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  • Disputation: 2017-12-15 13:00 Schrödinger, E324, Fysikhuset, Linköping
    Løtvedt, Pia Katrine
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Domestication and early experiences in chickens: Behavior, stress and gene expression2017Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    A number of animal species have undergone domestication, the process of becoming adapted to living in captivity and in proximity to humans. Common for these species is that they have all developed certain traits, including changes to coat color, body size and level of fearfulness. This has been termed the domestic phenotype. Among these traits is also an attenuation of the response to stress, both behaviorally and physiologically. Thus, release of glucocorticoids such as cortisol or corticosterone is lower in domesticated species. However, the underlying mechanism for this is not yet well understood. In this thesis, we have investigated genetic mechanisms for the attenuation of the physiological stress response in ancestral chickens, the Red Junglefowl, and domesticated chickens, the White Leghorn.

    We found a number of genes that differed in expression between the two breeds in several tissues involved in the stress response. Among the most interesting findings were lower expression of genes involved in production and secretion of ACTH in the pituitary, and in the production of glucocorticoids in the adrenal glands, in the domesticated White Leghorns. We also found higher expression of the glucocorticoid receptor in White Leghorns, indicating that they may have a more efficient negative feedback of the physiological stress response.

    We then investigated the transcriptome of the chicken pituitary more closely, and we discovered that a number of genes highly involved in several important physiological axes showed differential expression between the ancestral and the domesticated breed. Among these were genes involved in the stress response, the reproductive system, and in metabolism and growth. As these traits are modified in domesticated species, our results suggest that changes to gene expression in the pituitary may be an important underlying factor of the domestic phenotype.

    A separate aim of this thesis was to investigate effects of hatching time in chickens on their subsequent phenotype. Time of hatching constitutes an early experience that may differ between individuals, and we therefore hypothesized that differences in hatching time would affect chickens later in life. While a number of studies have been performed on hatching time and post-hatch growth, very little work has been done on effects on behavior. We found that the time of hatching had sex-specific effects. Hatching times in females were negatively correlated with body weight, whereas in males, behaviors such as reaction to novelty and spatial learning were affected.

    As time of hatching is governed by various hormones, including thyroid hormone and corticosterone, we suggest that changes to the levels of these hormones could affect both hatching time and post-hatch phenotypes. Understanding these mechanisms better would be beneficial in terms of production, where batch homogeneity is important, in research on early experiences and the potential for maternal programming, and in evolutionary questions on trade-off between different life strategies.

  • Disputation: 2017-12-07 12:22 F3, Stockholm
    Viveca, Lindahl
    KTH, Skolan för teknikvetenskap (SCI), Fysik.
    Optimizing sampling of important events in complex biomolecular systems2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Proteins and DNA are large, complex molecules that carry out biologicalfunctions essential to all life. Their successful operation relies on adoptingspecific structures, stabilized by intra-molecular interactions between atoms.The spatial and temporal resolution required to study the mechanics of thesemolecules in full detail can only be obtained using computer simulations ofmolecular models. In a molecular dynamics simulation, a trajectory of thesystem is generated, which allows mapping out the states and dynamics ofthe molecule. However, the time and length scales characteristic of biologicalevents are many orders of magnitude larger than the resolution needed toaccurately describe the microscopic processes of the atoms. To overcome thisproblem, sampling methods have been developed that enhance the occurrenceof rare but important events, which improves the statistics of simulation data.

    This thesis summarizes my work on developing the AWH method, an al-gorithm that adaptively optimizes sampling toward a target function and si-multaneously finds and assigns probabilities to states of the simulated system.I have adapted AWH for use in molecular dynamics simulations. In doing so,I investigated the convergence of the method as a function of its input param-eters and improved the robustness of the method. I have also worked on agenerally applicable approach for calculating the target function in an auto-matic and non-arbitrary way. Traditionally, the target is set in an ad hoc way,while now sampling can be improved by 50% or more without extra effort. Ihave also used AWH to improve sampling in two biologically relevant applica-tions. In one paper, we study the opening of a DNA base pair, which due tothe stability of the DNA double helix only very rarely occurs spontaneously.We show that the probability of opening depends on both nearest-neighborand longer-range sequence effect and furthermore structurally characterizethe open states. In the second application the permeability and ammoniaselectivity of the membrane protein aquaporin is investigated and we showthat these functions are sensitive to specific mutations.

  • Løtvedt, Pia Katrine
    et al.
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Fallahsharoudi, Amir
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Bektic, Lejla
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Altimiras, Jordi
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Jensen, Per
    Linköpings universitet, Institutionen för fysik, kemi och biologi, Biologi. Linköpings universitet, Tekniska fakulteten.
    Chicken domestication changes expression of stress-related genes in brain, pituitary and adrenals.2017Ingår i: Neurobiology of stress, ISSN 2352-2895, Vol. 7, 113-121 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Domesticated species have an attenuated behavioral and physiological stress response compared to their wild counterparts, but the genetic mechanisms underlying this change are not fully understood. We investigated gene expression of a panel of stress response-related genes in five tissues known for their involvement in the stress response: hippocampus, hypothalamus, pituitary, adrenal glands and liver of domesticated White Leghorn chickens and compared it with the wild ancestor of all domesticated breeds, the Red Junglefowl. Gene expression was measured both at baseline and after 45 min of restraint stress. Most of the changes in gene expression related to stress were similar to mammals, with an upregulation of genes such as FKBP5, C-FOS and EGR1 in hippocampus and hypothalamus and StAR, MC2R and TH in adrenal glands. We also found a decrease in the expression of CRHR1 in the pituitary of chickens after stress, which could be involved in negative feedback regulation of the stress response. Furthermore, we observed a downregulation of EGR1 and C-FOS in the pituitary following stress, which could be a potential link between stress and its effects on reproduction and growth in chickens. We also found changes in the expression of important genes between breeds such as GR in the hypothalamus, POMC and PC1 in the pituitary and CYP11A1 and HSD3B2 in the adrenal glands. These results suggest that the domesticated White Leghorn may have a higher capacity for negative feedback of the HPA axis, a lower capacity for synthesis of ACTH in the pituitary and a reduced synthesis rate of corticosterone in the adrenal glands compared to Red Junglefowl. All of these findings could explain the attenuated stress response in the domesticated birds.

  • Disputation: 2017-12-13 10:15 D3, Stockholm
    Sundström, Elias
    KTH, Skolan för teknikvetenskap (SCI), Mekanik. KTH, Skolan för industriell teknik och management (ITM), Centra, Competence Center for Gas Exchange (CCGEx).
    Flow instabilities in centrifugal compressors at low mass flow rate2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    A centrifugal compressor is a mechanical machine with purpose to convert kineticenergy from a rotating impeller wheel into the fluid medium by compressingit. One application involves supplying boost air pressure to downsized internalcombustion engines (ICE). This allows, for a given combustion chamber volume,more oxygen to the combustion process, which is key for an elevated energeticefficiency and reducing emissions. However, the centrifugal compressor is limitedat off-design operating conditions by the inception of flow instabilities causingrotating stall and/or surge. These instabilities appear at low flow rates andtypically leads to large vibrations and stress levels. Such instabilities affectthe operating life-time of the machine and are associated with significant noiselevels.The flow in centrifugal compressors is complex due to the presence of a widerange of temporal- and spatial-scales and flow instabilities. The success fromconverting basic technology into a working design depends on understandingthe flow instabilities at off-design operating conditions, which limit significantlythe performance of the compressor. Therefore, the thesis aims to elucidate theunderlying flow mechanisms leading to rotating stall and/or surge by means ofnumerical analysis. Such knowledge may allow improved centrifugal compressordesigns enabling them to operate more silent over a broader operating range.Centrifugal compressors may have complex shapes with a rotating partthat generate turbulent flow separation, shear-layers and wakes. These flowfeatures must be assessed if one wants to understand the interactions among theflow structures at different locations within the compressor. For high fidelityprediction of the complex flow field, the Large Eddy Simulation (LES) approachis employed, which enables capturing relevant flow-driven instabilities underoff-design conditions. The LES solution sensitivity to the grid resolution usedand to the time-step employed has been assessed. Available experimentaldata in terms of compressor performance parameters, time-averaged velocity,pressure data (time-averaged and spectra) were used for validation purposes.LES produces a substantial amount of temporal and spatial flow data. Thisnecessitates efficient post-processing and introduction of statistical averagingin order to extract useful information from the instantaneous chaotic data. Inthe thesis, flow mode decomposition techniques and statistical methods, suchas Fourier spectra analysis, Dynamic Mode Decomposition (DMD), ProperOrthogonal Decomposition (POD) and two-point correlations, respectively, areemployed. These methods allow quantifying large coherent flow structures atvfrequencies of interest. Among the main findings a dominant mode was foundassociated with surge, which is categorized as a filling and emptying processof the system as a whole. The computed LES data suggest that it is causedby substantial periodic oscillation of the impeller blade incidence flow angleleading to complete system flow reversal. The rotating stall flow mode occurringprior to surge and co-existing with it, was also captured. It shows rotating flowfeatures upstream of the impeller as well as in the diffuser.

  • Lund, Allan A.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia.
    Lidt om arkæologi og racisme1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, Vol. 28, 357-360 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Edberg, Rune
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia.
    Tesch, Sten
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia.
    Nyfunna skeppsbilder från 1100-talet i Sigtuna1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, Vol. 28, 305-312 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Disputation: 2017-12-15 16:57 D3, Stockholm
    Fornari, Walter
    KTH, Skolan för teknikvetenskap (SCI), Mekanik.
    Suspensions of finite-size rigid particles in laminar and turbulent flows2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Dispersed multiphase flows occur in many biological, engineering and geophysical applications such as fluidized beds, soot particle dispersion and pyroclastic flows. Understanding the behavior of suspensions is a very difficult task. Indeed particles may differ in size, shape, density and stiffness, their concentration varies from one case to another, and the carrier fluid may be quiescent or turbulent. When turbulent flows are considered, the problem is further complicated by the interactions between particles and eddies of different size, ranging from the smallest dissipative scales up to the largest integral scales. Most of theinvestigations on this topic have dealt with heavy small particles (typically smaller than the dissipative scale) and in the dilute regime. Less is known regarding the behavior of suspensions of finite-size particles (particles that are larger than the smallest length scales of the fluid phase).

    In the present work, we numerically study the behavior of suspensions of finite-size rigid particles in different flows. In particular, we perform direct numerical simulations using an immersed boundary method to account for the solid phase. Firstly, the sedimentation of spherical particles slightly smaller than the Taylor microscale in sustained homogeneous isotropic turbulence and quiescent fluid is investigated. The results show that the mean settling velocity is lower in an already turbulent flow than in a quiescent fluid. By estimating the mean drag acting on the particles, we find that non stationary effects explain the increased reduction in mean settling velocity in turbulent environments. Moreover, when the turbulence root-mean-square velocity is larger than the terminal speed of a particle, the overall drag is further enhanced due to the large particles cross-flow velocities.

    We also investigate the settling in quiescent fluid of oblate particles. We find that at low volume fractions the mean settling speed of the suspension is substantially larger than the terminal speed of an isolated oblate. This is due to the formation of clusters that appear as columnar-like structures.

    Suspensions of finite-size spheres are also studied in turbulent channel flow. We change the solid volume and mass fractions, and the solid-to-fluid density ratio in an idealized scenario where gravity is neglected. The aim is to independently understand the effects of these parameters on both fluid and solid phases statistics. It is found that the statistics are substantially altered by changes in volume fraction, while the main effect of increasing the density ratio is a shear-induced migration toward the centerline. However, at very high density ratios (∼ 1000) the solid phase decouples from the fluid, and the particles behave as a dense gas.

    In this flow case, we also study the effects of polydispersity by considering Gaussian distributions of particle radii (with increasing standard deviation), at constant volume fraction. We find that fluid and particle statistics are almost unaltered with respect to the reference monodisperse suspension. These results confirm the importance of the solid volume fraction in determing the behavior of a suspension of spheres.

    We then consider suspensions of solid spheres in turbulent duct flows. We see that particles accumulate mostly at the corners. However, at large volume fractions the particles concentrate mostly at the duct core. Secondary motions are enhanced by increasing the volume fraction, until excluded volume effects are so strong that the turbulence activity is reduced. The same is found for the mean friction Reynolds number.

    The inertial migration of spheres in laminar square duct flows is also investigated. We consider dilute and semi-dilute suspensions at different bulk Reynolds numbers and duct-to-particle size ratios. The highest particle concentration is found in regions around the focusing points, except at very large volume fractions since particles distribute uniformly in the cross-section. Particles also induce secondary fluid motions that become more intense with the volume fraction, until a critical value of the latter quantity is reached.

    Finally we study the rheology of confined dense suspensions of spheres in simple shear flow. We focus on the weakly inertial regime and show that the suspension effective viscosity varies non-monotonically with increasing confinement. The minima of the effective viscosity occur when the channel width is approximately an integer number of particle diameters. At these confinements, the particles self-organize into two-dimensional frozen layers that slide onto each other.

  • Sartor, O.
    et al.
    Heinrich, D.
    Mariados, N.
    Mendez Vidal, M. J.
    Keizman, D.
    Thellenberg Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Peer, A.
    Procopio, G.
    Frank, S. J.
    Pulkkanen, K.
    Rosenbaum, E.
    Severi, S.
    Trigo Perez, J. M.
    Wagner, V.
    Li, R.
    Nordquist, L. T.
    Re-treatment with radium-223: first experience from an international, open-label, phase I/II study in patients with castration-resistant prostate cancer and bone metastases2017Ingår i: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, nr 10, 2464-2471 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Six radium-223 injections at 4-week intervals is indicated for patients with castration-resistant prostate cancer and symptomatic bone metastases. However, patients usually develop disease progression after initial treatment. This prospective phase I/II study assessed re-treatment safety and efficacy of up to six additional radium-223 injections. Patients and methods: Patients had castration-resistant prostate cancer and bone metastases and six initial radium-223 injections with no on-treatment bone progression; all had subsequent radiologic or clinical progression. Concomitant agents were allowed at investigator discretion, excluding chemotherapy and initiation of new abiraterone or enzalutamide. The primary endpoint was safety; additional exploratory endpoints included time to radiographic bone progression, time to total alkaline phosphatase and prostate-specific antigen progression, radiographic progression-free survival, overall survival, time to first symptomatic skeletal event (SSE), SSE-free survival, and time to pain progression. Results: Among 44 patients, 29 (66%) received all six re-treatment injections. Median time from end of initial radium-223 treatment was 6 months. Forty-one (93%) reported >= 1 treatment-emergent adverse event. No grade 4-5 hematologic treatment-emergent adverse events occurred. Only one (2%) patient had radiographic bone progression; eight (18%) had radiographic soft tissue tumor progression (three lymph node and five visceral metastases). Median times to total alkaline phosphatase and prostate-specific antigen progression were not reached and 2.2 months, respectively. Median radiographic progression-free survival was 9.9 months (12.8-month maximum follow-up). Five (11%) patients died and eight (18%) experienced first SSEs. Median overall survival, time to first SSE, and SSE-free survival were not reached. Five (14%) of 36 evaluable patients (baseline worst pain score <= 7) had pain progression. After 2 years of follow-up, 28 (64%) patients died, and the median overall survival was 24.4 months. Conclusions: Re-treatment with a second course of six radium-223 injections after disease progression is well tolerated, with minimal hematologic toxicity and low radiographic bone progression rates in this small study with limited follow-up. Favorable safety and early effects on disease progression indicate that radium-223 re-treatment is feasible and warrants further evaluation in larger prospective trials.

  • Juma, Abdurahman
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia.
    Muslim Burial Customs on the East African coast.1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, Vol. 28, 249-356 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Notelid, Michel
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia, Afrikansk och jämförande arkeologi.
    Vetenskap och religion i negativ dialog1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, Vol. 28, 313-348 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Herschend, Frands
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia, Arkeologi.
    A Note on Late Iron Age Kingship Mythology1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, 283-304 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Brink, Stefan
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia.
    Political and Social Structures in Early Scandinavia: A Settlement-historical Pre-study of the Central Place1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, Vol. 28, 235-282 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Wang, Tao
    et al.
    Moon, Jee-Young
    Wu, Yiqun
    Amos, Christopher I.
    Hung, Rayjean J.
    Tardon, Adonina
    Andrew, Angeline
    Chen, Chu
    Christiani, David C.
    Albanes, Demetrios
    van der Heijdendr, Erik H. F. M.
    Duell, Eric
    Rennert, Gadi
    Goodman, Gary
    Liu, Geoffrey
    Mckay, James D.
    Yuan, Jian-Min
    Field, John K.
    Manjer, Jonas
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Kiemeney, Lambertus A.
    Le Marchand, Loic
    Teare, M. Dawn
    Schabath, Matthew B.
    Johansson, Mattias
    Aldrich, Melinda C.
    Davies, Michael
    Johansson, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Tsao, Ming-Sound
    Caporaso, Neil
    Lazarus, Philip
    Lam, Stephen
    Bojesen, Stig E.
    Arnold, Susanne
    Wu, Xifeng
    Zong, Xuchen
    Hong, Yun-Chul
    Ho, Gloria Y. F.
    Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from the Oncoarray Project of The International Lung Cancer Consortium2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 9, e0185660Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Obesity and cigarette smoking are correlated through complex relationships. Common genetic causes may contribute to these correlations. In this study, we selected 241 loci potentially associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037 individuals of European descent from the Oncoarray Project of the International Lung Cancer Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016 and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively correlated with pack-years of smoking (p<0.001) in smokers. Based on causal network inference analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking status and BMI/pack-years, respectively. Among them, three and four SNPs associated with smoking status and pack-years (p<0.05), respectively, were followed up in the ever-smoking data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate SNPs, one SNP (rs11030104, BDNF) achieved statistical significance after Bonferroni correction for multiple testing, and three suggestive SNPs (rs13021737, TMEM18; rs11583200, ELAVL4; and rs6990042, SGCZ) achieved a nominal statistical significance. Our results suggest that there is a common genetic component between BMI and smoking, and pleiotropy analysis can be useful to identify novel genetic loci of complex phenotypes.

  • Hedeager, Lotte
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia.
    Myter og materiel kultur: Den nordiske oprindelsesmyte i det tidlige kristne Europa1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, Vol. 28, 217-234 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Herschend, Frands
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia, Arkeologi.
    Verses for Lupus, Duke of Champagne. Four Poems by Venantius Fortunatus1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, 209-2016 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Flemberg, Johan
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Institutionen för arkeologi och antik historia.
    Four Poems by Venantius Fortunatus concerning Duke Lupus. Translated into Swedish and English1996Ingår i: Tor: meddelanden från Uppsala universitets museum för nordiska fornsaker, ISSN 0495-8772, Vol. 28, 189-208 s.Artikel i tidskrift (Övrigt vetenskapligt)
  • Disputation: 2017-12-15 18:25
    Amvrosiadi, Nino
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper, Luft-, vatten och landskapslära.
    The value of experimental data and modelling for exploration of hydrological functioning: The case of a till hillslope2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Successfully modeling one system response (e.g. hydrograph or solute transport) sometimes gives the false sense of well-characterizing the modeled system. This is partly because of the well-known equifinality issue; during the calibration process multiple parameter combinations can produce similarly good results. One step forward towards a better-defined system is using measured (at relevant scale) values for the model parameters, as well as using multiple conditions to constrain the model.

    But when not enough, or relevant, field measurements are available, virtual experiments (VE’s) can be used as a supplementary method to model calibration. The advantage of VE’s over model calibration is that they can also be used to explore assumptions both on the system hydrological processes, and on the model structure.

    One goal of this study was to utilize both field measurements and models for better characterization of the S-transect hillslope, located in Västrabäcken catchment, Northern Sweden. This included (a) characteristics in space: system vertical boundaries, hydraulic parameters, pore water velocity distribution, spatial correlation of flowpaths, soil water retention properties; (b) characteristic of system’s dynamic behavior: storage – discharge relationship, transit time distribution, turnover time; and (c) outputs’ sensitivity to external forcing, and to small scale structure assumptions. The second goal was to comment on the value of field measurements and virtual experiments for extracting information about the studied system.

    An intensely monitored study hillslope was chosen for this work. Although the hillslope has already been the subject of multiple field and modelling studies, there are still open questions regarding the characteristics listed above. The models used were the Vertical Equilibrium Model (VEM), and the Multiple Interacting Pathways (MIPs) model.

    It was found that the hillslope was well connected; from the near-stream areas up to the water divide the storage – discharge relationship could be described as an exponential function. Also, the dynamic storage (which controls the hydrograph dynamics) was much smaller comparing to the total hillslope storage. The unsaturated soil storage was found to be more sensitive to water table positions than vertical flux magnitude. The dynamic condition of external forcing (precipitation and evapotranspiration) affected the transit time distribution (TTD) shape. And, opposite to expectations, TTD was not sensitive to micro-scale structural assumptions tested here.

  • van Krieken, Pim P.
    et al.
    Dicker, Andrea
    Eriksson, Maria
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Herrera, Pedro L.
    Ahlgren, Ulf
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    Berggren, Per-Olof
    Ilegems, Erwin
    Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes2017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 12440Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Functional beta cell mass is an essential biomarker for the diagnosis and staging of diabetes. It has however proven technically challenging to study this parameter during diabetes progression. Here we have detailed the kinetics of the rapid decline in functional beta cell mass in the RIP-DTR mouse, a model of hyperglycemia resulting from diphtheria toxin induced beta cell ablation. A novel combination of imaging modalities was employed to study the pattern of beta cell destruction. Optical projection tomography of the pancreas and longitudinal in vivo confocal microscopy of islets transplanted into the anterior chamber of the eye allowed to investigate kinetics and tomographic location of beta cell mass decay in individual islets as well as at the entire islet population level. The correlation between beta cell mass and function was determined by complementary in vivo and ex vivo characterizations, demonstrating that beta cell function and glucose tolerance were impaired within the first two days following treatment when more than 50% of beta cell mass was remaining. Our results illustrate the importance of acquiring quantitative functional and morphological parameters to assess the functional status of the endocrine pancreas.

  • Disputation: 2017-12-08 10:00 11D227
    Westman, Jessica
    Karlstads universitet, Fakulteten för humaniora och samhällsvetenskap (from 2013), Institutionen för sociala och psykologiska studier.
    Drivers of Children's Travel Satisfaction2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Den här avhandlingen har två delsyften. Först undersöks vilka skäl föräldrar anger för varför deväljer att skjutsa sina barn till skolan med bil. Ett andra syfte är att undersöka hur detta val påverkarbarns mentala hälsa via självskattad upplevelse av skolresan och hur de känner sig vid ankomst(humör). Ytterligare ett syfte är att undersöka hur upplevelsen av skolresan påverkar hur barnenpresterar när de kommer till skolan. Avhandlingen innehåller tre artiklar. I Artikel I deltog 245föräldrar till barn i årskurs 4, 6 och 8 i värmländska skolor. Föräldrarna angav i vilken utsträckningolika skäl påverkar deras val att skjutsa barnen till skolan med bil. I artikel II deltog 237 barn (varav101 flickor) från årskurs 4 i Staffanstorp, Skåne. Barnen förde resdagbok över alla resor de gjordeunder en vecka. I dagboken beskrev de vart de reste, vilka färdmedel de använt, deras humör underresan (som skattades som ledsen-glad och trött-pigg), vilka aktiviteter de ägnat sig åt vidslutdestinationen samt deras upplevelser av dessa aktiviteter. I Artikel III deltog 345 barn frånårskurs 4, 6 och 8 i Värmland. Istället för resdagbok skattade barnen sitt humör, hur nöjda de varmed resan genom att fylla i Satisfaction with Travel Scale adapted for Children (STS-C), resedetaljersamt gjorde ett ordflödestest direkt vid ankomst i skolan.

    Resultaten visar bland annat att föräldrars önskan att spendera tid med sina barn och praktiskaaspekter med bil ligger till grund för valet av bil. Huruvida det är ett långt eller kort avstånd tillskolan påverkar inte valet att använda bil. Barns humör varierar beroende på hur de reser(färdmedel) och vart de reser (destination). En skillnad observerades också mellan flickor ochpojkar och mellan olika årskurser där t.ex. fickor påverkades mer negativt av att resa med bil änpojkar. Barn som reser med bil till skolan är minst nöjda (upplevde en lägre grad av kvalitet) ochpå sämre humör (är känslomässigt mindre aktiva) vilket också håller i sig under skoldagen. Att ägnasig åt sociala aktiviteter (konversera med vänner och familj) under resan bidrar till en högre upplevdkvalitet och mer upprymdhet medan barn som ägnat sig åt aktiviteter utan sällskap upplever enhögre grad av stress. Resultaten visar också att barn som använder sin smartphone eller kombinerarolika aktiviteter under resan presterar bättre på kognitivt test.

  • Aad, G.
    et al.
    CPPM, Aix-Marseille Université and CNRS/IN2P3MarseilleFrance.
    Bergeås, Elin Kuutmann
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Brenner, Richard
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Ekelöf, Tord
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Ellert, Mattias
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Ferrari, Arnaud
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Gradin, P. O. Joakim
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Isaksson, Charlie
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Öhman, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Pelikan, Daniel
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Rangel-Smith, Camilla
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Institutionen för fysik och astronomi, Högenergifysik.
    Zwalinski, L.
    CERN, Geneva, Switzerland.
    Topological cell clustering in the ATLAS calorimeters and its performance in LHC Run 12017Ingår i: European Physical Journal C, ISSN 1434-6044, E-ISSN 1434-6052, Vol. 77, nr 7, 490Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Event-shape observables measured using charged particles in inclusive Z-boson events are presented, using the electron and muon decay modes of the Z bosons. The measurements are based on an integrated luminosity of 1.1 fb(-1) of proton-proton collisions recorded by the ATLAS detector at the LHC at a centre-of-mass energy root s = 7 TeV. Charged-particle distributions, excluding the lepton-antilepton pair from the Z-boson decay, are measured in different ranges of transverse momentum of the Z boson. Distributions include multiplicity, scalar sum of transverse momenta, beam thrust, transverse thrust, spherocity, and F-parameter, which are in particular sensitive to properties of the underlying event at small values of the Z-boson transverse momentum. The measured observables are compared with predictions from PYTHIA 8, Sherpa, and HERWIG 7. Typically, all three Monte Carlo generators provide predictions that are in better agreement with the data at high Z-boson transverse momenta than at low Z-boson transverse momenta, and for the observables that are less sensitive to the number of charged particles in the event.

  • Disputation: 2017-12-18 13:00 E52, Stockholm
    Lupo, Giandomenico
    KTH, Skolan för teknikvetenskap (SCI), Mekanik.
    Detailed simulations of droplet evaporation2017Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Droppförångning (och kondensation) är en av de vanligaste fallen av flerfasflöde med fasförändring, både i naturen och i tekniska och industriella tillämpningar. Exempel är fallande regndroppar, dimma, aerosol-tillämpningar som elektroniskacigaretter och läkemedelsleverans via inandning, tekniska tillämpningar som sprayförbränning, våtskrubbning med sprayning, gasabsorption, spraytorkning samt flammsprayspyrolys. Flerfasflöde med fasförändring är ett utmanande ämne på grund av de sammanflätade fysikaliska fenomen som styr dess dynamik. Numerisk simulering är ett utmärkt verktyg som gör det möjligt för oss att få insikt i detaljerna i fysiken, ofta i fall då experimentella studier skulle vara för dyra, opraktiska eller begränsade. I det nuvarande arbetet fokuserar vi på simulering av förångning av små droppar. Vi utför simulering av förångning av en ren och två−komponentdroppe, som inkluderar detaljerad termodynamik samt varierande fysikaliska och transportegenskaper. Några av de slutsatser som dras inbegriper betydelsen av entalpitransport genom diffusion av olika ämnen i systemets termiska budget samt identifieringen och karakterisering av förångningsregimer för en azeotropiskdroppe. I den andra delen utvecklar vi en metod baserad på det nedsänkta rand konceptet för gränssnittskompletterad numerisk simulering av laminära och turbulenta flöden med ett stort antal sfäriska droppar som genomgår förångning eller kondensering.

  • Loeb, Stacy
    et al.
    NYU, Dept Urol, New York, NY USA.;NYU, New York, NY USA.;Manhattan VA, New York, NY USA..
    Ventimiglia, Eugenio
    IRCCS Osped San Raffaele, Div Expt Oncol, Unit Urol, URI, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy.;Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Salonia, Andrea
    IRCCS Osped San Raffaele, Div Expt Oncol, Unit Urol, URI, Milan, Italy.;Univ Vita Salute San Raffaele, Milan, Italy..
    Folkvaljon, Yasin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
    Stattin, Pär
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Urologkirurgi. Umea Univ Hosp, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden..
    Meta-Analysis of the Association Between Phosphodiesterase Inhibitors (PDE5Is) and Risk of Melanoma2017Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 109, nr 8, djx086Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The US Food and Drug Administration recently announced the need to evaluate the association between PDE5is and melanoma. We performed a meta-analysis on the association between PDE5i and melanoma using random effects models and examined whether it met Hill's criteria for causality. A systematic search of Medline, EMBASE, and the Cochrane Library from 1998 to 2016 identified three case-control studies and two cohort studies, including a total of 866 049 men, of whom 41 874 were diagnosed with melanoma. We found a summary estimate indicating an increased risk of melanoma in PDE5i users (relative risk = 1.12, 95% confidence interval = 1.02 to 1.23). However, there was no difference in risk between men with low and high exposure to PDE5i, and risk was higher for in situ melanoma than localized and high-risk melanoma, suggesting a lack of dose response and biological gradient. PDE5i use was also associated with basal cell cancer, suggesting a lack of specificity and likely confounding by ultraviolet exposure. Thus, although this meta-analysis found a statistically significant association between PDE5i and melanoma, it did not satisfy Hill's criteria for causality.

  • Disputation: 2017-12-08 10:15 Brusewitz-salen, Uppsala
    Karlén, Niklas
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Institutionen för freds- och konfliktforskning.
    Sponsors of War: State Support for Rebel Groups in Civil Conflicts2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Many civil wars are illustrative of wider international tensions and connections that transcend state borders. States often intervene to influence the trajectory and outcome of civil conflicts by providing external support to warring parties. This assistance ranges from direct military intervention to the provision of weapons, training, funds, safe havens, intelligence, logistics and other critical resources. This dissertation contains four individual essays that each seeks to advance our knowledge of state support to rebel movements. The first essays (I and II) add to our understanding of how external state support influences conflict dynamics while the latter (III and IV) begin to unpack the political decision-making process behind decisions that alter the original support commitment. Essay I evaluates whether state support to rebels increases the probability of civil war negotiations being initiated. The findings question a widespread belief among policymakers that support can foster negotiations. Essay II explores if external support influences the risk of conflict recurrence. It finds that state support to rebels can increase the risk of conflict recurrence in the short-term while there is no equivalent effect of support provided to governments. Essay III is the first global analysis of support termination and it thereby opens up an entirely new research field. The results suggest that the causes related to the initiation of support and its termination are largely distinct while the transition from the Cold War and the absence of ethnic kinship ties offer some insights into when states are more likely to terminate support. Essay IV unpacks the political decision-making process of the United States’ support to the armed opposition in Nicaragua in the 1980s and in Syria in the 2010s. The results indicate that adverse feedback functions as a trigger for increasing previous commitments as long as policy failure can be attributed to external actors, while reduced support is often a result of attributing failure to the state sponsor’s own actions. Taken together, the essays make significant contributions to advance our understanding of biased third-party interventions, conflict recurrence, civil war negotiations, foreign policy decision-making and state sponsorship of terrorism.

  • Fridriksson, Jon Örn
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Folkvaljon, Yasin
    Lundström, Karl-Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Robinson, David
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Urology, Ryhov Hospital, Jönköping, Sweden.
    Carlsson, Stefan
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Long-term adverse effects after retropubic and robot-assisted radical prostatectomy: Nationwide, population-based study2017Ingår i: Journal of Surgical Oncology, ISSN 0022-4790, E-ISSN 1096-9098, Vol. 116, nr 4, 500-506 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Objectives: Surgery for prostate cancer is associated with adverse effects. We studied long-term risk of adverse effects after retropubic (RRP) and robot-assisted radical prostatectomy (RARP).

    Methods: In the National Prostate Cancer Register of Sweden, men who had undergone radical prostatectomy (RP) between 2004 and 2014 were identified. Diagnoses and procedures indicating adverse postoperative effects were retrieved from the National Patient Register. Relative risk (RR) of adverse effects after RARP versus RRP was calculated in multivariable analyses adjusting for year of surgery, hospital surgical volume, T stage, Gleason grade, PSA level at diagnosis, patient age, comorbidity, and educational level.

    Results: A total of 11 212 men underwent RRP and 8500 RARP. Risk of anastomotic stricture was lower after RARP than RRP, RR for diagnoses 0.51 (95%CI = 0.42-0.63) and RR for procedures 0.46 (95%CI = 0.38-0.55). Risk of inguinal hernia was similar after RARP and RRP but risk of incisional hernia was higher after RARP, RR for diagnoses 1.48 (95%CI = 1.01-2.16), and RR for procedures 1.52 (95%CI = 1.02-2.26).

    Conclusions: The postoperative risk profile for RARP and RRP was quite similar. However, risk of anastomotic stricture was lower and risk of incisional hernia higher after RARP.

  • Disputation: 2017-12-14 13:00 Konferensrummet Arbets- och miljömedicin, Uppsala
    Palm, Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Arbets- och miljömedicin.
    Methods to assess physical load at work: With a focus on the neck and upper extremities2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    To prevent work-related musculoskeletal disorders (MSDs), useful, reliable and valid methods for assessing physical workload and risks for MSDs are needed. Ergonomists often assess work by short visual observations without a specific tool. A branch-specific tool was developed for assessing working technique during cash register work (BAsiK observation protocol).

    Inclinometers are an alternative for assessing upper arm postures - over several days. Ergonomists need guidelines explaining how to analyze and interpret such data.

    The aim was to examine and investigate methods for assessing physical load at work, with focus on the neck and upper extremities.

    In Paper:

    I, the reliability and criterion validity of the BAsIK observation protocol were assessed.

    II, the reliability of risk assessments of repetitive work, based on visual observations performed by 21 ergonomists without a specific tool, was assessed.

    III, whole-day inclinometer measurements of upper arm elevation were compared between work and leisure, across 13 different occupations – before and after arm elevations during sitting time was excluded.

    IV, the association between inclinometer-based upper arm elevation and neck/shoulder pain was assessed among 654 blue-collar workers.


    The intra-observer reliability of the BAsIK protocol was deemed acceptable, but only 3 of 10 questions in the protocol showed acceptable inter-observer reliability, and 3 showed acceptable criterion validity.

    Neither the inter- or intra-observer reliability of risk assessment without any specific method was acceptable for any upper body regions.

    None of the occupation groups, in paper III, had higher proportion of time with arm elevation during work than leisure. However, when arm elevation during sitting was excluded, 8 occupation groups had higher proportion of time with elevated arms during work than leisure.

    Whole-workday inclinometer-based upper arm elevation was not associated with neck/shoulder pain within the assessed population.

       The results indicate that, in most cases, a single visual observation of a work sequence is not a reliable means of assessing repetitive work. A large proportion of arm elevation may derive from sitting time. At low exposure levels, arm elevation per se may not be a risk factor for neck/shoulder pain.

    This must be taken into account when evaluating the risk for MSDs.

  • Disputation: 2017-12-08 10:00 Hambergsalen, Uppsala
    Klonowska, Iwona
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Geovetenskapliga sektionen, Institutionen för geovetenskaper.
    Deep subduction of the Seve Nappe Complex in the Scandinavian Caledonides2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis seeks to improve our understanding of the processes involved in continental collision zones, with a particular focus on subduction-exhumation. The main objective of this work has been to define the tectonometamorphic evolution of the deeply subducted Seve Nappe Complex (SNC) in the Scandinavian Caledonides. I utilize mineralogy, petrology and geochronology to constrain the P-T-t paths of the SNC rocks in Sweden.

    The research has focused on the high grade rocks of the SNC and resulted in the discovery of metamorphic diamonds within the gneisses in west-central Jämtland and southern Västerbotten. Microdiamonds provided evidence for the ultra-high pressure metamorphism (UHPM) and subduction of continental rocks to mantle depths. The UHPM in these rocks was confirmed by calculations of the P-T conditions. The UHPM is further recorded by eclogites and garnet pyroxenites from northern Jämtland and eclogites from Norrbotten. All these findings provide compelling evidence for regional UHPM of vast parts of the SNC (at least 400 km along the strike of this allochthonous unit). The SNC rocks followed nearly isothermal decompression paths and paragneisses have locally experienced partial melting during exhumation. Formation of the peculiar Ba- and Ti-enriched dark mica in the Tväråklumparna metasediments is related to the latter stage.

    In-situ monazite dating of the diamond-bearing gneisses from west-central Jämtland supports previous geochronological data inferring that the peak of metamorphism is probably Middle Ordovician and was followed by Early Silurian partial melting. The exact timing of the UHPM here still remains to be resolved. The Lu-Hf garnet and U-Pb zircon dating of eclogite and gneiss from northern Jämtland confirms the Middle Ordovician age of the UHP-HP metamorphism of the SNC rocks. The chemical dating of monazite from the Marsfjället gneiss suggests an earlier UHP history of the Seve rocks in southern Västerbotten as a post-UHP uplift is dated to ca. 470 Ma.

    Based on the P-T-t data obtained in this thesis, particularly on the evidence for Middle Ordovician UHPM and subsequent Silurian exhumation, a new tectonic model for the Scandinavian Caledonides has been proposed. The outcomes of this thesis therefore improve our understanding of the tectonometamorphic history of the Caledonides.

  • Moldeus, Karolina
    et al.
    Karolinska Univ Hosp & Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Visby Hosp, Dept Obstet & Gynecol, Visby, Sweden..
    Cheng, Yvonne W.
    Univ Calif Davis, Dept Surg, Davis, CA 95616 USA.;Calif Pacific Med Ctr, Dept Obstet & Gynecol, San Francisco, CA USA..
    Wikström, Anna-Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Obstetrisk forskning. Karolinska Univ Hosp & Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.
    Stephansson, Olof
    Karolinska Univ Hosp & Inst, Dept Med Solna, Clin Epidemiol Unit, Stockholm, Sweden.;Karolinska Inst, Div Obstet & Gynecol, Dept Womens & Childrens Hlth, Stockholm, Sweden..
    Induction of labor versus expectant management of large-for-gestational-age infants in nulliparous women2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 7, e0180748Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background There is no apparent consensus on obstetric management, i.e., induction of labor or expectant management of women with suspected large-for-gestational-age (LGA)-fetuses. Methods and findings To further examine the subject, a nationwide population-based cohort study from the Swedish Medical Birth Register in nulliparous non-diabetic women with singleton, vertex LGA (> 90 th centile) births, 1992-2013, was performed. Delivery of a live-born LGA infant induced at 38 completed weeks of gestation in non-preeclamptic pregnancies, was compared to those of expectant management, with delivery at 39, 40, 41, or 42 completed weeks of gestation and beyond, either by labor induction or via spontaneous labor. Primary outcome was mode of delivery. Secondary outcomes included obstetric anal sphincter injury, 5-minute Apgar< 7 and birth injury. Multivariable logistic regression analysis was performed to control for potential confounding. We found that among the 722 women induced at week 38, there was a significantly increased risk of cesarean delivery (aOR = 1.44 95% CI: 1.20-1.72), compared to those with expectant management (n = 44 081). There was no significant difference between the groups in regards to risk of instrumental vaginal delivery (aOR = 1.05, 95% CI: 0.85-1.30), obstetric anal sphincter injury (aOR = 0.81, 95% CI: 0.55-1.19), nor 5minute Apgar<7 (aOR = 1.06, 95% CI: 0.58-1.94) or birth injury (aOR = 0.82, 95% CI: 0.49- 1.38). Similar comparisons for induction of labor at 39, 40 or 41 weeks compared to expectant management with delivery at a later gestational age, showed increased rates of cesarean delivery for induced women. Conclusions In women with LGA infants, induction of labor at 38 weeks gestation is associated with increased risk of cesarean delivery compared to expectant management, with no difference in neonatal morbidity.

  • Disputation: 2017-12-08 10:00 Hörsal B, Samhällsvetarhuset, Umeå
    Marsja, Erik
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Attention capture by sudden and unexpected changes: a multisensory perspective2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The main focus for this thesis was cross-modal attention capture by sudden and unexpected sounds and vibrations, known as deviants, presented in a stream the same to-be-ignored stimulus. More specifically, the thesis takes a multisensory perspective and examines the possible similarities and differences in how deviant vibrations and sounds affect visual task performance (Study I), and whether the deviant and standard stimuli have to be presented within the same modality to capture attention away from visual tasks (Study II). Furthermore, by presenting spatial deviants (changing the source of the stimuli from one side of the body to the other) in audiotactile (bimodal), tactile, and auditory to-be-ignored, it explores whether bimodal stimuli are more salient compared to unimodal (Study III). In addition, Study III tested the claims that short-term memory is domain-specific.

    In line with previous research, Study I found that both auditory and tactile deviants captured attention away from the visual task. However, the temporal dynamics between the two modalities seem to differ. That is, it seems like practice causes the effect of vibratory deviants to reduce, whereas this is not the case for auditory deviants. This suggests that there are central mechanisms (detection of the change) and sensory-specific mechanisms.

    Study II found that the deviant and standard stimuli must be presented within the same modality. If attention capture by deviants is produced by a mismatch within a neural model predicting upcoming stimuli, the neural model is likely built on stimuli within each modality separately.

    The results of Study III revealed that spatial and verbal short-term memory are negatively affected by a spatial change in to-be-ignored sequences, but only when the change is within a bimodal sequence. These results can be taken as evidence for a unitary account of short-term memory (verbal and spatial information stored in the same storage) and that bimodal stimuli may be integrated into a unitary percept that make any change in the stream more salient. 

  • Disputation: 2017-12-08 13:15 Geijersalen (6-1023), Uppsala
    Berglund, Karl
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Historisk-filosofiska fakulteten, Litteraturvetenskapliga institutionen, Avdelningen för litteratursociologi.
    Mordens marknad: Litteratursociologiska studier i det tidiga 2000-talets svenska kriminallitteratur2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This dissertation deals with Swedish crime fiction and its successes on the Swedish book market in the early 2000s. The genre’s expansion, marketing and literary content is mapped and analysed in three studies that together paint a thorough picture of this literary phenomena in Swedish book trade.

    In study no 1 the development of the genre in Sweden in the last 40 years is discussed from a quantitative perspective. With the base in bibliographies of Swedish crime fiction publication trends are analysed in several ways and concerning topics such as genre growth, gender balance, publishing houses, successful authorships, bestsellers and library lending. The results include: a significant genre expansion in the 2000s; a great dominance for the genre on the bestseller charts in the 2000s; and a shift in the author group, from male dominance to even gender balance.

    In study no 2 the marketing of the genre is examined through an analysis of book covers, titles and other elements in the concrete packaging of just over 150 Swedish crime fiction paperbacks. With book history as an important theoretical influence book covers and other peritextual elements are understood as a significant part of the marketing of the genre, but also – and wider – as of crucial importance for how genres themselves are established, withheld and re-negotiated in the interplay between different actors in the society of literature – publishers, authors, booksellers, readers.

    In study no 3 a quantitative content analysis of 116 Swedish crime novels published 1998–2015 is used to chart and discuss recurring themes and tropes within the genre. Focus is primarily directed towards what is understood as the most central parts of crime fiction: murderers and their motives; methods used in committing murder; victims of murder; and detectives and other protagonists. The results include: a distinct dominance of female protagonists; a partial realism, where depictions of everyday life in general is realistic while the murder plots are spectacular and sensational; and a dominance of normality, where main characters and innocent victims confirms normality, while killers and unsympathetic victims are depicted as deviants in stark contrast with normality.

  • Disputation: 2017-12-08 09:15 Rudbecksalen, Uppsala
    Baskaran, Sathishkumar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Neuroonkologi. Department of IGP, Uppsala University.
    New Molecular Approaches to Glioblastoma Therapy2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Glioblastoma (GBM) is the most common high-grade brain tumor diagnosed in patients who are more than 50 years of age. The standard of care treatment is surgery, followed by radiotherapy and chemotherapy. The median life expectancy of patients is only between 12 to 15 months after receiving current treatment regimes. Hence, identification of new therapeutic compounds and gene targets are highly warranted. This thesis describes four interlinked studies to attain this goal. In study 1, we explored drug combination effects in a material of 41 patient-derived GBM cell (GC) cultures. Synergies between three compounds, pterostilbene, gefitinib, and sertraline, resulted in effective killing of GC and can be predicted by biomarkers. In study 2, we performed a large-scale screening of FDA approved compounds (n=1544) in a larger panel of GCs (n=106). By combining the large-scale drug response data with GCs genomics data, we built a novel computational model to predict the sensitivity of each compound for a given GC. A notable finding was that GCs respond very differently to proteasome inhibitors in both in-vitro and in-vivo. In study 3, we explored new gene targets by RNAi (n=1112) in a panel of GC cells. We found that loss of transcription factor ZBTB16/PLZF inhibits GC cell viability, proliferation, migration, and invasion. These effects were due to downregulation of c-MYC and Cyclin B1 after the treatment. In study 4, we tested the genomic stability of three GCs upon multiple passaging. Using molecular and mathematical analyses, we showed that the GCs undergo both systematic adaptations and sequential clonal takeovers. Such changes tend to affect a broad spectrum of pathways. Therefore, a systematic analysis of cell culture stability will be essential to make use of primary cells for translational oncology.

    Taken together, these studies deepen our knowledge of the weak points of GBM and provide several targets and biomarkers for further investigation. The work in this thesis can potentially facilitate the development of targeted therapies and result in more accurate tools for patient diagnostics and stratification. 

  • Eriksson, Louise
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för geografi och ekonomisk historia.
    Conventional and new ways of governing forest threats: a study of stakeholder coherence in Sweden2017Ingår i: Environmental Management, ISSN 0364-152X, E-ISSN 1432-1009Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Based on a framework for analyzing stakeholder coherence horizontally and vertically, the present study examined the governance of forest threats in Sweden. Opinions of forest risk governance in stakeholder groups with and without a connection to private forestry were compared (n = 2496) and the opinions were analyzed in relation to current governance practices. More specifically, forest threat appraisals, trust in the Swedish Forest Agency (SFA), and the acceptability of forest risk policy measures directed at private forest owners were assessed. Results revealed an overall coherence between different stakeholders in this context. However, the groups differed in, for example, the acceptability of the hypothetical regulative measure aiming to reduce damages threatening the forest long-term (e.g., climate change). Furthermore, an extensive use of advice for a fee may challenge particularly the internal, but also the external, legitimacy of forest risk governance. The forest owner stakeholder group showed lower threat appraisals when evaluating threat to one’s own forest rather than to the Swedish forest, except regarding browsing by animals. Regulations were not disapproved of in any of the stakeholder groups, although the forest owner group generally displayed higher acceptability of encouraging measures compared to the general public. Trust in the SFA was furthermore confirmed as an important driver of policy acceptability, and higher threat appraisals of novel threats, such as climate change and fire, resulted in a higher acceptability of measures less central or new in this context. The value of analyzing stakeholder coherence for natural resource management and governance is discussed.

  • Disputation: 2017-12-12 10:00 Magnélisalen Kemiska övningslaboratoriet, Stockholm
    Muheim, Claudio
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Antibiotic uptake in Gram-negative bacteria2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The increasing emergence and spread of antibiotic-resistant bacteria is a serious threat to public health. Of particular concern are Gram-negative bacteria such as Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae or Pseudomonas aeruginosa. Some of these strains are resistant to a large number of antibiotics and thus our treatment options are rapidly declining. In addition to the increasing number of antibiotic-resistant bacteria, a major problem is that many of the antibiotics at our disposal are ineffective against Gram-negative bacteria. This is partly due to the properties of the outer membrane (OM) which prevents efficient uptake. The overarching goal of this thesis was to investigate how the OM of the Gram-negative bacterium E. coli could be weakened to improve the activity of antibiotics.

    In the first two papers of my thesis (paper I + II), I investigated the periplasmic chaperone network which consists of the two parallel pathways SurA and Skp/DegP. This network is essential for the integrity of the OM and strains lacking either SurA or Skp are defective in the assembly of the OM, which results in an increased sensitivity towards vancomycin and other antimicrobials. We identified a novel component of the periplasmic chaperone network, namely YfgM, and showed that it operates in the same network as Skp and SurA/DegP. In particular, we demonstrated that deletion of YfgM in strains with either a ΔsurA or Δskp background further compromised the integrity of the OM, as evidenced by an increased sensitivity towards vancomycin.

    In the remaining two papers of my thesis (paper III + IV), the goal was to characterize small molecules that permeabilize the OM and thus could be used to improve the activity of antibiotics. Towards this goal, we performed a high-throughput screen and identified an inhibitor of the periplasmic chaperone LolA, namely MAC-13243, and showed that it can be used to permeabilize the OM of E. coli (paper III). We further demonstrated that MAC-13243 can be used to potentiate the activity of antibiotics which are normally ineffective against E. coli. In the last paper of my thesis (paper IV), we undertook a more specific approach and wanted to identify an inhibitor against the glycosyltransferase WaaG. This enzyme is involved in the synthesis of LPS and genetic inactivation of WaaG results in a defect in the OM, which leads to an increased sensitivity to various antibiotics. In this paper, we identified a small molecular fragment (compound L1) and showed that it can be used to inhibit the activity of WaaG in vitro.

    To summarize, this thesis provides novel insights into how the OM of the Gram-negative bacterium E. coli can be weakened by using small molecules. We believe that the two identified small molecules represent important first steps towards the design of more potent inhibitors that could be used in clinics to enhance the activity of antibiotics.

  • Disputation: 2017-12-12 13:00 sal 14, hus 5, Kräftriket, Stockholm
    Fetisova, Ekaterina
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Towards a flexible statistical modelling by latent factors for evaluation of simulated responses to climate forcings2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    In this thesis, using the principles of confirmatory factor analysis (CFA) and the cause-effect concept associated with structural equation modelling (SEM), a new flexible statistical framework for evaluation of climate model simulations against observational data is suggested. The design of the framework also makes it possible to investigate the magnitude of the influence of different forcings on the temperature as well as to investigate a general causal latent structure of temperature data. In terms of the questions of interest, the framework suggested here can be viewed as a natural extension of the statistical approach of 'optimal fingerprinting', employed in many Detection and Attribution (D&A) studies. Its flexibility means that it can be applied under different circumstances concerning such aspects as the availability of simulated data, the number of forcings in question, the climate-relevant properties of these forcings, and the properties of the climate model under study, in particular, those concerning the reconstructions of forcings and their implementation. It should also be added that although the framework involves the near-surface temperature as a climate variable of interest and focuses on the time period covering approximately the last millennium prior to the industrialisation period, the statistical models, included in the framework, can in principle be generalised to any period in the geological past as soon as simulations and proxy data on any continuous climate variable are available.  Within the confines of this thesis, performance of some CFA- and SEM-models is evaluated in pseudo-proxy experiments, in which the true unobservable temperature series is replaced by temperature data from a selected climate model simulation. The results indicated that depending on the climate model and the region under consideration, the underlying latent structure of temperature data can be of varying complexity, thereby rendering our statistical framework, serving as a basis for a wide range of CFA- and SEM-models, a powerful and flexible tool. Thanks to these properties, its application ultimately may contribute to an increased confidence in the conclusions about the ability of the climate model in question to simulate observed climate changes.

  • Disputation: 2017-12-08 10:00 MB 416, Huddinge
    Börjeson, Natasja
    Södertörns högskola, Institutionen för naturvetenskap, miljö och teknik, Miljövetenskap. natasja.borjeson@sh.se.
    Toxic Textiles: Towards Responsibility in Complex Supply Chains2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    En av våra samtida stora utmaningar är hanteringen av de miljö- och hälsoproblem som följer i svallvågorna av en globaliserad handel. En av dessa utmaningar rör hanteringen av kemikalierisker. Inom textilbranschen är produktionen kemikalieintensiv och handelsmönstren karakteriseras av komplexa varukedjor som inte sällan sträcker sig över flera kontinenter. Samtidigt pågår en förändring av inblandade aktörers roller, där marknadsaktörer uppmanas att på ett ansvarstagande sätt hantera frågan om kemikalierisker och de utmaningar som hör därtill. Denna process försvåras ofta till följd av ett komplext samhälle präglat av kunskapsbrister. Detta komplicerar ansvarstagande och gör det svårt att hålla specifika aktörer, såsom företag och inköpande organisationer, ansvariga, då det inte är uppenbart vem som är ansvarig för vad. Denna avhandling undersöker hur en grupp marknadsaktörer – privata och offentliga textilinköpare – tar ansvar för kemikalierisker längs med sina varukedjor i en situation som karaktäriseras av osäkerhet och komplexitet. Avhandlingen syftar till att fördjupa förståelsen för vad som händer när marknadsaktörer uppmanas att hantera miljö- och hälsorisker från till exempel kemikalier i textil. Fokus ligger på svenska privata och offentliga textilinköpare, som exempelvis kläd- och textilföretag, offentlig förvaltning och andra inköpande organisationer. I avhandlingen konstrueras en analytisk modell baserad på nyckelbegreppen responsible governance, responsibilisation och responsible supply chain management. Avhandlingen är explorativ och genom intervjuer, deltagande observationer och litteraturstudier samt fallstudier undersöks en potentiell process av ansvarstagande samt de hinder, utmaningar och möjligheter som de inköpande organisationerna möter i sitt arbete med kemikalierisker längs med sina varukedjor. Resultaten belyser en pågående process av ansvarsförfarande på både organisations och sektornsivå. Avhandlingen visar också att på grund av kedjans komplexa struktur så förekommer större hinder och utmaningar än möjligheter för de textilinköpare som strävar efter ansvarstagande. Trots detta pekar resultaten på att samarbete, kraftfullare styrmedel och ett reflexivt tillvägagångssätt skulle kunna vara en väg mot ökat ansvarstagande inom textilsektorn.

  • Ibidunmoye, Olumuyiwa
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Lakew, Ewnetu Bayuh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Elmroth, Erik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    A Black-box Approach for Detecting Systems Anomalies in Virtualized Environments2017Ingår i: 2017 IEEE International Conference on Cloud and Autonomic Computing (ICCAC 2017), IEEE, 2017, 22-33 s.Konferensbidrag (Refereegranskat)
    Abstract [en]

    Virtualization technologies allow cloud providers to optimize server utilization and cost by co-locating services in as few servers as possible. Studies have shown how applications in multi-tenant environments are susceptible to systems anomalies such as abnormal resource usage due to performance interference. Effective detection of such anomalies requires techniques that can adapt autonomously with dynamic service workloads, require limited instrumentation to cope with diverse applications services, and infer relationship between anomalies non-intrusively to avoid "alarm fatigue" due to scale. We propose a black-box framework that includes an unsupervised prediction-based mechanism for automated anomaly detection in multi-dimensional resource behaviour of datacenter nodes and a graph-theoretic technique for ranking anomalous nodes across the datacenter. The proposed framework is evaluated using resource traces of over 100 virtual machines obtained from a production cluster as well as traces obtained from an experimental testbed under realistic service composition. The technique achieve average normalized root mean squared forecast error and R^2 of (0.92, 0.07) across hosts servers and (0.70, 0.39) across virtual machines. Also, the average detection rate is 88% while explaining 62% of SLA violations with an average lead-time of 6 time-points when the testbed is actively perturbed under three contention scenarios. 

  • Ibidunmoye, Olumuyiwa
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Ali-Reza, Rezaie
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Elmroth, Erik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Adaptive Anomaly Detection in Performance Metric Streams2017Ingår i: IEEE Transactions on Network and Service Management, ISSN 1932-4537, E-ISSN 1932-4537, Vol. 14, nr 8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Continuous detection of performance anomalies such as service degradations has become critical in cloud and Internet services due to impact on quality of service and end-user experience. However, the volume and fast changing behaviour of metric streams have rendered it a challenging task. Many diagnosis frameworks often rely on thresholding with stationarity or normality assumption, or on complex models requiring extensive offline training. Such techniques are known to be prone to spurious false-alarms in online settings as metric streams undergo rapid contextual changes from known baselines. Hence, we propose two unsupervised incremental techniques following a two-step strategy. First, we estimate an underlying temporal property of the stream via adaptive learning and, then we apply statistically robust control charts to recognize deviations. We evaluated our techniques by replaying over 40 time-series streams from the Yahoo! Webscope S5 datasets as well as 4 other traces of real web service QoS and ISP traffic measurements. Our methods achieve high detection accuracy and few false-alarms, and better performance in general compared to an open-source package for time-series anomaly detection.

  • Disputation: 2017-12-08 09:00 KB.E3.01, Umeå
    Borén, Eleonora
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Off-gassing from thermally treated lignocellulosic biomass2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Off-gassing of hazardous compounds is, together with self-heating and dust explosions, the main safety hazards within large-scale biomass storage and handling. Formation of CO, CO2, and VOCs with concurrent O2 depletion can occur to hazardous levels in enclosed stored forest products. Several incidents of CO poisoning and suffocation of oxygen depletion have resulted in fatalities and injuries during cargo vessel discharge of forest products and in conjunction with wood pellet storage rooms and silos. Technologies for torrefaction and steam explosion for thermal treatment of biomass are under development and approaching commercialization, but their off-gassing behavior is essentially unknown.

    The overall objective of this thesis was to provide answers to one main question: “What is the off-gassing behaviour of thermally treated lignocellulosic biomass during storage?”. This was achieved by experimental studies and detailed analysis of off-gassing compounds sampled under realistic conditions, with special emphasis on the VOCs.

    Presented results show that off-gassing behavior is influenced by numerous factors, in the following ways. CO, CO2 and CH4 off-gassing levels from torrefied and stream-exploded biomass and pellets, and accompanying O2 depletion, are comparable to or lower than corresponding from untreated biomass. The treatments also cause major compositional shifts in VOCs; emissions of terpenes and native aldehydes decline, but levels of volatile cell wall degradation products (notably furans and aromatics) increase. The severity of the thermal treatment is also important; increases in torrefaction severity increase CO off-gassing from torrefied pine to levels comparable to emissions from conventional pellets, and increase O2 depletion for both torrefied chips and pellets. Both treatment temperature and duration also influence degradation rates and VOC composition. The product cooling technique is influential too; water spraying in addition to heat exchange increased CO2 and VOCs off-gassing from torrefied pine chips, as well as O2 depletion. Moreover, the composition of emitted gases co-varied with pellets’ moisture content; pellets of more severely treated material retained less moisture, regardless of their pre-conditioning moisture content. However, no co-variance was found between off-gassing and pelletization settings, the resulting pellet quality, or storage time of torrefied chips before pelletization. Pelletization of steam-exploded bark increased subsequent VOC off-gassing, and induced compositional shifts relative to emissions from unpelletized steam-exploded material. In addition, CO, CO2 and CH4 off-gassing, and O2 depletion, were positively correlated with the storage temperature of torrefied softwood. Similarly, CO and CH4 emissions from steam-exploded softwood increased with increases in storage temperature, and VOC off-gassing from both torrefied and steam-exploded softwood was more affected by storage temperature than by treatment severity. Levels of CO, CO2 and CH4 increased, while levels of O2 and most VOCs decreased, during storage of both torrefied and steam-exploded softwood.CO, CO2 and O2 levels were more affected by storage time than by treatment severity. Levels of VOCs were not significantly decreased or altered by nitrogen purging of storage spaces of steam-exploded or torrefied softwood, or controlled headspace gas exchange (intermittent ventilation) during storage of steam-exploded bark.

    In conclusion, rates of off-gassing of CO and CO2 from thermally treated biomass, and associated O2 depletion, are comparable to or lower than corresponding rates for untreated biomass. Thermal treatment induces shifts in both concentrations and profiles of VOCs. It is believed that the knowledge and insights gained provide refined foundations for future research and safe implementation of thermally treated fuels as energy carriers in renewable energy process chains.

  • Disputation: 2017-12-08 09:00 Aulan, Kiruna
    Ramstad, Robin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Swedish Institute of Space Physics, Kiruna.
    Ion escape from Mars: measurements in the present to understand the past2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Present-day Mars is a cold and dry planet with a thin CO2-dominated atmosphere comprising only a few ­­­mbar pressure at low altitudes. However, the Martian surface is marked with valley networks, hydrated mineral clays, carbonates and the remains of deltas and meandering rivers, i.e. traces of an active hydrological cycle present early in the planet's geological history. A strong greenhouse effect, and thus a thicker atmosphere, would have been required to sustain a sufficiently warm environment, particularly under the weaker luminosity of the early Sun. The fate of this early atmosphere is currently unknown.

    While several mechanisms can remove atmospheric mass over time, a prominent hypothesis suggests that the lack of an intrinsic Earth-like global magnetic dipole has allowed the solar wind to erode the early Martian atmosphere by imparting energy to the planet's ionosphere which subsequently flows out as ion escape, over time depleting the greenhouse gasses and collapsing the ancient hydrological cycle. Previous studies have found insignificant ion escape rates under present-day conditions, however, the young Sun emitted significantly stronger solar wind and photoionizing radiation flux compared to the present. The geological record establishes the time of collapse of the hydrological cycle, estimated to have occurred in the mid-late Hesperian period (~3.3 billion years ago) at latest. To constrain the amount of atmosphere lost through ion escape since, we use the extensive database of ion flux measurements from the Analyzer of Space Plasmas and Energetic Atoms (ASPERA-3) particles package on the Mars Express orbiter (2004-present) to quantify the ion escape rate dependence on upstream solar wind and solar radiation conditions.

    The Martian ion escape rate is shown to be insensitive to solar wind parameters with a weak inverse dependence on solar wind dynamic pressure, and linearly dependent on solar ionizing photon flux, indicating efficient screening of the bulk ionosphere by the induced magnetic fields. The impact of an extreme coronal mass ejection is studied and found to have no significant effect on the ion escape rate. Instead, intense solar wind is shown to only increase the escaping energy flux, i.e. total power of escaping ions, without increasing the rate by accelerating already escaping ions. The orientation of the strongest magnetized crustal fields are shown to modulate the ion escape rate, though to have no significant time-averaged effect. We also study the influence of solar wind and solar radiation on the major Martian plasma boundaries and discuss factors that might limit the ion escape rate, including solar wind-ion escape coupling, which is found to be ≲1% and decreasing with increased solar wind dynamic pressure. The significant escape rate dependencies found are extrapolated back in time, considering the evolution of solar wind and ionizing radiation, and shown to account for only 4.8 ± 1.1 mbar equivalent surface pressure loss since the time of collapse of the Martian hydrosphere in the Hesperian, with ~6 mbar as an upper estimate. Extended to the late Noachian period (3.9 billion years ago), the found dependencies can only account for ≲10 mbar removed through ion escape, an insignificant amount compared to the ≳1 bar surface pressure required to sustain a warm climate on early Mars.

  • Disputation: 2017-12-08 10:00 Hörsal F, Humanisthuset, Umeå
    Lindblom, Ina
    Umeå universitet, Humanistiska fakulteten, Institutionen för idé- och samhällsstudier.
    Känslans patriark: sensibilitet och känslopraktiker i Carl Christoffer Gjörwells familj och vänskapskrets, ca 1790-18102017Doktorsavhandling, monografi (Övrigt vetenskapligt)
    Abstract [en]

    This dissertation is a study of how the culture of sensibility was expressed in the everyday practices and social relations of the Gjörwell family. Headed by publicist, publisher and royal librarian Carl Christoffer Gjörwell (1731-1811), the Gjörwell family served as the centre of a wide circle of friends in late 18th-century Stockholm. Gjörwell has been regarded as one of the first Swedish representatives of 18th-century sensibility as well as an archetype of the Swedish cult of friendship. Due to his effusive emotional expressiveness and passionate friendships with other men, Gjörwell has largely been derided as effeminate by researchers from the 19th century onwards.

    Using theoretical perspectives from the field of the history of emotions (more concretely the perspectives of William Reddy, Barbara Rosenwein and Monique Scheer) this study centres on the emotional practices of the Gjörwell family, especially taking aspects of gender, class, sexuality and power into account. Gjörwell’s vast collection of family and friendship correspondence forms the empirical basis of this study.

    This study shows that the Gjörwell family and circle of friends in many ways could be regarded as an emotional community in which primarily emotions of happiness and joy are expressed. Furthermore, this study shows how the exercise of power could form part in the creation of an emotional community, as Gjörwell makes constant attempts to influence the way family members and friends manage their emotions, strongly dissuading them from the expression of melancholy.

    Although he has been viewed as effeminate by posterity, Gjörwell in fact regards himself as manly. This is due to his ability to remain joyful through adversities which testifies to his strong, and therefore manly, nervous organisation. This study thus further illustrates how a marked shift in masculine gender norms took place between the 18th and 19th centuries.

    This study also shows how expression of tender emotion could be a way of reinforcing personal status. This was due to the close association made between sensibility and virtue, in itself a central concept during this era. As Gjörwell is denied recognition in his professional life, the expression of tender emotion – and thus of virtue – becomes an important aspect of his personal life. 

  • Disputation: 2017-12-08 09:00 N320, Umeå Universitet, Umeå
    Renström, Lina
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Idrottsmedicin.
    The involvement of the TNF-alpha system in skeletal muscle in response to marked overuse2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Smärta och funktionsbortfall från rörelseapparaten är vanligt förekommande. Mellan 20-40% av alla besök i primärvården är kopplade till smärta från rörelseapparaten. Det är också en vanlig orsak till sjukfrånvaro. Överansträngning inklusive repetitivt enformigt muskelarbete kan leda till muskelsmärta och bristande muskelfunktion (ex nedsatt styrka och uthållighet, inskränkt rörlighet). Muskelvävnad är en dynamisk vävnad som kan ändras utefter vilka påfrestningar den utsätts för och därigenom vilka behov den ställs inför. Men om belastningen blir för hård, alternativt återhämtningen blir för kort, kan negativa förändringar i vävnadsstrukturen uppstå, inklusive celldöd och vävnadsskada.

    Förlängningen av muskeln är senan. Senan är den vävnad som förbinder muskeln med skelettet. Tendinopati innefattar smärtsamma sjukdomstillstånd i senan. När sjukdom i en sena uppstår, exempelvis en smärtande hälsena, har man sett att den lösa bindväven som omger senan är av betydelse. Den genomgår morfologiska förändringar och man tror att det är den som är med och bidrar till smärtan vid tillståndet. Akillessenan och ”tennis-armbåge” är vanliga ställen för tendinopati. Akillessenan förbinder den trehövdade vadmuskeln med hälbenet. Tennis-armbåge omfattar ett område för flera musklers ursprung vid armbågen. Dessa muskler ansvarar framför allt för att sträcka i handleden.

    TNF-alfa är en signalsubstans som är involverad i flertalet biologiska processer. Den är känd för sin del i immunförsvaret och den är ett viktigt mål för behandling av autoimmuna sjukdomar som exempelvis reumatoid artrit. Det är inte känt om TNF-alfa är inblandad i processen som uppstår vid muskelinflammation/muskelskada efter kraftig överansträngning. TNF-alfa har flera receptorer, i det här arbetet har utbredning av TNFR1 och TNFR2 analyserats.

    Studier har utförts på djur (kaniner) och människa. Kaniner har genomgått ett träningsexperiment, där de utsatts för repetitiva muskelkontraktioner som lett till överansträngningsskador och muskelinflammation. Den muskel som studerats är soleus-muskeln, en del i den trehövdade vadmuskeln. Vävnadsprover har tagits från patienter med smärta i Akillessenan eller tennisarmbåge. Vävnadsproverna från kanin och människa har analyserats med färgningar för morfologi, immunohistokemi för detektering av TNF-alfa och dess receptorer samt för in situ hybridisering för detektion av mRNA i TNF-alfa systemet. Parallellt med färgningar för faktorerna i TNF-alfa systemet har uttryck för andra faktorer studerats. Ensidig överbelastning hos kaniner ledde till samma morfologiska förändringar på båda sidor, det vill säga även i muskeln i det ben som inte hade genomgått träningsexperimentet. Ju längre experimentet pågick, desto större blev de morfologiska förändringarna. TNF-alfa sågs i vita blodkroppar, TNF-alfa mRNA sågs även i förändrade muskelfibrer. Resultatet av parallella dubbelfärgningar tolkades som att dessa muskelfibrer antingen var i en regenererande process eller i en destruktiv process. TNFR1 och TNFR2 uttrycktes i större utsträckning ju längre experimentet pågick och ju mer muskelvävnaden var påverkad av inflammation. TNF receptorer sågs i vita blodkroppar, fibroblaster, muskelfibrer och nervstrukturer hos experimentdjuren. Det såg lika ut på båda sidor, inklusive det ben som inte ingått i experimentet. De två receptorerna skilde sig åt i uttryck.

    Vävnad från patienter med smärtande senor/smärta vid muskelursprungs-region genomgick också färgningar för faktorer i TNF-alfa systemet. Man kunde se att den lösa bindväven runt senan (den peritendinösa vävnaden) innehöll mycket blodkärl och nerver. De nerver som sågs i denna vävnad var av två typer, en som såg normal ut och en typ som uppvisade tecken på förlust av axoner. Den senare varianten hade en tydlig uppreglering av båda TNF receptorerna.

    Dessa resultat tyder på att TNF-alfa systemet är involverat i muskelsjukdomar som rör muskelinflammation till följd av kraftig överansträngning och i processerna i bindväven vid smärtande senor. TNF-alfa och dess receptorer verkar vara inblandade i både nedbrytning och uppbyggnad av muskelvävnad, samt påverka nerver som visar tecken på förlust av axoner. Förändringarna i TNF-alfa systemet sågs både på experimentsidan och kontralateralt.

  • Leander, John
    et al.
    KTH Royal Institute of Technology, Sweden.
    Honfi, Dániel
    RISE - Research Institutes of Sweden, Säkerhet och transport, Safety.
    Björnsson, Ívar
    Lund University, Sweden.
    Risk-based planning of assessment actions for fatigue life prediction2017Ingår i: procedia structural integrity, Vol. 5, 1221-1228 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It is vital to extend the service life of existing bridges as far as possible as a means for improved sustainability leading to reduced economic cost and resource consumption. This requirement is especially valid for bridges which are critical components of highly vulnerable infrastructure systems. Achieving this aim requires enhanced methods involving various actions and methods influencing different aspects of the assessment process. A framework is presented in this paper based on three common factors used to describe the assessment actions of existing bridges; (i) model sophistication, (ii) uncertainty consideration, and (iii) knowledge content. The framework elucidates the influence of different decisions on the assessment process and facilitates the planning of appropriate assessment actions. Furthermore, it provides a basic scheme for a risk-based decision analysis for determining suitable assessment actions or activities. A fatigue assessment of an existing bridge detail is used to demonstrate the application of the framework in practical cases.

  • Lundberg, Jacob
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Nationalekonomiska institutionen.
    Analyzing tax reforms using the SwedishLabour Income Microsimulation Model2017Rapport (Övrigt vetenskapligt)
    Abstract [en]

    Labour income taxation is a central policy topic because labour income makes up the majority of national income and most taxes are in the end taxes on labour. In order to quantify how behavioural responses of labour income earners affect tax revenue, the Swedish Labour Income Microsimulation Model (SLIMM) is constructed and used to evaluate tax reforms. The model simulates taxable income responses, participation responses and income effects. Elasticities are calibrated to match midpoints of estimates found in the quasiexperimental literature. SLIMM is solidly microfounded and uses administrative register data. The model is used to analyze changes to the earned income tax credit (EITC), municipal income taxes and the central government income tax paid by high-income earners. The simulations indicate that the EITC has increased employment by 128,000 and has a degree of self-financing of 21 percent. Almost half of the revenue increase from higher municipal tax rates would disappear due to behavioural responses. Tax cuts for the richest fifth of working Swedes are completely self-financing.

  • Honfi, Dániel
    et al.
    RISE - Research Institutes of Sweden, Säkerhet och transport, Safety.
    Lechner, Thomas
    NCC AB, Sweden.
    Köhler, Jochen
    NTNU, Norway.
    Rational maintenance of timber bridges2017Ingår i: Conference proceedings, ICTB 2017. 3rd International Conference on Timber Bridges / [ed] Gustafsson, Anders; Pousette, Anna; Hagman, Olle; Ekevad, Mats, 2017Konferensbidrag (Refereegranskat)
    Abstract [en]

    The present paper provides some ideas about how decisions concerning maintenance of timber bridges should be made in a rational way. First, a brief discussion is provided concerning the evolution of maintenance strategies in general and it is suggested that maintenance of timber bridges should follow a risk-based approach. Then the discussion moves on to the condition assessment of timber bridges with a main focus on inspection and monitoring. The use of non-destructive testing methods and structural health monitoring is highlighted with regard to collecting useful information for maintenance decisions. It is argued that the information collected, should be used in a Bayesian decision analysis framework, which is especially useful in quantifying to value of information and thus the worth of various inspection and monitoring alternatives.

  • Sepahvand, Mohammad H.
    et al.
    Uppsala universitet, Humanistisk-samhällsvetenskapliga vetenskapsområdet, Samhällsvetenskapliga fakulteten, Nationalekonomiska institutionen.
    Shahbazian, Roujman
    Swedish Institute for Social Research, Stockholm University,.
    Individual’s Risk Attitudes in sub-Saharan Africa:Determinants and Reliability of Self-reported Risk in Burkina Faso2017Rapport (Övrigt vetenskapligt)
  • Zhang, Lu
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Ding, Zhoujie
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Heyman, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    IgG3-antigen complexes are deposited on follicular dendritic cells in the presence of C1q and C32017Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, 5400Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    IgG3, passively administered together with small proteins, induces enhanced primary humoral responses against these proteins. We previously found that, within 2 h of immunization, marginal zone (MZ) B cells capture IgG3-antigen complexes and transport them into splenic follicles and that this requires the presence of complement receptors 1 and 2. We have here investigated the localization of IgG3 anti-2, 4, 6-trinitrophenyl (TNP)/biotin-ovalbumin-TNP immune complexes in the follicles and the involvement of classical versus total complement activation in this process. The majority (50-90%) of antigen inside the follicles of mice immunized with IgG3-antigen complexes co-localized with the follicular dendritic cell (FDC) network. Capture of antigen by MZ B cells as well as antigen deposition on FDC was severely impaired in mice lacking C1q or C3, and lack of either C1q or C3 also impaired the ability of IgG3 to enhance antibody responses. Finally, IgG3 efficiently primed for a memory response against small proteins as well as against the large protein keyhole limpet hemocyanine.

  • Disputation: 2017-12-14 10:15 ACAS, A-huset, Linköping
    Posadzy, Kinga
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Nationalekonomi. Linköpings universitet, Filosofiska fakulteten.
    Social and Economic Factors in Decision Making under Uncertainty: Five Essays in Behavioral Economics2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The objective of this thesis is to improve the understanding of human behavior that goes beyond monetary rewards. In particular, it investigates social influences in individual’s decision making in situations that involve coordination, competition, and deciding for others. Further, it compares how monetary and social outcomes are perceived. The common theme of all studies is uncertainty. The first four essays study individual decisions that have uncertain consequences, be it due to the actions of others or chance. The last essay, in turn, uses the advances in research on decision making under uncertainty to predict behavior in riskless choices.

    The first essay, Fairness Versus Efficiency: How Procedural Fairness Concerns Affect Coordination, investigates whether preferences for fair rules undermine the efficiency of coordination mechanisms that put some individuals at a disadvantage. The results from a laboratory experiment show that the existence of coordination mechanisms, such as action recommendations, increases efficiency, even if one party is strongly disadvantaged by the mechanism. Further, it is demonstrated that while individuals’ behavior does not depend on the fairness of the coordination mechanism, their beliefs about people’s behavior do.

    The second essay, Dishonesty and Competition. Evidence from a stiff competition environment, explores whether and how the possibility to behave dishonestly affects the willingness to compete and who the winner is in a competition between similarly skilled individuals. We do not find differences in competition entry between competitions in which dishonesty is possible and in which it is not. However, we find that due to the heterogeneity in propensity to behave dishonestly, around 20% of winners are not the best-performing individuals. This implies that the efficient allocation of resources cannot be ensured in a stiff competition in which behavior is unmonitored.

    The third essay, Tracing Risky Decision Making for Oneself and Others: The Role of Intuition and Deliberation, explores how individuals make choices under risk for themselves and on behalf of other people. The findings demonstrate that while there are no differences in preferences for taking risks when deciding for oneself  and for others, individuals have greater decision error when choosing for other individuals. The differences in the decision error can be partly attributed to the differences in information processing; individuals employ more deliberative cognitive processing when deciding for themselves than when deciding for others. Conducting more information processing when deciding for others is related to the reduction in decision error.

    The fourth essay, The Effect of Decision Fatigue on Surgeons’ Clinical Decision Making, investigates how mental depletion, caused by a long session of decision making, affects surgeon’s decision to operate. Exploiting a natural experiment, we find that surgeons are less likely to schedule an operation for patients who have appointment late during the work shift than for patients who have appointment at the beginning of the work shift. Understanding how the quality of medical decisions depends on when the patient is seen is important for achieving both efficiency and fairness in health care, where long shifts are popular.

    The fifth essay, Preferences for Outcome Editing in Monetary and Social Contexts, compares whether individuals use the same rules for mental representation of monetary outcomes (e.g., purchases, expenses) as for social outcomes (e.g., having nice time with friends). Outcome editing is an operation in mental accounting that determines whether individuals prefer to first combine multiple outcomes before their evaluation (integration) or evaluate each outcome separately (segregation). I find that the majority of individuals express different preferences for outcome editing in the monetary context than in the social context. Further, while the results on the editing of monetary outcomes are consistent with theoretical predictions, no existing model can explain the editing of social outcomes.

  • Khoshnood, Behzad
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Dacklin, Ingrid
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Grabbe, Caroline
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    A proteomics approach to identify targets of the ubiquitin-like molecule Urm1 in Drosophila melanogaster2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 9, e0185611Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    By covalently conjugating to target proteins, ubiquitin-like modifiers (UBLs) act as important regulators of target protein localization and activity, thereby playing a critical role in the orchestration of cellular biology. The most ancient and one of the least studied UBLs is Urm1, a dual-function protein that in parallel to performing similar functions as its prokaryotic ancestors in tRNA modification, also has adopted the capacity to conjugate to cellular proteins analogous to ubiquitin and other UBL modifiers. In order to increase the understanding of Urm1 and its role in multicellular organisms, we have used affinity purification followed by mass spectrometry to identify putative targets of Urm1 conjugation (urmylation) at three developmental stages of the Drosophila melanogaster lifecycle. Altogether we have recovered 79 Urm1-interacting proteins in Drosophila, which include the already established Urm1 binding partners Prx5 and Uba4, together with 77 candidate urmylation targets that are completely novel in the fly. Among these, the majority was exclusively identified during either embryogenesis, larval stages or in adult flies. We further present biochemical evidence that four of these proteins are covalently conjugated by Urm1, whereas the fifth verified Urm1-binding protein appears to interact with Urm1 via non-covalent means. Besides recapitulating the previously established roles of Urm1 in tRNA modification and during oxidative stress, functional clustering of the newly identified Urm1-associated proteins further positions Urm1 in protein networks that control other types of cellular stress, such as immunological threats and DNA damage. In addition, the functional characteristics of several of the candidate targets strongly match the phenotypes displayed by Urm1(n123) null animals, including embryonic lethality, reduced fertility and shortened lifespan. In conclusion, this identification of candidate targets of urmylation significantly increases the knowledge of Urm1 and presents an excellent starting point for unravelling the role of Urm1 in the context of a complex living organism.

  • Zhang, Yi
    et al.
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Zhang, Gan-Lin
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Sun, Xu
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Cao, Ke-Xin
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Shang, Ya-Wen
    Capital Med Univ, Sch Tradit Chinese Med, Beijing 100069, Peoples R China..
    Gong, Mu-Xin
    Capital Med Univ, Sch Tradit Chinese Med, Beijing 100069, Peoples R China..
    Ma, Cong
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Nan, Nan
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Li, Jin-Ping
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Yu, Ming-Wei
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Yang, Guo-Wang
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Wang, Xiao-Min
    Capital Med Univ, Beijing Hosp Tradit Chinese Med, Dept Oncol, Beijing 100010, Peoples R China..
    Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways2017Ingår i: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 22, nr 5, 787Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.

  • Wilms, Torben
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Khan, Gulfaraz
    Coates, Philip J
    Sgaramella, Nicola
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Fåhraeus, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Masaryk Mem Canc Inst, RECAMO, Zluty Kopec 7, Brno, Czech Republic; Univ Paris Diderot, INSERM, UMRS1162, 27 Rue Juliette Dodu, Paris, France .
    Hassani, Asma
    Philip, Pretty S
    Norberg Spaak, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Califano, Luigi
    Colella, Giuseppe
    Olofsson, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Loizou, Christos
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Öron- näs- och halssjukdomar.
    Franco, Renato
    Nylander, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    No evidence for the presence of Epstein-Barr virus in squamous cell carcinoma of the mobile tongue2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 9, e0184201Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Squamous cell carcinoma of the head and neck (SCCHN) comprises a large group of cancers in the oral cavity and nasopharyngeal area that typically arise in older males in association with alcohol/tobacco usage. Within the oral cavity, the mobile tongue is the most common site for tumour development. The incidence of tongue squamous cell carcinoma (TSCC) is increasing in younger people, which has been suggested to associate with a viral aetiology. Two common human oncogenic viruses, human papilloma virus (HPV) and Epstein-Barr virus (EBV) are known causes of certain types of SCCHN, namely the oropharynx and nasopharynx, respectively. EBV infects most adults worldwide through oral transmission and establishes a latent infection, with sporadic productive viral replication and release of virus in the oral cavity throughout life. In view of the prevalence of EBV in the oral cavity and recent data indicating that it infects tongue epithelial cells and establishes latency, we examined 98 cases of primary squamous cell carcinoma of the mobile tongue and 15 cases of tonsillar squamous cell carcinoma for the presence of EBV-encoded RNAs (EBERs), EBV DNA and an EBV-encoded protein, EBNA-1. A commercially available in situ hybridisation kit targeting EBER transcripts (EBER-ISH) showed a positive signal in the cytoplasm and/or nuclei of tumour cells in 43% of TSCCs. However, application of control probes and RNase A digestion using in-house developed EBER-ISH showed identical EBER staining patterns, indicating non-specific signals. PCR analysis of the BamH1 W repeat sequences did not identify EBV genomes in tumour samples. Immunohistochemistry for EBNA-1 was also negative. These data exclude EBV as a potential player in TSCC in both old and young patients and highlight the importance of appropriate controls for EBER-ISH in investigating EBV in human diseases.

  • Cao, Sha
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Huseby, Douglas L
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Brandis, Gerrit
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hughes, Diarmaid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Alternative Evolutionary Pathways for Drug-Resistant Small Colony Variant Mutants in Staphylococcus aureus2017Ingår i: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 8, nr 3, e00358-17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Staphylococcus aureus is known to generate small colony variants (SCVs) that are resistant to aminoglycoside antibiotics and can cause persistent and recurrent infections. The SCV phenotype is unstable, and compensatory mutations lead to restored growth, usually with loss of resistance. However, the evolution of improved growth, by mechanisms that avoid loss of antibiotic resistance, is very poorly understood. By selection with serial passaging, we isolated and characterized different classes of extragenic suppressor mutations that compensate for the slow growth of small colony variants. Compensation occurs by two distinct bypass mechanisms: (i) translational suppression of the initial SCV mutation by mutant tRNAs, ribosomal protein S5, or release factor 2 and (ii) mutations that cause the constitutive activation of the SrrAB global transcriptional regulation system. Although compensation by translational suppression increases growth rate, it also reduces antibiotic susceptibility, thus restoring a pseudo-wild-type phenotype. In contrast, an evolutionary pathway that compensates for the SCV phenotype by activation of SrrAB increases growth rate without loss of antibiotic resistance. RNA sequence analysis revealed that mutations activating the SrrAB pathway cause upregulation of genes involved in peptide transport and in the fermentation pathways of pyruvate to generate ATP and NAD(+), thus explaining the increased growth. By increasing the growth rate of SCVs without the loss of aminoglycoside resistance, compensatory evolution via the SrrAB activation pathway represents a threat to effective antibiotic therapy of staphylococcal infections. IMPORTANCE Small colony variants (SCVs) of Staphylococcus aureus are a significant clinical problem, causing persistent and antibiotic-resistant infections. However, SCVs are unstable and can rapidly evolve growth-compensated mutants. Previous data suggested that growth compensation only occurred with the loss of antibiotic resistance. We have used selection with serial passaging to uncover four distinct pathways of growth compensation accessible to SCVs. Three of these paths (reversion, intragenic suppression, and translational suppression) increase growth at the expense of losing antibiotic resistance. The fourth path activates an alternative transcriptional program and allows the bacteria to produce the extra ATP required to support faster growth, without losing antibiotic resistance. The importance of this work is that it shows that drug-resistant SCVs can evolve faster growth without losing antibiotic resistance.