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Sökning: WFRF:(Johansson Niklas) > (2010-2014)

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1.
  • Elert, Niklas, 1983- (författare)
  • Economic dynamism : essays on firm entry and firm growth
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The topic of this thesis is economic dynamism. The five articles contribute to the literature on firm entry and firm growth. Studies are based on a dataset covering all Swedish limited liability firms between 1997 and 2010.The first article investigates conditions for firm entry in Sweden, distinguishing regular entrants from entrants that survive for at least two years, modelling the firm entry decision using count data models. While high income and a well-educated population had a positive effect, the effect was more important for surviving entrants. The second article uses a similar method, but focuses on wholesale industries and distinguishes between regular entry and in migration of firms, i.e. when an incumbent firm relocates its operations. Access to a university, many educated workers and low local taxes had positive effects. Better access to infrastructure had a strong positive effect on entrants, but it was smaller for in-migrating firms. The third article investigates if the industry context matters for whether Gibrat’s law holds, i.e. whether firm growth is independent of firm size. The law is found more likely to be rejected in industries with a high minimum efficient scale and a large number of firms located in metropolitan areas, but more likely to hold in industries with high market concentration and more group ownership. The fourth and fifth article contribute to the high-growth firms (HGFs) literature. In the fourth article it is examined whether the way HGFs are defined matters for the policy implications. It is found that the economic contributions of HGFs differ significantly depending on definition. Young firms are however more likely to be HGFs irrespective of definition. The fifth article considers the frequent argument that policymakers should target high-tech firms, i.e., firms with high R&D intensity, because such firms are thought more likely to become HGFs. We examine this assumption by studying the industry distribution of HGFs. Results indicate that industries with high R&D intensity, ceteris paribus, can be expected to have a lower share of HGFs than can industries with lower R&D intensity. By contrast, we find that HGFs are overrepresented in service industries with a high share of human capital.
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2.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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4.
  • Johansson, Per, et al. (författare)
  • Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Diagnostic Performance in a Homogeneous Mono-Center Population
  • 2011
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 24:3, s. 537-546
  • Tidskriftsartikel (refereegranskat)abstract
    • The cerebrospinal fluid (CSF) biomarkers amyloid-beta (A beta)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A beta(1-42), T-tau, P-tau, A beta(X-38), A beta(X-40), A beta(X-42), sA beta PP alpha, and sA beta PP beta. In multivariate analysis, the core biomarkers A beta(1-42), T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p < 0.0001), this increase mainly mediated by A beta(X-42). In conclusion, CSF biomarkers A beta(1-42), T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used.
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6.
  • Johansson, Per, et al. (författare)
  • Convergence of chromogranin and amyloid metabolism in the brain.
  • 2010
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5279 .- 1552-5260. ; 6:4, s. 511-511
  • Konferensbidrag (refereegranskat)abstract
    • Background: Much is unknown regarding the regulation of amyloid precursor protein (APP) processing in the human central nervous system. It has been hypothesized that amyloidogenic APP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of APP-derived molecules in CSF with chromogranin (Cg) derived peptides, representing the regulated secretion. Methods: Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50) and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides Aβ1-42, Aβx-42, Aβx-40, Aβx-38, α-cleaved soluble APP (α-sAPP), β-cleaved soluble APP (β-sAPP), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes APP into Aβ, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. Results: CSF Cg levels correlated to sAPP and Aβ peptides in AD, MS and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. Conclusions: These results suggest that a large part of APP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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7.
  • Johansson, Per, 1966, et al. (författare)
  • Mild dementia is associated with increased adrenal secretion of cortisol and precursor sex steroids in women.
  • 2011
  • Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 75:3, s. 301-308
  • Tidskriftsartikel (refereegranskat)abstract
    • Context Sex steroid levels decrease with increasing age, but little is known whether this is of importance for the age-related decline in cognitive function. Design and patients A cross-sectional study of 50 (26 men) consecutive patients under primary evaluation of cognitive impairment (D group) and 18 (9 men) matched healthy controls (C group). Measurements Sex steroid and precursor levels were determined in serum and, when measurable, in cerebrospinal fluid (CSF) using gas chromatography/mass spectroscopy (GC-MS) or liquid chromatography/mass spectroscopy (LC-MS). Sex hormone binding globulin (SHBG) and cortisol concentrations were measured using conventional assays. Results Patients in the D group had higher 24-h urine cortisol levels and increased serum levels of dehydroepiandrosterone (DHEA) and its sulphate ester dihydroepiandrosterone sulphate (DHEAS), androsterone (ADT), and oestrone (E1) and its sulphate ester E1S, compared with the controls. When men and women were analysed separately, increased serum concentrations of E1 and E1S were observed in both D men and D women, whereas increased levels of other sex steroids and cortisol were seen only in D women. Conclusions In both D men and women, serum E1 and E1S levels were increased, whereas other changes were gender specific and only seen in D women. Further studies are needed to determine whether these changes are a cause of, or merely a consequence of, cognitive impairment in elderly subjects.
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8.
  • Johansson, Per, et al. (författare)
  • Reduced cerebrospinal fluid level of thyroxine in patients with Alzheimer's disease
  • 2013
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 1873-3360 .- 0306-4530. ; 38:7, s. 1058-1066
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Little is known of the association between thyroid hormones in the central nervous system and Alzheimer's disease (AD). We determined thyroid hormone levels in serum and cerebrospinal fluid (CSF) in a well-defined homogeneous mono-center population. Methods: Fifty-nine consecutive patients under primary evaluation for cognitive impairment were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 31), patients with stable MCI (SMCI, n = 13), patients with other dementias (n = 15), and healthy controls (n = 19). Thyroid hormones in serum and CSF and AD biomarkers in CSF were analyzed using established immunochemical assays. Cognitive impairment was estimated using mini-mental state examination (MMSE). Results: Serum levels of free and total thyroxine (T4) and triiodothyronine (T3) were similar in all groups whereas a marginal increase in serum thyroid-stimulating hormone (TSH) level was observed in the AD patients. The CSF level of total T4 was decreased in patients with AD and other dementias compared to SMCI (both P = 0.01) and healthy controls (both P = 0.001), whereas CSF levels of TSH and total T3 were unchanged. In the total study population, CSF total 14 level correlated positively with MMSE score (r = 0.26, P < 0.05) and negatively with CSF total-tau (T-Tau) level (r = -0.23, P < 0.05). Conclusion: Patients with AD as well as other dementias had signs of mild brain hypothyroidism, which could only to a small extent be detected in serum values. (C) 2012 Elsevier Ltd. All rights reserved.
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10.
  • Johansson, Rolf, et al. (författare)
  • Bokslutet från början
  • 2013
  • Bok (populärvet., debatt m.m.)abstract
    • Bokslutet från början är en kombinerad fakta- och övningsbok. Steg för steg behandlas de olika områden man måste behärska för att kunna upprätta ett fullständigt bokslut med årsredovisning i enlighet med årsredovisningslagens krav.
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11.
  • Johansson, Rolf, et al. (författare)
  • Bokslutet från början
  • 2011
  • Bok (populärvet., debatt m.m.)abstract
    • Bokslutet från början är en kombinerad fakta- och övningsbok som är en direkt fortsättning på grundboken i bokföring, Bokföring från början. I denna bok fördjupas kunskaperna. Steg för steg behandlas de olika områden man måste behärska för att kunna upprätta ett fullständigt bokslut med årsredovisning i enlighet med årsredovisningslagens krav. För varje moment finns ett stort antal övningar.
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14.
  • Mattsson, Niklas, 1979, et al. (författare)
  • Cerebrospinal Fluid Microglial Markers in Alzheimer's Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility
  • 2011
  • Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 151-159
  • Tidskriftsartikel (refereegranskat)abstract
    • Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid beta-plaques in Alzheimer's disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these cells. We therefore examined cerebrospinal fluid (CSF) biomarkers in patients with AD, other dementias, mild cognitive impairment and in healthy controls. Samples were analyzed for markers with known association to macrophage activity, including chitotriosidase, YKL-40 (CHI3L1, HC gp-39) and chemokine CC motif ligand 2 (CCL2, MCP1). Patients with AD had higher chitotriosidase activity than controls and patients with stable mild cognitive impairment, consistent with the presence of activated microglial cells in AD brains, but with large overlaps between groups. CCL2 and YKL-40 concentrations did not differ among groups. Microglial markers are unlikely to be useful for AD diagnosis, but might be useful for identification of distinct subgroups of patients, and for the development and implementation of drugs targeting microglial pathology.
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15.
  • Mattsson, Niklas, 1979, et al. (författare)
  • Converging Pathways of Chromogranin and Amyloid Metabolism in the Brain
  • 2010
  • Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 20:4, s. 1039-1048
  • Tidskriftsartikel (refereegranskat)abstract
    • Much is unknown regarding the regulation of Alzheimer-related amyloid-beta protein precursor (A beta PP)-processing in the human central nervous system. It has been hypothesized that amyloidogenic A beta PP-processing preferentially occurs in the regulated secretory pathway of neurons. To test this hypothesis we looked for correlations of A beta PP-derived molecules in cerebrospinal fluid (CSF) with chromogranin (Cg) derived peptides, representing the regulated secretion. Patients with Alzheimer's disease (AD, N = 32), multiple sclerosis (MS, N = 50), and healthy controls (N = 70) were enrolled. CSF was analyzed for the amyloid peptides A beta(1-42), A beta(x-42), A beta(x-40), A beta(x-38), alpha-cleaved soluble A beta PP (sA beta PP alpha), beta-cleaved soluble A beta PP (sA beta PP beta), and peptides derived from CgB and SgII (Secretogranin-II, CgC). We investigated CSF levels of the protease BACE1, which processes A beta PP into A beta, in relation to Cg-levels. Finally, we measured Cg levels in cell media from untreated and BACE1-inhibited SH-SY5Y human neuroblastoma cells. CSF Cg levels correlated to sA beta PP and A beta peptides in AD, MS, and controls, and to CSF BACE1. Cell medium from BACE1-inhibited cells had decreased CgB levels. These results suggest that a large part of A beta PP in the human central nervous system is processed in the regulated secretory pathway of neurons.
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16.
  • Movérare-Skrtic, Sofia, et al. (författare)
  • Leukocyte Telomere Length (LTL) is reduced in stable mild cognitive impairment but low LTL is not associated with conversion to Alzheimer's Disease: A pilot study
  • 2012
  • Ingår i: Experimental Gerontology. - : Elsevier BV. - 1873-6815 .- 0531-5565. ; 47:2, s. 179-182
  • Tidskriftsartikel (refereegranskat)abstract
    • Leukocyte telomere length (LTL) is associated with the aging process and may be related to cognitive aging. Previous studies have shown conflicting results whether LTL is affected in patients with Alzheimer's disease (AD). In this pilot study, we investigated LTL in a well-defined homogeneous mono-center population. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n=32), patients with stable MCI (n=13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n=15), and healthy controls (n=20). LTL was determined using a quantitative PCR assay. Patients with AD had similar LTL as healthy controls. Patients with stable MCI had reduced LTL both compared to AD patients (p=0.02) and controls (p=0.008). Subanalyses within the AD group showed that patients with MCI that later converted to AD had similar LTL as patients with clinical diagnosis of AD at primary evaluation and healthy controls whereas the LTL was longer compared to the stable MCI group (p=0.02). There were no correlations between LTL and the core AD biomarkers A beta(1-42), T-tau and P-tau. In conclusion, in this pilot study, patients with AD or MCI that later converted to AD had similar LTL as healthy controls. Patients with stable MCI that did not progress to dementia had reduced LTL compared to controls, which might suggest a more marked biological aging as a cause of the cognitive symptoms in this group. (C) 2011 Elsevier Inc. All rights reserved.
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17.
  • Norrby, Niklas (författare)
  • High pressure and high temperature behavior of TiAlN
  • 2012
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This licentiate thesis mainly reports about the behavior of arc evaporated TiAlN at high pressures and high temperatures. The extreme conditions have been obtained in metal cutting, multi anvil presses or diamond anvil cells. Several characterization techniques have been used, including x-ray diffraction and transmission electron microscopy.Results obtained during metal cutting show that the coatings are subjected to a peak normal stress in the GPa region and temperatures around 900 °C. The samples after metal cutting are shown to have a stronger tendency towards the favorable spinodal decomposition compared to heat treatments at comparable temperatures. We have also shown an increased anisotropy of the spinodally decomposed domains which scales with Al composition and results in different microstructure evolutions. Furthermore, multi anvil press and diamond anvil cell at even higher pressures and temperatures (up to 23 GPa and 2200 °C) also show that the unwanted transformation of cubic AlN into hexagonal AlN is suppressed with an increased pressure and/or temperature.
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18.
  • Rosén, Christoffer, 1986, et al. (författare)
  • Discriminatory analysis of biochip-derived protein patterns in CSF and plasma in neurodegenerative diseases
  • 2011
  • Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of biomarkers in neurodegenerative diseases has been emphasized by recent research. Future clinical demands for identifying diseases at an early stage may render them essential. The aim of this pilot study was to test the analytical performance of two multiplex assays of cerebral markers on a well-defined clinical material consisting of patients with various neurodegenerative diseases. We measured 10 analytes in plasma and cerebrospinal fluid (CSF) from 60 patients suffering from Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, dementia with Lewy bodies, or mild cognitive impairment, as well as 20 cognitively healthy controls. We used the Randox biochip-based Evidence Investigator™ system to measure the analytes. We found it possible to measure most analytes in both plasma and CSF, and there were some interesting differences between the diagnostic groups, although with large overlaps. CSF heart-type fatty acid-binding protein was increased in AD. Glial fibrillary acidic protein and neutrophil gelatinase-associated lipocalin in CSF and D-dimer in plasma were elevated in patients with cerebrovascular disease. A multivariate statistical analysis revealed that the pattern of analytes could help to differentiate the conditions, although more studies are required to verify this.
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19.
  • Andersson Chan, Anneli, 1971-, et al. (författare)
  • Increased nitrogen removal in existing volumes at Sundet wastewater treatment plant, Växjö
  • 2014
  • Ingår i: Water practice and technology. - : IWA Publishing. - 1751-231X. ; 9:2, s. 215-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Many wastewater treatment plants need to improve their nitrogen removal due to stricter requirements and increasing loads. This often means larger bioreactor volumes, which can be very expensive and is sometimes impossible if space is limited. Therefore, there is a need for compact hybrid solutions that can increase capacity within existing volumes. Two full-scale demonstration projects using moving bed biofilm reactor (MBBR) technology has proven to be an efficient way to treat nitrogen in existing volumes at Sundet wastewater treatment plant in Växjö. Increased nitrification and denitrification capacity in parts of the main stream were demonstrated through the Hybas™ process, a combination of MBBR and activated sludge using the integrated fixed-film activated sludge technology. The ANITA™ Mox process, using autotrophic N-removal through anaerobic ammonium oxidation (anammox), provided high nitrogen removal for the sludge liquor. Data collected on-site for over a year are analyzed and compared with the performance of conventional treatment systems. These two full-scale demonstration projects have been a successful learning experience in identifying and correcting both process and operational issues, which may not have arisen at pilot scale. The set objectives in terms of nitrogen removal were met for both processes and design modifications have been identified that will improve future operation at Sundet WWTP.
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20.
  • Anselmsson, Johan, et al. (författare)
  • Brand image and customers’ willingness to pay a price premium for food brands
  • 2014
  • Ingår i: Journal of Product & Brand Management. - 1061-0421. ; 23:2, s. 90-102
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose – The aim is to understand customers' willingness, or unwillingness, to pay a price premium in the market for consumer packaged food and what kind of images brands can use in order to achieve a price premium. Design/methodology/approach – The study is based on a quantitative survey of brand images found in food and branding literature and their impact on loyalty as well as customers' willingness to pay a price premium for consumer packaged food. Findings – The survey shows that quality is a significant determinant of price premium, but adding other image dimensions doubles the predictability and understanding about price premium. The strongest determinants of price premium are social image, uniqueness and home country origin. Other significant determinants are corporate social responsibility (CSR) and awareness. Practical implications – The results help brand managers to recognise the importance of incorporating price premium and to develop a better understanding of what drives price premium in addition to more traditional dimensions as quality and loyalty. Originality/value – In grocery retailing, the competition for customers, margins and price premiums between manufacturer and private labels is fierce. Traditionally, the literature on this competition has focused on quality and product improvements as the main tool for creating distance to low priced competition. This study looks into other more branding related dimensions to distance from price competition
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21.
  • Barclay, Victoria K.H., et al. (författare)
  • Chiral analysis of metoprolol and two of its metabolites, alpha‑hydroxymetoprolol and deaminated metoprolol, in wastewater using liquid chromatography-tandem mass spectrometry
  • 2012
  • Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1269:SI, s. 208-217
  • Tidskriftsartikel (refereegranskat)abstract
    • A LC–MS/MS method for the chiral separation of metoprolol and two of its main metabolites, α-hydroxymetoprolol (α-OH-Met) and deaminated metoprolol (COOH-Met), in environmental water samples has been developed. The target bases, metoprolol and α-OH-Met, as well as the acidic metabolite (COOH-Met) were extracted from water samples by a solid phase extraction method employing Oasis HLB cartridges. The extraction recoveries were ≥73% for all compounds in surface water. Four different types of chiral stationary phases were investigated for the separation of the eight stereoisomers of metoprolol and its metabolites, Chiralcel OD-H, Chirobiotic V, Chiral AGP and Chiral CBH. In the final method, the enantiomers of metoprolol and four stereoisomers of α-OH-Met were separated using Chiral CBH, the enantiomers of COOH-Met were separated employing Chiral AGP. The analytes were detected in SRM mode by triple quadrupole mass spectrometry. The method was applied for the chiral analysis of the analytes in treated wastewater samples from Uppsala, Sweden. The enantiomers and diastereoisomers of α-OH-Met were detected and analyzed in the samples. The concentrations of the three first eluting stereoisomers of α-OH-Met were between 54 and 61 pM. Interestingly, the last eluting stereoisomer was found to be present at a concentration of 151 pM at the same sampling occasion. This is, to the best of the authors’ knowledge, the first time the stereoisomers of α-OH-Met have been detected in wastewater samples. The enantiomers of metoprolol were determined to be 1.77 and 1.86 nM in the same matrix. The enantiomers of COOH-Met were not detected above the method detection limit (42 pM) in treated wastewater samples. The developed LC–MS/MS methods were validated in wastewater samples.
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22.
  • Barclay, Victoria K.H. (författare)
  • Development of LC-MS/MS Methods for the Analysis of Chiral and Achiral Pharmaceuticals and Metabolites in Aqueous Environmental Matrices
  • 2012
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis describes the development of liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for the trace analysis of active pharmaceutical ingredients (APIs) and their metabolites in aqueous environmental matrices. The research was focused on the development of chiral LC-MS/MS methods for the analysis of fluoxetine and metoprolol, as well as their chiral metabolites in environmental water samples. A method was also developed for the achiral compounds, diazepam and nordiazepam. The LC-MS/MS methods were validated by the use of the isotope-labeled compounds. As these isotope-labeled compounds were not found in the wastewater samples, the validation could be assessed at trace level concentrations in the actual matrices in which the analytes were detected. The analytes were extracted from the water samples using solid phase extraction methods. Different types of solid phase extraction sorbents were evaluated. Fluoxetine and norfluoxetine were extracted through the use of a mixed mode polymeric based extraction sorbent. A hydrophilic and lipophilic balanced sorbent was employed for the simultaneous extraction of metoprolol and its metabolites, the base α-hydroxymetoprolol and the acidic metabolite deaminated metoprolol. Moreover, silica based C18 extraction discs were applied for the sample preparation of diazepam and nordiazepam. The chromatographic separations were conducted in reversed phase LC with MS compatible mobile phases. The enantiomers of fluoxetine and norfluoxetine were simultaneously separated using the chiral stationary phase (CSP), α1-acid glycoprotein (AGP). The Chiral AGP column was also applied for the separation of the enantiomers of deaminated metoprolol. For the simultaneous separation of the metoprolol enantiomers and the four stereoisomers of α-hydroxymetoprolol, the cellobiohydrolase (CBH) protein based CSP was used. An octadecyl silica based LC column was applied for the separation of diazepam and nordiazepam. The analytes were detected by the use of tandem quadrupole mass spectrometry operating in selective reactive monitoring mode. High resolution MS, employing a quadrupole time-of-flight (QqTOF) mass analyzer, was utilized for the identification of an unknown compound in wastewater samples. The APIs and their metabolites, as well as their respective enantiomers, were quantified in raw and treated wastewater from Uppsala, Sweden along with surface water from the River Fyris in Uppsala.
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23.
  • Barclay, Victoria K. H., et al. (författare)
  • Trace analysis of fluoxetine and its metabolite norfluoxetine : Part I: Development of a chiral liquid chromatography-tandem mass spectrometry method for wastewater samples
  • 2011
  • Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1218:33, s. 5587-5596
  • Tidskriftsartikel (refereegranskat)abstract
    • An enantioselective method for the determination of fluoxetine (a selective serotonin reuptake inhibitor) and its pharmacologically active metabolite norfluoxetine has been developed for raw and treated wastewater samples. The stable isotope-labeled fluoxetine and norfluoxetine were used in an extended way for extraction recovery calculations at trace level concentrations in wastewater. Wastewater samples were enriched by solid phase extraction (SPE) with Evolute CX-50 extraction cartridges. The obtained extraction recoveries ranged between 65 and 82% in raw and treated wastewater at a trace level concentration of 50 pM (15-16 ng L(-1)). The target compounds were identified by the use of chiral liquid chromatography tandem mass spectrometry (LC-MS/MS) in selected reaction monitoring (SRM) mode. The enantiomers were successfully resolved on a chiral alpha(1)-acid glycoprotein column (chiral AGP) with acetonitrile and 10 mM ammonium acetate buffer at pH 4.4 (3/97, v/v) as the mobile phase. The effects of pH, amount of organic modifier and buffer concentration in the mobile phase were investigated on the enantiomeric resolution (R(s)) of the target compounds. Enantiomeric R(s)-values above 2.0 (1.03 RSD%, n = 3) were achieved for the enantiomers of fluoxetine and norfluoxetine in all mobile phases investigated. The method was validated by assessing parameters such as cross-contamination and carryover during SPE and during LC analysis. Cross-talk effects were examined during the detection of the analytes in SRM mode. In addition, the isotopic purity of fluoxetine-d(5) and norfluoxetine-d(5) were assessed to exclude the possibility of self-contamination. The interassay precision of the chromatographic separation was excellent, with relative standard deviations (RSD) equal to or lower than 0.56 and 0.81% in raw and treated wastewaters, respectively. The method detection and quantification limits (respectively, MDL and MQL) were determined by the use of fluoxetine-d5 and norfluoxetine-d5. The MQL for the single enantiomers ranged from 12 to 14 pM (3.6-4.3 ng L(-1)) in raw wastewater and from 3 to 4 pM (0.9-1 ng L(-1)) in treated wastewater. The developed method has been employed for the quantification of (R)-fluoxetine, (S)-fluoxetine and the enantiomers of norfluoxetine in raw and treated wastewater samples to be presented in Part II of this study.
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24.
  • Barclay, Victoria K H, et al. (författare)
  • Trace analysis of fluoxetine and its metabolite norfluoxetine. Part II : Enantioselective quantification and studies of matrix effects in raw and treated wastewater by solid phase extraction and liquid chromatography-tandem mass spectrometry
  • 2012
  • Ingår i: Journal of Chromatography A. - : Elsevier BV. - 0021-9673 .- 1873-3778. ; 1227, s. 105-114
  • Tidskriftsartikel (refereegranskat)abstract
    • The isotope-labeled compounds fluoxetine-d5 and norfluoxetine-d5 were used to study matrix effects caused by co-eluting compounds originating from raw and treated wastewater samples, collected in Uppsala, Sweden. The matrix effects were investigated by the determination of matrix factors (MF) and by a post-column infusion method. The matrix factors were determined to be 38–47% and 71–86% for the enantiomers of norfluoxetine-d5 and fluoxetine-d5, respectively. The influence of matrix effects when quantifying the enantiomers of the active pharmaceutical ingredient and the metabolite in wastewater samples with LC–MS/MS is discussed and methods to overcome the problem are presented. The enantiomeric concentrations of fluoxetine and its human metabolite norfluoxetine, quantified by a one-point calibration method, were 12–52 pM (3.5–16 ng L−1) in raw wastewater and 4–48 pM (1.2–15 ng L−1) in treated wastewater. Furthermore, the calculated enantiomeric fractions (EF) of the substances were found to be between 0.68 and 0.71 in both matrices. Neither the EF values for fluoxetine nor those for norfluoxetine were significantly different in the raw wastewater compared to the treated wastewater. Interestingly, the concentration of (S)-fluoxetine was found to be higher than the concentration of (R)-fluoxetine in both raw and treated wastewater. These results are different from other results presented in the literature, which shows that the relative concentrations of the enantiomers of a chiral active pharmaceutical ingredient might be significantly different in wastewater samples from different treatment systems. We report, for the first time, the concentrations of the enantiomers of norfluoxetine in wastewater samples. The concentrations of (S)-norfluoxetine were found to be higher than the concentration of (R)-norfluoxetine in the raw as well as in the treated wastewater samples.
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25.
  • Bengtsson Ryberg, Johanna, et al. (författare)
  • The Effects of Wind Power on Human Interests : A Synthesis
  • 2013
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • PrefaceThere is a great need for knowledge concerning the impacts of wind power on humans, landscapes, the marine environment, birds, bats and other mammals.Previous studies of these environmental impacts have lacked an overall view of the effects. This has led to deficiencies in the processes surrounding the establishment of new wind farms. Vindval is a knowledge programme undertaken as a collaboration between the Swedish Energy Agency and the Swedish Environmental Protection Agency. Its aim is to gather and communicate scientific knowledge about the impacts of wind power on people and the natural environment. The programme continues until 2013.Vindval comprises some 30 individual research projects, together with four synthesis projects. Syntheses are prepared by experts, who compile and assess overall research results and experience regarding the effects of wind power in four different areas – humans, birds/bats, marine life and terrestrial mammals.The results of this research and synthesis work will provide a basis for environmental impact assessments and for the planning and permitting processes associated with wind power installations. Vindval requires high standards in the review and approval of research proposals, in order to ensure high-quality reports. The same high standards apply to the reporting, approval and publication of research results from the projects.This report was written by Johanna Bengtsson Ryberg, Gösta Bluhm, Karl Bolin, Bosse Bodén, Kristina Ek, Karin Hammarlund, Marianne Henningsson, Inga-Lena Hannukka, Carina Johansson, Sofia Jönsson, Sanna Mels, Tom Mels, Mats Nilsson, Erik Skärbäck, Patrik Söderholm, Åsa Waldo, Ingegärd Widerström, Niklas Åkerman.This report is a translation of the previous report in Swedish “Vindkraftens påverkan på människors intressen” (Naturvårdsverket report no 6497). Translated by Sofia Jönsson.The contents of the report are the responsibility of the authors.
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26.
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27.
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28.
  • Beronius, Anna, et al. (författare)
  • The influence of study design and sex-differences on results from developmental neurotoxicity studies of bisphenol A, implications for toxicity testing
  • 2013
  • Ingår i: Toxicology. - : Elsevier BV. - 0300-483X .- 1879-3185. ; 311:1-2, s. 13-26
  • Tidskriftsartikel (refereegranskat)abstract
    • Developmental neurotoxicity (DNT) of bisphenol A (BPA) has been investigated in a large number of studies. However, there are discrepancies in the results reported between the studies. The aim of this study was to identify and analyze factors that may contribute to these differences and to assess whether there are sex-differences in the sensitivity of certain endpoints or tests used in DNT-studies. Forty-four DNT studies of BPA were identified from the open literature. Details about study design and results from each study, as well as the criteria for DNT testing according to the standardized OECD test guideline (TG) 426, were collected in a database. This enabled systematic and detailed comparisons between studies as well as to the criteria and recommendations stated in TG 426. Multivariate analyses were also used to investigate how different factors of the study design contributed to differences in study results. The analyses showed behavioral effects were often observed for endpoints that are not required according to OECD TG 426, such as anxiety-related, social and sexual behaviors, especially at very low doses and in female offspring. On the other hand relatively few studies observed any effects on motor activity, which is commonly used in screening for neurotoxic effects in regulatory testing. However, varied and to some extent seemingly contradictory results have been reported in these studies, especially for endpoints related to motor activity and anxiety and exploration. Many studies were also poorly reported, limiting these analyses. No strong conclusions could be drawn from the multivariate analyses. A few factors of study design, such as the size of the dose and number of dose levels used and the use of litter or individual pup as statistical unit seemed to have some influence on study results. In conclusion, this analysis suggests that DNT-studies conducted according to the standardized OECD TG 426 may overlook sensitive effects of BPA, and possibly other potential endocrine disruptors, especially in female offspring.
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29.
  • Bjohle, J, et al. (författare)
  • Serum thymidine kinase activity compared with CA 15-3 in locally advanced and metastatic breast cancer within a randomized trial
  • 2013
  • Ingår i: Breast Cancer Research and Treatment. - : Springer Verlag (Germany). - 0167-6806 .- 1573-7217. ; 139:3, s. 751-758
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary objective was to estimate serum thymidine kinase 1 (TK1) activity, reflecting total body cell proliferation rate including cancer cell proliferation, in women with loco regional inoperable or metastatic breast cancer participating in a prospective and randomized study. Secondary objectives were to analyze TK1 in relation to progression-free survival (PFS), overall survival (OS), therapy response and other tumour characteristics, including CA 15-3, widely used as a standard serum marker for disease progression. TK1 and CA 15-3 were analysed in 198 serum samples collected prospectively from women included in the randomized TEX trial between December 2002 and June 2007. TK1 activity was determined by the ELISA based DiviTum (TM) assay, and CA 15-3 analyses was generated with the electrochemiluminescence immunoassay Cobas Elecsys CA 15-3 II. High pre-treatment TK1 activity predicted shorter PFS (10 vs. 15 months p = 0.02) and OS (21 vs. 38 months, p andlt; 0.0001), respectively. After adjustment for age, metastatic site and study treatment TK1 showed a trend as predictor of PFS (p = 0.059) and was an independent prognostic factor for OS, (HR 1.81, 95 % confidence interval (CI) 1.26-2.61, p = 0.001). There was a trend of shortened OS for women with high CA 15-3 (p = 0.054) in univariate analysis, but not after adjustment for the above mentioned covariates. Both TK1 (p = 0.0011) and CA 15-3 (p = 0.0004) predicted response to treatment. There were statistically different distributions of TK1 and CA 15-3 in relation to the site of metastases. TK1 activity measured by DiviTum (TM) predicted therapy response, PFS and OS in loco regional inoperable or disseminated breast cancer. These results suggest that this factor is a useful serum marker. In the present material, a prognostic value of CA 15-3 could not be proven.
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30.
  • Bruun, Niklas, et al. (författare)
  • Sanctions for Unlawful Collective Action in the Nordic Countries and Germany
  • 2014
  • Ingår i: International Journal of Comparative Labour Law and Industrial Relations. - Alphen aan den Rijn : Kluwer Law International. - 0952-617X .- 1875-838X. ; 30:3, s. 253-271
  • Tidskriftsartikel (refereegranskat)abstract
    • This article compares the industrial relations systems in Finland, Sweden, Norway, Denmark, and Germany with the aim of exploring the approach to remedies and sanctions in order to find out whether national remedies and sanctions for unlawful industrial action could also be applicable to situations of 'unlawful Collective Action under EU law'. In our opinion, it is crucial for such a comparison to focus not just on the legal remedies at hand in the national legal context, but also to take into account the context of industrial relations in which they function. A comparative study of sanctions and remedies in the Nordic countries and Germany opens up a spectrum of rather complicated rules that have been fine-tuned in legal practice at national level over several decades, including rules on defining lawful collective action, mediation, and interim injunctions. The legislator and the courts have built national systems that are based on an acceptance of Collective Action as a legitimate tool for trade unions, a tool that is not allowed to be misused and that has been developed to support and fit into the national industrial relations system and traditions of collective bargaining. The starting point is that unlawful Collective Action should be subject to economic sanctions, but these sanctions should not endanger continued contractual relations between the labour market parties. Economic sanctions are not primarily calculated on the basis of economic loss on the part of the employers, but many factors are taken into account, such as the size of the trade union as well as any mitigating and aggravating factors in accordance with national law and practice. These aspects should be taken into account also in cases of 'EU-unlawful' collective action.
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31.
  • Caesarius, Leon Michael, 1971-, et al. (författare)
  • Developing Innovative Services Based on Big Data : The Case of Go:Smart
  • 2013
  • Konferensbidrag (refereegranskat)abstract
    •  The purpose of this paper is to illuminate the challenges associated with developing innovative technology-based services based on big data. The paper presents and analyzes a case study of GO:SMART, a project with the aim to develop an innovative service for promoting sustainable transportation in urban areas. The challenges identified relate to epistemological and methodological directives that affect the process and outcome of big data-based new service development projects. 
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32.
  • Callaghan, Terry V., et al. (författare)
  • Changing snow cover and its impacts
  • 2011
  • Ingår i: Snow, Water, Ice and Permafrost in the Arctic (SWIPA). - Oslo : Arctic Monitoring and Assessment Programme. - 9788279710714 ; , s. 4:1-4:58
  • Bokkapitel (refereegranskat)
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33.
  • Callaghan, Terry V., et al. (författare)
  • Multiple Effects of Changes in Arctic Snow Cover
  • 2011
  • Ingår i: Ambio: a Journal of Human Environment. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 40, s. 32-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Snow cover plays a major role in the climate, hydrological and ecological systems of the Arctic and other regions through its influence on the surface energy balance (e.g. reflectivity), water balance (e.g. water storage and release), thermal regimes (e.g. insulation), vegetation and trace gas fluxes. Feedbacks to the climate system have global consequences. The livelihoods and well-being of Arctic residents and many services for the wider population depend on snow conditions so changes have important consequences. Already, changing snow conditions, particularly reduced summer soil moisture, winter thaw events and rain-on-snow conditions have negatively affected commercial forestry, reindeer herding, some wild animal populations and vegetation. Reductions in snow cover are also adversely impacting indigenous peoples' access to traditional foods with negative impacts on human health and well-being. However, there are likely to be some benefits from a changing Arctic snow regime such as more even run-off from melting snow that favours hydropower operations.
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34.
  • Callaghan, Terry V., et al. (författare)
  • The Changing Face of Arctic Snow Cover: A Synthesis of Observed and Projected Changes
  • 2011
  • Ingår i: Ambio: a Journal of Human Environment. - : Springer Science and Business Media LLC. - 0044-7447. ; 40, s. 17-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Analysis of in situ and satellite data shows evidence of different regional snow cover responses to the widespread warming and increasing winter precipitation that has characterized the Arctic climate for the past 40-50 years. The largest and most rapid decreases in snow water equivalent (SWE) and snow cover duration (SCD) are observed over maritime regions of the Arctic with the highest precipitation amounts. There is also evidence of marked differences in the response of snow cover between the North American and Eurasian sectors of the Arctic, with the North American sector exhibiting decreases in snow cover and snow depth over the entire period of available in situ observations from around 1950, while widespread decreases in snow cover are not apparent over Eurasia until after around 1980. However, snow depths are increasing in many regions of Eurasia. Warming and more frequent winter thaws are contributing to changes in snow pack structure with important implications for land use and provision of ecosystem services. Projected changes in snow cover from Global Climate Models for the 2050 period indicate increases in maximum SWE of up to 15% over much of the Arctic, with the largest increases (15-30%) over the Siberian sector. In contrast, SCD is projected to decrease by about 10-20% over much of the Arctic, with the smallest decreases over Siberia (<10%) and the largest decreases over Alaska and northern Scandinavia (30-40%) by 2050. These projected changes will have far-reaching consequences for the climate system, human activities, hydrology, and ecology.
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35.
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36.
  • Carling, Gerd, et al. (författare)
  • Scandoromani : Remnants of a mixed language
  • 2014
  • Bok (refereegranskat)abstract
    • Scandoromani: Remnants of a Mixed Language is the first, comprehensive, international description of the language of the Swedish and Norwegian Romano, also labeled resande/reisende. The language, an official minority language in Sweden and Norway, has a history in Scandinavia going back to the early 16th century. A mixed language of Romani and Scandinavian, it is spoken today by a vanishingly small population of mainly elderly people.This book is based on in-depth linguistic interviews with two native speakers of different families (one of whom is the co-author) as well as reviews of earlier sources on Scandoromani. The study reveals a number of interesting features of the language, as well as of mixed languages in general. In particular, the study gives support to the model of autonomy of mixed languages.
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37.
  • Daunfeldt, Sven-Olov, et al. (författare)
  • The economic contribution of high-growth firms : Do definitions matter?
  • 2010
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Prior studies have defined high-growth firms (HGFs) in terms of sales or employment, and analyzed their contribution to employment growth. We define HGFs by employment and sales and add definitions of value added and productivity. We examine the contribution of HGFs to employment growth, economic growth, productivity growth, and sales growth. All HGFs give a disproportionately large positive contribution to economic growth and most also give large positive contributions to growth in employment, productivity and sales. Although HGFs of different definitions are usually not the same firms, young firms are more likely to be HGFs irrespective of definition
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38.
  • Daunfeldt, Sven-Olov, 1970-, et al. (författare)
  • The economic contribution of high-growth firms : do policy implications depend on the choice of growth indicator?
  • 2014
  • Ingår i: Journal of Industry, Competition and Trade. - : Springer Science and Business Media LLC. - 1566-1679 .- 1573-7012. ; 14:3, s. 337-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Prior studies have defined high-growth firms (HGFs) in terms of growth in firm employment or firm sales, and primarily analyzed their contribution to overall employment growth. In this paper we define HGFs using the commonly applied growth indicators (employment and sales), but also add definitions based on growth in value added and productivity. Our results indicate that HGFs in terms of employment are not the same firms as HGFs in terms of productivity, and that their economic contributions differ significantly. Economic policy promoting fast growth in employment may therefore come at the cost of reduced productivity growth. Although HGFs of different definitions may not be the same firms, young firms are more likely to be HGFs irrespective of definition. This suggests that economic policy should focus on the conditions for new firm formation and early growth of firms, rather than target a particular type of HGFs.
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39.
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40.
  • Elvers, Ingegerd, et al. (författare)
  • CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation
  • 2012
  • Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 40:17, s. 8440-8448
  • Tidskriftsartikel (refereegranskat)abstract
    • Ultraviolet (UV)-induced DNA damage causes an efficient block of elongating replication forks. The checkpoint kinase, CHK1 has been shown to stabilize replication forks following hydroxyurea treatment. Therefore, we wanted to test if the increased UV sensitivity caused by the unspecific kinase inhibitor caffeine-inhibiting ATM and ATR amongst other kinases-is explained by inability to activate the CHK1 kinase to stabilize replicative structures. For this, we used cells deficient in polymerase eta (Pol eta), a translesion synthesis polymerase capable of properly bypassing the UV-induced cis-syn TT pyrimidine dimer, which blocks replication. These cells accumulate gaps behind progressing replication forks after UV exposure. We demonstrate that both caffeine and CHK1 inhibition, equally retards continuous replication fork elongation after UV treatment. Interestingly, we found more pronounced UV-sensitization by caffeine than with the CHK1 inhibitor in clonogenic survival experiments. Furthermore, we demonstrate an increased collapse of replicative structures after caffeine treatment, but not after CHK1 inhibition, in UV-irradiated cells. This demonstrates that CHK1 activity is not required for stabilization of gaps induced during replication of UV-damaged DNA. These data suggest that elongation and stabilization of replicative structures at UV-induced DNA damage are distinct mechanisms, and that CHK1 is only involved in replication elongation.
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41.
  • Friedler, Niklas, et al. (författare)
  • The automation equipment acquisition process – experienced users’ perspective
  • 2013
  • Ingår i: International Conference on Production Research.
  • Konferensbidrag (refereegranskat)abstract
    • Automation technology can increase company’s competiveness if it is used correctly. One step on the way to achieve this is to acquire proper automation technology. This paper describes how nine manufacturing companies in Sweden work when they acquire advanced manufacturing technologies (AMT) with automation investments in focus. These nine companies are located all over Sweden and they are considered to be amongst the most experienced in Sweden, running automation investments. The respectively companies way of working is described and analyzed. Most of the companies had a quite extensive model for their acquisition process. Main reason for investing in automation, key factors for successful implementation of automation equipment and suggested improvements to the described acquisition models, are discussed in the paper.
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42.
  • Frisk, Karin, et al. (författare)
  • Compound materials by PM-HIP
  • 2014
  • Ingår i: Powder Metallurgy. - 0032-5899 .- 1743-2901. ; 57:5, s. 341-347
  • Tidskriftsartikel (refereegranskat)abstract
    • There are many applications where compound materials can be of interest, for example when different properties are needed in different parts of a component. Compound materials can be produced by hot isostatic pressing (HIP) of powder metallurgical materials. One aspect that should be considered in the design is the quality of the interface between the two different material compositions. Diffusion during HIP can cause formation of brittle phases in the interface or deteriorate properties by diffusion of alloying elements. The present work shows results from a study where different steel types were joined (quench and temper steel/air hardening steel/bearing steel with a tool steel/corrosion resistant martensitic steel). The evaluation was performed by computational predictions and by small scale HIP experiments that were evaluated by microstructure analysis and chemical analysis. © 2014 Institute of Materials, Minerals and Mining.
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43.
  • Ghasemi, Yahya, 1982-, et al. (författare)
  • Particle packing of aggregates for concrete mix design : Models and methods
  • 2014
  • Ingår i: Nordic Concrete Research. - Oslo : Nordic Concrete Federation. - 0800-6377. ; :50, s. 109-112
  • Tidskriftsartikel (refereegranskat)abstract
    • An optimized aggregate particle packing density used as a base for concrete mix design provides economic, environmental and technical advantages. The particle packing density can be determined by many methods and predicted by different models. This paper reviews common packing and procedures and compares predictions of three common packing models to each other. It was found that the models tend to show different packing densities and percentage of ingredients for the same mixture. A test setup is proposed to determine the accuracy of each model’s prediction
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44.
  • Goryashko, Vitaliy, 1982-, et al. (författare)
  • Proposal for Design and Test of a 352 MHz Spoke RF Source
  • 2012
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • More than a dozen of spoke resonators prototypes (SSR, DSR, TSR) have been constructed and tested worldwide. None have accelerated beam until now and the ESS LINAC will be the first accelerator to operate with spoke cavities. Experience with other types of superconducting cavities indicates that high-power test is vital for reliable operation of the cavity in an accelerator. Although characteristics of a bare cavity can be obtained in a low-power test some important features of a `dressed' cavity like the electroacoustic stability and tuning system can be studied only in a high-power test stand. The ESS LINAC is a pulsed machine and the Lorentz detuning originating from the electromagnetic pressure on the cavity walls is expected to be strong. The Lorentz force along with the cavity sensitivity to mechanical excitations at some resonant frequencies may lead to self-sustained mechanical vibrations which make cavity operation dicult. Practical experience shows that increasing the boundary stiness will decrease the static Lorentz force detuning but not necessarily the dynamic one. Therefore, the FREIA group at Uppsala University is building a high-power test stand able to study performance of the ESS spoke cavity at high power. The RF test stand will be able to drive the cavity not only in the self-excitation mode but also with closed RF loop and fixed frequency. The later technique will be used to reproduce the shape of the cavity voltage pulse as it is expected to be in the cavity operating in the ESS LINAC such that the cavity tuning compensation system will be tested under realistic conditions.
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45.
  • Groth, Petra, et al. (författare)
  • Methylated DNA Causes a Physical Block to Replication Forks Independently of Damage Signalling, O-6-Methylguanine or DNA Single-Strand Breaks and Results in DNA Damage
  • 2010
  • Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 402:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Even though DNA alkylating agents have been used for many decades in the treatment of cancer, it remains unclear what happens when replication forks encounter alkylated DNA. Here, we used the DNA fibre assay to study the impact of alkylating agents on replication fork progression. We found that the alkylator methyl methanesulfonate (MMS) inhibits replication elongation in a manner that is dose dependent and related to the overall alkylation grade. Replication forks seem to be completely blocked as no nucleotide incorporation can be detected following 1 h of MMS treatment. A high dose of 5 mM caffeine, inhibiting most DNA damage signalling, decreases replication rates overall but does not reverse MMS-induced replication inhibition, showing that the replication block is independent of DNA damage signalling. Furthermore, the block of replication fork progression does not correlate with the level of DNA single-strand breaks. Overexpression of O-6-methylguanine (O6meG)-DNA methyltransferase protein, responsible for removing the most toxic alkylation, O6meG, did not affect replication elongation following exposure to N-methyl-M-nitro-N-nitrosoguanidine. This demonstrates that O6meG lesions are efficiently bypassed in mammalian cells. In addition, we find that MMS-induced gamma H2AX foci co-localise with 53BP1 foci and newly replicated areas, suggesting that DNA double-strand breaks are formed at MMS-blocked replication forks. Altogether, our data suggest that N-alkylations formed during exposure to alkylating agents physically block replication fork elongation in mammalian cells, causing formation of replication-associated DNA lesions, likely double-strand breaks.
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46.
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47.
  • Hesse, Camilla, et al. (författare)
  • The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
  • 2011
  • Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3, s. 494-499
  • Tidskriftsartikel (refereegranskat)abstract
    • α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
  •  
48.
  • Hooper, Sean D., et al. (författare)
  • Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder
  • 2012
  • Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 13, s. 123-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Tourette Syndrome (TS) is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood. Methods: Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22)(q16.2;p13) in a male patient with TS and obsessive-compulsive disorder (OCD). In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband. Results: Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32) and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband's mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome. Conclusions: We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.
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49.
  • Johansson, Emma M. (författare)
  • Controlling the Pore Size and Morphology of Mesoporous Silica
  • 2010
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Mesoporous silica with a hexagonally ordered pore structure (SBA-15) has been synthesized. Through variations in the synthesis conditions several morphologies, such as fibers, sheets and separate rods, have been realized. Furthermore, additions of heptane and NH4F make it possible to synthesize SBA-15 with pores as large as 18 nm in the sheet morphology. Mechanisms for the formation of different morphologies have been suggested. In the case of fibers and sheets, the amount of heptane present during the synthesis determines the final morphology. For low concentrations, the heptane enters the micelles and increases the pore size while the particles (crystallites) attaches to each other end to end. When the heptane concentration increases, the heptane droplets increase in size, and above a critical droplet size the crystallites attach with one short end towards the droplet, forming the sheet morphology. The crystallites can also be separated. This is the case of the rod morphology. The separation is performed by shortening the stirring time and increasing the HCl concentration. The increased amount of HCl increases the hydration rate of the silica precursor, which can be used to control the thickness and length of the rods. Furthermore, the reaction time has been decreased from 20 h for all morphologies to less than 4 hours. The materials have been characterized with nitrogen sorption, electron microscopy and x-ray diffraction. Also, thermogravimetric analysis and fourier transformed infrared spectroscopy have been used for studying the removal of surfactants.
  •  
50.
  • Johansson, Johan, 1980, et al. (författare)
  • Covalent functionalization of carbon nanotube forests grown in situ on a metal-silicon chip
  • 2012
  • Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. - 9780819490018 ; 8344
  • Konferensbidrag (refereegranskat)abstract
    • We report on the successful covalent functionalization of carbon nanotube (CNT) forests, in situ grown on a silicon chip with thin metal contact film as the buffer layer between the CNT forests and the substrate. The CNT forests were successfully functionalized with active amine and azide groups, which can be used for further chemical reactions. The morphology of the CNT forests was maintained after the functionalization. We thus provide a promising foundation for a miniaturized biosensor arrays system that can be easily integrated with Complementary Metal-Oxide Semiconductor (CMOS) technology.
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