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- Hedskog, Charlotte
(författare)
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Ultra-deep characterization of viral quasispecies in HIV infection
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- HIV-1 has the ability to rapidly diversify and adapt to changes in its environment, such as evading the host immune response, altering cell tropism, and developing resistance to antiretroviral drugs. Minority HIV-1 variants have been shown to be of clinical significance, especially those with non-nucleoside reverse transcriptase inhibitor (NNRTI) drug resistance mutations or determinants of CXCR4 phenotype (X4-virus). In this thesis a next generation sequencing technology, ultra-deep pyrosequencing (UDPS), has been used to dissect HIV-1 quasispecies in infected patients to study the evolution of drug resistance and cell tropism. The depth of UDPS depends on the number of viral templates that can be successfully extracted and amplified from a plasma sample, the error rate of PCR and UDPS, and the efficiency of cleaning the UDPS data from such errors. For this reason, we developed an experimental design that allows high recovery of HIV-1 templates and an efficient data cleaning strategy. Our data cleaning strategy reduced the UDPS error rate approximately 10-fold. We carefully evaluated the performance of our UDPS protocol and found that the repeatability of detection of major as well as minor variants in patient plasma samples was good. This indicated that the experimental noise introduced during RNA extraction, cDNA synthesis, PCR and UDPS was low. However, for rare variants in vitro PCR recombination and effects of sequence direction need to be considered. Finally, the design of primers for PCR amplification is of special importance during UDPS, since we observed that primer-related selective amplification can skew the frequency estimates of genetic variants. We investigated the levels of pre-existing drug resistance mutations in plasma samples from five treatment-naive patients. In four of five patients we found low levels of pre-existing drug resistance mutations at two positions (M184I, T215A/I), whereas other mutations (M184V, Y181C, Y188C and T215Y/F) were not detected. During treatment failure and treatment interruption, we found almost complete replacement of wild-type and drug-resistant variants, respectively. This implies that the proportion of minority variants with drug resistance in patients with previous treatment failure or transmitted drug resistance can be too low to be detectible even with highly sensitive UDPS. In another study, the HIV-1 populations from three patients with HIV-1 populations that switched coreceptor use were investigated longitudinally. UDPS analysis showed that the X4-virus that emerged after coreceptor switch was not detected during primary HIV-1 infection (PHI) and that the X4 population most probably evolved from the CCR5-using population during the course of infection rather than was transmitted as minor variants. Moreover, one to three major variants were found during PHI, supporting that infection usually is established with one or just a few viral particles. The frequency and type of errors that occurred during UDPS were investigated. The errors that remained after data cleaning were significantly more often transitions than transversions, which indicates that a substantial proportion of errors were introduced during PCR rather than UDPS itself. This affects the limits of detection of minority mutations since UDPS analyses of HIV-1 are preceded by a PCR step. To further reduce the UDPS error rate we developed a new, improved methodology, based on re-sequencing of molecularly tagged template molecules. Preliminary results showed that this method has the potential to increase the sensitivity of UDPS analyses 1000-fold and thus is close to error-free. Taken together, this thesis adds knowledge on the use of UDPS to gain new insights in HIV evolution and resistance and is relevant for the possible future clinical use of this technology.
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- Jonasson, Mats
(författare)
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Aspects of autonomous corner modules as an enabler for new vehicle chassis solutions
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis adopts a novel approach to propelling and controlling the dynamics of a vehicle by using autonomous corner modules (ACM). This configuration is characterised by vehicle controlled functions and distributed actuation and offers active and individual control of steering, camber, propulsion/braking and vertical load. Algorithms which control vehicles with ACMs from a state-space trajectory description are reviewed and further developed. This principle involves force allocation, where forces to each tyre are distributed within their limitations. One force allocation procedure proposed and used is based on a constrained, linear, least-square optimisation, where cost functions are used to favour solutions directed to specific attributes. The ACM configuration reduces tyre force constraints, due to lessen estrictions in wheel kinematics compared to conventional vehicles. Thus, the tyres can generate forces considerably differently, which in turn, enables a new motion pattern. This is used to control vehicle slip and vehicle yaw independently. The ACM shows one important potential; the extraordinary ability to ensure vehicle stability. This is feasible firstly due to closed-loop control of a large number of available actuators and secondly due to better use of adhesion potential. The ability to ensure vehicle stability was demonstrated by creating actuator faults. This thesis also offers an insight in ACM actuators and their interaction, as a result of the force allocation procedure.
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- Andersson, Svante, 1962-, et al.
(författare)
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How do mature born globals create customer value to achieve international growth?
- 2020
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Ingår i: International Marketing Review. - Bingley : Emerald Group Publishing Limited. - 0265-1335 .- 1758-6763. ; 37:2, s. 185-211
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – This study aims to investigate how mature born global firms create value for customers to achieve continued international growth.Design/methodology/approach – The study employs a case study approach to investigate the underresearched area of how mature born globals create value for customers and, by doing so, contribute to their continued international growth. This in-depth examination of how three born globals developed over time uses interviews, observation and secondary data.Findings – The findings indicate that the entrepreneurs of born global firms, that continued to grow, created a culture in the early stages that supported value creation for foreign customers. These firms have built a competitive position by developing international niche products. They have also implemented a combination of proactive and reactive market orientation to facilitate the creation and delivery of value to customers. To maintain growth, they further invest the revenues earned on additional international marketing activities and continuously enhance their focal products.Research limitations/implications – The study relies on three cases. We therefore recommend that future studies extend the scope of the research to several companies in various industries and countries, in which the theoretical arguments can be applied. In addition, further studies that test the propositions developed in this study, in different contexts, are highly recommended.Practical implications – To gain international growth, managers should create an organizational culture that facilitates satisfying international customer needs. Firms should continuously invest in sales and market development (e.g. social media marketing, personal selling) and undertake technology development of niche rather than new products. To achieve international growth, managers need to standardize part of the offer to achieve economies of scale and adapt the other part to international customers’ needs.Originality/value – Research on born globals has focused on the early stages of their internationalization processes, while largely neglecting the later stages (mature born globals) or the factors that lead to continued international growth. To address this gap, this study explores what happens when born globals ‘grow up’. This study contributes to the literature by capturing the factors and processes underlying how mature born globals create value for customers, for international growth. In particular, the study shows that the culture and strategies developed in the born globals’ early stages also lead to international growth in later stages. The mature born globals have also invested in niche products, brand building, and effective market channels and adopted a combination of proactive and reactive market orientations.
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- Bergenståhl, B, et al.
(författare)
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Surface forces in emulsions
- 1997. - 3
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Ingår i: Food Emulsions. - : Marcel Dekker. ; , s. 57-109
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Bokkapitel (refereegranskat)abstract
- Emulsions are thermodynamically unstable systems. Therefore, the technical aim of creating "stable emulsions" has to be limited to a control of the instabillity processes (e.g., coalescence, flocculation, creaming, and Ostwald ripening). For this purpose the technologist, in principle, has two tools available: the use of mechanical devices to disperce the system, and the addition of stabilizing additives (natural or artificial) to keep it dispersed. This chapter discusses how the emulsifying additives give rise to stabilizing forces; how these forces affect the kinetics of the instability processes; how they determine the phase behavior of emulsifers; and their relation to the HLB value. The interparticle interactions are determined mainly is coated by lipids and/or proteins. In this chapter we try to point out how a knowledge of interparticle forces, phase behavior, and adsorption may provide an understanding and rationalization of many of the properties of food emulsions.
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| 9. |
- Bergentall, Martina, et al.
(författare)
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Malolactic fermentation in lingonberry juice and its use as a preservative
- 2024
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Ingår i: Food microbiology (Print). - 0740-0020 .- 1095-9998. ; 121
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Tidskriftsartikel (refereegranskat)abstract
- Lingonberry is a common wild berry that is often sold as jams and beverages. It naturally contains high amounts of the weak acid preservative benzoic acid making it an interesting ingredient for shelf-life extension. Despite this, their use as a raw ingredient is limited by the inherently intense sour taste. This study aimed to improve the taste of lingonberry juice by subjecting it to malolactic fermentation in order to reduce the sourness, and to investigate the benzoic acid in lingonberries as a natural preservative in juice blends by determining the microbial stability. After initial screening of lactic acid bacteria, a Lactiplantibacillus plantarum strain was used as the starter for subsequent investigations. Upon raising the pH, all malic acid was completely converted to lactic acid after seven days. The fermented juice was mixed with blackcurrant juice in different proportions. Challenge tests of the blends showed Listeria monocytogenes could not grow in any juice samples, while Candida albicans only grew in the pure blackcurrant juice. Aspergillus brasiliensis growth was delayed in all samples containing benzoic acid in a concentration-dependent manner. The sourness and astringency were substantially reduced in the juice with added L. plantarum compared to the unfermented juice. © 2024 The Authors
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- Bergentall, Martina, et al.
(författare)
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Reduction of malic acid in bilberry juice by Lactiplantibacillus plantarum-mediated malolactic fermentation
- 2024
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Ingår i: European Food Research and Technology. - : Springer Science and Business Media Deutschland GmbH. - 1438-2377 .- 1438-2385. ; 250:3, s. 811-
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Tidskriftsartikel (refereegranskat)abstract
- Bilberries (Vaccinium myrtillus) are the most common wild berries in Northern Europe. A substantial amount of the berries are picked with the objective to extract highly valued products such as anthocyanins. A smaller amount of the bilberries is used to make jams and drinks, and these are generally restricted to the domestic market. One reason is the sour taste, partly as a result of the high content of malic acid. By using certain strains of lactic acid bacteria with the ability to convert malic acid to lactic acid, the taste is predicted to be more pleasant. This process is called malolactic fermentation, and historically it has mostly been used in winemaking. After testing five different starter cultures, we identified that the strain, Lactiplantibacillus plantarum LP58, can rapidly convert malic acid to lactic acid without any loss of sugar or citric acid, which strongly indicates a successful malolactic acid fermentation. As it has been reported that other strains of L. plantarum can be used as biopreservative agents, the resulting product was also tested in terms of microbial safety after prolonged storage, and by means of metagenome sequencing. The obtained product was quite tolerant to microbial growth, but this observation was rather due to an initial heat treatment than the addition of lactobacilli. Potentially, starter cultures with documented biopreservative activity can be combined with L. plantarum LP58 to obtain a more stable product. Until then, the fermented bilberry juice must be processed and preserved like non-fermented bilberry products. © 2023, The Author(s).
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