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PubMed2000

The Huygens entrainment phenomenon and thermoacoustic engines

The earliest known reference to the mode-locking, or entrainment, of two maintained oscillators is Christiaan Huygens' description of two pendulum clocks "falling into synchrony" when hung on the same wall. We describe an analogous phenomenon in acoustics-the mode-locking of two thermoacoustic engines which have their cases rigidly welded together, but which are otherwise uncoupled. This "mass-coupling" might compete with acoustic coupling when the latter is used to enforce antiphase mode-locking in such engines, for vibration cancellation. A simple theory relating the phase difference between the engines in the locked state to the corresponding ratio of their pressure amplitudes is in excellent agreement with theory and numerical simulations. The theory's prediction relating the phase difference to the engines' natural frequency difference is qualitatively confirmed by experiment, despite larger experimental uncertainties. The mass coupling is relatively weak compared to the aforementioned acoustic coupling, and in general occurs in antiphase, so we conclude that mass coupling will not interfere with vibration cancellation by acoustic coupling in most circumstances.

Journal Article↗

PubMed2002

Thermal barrier coatings for gas-turbine engine applications.

Hundreds of different types of coatings are used to protect a variety of structural engineering materials from corrosion, wear, and erosion, and to provide lubrication and thermal insulation. Of all these, thermal barrier coatings (TBCs) have the most complex structure and must operate in the most demanding high-temperature environment of aircraft and industrial gas-turbine engines. TBCs, which comprise metal and ceramic multilayers, insulate turbine and combustor engine components from the hot gas stream, and improve the durability and energy efficiency of these engines. Improvements in TBCs will require a better understanding of the complex changes in their structure and properties that occur under operating conditions that lead to their failure. The structure, properties, and failure mechanisms of TBCs are herein reviewed, together with a discussion of current limitations and future opportunities.

Journal Article↗

PubMed2005

Improved effector functions of a therapeutic monoclonal Lewis Y-specific antibody by glycoform engineering.

The aim of the present study was to produce glycosylation variants of the therapeutic Lewis Y-specific humanized IgG1 antibody IGN311 to enhance cell-killing effector function. This was achieved via genetic engineering of the glycosylation machinery of the antibody-producing host. Antibody genes were transiently cotransfected with acetyl-glycosaminyltransferase-III genes into human embryonic kidney-EBV nuclear antigen cells. A control wild-type antibody, IGN311wt, was expressed in the same host using identical expression vectors, but without cotransfection of genes for acetyl-glycosaminyltransferase-III expression. Both expression products were purified to homogeneity and characterized. The glyco-engineered expression product (IGN312-Glyco-I) showed a remarkably homogenous N-linked glycosylation pattern consisting of one major hybrid-type, non-fucosylated and agalactosylated form carrying a bisecting GlcNAc-group. Wild-type expression product (IGN311wt) on the other hand was glycosylated by a multitude of different core-fucosylated complex-type structures of variable degrees of galactosylation. Target affinity of the glyco-engineered antibody as well as heavy and light chain assembly were not affected by acetyl-glycosaminyltransferase-III expression. In vitro experiments showed a approximately 10-fold increase of antibody-dependent cellular cytotoxicity of the glyco-engineered antibody using different Lewis Y-positive target cancer cell lines (SK-BR-3, SK-BR-5, OVCAR-3, and Kato-III). Complement-mediated cytotoxicity of IGN312-Glyco-I was 0.4-fold reduced using SK-BR-5 as target cell line. The reduction of complement activation could be prevented and even converted into a slight increase of activity by using a different molecular-biological approach directing the glycosylation towards increased levels of complex N-linked oligosaccharides of bisected, non-fucosylated type, as a result of cotransfection of mannosidase II together with acetyl-glycosaminyltransferase-III.

Antibodies, Monoclonal↗

PubMed2005

Induction of T-cell apoptosis in rats by genetically engineered glioma cells expressing granulocyte-macrophage colony-stimulating factor and B7.1.

PURPOSE: To evaluate antitumor effects on intracerebral gliomas of genetically engineered tumor vaccines expressing granulocyte-macrophage colony-timulating factor (GM-CSF), B7.1, or both (combination). EXPERIMENTAL DESIGN: A rat glioma cell line, RT-2, was engineered with a retroviral vector to express GM-CSF, B7.1, or combination. Tumorigenicity of engineered cells and therapeutic effects of s.c. given irradiated or live tumor vaccines on parental intracerebral gliomas were studied. Immune cell infiltration induced at vaccine and tumor sites was examined by histologic and immunohistochemical staining. Apoptosis of T cells from vaccine sites was analyzed with fluorescence-activated cell sorting. RESULTS: Engineered RT-2 cells exhibited reduced s.c. tumorigenicity in rats with reduced tumor growth and prolonged animal survival time compared with control rats. Rats with intracerebral gliomas s.c. treated with irradiated or live GM-CSF-expressing vaccines had 60% and 100% survival rates, respectively, significantly better than the control groups (P < 0.05). In contrast, rats treated with vaccines expressing B7.1 or the combination had no or mild therapeutic effects. Studies revealed less T-cell infiltration at both vaccine and tumor sites in rats treated with vaccines expressing B7.1 or the combination than in rats treated with a vaccine expressing GM-CSF. Cell sorting analyses revealed higher proportions of apoptotic T cells at vaccine sites of rats treated with the combination than those treated with vaccine expressing GM-CSF. CONCLUSIONS: Combination of GM-CSF- and B7.1-expressing tumor vaccines exerted no synergistic, or even worse, therapeutic effects on gliomas compared with single GM-CSF-secreting tumor vaccine. The worse therapeutic effects of the GM-B7.1-expressing tumor vaccine than the GM-CSF-expressing tumor vaccine were related to the reduced T-cell amount and increased T-cell apoptosis in the former.

Animals↗

PubMed2000

Tissue engineering of pulmonary heart valves on allogenic acellular matrix conduits: in vivo restoration of valve tissue.

BACKGROUND: Tissue engineering using in vitro-cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. METHODS AND RESULTS: Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (alpha-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. CONCLUSIONS: The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

Animals↗

PubMedDate not supplied

Fusion hybrid of dendritic cells and engineered tumor cells expressing interleukin-12 induces type 1 immune responses against tumor.

AIMS AND BACKGROUND: Dendritic cell (DC)-tumor fusion hybrid vaccinees that facilitate antigen presentation represent a novel powerful strategy in cancer immunotherapy. Preclinical studies have demonstrated that IL-12 promotes specific antitumor immunity mediated by T cells in several types of tumors. In the present study, we investigated the antitumor immunity derived from vaccination of fusion hybrids between DCs and engineered J558/IL-12 myeloma cells secreting Th1 cytokine IL-12. METHODS: The expression vector pcDNA-IL-12 was generated and transfected into J558 myeloma cells and then bone marrow-derived DCs were fused with engineered J558/IL-12 cells. The antitumor immunity derived from vaccination of the fusion hybrid DC/J558/IL-12 was evaluated in vitro and in vivo. RESULTS: DC/J558/IL-12 cells secreted recombinant IL-12 (1.6 ng/mL), and inoculation of BALB/c mice with DC/J558/IL-12 hybrid induced a Th1 dominant immune response and resulted in tumor regression. Immunization of mice with engineered DC/J558/IL-12 hybrid elicited stronger J558 tumor-specific cytotoxic T lymphocyte (CTL) responses in vitro as well as more potent protective immunity against J558 tumor challenge in vivo than immunization with the mixture of DCs and J558/IL-12, J558/IL-12 and J558, respectively. Furthermore, the anti-tumor immunity mediated by DC/J558/IL-12 tumor cell vaccination in vivo appeared to be dependent on CD8+ CTL. CONCLUSIONS: These results demonstrate that the engineered fusion hybrid vaccines that combine Th1 cytokine gene-modified tumor cells with DCs may be an attractive strategy for cancer immunotherapy.

Animals↗

PubMedDate not supplied

Medical error and human factors engineering: where are we now?

The goal of human factors engineering is to optimize the relationship between humans and systems by studying human behavior, abilities, and limitations and using this knowledge to design systems for safe and effective human use. With the assumption that the human component of any system will inevitably produce errors, human factors engineers design systems and human/machine interfaces that are robust enough to reduce error rates and the effect of the inevitable error within the system. In this article, we review the extent and nature of medical error and then discuss human factors engineering tools that have potential applicability. These tools include taxonomies of human and system error and error data collection and analysis methods. Finally, we describe studies that have examined medical error, and on the basis of these studies, present conclusions about how human factors engineering can significantly reduce medical errors and their effects.

Ergonomics↗

PubMed2000

Somatic risk factors for myocardial infarction among Swedish railway engine drivers.

BACKGROUND: Previous studies have indicated an increased incidence of myocardial infarction among railway engine drivers. OBJECTIVE: To analyse whether somatic risk factors for myocardial infarction among male drivers in different geographical areas in Sweden differed from that in general population samples drawn from the same geographical areas. DESIGN: A cross-sectional study comparing drivers and men from the general population. METHODS: Engine railway drivers aged 25-59 years (n = 2318) were compared with randomly selected men (n = 3016) with respect to their serum cholesterol, systolic and diastolic blood pressures and smoking habits. RESULTS: The levels of the risk factors did not differ between engine drivers and the reference groups except for the Stockholm area which showed a higher percentage of tobacco smokers as well as higher means for systolic and diastolic blood pressures. The risk ratio compared with the reference samples was significantly elevated in Stockholm but not in any of the other areas. CONCLUSIONS: These somatic risk factors for myocardial infarction do not explain the approximately 40% reported increase in myocardial infarction incidence among railway engine drivers. In the following study, psychosocial factors will also be examined.

Adult↗

PubMed2006

Can electronic search engines optimize screening of search results in systematic reviews: an empirical study.

BACKGROUND: Most electronic search efforts directed at identifying primary studies for inclusion in systematic reviews rely on the optimal Boolean search features of search interfaces such as DIALOG and Ovid. Our objective is to test the ability of an Ultraseek search engine to rank MEDLINE records of the included studies of Cochrane reviews within the top half of all the records retrieved by the Boolean MEDLINE search used by the reviewers. METHODS: Collections were created using the MEDLINE bibliographic records of included and excluded studies listed in the review and all records retrieved by the MEDLINE search. Records were converted to individual HTML files. Collections of records were indexed and searched through a statistical search engine, Ultraseek, using review-specific search terms. Our data sources, systematic reviews published in the Cochrane library, were included if they reported using at least one phase of the Cochrane Highly Sensitive Search Strategy (HSSS), provided citations for both included and excluded studies and conducted a meta-analysis using a binary outcome measure. Reviews were selected if they yielded between 1000-6000 records when the MEDLINE search strategy was replicated. RESULTS: Nine Cochrane reviews were included. Included studies within the Cochrane reviews were found within the first 500 retrieved studies more often than would be expected by chance. Across all reviews, recall of included studies into the top 500 was 0.70. There was no statistically significant difference in ranking when comparing included studies with just the subset of excluded studies listed as excluded in the published review. CONCLUSION: The relevance ranking provided by the search engine was better than expected by chance and shows promise for the preliminary evaluation of large results from Boolean searches. A statistical search engine does not appear to be able to make fine discriminations concerning the relevance of bibliographic records that have been pre-screened by systematic reviewers.

Abstracting and Indexing↗

PubMed1998

Genetic engineering, welfare, and accountability.

Comments on the implications of genetic engineering for animal welfare. Welfare problems associated with techniques used to achieve genetic changes; Detrimental effects of genetic modifications to welfare; Modification of farm animals for biomedical products. Implications of genetic engineering for animal welfare are changing rapidly and need to be reviewed regularly. They include the welfare problems associated with techniques used to achieve genetic changes, which are similar to problems of other experimental approaches; these should be considered carefully, especially where techniques are used on a routine basis. When it comes to the genetic modifications themselves, some are detrimental to welfare, some are neutral, and some are beneficial; these results include direct effects of the intended change, side effects, and indirect effects. Currently, the two main applications are modification of farm animals for biomedical products--which appears to be largely neutral for welfare--and modification of mice as models for human disease, which results in suffering, often severe suffering. Beneficial applications are rare and still experimental or theoretical. The situation is similar with regard to the use of recombinant hormones and viruses; use of recombinant vaccines has potential for improving welfare, but may raise other ethical problems. Although few, if any, of these concerns are specific to genetic engineering, various factors combine to suggest that particular safeguards are needed in this field. These include the facts that changes can be produced rapidly and repeatedly, and that one of the driving forces behind genetic engineering is commercial exploitation of technology. In general, ethical evaluation still is done on a case-by-case basis, using the limited criteria seen as directly relevant to each case, rather than on a broader framework. There also is little public accountability, whereby the public can have confidence that such evaluation is being carried out properly. Calls for advisory "watchdog" committees to consider ethical questions on the use of animals are endorsed by this article. Furthermore, it is essential for public confidence in the safeguarding of animal welfare that the procedures of such committees should be well-publicized.

Journal Article↗

PubMed2005

Can we use routine data to evaluate organizational change? Lessons from the evaluation of business process re-engineering in a UK teaching hospital.

OBJECTIVE: To review and critically evaluate a multidisciplinary independent evaluation of business process re-engineering within a UK hospital using routine data. METHODS: Routine data measures of hospital cost efficiency are used to compare rates of changes at Leicester Royal Infirmary (LRI) with a 'peer group' of 22 teaching hospitals and to ascertain changes attributable to re-engineering. Different adjustment factors are quantified and the robustness of individual measures discussed. In addition to providing context to the quantitative primary research and the qualitative research on change management, service performance and quality indicators not captured in overall efficiency measures are assessed using detailed routine data measures. RESULTS: LRI is one of the most efficient teaching hospitals in England and continued improvement during re-engineering is shown to be at a faster rate than the peer group average, although attribution of changes is difficult. Lack of availability and inconsistency of data for support services meant that many re-engineering initiatives are not quantifiable using routine data measures. CONCLUSIONS: When combining different measures, routine data is a valuable tool in evaluating organizational change initiatives. However, use in future evaluations would require consistent benchmarking of routine data.

Benchmarking↗

PubMed1995

Diesel engine exhaust and lung cancer: an unproven association.

The risk of lung cancer associated with diesel exhaust has been calculated from 14 case-control or cohort studies. We evaluated the findings from these studies to determine whether there is sufficient evidence to implicate diesel exhaust as a human lung carcinogen. Four studies found increased risks associated with long-term exposure, although two of the four studies were based on the same cohort of railroad workers. Six studies were inconclusive due to missing information on smoking habits, internal inconsistencies, or inadequate characterization of diesel exposure. Four studies found no statistically significant associations. It can be concluded that short-term exposure to diesel engine exhaust (< 20 years) does not have a causative role in human lung cancer. There is statistical but not causal evidence that long-term exposure to diesel exhaust (> 20 years) increases the risk of lung cancer for locomotive engineers, brakemen, and diesel engine mechanics. There is inconsistent evidence on the effects of long-term exposure to diesel exhaust in the trucking industry. There is no evidence for a joint effect of diesel exhaust and cigarette smoking on lung cancer risk. Using common criteria for determining causal associations, the epidemiologic evidence is insufficient to establish diesel engine exhaust as a human lung carcinogen.

Animals↗

PubMed2004

Integrated gas analyzer for complete monitoring of turbine engine test cells.

Fourier transform infrared (FT-IR) spectroscopy is proving to be reliable and economical for the quantification of many gas-phase species during testing and development of gas turbine engines in ground-based facilities such as sea-level test cells and altitude test cells. FT-IR measurement applications include engine-generated exhaust gases, facility air provided as input to engines, and ambient air in and around test cells. Potentially, the traditionally used assembly of many gas-specific single gas analyzers will be eliminated. However, the quest for a single instrument capable of complete gas-phase monitoring at turbine engine test cells has previously suffered since the FT-IR method cannot measure infrared-inactive oxygen molecules, a key operational gas to both air-breathing propulsion systems and test cell personnel. To further the quest, the FT-IR sensor used for the measurements presented in this article was modified by integration of a miniature, solid-state electrochemical oxygen sensor. Embedded in the FT-IR unit at a location near the long-effective-optical-path-length gas sampling cell, the amperometric oxygen sensor provides simultaneous, complementary information to the wealth of spectroscopic data provided by the FT-IR method.

Journal Article↗

PubMed1990

[Mental health in software engineers. I. Frequency of mental complaints, physical complaints and psychiatric disorders].

This study examined the physical complaints, mental complaints and psychiatric disorders in software engineers. Subjects were 101 male software engineers. They were evaluated by a semistructured interview. Psychiatric diagnosis was based on DSM-III (Diagnostic and Statistical Manual of Mental Disorders, third edition). The results are summarized as follows: 1) Physical complaints were observed in 68% of the subjects with 25% of the subjects complaining of physical ill-health. This study showed that 12% of the subjects had hypertension, 12%, gastritis or gastro-duodenal ulcer, 14%, allergic disease, and 19% miscellaneous diseases. 2) Of the subjects 62% had mental complaints and 31% mental ill-health. Depressive symptom was the most frequent mental complaint with 32% of the subjects diagnosed as DSM-III. The common diagnoses were adjustment disorders (19%), major affective disorders (6%), psychological factors affecting physical condition (5%) and dysthymic disorder (3%). Only one subject sought professional help from a psychiatrist for relief of mental complaints. The data suggest the severity of mental ill health in software engineers, but methodological limitations preclude a firm conclusion at this time. Further studies should be made on the mental health state in software engineers.

Adult↗

PubMedDate not supplied

Three-dimensional transient numerical simulation for intake process in the engine intake port-valve-cylinder system.

This paper presents a KIVA-3 code based numerical model for three-dimensional transient intake flow in the intake port-valve-cylinder system of internal combustion engine using body-fitted technique, which can be used in numerical study on internal combustion engine with vertical and inclined valves, and has higher calculation precision. A numerical simulation (on the intake process of a two-valve engine with a semi-sphere combustion chamber and a radial intake port) is provided for analysis of the velocity field and pressure field of different plane at different crank angles. The results revealed the formation of the tumble motion, the evolution of flow field parameters and the variation of tumble ratios as important information for the design of engine intake system.

Air Movements↗

PubMed2001

New directions in carbohydrate engineering: a metabolic substrate-based approach to modify the cell surface display of sialic acids.

This review discusses new directions in the emerging field of carbohydrate engineering. Specifically, it describes substrate-based methodologies that are complementary to the recombinant DNA techniques that now dominate metabolic and cellular engineering endeavors. A substrate-based approach consists of intercepting a biosynthetic pathway with an unnatural analog of a metabolic intermediate. The unnatural compound competes with the endogenous substrate for biosynthetic incorporation into a cellular component by action of the natural enzymes of the cell. The incorporation of the unnatural compound into the cellular architecture can directly modulate cellular properties and biological processes. Alternatively, a molecular handle can be included in the design of the unnatural substrate that allows further elaboration upon reaction with an externally delivered reagent. The sialic acid biosynthetic pathway is presented as a model system to illustrate both the practical aspects and theoretical considerations of a substrate-based cellular engineering approach. Specific applications of carbohydrate-based cell surface engineering include chemical construction of new glycosylation patterns on cells, new approaches to targeting tumor cell with either diagnostic or therapeutic agents, and installation of novel receptors on cells for facilitating viral-mediated gene delivery.

Biotechnology↗

PubMed1997

Regulation of insulin secretion from novel engineered insulinoma cell lines.

In the accompanying article, we describe the creation of novel cell lines derived from RIN 1046-38 rat insulinoma cells by stable transfection with combinations of genes encoding human insulin, GLUT2, and glucokinase. Herein we describe the regulation of insulin secretion and glucose metabolism in these new cell lines. A cell line (betaG I/17) expressing only the human proinsulin transgene exhibits a clear increase in basal insulin production (measured in the absence of secretagogues) relative to parental RIN 1046-38 cells. betaG I/17 cells engineered for high levels of GLUT2 expression and a twofold increase in glucokinase activity (betaG 49/206) or engineered for a 10-fold increase in glucokinase activity alone (betaG 40/110) exhibit a 66% and 80% suppression in basal insulin secretion relative to betaG I/17 cells, respectively. As a result, betaG 49/206 and betaG 40/110 cells exhibit potent insulin-secretory responses to glucose alone (6.1- and 7.6-fold, respectively) or to glucose plus isobutylmethylxanthine (10.8- and 15.1-fold, respectively) that are clearly larger than the corresponding responses of betaG I/17 or parental RIN 1046-38 cells. betaG 49/206 and betaG 40/110 cells also exhibit a rapid and sustained response to glucose plus isobutyl-methylxanthine in perifusion studies that is clearly larger in magnitude than that of the two control lines. Glucose dose-response studies show that both engineered and non-engineered lines respond maximally to submillimolar concentrations of glucose and that betaG 49/206 cells are the most sensitive to low concentrations of the hexose, consistent with their clearly elevated rate of [5-3H]glucose usage. Finally, 5-thioglucose, a potent inhibitor of low-K(m) hexokinases, most effectively normalizes glucose concentration dependence for insulin secretion in the cell line with highest glucokinase expression (betaG 40/110). We conclude that GLUT2 and/or glucokinase expression imposes tight regulation of basal insulin secretion in cell lines that overexpress human proinsulin, allowing a marked improvement in the range of secretagogue responsiveness in such cells.

1-Methyl-3-isobutylxanthine↗

PubMed1978

Work conditions and health of locomotive engineers. II. Questionnaire study, mortality and disability.

A questionnaire study on work conditions, work organization, leisure time, social problems, and health was directed toward active and retired locomotive engineers. This article mainly presents responses of the active engineers. The active locomotive engineers quoted the irregular work hours as the worst occupational problem. They judged noise and vibration in the locomotive cabs as disturbing. The majority of the desired changes in the work and work conditions concerned work time. The most common complaints given on the questionnaire were back trouble, hypertension and dermatitis. Tiredness and exhaustion were the most prevalent neuropsychological symptoms. A retrospective follow-up survey on invalidity and mortality was made. Trainmen and railroad clerks were used as reference cohorts.The engineers had relatively high invalidity and mortality rates in comparison to the reference groups, especially with respect to cardiovascular diseases and malignant tumors. Higher rates for disease of the digestive system and hearing loss were also suggested by the results.

Adult↗