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1.
  • Petkevicius, K., et al. (author)
  • TLCD1 and TLCD2 regulate cellular phosphatidylethanolamine composition and promote the progression of non-alcoholic steatohepatitis
  • 2022
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
  • Journal article (peer-reviewed)abstract
    • The regulation of cellular phosphatidylethanolamine (PE) acyl chain composition is poorly understood. Here, the authors show that TLCD1 and TLCD2 proteins mediate the formation of monounsaturated fatty acid-containing PE species and promote the progression of non-alcoholic steatohepatitis. The fatty acid composition of phosphatidylethanolamine (PE) determines cellular metabolism, oxidative stress, and inflammation. However, our understanding of how cells regulate PE composition is limited. Here, we identify a genetic locus on mouse chromosome 11, containing two poorly characterized genes Tlcd1 and Tlcd2, that strongly influences PE composition. We generated Tlcd1/2 double-knockout (DKO) mice and found that they have reduced levels of hepatic monounsaturated fatty acid (MUFA)-containing PE species. Mechanistically, TLCD1/2 proteins act cell intrinsically to promote the incorporation of MUFAs into PEs. Furthermore, TLCD1/2 interact with the mitochondria in an evolutionarily conserved manner and regulate mitochondrial PE composition. Lastly, we demonstrate the biological relevance of our findings in dietary models of metabolic disease, where Tlcd1/2 DKO mice display attenuated development of non-alcoholic steatohepatitis compared to controls. Overall, we identify TLCD1/2 proteins as key regulators of cellular PE composition, with our findings having broad implications in understanding and treating disease.
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  • Jensen, M. S., et al. (author)
  • Phospholipid flipping involves a central cavity in P4 ATPases
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1
  • Journal article (peer-reviewed)abstract
    • P4 ATPase flippases translocate phospholipids across biomembranes, thus contributing to the establishment of transmembrane lipid asymmetry, a feature important for multiple cellular processes. The mechanism by which such phospholipid flipping occurs remains elusive as P4 ATPases transport a giant substrate very different from that of other P-type ATPases such as Na+/K+-and Ca2+-ATPases. Based on available crystal structures of cation-transporting P-type ATPases, we generated a structural model of the broad-specificity flippase ALA10. In this model, a cavity delimited by transmembrane segments TM3, TM4, and TM5 is present in the transmembrane domain at a similar position as the cation-binding region in related P-type ATPases. Docking of a phosphatidylcholine headgroup in silico showed that the cavity can accommodate a phospholipid headgroup, likely leaving the fatty acid tails in contact with the hydrophobic portion of the lipid bilayer. Mutagenesis data support this interpretation and suggests that two residues in TM4 (Y374 and F375) are important for coordination of the phospholipid headgroup. Our results point to a general mechanism of lipid translocation by P4 ATPases, which closely resembles that of cation-transporting pumps, through coordination of the hydrophilic portion of the substrate in a central membrane cavity.
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  • Almqvist, Catarina, et al. (author)
  • LifeGene - A large prospective population-based study of global relevance
  • 2011
  • In: European Journal of Epidemiology. - Stockholm : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 26:1, s. 67-77
  • Journal article (peer-reviewed)abstract
    • Studying gene-environment interactions requires that the amount and quality of the lifestyle data is comparable to what is available for the corresponding genomic data. Sweden has several crucial prerequisites for comprehensive longitudinal biomedical research, such as the personal identity number, the universally available national health care system, continuously updated population and health registries and a scientifically motivated population. LifeGene builds on these strengths to bridge the gap between basic research and clinical applications with particular attention to populations, through a unique design in a research-friendly setting. LifeGene is designed both as a prospective cohort study and an infrastructure with repeated contacts of study participants approximately every 5 years. Index persons aged 18-45 years old will be recruited and invited to include their household members (partner and any children). A comprehensive questionnaire addressing cutting-edge research questions will be administered through the web with short follow-ups annually. Biosamples and physical measurements will also be collected at baseline, and re-administered every 5 years thereafter. Event-based sampling will be a key feature of LifeGene. The household-based design will give the opportunity to involve young couples prior to and during pregnancy, allowing for the first study of children born into cohort with complete pre-and perinatal data from both the mother and father. Questions and sampling schemes will be tailored to the participants' age and life events. The target of LifeGene is to enrol 500,000 Swedes and follow them longitudinally for at least 20 years.
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  • Barkholt, L M, et al. (author)
  • Stool cultures obtained before liver transplantation are useful for choice of perioperative antibiotic prophylaxis
  • 1997
  • In: Transplant International. - : Frontiers Media SA. - 0934-0874 .- 1432-2277. ; 10:6, s. 432-438
  • Journal article (peer-reviewed)abstract
    • Bacterial infections, especially cholangitis, are still common complications after liver transplantation (LTx). During recent years, multiresistant enterococci have become a nosocomial problem in transplant units. The present prospective study on 26 patients, including 24 patients with chronic liver disease, demonstrated that enterococci were the predominant micro-organism involved in post-LTx bacterial infections. They were cultured in the feces and in other sites of 10 out of 13 (77%) patients who underwent extensive examinations. Ampicillin-resistant Enterococcus faecium strains were isolated in urine or feces of 2 of the 13 patients prior to LTx. Similarly, resistance to ampicillin and gentamicin, the empirically used antibiotics for patients with fever of unknown origin, was found in E. faecium strains in 3 and 2 patients, respectively. Moreover, multiresistant E. faecium and E. faecalis strains were demonstrated in 46% of the patients in the postoperative period (3 months). However, no vancomycin-resistant enterococci were isolated. The use of antibiotics within 4 months prior to LTx significantly increased the risk of developing ampicillin-resistant bacteria at the time of LTx and of infections with bacteria of enteric origin after LTx (P = 0.03 and 0.01, respectively). We conclude that stool and urine cultures performed prior to LTX may be useful for selecting prophylactic antibiotic regimens.
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  • Barregård, Lars, 1948, et al. (author)
  • Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
  • 2013
  • In: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
  • Journal article (peer-reviewed)abstract
    • Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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  • Bill-Axelson, Anna, et al. (author)
  • Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
  • 2008
  • In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. 
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  • Borestrom, C., et al. (author)
  • A CRISP(e)R view on kidney organoids allows generation of an induced pluripotent stem cell-derived kidney model for drug discovery
  • 2018
  • In: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 94:6, s. 1099-1110
  • Journal article (peer-reviewed)abstract
    • Development of physiologically relevant cellular models with strong translatability to human pathophysiology is critical for identification and validation of novel therapeutic targets. Herein we describe a detailed protocol for generation of an advanced 3-dimensional kidney cellular model using induced pluripotent stem cells, where differentiation and maturation of kidney progenitors and podocytes can be monitored in live cells due to CRISPR/Cas9-mediated fluorescent tagging of kidney lineage markers (SIX2 and NPHS1). Utilizing these cell lines, we have refined the previously published procedures to generate a new, higher throughput protocol suitable for drug discovery. Using paraffin-embedded sectioning and whole-mount immunostaining, we demonstrated that organoids grown in suspension culture express key markers of kidney biology (WT1, ECAD, LTL, nephrin) and vasculature (CD31) within renal cortical structures with microvilli, tight junctions and podocyte foot processes visualized by electron microscopy. Additionally, the organoids resemble the adult kidney transcriptomics profile, thereby strengthening the translatability of our in vitro model. Thus, development of human nephron-like structures in vitro fills a major gap in our ability to assess the effect of potential treatment on key kidney structures, opening up a wide range of possibilities to improve clinical translation.
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  • Casper, Charlotte, et al. (author)
  • Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding : A Randomized Phase 3 Study
  • 2016
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
  • Journal article (peer-reviewed)abstract
    • Introduction Feeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL), present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL) improves growth in preterm infants when added to formula or pasteurized breast milk. Patients and Methods LAIF (Lipase Added to Infant Feeding) was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day) during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries. Results In total 415 patients were randomized (rhBSSL n = 207, placebo n = 208), 410 patients were analyzed (rhBSSL n = 206, placebo n = 204) and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83]), nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment. Conclusions Although this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants.
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  • Dominicus, Annica, 1976- (author)
  • Latent variable models for longitudinal twin data
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Longitudinal twin data provide important information for exploring sources of variation in human traits. In statistical models for twin data, unobserved genetic and environmental factors influencing the trait are represented by latent variables. In this way, trait variation can be decomposed into genetic and environmental components. With repeated measurements on twins, latent variables can be used to describe individual trajectories, and the genetic and environmental variance components are assessed as functions of age. This thesis contributes to statistical methodology for analysing longitudinal twin data by (i) exploring the use of random change point models for modelling variance as a function of age, (ii) assessing how nonresponse in twin studies may affect estimates of genetic and environmental influences, and (iii) providing a method for hypothesis testing of genetic and environmental variance components. The random change point model, in contrast to linear and quadratic random effects models, is shown to be very flexible in capturing variability as a function of age. Approximate maximum likelihood inference through first-order linearization of the random change point model is contrasted with Bayesian inference based on Markov chain Monte Carlo simulation. In a set of simulations based on a twin model for informative nonresponse, it is demonstrated how the effect of nonresponse on estimates of genetic and environmental variance components depends on the underlying nonresponse mechanism. This thesis also reveals that the standard procedure for testing variance components is inadequate, since the null hypothesis places the variance components on the boundary of the parameter space. The asymptotic distribution of the likelihood ratio statistic for testing variance components in classical twin models is derived, resulting in a mixture of chi-square distributions. Statistical methodology is illustrated with applications to empirical data on cognitive function from a longitudinal twin study of aging.
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  • Dominicus, Annica, et al. (author)
  • Likelihood ratio tests in behavioral genetics: Problems and solutions
  • 2006
  • In: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 36:2, s. 331-340
  • Journal article (peer-reviewed)abstract
    •     The likelihood ratio test of nested models for family data plays an important role in the assessment of genetic and environmental influences on the variation in traits. The test is routinely based on the assumption that the test statistic follows a chi-square distribution under the null, with the number of restricted parameters as degrees of freedom. However, tests of variance components constrained to be non-negative correspond to tests of parameters on the boundary of the parameter space. In this situation the standard test procedure provides too large p-values and the use of the Akaike Information Criterion (AIC) or the Bayesian Information Criterion (BIC) for model selection is problematic. Focusing on the classical ACE twin model for univariate traits, we adapt existing theory to show that the asymptotic distribution for the likelihood ratio statistic is a mixture of chi-square distributions, and we derive the mixing probabilities. We conclude that when testing the AE or the CE model against the ACE model, the p-values obtained from using the v2 (1 df) as the reference distribution should be halved. When the E model is tested against the ACE model, a mixture of v2(0 df), v2(1 df) and v2 (2 df) should be used as the reference distribution, and we provide a simple formula to compute the mixing probabilities. Similar results for tests of the AE, DE and E models against the ADE model are also derived. Failing to use the appropriate reference distribution can lead to invalid conclusions.
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  • Fic, A, et al. (author)
  • Genome-wide gene expression profiling of low-dose, long-term exposure of human osteosarcoma cells to bisphenol A and its analogs bisphenols AF and S.
  • 2015
  • In: Toxicology in Vitro. - : Elsevier BV. - 1879-3177 .- 0887-2333. ; 29:5, s. 1060-1069
  • Journal article (peer-reviewed)abstract
    • The bisphenols AF (BPAF) and S (BPS) are structural analogs of the endocrine disruptor bisphenol A (BPA), and are used in common products as a replacement for BPA. To elucidate genome-wide gene expression responses, estrogen-dependent osteosarcoma cells were cultured with 10nM BPA, BPAF, or BPS, for 8h and 3months. Genome-wide gene expression was analyzed using the Illumina Expression BeadChip. Three months exposure had significant effects on gene expression, particularly for BPS, followed by BPAF and BPA, according to the number of differentially expressed genes (1980, 778, 60, respectively), the magnitude of changes in gene expression, and the number of enriched biological processes (800, 415, 33, respectively) and pathways (77, 52, 6, respectively). 'Embryonic skeletal system development' was the most enriched bone-related process, which was affected only by BPAF and BPS. Interestingly, all three bisphenols showed highest down-regulation of genes related to the cardiovascular system (e.g., NPPB, NPR3, TXNIP). BPA only and BPA/BPAF/BPS also affected genes related to the immune system and fetal development, respectively. For BPAF and BPS, the 'isoprenoid biosynthetic process' was enriched (up-regulated genes: HMGCS1, PDSS1, ACAT2, RCE1, DHDDS). Compared to BPA, BPAF and BPS had more effects on gene expression after long-term exposure. These findings stress the need for careful toxicological characterization of BPA analogs in the future.
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  • Fischer, Gerhard, 1978, et al. (author)
  • Crystal structure of a yeast aquaporin at 1.15 angstrom reveals a novel gating mechanism.
  • 2009
  • In: PLoS biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 7:6
  • Journal article (peer-reviewed)abstract
    • Aquaporins are transmembrane proteins that facilitate the flow of water through cellular membranes. An unusual characteristic of yeast aquaporins is that they frequently contain an extended N terminus of unknown function. Here we present the X-ray structure of the yeast aquaporin Aqy1 from Pichia pastoris at 1.15 A resolution. Our crystal structure reveals that the water channel is closed by the N terminus, which arranges as a tightly wound helical bundle, with Tyr31 forming H-bond interactions to a water molecule within the pore and thereby occluding the channel entrance. Nevertheless, functional assays show that Aqy1 has appreciable water transport activity that aids survival during rapid freezing of P. pastoris. These findings establish that Aqy1 is a gated water channel. Mutational studies in combination with molecular dynamics simulations imply that gating may be regulated by a combination of phosphorylation and mechanosensitivity.
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  • Humphreys, Keith, et al. (author)
  • The Genetic Structure of the Swedish Population
  • 2011
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:8, s. e22547-
  • Journal article (peer-reviewed)abstract
    • Patterns of genetic diversity have previously been shown to mirror geography on a global scale and within continents and individual countries. Using genome-wide SNP data on 5174 Swedes with extensive geographical coverage, we analyzed the genetic structure of the Swedish population. We observed strong differences between the far northern counties and the remaining counties. The population of Dalarna county, in north middle Sweden, which borders southern Norway, also appears to differ markedly from other counties, possibly due to this county having more individuals with remote Finnish or Norwegian ancestry than other counties. An analysis of genetic differentiation (based on pairwise F(st)) indicated that the population of Sweden's southernmost counties are genetically closer to the HapMap CEU samples of Northern European ancestry than to the populations of Sweden's northernmost counties. In a comparison of extended homozygous segments, we detected a clear divide between southern and northern Sweden with small differences between the southern counties and considerably more segments in northern Sweden. Both the increased degree of homozygosity in the north and the large genetic differences between the south and the north may have arisen due to a small population in the north and the vast geographical distances between towns and villages in the north, in contrast to the more densely settled southern parts of Sweden. Our findings have implications for future genome-wide association studies (GWAS) with respect to the matching of cases and controls and the need for within-county matching. We have shown that genetic differences within a single country may be substantial, even when viewed on a European scale. Thus, population stratification needs to be accounted for, even within a country like Sweden, which is often perceived to be relatively homogenous and a favourable resource for genetic mapping, otherwise inferences based on genetic data may lead to false conclusions.
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  • Jiao, Yu, et al. (author)
  • BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage
  • 2014
  • In: BioMed Research International. - : Hindawi Publishing Corporation. - 2314-6133 .- 2314-6141. ; 2014
  • Journal article (peer-reviewed)abstract
    • Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM). Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel), in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC) integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF) treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN).
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  • Leu, Monica, et al. (author)
  • NordicDB : a Nordic pool and portal for genome-wide control data
  • 2010
  • In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 18:12, s. 1322-1326
  • Journal article (peer-reviewed)abstract
    • A cost-efficient way to increase power in a genetic association study is to pool controls from different sources. The genotyping effort can then be directed to large case series. The Nordic Control database, NordicDB, has been set up as a unique resource in the Nordic area and the data are available for authorized users through the web portal (http://www.nordicdb.org). The current version of NordicDB pools together high-density genome-wide SNP information from similar to 5000 controls originating from Finnish, Swedish and Danish studies and shows country-specific allele frequencies for SNP markers. The genetic homogeneity of the samples was investigated using multidimensional scaling (MDS) analysis and pairwise allele frequency differences between the studies. The plot of the first two MDS components showed excellent resemblance to the geographical placement of the samples, with a clear NW-SE gradient. We advise researchers to assess the impact of population structure when incorporating NordicDB controls in association studies. This harmonized Nordic database presents a unique genome-wide resource for future genetic association studies in the Nordic countries. European Journal of Human Genetics (2010) 18, 1322-1326; doi: 10.1038/ejhg.2010.112; published online 28 July 2010
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  • López-Marqués, Rosa L., et al. (author)
  • The transport mechanism of P4 ATPase lipid flippases
  • 2020
  • In: The Biochemical journal. - 0264-6021. ; 477:19, s. 3769-3790
  • Journal article (peer-reviewed)abstract
    • P4 ATPase lipid flippases are ATP-driven transporters that translocate specific lipids from the exoplasmic to the cytosolic leaflet of biological membranes, thus establishing a lipid gradient between the two leaflets that is essential for many cellular processes. While substrate specificity, subcellular and tissue-specific expression, and physiological functions have been assigned to a number of these transporters in several organisms, the mechanism of lipid transport has been a topic of intense debate in the field. The recent publication of a series of structural models based on X-ray crystallography and cryo-EM studies has provided the first glimpse into how P4 ATPases have adapted the transport mechanism used by the cation-pumping family members to accommodate a substrate that is at least an order of magnitude larger than cations.
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  • Ragazzon, Davide, et al. (author)
  • Chemical vapor deposition of ordered TiOx nanostructures on Au(111)
  • 2013
  • In: Surface Science. - : Elsevier BV. - 0039-6028 .- 1879-2758. ; 617, s. 211-217
  • Journal article (peer-reviewed)abstract
    • The deposition of TiOx (x <= 2) structures on Au(111) by chemical vapor deposition (CVD) in ultrahigh vacuum (UHV) has been investigated with high-resolution core level photoelectron spectroscopy (PES), low-energy electron diffraction (LEED) and scanning tunneling microscopy (STM). Using titanium tetra-isopropoxide as single source precursor it is possible to form different TiOx phases on the surface after deposition: at low coverages, we observe large two-dimensional (2D) honeycomb-lattice Ti2O3 islands with a (2 x 2) registry with the substrate. Higher coverages are dominated by the formation of three-dimensional (3D) TiO2 structures. The TiO2 structures are atomically well ordered provided that the deposition temperature is high enough (500 degrees C). The ordered structure exhibits a LEED pattern characteristic for a rectangular surface unit cell. By performing the deposition at different temperatures it is possible to tune the balance between the 2D and 3D phases: Growth at 500 degrees C significantly favors the formation of 3D TiO2 islands as compared to growth at 200 degrees C and 300 degrees C. (C) 2013 Elsevier B.V. All rights reserved.
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  • Spjuth, Ola, 1977-, et al. (author)
  • Harmonising and linking biomedical and clinical data across disparate data archives to enable integrative cross-biobank research
  • 2016
  • In: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 24:4, s. 521-528
  • Journal article (peer-reviewed)abstract
    • A wealth of biospecimen samples are stored in modern globally distributed biobanks. Biomedical researchers worldwide need to be able to combine the available resources to improve the power of large-scale studies. A prerequisite for this effort is to be able to search and access phenotypic, clinical and other information about samples that are currently stored at biobanks in an integrated manner. However, privacy issues together with heterogeneous information systems and the lack of agreed-upon vocabularies have made specimen searching across multiple biobanks extremely challenging. We describe three case studies where we have linked samples and sample descriptions in order to facilitate global searching of available samples for research. The use cases include the ENGAGE (European Network for Genetic and Genomic Epidemiology) consortium comprising at least 39 cohorts, the SUMMIT (surrogate markers for micro- and macro-vascular hard endpoints for innovative diabetes tools) consortium and a pilot for data integration between a Swedish clinical health registry and a biobank. We used the Sample avAILability (SAIL) method for data linking: first, created harmonised variables and then annotated and made searchable information on the number of specimens available in individual biobanks for various phenotypic categories. By operating on this categorised availability data we sidestep many obstacles related to privacy that arise when handling real values and show that harmonised and annotated records about data availability across disparate biomedical archives provide a key methodological advance in pre-analysis exchange of information between biobanks, that is, during the project planning phase.
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  • Stangeland, B., et al. (author)
  • P-type H(+)- and Ca(2+)-ATPases in plant cells
  • 1997
  • In: Na/K-ATPase and related transport ATPases. - New York : New York Academy of Sciences. - 1573310603 ; , s. 77-87
  • Book chapter (peer-reviewed)
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  • Unger, Eva L., et al. (author)
  • Effect of the Preparation Procedure on the Morphology of Thin TiO2 Films and Their Device Performance in Small-Molecule Bilayer Hybrid Solar Cells
  • 2012
  • In: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 4:11, s. 5997-6004
  • Journal article (peer-reviewed)abstract
    • Flat titanium dioxide films, to be used as the acceptor layer in bilayer hybrid solar cell devices, were prepared by spray-pyrolysis and by spin-casting. Both preparation methods resulted in anatase titania films with similar optical and electronic properties but considerably different film morphologies. Spray pyrolysis resulted in dense TiO2 films grown onto and affected by the surface roughness of the underlying conducting glass substrates. The spin-casting preparation procedure resulted in nanoporous titania films. Hybrid solar cell devices with varying layer thickness of the small-molecule semiconducting dye TDCV-TPA were investigated. Devices built with spray-pyrolyzed titania substrates yielded conversion efficiencies up to 0.47%. Spin-cast titania substrates exhibited short circuits for thin dye layer thickness. For thicker dye layers the performance of these devices was up to 0.6% due to the higher interfacial area for charge separation of these nanoporous TiO2 substrates.
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  • Weman, Helge, 1960-, et al. (author)
  • Semiconductor Quantum-Wires and Nano-Wires for optoelectronic Applications
  • 2009
  • In: Journal of materials science. Materials in electronics. - : Springer Science and Business Media LLC. - 0957-4522 .- 1573-482X. ; 20:1, s. S94-S101
  • Journal article (peer-reviewed)abstract
    • Exciton transfer between two parallel GaAs V-groove quantum wires (QWRs) or two planar quantum wells (QWs) separated by AlGaAs barriers ranging from 5.5 nm to 20 nm thickness is studied by photoluminescence (PL) and PL excitation (PLE) spectroscopy. It is found that the transfer is strongly reduced between the widely spaced QWRs as compared with QWs. We have also investigated the optical absorption in single QWRs embedded in an AlGaAs V-shaped channel waveguide. Using a combination of PLE and absorption measurements we construct the full dependence of absorption spectra on the linear polarization. Our studies reveal the importance of inter-subband mixing in determining the energies of the light-hole-like transitions and thus the QWR absorption. Finally we present recent results on the fabrication and structural characterization of GaAs and GaP nanowires (NWs) grown by molecular beam epitaxy (MBE) on GaAs(111)B and Si(111) substrates, using Au-catalyzed vapor–liquid–solid growth technique. It is shown that, apart from optimizing the NW growth parameters, substrate material and the procedure for preparing the substrate before the MBE growth play an important role in controlling the NWs.
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  • Wikström, Maude, 1945, et al. (author)
  • Effect of 12-month weekly professional oral hygiene care on the composition of the oral flora in dentate, dependent elderly residents: A prospective study.
  • 2017
  • In: Gerodontology. - : Wiley. - 1741-2358 .- 0734-0664. ; 34:2, s. 240-248
  • Journal article (peer-reviewed)abstract
    • To study the effect of weekly professional oral hygiene care on the proportion of micro-organisms associated with good oral health, caries, and periodontal and soft tissue diseases in oral biofilms in dentate, dependent elderly residents.Assisted oral hygiene care reduces the plaque score and number of micro-organisms in the oral biofilms in elderly residents. Less is known about the effect on the quality/composition of the remaining oral flora.Participants comprised 33 residents in the study and 35 in the control group. Dental status (≥10 natural teeth and no removable dentures to be included), plaque score, salivary secretion rate and prescription medicines were recorded. Duplicate samples, collected from supragingival plaque and tongue, were analysed using cultivation technique. Differences between and within groups were analysed using one-way and two-way ANOVA, respectively.At the baseline, the number of teeth in the participants (mean age, 83.7±7.4years) was 22.0±4.5. The number of prescription medicines was 9.4±4.5. Seventy-six per cent had low salivary secretion rate. Fifty per cent had "visible thick" supragingival plaque. At the 12-month registration, "no visible" or "visible but thin" plaque was recorded in 92% in the study group. The proportions of bacteria associated with good oral health and periodontal diseases were decreased over time, while the frequency and proportions of micro-organisms associated with caries and soft tissue infection were unaffected or increased.The results indicate that assisted oral hygiene care alone is not sufficient to regain an oral microbial flora associated with good oral health in dentate, dependent elderly residents.
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