Novel applications of shotgun phage display

In a shotgun phage display library, theoretically, the entire proteome of a bacterium is represented. Phages displaying specific polypeptides can be isolated by affinity selection, while the corresponding gene remains physically linked to the gene product. The overall objective of the study in this thesis was to explore the shotgun phage display technique in new areas. Initially, it was used to study interactions between Staphylococcus aureus and an in vivo coated biomaterial. It was shown to be well suited for the identification of bacterial proteins that bind to ex vivo central venous catheters. Several known interactions were detected, but it was also found that β2-glycoprotein I (β2-GPI) is deposited on this type of biomaterial – a finding that is of interest both for the adherence of S. aureus, but perhaps also in view of the occurrence of autoantibodies in certain autoimmune diseases. Further, it is of interest to identify the subset of extracellular proteins in a bacterium since they are involved in important functions like pathogenesis and symbiosis. A method that allows for the rapid and general isolation of extracellular proteins is desirable, and may prove particularly useful when applied to bacteria for which the genome sequences are not known. For this purpose, a specialised phage display method was developed to isolate extracellular proteins by virtue of the presence of signal peptides (SS phage display). It was successfully applied to S. aureus and, on a larger scale, to the symbiotic bacterium Bradyrhizobium japonicum. In elaboration of the SS phage display method, an inducible antisense RNA system was incorporated to enable gene silencing of the isolated genes. A tetracycline-regulated promoter was inserted in such a way, that an antisense RNA covering the cloned gene could be expressed. The new element was shown to be compatible with the properties of SS phage display, and to promote gene expression upon induction on both the transcriptional and translational level. However, screening for clones affected by the induction of antisense RNA transcription was unsuccessful, and further developments of the system are required to improve the efficiency of this attractive application

Aspects of locally advanced colon cancer

In Sweden, nearly 5000 patients are diagnosed with colon cancer annually and about 20% of these patients have a locally advanced tumor at the time of diagnosis. These tumors are challenging for both surgeons and oncologists and a multimodal treatment strategy is necessary to offer cure. To accomplish a radical resection, the tumor has to be resected en bloc with surrounding invaded tissues. Many of the patients with locally advanced colon cancer present with an emergent obstruction, which is associated with higher morbidity and mortality compared to the elective setting. Our overall aim with this thesis was to identify important cornerstones in the multimodal treatment of locally advanced colon cancer to improve outcome in these patients. In paper I, management and outcomes after multivisceral resection in patients with locally advanced colon cancer were described and evaluated. All patients operated for locally advanced colon cancer with en bloc multivisceral resections at Karolinska University Hospital between 2007 and 2014 were included (n=121). Malignant invasion in resected tissues were found in 77 patients and inflammatory adhesions were found in 44 patients. The proportion of radical (R0) resections was 91% in patients with tumor infiltration and 96% in patients with inflammation. Five-year overall survival was 61% and 87%, respectively. Female sex, low tumor stage, adjuvant chemotherapy and radical resection were independently associated with improved overall survival in the regression analysis. Age, ASA score, and tumor infiltration had no influence on survival in the model. In paper II, the effect of preoperative MDT assessment on survival was assessed in a national register-based study. All patients diagnosed with non-metastatic locally advanced colon cancer who underwent elective tumor resection between 2010 and 2017 in Sweden were included in the study. Preoperative MDT assessment was performed in 2663 patients (84%) of 3157 included patients. Three-year colon cancer-specific survival was 80% in the MDT-group and 68% in the non-MDT group. Preoperative MDT assessment was independently associated with reduced colon cancer-specific mortality after adjustments for sex, age, ASA grade, CCI, year of diagnosis, pN stage and region. In paper III, diverting stoma followed by elective resection was assessed as an alternative to emergency resection in patients with obstructive locally advanced colon cancer. In this national register-based study, all patients with obstructive locally advanced colon cancer treated with diverting stoma followed by elective resection or emergency resection between 2007 and 2017 in Sweden were included. A total of 751 patients with a right-sided tumor and 700 patients with a left-sided tumor were assessed. Diverting stoma followed by elective resection was more common in left-sided tumors (31%) than in right-sided tumors (9%). Emergency resection was independently associated with increased all-cause mortality in patients with a left-sided tumor (1.63, 95% CI 1.21-2.19). No such association could be found in patients with a right-sided tumor. In paper IV, the effect of hospital volume on mortality in patients with locally advanced colon cancer was studied. All 5421 patients included in this national register-based study had been diagnosed with a non-metastatic locally advanced colon cancer between 2007 and 2017. Hospital volume of locally advanced colon cancer resections were presented as tertiles (1-10, 11-19 and >19 resections per year). An association was shown between high hospital volume and reduced all-cause mortality (HR 0.76, 95% CI 0.68-9.84) and colon cancer-specific mortality (HR 0.73, 95% CI 0.64-0.84) after adjustments for potential confounders (age, sex, year of diagnosis, comorbidity, emergency resection and university hospital) and mediators (preoperative MDT assessment, neoadjuvant chemotherapy and radical resection). In conclusion, patients with a locally advanced colon cancer can be cured with a radical multivisceral resection. Preoperative MDT assessment and high hospital volume is associated with improved survival in these patients and centralization to high volume units with mandatory preoperative MDT assessment should be recommended. Diverting stoma followed by elective resection i

Jordtrötthet i skånska rosodlingar – förekomst av rotsårsnematoden Pratylenchus penetrans

Denna uppsats handlar om jordtrötthet och förekomst av rotsårsnematoder. Odlingen av rosor ökar både i hemträdgårdar och offentliga trädgårdar vilket gör det till ett aktuellt problem värt att uppmärksamma. Syftet med uppsatsen var att göra en översiktlig sammanställning av hur utbredd nematodförekomsten för närvarande är, framför allt av arten Pratylenchus penetrans, i en del rosodlingar och plantskolor i Skåne. Med det alltmer stigande intresset för rosodling blir det angeläget att sprida mer kunskap om jordtrötthet, samt att utforma gemensamma riktlinjer för att motverka problem. Resultaten från intervjuerna visar att jordtrötthet tycks vara ett allmänt känt begrepp i samband med odling av rosor. Samtliga personer jag samtalade med kände väl till denna problematik samt även rådet att byta ut jorden vid nyplantering av rosor. 6 av 12 intervjuade hade viss egen erfarenhet av problem med nematodförekomst, och några hade haft mycket stora odlingsproblem. Resultaten från denna empiriska studie indikerar på en ganska utbredd förekomst av olika rotsårsnematoder i skånska rosodlingar. Nematoderna förekommer på olika typer av jordar, i skilda typer av odlingar samt på olika sorters rosor. Det tycks inte vara någon större skillnad i mottaglighet mellan gammaldags rosor och moderna rosor. Jordtrötthet hos rosor är ett omtalat fenomen men det behövs regelbunden jordprovtagning för att bekräfta en eventuell förekomst av nematoder. De framkomna resultaten angående förekomst av nematoder i de odlingar som ingick i denna empiriska studie ger en indikation om att lagstiftningen kanske bör ses över och eventuellt skärpas

Interactivity and Spatiality. Design of Future IT-enhanced Work Places

In this paper I will discuss interactivity and spatiality, including the relationships between technology-in-use, design and everyday practices. The paper reports some initial experiences from a field study at a technology-intensive control room and of using work-oriented approaches for collaborative design. In several studies a group of multidisciplinary researchers has carried out experiments of collaborative design in full-scale as well as virtual environments. The aim was to invetigate how well these methods could support participatory design of work environments. Some important concerns I believe we need to face are how the characteristics of technology-enhanced environments may influence the development of new work practices when emergent technologies give entirely new possibilities for communication and co-ordination over extended distances. Hence, an urgent matter is to create a holistic view on design of future IT-enhanced work places that takes into account the users experiences and everyday practices

Images of Reality - Interacton space analysis and large-scale design in open office landscape environments

This chapter explores communication patterns and media choices among employees, as well as their connection with the ongoing changes in workplace design. It presents a multiple case study of communication and co-ordination in open landscape office environments. The study was carried out in three different organisations; an advertising firm, a manufacturing business, and an IT development office. In the organisations the work practice was to some degree dependent on possibilities to communicate from various locations among co-workers, both within and outside the office. This paper suggests that utilising more personalised and effective communication media could provide necessary means for more efficient support of co-operative work. The issues of interaction space analysis and large-scale design, i.e. integration with the existing installed base of services and infrastructures, both technical and social, were here put into focus as influencing factors. To Trevino et al’s (1990) three factors I have added a forth factor, namely company culture that I believe has a great influence on employee’s media choices. The conclusions were that the organisational culture had deep impact on how the technology features were accepted and incorporated in the work practice for communication purposes

Lattice dynamics in perovskites for green energy applications: A theoretical perspective

Electrolyzers and fuel cells are used in green energy applications, electrolyzers split water to produce hydrogen, which can then be used in fuel cells to produce energy. Oxide perovskites have shown favorable properties for applications in this area, e.g., as electrolyte and cathode material in fuel cells and electrolyzers. The important property is the conductivity of protons, which depends sensitively on the hydrogen concentration and mobility. The concentration depends on the efficiency of the hydration reaction, which is the primary way to incorporate protons in perovskites. An example of an excellent proton conductor is acceptor doped BaZrO3. Hence, some of the most crucial material properties derive from defect properties. This thesis also explore the halide perovskites CsPbBr3, which have proven to be auspicious for photovoltaics. Insights into phase stability, phase transitions and the underlying dynamics in these materials are crucial. Thus, the understanding of microscopic properties is the cornerstone of this thesis.In the present thesis, density functional theory is utilized to obtain training data for construction of potentials. The potentials that have been used are either force constant potentials or neural network potentials. The potential are then used to run lattice dynamics. To vastly extend the total simulation time or simply decrease the computational time, graphical processing units are also employed. Furthermore, defect models are applied to understand reaction kinetics.More specifically, the vibrational defect thermodynamics of BaZrO3 was examined within the harmonic approximation. We also elaborate on the soft antiferrodistortive phonon mode found in this material using self-consistent phonons and molecular dynamics. This soft mode, should ultimately be the deciding factor for which structure \ch{BaZrO3} exhibit at low temperatures. Similar methods were also employed to investigate phonon dynamics in the very anharmonic perovskite, CsPbBr3. These type of insights can, e.g., further guide the development of new materials by fine-tuning of properties

Interactivity and Spatiality - Experiences of Modelling Real Work Places as Virtual Places in a VR Collabortive Environment

In this paper I will discuss interactivity and spatiality, including the relationships between virtual places and work places. The paper reports some initial experiences of using a virtual reality (VR) tool for collaborative modelling. The aim was to investigate how well this technology could support participatory design of work environments. In a pilot study a group of researchers carried out an experiment of long distance collaborative design in a virtual environment. Interactivity and spatiality are important aspects that need to be considered in connection with emerging new technologies. In the experimental study the virtual environment represented a real work place quite satisfactory. The participants apprehended the virtual place as an interaction space for designing and communicating ideas in a smooth and unconstrained way. This initial work lays the basis for further research about future work places and use of new information technology, in a context of distributed work and various work environments including virtual places

Enhanced Mobility - Augmented Possibility? Developments in Co-operative Work

This paper enlightens enhanced mobility and the ongoing changes in collaboration forms. It reports on studies of communication and co-ordination in a work setting, including discussing the implications of the observations for enhancing mobility in co-operational work. In the analysis this paper use a framework developed by Lyytinen and Yoo (2001), in order to analyse a heterogeneous interconnected technological and organisational environment, which enables both physical and social mobility of computing and communication services between and across organisational actors. In response to earlier ignoration, the issues of large-scale design and integration to the existing installed base of services and infrastructures, both technical and social, are here put into focus. The framework consists at the fundamental level of three technological trends that drive the developments in mobile technology: mobility, convergence and mass scale. These factors influence in turn the developments in infrastructure and services, which encompass both technical and social elements. The empirical study took place in an IT-organisation, in one of the world’s leading Internet consulting companies. In the networked organisation the work practice is dependent on the co-workers ability to co-operate from various, constantly shifting, locations. This paper suggests that utilise Web-based Information Systems as communication media could initially provide necessary means to support mobility in their co-operational work. Our conclusions are that mobility is a fast-growing phenomenon, which will considerably change the terms and developments in co-operative work. Further, that the organisational culture will have deep impact on how the technology features are accepted and incorporated in the work practice. There is diversity in the use of the concept mobility, in relation to research. To meet this, the authors suggest a general Framework of Interaction Patterns model. The overall organisation of the framework is build around a dichotomy of variables, and it can be used normative in a design context or for descriptive purposes

Field Study on the Prevalence of Ovine Footrot, Contagious Ovine Digital Dermatitis, and Their Associated Bacterial Species in Swedish Sheep Flocks

Ovine footrot and contagious ovine digital dermatitis (CODD) cause lameness in sheep, affecting welfare and economics. Previous Swedish studies focused on individual slaughter lambs, leaving flock-wide prevalence less explored. This study examined the prevalence of footrot and CODD in Swedish sheep flocks, focusing on adult sheep. From 99 flocks, 297 swabs were analysed using real-time PCR for Dichelobacter nodosus, Fusobacterium necrophorum, and Treponema spp. Sampled feet were photographed and assessed using scoring systems for footrot and CODD. Results indicated footrot prevalences (footrot score >= 2) of 0.7% and 2.0% at the individual and flock levels, respectively, whereas there were no signs of CODD. The individual footrot prevalence was lower than that from a 2009 study but aligned with a 2020 study, both conducted on slaughter lambs. Dichelobacter nodosus, F. necrophorum, and Treponema spp. were found in 5.7%, 1.3%, and 65.0% of sheep, and in 9.1%, 3.0%, and 82.8% of flocks, respectively. Compared to the 2020 study, there was a notable decrease in F. necrophorum and Treponema spp., while D. nodosus was consistent. In conclusion, the findings show a low prevalence of footrot, CODD, D. nodosus, and F. necrophorum in Swedish sheep flocks. Continuous surveillance and owner education are important to maintain this favourable status

Doctor of Philosophy

dissertationCallous-unemotional (CU) traits are an important distinguishing characteristic among delinquent youth, as youth displaying CU traits tend to commit the most severe offenses. CU traits have typically been conceptualized as biologically ingrained traits; however, recent research suggests that some youth may "acquire" CU traits in response to trauma. With the intention of increasing knowledge of the emotional processes associated with acquired callousness, the current study proposes a refined version of betrayal trauma theory which subsequently informed the inclusion of experiential avoidance and emotional numbing in potential models of acquired callousness. Structural equation modeling was used to test the proposed models of acquired callousness in a sample of 213 detained youth. Results of confirmatory factor analyses used to identify a measurement model with adequate fit necessitated examining different forms of experiential avoidance and emotional numbing in the structural models tested. Overall, results were consistent with a "partial serial mediation model" of acquired callousness, in which experiential avoidance fully mediates the association between betrayal trauma and emotional numbing, and emotional numbing, in turn, partially mediates the association between experiential avoidance and callousness. Results indicated that these findings were specific to models that included tension reduction behaviors as an index of experiential avoidance and general numbing as an index of emotional numbing. These findings suggest that maladaptive forms of experiential avoidance may help to explain the association between betrayal trauma and callousness. Furthermore, numbing of specific emotions, such as sadness, may reflect different variants of emotional detachment as compared to general numbing and may have different implications for acquired callousness. To further expand on prior research, the current study compared the effects of betrayal trauma occurring in different developmental time periods and found that only betrayal trauma occurring in adolescence contributed to youth callousness. Taken together, the findings of the current study offer insight into the circumstances under which both experiential avoidance and emotional numbing may contribute to callousness and contribute to the growing body of literature that suggests that some youth may acquire callousness in response to the experience of trauma