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| 4. |
- Edoff, Petra, 1984-
(författare)
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Managing offshoring of complex products : Strategy and capabilities
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Offshoring is a hot topic in the industrial and academic community over the last few years, evolving from a focus on manufacturing to product development and R&D. Offshoring refers to the process of sourcing and coordinating tasks across national borders and can include both in-house and outsourced activities performed by a supplier. There is a lot of research guiding the decision of what, where and how to offshore, but research on how to implement offshoring strategies is rare. The purpose of this dissertation is to contribute to the knowledge on how companies deal with offshoring in practice, relating to strategy, planning and routines. It discusses what type of capabilities that is needed to gain the benefits of offshoring implementations.The research builds on case studies from two multinational companies offshoring product development from Sweden to captive and offshore development centres in India and China through a series of interviews, review of business documentation and other types of active engagements over time.This research highlights how the development and implementation of offshoring can be better understood by focusing on the middle management in the organization and how they relate to the top management directives when implementing an offshoring strategy. The thesis contributes to existing theory by explaining offshoring as a process, situated in a certain context and time. It defines key routines and capabilities needed to facilitate offshoring of complex product systems. Including context, timing and sequence when analysing offshoring help explain why some organizations fail to implement offshoring initiatives.The companies had an iterative learning process to deal with offshoring, and inclusion of all levels in an organization was highlighted as a key success factor for the implementation of offshoring. The results extend current understanding of offshoring of complex products to Asia and provide useful guidelines for managers on the key issues they need to consider.
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| 5. |
- Hu, Lan
(författare)
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Molten carbonate fuel cells for electrolysis
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The molten carbonate fuel cell has evolved to current megawatt-scale commercial power plants. When using the fuel cell for electrolysis, it provides a promising option for producing fuel gases such as hydrogen and syngas. The cell can thereby operate reversibly as a dual energy converter for electricity generation and fuel gas production. The so-called reversible molten carbonate fuel cell will probably increase the usefulness of the system and improve the economic benefits.This work has investigated the performance and durability of the cell in electrolysis and reversible operations. A lower polarization loss is found for the electrolysis cell than for the fuel cell, mainly due to the NiO electrode performing better in the MCEC. The stability of the cell in long-term tests evidences the feasibility of the MCEC and the RMCFC using a conventional fuel cell set-up, at least in lab-scale.This study elucidates the electrode kinetics of hydrogen production and oxygen production. The experimentally obtained partial pressure dependencies for hydrogen production are high, and they do not reasonably satisfy the reverse pathways of the hydrogen oxidation mechanisms. The reverse process of an oxygen reduction mechanism in fuel cell operation is found to suitably describe oxygen production in the MCEC.To evaluate the effect of the reverse water-gas shift reaction and the influence of the gas phase mass transport on the porous Ni electrode in the electrolysis cell, a mathematical model is applied in this study. When the humidified inlet gas compositions enter the current collector the decrease of the shift reaction rate increases the electrode performance. The model well describes the polarization behavior of the Ni electrode when the inlet gases have low contents of reactants. The experimental data and modeling results are consistent in that carbon dioxide has a stronger effect on the gas phase mass transport than other components, i.e. water and hydrogen.
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| 7. |
- Jensen, Martin, et al.
(författare)
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Neurofeedback for tinnitus : study protocol for a randomised controlled trial assessing the specificity of an alpha/delta neurofeedback training protocol in alleviating both sound perception and psychological distress in a cohort of chronic tinnitus sufferers
- 2020
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Ingår i: Trials. - : BioMed Central. - 1745-6215. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTinnitus is a particularly common condition and can have debilitating psychological consequences for certain people. Although several interventions have been helpful in teaching individuals to better cope with tinnitus, no cure exists at present. Neurofeedback is an emerging treatment modality in tinnitus. Previous studies, utilising an alpha/delta training protocol, have shown promise. However, they were characterised by small sample sizes and a lack of neurofeedback control conditions. Therefore, the aim of this study is to investigate whether an alpha/delta neurofeedback training protocol, compared to beta/theta neurofeedback or a diary control group, is effective in reducing not only the tinnitus sound perception but also the psychological symptoms associated with the condition.MethodsThe study is designed as a three-armed randomised controlled trial. Participants are randomly assigned to a) an established neurofeedback protocol for tinnitus (alpha/delta training), b) an active control group (beta/theta training) or c) a diary control group. In the 4-week intervention period, participants in both neurofeedback groups undergo 10 sessions, whereas participants in the diary control group complete a bi-weekly diary. The primary outcomes are between group differences in tinnitus sound perception change, as measured with the Tinnitus Magnitude Index (TMI), and changes in tinnitus distress, measured with the Tinnitus Handicap Inventory (THI), 4 weeks after the start of the intervention. Secondary outcome measures include changes in tinnitus distress, sleep quality, depressive symptoms and whether neurofeedback leads to specific power changes in the trained frequency bands.DiscussionThis is the first randomised controlled trial examining the efficacy of an alpha/delta neurofeedback training protocol in reducing tinnitus sound perception and the distress associated with the condition. Compared to former studies, the present study is designed to assess both the specificity of an alpha/delta neurofeedback training protocol by including an active comparator and beta/theta neurofeedback training, in addition to controlling for placebo effects by the inclusion of a diary control group. This study aims to contribute to an understanding of the influences of both specific and non-specific effects in neurofeedback treatment for tinnitus.
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| 10. |
- Mukwaya, Anthony
(författare)
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Regulation of inflammation and angiogenesis in the cornea
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammation and angiogenesis, the growth of new blood vessels from pre-existing ones, are involved in tumor growth, ocular diseases and wound healing. In ocular angiogenesis, new pathological vessels grow into a specific eye tissue, leak fluid, and disrupt vision. The development of safe and effective therapies for ocular angiogenesis is of great importance for preventing blindness, given that current treatments have limited efficacy or are associated with undesirable side effects. The search for alternative treatment targets requires a deeper understanding of inflammation and how it can lead to angiogenesis in the eye in pathologic situations. This thesis provides new insights into the regulation of inflammation and angiogenesis, particularly at the gene expression and phenotypic levels, in different situations characterized by angiogenesis of the cornea, often called corneal neovascularization. For instance, specific genes and pathways are either endogenously activated or suppressed during active inflammation, wound healing, and during resolution of inflammation and angiogenesis, serving as potential targets to modulate the inflammatory and angiogenic response. In addition, as part of the healing response to restore corneal transparency, inflammation and angiogenesis subside with time in the cornea. In this context, LXR/RXR signaling was found to be activated in a time-dependent manner, to potentially regulate resolution of inflammation and angiogenesis. During regression of new angiogenic capillaries, ghost vessels and empty basement membrane sleeves are formed, which can persist in the cornea for a long time. Here, ghost vessels were found to facilitate subsequent revascularization of the cornea, while empty basement membrane sleeves did not revascularize. The revascularization response observed here was characterised by vasodilation, increased inflammatory cell infiltration and by sprouting at the front of the reperfused vessels. Importantly, reactive oxygen species and nitrous oxide signaling among other pro-inflammatory pathways were activated, and at the same time anti-inflammatory LXR/RXR signaling was inhibited. The interplay between activation and inhibition of these pathways highlights potential mechanisms that regulate corneal revascularization. When treating corneal neovascularization clinically, corticosteroids are in widespread use due to their effectiveness. To minimize the many undesirable side effects associated with corticosteroid use, however, identifying new and more selective agents is of great importance. Here, it was observed that corticosteroids not only suppressed pro-inflammatory chemokines and cytokines, but also activated the classical complement pathway. Classical complement may represent a candidate for further selective therapeutic manipulation to investigate its effect on treatment of corneal neovascularization.In summary, this thesis identifies genes, pathways, and phenotypic responses involved in sprouting and remodeling of corneal capillaries, highlights novel pathways and factors that may regulate inflammation and angiogenesis in the cornea, and provides insights into regulation of capillary regression and reactivation. Further investigation of these regulatory mechanisms may offer alternative and effective treatment targets for the treatment of corneal inflammation and angiogenesis.
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| 11. |
- Olsson, Simon, 1983-
(författare)
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Al-based Thin Film Quasicrystals and Approximants
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this work, Al-based quasicrystalline and approximant phases have been synthesized in thin films using magnetron sputter deposition. Quasicrystals are structures having long-range order and rotational symmetries which are inconsistent with periodicity. Due to their unusual structure, quasicrystals show many anomalous and unique physical properties, including; high hardness, wear resistance, low friction, and low electrical and thermal conductivities. Approximants are a family of periodic phases that are related to the quasicrystals. These phases share the local atomic arrangement of quasicrystals and have as a result many similar physical properties. Bulk quasicrystals are too brittle for many of the suggested applications, and instead the most important area of applications concerns that of surface coatings.Multilayered Al/Cu/Fe thin films, with a nominal global composition corresponding to the quasicrystalline phase, have been deposited onto Si and Al2O3 substrates. During isothermal annealing at temperatures up to 700 °C homogeneous thin films were formed. When Si was used as substrate a film-substrate reaction occured already below 390 °C, where Si diffused into the film. This changed the composition, and promoted the formation of the cubic α-approximant phase. Annealing at 600 °C for 4 h the cubic α-approximant phase formed in a polycrystalline state, with a small amount of a second phase, τ7-Al3Fe2Si3. The film was within 1.5 at.% of the ideal composition of the α-approximant phase and contained 8 at.% Si. Continued annealing for 64 h provided for more diffusion of Si to 12 at.%. No degradation of the crystal quality of the remaining α-phase was observed even after as much as 150 h of treatment.Nanomechanical and nanotribological properties, including hardness, elastic modulus, friction and toughness, were investigated for the approximant and quasicrystalline samples. The approximant phase, annealed at 600 °C for 4 h, proved to be harder and had higher elastic modulus values than the quasicrystalline phase, about, 15.6 GPa and 258 GPa, respectively. The fracture toughness of the approximant, on the other hand, <0.1 MPa/m½, was inferior to that of the quasicrystals with 1.5 MPa/m½. Low friction coefficients of about 0.13 were measured for both phases.When annealing multilayered Al/Cu/Co thin films on Al2O3 the decagonal quasicrystal d-Al-Cu-Co was formed at 500 °C. The XRD peak intensities were rather low, but after raising the temperature to 850 °C a large increase in intensity and a complete texturing with the 10-fold periodic axis aligned with the substrate normal occurred. When annealing the same samples on Si, the decagonal quasicrystal was again found, however, TEM and EDX measurements identified 3-6 at.% Si inside the quasicrystalline grains. Also the decagonal d-Al-Cu-Co-Si quasicrystal was textured with the 10-fold periodic axis aligned with the surface normal. The texture was however not complete as in the thin films grown on Al2O3. Raising the temperature to over 700 °C led to the formation of other crystalline phases in favor of the decagonal d-Al-Cu-Co-Si.For the Cu-Al-Sc system quasicrystalline thin films were grown directly from the vapor phase by utilizing ion-assistance during growth at low temperatures, thus eliminating the need for post-annealing. Diffraction experiments revealed that amorphous films were formed at room temperature. The quasicrystalline phase formed at a substrate temperature of 340 °C with an improved quality at higher temperatures up to 460 °C. The quasicrystal film quality was improved by increasing the ion-flux during with ion energies of 26.7 eV. Increasing the ion energy further was however found to cause resputtering and defects in the films. Electron microscopy revealed a polycrystalline microstructure with crystal grains in the shape of thin needles.
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| 12. |
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| 13. |
- Sundman, Ann-Sofie, 1982-
(författare)
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Dog behaviour : Intricate picture of genetics, epigenetics, and human-dog relations
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dogs, Canis familiaris, share the lives of humans all over the world. That dogs, and the behavior of dogs, are of interest to many is therefore no surprise. In this thesis, the main aim has been to identify factors that affect dogs’ behaviours.The dog, Canis familiaris, is our first domesticated animal. Since domestication, various types of dogs have developed through adaptation to an environment shared with humans and through our selective breeding, resulting in a unique variation in morphology and behaviour. Although there is an individual variation in the behaviour of dogs, there is also a difference between breeds. Moreover, selection during the last decades has split some breeds into divergent types. Labrador and golden retrievers are divided into a common type, for show and companionship, and a field type, for hunting. By comparing the breed types, we can study the effects of recent selection. In Paper I, we investigate differences in general behavioural traits between Labrador and golden retriever and between common and field type within the two breeds by using results from the standardized behaviour test Dog Mentality Assessment. There were differences between breeds and types for all behavioural traits. However, there was also an interaction between breed and type. Thus, a common/field-type Labrador does not behave like a common/field-type golden retriever. Even though they have been selected for similar traits, the selection has affected the general behavioural traits differently in the two breeds.In paper II, we were interested in dogs’ human-directed social skills. Dogs have a high social competence when it comes to humans. Two experiments commonly used to study these skills are the problem-solving test, where dogs’ human-directed behaviours when faced with a problem are measured, and the pointing test, where dogs are tested on how well they understand human gestures. We compared the social skills of German shepherds and Labrador retrievers, and of common- and field-type Labradors. Labradors were more successful in the pointing test and German shepherds stayed closer to their owners during the problem solving. Among Labrador types, the field type had more human eye contact than the common type. Importantly, when comparing the two experiments, we found no positive correlations between the problem-solving test and the pointing test, suggesting that the two tests measure different aspects of human-directed social behaviour in dogs.A previous study has identified two suggestive genetic regions for human-directed social behaviours during the problem-solving test in beagles. In paper III, we show that these SNPs are also associated to social behaviours in Labrador and golden retrievers. Moreover, the Labrador breed types differed significantly in allele frequencies. This indicates that the two SNPs have been affected by recent selection and may have a part in the differences in sociability between common and field type.The behaviour of dogs cannot simply be explained by genetics, there is also an environmental component. In paper IV, we study which factors that affect long-term stress in dogs. Long-term cortisol can be measured by hair samples. We found a clear synchronization in hair cortisol concentrations between dogs and their owners. Neither dogs’ activity levels nor their behavioural traits affected the cortisol, however, the personality of the owners did. Therefore, we suggest that dogs mirror the stress level of their owners.The mediator between genes and the environment is epigenetics, and one epigenetic factor is DNA methylation. In paper V, we compared methylation patterns of wolves and dogs as well as dog breeds. Between both wolves and dogs and among dogs there were substantial differences in methylated DNA regions, suggesting that DNA methylation is likely to contribute to the vast variation among canines. We hypothesize that epigenetic factors have been important during domestication and in breed formation.In this thesis, I cover several aspects on how dogs’ behaviours can be affected, and paint an intricate picture on how genetics, epigenetics, and human-dog relations forms dog behaviour.
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| 14. |
- Åhlfeldt, Emanuel
(författare)
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Hållbart utvecklingsarbete i vård och omsorg : Ett institutionellt perspektiv på projekt i en professionell och byråkratisk kontext
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Det drivs många utvecklingsprojekt inom offentlig sektor, men det saknas kunskap om hur dessa projekt kan bidra till ett hållbart utvecklingsarbete. Syftet med avhandlingen är att förstå och förklara hur resultat och kunskap från utvecklingsprojekt kan integreras i den ordinarie verksamheten i offentliga organisationer och bidra till långsiktiga effekter, som har ett värde för brukarna, organisationen och de anställda.I forskningen saknas en etablerad begreppsapparat för att studera hållbar utveckling i organisationer. En utmaning har därför varit att identifiera och analysera tidigare forskning, för att därigenom definiera begreppet hållbart utvecklingsarbete och viktiga förutsättningar för ett sådant arbete. Den teoretiska referensramen baseras på ett institutionellt perspektiv: nyinstitutionell organisationsteori kombineras med Giddens struktureringsteori och sociologisk professionsteori, som synliggör spänningar mellan konkurrerande styrformer som byråkrati, marknad och professionalism.Avhandlingen utgår från en interaktiv forskningsansats och består av två empiriska delar: en kvantitativ enkätstudie som inkluderar 348 utvecklingsprojekt inom vård och omsorg samt en kvalitativ flerfallstudie av fyra utvecklingsprojekt.Studierna visar att olika faktorer främjade projekten på kort och lång sikt. Tydliga projektmål, styrning och kompetent projektledning hade betydelse för de kortsiktiga projektresultaten, men mycket begränsat påverkan på den långsiktiga hållbarheten. Istället var det ett aktivt ägarskap, och andra faktorer kopplade till ledningen i mottagarorganisationerna, som tydligast främjade ett hållbart utvecklingsarbete. Studierna visar även hur konflikter och motstånd i projekten påverkade förutsättningarna för långsiktig hållbarhet. Det gällde konflikter mellan olika yrkesgrupper, mellan ledning och professionella samt mellan byråkratiska och professionella styrformer. En slutsats är att en analysmodell för hållbart utvecklingsarbete behöver komplettera ett organisatoriskt och institutionellt perspektiv med ett professionsperspektiv.
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| 15. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 16. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 17. |
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| 18. |
- Agnvall, Beatrix
(författare)
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Early domestication? : Phenotypic alterations of Red Junglefowl selected for divergent fear of humans
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Domestication is the process through which animals adapt to conditions provided by humans. The domesticated phenotype differs from wild ancestors in a number of traits relating to physiology, morphology and behaviour. One of the most striking differences is the animals’ fear response towards humans, and reduced fear of humans is assumed to have been an early prerequisite for the success of domestication. The early alterations seen in the domesticated phenotype may be traits developed as a correlated selection response due to tameness rather than selected upon one by one.This thesis summarizes a project where Red Junglefowl were selected for divergent fear of humans during six generations. In every generation, fear response to human was assessed in a standardized test and, according to fear score, the animals were bred for either high fear of humans (H) or low fear of humans (L). The animals were, above that of the standardized selection test, behaviourally phenotyped in different tests in each generation mainly focusing on fear, exploration and social behaviour. In addition to behaviour, the animals were phenotyped for body weight, egg weight, metabolism, feed intake, plumage condition, blood plasma corticosterone and peripheral serotonin. After culling, vital organs and brains were harvested and weighed.In paper I, we demonstrated that the selection trait has a significant genetic heritability and is genetically correlated with other behavioural responses associated with fearfulness and exploration. In paper II, we concluded that animals from the L strain had better plumage condition, higher weight, laid larger eggs and also generated larger offspring. Furthermore, when tested in a social dominance test with a limited resource, they received less and performed more aggression regardless of whether the restricted source was edible or not. In paper III, we revealed that animals from the L strain had higher basal metabolic rate as chicks, gained more weight in relation to feed intake and were bolder in a Novel Object test. Furthermore, the L males had higher plasma levels of peripheral serotonin, but the corticosterone after a restraint stress test did not differ. In paper IV and V, we concluded the project by comparing brain and organ weights as well as behaviour of the parental generation (P0) with the fifth selected generation (S5). The absolute brain weight as well as the weight specific brain weight were larger in the animals selected on H than in the L-animals. The relative weight of telencephalon was significantly higher in H whereas relative weight of cerebellum was significantly lower. Heart, liver, spleen and testes were all relatively heavier in H animals than in L. Interestingly, the behaviours assessed in P0 and S5 seemed to be rather resilient to the selection with only small differences in S5.To summarize, the selection on divergent tameness in Red Junglefowl has affected several phenotypic traits associated with the domesticated phenotype. The results of this project indicate that tameness in Red Junglefowl could be an underlying factor driving trait modifications towards the domesticated phenotype.
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| 29. |
- Alizadeh Khameneh, Mohammad Amin, 1983-
(författare)
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Optimal Design in Geodetic GNSS-based Networks
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An optimal design of a geodetic network helps the surveying engineers maximise the efficiency of the network. A number of pre-defined quality requirements, i.e. precision, reliability, and cost, of the network are fulfilled by performing an optimisation procedure. Today, this is almost always accomplished by implementing analytical solutions, where the human intervention in the process cycle is limited to defining the requirements. Nevertheless, a trial and error method can be beneficial to some applications. In order to analytically solve an optimisation problem, it can be classified to different orders, where an optimal datum, configuration, and optimal observation weights can be sought such that the precision, reliability and cost criteria are satisfied.In this thesis, which is a compilation of six peer-reviewed papers, we optimised and redesigned a number of GNSS-based monitoring networks in Sweden by developing new methodologies. In addition, optimal design and efficiency of total station establishment with RTK-GNSS is investigated in this research.Sensitivity of a network in detecting displacements is of importance for monitoring purposes. In the first paper, a precision criterion was defined to enable a GNSS-based monitoring network to detect 5 mm displacements at each network point. Developing an optimisation model by considering this precision criterion, reliability and cost yielded a decrease of 17% in the number of observed single baselines implying a reliable and precise network at lower cost. The second paper concerned a case, where the precision of observations could be improved in forthcoming measurements. Thus a new precision criterion was developed to consider this assumption. A significant change was seen in the optimised design of the network for subsequent measurements. As yet, the weight of single baselines was subject to optimisation, while in the third paper, the effect of mathematical correlations between GNSS baselines was considered in the optimisation. Hence, the sessions of observations, including more than two receivers, were optimised. Four out of ten sessions with three simultaneous operating receivers were eliminated in a monitoring network with designed displacement detection of 5 mm. The sixth paper was the last one dealing with optimisation of GNSS networks. The area of interest was divided into a number of three-dimensional elements and the precision of deformation parameters was used in developing a precision criterion. This criterion enabled the network to detect displacements of 3 mm at each point.A total station can be set up in the field by different methods, e.g. free station or setup over a known point. A real-time updated free station method uses RTK-GNSS to determine the coordinates and orientation of a total station. The efficiency of this method in height determination was investigated in the fourth paper. The research produced promising results suggesting using the method as an alternative to traditional levelling under some conditions. Moreover, an optimal location for the total station in free station establishment was studied in the fifth paper. It was numerically shown that the height component has no significant effect on the optimal localisation.
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| 30. |
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| 31. |
- Barnes, DR, et al.
(författare)
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Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 114:1, s. 109-122
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers.Methods483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)–negative (PRSER-), or ER-positive (PRSER+) breast cancer risk.ResultsPRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions.ConclusionsPopulation-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.
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| 32. |
- Bergfeldt, Erik
(författare)
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Available-Bandwidth Estimation in Packet-Switched Communication Networks
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents novel methods that are able to perform real-time estimation of the available bandwidth of a network path. In networks such as the Internet, knowledge of bandwidth characteristics is of great significance in, e.g., network monitoring, admission control, and audio/video streaming.The term bandwidth describes the amount of information a network can deliver per unit of time. For network end users, it is only feasible to obtain bandwidth properties of a path by actively probing the network with probe packets, and to perform estimation based on received measurements. In this thesis, two active-probing based methods for real-time available-bandwidth estimation are presented and evaluated.The first method, BART (Bandwidth Available in Real-Time), uses Kalman filtering for the analysis of received probe packets. BART is examined analytically and through experiments which are carried out in wired and wireless laboratory networks as well as over the Internet and commercial mobile broadband networks. The opportunity of tuning the Kalman filter and enhancing the performance by introducing change detection are investigated in more detail. Generally, the results show accurate estimation with only modest computational efforts and minor injections of probe packets.However, it is possible to identify weaknesses of BART, and a summary of these as well as general problems and challenges in the field of available-bandwidth estimation are laid out in the thesis. The second method, E-MAP (Expectation-Maximization Active Probing), is designed to overcome some of these issues. E-MAP modifies the active-probing scheme of BART and utilizes the expectation-maximization algorithm before filtering is used to generate a bandwidth estimate.Overall, this thesis shows that in many cases it is achievable to obtain efficient and reliable real-time estimation of available bandwidth by using light-weight analysis techniques and negligible probe-traffic overhead. Hence, this opens up exciting new possibilities for a range of applications and services in communication networks.
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| 33. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 34. |
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| 35. |
- Bousquet, J, et al.
(författare)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Tidskriftsartikel (refereegranskat)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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| 36. |
- Coignard, J, et al.
(författare)
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A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers
- 2021
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 1078-
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Tidskriftsartikel (refereegranskat)abstract
- Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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| 37. |
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| 38. |
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| 39. |
- Dareng, EO, et al.
(författare)
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Polygenic risk modeling for prediction of epithelial ovarian cancer risk
- 2022
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Ingår i: European journal of human genetics : EJHG. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 30:3, s. 349-362
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, “select and shrink for summary statistics” (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction. We developed the models in a dataset consisting of 23,564 non-mucinous EOC cases and 40,138 controls participating in the Ovarian Cancer Association Consortium (OCAC) and validated the best models in three populations of different ancestries: prospective data from 198,101 women of European ancestries; 7,669 women of East Asian ancestries; 1,072 women of African ancestries, and in 18,915 BRCA1 and 12,337 BRCA2 pathogenic variant carriers of European ancestries. In the external validation data, the model with the strongest association for non-mucinous EOC risk derived from the OCAC model development data was the S4 model (27,240 SNPs) with odds ratios (OR) of 1.38 (95% CI: 1.28–1.48, AUC: 0.588) per unit standard deviation, in women of European ancestries; 1.14 (95% CI: 1.08–1.19, AUC: 0.538) in women of East Asian ancestries; 1.38 (95% CI: 1.21–1.58, AUC: 0.593) in women of African ancestries; hazard ratios of 1.36 (95% CI: 1.29–1.43, AUC: 0.592) in BRCA1 pathogenic variant carriers and 1.49 (95% CI: 1.35–1.64, AUC: 0.624) in BRCA2 pathogenic variant carriers. Incorporation of the S4 PRS in risk prediction models for ovarian cancer may have clinical utility in ovarian cancer prevention programs.
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| 40. |
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| 41. |
- Diwakarla, Shanti, et al.
(författare)
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Binding to and Inhibition of Insulin-Regulated Aminopeptidase (IRAP) by Macrocyclic Disulfides Enhances Spine Density
- 2016
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Ingår i: Molecular Pharmacology. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0026-895X .- 1521-0111. ; 89:4, s. 413-424
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin IV (Ang IV) and related peptide analogues, as well as non-peptide inhibitors of insulin-regulated aminopeptidase (IRAP), have previously been shown to enhance memory and cognition in animal models. Furthermore, the endogenous IRAP substrates oxytocin and vasopressin are known to facilitate learning and memory. In this study, the two recently synthesized 13-membered macrocylic competitive IRAP inhibitors HA08 and HA09, which were designed to mimic the N-terminal of oxytocin and vasopressin, were assessed and compared based on their ability to bind to the IRAP active site, and alter dendritic spine density in rat hippocampal primary cultures. The binding modes of the IRAP inhibitors HA08, HA09 and of Ang IV in either the extended or γ-turn conformation at the C-terminal to human IRAP were predicted by docking and molecular dynamics (MD) simulations. The binding free energies calculated with the linear interaction energy (LIE) method, which are in excellent agreement with experimental data and simulations, have been used to explain the differences in activities of the IRAP inhibitors, both of which are structurally very similar, but differ only with regard to one stereogenic center. In addition, we show that HA08, which is 100-fold more potent than the epimer HA09, can enhance dendritic spine number and alter morphology, a process associated with memory facilitation. Therefore, HA08, one of the most potent IRAP inhibitors known today, may serve as a suitable starting point for medicinal chemistry programs aided by MD simulations aimed at discovering more drug-like cognitive enhancers acting via augmenting synaptic plasticity.
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| 42. |
- Gao, Hong, et al.
(författare)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
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Tidskriftsartikel (refereegranskat)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 43. |
- Garnham, Laura, 1988-
(författare)
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Causes and Consequences of Impulsivity in Red Junglefowl
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Throughout the animal kingdom, animals vary in cognition (i.e., how they acquire, process, store, and act on environmental information). Yet, the causes and consequences of this variation are currently unclear. Inhibitory control is one such aspect of cognition that typically varies between individuals within all species investigated. Variation in inhibitory control underlies variation in impulsivity (i.e., the tendency to act without planning or considering the consequences). The causes and consequences of variation in impulsivity are, themselves, rarely explored, despite that these may have important ecological and evolutionary implications. My thesis (spanning 5 papers), therefore, aimed to fill some of these gaps by taking a holistic approach and investigating causes and consequences of variation in impulsivity (specifically, impulsive action and persistence measured in a detour task) in red junglefowl (Gallus gallus) males and females, chicks and adults. The red junglefowl was an ideal species for this investigation. Firstly, they show individual variation in impulsivity throughout their lives. They are also typically food motivated, and easily habituated to handling and new situations, which means they commonly willingly participate in behavioural and cognitive tests. Furthermore, they are precocial, which means that they can be hatched and raised without mothers, thus reducing parental effects. Finally, the large, accumulated knowledge of red junglefowl behaviour and cognition aids interpretations regarding this. As differences in experience early in life have been found to affect impulsivity, papers I and II empirically explored whether variation in two previously uninvestigated experiences in early life (exposure to enrichment, and social group size, respectively) influenced impulsivity. The dopaminergic and serotonergic systems are important signalling systems in the brain, which have been found to link to impulsivity in other species. Therefore, in paper I, I also explored if variation in impulsive action and persistence was connected to variation in dopaminergic or serotonergic gene expression. As impulsivity links to inhibitory control, in looking at the effect of group size on impulsivity, paper II explored the hypotheses that social environment affects cognition (e.g., that social environments which are assumed to be more cognitively demanding will lead to better cognitive performance, a.k.a., the social intelligence hypothesis). To uncover potential mechanisms by which group size could affect impulsivity, besides from variation in cognitive demand, paper II also investigated if behaviours that could covary with group size linked to impulsivity. As emotional arousal has been linked to impulsivity, in another species, and impulsivity is implicated in welfare issues, paper III looked into how both positive and negative affective states (which can be used to measure welfare) related to impulsivity. Prior to my thesis, whether variation in impulsivity could potentially affect animal welfare was scarcely explored. To better understand the potential consequences of impulsivity, and, thus, how selection could act on impulsivity, papers IV and V looked at potential implications of variation in impulsivity for social status (paper IV and V), foraging efficiency, and risk taking (paper V). My results showed that impulsivity could be consistent over time periods of weeks (in chicks, paper II) to months (in adults, paper V). Thus, impulsivity describes a characteristic of the individual. However, individuals could still learn to become less impulsive (paper I). Exposure to enrichment in early life could affect how impulsively individuals behaved. Environmental enrichment increased impulsivity, as did cognitive enrichment to a greater degree (paper I). Impulsive action, and persistence, correlated somewhat with brain gene expression of dopaminergic and serotonergic genes (DRD1, TPH; paper I). The social group size individuals experimentally experienced in early life did not affect their impulsivity (paper II). However, variation in impulsivity was connected to variation in activity, boldness, neophobia, and stress (paper II). Further, more impulsive individuals had less negative, more positive, affective states, but only when they were young chicks, and not as older chicks or adults (paper VI). No links were found between impulsivity and social status (paper IV and V), foraging efficiency, or risk taking (paper V). Taken together, paper I suggests that underlying explanations to observed individual variation in impulsivity could include variation in early life experiences and in dopaminergic and serotonergic gene expression, while paper II suggests that impulsivity may not be influenced by social aspects early in life. Papers II and III demonstrate that variation in impulsivity can associate with variation in behaviours and affective states (though these associations may vary over ontogeny), with the latter finding implying that variation in impulsivity could have welfare implications. Papers IV and V indicate that variation in impulsivity may have limited consequences for individuals in contexts that could affect reproduction or survival. Thus, it may not necessarily be costly to individuals if they are more impulsive than others. This, in turn, could help explain why variation in inhibitory control exists, because limited consequences of variation could result in low selection against variation. Overall, through the investigations conducted in its 5 papers, my thesis improves our understanding the potential causes and consequences of variation in impulsivity. As impulsivity is underlain by an aspect of cognition (inhibitory control), in exploring the causes and consequences of variation in impulsivity, my thesis also provides knowledge on causes and consequences of individual variation in cognition.
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| 44. |
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| 45. |
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| 46. |
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| 47. |
- Grahn, Karl-Johan, 1981-
(författare)
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Measurement of Multi-Jet Production in Proton-Proton Collisions at 7 TeV Center-of-Mass Energy and Hadronic Calibration Studies with the ATLAS Detector at CERN
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The ATLAS experiment – situated at the Large Hadron Collider (LHC) at the European Organization for Nuclear Research (CERN) in Geneva – took its first collsion data in 2010. Physics topics include finding the Higgs boson, heavy quark physics, and looking for extensions of the Standard Model of Particle Physics such as supersymmetry. In this thesis, inclusive multi-jet production has been studied with the ATLAS detector in proton-proton collisions at a center-of-mass energy of 7 TeV, using an integrated luminosity of 17 nb−1. The anti-kt algorithm with distance parameter ℝ = 0.6 is used to identify jets. The inclusive multi-jet cross section is measured, as well as the ratio ofcross sections for inclusive production of n − 1 and n jets for n ≤ 6. The differential cross sections of the first, second, third and fourth leading jets as a function of transverse momentum, and the differential cross section as a function of the scalar sum of the pT of selected jets, HT, for different jet multiplicities are presented. The ratio of the differential cross section as a function of HT for 3-jet and 2-jet events is also measured. The results are compared to expectations based on leading order QCD, which agree with the data. In addition, a new method for calibrating the hadron response of a segmented calorim-ter is developed and successfully applied to 2004 ATLAS combined beam test data. It is based on a principal component analysis of the calorimeter layer energy deposits, exploiting longitudinal shower development information to improve the measured energyresolution. For pion beams with energies between 20 and 180 GeV, the particle energy is reconstructed within 3% and the energy resolution is improved by 11% to 25% comparedto the response at the electromagnetic scale. Multi-mode optical readout cables for the ATLAS liquid argon calorimeters, about one hundred meters in length, were installed between the main ATLAS cavern and the counting room in the USA15 cavern. Patch cables were spliced onto the ribbons and the fiber attenuation was measured. For 1296 fiber pairs in 54 cables, the average attenuation was 0.69 dB. Only five fibers were found to have losses exceeding 4 dB, resulting in a failure rate of less than 2 per mill. In the ATLAS liquid argon barrel presampler, short circuits consisting of small pieces of dust, metal, etc. can be burned away in situ by discharging a capacitor over the high voltage lines. In a burning campaign in November 2006, seventeen existing short circuits were successfully removed. An investigation on how to implement saturation effects in liquid argon due to high ionization densities resulted in the implementation of the effect in the ATLAS Monte Carlo code, improving agreement with beam test data. The timing structure of hadronic showers was investigated using a Geant4 Monte Carlo. The expected behavior as described in the literature was reproduced, with the exception that some sets of physics models gave unphysical gamma energies from nuclear neutron capture.
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| 48. |
- Hansson, Per
(författare)
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First determination of the electric charge of the top quark
- 2006
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In this thesis, the first determination of the electric charge of the top quark is presented using 370pb-1 of data recorded by the DØ detector at the Fermilab Tevatron accelerator. ttbar events are selected with one isolated electron or muon and at least four jets out of which two are b-tagged by reconstruction of a secondary decay vertex (SVT). The method is based on the discrimination between b- and b-quark jets using a jet charge algorithm applied to SVT-tagged jets. A method to calibrate the jet charge algorithm with data is developed. A constrained kinematic fit is performed to associate the W bosons to the correct b-quark jets in the event and extract the top quark electric charge. The data is in good agreement with the Standard Model top quark electric charge of 2e/3. The scenario where the selected sample is solely composed of an exotic quark Q with charge 4e/3 is excluded at 92% confidence level. Using a Bayesian approach, an upper limit on the fraction of exotic quarks p < 0.80 at 90% confidence level is obtained.
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| 49. |
- Håkansson, Jennie, 1976-
(författare)
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Behavioural aspects of conservation breeding : Red junglefowl (Gallus gallus) as a case study
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ett stort antal utrotningshotade djurarter ingår idag i bevarandeprogram världen över. Små populationer hålls då i skyddade miljöer, exempelvis i djurparker, och i många fall är målet att återintroducera djur till naturen. Dessvärre är det vanligt att det uppstår problem när djur återintroduceras vilket kan bero på beteendemässiga anpassningar som uppkommit under tiden i fångenskap. Syftet med den här studien var därför att undersöka beteendemässiga aspekter på bevarandeavel och försöka ta reda på om och hur djur påverkas beteendemässigt av att hållas i skyddade fångenskapsmiljöer. I projektet användes röda djungelhöns (Gallus gallus) som en fallstudie. En granskning av beteendevariation mellan olika populationer av röda djungelhöns i fångenskap konstaterade skillnader i antipredatorbeteende, socialt beteende och födosöksbeteende. Vid en genetisk studie av samma populationer upptäcktes dessutom ett samband mellan genetisk diversitet och beteendevariation som potentiellt kan vara intressant ur ett bevarandeperspektiv. Socialt beteende, födosöksbeteende och olika aspekter av rädsla studerades vidare i populationer med olika bakgrund som fick växa upp tillsammans i en grupp. Resultaten visade att populationerna bara skilde sig åt i rädslebeteenden vilket antyder att denna typ av beteende i större utsträckning påverkas av långvarig avel i en viss fångenskapsmiljö medan socialt beteende och födosöksbeteende istället kan bero på den omedelbara sociala eller fysiska miljön. Antipredatorbeteende studerades också i en longitudinell studie av två populationer över fyra generationer och det visade sig att populationerna blev mer lika varandra ju längre tiden gick då de hölls under likadana miljöförhållanden. Det verkar alltså som om antipredatorbeteende kan förändras av avel i en viss miljö efter bara ett fåtal generationer. Utöver detta studerades även dagliga beteendemönster i olika djurparksmiljöer samt dygnsrytm av galanden hos både vilda populationer och djurparkspopulationer inom artens naturliga utbredningsområde. Resultaten tyder på att sådana beteendemönster inte påverkas nämnvärt av att djur hålls i fångenskap. Fallstudien som presenteras här är ett av de första försöken att, ur ett bevarandeperspektiv, studera hur fångenskapsmiljöer kan påverka djurs beteende och resultaten talar för att dessa aspekter är viktiga att ta hänsyn till vid planering av bevarandeavel.
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| 50. |
- Jensen, Axel, et al.
(författare)
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Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation
- 2023
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Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 40:12
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation.
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