of California Storm and Tidal Waves Study. Shoreline Movement Data Report. Portuguese Point to Mexican Border (1852-1982),

DTIC Science & Technology

1985-12-01

34.uld not be used for site-specific shoreline ch~n i analisi For USe in engieering or planning studies, the companion analysis report haid be consulted...compiled from aerial photoraphy talum 1982. This is a speciat poros map designed for use by the U.S. Army Corps of Engineers. Natonal Oceanic and...is a speciat purpose map deisigned for use by the U.S. Army Corps of Engineers, National Ocemc and Atmospheric Administration. andother agencies

megaTALs: a rare-cleaving nuclease architecture for therapeutic genome engineering.

PubMed

Boissel, Sandrine; Jarjour, Jordan; Astrakhan, Alexander; Adey, Andrew; Gouble, Agnès; Duchateau, Philippe; Shendure, Jay; Stoddard, Barry L; Certo, Michael T; Baker, David; Scharenberg, Andrew M

2014-02-01

Rare-cleaving endonucleases have emerged as important tools for making targeted genome modifications. While multiple platforms are now available to generate reagents for research applications, each existing platform has significant limitations in one or more of three key properties necessary for therapeutic application: efficiency of cleavage at the desired target site, specificity of cleavage (i.e. rate of cleavage at 'off-target' sites), and efficient/facile means for delivery to desired target cells. Here, we describe the development of a single-chain rare-cleaving nuclease architecture, which we designate 'megaTAL', in which the DNA binding region of a transcription activator-like (TAL) effector is used to 'address' a site-specific meganuclease adjacent to a single desired genomic target site. This architecture allows the generation of extremely active and hyper-specific compact nucleases that are compatible with all current viral and nonviral cell delivery methods.

Remedial Action Plan and site design for stabilization of the inactive uranium mill tailings site at Durango, Colorado: Attachment 2, Geology report. Revised final report

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

Not Available

1991-12-01

Detailed investigations of geologic, geomorphic, and seismic conditions at the Bodo Canyon disposal site were conducted. The purpose of these investigations was basic site characterization and identification of potential geologic hazards that could affect long-term site stability. Subsequent engineering studies, such as analyses of hydrologic and liquefaction hazards, used the data developed in these studies. The geomorphic analysis was employed in the design of effective erosion protection. Studies of the regional and local seismotectonic setting, which included a detailed search for possible capable faults within a 65 kilometer radius of the site, provided the basis for seismic design parameters. Themore » scope of work performed included the following: Compilation and analysis of previous published and unpublished geologic literature and maps; Review of historical and instrumental earthquake data; Review of site-specific subsurface geologic data, including lithologic and geophysical logs of exploratory boreholes advanced in the site area; Photogeologic interpretations of existing conventional aerial photographs; and, Ground reconnaissance and mapping of the site region.« less

KSC-2012-6404

NASA Image and Video Library

2012-09-20

CAPE CANAVERAL, Fla. -- At NASA’s Kennedy Space Center in Florida, a groundbreaking was held to mark the start of construction on the Antenna Test Bed Array for the Ka-Band Objects Observation and Monitoring, or Ka-BOOM system. Holding ceremonial shovels, from left are Michael Le, lead design engineer and construction manager Sue Vingris, Cape Design Engineer Co. project manager Kannan Rengarajan, chief executive officer of Cape Design Engineer Co. Lutfi Mized, president of Cape Design Engineer Co. David Roelandt, construction site superintendent with Cape Design Engineer Co. Marc Seibert, NASA project manager Michael Miller, NASA project manager Peter Aragona, KSC’s Electromagnetic Lab manager Stacy Hopper, KSCs master planning supervisor Dr. Bary Geldzabler, NASA chief scientist and KSC’s Chief Technologist Karen Thompson. The construction site is near the former Vertical Processing Facility, which has been demolished. Workers will begin construction on the pile foundations for the 40-foot-diameter dish antenna arrays and their associated utilities, and prepare the site for the operations command center facility. Photo credit: NASA/Charisse Nahser

78 FR 38672 - Ocean Dumping; Sabine-Neches Waterway (SNWW) Ocean Dredged Material Disposal Site Designation

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-27

... March 2011 prepared by the U.S. Army Corps of Engineers (also Corps or USACE). Appendix B of Volume III... be considered on the proposed site designations. The U.S. Army Corps of Engineers Final EIS for the... of dredged material from the Sabine-Neches Waterway. Currently, the US Army Corps of Engineers will...

Engineering peptide ligase specificity by proteomic identification of ligation sites.

PubMed

Weeks, Amy M; Wells, James A

2018-01-01

Enzyme-catalyzed peptide ligation is a powerful tool for site-specific protein bioconjugation, but stringent enzyme-substrate specificity limits its utility. We developed an approach for comprehensively characterizing peptide ligase specificity for N termini using proteome-derived peptide libraries. We used this strategy to characterize the ligation efficiency for >25,000 enzyme-substrate pairs in the context of the engineered peptide ligase subtiligase and identified a family of 72 mutant subtiligases with activity toward N-terminal sequences that were previously recalcitrant to modification. We applied these mutants individually for site-specific bioconjugation of purified proteins, including antibodies, and in algorithmically selected combinations for sequencing of the cellular N terminome with reduced sequence bias. We also developed a web application to enable algorithmic selection of the most efficient subtiligase variant(s) for bioconjugation to user-defined sequences. Our methods provide a new toolbox of enzymes for site-specific protein modification and a general approach for rapidly defining and engineering peptide ligase specificity.

Engineering synthetic TAL effectors with orthogonal target sites

PubMed Central

Garg, Abhishek; Lohmueller, Jason J.; Silver, Pamela A.; Armel, Thomas Z.

2012-01-01

The ability to engineer biological circuits that process and respond to complex cellular signals has the potential to impact many areas of biology and medicine. Transcriptional activator-like effectors (TALEs) have emerged as an attractive component for engineering these circuits, as TALEs can be designed de novo to target a given DNA sequence. Currently, however, the use of TALEs is limited by degeneracy in the site-specific manner by which they recognize DNA. Here, we propose an algorithm to computationally address this problem. We apply our algorithm to design 180 TALEs targeting 20 bp cognate binding sites that are at least 3 nt mismatches away from all 20 bp sequences in putative 2 kb human promoter regions. We generated eight of these synthetic TALE activators and showed that each is able to activate transcription from a targeted reporter. Importantly, we show that these proteins do not activate synthetic reporters containing mismatches similar to those present in the genome nor a set of endogenous genes predicted to be the most likely targets in vivo. Finally, we generated and characterized TALE repressors comprised of our orthogonal DNA binding domains and further combined them with shRNAs to accomplish near complete repression of target gene expression. PMID:22581776

Human Mars Ascent Vehicle Performance Sensitivities

NASA Technical Reports Server (NTRS)

Polsgrove, Tara P.; Thomas, Herbert D.

2016-01-01

Human Mars mission architecture studies have shown that the ascent vehicle mass drives performance requirements for the descent and in-space transportation elements. Understanding the sensitivity of Mars ascent vehicle (MAV) mass to various mission and vehicle design choices enables overall transportation system optimization. This paper presents the results of a variety of sensitivity trades affecting MAV performance including: landing site latitude, target orbit, initial thrust to weight ratio, staging options, specific impulse, propellant type and engine design.

A Molecular Toolbox to Engineer Site-Specific DNA Replication Perturbation.

PubMed

Larsen, Nicolai B; Hickson, Ian D; Mankouri, Hocine W

2018-01-01

Site-specific arrest of DNA replication is a useful tool for analyzing cellular responses to DNA replication perturbation. The E. coli Tus-Ter replication barrier can be reconstituted in eukaryotic cells as a system to engineer an unscheduled collision between a replication fork and an "alien" impediment to DNA replication. To further develop this system as a versatile tool, we describe a set of reagents and a detailed protocol that can be used to engineer Tus-Ter barriers into any locus in the budding yeast genome. Because the Tus-Ter complex is a bipartite system with intrinsic DNA replication-blocking activity, the reagents and protocols developed and validated in yeast could also be optimized to engineer site-specific replication fork barriers into other eukaryotic cell types.

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

Peck, T; Sparkman, D; Storch, N

''The LLNL Site-Specific Advanced Simulation and Computing (ASCI) Software Quality Engineering Recommended Practices VI.I'' document describes a set of recommended software quality engineering (SQE) practices for ASCI code projects at Lawrence Livermore National Laboratory (LLNL). In this context, SQE is defined as the process of building quality into software products by applying the appropriate guiding principles and management practices. Continual code improvement and ongoing process improvement are expected benefits. Certain practices are recommended, although projects may select the specific activities they wish to improve, and the appropriate time lines for such actions. Additionally, projects can rely on the guidance ofmore » this document when generating ASCI Verification and Validation (VSrV) deliverables. ASCI program managers will gather information about their software engineering practices and improvement. This information can be shared to leverage the best SQE practices among development organizations. It will further be used to ensure the currency and vitality of the recommended practices. This Overview is intended to provide basic information to the LLNL ASCI software management and development staff from the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I'' document. Additionally the Overview provides steps to using the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I'' document. For definitions of terminology and acronyms, refer to the Glossary and Acronyms sections in the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I''.« less

Utilizing Unnatural Amino Acids to Illustrate Protein Structure-Function Relationships: An Experiment Designed for an Undergraduate Biochemistry Laboratory

ERIC Educational Resources Information Center

Maza, Johnathan C.; Villa, Jordan K.; Landino, Lisa M.; Young, Douglas D

2016-01-01

The site-specific introduction of unnatural amino acids (UAAs) has been demonstrated to be a useful tool in protein engineering. Moreover, the incorporation of a UAA into a protein has become feasible with the increased commercial availability of UAAs and robust expression plasmids. In addition to the ease of incorporation, the concepts utilized…

Evolution of a designed retro-aldolase leads to complete active site remodeling

PubMed Central

Giger, Lars; Caner, Sami; Obexer, Richard; Kast, Peter; Baker, David; Ban, Nenad; Hilvert, Donald

2013-01-01

Evolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that dramatic molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400 fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate, and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. PMID:23748672

Management and integration of engineering and construction activities: Lessons learned from the AP1000{sup R} nuclear power plant China project

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

McCullough, M. C.; Ebeling-Koning, D.; Evans, M. C.

2012-07-01

The lessons learned during the early phase of design engineering and construction activities for the AP1000 China Project can be applied to any project involving multiple disciplines and multiple organizations. Implementation of a first-of-a-kind design to directly support construction activities utilizing resources assigned to design development and design delivery creates challenges with prioritization of activities, successful closure of issues, and communication between site organizations and the home office. To ensure successful implementation, teams were assigned and developed to directly support construction activities including prioritization of activities, site communication and ensuring closure of site emergent issues. By developing these teams, themore » organization is better suited to meet the demands of the construction schedule while continuing with design evolution of a standard plant and engineering delivery for multiple projects. For a successful project, proper resource utilization and prioritization are key for overcoming obstacles and ensuring success of the engineering organization. (authors)« less

Design of self-assembling beta-hairpin pepide-based hydrogels for tissue engineering applications

NASA Astrophysics Data System (ADS)

Butterick, Lisa Ann

The field of tissue engineering aims to repair damaged tissues and organs with diminished function. One approach used in tissue engineering is to introduce cells and/or growth factors to the damaged tissue in either one of two ways. The first method is an invasive procedure where cells are introduced to a preformed scaffold and cultured in vitro. The scaffold is then inserted into the host by making an incision at the site of interest, which must be as large as the preformed scaffold. The second method is a minimally invasive procedure where cells are suspended in a polymeric solution and injected via syringe. After leaving the syringe, the material undergoes a phase transition to form a hydrogel at the site of introduction. Regardless of the delivery mechanism employed, development of an appropriate scaffold conducive to cellular proliferation and extracellular matrix production is critical to the success of the implanted material in persuading the body to repair itself. In working toward this goal, we have developed a family of beta-hairpin peptides, based on the design MAX1, that undergoes intramolecular folding and self-assembly to form rigid hydrogels in response to changes in pH, ionic strength, and temperature. From a molecular design standpoint of view, site specific N-methylation of MAX1 was performed to determine the importance of forming hydrogen bonds during the self-assembly event and its effect on hydrogelation. The remainder of this thesis is dedicated to the development of materials and minimally methodologies to deliver gel/cell constructs via syringe to target sites to aid in tissue repair. A peptide, MAX7CNB was designed that undergoes folding and assembly in response to ultraviolet light to form hydrogel material. In addition, MAX8 was rationally designed to display the appropriate hydrogelation kinetics to achieve homogenous cellular encapsulation throughout the gel matrix. MAX8 gel/cell scaffolds can be easily delivered via syringe to secondary target sites while maintaining cellular homogeneity, viability and remain fixed at the site of introduction. Additionally, preliminary in vitro based studies employing mouse peritoneal macrophages suggest the MAX8 gels are non-inflammatory in nature and may not elicit an in vivo immune response upon implantation. It has been demonstrated throughout this thesis that by employing amino acids as fundamental building blocks, peptide sequences can be designed to undergo molecular recognition, resulting in hydrogel material for use in tissue engineering applications.

Nuclease-mediated genome editing: At the front-line of functional genomics technology.

PubMed

Sakuma, Tetsushi; Woltjen, Knut

2014-01-01

Genome editing with engineered endonucleases is rapidly becoming a staple method in developmental biology studies. Engineered nucleases permit random or designed genomic modification at precise loci through the stimulation of endogenous double-strand break repair. Homology-directed repair following targeted DNA damage is mediated by co-introduction of a custom repair template, allowing the derivation of knock-out and knock-in alleles in animal models previously refractory to classic gene targeting procedures. Currently there are three main types of customizable site-specific nucleases delineated by the source mechanism of DNA binding that guides nuclease activity to a genomic target: zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR). Among these genome engineering tools, characteristics such as the ease of design and construction, mechanism of inducing DNA damage, and DNA sequence specificity all differ, making their application complementary. By understanding the advantages and disadvantages of each method, one may make the best choice for their particular purpose. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

A WEB based approach in biomedical engineering design education.

PubMed

Enderle, J D; Browne, A F; Hallowell, M B

1997-01-01

As part of the accreditation process for university engineering programs, students are required to complete a minimum number of design credits in their course of study, typically at the senior level. Many call this the capstone course. Engineering design is a course or series of courses that bring together concepts and principles that students learn in their field of study--it involves the integration and extension of material learned in their major toward a specific project. Most often, the student is exposed to system-wide analysis, critique and evaluation for the first time. Design is an iterative, decision making process in which the student optimally applies previously learned material to meet a stated objective. At the University of Connecticut, students work in teams of 3-4 members and work on externally sponsored projects. To facilitate working with sponsors, a WEB based approach is used for reporting the progress on projects. Students are responsible for creating their own WEB sites that support both html and pdf formats. Students provide the following deliverables: weekly progress reports, project statement, specifications, project proposal, interim report, and final report. A senior design homepage also provides links to data books and other resources for use by students. We are also planning distance learning experiences between two campuses so students can work on projects that involve the use of video conferencing.

Collection, processing and dissemination of data for the national solar demonstration program

NASA Technical Reports Server (NTRS)

Day, R. E.; Murphy, L. J.; Smok, J. T.

1978-01-01

A national solar data system developed for the DOE by IBM provides for automatic gathering, conversion, transfer, and analysis of demonstration site data. NASA requirements for this system include providing solar site hardware, engineering, data collection, and analysis. The specific tasks include: (1) solar energy system design/integration; (2) developing a site data acquisition subsystem; (3) developing a central data processing system; (4) operating the test facility at Marshall Space Flight Center; (5) collecting and analyzing data. The systematic analysis and evaluation of the data from the National Solar Data System is reflected in a monthly performance report and a solar energy system performance evaluation report.

Emerging engineering principles for yield improvement in microbial cell design.

PubMed

Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo

2012-01-01

Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling.

Emerging engineering principles for yield improvement in microbial cell design

PubMed Central

Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo

2012-01-01

Metabolic Engineering has undertaken a rapid transformation in the last ten years making real progress towards the production of a wide range of molecules and fine chemicals using a designed cellular host. However, the maximization of product yields through pathway optimization is a constant and central challenge of this field. Traditional methods used to improve the production of target compounds from engineered biosynthetic pathways in non-native hosts include: codon usage optimization, elimination of the accumulation of toxic intermediates or byproducts, enhanced production of rate-limiting enzymes, selection of appropriate promoter and ribosome binding sites, application of directed evolution of enzymes, and chassis re-circuit. Overall, these approaches tend to be specific for each engineering project rather than a systematic practice based on a more generalizable strategy. In this mini-review, we highlight some novel and extensive approaches and tools intended to address the improvement of a target product formation, founded in sophisticated principles such as dynamic control, pathway genes modularization, and flux modeling. PMID:24688676

Eco-Design of River Fishways for Upstream Passage: Application for Hanfeng Dam, Pengxi River, China

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

Johnson, Gary E.; Rainey, William S.

2012-05-20

This paper provides a scientific approach to eco-design of river fishways to allow upstream movement of fish past new and existing dams in China. This eco-design approach integrates principles of fish ecology/behavior and engineering, a scientific field also known as bio-engineering or eco-hydraulics. We define a fishway as a structure or mechanism to convey fish upstream past a dam. Man-made or natural stream beds can be part of the fishway mechanism. Fish include bony and non-bony fishes, and upstream passage is the concern here, not downstream passage. The problem is dams block access to upstream habitat used for spawning, rearing,more » and refuge, i.e., dams decrease habitat connectivity. A solution to alleviate this problem is to design fishways, preferably while the dam is being designed, but if necessary, as retrofits afterward to provide a route that fish can and will use to pass safely upstream without undue delay. Our eco-design approach for fishways involves eight steps: 1) identify the primary species of importance; 2) understand basic ecology and behavior of these fish; 3) characterize the environmental conditions where passage is or will be blocked; 4 identify fishway alternatives and select a preferred alternative; 5) establish eco-design criteria for the fishway, either from management agencies or, if necessary, developed specifically for the given site; 6) where needed, identify and perform research required to resolve critical uncertainties and finalize the eco-design criteria; 7) apply the eco-design criteria and site-specific considerations to design the fishway, involving peer-review by local stakeholders in the process; 8) build the fishway, monitor its effectiveness, and apply the lessons learned. Example fishways are described showing a range of eco-designs depending on the dam site and fish species of concern. We apply the eco-design principles to recommend an approach and next steps for a fishway to pass fish upstream at Hanfeng Dam, an existing regulating dam forming Hanfeng Lake on the Pengxi River near Kaixian, China.« less

Site-Specific Genome Engineering in Human Pluripotent Stem Cells.

PubMed

Merkert, Sylvia; Martin, Ulrich

2016-06-24

The possibility to generate patient-specific induced pluripotent stem cells (iPSCs) offers an unprecedented potential of applications in clinical therapy and medical research. Human iPSCs and their differentiated derivatives are tools for diseases modelling, drug discovery, safety pharmacology, and toxicology. Moreover, they allow for the engineering of bioartificial tissue and are promising candidates for cellular therapies. For many of these applications, the ability to genetically modify pluripotent stem cells (PSCs) is indispensable, but efficient site-specific and safe technologies for genetic engineering of PSCs were developed only recently. By now, customized engineered nucleases provide excellent tools for targeted genome editing, opening new perspectives for biomedical research and cellular therapies.

Viral proteases: an emerging therapeutic target.

PubMed

Korant, B D

1988-01-01

Only a few viral diseases are presently treatable because of our limited knowledge of specific viral target molecules. An attractive class of viral molecules toward which chemotherapeutic agents could be aimed are proteases coded by some virus groups such as retro- or picornaviruses (poliomyelitis, common cold virus). The picornavirus enzymes were discovered first, and they have now been characterized by a combination of molecular-genetic and biochemical approaches. Several laboratories have expressed the picornaviral enzymes in heterologous systems and have reported proteolytic activity, as well as the high cleavage fidelity diagnostic of the viral proteases. After dealing with several technical difficulties often encountered in standard genetic engineering approaches, one viral protease is now available to us in quantity and is amendable to mutagenic procedures. The initial outcome of the mutagenesis studies has been the confirmation of our earlier work with inhibitors, which suggested a cysteine active-site class. There is a clustering of active-site residues which may be unique to these viruses. The requirement for an active-site cysteine-histidine pair in combination with detailed information on the viral cleavage sites has permitted design of selective inhibitors with attractive antiviral properties. Future goals include investigation of the structural basis for selective processing and application of the cleavage specificity to general problems in genetic engineering.

The ARCO 1 megawatt Photovoltaic Power Plant

NASA Astrophysics Data System (ADS)

Rhodes, G. W.; Reilly, M. R.

The world's largest Photovoltaic Power Plant is in operation and meeting performance specifications on the Southern California Edison (SCE) grid near Hesperia, California. The 1 MW plant designed and constructed by The BDM Corporation, for ARCO Solar Inc., occupies a 20 acre site adjacent to the SCE Lugo substation. The entire design and construction process took 7 1/2 months and was not only on schedule but below budget. Because of its vast photovoltaic experience, BDM was chosen over several engineering firms to perform this complex job. We were provided a conceptual design from ARCO which we quickly refined and immediately initiated construction.

Size Matters: Developing Design Rules to Engineer Nanoparticles for Solid Tumour Targeting

NASA Astrophysics Data System (ADS)

Sykes, Edward Alexander

Nanotechnology enables the design of highly customizable platforms for producing minimally invasive and programmable strategies for cancer diagnosis and treatment. Advances in this field have demonstrated that nanoparticles can enhance specificity of anti-cancer agents, respond to tumour-specific cues, and direct the visualization of biological targets in vivo. . Nanoparticles can be synthesized within the 1 to 100 nm range to achieve different electromagnetic properties and specifically interact with biological tissues by tuning their size, shape, and surface chemistry. However, it remains unclear which physicochemical parameters are critical for delivering nanomaterials to the tumour site. With less than 5% of administered nanoparticles reaching the tumour, engineering of nanoparticles for effective delivery to solid tumours remains a critical challenge to cancer nanomedicine. A more comprehensive understanding of the interplay between the nanomaterial physicochemical properties and biological systems is necessary to enhance the efficacy of nanoparticle tumour targeting. This thesis explores how nanoparticle size and functionalization with cancer cell specific agents impact nanoparticle delivery to tumours. Furthermore, this doctoral work (i) discusses how tumour structure evolves with growth, (ii) elucidates how such changes modulate nanoparticle accumulation, and (iii) identifies how the skin serves as a significant off-target site for nanoparticle uptake. This thesis also demonstrates the utility of empirically-derived parametric models, Monte Carlo simulations, and decision matrices for mechanistically understanding and predicting the impact of nanomaterial features and tumour biology on nanoparticle fate in vivo. These topics establish key design considerations to tailor nanoparticles for enhanced tumour targeting. Collectively, the concepts presented herein form a fundamental framework for the development of personalized nanomedicine and nano-diagnostic agents in the future.

FLP recombinase-mediated site-specific recombination in silkworm, Bombyx mori

USDA-ARS?s Scientific Manuscript database

A comprehensive understanding of gene function and the production of site-specific genetically modified mutants are two major goals of genetic engineering in the post-genomic era. Although site-specific recombination systems have been powerful tools for genome manipulation of many organisms, they h...

Dengue Virus NS2B/NS3 Protease Inhibitors Exploiting the Prime Side.

PubMed

Lin, Kuan-Hung; Ali, Akbar; Rusere, Linah; Soumana, Djade I; Kurt Yilmaz, Nese; Schiffer, Celia A

2017-05-15

The mosquito-transmitted dengue virus (DENV) infects millions of people in tropical and subtropical regions. Maturation of DENV particles requires proper cleavage of the viral polyprotein, including processing of 8 of the 13 substrate cleavage sites by dengue virus NS2B/NS3 protease. With no available direct-acting antiviral targeting DENV, NS2/NS3 protease is a promising target for inhibitor design. Current design efforts focus on the nonprime side of the DENV protease active site, resulting in highly hydrophilic and nonspecific scaffolds. However, the prime side also significantly modulates DENV protease binding affinity, as revealed by engineering the binding loop of aprotinin, a small protein with high affinity for DENV protease. In this study, we designed a series of cyclic peptides interacting with both sides of the active site as inhibitors of dengue virus protease. The design was based on two aprotinin loops and aimed to leverage both key specific interactions of substrate sequences and the entropic advantage driving aprotinin's high affinity. By optimizing the cyclization linker, length, and amino acid sequence, the tightest cyclic peptide achieved a K i value of 2.9 μM against DENV3 wild-type (WT) protease. These inhibitors provide proof of concept that both sides of DENV protease active site can be exploited to potentially achieve specificity and lower hydrophilicity in the design of inhibitors targeting DENV. IMPORTANCE Viruses of the flaviviral family, including DENV and Zika virus transmitted by Aedes aegypti , continue to be a threat to global health by causing major outbreaks in tropical and subtropical regions, with no available direct-acting antivirals for treatment. A better understanding of the molecular requirements for the design of potent and specific inhibitors against flaviviral proteins will contribute to the development of targeted therapies for infections by these viruses. The cyclic peptides reported here as DENV protease inhibitors provide novel scaffolds that enable exploiting the prime side of the protease active site, with the aim of achieving better specificity and lower hydrophilicity than those of current scaffolds in the design of antiflaviviral inhibitors. Copyright © 2017 American Society for Microbiology.

Context influences on TALE–DNA binding revealed by quantitative profiling

PubMed Central

Rogers, Julia M.; Barrera, Luis A.; Reyon, Deepak; Sander, Jeffry D.; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L.

2015-01-01

Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE–DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000–20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE–DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design. PMID:26067805

Context influences on TALE-DNA binding revealed by quantitative profiling.

PubMed

Rogers, Julia M; Barrera, Luis A; Reyon, Deepak; Sander, Jeffry D; Kellis, Manolis; Joung, J Keith; Bulyk, Martha L

2015-06-11

Transcription activator-like effector (TALE) proteins recognize DNA using a seemingly simple DNA-binding code, which makes them attractive for use in genome engineering technologies that require precise targeting. Although this code is used successfully to design TALEs to target specific sequences, off-target binding has been observed and is difficult to predict. Here we explore TALE-DNA interactions comprehensively by quantitatively assaying the DNA-binding specificities of 21 representative TALEs to ∼5,000-20,000 unique DNA sequences per protein using custom-designed protein-binding microarrays (PBMs). We find that protein context features exert significant influences on binding. Thus, the canonical recognition code does not fully capture the complexity of TALE-DNA binding. We used the PBM data to develop a computational model, Specificity Inference For TAL-Effector Design (SIFTED), to predict the DNA-binding specificity of any TALE. We provide SIFTED as a publicly available web tool that predicts potential genomic off-target sites for improved TALE design.

Bridge scour countermeasure assessments at select bridges in the United States, 2014–16

USGS Publications Warehouse

Dudunake, Taylor J.; Huizinga, Richard J.; Fosness, Ryan L.

2017-05-23

In 2009, the Federal Highway Administration published Hydraulic Engineering Circular No. 23 (HEC-23) to provide specific design and implementation guidelines for bridge scour and stream instability countermeasures. However, the effectiveness of countermeasures implemented over the past decade following those guidelines has not been evaluated. Therefore, in 2013, the U.S. Geological Survey, in cooperation with the Federal Highway Administration, began a study to assess the current condition of bridge-scour countermeasures at selected sites to evaluate their effectiveness. Bridge-scour countermeasures were assessed during 2014-2016. Site assessments included reviewing countermeasure design plans, summarizing the peak and daily streamflow history, and assessments at each site. Each site survey included a photo log summary, field form, and topographic and bathymetric geospatial data and metadata. This report documents the study area and site-selection criteria, explains the survey methods used to evaluate the condition of countermeasures, and presents the complete documentation for each countermeasure assessment.

Engineering design skills coverage in K-12 engineering program curriculum materials in the USA

NASA Astrophysics Data System (ADS)

Chabalengula, Vivien M.; Mumba, Frackson

2017-11-01

The current K-12 Science Education framework and Next Generation Science Standards (NGSS) in the United States emphasise the integration of engineering design in science instruction to promote scientific literacy and engineering design skills among students. As such, many engineering education programmes have developed curriculum materials that are being used in K-12 settings. However, little is known about the nature and extent to which engineering design skills outlined in NGSS are addressed in these K-12 engineering education programme curriculum materials. We analysed nine K-12 engineering education programmes for the nature and extent of engineering design skills coverage. Results show that developing possible solutions and actual designing of prototypes were the highly covered engineering design skills; specification of clear goals, criteria, and constraints received medium coverage; defining and identifying an engineering problem; optimising the design solution; and demonstrating how a prototype works, and making iterations to improve designs were lowly covered. These trends were similar across grade levels and across discipline-specific curriculum materials. These results have implications on engineering design-integrated science teaching and learning in K-12 settings.

Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition

DOE PAGES

Melero, Cristina; Ollikainen, Noah; Harwood, Ian; ...

2014-10-13

Re-engineering protein–protein recognition is an important route to dissecting and controlling complex interaction networks. Experimental approaches have used the strategy of “second-site suppressors,” where a functional interaction is inferred between two proteins if a mutation in one protein can be compensated by a mutation in the second. Mimicking this strategy, computational design has been applied successfully to change protein recognition specificity by predicting such sets of compensatory mutations in protein–protein interfaces. To extend this approach, it would be advantageous to be able to “transplant” existing engineered and experimentally validated specificity changes to other homologous protein–protein complexes. Here, we test thismore » strategy by designing a pair of mutations that modulates peptide recognition specificity in the Syntrophin PDZ domain, confirming the designed interaction biochemically and structurally, and then transplanting the mutations into the context of five related PDZ domain–peptide complexes. We find a wide range of energetic effects of identical mutations in structurally similar positions, revealing a dramatic context dependence (epistasis) of designed mutations in homologous protein–protein interactions. To better understand the structural basis of this context dependence, we apply a structure-based computational model that recapitulates these energetic effects and we use this model to make and validate forward predictions. The context dependence of these mutations is captured by computational predictions, our results both highlight the considerable difficulties in designing protein–protein interactions and provide challenging benchmark cases for the development of improved protein modeling and design methods that accurately account for the context.« less

Quantification of the transferability of a designed protein specificity switch reveals extensive epistasis in molecular recognition

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

Melero, Cristina; Ollikainen, Noah; Harwood, Ian

Re-engineering protein–protein recognition is an important route to dissecting and controlling complex interaction networks. Experimental approaches have used the strategy of “second-site suppressors,” where a functional interaction is inferred between two proteins if a mutation in one protein can be compensated by a mutation in the second. Mimicking this strategy, computational design has been applied successfully to change protein recognition specificity by predicting such sets of compensatory mutations in protein–protein interfaces. To extend this approach, it would be advantageous to be able to “transplant” existing engineered and experimentally validated specificity changes to other homologous protein–protein complexes. Here, we test thismore » strategy by designing a pair of mutations that modulates peptide recognition specificity in the Syntrophin PDZ domain, confirming the designed interaction biochemically and structurally, and then transplanting the mutations into the context of five related PDZ domain–peptide complexes. We find a wide range of energetic effects of identical mutations in structurally similar positions, revealing a dramatic context dependence (epistasis) of designed mutations in homologous protein–protein interactions. To better understand the structural basis of this context dependence, we apply a structure-based computational model that recapitulates these energetic effects and we use this model to make and validate forward predictions. The context dependence of these mutations is captured by computational predictions, our results both highlight the considerable difficulties in designing protein–protein interactions and provide challenging benchmark cases for the development of improved protein modeling and design methods that accurately account for the context.« less

In Situ Chemical Oxidation for Groundwater Remediation: Site-Specific Engineering & Technology Application

DTIC Science & Technology

2010-10-01

PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Colorado School of Mines,1500 Illinois St, Golden ,CO,80401 8. PERFORMING ORGANIZATION REPORT NUMBER 9...Protocol page 13 Overall ISCO Protocol Flow Diagram addition, laboratory studies may be used to select optimal chemistry parameters to maximize oxidant...Design Process 5. Because of the complexity of these oxidants’ chemistry and implementation, with much of the knowledge base residing with those

AAV Vectorization of DSB-mediated Gene Editing Technologies.

PubMed

Moser, Rachel J; Hirsch, Matthew L

2016-01-01

Recent work both at the bench and the bedside demonstrate zinc-finger nucleases (ZFNs), CRISPR/Cas9, and other programmable site-specific endonuclease technologies are being successfully utilized within and alongside AAV vectors to induce therapeutically relevant levels of directed gene editing within the human chromosome. Studies from past decades acknowledge that AAV vector genomes are enhanced substrates for homology-directed repair in the presence or absence of targeted DNA damage within the host genome. Additionally, AAV vectors are currently the most efficient format for in vivo gene delivery with no vector related complications in >100 clinical trials for diverse diseases. At the same time, advancements in the design of custom-engineered site-specific endonucleases and the utilization of elucidated endonuclease formats have resulted in efficient and facile genetic engineering for basic science and for clinical therapies. AAV vectors and gene editing technologies are an obvious marriage, using AAV for the delivery of repair substrate and/or a gene encoding a designer endonuclease; however, while efficient delivery and enhanced gene targeting by vector genomes are advantageous, other attributes of AAV vectors are less desirable for gene editing technologies. This review summarizes the various roles that AAV vectors play in gene editing technologies and provides insight into its trending applications for the treatment of genetic diseases.

Recent advances in the use of ZFN-mediated gene editing for human gene therapy.

PubMed

Chandrasegaran, Srinivasan

2017-01-01

Targeted genome editing with programmable nucleases has revolutionized biomedical research. The ability to make site-specific modifications to the human genome, has invoked a paradigm shift in gene therapy. Using gene editing technologies, the sequence in the human genome can now be precisely engineered to achieve a therapeutic effect. Zinc finger nucleases (ZFNs) were the first programmable nucleases designed to target and cleave custom sites. This article summarizes the advances in the use of ZFN-mediated gene editing for human gene therapy and discusses the challenges associated with translating this gene editing technology into clinical use.

Tools and Methods for Risk Management in Multi-Site Engineering Projects

NASA Astrophysics Data System (ADS)

Zhou, Mingwei; Nemes, Laszlo; Reidsema, Carl; Ahmed, Ammar; Kayis, Berman

In today's highly global business environment, engineering and manufacturing projects often involve two or more geographically dispersed units or departments, research centers or companies. This paper attempts to identify the requirements for risk management in a multi-site engineering project environment, and presents a review of the state-of-the-art tools and methods that can be used to manage risks in multi-site engineering projects. This leads to the development of a risk management roadmap, which will underpin the design and implementation of an intelligent risk mapping system.

Engineering and technology of industrial water power at Castleford Mills from the seventeenth century to the twentieth century

PubMed Central

Rollinson, Andrew N.

2016-01-01

This article tells the story of engineering and technology at Castleford Water Mills from the seventeenth century to the twentieth century through the presentation of recently discovered design plans and deeds, supplemented by other historical research. One of Castleford's mills was operated by Dr Thomas Allinson's Natural Food Company and therefore retained stoneground milling when fashions for white flour prompted other mills to switch to roller systems. The millstones were powered by a high-efficiency breastshot wheel, believed to be the last of its type taken out of industrial service in Britain. Many of its features, and its subsequent longevity, can be attributed to the influential works of William Fairbairn and John Smeaton. Detailed colour designs show the construction specifications of this water-wheel and its civil housing, along with other engineering plans such as a previously unrecorded Henry Simon horizontal turbine. Links with John Smeaton and the entry in his catalogue of designs for Castleford Oil Mill are also explored, and a former flood mill is identified at the site.

Substrate tunnels in enzymes: structure-function relationships and computational methodology.

PubMed

Kingsley, Laura J; Lill, Markus A

2015-04-01

In enzymes, the active site is the location where incoming substrates are chemically converted to products. In some enzymes, this site is deeply buried within the core of the protein, and, in order to access the active site, substrates must pass through the body of the protein via a tunnel. In many systems, these tunnels act as filters and have been found to influence both substrate specificity and catalytic mechanism. Identifying and understanding how these tunnels exert such control has been of growing interest over the past several years because of implications in fields such as protein engineering and drug design. This growing interest has spurred the development of several computational methods to identify and analyze tunnels and how ligands migrate through these tunnels. The goal of this review is to outline how tunnels influence substrate specificity and catalytic efficiency in enzymes with buried active sites and to provide a brief summary of the computational tools used to identify and evaluate these tunnels. © 2015 Wiley Periodicals, Inc.

IN-SITU CHEMICAL OXIDATION--ENGINEERING ISSUE

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Engineering Issue Papers are a series of technology transfer documents that summarize the latest available information on specific technical issues, including fate and transport, specific contaminants, selected treatment and site rem...

Advanced 35 W Free-Piston Stirling Engine for Space Power Applications

NASA Astrophysics Data System (ADS)

Wood, J. Gary; Lane, Neill

2003-01-01

This paper presents the projected performance and overall design characteristics of a high efficiency, low mass 35 W free-piston Stirling engine design. Overall (engine plus linear alternator) thermodynamic performance greater than 50% of Carnot, with a specific power close to 100 W/kg appears to be a reasonable goal at this small power level. Supporting test data and analysis results from exiting engines are presented. Design implications of high specific power in relatively low power engines is presented and discussed.

Groundwater contamination from waste management sites: The interaction between risk-based engineering design and regulatory policy: 2. Results

NASA Astrophysics Data System (ADS)

Massmann, Joel; Freeze, R. Allan

1987-02-01

The risk-cost-benefit analysis developed in the companion paper (J. Massmann and R. A. Freeze, this issue) is here applied to (1) an assessment of the relative worth of containment-construction activities, site-exploration activities, and monitoring activities as components of a design strategy for the owner/operator of a waste management facility; (2) an assessment of alternative policy options available to a regulatory agency; and (3) a case history. Sensitivity analyses designed to address the first issue show that the allocation of resources by the owner/operator is sensitive to the stochastic parameters used to describe the hydraulic conductivity field at a site. For the cases analyzed, the installation of a dense monitoring network is of less value to the owner/operator than a more conservative containment design. Sensitivity analyses designed to address the second issue suggest that from a regulatory perspective, design standards should be more effective than performance standards in reducing risk, and design specifications on the containment structure should be more effective than those on the monitoring network. Performance bonds posted before construction have a greater potential to influence design than prospective penalties to be imposed at the time of failure. Siting on low-conductivity deposits is a more effective method of risk reduction than any form of regulatory influence. Results of the case history indicate that the methodology can be successfully applied at field sites.

Configuration management program plan for Hanford site systems engineering

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

Kellie, C.L.

This plan establishes the integrated management program for the evolving technical baseline developed through the systems engineering process. This configuration management program aligns with the criteria identified in the DOE Standard, DOE-STD-1073-93. Included are specific requirements for control of the systems engineering RDD-100 database, and electronic data incorporated in the database that establishes the Hanford Site Technical Baseline.

Cost estimation and analysis using the Sherpa Automated Mine Cost Engineering System

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

Stebbins, P.E.

1993-09-01

The Sherpa Automated Mine Cost Engineering System is a menu-driven software package designed to estimate capital and operating costs for proposed surface mining operations. The program is engineering (as opposed to statistically) based, meaning that all equipment, manpower, and supply requirements are determined from deposit geology, project design and mine production information using standard engineering techniques. These requirements are used in conjunction with equipment, supply, and labor cost databases internal to the program to estimate all associated costs. Because virtually all on-site cost parameters are interrelated within the program, Sherpa provides an efficient means of examining the impact of changesmore » in the equipment mix on total capital and operating costs. If any aspect of the operation is changed, Sherpa immediately adjusts all related aspects as necessary. For instance, if the user wishes to examine the cost ramifications of selecting larger trucks, the program not only considers truck purchase and operation costs, it also automatically and immediately adjusts excavator requirements, operator and mechanic needs, repair facility size, haul road construction and maintenance costs, and ancillary equipment specifications.« less

Precipitation Depth-Duration-Frequency Analysis for the Nevada National Security Site and Surrounding Areas

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

Chen, Li; Miller, Julianne J.

Accurate precipitation frequency data are important for Environmental Management Soils Activities on the Nevada National Security Site (NNSS). These data are important for environmental assessments performed for regulatory closure of Soils Corrective Action Unit (CAU) Sites, as well as engineering mitigation designs and post-closure monitoring strategies to assess and minimize potential contaminant migration from Soils CAU Sites. Although the National Oceanic and Atmospheric Administration (NOAA) Atlas 14 (Bonnin et al., 2011) provides precipitation frequency data for the NNSS area, the NNSS-specific observed precipitation data were not consistent with the NOAA Atlas 14 predicted data. This is primarily due to themore » NOAA Atlas 14 products being produced from analyses without including the approximately 30 NNSS precipitation gage records, several of which approach or exceed 50 year of record. Therefore, a study of precipitation frequency that incorporated the NNSS precipitation gage records into the NOAA Atlas 14 dataset, was performed specifically for the NNSS to derive more accurate site-specific precipitation data products. Precipitation frequency information, such as the depth-duration-frequency (DDF) relationships, are required to generate synthetic standard design storm hydrographs and assess actual precipitation events. In this study, the actual long-term NNSS precipitation gage records, some of which are the longest gage records in southern and central Nevada, were analyzed to allow for more accurate precipitation DDF estimates to be developed for the NNSS. Gridded maps of precipitation frequency for the NNSS and surrounding areas were then produced.« less

Engineering of a target site-specific recombinase by a combined evolution- and structure-guided approach

PubMed Central

Abi-Ghanem, Josephine; Chusainow, Janet; Karimova, Madina; Spiegel, Christopher; Hofmann-Sieber, Helga; Hauber, Joachim; Buchholz, Frank; Pisabarro, M. Teresa

2013-01-01

Site-specific recombinases (SSRs) can perform DNA rearrangements, including deletions, inversions and translocations when their naive target sequences are placed strategically into the genome of an organism. Hence, in order to employ SSRs in heterologous hosts, their target sites have to be introduced into the genome of an organism before the enzyme can be practically employed. Engineered SSRs hold great promise for biotechnology and advanced biomedical applications, as they promise to extend the usefulness of SSRs to allow efficient and specific recombination of pre-existing, natural genomic sequences. However, the generation of enzymes with desired properties remains challenging. Here, we use substrate-linked directed evolution in combination with molecular modeling to rationally engineer an efficient and specific recombinase (sTre) that readily and specifically recombines a sequence present in the HIV-1 genome. We elucidate the role of key residues implicated in the molecular recognition mechanism and we present a rationale for sTre’s enhanced specificity. Combining evolutionary and rational approaches should help in accelerating the generation of enzymes with desired properties for use in biotechnology and biomedicine. PMID:23275541

Leachate management design in Mexico

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

Lange, D.A.; Broscious, J.C.; Zullo, E.G.

1996-02-01

As part of a project to provide solid waste master plans for 25 cities in Mexico, an American engineering firm, Paul C. Rizzo Associates (Monroeville, Pa.), was contracted to design a comprehensive leachate management system for landfills in the chosen cities. The solid waste master plan project was administered by the Mexican federal government Secretaria de Desarrollo Social (SEDESOL) with funding from the World Bank. While Paul C. Rizzo was the prime contractor for the project, which was completed in 1994, work was also subcontracted to a local Mexican engineering firm. The lack of specific design criteria for leachate managementmore » in current Mexican regulations enabled the use of a creative design for the system based on experience and technical judgment. Important design considerations included the current, primitive open-dump/burning/scavenging method of disposal and recycling of wastes, and the need for a minimal-cost solution in this developing country. The economic situation made the need for minimal expenditures to upgrade infrastructure equally important. The purpose of the design effort was to use evaporation and recirculation methods of landfill leachate management to minimize the amount of leachate that required treatment. Engineers in the project sought an ultimate goal of achieving zero excess leachate at the landfill sites.« less

Genetically engineered nanocarriers for drug delivery.

PubMed

Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

2014-01-01

Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins.

Genetically engineered nanocarriers for drug delivery

PubMed Central

Shi, Pu; Gustafson, Joshua A; MacKay, J Andrew

2014-01-01

Cytotoxicity, low water solubility, rapid clearance from circulation, and off-target side-effects are common drawbacks of conventional small-molecule drugs. To overcome these shortcomings, many multifunctional nanocarriers have been proposed to enhance drug delivery. In concept, multifunctional nanoparticles might carry multiple agents, control release rate, biodegrade, and utilize target-mediated drug delivery; however, the design of these particles presents many challenges at the stage of pharmaceutical development. An emerging solution to improve control over these particles is to turn to genetic engineering. Genetically engineered nanocarriers are precisely controlled in size and structure and can provide specific control over sites for chemical attachment of drugs. Genetically engineered drug carriers that assemble nanostructures including nanoparticles and nanofibers can be polymeric or non-polymeric. This review summarizes the recent development of applications in drug and gene delivery utilizing nanostructures of polymeric genetically engineered drug carriers such as elastin-like polypeptides, silk-like polypeptides, and silk-elastin-like protein polymers, and non-polymeric genetically engineered drug carriers such as vault proteins and viral proteins. PMID:24741309

Catalysis by a de novo zinc-mediated protein interface: implications for natural enzyme evolution and rational enzyme engineering.

PubMed

Der, Bryan S; Edwards, David R; Kuhlman, Brian

2012-05-08

Here we show that a recent computationally designed zinc-mediated protein interface is serendipitously capable of catalyzing carboxyester and phosphoester hydrolysis. Although the original motivation was to design a de novo zinc-mediated protein-protein interaction (called MID1-zinc), we observed in the homodimer crystal structure a small cleft and open zinc coordination site. We investigated if the cleft and zinc site at the designed interface were sufficient for formation of a primitive active site that can perform hydrolysis. MID1-zinc hydrolyzes 4-nitrophenyl acetate with a rate acceleration of 10(5) and a k(cat)/K(M) of 630 M(-1) s(-1) and 4-nitrophenyl phosphate with a rate acceleration of 10(4) and a k(cat)/K(M) of 14 M(-1) s(-1). These rate accelerations by an unoptimized active site highlight the catalytic power of zinc and suggest that the clefts formed by protein-protein interactions are well-suited for creating enzyme active sites. This discovery has implications for protein evolution and engineering: from an evolutionary perspective, three-coordinated zinc at a homodimer interface cleft represents a simple evolutionary path to nascent enzymatic activity; from a protein engineering perspective, future efforts in de novo design of enzyme active sites may benefit from exploring clefts at protein interfaces for active site placement.

All-in-One CRISPR-Cas9/FokI-dCas9 Vector-Mediated Multiplex Genome Engineering in Cultured Cells.

PubMed

Sakuma, Tetsushi; Sakamoto, Takuya; Yamamoto, Takashi

2017-01-01

CRISPR-Cas9 enables highly convenient multiplex genome engineering in cultured cells, because it utilizes generic Cas9 nuclease and an easily customizable single-guide RNA (sgRNA) for site-specific DNA double-strand break induction. We previously established a multiplex CRISPR-Cas9 assembly system for constructing an all-in-one vector simultaneously expressing multiple sgRNAs and Cas9 nuclease or other Cas9 variants including FokI-dCas9, which supersedes the wild-type Cas9 with regard to high specificity. In this chapter, we describe a streamlined protocol to design and construct multiplex CRISPR-Cas9 or FokI-dCas9 vectors, to introduce them into cultured cells by lipofection or electroporation, to enrich the genomically edited cells with a transient puromycin selection, to validate the mutation efficiency by Surveyor nuclease assay, and to perform off-target analyses. We show that our protocol enables highly efficient multiplex genome engineering even in hard-to-transfect HepG2 cells.

Surface Sites for Engineering Allosteric Control in Proteins

PubMed Central

Lee, Jeeyeon; Natarajan, Madhusudan; Nashine, Vishal C.; Socolich, Michael; Vo, Tina; Russ, William P.; Benkovic, Stephen J.; Ranganathan, Rama

2010-01-01

Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites. PMID:18927392

CF60 Concrete Composition Design and Application on Fudiankou Xijiang Super Large Bridge

NASA Astrophysics Data System (ADS)

Qiu, Yi Mei; Wen, Sen Yuan; Chen, Jun Xiang

2018-06-01

Guangxi Wuzhou City Ring Road Fudiankou Xijiang super large bridge CF60 concrete is a new multi-phase composite high-performance concrete, this paper for the Fudiankou Xijiang bridge structure and characteristics of the project, in accordance with the principle of local materials and technical specification requirements, combined with the site conditions of CF60 engineering high performance concrete component materials, proportion and the technical performance, quantify the main physical and mechanical performance index. Analysis main influencing factors of the technical indicators, reasonable adjustment of concrete mix design parameters, and the use of technical means of admixture and multi-function composite admixture of concrete, obtain the optimal proportion of good work, process, mechanical properties stability and durability of engineering properties, recommend and verification of concrete mix; to explore the CF60 high performance concrete Soil in the Fudiankou Xijiang bridge application technology, detection and tracking the quality of concrete construction, concrete structure during the construction of the key technology and control points is proposed, evaluation of CF60 high performance concrete in the actual engineering application effect and benefit to ensure engineering quality of bridge structure and service life, and super long span bridge engineering construction to provide basis and reference.

Elucidating the design principles of photosynthetic electron-transfer proteins by site-directed spin labeling EPR spectroscopy.

PubMed

Ishara Silva, K; Jagannathan, Bharat; Golbeck, John H; Lakshmi, K V

2016-05-01

Site-directed spin labeling electron paramagnetic resonance (SDSL EPR) spectroscopy is a powerful tool to determine solvent accessibility, side-chain dynamics, and inter-spin distances at specific sites in biological macromolecules. This information provides important insights into the structure and dynamics of both natural and designed proteins and protein complexes. Here, we discuss the application of SDSL EPR spectroscopy in probing the charge-transfer cofactors in photosynthetic reaction centers (RC) such as photosystem I (PSI) and the bacterial reaction center (bRC). Photosynthetic RCs are large multi-subunit proteins (molecular weight≥300 kDa) that perform light-driven charge transfer reactions in photosynthesis. These reactions are carried out by cofactors that are paramagnetic in one of their oxidation states. This renders the RCs unsuitable for conventional nuclear magnetic resonance spectroscopy investigations. However, the presence of native paramagnetic centers and the ability to covalently attach site-directed spin labels in RCs makes them ideally suited for the application of SDSL EPR spectroscopy. The paramagnetic centers serve as probes of conformational changes, dynamics of subunit assembly, and the relative motion of cofactors and peptide subunits. In this review, we describe novel applications of SDSL EPR spectroscopy for elucidating the effects of local structure and dynamics on the electron-transfer cofactors of photosynthetic RCs. Because SDSL EPR Spectroscopy is uniquely suited to provide dynamic information on protein motion, it is a particularly useful method in the engineering and analysis of designed electron transfer proteins and protein networks. This article is part of a Special Issue entitled Biodesign for Bioenergetics--the design and engineering of electronic transfer cofactors, proteins and protein networks, edited by Ronald L. Koder and J.L. Ross Anderson. Copyright © 2016. Published by Elsevier B.V.

[Development of domain specific search engines].

PubMed

Takai, T; Tokunaga, M; Maeda, K; Kaminuma, T

2000-01-01

As cyber space exploding in a pace that nobody has ever imagined, it becomes very important to search cyber space efficiently and effectively. One solution to this problem is search engines. Already a lot of commercial search engines have been put on the market. However these search engines respond with such cumbersome results that domain specific experts can not tolerate. Using a dedicate hardware and a commercial software called OpenText, we have tried to develop several domain specific search engines. These engines are for our institute's Web contents, drugs, chemical safety, endocrine disruptors, and emergent response for chemical hazard. These engines have been on our Web site for testing.

Effective hydrogen generator testing for on-site small engine

NASA Astrophysics Data System (ADS)

Chaiwongsa, Praitoon; Pornsuwancharoen, Nithiroth; Yupapin, Preecha P.

2009-07-01

We propose a new concept of hydrogen generator testing for on-site small engine. In general, there is a trade-off between simpler vehicle design and infrastructure issues, for instance, liquid fuels such as gasoline and methanol for small engine use. In this article we compare the hydrogen gases combination the gasoline between normal systems (gasoline only) for small engine. The advantage of the hydrogen combines gasoline for small engine saving the gasoline 25%. Furthermore, the new concept of hydrogen combination for diesel engine, bio-diesel engine, liquid petroleum gas (LPG), natural gas vehicle (NGV), which is discussed in details.

Eucalyptus Energy Farm: feasibility study and demonstration. Phase 1: site and species selection

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

Mariani, E.O.; Wood, W.A.; Kouchoukos, P.C.

1978-06-01

The results of investigations to determine the feasibility for establishing ''Eucalyptus Energy Farms'' as a potential source of biomass derived energy are presented. Included in this report are: the results of an extensive literature search and numerous field interviews (both domestically and internationally) to identify those Eucalyptus species most suitable for use within the United States; a description of the site selection criteria, site selection process, and identification of potential sites for use in testing the Eucalyptus Energy Farm concept; a description of the Eucalyptus species selection criteria, species selection process, and an identification of the specific species recommended formore » testing at specific sites; preliminary engineering designs for each of the proposed plantation sites; and environmental impact considerations related to Eucalyptus growing. It is concluded that although the Eucalyptus are extremely temperature sensitive and the geographic areas which appear suitable for their planting (within the United States) are principally confined to western and central California and the warmest regions of the southeastern United States, each of the areas contain large amounts of marginal land which could be converted into Eucalyptus based biomass plantations. Suitable sites, which are representative of the larger marginal land areas, are immediately available for use in establishing Eucalyptus screening test sites. Furthermore, there are not significant environmental conditions which would preclude the establishment of these initial test sites. It is therefore recommended that efforts be initiated to obtain selected provenances of Eucalyptus seeds (of the designated species) for further field testing and data collection within the United States, and that actual site selection be initiated.« less

Site-specific PEGylation of human thyroid stimulating hormone to prolong duration of action.

PubMed

Qiu, Huawei; Boudanova, Ekaterina; Park, Anna; Bird, Julie J; Honey, Denise M; Zarazinski, Christine; Greene, Ben; Kingsbury, Jonathan S; Boucher, Susan; Pollock, Julie; McPherson, John M; Pan, Clark Q

2013-03-20

Recombinant human thyroid stimulating hormone (rhTSH or Thyrogen) has been approved for thyroid cancer diagnostics and treatment under a multidose regimen due to its short circulating half-life. To reduce dosing frequency, PEGylation strategies were explored to increase the duration of action of rhTSH. Lysine and N-terminal PEGylation resulted in heterogeneous product profiles with 40% or lower reaction yields of monoPEGylated products. Eleven cysteine mutants were designed based on a structure model of the TSH-TSH receptor (TSHR) complex to create unique conjugation sites on both α and β subunits for site-specific conjugation. Sequential screening of mutant expression level, oligomerization tendency, and conjugation efficiency resulted in the identification of the αG22C rhTSH mutant for stable expression and scale-up PEGylation. The introduced cysteine in the αG22C rhTSH mutant was partially blocked when isolated from conditioned media and could only be effectively PEGylated after mild reduction with cysteine. This produced a higher reaction yield, ~85%, for the monoPEGylated product. Although the mutation had no effect on receptor binding, PEGylation of αG22C rhTSH led to a PEG size-dependent decrease in receptor binding. Nevertheless, the 40 kDa PEG αG22C rhTSH showed a prolonged duration of action compared to rhTSH in a rat pharmacodynamics model. Reverse-phase HPLC and N-terminal sequencing experiments confirmed site-specific modification at the engineered Cys 22 position on the α-subunit. This work is another demonstration of successful PEGylation of a cysteine-knot protein by an engineered cysteine mutation.

Configuration management program plan for Hanford site systems engineering

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

Hoffman, A.G.

This plan establishes the integrated configuration management program for the evolving technical baseline developed through the systems engineering process. This configuration management program aligns with the criteria identified in the DOE Standard, DOE-STD-1073-93. Included are specific requirements for control of the systems engineering RDD-100 database, and electronic data incorporated in the database that establishes the Hanford site technical baseline.

Design-Build-Write: Increasing the Impact of English for Specific Purposes Learning and Teaching in Aeronautical Engineering Education through Multiple Intelligences Task Design

ERIC Educational Resources Information Center

Tatzl, Dietmar

2011-01-01

This article presents an English for Specific Purposes (ESP) task developed for teaching aeronautical engineering students. The task Design-Build-Write rests on the assumption that engineering students are skilled at mathematical reasoning, problem solving, drawing and constructing. In Gardner's 1983 Multiple Intelligences (MI) theory, these…

The 2015-2016 SEPMAP Program at NASA JSC: Science, Engineering, and Program Management Training

NASA Technical Reports Server (NTRS)

Graham, L.; Archer, D.; Bakalyar, J.; Berger, E.; Blome, E.; Brown, R.; Cox, S.; Curiel, P.; Eid, R.; Eppler, D.;

A new generation of high performance engines for spacecraft propulsion

NASA Technical Reports Server (NTRS)

Rosenberg, Sanders D.; Schoenman, Leonard

1991-01-01

Experimental data validating advanced engine designs at three thrust levels (5, 15, and 100 lbF) is presented. All of the three engine designs considered employ a Moog bipropellant torque motor valve, platelet injector design, and iridium-lined rhenium combustion chamber. Attention is focused on the performance, robustness, duration, and flexibility characteristics of the engines. It is noted that the 5- and 15-lbF thrust engines can deliver a steady state specific impulse in excess of 310 lbF-sec/lbm at an area ratio of 150:1, while the 150-lbF thrust engines deliver a steady state specific impulse of 320 lbF-sec/lbm at an area ratio of 250:1. The hot-fire test results reveal specific impulse improvements of 15 to 25 sec over conventional fuel film cooled columbium chamber designs while operating at maximum chamber temperatures.

Rational design of p53, an intrinsically unstructured protein, for the fabrication of novel molecular sensors.

PubMed

Geddie, Melissa L; O'Loughlin, Taryn L; Woods, Kristen K; Matsumura, Ichiro

2005-10-21

The dominant paradigm of protein engineering is structure-based site-directed mutagenesis. This rational approach is generally more effective for the engineering of local properties, such as substrate specificity, than global ones such as allostery. Previous workers have modified normally unregulated reporter enzymes, including beta-galactosidase, alkaline phosphatase, and beta-lactamase, so that the engineered versions are activated (up to 4-fold) by monoclonal antibodies. A reporter that could easily be "reprogrammed" for the facile detection of novel effectors (binding or modifying activities) would be useful in high throughput screens for directed evolution or drug discovery. Here we describe a straightforward and general solution to this potentially difficult design problem. The transcription factor p53 is normally regulated by a variety of post-translational modifications. The insertion of peptides into intrinsically unstructured domains of p53 generated variants that were activated up to 100-fold by novel effectors (proteases or antibodies). An engineered p53 was incorporated into an existing high throughput screen for the detection of human immunodeficiency virus protease, an arbitrarily chosen novel effector. These results suggest that the molecular recognition properties of intrinsically unstructured proteins are relatively easy to engineer and that the absence of crystal structures should not deter the rational engineering of this class of proteins.

Integrating enzyme immobilization and protein engineering: An alternative path for the development of novel and improved industrial biocatalysts.

PubMed

Bernal, Claudia; Rodríguez, Karen; Martínez, Ronny

2018-06-09

Enzyme immobilization often achieves reusable biocatalysts with improved operational stability and solvent resistance. However, these modifications are generally associated with a decrease in activity or detrimental modifications in catalytic properties. On the other hand, protein engineering aims to generate enzymes with increased performance at specific conditions by means of genetic manipulation, directed evolution and rational design. However, the achieved biocatalysts are generally generated as soluble enzymes, -thus not reusable- and their performance under real operational conditions is uncertain. Combined protein engineering and enzyme immobilization approaches have been employed as parallel or consecutive strategies for improving an enzyme of interest. Recent reports show efforts on simultaneously improving both enzymatic and immobilization components through genetic modification of enzymes and optimizing binding chemistry for site-specific and oriented immobilization. Nonetheless, enzyme engineering and immobilization are usually performed as separate workflows to achieve improved biocatalysts. In this review, we summarize and discuss recent research aiming to integrate enzyme immobilization and protein engineering and propose strategies to further converge protein engineering and enzyme immobilization efforts into a novel "immobilized biocatalyst engineering" research field. We believe that through the integration of both enzyme engineering and enzyme immobilization strategies, novel biocatalysts can be obtained, not only as the sum of independently improved intrinsic and operational properties of enzymes, but ultimately tailored specifically for increased performance as immobilized biocatalysts, potentially paving the way for a qualitative jump in the development of efficient, stable biocatalysts with greater real-world potential in challenging bioprocess applications. Copyright © 2018. Published by Elsevier Inc.

Adolescents Searching for Health Information on the Internet: An Observational Study

PubMed Central

Derry, Holly A; Resnick, Paul J; Richardson, Caroline R

2003-01-01

Background Adolescents' access to health information on the Internet is partly a function of their ability to search for and find answers to their health-related questions. Adolescents may have unique health and computer literacy needs. Although many surveys, interviews, and focus groups have been utilized to understand the information-seeking and information-retrieval behavior of adolescents looking for health information online, we were unable to locate observations of individual adolescents that have been conducted in this context. Objective This study was designed to understand how adolescents search for health information using the Internet and what implications this may have on access to health information. Methods A convenience sample of 12 students (age 12-17 years) from 1 middle school and 2 high schools in southeast Michigan were provided with 6 health-related questions and asked to look for answers using the Internet. Researchers recorded 68 specific searches using software that captured screen images as well as synchronized audio recordings. Recordings were reviewed later and specific search techniques and strategies were coded. A qualitative review of the verbal communication was also performed. Results Out of 68 observed searches, 47 (69%) were successful in that the adolescent found a correct and useful answer to the health question. The majority of sites that students attempted to access were retrieved directly from search engine results (77%) or a search engine's recommended links (10%); only a small percentage were directly accessed (5%) or linked from another site (7%). The majority (83%) of followed links from search engine results came from the first 9 results. Incorrect spelling (30 of 132 search terms), number of pages visited within a site (ranging from 1-15), and overall search strategy (eg, using a search engine versus directly accessing a site), were each important determinants of success. Qualitative analysis revealed that participants used a trial-and-error approach to formulate search strings, scanned pages randomly instead of systematically, and did not consider the source of the content when searching for health information. Conclusions This study provides a useful snapshot of current adolescent searching patterns. The results have implications for constructing realistic simulations of adolescent search behavior, improving distribution and usefulness of Web sites with health information relevant to adolescents, and enhancing educators' knowledge of what specific pitfalls students are likely to encounter. PMID:14713653

Quantitative Tracking of Combinatorially Engineered Populations with Multiplexed Binary Assemblies.

PubMed

Zeitoun, Ramsey I; Pines, Gur; Grau, Willliam C; Gill, Ryan T

2017-04-21

Advances in synthetic biology and genomics have enabled full-scale genome engineering efforts on laboratory time scales. However, the absence of sufficient approaches for mapping engineered genomes at system-wide scales onto performance has limited the adoption of more sophisticated algorithms for engineering complex biological systems. Here we report on the development and application of a robust approach to quantitatively map combinatorially engineered populations at scales up to several dozen target sites. This approach works by assembling genome engineered sites with cell-specific barcodes into a format compatible with high-throughput sequencing technologies. This approach, called barcoded-TRACE (bTRACE) was applied to assess E. coli populations engineered by recursive multiplex recombineering across both 6-target sites and 31-target sites. The 31-target library was then tracked throughout growth selections in the presence and absence of isopentenol (a potential next-generation biofuel). We also use the resolution of bTRACE to compare the influence of technical and biological noise on genome engineering efforts.

Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado

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

Not Available

1992-02-01

This appendix assesses the present conditions and data gathered about the two inactive uranium mill tailings sites near Rifle, Colorado, and the designated disposal site six miles north of Rifle in the area of Estes Gulch. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill, tailings, and disposal site so that the Remedial Action Contractor (RAC) may complete final designs for the remedial actions.

22 CFR 126.5 - Canadian exemptions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... such persons publicly available through the Internet Web site of the Directorate of Defense Trade... that a foreign consignee can produce a defense article from engineering drawings without any technical...); and does not include (v) Design methodology, such as: The underlying engineering methods and design...

Engineering synthetic TALE and CRISPR/Cas9 transcription factors for regulating gene expression.

PubMed

Kabadi, Ami M; Gersbach, Charles A

2014-09-01

Engineered DNA-binding proteins that can be targeted to specific sites in the genome to manipulate gene expression have enabled many advances in biomedical research. This includes generating tools to study fundamental aspects of gene regulation and the development of a new class of gene therapies that alter the expression of endogenous genes. Designed transcription factors have entered clinical trials for the treatment of human diseases and others are in preclinical development. High-throughput and user-friendly platforms for designing synthetic DNA-binding proteins present innovative methods for deciphering cell biology and designing custom synthetic gene circuits. We review two platforms for designing synthetic transcription factors for manipulating gene expression: Transcription activator-like effectors (TALEs) and the RNA-guided clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system. We present an overview of each technology and a guide for designing and assembling custom TALE- and CRISPR/Cas9-based transcription factors. We also discuss characteristics of each platform that are best suited for different applications. Copyright © 2014 Elsevier Inc. All rights reserved.

Building Safer Systems With SpecTRM

NASA Technical Reports Server (NTRS)

2003-01-01

System safety, an integral component in software development, often poses a challenge to engineers designing computer-based systems. While the relaxed constraints on software design allow for increased power and flexibility, this flexibility introduces more possibilities for error. As a result, system engineers must identify the design constraints necessary to maintain safety and ensure that the system and software design enforces them. Safeware Engineering Corporation, of Seattle, Washington, provides the information, tools, and techniques to accomplish this task with its Specification Tools and Requirements Methodology (SpecTRM). NASA assisted in developing this engineering toolset by awarding the company several Small Business Innovation Research (SBIR) contracts with Ames Research Center and Langley Research Center. The technology benefits NASA through its applications for Space Station rendezvous and docking. SpecTRM aids system and software engineers in developing specifications for large, complex safety critical systems. The product enables engineers to find errors early in development so that they can be fixed with the lowest cost and impact on the system design. SpecTRM traces both the requirements and design rationale (including safety constraints) throughout the system design and documentation, allowing engineers to build required system properties into the design from the beginning, rather than emphasizing assessment at the end of the development process when changes are limited and costly.System safety, an integral component in software development, often poses a challenge to engineers designing computer-based systems. While the relaxed constraints on software design allow for increased power and flexibility, this flexibility introduces more possibilities for error. As a result, system engineers must identify the design constraints necessary to maintain safety and ensure that the system and software design enforces them. Safeware Engineering Corporation, of Seattle, Washington, provides the information, tools, and techniques to accomplish this task with its Specification Tools and Requirements Methodology (SpecTRM). NASA assisted in developing this engineering toolset by awarding the company several Small Business Innovation Research (SBIR) contracts with Ames Research Center and Langley Research Center. The technology benefits NASA through its applications for Space Station rendezvous and docking. SpecTRM aids system and software engineers in developing specifications for large, complex safety critical systems. The product enables engineers to find errors early in development so that they can be fixed with the lowest cost and impact on the system design. SpecTRM traces both the requirements and design rationale (including safety constraints) throughout the system design and documentation, allowing engineers to build required system properties into the design from the beginning, rather than emphasizing assessment at the end of the development process when changes are limited and costly.

Advances and Computational Tools towards Predictable Design in Biological Engineering

PubMed Central

2014-01-01

The design process of complex systems in all the fields of engineering requires a set of quantitatively characterized components and a method to predict the output of systems composed by such elements. This strategy relies on the modularity of the used components or the prediction of their context-dependent behaviour, when parts functioning depends on the specific context. Mathematical models usually support the whole process by guiding the selection of parts and by predicting the output of interconnected systems. Such bottom-up design process cannot be trivially adopted for biological systems engineering, since parts function is hard to predict when components are reused in different contexts. This issue and the intrinsic complexity of living systems limit the capability of synthetic biologists to predict the quantitative behaviour of biological systems. The high potential of synthetic biology strongly depends on the capability of mastering this issue. This review discusses the predictability issues of basic biological parts (promoters, ribosome binding sites, coding sequences, transcriptional terminators, and plasmids) when used to engineer simple and complex gene expression systems in Escherichia coli. A comparison between bottom-up and trial-and-error approaches is performed for all the discussed elements and mathematical models supporting the prediction of parts behaviour are illustrated. PMID:25161694

Precise and heritable genome editing in evolutionarily diverse nematodes using TALENs and CRISPR/Cas9 to engineer insertions and deletions.

PubMed

Lo, Te-Wen; Pickle, Catherine S; Lin, Steven; Ralston, Edward J; Gurling, Mark; Schartner, Caitlin M; Bian, Qian; Doudna, Jennifer A; Meyer, Barbara J

2013-10-01

Exploitation of custom-designed nucleases to induce DNA double-strand breaks (DSBs) at genomic locations of choice has transformed our ability to edit genomes, regardless of their complexity. DSBs can trigger either error-prone repair pathways that induce random mutations at the break sites or precise homology-directed repair pathways that generate specific insertions or deletions guided by exogenously supplied DNA. Prior editing strategies using site-specific nucleases to modify the Caenorhabditis elegans genome achieved only the heritable disruption of endogenous loci through random mutagenesis by error-prone repair. Here we report highly effective strategies using TALE nucleases and RNA-guided CRISPR/Cas9 nucleases to induce error-prone repair and homology-directed repair to create heritable, precise insertion, deletion, or substitution of specific DNA sequences at targeted endogenous loci. Our robust strategies are effective across nematode species diverged by 300 million years, including necromenic nematodes (Pristionchus pacificus), male/female species (Caenorhabditis species 9), and hermaphroditic species (C. elegans). Thus, genome-editing tools now exist to transform nonmodel nematode species into genetically tractable model organisms. We demonstrate the utility of our broadly applicable genome-editing strategies by creating reagents generally useful to the nematode community and reagents specifically designed to explore the mechanism and evolution of X chromosome dosage compensation. By developing an efficient pipeline involving germline injection of nuclease mRNAs and single-stranded DNA templates, we engineered precise, heritable nucleotide changes both close to and far from DSBs to gain or lose genetic function, to tag proteins made from endogenous genes, and to excise entire loci through targeted FLP-FRT recombination.

Performance Benefits for Wave Rotor-Topped Gas Turbine Engines

NASA Technical Reports Server (NTRS)

Jones, Scott M.; Welch, Gerard E.

1996-01-01

The benefits of wave rotor-topping in turboshaft engines, subsonic high-bypass turbofan engines, auxiliary power units, and ground power units are evaluated. The thermodynamic cycle performance is modeled using a one-dimensional steady-state code; wave rotor performance is modeled using one-dimensional design/analysis codes. Design and off-design engine performance is calculated for baseline engines and wave rotor-topped engines, where the wave rotor acts as a high pressure spool. The wave rotor-enhanced engines are shown to have benefits in specific power and specific fuel flow over the baseline engines without increasing turbine inlet temperature. The off-design steady-state behavior of a wave rotor-topped engine is shown to be similar to a conventional engine. Mission studies are performed to quantify aircraft performance benefits for various wave rotor cycle and weight parameters. Gas turbine engine cycles most likely to benefit from wave rotor-topping are identified. Issues of practical integration and the corresponding technical challenges with various engine types are discussed.

Inspection of Construction Works According to Polish Construction Law

NASA Astrophysics Data System (ADS)

Czemplik, A.

2015-11-01

Construction regulations are still different in many European countries, even though the European Union directives have unified many acts for construction works and construction products in the member countries. The scheme of the construction process presented in the paper could be valid for most countries, despite of detailed regulations of legal systems. The number of construction regulations to be followed in order to get the Construction Permit in Poland is rather big, so the time between the start of the investment process and the day when the Construction Permit is issued could be several months. Only licensed professional engineers can play the role of site managers, site inspectors and designers, registered for the given construction project. Duties and responsibilities (civil liability) of these engineers are strictly defined by regulations. The obligatory inspection of construction works should be executed by the licensed site inspectors. Moreover, the works can be incidentally inspected by Authority, banks, insurance companies or designers. Foreign designers and foreign site engineers in order to be allowed by respective Authority to play official roles on Polish construction sites should present documents proving that they can do the same jobs in their countries as per regulations obligatory there.

Test results and description of a 1-kW free-piston Stirling engine with a dashpot load

NASA Technical Reports Server (NTRS)

Schreiber, J.

1983-01-01

A 1 kW (1.33 hp) single cylinder free piston Stirling engine was installed in the test facilities at the Lewis laboratory. The engine was designed specifically for research of the dynamics of its operation. A more complete description of the engine and its instrumentation is provided in a prior NASA paper TM-82999 by J. G. Schreiber. Initial tests at Lewis showed the power level and efficiency of the engine to be below design level. Tests were performed to help determine the specific problems in the engine causing the below design level performance. Modifications to engine hardware and to the facility where performed in an effort to bring the power output and efficiency to their design values. As finally configured the engine generated more than 1250 watts of output power at an engine efficiency greater than 32 percent. This report presents the tests performed to help determine the specific problems, the results if the problem was eliminated, the fix performed to the hardware, and the test results after the engine was tested. In cases where the fix did not cause the anticipated effects, a possible explanation is given.

Performance (Off-Design) Cycle Analysis for a Turbofan Engine With Interstage Turbine Burner

NASA Technical Reports Server (NTRS)

Liew, K. H.; Urip, E.; Yang, S. L.; Mattingly, J. D.; Marek, C. J.

2005-01-01

This report presents the performance of a steady-state, dual-spool, separate-exhaust turbofan engine, with an interstage turbine burner (ITB) serving as a secondary combustor. The ITB, which is located in the transition duct between the high- and the low-pressure turbines, is a relatively new concept for increasing specific thrust and lowering pollutant emissions in modern jet-engine propulsion. A detailed off-design performance analysis of ITB engines is written in Microsoft(Registered Trademark) Excel (Redmond, Washington) macrocode with Visual Basic Application to calculate engine performances over the entire operating envelope. Several design-point engine cases are pre-selected using a parametric cycle-analysis code developed previously in Microsoft(Registered Trademark) Excel, for off-design analysis. The off-design code calculates engine performances (i.e. thrust and thrust-specific-fuel-consumption) at various flight conditions and throttle settings.

In vivo modification of a maize engineered minichromosome.

PubMed

Gaeta, Robert T; Masonbrink, Rick E; Zhao, Changzeng; Sanyal, Abhijit; Krishnaswamy, Lakshminarasimhan; Birchler, James A

2013-06-01

Engineered minichromosomes provide efficient platforms for stacking transgenes in crop plants. Methods for modifying these chromosomes in vivo are essential for the development of customizable systems for the removal of selection genes or other sequences and for the addition of new genes. Previous studies have demonstrated that Cre, a site-specific recombinase, could be used to modify lox sites on transgenes on maize minichromosomes; however, these studies demonstrated somatic recombination only, and modified minichromosomes could not be recovered. We describe the recovery of an engineered chromosome composed of little more than a centromere plus transgene that was derived by telomere-mediated truncation. We used the fiber fluorescence in situ hybridization technique and detected a transgene on the minichromosome inserted among stretches of CentC centromere repeats, and this insertion was large enough to suggest a tandem insertion. By crossing the minichromosome to a plant expressing Cre-recombinase, the Bar selection gene was removed, leaving behind a single loxP site. This study demonstrates that engineered chromosomes can be modified in vivo using site-specific recombinases, a demonstration essential to the development of amendable chromosome platforms in plants.

Onsite biological treatment of an industrial landfill leachate: Microbiological and engineering considerations

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

Skladany, G.J.

Successful biological treatment of ground waters, leachates, or industrial process waters requires the combined action of basic microbiological processes with sound process engineering designs. Such a treatment system is then able to both efficiently and cost-effectively remediate the contaminants present. In this case study, laboratory treatability studies were initially used to demonstrate that toluic acids present in an industrial landfill leachate were amenable to biological treatment. A continuous flow submerged fixed-film bioreactor was then chosen as the optimal equipment design for use at the site. The system was designed to treat a leachate flow of 800 to 2,000 gallons permore » day (gpd) containing total isomeric toluic acid concentrations of 300 to 400 parts per million (ppm). The treatment equipment has been in continuous operation since July 1987. During this period, the total influent isomertic toluic acid concentration has decreased to approximately 45 ppm, and specific effluent toluic acid concentrations have remained below the 0.5 ppm detection limit.« less

Genetic code expansion for multiprotein complex engineering.

PubMed

Koehler, Christine; Sauter, Paul F; Wawryszyn, Mirella; Girona, Gemma Estrada; Gupta, Kapil; Landry, Jonathan J M; Fritz, Markus Hsi-Yang; Radic, Ksenija; Hoffmann, Jan-Erik; Chen, Zhuo A; Zou, Juan; Tan, Piau Siong; Galik, Bence; Junttila, Sini; Stolt-Bergner, Peggy; Pruneri, Giancarlo; Gyenesei, Attila; Schultz, Carsten; Biskup, Moritz Bosse; Besir, Hueseyin; Benes, Vladimir; Rappsilber, Juri; Jechlinger, Martin; Korbel, Jan O; Berger, Imre; Braese, Stefan; Lemke, Edward A

2016-12-01

We present a baculovirus-based protein engineering method that enables site-specific introduction of unique functionalities in a eukaryotic protein complex recombinantly produced in insect cells. We demonstrate the versatility of this efficient and robust protein production platform, 'MultiBacTAG', (i) for the fluorescent labeling of target proteins and biologics using click chemistries, (ii) for glycoengineering of antibodies, and (iii) for structure-function studies of novel eukaryotic complexes using single-molecule Förster resonance energy transfer as well as site-specific crosslinking strategies.

SUPERFUND TREATABILITY CLEARINGHOUSE: EVALUATION OF AN ENGINEERED BIODEGRADATION SYSTEM AT THE NASHUA, N.H. SITE

EPA Science Inventory

The treatability study report presents the results of both laboratory and field studies conducted by Koppers on soils from the Nashua, N.H., NPL site. The purpose of these studies was to provide the necessary data to evaluate a ull-scale design for the Engineered Biodeg...

Seneca Compressed Air Energy Storage (CAES) Project

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

None, None

2012-11-30

Compressed Air Energy Storage (CAES) is a hybrid energy storage and generation concept that has many potential benefits especially in a location with increasing percentages of intermittent wind energy generation. The objectives of the NYSEG Seneca CAES Project included: for Phase 1, development of a Front End Engineering Design for a 130MW to 210 MW utility-owned facility including capital costs; project financials based on the engineering design and forecasts of energy market revenues; design of the salt cavern to be used for air storage; draft environmental permit filings; and draft NYISO interconnection filing; for Phase 2, objectives included plant constructionmore » with a target in-service date of mid-2016; and for Phase 3, objectives included commercial demonstration, testing, and two-years of performance reporting. This Final Report is presented now at the end of Phase 1 because NYSEG has concluded that the economics of the project are not favorable for development in the current economic environment in New York State. The proposed site is located in NYSEG’s service territory in the Town of Reading, New York, at the southern end of Seneca Lake, in New York State’s Finger Lakes region. The landowner of the proposed site is Inergy, a company that owns the salt solution mining facility at this property. Inergy would have developed a new air storage cavern facility to be designed for NYSEG specifically for the Seneca CAES project. A large volume, natural gas storage facility owned and operated by Inergy is also located near this site and would have provided a source of high pressure pipeline quality natural gas for use in the CAES plant. The site has an electrical take-away capability of 210 MW via two NYSEG 115 kV circuits located approximately one half mile from the plant site. Cooling tower make-up water would have been supplied from Seneca Lake. NYSEG’s engineering consultant WorleyParsons Group thoroughly evaluated three CAES designs and concluded that any of the designs would perform acceptably. Their general scope of work included development of detailed project construction schedules, capital cost and cash flow estimates for both CAES cycles, and development of detailed operational data, including fuel and compression energy requirements, to support dispatch modeling for the CAES cycles. The Dispatch Modeling Consultant selected for this project was Customized Energy Solutions (CES). Their general scope of work included development of wholesale electric and gas market price forecasts and development of a dispatch model specific to CAES technologies. Parsons Brinkerhoff Energy Storage Services (PBESS) was retained to develop an air storage cavern and well system design for the CAES project. Their general scope of work included development of a cavern design, solution mining plan, and air production well design, cost, and schedule estimates for the project. Detailed Front End Engineering Design (FEED) during Phase 1 of the project determined that CAES plant capital equipment costs were much greater than the $125.6- million originally estimated by EPRI for the project. The initial air storage cavern Design Basis was increased from a single five million cubic foot capacity cavern to three, five million cubic foot caverns with associated air production wells and piping. The result of this change in storage cavern Design Basis increased project capital costs significantly. In addition, the development time required to complete the three cavern system was estimated at approximately six years. This meant that the CAES plant would initially go into service with only one third of the required storage capacity and would not achieve full capability until after approximately five years of commercial operation. The market price forecasting and dispatch modeling completed by CES indicated that the CAES technologies would operate at only 10 to 20% capacity factors and the resulting overall project economics were not favorable for further development. As a result of all of these factors, the Phase 1 FEED developed an installed CAES plant cost estimate of approximately $2,300/KW for the 210MW CAES 1A and 2 cycles. The capital cost for the 136 MW CAES 1 cycle was even higher due to the lower generating capacity of the cycle. Notably, the large equipment could have generated additional capacity (up to 270MW) which would have improved the cost per KW; however, the output was limited by the night time transmission system capability. The research herein, therefore, is particular to the site-specific factors that influenced the design and the current and forecasted generation mix and energy prices in Upstate New York and may not necessarily indicate that CAES plants cannot be economically constructed in other places in New York State or the world.« less

Report for the MPV Demonstration at New Boston Air Force Base, New Hampshire: UXO Characterization in Challenging Survey Environments Using the MPV

DTIC Science & Technology

2017-04-28

EM Electromagnetic EMI Electromagnetic Induction ERDC Engineering Research and Development Center ESTCP Environmental Security Technology... bombs , HE bombs and incendiary bombs . The site hosted demonstrations with the MPV and the 2x2 TEMTADS, both with crews from CH2MHill. Each study...array of five receiver units that measure all three components of the EM field (Figure 2). This second-generation MPV is specifically designed to

Analysis of the Quality of Information Obtained About Uterine Artery Embolization From the Internet

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

Tavare, Aniket N.; Alsafi, Ali, E-mail: ali.alsafi03@imperial.ac.uk; Hamady, Mohamad S.

Purpose: The Internet is widely used by patients to source health care-related information. We sought to analyse the quality of information available on the Internet about uterine artery embolization (UAE). Materials and Methods: We searched three major search engines for the phrase 'uterine artery embolization' and compiled the top 50 results from each engine. After excluding repeated sites, scientific articles, and links to documents, the remaining 50 sites were assessed using the LIDA instrument, which scores sites across the domains of accessibility, usability, and reliability. The Fleisch reading ease score (FRES) was calculated for each of the sites. Finally, wemore » checked the country of origin and the presence of certification by the Health On the Net Foundation (HONcode) as well as their effect on LIDA and FRES scores.ResultsThe following mean scores were obtained: accessibility 48/60 (80%), usability 42/54 (77%), reliability 20/51 (39%), total LIDA 110/165 (67%), and FRES 42/100 (42%). Nine sites had HONcode certification, and this was associated with significantly greater (p < 0.05) reliability and total LIDA and FRES scores. When comparing sites between United Kingdom and United States, there was marked variation in the quality of results obtained when searching for information on UAE (p < 0.05). Conclusion: In general, sites were well designed and easy to use. However, many scored poorly on the reliability of their information either because they were produced in a non-evidence-based way or because they lacking currency. It is important that patients are guided to reputable, location-specific sources of information online, especially because prominent search engine rank does not guarantee reliability of information.« less

Site-Specific Antibody–Drug Conjugates: The Nexus of Bioorthogonal Chemistry, Protein Engineering, and Drug Development

PubMed Central

2015-01-01

Antibody–drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering. PMID:25494884

Site-specific antibody-drug conjugates: the nexus of bioorthogonal chemistry, protein engineering, and drug development.

PubMed

Agarwal, Paresh; Bertozzi, Carolyn R

2015-02-18

Antibody-drug conjugates (ADCs) combine the specificity of antibodies with the potency of small molecules to create targeted drugs. Despite the simplicity of this concept, generation of clinically successful ADCs has been very difficult. Over the past several decades, scientists have learned a great deal about the constraints on antibodies, linkers, and drugs as they relate to successful construction of ADCs. Once these components are in hand, most ADCs are prepared by nonspecific modification of antibody lysine or cysteine residues with drug-linker reagents, which results in heterogeneous product mixtures that cannot be further purified. With advances in the fields of bioorthogonal chemistry and protein engineering, there is growing interest in producing ADCs by site-specific conjugation to the antibody, yielding more homogeneous products that have demonstrated benefits over their heterogeneous counterparts in vivo. Here, we chronicle the development of a multitude of site-specific conjugation strategies for assembly of ADCs and provide a comprehensive account of key advances and their roots in the fields of bioorthogonal chemistry and protein engineering.

Substrate Tunnels in Enzymes: Structure-Function Relationships and Computational Methodology

PubMed Central

Kingsley, Laura J.; Lill, Markus A.

2015-01-01

In enzymes, the active site is the location where incoming substrates are chemically converted to products. In some enzymes, this site is deeply buried within the core of the protein and in order to access the active site, substrates must pass through the body of the protein via a tunnel. In many systems, these tunnels act as filters and have been found to influence both substrate specificity and catalytic mechanism. Identifying and understanding how these tunnels exert such control has been of growing interest over the past several years due to implications in fields such as protein engineering and drug design. This growing interest has spurred the development of several computational methods to identify and analyze tunnels and how ligands migrate through these tunnels. The goal of this review is to outline how tunnels influence substrate specificity and catalytic efficiency in enzymes with tunnels and to provide a brief summary of the computational tools used to identify and evaluate these tunnels. PMID:25663659

Data Integration Tool: Permafrost Data Debugging

NASA Astrophysics Data System (ADS)

Wilcox, H.; Schaefer, K. M.; Jafarov, E. E.; Pulsifer, P. L.; Strawhacker, C.; Yarmey, L.; Basak, R.

2017-12-01

We developed a Data Integration Tool (DIT) to significantly speed up the time of manual processing needed to translate inconsistent, scattered historical permafrost data into files ready to ingest directly into the Global Terrestrial Network-Permafrost (GTN-P). The United States National Science Foundation funded this project through the National Snow and Ice Data Center (NSIDC) with the GTN-P to improve permafrost data access and discovery. We leverage this data to support science research and policy decisions. DIT is a workflow manager that divides data preparation and analysis into a series of steps or operations called widgets (https://github.com/PermaData/DIT). Each widget does a specific operation, such as read, multiply by a constant, sort, plot, and write data. DIT allows the user to select and order the widgets as desired to meet their specific needs, incrementally interact with and evolve the widget workflows, and save those workflows for reproducibility. Taking ideas from visual programming found in the art and design domain, debugging and iterative design principles from software engineering, and the scientific data processing and analysis power of Fortran and Python it was written for interactive, iterative data manipulation, quality control, processing, and analysis of inconsistent data in an easily installable application. DIT was used to completely translate one dataset (133 sites) that was successfully added to GTN-P, nearly translate three datasets (270 sites), and is scheduled to translate 10 more datasets ( 1000 sites) from the legacy inactive site data holdings of the Frozen Ground Data Center (FGDC). Iterative development has provided the permafrost and wider scientific community with an extendable tool designed specifically for the iterative process of translating unruly data.

Remedial action plan and site design for stabilization of the inactive uranium mill tailings sites at Rifle, Colorado. Volume 2, Appendices D and E: Final report

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

Not Available

1992-02-01

This appendix assesses the present conditions and data gathered about the two inactive uranium mill tailings sites near Rifle, Colorado, and the designated disposal site six miles north of Rifle in the area of Estes Gulch. It consolidates available engineering, radiological, geotechnical, hydrological, meteorological, and other information pertinent to the design of the Remedial Action Plan (RAP). The data characterize conditions at the mill, tailings, and disposal site so that the Remedial Action Contractor (RAC) may complete final designs for the remedial actions.

Design and test of aircraft engine isolators for reduced interior noise

NASA Technical Reports Server (NTRS)

Unruh, J. F.; Scheidt, D. C.

1982-01-01

Improved engine vibration isolation was proposed to be the most weight and cost efficient retrofit structure-borne noise control measure for single engine general aviation aircraft. A study was carried out the objectives: (1) to develop an engine isolator design specification for reduced interior noise transmission, (2) select/design candidate isolators to meet a 15 dB noise reduction design goal, and (3) carry out a proof of concept evaluation test. Analytical model of the engine, vibration isolators and engine mount structure were coupled to an empirical model of the fuselage for noise transmission evaluation. The model was used to develop engine isolator dynamic properties design specification for reduced noise transmission. Candidate isolators ere chosen from available product literature and retrofit to a test aircraft. A laboratory based test procedure was then developed to simulate engine induced noise transmission in the aircraft for a proof of concept evaluation test. Three candidate isolator configurations were evaluated for reduced structure-borne noise transmission relative to the original equipment isolators.

Engineering of synthetic, stress-responsive yeast promoters

PubMed Central

Rajkumar, Arun S.; Liu, Guodong; Bergenholm, David; Arsovska, Dushica; Kristensen, Mette; Nielsen, Jens; Jensen, Michael K.; Keasling, Jay D.

2016-01-01

Advances in synthetic biology and our understanding of the rules of promoter architecture have led to the development of diverse synthetic constitutive and inducible promoters in eukaryotes and prokaryotes. However, the design of promoters inducible by specific endogenous or environmental conditions is still rarely undertaken. In this study, we engineered and characterized a set of strong, synthetic promoters for budding yeast Saccharomyces cerevisiae that are inducible under acidic conditions (pH ≤ 3). Using available expression and transcription factor binding data, literature on transcriptional regulation, and known rules of promoter architecture we improved the low-pH performance of the YGP1 promoter by modifying transcription factor binding sites in its upstream activation sequence. The engineering strategy outlined for the YGP1 promoter was subsequently applied to create a response to low pH in the unrelated CCW14 promoter. We applied our best promoter variants to low-pH fermentations, enabling ten-fold increased production of lactic acid compared to titres obtained with the commonly used, native TEF1 promoter. Our findings outline and validate a general strategy to iteratively design and engineer synthetic yeast promoters inducible to environmental conditions or stresses of interest. PMID:27325743

The Solution to Pollution is Distribution: Design Your Own Chaotic Flow

NASA Astrophysics Data System (ADS)

Tigera, R. G.; Roth, E. J.; Neupauer, R.; Mays, D. C.

2015-12-01

Plume spreading promotes the molecular mixing that drives chemical reactions in porous media in general, and remediation reactions in groundwater aquifers in particular. Theoretical analysis suggests that engineered injection and extraction, a specific sequence of pumping through wells surrounding a contaminant plume, can improve groundwater remediation through chaotic advection. Selection of an engineered injection and extraction scheme is difficult, however, because the engineer is faced with the difficulty of recommending a pumping scheme for a contaminated site without having any previous knowledge of how the scheme will perform. To address this difficulty, this presentation describes a Graphical User Interface (GUI) designed to help engineers develop, test, and observe pumping schemes as described in previous research (Mays, D.C. and Neupauer, R.M., 2012, Plume spreading in groundwater by stretching and folding, Water Resour. Res., 48, W07501, doi:10.1029/2011WR011567). The inputs allow the user to manipulate the model conditions such as number of wells, plume size, and pumping scheme. Plume evolution is modeled, assuming no diffusion or dispersion, using analytical solutions for injection or extraction through individual wells or pairs or wells (i.e., dipoles). Using the GUI, an engineered injection and extraction scheme can be determined that best fits the remediation needs of the contaminated site. By creating multiple injection and extraction schemes, the user can learn about the plume shapes created from different schemes and, ultimately, recommend a pumping scheme based on some experience of fluid flow as shown in the GUI. The pumping schemes developed through this GUI are expected to guide more advanced modeling and laboratory studies that account for the crucial role of dispersion in groundwater remediation.

Integrated Logistics Support approach: concept for the new big projects: E-ELT, SKA, CTA

NASA Astrophysics Data System (ADS)

Marchiori, G.; Rampini, F.; Formentin, F.

2014-08-01

The Integrated Logistic Support is a process supporting strategies and optimizing activities for a correct project management and system engineering development. From the design & engineering of complex technical systems, to the erection on site, acceptance and after-sales service, EIE GROUP covers all aspects of the Integrated Logistics Support (ILS) process that includes: costing process centered around the life cycle cost and Level of Repair Analyses; engineering process which influences the design via means of reliability, modularization, etc.; technical publishing process based on international specifications; ordering administration process for supply support. Through the ILS, EIE GROUP plans and directs the identification and development of logistics support and system requirements for its products, with the goal of creating systems that last longer and require less support, thereby reducing costs and increasing return on investments. ILS therefore, addresses these aspects of supportability not only during acquisition, but also throughout the operational life cycle of the system. The impact of the ILS is often measured in terms of metrics such as reliability, availability, maintainability and testability (RAMT), and System Safety (RAMS). Example of the criteria and approach adopted by EIE GROUP during the design, manufacturing and test of the ALMA European Antennas and during the design phase of the E-ELT telescope and Dome are presented.

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

Reggio, R.; Haun, R.

This paper reviews the engineering and design work along with the installation procedures for a Persian Gulf natural gas pipeline. OPMI Ltd., a joint venture of Offshore Pipelines, Inc., Houston, and Maritime Industrial Services Co., Ltd., United Arab Emirates (UAE), successfully completed this 57.4 mile, 16-inch gas export pipeline for Consolidated Transmissions Inc. The pipeline begins at a platform in the Mubarek field offshore Sharjah, UAE, and runs to a beach termination at the Dugas treatment plant, Jebel Ali, Dubai. The paper describes the site preparation required for installation of the pipeline along with the specific design of the pipelinemore » itself to deal with corrosion, welding processes, condensate dropout, and temperature gradients.« less

Engineering the Pseudomonas aeruginosa II lectin: designing mutants with changed affinity and specificity

NASA Astrophysics Data System (ADS)

Kříž, Zdeněk; Adam, Jan; Mrázková, Jana; Zotos, Petros; Chatzipavlou, Thomais; Wimmerová, Michaela; Koča, Jaroslav

2014-09-01

This article focuses on designing mutations of the PA-IIL lectin from Pseudomonas aeruginosa that lead to change in specificity. Following the previous results revealing the importance of the amino acid triad 22-23-24 (so-called specificity-binding loop), saturation in silico mutagenesis was performed, with the intent of finding mutations that increase the lectin's affinity and modify its specificity. For that purpose, a combination of docking, molecular dynamics and binding free energy calculation was used. The combination of methods revealed mutations that changed the performance of the wild-type lectin and its mutants to their preferred partners. The mutation at position 22 resulted in 85 % in inactivation of the binding site, and the mutation at 23 did not have strong effects thanks to the side chain being pointed away from the binding site. Molecular dynamics simulations followed by binding free energy calculation were performed on mutants with promising results from docking, and also at those where the amino acid at position 24 was replaced for bulkier or longer polar chain. The key mutants were also prepared in vitro and their binding properties determined by isothermal titration calorimetry. Combination of the used methods proved to be able to predict changes in the lectin performance and helped in explaining the data observed experimentally.

Modeling Groundwater Flow and Infiltration at Potential Low-Level Radioactive Waste Disposal Sites in Taiwan

NASA Astrophysics Data System (ADS)

Arnold, B. W.; Lee, C.; Ma, C.; Knowlton, R. G.

2006-12-01

Taiwan is evaluating representative sites for the potential disposal of low-level radioactive waste (LLW), including consideration of shallow land burial and cavern disposal concepts. A representative site for shallow land burial is on a small island in the Taiwan Strait with basalt bedrock. The shallow land burial concept includes an engineered cover to limit infiltration into the waste disposal cell. A representative site for cavern disposal is located on the southeast coast of Taiwan. The tunnel system for this disposal concept would be several hundred meters below the mountainous land surface in argillite bedrock. The LLW will consist of about 966,000 drums, primarily from the operation and decommissioning of four nuclear power plants. Sandia National Laboratories and the Institute of Nuclear Energy Research have collaborated to develop performance assessment models to evaluate the long-term safety of LLW disposal at these representative sites. Important components of the system models are sub-models of groundwater flow in the natural system and infiltration through the engineered cover for the shallow land burial concept. The FEHM software code was used to simulate groundwater flow in three-dimensional models at both sites. In addition, a higher-resolution two-dimensional model was developed to simulate flow through the engineered tunnel system at the cavern site. The HELP software was used to simulate infiltration through the cover at the island site. The primary objective of these preliminary models is to provide a modeling framework, given the lack of site-specific data and detailed engineering design specifications. The steady-state groundwater flow model at the island site uses a specified recharge boundary at the land surface and specified head at the island shoreline. Simulated groundwater flow vectors are extracted from the FEHM model along a cross section through one of the LLW disposal cells for utilization in radionuclide transport simulations in the performance assessment model with the BLT-MS software. Infiltration through the engineered cover is simulated to be about 3 mm/yr and 49 mm/yr, with and without a geomembrane layer, respectively. For the cavern LLW disposal site, the FEHM basin-scale flow model uses specified recharge flux, constant head at the ocean shoreline, and head-dependent flux boundaries along flowing streams. Groundwater flow vectors are extracted along a cross section for use in radionuclide transport simulations. Transport simulations indicate that a significant fraction of contaminants may ultimately discharge to nearby streams. FEHM flow simulations with the drift-scale model indicate that the flow rates within the backfilled tunnels may be more than two orders of magnitude lower than in the host rock. Sandia National Laboratories is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy under Contract DE-AC04-94AL85000.

Structure and specificity of the RNA-guided endonuclease Cas9 during DNA interrogation, target binding and cleavage

PubMed Central

Josephs, Eric A.; Kocak, D. Dewran; Fitzgibbon, Christopher J.; McMenemy, Joshua; Gersbach, Charles A.; Marszalek, Piotr E.

2015-01-01

CRISPR-associated endonuclease Cas9 cuts DNA at variable target sites designated by a Cas9-bound RNA molecule. Cas9's ability to be directed by single ‘guide RNA’ molecules to target nearly any sequence has been recently exploited for a number of emerging biological and medical applications. Therefore, understanding the nature of Cas9's off-target activity is of paramount importance for its practical use. Using atomic force microscopy (AFM), we directly resolve individual Cas9 and nuclease-inactive dCas9 proteins as they bind along engineered DNA substrates. High-resolution imaging allows us to determine their relative propensities to bind with different guide RNA variants to targeted or off-target sequences. Mapping the structural properties of Cas9 and dCas9 to their respective binding sites reveals a progressive conformational transformation at DNA sites with increasing sequence similarity to its target. With kinetic Monte Carlo (KMC) simulations, these results provide evidence of a ‘conformational gating’ mechanism driven by the interactions between the guide RNA and the 14th–17th nucleotide region of the targeted DNA, the stabilities of which we find correlate significantly with reported off-target cleavage rates. KMC simulations also reveal potential methodologies to engineer guide RNA sequences with improved specificity by considering the invasion of guide RNAs into targeted DNA duplex. PMID:26384421

Energy Efficient Engine Flight Propulsion System Preliminary Analysis and Design Report

NASA Technical Reports Server (NTRS)

Bisset, J. W.; Howe, D. C.

1983-01-01

The final design and analysis of the flight propulsion system is presented. This system is the conceptual study engine defined to meet the performance, economic and environmental goals established for the Energy Efficient Engine Program. The design effort included a final definition of the engine, major components, internal subsystems, and nacelle. Various analytical representations and results from component technology programs are used to verify aerodynamic and structural design concepts and to predict performance. Specific design goals and specifications, reflecting future commercial aircraft propulsion system requirements for the mid-1980's, are detailed by NASA and used as guidelines during engine definition. Information is also included which details salient results from a separate study to define a turbofan propulsion system, known as the maximum efficiency engine, which reoptimized the advanced fuel saving technologies for improved fuel economy and direct operating costs relative to the flight propulsion system.

Site systems engineering fiscal year 1999 multi-year work plan (MYWP) update for WBS 1.8.2.2

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

GRYGIEL, M.L.

1998-10-08

Manage the Site Systems Engineering process to provide a traceable integrated requirements-driven, and technically defensible baseline. Through the Site Integration Group(SIG), Systems Engineering ensures integration of technical activities across all site projects. Systems Engineering's primary interfaces are with the RL Project Managers, the Project Direction Office and with the Project Major Subcontractors, as well as with the Site Planning organization. Systems Implementation: (1) Develops, maintains, and controls the site integrated technical baseline, ensures the Systems Engineering interfaces between projects are documented, and maintain the Site Environmental Management Specification. (2) Develops and uses dynamic simulation models for verification of the baselinemore » and analysis of alternatives. (3) Performs and documents fictional and requirements analyses. (4) Works with projects, technology management, and the SIG to identify and resolve technical issues. (5) Supports technical baseline information for the planning and budgeting of the Accelerated Cleanup Plan, Multi-Year Work Plans, Project Baseline Summaries as well as performance measure reporting. (6) Works with projects to ensure the quality of data in the technical baseline. (7) Develops, maintains and implements the site configuration management system.« less

In vivo tissue engineering of musculoskeletal tissues.

PubMed

McCullen, Seth D; Chow, Andre G Y; Stevens, Molly M

2011-10-01

Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

Engineering Issue: Technology Alternatives for the Remediation of PCB Contaminated Soils and Sediments

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA) Engineering Issue papers are a series of documents that summarize the available information on specific contaminates, selected treatment and site remediation technologies, and related issues. This Engineering Issue paper is intended...

Crew Health Care System (CHeCS) Design Research, Documentations, and Evaluations

NASA Technical Reports Server (NTRS)

CLement, Bethany M.

2011-01-01

The Crew Health Care System (CHeCS) is a group within the Space Life Science Directorate (SLSD) that focuses on the overall health of astronauts by reinforcing the three divisions - the Environmental Maintenance System (EMS), the Countermeasures System (CMS), and the Health Maintenance System (HMS). This internship provided opportunity to gain knowledge, experience, and skills in CHeCS engineering and operations tasks. Various and differing tasks allowed for occasions to work independently, network to get things done, and show leadership abilities. Specific exercises included reviewing hardware certification, operations, and documentation within the ongoing Med Kit Redesign (MKR) project, and learning, writing, and working various common pieces of paperwork used in the engineering and design process. Another project focused on the distribution of various pieces of hardware to off-site research facilities with an interest in space flight health care. The main focus of this internship, though, was on a broad and encompassing understanding of the engineering process as time was spent looking at each individual step in a variety of settings and tasks.

Engineered containment and control systems: nurturing nature.

PubMed

Clarke, James H; MacDonell, Margaret M; Smith, Ellen D; Dunn, R Jeffrey; Waugh, W Jody

2004-06-01

The development of engineered containment and control systems for contaminated sites must consider the environmental setting of each site. The behaviors of both contaminated materials and engineered systems are affected by environmental conditions that will continue to evolve over time as a result of such natural processes as climate change, ecological succession, pedogenesis, and landform changes. Understanding these processes is crucial to designing, implementing, and maintaining effective systems for sustained health and environmental protection. Traditional engineered systems such as landfill liners and caps are designed to resist natural processes rather than working with them. These systems cannot be expected to provide long-term isolation without continued maintenance. In some cases, full-scale replacement and remediation may be required within 50 years, at an effort and cost much higher than for the original cleanup. Approaches are being developed to define smarter containment and control systems for stewardship sites, considering lessons learned from implementing prescriptive waste disposal regulations enacted since the 1970s. These approaches more effectively involve integrating natural and engineered systems; enhancing sensors and predictive tools for evaluating performance; and incorporating information on failure events, including precursors and consequences, into system design and maintenance. An important feature is using natural analogs to predict environmental conditions and system responses over the long term, to accommodate environmental change in the design process, and, as possible, to engineer containment systems that mimic favorable natural systems. The key emphasis is harmony with the environment, so systems will work with and rely on natural processes rather than resisting them. Implementing these new integrated systems will reduce current requirements for active management, which are resource-intensive and expensive.

ADVANCED SEISMIC BASE ISOLATION METHODS FOR MODULAR REACTORS

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

E. Blanford; E. Keldrauk; M. Laufer

2010-09-20

Advanced technologies for structural design and construction have the potential for major impact not only on nuclear power plant construction time and cost, but also on the design process and on the safety, security and reliability of next generation of nuclear power plants. In future Generation IV (Gen IV) reactors, structural and seismic design should be much more closely integrated with the design of nuclear and industrial safety systems, physical security systems, and international safeguards systems. Overall reliability will be increased, through the use of replaceable and modular equipment, and through design to facilitate on-line monitoring, in-service inspection, maintenance, replacement,more » and decommissioning. Economics will also receive high design priority, through integrated engineering efforts to optimize building arrangements to minimize building heights and footprints. Finally, the licensing approach will be transformed by becoming increasingly performance based and technology neutral, using best-estimate simulation methods with uncertainty and margin quantification. In this context, two structural engineering technologies, seismic base isolation and modular steel-plate/concrete composite structural walls, are investigated. These technologies have major potential to (1) enable standardized reactor designs to be deployed across a wider range of sites, (2) reduce the impact of uncertainties related to site-specific seismic conditions, and (3) alleviate reactor equipment qualification requirements. For Gen IV reactors the potential for deliberate crashes of large aircraft must also be considered in design. This report concludes that base-isolated structures should be decoupled from the reactor external event exclusion system. As an example, a scoping analysis is performed for a rectangular, decoupled external event shell designed as a grillage. This report also reviews modular construction technology, particularly steel-plate/concrete construction using factory prefabricated structural modules, for application to external event shell and base isolated structures.« less

Space shuttle hypergolic bipropellant RCS engine design study, Bell model 8701

NASA Technical Reports Server (NTRS)

1974-01-01

A research program was conducted to define the level of the current technology base for reaction control system rocket engines suitable for space shuttle applications. The project consisted of engine analyses, design, fabrication, and tests. The specific objectives are: (1) extrapolating current engine design experience to design of an RCS engine with required safety, reliability, performance, and operational capability, (2) demonstration of multiple reuse capability, and (3) identification of current design and technology deficiencies and critical areas for future effort.

40 CFR 98.468 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... design capacity, the calculation must include a site-specific density. If the design capacity is within... process that can reasonably be expected to change the site-specific waste density, the site-specific waste density must be redetermined and the design capacity must be recalculated based on the new waste density...

40 CFR 98.468 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... design capacity, the calculation must include a site-specific density. If the design capacity is within... process that can reasonably be expected to change the site-specific waste density, the site-specific waste density must be redetermined and the design capacity must be recalculated based on the new waste density...

Quality analysis of patient information about knee arthroscopy on the World Wide Web.

PubMed

Sambandam, Senthil Nathan; Ramasamy, Vijayaraj; Priyanka, Priyanka; Ilango, Balakrishnan

2007-05-01

This study was designed to ascertain the quality of patient information available on the World Wide Web on the topic of knee arthroscopy. For the purpose of quality analysis, we used a pool of 232 search results obtained from 7 different search engines. We used a modified assessment questionnaire to assess the quality of these Web sites. This questionnaire was developed based on similar studies evaluating Web site quality and includes items on illustrations, accessibility, availability, accountability, and content of the Web site. We also compared results obtained with different search engines and tried to establish the best possible search strategy to attain the most relevant, authentic, and adequate information with minimum time consumption. For this purpose, we first compared 100 search results from the single most commonly used search engine (AltaVista) with the pooled sample containing 20 search results from each of the 7 different search engines. The search engines used were metasearch (Copernic and Mamma), general search (Google, AltaVista, and Yahoo), and health topic-related search engines (MedHunt and Healthfinder). The phrase "knee arthroscopy" was used as the search terminology. Excluding the repetitions, there were 117 Web sites available for quality analysis. These sites were analyzed for accessibility, relevance, authenticity, adequacy, and accountability by use of a specially designed questionnaire. Our analysis showed that most of the sites providing patient information on knee arthroscopy contained outdated information, were inadequate, and were not accountable. Only 16 sites were found to be providing reasonably good patient information and hence can be recommended to patients. Understandably, most of these sites were from nonprofit organizations and educational institutions. Furthermore, our study revealed that using multiple search engines increases patients' chances of obtaining more relevant information rather than using a single search engine. Our study shows the difficulties encountered by patients in obtaining information regarding knee arthroscopy and highlights the duty of knee surgeons in helping patients to identify the relevant and authentic information in the most efficient manner from the World Wide Web. This study highlights the importance of the role of orthopaedic surgeons in helping their patients to identify the best possible information on the World Wide Web.

Theoretical Acoustic Absorber Design Approach for LOX/LCH4 Pintle Injector Rocket Engines

NASA Astrophysics Data System (ADS)

Candelaria, Jonathan

Liquid rocket engines, or LREs, have served a key role in space exploration efforts. One current effort involves the utilization of liquid oxygen (LOX) and liquid methane (LCH4) LREs to explore Mars with in-situ resource utilization for propellant production. This on-site production of propellant will allow for greater payload allocation instead of fuel to travel to the Mars surface, and refueling of propellants to travel back to Earth. More useable mass yields a greater benefit to cost ratio. The University of Texas at El Paso's (UTEP) Center for Space Exploration and Technology Research Center (cSETR) aims to further advance these methane propulsion systems with the development of two liquid methane - liquid oxygen propellant combination rocket engines. The design of rocket engines, specifically liquid rocket engines, is complex in that many variables are present that must be taken into consideration in the design. A problem that occurs in almost every rocket engine development program is combustion instability, or oscillatory combustion. It can result in the destruction of the rocket, subsequent destruction of the vehicle and compromise the mission. These combustion oscillations can vary in frequency from 100 to 20,000 Hz or more, with varying effects, and occur from different coupling phenomena. It is important to understand the effects of combustion instability, its physical manifestations, how to identify the instabilities, and how to mitigate or dampen them. Linear theory methods have been developed to provide a mathematical understanding of the low- to mid-range instabilities. Nonlinear theory is more complex and difficult to analyze mathematically, therefore no general analytical method that yields a solution exists. With limited resources, time, and the advice of our NASA mentors, a data driven experimental approach utilizing quarter wave acoustic dampener cavities was designed. This thesis outlines the methodology behind the design of an acoustic dampening system for a 500 lbf and a 2000 lbf throttleable liquid oxygen liquid methane pintle injector rocket engine.

Engineering a switch-on peptide to ricin A chain for increasing its specificity towards HIV-infected cells.

PubMed

Au, Ka-Yee; Wang, Rui-Rui; Wong, Yuen-Ting; Wong, Kam-Bo; Zheng, Yong-Tang; Shaw, Pang-Chui

2014-03-01

Ricin is a type II ribosome-inactivating protein (RIP) that potently inactivates eukaryotic ribosomes by removing a specific adenine residue at the conserved α-sarcin/ricin loop of 28S ribosomal RNA (rRNA). Here, we try to increase the specificity of the enzymatically active ricin A chain (RTA) towards human immunodeficiency virus type 1 (HIV-1) by adding a loop with HIV protease recognition site to RTA. HIV-specific RTA variants were constructed by inserting a peptide with HIV-protease recognition site either internally or at the C-terminal region of wild type RTA. Cleavability of variants by viral protease was tested in vitro and in HIV-infected cells. The production of viral p24 antigen and syncytium in the presence of C-terminal variants was measured to examine the anti-HIV activities of the variants. C-terminal RTA variants were specifically cleaved by HIV-1 protease both in vitro and in HIV-infected cells. Upon proteolysis, the processed variants showed enhanced antiviral effect with low cytotoxicity towards uninfected cells. RTA variants with HIV protease recognition sequence engineered at the C-terminus were cleaved and the products mediated specific inhibitory effect towards HIV replication. Current cocktail treatment of HIV infection fails to eradicate the virus from patients. Here we illustrate the feasibility of targeting an RIP towards HIV-infected cells by incorporation of HIV protease cleavage sequence. This approach may be generalized to other RIPs and is promising in drug design for combating HIV. Copyright © 2013 Elsevier B.V. All rights reserved.

An engineering evaluation of the Space Shuttle OMS engine after 5 orbital flights

NASA Technical Reports Server (NTRS)

David, D.

1983-01-01

Design features, performances on the first five flights, and condition of the Shuttle OMS engines are summarized. The engines were designed to provide a vacuum-fed 6000 lb of thrust and a 310 sec specific impulse, fueled by a combination of N2O4 and monomethylhydrazine (MMH) at a mixture ratio of 1.65. The design lifetime is 1000 starts and 15 hr of cumulative firing duration. The engine assembly is throat gimballed and features yaw actuators. No degradation of the hot components was observed during the first five flights, and the injector pattern maintained a uniform, enduring level of performance. An increase in the take-off loads have led to enhancing the wall thickness in the nozzle in affected areas. The engine is concluded to be performing to design specifications and is considered an operational system.

Genome Integration and Excision by a New Streptomyces Bacteriophage, ϕJoe

PubMed Central

Haley, Joshua A.; Stark, W. Marshall

2016-01-01

ABSTRACT Bacteriophages are the source of many valuable tools for molecular biology and genetic manipulation. In Streptomyces, most DNA cloning vectors are based on serine integrase site-specific DNA recombination systems derived from phage. Because of their efficiency and simplicity, serine integrases are also used for diverse synthetic biology applications. Here, we present the genome of a new Streptomyces phage, ϕJoe, and investigate the conditions for integration and excision of the ϕJoe genome. ϕJoe belongs to the largest Streptomyces phage cluster (R4-like) and encodes a serine integrase. The attB site from Streptomyces venezuelae was used efficiently by an integrating plasmid, pCMF92, constructed using the ϕJoe int-attP locus. The attB site for ϕJoe integrase was occupied in several Streptomyces genomes, including that of S. coelicolor, by a mobile element that varies in gene content and size between host species. Serine integrases require a phage-encoded recombination directionality factor (RDF) to activate the excision reaction. The ϕJoe RDF was identified, and its function was confirmed in vivo. Both the integrase and RDF were active in in vitro recombination assays. The ϕJoe site-specific recombination system is likely to be an important addition to the synthetic biology and genome engineering toolbox. IMPORTANCE Streptomyces spp. are prolific producers of secondary metabolites, including many clinically useful antibiotics. Bacteriophage-derived integrases are important tools for genetic engineering, as they enable integration of heterologous DNA into the Streptomyces chromosome with ease and high efficiency. Recently, researchers have been applying phage integrases for a variety of applications in synthetic biology, including rapid assembly of novel combinations of genes, biosensors, and biocomputing. An important requirement for optimal experimental design and predictability when using integrases, however, is the need for multiple enzymes with different specificities for their integration sites. In order to provide a broad platform of integrases, we identified and validated the integrase from a newly isolated Streptomyces phage, ϕJoe. ϕJoe integrase is active in vitro and in vivo. The specific recognition site for integration is present in a wide range of different actinobacteria, including Streptomyces venezuelae, an emerging model bacterium in Streptomyces research. PMID:28003200

Data Concentrator

NASA Technical Reports Server (NTRS)

Willett, Mike

2015-01-01

Orbital Research, Inc., developed, built, and tested three high-temperature components for use in the design of a data concentrator module in distributed turbine engine control. The concentrator receives analog and digital signals related to turbine engine control and communicates with a full authority digital engine control (FADEC) or high-level command processor. This data concentrator follows the Distributed Engine Controls Working Group (DECWG) roadmap for turbine engine distributed controls communication development that operates at temperatures at least up to 225 C. In Phase I, Orbital Research developed detailed specifications for each component needed for the system and defined the total system specifications. This entailed a combination of system design, compiling existing component specifications, laboratory testing, and simulation. The results showed the feasibility of the data concentrator. Phase II of this project focused on three key objectives. The first objective was to update the data concentrator design modifications from DECWG and prime contractors. Secondly, the project defined requirements for the three new high-temperature, application-specific integrated circuits (ASICs): one-time programmable (OTP), transient voltage suppression (TVS), and 3.3V. Finally, the project validated each design by testing over temperature and under load.

Emergence of new red-shifted carbon nanotube photoluminescence based on proximal doped-site design

NASA Astrophysics Data System (ADS)

Shiraki, Tomohiro; Shiraishi, Tomonari; Juhász, Gergely; Nakashima, Naotoshi

2016-06-01

Single-walled carbon nanotubes (SWNTs) show unique photoluminescence (PL) in the near-infrared (NIR) region. Here we propose a concept based on the proximal modification in local covalent functionalization of SWNTs. Quantum mechanical simulations reveal that the SWNT band gap changes specifically based on the proximal doped-site design. Thus, we synthesize newly-designed bisdiazonium molecules and conduct local fucntionalisation of SWNTs. Consequently, new red-shifted PL (E112*) from the bisdiazonium-modified SWNTs with (6, 5) chirality is recognized around 1250 nm with over ~270 nm Stokes shift from the PL of the pristine SWNTs and the PL wavelengths are shifted depending on the methylene spacer lengths of the modifiers. The present study revealed that SWNT PL modulation is enable by close-proximity-local covalent modification, which is highly important for fundamental understanding of intrinsic SWNT PL properties as well as exciton engineering-based applications including photonic devices and (bio)imaging/sensing.

A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX

DOE PAGES

Pinard, Melissa A.; Aggarwal, Mayank; Mahon, Brian P.; ...

2015-09-23

Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO 2to HCO 3 $-$, thereby playing a role in pH regulation. The majority of normal functioning cells exhibit low-level expression of CA IX. However, in cancer cells CA IX is upregulated as a consequence of a metabolic transition known as the Warburg effect. The upregulation of CA IX for cancer progression has drawn interest in it being a potential therapeutic target. CA IX is a transmembrane protein, and its purification, yield and crystallization have proven challenging to structure-basedmore » drug design, whereas the closely related cytosolic soluble isoform CA II can be expressed and crystallized with ease. Therefore, we have utilized structural alignments and site-directed mutagenesis to engineer a CA II that mimics the active site of CA IX. In this paper, the X-ray crystal structure of this CA IX mimic in complex with sucrose is presented and has been refined to a resolution of 1.5 Å, anR cryst of 18.0% and anR free of 21.2%. Finally, the binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.« less

Wave rotor-enhanced gas turbine engines

NASA Technical Reports Server (NTRS)

Welch, Gerard E.; Scott, Jones M.; Paxson, Daniel E.

1995-01-01

The benefits of wave rotor-topping in small (400 to 600 hp-class) and intermediate (3000 to 4000 hp-class) turboshaft engines, and large (80,000 to 100,000 lb(sub f)-class) high bypass ratio turbofan engines are evaluated. Wave rotor performance levels are calculated using a one-dimensional design/analysis code. Baseline and wave rotor-enhanced engine performance levels are obtained from a cycle deck in which the wave rotor is represented as a burner with pressure gain. Wave rotor-toppings is shown to significantly enhance the specific fuel consumption and specific power of small and intermediate size turboshaft engines. The specific fuel consumption of the wave rotor-enhanced large turbofan engine can be reduced while operating at significantly reduced turbine inlet temperature. The wave rotor-enhanced engine is shown to behave off-design like a conventional engine. Discussion concerning the impact of the wave rotor/gas turbine engine integration identifies tenable technical challenges.

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

Shafer, A.L.; Purdy, S.; Tempelis, D.

The La Paz County Regional Landfill is a 65 hectare (160 acre) municipal waste site located near the western border of Arizona between the cities of Parker and Quartzsite. The site is operated under a public/private partnership between the County of La Paz and Browning-Ferris Industries, Inc. (BFI). The County owns the landfill and infrastructure and BFI is responsible for facility improvements, environmental compliance, and daily operations. Following the initial permitting and construction of the first landfill cell, a value engineering review was conducted on the site design and permit requirements. Based on this review, substantial cost saving opportunities weremore » identified. In order to implement the value engineering ideas, the site permit was modified and a new Solid Waste Facilities Plan was Submitted to the Arizona Department of Environmental Quality. This paper discusses the value engineering modifications that were conducted, the revisions to the permits, and the relative cost savings that were realized. The areas addressed include the liner system design, closure design, disposal capacity, and operations plan. Through the use of alternative liners a cost savings of well over 50 percent (as compared to the original permit) will be realized over the life of the landfill.« less

EARLY ENTRANCE COPRODUCTION PLANT

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

David Storm; Govanon Nongbri; Steve Decanio

2004-01-12

The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase IImore » is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc., GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. During Phase I, a design basis for the Fischer-Tropsch Synthesis section was developed based on limited experience with the specified feed gas and operating conditions. The objective of this Task in Phase II RD&T work was to confirm the performance of the F-T reactor at the set design conditions. Although much of the research, development, and testing work were done by TES outside of this project, several important issues were addressed in this phase of the project. They included Rejuvenation/Regeneration of the Fischer-Tropsch Catalyst, online Catalyst Withdrawal and Addition from the synthesis reactor, and the Fischer-Tropsch Design Basis Confirmation. In Phase III the results from these RD&T work will be incorporated in developing the engineering design package. This Topical Report documents the Phase II RD&T work that was completed for this task.« less

40 CFR 1045.105 - What exhaust emission standards must my sterndrive/inboard engines meet?

Code of Federal Regulations, 2011 CFR

2011-07-01

... the fuel type on which the engines in the engine family are designed to operate. You must meet the... data, such as data from research engines or similar engine models that are already in production. Your... for the engine or its components, and any relevant customer design specifications. Your demonstration...

40 CFR 1045.105 - What exhaust emission standards must my sterndrive/inboard engines meet?

Code of Federal Regulations, 2012 CFR

2012-07-01

... the fuel type on which the engines in the engine family are designed to operate. You must meet the... data, such as data from research engines or similar engine models that are already in production. Your... for the engine or its components, and any relevant customer design specifications. Your demonstration...

40 CFR 1045.105 - What exhaust emission standards must my sterndrive/inboard engines meet?

Code of Federal Regulations, 2014 CFR

2014-07-01

... the fuel type on which the engines in the engine family are designed to operate. You must meet the... data, such as data from research engines or similar engine models that are already in production. Your... for the engine or its components, and any relevant customer design specifications. Your demonstration...

40 CFR 1045.105 - What exhaust emission standards must my sterndrive/inboard engines meet?

Code of Federal Regulations, 2013 CFR

2013-07-01

... the fuel type on which the engines in the engine family are designed to operate. You must meet the... data, such as data from research engines or similar engine models that are already in production. Your... for the engine or its components, and any relevant customer design specifications. Your demonstration...

40 CFR 1045.105 - What exhaust emission standards must my sterndrive/inboard engines meet?

Code of Federal Regulations, 2010 CFR

2010-07-01

... the fuel type on which the engines in the engine family are designed to operate. You must meet the... data, such as data from research engines or similar engine models that are already in production. Your... for the engine or its components, and any relevant customer design specifications. Your demonstration...

Fish-Friendly Hydropower Turbine Development & Deployment: Alden Turbine Preliminary Engineering and Model Testing

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

Foust, J.; Hecker, G.; Li, S.

2011-10-01

The Alden turbine was developed through the U.S. Department of Energy's (DOE's) former Advanced Hydro Turbine Systems Program (1994-2006) and, more recently, through the Electric Power Research Institute (EPRI) and the DOE's Wind & Water Power Program. The primary goal of the engineering study described here was to provide a commercially competitive turbine design that would yield fish passage survival rates comparable to or better than the survival rates of bypassing or spilling flow. Although the turbine design was performed for site conditions corresponding to 92 ft (28 m) net head and a discharge of 1500 cfs (42.5 cms), themore » design can be modified for additional sites with differing operating conditions. During the turbine development, design modifications were identified for the spiral case, distributor (stay vanes and wicket gates), runner, and draft tube to improve turbine performance while maintaining features for high fish passage survival. Computational results for pressure change rates and shear within the runner passage were similar in the original and final turbine geometries, while predicted minimum pressures were higher for the final turbine. The final turbine geometry and resulting flow environments are expected to further enhance the fish passage characteristics of the turbine. Computational results for the final design were shown to improve turbine efficiencies by over 6% at the selected operating condition when compared to the original concept. Prior to the release of the hydraulic components for model fabrication, finite element analysis calculations were conducted for the stay vanes, wicket gates, and runner to verify that structural design criteria for stress and deflections were met. A physical model of the turbine was manufactured and tested with data collected for power and efficiency, cavitation limits, runaway speed, axial and radial thrust, pressure pulsations, and wicket gate torque. All parameters were observed to fall within ranges expected for conventional radial flow machines. Based on these measurements, the expected efficiency peak for prototype application is 93.64%. These data were used in the final sizing of the supporting mechanical and balance of plant equipment. The preliminary equipment cost for the design specification is $1450/kW with a total supply schedule of 28 months. This equipment supply includes turbine, generator, unit controls, limited balance of plant equipment, field installation, and commissioning. Based on the selected head and flow design conditions, fish passage survival through the final turbine is estimated to be approximately 98% for 7.9-inch (200-mm) fish, and the predicted survival reaches 100% for fish 3.9 inches (100 mm) and less in length. Note that fish up to 7.9- inches (200 mm) in length make up more than 90% of fish entrained at hydro projects in the United States. Completion of these efforts provides a mechanical and electrical design that can be readily adapted to site-specific conditions with additional engineering development comparable to costs associated with conventional turbine designs.« less

Targeted inhibition of oncogenic miR-21 maturation with designed RNA-binding proteins

PubMed Central

Chen, Yu; Yang, Fan; Zubovic, Lorena; Pavelitz, Tom; Yang, Wen; Godin, Katherine; Walker, Matthew; Zheng, Suxin; Macchi, Paolo; Varani, Gabriele

2016-01-01

The RNA Recognition Motif (RRM) is the largest family of eukaryotic RNA-binding proteins. Engineered RRMs with new specificity would provide valuable tools and an exacting test of our understanding of specificity. We have achieved the first successful re-design of the specificity of an RRM using rational methods and demonstrated re-targeting of activity in cells. We engineered the conserved RRM of human Rbfox proteins to specifically bind to the terminal loop of miR-21 precursor with high affinity and inhibit its processing by Drosha and Dicer. We further engineered Giardia Dicer by replacing its PAZ domain with the designed RRM. The reprogrammed enzyme degrades pre-miR-21 specifically in vitro and suppresses mature miR-21 levels in cells, which results in increased expression of PDCD4 and significantly decreased viability for cancer cells. The results demonstrate the feasibility of engineering the sequence-specificity of RRMs and of using this ubiquitous platform for diverse biological applications. PMID:27428511

Applying design principles to fusion reactor configurations for propulsion in space

NASA Technical Reports Server (NTRS)

Carpenter, Scott A.; Deveny, Marc E.; Schulze, Norman R.

1993-01-01

The application of fusion power to space propulsion requires rethinking the engineering-design solution to controlled-fusion energy. Whereas the unit cost of electricity (COE) drives the engineering-design solution for utility-based fusion reactor configurations; initial mass to low earth orbit (IMLEO), specific jet power (kW(thrust)/kg(engine)), and reusability drive the engineering-design solution for successful application of fusion power to space propulsion. We applied three design principles (DP's) to adapt and optimize three candidate-terrestrial-fusion-reactor configurations for propulsion in space. The three design principles are: provide maximum direct access to space for waste radiation, operate components as passive radiators to minimize cooling-system mass, and optimize the plasma fuel, fuel mix, and temperature for best specific jet power. The three candidate terrestrial fusion reactor configurations are: the thermal barrier tandem mirror (TBTM), field reversed mirror (FRM), and levitated dipole field (LDF). The resulting three candidate space fusion propulsion systems have their IMLEO minimized and their specific jet power and reusability maximized. We performed a preliminary rating of these configurations and concluded that the leading engineering-design solution to space fusion propulsion is a modified TBTM that we call the Mirror Fusion Propulsion System (MFPS).

10 CFR Appendix C to Part 52 - Design Certification Rule for the AP600 Design

Code of Federal Regulations, 2011 CFR

2011-01-01

..., Manager, Passive Plant Engineering, Westinghouse Electric Company, P.O. Box 355, Pittsburgh, Pennsylvania... Web site, http://www.nrc.gov, and/or at the NRC Public Document Room, is insufficient; c. The...) Fuel criteria evaluation process. (4) Fire areas. (5) Human factors engineering. c. A licensee who...

10 CFR Appendix C to Part 52 - Design Certification Rule for the AP600 Design

Code of Federal Regulations, 2010 CFR

2010-01-01

..., Manager, Passive Plant Engineering, Westinghouse Electric Company, P.O. Box 355, Pittsburgh, Pennsylvania... Web site, http://www.nrc.gov, and/or at the NRC Public Document Room, is insufficient; c. The...) Fuel criteria evaluation process. (4) Fire areas. (5) Human factors engineering. c. A licensee who...

Grooker, KartOO, Addict-o-Matic and More: Really Different Search Engines

ERIC Educational Resources Information Center

Descy, Don E.

2009-01-01

There are hundreds of unique search engines in the United States and thousands of unique search engines around the world. If people get into search engines designed just to search particular web sites, the number is in the hundreds of thousands. This article looks at: (1) clustering search engines, such as KartOO (www.kartoo.com) and Grokker…

26 CFR 1.460-2 - Long-term manufacturing contracts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... specific customer, a taxpayer must consider the extent to which research, development, design, engineering... substantial amount of research, design, and engineering to produce, C determines that the equipment is a... produce, will be delivered to B in 2003. C determines that the research, design, engineering, retooling...

Detection of specific protein-protein interactions in nanocages by engineering bipartite FlAsH binding sites.

PubMed

Cornell, Thomas A; Fu, Jing; Newland, Stephanie H; Orner, Brendan P

2013-11-06

Proteins that form cage-like structures have been of much recent cross-disciplinary interest due to their application to bioconjugate and materials chemistry, their biological functions spanning multiple essential cellular processes, and their complex structure, often defined by highly symmetric protein–protein interactions. Thus, establishing the fundamentals of their formation, through detecting and quantifying important protein–protein interactions, could be crucial to understanding essential cellular machinery, and for further development of protein-based technologies. Herein we describe a method to monitor the assembly of protein cages by detecting specific, oligomerization state dependent, protein–protein interactions. Our strategy relies on engineering protein monomers to include cysteine pairs that are presented proximally if the cage state assembles. These assembled pairs of cysteines act as binding sites for the fluorescent reagent FlAsH, which, once bound, provides a readout for successful oligomerization. As a proof of principle, we applied this technique to the iron storage protein, DNA-binding protein from starved cells from E. coli. Several linker lengths and conformations for the presentation of the cysteine pairs were screened to optimize the engineered binding sites. We confirmed that our designs were successful in both lysates and with purified proteins, and that FlAsH binding was dependent upon cage assembly. Following successful characterization of the assay, its throughput was expanded. A two-dimension matrix of pH and denaturing buffer conditions was screened to optimize nanocage stability. We intend to use this method for the high throughput screening of protein cage libraries and of conditions for the generation of inorganic nanoparticles within the cavity of these and other cage proteins.

A Design Pattern for Decentralised Decision Making

PubMed Central

Valentini, Gabriele; Fernández-Oto, Cristian; Dorigo, Marco

2015-01-01

The engineering of large-scale decentralised systems requires sound methodologies to guarantee the attainment of the desired macroscopic system-level behaviour given the microscopic individual-level implementation. While a general-purpose methodology is currently out of reach, specific solutions can be given to broad classes of problems by means of well-conceived design patterns. We propose a design pattern for collective decision making grounded on experimental/theoretical studies of the nest-site selection behaviour observed in honeybee swarms (Apis mellifera). The way in which honeybee swarms arrive at consensus is fairly well-understood at the macroscopic level. We provide formal guidelines for the microscopic implementation of collective decisions to quantitatively match the macroscopic predictions. We discuss implementation strategies based on both homogeneous and heterogeneous multiagent systems, and we provide means to deal with spatial and topological factors that have a bearing on the micro-macro link. Finally, we exploit the design pattern in two case studies that showcase the viability of the approach. Besides engineering, such a design pattern can prove useful for a deeper understanding of decision making in natural systems thanks to the inclusion of individual heterogeneities and spatial factors, which are often disregarded in theoretical modelling. PMID:26496359

Analytical evaluation of the impact of broad specification fuels on high bypass turbofan engine combustors

NASA Technical Reports Server (NTRS)

Taylor, J. R.

1979-01-01

Six conceptual combustor designs for the CF6-50 high bypass turbofan engine and six conceptual combustor designs for the NASA/GE E3 high bypass turbofan engine were analyzed to provide an assessment of the major problems anticipated in using broad specification fuels in these aircraft engine combustion systems. Each of the conceptual combustor designs, which are representative of both state-of-the-art and advanced state-of-the-art combustion systems, was analyzed to estimate combustor performance, durability, and pollutant emissions when using commercial Jet A aviation fuel and when using experimental referee board specification fuel. Results indicate that lean burning, low emissions double annular combustor concepts can accommodate a wide range of fuel properties without a serious deterioration of performance or durability. However, rich burning, single annular concepts would be less tolerant to a relaxation of fuel properties. As the fuel specifications are relaxed, autoignition delay time becomes much smaller which presents a serious design and development problem for premixing-prevaporizing combustion system concepts.

78 FR 3921 - Proposed Models for Plant-Specific Adoption of Technical Specifications Task Force Traveler TSTF...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-17

... Specifications Combustion Engineering Plants.'' Specifically, the proposed change revises various TSs to add a... Technical Details TSTF-426, Revision 5, is applicable to all Combustion Engineering- designed nuclear power...

Numerical Modelling of Rayleigh Wave Propagation in Course of Rapid Impulse Compaction

NASA Astrophysics Data System (ADS)

Herbut, Aneta; Rybak, Jarosław

2017-10-01

As the soil improvement technologies are the area of a rapid development, they require designing and implementing novel methods of control and calibration in order to ensure the safety of geotechnical works. At Wroclaw University of Science and Technology (Poland), these new methods are continually developed with the aim to provide the appropriate tools for the preliminary design of work process, as well as for the further ongoing on-site control of geotechnical works (steel sheet piling, pile driving or soil improvement technologies). The studies include preliminary numerical simulations and field tests concerning measurements and continuous histogram recording of shocks and vibrations and its ground-born dynamic impact on engineering structures. The impact of vibrations on reinforced concrete and masonry structures in the close proximity of the construction site may be destroying in both architectural and structural meaning. Those limits are juxtaposed in codes of practice, but always need an individual judgment. The results and observations make it possible to delineate specific modifications to the parameters of technology applied (e.g. hammer drop height). On the basis of numerous case studies of practical applications, already summarized and published, we were able to formulate the guidelines for work on the aforementioned sites. This work presents specific aspects of the active design (calibration of building site numerical model) by means of technology calibration, using the investigation of the impact of vibrations that occur during the Impulse Compaction on adjacent structures. A case study entails the impact of construction works on Rayleigh wave propagation in the zone of 100 m (radius) around the Compactor.

Designing and Testing of Novel Taxanes to Probe the Highly Complex Mechanisms by Which Taxanes Bind to Microtubules and Cause Cytotoxicity to Cancer Cells

PubMed Central

St. George, Marc; Ayoub, Ahmed T.; Banerjee, Asok; Churchill, Cassandra D. M.; Winter, Philip; Klobukowski, Mariusz; Cass, Carol E.; Ludueña, Richard F.; Tuszynski, Jack A.; Damaraju, Sambasivarao

2015-01-01

Our previous work identified an intermediate binding site for taxanes in the microtubule nanopore. The goal of this study was to test derivatives of paclitaxel designed to bind to this intermediate site differentially depending on the isotype of β-tubulin. Since β-tubulin isotypes have tissue-dependent expression—specifically, the βIII isotype is very abundant in aggressive tumors and much less common in normal tissues—this is expected to lead to tubulin targeted drugs that are more efficacious and have less side effects. Seven derivatives of paclitaxel were designed and four of these were amenable for synthesis in sufficient purity and yield for further testing in breast cancer model cell lines. None of the derivatives studied were superior to currently used taxanes, however computer simulations provided insights into the activity of the derivatives. Our results suggest that neither binding to the intermediate binding site nor the final binding site is sufficient to explain the activities of the derivative taxanes studied. These findings highlight the need to iteratively improve on the design of taxanes based on their activity in model systems. Knowledge gained on the ability of the engineered drugs to bind to targets and bring about activity in a predictable manner is a step towards personalizing therapies. PMID:26052950

Integrated flight/propulsion control system design based on a decentralized, hierarchical approach

NASA Technical Reports Server (NTRS)

Mattern, Duane; Garg, Sanjay; Bullard, Randy

1989-01-01

A sample integrated flight/propulsion control system design is presented for the piloted longitudinal landing task with a modern, statistically unstable fighter aircraft. The design procedure is summarized. The vehicle model used in the sample study is described, and the procedure for partitioning the integrated system is presented along with a description of the subsystems. The high-level airframe performance specifications and control design are presented and the control performance is evaluated. The generation of the low-level (engine) subsystem specifications from the airframe requirements are discussed, and the engine performance specifications are presented along with the subsystem control design. A compensator to accommodate the influence of airframe outputs on the engine subsystem is also considered. Finally, the entire closed loop system performance and stability characteristics are examined.

Integrated flight/propulsion control system design based on a decentralized, hierarchical approach

NASA Technical Reports Server (NTRS)

Mattern, Duane; Garg, Sanjay; Bullard, Randy

1989-01-01

A sample integrated flight/propulsion control system design is presented for the piloted longitiudinal landing task with a modern, statistically unstable fighter aircraft. The design procedure is summarized, the vehicle model used in the sample study is described, and the procedure for partitioning the integrated system is presented along with a description of the subsystems. The high-level airframe performance specifications and control design are presented and the control performance is evaluated. The generation of the low-level (engine) subsystem specifications from the airframe requirements are discussed, and the engine performance specifications are presented along with the subsystem control design. A compensator to accommodate the influence of airframe outputs on the engine subsystem is also considered. Finally, the entire closed loop system performance and stability characteristics are examined.

Use of tissue-specific microRNA to control pathology of wild-type adenovirus without attenuation of its ability to kill cancer cells.

PubMed

Cawood, Ryan; Chen, Hannah H; Carroll, Fionnadh; Bazan-Peregrino, Miriam; van Rooijen, Nico; Seymour, Leonard W

2009-05-01

Replicating viruses have broad applications in biomedicine, notably in cancer virotherapy and in the design of attenuated vaccines; however, uncontrolled virus replication in vulnerable tissues can give pathology and often restricts the use of potent strains. Increased knowledge of tissue-selective microRNA expression now affords the possibility of engineering replicating viruses that are attenuated at the RNA level in sites of potential pathology, but retain wild-type replication activity at sites not expressing the relevant microRNA. To assess the usefulness of this approach for the DNA virus adenovirus, we have engineered a hepatocyte-safe wild-type adenovirus 5 (Ad5), which normally mediates significant toxicity and is potentially lethal in mice. To do this, we have included binding sites for hepatocyte-selective microRNA mir-122 within the 3' UTR of the E1A transcription cassette. Imaging versions of these viruses, produced by fusing E1A with luciferase, showed that inclusion of mir-122 binding sites caused up to 80-fold decreased hepatic expression of E1A following intravenous delivery to mice. Animals administered a ten-times lethal dose of wild-type Ad5 (5x10(10) viral particles/mouse) showed substantial hepatic genome replication and extensive liver pathology, while inclusion of 4 microRNA binding sites decreased replication 50-fold and virtually abrogated liver toxicity. This modified wild-type virus retained full activity within cancer cells and provided a potent, liver-safe oncolytic virus. In addition to providing many potent new viruses for cancer virotherapy, microRNA control of virus replication should provide a new strategy for designing safe attenuated vaccines applied across a broad range of viral diseases.

Performance Optimization of Storable Bipropellant Engines to Fully Exploit Advanced Material Technologies

NASA Technical Reports Server (NTRS)

Miller, Scott; Henderson, Scott; Portz, Ron; Lu, Frank; Wilson, Kim; Krismer, David; Alexander, Leslie; Chapman, Jack; England, Chris

2007-01-01

This paper summarizes the work performed to dale on the NASA Cycle 3A Advanced Chemical Propulsion Technology Program. The primary goals of the program are to design, fabricate, and test high performance bipropellant engines using iridium/rhenium chamber technology to obtain 335 seconds specific impulse with nitrogen tetroxide/hydrazine propellants and 330 seconds specific impulse with nitrogen tetroxide/monomethylhydrazine propellants. Aerojet has successfully completed the Base Period of this program, wherein (1) mission and system studies have been performed to verify system performance benefits and to determine engine physical and operating parameters, (2) preliminary chamber and nozzle designs have been completed and a chamber supplier has been downselected, (3) high temperature, high pressure off-nominal hot fire testing of an existing state-of-the-art high performance bipropellant engine has been completed, and (4) thermal and performance data from the engine test have been correlated with new thermal models to enable design of the new engine injector and injector/chamber interface. In the next phase of the program, Aerojet will complete design, fabrication, and test of the nitrogen tetroxide/hydrazine engine to demonstrate 335 seconds specific impulse, and also investigate improved technologies for iridium/rhenium chamber fabrication. Achievement of the NRA goals will significantly benefit NASA interplanetary missions and other government and commercial opportunities by enabling reduced launch weight and/or increased payload. At the conclusion of the program, the objective is to have an engine ready for final design and qualification for a specific science mission or commercial application. The program also constitutes a stepping stone to future, development, such as higher pressure pump-fed in-space storable engines.

Natural attenuation software (NAS): Assessing remedial strategies and estimating timeframes

USGS Publications Warehouse

Mendez, E.; Widdowson, M.; Chapelle, F.; Casey, C.

2005-01-01

Natural Attenuation Software (NAS) is a screening tool to estimate remediation timeframes for monitored natural attenuation (MNA) and to assist in decision-making on the level of source zone treatment in conjunction with MNA using site-specific remediation objectives. Natural attenuation processes that NAS models include are advection, dispersion, sorption, non-aqueous phase liquid (NAPL) dissolution, and biodegradation of either petroleum hydrocarbons or chlorinated ethylenes. Newly-implemented enhancements to NAS designed to maximize the utility of NAS for site managers were observed. NAS has expanded source contaminant specification options to include chlorinated ethanes and chlorinated methanes, and to allow for the analysis of any other user-defined contaminants that may be subject to microbially-mediated transformations (heavy metals, radioisotopes, etc.). Included is the capability to model co-mingled plumes, with constituents from multiple contaminant categories. To enable comparison of remediation timeframe estimates between MNA and specific engineered remedial actions , NAS was modified to incorporate an estimation technique for timeframes associated with pump-and-treat remediation technology for comparison to MNA. This is an abstract of a paper presented at the 8th International In Situ and On-Site Bioremediation Symposium (Baltimore, MD 6/6-9/2005).

Grand challenges in bioengineered nanorobotics for cancer therapy.

PubMed

Lenaghan, Scott C; Wang, Yongzhong; Xi, Ning; Fukuda, Toshio; Tarn, Tzyhjong; Hamel, William R; Zhang, Mingjun

2013-03-01

One of the grand challenges currently facing engineering, life sciences, and medicine is the development of fully functional nanorobots capable of sensing, decision making, and actuation. These nanorobots may aid in cancer therapy, site-specific drug delivery, circulating diagnostics, advanced surgery, and tissue repair. In this paper, we will discuss, from a bioinspired perspective, the challenges currently facing nanorobotics, including core design, propulsion and power generation, sensing, actuation, control, decision making, and system integration. Using strategies inspired from microorganisms, we will discuss a potential bioengineered nanorobot for cancer therapy.

Connecting Projects to Complete the In Situ Resource Utilization Paradigm

NASA Technical Reports Server (NTRS)

Linne, Diane L.; Sanders, Gerald B.

2017-01-01

Terrain Identify specifics such as slope, rockiness, traction parameters Identify what part of ISRU needs each Physical Geotechnical Hardness, density, cohesion, etc. Identify what part of ISRU needs each (e.g., excavation needs to know hardness, density; soil processing needs to know density, cohesion; etc.)Mineral Identify specifics Identify what part of ISRU needs each Volatile Identify specifics Identify what part of ISRU needs each Atmosphere Identify specifics Identify what part of ISRU needs each Environment Identify specifics Identify what part of ISRU needs each Resource Characterization What: Develop an instrument suite to locate and evaluate the physical, mineral, and volatile resources at the lunar poles Neutron Spectrometer Near Infrared (IR) to locate subsurface hydrogen surface water Near IR for mineral identification Auger drill for sample removal down to 1 m Oven with Gas Chromatograph Mass Spectrometer to quantify volatiles present ISRU relevance: Water volatile resource characterization and subsurface material access removal Site Evaluation Resource Mapping What: Develop and utilize new data products and tools for evaluating potential exploration sites for selection and overlay mission data to map terrain, environment, and resource information e.g., New techniques applied to generate Digital Elevation Map (DEMs) at native scale of images (1mpxl)ISRU relevance: Resource mapping and estimation with terrain and environment information is needed for extraction planning Mission Planning and Operations What: Develop and utilize tools and procedures for planning mission operations and real time changes Planning tools include detailed engineering models (e.g., power and data) of surface segment systems allows evaluation of designs ISRU relevance: Allows for iterative engineering as a function of environment and hardware performance.

40 CFR 35.937 - Subagreements for architectural or engineering services.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., surveys, evaluations, consultations, planning, programing, conceptual designs, plans and specifications... engineering services. Those professional services associated with research, development, design and...

40 CFR 35.937 - Subagreements for architectural or engineering services.

Code of Federal Regulations, 2011 CFR

2011-07-01

... engineering services. Those professional services associated with research, development, design and..., surveys, evaluations, consultations, planning, programing, conceptual designs, plans and specifications...

40 CFR 35.937 - Subagreements for architectural or engineering services.

Code of Federal Regulations, 2014 CFR

2014-07-01

... engineering services. Those professional services associated with research, development, design and..., surveys, evaluations, consultations, planning, programing, conceptual designs, plans and specifications...

40 CFR 35.937 - Subagreements for architectural or engineering services.

Code of Federal Regulations, 2012 CFR

2012-07-01

... engineering services. Those professional services associated with research, development, design and..., surveys, evaluations, consultations, planning, programing, conceptual designs, plans and specifications...

40 CFR 35.937 - Subagreements for architectural or engineering services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... engineering services. Those professional services associated with research, development, design and..., surveys, evaluations, consultations, planning, programing, conceptual designs, plans and specifications...

Incorporating the site variability and laboratory/in-situ testing variability of soil properties in geotechnical engineering design : research project capsule : technology transfer program.

DOT National Transportation Integrated Search

2016-04-01

While structural engineering deals with mostly homogeneous manmade materials : (e.g., concrete and steel), geotechnical engineering typically involves highly varied : natural materials (e.g., soil and rock). As a result, high variance of the resistan...

MHD program plan, FY 1991

NASA Astrophysics Data System (ADS)

1990-10-01

The current magnetohydrodynamic MHD program being implemented is a result of a consensus established in public meetings held by the Department of Energy in 1984. The public meetings were followed by the formulation of a June 1984 Coal-Fired MHD Preliminary Transition and Program Plan. This plan focused on demonstrating the proof-of-concept (POC) of coal-fired MHD electric power plants by the early 1990s. MHD test data indicate that while there are no fundamental technical barriers impeding the development of MHD power plants, technical risk remains. To reduce the technical risk three key subsystems (topping cycle, bottoming cycle, and seed regeneration) are being assembled and tested separately. The program does not require fabrication of a complete superconducting magnet, but rather the development and testing of superconductor cables. The topping cycle system test objectives can be achieved using a conventional iron core magnet system already in place at a DOE facility. Systems engineering-derived requirements and analytical modeling to support scale-up and component design guide the program. In response to environmental, economic, engineering, and utility acceptance requirements, design choices and operating modes are tested and refined to provide technical specifications for meeting commercial criteria. These engineering activities are supported by comprehensive and continuing systems analyses to establish realistic technical requirements and cost data. Essential elements of the current program are to: develop technical and environmental data for the integrated MHD topping cycle and bottoming cycle systems through POC testing (1000 and 4000 hours, respectively); design, construct, and operate a POC seed regeneration system capable of processing spent seed materials from the MHD bottoming cycle; prepare conceptual designs for a site specific MHD retrofit plant; and continue supporting research necessary for system testing.

10 CFR 960.3-1-4-2 - Site nomination for characterization.

Code of Federal Regulations, 2012 CFR

2012-01-01

... testing of core samples for the evaluation of geochemical and engineering rock properties, and chemical... industrial activities; and extrapolations of regional data to estimate site-specific characteristics and...

10 CFR 960.3-1-4-2 - Site nomination for characterization.

Code of Federal Regulations, 2013 CFR

2013-01-01

... testing of core samples for the evaluation of geochemical and engineering rock properties, and chemical... industrial activities; and extrapolations of regional data to estimate site-specific characteristics and...

10 CFR 960.3-1-4-2 - Site nomination for characterization.

Code of Federal Regulations, 2011 CFR

2011-01-01

... testing of core samples for the evaluation of geochemical and engineering rock properties, and chemical... industrial activities; and extrapolations of regional data to estimate site-specific characteristics and...

10 CFR 960.3-1-4-2 - Site nomination for characterization.

Code of Federal Regulations, 2014 CFR

2014-01-01

... testing of core samples for the evaluation of geochemical and engineering rock properties, and chemical... industrial activities; and extrapolations of regional data to estimate site-specific characteristics and...

Structural analysis of color video camera installation on tank 241AW101 (2 Volumes)

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

Strehlow, J.P.

1994-08-24

A video camera is planned to be installed on the radioactive storage tank 241AW101 at the DOE` s Hanford Site in Richland, Washington. The camera will occupy the 20 inch port of the Multiport Flange riser which is to be installed on riser 5B of the 241AW101 (3,5,10). The objective of the project reported herein was to perform a seismic analysis and evaluation of the structural components of the camera for a postulated Design Basis Earthquake (DBE) per the reference Structural Design Specification (SDS) document (6). The detail of supporting engineering calculations is documented in URS/Blume Calculation No. 66481-01-CA-03 (1).

30 CFR 1220.011 - Schedule of allowable direct and allocable joint costs and credits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... engineering design problems related to equipment or facilities required for NPSL operations. (4) The cost of any contract service related to research and development is specifically excluded, as are contract services calling for feasibility studies not directly related to specific engineering design problems or...

Protein Design for Pathway Engineering

PubMed Central

Eriksen, Dawn T.; Lian, Jiazhang; Zhao, Huimin

2013-01-01

Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. PMID:23558037

Protein design for pathway engineering.

PubMed

Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin

2014-02-01

Design and construction of biochemical pathways has increased the complexity of biosynthetically-produced compounds when compared to single enzyme biocatalysis. However, the coordination of multiple enzymes can introduce a complicated set of obstacles to overcome in order to achieve a high titer and yield of the desired compound. Metabolic engineering has made great strides in developing tools to optimize the flux through a target pathway, but the inherent characteristics of a particular enzyme within the pathway can still limit the productivity. Thus, judicious protein design is critical for metabolic and pathway engineering. This review will describe various strategies and examples of applying protein design to pathway engineering to optimize the flux through the pathway. The proteins can be engineered for altered substrate specificity/selectivity, increased catalytic activity, reduced mass transfer limitations through specific protein localization, and reduced substrate/product inhibition. Protein engineering can also be expanded to design biosensors to enable high through-put screening and to customize cell signaling networks. These strategies have successfully engineered pathways for significantly increased productivity of the desired product or in the production of novel compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

The artificial zinc finger coding gene 'Jazz' binds the utrophin promoter and activates transcription.

PubMed

Corbi, N; Libri, V; Fanciulli, M; Tinsley, J M; Davies, K E; Passananti, C

2000-06-01

Up-regulation of utrophin gene expression is recognized as a plausible therapeutic approach in the treatment of Duchenne muscular dystrophy (DMD). We have designed and engineered new zinc finger-based transcription factors capable of binding and activating transcription from the promoter of the dystrophin-related gene, utrophin. Using the recognition 'code' that proposes specific rules between zinc finger primary structure and potential DNA binding sites, we engineered a new gene named 'Jazz' that encodes for a three-zinc finger peptide. Jazz belongs to the Cys2-His2 zinc finger type and was engineered to target the nine base pair DNA sequence: 5'-GCT-GCT-GCG-3', present in the promoter region of both the human and mouse utrophin gene. The entire zinc finger alpha-helix region, containing the amino acid positions that are crucial for DNA binding, was specifically chosen on the basis of the contacts more frequently represented in the available list of the 'code'. Here we demonstrate that Jazz protein binds specifically to the double-stranded DNA target, with a dissociation constant of about 32 nM. Band shift and super-shift experiments confirmed the high affinity and specificity of Jazz protein for its DNA target. Moreover, we show that chimeric proteins, named Gal4-Jazz and Sp1-Jazz, are able to drive the transcription of a test gene from the human utrophin promoter.

Senior Design in Agricultural Engineering--Progress and Pitfalls.

ERIC Educational Resources Information Center

Holmes, R. G.; Rohrbach, R. P.

1979-01-01

Describes a specific senior design course and its objectives. Explains the basic deficiencies and problems for design education in agricultural engineering. Also stresses the effect the project advisor has on students' attitudes toward design and the applications of the course. (SMB)

Mechanical control of tissue-engineered bone.

PubMed

Hung, Ben P; Hutton, Daphne L; Grayson, Warren L

2013-01-31

Bone is a load-bearing tissue and physical forces play key roles in the development and maintenance of its structure. Mechanical cues can stimulate the expression of an osteogenic phenotype, enhance matrix and mineral deposition, and influence tissue organization to improve the functional outcome of engineered bone grafts. In recent years, a number of studies have investigated the effects of biophysical forces on the bone formation properties of osteoprogenitor cells. The application of physiologically relevant stimuli to tissue-engineered bone may be determined through observation and understanding of forces to which osteoblasts, osteoclasts, and osteocytes are exposed in native bone. Subsequently, these cues may be parameterized and their effects studied in well-defined in vitro systems. The osteo-inductive effects of three specific mechanical cues - shear stress, substrate rigidity, and nanotopography - on cells cultured in monolayer or in three-dimensional biomaterial scaffolds in vitro are reviewed. Additionally, we address the time-dependent effects of mechanical cues on vascular infiltration and de novo bone formation in acellular scaffolds implanted into load-bearing sites in vivo. Recent studies employing cutting-edge advances in biomaterial fabrication and bioreactor design have provided key insights into the role of mechanical cues on cellular fate and tissue properties of engineered bone grafts. By providing mechanistic understanding, future studies may go beyond empirical approaches to rational design of engineering systems to control tissue development.

VSCE technology definition study

NASA Technical Reports Server (NTRS)

Howlett, R. A.; Hunt, R. B.

1979-01-01

Refined design definition of the variable stream control engine (VSCE) concept for advanced supersonic transports is presented. Operating and performance features of the VSCE are discussed, including the engine components, thrust specific fuel consumption, weight, noise, and emission system. A preliminary engine design is presented.

Analytical Design Package (ADP2): A computer aided engineering tool for aircraft transparency design

NASA Technical Reports Server (NTRS)

Wuerer, J. E.; Gran, M.; Held, T. W.

1994-01-01

The Analytical Design Package (ADP2) is being developed as a part of the Air Force Frameless Transparency Program (FTP). ADP2 is an integrated design tool consisting of existing analysis codes and Computer Aided Engineering (CAE) software. The objective of the ADP2 is to develop and confirm an integrated design methodology for frameless transparencies, related aircraft interfaces, and their corresponding tooling. The application of this methodology will generate high confidence for achieving a qualified part prior to mold fabrication. ADP2 is a customized integration of analysis codes, CAE software, and material databases. The primary CAE integration tool for the ADP2 is P3/PATRAN, a commercial-off-the-shelf (COTS) software tool. The open architecture of P3/PATRAN allows customized installations with different applications modules for specific site requirements. Integration of material databases allows the engineer to select a material, and those material properties are automatically called into the relevant analysis code. The ADP2 materials database will be composed of four independent schemas: CAE Design, Processing, Testing, and Logistics Support. The design of ADP2 places major emphasis on the seamless integration of CAE and analysis modules with a single intuitive graphical interface. This tool is being designed to serve and be used by an entire project team, i.e., analysts, designers, materials experts, and managers. The final version of the software will be delivered to the Air Force in Jan. 1994. The Analytical Design Package (ADP2) will then be ready for transfer to industry. The package will be capable of a wide range of design and manufacturing applications.

Engineering applications of strong ground motion simulation

NASA Astrophysics Data System (ADS)

Somerville, Paul

1993-02-01

The formulation, validation and application of a procedure for simulating strong ground motions for use in engineering practice are described. The procedure uses empirical source functions (derived from near-source strong motion recordings of small earthquakes) to provide a realistic representation of effects such as source radiation that are difficult to model at high frequencies due to their partly stochastic behavior. Wave propagation effects are modeled using simplified Green's functions that are designed to transfer empirical source functions from their recording sites to those required for use in simulations at a specific site. The procedure has been validated against strong motion recordings of both crustal and subduction earthquakes. For the validation process we choose earthquakes whose source models (including a spatially heterogeneous distribution of the slip of the fault) are independently known and which have abundant strong motion recordings. A quantitative measurement of the fit between the simulated and recorded motion in this validation process is used to estimate the modeling and random uncertainty associated with the simulation procedure. This modeling and random uncertainty is one part of the overall uncertainty in estimates of ground motions of future earthquakes at a specific site derived using the simulation procedure. The other contribution to uncertainty is that due to uncertainty in the source parameters of future earthquakes that affect the site, which is estimated from a suite of simulations generated by varying the source parameters over their ranges of uncertainty. In this paper, we describe the validation of the simulation procedure for crustal earthquakes against strong motion recordings of the 1989 Loma Prieta, California, earthquake, and for subduction earthquakes against the 1985 Michoacán, Mexico, and Valparaiso, Chile, earthquakes. We then show examples of the application of the simulation procedure to the estimatation of the design response spectra for crustal earthquakes at a power plant site in California and for subduction earthquakes in the Seattle-Portland region. We also demonstrate the use of simulation methods for modeling the attenuation of strong ground motion, and show evidence of the effect of critical reflections from the lower crust in causing the observed flattening of the attenuation of strong ground motion from the 1988 Saguenay, Quebec, and 1989 Loma Prieta earthquakes.

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

Robichaud, R.; Fields, J.; Roberts, J. O.

The U.S. Environmental Protection Agency (EPA) launched the RE-Powering America's Land initiative to encourage development of renewable energy (RE) on potentially contaminated land and mine sites. EPA is collaborating with the U.S. Department of Energy's (DOE's) National Renewable Energy Laboratory (NREL) to evaluate RE options at Naval Station (NAVSTA) Newport in Newport, Rhode Island where multiple contaminated areas pose a threat to human health and the environment. Designated a superfund site on the National Priorities List in 1989, the base is committed to working toward reducing the its dependency on fossil fuels, decreasing its carbon footprint, and implementing RE projectsmore » where feasible. The Naval Facilities Engineering Service Center (NFESC) partnered with NREL in February 2009 to investigate the potential for wind energy generation at a number of Naval and Marine bases on the East Coast. NAVSTA Newport was one of several bases chosen for a detailed, site-specific wind resource investigation. NAVSTA Newport, in conjunction with NREL and NFESC, has been actively engaged in assessing the wind resource through several ongoing efforts. This report focuses on the wind resource assessment, the estimated energy production of wind turbines, and a survey of potential wind turbine options based upon the site-specific wind resource.« less

Masked Chimeric Antigen Receptor for Tumor-Specific Activation.

PubMed

Han, Xiaolu; Bryson, Paul D; Zhao, Yifan; Cinay, Gunce E; Li, Si; Guo, Yunfei; Siriwon, Natnaree; Wang, Pin

2017-01-04

Adoptive cellular therapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells is a powerful form of cancer immunotherapy. CAR-T cells can be redirected to specifically recognize tumor-associated antigens (TAAs) and induce high levels of antitumor activity. However, they may also display "on-target off-tumor" toxicities, resulting from low-level expression of TAAs in healthy tissues. These adverse effects have raised considerable safety concerns and limited the clinical application of this otherwise promising therapeutic modality. To minimize such side effects, we have designed an epidermal growth factor receptor (EGFR)-specific masked CAR (mCAR), which consists of a masking peptide that blocks the antigen-binding site and a protease-sensitive linker. Proteases commonly active in the tumor microenvironment can cleave the linker and disengage the masking peptide, thereby enabling CAR-T cells to recognize target antigens only at the tumor site. In vitro mCAR showed dramatically reduced antigen binding and antigen-specific activation in the absence of proteases, but normal levels of binding and activity upon treatment with certain proteases. Masked CAR-T cells also showed antitumor efficacy in vivo comparable to that of unmasked CAR. Our study demonstrates the feasibility of improving the safety profile of conventional CARs and may also inspire future design of CAR molecules targeting broadly expressed TAAs. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Electro-impulse de-icing of a turbofan engine inlet

NASA Technical Reports Server (NTRS)

Zumwalt, G. W.

1985-01-01

The application of electromagnetic impulse deicing (EIDI) systems to turbofan engine inlets on business aircraft has been investigated experimentally. The tests were performed in the Icing Research Tunnel at NASA's Lewis Research Center. The deicing system testbed was a Falcon Fanjet 20 engine nacelle. The effectiveness of various deicing coil configurations and mount designs were compared, and design parameters were developed specifically for EIDI systems in turbofan engines. Flight tests were also carried out at altitudes in the range 3000-6000 ft corresponding to a temperature range of -3 to -8 C. It is shown that the ice particles removed from the engine inlet by the deicing system were small enough for the engine to ingest. Tentative design specifications are given with respect to the optimum coil configuration, and operating power of a EIDI production candidate.

Recent Methods for Purification and Structure Determination of Oligonucleotides.

PubMed

Zhang, Qiulong; Lv, Huanhuan; Wang, Lili; Chen, Man; Li, Fangfei; Liang, Chao; Yu, Yuanyuan; Jiang, Feng; Lu, Aiping; Zhang, Ge

2016-12-18

Aptamers are single-stranded DNA or RNA oligonucleotides that can interact with target molecules through specific three-dimensional structures. The excellent features, such as high specificity and affinity for target proteins, small size, chemical stability, low immunogenicity, facile chemical synthesis, versatility in structural design and engineering, and accessible for site-specific modifications with functional moieties, make aptamers attractive molecules in the fields of clinical diagnostics and biopharmaceutical therapeutics. However, difficulties in purification and structural identification of aptamers remain a major impediment to their broad clinical application. In this mini-review, we present the recently attractive developments regarding the purification and identification of aptamers. We also discuss the advantages, limitations, and prospects for the major methods applied in purifying and identifying aptamers, which could facilitate the application of aptamers.

Teaching Risk Analysis in an Aircraft Gas Turbine Engine Design Capstone Course

DTIC Science & Technology

2016-01-01

American Institute of Aeronautics and Astronautics 1 Teaching Risk Analysis in an Aircraft Gas Turbine Engine Design Capstone Course...development costs, engine production costs, and scheduling (Byerley A. R., 2013) as well as the linkage between turbine inlet temperature, blade cooling...analysis SE majors have studied and how this is linked to the specific issues they must face in aircraft gas turbine engine design. Aeronautical and

Design and engineering of water-soluble light-harvesting protein maquettes

DOE PAGES

Kodali, Goutham; Mancini, Joshua A.; Solomon, Lee A.; ...

2017-01-01

Natural selection in photosynthesis has engineered tetrapyrrole based, nanometer scale, light harvesting and energy capture in light-induced charge separation. By designing and creating nanometer scale artificial light harvesting and charge separating proteins, we have the opportunity to reengineer and overcome the limitations of natural selection to extend energy capture to new wavelengths and to tailor efficient systems that better meet human as opposed to cellular energetic needs. While tetrapyrrole cofactor incorporation in natural proteins is complex and often assisted by accessory proteins for cofactor transport and insertion, artificial protein functionalization relies on a practical understanding of the basic physical chemistrymore » of protein and cofactors that drive nanometer scale self-assembly. Patterning and balancing of hydrophobic and hydrophilic tetrapyrrole substituents is critical to avoid natural or synthetic porphyrin and chlorin aggregation in aqueous media and speed cofactor partitioning into the non-polar core of a man-made water soluble protein designed according to elementary first principles of protein folding. In conclusion, this partitioning is followed by site-specific anchoring of tetrapyrroles to histidine ligands strategically placed for design control of rates and efficiencies of light energy and electron transfer while orienting at least one polar group towards the aqueous phase.« less

Methods in Enzymology: “Flexible backbone sampling methods to model and design protein alternative conformations”

PubMed Central

Ollikainen, Noah; Smith, Colin A.; Fraser, James S.; Kortemme, Tanja

2013-01-01

Sampling alternative conformations is key to understanding how proteins work and engineering them for new functions. However, accurately characterizing and modeling protein conformational ensembles remains experimentally and computationally challenging. These challenges must be met before protein conformational heterogeneity can be exploited in protein engineering and design. Here, as a stepping stone, we describe methods to detect alternative conformations in proteins and strategies to model these near-native conformational changes based on backrub-type Monte Carlo moves in Rosetta. We illustrate how Rosetta simulations that apply backrub moves improve modeling of point mutant side chain conformations, native side chain conformational heterogeneity, functional conformational changes, tolerated sequence space, protein interaction specificity, and amino acid co-variation across protein-protein interfaces. We include relevant Rosetta command lines and RosettaScripts to encourage the application of these types of simulations to other systems. Our work highlights that critical scoring and sampling improvements will be necessary to approximate conformational landscapes. Challenges for the future development of these methods include modeling conformational changes that propagate away from designed mutation sites and modulating backbone flexibility to predictively design functionally important conformational heterogeneity. PMID:23422426

Design and engineering of water-soluble light-harvesting protein maquettes

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

Kodali, Goutham; Mancini, Joshua A.; Solomon, Lee A.

Natural selection in photosynthesis has engineered tetrapyrrole based, nanometer scale, light harvesting and energy capture in light-induced charge separation. By designing and creating nanometer scale artificial light harvesting and charge separating proteins, we have the opportunity to reengineer and overcome the limitations of natural selection to extend energy capture to new wavelengths and to tailor efficient systems that better meet human as opposed to cellular energetic needs. While tetrapyrrole cofactor incorporation in natural proteins is complex and often assisted by accessory proteins for cofactor transport and insertion, artificial protein functionalization relies on a practical understanding of the basic physical chemistrymore » of protein and cofactors that drive nanometer scale self-assembly. Patterning and balancing of hydrophobic and hydrophilic tetrapyrrole substituents is critical to avoid natural or synthetic porphyrin and chlorin aggregation in aqueous media and speed cofactor partitioning into the non-polar core of a man-made water soluble protein designed according to elementary first principles of protein folding. In conclusion, this partitioning is followed by site-specific anchoring of tetrapyrroles to histidine ligands strategically placed for design control of rates and efficiencies of light energy and electron transfer while orienting at least one polar group towards the aqueous phase.« less

A Web Based Collaborative Design Environment for Spacecraft

NASA Technical Reports Server (NTRS)

Dunphy, Julia

1998-01-01

In this era of shrinking federal budgets in the USA we need to dramatically improve our efficiency in the spacecraft engineering design process. We have come up with a method which captures much of the experts' expertise in a dataflow design graph: Seamlessly connectable set of local and remote design tools; Seamlessly connectable web based design tools; and Web browser interface to the developing spacecraft design. We have recently completed our first web browser interface and demonstrated its utility in the design of an aeroshell using design tools located at web sites at three NASA facilities. Multiple design engineers and managers are now able to interrogate the design engine simultaneously and find out what the design looks like at any point in the design cycle, what its parameters are, and how it reacts to adverse space environments.

Precision control of recombinant gene transcription for CHO cell synthetic biology.

PubMed

Brown, Adam J; James, David C

2016-01-01

The next generation of mammalian cell factories for biopharmaceutical production will be genetically engineered to possess both generic and product-specific manufacturing capabilities that may not exist naturally. Introduction of entirely new combinations of synthetic functions (e.g. novel metabolic or stress-response pathways), and retro-engineering of existing functional cell modules will drive disruptive change in cellular manufacturing performance. However, before we can apply the core concepts underpinning synthetic biology (design, build, test) to CHO cell engineering we must first develop practical and robust enabling technologies. Fundamentally, we will require the ability to precisely control the relative stoichiometry of numerous functional components we simultaneously introduce into the host cell factory. In this review we discuss how this can be achieved by design of engineered promoters that enable concerted control of recombinant gene transcription. We describe the specific mechanisms of transcriptional regulation that affect promoter function during bioproduction processes, and detail the highly-specific promoter design criteria that are required in the context of CHO cell engineering. The relative applicability of diverse promoter development strategies are discussed, including re-engineering of natural sequences, design of synthetic transcription factor-based systems, and construction of synthetic promoters. This review highlights the potential of promoter engineering to achieve precision transcriptional control for CHO cell synthetic biology. Copyright © 2015. Published by Elsevier Inc.

An Evaluation of HigherEd 2.0 Technologies in Undergraduate Mechanical Engineering Courses

ERIC Educational Resources Information Center

Orange, Amy; Heinecke, Walter; Berger, Edward; Krousgrill, Charles; Mikic, Borjana; Quinn, Dane

2012-01-01

Between 2006 and 2010, sophomore engineering students at four universities were exposed to technologies designed to increase their learning in undergraduate engineering courses. Our findings suggest that students at all sites found the technologies integrated into their courses useful to their learning. Video solutions received the most positive…

40 CFR 1042.140 - Maximum engine power, displacement, power density, and maximum in-use engine speed.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE... procedures of 40 CFR part 1065, based on the manufacturer's design and production specifications for the... swept volume from the design specifications for the cylinders using enough significant figures to allow...

40 CFR 1042.140 - Maximum engine power, displacement, power density, and maximum in-use engine speed.

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE... procedures of 40 CFR part 1065, based on the manufacturer's design and production specifications for the... swept volume from the design specifications for the cylinders using enough significant figures to allow...

40 CFR 1042.140 - Maximum engine power, displacement, power density, and maximum in-use engine speed.

Code of Federal Regulations, 2014 CFR

2014-07-01

... ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE... procedures of 40 CFR part 1065, based on the manufacturer's design and production specifications for the... swept volume from the design specifications for the cylinders using enough significant figures to allow...

Green engineering education through a U.S. EPA/academia collaboration.

PubMed

Shonnard, David R; Allen, David T; Nguyen, Nhan; Austin, Sharon Weil; Hesketh, Robert

2003-12-01

The need to use resources efficiently and reduce environmental impacts of industrial products and processes is becoming increasingly important in engineering design; therefore, green engineering principles are gaining prominence within engineering education. This paper describes a general framework for incorporating green engineering design principles into engineering curricula, with specific examples for chemical engineering. The framework for teaching green engineering discussed in this paper mirrors the 12 Principles of Green Engineering proposed by Anastas and Zimmerman (Environ. Sci. Technol. 2003, 37, 94A-101A), especially in methods for estimating the hazardous nature of chemicals, strategies for pollution prevention, and approaches leading to efficient energy and material utilization. The key elements in green engineering education, which enlarge the "box" for engineering design, are environmental literacy, environmentally conscious design, and beyond-the-plant boundary considerations.

7 CFR 4288.2 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 12 months of data supported by engineering and design calculations, and site plans, prepared by the construction engineering firm. Biobased products. Products determined by the Secretary to be commercial or... biological products, including renewable domestic agricultural materials and forestry materials; or (2...

7 CFR 4288.2 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 12 months of data supported by engineering and design calculations, and site plans, prepared by the construction engineering firm. Biobased products. Products determined by the Secretary to be commercial or... biological products, including renewable domestic agricultural materials and forestry materials; or (2...

7 CFR 4288.2 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 12 months of data supported by engineering and design calculations, and site plans, prepared by the construction engineering firm. Biobased products. Products determined by the Secretary to be commercial or... biological products, including renewable domestic agricultural materials and forestry materials; or (2...

Engineering issue: Indoor Air Vapor Intrusion Mitigation Approaches

EPA Science Inventory

The US Environmental Protection Agency (EPA) Engineering Issues are a new series of technology transfer documents that summarize the latest available information on selected treatment and site remeediation technologies and related issues. They are designed to help remedial projec...

Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5

PubMed Central

Azoitei, M.L.; Ban, Y.A.; Kalyuzhny, O.; Guenaga, J.; Schroeter, A.; Porter, J.; Wyatt, R.; Schief, W.R.

2015-01-01

Rational design of proteins with novel binding specificities and increased affinity is one of the major goals of computational protein design. Epitope-scaffolds are a new class of antigens engineered by transplanting viral epitopes of pre-defined structure to protein scaffolds, or by building protein scaffolds around such epitopes. Epitope-scaffolds are of interest as vaccine components to attempt to elicit neutralizing antibodies targeting the specified epitope. In this study we developed a new computational protocol, MultiGraft Interface, that transplants epitopes but also designs additional scaffold features outside the epitope to enhance antibody-binding specificity and potentially influence the specificity of elicited antibodies. We employed MultiGraft Interface to engineer novel epitope-scaffolds that display the known epitope of HIV-1 neutralizing antibody 2F5 and that also interact with the functionally important CDR H3 antibody loop. MultiGraft Interface generated an epitope-scaffold that bound 2F5 with sub-nanomolar affinity (KD = 400 pM) and that interacted with the antibody CDR H3 loop through computationally designed contacts. Substantial structural modifications were necessary to engineer this antigen, with the 2F5 epitope replacing a helix in the native scaffold and with 15% of the native scaffold sequence being modified in the design stage. This epitope-scaffold represents a successful example of rational protein backbone engineering and protein-protein interface design and could prove useful in the field of HIV vaccine design. MultiGraft Interface can be generally applied to engineer novel binding partners with altered specificity and optimized affinity. PMID:25043744

Liquid rocket engine turbines

NASA Technical Reports Server (NTRS)

1974-01-01

Criteria for the design and development of turbines for rocket engines to meet specific performance, and installation requirements are summarized. The total design problem, and design elements are identified, and the current technology pertaining to these elements is described. Recommended practices for achieving a successful design are included.

Orbit Transfer Vehicle (OTV) advanced expander cycle engine point design study, volume 2

NASA Technical Reports Server (NTRS)

1981-01-01

The engine requirements are emphasized and include: high specific impulse within a restricted installed length constraint, long life, multiple starts, different thrust levels, and man-rated reliability. The engine operating characteristics and the major component analytical design are summarized.

Geohydrologic aspects for siting and design of low-level radioactive-waste disposal

USGS Publications Warehouse

Bedinger, M.S.

1989-01-01

The objective for siting and design of low-level radioactive-waste repository sites is to isolate the waste from the biosphere until the waste no longer poses an unacceptable hazard as a result of radioactive decay. Low-level radioactive waste commonly is isolated at shallow depths with various engineered features to stabilize the waste and to reduce its dissolution and transport by ground water. The unsaturated zone generally is preferred for isolating the waste. Low-level radioactive waste may need to be isolated for 300 to 500 years. Maintenance and monitoring of the repository site are required by Federal regulations for only the first 100 years. Therefore, geohydrology of the repository site needs to provide natural isolation of the waste for the hazardous period following maintenance of the site. Engineering design of the repository needs to be compatible with the natural geohydrologic conditions at the site. Studies at existing commercial and Federal waste-disposal sites provide information on the problems encountered and the basis for establishing siting guidelines for improved isolation of radioactive waste, engineering design of repository structures, and surveillance needs to assess the effectiveness of the repositories and to provide early warning of problems that may require remedial action.Climate directly affects the hydrology of a site and probably is the most important single factor that affects the suitability of a site for shallow-land burial of low-level radioactive waste. Humid and subhumid regions are not well suited for shallow isolation of low-level radioactive waste in the unsaturated zone; arid regions with zero to small infiltration from precipitation, great depths to the water table, and long flow paths to natural discharge areas are naturally well suited to isolation of the waste. The unsaturated zone is preferred for isolation of low-level radioactive waste. The guiding rationale is to minimize contact of water with the waste and to minimize transport of waste from the repository. The hydrology of a flow system containing a repository is greatly affected by the engineering of the repository site. Prediction of the performance of the repository is a complex problem, hampered by problems of characterizing the natural and manmade features of the flow system and by the limitations of models to predict flow and geochemical processes in the saturated and unsaturated zones. Disposal in low-permeability unfractured clays in the saturated zone may be feasible where the radionuclide transport is controlled by diffusion rather than advection.

Photographic copy of original design drawing, dated January 1970, revised ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photographic copy of original design drawing, dated January 1970, revised 24 May 1972 (original Army Operational Drawing in the possession of U.S. Army Corps of Engineers, Huntsville, Division). MSRPP general floor plan, lower level - Stanely R. Mickelsen Safeguard Complex, Missile Site Radar Power Plant, Southeast of, & adjacent to, Missile Site Control Building, Nekoma, Cavalier County, ND

Cell-free synthetic biology for in vitro prototype engineering.

PubMed

Moore, Simon J; MacDonald, James T; Freemont, Paul S

2017-06-15

Cell-free transcription-translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. © 2017 The Author(s).

Cell-free synthetic biology for in vitro prototype engineering

PubMed Central

Moore, Simon J.; MacDonald, James T.

2017-01-01

Cell-free transcription–translation is an expanding field in synthetic biology as a rapid prototyping platform for blueprinting the design of synthetic biological devices. Exemplar efforts include translation of prototype designs into medical test kits for on-site identification of viruses (Zika and Ebola), while gene circuit cascades can be tested, debugged and re-designed within rapid turnover times. Coupled with mathematical modelling, this discipline lends itself towards the precision engineering of new synthetic life. The next stages of cell-free look set to unlock new microbial hosts that remain slow to engineer and unsuited to rapid iterative design cycles. It is hoped that the development of such systems will provide new tools to aid the transition from cell-free prototype designs to functioning synthetic genetic circuits and engineered natural product pathways in living cells. PMID:28620040

Effects of Engineering Design-Based Science on Elementary School Science Students' Engineering Identity Development across Gender and Grade

ERIC Educational Resources Information Center

Capobianco, Brenda M.; Yu, Ji H.; French, Brian F.

2015-01-01

The integration of engineering concepts and practices into elementary science education has become an emerging concern for science educators and practitioners, alike. Moreover, how children, specifically preadolescents (grades 1-5), engage in engineering design-based learning activities may help science educators and researchers learn more about…

Problems Related to the Siting of the Laboratory Building for Civil Engineering Department at the University of Warmia and Mazury in Olsztyn, Poland

NASA Astrophysics Data System (ADS)

Zagroba, Marek

2016-10-01

This paper deals with the conditions underlying and the problems arising from the siting of a building with specialist laboratories in a developed part of the university campus in Olsztyn, Poland. The topography of the terrain and the need to house civil engineering laboratories in the planned building had an immense impact on the shape of the building and consequently on its foundations, whose dimensions responded to the ground conditions and the specification of various loads they would have to support, including the equipment for the laboratories. The siting of a building as a step in the construction process entails several problems, which are first taken into consideration at the stage of making preliminary concept plans and are subsequently verified while working on the final construction plan. The required information included geotechnical documentation, survey of the ground conditions and the data regarding the predicted loads on the building, necessary to select the right type of foundations. All these problems grow in importance when dealing with such unique buildings like the discussed example of a laboratory building for the Civil Engineering Department, built on a site within a conservation zone on the campus of the University of Warmia and Mazury in Olsztyn, Poland. The specific character of the building and the specialist equipment with which it was to be furnished (a resistance testing machine, a 17-meter-long wave flume) necessitated a series of analyses prior to the siting of the building and selecting suitable foundations. In turn, the fact that the new building was to be erected in the conservation zone meant that collaboration with the Heritage Conservation Office had to be undertaken at the stage of making the plan and continued during the construction works. The Heritage Officer's recommendations concerning the building's shape, divisions, dimensions, materials used, etc., created a situation where the team of designers and architects had to become engaged in the process of landscape and spatial management. The above requirements concerned the functions of the building and its siting on a land parcel that was difficult to handle, also because of the protected trees growing there. Other constraints included the small size of this site, the developed surroundings, and the pre-defined programme of functions and use of the new building. On the other hand, the siting of the planned building had to be accommodated to the existing underground infrastructure (utilities). All the above circumstances made the task difficult and demanded good coordination between individual teams of engineers and architects, both at the stage of making the plan and during the construction works.

Improving 1D Site Specific Velocity Profiles for the Kik-Net Network

NASA Astrophysics Data System (ADS)

Holt, James; Edwards, Benjamin; Pilz, Marco; Fäh, Donat; Rietbrock, Andreas

2017-04-01

Ground motion predication equations (GMPEs) form the cornerstone of modern seismic hazard assessments. When produced to a high standard they provide reliable estimates of ground motion/spectral acceleration for a given site and earthquake scenario. This information is crucial for engineers to optimise design and for regulators who enforce legal minimum safe design capacities. Classically, GMPEs were built upon the assumption that variability around the median model could be treated as aleatory. As understanding improved, it was noted that the propagation could be segregated into the response of the average path from the source and the response of the site. This is because the heterogeneity of the near-surface lithology is significantly different from that of the bulk path. It was then suggested that the semi-ergodic approach could be taken if the site response could be determined, moving uncertainty away from aleatory to epistemic. The determination of reliable site-specific response models is therefore becoming increasingly critical for ground motion models used in engineering practice. Today it is common practice to include proxies for site response within the scope of a GMPE, such as Vs30 or site classification, in an effort to reduce the overall uncertainty of the predication at a given site. However, these proxies are not always reliable enough to give confident ground motion estimates, due to the complexity of the near-surface. Other approaches of quantifying the response of the site include detailed numerical simulations (1/2/3D - linear, EQL, non-linear etc.). However, in order to be reliable, they require highly detailed and accurate velocity and, for non-linear analyses, material property models. It is possible to obtain this information through invasive methods, but is expensive, and not feasible for most projects. Here we propose an alternative method to derive reliable velocity profiles (and their uncertainty), calibrated using almost 20 years of recorded data from the Kik-Net network. First, using a reliable subset of sites, the empirical surface to borehole (S/B) ratio is calculated in the frequency domain using all events recorded at that site. In a subsequent step, we use numerical simulation to produce 1D SH transfer function curves using a suite of stochastic velocity models. Comparing the resulting amplification with the empirical S/B ratio we find optimal 1D velocity models and their uncertainty. The method will be tested to determine the level of initial information required to obtain a reliable Vs profile (e.g., starting Vs model, only Vs30, site-class, H/V ratio etc.) and then applied and tested against data from other regions using site-to-reference or empirical spectral model amplification.

Variable speed gas engine-driven air compressor system

NASA Astrophysics Data System (ADS)

Morgan, J. R.; Ruggles, A. E.; Chen, T. N.; Gehret, J.

1992-11-01

Tecogen Inc. and Ingersoll-Rand Co. as a subcontractor have designed a nominal 150-hp gas engine-driven air compressor utilizing the TECODRIVE 8000 engine and the Ingersoll-Rand 178.5-mm twin screw compressor. Phase 1 included the system engineering and design, economic and applications studies, and a draft commercialization plan. Phase 2 included controls development, laboratory prototype construction, and performance testing. The testing conducted verified that the compressor meets all design specifications.

Contextual Shaping of Student Design Practices: The Role of Constraint in First-Year Engineering Design

NASA Astrophysics Data System (ADS)

Goncher, Andrea M.

thResearch on engineering design is a core area of concern within engineering education, and a fundamental understanding of how engineering students approach and undertake design is necessary in order to develop effective design models and pedagogies. This dissertation contributes to scholarship on engineering design by addressing a critical, but as yet underexplored, problem: how does the context in which students design shape their design practices? Using a qualitative study comprising of video data of design sessions, focus group interviews with students, and archives of their design work, this research explored how design decisions and actions are shaped by context, specifically the context of higher education. To develop a theoretical explanation for observed behavior, this study used the nested structuration. framework proposed by Perlow, Gittell, & Katz (2004). This framework explicated how teamwork is shaped by mutually reinforcing relationships at the individual, organizational, and institutional levels. I appropriated this framework to look specifically at how engineering students working on a course-related design project identify constraints that guide their design and how these constraints emerge as students interact while working on the project. I first identified and characterized the parameters associated with the design project from the student perspective and then, through multi-case studies of four design teams, I looked at the role these parameters play in student design practices. This qualitative investigation of first-year engineering student design teams revealed mutual and interconnected relationships between students and the organizations and institutions that they are a part of. In addition to contributing to research on engineering design, this work provides guidelines and practices to help design educators develop more effective design projects by incorporating constraints that enable effective design and learning. Moreover, I found that when appropriated in the context of higher education, multiple sublevels existed within nested structuration's organizational context and included course-level and project-level factors. The implications of this research can be used to improve the design of engineering course projects as well as the design of research efforts related to design in engineering education.

Research on Building Education & Workforce Capacity in Systems Engineering

DTIC Science & Technology

2011-02-07

manufacturing or design sites where students could observe engineering processes related to their projects Mentors with the highest level of student ... engagement interacted with students in every single activity area and with frequency, while others provided only intermittent correspondence. Note

Biocatalysts: application and engineering for industrial purposes.

PubMed

Jemli, Sonia; Ayadi-Zouari, Dorra; Hlima, Hajer Ben; Bejar, Samir

2016-01-01

Enzymes are widely applied in various industrial applications and processes, including the food and beverage, animal feed, textile, detergent and medical industries. Enzymes screened from natural origins are often engineered before entering the market place because their native forms do not meet the requirements for industrial application. Protein engineering is concerned with the design and construction of novel enzymes with tailored functional properties, including stability, catalytic activity, reaction product inhibition and substrate specificity. Two broad approaches have been used for enzyme engineering, namely, rational design and directed evolution. The powerful and revolutionary techniques so far developed for protein engineering provide excellent opportunities for the design of industrial enzymes with specific properties and production of high-value products at lower production costs. The present review seeks to highlight the major fields of enzyme application and to provide an updated overview on previous protein engineering studies wherein natural enzymes were modified to meet the operational conditions required for industrial application.

Acoustic specifications for the design of jet engine test facilities on an airbase

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

Strumpf, F.M.

1982-01-01

The use of engine run up test arrangements was common in Israeli air-bases since the forties, when engines for the Mustang, Mosquito, Harward and other propellor powered planes were used. The era of jet engine propulsion boosted the noise levels, and the use of fighters with afterburners in the new engines of the 80's brought it up to unbearable levels. Thus, the growth of the Israeli Air Force demanded the use of efficient noise suppression devices. These were divided into engine run-up noise suppressors, and aircraft noise suppessors (Hush Houses). For both of the bove ground arrangements, acoustic specifications hadmore » to be given. They were, as well as design goals for the manufacturers, also needed to restrict noise levels on the air-base as well as its surroundings. The acoustic specifications discussed are based on measured data, and permitted noise levels in the homes on the base being as far as 2500 meters from the engine exhaust silencer. For the special air-base discussed, various criteria were tested, including US Military Specifications, none of which were acceptable, and a special specification was therefore prepared.« less

Translation system engineering in Escherichia coli enhances non-canonical amino acid incorporation into proteins.

PubMed

Gan, Rui; Perez, Jessica G; Carlson, Erik D; Ntai, Ioanna; Isaacs, Farren J; Kelleher, Neil L; Jewett, Michael C

2017-05-01

The ability to site-specifically incorporate non-canonical amino acids (ncAAs) into proteins has made possible the study of protein structure and function in fundamentally new ways, as well as the bio synthesis of unnatural polymers. However, the task of site-specifically incorporating multiple ncAAs into proteins with high purity and yield continues to present a challenge. At the heart of this challenge lies the lower efficiency of engineered orthogonal translation system components compared to their natural counterparts (e.g., translation elements that specifically use a ncAA and do not interact with the cell's natural translation apparatus). Here, we show that evolving and tuning expression levels of multiple components of an engineered translation system together as a whole enhances ncAA incorporation efficiency. Specifically, we increase protein yield when incorporating multiple p-azido-phenylalanine(pAzF) residues into proteins by (i) evolving the Methanocaldococcus jannaschii p-azido-phenylalanyl-tRNA synthetase anti-codon binding domain, (ii) evolving the elongation factor Tu amino acid-binding pocket, and (iii) tuning the expression of evolved translation machinery components in a single vector. Use of the evolved translation machinery in a genomically recoded organism lacking release factor one enabled enhanced multi-site ncAA incorporation into proteins. We anticipate that our approach to orthogonal translation system development will accelerate and expand our ability to site-specifically incorporate multiple ncAAs into proteins and biopolymers, advancing new horizons for synthetic and chemical biotechnology. Biotechnol. Bioeng. 2017;114: 1074-1086. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Space power demonstrator engine, phase 1

NASA Technical Reports Server (NTRS)

1987-01-01

The design, analysis, and preliminary test results for a 25 kWe Free-Piston Stirling engine with integral linear alternators are described. The project is conducted by Mechanical Technology under the direction of LeRC as part of the SP-100 Nuclear Space Power Systems Program. The engine/alternator system is designed to demonstrate the following performance: (1) 25 kWe output at a specific weight less than 8 kg/kW; (2) 25 percent efficiency at a temperature ratio of 2.0; (3) low vibration (amplitude less than .003 in); (4) internal gas bearings (no wear, no external pump); and (5) heater temperature/cooler temperature from 630 to 315 K. The design approach to minimize vibration is a two-module engine (12.5 kWe per module) in a linearly-opposed configuration with a common expansion space. The low specific weight is obtained at high helium pressure (150 bar) and high frequency (105 Hz) and by using high magnetic strength (samarium cobalt) alternator magnets. Engine tests began in June 1985; 16 months following initiation of engine and test cell design. Hydrotest and consequent engine testing to date has been intentionally limited to half pressure, and electrical power output is within 15 to 20 percent of design predictions.

Lower Methow tributaries intensive effectiveness monitoring study. Interim report

USGS Publications Warehouse

Martens, Kyle D.; Connolly, Patrick J.

2008-01-01

Actions have been taken to replace diversion dams in lower Beaver Creek with a series of rock vortex weirs. Some of these diversion dams have been in place for over 100 years, and they have impaired or completely blocked upstream migration of fish. Three diversion dams were replaced in 2003 (Lower Stokes, Thurlow Transfer, and Upper Stokes), and a forth diversion dam was replaced in 2004 (Fort-Thurlow). These vortex weirs were designed and installed under the supervision of U.S. Bureau of Reclamation (BOR) engineers and completed in accordance to National Marine Fisheries Service (NMFS) and Washington Department of Fisheries and Wildlife (WDFW) fish passage criteria. The projects were designed to meet fish species recovery needs described by the Endangered Species Act (ESA) and the “BiOp” issued by NMFS (2000a). Since no specific guidelines have been identified to date specifically addressing diversion dams, WDFW and NMFS guidelines are being considered as the target design and performance criteria for the sites monitored as part of this project. Where used, the vortex weirs were designed to maintain irrigation diversion capabilities while improving fish passage.

Impact of Site Elevation on Mg Smelter Design

NASA Astrophysics Data System (ADS)

Baker, Phillip W.

Site elevation has many surprising and significant impacts on the engineering design of metallurgical plant of all types. Electrolytic magnesium smelters maybe built at high elevation for a variety of reasons including availability of raw material, energy or electric power. Because of the unit processes they typically involve, Mg smelters can be extensively impacted by site elevation. In this paper, generic examples of the design changes required to adapt a smelter originally designed for sea level to operate at 2700 m are presented. While the examples are drawn from a magnesium plant design case, these changes are generically applicable to all industrial plants utilizing similar unit processes irrespective of product.

Engineering High Assurance Distributed Cyber Physical Systems

DTIC Science & Technology

2015-01-15

decisions: number of interacting agents and co-dependent decisions made in real-time without causing interference . To engineer a high assurance DART...environment specification, architecture definition, domain-specific languages, design patterns, code - generation, analysis, test-generation, and simulation...include synchronization between the models and source code , debugging at the model level, expression of the design intent, and quality of service

Rational design of aminoacyl-tRNA synthetase specific for p-acetyl-L-phenylalanine.

PubMed

Sun, Renhua; Zheng, Heng; Fang, Zhengzhi; Yao, Wenbing

2010-01-01

The Methanococcus jannaschii tRNA(Tyr)/tyrosyl-tRNA synthetase pair has been engineered to incorporate unnatural amino acids into proteins in Escherichia coli site-specifically. In order to add other unnatural amino acids into proteins by this approach, the amino acid binding site of M. jannaschii tyrosyl-tRNA synthetase need to be mutated. The crystal structures of M. jannaschii tyrosyl-tRNA synthetase and its mutations were determined, which provided an opportunity to design aminoacyl-tRNA synthetases specific for other unnatural amino acids. In our study, we attempted to design aminoacyl-tRNA synthetases being able to deliver p-acetyl-L-phenylalanine into proteins. p-Acetyl-L-phenylalanine was superimposed on tyrosyl in M. jannaschii tyrosyl-tRNA synthetase-tyrosine complex. Tyr32 needed to be changed to non-polar amino acid with shorter side chain, Val, Leu, Ile, Gly or Ala, in order to reduce steric clash and provide hydrophobic environment to acetyl on p-acetyl-L-phenylalanine. Asp158 and Ile159 would be changed to specific amino acids for the same reason. So we designed 60 aminoacyl-tRNA synthetases. Binding of these aminoacyl-tRNA synthetases with p-acetyl-L-phenylalanine indicated that only 15 of them turned out to be able to bind p-acetyl-L-phenylalanine with reasonable poses. Binding affinity computation proved that the mutation of Tyr32Leu and Asp158Gly benefited p-acetyl-L-phenylalanine binding. And two of the designed aminoacyl-tRNA synthetases had considerable binding affinities. They seemed to be very promising to be able to incorporate p-acetyl-L-phenylalanine into proteins in E. coli. The results show that the combination of homology modeling and molecular docking is a feasible method to filter inappropriate mutations in molecular design and point out beneficial mutations. Copyright 2009 Elsevier Inc. All rights reserved.

Analyzing Web Server Logs to Improve a Site's Usage. The Systems Librarian

ERIC Educational Resources Information Center

Breeding, Marshall

2005-01-01

This column describes ways to streamline and optimize how a Web site works in order to improve both its usability and its visibility. The author explains how to analyze logs and other system data to measure the effectiveness of the Web site design and search engine.

Development and Application of a Systems Engineering Framework to Support Online Course Design and Delivery

ERIC Educational Resources Information Center

Bozkurt, Ipek; Helm, James

2013-01-01

This paper develops a systems engineering-based framework to assist in the design of an online engineering course. Specifically, the purpose of the framework is to provide a structured methodology for the design, development and delivery of a fully online course, either brand new or modified from an existing face-to-face course. The main strength…

Optical design for consumer products

NASA Astrophysics Data System (ADS)

Gupta, Anurag

2014-10-01

Optical engineers often limit their focus on meeting the provided targets on performance and geometry and assume that the specifications are largely non-negotiable. Such approach ignores the value proposition behind the product and the challenges associated with overall product design, manufacturing, business development and legal issues. As a result, the design effort can be expensive, time consuming and can result in product failure. We discuss a product based systems engineering approach that leads to an application specific optical design that is more effective and efficient to implement.

Effects of Engineering Design-Based Science on Elementary School Science Students' Engineering Identity Development across Gender and Grade

NASA Astrophysics Data System (ADS)

Capobianco, Brenda M.; Yu, Ji H.; French, Brian F.

2015-04-01

The integration of engineering concepts and practices into elementary science education has become an emerging concern for science educators and practitioners, alike. Moreover, how children, specifically preadolescents (grades 1-5), engage in engineering design-based learning activities may help science educators and researchers learn more about children's earliest identification with engineering. The purpose of this study was to examine the extent to which engineering identity differed among preadolescents across gender and grade, when exposing students to engineering design-based science learning activities. Five hundred fifty preadolescent participants completed the Engineering Identity Development Scale (EIDS), a recently developed measure with validity evidence that characterizes children's conceptions of engineering and potential career aspirations. Data analyses of variance among four factors (i.e., gender, grade, and group) indicated that elementary school students who engaged in the engineering design-based science learning activities demonstrated greater improvements on the EIDS subscales compared to those in the comparison group. Specifically, students in the lower grade levels showed substantial increases, while students in the higher grade levels showed decreases. Girls, regardless of grade level and participation in the engineering learning activities, showed higher scores in the academic subscale compared to boys. These findings suggest that the integration of engineering practices in the science classroom as early as grade one shows potential in fostering and sustaining student interest, participation, and self-concept in engineering and science.

Engineered Aptamers to Probe Molecular Interactions on the Cell Surface

PubMed Central

Batool, Sana; Bhandari, Sanam; George, Shanell; Okeoma, Precious; Van, Nabeela; Zümrüt, Hazan E.; Mallikaratchy, Prabodhika

2017-01-01

Significant progress has been made in understanding the nature of molecular interactions on the cell membrane. To decipher such interactions, molecular scaffolds can be engineered as a tool to modulate these events as they occur on the cell membrane. To guarantee reliability, scaffolds that function as modulators of cell membrane events must be coupled to a targeting moiety with superior chemical versatility. In this regard, nucleic acid aptamers are a suitable class of targeting moieties. Aptamers are inherently chemical in nature, allowing extensive site-specific chemical modification to engineer sensing molecules. Aptamers can be easily selected using a simple laboratory-based in vitro evolution method enabling the design and development of aptamer-based functional molecular scaffolds against wide range of cell surface molecules. This article reviews the application of aptamers as monitors and modulators of molecular interactions on the mammalian cell surface with the aim of increasing our understanding of cell-surface receptor response to external stimuli. The information gained from these types of studies could eventually prove useful in engineering improved medical diagnostics and therapeutics. PMID:28850067

Genome Integration and Excision by a New Streptomyces Bacteriophage, ϕJoe.

PubMed

Fogg, Paul C M; Haley, Joshua A; Stark, W Marshall; Smith, Margaret C M

2017-03-01

Bacteriophages are the source of many valuable tools for molecular biology and genetic manipulation. In Streptomyces , most DNA cloning vectors are based on serine integrase site-specific DNA recombination systems derived from phage. Because of their efficiency and simplicity, serine integrases are also used for diverse synthetic biology applications. Here, we present the genome of a new Streptomyces phage, ϕJoe, and investigate the conditions for integration and excision of the ϕJoe genome. ϕJoe belongs to the largest Streptomyces phage cluster (R4-like) and encodes a serine integrase. The attB site from Streptomyces venezuelae was used efficiently by an integrating plasmid, pCMF92, constructed using the ϕJoe int-attP locus. The attB site for ϕJoe integrase was occupied in several Streptomyces genomes, including that of S. coelicolor , by a mobile element that varies in gene content and size between host species. Serine integrases require a phage-encoded recombination directionality factor (RDF) to activate the excision reaction. The ϕJoe RDF was identified, and its function was confirmed in vivo Both the integrase and RDF were active in in vitro recombination assays. The ϕJoe site-specific recombination system is likely to be an important addition to the synthetic biology and genome engineering toolbox. IMPORTANCE Streptomyces spp. are prolific producers of secondary metabolites, including many clinically useful antibiotics. Bacteriophage-derived integrases are important tools for genetic engineering, as they enable integration of heterologous DNA into the Streptomyces chromosome with ease and high efficiency. Recently, researchers have been applying phage integrases for a variety of applications in synthetic biology, including rapid assembly of novel combinations of genes, biosensors, and biocomputing. An important requirement for optimal experimental design and predictability when using integrases, however, is the need for multiple enzymes with different specificities for their integration sites. In order to provide a broad platform of integrases, we identified and validated the integrase from a newly isolated Streptomyces phage, ϕJoe. ϕJoe integrase is active in vitro and in vivo The specific recognition site for integration is present in a wide range of different actinobacteria, including Streptomyces venezuelae , an emerging model bacterium in Streptomyces research. Copyright © 2017 Fogg et al.

Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate serine recombinases for the integration of DNA into the human genome

PubMed Central

2013-01-01

Background Phage-encoded serine integrases, such as φC31 integrase, are widely used for genome engineering. Fifteen such integrases have been described but their utility for genome engineering has not been compared in uniform assays. Results We have compared fifteen serine integrases for their utility for DNA manipulations in mammalian cells after first demonstrating that all were functional in E. coli. Chromosomal recombination reporters were used to show that seven integrases were active on chromosomally integrated DNA in human fibroblasts and mouse embryonic stem cells. Five of the remaining eight enzymes were active on extra-chromosomal substrates thereby demonstrating that the ability to mediate extra-chromosomal recombination is no guide to ability to mediate site-specific recombination on integrated DNA. All the integrases that were active on integrated DNA also promoted DNA integration reactions that were not mediated through conservative site-specific recombination or damaged the recombination sites but the extent of these aberrant reactions varied over at least an order of magnitude. Bxb1 integrase yielded approximately two-fold more recombinants and displayed about two fold less damage to the recombination sites than the next best recombinase; φC31 integrase. Conclusions We conclude that the Bxb1 and φC31 integrases are the reagents of choice for genome engineering in vertebrate cells and that DNA damage repair is a major limitation upon the utility of this class of site-specific recombinase. PMID:24139482

Rapid and highly efficient construction of TALE-based transcriptional regulators and nucleases for genome modification.

PubMed

Li, Lixin; Piatek, Marek J; Atef, Ahmed; Piatek, Agnieszka; Wibowo, Anjar; Fang, Xiaoyun; Sabir, J S M; Zhu, Jian-Kang; Mahfouz, Magdy M

2012-03-01

Transcription activator-like effectors (TALEs) can be used as DNA-targeting modules by engineering their repeat domains to dictate user-selected sequence specificity. TALEs have been shown to function as site-specific transcriptional activators in a variety of cell types and organisms. TALE nucleases (TALENs), generated by fusing the FokI cleavage domain to TALE, have been used to create genomic double-strand breaks. The identity of the TALE repeat variable di-residues, their number, and their order dictate the DNA sequence specificity. Because TALE repeats are nearly identical, their assembly by cloning or even by synthesis is challenging and time consuming. Here, we report the development and use of a rapid and straightforward approach for the construction of designer TALE (dTALE) activators and nucleases with user-selected DNA target specificity. Using our plasmid set of 100 repeat modules, researchers can assemble repeat domains for any 14-nucleotide target sequence in one sequential restriction-ligation cloning step and in only 24 h. We generated several custom dTALEs and dTALENs with new target sequence specificities and validated their function by transient expression in tobacco leaves and in vitro DNA cleavage assays, respectively. Moreover, we developed a web tool, called idTALE, to facilitate the design of dTALENs and the identification of their genomic targets and potential off-targets in the genomes of several model species. Our dTALE repeat assembly approach along with the web tool idTALE will expedite genome-engineering applications in a variety of cell types and organisms including plants.

7 CFR 1726.404 - Non-site specific construction contract closeout.

Code of Federal Regulations, 2014 CFR

2014-01-01

... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Contract... equipment is supplied under a construction contract, the borrower (acting through its engineer, if... equipment. The borrower (acting through its engineer, if applicable) will schedule such inspection and...

7 CFR 1726.404 - Non-site specific construction contract closeout.

Code of Federal Regulations, 2010 CFR

2010-01-01

... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Contract... equipment is supplied under a construction contract, the borrower (acting through its engineer, if... equipment. The borrower (acting through its engineer, if applicable) will schedule such inspection and...

7 CFR 1726.404 - Non-site specific construction contract closeout.

Code of Federal Regulations, 2011 CFR

2011-01-01

... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Contract... equipment is supplied under a construction contract, the borrower (acting through its engineer, if... equipment. The borrower (acting through its engineer, if applicable) will schedule such inspection and...

7 CFR 1726.404 - Non-site specific construction contract closeout.

Code of Federal Regulations, 2012 CFR

2012-01-01

... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Contract... equipment is supplied under a construction contract, the borrower (acting through its engineer, if... equipment. The borrower (acting through its engineer, if applicable) will schedule such inspection and...

7 CFR 1726.404 - Non-site specific construction contract closeout.

Code of Federal Regulations, 2013 CFR

2013-01-01

... UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Contract... equipment is supplied under a construction contract, the borrower (acting through its engineer, if... equipment. The borrower (acting through its engineer, if applicable) will schedule such inspection and...

40 CFR 300.810 - Contents of the administrative record file.

Code of Federal Regulations, 2013 CFR

2013-07-01

... determination of imminent and substantial endangerment, public health evaluations, and technical and engineering... and appropriate requirements, guidance on risk/exposure assessments, engineering handbooks, articles from technical journals, memoranda on the application of a specific regulation to a site, and memoranda...

40 CFR 300.810 - Contents of the administrative record file.

Code of Federal Regulations, 2012 CFR

2012-07-01

... determination of imminent and substantial endangerment, public health evaluations, and technical and engineering... and appropriate requirements, guidance on risk/exposure assessments, engineering handbooks, articles from technical journals, memoranda on the application of a specific regulation to a site, and memoranda...

40 CFR 300.810 - Contents of the administrative record file.

Code of Federal Regulations, 2011 CFR

2011-07-01

... determination of imminent and substantial endangerment, public health evaluations, and technical and engineering... and appropriate requirements, guidance on risk/exposure assessments, engineering handbooks, articles from technical journals, memoranda on the application of a specific regulation to a site, and memoranda...

40 CFR 300.810 - Contents of the administrative record file.

Code of Federal Regulations, 2014 CFR

2014-07-01

... determination of imminent and substantial endangerment, public health evaluations, and technical and engineering... and appropriate requirements, guidance on risk/exposure assessments, engineering handbooks, articles from technical journals, memoranda on the application of a specific regulation to a site, and memoranda...

40 CFR 1039.205 - What must I include in my application?

Code of Federal Regulations, 2014 CFR

2014-07-01

... engine family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1039.205 - What must I include in my application?

Code of Federal Regulations, 2010 CFR

2010-07-01

... engine family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1039.205 - What must I include in my application?

Code of Federal Regulations, 2013 CFR

2013-07-01

... engine family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1039.205 - What must I include in my application?

Code of Federal Regulations, 2012 CFR

2012-07-01

... engine family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1039.205 - What must I include in my application?

Code of Federal Regulations, 2011 CFR

2011-07-01

... engine family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

United States Air Force 611th Civil Engineer Squadron, Elmendorf AFB, Alaska. Final engineering evaluation/cost analysis: Petroleum, oil, and lubricants area, Galena Airport, Alaska

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

NONE

1996-02-05

This decision document presents the selected removal action for the Installation Restoration Program (IRP) site ST005, otherwise known as the POL Tank Farm, at Galena Airport, Alaska. This decision is based on the administrative record for this site, specifically the draft Remedial Investigation Report (March 1995) and the Treatability Study Report (January 1995) (PB95-225314). The information from these documents is summarized, along with an analysis of potential removal action alternatives in the Engineering Evaluation/Cost Analysis (EE/CA).

Genome engineering in cattle: recent technological advancements.

PubMed

Wang, Zhongde

2015-02-01

Great strides in technological advancements have been made in the past decade in cattle genome engineering. First, the success of cloning cattle by somatic cell nuclear transfer (SCNT) or chromatin transfer (CT) is a significant advancement that has made obsolete the need for using embryonic stem (ES) cells to conduct cell-mediated genome engineering, whereby site-specific genetic modifications can be conducted in bovine somatic cells via DNA homologous recombination (HR) and whereby genetically engineered cattle can subsequently be produced by animal cloning from the genetically modified cells. With this approach, a chosen bovine genomic locus can be precisely modified in somatic cells, such as to knock out (KO) or knock in (KI) a gene via HR, a gene-targeting strategy that had almost exclusively been used in mouse ES cells. Furthermore, by the creative application of embryonic cloning to rejuvenate somatic cells, cattle genome can be sequentially modified in the same line of somatic cells and complex genetic modifications have been achieved in cattle. Very recently, the development of designer nucleases-such as zinc finger nucleases (ZFNs) and transcription activator-like effector nuclease (TALENs), and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-has enabled highly efficient and more facile genome engineering in cattle. Most notably, by employing such designer nucleases, genomes can be engineered at single-nucleotide precision; this process is now often referred to as genome or gene editing. The above achievements are a drastic departure from the traditional methods of creating genetically modified cattle, where foreign DNAs are randomly integrated into the animal genome, most often along with the integrations of bacterial or viral DNAs. Here, I review the most recent technological developments in cattle genome engineering by highlighting some of the major achievements in creating genetically engineered cattle for agricultural and biomedical applications.

47 CFR 27.1164 - The cost-sharing formula.

Code of Federal Regulations, 2010 CFR

2010-10-01

... control equipment; engineering costs (design/path survey); installation; systems testing; FCC filing costs; site acquisition and civil works; zoning costs; training; disposal of old equipment; test equipment... a replacement system, such as equipment and engineering expenses. C may not exceed $250,000 per...

Lightweight diesel engine designs for commuter type aircraft

NASA Technical Reports Server (NTRS)

Brouwers, A. P.

1981-01-01

Conceptual designs and performance of advanced technology lightweight diesel engines, suitable for commuter type aircraft power plants are defined. Two engines are discussed, a 1491 kW (2000 SHP) eight-cylinder engine and a 895 kW (1200 SHP) six-cylinder engine. High performance and related advanced technologies are proposed such as insulated cylinders, very high injection pressures and high compressor and turbine efficiencies. The description of each engine includes concept drawings, a performance analysis, and weight data. Fuel flow data are given for full and partial power up to 7620m altitude. The performance data are also extrapolated over a power range from 671 kW(900SHP) to 1864 kW (2500 SHP). The specific fuel consumption of the 1491 kW (2000 SHP) engine is 182 g/hWh (.299 lb/HPh) at cruise altitude, its weight 620 kg (1365 lb.) and specific weight .415 kg/kW (.683 lb/HP). The specific fuel consumption of the 895 kW (1200 SHP) engine is 187 g/hWh (.308 lb/HPh) at cruise altitude, its weight 465 kg (1025 lb.) and specific weight .520 kg/kW (.854 lb/HP).

A portable bioelectronic sensing system (BESSY) for environmental deployment incorporating differential microbial sensing in miniaturized reactors

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

Zhou, Alyssa Y.; Baruch, Moshe; Ajo-Franklin, Caroline M.

Current technologies are lacking in the area of deployable, in situ monitoring of complex chemicals in environmental applications. Microorganisms metabolize various chemical compounds and can be engineered to be analyte-specific making them naturally suited for robust chemical sensing. But, current electrochemical microbial biosensors use large and expensive electrochemistry equipment not suitable for on-site, real-time environmental analysis. We demonstrate a miniaturized, autonomous bioelectronic sensing system (BESSY) suitable for deployment for instantaneous and continuous sensing applications. We developed a 2x2 cm footprint, low power, two-channel, three-electrode electrochemical potentiostat which wirelessly transmits data for on-site microbial sensing. Furthermore, we designed a new waymore » of fabricating self-contained, submersible, miniaturized reactors (m-reactors) to encapsulate the bacteria, working, and counter electrodes. We have validated the BESSY’s ability to specifically detect a chemical amongst environmental perturbations using differential current measurements. This work paves the way for in situ microbial sensing outside of a controlled laboratory environment.« less

A portable bioelectronic sensing system (BESSY) for environmental deployment incorporating differential microbial sensing in miniaturized reactors

DOE PAGES

Zhou, Alyssa Y.; Baruch, Moshe; Ajo-Franklin, Caroline M.; ...

2017-09-15

Current technologies are lacking in the area of deployable, in situ monitoring of complex chemicals in environmental applications. Microorganisms metabolize various chemical compounds and can be engineered to be analyte-specific making them naturally suited for robust chemical sensing. But, current electrochemical microbial biosensors use large and expensive electrochemistry equipment not suitable for on-site, real-time environmental analysis. We demonstrate a miniaturized, autonomous bioelectronic sensing system (BESSY) suitable for deployment for instantaneous and continuous sensing applications. We developed a 2x2 cm footprint, low power, two-channel, three-electrode electrochemical potentiostat which wirelessly transmits data for on-site microbial sensing. Furthermore, we designed a new waymore » of fabricating self-contained, submersible, miniaturized reactors (m-reactors) to encapsulate the bacteria, working, and counter electrodes. We have validated the BESSY’s ability to specifically detect a chemical amongst environmental perturbations using differential current measurements. This work paves the way for in situ microbial sensing outside of a controlled laboratory environment.« less

Resource Quantity and Quality Determine the Inter-Specific Associations between Ecosystem Engineers and Resource Users in a Cavity-Nest Web

PubMed Central

Robles, Hugo; Martin, Kathy

2013-01-01

While ecosystem engineering is a widespread structural force of ecological communities, the mechanisms underlying the inter-specific associations between ecosystem engineers and resource users are poorly understood. A proper knowledge of these mechanisms is, however, essential to understand how communities are structured. Previous studies suggest that increasing the quantity of resources provided by ecosystem engineers enhances populations of resource users. In a long-term study (1995-2011), we show that the quality of the resources (i.e. tree cavities) provided by ecosystem engineers is also a key feature that explains the inter-specific associations in a tree cavity-nest web. Red-naped sapsuckers ( Sphyrapicus nuchalis ) provided the most abundant cavities (52% of cavities, 0.49 cavities/ha). These cavities were less likely to be used than other cavity types by mountain bluebirds ( Sialia currucoides ), but provided numerous nest-sites (41% of nesting cavities) to tree swallows ( Tachycineta bicolour ). Swallows experienced low reproductive outputs in northern flicker ( Colaptes auratus ) cavities compared to those in sapsucker cavities (1.1 vs. 2.1 fledglings/nest), but the highly abundant flickers (33% of cavities, 0.25 cavities/ha) provided numerous suitable nest-sites for bluebirds (58%). The relative shortage of cavities supplied by hairy woodpeckers ( Picoides villosus ) and fungal/insect decay (<10% of cavities each, <0.09 cavities/ha) provided fewer breeding opportunities (<15% of nests), but represented high quality nest-sites for both bluebirds and swallows. Because both the quantity and quality of resources supplied by different ecosystem engineers may explain the amount of resources used by each resource user, conservation strategies may require different management actions to be implemented for the key ecosystem engineer of each resource user. We, therefore, urge the incorporation of both resource quantity and quality into models that assess community dynamics to improve conservation actions and our understanding of ecological communities based on ecosystem engineering. PMID:24040324

Resource quantity and quality determine the inter-specific associations between ecosystem engineers and resource users in a cavity-nest web.

PubMed

Robles, Hugo; Martin, Kathy

2013-01-01

While ecosystem engineering is a widespread structural force of ecological communities, the mechanisms underlying the inter-specific associations between ecosystem engineers and resource users are poorly understood. A proper knowledge of these mechanisms is, however, essential to understand how communities are structured. Previous studies suggest that increasing the quantity of resources provided by ecosystem engineers enhances populations of resource users. In a long-term study (1995-2011), we show that the quality of the resources (i.e. tree cavities) provided by ecosystem engineers is also a key feature that explains the inter-specific associations in a tree cavity-nest web. Red-naped sapsuckers (Sphyrapicusnuchalis) provided the most abundant cavities (52% of cavities, 0.49 cavities/ha). These cavities were less likely to be used than other cavity types by mountain bluebirds (Sialiacurrucoides), but provided numerous nest-sites (41% of nesting cavities) to tree swallows (Tachycinetabicolour). Swallows experienced low reproductive outputs in northern flicker (Colaptesauratus) cavities compared to those in sapsucker cavities (1.1 vs. 2.1 fledglings/nest), but the highly abundant flickers (33% of cavities, 0.25 cavities/ha) provided numerous suitable nest-sites for bluebirds (58%). The relative shortage of cavities supplied by hairy woodpeckers (Picoidesvillosus) and fungal/insect decay (<10% of cavities each, <0.09 cavities/ha) provided fewer breeding opportunities (<15% of nests), but represented high quality nest-sites for both bluebirds and swallows. Because both the quantity and quality of resources supplied by different ecosystem engineers may explain the amount of resources used by each resource user, conservation strategies may require different management actions to be implemented for the key ecosystem engineer of each resource user. We, therefore, urge the incorporation of both resource quantity and quality into models that assess community dynamics to improve conservation actions and our understanding of ecological communities based on ecosystem engineering.

Improving design phase evaluations for high pile rebound sites : final report.

DOT National Transportation Integrated Search

2016-05-31

A testing program performed to help determine typical soils properties encountered during pile installation when high rebound : occurs produced a decision matrix for geotechnical engineers. High pile rebound (HPR) occurred at numerous sites in Florid...

Propulsion system performance resulting from an integrated flight/propulsion control design

NASA Technical Reports Server (NTRS)

Mattern, Duane; Garg, Sanjay

1992-01-01

Propulsion-system-specific results are presented from the application of the integrated methodology for propulsion and airframe control (IMPAC) design approach to integrated flight/propulsion control design for a 'short takeoff and vertical landing' (STOVL) aircraft in transition flight. The IMPAC method is briefly discussed and the propulsion system specifications for the integrated control design are examined. The structure of a linear engine controller that results from partitioning a linear centralized controller is discussed. The details of a nonlinear propulsion control system are presented, including a scheme to protect the engine operational limits: the fan surge margin and the acceleration/deceleration schedule that limits the fuel flow. Also, a simple but effective multivariable integrator windup protection scheme is examined. Nonlinear closed-loop simulation results are presented for two typical pilot commands for transition flight: acceleration while maintaining flightpath angle and a change in flightpath angle while maintaining airspeed. The simulation nonlinearities include the airframe/engine coupling, the actuator and sensor dynamics and limits, the protection scheme for the engine operational limits, and the integrator windup protection. Satisfactory performance of the total airframe plus engine system for transition flight, as defined by the specifications, was maintained during the limit operation of the closed-loop engine subsystem.

Photographic copy of original design drawing, dated January 1970, revised ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Photographic copy of original design drawing, dated January 1970, revised 12 March 1971 (original Army Operational Drawing in the possession of U.S. Army Corps of Engineers, Huntsville, Division). MSRPP interior elevations, corridors #216, upper and lower levels - Stanely R. Mickelsen Safeguard Complex, Missile Site Radar Power Plant, Southeast of, & adjacent to, Missile Site Control Building, Nekoma, Cavalier County, ND

How field monitoring of green infrastructure stormwater practices has led to changes in North Carolina's Stormwater BMP design manual

NASA Astrophysics Data System (ADS)

Hunt, W. F.; Winston, R. J.

2011-12-01

Green Infrastructure stormwater management is comprised of many biologically-based stormwater treatment practices. Two of which, bioretention and level spreader- vegetative filter strips, have been extensively studied at over 10 different field locations across North Carolina by NC State University. The result of this research has been dramatic changes to the state of North Carolina's stormwater BMP Design Manual, which now allows a greater amount of flexibility for the design of each practice than most other design manuals. The purpose of this presentation is to present a summary of research conducted in North Carolina and associate that research with specific changes made in the state's design guidance for both bioretention (Table 1) and level spreader- vegetated filter strip systems (Table 2). Among the changes are type of vegetation, ratio of hydraulic loading, underdrainage configuration, and fill media selection. References (in print) associated with the tables are listed below: Hathaway, J.M. and W.F. Hunt. 2008. Field Evaluation of Level Spreaders in the Piedmont of North Carolina. Journal of Irrigation and Drainage Engineering, 134(4):538-542. Hunt, W.F., A.R. Jarrett, J.T. Smith, L.J. Sharkey. 2006. Evaluating Bioretention Hydrology and Nutrient Removal at Three Field Sites in North Carolina. Journal of Irrigation and Drainage Engineering, 132 (6): 600-608. Hunt, W.F., J.M. Hathaway, R.J. Winston, and S.J. Jadlocki. 2010. Runoff Volume Reduction by a Level Spreader - Vegetated Filter Strip System in Suburban Charlotte, NC. Journal of Hydrologic Engineering, 15(6): 399-503. Jones, M.P. and W.F. Hunt. 2009. Bioretention Impact on Runoff Temperature in Trout Sensitive Waters. Journal of Environmental Engineering, 135(8): 577-585. Li, H., L.J. Sharkey, W.F. Hunt, A.P. Davis. 2009. Mitigation of Impervious Surface Hydrology using Bioretention in North Carolina and Maryland. Journal of Hydrologic Engineering, 14(4): 407-415. Line, D.E. and W.F. Hunt. 2009. Performance of a Bioretention Area and a Level Spreader-Grass Filter Strip at Two Highway Sites in North Carolina. Journal of Irrigation and Drainage Engineering, 135(2): 217-224. Passeport, E., W.F. Hunt, D.E. Line, R.A. Smith, and R.A. Brown. 2009. Field Study of the Ability of Two Grassed Bioretention Cells to Reduce Stormwater Runoff Pollution. Journal of Irrigation and Drainage Engineering, 135(4): 505-510. Winston, R.J., W.F. Hunt, D.L. Osmond, W.G. Lord, and M.D. Woodward. 2011. Field Evaluation of Four Level Spreader - Vegetative Filter Strips to Improve Urban Stormwater Quality. Journal of Irrigation and Drainage Engineering. 137(3): 170-182.
Table 1 - Research-Based Design Changes for Bioretention in North Carolina Table 2 - Level Spreader - Vegetated Filter Strip Design Evolution in North Carolina

Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5.

PubMed

Azoitei, M L; Ban, Y A; Kalyuzhny, O; Guenaga, J; Schroeter, A; Porter, J; Wyatt, R; Schief, William R

2014-10-01

Rational design of proteins with novel binding specificities and increased affinity is one of the major goals of computational protein design. Epitope-scaffolds are a new class of antigens engineered by transplanting viral epitopes of predefined structure to protein scaffolds, or by building protein scaffolds around such epitopes. Epitope-scaffolds are of interest as vaccine components to attempt to elicit neutralizing antibodies targeting the specified epitope. In this study we developed a new computational protocol, MultiGraft Interface, that transplants epitopes but also designs additional scaffold features outside the epitope to enhance antibody-binding specificity and potentially influence the specificity of elicited antibodies. We employed MultiGraft Interface to engineer novel epitope-scaffolds that display the known epitope of human immunodeficiency virus 1 (HIV-1) neutralizing antibody 2F5 and that also interact with the functionally important CDR H3 antibody loop. MultiGraft Interface generated an epitope-scaffold that bound 2F5 with subnanomolar affinity (K(D) = 400 pM) and that interacted with the antibody CDR H3 loop through computationally designed contacts. Substantial structural modifications were necessary to engineer this antigen, with the 2F5 epitope replacing a helix in the native scaffold and with 15% of the native scaffold sequence being modified in the design stage. This epitope-scaffold represents a successful example of rational protein backbone engineering and protein-protein interface design and could prove useful in the field of HIV vaccine design. MultiGraft Interface can be generally applied to engineer novel binding partners with altered specificity and optimized affinity. © 2014 Wiley Periodicals, Inc.

Can enzyme engineering benefit from the modulation of protein motions? Lessons learned from NMR relaxation dispersion experiments.

PubMed

Doucet, Nicolas

2011-04-01

Despite impressive progress in protein engineering and design, our ability to create new and efficient enzyme activities remains a laborious and time-consuming endeavor. In the past few years, intricate combinations of rational mutagenesis, directed evolution and computational methods have paved the way to exciting engineering examples and are now offering a new perspective on the structural requirements of enzyme activity. However, these structure-function analyses are usually guided by the time-averaged static models offered by enzyme crystal structures, which often fail to describe the functionally relevant 'invisible states' adopted by proteins in space and time. To alleviate such limitations, NMR relaxation dispersion experiments coupled to mutagenesis studies have recently been applied to the study of enzyme catalysis, effectively complementing 'structure-function' analyses with 'flexibility-function' investigations. In addition to offering quantitative, site-specific information to help characterize residue motion, these NMR methods are now being applied to enzyme engineering purposes, providing a powerful tool to help characterize the effects of controlling long-range networks of flexible residues affecting enzyme function. Recent advancements in this emerging field are presented here, with particular attention to mutagenesis reports highlighting the relevance of NMR relaxation dispersion tools in enzyme engineering.

Evolutionary and biological metaphors for engineering design

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

Jakiela, M.

1994-12-31

Since computing became generally available, there has been strong interest in using computers to assist and automate engineering design processes. Specifically, for design optimization and automation, nonlinear programming and artificial intelligence techniques have been extensively studied. New computational techniques, based upon the natural processes of evolution, adaptation, and learing, are showing promise because of their generality and robustness. This presentation will describe the use of two such techniques, genetic algorithms and classifier systems, for a variety of engineering design problems. Structural topology optimization, meshing, and general engineering optimization are shown as example applications.

Tool for Turbine Engine Closed-Loop Transient Analysis (TTECTrA) Users' Guide

NASA Technical Reports Server (NTRS)

Csank, Jeffrey T.; Zinnecker, Alicia M.

2014-01-01

The tool for turbine engine closed-loop transient analysis (TTECTrA) is a semi-automated control design tool for subsonic aircraft engine simulations. At a specific flight condition, TTECTrA produces a basic controller designed to meet user-defined goals and containing only the fundamental limiters that affect the transient performance of the engine. The purpose of this tool is to provide the user a preliminary estimate of the transient performance of an engine model without the need to design a full nonlinear controller.

Simulation Data Management - Requirements and Design Specification

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

Clay, Robert L.; Friedman-Hill, Ernest J.; Gibson, Marcus J.

Simulation Data Management (SDM), the ability to securely organize, archive, and share analysis models and the artifacts used to create them, is a fundamental requirement for modern engineering analysis based on computational simulation. We have worked separately to provide secure, network SDM services to engineers and scientists at our respective laboratories for over a decade. We propose to leverage our experience and lessons learned to help develop and deploy a next-generation SDM service as part of a multi-laboratory team. This service will be portable across multiple sites and platforms, and will be accessible via a range of command-line tools andmore » well-documented APIs. In this document, we’ll review our high-level and low-level requirements for such a system, review one existing system, and briefly discuss our proposed implementation.« less

46 CFR 162.050-25 - Cargo monitor: Design specification.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Cargo monitor: Design specification. 162.050-25 Section 162.050-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Pollution Prevention Equipment § 162.050-25 Cargo monitor: Design specification. (...

46 CFR 162.050-21 - Separator: Design specification.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 6 2014-10-01 2014-10-01 false Separator: Design specification. 162.050-21 Section 162.050-21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Pollution Prevention Equipment § 162.050-21 Separator: Design specification. (a) A...

46 CFR 162.050-25 - Cargo monitor: Design specification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Cargo monitor: Design specification. 162.050-25 Section 162.050-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Pollution Prevention Equipment § 162.050-25 Cargo monitor: Design specification. (...

46 CFR 162.050-21 - Separator: Design specification.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 6 2013-10-01 2013-10-01 false Separator: Design specification. 162.050-21 Section 162.050-21 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Pollution Prevention Equipment § 162.050-21 Separator: Design specification. (a) A...

UAF Space Systems Engineering Program: Engaging Students through an Apprenticeship Model

NASA Astrophysics Data System (ADS)

Thorsen, D.

2017-12-01

Learning by doing has been the mantra of engineering education for decades, however, the constraints of semester length courses limits the types and size of experiences that can be offered to students. The Space Systems Engineering Program (SSEP) at the University of Alaska Fairbanks provides interdisciplinary engineering and science students with hands-on experience in all aspects of space systems engineering through a design, build, launch paradigm applied to balloon and rocket payloads and small satellites. The program is structured using an apprenticeship model such that students, freshmen through graduate, can participate in multi-year projects thereby gaining experiences appropriate to their level in college. Students enter the lab in a trainee position and receive training on lab processes and design software. Depending on the student's interests they learn how to use specific lab equipment and software design tools. Trainees provide support engineering under guidance of an upper classman. As the students' progress in their degree program and gain more expertise, they typically become part of a specific subsystem team, where they receive additional training in developing design documents and in writing requirements and test documents, and direct their efforts to meeting specific objectives. By the time the student reaches their senior year, they have acquired the leadership role for a specific subsystem and/or a general leadership role in the lab. If students stay to pursue graduate degrees, they assume the responsibility of training and mentoring other undergraduates in their areas of expertise. Throughout the program upper class students mentor the newer students. The Space Systems Engineering Program strives to reinforce a student's degree program through these large scale projects that place engineering in context.

Structure-Energy Relationships of Halogen Bonds in Proteins.

PubMed

Scholfield, Matthew R; Ford, Melissa Coates; Carlsson, Anna-Carin C; Butta, Hawera; Mehl, Ryan A; Ho, P Shing

2017-06-06

The structures and stabilities of proteins are defined by a series of weak noncovalent electrostatic, van der Waals, and hydrogen bond (HB) interactions. In this study, we have designed and engineered halogen bonds (XBs) site-specifically to study their structure-energy relationship in a model protein, T4 lysozyme. The evidence for XBs is the displacement of the aromatic side chain toward an oxygen acceptor, at distances that are equal to or less than the sums of their respective van der Waals radii, when the hydroxyl substituent of the wild-type tyrosine is replaced by a halogen. In addition, thermal melting studies show that the iodine XB rescues the stabilization energy from an otherwise destabilizing substitution (at an equivalent noninteracting site), indicating that the interaction is also present in solution. Quantum chemical calculations show that the XB complements an HB at this site and that solvent structure must also be considered in trying to design molecular interactions such as XBs into biological systems. A bromine substitution also shows displacement of the side chain, but the distances and geometries do not indicate formation of an XB. Thus, we have dissected the contributions from various noncovalent interactions of halogens introduced into proteins, to drive the application of XBs, particularly in biomolecular design.

Design Standards for Engineered Tissues

PubMed Central

Nawroth, Janna C.; Parker, Kevin Kit

2013-01-01

Traditional technologies are required to meet specific, quantitative standards of safety and performance. In tissue engineering, similar standards will have to be developed to enable routine clinical use and customized tissue fabrication. In this essay, we discuss a framework of concepts leading towards general design standards for tissue-engineering, focusing in particular on systematic design strategies, control of cell behavior, physiological scaling, fabrication modes and functional evaluation. PMID:23267860

Design of the Curriculum for a Second-Cycle Course in Civil Engineering in the Context of the Bologna Framework

ERIC Educational Resources Information Center

Gavin, K. G.

2010-01-01

This paper describes the design of the curriculum for a Master of Engineering programme in civil engineering at University College Dublin. The revised programme was established to meet the requirements of the Bologna process and this paper specifically considers the design of a new, second-cycle master's component of the programme. In addition to…

Assessment Engineering Task Model Maps, Task Models and Templates as a New Way to Develop and Implement Test Specifications

ERIC Educational Resources Information Center

Luecht, Richard M.

2013-01-01

Assessment engineering is a new way to design and implement scalable, sustainable and ideally lower-cost solutions to the complexities of designing and developing tests. It represents a merger of sorts between cognitive task modeling and engineering design principles--a merger that requires some new thinking about the nature of score scales, item…

Bioremediation 3.0: Engineering pollutant-removing bacteria in the times of systemic biology.

PubMed

Dvořák, Pavel; Nikel, Pablo I; Damborský, Jiří; de Lorenzo, Víctor

2017-11-15

Elimination or mitigation of the toxic effects of chemical waste released to the environment by industrial and urban activities relies largely on the catalytic activities of microorganisms-specifically bacteria. Given their capacity to evolve rapidly, they have the biochemical power to tackle a large number of molecules mobilized from their geological repositories through human action (e.g., hydrocarbons, heavy metals) or generated through chemical synthesis (e.g., xenobiotic compounds). Whereas naturally occurring microbes already have considerable ability to remove many environmental pollutants with no external intervention, the onset of genetic engineering in the 1980s allowed the possibility of rational design of bacteria to catabolize specific compounds, which could eventually be released into the environment as bioremediation agents. The complexity of this endeavour and the lack of fundamental knowledge nonetheless led to the virtual abandonment of such a recombinant DNA-based bioremediation only a decade later. In a twist of events, the last few years have witnessed the emergence of new systemic fields (including systems and synthetic biology, and metabolic engineering) that allow revisiting the same environmental pollution challenges through fresh and far more powerful approaches. The focus on contaminated sites and chemicals has been broadened by the phenomenal problems of anthropogenic emissions of greenhouse gases and the accumulation of plastic waste on a global scale. In this article, we analyze how contemporary systemic biology is helping to take the design of bioremediation agents back to the core of environmental biotechnology. We inspect a number of recent strategies for catabolic pathway construction and optimization and we bring them together by proposing an engineering workflow. Copyright © 2017 Elsevier Inc. All rights reserved.

40 CFR 1039.140 - What is my engine's maximum engine power?

Code of Federal Regulations, 2014 CFR

2014-07-01

...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES... 1065, based on the manufacturer's design and production specifications for the engine. This information... power values for an engine are based on maximum engine power. For example, the group of engines with...

40 CFR 1039.140 - What is my engine's maximum engine power?

Code of Federal Regulations, 2011 CFR

2011-07-01

...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES... 1065, based on the manufacturer's design and production specifications for the engine. This information... power values for an engine are based on maximum engine power. For example, the group of engines with...

40 CFR 1039.140 - What is my engine's maximum engine power?

Code of Federal Regulations, 2010 CFR

2010-07-01

...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES... 1065, based on the manufacturer's design and production specifications for the engine. This information... power values for an engine are based on maximum engine power. For example, the group of engines with...

40 CFR 1039.140 - What is my engine's maximum engine power?

Code of Federal Regulations, 2012 CFR

2012-07-01

...) AIR POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW AND IN-USE NONROAD COMPRESSION-IGNITION ENGINES... 1065, based on the manufacturer's design and production specifications for the engine. This information... power values for an engine are based on maximum engine power. For example, the group of engines with...

Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen Receptor to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1α-secreting Glioblastoma.

PubMed

Müller, Nadja; Michen, Susanne; Tietze, Stefanie; Töpfer, Katrin; Schulte, Alexander; Lamszus, Katrin; Schmitz, Marc; Schackert, Gabriele; Pastan, Ira; Temme, Achim

2015-06-01

Natural killer (NK) cells are promising effector cells for adjuvant immunotherapy of cancer. So far, several preclinical studies have shown the feasibility of gene-engineered NK cells, which upon expression of chimeric antigen receptors (CARs) are redirected to otherwise NK cell-resistant tumors. Yet, we reasoned that the efficiency of an immunotherapy using CAR-modified NK cells critically relies on efficient migration to the tumor site and might be improved by the engraftment of a receptor specific for a chemokine released by the tumor. On the basis of the DNAX-activation protein 12 (DAP12), a signaling adapter molecule involved in signal transduction of activating NK cell receptors, we constructed an epidermal growth factor variant III (EGFRvIII)-CAR, designated MR1.1-DAP12 which confers specific cytotoxicity of NK cell towards EGFRvIII glioblastoma cells in vitro and to established subcutaneous U87-MG tumor xenografts. So far, infusion of NK cells with expression of MR1.1-DAP12 caused a moderate but significantly delayed tumor growth and increased median survival time when compared with NK cells transduced with an ITAM-defective CAR. Notably, the further genetic engineering of these EGFRvIII-specific NK cells with the chemokine receptor CXCR4 conferred a specific chemotaxis to CXCL12/SDF-1α secreting U87-MG glioblastoma cells. Moreover, the administration of such NK cells resulted in complete tumor remission in a number of mice and a significantly increased survival when compared with the treatment of xenografts with NK cells expressing only the EGFRvIII-specific CAR or mock control. We conclude that chemokine receptor-engineered NK cells with concomitant expression of a tumor-specific CAR are a promising tool to improve adoptive tumor immunotherapy.

48 CFR 36.601-4 - Implementation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... engineering nature associated with design or construction of real property. (3) Other professional services of..., investigations, surveying and mapping, tests, evaluations, consultations, comprehensive planning, program management, conceptual designs, plans and specifications, value engineering, construction phase services...

48 CFR 36.601-4 - Implementation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... engineering nature associated with design or construction of real property. (3) Other professional services of..., investigations, surveying and mapping, tests, evaluations, consultations, comprehensive planning, program management, conceptual designs, plans and specifications, value engineering, construction phase services...

48 CFR 36.601-4 - Implementation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... engineering nature associated with design or construction of real property. (3) Other professional services of..., investigations, surveying and mapping, tests, evaluations, consultations, comprehensive planning, program management, conceptual designs, plans and specifications, value engineering, construction phase services...

48 CFR 36.601-4 - Implementation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... engineering nature associated with design or construction of real property. (3) Other professional services of..., investigations, surveying and mapping, tests, evaluations, consultations, comprehensive planning, program management, conceptual designs, plans and specifications, value engineering, construction phase services...

48 CFR 36.601-4 - Implementation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... engineering nature associated with design or construction of real property. (3) Other professional services of..., investigations, surveying and mapping, tests, evaluations, consultations, comprehensive planning, program management, conceptual designs, plans and specifications, value engineering, construction phase services...

40 CFR 1068.110 - What other provisions apply to engines/equipment in service?

Code of Federal Regulations, 2013 CFR

2013-07-01

... information regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies. It is a violation of the Clean Air Act for anyone to make...

40 CFR 1068.110 - What other provisions apply to engines/equipment in service?

Code of Federal Regulations, 2014 CFR

2014-07-01

... information regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies. It is a violation of the Clean Air Act for anyone to make...

40 CFR 1068.110 - What other provisions apply to engines/equipment in service?

Code of Federal Regulations, 2012 CFR

2012-07-01

... information regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies. It is a violation of the Clean Air Act for anyone to make...

Advanced engineering environment collaboration project.

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

Lamph, Jane Ann; Pomplun, Alan R.; Kiba, Grant W.

2008-12-01

The Advanced Engineering Environment (AEE) is a model for an engineering design and communications system that will enhance project collaboration throughout the nuclear weapons complex (NWC). Sandia National Laboratories and Parametric Technology Corporation (PTC) worked together on a prototype project to evaluate the suitability of a portion of PTC's Windchill 9.0 suite of data management, design and collaboration tools as the basis for an AEE. The AEE project team implemented Windchill 9.0 development servers in both classified and unclassified domains and used them to test and evaluate the Windchill tool suite relative to the needs of the NWC using weaponsmore » project use cases. A primary deliverable was the development of a new real time collaborative desktop design and engineering process using PDMLink (data management tool), Pro/Engineer (mechanical computer aided design tool) and ProductView Lite (visualization tool). Additional project activities included evaluations of PTC's electrical computer aided design, visualization, and engineering calculations applications. This report documents the AEE project work to share information and lessons learned with other NWC sites. It also provides PTC with recommendations for improving their products for NWC applications.« less

Generation and genetic engineering of human induced pluripotent stem cells using designed zinc finger nucleases.

PubMed

Ramalingam, Sivaprakash; London, Viktoriya; Kandavelou, Karthikeyan; Cebotaru, Liudmila; Guggino, William; Civin, Curt; Chandrasegaran, Srinivasan

2013-02-15

Zinc finger nucleases (ZFNs) have become powerful tools to deliver a targeted double-strand break at a pre-determined chromosomal locus in order to insert an exogenous transgene by homology-directed repair. ZFN-mediated gene targeting was used to generate both single-allele chemokine (C-C motif) receptor 5 (CCR5)-modified human induced pluripotent stem cells (hiPSCs) and biallele CCR5-modified hiPSCs from human lung fibroblasts (IMR90 cells) and human primary cord blood mononuclear cells (CBMNCs) by site-specific insertion of stem cell transcription factor genes flanked by LoxP sites into the endogenous CCR5 locus. The Oct4 and Sox2 reprogramming factors, in combination with valproic acid, induced reprogramming of human lung fibroblasts to form CCR5-modified hiPSCs, while 5 factors, Oct4/Sox2/Klf4/Lin28/Nanog, induced reprogramming of CBMNCs. Subsequent Cre recombinase treatment of the CCR5-modified IMR90 hiPSCs resulted in the removal of the Oct4 and Sox2 transgenes. Further genetic engineering of the single-allele CCR5-modified IMR90 hiPSCs was achieved by site-specific addition of the large CFTR transcription unit to the remaining CCR5 wild-type allele, using CCR5-specific ZFNs and a donor construct containing tdTomato and CFTR transgenes flanked by CCR5 homology arms. CFTR was expressed efficiently from the endogenous CCR5 locus of the CCR5-modified tdTomato/CFTR hiPSCs. These results suggest that it might be feasible to use ZFN-evoked strategies to (1) generate precisely targeted genetically well-defined patient-specific hiPSCs, and (2) then to reshape their function by targeted addition and expression of therapeutic genes from the CCR5 chromosomal locus for autologous cell-based transgene-correction therapy to treat various recessive monogenic human diseases in the future.

Systematic Functional Analysis of Active-Site Residues in l-Threonine Dehydrogenase from Thermoplasma volcanium

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

Desjardins, Morgan; Mak, Wai Shun; O’Brien, Terrence E.

Enzymes have been through millions of years of evolution during which their active-site microenvironments are fine-tuned. Active-site residues are commonly conserved within protein families, indicating their importance for substrate recognition and catalysis. In this work, we systematically mutated active-site residues of l-threonine dehydrogenase from Thermoplasma volcanium and characterized the mutants against a panel of substrate analogs. Our results demonstrate that only a subset of these residues plays an essential role in substrate recognition and catalysis and that the native enzyme activity can be further enhanced roughly 4.6-fold by a single point mutation. Kinetic characterization of mutants on substrate analogs showsmore » that l-threonine dehydrogenase possesses promiscuous activities toward other chemically similar compounds not previously observed. Quantum chemical calculations on the hydride-donating ability of these substrates also reveal that this enzyme did not evolve to harness the intrinsic substrate reactivity for enzyme catalysis. Our analysis provides insights into connections between the details of enzyme active-site structure and specific function. Finally, these results are directly applicable to rational enzyme design and engineering.« less

Systematic Functional Analysis of Active-Site Residues in l-Threonine Dehydrogenase from Thermoplasma volcanium

DOE PAGES

Desjardins, Morgan; Mak, Wai Shun; O’Brien, Terrence E.; ...

2017-07-07

Enzymes have been through millions of years of evolution during which their active-site microenvironments are fine-tuned. Active-site residues are commonly conserved within protein families, indicating their importance for substrate recognition and catalysis. In this work, we systematically mutated active-site residues of l-threonine dehydrogenase from Thermoplasma volcanium and characterized the mutants against a panel of substrate analogs. Our results demonstrate that only a subset of these residues plays an essential role in substrate recognition and catalysis and that the native enzyme activity can be further enhanced roughly 4.6-fold by a single point mutation. Kinetic characterization of mutants on substrate analogs showsmore » that l-threonine dehydrogenase possesses promiscuous activities toward other chemically similar compounds not previously observed. Quantum chemical calculations on the hydride-donating ability of these substrates also reveal that this enzyme did not evolve to harness the intrinsic substrate reactivity for enzyme catalysis. Our analysis provides insights into connections between the details of enzyme active-site structure and specific function. Finally, these results are directly applicable to rational enzyme design and engineering.« less

Challenges and Advances for Genetic Engineering of Non-model Bacteria and Uses in Consolidated Bioprocessing

PubMed Central

Yan, Qiang; Fong, Stephen S.

2017-01-01

Metabolic diversity in microorganisms can provide the basis for creating novel biochemical products. However, most metabolic engineering projects utilize a handful of established model organisms and thus, a challenge for harnessing the potential of novel microbial functions is the ability to either heterologously express novel genes or directly utilize non-model organisms. Genetic manipulation of non-model microorganisms is still challenging due to organism-specific nuances that hinder universal molecular genetic tools and translatable knowledge of intracellular biochemical pathways and regulatory mechanisms. However, in the past several years, unprecedented progress has been made in synthetic biology, molecular genetics tools development, applications of omics data techniques, and computational tools that can aid in developing non-model hosts in a systematic manner. In this review, we focus on concerns and approaches related to working with non-model microorganisms including developing molecular genetics tools such as shuttle vectors, selectable markers, and expression systems. In addition, we will discuss: (1) current techniques in controlling gene expression (transcriptional/translational level), (2) advances in site-specific genome engineering tools [homologous recombination (HR) and clustered regularly interspaced short palindromic repeats (CRISPR)], and (3) advances in genome-scale metabolic models (GSMMs) in guiding design of non-model species. Application of these principles to metabolic engineering strategies for consolidated bioprocessing (CBP) will be discussed along with some brief comments on foreseeable future prospects. PMID:29123506

Coenzyme Engineering of a Hyperthermophilic 6-Phosphogluconate Dehydrogenase from NADP+ to NAD+ with Its Application to Biobatteries

NASA Astrophysics Data System (ADS)

Chen, Hui; Zhu, Zhiguang; Huang, Rui; Zhang, Yi-Heng Percival

2016-11-01

Engineering the coenzyme specificity of redox enzymes plays an important role in metabolic engineering, synthetic biology, and biocatalysis, but it has rarely been applied to bioelectrochemistry. Here we develop a rational design strategy to change the coenzyme specificity of 6-phosphogluconate dehydrogenase (6PGDH) from a hyperthermophilic bacterium Thermotoga maritima from its natural coenzyme NADP+ to NAD+. Through amino acid-sequence alignment of NADP+- and NAD+-preferred 6PGDH enzymes and computer-aided substrate-coenzyme docking, the key amino acid residues responsible for binding the phosphate group of NADP+ were identified. Four mutants were obtained via site-directed mutagenesis. The best mutant N32E/R33I/T34I exhibited a ~6.4 × 104-fold reversal of the coenzyme selectivity from NADP+ to NAD+. The maximum power density and current density of the biobattery catalyzed by the mutant were 0.135 mW cm-2 and 0.255 mA cm-2, ~25% higher than those obtained from the wide-type 6PGDH-based biobattery at the room temperature. By using this 6PGDH mutant, the optimal temperature of running the biobattery was as high as 65 °C, leading to a high power density of 1.75 mW cm-2. This study demonstrates coenzyme engineering of a hyperthermophilic 6PGDH and its application to high-temperature biobatteries.

Compressed-air energy-storage preliminary design and site-development program in an aquifer. Volume 9: Cost estimate and schedule

NASA Astrophysics Data System (ADS)

1982-12-01

The behavior and suitability of aquifers as compressed-air energy-storage sites is discussed. The engineering and construction schedule, facilities capital-cost estimate, and corresponding cash-flow requirements are given.

Human Factors Engineering. Part 2. HEDGE (Human Factors Engineering Data Guide for Evaluation)

DTIC Science & Technology

1983-11-30

Use.Condit ions 0 7ý est Item ComoentsTask Categories EPurposes 2 ;c . INDEX TO THE INDEX MAN/ITEM TASK SHEET DETAILED DESIGN CONSIDERATION The purpose of...The use of these materials, in addition to standard Task and Design Checklists and Questionnaires, will enable you to tailor your FIFE subtest to a...specific Con item. The These materials have been prepared especially for you: I. They are intended to support test engineers not design engineers. 2

Re-engineering specificity in 1,3-1, 4-β-glucanase to accept branched xyloglucan substrates.

PubMed

Addington, Trevor; Calisto, Barbara; Alfonso-Prieto, Mercedes; Rovira, Carme; Fita, Ignasi; Planas, Antoni

2011-02-01

Family 16 carbohydrate active enzyme members Bacillus licheniformis 1,3-1,4-β-glucanase and Populus tremula x tremuloides xyloglucan endotransglycosylase (XET16-34) are highly structurally related but display different substrate specificities. Although the first binds linear gluco-oligosaccharides, the second binds branched xylogluco-oligosaccharides. Prior engineered nucleophile mutants of both enzymes are glycosynthases that catalyze the condensation between a glycosyl fluoride donor and a glycoside acceptor. With the aim of expanding the glycosynthase technology to produce designer oligosaccharides consisting of hybrids between branched xylogluco- and linear gluco-oligosaccharides, enzyme engineering on the negative subsites of 1,3-1,4-β-glucanase to accept branched substrates has been undertaken. Removal of the 1,3-1,4-β-glucanase major loop and replacement with that of XET16-34 to open the binding cleft resulted in a folded protein, which still maintained some β-glucan hydrolase activity, but the corresponding nucleophile mutant did not display glycosynthase activity with either linear or branched glycosyl donors. Next, point mutations of the 1,3-1,4-β-glucanase β-sheets forming the binding site cleft were mutated to resemble XET16-34 residues. The final chimeric protein acquired binding affinity for xyloglucan and did not bind β-glucan. Therefore, binding specificity has been re-engineered, but affinity was low and the nucleophile mutant of the chimeric enzyme did not show glycosynthase activity to produce the target hybrid oligosaccharides. Structural analysis by X-ray crystallography explains these results in terms of changes in the protein structure and highlights further engineering approaches toward introducing the desired activity. © 2010 Wiley-Liss, Inc.

40 CFR 1048.205 - What must I include in my application?

Code of Federal Regulations, 2014 CFR

2014-07-01

... POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW, LARGE NONROAD SPARK-IGNITION ENGINES Certifying Engine...'s specifications and other basic parameters of the engine's design and emission controls. List the... each distinguishable engine configuration in the engine family. (b) Explain how the emission control...

40 CFR 1048.205 - What must I include in my application?

Code of Federal Regulations, 2013 CFR

2013-07-01

... POLLUTION CONTROLS CONTROL OF EMISSIONS FROM NEW, LARGE NONROAD SPARK-IGNITION ENGINES Certifying Engine...'s specifications and other basic parameters of the engine's design and emission controls. List the... each distinguishable engine configuration in the engine family. (b) Explain how the emission control...

Systems Engineering in NASA's R&TD Programs

NASA Technical Reports Server (NTRS)

Jones, Harry

2005-01-01

Systems engineering is largely the analysis and planning that support the design, development, and operation of systems. The most common application of systems engineering is in guiding systems development projects that use a phased process of requirements, specifications, design, and development. This paper investigates how systems engineering techniques should be applied in research and technology development programs for advanced space systems. These programs should include anticipatory engineering of future space flight systems and a project portfolio selection process, as well as systems engineering for multiple development projects.

The Role of Bioreactors in Ligament and Tendon Tissue Engineering.

PubMed

Mace, James; Wheelton, Andy; Khan, Wasim S; Anand, Sanj

2016-01-01

Bioreactors are pivotal to the emerging field of tissue engineering. The formation of neotissue from pluripotent cell lineages potentially offers a source of tissue for clinical use without the significant donor site morbidity associated with many contemporary surgical reconstructive procedures. Modern bioreactor design is becoming increasingly complex to provide a both an expandable source of readily available pluripotent cells and to facilitate their controlled differentiation into a clinically applicable ligament or tendon like neotissue. This review presents the need for such a method, challenges in the processes to engineer neotissue and the current designs and results of modern bioreactors in the pursuit of engineered tendon and ligament.

Deciphering the genomic targets of alkylating polyamide conjugates using high-throughput sequencing

PubMed Central

Chandran, Anandhakumar; Syed, Junetha; Taylor, Rhys D.; Kashiwazaki, Gengo; Sato, Shinsuke; Hashiya, Kaori; Bando, Toshikazu; Sugiyama, Hiroshi

2016-01-01

Chemically engineered small molecules targeting specific genomic sequences play an important role in drug development research. Pyrrole-imidazole polyamides (PIPs) are a group of molecules that can bind to the DNA minor-groove and can be engineered to target specific sequences. Their biological effects rely primarily on their selective DNA binding. However, the binding mechanism of PIPs at the chromatinized genome level is poorly understood. Herein, we report a method using high-throughput sequencing to identify the DNA-alkylating sites of PIP-indole-seco-CBI conjugates. High-throughput sequencing analysis of conjugate 2 showed highly similar DNA-alkylating sites on synthetic oligos (histone-free DNA) and on human genomes (chromatinized DNA context). To our knowledge, this is the first report identifying alkylation sites across genomic DNA by alkylating PIP conjugates using high-throughput sequencing. PMID:27098039

Multicriteria Gain Tuning for Rotorcraft Flight Controls (also entitled The Development of the Conduit Advanced Control System Design and Evaluation Interface with a Case Study Application Fly by Wire Helicopter Design)

NASA Technical Reports Server (NTRS)

Biezad, Daniel

1997-01-01

Handling qualities analysis and control law design would seem to be naturally complimenting components of aircraft flight control system design, however these two closely coupled disciplines are often not well integrated in practice. Handling qualities engineers and control system engineers may work in separate groups within an aircraft company. Flight control system engineers and handling quality specialists may come from different backgrounds and schooling and are often not aware of the other group's research. Thus while the handling qualities specifications represent desired aircraft response characteristics, these are rarely incorporated directly in the control system design process. Instead modem control system design techniques are based on servo-loop robustness specifications, and simple representations of the desired control response. Comprehensive handling qualities analysis is often left until the end of the design cycle and performed as a check of the completed design for satisfactory performance. This can lead to costly redesign or less than satisfactory aircraft handling qualities when the flight testing phase is reached. The desire to integrate the fields of handling qualities and flight,control systems led to the development of the CONDUIT system. This tool facilitates control system designs that achieve desired handling quality requirements and servo-loop specifications in a single design process. With CONDUIT, the control system engineer is now able to directly design and control systems to meet the complete handling specifications. CONDUIT allows the designer to retain a preferred control law structure, but then tunes the system parameters to meet the handling quality requirements.

Revealing the Double-Edged Sword Role of Graphene on Boosted Charge Transfer versus Active Site Control in TiO2 Nanotube Arrays@RGO/MoS2 Heterostructure.

PubMed

Quan, Quan; Xie, Shunji; Weng, Bo; Wang, Ye; Xu, Yi-Jun

2018-05-01

Charge separation/transfer is generally believed to be the most key factor affecting the efficiency of photocatalysis, which however will be counteracted if not taking the active site engineering into account for a specific photoredox reaction. Here, a 3D heterostructure composite is designed consisting of MoS 2 nanoplatelets decorated on reduced graphene oxide-wrapped TiO 2 nanotube arrays (TNTAs@RGO/MoS 2 ). Such a cascade configuration renders a directional migration of charge carriers and controlled immobilization of active sites, thereby showing much higher photoactivity for water splitting to H 2 than binary TNTAs@RGO and TNTAs/MoS 2 . The photoactivity comparison and mechanistic analysis reveal the double-edged sword role of RGO on boosted charge separation/transfer versus active site control in this composite system. The as-observed inconsistency between boosted charge transfer and lowered photoactivity over TNTAs@RGO is attributed to the decrease of active sites for H 2 evolution, which is significantly different from the previous reports in literature. The findings of the intrinsic relationship of balanced benefits from charge separation/transfer and active site control could promote the rational optimization of photocatalyst design by cooperatively manipulating charge flow and active site control, thereby improving the efficiency of photocatalysis for target photoredox processes. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 86.1809-12 - Prohibition of defeat devices.

Code of Federal Regulations, 2014 CFR

2014-07-01

... manufacturer must provide an explanation containing detailed information regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies..., with the Part II certification application, an engineering evaluation demonstrating to the satisfaction...

Space engine safety system

NASA Technical Reports Server (NTRS)

Maul, William A.; Meyer, Claudia M.

1991-01-01

A rocket engine safety system was designed to initiate control procedures to minimize damage to the engine or vehicle or test stand in the event of an engine failure. The features and the implementation issues associated with rocket engine safety systems are discussed, as well as the specific concerns of safety systems applied to a space-based engine and long duration space missions. Examples of safety system features and architectures are given, based on recent safety monitoring investigations conducted for the Space Shuttle Main Engine and for future liquid rocket engines. Also, the general design and implementation process for rocket engine safety systems is presented.

47 CFR 27.1180 - The cost-sharing formula.

Code of Federal Regulations, 2010 CFR

2010-10-01

...); towers and/or modifications; back-up power equipment; monitoring or control equipment; engineering costs (design/path survey); installation; systems testing; FCC filing costs; site acquisition and civil works... as equipment and engineering expenses. There is no cap on the actual costs of relocation. (c) An AWS...

Evaluation and implementation of an improved methodology for earthquake ground response analysis : uniform treatment source, path and site effects.

DOT National Transportation Integrated Search

2008-12-01

Shortly after the 1994 Northridge Earthquake, Caltrans geotechnical engineers charged with developing site-specific : response spectra for high priority California bridges initiated a research project aimed at broadening their perspective : from simp...

Human Factors Engineering Guidelines for Overhead Cranes

NASA Technical Reports Server (NTRS)

Chandler, Faith; Delgado, H. (Technical Monitor)

2001-01-01

This guideline provides standards for overhead crane cabs that can be applied to the design and modification of crane cabs to reduce the potential for human error due to design. This guideline serves as an aid during the development of a specification for purchases of cranes or for an engineering support request for crane design modification. It aids human factors engineers in evaluating existing cranes during accident investigations or safety reviews.

Corporate ergonomics programme at BCM Airdrie. Boots Contract Manufacturing.

PubMed

Smyth, Joanne

2003-01-01

The production processes at the BCM Airdrie site range from manual loading tasks in the manufacturing areas to high frequency packaging assembly tasks on the production lines. Both are jobs that are known to carry risk to musculoskeletal health, so an ergonomist was appointed to design and co-ordinate an ergonomics programme for the site to control these risks. This paper details the programme that has evolved to proactively manage musculoskeletal risks in the design of both new and existing equipment and processes. The ergonomics procedures described primarily involve the engineers from all areas of the factory, and the process for ergonomics involvement with engineering design projects is described. Shop-floor personnel involvement is considered to be an essential part of the programme and 'Ergonomics Champions' are being trained on the packing lines to monitor the risks that are sometimes introduced with the different designs of product packaging.

Incorporating metals into de novo proteins.

PubMed

Peacock, Anna F A

2013-12-01

The de novo design of artificial metalloproteins from first-principles is a powerful strategy with which to establish the minimum structure required for function, as well as to identify the important design features for tuning the chemistry of the coordinated metal ion. Herein we describe recent contributions to this field, covering metallo-porphyrin, mononuclear and multinuclear metal ion sites engineered into de novo proteins. Using miniature artificial scaffolds these examples demonstrate that complex natural protein folds are not required to mimic naturally occurring metal ion sites in proteins. More importantly progress is being made to engineer de novo metalloproteins capable of performing functions not in the repertoire of biology. Copyright © 2013 Elsevier Ltd. All rights reserved.

West Virginia Geological Survey's role in siting fluidized bed combustion facilities

USGS Publications Warehouse

Smith, C.J.; King, Hobart M.; Ashton, K.C.; Kirstein, D.S.; McColloch, G.H.

1989-01-01

A project is presented which demonstrates the role of geology in planning and siting a fluidized bed combustion facility. Whenever a project includes natural resource utilization, cooperation between geologists and design engineers will provide an input that could and should save costs, similar to the one stated in our initial premise. Regardless of whether cost reductions stem from a better knowledge of fuel and sorbent availabilities, or a better understanding of the local hydrology, susceptibility to mine-subsidence, or other geologic hazards, the geological survey has a vital role in planning. Input to planning could help the fluidized-bed developer and design-engineer solve some economic questions and stretch the financial resources at their disposal.

40 CFR 1054.205 - What must I include in my application?

Code of Federal Regulations, 2012 CFR

2012-07-01

... emission family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, all-season gasoline... emission control systems operate. Describe the evaporative emission controls and show how your design will...

40 CFR 1054.205 - What must I include in my application?

Code of Federal Regulations, 2011 CFR

2011-07-01

... emission family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, all-season gasoline... emission control systems operate. Describe the evaporative emission controls and show how your design will...

40 CFR 1054.205 - What must I include in my application?

Code of Federal Regulations, 2010 CFR

2010-07-01

... emission family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, all-season gasoline... emission control systems operate. Describe the evaporative emission controls and show how your design will...

40 CFR 1054.205 - What must I include in my application?

Code of Federal Regulations, 2013 CFR

2013-07-01

... emission family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, all-season gasoline... emission control systems operate. Describe the evaporative emission controls and show how your design will...

40 CFR 1054.205 - What must I include in my application?

Code of Federal Regulations, 2014 CFR

2014-07-01

... emission family's specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, all-season gasoline... emission control systems operate. Describe the evaporative emission controls and show how your design will...

Feasibility of magnetic bearings for advanced gas turbine engines

NASA Technical Reports Server (NTRS)

Hibner, David; Rosado, Lewis

1992-01-01

The application of active magnetic bearings to advanced gas turbine engines will provide a product with major improvements compared to current oil lubricated bearing designs. A rethinking of the engine rotating and static structure design is necessary and will provide the designer with significantly more freedom to meet the demanding goals of improved performance, increased durability, higher reliability, and increased thrust to weight ratio via engine weight reduction. The product specific technology necessary for this high speed, high temperature, dynamically complex application has been defined. The resulting benefits from this approach to aircraft engine rotor support and the complementary engine changes and improvements have been assessed.

Specific features of modern multifunctional high-rise building construction

NASA Astrophysics Data System (ADS)

Manukhina, Lyubov; Samosudova, Natal'ja

2018-03-01

The article analyzes the main reasons for the development of high-rise building construction the most important of which-is a limitation of the urban areas and, consequently, the high price of land reserved for construction. New engineering and compositional solutions for the creation of new types of buildings are considered - complex technical designs of a large number of storeys completely meet the new requirements for safety and comfort. Some peculiarities of designing high-rise buildings and searching for optimal architectural and planning solutions are revealed since, with external architectural simplicity, high-rise buildings have complex structural and technological and space-planning solutions. We consider the specific features of a high-rise housing in various countries around the world, including Russia, such as the layout of the multi-storey residential buildings, depending on the climatic characteristics of the regions, assessment of the geological risk of the construction site, the choice of parameters and functional purpose of the sections of the territory of high-rise construction, location of the town-planning object for substantiating the overall dimensions of the building, assessment of changes aeration and engineering and hydrological conditions of the site. A special place in the article on the problems of improvement of the territory, the device of courtyards, landscaping, the device of playing and sports grounds. The main conclusion in the article is the following problem - when developing high-rise housing construction, the development of high-rise housing, and an increase in the population density in the territory of large cities of Russia, necessary to create a comfortable and safe level of residents living and not a decrease, but an improvement in the quality of the urban environment.

Advanced Turbine Technology Applications Project (ATTAP)

NASA Technical Reports Server (NTRS)

1991-01-01

ATTAP activities were highlighted by test bed engine design and development activities; ceramic component design; materials and engine component characterization; ceramic component process development and fabrication; component rig testing; and test bed engine fabrication and testing. Specifically, ATTAP aims to develop and demonstrate the technology of structural ceramics that have the potential for competitive automotive engine life cycle cost and for operating for 3500 hours in a turbine engine environment at temperatures up to 1371 C (2500 F).

Geotechnical engineering for ocean waste disposal. An introduction

USGS Publications Warehouse

Lee, Homa J.; Demars, Kenneth R.; Chaney, Ronald C.; ,

1990-01-01

As members of multidisciplinary teams, geotechnical engineers apply quantitative knowledge about the behavior of earth materials toward designing systems for disposing of wastes in the oceans and monitoring waste disposal sites. In dredge material disposal, geotechnical engineers assist in selecting disposal equipment, predict stable characteristics of dredge mounds, design mound caps, and predict erodibility of the material. In canister disposal, geotechnical engineers assist in specifying canister configurations, predict penetration depths into the seafloor, and predict and monitor canister performance following emplacement. With sewage outfalls, geotechnical engineers design foundation and anchor elements, estimate scour potential around the outfalls, and determine the stability of deposits made up of discharged material. With landfills, geotechnical engineers evaluate the stability and erodibility of margins and estimate settlement and cracking of the landfill mass. Geotechnical engineers also consider the influence that pollutants have on the engineering behavior of marine sediment and the extent to which changes in behavior affect the performance of structures founded on the sediment. In each of these roles, careful application of geotechnical engineering principles can contribute toward more efficient and environmentally safe waste disposal operations.

A systematic approach to engineering ethics education.

PubMed

Li, Jessica; Fu, Shengli

2012-06-01

Engineering ethics education is a complex field characterized by dynamic topics and diverse students, which results in significant challenges for engineering ethics educators. The purpose of this paper is to introduce a systematic approach to determine what to teach and how to teach in an ethics curriculum. This is a topic that has not been adequately addressed in the engineering ethics literature. This systematic approach provides a method to: (1) develop a context-specific engineering ethics curriculum using the Delphi technique, a process-driven research method; and (2) identify appropriate delivery strategies and instructional strategies using an instructional design model. This approach considers the context-specific needs of different engineering disciplines in ethics education and leverages the collaboration of engineering professors, practicing engineers, engineering graduate students, ethics scholars, and instructional design experts. The proposed approach is most suitable for a department, a discipline/field or a professional society. The approach helps to enhance learning outcomes and to facilitate ethics education curriculum development as part of the regular engineering curriculum.

Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific Auricles In Vivo

PubMed Central

Cohen, Benjamin Peter; Hooper, Rachel C.; Puetzer, Jennifer L.; Nordberg, Rachel; Asanbe, Ope; Hernandez, Karina A.; Spector, Jason A.

2016-01-01

Current techniques for autologous auricular reconstruction produce substandard ear morphologies with high levels of donor-site morbidity, whereas alloplastic implants demonstrate poor biocompatibility. Tissue engineering, in combination with noninvasive digital photogrammetry and computer-assisted design/computer-aided manufacturing technology, offers an alternative method of auricular reconstruction. Using this method, patient-specific ears composed of collagen scaffolds and auricular chondrocytes have generated auricular cartilage with great fidelity following 3 months of subcutaneous implantation, however, this short time frame may not portend long-term tissue stability. We hypothesized that constructs developed using this technique would undergo continued auricular cartilage maturation without degradation during long-term (6 month) implantation. Full-sized, juvenile human ear constructs were injection molded from high-density collagen hydrogels encapsulating juvenile bovine auricular chondrocytes and implanted subcutaneously on the backs of nude rats for 6 months. Upon explantation, constructs retained overall patient morphology and displayed no evidence of tissue necrosis. Limited contraction occurred in vivo, however, no significant change in size was observed beyond 1 month. Constructs at 6 months showed distinct auricular cartilage microstructure, featuring a self-assembled perichondrial layer, a proteoglycan-rich bulk, and rounded cellular lacunae. Verhoeff's staining also revealed a developing elastin network comparable to native tissue. Biochemical measurements for DNA, glycosaminoglycan, and hydroxyproline content and mechanical properties of aggregate modulus and hydraulic permeability showed engineered tissue to be similar to native cartilage at 6 months. Patient-specific auricular constructs demonstrated long-term stability and increased cartilage tissue development during extended implantation, and offer a potential tissue-engineered solution for the future of auricular reconstructions. PMID:26847742

Toward a patient-specific tissue engineered vascular graft

PubMed Central

Best, Cameron; Strouse, Robert; Hor, Kan; Pepper, Victoria; Tipton, Amy; Kelly, John; Shinoka, Toshiharu; Breuer, Christopher

2018-01-01

Integrating three-dimensional printing with the creation of tissue-engineered vascular grafts could provide a readily available, patient-specific, autologous tissue source that could significantly improve outcomes in newborns with congenital heart disease. Here, we present the recent case of a candidate for our tissue-engineered vascular graft clinical trial deemed ineligible due to complex anatomical requirements and consider the application of three-dimensional printing technologies for a patient-specific graft. We 3D-printed a closed-disposable seeding device and validated that it performed equivalently to the traditional open seeding technique using ovine bone marrow–derived mononuclear cells. Next, our candidate’s preoperative imaging was reviewed to propose a patient-specific graft. A seeding apparatus was then designed to accommodate the custom graft and 3D-printed on a commodity fused deposition modeler. This exploratory feasibility study represents an important proof of concept advancing progress toward a rationally designed patient-specific tissue-engineered vascular graft for clinical application. PMID:29568478

Test Method Designed to Evaluate Cylinder Liner-Piston Ring Coatings for Advanced Heat Engines

NASA Technical Reports Server (NTRS)

Radil, Kevin C.

1997-01-01

Research on advanced heat engine concepts, such as the low-heat-rejection engine, have shown the potential for increased thermal efficiency, reduced emissions, lighter weight, simpler design, and longer life in comparison to current diesel engine designs. A major obstacle in the development of a functional advanced heat engine is overcoming the problems caused by the high combustion temperatures at the piston ring/cylinder liner interface, specifically at top ring reversal (TRR). Therefore, advanced cylinder liner and piston ring materials are needed that can survive under these extreme conditions. To address this need, researchers at the NASA Lewis Research Center have designed a tribological test method to help evaluate candidate piston ring and cylinder liner materials for advanced diesel engines.

40 CFR 86.1809-10 - Prohibition of defeat devices.

Code of Federal Regulations, 2012 CFR

2012-07-01

... detailed information regarding test programs, engineering evaluations, design specifications, calibrations, on-board computer algorithms, and design strategies incorporated for operation both during and... HLDT/MDPVs the manufacturer must submit, with the Part II certification application, an engineering...

DNA-binding specificity prediction with FoldX.

PubMed

Nadra, Alejandro D; Serrano, Luis; Alibés, Andreu

2011-01-01

With the advent of Synthetic Biology, a field between basic science and applied engineering, new computational tools are needed to help scientists reach their goal, their design, optimizing resources. In this chapter, we present a simple and powerful method to either know the DNA specificity of a wild-type protein or design new specificities by using the protein design algorithm FoldX. The only basic requirement is having a good resolution structure of the complex. Protein-DNA interaction design may aid the development of new parts designed to be orthogonal, decoupled, and precise in its target. Further, it could help to fine-tune the systems in terms of specificity, discrimination, and binding constants. In the age of newly developed devices and invented systems, computer-aided engineering promises to be an invaluable tool. Copyright © 2011 Elsevier Inc. All rights reserved.

Molecular biomimetics: GEPI-based biological routes to technology.

PubMed

Tamerler, Candan; Khatayevich, Dmitriy; Gungormus, Mustafa; Kacar, Turgay; Oren, E Emre; Hnilova, Marketa; Sarikaya, Mehmet

2010-01-01

In nature, the viability of biological systems is sustained via specific interactions among the tens of thousands of proteins, the major building blocks of organisms from the simplest single-celled to the most complex multicellular species. Biomolecule-material interaction is accomplished with molecular specificity and efficiency leading to the formation of controlled structures and functions at all scales of dimensional hierarchy. Through evolution, Mother Nature developed molecular recognition by successive cycles of mutation and selection. Molecular specificity of probe-target interactions, e.g., ligand-receptor, antigen-antibody, is always based on specific peptide molecular recognition. Using biology as a guide, we can now understand, engineer, and control peptide-material interactions and exploit them as a new design tool for novel materials and systems. We adapted the protocols of combinatorially designed peptide libraries, via both cell surface or phage display methods; using these we select short peptides with specificity to a variety of practical materials. These genetically engineered peptides for inorganics (GEPI) are then studied experimentally to establish their binding kinetics and surface stability. The bound peptide structure and conformations are interrogated both experimentally and via modeling, and self-assembly characteristics are tested via atomic force microscopy. We further engineer the peptide binding and assembly characteristics using a computational biomimetics approach where bioinformatics based peptide-sequence similarity analysis is developed to design higher generation function-specific peptides. The molecular biomimetic approach opens up new avenues for the design and utilization of multifunctional molecular systems in a wide-range of applications from tissue engineering, disease diagnostics, and therapeutics to various areas of nanotechnology where integration is required among inorganic, organic and biological materials. Here, we describe lessons from biology with examples of protein-mediated functional biological materials, explain how novel peptides can be designed with specific affinity to inorganic solids using evolutionary engineering approaches, give examples of their potential utilizations in technology and medicine, and, finally, provide a summary of challenges and future prospects. (c) 2010 Wiley Periodicals, Inc.

Magnetohydrodynamics (MHD) Engineering Test Facility (ETF) 200 MWe power plant. Conceptual Design Engineering Report (CDER). Volume 2: Engineering. Volume 3: Costs and schedules

NASA Astrophysics Data System (ADS)

1981-09-01

Engineering design details for the principal systems, system operating modes, site facilities, and structures of an engineering test facility (ETF) of a 200 MWE power plant are presented. The ETF resembles a coal-fired steam power plant in many ways. It is analogous to a conventional plant which has had the coal combustor replaced with the MHD power train. Most of the ETF components are conventional. They can, however, be sized or configured differently or perform additional functions from those in a conventional coal power plant. The boiler not only generates steam, but also performs the functions of heating the MHD oxidant, recovering seed, and controlling emissions.

Magnetohydrodynamics (MHD) Engineering Test Facility (ETF) 200 MWe power plant. Conceptual Design Engineering Report (CDER). Volume 2: Engineering. Volume 3: Costs and schedules

NASA Technical Reports Server (NTRS)

1981-01-01

Engineering design details for the principal systems, system operating modes, site facilities, and structures of an engineering test facility (ETF) of a 200 MWE power plant are presented. The ETF resembles a coal-fired steam power plant in many ways. It is analogous to a conventional plant which has had the coal combustor replaced with the MHD power train. Most of the ETF components are conventional. They can, however, be sized or configured differently or perform additional functions from those in a conventional coal power plant. The boiler not only generates steam, but also performs the functions of heating the MHD oxidant, recovering seed, and controlling emissions.

14 CFR 136.1 - Applicability and definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (powered or un-powered), parachutes (powered or un-powered), gyroplanes, or airships. (d) For the purposes... site-specific areas would provide an emergency landing area for a single-engine helicopter or a multiengine helicopter that does not have the capability to reach a safe landing area after an engine power...

14 CFR 136.1 - Applicability and definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (powered or un-powered), parachutes (powered or un-powered), gyroplanes, or airships. (d) For the purposes... site-specific areas would provide an emergency landing area for a single-engine helicopter or a multiengine helicopter that does not have the capability to reach a safe landing area after an engine power...

14 CFR 136.1 - Applicability and definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... (powered or un-powered), parachutes (powered or un-powered), gyroplanes, or airships. (d) For the purposes... site-specific areas would provide an emergency landing area for a single-engine helicopter or a multiengine helicopter that does not have the capability to reach a safe landing area after an engine power...

14 CFR 136.1 - Applicability and definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... (powered or un-powered), parachutes (powered or un-powered), gyroplanes, or airships. (d) For the purposes... site-specific areas would provide an emergency landing area for a single-engine helicopter or a multiengine helicopter that does not have the capability to reach a safe landing area after an engine power...

14 CFR 136.1 - Applicability and definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (powered or un-powered), parachutes (powered or un-powered), gyroplanes, or airships. (d) For the purposes... site-specific areas would provide an emergency landing area for a single-engine helicopter or a multiengine helicopter that does not have the capability to reach a safe landing area after an engine power...

Searchers Net Treasure in Monterey.

ERIC Educational Resources Information Center

McDermott, Irene E.

1999-01-01

Reports on Web keyword searching, metadata, Dublin Core, Extensible Markup Language (XML), metasearch engines (metasearch engines search several Web indexes and/or directories and/or Usenet and/or specific Web sites), and the Year 2000 (Y2K) dilemma, all topics discussed at the second annual Internet Librarian Conference sponsored by Information…

Science through Engineering in Elementary School: Comparing Three Enactments of an Engineering-Design-Based Curriculum on the Science of Sound

ERIC Educational Resources Information Center

Wendell, Kristen Bethke

2011-01-01

This research illustrates how varying enactments of an engineering-design-based science curriculum shaped the development of students' domain-specific scientific ideas and practices. In this comparative case study rooted in the analytical perspectives of activity theory and learning environments, student and teacher participants in three…

Engineering Design Processes in Seventh-Grade Classrooms: Bridging the Engineering Education Gap

ERIC Educational Resources Information Center

English, Lyn D.; Hudson, Peter B.; Dawes, Les

2012-01-01

This paper reports on some findings from the first year of a three-year longitudinal study, in which seventh- to ninth-graders were introduced to engineering education. Specifically, the paper addresses students' responses to an initial design activity involving bridge construction, which was implemented at the end of seventh grade. This paper…

Methodology for the systems engineering process. Volume 1: System functional activities

NASA Technical Reports Server (NTRS)

Nelson, J. H.

1972-01-01

Systems engineering is examined in terms of functional activities that are performed in the conduct of a system definition/design, and system development is described in a parametric analysis that combines functions, performance, and design variables. Emphasis is placed on identification of activities performed by design organizations, design specialty groups, as well as a central systems engineering organizational element. Identification of specific roles and responsibilities for doing functions, and monitoring and controlling activities within the system development operation are also emphasized.

QCGAT aircraft/engine design for reduced noise and emissions

NASA Technical Reports Server (NTRS)

Lanson, L.; Terrill, K. M.

1980-01-01

The high bypass ratio QCGAT engine played an important role in shaping the aircraft design. The aircraft which evolved is a sleek, advanced design, six-place aircraft with 3538 kg (7,800 lb) maximum gross weight. It offers a 2778 kilometer (1500 nautical mile) range with cruise speed of 0.5 Mach number and will take-off and land on the vast majority of general aviation airfields. Advanced features include broad application of composite materials and a supercritical wing design with winglets. Full-span fowler flaps were introduced to improve landing capability. Engines are fuselage-mounted with inlets over the wing to provide shielding of fan noise by the wing surfaces. The design objectives, noise, and emission considerations, engine cycle and engine description are discussed as well as specific design features.

Upscaling the pollutant emission from mixed recycled aggregates under compaction for civil applications.

PubMed

Galvín, Adela P; Ayuso, Jesús; Barbudo, Auxi; Cabrera, Manuel; López-Uceda, Antonio; Rosales, Julia

2017-12-27

In general terms, plant managers of sites producing construction wastes assess materials according to concise, legally recommended leaching tests that do not consider the compaction stage of the materials when they are applied on-site. Thus, the tests do not account for the real on-site physical conditions of the recycled aggregates used in civil works (e.g., roads or embankments). This leads to errors in estimating the pollutant potential of these materials. For that reason, in the present research, an experimental procedure is designed as a leaching test for construction materials under compaction. The aim of this laboratory test (designed specifically for the granular materials used in civil engineering infrastructures) is to evaluate the release of pollutant elements when the recycled aggregate is tested at its commercial grain-size distribution and when the material is compacted under on-site conditions. Two recycled aggregates with different gypsum contents (0.95 and 2.57%) were used in this study. In addition to the designed leaching laboratory test, the conventional compliance leaching test and the Dutch percolation test were performed. The results of the new leaching method were compared with the conventional leaching test results. After analysis, the chromium and sulphate levels obtained from the newly designed test were lower than those obtained from the conventional leaching test, and these were considered more seriously pollutant elements. This result confirms that when the leaching behaviour is evaluated for construction aggregates without density alteration, crushing the aggregate and using only the finest fraction, as is done in the conventional test (which is an unrealistic situation for aggregates that are applied under on-site conditions), the leaching behaviour is not accurately assessed.

Transporting Radioactive Waste: An Engineering Activity. Grades 5-12.

ERIC Educational Resources Information Center

HAZWRAP, The Hazardous Waste Remedial Actions Program.

This brochure contains an engineering activity for upper elementary, middle school, and high school students that examines the transportation of radioactive waste. The activity is designed to inform students about the existence of radioactive waste and its transportation to disposal sites. Students experiment with methods to contain the waste and…

Stationary diesel engines for use with generators to supply electric power

NASA Technical Reports Server (NTRS)

1977-01-01

The procurement of stationary diesel engines for on-site generation of electric power deals with technical criteria and policy relating to federal agency, not electrical components of diesel-generator sets or for the design of electric-power generating plants or their air-pollution or noise control equipment.

Employees' Perceptions of Barriers to Participation in Training and Development in Small Engineering Businesses

ERIC Educational Resources Information Center

Susomrith, Pattanee; Coetzer, Alan

2015-01-01

Purpose: This paper aims to investigate barriers to employee participation in voluntary formal training and development opportunities from the perspective of employees in small engineering businesses. Design/methodology/approach: An exploratory qualitative methodology involving data collection via site visits and in-depth semi-structured…

Inducible CRISPR genome-editing tool: classifications and future trends.

PubMed

Dai, Xiaofeng; Chen, Xiao; Fang, Qiuwu; Li, Jia; Bai, Zhonghu

2018-06-01

The discovery of CRISPR-Cas9/dCas9 system has reinforced our ability and revolutionized our history in genome engineering. While Cas9 and dCas9 are programed to modulate gene expression by introducing DNA breaks, blocking transcription factor recruitment or dragging functional groups towards the targeted sites, sgRNAs determine the genomic loci where the modulation occurs. The off-target problem, due to limited sgRNA specificity and genome complexity of many species, has posed concerns for the wide application of this revolutionary technique. To solve this problem and, more importantly, gain power over gene functionality and cell fate control, inducible strategies have been continuously evolved to offer tailored solutions to address specific biological questions. By reviewing recent advances in inducible CRISPR system design and critical elements potentially adding values to such systems, we classify current approaches in this domain into four mechanically distinct categories, namely, "split system", "allosteric system", "combinatorial system", and "transient delivery system", discuss the pros and cons of each system, and point out the under-explored areas and future directions, with the aim of enriching our toolbox of delicate life engineering.

DNA-Templated Introduction of an Aldehyde Handle in Proteins.

PubMed

Kodal, Anne Louise B; Rosen, Christian B; Mortensen, Michael R; Tørring, Thomas; Gothelf, Kurt V

2016-07-15

Many medical and biotechnological applications rely on protein labeling, but a key challenge is the production of homogeneous and site-specific conjugates. This can rarely be achieved by simple residue-specific random labeling, but generally requires genetic engineering. Using site-selective DNA-templated reductive amination, we created DNA-protein conjugates with control over labeling stoichiometry and without genetic engineering. A guiding DNA strand with a metal-binding functionality facilitates site-selectivity by directing the coupling of a second reactive DNA strand in the vicinity of a protein metal-binding site. We demonstrate DNA-templated reductive amination for His6 -tagged proteins and metal-binding proteins, including IgG1 antibodies. We also used a cleavable linker between the DNA and the protein to remove the DNA and introduce a single aldehyde on the protein. This functions as a handle for further modifications with desired labels. In addition to directing the aldehyde positioning, the DNA provides a straightforward route for purification between reaction steps. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

MAN-004 Design Standards Manual

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

Peterson, Timothy L.

2014-07-01

At Sandia National Laboratories in New Mexico (SNL/NM), the design, construction, operation, and maintenance of facilities is guided by industry standards, a graded approach, and the systematic analysis of life cycle benefits received for costs incurred. The design of the physical plant must ensure that the facilities are "fit for use," and provide conditions that effectively, efficiently, and safely support current and future mission needs. In addition, SNL/NM applies sustainable design principles, using an integrated whole-building design approach, from site planning to facility design, construction, and operation to ensure building resource efficiency and the health and productivity of occupants. Themore » safety and health of the workforce and the public, any possible effects on the environment, and compliance with building codes take precedence over project issues, such as performance, cost, and schedule. These design standards generally apply to all disciplines on all SNL/NM projects. Architectural and engineering design must be both functional and cost-effective. Facility design must be tailored to fit its intended function, while emphasizing low-maintenance, energy-efficient, and energy-conscious design. Design facilities that can be maintained easily, with readily accessible equipment areas, low maintenance, and quality systems. To promote an orderly and efficient appearance, architectural features of new facilities must complement and enhance the existing architecture at the site. As an Architectural and Engineering (A/E) professional, you must advise the Project Manager when this approach is prohibitively expensive. You are encouraged to use professional judgment and ingenuity to produce a coordinated interdisciplinary design that is cost-effective, easily contractible or buildable, high-performing, aesthetically pleasing, and compliant with applicable building codes. Close coordination and development of civil, landscape, structural, architectural, fire protection, mechanical, electrical, telecommunications, and security features is expected to ensure compatibility with planned functional equipment and to facilitate constructability. If portions of the design are subcontracted to specialists, delivery of the finished design documents must not be considered complete until the subcontracted portions are also submitted for review. You must, along with support consultants, perform functional analyses and programming in developing design solutions. These solutions must reflect coordination of the competing functional, budgetary, and physical requirements for the project. During design phases, meetings between you and the SNL/NM Project Team to discuss and resolve design issues are required. These meetings are a normal part of the design process. For specific design-review requirements, see the project-specific Design Criteria. In addition to the design requirements described in this manual, instructive information is provided to explain the sustainable building practice goals for design, construction, operation, and maintenance of SNL/NM facilities. Please notify SNL/NM personnel of design best practices not included in this manual, so they can be incorporated in future updates.« less

Eeap-lighting survey study at the Red River Army Depot Texarkana, Texas. Final report, 17 October 1994-14 April 1995

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

Pieper, C.A.; Luckett, T.

This energy conservation study was performed by Huitt-Zollars Inc, for the U.S. Army Engineer District (USAED), Fort Worth, under contract number DACAC63-94-D-00l5. The study was conducted at Red River Army Depot (RRAD) in Texarkana, Texas, between October 17, 1994 and April 14, 1995. The site survey and data collection were performed by C.A. Pieper, P.E. and Tom Luckett, Lighting Designer. The purpose of the study was to perform a limited site survey of specific buildings at the facility, identify Conservation Opportunities (ECOs) that exist, and then evaluate these ECOs for technical and economic feasibility. These ECOs were limited to buildingmore » interior lighting and it`s effects on the heating, ventilating and air conditioning (HVAC) systems.« less

Application of Hybrid Geo-Spatially Granular Fragility Curves to Improve Power Outage Predictions

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

Fernandez, Steven J; Allen, Melissa R; Omitaomu, Olufemi A

2014-01-01

Fragility curves depict the relationship between a weather variable (wind speed, gust speed, ice accumulation, precipitation rate) and the observed outages for a targeted infrastructure network. This paper describes an empirical study of the county by county distribution of power outages and one minute weather variables during Hurricane Irene with the objective of comparing 1) as built fragility curves (statistical approach) to engineering as designed (bottom up) fragility curves for skill in forecasting outages during future hurricanes; 2) county specific fragility curves to find examples of significant deviation from average behavior; and 3) the engineering practices of outlier counties tomore » suggest future engineering studies of robustness. Outages in more than 90% of the impacted counties could be anticipated through an average or generic fragility curve. The remaining counties could be identified and handled as exceptions through geographic data sets. The counties with increased or decreased robustness were characterized by terrain more or less susceptible to persistent flooding in areas where above ground poles located their foundations. Land use characteristics of the area served by the power distribution system can suggest trends in the as built power grid vulnerabilities to extreme weather events that would be subjects for site specific studies.« less

Collaborative engineering and design management for the Hobby-Eberly Telescope tracker upgrade

NASA Astrophysics Data System (ADS)

Mollison, Nicholas T.; Hayes, Richard J.; Good, John M.; Booth, John A.; Savage, Richard D.; Jackson, John R.; Rafal, Marc D.; Beno, Joseph H.

2010-07-01

The engineering and design of systems as complex as the Hobby-Eberly Telescope's* new tracker require that multiple tasks be executed in parallel and overlapping efforts. When the design of individual subsystems is distributed among multiple organizations, teams, and individuals, challenges can arise with respect to managing design productivity and coordinating successful collaborative exchanges. This paper focuses on design management issues and current practices for the tracker design portion of the Hobby-Eberly Telescope Wide Field Upgrade project. The scope of the tracker upgrade requires engineering contributions and input from numerous fields including optics, instrumentation, electromechanics, software controls engineering, and site-operations. Successful system-level integration of tracker subsystems and interfaces is critical to the telescope's ultimate performance in astronomical observation. Software and process controls for design information and workflow management have been implemented to assist the collaborative transfer of tracker design data. The tracker system architecture and selection of subsystem interfaces has also proven to be a determining factor in design task formulation and team communication needs. Interface controls and requirements change controls will be discussed, and critical team interactions are recounted (a group-participation Failure Modes and Effects Analysis [FMEA] is one of special interest). This paper will be of interest to engineers, designers, and managers engaging in multi-disciplinary and parallel engineering projects that require coordination among multiple individuals, teams, and organizations.

DEVELOPMENT OF A SUPERSONIC TRANSPORT AIRCRAFT ENGINE - PHASE II-A.

DTIC Science & Technology

JET TRANSPORT PLANES, *SUPERSONIC AIRCRAFT ) (U) TURBOJET ENGINES , PERFORMANCE( ENGINEERING ), TURBOFAN ENGINES , AFTERBURNING, SPECIFICATIONS...COMPRESSORS, GEOMETRY, TURBOJET INLETS, COMBUSTION, TEST EQUIPMENT, TURBINE BLADES , HEAT TRANSFER, AIRFOILS , CASCADE STRUCTURES, EVAPOTRANSPIRATION, PLUG NOZZLES, ANECHOIC CHAMBERS, BEARINGS, SEALS, DESIGN, FATIGUE(MECHANICS)

Engineering Enriched Microenvironments with Gradients of Platelet Lysate in Hydrogel Fibers.

PubMed

Santo, Vítor E; Babo, Pedro; Amador, Miguel; Correia, Cláudia; Cunha, Bárbara; Coutinho, Daniela F; Neves, Nuno M; Mano, João F; Reis, Rui L; Gomes, Manuela E

2016-06-13

Gradients of physical and chemical cues are characteristic of specific tissue microenvironments and contribute toward morphogenesis and tissue regeneration upon injury. Recent advances on microfluidics and hydrogel manipulation raised the possibility of generating biomimetic biomaterials enriched with bioactive factors and encapsulating cells following designs specifically tailored for a target application. The novelty of this work relies on the combination of methacrylated gellan gum (MeGG) with platelet lysate (PL), aiming to generate novel advanced 3D PL-enriched photo-cross-linkable hydrogels and overcoming the lack of adhesion sites provided by the native MeGG hydrogels. This combination takes advantage of the availability, enriched growth factor composition, and potential autologous application of PL while simultaneously preserving the ability provided by MeGG to tailor mechanical properties, protein release kinetics, and shape of the construct according to the desired goal. Incorporation of PL in the hydrogels significantly improved cellular adhesion and viability in the constructs. The use of microfluidic tools allowed the design of a fiber-like hydrogel incorporating a gradient of PL along the length of the fiber. These spatial protein gradients led to the viability and cell number gradients caused by maintenance of human umbilical vein endothelial cells (HUVECs) survival in the fibers toward the PL-enriched sections in comparison with the nonloaded MeGG sections of the fibers. Altogether, we propose a proof of concept strategy to design a PL gradient biomaterial with potential in tissue engineering approaches and analysis of cell-microenvironment interactions.

18 CFR 157.34 - Notice of open season.

Code of Federal Regulations, 2011 CFR

2011-04-01

... including postings on Internet Web sites, press releases, direct mail solicitations, and other advertising... open season or allocation of capacity that is not posted on the open season Internet Web site or that... due to economic, engineering, design, capacity or operational constraints, or accommodating the...

ONR K-16 Engineering Pipeline: Engineering Success in STEM Project

DTIC Science & Technology

2016-10-19

contributed to fewer items being rated as significantly higher on the post - test . Most of these items were designed to assess confidence with specific...the second group talked about the application of the EDP in many different content areas. One stated , "What I like about the engineering design ... designating a point person at each school and providing some direction for unit development to get groups started. One example was the suggestion to

Liquid rocket engine centrifugal flow turbopumps. [design criteria

NASA Technical Reports Server (NTRS)

1973-01-01

Design criteria and recommended practices are discussed for the following configurations selected from the design sequence of a liquid rocket engine centrifugal flow turbopump: (1) pump performance including speed, efficiency, and flow range; (2) impeller; (3) housing; and (4) thrust balance system. Hydrodynamic, structural, and mechanical problems are addressed for the achievement of required pump performance within the constraints imposed by the engine/turbopump system. Materials and fabrication specifications are also discussed.

The prospect of using large eddy and detached eddy simulations in engineering design, and the research required to get there

PubMed Central

Larsson, Johan; Wang, Qiqi

2014-01-01

In this paper, we try to look into the future to envision how large eddy and detached eddy simulations will be used in the engineering design process about 20–30 years from now. Some key challenges specific to the engineering design process are identified, and some of the critical outstanding problems and promising research directions are discussed. PMID:25024421

Functional Cellular Mimics for the Spatiotemporal Control of Multiple Enzymatic Cascade Reactions.

PubMed

Liu, Xiaoling; Formanek, Petr; Voit, Brigitte; Appelhans, Dietmar

2017-12-18

Next-generation therapeutic approaches are expected to rely on the engineering of biomimetic cellular systems that can mimic specific cellular functions. Herein, we demonstrate a highly effective route for constructing structural and functional eukaryotic cell mimics by loading pH-sensitive polymersomes as membrane-associated and free-floating organelle mimics inside the multifunctional cell membrane. Metabolism mimicry has been validated by performing successive enzymatic cascade reactions spatially separated at specific sites of cell mimics in the presence and absence of extracellular organelle mimics. These enzymatic reactions take place in a highly controllable, reproducible, efficient, and successive manner. Our biomimetic approach to material design for establishing functional principles brings considerable enrichment to the fields of biomedicine, biocatalysis, biotechnology, and systems biology. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gas Station Pricing Game: A Lesson in Engineering Economics and Business Strategies.

ERIC Educational Resources Information Center

Sin, Aaron; Center, Alfred M.

2002-01-01

Describes an educational game designed for engineering majors that demonstrates engineering economics and business strategies, specifically the concepts of customer perception of product value, convenience, and price differentiation. (YDS)

Summary of the US Army Corps of Engineers/US Environmental Protection Agency Field Verification Program

DTIC Science & Technology

1988-10-01

sites tend to be colonized by aquatic organisms adapted to an intertidal existence and by typical wetland plants. These plants may or may not be the...the upland site and within the intertidal range for the wetland site. Site Selection and Design Site selection 15. Acceptable sites for upland and... intertidal range. Along one side of the site, a sandbag dike was constructed that could be removed after filling to provide easy tidal interchange

Experimental Flow Models for SSME Flowfield Characterization

NASA Technical Reports Server (NTRS)

Abel, L. C.; Ramsey, P. E.

1989-01-01

Full scale flow models with extensive instrumentation were designed and manufactured to provide data necessary for flow field characterization in rocket engines of the Space Shuttle Main Engine (SSME) type. These models include accurate flow path geometries from the pre-burner outlet through the throat of the main combustion chamber. The turbines are simulated with static models designed to provide the correct pressure drop and swirl for specific power levels. The correct turbopump-hot gas manifold interfaces were designed into the flow models to permit parametric/integration studies for new turbine designs. These experimental flow models provide a vehicle for understanding the fluid dynamics associated with specific engine issues and also fill the more general need for establishing a more detailed fluid dynamic base to support development and verification of advanced math models.

Progress of targeted genome modification approaches in higher plants.

PubMed

Cardi, Teodoro; Neal Stewart, C

2016-07-01

Transgene integration in plants is based on illegitimate recombination between non-homologous sequences. The low control of integration site and number of (trans/cis)gene copies might have negative consequences on the expression of transferred genes and their insertion within endogenous coding sequences. The first experiments conducted to use precise homologous recombination for gene integration commenced soon after the first demonstration that transgenic plants could be produced. Modern transgene targeting categories used in plant biology are: (a) homologous recombination-dependent gene targeting; (b) recombinase-mediated site-specific gene integration; (c) oligonucleotide-directed mutagenesis; (d) nuclease-mediated site-specific genome modifications. New tools enable precise gene replacement or stacking with exogenous sequences and targeted mutagenesis of endogeneous sequences. The possibility to engineer chimeric designer nucleases, which are able to target virtually any genomic site, and use them for inducing double-strand breaks in host DNA create new opportunities for both applied plant breeding and functional genomics. CRISPR is the most recent technology available for precise genome editing. Its rapid adoption in biological research is based on its inherent simplicity and efficacy. Its utilization, however, depends on available sequence information, especially for genome-wide analysis. We will review the approaches used for genome modification, specifically those for affecting gene integration and modification in higher plants. For each approach, the advantages and limitations will be noted. We also will speculate on how their actual commercial development and implementation in plant breeding will be affected by governmental regulations.

Photovoltaic balance-of-system designs and costs at PVUSA

NASA Astrophysics Data System (ADS)

Reyes, A. B.; Jennings, C.

1995-05-01

This report is one in a series of 1994-1995 PVUSA reports that document PVUSA lessons learned at demonstration sites in California and Texas. During the last 7 years (1988 to 1994), 16 PV systems ranging from 20 kW to 500 kW have been installed. Six 20-kW emerging module technology (EMT) arrays and three turnkey (i.e., vendor designed and integrated) utility-scale systems were procured and installed at PVUSA's main test site in Davis, California. PVUSA host utilities have installed a total of seven EMT arrays and utility-scale systems in their service areas. Additional systems at Davis and host utility sites are planned. One of PVUSA's key objectives is to evaluate the performance, reliability, and cost of PV balance-of-system (BOS). In the procurement stage PVUSA encouraged innovative design to improve upon present practice by reducing maintenance, improving reliability, or lowering manufacturing or construction costs. The project team worked closely with suppliers during the design stage not only to ensure designs met functional and safety specifications, but to provide suggestions for improvement. This report, intended for the photovoltaic (PV) industry and for utility project managers and engineers considering PV plant construction and ownership, documents PVUSA utility-scale system design and cost lessons learned. Complementary PVUSA topical reports document: construction and safety experience; five-year assessment of EMTs; validation of the Kerman 500-kW grid-support PV plant benefits; PVUSA instrumentation and data analysis techniques; procurement, acceptance, and rating practices for PV power plants; experience with power conditioning units and power quality.

TMF design considerations in turbine airfoils of advanced turbine engines

NASA Astrophysics Data System (ADS)

Date, C. G.; Zamrik, S. Y.; Adams, J. H.; Frani, N. E.

A review of thermal-mechanicalfatigue (TMF) in advanced turbine engines is presented. The review includes examples of typical thermal-mechnical loadings encountered in the design of hot section blades and vanes. Specific issues related to TMF behavior are presented and the associated impact on component life analysis and design is discussed.

SU-E-T-785: Using Systems Engineering to Design HDR Skin Treatment Operation for Small Lesions to Enhance Patient Safety

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

Saw, C; Baikadi, M; Peters, C

2015-06-15

Purpose: Using systems engineering to design HDR skin treatment operation for small lesions using shielded applicators to enhance patient safety. Methods: Systems engineering is an interdisciplinary field that offers formal methodologies to study, design, implement, and manage complex engineering systems as a whole over their life-cycles. The methodologies deal with human work-processes, coordination of different team, optimization, and risk management. The V-model of systems engineering emphasize two streams, the specification and the testing streams. The specification stream consists of user requirements, functional requirements, and design specifications while the testing on installation, operational, and performance specifications. In implementing system engineering tomore » this project, the user and functional requirements are (a) HDR unit parameters be downloaded from the treatment planning system, (b) dwell times and positions be generated by treatment planning system, (c) source decay be computer calculated, (d) a double-check system of treatment parameters to comply with the NRC regulation. These requirements are intended to reduce human intervention to improve patient safety. Results: A formal investigation indicated that the user requirements can be satisfied. The treatment operation consists of using the treatment planning system to generate a pseudo plan that is adjusted for different shielded applicators to compute the dwell times. The dwell positions, channel numbers, and the dwell times are verified by the medical physicist and downloaded into the HDR unit. The decayed source strength is transferred to a spreadsheet that computes the dwell times based on the type of applicators and prescribed dose used. Prior to treatment, the source strength, dwell times, dwell positions, and channel numbers are double-checked by the radiation oncologist. No dosimetric parameters are manually calculated. Conclusion: Systems engineering provides methodologies to effectively design the HDR treatment operation that minimize human intervention and improve patient safety.« less

Optimizing Characterization of Site Hydrology in Support of New Reactor Licensing at the U.S. Nuclear Regulatory Commission (Invited)

NASA Astrophysics Data System (ADS)

Nicholson, T. J.; Raione, R.; Ahn, H.; Barnhurst, D.; Giacinto, J.; McBride, M.; Tiruneh, N. D.

2009-12-01

The NRC regulates the civilian use of radioactive materials and facilities in an open and transparent manner. The NRC regulatory criteria are designed to protect human health and safety, and the environment by regulating nuclear facilities. During review of new reactor licensing applications, NRC staff reviews and independently verifies hydrogeologic information submitted by the applicant in several topical areas such as development and testing of Conceptual Site Models (CSM) which may involve perched aquifers; engineered water level fluctuations of surface-water reservoirs; ground-water collector wells and local ground-water uses; design-basis ground-water levels for structural analysis; analysis of scenarios for potential release of radionuclides to the subsurface; deep well injection of effluents; and monitoring to detect radionuclide releases. This information is reviewed in a systematic manner in accordance with NRC requirements and guidance to evaluate safety and environmental impacts and reduce the uncertainties for these impacts. NRC licensing staff is reviewing 14 applications for siting new reactors. Experience gained through these licensing activities has shown the value of using site-specific data to evaluate the CSM and its use to assess design and operational issues. Optimizing the information flow process through a systemically and thorough review process creates efficiencies. Through an iterative process of evaluating various geographical settings and associated ground-water conditions, NRC staff has developed methods to minimize prediction uncertainty through the use of confirmatory analyses performed under conservative, hierarchal approaches.

40 CFR Appendix C-1 to Subpart E... - Required Provisions-Consulting Engineering Agreements

Code of Federal Regulations, 2014 CFR

2014-07-01

... Engineering Agreements C Appendix C-1 to Subpart E of Part 35 Protection of Environment ENVIRONMENTAL... Provisions—Consulting Engineering Agreements 1. General 2. Responsibility of the Engineer 3. Scope of Work 4... drawings, designs, specifications, reports, and incidental engineering work or materials furnished...

40 CFR Appendix C-1 to Subpart E... - Required Provisions-Consulting Engineering Agreements

Code of Federal Regulations, 2013 CFR

2013-07-01

... Engineering Agreements C Appendix C-1 to Subpart E of Part 35 Protection of Environment ENVIRONMENTAL... Provisions—Consulting Engineering Agreements 1. General 2. Responsibility of the Engineer 3. Scope of Work 4... drawings, designs, specifications, reports, and incidental engineering work or materials furnished...

40 CFR Appendix C-1 to Subpart E... - Required Provisions-Consulting Engineering Agreements

Code of Federal Regulations, 2011 CFR

2011-07-01

... Engineering Agreements C Appendix C-1 to Subpart E of Part 35 Protection of Environment ENVIRONMENTAL... Provisions—Consulting Engineering Agreements 1. General 2. Responsibility of the Engineer 3. Scope of Work 4... drawings, designs, specifications, reports, and incidental engineering work or materials furnished...

40 CFR Appendix C-1 to Subpart E... - Required Provisions-Consulting Engineering Agreements

Code of Federal Regulations, 2012 CFR

2012-07-01

... Engineering Agreements C Appendix C-1 to Subpart E of Part 35 Protection of Environment ENVIRONMENTAL... Provisions—Consulting Engineering Agreements 1. General 2. Responsibility of the Engineer 3. Scope of Work 4... drawings, designs, specifications, reports, and incidental engineering work or materials furnished...

A biosensor generated via high throughput screening quantifies cell edge Src dynamics

PubMed Central

Gulyani, Akash; Vitriol, Eric; Allen, Richard; Wu, Jianrong; Gremyachinskiy, Dmitriy; Lewis, Steven; Dewar, Brian; Graves, Lee M.; Kay, Brian K.; Kuhlman, Brian; Elston, Tim; Hahn, Klaus M.

2011-01-01

Fluorescent biosensors for living cells currently require laborious optimization and a unique design for each target. They are limited by the availability of naturally occurring ligands with appropriate target specificity. Here we describe a biosensor based on an engineered fibronectin monobody scaffold that can be tailored to bind different targets via high throughput screening. This Src family kinase (SFK) biosensor was made by derivatizing a monobody specific for activated SFK with a bright dye whose fluorescence increases upon target binding. We identified sites for dye attachment and alterations to eliminate vesiculation in living cells, providing a generalizable scaffold for biosensor production. This approach minimizes cell perturbation because it senses endogenous, unmodified target, and because sensitivity is enhanced by direct dye excitation. Automated correlation of cell velocities and SFK activity revealed that SFK are activated specifically during protrusion. Activity correlates with velocity, and peaks 1–2 microns from the leading edge. PMID:21666688

Turbine Internal and Film Cooling Modeling For 3D Navier-Stokes Codes

NASA Technical Reports Server (NTRS)

DeWitt, Kenneth; Garg Vijay; Ameri, Ali

2005-01-01

The aim of this research project is to make use of NASA Glenn on-site computational facilities in order to develop, validate and apply aerodynamic, heat transfer, and turbine cooling models for use in advanced 3D Navier-Stokes Computational Fluid Dynamics (CFD) codes such as the Glenn-" code. Specific areas of effort include: Application of the Glenn-HT code to specific configurations made available under Turbine Based Combined Cycle (TBCC), and Ultra Efficient Engine Technology (UEET) projects. Validating the use of a multi-block code for the time accurate computation of the detailed flow and heat transfer of cooled turbine airfoils. The goal of the current research is to improve the predictive ability of the Glenn-HT code. This will enable one to design more efficient turbine components for both aviation and power generation. The models will be tested against specific configurations provided by NASA Glenn.

Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

PubMed

Cui, Wei; Li, Junbai; Decher, Gero

2016-02-10

Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PV output smoothing using a battery and natural gas engine-generator.

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

Johnson, Jay Dean; Ellis, Abraham; Denda, Atsushi

2013-02-01

In some situations involving weak grids or high penetration scenarios, the variability of photovoltaic systems can affect the local electrical grid. In order to mitigate destabilizing effects of power fluctuations, an energy storage device or other controllable generation or load can be used. This paper describes the development of a controller for coordinated operation of a small gas engine-generator set (genset) and a battery for smoothing PV plant output. There are a number of benefits derived from using a traditional generation resource in combination with the battery; the variability of the photovoltaic system can be reduced to a specific levelmore » with a smaller battery and Power Conditioning System (PCS) and the lifetime of the battery can be extended. The controller was designed specifically for a PV/energy storage project (Prosperity) and a gas engine-generator (Mesa Del Sol) currently operating on the same feeder in Albuquerque, New Mexico. A number of smoothing simulations of the Prosperity PV were conducted using power data collected from the site. By adjusting the control parameters, tradeoffs between battery use and ramp rates could be tuned. A cost function was created to optimize the control in order to balance, in this example, the need to have low ramp rates with reducing battery size and operation. Simulations were performed for cases with only a genset or battery, and with and without coordinated control between the genset and battery, e.g., without the communication link between sites or during a communication failure. The degree of smoothing without coordinated control did not change significantly because the battery dominated the smoothing response. It is anticipated that this work will be followed by a field demonstration in the near future.« less

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration* ♦

PubMed Central

Koenig, Patrick; Lee, Chingwei V.; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F.; Fuh, Germaine

2015-01-01

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. PMID:26088137

Systems integrated human engineering on the Navy's rapid acquisition of manufactured parts/test and integration facility

NASA Technical Reports Server (NTRS)

Gallaway, Glen R.

1987-01-01

Human Engineering in many projects is at best a limited support function. In this Navy project the Human Engineering function is an integral component of the systems design and development process. Human Engineering is a member of the systems design organization. This ensures that people considerations are: (1) identified early in the project; (2) accounted for in the specifications; (3) incorporated into the design; and (4) the tested product meets the needs and expectations of the people while meeting the overall systems requirements. The project exemplifies achievements that can be made by the symbiosis between systems designers, engineers and Human Engineering. This approach increases Human Engineering's effectiveness and value to a project because it becomes an accepted, contributing team member. It is an approach to doing Human Engineering that should be considered for most projects. The functional and organizational issues giving this approach strength are described.

A History of Welding on the Space Shuttle Main Engine (1975 to 2010)

NASA Technical Reports Server (NTRS)

Zimmerman, Frank R.; Russell, Carolyn K.

2010-01-01

The Space Shuttle Main Engine (SSME) is a high performance, throttleable, liquid hydrogen fueled rocket engine. High thrust and specific impulse (Isp) are achieved through a staged combustion engine cycle, combined with high combustion pressure (approx.3000psi) generated by the two-stage pump and combustion process. The SSME is continuously throttleable from 67% to 109% of design thrust level. The design criteria for this engine maximize performance and weight, resulting in a 7,800 pound rocket engine that produces over a half million pounds of thrust in vacuum with a specific impulse of 452/sec. It is the most reliable rocket engine in the world, accumulating over one million seconds of hot-fire time and achieving 100% flight success in the Space Shuttle program. A rocket engine with the unique combination of high reliability, performance, and reusability comes at the expense of manufacturing simplicity. Several innovative design features and fabrication techniques are unique to this engine. This is as true for welding as any other manufacturing process. For many of the weld joints it seemed mean cheating physics and metallurgy to meet the requirements. This paper will present a history of the welding used to produce the world s highest performance throttleable rocket engine.

COMETBOARDS Can Optimize the Performance of a Wave-Rotor-Topped Gas Turbine Engine

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.

1997-01-01

A wave rotor, which acts as a high-technology topping spool in gas turbine engines, can increase the effective pressure ratio as well as the turbine inlet temperature in such engines. The wave rotor topping, in other words, may significantly enhance engine performance by increasing shaft horse power while reducing specific fuel consumption. This performance enhancement requires optimum selection of the wave rotor's adjustable parameters for speed, surge margin, and temperature constraints specified on different engine components. To examine the benefit of the wave rotor concept in engine design, researchers soft coupled NASA Lewis Research Center's multidisciplinary optimization tool COMETBOARDS and the NASA Engine Performance Program (NEPP) analyzer. The COMETBOARDS-NEPP combined design tool has been successfully used to optimize wave-rotor-topped engines. For illustration, the design of a subsonic gas turbine wave-rotor-enhanced engine with four ports for 47 mission points (which are specified by Mach number, altitude, and power-setting combinations) is considered. The engine performance analysis, constraints, and objective formulations were carried out through NEPP, and COMETBOARDS was used for the design optimization. So that the benefits that accrue from wave rotor enhancement could be examined, most baseline variables and constraints were declared to be passive, whereas important parameters directly associated with the wave rotor were considered to be active for the design optimization. The engine thrust was considered as the merit function. The wave rotor engine design, which became a sequence of 47 optimization subproblems, was solved successfully by using a cascade strategy available in COMETBOARDS. The graph depicts the optimum COMETBOARDS solutions for the 47 mission points, which were normalized with respect to standard results. As shown, the combined tool produced higher thrust for all mission points than did the other solution, with maximum benefits around mission points 11, 25, and 31. Such improvements can become critical, especially when engines are sized for these specific mission points.

Lessons Learned about Liquid Metal Reactors from FFTF Experience

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

Wootan, David W.; Casella, Andrew M.; Omberg, Ronald P.

2016-09-20

The Fast Flux Test Facility (FFTF) is the most recent liquid-metal reactor (LMR) to operate in the United States, from 1982 to 1992. FFTF is located on the DOE Hanford Site near Richland, Washington. The 400-MWt sodium-cooled, low-pressure, high-temperature, fast-neutron flux, nuclear fission test reactor was designed specifically to irradiate Liquid Metal Fast Breeder Reactor (LMFBR) fuel and components in prototypical temperature and flux conditions. FFTF played a key role in LMFBR development and testing activities. The reactor provided extensive capability for in-core irradiation testing, including eight core positions that could be used with independent instrumentation for the test specimens.more » In addition to irradiation testing capabilities, FFTF provided long-term testing and evaluation of plant components and systems for LMFBRs. The FFTF was highly successful and demonstrated outstanding performance during its nearly 10 years of operation. The technology employed in designing and constructing this reactor, as well as information obtained from tests conducted during its operation, can significantly influence the development of new advanced reactor designs in the areas of plant system and component design, component fabrication, fuel design and performance, prototype testing, site construction, and reactor operations. The FFTF complex included the reactor, as well as equipment and structures for heat removal, containment, core component handling and examination, instrumentation and control, and for supplying utilities and other essential services. The FFTF Plant was designed using a “system” concept. All drawings, specifications and other engineering documentation were organized by these systems. Efforts have been made to preserve important lessons learned during the nearly 10 years of reactor operation. A brief summary of Lessons Learned in the following areas will be discussed: Acceptance and Startup Testing of FFTF FFTF Cycle Reports« less

Current progress of targetron technology: development, improvement and application in metabolic engineering.

PubMed

Liu, Ya-Jun; Zhang, Jie; Cui, Gu-Zhen; Cui, Qiu

2015-06-01

Targetrons are mobile group II introns that can recognize their DNA target sites by base-pairing RNA-DNA interactions with the aid of site-specific binding reverse transcriptases. Targetron technology stands out from recently developed gene targeting methods because of the flexibility, feasibility, and efficiency, and is particularly suitable for the genetic engineering of difficult microorganisms, including cellulolytic bacteria that are considered promising candidates for biomass conversion via consolidated bioprocessing. Along with the development of the thermotargetron method for thermophiles, targetron technology becomes increasingly important for the metabolic engineering of industrial microorganisms aiming at biofuel/chemical production. To summarize the current progress of targetron technology and provide new insights on the use of the technology, this paper reviews the retrohoming mechanisms of both mesophilic and thermophilic targetron methods based on various group II introns, investigates the improvement of targetron tools for high target efficiency and specificity, and discusses the current applications in the metabolic engineering for bacterial producers. Although there are still intellectual property and technical restrictions in targetron applications, we propose that targetron technology will contribute to both biochemistry research and the metabolic engineering for industrial productions. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wave Engine Topping Cycle Assessment

NASA Technical Reports Server (NTRS)

Welch, Gerard E.

1996-01-01

The performance benefits derived by topping a gas turbine engine with a wave engine are assessed. The wave engine is a wave rotor that produces shaft power by exploiting gas dynamic energy exchange and flow turning. The wave engine is added to the baseline turboshaft engine while keeping high-pressure-turbine inlet conditions, compressor pressure ratio, engine mass flow rate, and cooling flow fractions fixed. Related work has focused on topping with pressure-exchangers (i.e., wave rotors that provide pressure gain with zero net shaft power output); however, more energy can be added to a wave-engine-topped cycle leading to greater engine specific-power-enhancement The energy addition occurs at a lower pressure in the wave-engine-topped cycle; thus the specific-fuel-consumption-enhancement effected by ideal wave engine topping is slightly lower than that effected by ideal pressure-exchanger topping. At a component level, however, flow turning affords the wave engine a degree-of-freedom relative to the pressure-exchanger that enables a more efficient match with the baseline engine. In some cases, therefore, the SFC-enhancement by wave engine topping is greater than that by pressure-exchanger topping. An ideal wave-rotor-characteristic is used to identify key wave engine design parameters and to contrast the wave engine and pressure-exchanger topping approaches. An aerodynamic design procedure is described in which wave engine design-point performance levels are computed using a one-dimensional wave rotor model. Wave engines using various wave cycles are considered including two-port cycles with on-rotor combustion (valved-combustors) and reverse-flow and through-flow four-port cycles with heat addition in conventional burners. A through-flow wave cycle design with symmetric blading is used to assess engine performance benefits. The wave-engine-topped turboshaft engine produces 16% more power than does a pressure-exchanger-topped engine under the specified topping constraints. Positive and negative aspects of wave engine topping in gas turbine engines are identified.

Crystallographic structure of a small molecule SIRT1 activator-enzyme complex

NASA Astrophysics Data System (ADS)

Dai, Han; Case, April W.; Riera, Thomas V.; Considine, Thomas; Lee, Jessica E.; Hamuro, Yoshitomo; Zhao, Huizhen; Jiang, Yong; Sweitzer, Sharon M.; Pietrak, Beth; Schwartz, Benjamin; Blum, Charles A.; Disch, Jeremy S.; Caldwell, Richard; Szczepankiewicz, Bruce; Oalmann, Christopher; Yee Ng, Pui; White, Brian H.; Casaubon, Rebecca; Narayan, Radha; Koppetsch, Karsten; Bourbonais, Francis; Wu, Bo; Wang, Junfeng; Qian, Dongming; Jiang, Fan; Mao, Cheney; Wang, Minghui; Hu, Erding; Wu, Joe C.; Perni, Robert B.; Vlasuk, George P.; Ellis, James L.

2015-07-01

SIRT1, the founding member of the mammalian family of seven NAD+-dependent sirtuins, is composed of 747 amino acids forming a catalytic domain and extended N- and C-terminal regions. We report the design and characterization of an engineered human SIRT1 construct (mini-hSIRT1) containing the minimal structural elements required for lysine deacetylation and catalytic activation by small molecule sirtuin-activating compounds (STACs). Using this construct, we solved the crystal structure of a mini-hSIRT1-STAC complex, which revealed the STAC-binding site within the N-terminal domain of hSIRT1. Together with hydrogen-deuterium exchange mass spectrometry (HDX-MS) and site-directed mutagenesis using full-length hSIRT1, these data establish a specific STAC-binding site and identify key intermolecular interactions with hSIRT1. The determination of the interface governing the binding of STACs with human SIRT1 facilitates greater understanding of STAC activation of this enzyme, which holds significant promise as a therapeutic target for multiple human diseases.

Design control for clinical translation of 3D printed modular scaffolds.

PubMed

Hollister, Scott J; Flanagan, Colleen L; Zopf, David A; Morrison, Robert J; Nasser, Hassan; Patel, Janki J; Ebramzadeh, Edward; Sangiorgio, Sophia N; Wheeler, Matthew B; Green, Glenn E

2015-03-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion.

Design Control for Clinical Translation of 3D Printed Modular Scaffolds

PubMed Central

Hollister, Scott J.; Flanagan, Colleen L.; Zopf, David A.; Morrison, Robert J.; Nasser, Hassan; Patel, Janki J.; Ebramzadeh, Edward; Sangiorgio, Sophia N.; Wheeler, Matthew B.; Green, Glenn E.

2015-01-01

The primary thrust of tissue engineering is the clinical translation of scaffolds and/or biologics to reconstruct tissue defects. Despite this thrust, clinical translation of tissue engineering therapies from academic research has been minimal in the 27 year history of tissue engineering. Academic research by its nature focuses on, and rewards, initial discovery of new phenomena and technologies in the basic research model, with a view towards generality. Translation, however, by its nature must be directed at specific clinical targets, also denoted as indications, with associated regulatory requirements. These regulatory requirements, especially design control, require that the clinical indication be precisely defined a priori, unlike most academic basic tissue engineering research where the research target is typically open-ended, and furthermore requires that the tissue engineering therapy be constructed according to design inputs that ensure it treats or mitigates the clinical indication. Finally, regulatory approval dictates that the constructed system be verified, i.e., proven that it meets the design inputs, and validated, i.e., that by meeting the design inputs the therapy will address the clinical indication. Satisfying design control requires (1) a system of integrated technologies (scaffolds, materials, biologics), ideally based on a fundamental platform, as compared to focus on a single technology, (2) testing of design hypotheses to validate system performance as opposed to mechanistic hypotheses of natural phenomena, and (3) sequential testing using in vitro, in vivo, large preclinical and eventually clinical tests against competing therapies, as compared to single experiments to test new technologies or test mechanistic hypotheses. Our goal in this paper is to illustrate how design control may be implemented in academic translation of scaffold based tissue engineering therapies. Specifically, we propose to (1) demonstrate a modular platform approach founded on 3D printing for developing tissue engineering therapies and (2) illustrate the design control process for modular implementation of two scaffold based tissue engineering therapies: airway reconstruction and bone tissue engineering based spine fusion. PMID:25666115

Wave-Rotor-Enhanced Gas Turbine Engine Demonstrator

NASA Technical Reports Server (NTRS)

Welch, Gerard E.; Paxson, Daniel E.; Wilson, Jack; Synder, Philip H.

1999-01-01

The U.S. Army Research Laboratory, NASA Glenn Research Center, and Rolls-Royce Allison are working collaboratively to demonstrate the benefits and viability of a wave-rotor-topped gas turbine engine. The self-cooled wave rotor is predicted to increase the engine overall pressure ratio and peak temperature by 300% and 25 to 30%. respectively, providing substantial improvements in engine efficiency and specific power. Such performance improvements would significantly reduce engine emissions and the fuel logistics trails of armed forces. Progress towards a planned demonstration of a wave-rotor-topped Rolls-Royce Allison model 250 engine has included completion of the preliminary design and layout of the engine, the aerodynamic design of the wave rotor component and prediction of its aerodynamic performance characteristics in on- and off-design operation and during transients, and the aerodynamic design of transition ducts between the wave rotor and the high pressure turbine. The topping cycle increases the burner entry temperature and poses a design challenge to be met in the development of the demonstrator engine.

Sequence-specific DNA binding activity of the cross-brace zinc finger motif of the piggyBac transposase

PubMed Central

Morellet, Nelly; Li, Xianghong; Wieninger, Silke A; Taylor, Jennifer L; Bischerour, Julien; Moriau, Séverine; Lescop, Ewen; Bardiaux, Benjamin; Mathy, Nathalie; Assrir, Nadine; Bétermier, Mireille; Nilges, Michael; Hickman, Alison B; Dyda, Fred; Craig, Nancy L; Guittet, Eric

2018-01-01

Abstract The piggyBac transposase (PB) is distinguished by its activity and utility in genome engineering, especially in humans where it has highly promising therapeutic potential. Little is known, however, about the structure–function relationships of the different domains of PB. Here, we demonstrate in vitro and in vivo that its C-terminal Cysteine-Rich Domain (CRD) is essential for DNA breakage, joining and transposition and that it binds to specific DNA sequences in the left and right transposon ends, and to an additional unexpectedly internal site at the left end. Using NMR, we show that the CRD adopts the specific fold of the cross-brace zinc finger protein family. We determine the interaction interfaces between the CRD and its target, the 5′-TGCGT-3′/3′-ACGCA-5′ motifs found in the left, left internal and right transposon ends, and use NMR results to propose docking models for the complex, which are consistent with our site-directed mutagenesis data. Our results provide support for a model of the PB/DNA interactions in the context of the transpososome, which will be useful for the rational design of PB mutants with increased activity. PMID:29385532

Urban Watershed Forestry Manual Part 2 Conserving and Planting Trees at Development Sites

Treesearch

Karen Cappiella; Tom Schueler; Tiffany Wright

2006-01-01

This manual is the second in a three-part series on using trees to protect and restore urban watersheds. A brief description of each part follows. Part 2. Conserving and Planting Trees at Development Sites presents specific ways to enable developers, engineers, or landscape architects to incorporate more trees into a development site. The proposed approach focuses...

Overview of engineering activities at the SMA

NASA Astrophysics Data System (ADS)

Christensen, R. D.; Kubo, D. Y.; Rao, Ramprasad

2008-07-01

The Submillmeter Array (SMA) consists of 8 6-meter telescopes on the summit of Mauna Kea. The array has been designed to operate from the summit of Mauna Kea and from 3 remote facilities: Hilo, Hawaii, Cambridge, Massachusetts and Taipei, Taiwan. The SMA provides high-resolution scientific observations in most of the major atmospheric windows from 180 to 700 GHz. Each telescope can house up to 8 receivers in a single cryostat and can operate with one or two receiver bands simultaneously. The array being a fully operational observatory, the demand for science time is extremely high. As a result specific time frames have been set-aside during both the day and night for engineering activities. This ensures that the proper amount of time can be spent on maintaining existing equipment or upgrading the system to provide high quality scientific output during nighttime observations. This paper describes the methods employed at the SMA to optimize engineering development of the telescopes and systems such that the time available for scientific observations is not compromised. It will also examine some of the tools used to monitor the SMA during engineering and science observations both at the site and remote facilities.

Engineering Strategies to Decode and Enhance the Genomes of Coral Symbionts.

PubMed

Levin, Rachel A; Voolstra, Christian R; Agrawal, Shobhit; Steinberg, Peter D; Suggett, David J; van Oppen, Madeleine J H

2017-01-01

Elevated sea surface temperatures from a severe and prolonged El Niño event (2014-2016) fueled by climate change have resulted in mass coral bleaching (loss of dinoflagellate photosymbionts, Symbiodinium spp., from coral tissues) and subsequent coral mortality, devastating reefs worldwide. Genetic variation within and between Symbiodinium species strongly influences the bleaching tolerance of corals, thus recent papers have called for genetic engineering of Symbiodinium to elucidate the genetic basis of bleaching-relevant Symbiodinium traits. However, while Symbiodinium has been intensively studied for over 50 years, genetic transformation of Symbiodinium has seen little success likely due to the large evolutionary divergence between Symbiodinium and other model eukaryotes rendering standard transformation systems incompatible. Here, we integrate the growing wealth of Symbiodinium next-generation sequencing data to design tailored genetic engineering strategies. Specifically, we develop a testable expression construct model that incorporates endogenous Symbiodinium promoters, terminators, and genes of interest, as well as an internal ribosomal entry site from a Symbiodinium virus. Furthermore, we assess the potential for CRISPR/Cas9 genome editing through new analyses of the three currently available Symbiodinium genomes. Finally, we discuss how genetic engineering could be applied to enhance the stress tolerance of Symbiodinium , and in turn, coral reefs.

Design and analysis report for the flight weight 20-inch Columbium secondary nozzle for the RL10 engine

NASA Technical Reports Server (NTRS)

Castro, J. H.

1989-01-01

Pratt & Whitney (P and W) is currently under contract to NASA-LeRC for a multi-year program to evaluate the feasibility of the RL10-IIB/IIC engine models and the various improvements which broaden the engine capabilities and range of applications. The features being evaluated include the operation of the RL10 engine at low thrust levels and/or high mixture ratio levels and the addition of a high area ratio (250:1) translating nozzle to the engine to increase its specific impulse while shortening the installed engine length. The translating nozzle for the RL10-IIB/IIC engine is approximately 55 inches long with an exit plane diameter of 71 inches and an inlet plane diameter of 40 inches. This report documents the design and analysis work done investigating a small subscale Columbium nozzle which could be built and tested to provide findings which then could be incorporated into the high area ratio nozzle final design for the RL10-IIB/IIC engine. This report documents the design and analysis work done investigating a small subscale Columbium nozzle which could be built and tested to provide findings which then could be incorporated into the high area ratio nozzle final design for the RL10-IIB/IIC engine. The length of the subscale nozzle is 20 in.; its exit diameter is 46 in. With the nozzle in the stowed position, an RL10A-3-3A engine system is 70 inches long (Area Ratio = 61:1); with the nozzle deployed the engine length and area ratio are increased to 90 inches and 83:1 respectively. The increase in area ratio provides a calculated increase of 7 + or - 1 second of specific impulse.

Orbit Transfer Vehicle (OTV) advanced expander cycle engine point design study. Volume 3: Engine data summary

NASA Technical Reports Server (NTRS)

1981-01-01

The engine operating characteristics were examined. Inlet pressure effects, tank pressurization effects, steady-state specific impulse, and the steady-state cycle were studied. The propellant flow schematic and operating sequence are presented. Engine hardware drawings are included.

Towards a behavioral-matching based compilation of synthetic biology functions.

PubMed

Basso-Blandin, Adrien; Delaplace, Franck

2015-09-01

The field of synthetic biology is looking forward engineering framework for safely designing reliable de-novo biological functions. In this undertaking, Computer-Aided-Design (CAD) environments should play a central role for facilitating the design. Although, CAD environment is widely used to engineer artificial systems the application in synthetic biology is still in its infancy. In this article we address the problem of the design of a high level language which at the core of CAD environment. More specifically the Gubs (Genomic Unified Behavioural Specification) language is a specification language used to describe the observations of the expected behaviour. The compiler appropriately selects components such that the observation of the synthetic biological function resulting to their assembly complies to the programmed behaviour.

An iterative synthetic approach to engineer a high-performing PhoB-specific reporter.

PubMed

Stoudenmire, Julie L; Essock-Burns, Tara; Weathers, Erena N; Solaimanpour, Sina; Mrázek, Jan; Stabb, Eric V

2018-05-11

Transcriptional reporters are common tools for analyzing either the transcription of a gene of interest or the activity of a specific transcriptional regulator. Unfortunately, the latter application has the shortcoming that native promoters did not evolve as optimal readouts for the activity of a particular regulator. We sought to synthesize an optimized transcriptional reporter for assessing PhoB activity, aiming for maximal "on" expression when PhoB is active, minimal background in the "off" state, and no control elements for other regulators. We designed specific sequences for promoter elements with appropriately spaced PhoB-binding sites, and at nineteen additional intervening nucleotide positions for which we did not predict sequence-specific effects the bases were randomized. Eighty-three such constructs were screened in Vibrio fischeri , enabling us to identify bases at particular randomized positions that significantly correlated with high "on" or low "off" expression. A second round of promoter design rationally constrained thirteen additional positions, leading to a reporter with high PhoB-dependent expression, essentially no background, and no other known regulatory elements. As expressed reporters, we used both stable and destabilized GFP, the latter with a half-life of eighty-one minutes in V. fischeri In culture, PhoB induced the reporter when phosphate was depleted below 10 μM. During symbiotic colonization of its host squid Euprymna scolopes , the reporter indicated heterogeneous phosphate availability in different light-organ microenvironments. Finally, testing this construct in other Proteobacteria demonstrated its broader utility. The results illustrate how a limited ability to predict synthetic promoter-reporter performance can be overcome through iterative screening and re-engineering. IMPORTANCE Transcriptional reporters can be powerful tools for assessing when a particular regulator is active; however, native promoters may not be ideal for this purpose. Optimal reporters should be specific to the regulator being examined and should maximize the difference between "on" and "off" states; however, these properties are distinct from the selective pressures driving the evolution of natural promoters. Synthetic promoters offer a promising alternative, but our understanding often does not enable fully predictive promoter design, and the large number of alternative sequence possibilities can be intractable. In a synthetic promoter region with over thirty-four billion sequence variants, we identified bases correlated with favorable performance by screening only eighty-three candidates, allowing us to rationally constrain our design. We thereby generated an optimized reporter that is induced by PhoB and used it to explore the low-phosphate response of V. fischeri This promoter-design strategy will facilitate the engineering of other regulator-specific reporters. Copyright © 2018 American Society for Microbiology.

Program For Optimization Of Nuclear Rocket Engines

NASA Technical Reports Server (NTRS)

Plebuch, R. K.; Mcdougall, J. K.; Ridolphi, F.; Walton, James T.

1994-01-01

NOP is versatile digital-computer program devoloped for parametric analysis of beryllium-reflected, graphite-moderated nuclear rocket engines. Facilitates analysis of performance of engine with respect to such considerations as specific impulse, engine power, type of engine cycle, and engine-design constraints arising from complications of fuel loading and internal gradients of temperature. Predicts minimum weight for specified performance.

30 CFR 784.16 - Reclamation plan: Siltation structures, impoundments, and refuse piles.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Resources Conservation Service's Web site athttp://www.info.usda.gov/scripts/lpsiis.dll/TR/TR_210_60.htm... State program approval process engineering design standards that ensure stability comparable to a 1.3 minimum static safety factor in lieu of engineering tests to establish compliance with the minimum static...

30 CFR 780.25 - Reclamation plan: Siltation structures, impoundments, and refuse piles.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Resources Conservation Service's Web site at http://www.info.usda.gov/scripts/lpsiis.dll/TR/TR_210_60.htm... authority may establish through the State program approval process, engineering design standards that ensure stability comparable to a 1.3 minimum static safety factor in lieu of engineering tests to establish...

Science Educators Teaching Engineering Design: An Examination across Science Professional Development Sites

ERIC Educational Resources Information Center

Grubbs, Michael E.; Love, Tyler S.; Long, David E.; Kittrell, Danielle

2016-01-01

Although the currently employed STEM (science, technology, engineering, and mathematics) acronym is of recent origin, dating to the early 2000s (Chute, 2009), the United States has long emphasized the importance of teaching STEM in its public schools. Early efforts, such as "Science, the Endless Frontier" (Bush, 1945) and the…

CanSat Competition: Contributing to the Development of NASA's Vision for Robotic Space Exploration

NASA Technical Reports Server (NTRS)

Berman, Joshua; Berman, Timothy; Billheimer, Thomas; Biclmer. Elizabeth; Hood, Stuart; Neas, Charles

2007-01-01

CanSat is an international student design-build-launch competition organized by the American Astronautical Society (AAS) and American Institute of Aeronautics and Astronautics (AIAA). The competition is also sponsored by the Naval Research Laboratory (NRL) and the National Aeronautics and Space Administration (NASA). The CanSat competition is designed for college, university and high school students wanting to participate in an applicable space-related competition. The objective of the CanSat competition is to complete space exploration missions by designing a specific system for a small sounding rocket payload which will follow and perform to a specific set of rules and guidelines for each year's competition. The competition encompasses a complete life-cycle of one year which includes all phases of design, integration, testing, judging and competition. The mission guidelines are based from space exploration missions and include bonus requirement options which teams may choose to participate in. The fundamental goal of the competition is to educate future engineers and scientists. This is accomplished by students applying systems engineering practices to a development project that incorporates an end-to-end life cycle, from requirements analysis, through preliminary design, integration and testing, an actual flight of the CanSat, and concluding with a post-mission debrief. This is done specifically with space related missions to bring a unique aspect of engineering and design to the competition. The competition has been progressing since its creation in 2005. The competition was originally meant to purely convey the engineering and design process to its participants, but through many experiences the competition has also undergone a learning experience with respect to systems engineering process and design. According

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.

Photoreactive elastin-like proteins for use as versatile bioactive materials and surface coatings

PubMed Central

Raphel, Jordan; Parisi-Amon, Andreina; Heilshorn, Sarah

2012-01-01

Photocrosslinkable, protein-engineered biomaterials combine a rapid, controllable, cytocompatible crosslinking method with a modular design strategy to create a new family of bioactive materials. These materials have a wide range of biomedical applications, including the development of bioactive implant coatings, drug delivery vehicles, and tissue engineering scaffolds. We present the successful functionalization of a bioactive elastin-like protein with photoreactive diazirine moieties. Scalable synthesis is achieved using a standard recombinant protein expression host followed by site-specific modification of lysine residues with a heterobifunctional N-hydroxysuccinimide ester-diazirine crosslinker. The resulting biomaterial is demonstrated to be processable by spin coating, drop casting, soft lithographic patterning, and mold casting to fabricate a variety of two- and three-dimensional photocrosslinked biomaterials with length scales spanning the nanometer to millimeter range. Protein thin films proved to be highly stable over a three-week period. Cell-adhesive functional domains incorporated into the engineered protein materials were shown to remain active post-photo-processing. Human adipose-derived stem cells achieved faster rates of cell adhesion and larger spread areas on thin films of the engineered protein compared to control substrates. The ease and scalability of material production, processing versatility, and modular bioactive functionality make this recombinantly engineered protein an ideal candidate for the development of novel biomaterial coatings, films, and scaffolds. PMID:23015764

Photoreactive elastin-like proteins for use as versatile bioactive materials and surface coatings.

PubMed

Raphel, Jordan; Parisi-Amon, Andreina; Heilshorn, Sarah

2012-10-07

Photocrosslinkable, protein-engineered biomaterials combine a rapid, controllable, cytocompatible crosslinking method with a modular design strategy to create a new family of bioactive materials. These materials have a wide range of biomedical applications, including the development of bioactive implant coatings, drug delivery vehicles, and tissue engineering scaffolds. We present the successful functionalization of a bioactive elastin-like protein with photoreactive diazirine moieties. Scalable synthesis is achieved using a standard recombinant protein expression host followed by site-specific modification of lysine residues with a heterobifunctional N-hydroxysuccinimide ester-diazirine crosslinker. The resulting biomaterial is demonstrated to be processable by spin coating, drop casting, soft lithographic patterning, and mold casting to fabricate a variety of two- and three-dimensional photocrosslinked biomaterials with length scales spanning the nanometer to millimeter range. Protein thin films proved to be highly stable over a three-week period. Cell-adhesive functional domains incorporated into the engineered protein materials were shown to remain active post-photo-processing. Human adipose-derived stem cells achieved faster rates of cell adhesion and larger spread areas on thin films of the engineered protein compared to control substrates. The ease and scalability of material production, processing versatility, and modular bioactive functionality make this recombinantly engineered protein an ideal candidate for the development of novel biomaterial coatings, films, and scaffolds.

Programmable RNA recognition and cleavage by CRISPR/Cas9.

PubMed

O'Connell, Mitchell R; Oakes, Benjamin L; Sternberg, Samuel H; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A

2014-12-11

The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms, but it has been thought to be incapable of targeting RNA. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags.

Programmable RNA recognition and cleavage by CRISPR/Cas9

PubMed Central

O’Connell, Mitchell R.; Oakes, Benjamin L.; Sternberg, Samuel H.; East-Seletsky, Alexandra; Kaplan, Matias; Doudna, Jennifer A.

2014-01-01

The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA:DNA complementarity to identify target sites for sequence-specific doublestranded DNA (dsDNA) cleavage1-5. In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, the protospacer adjacent motif (PAM), next to and on the strand opposite the 20-nucleotide target site in dsDNA4-7. Cas9 has proven to be a versatile tool for genome engineering and gene regulation in many cell types and organisms8, but it has been thought to be incapable of targeting RNA5. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in trans as a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalyzed DNA cleavage7. Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous mRNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable and tagless transcript recognition. PMID:25274302

Quantifying Construction Site Sediment Discharge Risk and Treatment Potential

NASA Astrophysics Data System (ADS)

Ferrell, L.; Beighley, R. E.

2006-12-01

Dealing with soil erosion and sediment transport can be a significant challenge during the construction process due to the potentially large spatial and temporal extent and conditions of bare soils. Best Management Practices (BMP) are commonly used to eliminate or reduce offsite discharge of sediment. However, few efforts have investigated the time varying risk of sediment discharge from construction sites, which often have dynamic soil conditions and the potential for less than optimal BMP installations. The goal of this research is to improve the design, implementation and effectiveness of sediment and erosion control at construction sites using site specific, temporal distributions of sediment discharge risk. Sediment risk is determined from individual factors leading to sediment expert, such as rainfall frequency, the adequacy of BMP installations, and the extent and duration of bare soil conditions. This research specifically focuses on quantifying: (a) the effectiveness of temporary sediment and control erosion control BMPs in preventing, containing, and/or treating construction site sediment discharge at varying levels of "proper" installation, and (b) sediment discharge potential from construction sites during different phases of construction, (ex., disturbed earth operations). BMPs are evaluated at selected construction sites in southern California and at the Soil Erosion Research Laboratory (SERL) in the Civil and Environmental Engineering department at San Diego State University. SERL experiments are performed on a 3-m by 10-m tilting soil bed with soil depths up to 1 meter, slopes ranging from 0 to 50 percent, and rainfall rates up to 150 mm/hr (6 in/hr). BMP performance is assessed based on experiments where BMPs are installed per manufacture specifications, potential less than optimal installations, and no treatment conditions. Soil conditions are also varied to represent site conditions during different phases of construction (i.e., loose lifts, stock piles, temporary roads, finished grade, others). Preliminary site monitoring, experimental results, and a conceptual model for estimating the time depend risk of sediment discharge over the duration of a construction project are presented.

40 CFR 1042.205 - Application requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

...'s specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel fuel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1042.205 - Application requirements.

Code of Federal Regulations, 2014 CFR

2014-07-01

...'s specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel fuel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1042.205 - Application requirements.

Code of Federal Regulations, 2011 CFR

2011-07-01

...'s specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel fuel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1042.205 - Application requirements.

Code of Federal Regulations, 2012 CFR

2012-07-01

...'s specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel fuel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

40 CFR 1042.205 - Application requirements.

Code of Federal Regulations, 2013 CFR

2013-07-01

...'s specifications and other basic parameters of the engine's design and emission controls. List the fuel type on which your engines are designed to operate (for example, ultra low-sulfur diesel fuel... or modulate the same parameter. Describe whether the strategies interact in a comparative or additive...

The morphological development of newly inundated intertidal areas: the mechanisms driving the early evolution of an estuarine environment designed and constructed by humans

NASA Astrophysics Data System (ADS)

Dale, Jonathan; Burgess, Heidi; Cundy, Andrew

2017-04-01

Intertidal saltmarsh and mudflat habitats are of global importance due to the ecosystem, economic and cultural services they provide. These services include wildlife habitat provision and species diversity, immobilisation of pollutants and protection from coastal flooding. Saltmarsh and mudflat environments are, however, being lost and degraded due to erosion caused by rising sea levels and increased storminess. These losses are exacerbated by anthropogenic influences including land reclamation, increased coastal development and the construction of coastal flood defences which prevent the landwards migration of saltmarsh and mudflat environments, resulting in coastal squeeze. To compensate for saltmarsh and mudflat losses areas of the coastal hinterland are being inundated by breaching defences and constructing new defences inland, thus extending or constructing new estuarine environments; a processes known as de-embankment or managed realignment. Morphological engineering and landscaping within managed realignment sites prior to site inundation varies depending on the aims of the scheme. However, there is a shortage of data on the morphological evolution within these sites post site inundation impeding the ability of coastal engineers to effectively design and construct future sites. To date there has been a focus on the colonisation of marine macro fauna and flora within newly inundated managed realignment sites, which can be relatively rapid and easily quantified. Little is known of the morphological evolution in response to altered sedimentary processes, its driving mechanisms and therefore the success and ecological sustainability of these sites. This study evaluates the post-inundation morphological development of the largest open coast managed realignment site in Europe, at Medmerry on the south coast of the United Kingdom. Inundated in September 2013, the Medmerry Managed Realignment Site consists of a mosaic of former agricultural land and areas of lower elevation excavated during site construction, drained by a series of natural and engineered channels. Results indicate different rates and patterns of sedimentation and resulting morphology across the site. Near the breach continuous sedimentation of > 15cm over a 1 year period was measured, compared to rhythmic periods of accretion and erosion inland. These variations have been related to site design, former land-use and different sediment sources. The evolution of developing creek networks, formed by pluvial action and sediment "piping", are controlled by unconformities found in the sub-surface sediment related to Holocene site evolution. Analysis of the sedimentary processes and subsequent morphological development of these areas provides a new insight into coastal and estuarine evolution in an anthropogenically designed and constructed estuarine environment.

Integration of a NASA faculty fellowship project within an undergraduate engineering capstone design class

NASA Astrophysics Data System (ADS)

Carmen, C.

2012-11-01

The United States (US) National Aeronautics and Space Administration (NASA) Exploration Systems Mission Directorate (ESMD) provides university faculty fellowships that prepare the faculty to implement engineering design class projects that possess the potential to contribute to NASA ESMD objectives. The goal of the ESMD is to develop new capabilities, support technologies and research that will enable sustained and affordable human and robotic space exploration. In order to create a workforce that will have the desire and skills necessary to achieve these goals, the NASA ESMD faculty fellowship program enables university faculty to work on specific projects at a NASA field center and then implement the project within their capstone engineering design class. This allows the senior - or final year - undergraduate engineering design students, the opportunity to develop critical design experience using methods and design tools specified within NASA's Systems Engineering (SE) Handbook. The faculty fellowship projects focus upon four specific areas critical to the future of space exploration: spacecraft, propulsion, lunar and planetary surface systems and ground operations. As the result of a 2010 fellowship, whereby faculty research was conducted at Marshall Space Flight Center (MSFC) in Huntsville, Alabama (AL), senior design students in the Mechanical and Aerospace Engineering (MAE) department at the University of Alabama in Huntsville (UAH) had the opportunity to complete senior design projects that pertained to current work conducted to support ESMD objectives. Specifically, the UAH MAE students utilized X-TOOLSS (eXploration Toolset for the Optimization Of Launch and Space Systems), an Evolutionary Computing (EC) design optimization software, as well as design, analyze, fabricate and test a lunar regolith burrowing device - referred to as the Lunar Wormbot (LW) - that is aimed at exploring and retrieving samples of lunar regolith. These two projects were implemented during the 2010-2011 academic year at UAH and have proven to significantly motivate and enhance the students understanding of the design, development and optimization of space systems. The current paper provides an overview of the NASA ESMD faculty fellowship program, the 2010 fellowship projects, a detailed description of the means of integrating the X-TOOLSS and LW projects within the UAH MAE senior design class, the MAE student design project results, as well as the learning outcome and impact of the ESMD project had upon the engineering students.

A 2.5 kW advanced technology ion thruster

NASA Technical Reports Server (NTRS)

Poeschel, R. L.

1974-01-01

A program has been conducted in order to improve the performance characteristics of 30 cm thrusters. This program was divided into three distinct, but related tasks: (1) the discharge chamber and component design modifications proposed for inclusion in the engineering model thruster were evaluated and engineering specifications were verified; (2) thrust losses which result from the contributions of double charged ions and nonaxial ion trajectories to the ion beam current were measured and (3) the specification and verification of power processor and control requirements of the engineering model thruster design were demonstrated. Proven design modifications which provide improved efficiencies are incorporated into the engineering model thruster during a structural re-design without introducing additional delay in schedule or new risks. In addition, a considerable amount of data is generated on the relation of double ion production and beam divergence to thruster parameters. Overall thruster efficiency is increased from 68% to 71% at full power, including corrections for double ion and beam divergence thrust losses.

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

Pawlowski, Alexander; Splitter, Derek A

It is well known that spark ignited engine performance and efficiency is closely coupled to fuel octane number. The present work combines historical and recent trends in spark ignition engines to build a database of engine design, performance, and fuel octane requirements over the past 80 years. The database consists of engine compression ratio, required fuel octane number, peak mean effective pressure, specific output, and combined unadjusted fuel economy for passenger vehicles and light trucks. Recent trends in engine performance, efficiency, and fuel octane number requirement were used to develop correlations of fuel octane number utilization, performance, specific output. Themore » results show that historically, engine compression ratio and specific output have been strongly coupled to fuel octane number. However, over the last 15 years the sales weighted averages of compression ratios, specific output, and fuel economy have increased, while the fuel octane number requirement has remained largely unchanged. Using the developed correlations, 10-year-out projections of engine performance, design, and fuel economy are estimated for various fuel octane numbers, both with and without turbocharging. The 10-year-out projection shows that only by keeping power neutral while using 105 RON fuel will allow the vehicle fleet to meet CAFE targets if only the engine is relied upon to decrease fuel consumption. If 98 RON fuel is used, a power neutral fleet will have to reduce vehicle weight by 5%.« less

Integrating Science and Engineering to Implement Evidence-Based Practices in Health Care Settings.

PubMed

Wu, Shinyi; Duan, Naihua; Wisdom, Jennifer P; Kravitz, Richard L; Owen, Richard R; Sullivan, J Greer; Wu, Albert W; Di Capua, Paul; Hoagwood, Kimberly Eaton

2015-09-01

Integrating two distinct and complementary paradigms, science and engineering, may produce more effective outcomes for the implementation of evidence-based practices in health care settings. Science formalizes and tests innovations, whereas engineering customizes and optimizes how the innovation is applied tailoring to accommodate local conditions. Together they may accelerate the creation of an evidence-based healthcare system that works effectively in specific health care settings. We give examples of applying engineering methods for better quality, more efficient, and safer implementation of clinical practices, medical devices, and health services systems. A specific example was applying systems engineering design that orchestrated people, process, data, decision-making, and communication through a technology application to implement evidence-based depression care among low-income patients with diabetes. We recommend that leading journals recognize the fundamental role of engineering in implementation research, to improve understanding of design elements that create a better fit between program elements and local context.

Computational characterization of DNA/peptide/nanotube self assembly for bioenergy applications

NASA Astrophysics Data System (ADS)

Ortiz, Vanessa; Araki, Ruriko; Collier, Galen

2012-02-01

Multi-enzyme pathways have become a subject of increasing interest for their role in the engineering of biomimetic systems for applications including biosensors, bioelectronics, and bioenergy. The efficiencies found in natural metabolic pathways partially arise from biomolecular self-assembly of the component enzymes in an effort to avoid transport limitations. The ultimate goal of this effort is to design and build biofuel cells with efficiencies similar to those of native systems by introducing biomimetic structures that immobilize multiple enzymes in specific orientations on a bioelectrode. To achieve site-specific immobilization, the specificity of DNA-binding domains is exploited with an approach that allows any redox enzyme to be modified to site-specifically bind to double stranded (ds) DNA while retaining activity. Because of its many desirable properties, the bioelectrode of choice is single-wall carbon nanotubes (SWNTs), but little is known about dsDNA/SWNT assembly and how this might affect the activity of the DNA-binding domains. Here we evaluate the feasibility of the proposed assembly by performing atomistic molecular dynamics simulations to look at the stability and conformations adopted by dsDNA when bound to a SWNT. We also evaluate the effects of the presence of a SWNT on the stability of the complex formed by a DNA-binding domain and DNA.

Towards Requirements in Systems Engineering for Aerospace IVHM Design

NASA Technical Reports Server (NTRS)

Saxena, Abhinav; Roychoudhury, Indranil; Lin, Wei; Goebel, Kai

2013-01-01

Health management (HM) technologies have been employed for safety critical system for decades, but a coherent systematic process to integrate HM into the system design is not yet clear. Consequently, in most cases, health management resorts to be an after-thought or 'band-aid' solution. Moreover, limited guidance exists for carrying out systems engineering (SE) on the subject of writing requirements for designs with integrated vehicle health management (IVHM). It is well accepted that requirements are key to developing a successful IVHM system right from the concept stage to development, verification, utilization, and support. However, writing requirements for systems with IVHM capability have unique challenges that require the designers to look beyond their own domains and consider the constraints and specifications of other interlinked systems. In this paper we look at various stages in the SE process and identify activities specific to IVHM design and development. More importantly, several relevant questions are posed that system engineers must address at various design and development stages. Addressing these questions should provide some guidance to systems engineers towards writing IVHM related requirements to ensure that appropriate IVHM functions are built into the system design.

Roads and Airfields I (Programed Instruction). Engineer Subcourse 64-9.

ERIC Educational Resources Information Center

Army Engineer School, Fort Belvoir, VA.

The document is a programed text for a correspondence course in the planning, construction, and maintenance of military roads and airfields. There are seven lessons: construction requirements and design criteria; road reconnaissance and site selection; airfield reconnaissance and site selection; layout procedures, construction staking, and field…

The Role of Authenticity in Design-Based Learning Environments: The Case of Engineering Education

ERIC Educational Resources Information Center

Strobel, J.; Wang, J.; Weber, N. R.; Dyehouse, M.

2013-01-01

The term "authenticity" is pervasive in the education literature in general and specifically in the design education and engineering education literature; yet, the construct is often used un-reflected and ill defined. The purpose of this paper is (1) to critically examine current conceptualizations of authenticity as principles to design learning…

A Virtual Mission Operations Center: Collaborative Environment

NASA Technical Reports Server (NTRS)

Medina, Barbara; Bussman, Marie; Obenschain, Arthur F. (Technical Monitor)

2002-01-01

The Virtual Mission Operations Center - Collaborative Environment (VMOC-CE) intent is to have a central access point for all the resources used in a collaborative mission operations environment to assist mission operators in communicating on-site and off-site in the investigation and resolution of anomalies. It is a framework that as a minimum incorporates online chat, realtime file sharing and remote application sharing components in one central location. The use of a collaborative environment in mission operations opens up the possibilities for a central framework for other project members to access and interact with mission operations staff remotely. The goal of the Virtual Mission Operations Center (VMOC) Project is to identify, develop, and infuse technology to enable mission control by on-call personnel in geographically dispersed locations. In order to achieve this goal, the following capabilities are needed: Autonomous mission control systems Automated systems to contact on-call personnel Synthesis and presentation of mission control status and history information Desktop tools for data and situation analysis Secure mechanism for remote collaboration commanding Collaborative environment for remote cooperative work The VMOC-CE is a collaborative environment that facilitates remote cooperative work. It is an application instance of the Virtual System Design Environment (VSDE), developed by NASA Goddard Space Flight Center's (GSFC) Systems Engineering Services & Advanced Concepts (SESAC) Branch. The VSDE is a web-based portal that includes a knowledge repository and collaborative environment to serve science and engineering teams in product development. It is a "one stop shop" for product design, providing users real-time access to product development data, engineering and management tools, and relevant design specifications and resources through the Internet. The initial focus of the VSDE has been to serve teams working in the early portion of the system/product lifecycle - concept development, proposal preparation, and formulation. The VMOC-CE expands the application of the VSDE into the operations portion of the system lifecycle. It will enable meaningful and real-time collaboration regardless of the geographical distribution of project team members. Team members will be able to interact in satellite operations, specifically for resolving anomalies, through access to a desktop computer and the Internet. Mission Operations Management will be able to participate and monitor up to the minute status of anomalies or other mission operations issues. In this paper we present the VMOC-CE project, system capabilities, and technologies.

Coenzyme engineering of a hyperthermophilic 6-phosphogluconate dehydrogenase from NADP + to NAD + with its application to biobatteries

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

Chen, Hui; Zhu, Zhiguang; Huang, Rui

Engineering the coenzyme specificity of redox enzymes plays an important role in metabolic engineering, synthetic biology, and biocatalysis, but it has rarely been applied to bioelectrochemistry. Here we develop a rational design strategy to change the coenzyme specificity of 6-phosphogluconate dehydrogenase (6PGDH) from a hyperthermophilic bacterium Thermotoga maritima from its natural coenzyme NADP + to NAD +. Through amino acid-sequence alignment of NADP +- and NAD +-preferred 6PGDH enzymes and computer-aided substrate-coenzyme docking, the key amino acid residues responsible for binding the phosphate group of NADP + were identified. Four mutants were obtained via site-directed mutagenesis. The best mutant N32E/R33I/T34Imore » exhibited a ~6.4 × 10 4-fold reversal of the coenzyme selectivity from NADP + to NAD +. The maximum power density and current density of the biobattery catalyzed by the mutant were 0.135 mW cm -2 and 0.255 mA cm -2, ~25% higher than those obtained from the wide-type 6PGDH-based biobattery at the room temperature. By using this 6PGDH mutant, the optimal temperature of running the biobattery was as high as 65 °C, leading to a high power density of 1.75 mW cm -2. As a result, this study demonstrates coenzyme engineering of a hyperthermophilic 6PGDH and its application to high-temperature biobatteries.« less

Coenzyme engineering of a hyperthermophilic 6-phosphogluconate dehydrogenase from NADP + to NAD + with its application to biobatteries

DOE PAGES

Chen, Hui; Zhu, Zhiguang; Huang, Rui; ...

2016-11-02

Engineering the coenzyme specificity of redox enzymes plays an important role in metabolic engineering, synthetic biology, and biocatalysis, but it has rarely been applied to bioelectrochemistry. Here we develop a rational design strategy to change the coenzyme specificity of 6-phosphogluconate dehydrogenase (6PGDH) from a hyperthermophilic bacterium Thermotoga maritima from its natural coenzyme NADP + to NAD +. Through amino acid-sequence alignment of NADP +- and NAD +-preferred 6PGDH enzymes and computer-aided substrate-coenzyme docking, the key amino acid residues responsible for binding the phosphate group of NADP + were identified. Four mutants were obtained via site-directed mutagenesis. The best mutant N32E/R33I/T34Imore » exhibited a ~6.4 × 10 4-fold reversal of the coenzyme selectivity from NADP + to NAD +. The maximum power density and current density of the biobattery catalyzed by the mutant were 0.135 mW cm -2 and 0.255 mA cm -2, ~25% higher than those obtained from the wide-type 6PGDH-based biobattery at the room temperature. By using this 6PGDH mutant, the optimal temperature of running the biobattery was as high as 65 °C, leading to a high power density of 1.75 mW cm -2. As a result, this study demonstrates coenzyme engineering of a hyperthermophilic 6PGDH and its application to high-temperature biobatteries.« less

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.

Developing a search engine for pharmacotherapeutic information that is not published in biomedical journals.

PubMed

Do Pazo-Oubiña, F; Calvo Pita, C; Puigventós Latorre, F; Periañez-Párraga, L; Ventayol Bosch, P

2011-01-01

To identify publishers of pharmacotherapeutic information not found in biomedical journals that focuses on evaluating and providing advice on medicines and to develop a search engine to access this information. Compiling web sites that publish information on the rational use of medicines and have no commercial interests. Free-access web sites in Spanish, Galician, Catalan or English. Designing a search engine using the Google "custom search" application. Overall 159 internet addresses were compiled and were classified into 9 labels. We were able to recover the information from the selected sources using a search engine, which is called "AlquimiA" and available from http://www.elcomprimido.com/FARHSD/AlquimiA.htm. The main sources of pharmacotherapeutic information not published in biomedical journals were identified. The search engine is a useful tool for searching and accessing "grey literature" on the internet. Copyright © 2010 SEFH. Published by Elsevier Espana. All rights reserved.

SLS Test Stand Site Selection

NASA Technical Reports Server (NTRS)

Crowe, Kathryn; Williams, Michael

2015-01-01

Test site selection is a critical element of the design, development and production of a new system. With the advent of the new Space Launch System (SLS), the National Aeronautics and Space Administration (NASA) had a number of test site selection decisions that needed to be made early enough in the Program to support the planned Launch Readiness Date (LRD). This case study focuses on decisions that needed to be made in 2011 and 2012 in preparation for the April 2013 DPMC decision about where to execute the Main Propulsion Test that is commonly referred to as "Green Run." Those decisions relied upon cooperative analysis between the Program, the Test Lab and Center Operations. The SLS is a human spaceflight vehicle designed to carry a crew farther into space than humans have previously flown. The vehicle consists of four parts: the crew capsule, the upper stage, the core stage, and the first stage solid rocket boosters. The crew capsule carries the astronauts, while the upper stage, the core stage, and solid rocket boosters provide thrust for the vehicle. In other words, the stages provide the "lift" part of the lift vehicle. In conjunction with the solid rocket boosters, the core stage provides the initial "get-off-the-ground" thrust to the vehicle. The ignition of the four core stage engines and two solid rocket boosters is the first step in the launch portion of the mission. The solid rocket boosters burn out after about 2 minutes of flight, and are then jettisoned. The core stage provides thrust until the vehicle reaches a specific altitude and speed, at which point the core stage is shut off and jettisoned, and the upper stage provides vehicle thrust for subsequent mission trajectories. The integrated core stage primarily consists of a liquid oxygen tank, a liquid hydrogen tank, and the four core stage engines. For the SLS program, four RS-25 engines were selected as the four core stage engines. The RS-25 engine is the same engine that was used for Space Shuttle. The test plan for the integrated core stage was broken down into several segments: Component testing, system level testing, and element level testing. In this context, components are items such as valves, controllers, sensors, etc. Systems are items such as an entire engine, a tank, or the outer stage body. The core stage itself is considered to be an element. The rocket engines are also considered an element. At the program level, it was decided to perform a single green run test on the integrated core stage prior to shipment of it to Kennedy Space Center (KSC) for use in the EM-1 test flight of the SLS vehicle. A green run test is the first live fire of the new integrated core stage and engine elements - without boosters of course. The SLS Program had to decide where to perform SLS green run testing.

Aero-acoustic performance comparison of core engine noise suppressors on NASA quiet engine 'C'

NASA Technical Reports Server (NTRS)

Bloomer, H. E.; Schaefer, J. W.

1977-01-01

The purpose of the experimental program reported herein was to evaluate and compare the relative aero-acoustic effectiveness of two core engine suppressors, a contractor-designed suppressor delivered with the Quiet Engine, and a NASA-designed suppressor, designed and built subsequently. The NASA suppressor was tested with and without a splitter making a total of three configurations being reported in addition to the baseline hardwall case. The aerodynamic results are presented in terms of tailpipe pressure loss, corrected net thrust, and corrected specific fuel consumption as functions of engine power setting. The acoustic results are divided into duct and far-field acoustic data. The NASA-designed core suppressor did the better job of suppressing aft end noise, but the splitter associated with it caused a significant engine performance penalty. The NASA core suppressor without the splitter suppressed most of the core noise without any engine performance penalty.

Reflection on Molecular Approaches Influencing State-of-the-Art Bioremediation Design: Culturing to Microbial Community Fingerprinting to Omics

PubMed Central

Czaplicki, Lauren M.; Gunsch, Claudia K.

2017-01-01

Bioremediation is generally viewed as a cost effective and sustainable technology because it relies on microbes to transform pollutants into benign compounds. Advances in molecular biological analyses allow unprecedented microbial detection and are increasingly incorporated into bioremediation. Throughout history, state-of-the-art techniques have informed bioremediation strategies. However, the insights those techniques provided were not as in depth as those provided by recently developed omics tools. Advances in next generation sequencing (NGS) have now placed metagenomics and metatranscriptomics within reach of environmental engineers. As NGS costs decrease, metagenomics and metatranscriptomics have become increasingly feasible options to rapidly scan sites for specific degradative functions and identify microorganisms important in pollutant degradation. These omic techniques are capable of revolutionizing biological treatment in environmental engineering by allowing highly sensitive characterization of previously uncultured microorganisms. Omics enables the discovery of novel microorganisms for use in bioaugmentation and supports systematic optimization of biostimulation strategies. This review describes the omics journey from roots in biology and medicine to its current status in environmental engineering including potential future directions in commercial application. PMID:28348455

Site- and strand-specific nicking of DNA by fusion proteins derived from MutH and I-SceI or TALE repeats.

PubMed

Gabsalilow, Lilia; Schierling, Benno; Friedhoff, Peter; Pingoud, Alfred; Wende, Wolfgang

2013-04-01

Targeted genome engineering requires nucleases that introduce a highly specific double-strand break in the genome that is either processed by homology-directed repair in the presence of a homologous repair template or by non-homologous end-joining (NHEJ) that usually results in insertions or deletions. The error-prone NHEJ can be efficiently suppressed by 'nickases' that produce a single-strand break rather than a double-strand break. Highly specific nickases have been produced by engineering of homing endonucleases and more recently by modifying zinc finger nucleases (ZFNs) composed of a zinc finger array and the catalytic domain of the restriction endonuclease FokI. These ZF-nickases work as heterodimers in which one subunit has a catalytically inactive FokI domain. We present two different approaches to engineer highly specific nickases; both rely on the sequence-specific nicking activity of the DNA mismatch repair endonuclease MutH which we fused to a DNA-binding module, either a catalytically inactive variant of the homing endonuclease I-SceI or the DNA-binding domain of the TALE protein AvrBs4. The fusion proteins nick strand specifically a bipartite recognition sequence consisting of the MutH and the I-SceI or TALE recognition sequences, respectively, with a more than 1000-fold preference over a stand-alone MutH site. TALE-MutH is a programmable nickase.

CRISPRdirect: software for designing CRISPR/Cas guide RNA with reduced off-target sites

PubMed Central

Naito, Yuki; Hino, Kimihiro; Bono, Hidemasa; Ui-Tei, Kumiko

2015-01-01

Summary: CRISPRdirect is a simple and functional web server for selecting rational CRISPR/Cas targets from an input sequence. The CRISPR/Cas system is a promising technique for genome engineering which allows target-specific cleavage of genomic DNA guided by Cas9 nuclease in complex with a guide RNA (gRNA), that complementarily binds to a ∼20 nt targeted sequence. The target sequence requirements are twofold. First, the 5′-NGG protospacer adjacent motif (PAM) sequence must be located adjacent to the target sequence. Second, the target sequence should be specific within the entire genome in order to avoid off-target editing. CRISPRdirect enables users to easily select rational target sequences with minimized off-target sites by performing exhaustive searches against genomic sequences. The server currently incorporates the genomic sequences of human, mouse, rat, marmoset, pig, chicken, frog, zebrafish, Ciona, fruit fly, silkworm, Caenorhabditis elegans, Arabidopsis, rice, Sorghum and budding yeast. Availability: Freely available at http://crispr.dbcls.jp/. Contact: y-naito@dbcls.rois.ac.jp Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25414360

Commercial products that convey personal health information in emergencies.

PubMed

Potini, Vishnu C; Weerasuriya, Dilani N; Lowery-North, Douglas W; Kellermann, Arthur L

2011-12-01

Describe commercially available products and services designed to convey personal health information in emergencies. The search engine Google®, supplemented by print ads, was used to identify companies and organizations that offer relevant products and services to the general market. Disease-specific, health system, and health plan-specific offerings were excluded. Vendor web sites were the primary sources of information, supplemented by telephone and e-mail queries to sales representatives. Perfect inter-rater agreement was achieved. Thirty-nine unique vendors were identified. Eight sell engraved jewelry. Three offer an embossed card or pamphlet. Twelve supply USB drives with various features. Eleven support password-protected web sites. Five maintain national call centers. Available media differed markedly with respect to capacity and accessibility. Quoted prices ranged from a one-time expenditure of $3.50 to an annual fee of $200. Associated features and annual fees varied widely. A wide range of products and services exist to help patients convey personal health information. Health care providers should be familiar with their features, so they can access the information in a disaster or emergency.

CFD in the context of IHPTET - The Integrated High Performance Turbine Engine Technology Program

NASA Technical Reports Server (NTRS)

Simoneau, Robert J.; Hudson, Dale A.

1989-01-01

The Integrated High Performance Turbine Engine Technology (IHPTET) Program is an integrated DOD/NASA technology program designed to double the performance capability of today's most advanced military turbine engines as we enter the twenty-first century. Computational Fluid Dynamics (CFD) is expected to play an important role in the design/analysis of specific configurations within this complex machine. In order to do this, a plan is being developed to ensure the timely impact of CFD on IHPTET. The developing philosophy of CFD in the context of IHPTET is discussed. The key elements in the developing plan and specific examples of state-of-the-art CFD efforts which are IHPTET turbine engine relevant are discussed.

Interdisciplinary and multilevel optimum design. [in aerospace structural engineering

NASA Technical Reports Server (NTRS)

Sobieszczanski-Sobieski, Jaroslaw; Haftka, Raphael T.

1987-01-01

Interactions among engineering disciplines and subsystems in engineering system design are surveyed and specific instances of such interactions are described. Examination of the interactions that a traditional design process in which the numerical values of major design variables are decided consecutively is likely to lead to a suboptimal design. Supporting numerical examples are a glider and a space antenna. Under an alternative approach introduced, the design and its sensitivity data from the subsystems and disciplines are generated concurrently and then made available to the system designer enabling him to modify the system design so as to improve its performance. Examples of a framework structure and an airliner wing illustrate that approach.

Molecular Structure of Photosynthetic Microbial Biofuels for Improved Engine Combustion and Emissions Characteristics

PubMed Central

Hellier, Paul; Purton, Saul; Ladommatos, Nicos

2015-01-01

The metabolic engineering of photosynthetic microbes for production of novel hydrocarbons presents an opportunity for development of advanced designer biofuels. These can be significantly more sustainable, throughout the production-to-consumption lifecycle, than the fossil fuels and crop-based biofuels they might replace. Current biofuels, such as bioethanol and fatty acid methyl esters, have been developed primarily as drop-in replacements for existing fossil fuels, based on their physical properties and autoignition characteristics under specific combustion regimes. However, advances in the genetic engineering of microalgae and cyanobacteria, and the application of synthetic biology approaches offer the potential of designer strains capable of producing hydrocarbons and oxygenates with specific molecular structures. Furthermore, these fuel molecules can be designed for higher efficiency of energy release and lower exhaust emissions during combustion. This paper presents a review of potential fuel molecules from photosynthetic microbes and the performance of these possible fuels in modern internal combustion engines, highlighting which modifications to the molecular structure of such fuels may enhance their suitability for specific combustion regimes. PMID:25941673

Molecular structure of photosynthetic microbial biofuels for improved engine combustion and emissions characteristics.

PubMed

Hellier, Paul; Purton, Saul; Ladommatos, Nicos

2015-01-01

The metabolic engineering of photosynthetic microbes for production of novel hydrocarbons presents an opportunity for development of advanced designer biofuels. These can be significantly more sustainable, throughout the production-to-consumption lifecycle, than the fossil fuels and crop-based biofuels they might replace. Current biofuels, such as bioethanol and fatty acid methyl esters, have been developed primarily as drop-in replacements for existing fossil fuels, based on their physical properties and autoignition characteristics under specific combustion regimes. However, advances in the genetic engineering of microalgae and cyanobacteria, and the application of synthetic biology approaches offer the potential of designer strains capable of producing hydrocarbons and oxygenates with specific molecular structures. Furthermore, these fuel molecules can be designed for higher efficiency of energy release and lower exhaust emissions during combustion. This paper presents a review of potential fuel molecules from photosynthetic microbes and the performance of these possible fuels in modern internal combustion engines, highlighting which modifications to the molecular structure of such fuels may enhance their suitability for specific combustion regimes.

40 CFR 92.113 - Fuel specifications.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.113 Fuel specifications. (a) Diesel test fuel. (1) The diesel fuels for testing locomotives or locomotive engines designed...) of this section shall be reported in accordance with § 92.133. (b) Natural gas test fuel (compressed...

40 CFR 92.113 - Fuel specifications.

Code of Federal Regulations, 2012 CFR

2012-07-01

...) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.113 Fuel specifications. (a) Diesel test fuel. (1) The diesel fuels for testing locomotives or locomotive engines designed... section shall be reported in accordance with § 92.133. (b) Natural gas test fuel (compressed natural gas...

40 CFR 92.113 - Fuel specifications.

Code of Federal Regulations, 2014 CFR

2014-07-01

...) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.113 Fuel specifications. (a) Diesel test fuel. (1) The diesel fuels for testing locomotives or locomotive engines designed... section shall be reported in accordance with § 92.133. (b) Natural gas test fuel (compressed natural gas...

40 CFR 92.113 - Fuel specifications.

Code of Federal Regulations, 2013 CFR

2013-07-01

...) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.113 Fuel specifications. (a) Diesel test fuel. (1) The diesel fuels for testing locomotives or locomotive engines designed... section shall be reported in accordance with § 92.133. (b) Natural gas test fuel (compressed natural gas...

40 CFR 92.113 - Fuel specifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) CONTROL OF AIR POLLUTION FROM LOCOMOTIVES AND LOCOMOTIVE ENGINES Test Procedures § 92.113 Fuel specifications. (a) Diesel test fuel. (1) The diesel fuels for testing locomotives or locomotive engines designed...) of this section shall be reported in accordance with § 92.133. (b) Natural gas test fuel (compressed...

40 CFR 89.129 - Right of entry.

Code of Federal Regulations, 2010 CFR

2010-07-01

... inspect and make copies of any such records, designs, or other documents; and (3) To inspect and... construction thereof. (c) To allow the Administrator to determine whether production engines conform in all material respects to the design specifications applicable to those engines, as described in the application...

46 CFR 162.050-33 - Bilge alarm: Design specification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 6 2010-10-01 2010-10-01 false Bilge alarm: Design specification. 162.050-33 Section 162.050-33 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) EQUIPMENT, CONSTRUCTION, AND MATERIALS: SPECIFICATIONS AND APPROVAL ENGINEERING EQUIPMENT Pollution Prevention Equipment § 162...

Earthquake ground motion: Chapter 3

USGS Publications Warehouse

Luco, Nicolas; Kircher, Charles A.; Crouse, C. B.; Charney, Finley; Haselton, Curt B.; Baker, Jack W.; Zimmerman, Reid; Hooper, John D.; McVitty, William; Taylor, Andy

2016-01-01

Most of the effort in seismic design of buildings and other structures is focused on structural design. This chapter addresses another key aspect of the design process—characterization of earthquake ground motion into parameters for use in design. Section 3.1 describes the basis of the earthquake ground motion maps in the Provisions and in ASCE 7 (the Standard). Section 3.2 has examples for the determination of ground motion parameters and spectra for use in design. Section 3.3 describes site-specific ground motion requirements and provides example site-specific design and MCER response spectra and example values of site-specific ground motion parameters. Section 3.4 discusses and provides an example for the selection and scaling of ground motion records for use in various types of response history analysis permitted in the Standard.

Design study of an air pump and integral lift engine ALF-504 using the Lycoming 502 core

NASA Technical Reports Server (NTRS)

Rauch, D.

1972-01-01

Design studies were conducted for an integral lift fan engine utilizing the Lycoming 502 fan core with the final MQT power turbine. The fan is designed for a 12.5 bypass ratio and 1.25:1 pressure ratio, and provides supercharging for the core. Maximum sea level static thrust is 8370 pounds with a specific fuel consumption of 0.302 lb/hr-lb. The dry engine weight without starter is 1419 pounds including full-length duct and sound-attenuating rings. The engine envelope including duct treatment but not localized accessory protrusion is 53.25 inches in diameter and 59.2 inches long from exhaust nozzle exit to fan inlet flange. Detailed analyses include fan aerodynamics, fan and reduction gear mechanical design, fan dynamic analysis, engine noise analysis, engine performance, and weight analysis.

Instructional design considerations promoting engineering design self-efficacy

NASA Astrophysics Data System (ADS)

Jackson, Andrew M.

Engineering design activities are frequently included in technology and engineering classrooms. These activities provide an open-ended context for practicing critical thinking, problem solving, creativity, and innovation---collectively part of the 21st Century Skills which are increasingly needed for success in the workplace. Self-efficacy is a perceptual belief that impacts learning and behavior. It has been shown to directly impact each of these 21st Century Skills but its relation to engineering design is only recently being studied. The purpose of this study was to examine how instructional considerations made when implementing engineering design activities might affect student self-efficacy outcomes in a middle school engineering classroom. Student responses to two self-efficacy inventories related to design, the Engineering Design Self-Efficacy Instrument and Creative Thinking Self-Efficacy Inventory, were collected before and after participation in an engineering design curriculum. Students were also answered questions on specific factors of their experience during the curriculum which teachers may exhibit control over: teamwork and feedback. Results were analyzed using Pearson's correlation coefficients, paired and independent t-tests, and structural equation modeling to better understand patterns for self-efficacy beliefs in students. Results suggested that design self-efficacy and creative thinking self-efficacy are significantly correlated, r(1541) = .783, p < .001, and increased following participation in a design curriculum, M diff = 1.32, t(133) = 7.60, p < .001 and Mdiff = 0.79, t(124) = 4.19, p < .001 respectively. Structural models also showed that students perceive team inclusion and feedback as significant contributors to their self-efficacy beliefs, while team diversity was not related to self-efficacy. Separate models for each predictor demonstrated good fit. Recommendations are made based on the corresponding nature of engineering design self-efficacy and creative thinking self-efficacy: strategies encouraging self-efficacy in these domains may be transferrable. Instructors are made aware of the significant impact of classroom strategies for increasing self-efficacy and given specific recommendations related to teamwork and feedback to support students. Finally, although there were weaknesses in the study related to the survey administration, future research opportunities are presented which may build from this work.

Stabilization of bacterially expressed erythropoietin by single site-specific introduction of short branched PEG chains at naturally occurring glycosylation sites.

PubMed

Hoffmann, E; Streichert, K; Nischan, N; Seitz, C; Brunner, T; Schwagerus, S; Hackenberger, C P R; Rubini, M

2016-05-24

The covalent attachment of polyethylene glycol (PEG) to therapeutic proteins can improve their physicochemical properties. In this work we utilized the non-natural amino acid p-azidophenylalanine (pAzF) in combination with the chemoselective Staudinger-phosphite reaction to install branched PEG chains to recombinant unglycosylated erythropoietin (EPO) at each single naturally occurring glycosylation site. PEGylation with two short 750 or 2000 Da PEG units at positions 24, 38, or 83 significantly decreased unspecific aggregation and proteolytic degradation while biological activity in vitro was preserved or even increased in comparison to full-glycosylated EPO. This site-specific bioconjugation approach permits to analyse the impact of PEGylation at single positions. These results represent an important step towards the engineering of site-specifically modified EPO variants from bacterial expression with increased therapeutic efficacy.

Development, Application, and Implementation of RAMCAP to Characterize Nuclear Power Plant Risk From Terrorism

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

Gaertner, John P.; Teagarden, Grant A.

2006-07-01

In response to increased interest in risk-informed decision making regarding terrorism, EPRI and ERIN Engineering were selected by U.S. DHS and ASME to develop and demonstrate the RAMCAP method for nuclear power plant (NPP) risk assessment. The objective is to characterize plant-specific NPP risk for risk management opportunities and to provide consistent information for DHS decision making. This paper is an update of this project presented at the American Nuclear Society (ANS) International Topical Meeting on Probabilistic Safety Analysis (PSA05) in September, 2005. The method uses a characterization of risk as a function of Consequence, Vulnerability, and Threat. For eachmore » site, worst case scenarios are developed for each of sixteen benchmark threats. Nuclear RAMCAP hypothesizes that the intent of the perpetrator is to cause offsite radiological consequences. Specific targets are the reactor core, the spent fuel pool, and nuclear spent fuel in a dry storage facility (ISFSI). Results for each scenario are presented as conditional risk for financial loss, early fatalities and early injuries. Expected consequences for each scenario are quantified, while vulnerability is estimated on a relative likelihood scale. Insights for other societal risks are provided. Although threat frequencies are not provided, target attractiveness and threat deterrence are estimated. To assure efficiency, completeness, and consistency; results are documented using standard RAMCAP Evaluator software. Trial applications were successfully performed at four plant sites. Implementation at all other U.S. commercial sites is underway, supported by the Nuclear Sector Coordinating Council (NSCC). Insights from RAMCAP results at 23 U.S. plants completed to date have been compiled and presented to the NSCC. Results are site-specific. Physical security barriers, an armed security force, preparedness for design-basis threats, rugged design against natural hazards, multiple barriers between fuel and environment, accident mitigation capability, severe accident management procedures, and offsite emergency plans are risk-beneficial against all threat types. (authors)« less

Structural, kinetic, and thermodynamic studies of specificity designed HIV-1 protease.

PubMed

Alvizo, Oscar; Mittal, Seema; Mayo, Stephen L; Schiffer, Celia A

2012-07-01

HIV-1 protease recognizes and cleaves more than 12 different substrates leading to viral maturation. While these substrates share no conserved motif, they are specifically selected for and cleaved by protease during viral life cycle. Drug resistant mutations evolve within the protease that compromise inhibitor binding but allow the continued recognition of all these substrates. While the substrate envelope defines a general shape for substrate recognition, successfully predicting the determinants of substrate binding specificity would provide additional insights into the mechanism of altered molecular recognition in resistant proteases. We designed a variant of HIV protease with altered specificity using positive computational design methods and validated the design using X-ray crystallography and enzyme biochemistry. The engineered variant, Pr3 (A28S/D30F/G48R), was designed to preferentially bind to one out of three of HIV protease's natural substrates; RT-RH over p2-NC and CA-p2. In kinetic assays, RT-RH binding specificity for Pr3 increased threefold compared to the wild-type (WT), which was further confirmed by isothermal titration calorimetry. Crystal structures of WT protease and the designed variant in complex with RT-RH, CA-p2, and p2-NC were determined. Structural analysis of the designed complexes revealed that one of the engineered substitutions (G48R) potentially stabilized heterogeneous flap conformations, thereby facilitating alternate modes of substrate binding. Our results demonstrate that while substrate specificity could be engineered in HIV protease, the structural pliability of protease restricted the propagation of interactions as predicted. These results offer new insights into the plasticity and structural determinants of substrate binding specificity of the HIV-1 protease. Copyright © 2012 The Protein Society.

HYNOL PROCESS ENGINEERING: PROCESS CONFIGURATION, SITE PLAN, AND EQUIPMENT DESIGN

EPA Science Inventory

The report describes the design of the hydropyrolysis reactor system of the Hynol process. (NOTE: A bench scale methanol production facility is being constructed to demonstrate the technical feasibility of producing methanol from biomass using the Hynol process. The plant is bein...

A Biophysical Model of CRISPR/Cas9 Activity for Rational Design of Genome Editing and Gene Regulation

PubMed Central

Farasat, Iman; Salis, Howard M.

2016-01-01

The ability to precisely modify genomes and regulate specific genes will greatly accelerate several medical and engineering applications. The CRISPR/Cas9 (Type II) system binds and cuts DNA using guide RNAs, though the variables that control its on-target and off-target activity remain poorly characterized. Here, we develop and parameterize a system-wide biophysical model of Cas9-based genome editing and gene regulation to predict how changing guide RNA sequences, DNA superhelical densities, Cas9 and crRNA expression levels, organisms and growth conditions, and experimental conditions collectively control the dynamics of dCas9-based binding and Cas9-based cleavage at all DNA sites with both canonical and non-canonical PAMs. We combine statistical thermodynamics and kinetics to model Cas9:crRNA complex formation, diffusion, site selection, reversible R-loop formation, and cleavage, using large amounts of structural, biochemical, expression, and next-generation sequencing data to determine kinetic parameters and develop free energy models. Our results identify DNA supercoiling as a novel mechanism controlling Cas9 binding. Using the model, we predict Cas9 off-target binding frequencies across the lambdaphage and human genomes, and explain why Cas9’s off-target activity can be so high. With this improved understanding, we propose several rules for designing experiments for minimizing off-target activity. We also discuss the implications for engineering dCas9-based genetic circuits. PMID:26824432

Tolerance design of patient-specific range QA using the DMAIC framework in proton therapy.

PubMed

Rah, Jeong-Eun; Shin, Dongho; Manger, Ryan P; Kim, Tae Hyun; Oh, Do Hoon; Kim, Dae Yong; Kim, Gwe-Ya

2018-02-01

To implement the DMAIC (Define-Measure-Analyze-Improve-Control) can be used for customizing the patient-specific QA by designing site-specific range tolerances. The DMAIC framework (process flow diagram, cause and effect, Pareto chart, control chart, and capability analysis) were utilized to determine the steps that need focus for improving the patient-specific QA. The patient-specific range QA plans were selected according to seven treatment site groups, a total of 1437 cases. The process capability index, C pm was used to guide the tolerance design of patient site-specific range. For prostate field, our results suggested that the patient range measurements were capable at the current tolerance level of ±1 mm in clinical proton plans. For other site-specific ranges, we analyzed that the tolerance tends to be overdesigned to insufficient process capability calculated by the patient-specific QA data. The customized tolerances were calculated for treatment sites. Control charts were constructed to simulate the patient QA time before and after the new tolerances were implemented. It is found that the total simulation QA time was decreased on average of approximately 20% after establishing new site-specific range tolerances. We simulated the financial impact of this project. The QA failure for whole process in proton therapy would lead up to approximately 30% increase in total cost. DMAIC framework can be used to provide an effective QA by setting customized tolerances. When tolerance design is customized, the quality is reasonably balanced with time and cost demands. © 2017 American Association of Physicists in Medicine.

Optimization of scaffold design for bone tissue engineering: A computational and experimental study.

PubMed

Dias, Marta R; Guedes, José M; Flanagan, Colleen L; Hollister, Scott J; Fernandes, Paulo R

2014-04-01

In bone tissue engineering, the scaffold has not only to allow the diffusion of cells, nutrients and oxygen but also provide adequate mechanical support. One way to ensure the scaffold has the right properties is to use computational tools to design such a scaffold coupled with additive manufacturing to build the scaffolds to the resulting optimized design specifications. In this study a topology optimization algorithm is proposed as a technique to design scaffolds that meet specific requirements for mass transport and mechanical load bearing. Several micro-structures obtained computationally are presented. Designed scaffolds were then built using selective laser sintering and the actual features of the fabricated scaffolds were measured and compared to the designed values. It was possible to obtain scaffolds with an internal geometry that reasonably matched the computational design (within 14% of porosity target, 40% for strut size and 55% for throat size in the building direction and 15% for strut size and 17% for throat size perpendicular to the building direction). These results support the use of these kind of computational algorithms to design optimized scaffolds with specific target properties and confirm the value of these techniques for bone tissue engineering. Copyright © 2014 IPEM. Published by Elsevier Ltd. All rights reserved.

Advanced Control Considerations for Turbofan Engine Design

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Csank, Jeffrey T.; Chicatelli, Amy

2016-01-01

This paper covers the application of a model-based engine control (MBEC) methodology featuring a self tuning on-board model for an aircraft turbofan engine simulation. The nonlinear engine model is capable of modeling realistic engine performance, allowing for a verification of the advanced control methodology over a wide range of operating points and life cycle conditions. The on-board model is a piece-wise linear model derived from the nonlinear engine model and updated using an optimal tuner Kalman Filter estimation routine, which enables the on-board model to self-tune to account for engine performance variations. MBEC is used here to show how advanced control architectures can improve efficiency during the design phase of a turbofan engine by reducing conservative operability margins. The operability margins that can be reduced, such as stall margin, can expand the engine design space and offer potential for efficiency improvements. Application of MBEC architecture to a nonlinear engine simulation is shown to reduce the thrust specific fuel consumption by approximately 1% over the baseline design, while maintaining safe operation of the engine across the flight envelope.

Toward intracellular targeted delivery of cancer therapeutics: progress and clinical outlook for brain tumor therapy.

PubMed

Pandya, Hetal; Debinski, Waldemar

2012-08-01

A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells.

Toward Intracellular Targeted Delivery of Cancer Therapeutics

PubMed Central

Pandya, Hetal; Debinski, Waldemar

2013-01-01

A number of anti-cancer drugs have their targets localized to particular intracellular compartments. These drugs reach the targets mainly through diffusion, dependent on biophysical and biochemical forces that allow cell penetration. This means that both cancer cells and normal cells will be subjected to such diffusion; hence many of these drugs, like chemotherapeutics, are potentially toxic and the concentration achieved at the site of their action is often suboptimal. The same relates to radiation that indiscriminately affects normal and diseased cells. However, nature-designed systems enable compounds present in the extracellular environment to end up inside the cell and even travel to more specific intracellular compartments. For example, viruses and bacterial toxins can more or less specifically recognize eukaryotic cells, enter these cells, and direct some protein portions to designated intracellular areas. These phenomena have led to creative thinking, such as employing viruses or bacterial toxins for cargo delivery to cells and, more specifically, to cancer cells. Proteins can be genetically engineered in order to not only mimic what viruses and bacterial toxins can do, but also to add new functions, extending or changing the intracellular routes. It is possible to make conjugates or, more preferably, single-chain proteins that recognize cancer cells and deliver cargo inside the cells, even to the desired subcellular compartment. These findings offer new opportunities to deliver drugs/labels only to cancer cells and only to their site of action within the cells. The development of such dual-specificity vectors for targeting cancer cells is an attractive and potentially safer and more efficacious way of delivering drugs. We provide examples of this approach for delivering brain cancer therapeutics, using a specific biomarker on glioblastoma tumor cells. PMID:22671766

Test results of the Chrysler upgraded automotive gas turbine engine: Initial design

NASA Technical Reports Server (NTRS)

Horvath, D.; Ribble, G. H., Jr.; Warren, E. L.; Wood, J. C.

1981-01-01

The upgraded engine as built to the original design was deficient in power and had excessive specific fuel consumption. A high instrumented version of the engine was tested to identify the sources of the engine problems. Analysis of the data shows the major problems to be low compressor and power turbine efficiency and excessive interstage duct losses. In addition, high HC and CO emission were measured at idle, and high NOx emissions at high energy speeds.

Cell mediated therapeutics for cancer treatment: Tumor homing cells as therapeutic delivery vehicles

NASA Astrophysics Data System (ADS)

Balivada, Sivasai

Many cell types were known to have migratory properties towards tumors and different research groups have shown reliable results regarding cells as delivery vehicles of therapeutics for targeted cancer treatment. Present report discusses proof of concept for 1. Cell mediated delivery of Magnetic nanoparticles (MNPs) and targeted Magnetic hyperthermia (MHT) as a cancer treatment by using in vivo mouse cancer models, 2. Cells surface engineering with chimeric proteins for targeted cancer treatment by using in vitro models. 1. Tumor homing cells can carry MNPs specifically to the tumor site and tumor burden will decrease after alternating magnetic field (AMF) exposure. To test this hypothesis, first we loaded Fe/Fe3O4 bi-magnetic NPs into neural progenitor cells (NPCs), which were previously shown to migrate towards melanoma tumors. We observed that NPCs loaded with MNPs travel to subcutaneous melanoma tumors. After alternating magnetic field (AMF) exposure, the targeted delivery of MNPs by the NPCs resulted in a mild decrease in tumor size (Chapter-2). Monocytes/macrophages (Mo/Ma) are known to infiltrate tumor sites, and also have phagocytic activity which can increase their uptake of MNPs. To test Mo/Ma-mediated MHT we transplanted Mo/Ma loaded with MNPs into a mouse model of pancreatic peritoneal carcinomatosis. We observed that MNP-loaded Mo/Ma infiltrated pancreatic tumors and, after AMF treatment, significantly prolonged the lives of mice bearing disseminated intraperitoneal pancreatic tumors (Chapter-3). 2. Targeted cancer treatment could be achieved by engineering tumor homing cell surfaces with tumor proteases cleavable, cancer cell specific recombinant therapeutic proteins. To test this, Urokinase and Calpain (tumor specific proteases) cleavable; prostate cancer cell (CaP) specific (CaP1 targeting peptide); apoptosis inducible (Caspase3 V266ED3)- rCasp3V266ED3 chimeric protein was designed in silico. Hypothesized membrane anchored chimeric protein (rCasp3V266ED3, rMcherry red) plasmids were constructed. Membrane anchoring and activity of designed proteins were analyzed in RAW264.7 Mo/Ma and HEK293 cells in vitro. Further, Urokinase (uPA) mediated cleavage and release of rCasp3V266ED3 from engineered cells was tested (Chapter-4). Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments. Final chapter of present report shows evidence for immune-deficient line of pigs as a model for human cancers (Chapter-5)

Study, optimization, and design of a laser heat engine. [for satellite applications

NASA Technical Reports Server (NTRS)

Taussig, R. T.; Cassady, P. E.; Zumdieck, J. F.

1978-01-01

Laser heat engine concepts, proposed for satellite applications, are analyzed to determine which engine concept best meets the requirements of high efficiency (50 percent or better), continuous operation in space using near-term technology. The analysis of laser heat engines includes the thermodynamic cycles, engine design, laser power sources, collector/concentrator optics, receiving windows, absorbers, working fluids, electricity generation, and heat rejection. Specific engine concepts, optimized according to thermal efficiency, are rated by their technological availability and scaling to higher powers. A near-term experimental demonstration of the laser heat engine concept appears feasible utilizing an Otto cycle powered by CO2 laser radiation coupled into the engine through a diamond window. Higher cycle temperatures, higher efficiencies, and scalability to larger sizes appear to be achievable from a laser heat engine design based on the Brayton cycle and powered by a CO laser.

Design variables for mechanical properties of bone tissue scaffolds.

PubMed

Howk, Daniel; Chu, Tien-Min G

2006-01-01

The reconstruction of segmental defect in long bone is a clinical challenge. Multiple surgeries are typically required to restore the structure and function of the affected defect site. In order to overcome this defect a biodegradable bone tissue engineering scaffold is used. This scaffold acts as a carrier of proteins and growth factors, while also supporting the load that the bone would normally sustain, until the natural bone can regenerate in its place. Work was done to optimize an existing solid free-form scaffold design. The goal of the optimization was to increase the porosity of the scaffold while maintaining the strength of a previously-tested prototype design. With this in mind, eight new designs were created. These designs were drawn using CAD software and then through the use of finite element analysis the theoretical ultimate compressive strength of each design was obtained. Each scaffold design was constructed by casting a thermal-curable poly(propylene fumarate)/tricalcium phosphate (PPF/TCP) suspension into wax molds fabricated on inkjet printing rapid prototyping machine. The constructs were then experimentally tested by applying a uniaxial compressive load. The theoretical and experimental values of ultimate compressive strength and specific strength of each design were compared. Theoretically, the best scaffold design produced from this work improved upon the current design by increasing the porosity by 46% and also increasing the ultimate compressive strength by 27%. The experimental data was found to match the theoretical strength in four designs, but deviate from the theoretical strength in five designs. The reasons for the deviations and their relation to the rapid prototyping manufacturing technique were discussed. The results of this work show that it is possible to increase the porosity and strength of a bone tissue engineering scaffold through simple iterations in architectural design.

Automated software development workstation

NASA Technical Reports Server (NTRS)

Prouty, Dale A.; Klahr, Philip

1988-01-01

A workstation is being developed that provides a computational environment for all NASA engineers across application boundaries, which automates reuse of existing NASA software and designs, and efficiently and effectively allows new programs and/or designs to be developed, catalogued, and reused. The generic workstation is made domain specific by specialization of the user interface, capturing engineering design expertise for the domain, and by constructing/using a library of pertinent information. The incorporation of software reusability principles and expert system technology into this workstation provide the obvious benefits of increased productivity, improved software use and design reliability, and enhanced engineering quality by bringing engineering to higher levels of abstraction based on a well tested and classified library.

Integrating computer programs for engineering analysis and design

NASA Technical Reports Server (NTRS)

Wilhite, A. W.; Crisp, V. K.; Johnson, S. C.

1983-01-01

The design of a third-generation system for integrating computer programs for engineering and design has been developed for the Aerospace Vehicle Interactive Design (AVID) system. This system consists of an engineering data management system, program interface software, a user interface, and a geometry system. A relational information system (ARIS) was developed specifically for the computer-aided engineering system. It is used for a repository of design data that are communicated between analysis programs, for a dictionary that describes these design data, for a directory that describes the analysis programs, and for other system functions. A method is described for interfacing independent analysis programs into a loosely-coupled design system. This method emphasizes an interactive extension of analysis techniques and manipulation of design data. Also, integrity mechanisms exist to maintain database correctness for multidisciplinary design tasks by an individual or a team of specialists. Finally, a prototype user interface program has been developed to aid in system utilization.

Design of an Oxygen Turbopump for a Dual Expander Cycle Rocket Engine

DTIC Science & Technology

2008-03-01

Scharrer, Tellier , and Hibbs mentioned several applications where this bearing design choice benefits the overall engine performance, specifically in...Hydrostatic Bearings, AIAA-92-3401. 27 Scharrer, J.K., Tellier , J.G., and Hibbs, R.I., Start Transient Testing of an Annular Hydrostatic Bearing in Liquid

Design, fabrication, and test of a trace contaminant control system. Appendixes A and B

NASA Technical Reports Server (NTRS)

1975-01-01

Engineering specifications of a trace contaminant control system designed for the Space Station Prototype (SSP) were given. These were divided into two appendices: (1) a list of nonmetallic materials used, and (2) engineering drawings of the overall system, sub-assemblies, and components.

TEACHING ENGINEERING DESIGN, A STUDY OF JOBSHOP.

ERIC Educational Resources Information Center

ENTWISLE, DORIS R.; HUGGINS, W.H.

THE USE OF A COMPUTER PROGRAM BY ENGINEERING STUDENTS TO SIMULATE A JOB SHOP THAT MANUFACTURES ELECTRONIC DEVICES HAS INDICATED THAT SIMULATION METHODS OFFER REALISTIC ASSISTANCE IN TEACHING. EACH STUDENT IN THE STUDY SUBMITTED SPECIFICATIONS FOR A CIRCUIT DESIGN AND, FROM THE COMPUTER, RECEIVED PERFORMANCE ASSESSMENTS OF THE CIRCUIT WHICH…

Successful Programs for Undergraduate Women in Science and Engineering: "Adapting" versus "Adopting" the Institutional Environment

ERIC Educational Resources Information Center

Fox, Mary Frank; Sonnert, Gerhard; Nikiforova, Irina

2009-01-01

This article focuses upon programs for undergraduate women in science and engineering, which are a strategic research site in the study of gender, science, and higher education. The design involves both quantitative and qualitative approaches, linking theory, method, questions, and analyses in ways not undertaken previously. Using a comprehensive,…

22 CFR 121.1 - General. The United States Munitions List.

Code of Federal Regulations, 2012 CFR

2012-04-01

... specifically designed or modified for the articles in this category: * (1) Guidance and control components for... controls of the ITAR. (f) Developmental aircraft, engines, and components thereof specifically designed... (including propellers) designed exclusively for civil, non-military aircraft (see § 121.3 of this subchapter...

22 CFR 121.1 - General. The United States Munitions List.

Code of Federal Regulations, 2013 CFR

2013-04-01

... specifically designed or modified for the articles in this category: * (1) Guidance and control components for... controls of the ITAR. (f) Developmental aircraft, engines, and components thereof specifically designed... (including propellers) designed exclusively for civil, non-military aircraft (see § 121.3 of this subchapter...

40 CFR Appendix A to Subpart I of... - Determination of Allowable Costs

Code of Federal Regulations, 2013 CFR

2013-07-01

... built in conformance with the design drawings and specifications. f. The costs (including legal... from defects in the plans, design drawings and specifications, or other subagreement documents only to... of architectural or engineering services incurred in preparing a facilities plan and the design...

40 CFR Appendix A to Subpart I of... - Determination of Allowable Costs

Code of Federal Regulations, 2014 CFR

2014-07-01

... built in conformance with the design drawings and specifications. f. The costs (including legal... from defects in the plans, design drawings and specifications, or other subagreement documents only to... of architectural or engineering services incurred in preparing a facilities plan and the design...

Data Validation in the AEDC Engine Test Facility

DTIC Science & Technology

2010-02-01

25 3.4.1 Pretest ...25 3.4.2 Test Period .............................................................................................. 26 3.4.3 Posttest ...use of the data is to assess the degree to which the engine meets its design intent or its specification requirements. When engine development or