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Morphologic and mechanical characteristics of engineered bovine arteries.

OBJECTIVE: The ideal small-caliber arterial graft remains elusive despite several decades of intense research. A novel approach to the development of small-caliber arterial prostheses with a biomimetic system for in vitro vessel culture has recently been described. In this study we examined the effects of culture time and tissue culture scaffolding on engineered vessel morphology and function and found that these parameters greatly influence the function of engineered vessels. METHODS: This report describes the effects of culture time and scaffold type on vessel morphology, cellular differentiation, and vessel mechanical characteristics. Engineered vessels were cultured from bovine aortic smooth muscle cells (SMCs) and endothelial cells that were seeded onto biodegradable polymer scaffolds and cultured under physiologically pulsatile conditions. Engineered vessels were subjected to histologic, ultrastructural, immunocytochemical, and mechanical analyses. RESULTS: Vessel morphology and mechanical characteristics improved as time in culture increased to 8 weeks. SMCs in the engineered vessel wall were organized into a highly lamellar structure, with cells separated by alternating layers of collagen fibrils. Polymer scaffold remnants were present in vessels cultured for 8 weeks, and SMCs that were in proximity to polymer remnants exhibited a dedifferentiated phenotype. CONCLUSIONS: These findings aid in the systematic understanding of the effects of in vitro parameters on engineered vessels and will be useful for the translation of vessel culture techniques to human cells for the development of autologous human vascular grafts.

Animals↗

A fuel-based assessment of off-road diesel engine emissions.

The use of diesel engines in off-road applications is a significant source of nitrogen oxides (NOx) and particulate matter (PM10). Such off-road applications include railroad locomotives, marine vessels, and equipment used for agriculture, construction, logging, and mining. Emissions from these sources are only beginning to be controlled. Due to the large number of these engines and their wide range of applications, total activity and emissions from these sources are uncertain. A method for estimating the emissions from off-road diesel engines based on the quantity of diesel fuel consumed is presented. Emission factors are normalized by fuel consumption, and total activity is estimated by the total fuel consumed. Total exhaust emissions from off-road diesel equipment (excluding locomotives and marine vessels) in the United States during 1996 have been estimated to be 1.2 x 10(9) kg NOx and 1.2 x 10(8) kg PM10. Emissions estimates published by the U.S. Environmental Protection Agency are 2.3 times higher for both NOx and exhaust PM10 emissions than estimates based directly on fuel consumption. These emissions estimates disagree mainly due to differences in activity estimates, rather than to differences in the emission factors. All current emission inventories for off-road engines are uncertain because of the limited in-use emissions testing that has been performed on these engines. Regional- and state-level breakdowns in diesel fuel consumption by off-road mobile sources are also presented. Taken together with on-road measurements of diesel engine emissions, results of this study suggest that in 1996, off-road diesel equipment (including agriculture, construction, logging, and mining equipment, but not locomotives or marine vessels) was responsible for 10% of mobile source NOx emissions nationally, whereas on-road diesel vehicles contributed 33%.

Air Pollutants, Occupational↗

Vocational rehabilitation of locomotive engineers with ischaemic heart disease.

BACKGROUND: There is resistance among railway companies and their occupational health services to rehabilitating locomotive engineers with ischaemic heart disease to their former driving work. AIM: To study the outcome of vocational rehabilitation for locomotive engineers with ischaemic heart disease. METHODS: In seven European countries, selected locomotive engineers with ischaemic heart disease were compared to a matched group of healthy engineers. At the end of each calendar year between 1990 and 1999, questionnaires were completed by local occupational health physicians to provide information on accidents, incidents (professional mistakes), sick leave, (recurrent) cardiac events, death and early retirement. We used the life table method with five follow-up years to calculate the risk of accidents, incidents and recurrent cardiac events. RESULTS: The accident rate for the cardiac group was 3.8 accidents per 100 person-years, as compared to a rate of 6.0 in the reference group. The rates for incidents were 0.9 and 2.0, respectively. Neither of these differences were statistically significant. The duration of sick leave was significantly longer among the cardiac group than it was among the reference group, but only in the first follow-up year. Thirteen recurrent cardiac events occurred in the cardiac group, as compared to a single cardiac event in the reference group. There was no difference in the proportion of retirement cases. One engineer in each of the two groups died of cardiac disease. CONCLUSIONS: Locomotive engineers can safely resume driving duties following onset of cardiac disease.

Accidents↗

Performance of discrete heat engines and heat pumps in finite time

The performance in finite time of a discrete heat engine with internal friction is analyzed. The working fluid of the engine is composed of an ensemble of noninteracting two level systems. External work is applied by changing the external field and thus the internal energy levels. The friction induces a minimal cycle time. The power output of the engine is optimized with respect to time allocation between the contact time with the hot and cold baths as well as the adiabats. The engine's performance is also optimized with respect to the external fields. By reversing the cycle of operation a heat pump is constructed. The performance of the engine as a heat pump is also optimized. By varying the time allocation between the adiabats and the contact time with the reservoir a universal behavior can be identified. The optimal performance of the engine when the cold bath is approaching absolute zero is studied. It is found that the optimal cooling rate converges linearly to zero when the temperature approaches absolute zero.

Journal Article↗

Characteristics of the limit cycle of a reciprocating quantum heat engine.

After starting a reciprocating heat engine it eventually settles to a stable mode of operation. A first principle quantum heat engine also approaches this stable limit cycle. The studied engine is based on a working medium consisting of an ensemble of quantum systems composed of two coupled spins. A four-stroke cycle of operation is studied, with two isochore branches where heat is transferred from the hot/cold baths and two adiabats where work is exchanged. The dynamics is generated by a completely positive map. It has been shown that the performance of this model resembles an engine with intrinsic friction. The quantum conditional entropy is employed to prove the monotonic approach to a limit cycle. Other convex measures such as the quantum distance display the same monotonic approach. The equations of motion of the engine are solved for the different branches and are combined to a global propagator that relates the state of the engine in the beginning of the cycle to the state after one period of operation of the cycle. The eigenvalues of the propagator define the rate of relaxation toward the limit cycle. A longitudinal and transverse mode of approach to the limit cycle is thus identified. The entropy balance is used to explore the necessary conditions which lead to a stable limit cycle. The phenomena of friction can be identified with a zero change in the von Neumann entropy of the working medium.

Journal Article↗

Leadership processes for re-engineering changes to the health care industry.

As health care organizations seek innovative ways to change financing and delivery mechanisms due to escalated health care costs and increased competition, drastic changes are being sought in the form of re-engineering. This study discusses the leader's role of re-engineering in health care. It specifically addresses the reasons for failures in re-engineering and argues that success depends on senior level leaders playing a critical role. Existing studies lack comprehensiveness in establishing models of re-engineering and management guidelines. This research focuses on integrating re-engineering and leadership processes in health care by creating a step-by-step model. Particularly, it illustrates the four Es: Examination, Establishment, Execution and Evaluation, as a comprehensive re-engineering process that combines managerial roles and activities to result in successfully changed and reengineered health care organizations.

Delivery of Health Care↗

A thermoacoustic-Stirling heat engine: detailed study

A new type of thermoacoustic engine based on traveling waves and ideally reversible heat transfer is described. Measurements and analysis of its performance are presented. This new engine outperforms previous thermoacoustic engines, which are based on standing waves and intrinsically irreversible heat transfer, by more than 50%. At its most efficient operating point, it delivers 710 W of acoustic power to its resonator with a thermal efficiency of 0.30, corresponding to 41% of the Carnot efficiency. At its most powerful operating point, it delivers 890 W to its resonator with a thermal efficiency of 0.22. The efficiency of this engine can be degraded by two types of acoustic streaming. These are suppressed by appropriate tapering of crucial surfaces in the engine and by using additional nonlinearity to induce an opposing time-averaged pressure difference. Data are presented which show the nearly complete elimination of the streaming convective heat loads. Analysis of these and other irreversibilities show which components of the engine require further research to achieve higher efficiency. Additionally, these data show that the dynamics and acoustic power flows are well understood, but the details of the streaming suppression and associated heat convection are only qualitatively understood.

Journal Article↗

Genetically Engineered Erwinia carotovora in Aquatic Microcosms: Survival and Effects on Functional Groups of Indigenous Bacteria.

The survival of genetically engineered Erwinia carotovora L-864, with a kanamycin resistance gene inserted in its chromosome, was monitored in the water and sediment of aquatic microcosms. The density of genetically engineered and wild-type E. carotovora strains declined at the same rate, falling in 32 days below the level of detection by viable counts. We examined the impact of the addition of genetically engineered and wild-type strains on indigenous bacteria belonging to specific functional groups important in nutrient cycling. For up to 16 days, the densities of total and proteolytic bacteria were significantly higher (P < 0.05) in microcosms inoculated with genetically engineered or wild-type E. carotovora, but by 32 days after inoculation, they had decreased to densities similar to those in control microcosms. Inoculation of genetically engineered or wild-type E. carotovora had no apparent effect on the density of amylolytic and pectolytic bacteria in water and sediment. Genetically engineered and wild-type E. carotovora did not have significantly different effects on the densities of specific functional groups of indigenous bacteria (P > 0.05).

Journal Article↗

Genetically Engineered Erwinia carotovora: Survival, Intraspecific Competition, and Effects upon Selected Bacterial Genera.

Environmental use of genetically engineered microorganisms has raised concerns about potential ecological impact. This research evaluated the survival, competitiveness, and effects upon selected bacterial genera of wild-type and genetically engineered Erwinia carotovora subsp. carotovora to ascertain if differences between the wild-type and genetically engineered strains exist in soil microcosms. The engineered strain contained a chromosomally inserted gene for kanamycin resistance. No significant differences in survival in nonsterile soil over 2 months or in the competitiveness of either strain were observed when the strains were added concurrently to microcosms. For reasons that remain unclear, the engineered strain did survive longer in sterilized soil. The effects of both strains on total bacteria, Pseudomonas and Staphylococcus strains, and actinomycetes were observed. While some apparent differences were observed, they were not statistically significant. A better understanding of the microbial ecology of engineered bacteria, especially pathogens genetically altered for use as biological control agents, is essential before commercial applications can be accomplished.

Journal Article↗

Systematic mapping of insertion-tolerant regions enables capsid engineering of an infectious RNA phage.

RNA phages are attractive platforms for the design of programmable bioparticles, but their development has been constrained by limited knowledge of genomic sites that can tolerate sequence insertion. Here, we combined MuA transposase-mediated in vitro insertion mutagenesis with our established reverse genetics systems to systematically identify insertion-tolerant regions (ITRs) in the RNA phages MS2 and PP7. Screening of 4,555 MS2 and 2,228 PP7 random insertion clones identified 29 and 26 non-redundant ITRs, respectively. We further analyzed and compared these ITRs in the context of RNA genome organization and virion architecture. Both phages contained ITRs within the maturation protein, whereas only PP7 tolerated insertions within the coat protein (CP). On the basis of structural location and plaque-forming capacity, an ITR situated between Gly74 and Glu75 (GGC^GAG) in the PP7 CP was selected for further study. Infectious phage particles generated from complementary DNA clones retained the 15-bp insertion at both the RNA and protein levels. Engineered PP7 phages carrying an Arg-Gly-Asp motif inserted into the CP at this ITR displayed enhanced in vivo clearance in a Drosophila model, despite having in vitro stability comparable to that of the wild type. These findings provide the first example of CP engineering in an infectious RNA phage and establish a framework for engineering RNA phages for biological and biotechnological applications.IMPORTANCEA major obstacle to developing RNA phages as synthetic biology platforms is the lack of design principles for genomic insertion. Here, we address this limitation by establishing a mutagenesis-and-recovery workflow that systematically identifies insertion-tolerant regions (ITRs) in the RNA phages MS2 and PP7. The resulting maps reveal distinct structural constraints in the two phages and enable rational engineering of a peptide-display site in the PP7 capsid. Using this approach, we generated an engineered infectious phage with a modified capsid, thereby providing the first demonstration of capsid engineering in an infectious RNA phage, to our knowledge. This study lays the groundwork for the rational design of live RNA phage virions as tractable and engineerable scaffolds for future biological and biotechnological applications.

Animals↗

Comparative study of the use of poly(glycolic acid), calcium alginate and pluronics in the engineering of autologous porcine cartilage.

New cartilage formation has been successfully achieved by technology referred to as tissue engineering. Polymers and hydrogels such as poly(glycolic acid), calcium alginate, and poly(ethylene) and poly(propylene) hydrogels have been used as cell carriers to regenerate cartilage in the nude mouse model. The next step toward human applications of engineered cartilage is to demonstrate their potential in immunocompetent animal models. This study compared the suitability of three polymers for generating tissue engineered elastic cartilage using autologous cells in an immuno-competent porcine animal model. Auricular cartilage was obtained from pigs. Chondrocytes were isolated onto fiber based poly(glycolic acid) (PGA) scaffolds or suspended in calcium alginate or pluronic F127 gel at constant concentrations. Chondrocyte-polymer constructs were either implanted (PGA) or injected (calcium alginate and pluronic) as autologous implants subcutaneously into the pigs from which the cells had been isolated. Specimens were harvested and analyzed grossly and historically after 6 weeks in vivo. All explants demonstrated cartilage formation to a variable degree. When using PGA or calcium alginate, the overall histological appearance of the tissue formed is that of fibrocartilage with thick bundles of collagen dispersed in the tissue. When using pluronics as scaffold, histologic features resemble those of native elastic cartilage, showing a more organized arrangement of the cells, which seems to correlate to functional properties as elastin presence in the tissue engineered cartilage. Elastic cartilage engineered in an immunocompetent animal model varies with the type of polymer used. The behavior of the cell-polymer constructs is not fully understood and outcome seems to be related to several factors, including inflammatory reaction. Further studies with similar models are needed to determine the feasibility of engineering tissue generated from different cell-polymer constructs prior to human application.

Alginates↗

Teen smoking cessation help via the Internet: a survey of search engines.

The objective of this study was to assess Web sites related to teen smoking cessation on the Internet. Seven Internet search engines were searched using the keywords teen quit smoking. The top 20 hits from each search engine were reviewed and categorized. The keywords teen quit smoking produced between 35 and 400,000 hits depending on the search engine. Of 140 potential hits, 62% were active, unique sites; 85% were listed by only one search engine; and 40% focused on cessation. Findings suggest that legitimate on-line smoking cessation help for teens is constrained by search engine choice and the amount of time teens spend looking through potential sites. Resource listings should be updated regularly. Smoking cessation Web sites need to be picked up on multiple search engine searches. Further evaluation of smoking cessation Web sites need to be conducted to identify the most effective help for teens.

Adolescent↗

Metabolic engineering of microbes for oligosaccharide and polysaccharide synthesis.

Metabolic engineering has recently been embraced as an effective tool for developing whole-cell biocatalysts for oligosaccharide and polysaccharide synthesis. Microbial catalysts now provide a practical means to derive many valuable oligosaccharides, previously inaccessible through other methods, in sufficient quantities to support research and clinical applications. The synthesis process based upon these microbes is scalable as it avoids expensive starting materials. Most impressive is the high product concentrations (up to 188 g/L) achieved through microbe-catalyzed synthesis. The overall cost for selected molecules has been brought to a reasonable range (estimated $30-50/g). Microbial synthesis of oligosaccharides and polysaccharides is a carbon-intensive and energy-intensive process, presenting some unique challenges in metabolic engineering. Unlike nicotinamide cofactors, the required sugar nucleotides are products of multiple interacting pathways, adding significant complexity to the metabolic engineering effort. Besides the challenge of providing the necessary mammalian-originated glycosyltransferases in active form, an adequate uptake of sugar acceptors can be an issue when another sugar is necessary as a carbon and energy source. These challenges are analyzed, and various strategies used to overcome these difficulties are reviewed in this article. Despite the impressive success of the microbial coupling strategy, there is a need to develop a single strain that can achieve at least the same efficiency. Host selection and the manner with which the synthesis interacts with the central metabolism are two important factors in the design of microbial catalysts. Additionally, unlike in vitro enzymatic synthesis, product degradation and byproduct formation are challenges of whole-cell systems that require additional engineering. A systematic approach that accounts for various and often conflicting requirements of the synthesis holds the key to deriving an efficient catalyst. Metabolic engineering strategies applied to selected polysaccharides (hyaluronan, alginate, and exopolysaccharides for food use) are reviewed in this article to highlight the recent progress in this area and similarity to challenges in oligosaccharide synthesis. Many naturally occurring microbes possess highly efficient mechanisms for polysaccharide synthesis. These mechanisms could potentially be engineered into a microbe for oligosaccharide and polysaccharide synthesis with enhanced efficiency.

Journal Article↗

Spatial confidentiality and GIS: re-engineering mortality locations from published maps about Hurricane Katrina.

BACKGROUND: Geographic Information Systems (GIS) can provide valuable insight into patterns of human activity. Online spatial display applications, such as Google Earth, can democratise this information by disseminating it to the general public. Although this is a generally positive advance for society, there is a legitimate concern involving the disclosure of confidential information through spatial display. Although guidelines exist for aggregated data, little has been written concerning the display of point level information. The concern is that a map containing points representing cases of cancer or an infectious disease, could be re-engineered back to identify an actual residence. This risk is investigated using point mortality locations from Hurricane Katrina re-engineered from a map published in the Baton Rouge Advocate newspaper, and a field team validating these residences using search and rescue building markings. RESULTS: We show that the residence of an individual, visualized as a generalized point covering approximately one and half city blocks on a map, can be re-engineered back to identify the actual house location, or at least a close neighbour, even if the map contains little spatial reference information. The degree of re-engineering success is also shown to depend on the urban characteristic of the neighborhood. CONCLUSION: The results in this paper suggest a need to re-evaluate current guidelines for the display of point (address level) data. Examples of other point maps displaying health data extracted from the academic literature are presented where a similar re-engineering approach might cause concern with respect to violating confidentiality. More research is also needed into the role urban structure plays in the accuracy of re-engineering. We suggest that health and spatial scientists should be proactive and suggest a series of point level spatial confidentiality guidelines before governmental decisions are made which may be reactionary toward the threat of revealing confidential information, thereby imposing draconian limits on research using a GIS.

Confidentiality↗

JNER: a forum to discuss how neuroscience and biomedical engineering are reshaping physical medicine & rehabilitation.

Advances in neuroscience and biomedical engineering deeply affect the clinical practice of physical medicine & rehabilitation. New research findings and engineering tools are continuously made available that have the potential of dramatically enhancing the ability of clinicians to design effective rehabilitation interventions. This quickly evolving research field is difficult to track because related literature appears in a wide range of scientific journals. There is a need for a scientific journal that offers to its readership a forum at the intersection of neuroscience, biomedical engineering, and physical medicine & rehabilitation. The Journal of NeuroEngineering and Rehabilitation (JNER) is intended to fill this gap and foster cross-fertilizations among these disciplines. By making readily available to clinicians selected studies with potential impact on physical medicine & rehabilitation, JNER is anticipated to foster the development of novel and more effective rehabilitation strategies. Conversely, by presenting clinical problems to a readership of neuroscientists and engineers, JNER is expected to generate innovative work in neuroscience and biomedical engineering with future applications to physical medicine & rehabilitation. JNER will leverage on Open Access as a means to guarantee that its content is readily available to scientists, clinicians, and the general public thus promoting scientific and technological advances that are relevant to rehabilitation. JNER is an Open Access initiative. Open Access assures dissemination to the widest possible audience and is seen by many as essential for publicly funded research. BioMed Central offers an outstanding platform to make JNER possible and allow neuroscientists, biomedical engineers, and clinicians to see their work published in a timely manner and thus make an immediate impact in the field of rehabilitation. JNER will focus on innovative work with higher likelihood of a dramatic impact on rehabilitation. Thus, priority will be given to outstanding and visionary scientific reports, i.e. those proposing exceptionally innovative concepts with great potential in the field.

Journal Article↗

Using Internet search engines to estimate word frequency.

The present research investigated Internet search engines as a rapid, cost-effective alternative for estimating word frequencies. Frequency estimates for 382 words were obtained and compared across four methods: (1) Internet search engines, (2) the Kucera and Francis (1967) analysis of a traditional linguistic corpus, (3) the CELEX English linguistic database (Baayen, Piepenbrock, & Gulikers, 1995), and (4) participant ratings of familiarity. The results showed that Internet search engines produced frequency estimates that were highly consistent with those reported by Kucera and Francis and those calculated from CELEX, highly consistent across search engines, and very reliable over a 6-month period of time. Additional results suggested that Internet search engines are an excellent option when traditional word frequency analyses do not contain the necessary data (e.g., estimates for forenames and slang). In contrast, participants' familiarity judgments did not correspond well with the more objective estimates of word frequency. Researchers are advised to use search engines with large databases (e.g., AltaVista) to ensure the greatest representativeness of the frequency estimates.

Databases, Factual↗

Architecture for a multipurpose guideline execution engine.

Integration of guideline knowledge into the clinical workflow is essential, for improving adherence to guidelines. Guidelines in structured formats can be utilized by computer programs to provide decision support in clinical information systems, as well as to facilitate workflow. We have designed an architecture for a flexible guideline execution engine that can be utilized in clinical decision support applications. The engine may be utilized for other applications such as referral management, medical education, and conducting clinical trials. The engine executes guidelines that are defined in an extension of the Guideline Interchange Format (GLIF). GLIF was extended to support representation of constructs that are essential to the execution of the guideline. A prototype of the engine was implemented based on this architecture. The engine is being utilized in two clinical applications that draw on guidelines for decision support. The engine was also used for developing an educational application aimed at testing knowledge of guideline recommendations.

Computer Systems↗

An overview of NASA ISS human engineering and habitability: past, present, and future.

The International Space Station (ISS) is the first major NASA project to provide human engineering an equal system engineering an equal system engineering status to other disciplines. The incorporation and verification of hundreds of human engineering requirements applied across-the-board to the ISS has provided for a notably more habitable environment to support long duration spaceflight missions than might otherwise have been the case. As the ISS begins to be inhabited and become operational, much work remains in monitoring the effectiveness of the Station's built environment in supporting the range of activities required of a long-duration vehicle. With international partner participation, NASA's ISS Operational Habitability Assessment intends to carry human engineering and habitability considerations into the next phase of the ISS Program with constant attention to opportunities for cost-effective improvements that need to be and can be made to the on-orbit facility. Too, during its operations the ISS must be effectively used as an on-orbit laboratory to promote and expand human engineering/habitability awareness and knowledge to support the international space faring community with the data needed to develop future space vehicles for long-duration missions. As future space mission duration increases, the rise in importance of habitation issues make it imperative that lessons are captured from the experience of human engineering's incorporation into the ISS Program and applied to future NASA programmatic processes.

Equipment Design↗