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1.
  • Björkenstam, Staffan C, 1981, et al. (författare)
  • A framework for motion planning of digital humans using discrete mechanics and optimal control
  • 2017
  • Ingår i: Proceedings of the 5th International Digital Human Modeling Symposium. - : Federal Institute for Occupational Safety and Health. ; , s. 64-71
  • Konferensbidrag (refereegranskat)abstract
    • In this paper we present a framework for digital human modelling using discrete mechanics and optimal control. Discrete mechanics is particularly well suited for modelling the dynamics of constrained mechanical systems, which is almost always the case when considering complex human models interacting with the environment. We demonstrate that, by using recently developed recursive dynamics algorithms, we are able to efficiently use discrete mechanics in direct optimal control methods to plan for complex motions. Besides a proper mechanical model, an appropriate objective function is paramount to achieve realistic motions as a solution to an optimal control problem. Hence, several different objective functions, such as for example minimum time or minimum applied torque over the joints, are compared, and the resulting motions are analyzed and evaluated. To further improve the model, we include basic muscular models for the muscles of the shoulder, arm and wrist, and examine how this affects the motions.
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3.
  • Hanson, Lars, et al. (författare)
  • Industrial path solutions - intelligently moving manikins
  • 2019
  • Ingår i: DHM and Posturography. - London : Academic Press. - 9780128167137 ; , s. 115-124
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • IPS IMMA (Industrial Path Solutions - Intelligently Moving Manikins) is a digital human modeling tool developed in close cooperation between academia and industry in Sweden. The academic consortium behind the software consists of expertise within applied mathematics, ergonomics, and engineering. The development of IMMA was initiated from the vehicle industries’ need of an effective, efficient, objective, and user-friendly software for verification of manufacturing ergonomics. The ‘Industrial path solutions - intelligently moving manikins’ chapter consists of two main sections: the first about the commercially available tool, and the second about current or recent research projects developing the software further. Commercial IPS IMMA is presented by describing the biomechanical model and appearance, anthropometrics module, motion prediction, instruction language, and ergonomics evaluation. The research projects focus on dynamic motions simulation, muscle modelling and application areas such as human-robot collaboration, occupant packaging, and layout planning.
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4.
  • Mårdberg, Peter, et al. (författare)
  • Using a formal high-level language and an automated manikin to automatically generate assembly instructions
  • 2014
  • Ingår i: International Journal of Human Factors Modelling and Simulation. - : InderScience Publishers. - 1742-5549. ; 4:3, s. 233-249
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents an approach to automatically generate predetermined motion time system (PMTS) based assembly instruction lists from simulations within digital human modelling (DHM) software. A formal high-level instruction language is used to instruct an automated manikin to perform assembly operations. The manikin, the language and the assembled objects are composed into a discrete model. In a post-computational step, the model is used to construct PMTS instruction lists by mapping the manikin motions, assembled objects and the language instructions onto a set of PMTS keywords. The described approach is implemented in the DHM software IMMA and tested on industrial cases of manual assembly in the automotive industry.
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5.
  • Svedberg, U. R. A., et al. (författare)
  • Emission of hexanal and carbon monoxide from storage of wood pellets, a potential occupational and domestic health hazard
  • 2004
  • Ingår i: Annals of Occupational Hygiene. - : Oxford University Press (OUP). - 0003-4878 .- 1475-3162. ; 48:4, s. 339-349
  • Tidskriftsartikel (refereegranskat)abstract
    •  Objectives: The objective of the present study was to investigate and describe the emissions of volatile compounds, particularly hexanal and carbon monoxide, from large- and small-scale storage of wood pellets.Methods: Air sampling was performed with Fourier transform infrared spectroscopy and adsorbent sampling in pellet warehouses, domestic storage rooms, lumber kiln dryers and experimental set-ups. Literature studies were included to describe the formation of hexanal and carbon monoxide and the toxicology of hexanal.Results: A geometric mean aldehyde level of 111 +/- 32 mg/m(3) was found in one warehouse, with a peak reading of 156 mg/m(3). A maximum aldehyde reading of 457 mg/m(3) was recorded at the surface of a pellet pile. Hexanal (70-80% w/w) and pentanal (10-15% w/w) dominated, but acetone (821 +/- 24 mg/m(3)), methanol (18 7 mg/m(3)) and carbon monoxide (56 +/- 4 mg/m(3)) were also found. The emissions in a domestic storage room varied with the ambient temperature and peaked after 2 months storage in the midst of the warm season. Aldehyde levels of 98 +/- 4 mg/m(3) and carbon monoxide levels of 123 +/- 10 mg/m(3) were recorded inside such storage rooms. Elevated levels of hexanal (0.084 mg/m(3)) were recorded inside domestic housing and 6 mg/m(3) in a room adjacent to a poorly sealed storage area. Experimental laboratory studies confirmed the findings of the field studies. A field study of the emissions from industrial lumber drying also showed the formation of aldehydes and carbon monoxide.Conclusions: High levels of hexanal and carbon monoxide were strongly associated with storage of wood pellets and may constitute an occupational and domestic health hazard. The results from lumber drying show that the emissions of hexanal and carbon monoxide are not limited to wood pellets but are caused by general degradation processes of wood, facilitated by drying at elevated temperature. Emission of carbon monoxide from wood materials at low temperatures (<100degreesC) has not previously been reported in the literature. We postulate that carbon monoxide is formed due to autoxidative degradation of fats and fatty acids. A toxicological literature survey showed that the available scientific information on hexanal is insufficient to determine the potential risks to health. However, the data presented in this paper seem sufficient to undertake preventive measures to reduce exposure to hexanal.
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6.
  • Thaning, Johan, et al. (författare)
  • Molecular Conformations in a Phospholipid Bilayer Extracted from Dipolar Couplings: A Computer Simulation Study
  • 2007
  • Ingår i: Journal of Physical Chemistry B. - : American Chemical Society. - 1520-6106 .- 1520-5207. ; 111:48, s. 13638-13644
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes an analysis of NMR dipolar couplings in a bilayer formed by dimyristoylphosphatidylcholine (DMPC). The couplings are calculated from a trajectory generated in a molecular dynamics (MD) simulation based on a realistic atom−atom interaction potential. The analysis is carried out employing a recently developed approach that focuses on the construction of the conformational distribution function. This approach is a combination of two models, the additive potential (AP) model and the maximum entropy (ME) method, and is therefore called APME. In contrast to the AP model, the APME procedure does not require an intuition-based choice of the functional form of the torsional potential and is, unlike the ME method, applicable to weakly ordered systems. The conformational distribution function for the glycerol moiety of the DMPC molecule derived from the APME analysis of the dipolar couplings is in reasonable agreement with the “true” distributions calculated from the trajectory. Analyses of dipolar couplings derived from MD trajectories can, in general, serve as guidelines for experimental investigations of bilayers and other complex biological systems.
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8.
  • Al-Anati, Lauy, et al. (författare)
  • Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene
  • 2015
  • Ingår i: Chemico-Biological Interactions. - : Elsevier. - 0009-2797 .- 1872-7786. ; 239, s. 164-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) and their hydroxyl metabolites (OH-PCBs) are ubiquitous environmental contaminants in human tissues and blood. The toxicological impact of these metabolites is poorly understood. In this study rats were exposed to ultrapure PCB180 (10-1000 mg/kg bw) for 28 days and induction of genotoxic stress in liver was investigated. DNA damage signaling proteins (pChk1Ser317 and gamma H2AXSer319) were increased dose dependently in female rats. This increase was paralleled by increasing levels of the metabolite 3'-OH-PCB180. pChk1 was the most sensitive marker. In in vitro studies HepG2 cells were exposed to 1 mu M of PCB180 and 3'-OH-PCB180 or the positive control benzo[a]pyrene (BaP, 5 mu M). 3'-OH-PCB180, but not PCB180, induced CYP1A1 mRNA and gamma H2AX. CYP1A1 mRNA induction was seen at 1 h, and gamma H2AX at 3 h. The anti-oxidant N-Acetyl-L-Cysteine (NAC) completely prevented, and 17 beta-estradiol amplified the gamma H2AX induction by 3'-OH-PCB180. As 3'-OH-PCB180 induced CYP1A1, a major BaP-metabolizing and activating enzyme, interactions between 3'-OH-PCB180 and BaP was also studied. The metabolite amplified the DNA damage signaling response to BaP. In conclusion, metabolism of PCB180 to its hydroxyl metabolite and the subsequent induction of CYP1A1 seem important for DNA damage induced by PCB180 in vivo. Amplification of the response with estradiol may explain why DNA damage was only seen in female rats.
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9.
  • Ali, Imran, et al. (författare)
  • Exposure to polychlorinated biphenyls and prostate cancer : population-based prospective cohort and experimental studies
  • 2016
  • Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 37:12, s. 1144-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.
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10.
  • Alsiö, Johan (författare)
  • From Food Preference to Craving : Behavioural Traits and Molecular Mechanisms
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Preference for palatable and energy-dense foods may be a risk factor for body weight gain and has both genetic and environmental components. Once obesity develops in an individual, weight loss is difficult to achieve. Indeed, obesity is often characterized by repeated attempts to reduce the overconsumption of energy-dense foods, followed by food craving and relapse to overconsumption. Relapse and loss of control over intake are observed also in drug addicts, and it has been shown that obesity and drug addiction not only share behavioural features but also neural circuitry, e.g. the mesolimbic dopamine pathway. In this thesis, we sought to investigate the mechanisms related to food preferences and craving using animal models previously used in addiction research. The risk of gaining weight may implicate behavioural traits and emotional states. We showed in rats that a risk-taking behavioural profile was associated both with increased preference for a high-fat (HF) diet and with increased motivational response to a palatable high-sucrose (HS) diet. Hypothalamic urocortin 2 expression was associated with the preference for the HF diet. We also tested the hypothesis that consumption of HS and HF diets separately or provided simultaneously (HFHS) affect anxiety-like behaviour and locomotion. Furthermore, we showed that withdrawal from HFHS food affects diet-induced obesity-prone (OP) and obesity-resistant (OR) animals differently. OP animals had increased motivation (craving) for HS food pellets as measured by the operant self-administration technique during withdrawal. Dopamine receptor expression in the striatum differed between OP and OR animals both at access to HFHS and during withdrawal. This strongly implicates dopaminergic signaling in the OP phenotype. In humans, food preferences may be monitored using questionnaires. We analyzed food preference data from parents of preschool children, and identified an inverse association of parental preference for high-fat high-protein food and overweight in children. In conclusion, we have employed animal models previously used in the addiction field to identify molecular mechanisms related both to food preference and vulnerability to obesity, and to food craving associated with withdrawal from palatable food. These findings add to our current understanding of obesity.  
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11.
  • Angulo, Julio, 1980-, et al. (författare)
  • What Would It Take for You to Tell Your Secrets to a Cloud? : Studying decision factors when disclosing information to cloud services
  • 2014
  • Ingår i: Secure IT Systems. - Cham : Springer. - 9783319115993 ; , s. 129-145
  • Konferensbidrag (refereegranskat)abstract
    • We investigate the end users’ behaviours and attitudes with regards to the control they place in the personal information that they disclose to cloud storage services. Three controlled experiments were carried out to study the influence in users’ decisions to retain or surrender control over their personal information depending on different factors. The results of these experiments reveal, among other things, the users’ willingness to surrender control over personal information that is perceived as non-sensitive in exchange for valuable rewards, and that users would value the possibility of knowing and controlling the parties who are granted access to their data in the cloud. Based on the results from the experiments we provide implications for the design of end-user tools that can promote transparency and accountability in cloud computing environments.
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12.
  • Askmyr, Maria, et al. (författare)
  • Modeling chronic myeloid leukemia in immunodeficient mice reveals expansion of aberrant mast cells and accumulation of pre-B cells.
  • 2014
  • Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm that, if not treated, will progress into blast crisis (BC) of either myeloid or B lymphoid phenotype. The BCR-ABL1 fusion gene, encoding a constitutively active tyrosine kinase, is thought to be sufficient to cause chronic phase (CP) CML, whereas additional genetic lesions are needed for progression into CML BC. To generate a humanized CML model, we retrovirally expressed BCR-ABL1 in the cord blood CD34(+) cells and transplanted these into NOD-SCID (non-obese diabetic/severe-combined immunodeficient) interleukin-2-receptor γ-deficient mice. In primary mice, BCR-ABL1 expression induced an inflammatory-like state in the bone marrow and spleen, and mast cells were the only myeloid lineage specifically expanded by BCR-ABL1. Upon secondary transplantation, the pronounced inflammatory phenotype was lost and mainly human mast cells and macrophages were found in the bone marrow. Moreover, a striking block at the pre-B-cell stage was observed in primary mice, resulting in an accumulation of pre-B cells. A similar block in B-cell differentiation could be confirmed in primary cells from CML patients. Hence, this humanized mouse model of CML reveals previously unexplored features of CP CML and should be useful for further studies to understand the disease pathogenesis of CML.
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14.
  • Bergman, Lina, 1982- (författare)
  • Cerebral biomarkers in women with preeclampsia
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
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15.
  • Birgner, Carolina, et al. (författare)
  • Reduced activity of monoamine oxidase in the rat brain following repeated nandrolone decanoate administration
  • 2008
  • Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1219, s. 103-110
  • Tidskriftsartikel (refereegranskat)abstract
    • Anabolic androgenic steroids (AAS) are known as doping agents within sports and body-building, but are currently also abused by other groups in society in order to promote increased courage and aggression. We previously showed that 14 days of daily intramuscular injections of the AAS nandrolone decanoate (15 mg/kg) reduced the extracellular levels of the dopaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens shell using microdialysis. The aim of the present study was to investigate whether the same dose regimen of nandrolone decanoate may affect the activities of the dopamine-metabolizing enzymes monoamine oxidases A and B (MAO-A and MAO-B). A radiometric assay was used to determine the activities of MAO-A and MAO-B in rat brain tissues after 14 days of daily i.m. nandrolone decanoate injections at the doses 3 and 15 mg/kg. Gene transcript contents of MAO-A, MAO-B and cathecol-O-methyltransferase (COMT) were measured with quantitative real-time reverse transcription PCR. 3 mg/kg of nandrolone decanoate significantly reduced the activity of both MAO-A and -B in the caudate putamen. 15 mg/kg of nandrolone decanoate significantly reduced the activity of MAO-A in the amygdala and increased the gene transcript level of MAO-B in the substantia nigra. In conclusion, imbalanced MAO activities may contribute to explain the impulsive and aggressive behaviour often described in AAS abusers. The reduced MAO activities observed are in line with our previously presented findings of decreased extracellular levels of DOPAC and HVA in the rat brain, indicating decreased monoaminergic activity following repeated AAS administration.
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16.
  • Birgner, Carolina, et al. (författare)
  • The anabolic androgenic steroid nandrolone decanoate affects mRNA expression of dopaminergic but not serotonergic receptors
  • 2008
  • Ingår i: Brain Research. - : Elsevier BV. - 0006-8993 .- 1872-6240. ; 1240, s. 221-228
  • Tidskriftsartikel (refereegranskat)abstract
    • The abuse of anabolic androgenic steroids (AASs) at supratherapeutic doses is a problem not only in the world of sports, but also among non-athletes using AASs to improve physical appearance and to become more bold and courageous. Investigations of the possible neurochemical effects of AAS have focused partially on the monoaminergic systems, which are involved in aggressive behaviours and the development of drug dependence. In the present study, we administered nandrolone decanoate (3 or 15 mg/kg/day for 14 days) and measured mRNA expression of dopaminergic and serotonergic receptors, transporters and enzymes in the male rat brain using quantitative real-time polymerase chain reaction. Expression of the dopamine D1-receptor transcript was elevated in the amygdala and decreased in the hippocampus while the transcript level of the dopamine D4-receptor was increased in the nucleus accumbens. No changes in transcriptional levels were detected among the serotonin-related genes examined in this study. The altered mRNA expression of the dopamine receptors may contribute to some of the behavioural changes often reported in AAS abusers of increased impulsivity, aggression and drug-seeking.
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17.
  • Björkesten, Johan, 1988- (författare)
  • Dried blood sampling and digital readout to advance molecular diagnostics
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • A drastically increased capacity to measure large sets of molecular features in numerous patient samples in great detail will be required to fulfill the vision of precision medicine and wellness, which may characterize molecular diagnostics in the 21st century. Also sampling procedures need a renaissance to permit continuous sampling at population levels at reasonable cost.Blood sampling is typically performed via venipuncture to draw several milliliters of blood for plasma isolation. This is inconvenient, time-consuming and costly, as well as hard to standardize. The effect on plasma protein profiles by pre-centrifugation delay was investigated in Paper II, demonstrating time- and temperature-dependent release of proteins from blood cells upon delayed plasma isolation, but almost no protein degradation as analyzed by two 92-plex protein panels (Olink® Proteomics). An alternative sampling method, where blood drops from a finger stick are collected dried on paper, is relatively non-invasive, potentially home-based and cheap. Dried blood spots can also be shipped via regular mail and compactly stored. The effect of drying and long term storage stability of a large set of proteins from dried blood spots was investigated in Paper I using Olink® technology. The main findings were that drying slightly but consistently influenced the recorded levels of blood proteins, and that long-term storage decreased the detected levels of some of the proteins with half-lives of decades.Some molecular diagnostic investigations require great accuracy to be useful, arguing for digital enumeration of individual molecules. Digital PCR is the gold standard but Paper III presents an alternative approach based on rolling circle amplification of single molecules. Another instance where extreme assay performance is required is for rare mutation detection from liquid biopsies. Paper V presents a new method offering essentially error-free genotyping of individual molecules by majority-vote decisions for counting rare mutant DNA in blood. Yet other diagnostic investigations require very simple assays. Paper IV presents a novel one-step method to detect nucleic acid sequences by combining the power of rolling circle amplification and the specificity of DNA strand displacement in a format simple enough to be used at the point of care.   Altogether, the thesis spans technologies for advanced molecular diagnostics, from sample collection over assay techniques to an improved readout.
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18.
  • Broström, Julia M., et al. (författare)
  • Toluene diisocyanate exposure and autotaxin–lysophosphatidic acid signalling
  • 2018
  • Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 0041-008X .- 1096-0333. ; 355, s. 43-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Toluene diisocyanate (TDI) is a reactive chemical used in manufacturing plastics. TDI exposure adversely affects workers' health, causing occupational asthma, but individuals differ in susceptibility. We recently suggested a role for signalling mediated by the enzyme autotaxin (ATX) and its product, lysophosphatidic acid (LPA), in TDI toxicity. Here we genotyped 118 TDI-exposed workers for six single-nucleotide polymorphisms (SNPs) in genes encoding proteins implicated in ATX–LPA signalling: purinergic receptor P2X7 (P2RX7), C–C motif chemokine ligand 2 (CCL2), interleukin 1β (IL1B), and caveolin 1 (CAV1). Two P2RX7 SNPs (rs208294 and rs2230911) significantly modified the associations between a biomarker of TDI exposure (urinary 2,4-toluene diamine) and plasma LPA; two IL1B SNPs (rs16944 and rs1143634) did not. CAV1 rs3807989 modified the associations, but the effect was not statistically significant (p = 0.05–0.09). In vitro, TDI-exposed bronchial epithelial cells (16HBE14o-) rapidly released ATX and IL-1β. P2X7 inhibitors attenuated both responses, but confocal microscopy showed non-overlapping localizations of ATX and IL-1β, and down-regulation of CAV1 inhibited the ATX response but not the IL-1β response. This study indicates that P2X7 is pivotal for TDI-induced ATX–LPA signalling, which was modified by genetic variation in P2RX7. Furthermore, our data suggest that the TDI-induced ATX and IL-1β responses occur independently.
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19.
  • Broström, Julia, et al. (författare)
  • Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.
  • 2015
  • Ingår i: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 287:3, s. 222-231
  • Tidskriftsartikel (refereegranskat)abstract
    • Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to <5ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting "sneezing", the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.
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21.
  • Castro, Vasco, et al. (författare)
  • NMR investigations of interactions between anesthetics and lipid bilayers
  • 2008
  • Ingår i: Biochimica et Biophysica Acta - Biomembranes. - : ELSEVIER SCIENCE BV. - 0005-2736 .- 1879-2642. ; 1178:11, s. 2604-2611
  • Tidskriftsartikel (refereegranskat)abstract
    • Interactions between anesthetics (lidocaine and short chain alcohols) and lipid membranes formed by dimyristoylphosphatidylcholine (DMPC) were studied using NMR spectroscopy. The orientational order of lidocaine was investigated using deuterium NMR on a selectively labelled compound whereas segmental ordering in the lipids was probed by two-dimensional 1H–13C separated local field experiments under magic-angle spinning conditions. In addition, trajectories generated in molecular dynamics (MD) computer simulations were used for interpretation of the experimental results. Separate simulations were carried out with charged and uncharged lidocaine molecules. Reasonable agreement between experimental dipolar interactions and the calculated counterparts was observed. Our results clearly show that charged lidocaine affects significantly the lipid headgroup. In particular the ordering of the lipids is increased accompanied by drastic changes in the orientation of the P–N vector in the choline group.
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22.
  • Delfs, Niclas, et al. (författare)
  • Introducing Stability of Forces to the Automatic Creation of Digital Human Postures
  • 2013
  • Ingår i: 2nd International Digital Human Modeling.
  • Konferensbidrag (refereegranskat)abstract
    • Although the degree of automation is increasing in manufacturing industries, many assembly operations are performed manually. To avoid injuries and to reach sustainable production of high quality, comfortable environments for the operators are vital. Poor station layouts, poor product designs or badly chosen assembly sequences are common sources leading to unfavorable poses and motions. To keep costs low, preventive actions should be taken early in a project, raising the need for feasibility and ergonomics studies in virtual environments long before physical prototypes are available. Today, in the automotive industries, such studies are conducted to some extent. The full potential, however, is far from reached due to limited software support in terms of capability for realistic pose prediction, motion generation and collision avoidance. As a consequence, ergonomics studies are time consuming and are mostly done for static poses, not for full assembly motions. Furthermore, these ergonomic studies, even though performed by a small group of highly specialized simulation engineers, show low reproducibility within the group.Effective simulation of manual assembly operations considering ergonomic load and clearance demands requires detailed modeling of human body kinematics and motions as well as a fast and robust inverse kinematics solver. In this paper we introduce a stability measure rewarding poses insensitive to variations in contact points and contact forces. Normally this has been neglected and only the balance of moment and forces has been taken into account. The manikin used in this work has 162 degrees of freedom and uses an exterior root. To describe operations and facilitate motion generation, the manikin is equipped with coordinate frames attached to end-effectors like hands and feet. The inverse kinematic problem is to find joint values such that the position and orientation of hands and feet matches certain target frames during an assembly motion. This inverse problem leads to an underdetermined system of equations since the number of joints exceeds the end-effectors’ constraints. Due to this redundancy there exist a set of solutions, allowing us to pick a solution that maximizes a scalar valued comfort function. Many objectives are included in the comfort function, for example in terms of joint angles, joint moments and solid objects’ distance to the manikin. The proposed stability measure complements the earlier balance criterion and is combined into the comfort function. By increasing the importance of this function the digital human model will reposition to a more stable pose. The digital human model will be tested on a set of challenging assembly operations taken from the automotive industry to show the effect of the stability measure.
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23.
  • Desai, Sameeksha, et al. (författare)
  • Pro-market reforms and allocation of capital in India
  • 2011
  • Ingår i: Journal of Financial Economic Policy. - : Emerald Group Publishing Limited. - 1757-6385 .- 1757-6393. ; 3:2, s. 123-139
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose – The purpose of this paper is to study the efficiency of capital allocation, across levels of ownership, in the aftermath of pro-market reforms in India. Design/methodology/approach – The paper measures investment efficiency using the accelerator principle and examines the effect of ownership type on capital allocation. Findings – No significant improvement in capital allocation during the period studied is found. The findings suggest firms face significant costs in adjusting their capital stock. Originality/value – The paper uses unique data to estimate the elasticity of capital with respect to output.
  •  
24.
  • Eriksson, Mia, et al. (författare)
  • Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NFκB-dependent differentiation of AML cells
  • 2017
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 1:23, s. 2046-2057
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38-cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 inMLL-AF9-driven human AML resulted in induction of apoptosis by p38 MAPK-dependent activation of Caspase 3 and myeloid differentiation in a NFκB-dependent manner. By using murineTrp53 -/- MLL-AF9AML cells, we demonstrate that p53 is dispensable for Pam3CSK4-induced apoptosis and differentiation. Moreover, murineAML1-ETO9a-driven AML cells also were forced into apoptosis and differentiation on TLR1/TLR2 activation, demonstrating that the antileukemic effects observed were not confined toMLL-rearranged AML. We further evaluated whether Pam3CSK4 would exhibit selective antileukemic effects. Ex vivo Pam3CSK4 treatment inhibited murine and human leukemia-initiating cells, whereas murine normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected. Consistent with these findings, primary human AML cells across several genetic subtypes of AML were more vulnerable for TLR1/TLR2 activation relative to normal human HSPCs. In theMLL-AF9AML mouse model, treatment with Pam3CSK4 provided proof of concept for in vivo therapeutic efficacy. Our results demonstrate that TLR1 and TLR2 are upregulated on primitive AML cells and that agonistic targeting of TLR1/TLR2 forces AML cells into apoptosis by p38 MAPK-dependent activation of Caspase 3, and differentiation by activating NFκB, thus revealing a new putative strategy for therapeutically targeting AML cells.
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25.
  • Evander, Mikael, et al. (författare)
  • Study of ATP-release from acoustically levitated eryhrocytes
  • 2007
  • Ingår i: The proceedings of micro total analysis systems 2007. - 9780979806407 ; 2, s. 1372-1374
  • Konferensbidrag (refereegranskat)abstract
    • Erythrocytes (red blood cells) are known to produce large amounts of Adenosine Triphosphate (ATP). It has recently become clear that the ATP-release is part of a mechanism controlling the dilation of the body’s blood vessels. The study of the erythrocyte’s behaviour is complicated by the fact that they respond easily to any physical contact. In this paper we propose a new method for studying the dynamics of the ATP-release by combining non-contact acoustic trapping in a microfluidic chip with a chemiluminiscent assay. Sensitivity levels down to 10 pM were achievable and the ATP-release from a cluster of levitated live erythrocytes was recorded.
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26.
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27.
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28.
  • Hallingbäck, Henrik, et al. (författare)
  • Optimal timing of early genetic selection for sawn timber traits in Picea abies
  • 2018
  • Ingår i: European Journal of Forest Research. - : Springer. - 1612-4669 .- 1612-4677. ; 137:4, s. 553-564
  • Tidskriftsartikel (refereegranskat)abstract
    • In breeding Norway spruce, selection for improved growth and survival is performed at age 10-15 years in order to optimize genetic gain per year. We investigated whether a selection based on wood traits such as density and grain angle, measured under bark in the field at the same age would be informative enough with respect to structural quality traits of sawn boards. To achieve this objective, a sawing study was conducted on the butt logs of 401 trees from a 34-year-old Norway spruce progeny trial situated in southern Sweden. Stem discs were excised from the top of the logs and radial profile data of grain angle, and wood density was recorded for specific annual rings. The sawn and dried boards were assessed for structural traits such as twist, board density, bending stiffness (static modulus of elasticity, sMoE) and bending strength (modulus of rupture, MoR). Additive genetic correlations (r (a)) between single annual ring density measurements and board density, sMoE and MoR were consistently strong (r (a)> 0.7) for annual rings 5-13. Genetic correlations of similar magnitude between grain angle and board twist were estimated for all investigated annual rings (from 2 to around 26 under bark). Consequently, it was found that indirect selection for wood density and grain angle at the tree age 10-16 years would result in more genetic gain per year than selection at later ages. This makes it feasible to perform simultaneous selection of progeny in the field for both growth and wood traits at similar ages.
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29.
  • Hanberg, Annika, et al. (författare)
  • Phthalates and their metabolites in human breast milk, blood and urine as measures for monitoring exposure in human risk groups
  • 2005
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • För att undersöka halter av ftalater i svenskar och vilken matris som bäst lämpar sig för hälsorelaterad miljöövervakning har ftalater och ftalatmetaboliter analyserats i en grupp kvinnor som nyligen fött barn. I samband med förlossning på Universitetssjukhuset i Lund tillfrågades förstföderskor om medverkan och 42 kvinnor kom att ingå i studien. När barnet var 2-3 veckor gammalt pumpade mamman ut 50 mL bröstmjölk. Blod- och urinprov togs en vecka senare. Omfattande förändringar av standardmetoder för provtagning av mjölk och blod gjordes för att minimera risken för kontaminering av proverna. För mjölkprovtagningen användes en specialkonstruerad manuell pump av polykarbonat med ftalatfri packning. Blodprov togs med hjälp av endast kanyl och provrör (eftersom propparna i vaccutainrör innehåller ftalater). Proverna förvarades i värmebehandlade glasbehållare och fosforsyra tillsattes för att motverka metabolism av ftalater i mjölk- och blodprover. Analyserna av bröstmjölk visade värden nära eller under detektionsgränsen (LOD) för flertalet ftalater eller deras metaboliter. Även i blod och serum var nivåerna vanligtvis nära eller under LOD. I urin analyserades endast metaboliter och dessa kunde kvantifieras i 53-100 % av proverna. Nivåerna av ftalatmetaboliter i urin hos de svenska kvinnorna var i paritet med nivåerna hos en allmänbefolkning i USA och Tyskland. Några klara korrelationer mellan nivåer i t ex urin och bröstmjölk respektive blod påvisades inte. Resultaten av studien anger att för närvarande är analys av ftalatmetaboliter i urin den mest framkomliga vägen för skattning av ftalatexponering hos människa. Provtagning och analys av mjölk och blod innebar betydligt större svårigheter. Framför allt framstår risken för kontaminering vid provtagning som betydande och en stor del av ftalaterna och dess metaboliter uppvisade låga halter, vid eller under LOD. Dessutom kan ftalater brytas ned i blod och mjölk. I flertalet internationella publicerade studier av ftalatexponering används urinmetabolit-analyser som ett mått på exponering för ftalater. I en nyligen publicerad amerikansk studie av ett 80-tal nyfödda pojkar sågs ett samband mellan kort ano-genitalt avstånd och nivåer av ftalatmetaboliter i urin hos deras mammor under graviditeten. Den amerikanska studien behöver bekräftas, men metaboliterna var desamma som i vår studie och en jämförelse visar att mediannivåerna var lägre för vissa men högre för andra metaboliter. Vår studie indikerar att svenska kvinnor i fertil ålder inte sällan exponeras för ftalater i nivåer som satts i samband med fosterpåverkan.
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30.
  • Hanson, Lars, et al. (författare)
  • IMMA – Intelligently Moving Manikin – Project Status
  • 2010
  • Ingår i: Proceedings of the 3rd Applied Human Factors and Ergonomics (AHFE) International Conference. - Louisville : AHFE International. - 9780979643545
  • Konferensbidrag (refereegranskat)abstract
    • The overall rationale and assumption for the research project presented in this paper is that a fast, easy to use, and reliable procedure to predict and validate manual assembly tasks is of major importance in product and production development processes to ensure high and robust product quality and process performance. A basic condition for the research is the belief that tools with such functionality are currently not available for companies to utilise in their development processes. Hence more research and development is needed in the area. This paper describes the basic concepts and initial steps taken in the recently commenced research project IMMA - Intelligently Moving Manikin.
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31.
  • Hanson, Lars, 1970, et al. (författare)
  • IMMA – Intelligently Moving Manikin – Project Status
  • 2010
  • Ingår i: Proceedings of 3rd Applied Human Factors and Ergonomics (AHFE) International Conference 2010, Karwowski, W. and Salvendy, G. (Eds.), USA. - 9780979643545
  • Konferensbidrag (refereegranskat)
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32.
  • Hanson, Lars, et al. (författare)
  • IMMA – Intelligently Moving Manikin – Project Status
  • 2011. - 1
  • Ingår i: Advances in Applied Digital Human Modeling. - Boca Raton : CRC Press. - 9781439835128 - 9781439835111 - 9780429151842 ; , s. 559-567
  • Bokkapitel (refereegranskat)abstract
    • The overall rationale and assumption for the research project presented is this paper is that a fast, easy to use, and reliable procedure to predict and validate manual assembly tasks is of major importance in product and production development processes to ensure high and robust product quality and process performance. A basic condition for the research is the belief that tools with such functionality are currently not available for companies to utilise in their development processes. Hence more research and development is needed in the area. This paper describes the basic concepts and initial steps taken in the recently commenced research project IMMA - Intelligently Moving Manikin. © 2011 by Taylor & Francis Group, LLC.
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33.
  • Hanson, Lars, et al. (författare)
  • IMMA - Intelligently Moving Manikins : Project Status 2011
  • 2011
  • Ingår i: Proceedings of the 1st International Symposium on Digital Human Modeling, Lyon, France, June. - : Université Claude Bernard Lyon. - 9782953951509
  • Konferensbidrag (refereegranskat)abstract
    • The overall rationale and assumption for the research project presented in this paper is that a fast, easy to use, and reliable procedure to predict and validate manual assembly tasks is of major importance in product and production development processes to ensure high and robust product quality and process performance. A basic condition for the research is the belief that tools with such functionality are currently not available for companies to utilise in their development process. Hence more research and development is needed in the area. This paper describes the status of the project IMMA - Intelligently Moving Manikins and discusses coming initiatives. The project status is portrayed by a conceivable simulation task of a digital test assembly of a centre console.
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34.
  • Hemmingsson, Jens, 1986, et al. (författare)
  • Autoradiography and biopsy measurements of a resected hepatocellular carcinoma treated with 90 yttrium radioembolization demonstrate large absorbed dose heterogeneities
  • 2018
  • Ingår i: Advances in Radiation Oncology. - : Elsevier BV. - 2452-1094. ; 3:3, s. 439-446
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2018 The Authors Purpose: Radioembolization is an alternative palliative treatment for hepatocellular carcinoma. Here, we examine the uptake differences between tumor tissue phenotypes and present a cross-section of the absorbed dose throughout a liver tissue specimen. Methods and materials: A patient with hepatocellular carcinoma was treated with90Y radioembolization followed by liver tissue resection. Gamma camera images and autoradiographs were collected and biopsy tissue samples were analyzed using a gamma well counter and light microscopy. Results: An analysis of 25 punched biopsy tissue samples identified 4 tissue regions: Normal tissue, viable tumor tissue with and without infarcted areas, and tumor areas with postnecrotic scar tissue. Autoradiography and biopsy tissue sample measurements showed large dose differences between viable and postnecrotic tumor tissue (159 Gy vs 23 Gy). Conclusions: Radioembolization of 90 yttrium with resin microspheres produces heterogeneous-absorbed dose distributions in the treatment of unifocal hepatic malignancies that could not be accurately determined with current gamma camera imaging techniques.
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35.
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36.
  • Hemmingsson, Jens, 1986, et al. (författare)
  • Simulation of 90Y microspheres in selective internal radiation therapy (SIRT) reveals different heterogeneity profiles for glass and resin microspheres.
  • 2016
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. 43 (Suppl 1): 1. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Aim: Selective internal radiation therapy (SIRT) can supply normal tissue in the liver with radiation doses exceeding tolerance without causing toxicity, an effect possibly explained by microsphere clustering causing heterogeneity in the distribution. Using a simulation of microspheres transported through a simplified arterial structure, the aim of this study has been to evaluate how the number of injected microspheres affect the dose distribution. Materials and methods: The simulation was based on observations in biopsies and autoradiographies from resected liver tissue receiving 90YSIRT. Individual microspheres, with diameter and density from literature, were followed through a simplistic bifurcations model in which three parameters were introduced and optimised to obtain results consistent with observations: an artery coefficient of variation, a reduction parameter for the arterial diameter and a distribution volume parameter for the arterial tree. In the model the arterial diameter decreases for higher artery generations and the probability of microsphere clustering increases successively in the artery tree. After simulation a 90Y dose kernel was applied to the 940 cm3 sized 3D-matrix of microspheres and the dose distribution throughout the matrix was evaluated using varying resolutions and computing the coefficient of variation (CV). A smaller number of simulated microspheres (10^5) corresponds to the higher activity/sphere found in glass spheres while a larger number (10^7) resembles resin spheres. Results: As the number of microspheres increase from thousands to 106 the CV of the absorbed dose decrease from over 80 % to 32 % in a volume corresponding to a lobuli (2 mm^3) and at 106 microspheres a plateau was reached. The simulation was consistent with biopsy and autoradiography observations regarding the formation of clusters. A large majority of the clusters contain few microspheres and a minority of the clusters are significantly more numerous in microspheres. Conclusion: For the high microsphere concentrations used with resin microspheres the CVof the absorbed doses was constant (32 %) while for the lower microsphere concentrations used for glass spheres the CV varied between 90 % and 40 %. These results implies that small scale dosimetry for 90Y-SIRT differs between resin and glass spheres.
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37.
  • Högberg, Andreas, 1980-, et al. (författare)
  • Promarket reforms and allocation of capital in India
  • 2009
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The government of India initiated pro-market reforms in the 1990s, after almost five decades of socialist planning. These and subsequent policy reforms are credited as the drivers of India’s radical economic transformation. Prior to reforms, private investment was strictly regulated and restricted to limited sectors. There have since been numerous changes in sectors important for investment, such as the bank sector, which affects outcomes of firm-level strategic decision making and investment behavior. By most estimates, India’s economy will continue to grow rapidly. The purpose of this paper is to investigate changes in investment behavior from the introduction of reforms to current conditions. Reforms changed several institutional frameworks for firm operations, allowing firms to pursue more competitive strategies. Given the importance of ownership in determining firm efficiency and access to capital, we examine the effect of ownership type, and also control for industry differences in capital allocation. We compute a measure of investment efficiency derived from the accelerator principle: Elasticity of capital with respect to output. We find that the allocation of capital has been slow to respond to reforms, indicating similar pace of firm responses. The findings suggest that firms face significant costs in adjusting their capital stock, which in turn leads to inefficient capital allocation. Surprisingly, we find no significant improvement over the 1991-2006 time period.
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38.
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39.
  • Högberg, Carl-Johan, et al. (författare)
  • Effect of Local Anesthetic Lidocaine on Electrostatic Properties of a Lipid Bilayer
  • 2008
  • Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495 .- 1542-0086. ; 94, s. 525-531
  • Tidskriftsartikel (refereegranskat)abstract
    • The influence of local anesthetic lidocaine on electrostatic properties of a lipid membrane bilayer was studied by molecular dynamics simulations. The electrostatic dipole potential, charge densities, and orientations of the headgroup angle have been examined in presence of different amounts of charged or uncharged forms of lidocaine. Important differences of the membrane properties caused by the presence of the both forms of lidocaine are presented and discussed. Our simulations have shown that both charged and uncharged lidocaine cause almost the same increase of the dipole electrostatic potential in the middle of membrane though for different reasons. The increase, being about 90 mV for 9 mol % of lidocaine and 220 mV for 28 mol% of lidocaine, is of the size which may affect the functioning of voltage-gated ion channels.
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40.
  • Högberg, Carl-Johan, et al. (författare)
  • Modification of the CHARMM force field for DMPC lipid bilayer
  • 2008
  • Ingår i: Journal of Computational Chemistry. - : Wiley. - 0192-8651 .- 1096-987X. ; 29:14, s. 2359-2369
  • Tidskriftsartikel (refereegranskat)abstract
    • The CHARMM force field for DMPC lipids was modified in order to improve agreement with experiment for a number of important properties of hydrated lipid bilayer. The modification consists in introduction of a scaling factor 0.83 for 1-4 electrostatic interactions (between atoms separated by three covalent bonds), which provides correct transgauche ratio in the alkane tails, and recalculation of the headgroup charges on the basis of HF/6-311(d,p) ab-initio computations. Both rigid TIP3P and flexible SPC water models were used with the new lipid model, showing similar results. The new model in a 75 ns simulation has shown a correct value of the area per lipid at zero surface tension, as well as good agreement with the experiment for the electron density, structure factor, and order parameters, including those in the headgroup part of lipids.
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41.
  • Högberg, Carl-Johan, 1972- (författare)
  • Molecular Dynamics Investigations of Structure and Dynamics of Lipid Bilayers and Associated Anesthetics
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Detailed understanding of lipid bilayers are of tremendous importance due to their role in many biological processes. This Thesis focuses on structural and dynamical properties of lipid bilayers and their interactions with locally acting anesthetics, studied by Molecular Dynamics simulations.The effect of dehydration of a lipid bilayer is a biologically important phenomenon which was investigated by detailed examination of a number of structural and dynamical lipid parameters at different levels of hydration. The result shows that whereas the structural properties of the bilayer only moderately depend on the degree of hydration, the dynamics of the system is affected very strongly.Related to changes in the bilayer caused by hydration are structural and dynamical changes caused by the presence of anesthetics. Lidocaine is a common, locally acting anesthetic that interacts with lipid bilayers. The difference in position, orientation and diffusional behavior for charged and uncharged lidocaine was examined. The overall results indicate a rather restricted motion, determined by the lipids for the charged lidocaine, whereas the uncharged molecules are more free to diffuse in the lateral direction, as well as able to cross the bilayer.For membrane associated anesthetics, the effect on the bilayer electrostatic potential when introducing anesthetic compounds could contribute to the anesthetic effect. When the change in electrostatic potential and headgroup orientation was examined, both properties were found to be changed by charged as well as uncharged lidocaine. Surprisingly, the potentials in the middle part of the bilayer were almost the same for the charged and uncharged form of lidocaine. The suggested explanation for this is that the uncharged lidocaine gives a significant contribution to the electrostatic potential due to its orientation.Knowledge about the three dimensional structure and structural changes of the lipids in a bilayer is an important biological question. The validity of a method based on the additive potential and maximum entropy model applied to a lipid bilayer was investigated by comparing distributions for two torsion angles extracted from simulations with their corresponding distributions received from the combined model. The results indicates that this new method could be used as a tool for interpretation of experimental data in bilayer systems.For better correspondence with experiment, a calibration of the CHARMM force field was conducted by changing interactions in the lipid tails and charges in the lipid head group. With these new parameters, the simulations gave a fraction of gauche conformations in the lipid tails close to the experimentally determined value, and a very good experimental agreement for the area per lipid, electron density, X-ray structure factor, and NMR order parameters.
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42.
  • Högberg, Dan, 1965-, et al. (författare)
  • Creating and shaping the DHM tool IMMA for ergonomic product and production design
  • 2016
  • Ingår i: International Journal of the Digital Human. - : InderScience Publishers. - 2046-3375 .- 2046-3383. ; 1:2, s. 132-152
  • Tidskriftsartikel (refereegranskat)abstract
    • The history, status and outlook of the research and development actions associated with the creation of the digital human modelling tool intelligently moving manikins (IMMA) are described. The underlying fundamental concepts are described and research and development results so far are illustrated or referred to. Two case studies illustrating use of IMMA on industry-based problems are described. The paper also covers reflections on conceptions for prospective DHM tool developments from a general perspective, relating to areas of ergonomics and design methodology, as well as describing some of the plans for further developments and applications of the IMMA tool. These may be of assistance when identifying challenges for future research and development of DHM tools that are used in product and production design processes in industry.
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43.
  • Högberg, Johan, et al. (författare)
  • Creating brand engagement through in-store gamified customer experiences
  • 2019
  • Ingår i: Journal of Retailing and Consumer Services. - : Elsevier. - 0969-6989 .- 1873-1384. ; 50, s. 122-130
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study is to understand how gamification contributes to customers’ value creation in a retail context and how this value creation relates to brand engagement. The study builds on a field experiment using a two-group between-subjects design combined with correlational research. The experiment involved 378 participants recruited at a major European sports retailer. Participants were exposed to one of two conditions: one with a gamified activity in a store, and one in which the participants performed the same activity without being exposed to any game elements. The findings show that gamification affects the hedonic value of an activity and that this effect can be partly explained by positive affect. When this hedonic value was compared to the satisfaction with a reward, the hedonic value was found to be a better predictor of continued engagement intention. Finally, gamification through continued engagement intention is positively associated with brand engagement.
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44.
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45.
  • Högberg, Johan, et al. (författare)
  • Gameful Experience Questionnaire (GAMEFULQUEST) : An instrument for measuring the perceived gamefulness of system use
  • 2019
  • Ingår i: User modeling and user-adapted interaction. - : Springer. - 0924-1868 .- 1573-1391. ; 29:3, s. 619-660
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, we present the development and validation of an instrument for measuring users’ gameful experience while using a service. Either intentionally or unintentionally, systems and services are becoming increasingly gamified and having a gameful experience is progressively important for the user’s overall experience of a service. Gamification refers to the transformation of technology to become more game-like, with the intention of evoking similar positive experiences and motivations that games do (the gameful experience) and affecting user behavior. In this study, we used a mixed-methods approach to develop an instrument for measuring the gameful experience. In a first qualitative study, we developed a model of the gameful experience using data from a questionnaire consisting of open-ended questions posed to users of Zombies, Run!, Duolingo, and Nike+ Run Club. In a second study, we developed the instrument and evaluated its dimensionality and psychometric properties using data from users of Zombies, Run! (N = 371). Based on the results of this second study, we further developed the instrument in a third study using data from users of Duolingo (N = 507), in which we repeated the assessment of dimensionality and psychometric properties, this time including confirmation of the model. As a result of this work, we devised GAMEFULQUEST, an instrument that can be used to model and measure an individual user’s gameful experience in systems and services, which can be used for user-adapted gamification and for informing user-modeling research within a gamification context.
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46.
  • Högberg, Johan, 1973- (författare)
  • Gameful experiences : The not so painful road to gainful behavior
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this work is to investigate the experiences that users make when using gamified services and the effect that such experiences have on the targeted behavioral outcomes. Considerable attention is dedicated to the gameful experience, since this experience is necessary for gamification to affect the target behavior. Moreover, the effectiveness of gamification at triggering different motivational mechanisms and the role of engagement is investigated.This dissertation contains three papers. Paper 1 uses a mixed-methods approach to develop a model and a measure of the gameful experience. Paper 2 uses a field experimental approach to investigate the effect of gamification on a decision to use offers in a store, and the role of engagement for this effect to occur. Finally, Paper 3 uses a field experiment to investigate the contribution of gamification to value creation in stores and how such value creation relates to brand engagement.The first main finding is a model of the gameful experience that includes the dimensions of accomplishment, challenge, competition, guided, immersion, playfulness, and social experience, and the instrument for measuring this experience. The second main finding is that challenge-based gamification can induce positive affect, which can influence evaluative judgments (thus utilizing the affective quality of System 1 to change the target behavior) and, ultimately, brand engagement. However, such challenge-based gamification does not seem to be effective when aiming to affect the biased System 1 through effort justification. The third main finding is the results that indicate that a user needs to be engaged in order for a gamified service to work properly.
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47.
  • Högberg, Johan, et al. (författare)
  • Gamified in-store mobile marketing : The mixed effect of gamified point-of-purchase advertising
  • 2019
  • Ingår i: Journal of Retailing and Consumer Services. - : Elsevier. - 0969-6989 .- 1873-1384. ; 50, s. 298-304
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates the effect of gamification on in-store mobile advertisement. More specifically, it investigates the effect of gamification on the inclination to act on offers gained at point of purchase. For this purpose, a field experiment was conducted at a supermarket, where real customers were recruited. Eye tracking, smartphone activity logging and choice were used to investigate the customers’ behaviour. The results reveal that gamification is not always useful for increasing the tendency to act on offers. In fact, engagement in a gamified shopping task is needed; otherwise, the tendency to act on offers might even decrease when gamifying.
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48.
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49.
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50.
  • Högberg, Jonas, 1976, et al. (författare)
  • Heterogeneity of microsphere distribution in resected liver and tumour tissue following selective intrahepatic radiotherapy
  • 2014
  • Ingår i: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X. ; 4:48
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND Selective arterial radioembolisation of liver tumours has increased, because of encouraging efficacy reports; however, therapeutic parameters used in external beam therapy are not applicable for understanding and predicting potential toxicity and efficacy, necessitating further studies of the physical and biological characteristics of radioembolisation. The aim was to characterise heterogeneity in the distribution of microspheres on a therapeutically relevant geometric scale considering the range of yttrium-90 (90Y) β-particles. METHODS Two patients with intrahepatic cholangiocarcinoma, marginally resectable, were treated by selective arterial embolisation with 90Y resin microspheres (SIRTEX®), followed 9 days post-infusion by resection, including macroscopic tumour tissue and surrounding normal liver parenchyma. Formalin-fixed, sectioned resected tissues were exposed to autoradiographic films, or tissue biopsies of various dimensions were punched out for activity measurements and microscopy. RESULTS Autoradiography and activity measurements revealed a higher activity in tumour tissue compared to normal liver parenchyma. Heterogeneity in activity distribution was evident in both normal liver and tumour tissue. Activity measurements were analysed in relation to the sample mass (5 to 422 mg), and heterogeneities were detected by statistical means; the larger the tissue biopsies, the smaller was the coefficient of variation. The skewness of the activity distributions increased with decreasing biopsy mass. CONCLUSIONS The tissue activity distributions in normal tissue were heterogeneous on a relevant geometric scale considering the range of the ionising electrons. Given the similar and repetitive structure of the liver parenchyma, this finding could partly explain the tolerance of a relatively high mean absorbed dose to the liver parenchyma from β-particles. Keywords: Radioembolisation; Y-90; SIR; Surgery; Activity heterogeneity
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