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Sökning: WFRF:(Andersson M) > Doktorsavhandling

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1.
  • Albrecht, Lisa M. (författare)
  • Antibiotic Resistance : Selection in the Presence of Metals and Antimicrobials
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The external environment is complex: Antibiotics, metals and antimicrobials do not exist in isolation but in mixtures. Human activities such as animal husbandry, fertilization of agricultural fields and human medicine release high amounts these compounds into the environment. The work in this thesis contributes to our understanding of how the selection of bacterial antibiotic resistance can be facilitated by the pollution by metals and antimicrobials. We show that low levels of antibiotics, metals and combinations thereof can lead to the selection of chromosomally encoded antibiotic resistance genes as well as a multidrug resistance plasmid. The underlying genetic and cellular mechanisms of selection identified relate to mutational changes in a plasmid-encoded metal resistance operon, and metal-associated increases in cellular membrane permeability. We further show that exposure to quaternary ammonium compounds can result in cross-resistance to antibiotics following genetic changes in genes related to efflux, membrane synthesis and transcription/translation. Taken together, the work in this thesis suggests that the stewardship of antibiotics should include prudent use of metals and antimicrobials. 
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3.
  • Andersson, Agneta M (författare)
  • Mapping the Golgi retention signal in the G1 membrane glycoprotein of Uukuniemi virus, a member of the Bunyaviridae family
  • 1999
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Newly synthesized secretory and integral membrane proteins destined for the plasma membrane are transported along the exocytic pathway from the endoplasmic reticulum (ER) via the Golgi complex (GC) to the cell surface. Some of the transported proteins contain information, which target them to their correct intracellular locations. Enveloped viruses have been useful tools for almost three decades to study the mechanisms of protein transport and sorting along the exocytic pathway. The simple structure of viruses force them to rely on host cell mechanisms. This includes the synthesis, processing, modification and transport o their membrane proteins. Enveloped viruses acquire their lipoprotein coat by budding through one of the cellular membranes. Some viruses bud at the plasma membrane whereas others mature at intracellular membranes. The site of budding is thought to be determined by the accumulation of viral membrane glycoproteins in the budding compartment. Such viral glycoproteins are likely to contain signals that retain them in the budding compartment. As a model system to study retention of proteins in the GC, we are using the viral heterodimeric spike glycoproteins G1 and G2 of Uukuniemi virus, a phlebovirus within the Bunyaviridae family. G1 and G2 are synthesized as a precursor protein (p110), which we have confirmed is cotranslationally cleaved immediately after the signal sequence of G2. We present evidence that the signal sequence of G2 remains attached to the C-terminus of G1. The glycoproteins are inserted in the membrane as type I membrane proteins with their C-terminal tails exposed in the cytoplasm. Using the T7 RNA polymerase-driven vaccinia virus expression system we found that G1 expressed alone was targeted to and retained in the GC, whereas G2 was dependent on G1 to exit the ER. Thus, we conclude that the signal for targeting the G1-G2 heterodimer to the GC resides in G1. We have constructed various chimeric proteins by replacing different domains of G1 with the corresponding domains of vesicular stomatitis virus (VSV) G protein, chicken lysozyme, or CD4, to locate the domain in G1 harboring the Golgi retention signal. In these experiments, the chimeras were expressed by using the Semliki Forest virus system. The results indicated that neither the ectodomain nor the transmembrane domain (TMD) of G1 is essential for Golgi localization. Instead, the cytoplasmic tail of G1 is both necessary and sufficient for Golgi retention. This was supported by the fact that the green fluorescent protein (GFP) could be targeted to the GC by attaching the G1 tail to either the N- or the C- terminus of GFP, a protein normally dispersed throughout the cytoplasm. To map the retention signal in more detail, we constructed CD4 chimeras with progressive C-terminal deletions of the G1 tail. The results indicated that the Golgi retention signal is located approximately between residues 10 to 50 counting from the TMD border. In this short region, two cysteines were found to be palmitylated. Replacement of both cysteines with alanins did not influence Golgi retention. To further narrow down the region harboring the Golgi retention signal, we expressed the cytoplasmic tail of G1 as a c-myc epitope-tagged 81 -residue peptide. The peptide was targeted to the GC but was also found associated with vacuolar structures, the identity of which remained unclear. Deletion of the 10 most N- terminal residues abolished the vacuolar staining. Progressive C-terminal deletions resulted in the detection of the shortest peptide, spanning from residues 10 to 40, still capable of becoming targeted to the GC. Additional deletions and alanine replacements revealed the importance of residues 10 to 15 and 35 to 40. The mechanism by which the G1 tail is able to retain the G1-G2 heterodimeric complex in the GC is still unclear. Different alternatives include recycling between the Golgi-cisternae, interactions between the spike protein heterodimers forming aggregates too large to be included in transport vesicles, or retention by binding to resident Golgi proteins or lipids.
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4.
  • Andersson, Charlotta, 1976- (författare)
  • Significance of Wilms’ tumor gene 1 as a biomarker in acute leukemia and solid tumors
  • 2016
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Wilms’ tumor gene 1 (WT1) is a zinc finger transcriptional regulator with crucial functions in embryonic development. Originally WT1 was described as a tumor suppressor gene, but later studies have shown oncogenic properties of WT1 in a variety of tumors. Because of its dual functions in tumorigenesis, WT1 has been described as a chameleon gene. In this thesis, the significance of WT1 as a biomarker was investigated in acute myeloid leukemia (AML), clear cell renal cell carcinoma (ccRCC), ovarian carcinoma (OC) and childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL).Previous studies have suggested that expression of WT1 is a potential marker for detection of minimal residual disease (MRD) in AML. We aimed to define expression of WT1 as an MRD marker in AML. In adult AML patients, we found that a reduction of WT1 expression in bone marrow (≥ 1-log) detected less than 1 month after diagnosis was associated with an improved overall survival (OS) and freedom from relapse (FFR). In peripheral blood, a reduction of WT1 expression (≥ 2-log) detected between 1 and 6 months after treatment initiation was associated with an improved OS and FFR.WT1 harbor pathogenic genetic variants in a considerable proportion of AML and T-lymphoblastic leukemia (T-ALL), but mutations have not been reported in BCP-ALL. We aimed to evaluate the clinical impact of WT1 mutations and single nucleotide polymorphisms (SNPs) in BCP-ALL. Pathogenic mutations in the WT1 gene were rarely seen in childhood BCP-ALL. However, five WT1 SNPs were identified. In survival analyses, WT1 SNP rs1799925 was found to be associated with worse OS, indicating that WT1 SNP rs1799925 may be a useful marker for clinical outcome in childhood BCP-ALL. We also explored whether WT1 mutations and SNPs in ccRCC could be used as biomarkers for risk and treatment stratification. We therefore examined whether SNPs or mutations in WT1 were associated with WT1 expression and clinical outcome. Sequencing analysis revealed that none of the previously reported WT1 mutations were found in ccRCC; however, we identified six different WT1 SNPs. Our data suggest that pathogenic WT1 mutations are not involved in ccRCC, and the prognostic significance of WT1 SNPs in ccRCC is considerably weak. However, a favorable OS and disease-specific survival were found in the few cases harboring the homozygous minor allele.OC has a poor prognosis, and early effective screening markers are lacking. Serous OCs are known to express the WT1 protein. Overexpressed oncogenic proteins can be considered potential candidate antigens for cancer vaccines and T-cell therapy. It was therefore of great interest to investigate whether anti-WT1 IgG antibody (Ab) measurements in plasma could serve as biomarkers of anti-OC response. We found limited prognostic impact, but the results indicated that anti-WT1 IgG Ab measurements in plasma and WT1 staining in tissue specimens could be potential biomarkers for patient outcome in the high-risk subtypes of OCs.In conclusion, the results of this thesis indicate that WT1 gene expression can provide information about MRD of patients with AML, and WT1 SNP rs1799925 may be used as a biomarker for predicting clinical outcome in childhood BCP-ALL. In ccRCC, the prognostic significance of WT1 SNPs is weak and limited to the subgroup of patients that are homozygous for the minor allele. In OCs anti-WT1 IgG Ab measurement in plasma and WT1 staining in tissue specimens could possibly be used as biomarkers for predicting patient outcome in the high-risk subtypes of OCs.
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5.
  • Andersson, Edith M (författare)
  • Acute confusion in orthopaedic care. With the emphasis on the patients' view and the episode of confusion.
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aims of this thesis were to investigate factors of significance for the development of acute confusional state (ACS), the confusional episodes, the lived experiences of having been confused in elderly patients admitted for emergency or elective surgery in orthopaedic care. A further aim was to investigate the nurses’ view of the ACS and the encounter with patients who developed ACS. A case study with one patient preceded the main study including 457 patients, of whom 51 patients developed ACS. Results are based on assessments of the patients’ orientation with Organic Brain Syndrome (OBS) scale, observations during the period of confusion, and interviews with patients who had developed ACS after the confusion had ceased and with nurses (n=48) who took care of the patients in connection with the ACS. Patients admitted for hip fracture had a higher incidence of ACS (20.2%) than patients admitted for elective surgery for coxarthrosis or gonarthrosis (3.6%). Factors associated with development of ACS were four or more physical diseases, emergency admission, impaired vision, more preoperative treatment because of cardiovascular or pulmonary problems, longer anaesthesia time, higher score on the OBS scale on admission and age. The higher the score on the OBS scale on admission, and the more rapid the development of ACS after admission, the longer the period of ACS. Disturbances in motor activity, speech and mood, and symptoms that developed rapidly and fluctuated during the day and from day to day were signs of the confusion. “Struggling to understand and to gain control when in a state of confusion and viewing oneself as being confused” was the main theme illuminated in the texts from the observations during the ACS. In the struggle to achieve understanding and take control over themselves and what was currently taking place, the patients used various strategies: trying to achieve clarity, making a sensible story out of the present and imputing meaning to the present by using their life story. The meaning of the patients’ lived experiences of being and having been confused was interpreted as “being trapped in incomprehensible experiences and a turmoil of past and present and here and there”. It meant that impressions of all kinds invaded the mind of the person and were experienced as reality. They seemed to be victims of these impressions rather than having control over what came into their mind. The findings indicated that one possible approach to the patients is to confirm and support them in narrating their experiences both during the confusion and also after the ACS has ceased. The nurses’ experiences of the encounter with acutely confused patients obtained from the interviews revealed that they had difficulties in reaching the patients and their reality, and understanding their experiences. The nurses found it difficult to reach the patients’ reality because the patients were felt to be in a divided and/or different world. The interaction with the confused patients indicated insufficient and/or broken reciprocity. The nurses used various strategies to meet the patients, being a companion and following the patients’ reality and/or being a surrogate and taking over the patients’ responsibility. The results were more successful when the strategies were derived from the nurses’ interpretation of the patients’ situation and the nurses paid attention to the patients and confirmed them, i.e. being a companion. The results of this thesis are basic for understanding and meeting people in acute confusional state. General vulnerability in elderly people means an increased risk of developing ACS, earlier debut and longer duration of confusion. The patients both understand and do not understand their situation and they struggle to recapture control during the confusion. After the confusion the patients remembered and could narrate their experiences. From the nurses’ perspective it was clear that they had lost contact with the patient during the confusion, and a helpful approach may be to alternate between the validation and the reality orientation approach.
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6.
  • Andersson, Eva M., 1968 (författare)
  • On Turning Point Detection in Cyclical Processes.With applications to the monitoring of business cycles
  • 2001
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In many areas it is important to detect the turning points in an on-going process. The main application in this thesis is detection of turns in business cycles. However, the methods presented here can also be used for other applications, one of which is natural family planning, where the detection of turns in body temperature and other indicators are important. The time of the detection is vital and this is considered in the theory of statistical surveillance. We study surveillance systems that are developed for cyclical processes in order to detect a turning point as soon as possible after it has occurred. A surveillance system is based on an alarm statistic and alarm limits. The main focus in the thesis is on a new approach, which is completely non-parametric regarding the shape of the turning point. The performance of this new method, where only monotonicity restrictions are use, is investigated with respect to different turning point times and different shapes of the turning point. Comparisons are made with other methods, which are in current use. This thesis is based on four papers. In Paper I a surveillance system for cyclical processes is presented and its basic properties are described. The aim is to detect a turning point as soon as possible after it has happened. The alarm statistic is based on the maximum likelihood ratio, with a non-parametric estimation procedure. Thus, no parametric function is assumed for the cyclical process, instead the likelihoods are maximized under monotonicity restriction. In Paper II the properties of the non-parametric maximum likelihood ratio method for different shapes of the turning point are investigated. A theoretical investigation is made on the effect of the slope after the turning point, regardless of parametric function. A simulation study is made regarding the effect of the symmetry, sharpness and smoothness of the peak. In Paper III the effect of methods for seasonal adjustment on the ability to detect a turning point is investigated. Since data on business cycles are often monthly or quarterly, seasonal adjustment is necessary. In Paper IV a comparison is made between different ways to specify the monitoring system. The similarities and differences between the surveillance approach and the Hidden Markov Model approach are investigated. Comparisons are made with regard to i) the amount of information used about earlier states of the process, ii) the assumptions about the frequency of turns in the cyclical process and iii) the assumptions about the parametric form and values of parameters of the
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7.
  • Andersson, Fräs Annika, 1974- (författare)
  • Determination of Volatile Sulfur Compounds in Air and other Gas Matrices : Development and Applications of Solid-Phase Microextraction
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Volatile sulphur compounds (VSCs) are frequently emitted during bioindustrial activities, such as production of biogas, sewage treatment, landfilling, pulpmilling, and the slaughtering of animals and meat processing. VSCs are reactive and malodorous, and they can also be detrimental to human health, therefore it is of great interest to be able to analyze these compounds.However, the standard techniques that are now available for determination of VSCs entail detection limits that in some cases exceed the odor thresholds, and, what is more, they require the use of solvents and toxic reagents. In addition, a single standard method does not exist that can be used to analyze all the VSCs that are most often associated with bioindustrial processes.In the present studies, a technique based on solid-phase microextraction (SPME) was developed for analysis of the VSCs that are commonly found in the bioindustry. The method could even be applied to very complex gas matrices representing point-source emissions of these compounds in amounts below their odor thresholds. Furthermore, the procedure constitutes an improvement compared to the other techniques employed to determine VSCs, because SPME is less time-consuming, it does not require the use of solvents or other chemicals, and it can extract all the compounds simultaneously. The potential of applying SPME for time-weighted average sampling of VSCs was also investigated. These experiments showed that the connnercially available fiber coating with the highest affmity for VSCs (i.e., Carboxen-polydimethylsiloxane)could achieve accurate determination of dimethyldisulfide, whereas use of thatcoating to collect the other compounds was highly influenced by externalparameters that are subject to variation. This work also included investigationsof several important aspects of SPME analysis of VSCs, such as the choice offiber coating, artifact formation, and the impact of various parameters on theextraction.The current results demonstrate that the SPME methodology that was developed can be used to determine VSCs in different matrices and contexts within the bioindustry. More precisely, the technique was successfully employed for the following purposes: to determine background levels ofVSCs to which workers were exposed; to monitor VSC emissions during the biogas process; to supervise the quality of produced biogas; to investigate the efficiency of processes used for abatement of VSCs; and to ascertain the cause of odor problems.
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8.
  • Andersson, Helena M., 1973- (författare)
  • The physiological impact of soccer on elite female players and the effects of active recovery training
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Female soccer is becoming more popular and professional in the world. There are, however, limited scientific data available on how elite female players respond to physical stress during soccer games. An effective recovery strategy following a game is important, because there are few recovery days between the games in international tournaments. The present thesis, which was designed to mirror a competitive situation, aimed to investigate changes in several physiological systems occurring in female elite players in response to two soccer games. It also aimed to investigate the effects of active recovery training on the recovery of several physiological systems. METHODS: Two elite female soccer teams played two 90-min games separated by 72 h active or passive recovery. The active recovery training (cycling at 60% HRpeak, resistance training at <50% 1RM) lasted one hour and was performed 22 and 46 h after the first game. Countermovement jump (CMJ), 20-m sprint time and isokinetic knee strength were measured before, immediately, 5, 21, 45, 51, and 69 h after the first game, and immediately after the second game. The physical stress markers (CK, urea), oxidative stress markers (e.g., GSSG, lipid peroxidation), endogenous (e.g., UA, thiols) and dietary antioxidants (e.g., tocopherols, carotenoids) and a large battery of cytokines (e.g., IL-6, TNF-α) were analysed in blood. RESULTS: No significant differences were observed in the performance parameters, oxidative stress and antioxidant levels or inflammatory response between the active and passive recovery groups. Sprint and isokinetic knee strength were reduced by the same extent after both games. CMJ decreased after the first game and remained reduced throughout the study period. Blood physical stress markers, GSSG and endogenous antioxidants increased with similar amplitude after both games together with unchanged lipid peroxidation. The dietary antioxidants showed either a rapid and persistent change (e.g., tocopherols) or a delayed rise (carotenoids) after the first game. A transient increase occurred in several pro- (e.g., IL-12, TNF-a, MCP-1), anti-inflammatory (e.g., IL-4, IL-10, INF-a) and mixed (IL-6) cytokines after the first game. Fewer cytokines increased in response to the second game. CONCLUSION: Two repeated elite female soccer games separated by 72 h induced similar acute changes in several physiological parameters. After the first game, differences in the recovery pattern of the neuromuscular parameters occurred. In particular, the slow recovery of CMJ indicates that special attention should be devoted to the training of explosive force. Furthermore, the recruitment of antioxidants in response to the transient increase in GSSG resulted in the maintenance of the redox-balance in female players. Similarly, a strong and balanced pro- and anti-inflammatory cytokine response occurred after one single female soccer game. The consequences of the dampened cytokine response during repeated soccer games are, however, unknown. In general, the majority of the parameters had recovered prior to the second game and the physiological alterations induced by the first game did not affect the performance of players in the second game. Finally, active recovery training conducted after a soccer game does not accelerate the recovery time for neuromuscular, oxidative stress, antioxidant and inflammatory responses in elite female players.
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9.
  • Andersson, Jens, 1965- (författare)
  • The development of resource polymorphism – Effects of diet, predation risk and population dynamical feedbacks.
  • 2005
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis deals with the evolution of individuals within a species adapted to utilize specific resources, i.e. resource polymorphism. Although a well-known phenomenon, the understanding of the mechanisms behind is not complete. Considering the ruling theories, resource polymorphism is suggested to depend on severe competition for resources, the presence of open niches to be occupied leading to a reduction in competition, and disruptive selection where generalist are out-competed due trade-offs in foraging efficiency for different prey. In order to study resource polymorphism, I have used fish as the animal group in focus and the methods I have used range over laboratory experiments, field experiments, literature surveys and theoretical modelling. In my work, I have showed that different resource use induces different body shapes and that the rate of change is dependent of the encounter rate of different resources. The induced body changes partly led to increased foraging efficiency but surprisingly I did not find any trade-offs due to specialization. However, when studying predation risk in relation to resource polymorphism, my studies point towards that resource use and predation risk may act as balancing factors in such a way that disruptive selection can take place. My work also shows that population feedbacks have to be explored when considering the evolution of resource polymorphism. In pond and field experiments, I found that changes in resource densities affected the actual resource use despite previous adaptations to certain resources. By performing a literature survey, I found that cannibalism indirectly by its effect on population dynamics seems to facilitate the evolution of resource polymorphism. Modelling a size-structured population, I found that resource dynamics were stabilized, and the relative availability of different resources was levelled out due to cannibalism. Taken together, my studies strongly suggest that to understand the development of resource polymorphism in consumer populations, future studies have to include the effect of a dynamic environment both with respect to resources and predators.
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10.
  • Andersson, Karin M., 1974- (författare)
  • Aqueous Processing of WC-Co Powders
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The object of this work is to obtain a fundamentalunderstanding of the principal issues concerning the handlingof an aqueous WC-Co powder suspension.The WO3 surface layer on the oxidised tungsten carbidepowder dissolves at pH>3 with the tungsten concentrationincreasing linearly with time. Adding cobalt powder to thetungsten carbide suspension resulted in a significant reductionof the dissolution rate at pH<10. Electrokinetic studiesindicated that the reduced dissolution rate may be related tothe formation of surface complexes; the experiments showed thatCo species in solution adsorb on the oxidised tungsten carbidepowder.The surface forces of oxidised tungsten and cobalt surfaceswere investigated using the atomic force microscope (AFM)colloidal probe technique. The interactions at various ionicstrengths and pH values are well described by DLVO theory. Theadsorption of cobalt ions to tungsten oxide surfaces resultedin an additional non-DLVO force and a reduced absolute value ofthe surface potential. It was shown that the adsorption ofpoly(ethylene imine) (PEI) to the WO3 surfaces induces anelectrosteric repulsion.The properties of spray-dried WC-Co granules were related tothe WC primary particle size, and the poly(ethylene glycol)(PEG) binder and PEI dispersant content in aqueous WC-Cosuspensions. The granule characterisation includes a new methodfor measuring the density of single granules. The increase inthe fracture strength of granules produced from suspensionsthat were stabilised with PEI was related to a more densepacking of the WC-Co particles.The AFM was used to study the friction and adhesion ofsingle spray-dried WC-Co granules containing various amounts ofPEG binder. The adhesion and friction force between two singlegranules (intergranular friction) and between a granule and ahard metal substrate (die-wall friction) have been determinedas a function of relative humidity. The granule-wall frictionincreases with binder content and relative humidity, whereasthe granule-granule friction is essentially independent of therelative humidity and substantially lower than the granule-wallfriction at all PEG contents.Key words:Hard Metal, Cemented Carbide, WC-Co, TungstenCarbide, Cobalt, Oxidation, Dissolution, Surface Complexation,XPS, AFM, Colloidal Probe, Hamaker Constant, Cauchy, WO3,CoOOH, ESCA, Zeta-Potential, Surface Potential, Poly(ethyleneimine), PEI, Suspension, van der Waals, Steric, Spray-Dried,Poly(ethylene glycol), Strength, Density, Friction, Adhesion,Granule, PEG, Pressing, FFM.
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