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Sökning: WFRF:(Meeker L David)

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  • Baumgarten, Thomas, 1985- (författare)
  • Protein production in the E. coli cell envelope
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Proteins fulfil essential functions in every cell and malfunctioning proteins are often the cause of diseases. On the other hand, proteins like antibody fragments or hormones can be used to treat diseases. Proteins are often produced in the bacterium Escherichia coli so that they can be studied to understand their (mal)function or so that they can be used to treat a disease. Unfortunately, producing proteins in the cell envelope of E. coli, like integral membrane proteins, which are important drug targets, and secretory proteins like antibody fragments and hormones, often results in unsatisfactory yields. Therefore, the objectives of this doctoral thesis were to identify bottlenecks that can limit the production of recombinant proteins in the cell envelope of E. coli and to try to overcome these bottlenecks. In the first study, we isolated and characterized the E. coli membrane protein production strain Mt56(DE3). This strain, in which the target gene expression intensity is strongly reduced, outcompetes the standard E. coli membrane protein production strains for most targets tested. In the second and third study we focused on the production of secretory proteins, i.e., proteins that are translocated across the inner membrane into the periplasm of E. coli. First, we investigated the impact of the targeting pathway used to direct a secretory protein to the translocation machinery on the cell physiology and protein production yields. We found that the co-translational targeting of a produced protein saturates the capacity of the translocation machinery resulting in heavily impaired biomass formation and low protein production yields. In contrast, post-translational targeting of a produced protein did not saturate the capacity of the protein translocation machinery resulting in hardly affected biomass formation and high protein production yields. In the third study we investigated how optimizing the production of a co-translationally targeted protein, by harmonizing its production rate with the capacity of the protein translocation machinery, affects the physiology of the cell. We found that, in stark contrast to the non-optimized condition, the optimized production did not affect the composition of the E. coli proteome. This surprising finding indicates that a protein can be produced efficiently in the periplasm of E. coli without compromising the physiology of the cell. In the last study we aimed at developing an outer membrane vesicle-based tuberculosis vaccine. To this end, an E. coli strain was created that produced outer membrane vesicles coated with different tuberculosis antigens. It was shown that a homogenous population of vesicles was produced, which will hopefully facilitate the isolation of these vesicles on an industrial scale.
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  • Baumgartinger-Seiringer, Simon, et al. (författare)
  • Reconsidering regional structural conditions for industrial renewal
  • 2022
  • Ingår i: Regional Studies. - : Informa UK Limited. - 0034-3404 .- 1360-0591. ; 56:4, s. 579-591
  • Tidskriftsartikel (refereegranskat)abstract
    • This article develops a more comprehensive understanding of innovation-based renewal of industries from a structural perspective. Arguably, established perspectives offer rather simplistic views, portraying structures as either enabling or constraining for certain forms of regional industrial change. Inspired by work in organizational institutionalism on ‘institutional infrastructures’, this article focuses on the degree of elaboration and coherence as decisive features of regional structural conditions. Arguably, this conceptual lens allows for a better understanding of the potentials and limitations for industrial change entailed in different structural configurations. Empirically, we investigate renewal processes in traditional automotive regions in Austria and Sweden.
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  • Baumgartner, J., et al. (författare)
  • Fatigue strength assessment of TIG-dressed welded steel joints by local approaches
  • 2019
  • Ingår i: International Journal of Fatigue. - : Elsevier Ltd. - 0142-1123 .- 1879-3452. ; 126, s. 72-78
  • Tidskriftsartikel (refereegranskat)abstract
    • Fatigue strength assessment methods by local approaches are widely used in the literature. This paper provides a comprehensive evaluation of published data for welded steel joints improved by TIG dressing methods. Fatigue classes for the local assessment methods with the available fatigue data are recommended. The available fatigue data extracted for transverse non-load carrying welds, cruciform joints as well as butt joints. In total, 17 published test series of weld details with various yield strengths and stress ratios are presented. Fatigue strength assessment is performed by considering the weld profile geometry within Finite Element models and taking the resulting stress gradients as basis for the evaluation. In addition, the influence of the steel grade is included. The most reliable results are derived by using the critical distance approach. Fatigue classes and critical distances are recommended as a result of the evaluations.
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  • Baumgartner, R W, et al. (författare)
  • Microembolic signal counts increase during hyperbaric exposure in patients with prosthetic heart valves
  • 2001
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - : Elsevier BV. - 1097-685X .- 0022-5223. ; 122:6, s. 1142-1146
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with prosthetic heart valves have an increased risk of thromboembolic events, and transcranial Doppler sonography reveals microembolic signals. Whereas microembolic signals were initially assumed to be of particulate matter, recent studies suggest that they are partially gaseous in origin. If this is true, alteration of environmental pressure should change microembolic signal counts. We undertook this study to evaluate the influence of hyperbaric exposure on microembolic signal counts in persons with prosthetic heart valves. METHODS AND RESULTS: Microembolic signal counts were monitored by transcranial Doppler sonography of both middle cerebral arteries under normobaria (normobaria 1), 2 subsequent periods of hyperbaria (2.5 and 1.75 bar), and a second period of normobaria (normobaria 2) in 15 patients with prosthetic heart valves. Each monitoring period lasted 30 minutes. Compression and decompression rates were 0.1 bar/min. Microembolic signal counts increased from 20 (12-78) at normobaria 1 to 79 (30-165) at 2.5 bar (P <.01 vs normobaria 1 and 2), decreased to 44 (18-128) at 1.75 bar (P <.01 vs normobaria 1 and 2.5 bar; P <.001 vs normobaria 2), and returned to 20 (8-96) at normobaria 2 (values are medians and 95% confidence intervals). CONCLUSIONS: Our results strongly suggest that gaseous bubbles are underlying material for part of the microembolic signals detected in patients with prosthetic heart valves.
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6.
  • Buckley, Jeffrey, 1992-, et al. (författare)
  • Exploring the Prototypical Definitions of Intelligent Engineers Held by Irish and Swedish Higher Education Engineering Students
  • 2021
  • Ingår i: Psychological Reports. - : SAGE Publications. - 0033-2941 .- 1558-691X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Males are generally overrepresented in higher education engineering. However, the magnitude of this variance differs between countries and engineering fields. Evidence associated with the field-specific ability beliefs hypothesis suggests that perceptions of intelligence held by actors within engineering affects the engagement of underrepresented groups. This study examined perceptions of an intelligent engineer held by undergraduate and postgraduate engineering students in Ireland and Sweden, countries selected based on their levels of female representation in engineering education. It was hypothesised that there would be a significant difference in perceptions between countries. A survey methodology was employed in which a random sample of Irish and Swedish university students completed two surveys. The first asked respondents to list characteristics of an intelligent engineer, and the second asked for ratings of importance for each unique characteristic. The results indicate that an intelligent engineer was perceived to be described by seven factors; practical problem solving, conscientiousness, drive, discipline knowledge, reasoning, negative attributes, and inquisitiveness when the data was analysed collectively, but only the five factors of practical problem solving, conscientiousness, drive, discipline knowledge and negative attributes were theoretically interpretable when the data from each country was analysed independently. A gender × country interaction effect was observed for each of these five factors. The results suggest that the factors which denote intelligence in engineering between Irish and Swedish males and females are similar, but differences exist in terms of how important these factors are in terms group level definitions. Future work should consider the self-concepts held by underrepresented groups with respect to engineering relative to the factors observed in this study.
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  • Burney, Peter, et al. (författare)
  • Chronic obstructive pulmonary disease mortality and prevalence : the associations with smoking and poverty-a BOLD analysis
  • 2014
  • Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 69:5, s. 465-473
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Chronic obstructive pulmonary disease (COPD) is a commonly reported cause of death and associated with smoking. However, COPD mortality is high in poor countries with low smoking rates. Spirometric restriction predicts mortality better than airflow obstruction, suggesting that the prevalence of restriction could explain mortality rates attributed to COPD. We have studied associations between mortality from COPD and low lung function, and between both lung function and death rates and cigarette consumption and gross national income per capita (GNI). Methods National COPD mortality rates were regressed against the prevalence of airflow obstruction and spirometric restriction in 22 Burden of Obstructive Lung Disease (BOLD) study sites and against GNI, and national smoking prevalence. The prevalence of airflow obstruction and spirometric restriction in the BOLD sites were regressed against GNI and mean pack years smoked. Results National COPD mortality rates were more strongly associated with spirometric restriction in the BOLD sites (<60 years: men r(s)=0.73, p=0.0001; women r(s)=0.90, p<0.0001; 60+ years: men r(s)=0.63, p=0.0022; women r(s)=0.37, p=0.1) than obstruction (<60 years: men r(s)=0.28, p=0.20; women r(s)=0.17, p<0.46; 60+ years: men r(s)=0.28, p=0.23; women r(s)=0.22, p=0.33). Obstruction increased with mean pack years smoked, but COPD mortality fell with increased cigarette consumption and rose rapidly as GNI fell below US$ 15 000. Prevalence of restriction was not associated with smoking but also increased rapidly as GNI fell below US$ 15 000. Conclusions Smoking remains the single most important cause of obstruction but a high prevalence of restriction associated with poverty could explain the high 'COPD' mortality in poor countries.
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9.
  • Burnie, David A., et al. (författare)
  • Far tail or extreme day returns, mutual fund cash flows and investment behaviour
  • 2010
  • Ingår i: Applied Financial Economics. - London : Routledge. - 0960-3107 .- 1466-4305. ; 20:16, s. 1241-1256
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examines the frequency of extreme trading days and investment behaviour in Sweden. We show that the frequency, as well as the magnitude of extreme trading days has increased over time. We also show that the frequency of extreme trading days in a year is positively correlated to the frequency the preceding year. Furthermore, we show that aggregate cash flows into equity and bond funds are unrelated to risk measured by standard deviation of return. Our findings show that investors, individuals as well as corporations, use simple passive investment strategies and hence, do not believe in market timing or wish to risk capital on capturing far tail or black swan type returns.
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  • Burns, R. E., et al. (författare)
  • Systemic Amyloidosis in an African Tiger Snake (Telescopus semiannulatus)
  • 2017
  • Ingår i: Journal of Comparative Pathology. - : ELSEVIER SCI LTD. - 0021-9975 .- 1532-3129. ; 157:2-3, s. 136-140
  • Tidskriftsartikel (refereegranskat)abstract
    • An adult male African tiger snake (Telescopts semiannulatus) was diagnosed with disseminated mycobacteriosis and a hepatic biliary cystadenocarcinoma. Histologically, the spleen was largely replaced by extracellular deposits of eosinophilic, fibrillar to hyaline material. Similar material was also present in the testicular interstitium and occasional blood vessel walls. This material was congophilic with strong green birefringence under polarized light and emitted fluorescence when bound to the luminescent-conjugated oligothiophene, h-FTAA, an amyloid binding probe. Ultrastructurally, deposits were composed of aggregates of haphazardly arranged, non-branching fibrils up to 8 nm in diameter and of indeterminate length. These findings all supported a diagnosis of amyloidosis, most likely amyloid A (AA) type based on concurrent inflammatory disease in this snake. However, immunohistochemistry for serum amyloid A was negative. There are only rare previous reports of amyloidosis in reptiles and many have been incompletely characterized. This case presents a thorough investigation into an occurrence of systemic amyloidosis in a snake, including a novel use of luminescent-conjugated oligothiophene binding in a reptile to confirm the diagnosis. (C) 2017 Elsevier Ltd. All rights reserved.
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