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| 4. |
- Broadaway, K Alaine, et al.
(författare)
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Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
- 2023
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Ingår i: American Journal of Human Genetics. - : Elsevier. - 0002-9297 .- 1537-6605. ; 110:2, s. 284-299
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is critical for glucose homeostasis, and increased levels of the precursor proinsulin relative to insulin indicate pancreatic islet beta-cell stress and insufficient insulin secretory capacity in the setting of insulin resistance. We conducted meta-analyses of genome-wide association results for fasting proinsulin from 16 European-ancestry studies in 45,861 individuals. We found 36 independent signals at 30 loci (p value < 5 × 10-8), which validated 12 previously reported loci for proinsulin and ten additional loci previously identified for another glycemic trait. Half of the alleles associated with higher proinsulin showed higher rather than lower effects on glucose levels, corresponding to different mechanisms. Proinsulin loci included genes that affect prohormone convertases, beta-cell dysfunction, vesicle trafficking, beta-cell transcriptional regulation, and lysosomes/autophagy processes. We colocalized 11 proinsulin signals with islet expression quantitative trait locus (eQTL) data, suggesting candidate genes, including ARSG, WIPI1, SLC7A14, and SIX3. The NKX6-3/ANK1 proinsulin signal colocalized with a T2D signal and an adipose ANK1 eQTL signal but not the islet NKX6-3 eQTL. Signals were enriched for islet enhancers, and we showed a plausible islet regulatory mechanism for the lead signal in the MADD locus. These results show how detailed genetic studies of an intermediate phenotype can elucidate mechanisms that may predispose one to disease.
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- Cecconello, Marco, et al.
(författare)
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Current profile modification experiments in EXTRAP T2R
- 2004
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 46:1, s. 145-161
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Tidskriftsartikel (refereegranskat)abstract
- Pulsed poloidal current drive (PPCD) experiments have been conducted in the resistive shell EXTRAP T2R reversed-field pinch experiment. During the current profile modification phase, the fluctuation level of the m = 1 internally resonant tearing modes decreases, and the velocity of these modes increases. The m = 0 modes are not affected during PPCD, although termination occurs with a burst in the m = 0 amplitude. The PPCD phase is characterized by an increase in the central electron temperature (up to 380 eV) and in the soft x-ray signal. Spectroscopic observations confirm an increase in the central electron temperature. During PPCD, the plasma poloidal beta increases to 14%, and the estimated energy confinement time doubles, reaching 380 mus. The reduction in the fluctuation level and the corresponding increase in the energy confinement time are qualitatively consistent with a reduction in parallel transport along stochastic magnetic field lines.
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- Khonsari, R H, et al.
(författare)
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Shape and volume of craniofacial cavities in intentional skull deformations
- 2013
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Ingår i: American Journal of Physical Anthropology. - : Wiley. - 0002-9483 .- 1096-8644. ; 151:1, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.
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| 13. |
- Venkatesan, M, et al.
(författare)
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Erratum
- 2019
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Ingår i: The American journal of tropical medicine and hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 100:3, s. 766-766
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Tidskriftsartikel (refereegranskat)
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| 15. |
- Almqvist, C, et al.
(författare)
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School as a risk environment for children allergic to cats and a site for transfer of cat allergen to homes
- 1999
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 103:6, s. 1012-1017
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many children are allergic to furred pets and avoid direct pet contact. The school may be a site of indirect exposure to pet allergens, which may induce or maintain symptoms of allergic diseases.OBJECTIVE: We sought to investigate airborne levels of cat allergen (Fel d 1) at schools and in homes with or without cats and to study clothes as a route for dissemination of allergens between homes and school.METHODS: Airborne cat allergen was collected with personal samplers from (1) children attending classes with many (>25%) or few (<10%) cat owners and (2) homes with or without cats. A recently developed amplified ELISA assay, which detects low levels of airborne cat allergen in pet-free environments, was used. Dust samples were collected from clothes and mattresses.RESULTS: There was a 5-fold difference in the median levels of airborne cat allergen between classes with many and few cat owners (2.94 vs 0.59 ng/m3; P <.001). The median airborne cat allergen concentration in classes with many cat owners was significantly higher than that found in the homes of non-cat owners (P <.001) but lower than that found in homes with cats (P <.001). Allergen levels in non-cat owners' clothes increased after a school day (P <.001). Non-cat owners in classes with many cat owners had higher levels of mattress-bound cat allergen (P =.01).CONCLUSION: The results indicate significant exposure to cat allergen at school. Allergen is spread through clothing from homes with cats to classrooms. There the allergen is dispersed in air and contaminates the clothes of children without cats. The allergen levels in non-cat owners' homes correlate with exposure to cat allergen at school.
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- Finsterle, S., et al.
(författare)
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Conceptual uncertainties in modelling the interaction between engineered and natural barriers of nuclear waste repositories in crystalline rocks
- 2019
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Ingår i: Geological Society Special Publication. - 0305-8719. ; 482:1, s. 261-283
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Tidskriftsartikel (refereegranskat)abstract
- Nuclear waste disposal in geological formations relies on a multi-barrier concept that includes engineered components – which, in many cases, include a bentonite buffer surrounding waste packages – and the host rock. Contrasts in materials, together with gradients across the interface between the engineered and natural barriers, lead to complex interactions between these two subsystems. Numerical modelling, combined with monitoring and testing data, can be used to improve our overall understanding of rock–bentonite interactions and to predict the performance of this coupled system. Although established methods exist to examine the prediction uncertainties due to uncertainties in the input parameters, the impact of conceptual model decisions on the quantitative and qualitative modelling results is more difficult to assess. A Swedish Nuclear Fuel and Waste Management Company Task Force project facilitated such an assessment. In this project, 11 teams used different conceptualizations and modelling tools to analyse the Bentonite Rock Interaction Experiment (BRIE) conducted at the Äspö Hard Rock Laboratory in Sweden. The exercise showed that prior system understanding along with the features implemented in the available simulators affect the processes included in the conceptual model. For some of these features, sufficient characterization data are available to obtain defensible results and interpretations, whereas others are less supported. The exercise also helped to identify the conceptual uncertainties that led to different assessments of the relative importance of the engineered and natural barrier subsystems. The range of predicted bentonite wetting times encompassed by the ensemble results were considerably larger than the ranges derived from individual models. This is a consequence of conceptual uncertainties, demonstrating the relevance of using a multi-model approach involving alternative conceptualizations.
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| 27. |
- Ivanov, A G, et al.
(författare)
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Photosynthetic electron transport adjustments in overwintering Scots pine (Pinus sylvestris L.)
- 2001
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Ingår i: Planta. - 0032-0935 .- 1432-2048. ; 213:4, s. 575-585
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Tidskriftsartikel (refereegranskat)abstract
- As shown before [C. Ottander et al. (1995) Planta 197:176-183], there is a severe inhibition of the photosystem (PS) II photochemical efficiency of Scots pine (Pinus sylvestris L.) during the winter. In contrast, the in vivo PSI photochemistry is less inhibited during winter as shown by in vivo measurements of DeltaA(820)/Delta (820) (P700(+)). There was also an enhanced cyclic electron transfer around PSI in winter-stressed needles as indicated by 4-fold faster reduction kinetics of P700(+). The differential functional stability of PSII and PSI was accompanied by a 3.7-fold higher intersystem electron pool size, and a 5-fold increase in the stromal electron pool available for P700(+) reduction. There was also a strong reduction of the QB band in the thermoluminescence glow curve and markedly slower Q-A re-oxidation in needles of winter pine, indicating an inhibition of electron transfer between QA and QB. The data presented indicate that the plastoquinone pool is largely reduced in winter pine, and that this reduced state is likely to be of metabolic rather than photochemical origin. The retention of PSI photochemistry, and the suggested metabolic reduction of the plastoquinone pool in winter stressed needles of Scots pine are discussed in terms of the need for enhanced photoprotection of the needles during the winter and the role of metabolically supplied energy for the recovery of photosynthesis from winter stress in evergreens.
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| 28. |
- Kouwenhoven, M. B. N., et al.
(författare)
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The formation of very wide binaries during the star cluster dissolution phase
- 2010
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Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 1365-2966 .- 0035-8711. ; 404:4, s. 1835-1848
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Forskningsöversikt (refereegranskat)abstract
- Over the past few decades, numerous wide (> 103 au) binaries in the Galactic field and halo have been discovered. Their existence cannot be explained by the process of star formation or by dynamical interactions in the field, and their origin has long been a mystery. We explain the origin of these wide binaries by formation during the dissolution phase of young star clusters: an initially unbound pair of stars may form a binary when their distance in phase space is small. Using N-body simulations, we find that the resulting wide binary fraction in the semimajor axis range 103 au < a < 0.1 pc for individual clusters is 1-30 per cent, depending on the initial conditions. The existence of numerous wide binaries in the field is consistent with observational evidence that most clusters start out with a large degree of substructure. The wide binary fraction decreases strongly with increasing cluster mass, and the semimajor axis of the newly formed binaries is determined by the initial cluster size. The resulting eccentricity distribution is thermal, and the mass ratio distribution is consistent with gravitationally focused random pairing. As a large fraction of the stars forms in primordial binaries, we predict that a large number of the observed 'wide binaries' are in fact triple or quadruple systems. By integrating over the initial cluster mass distribution, we predict a binary fraction of a few per cent in the semimajor axis range 103 au < a < 0.1 pc in the Galactic field, which is smaller than the observed wide binary fraction. However, this discrepancy may be solved when we consider a broad range of cluster morphologies.
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| 32. |
- Sternberg-Simon, M., et al.
(författare)
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Natural killer cell inhibitory receptor expression in humans and mice : A closer look
- 2013
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 4:March, s. 65-
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Tidskriftsartikel (refereegranskat)abstract
- The Natural Killer (NK) cell population is composed of subsets of varying sizes expressing different combinations of inhibitory receptors for MHC class I molecules. Genes within the NK gene complex, including the inhibitory receptors themselves, seem to be the primary intrinsic regulators of inhibitory receptor expression, but the MHC class I background is an additional Modulating factor. In this paper, we have performed a parallel study of the inhibitory receptor repertoire in inbred mice of the C57Bl/6 background and in a cohort of 44 humans. Deviations of subset frequencies from the "product rule (PR)," i.e., differences between observed and expected frequencies of NK cells, were used to identify MHC-independent and MHC-dependent control of receptor expression frequencies. Some deviations from the PR were similar in mice and humans, such as the decreased presence of NK cell subset lacking inhibitory receptors. Others were different, including a role for NKG2A in determining over- or under-representation of specific subsets in humans but not in mice. Thus, while human and murine inhibitory receptor repertoires differed in details, there may also be shared principles governing NK cell repertoire formation in these two species.
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| 33. |
- Wang, Z, et al.
(författare)
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Inhalation of swine dust induces cytokine release in the upper and lower airways
- 1997
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Ingår i: European Respiratory Journal. - 1399-3003. ; 10:2, s. 381-387
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Tidskriftsartikel (refereegranskat)abstract
- In healthy subjects, acute inhalation of swine dust causes an influx of inflammatory cells into the airways and increased bronchial responsiveness. The exposure may also cause fever and generalized symptoms. It seems likely that proinflammatory cytokines are involved in the response to inhaled swine dust. Nasal and bronchoalveolar lavage (BAL) were performed before, and 7 and 24 h after the start of 3 h exposure to swine dust, during a period of work in a swine confinement building, in 22 healthy subjects. Lavage fluids were analysed with regard to the cellular response and concentrations of interleukin (IL)-1 alpha, IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Each subject carried personal samplers for exposure measurements. Inhalable dust and airborne endotoxin, 3-hydroxylated (2-OH) fatty acid and muramic acid were measured. Bronchial responsiveness to methacholine was investigated 1-2 weeks before and 7 h after the start of the exposure. Exposure caused fever (> 38 degrees C) in three subjects, and approximately 25% of the subjects experienced symptoms. Bronchial responsiveness to methacholine increased by 3.5 (1.6-4.8) doubling doses (median (25th-75th percentile)). Following exposure, granulocytes increased more than 50 fold in BAL fluid and more than 40 fold in nasal lavage fluid. IL-1 alpha and IL-1 beta increased significantly in BAL fluid (p < 0.05) and nasal lavage fluid (p < 0.01). IL-6 increased 25 fold in BAL and 15 fold in nasal lavage fluid (p < 0.001). TNF-alpha was below detection limit (0.25 ng.L-1) in most subjects before exposure and increased following exposure to 3.8 (2.4-5.7) and 1.3 (0.6-2.3) ng.L-1 in BAL and nasal lavage fluid, respectively, (p < 0.001). Total inhalable dust was 20.5 (14.6-30.0) mg.m-3 and the concentrations of airborne endotoxin, 3-OH fatty acid and muramic acid were 1.2 (0.8-1.4), 3.5 (2.2-4.5) and 0.9 (0.3-1.9) microgram.m-3, respectively. There was a significant correlation between the IL-6 response in BAL fluid and exposure to dust endotoxin activity and 3-OH fatty acids (p < 0.05). Otherwise, no significant correlations were found between exposure and the cytokine response. We conclude that exposure to swine dust causes an intense upper and lower airway inflammation, which involves the proinflammatory cytokines interleukin-1, interleukin-6 and tumour necrosis factor-alpha.
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| 35. |
- Aguiar, A., et al.
(författare)
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Practices in prescribing protein substitutes for PKU in Europe : No uniformity of approach
- 2015
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Ingår i: Molecular Genetics and Metabolism. - : Elsevier BV. - 1096-7192 .- 1096-7206. ; 115:1, s. 17-22
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Tidskriftsartikel (refereegranskat)abstract
- Background: There appears little consensus concerning protein requirements in phenylketonuria (PKU). Methods: A questionnaire completed by 63 European and Turkish IMD centres from 18 countries collected data on prescribed total protein intake (natural/intact protein and phenylalanine-free protein substitute [PS]) by age, administration frequency and method, monitoring, and type of protein substitute. Data were analysed by European region using descriptive statistics. Results: The amount of total protein (from PS and natural/intact protein) varied according to the European region. Higher median amounts of total protein were prescribed in infants and children in Northern Europe (n = 24 centres) (infants <1 year, >2-3 g/kg/day; 1-3 years of age, >2-3 g/kg/day; 4-10 years of age, >1.5-2.5 g/kg/day) and Southern Europe (n = 10 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, 2 g/kg/day; 4-10 years of age, 1.5-2 g/kg/day), than by Eastern Europe (n = 4 centres) (infants <1 year, 2.5 g/kg/day, 1-3 years of age, >2-2.5 g/kg/day; 4-10 years of age, >1.5-2 g/kg/day) and with Western Europe (n = 25 centres) giving the least (infants <1 year, >2-2.5 g/kg/day, 1-3 years of age, 1.5-2 g/kg/day; 4-10 years of age, 1-1.5 g/kg/day). Total protein prescription was similar in patients aged >10 years (1-1.5 g/kg/day) and maternal patients (1-1.5 g/kg/day). Conclusions: The amounts of total protein prescribed varied between European countries and appeared to be influenced by geographical region. In PKU, all gave higher than the recommended 2007 WHO/FAO/UNU safe levels of protein intake for the general population.
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| 37. |
- Almgren, Karin, et al.
(författare)
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Role of fibre-fibre and fibre-matrix adhesion in stress transfer in composites made from resin-impregnated paper sheets.
- 2009
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Ingår i: International Journal of Adhesion and Adhesives. - : Elsevier BV. - 0143-7496 .- 1879-0127. ; 29:5, s. 551-557
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Tidskriftsartikel (refereegranskat)abstract
- Paper-reinforced plastics are gaining increased interest as packaging materials, where mechanical properties are of great importance. Strength and stress transfer in paper sheets are controlled by fibre-fibre bonds. In paper-reinforced plastics, where the sheet is impregnated with a polymer resin, other stress-transfer mechanisms may be more important. The influence of fibre-fibre bonds on the strength of paper-reinforced plastics was therefore investigated. Paper sheets with different degrees of fibre-fibre bonding were manufactured and used as reinforcement in a polymeric matrix. Image analysis tools were used to verify that the difference in the degree of fibre-fibre bonding had been preserved in the composite materials. Strength and stiffness of the composites were experimentally determined and showed no correlation to the degree of fibre-fibre bonding, in contrast to the behaviour of unimpregnated paper sheets. The degree of fibre-fibre bonding is therefore believed to have little importance in this type of material, where stress is mainly transferred through the fibre-matrix interface.
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| 40. |
- Bastos, Carlos A.P., et al.
(författare)
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Copper nanoparticles have negligible direct antibacterial impact
- 2020
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Ingår i: NanoImpact. - : Elsevier BV. - 2452-0748. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Soluble copper that can be acquired by bacteria is toxic and therefore antimicrobial. Whether nanostructured copper materials, in either disperse or agglomerated form, have antimicrobial impact, aside from that of their dissolution products, is not clear and was herein addressed. Methods: We took five nanostructured copper materials, two metallic, and three oxo-hydroxides with one of these being silicate-substituted. Four agglomerated in the bacterial growth media whilst the silicate-substituted material remained disperse and small (6.5 nm diameter). Antibacterial activity against E. coli was assessed with copper phase distribution measured over time. Using the dose of soluble copper, and benchmark dose non-linear regression modelling, we determined how well this phase predicted antimicrobial activity. Finally, we used Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis to investigate whether membrane adhe- sion effects by copper were plausible or if intracellular uptake most likely explained the bacterial impact of copper. Results: Comparison over time of antimicrobial activity against particulate or soluble phases of the aquated materials clearly demonstrated that soluble copper but not particulate forms were associated with inhibition of bacterial growth. Indeed, the benchmark dose modelling showed the soluble dose required to cause a 50% reduction in E. coli growth was strongly clustered – for all particle formulations – at 14.5 mg/L (10–19 mg/L 90% confidence interval). By comparison, total copper levels associated with the same reduction in viability varied widely (45–549 mg/L). Finally, in favour of this soluble product dominance in terms of antimicrobial activity, copper had low association with bacterial membrane (something both soluble and particulate materials could do) but showed high intra-bacterial levels (something only soluble copper could do). Conclusion: Taken together our data show that it is the uptake of soluble but not particulate copper, and the intracellular loading not just contact and membrane association, that drives copper toxicity to bacteria. Therapeutic strategies for novel antimicrobial copper compounds should consider these findings.
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| 45. |
- Björkdahl, Erika P, 1967-
(författare)
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Lojalitet och kontraktsliknande förhållanden : En civilrättslig studie av förutsättningarna för ansvar vid förhandlingar eller andra kontakter mellan avtalsmässigt obundna parter
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Björkdahl, E. P., 2007. Lojalitetsplikt och kontraktsliknande förhållanden. En civilrättslig studie av förutsättningarna för ansvar vid förhandlingar och andra kontakter mellan avtalsmässigt obundna parter A Pre-Contractual Basis for Liability - A Private Law Study of the Conditions for Liability based on Negotiations and Other Contacts between Parties not Contractually Bound.The research objective of this dissertation is to investigate and clarify those behaviors in negotiations and other contacts between parties not contractually bound that are not viewed as acceptable in the sense that they can result in private law sanctions. The objective in general with this dissertation is to provide a systematization that can be used in an explanatory model for a basis of liability with respect to blameworthy behavior with negotiations and other contacts in non-contractual situations. Included in this objective is clarifying under which circumstances pure economic losses that have arisen in such situations can be compensated. The study begins with certain contractual regulations in order to examine the criteria that can be viewed as included in the explanatory model as to that which is a basis for liable behavior.The first main part of the dissertation, concerns situations in which the preparatory contacts between two parties lead to a contract. Mapped out in this part is a number of selected contract law regulations. The ambition of this approach is to delineate with the help of these regulations an action norm that can be utilized in the investigation of that which is blameworthy behavior with negotiations and other contacts between parties not contractually bound. In the second main part of the dissertation conclusions from the first part are applied on the non-contractual area. This part concerns situations in which the preparatory contacts are focused on a contract being entered into later between those parties communicating with each other, but in which a contract for different reasons is not executed and such situations in which contacts have the purpose of creating a basis or information to an agreement that is to be taken with another party outside of these contacts.
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| 48. |
- Bornehag, CG, et al.
(författare)
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Dampness in buildings as a risk factor for health effects, EUROEXPO: a multidisciplinary review of the literature (1998-2000) on dampness and mite exposure in buildings and health effects
- 2004
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Ingår i: Indoor Air. - : Hindawi Limited. - 0905-6947 .- 1600-0668. ; 14:4, s. 243-257
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Forskningsöversikt (refereegranskat)abstract
- The scientific literature on health effects from dampness in buildings, including mite exposure over the period 1998-2000 has been reviewed by a European group (EUROEXPO) of eight scientists in experience from medicine, epidemiology, toxicology and engineering. Forty studies deemed relevant have been the foundation for the conclusions. Dampness in buildings is a risk factor for health effects among atopics and non-atopics both in domestic and in public environments. However, the literature is not conclusive in respect of causative agents, e.g. mites, microbiological agents and organic chemicals from degraded building materials. There is a strong need for more multidisciplinary studies including expertise from all relevant areas. A general conclusion from the work was that there is a strong need for multidisciplinary reviews in scientific journals of articles dealing with associations between indoor environmental factors and health effects.
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