| 1. |
- Holm, Anna M., 1989-
(författare)
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Human papillomavirus in sinonasal inverted papilloma, recurrent respiratory papilloma and non-malignant tonsils
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Human papillomavirus (HPV) is known to cause recurrent respiratory papilloma (RRP) and certain types of oropharyngeal cancer. HPV has also been associated with sinonasal inverted papilloma (SIP). HPV transmission routes are under investigation and the conviction is that the infection occurs sexually at an adult stage, however, vertical transmission at birth with a dormant viral condition until disease eruption/co-activation has been stated as a possibility.Purpose: The purpose of this work was to contribute to the understanding of HPV related chronic diseases in the airway. Specific aims were: 1. To increase understanding regarding changes in the immune system as well as of the glycosaminoglycan hyaluronan in patients with RRP. 2. To evaluate prevalence of HPV and its surrogate marker p16 in SIP as well as HPV, p16 and Epstein-Barr virus (EBV) in benign tonsillar disease. HPV and EBV in non-malignant tonsillar disease were studied due to the fact that incidence of HPV positive tonsillar cancer is increasing and the time of viral infection is unknown.Methods: A phenotypic characterization of peripheral blood from 16 RRP patients and 12 age-matched controls, using immunoflow cytometry, and monoclonal antibodies against differentiation and activation markers, was performed. The cytokine mRNA profile of monocytes, T helper-, T cytotoxic-, and NK cells was assessed using RT-qPCR. 54 SIP samples were studied of which 53 were available for analyzation with PCR. Genotype screening for 18 high risk and six low risk HPV types was performed using the PapilloCheck® HPV-screening test (a PCR method). 54 samples were immunohistochemically (IHC) stained for p16. Biopsies from vocal folds (VFs) and false vocal folds (FVFs) were collected from 24 patients with RRP, 12 were randomly selected to histochemistry for Hyaluronan (HA) and IHC staining for CD44 in the epithelium, stroma and RRP lesions. The remaining 12 patients were analyzed for HA molecular mass distribution with a gas-phase electrophoretic molecular mobility analyzer (GEMMA). Eight VF samples and four FVF samples were successfully analyzed. Biopsies from 40 non-malignant tonsils were analyzed using Papillocheck® for HPV, IHC for p16 and EBER analysis for EBV.Results: We found a dominance of cytotoxic T cells, activated NK cells, and high numbers of stressed MIC A/B (MHC class I chain-related molecule A/B) expressing lymphocytes. The HPV analysis was successful for 38 SIP samples and two (5%) were positive for HPV 11. Notably, p16 was present in the epithelia of all samples and in the papilloma portions in 37 of 38 samples. We found extensive HA staining in the stroma of both VFs and FVFs. CD44 was expressed throughout the epithelium, stroma, and RRP lesions in both FVFs and VFs, it did however, not concur with the expression of HA. Very high mass HA was found in both VFs and FVFs, though more variation regarding amounts of HA was seen in the VFs compared to FVFs. No HPV was found in non-malignant tonsils, the p16 levels were low and the counted EBER positive cells showed great variation in numbers.Conclusions: Our findings demonstrate an immune dysregulation with inverted CD4+/CD8+ ratio and aberrant cytokine mRNA production in RRP patients, compared to healthy controls. We concluded that p16 cannot be used as a surrogate marker for high-risk HPV-infection in SIP and that HPV incidence was low (5%). CD44 does not seem to bind to HA, which might explain the noninflammatory response previously described in RRP. Very high mass HA possibly crosslinked was seen in both VFs and FVFs. A possibility to counteract inflammatory crosslinking of HA may be found for medical treatment options in RRP.
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| 2. |
- Tran, Phong, et al.
(författare)
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De novo dNTP production is essential for normal postnatal murine heart development
- 2019
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Ingår i: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 394:44, s. 15889-15897
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Tidskriftsartikel (refereegranskat)abstract
- The building blocks of DNA, dNTPs, can be produced de novo or can be salvaged from deoxyribonucleosides. However, to what extent the absence of de novo dNTP production can be compensated for by the salvage pathway is unknown. Here, we eliminated de novo dNTP synthesis in the mouse heart and skeletal muscle by inactivating ribonucleotide reductase (RNR), a key enzyme for the de novo production of dNTPs, at embryonic day 13. All other tissues had normal de novo dNTP synthesis and theoretically could supply heart and skeletal muscle with deoxyribonucleosides needed for dNTP production by salvage. We observed that the dNTP and NTP pools in wild-type postnatal hearts are unexpectedly asymmetric, with unusually high dGTP and GTP levels compared with those in whole mouse embryos or murine cell cultures. We found that RNR inactivation in heart led to strongly decreased dGTP and increased dCTP, dTTP, and dATP pools; aberrant DNA replication; defective expression of muscle-specific proteins; progressive heart abnormalities; disturbance of the cardiac conduction system; and lethality between the second and fourth weeks after birth. We conclude that dNTP salvage cannot substitute for de novo dNTP synthesis in the heart and that cardiomyocytes and myocytes initiate DNA replication despite an inadequate dNTP supply. We discuss the possible reasons for the observed asymmetry in dNTP and NTP pools in wildtype hearts.
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| 3. |
- Ghorbani, Morteza, et al.
(författare)
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Unravelling the Acoustic and Thermal Responses of Perfluorocarbon Liquid Droplets Stabilized with Cellulose Nanofibers
- 2019
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Ingår i: Langmuir. - : American Chemical Society. - 0743-7463 .- 1520-5827. ; 35:40, s. 13090-13099
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Tidskriftsartikel (refereegranskat)abstract
- The attractive colloidal and physicochemical properties of cellulose nanofibers (CNFs) at interfaces have recently been exploited in the facile production of a number of environmentally benign materials, e.g. foams, emulsions, and capsules. Herein, these unique properties are exploited in a new type of CNF-stabilized perfluoropentane droplets produced via a straightforward and simple mixing protocol. Droplets with a comparatively narrow size distribution (ca. 1-5 μm in diameter) were fabricated, and their potential in the acoustic droplet vaporization process was evaluated. For this, the particle-stabilized droplets were assessed in three independent experimental examinations, namely temperature, acoustic, and ultrasonic standing wave tests. During the acoustic droplet vaporization (ADV) process, droplets were converted to gas-filled microbubbles, offering enhanced visualization by ultrasound. The acoustic pressure threshold of about 0.62 MPa was identified for the cellulose-stabilized droplets. A phase transition temperature of about 22 °C was observed, at which a significant fraction of larger droplets (above ca. 3 μm in diameter) were converted into bubbles, whereas a large part of the population of smaller droplets were stable up to higher temperatures (temperatures up to 45 °C tested). Moreover, under ultrasound standing wave conditions, droplets were relocated to antinodes demonstrating the behavior associated with the negative contrast particles. The combined results make the CNF-stabilized droplets interesting in cell-droplet interaction experiments and ultrasound imaging.
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| 4. |
- Kadefors, Anna, Professor, 1962-, et al.
(författare)
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Innovation processes and dissemination of research-based knowledge in Swedish rock engineering : Experiences in the trust geoinfra project
- 2019
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Innovation in the project-based construction industry is generally perceived to be complex and poorly understood on a system level. This report describes and discusses the innovation system in Swedish underground construction based on a study of knowledge dissemination and implementation in relation to the large collaborative R&D program TRUST, Transparent Underground Structures.The study is primarily based on interviews performed with representatives of clients, contractors, consultants, researchers and funding bodies within the TRUST program. There are two main focus areas: the innovation system level and the TRUST project. The innovation system level describes drivers, organization and processes for engaging in R&D and implementing results within the Swedish Transport Administration (STA), contractor companies and consultancy firms, but also interviewee opinions about the innovation culture in Swedish rock engineering and construction more generally. The section covering the TRUST project describes the background, performance and experiences from the TRUST collaboration as well as innovation processes within some of the sub-projects.Underground construction is a part of the construction sector where comparatively much research is carried out and university-industry collaboration is lively. Still, our results confirm many of the observations made by previous researchers on innovation in construction in general: the small resources within companies devoted to research and innovation, the importance of champions at the project level and the difficulties to disseminate knowledge and implement company level initiatives. The contractor interviews illustrate how sensitive their innovation processes are to chance factors such as timing of new relevant business projects and the experiences and knowledge of the individuals that happen to be assigned to a specific project. In this respect, the client is more in control. However, the interviewed client representatives from STA express the same kind of difficulties in driving innovation more strategically on the organizational level and convince their project managers to open up for R&D tests and new knowledge in their business projects.Previous research has also shown that there are many drivers for firms to engage in R&D collaborations with public funding. R&D collaboration provides access to knowledge networks by enabling participation in reference groups and communities. Important such networks in Swedish underground construction were BeFo and SBUF. Another driver for R&D collaboration was to support M Sc and PhD education for future recruitment. Thus, the individuals themselves were often the most important research output. Implementation of results was not a primary motivation although a more strategic approach was emerging among both public organizations and private companies, who put more emphasis than they used to on application in practice of research results. One consultancy company was especially active in developing their R&D strategy to support a business model based on premium services. In general, however, knowledge development for underground construction was still mainly driven by individual specialists based on their contacts in business projects. Organizations had developed centrally defined R&D strategies, but these did not deal explicitly with technical disciplines but tended to focus on general goals such as sustainability, or on participation in high profile research collaborations.Most specialists within academia as well as industry were involved in several networks and perceived these to provide useful interaction platforms. Research funding was governed by BeFo and SBUF, and these peer networks thus strongly influenced research strategy on a national level. The number of PhDs in industry had increased over the last years, and important informal networks developed over time between these individuals and their former university departments. Such relationships formed the basis for gaining research funding, which is often dependent on industry co-funding.When establishing TRUST, the assumption was that a large coordinated R&D project would be better for communicating with industry and implementing results than several smaller projects. However, it turned out to be more or less the other way around. The existing system could handle innovation in construction projects, but not innovation on the organizational level. This became apparent when trying to find a joint test site. In smaller research projects, access to business projects is provided by individuals on the client or supplier side, often with an R&D background, who use their personal contacts to provide access to researcher to perform measurements in ongoing construction projects. This often requires that site work is going well and that measurements are found not to cause too much disturbance. Large programs for site measurements involving numerous actors, such as TRUST, call for planning and upfront commitment. The failure to arrange fieldwork in TRUST illustrate the difficulties to take the step from a bottom up, ad-hoc, individual based regime to an organizational strategy with national level anchoring and implications. Thus, the TRUST program appeared to be an ideal partner for the Swedish Transport Administration, but in practice the size of the project turned out to be a major disadvantage.In general, the internal innovation capabilities of companies and client authorities need to be developed in order for organizations to benefit from the collaborative research programs and act upon the knowledge developed. One aspect is that measures should be taken to more explicitly involve business project managers in both R&D and implementation. Innovation capability development is needed especially on the client side, since long term strategies in supplier organizations will not develop if the strategies of the dominant clients is not clear. However, assuming that the geo area in general is largely an open innovation environment, it also seems useful to explore if different actors could perform complementary activities in an industry innovation system. For example, specialist networks both within organizations and on the industry level may be more formally mobilized in external monitoring, strategy development and evaluation. In the future, top management, technically oriented specialists and researchers need to develop a joint understanding of how the innovation system works, including the regulatory and contractual environment.There is also a need to invest also in research that is relatively far from application. Thus, evaluation processes and output measurement systems should be adapted to how close to implementation the research project is and also assess the need to build capabilities on the receiver side.
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