| 1. |
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| 2. |
- Davegårdh, Cajsa, et al.
(author)
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VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39(+/-) mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. Insulin resistance and lower muscle strength in relation to mass are hallmarks of type 2 diabetes. Here, the authors report alterations in muscle stem cells from individuals with type 2 diabetes that may contribute to these phenotypes through VPS39 mediated effects on autophagy and epigenetics.
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| 3. |
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Highlights from the first year of Odin observations
- 2003
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L39-L46
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Journal article (peer-reviewed)abstract
- Key Odin operational and instrumental features and highlights from our sub-millimetre and millimetre wave observations of H2O, H218O, NH3, 15NH3 and O2 are presented, with some insights into accompanying Odin Letters in this A&A issue. We focus on new results where Odin's high angular resolution, high frequency resolution, large spectrometer bandwidths, high sensitivity or/and frequency tuning capability are crucial: H2O mapping of the Orion KL, W3, DR21, S140 regions, and four comets; H2O observations of Galactic Centre sources, of shock enhanced H2O towards the SNR IC443, and of the candidate infall source IRAS 16293-2422; H218O detections in Orion KL and in comet Ikeya-Zhang; sub-mm detections of NH3 in Orion KL (outflow, ambient cloud and bar) and ρ Oph, and very recently, of 15NH3 in~Orion KL. Simultaneous sensitive searches for the 119 GHz line of O2 have resulted in very low abundance limits, which are difficult to accomodate in chemical models. We also demonstrate, by means of a quantitative comparison of Orion KL H2O results, that the Odin and SWAS observational data sets are very consistently calibrated. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and the Centre National d'études Spatiales (CNES, France). The Swedish Space Corporation (SSC) has been the prime industrial contractor, and is also responsible for the satellite operation from its Odin Mission Control Centre at SSC in Solna and its Odin Control Centre at ESRANGE near Kiruna in northern Sweden. See also the SNSB Odin web page: http://www.snsb.se/eng_odin_intro.shtml
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Sioris, C. E., et al.
(author)
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The atmospheric limb sounding satellite (ALISS)
- 2014
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In: Proceedings of the International Astronautical Congress, IAC. - 0074-1795. - 9781634399869 ; 4, s. 2382-2392
-
Conference paper (peer-reviewed)abstract
- The Atmospheric Limb Sounding Satellite (ALISS) is a joint Canadian-Swedish concept that is currently under study by agencies, industrial partners and academic institutions in both countries. Launch is not anticipated before late 2020. ALISS has significant heritage, resembling the current Odin mission in terms of some of the countries involved and the types of instruments. However, ALISS will have a focus on the upper troposphere in addition to Odin's primarily stratospheric focus. The ALISS mission has objectives relating to climate-chemistry coupling, UV radiation, dynamics, atmospheric composition in the upper troposphere and lower stratosphere, and in conjunction with nadir sensors, air quality, by virtue of the array of key atmospheric constituents that it will measure with an unprecedented combination of vertical and horizontal resolution for satellite-borne instruments. ALISS consists of four atmospheric limb remote sensing instruments. Three of these have space heritage and are: the Canadian-designed Atmospheric Tomography System (CATS) that is a derivative of the highly successful Optical Spectrograph and InfraRed Imaging System (OSIRIS) instrument, the Swedish-designed Stratosphere Troposphere Exchange And climate Monitoring Radiometer (STEAMR) that is a follow-on instrument to the sub-millimetre radiometer (SMR) that currently operates with OSIRIS on Odin, and a Global Positioning System Radio Occultation instrument. The fourth instrument, also Canadian, is the Spatial Heterodyne Observations of Water (SHOW). SHOW will measure profiles of water vapour using its near-infrared absorption. Among other things, the ALISS package will deliver atmospheric composition (O3, H2O, NO2, HNO3, BrO, CO, aerosol, and others) measurements within the extremely important upper troposphere and lower stratosphere region for chemistry and climate studies. One application of interest would be using these measurements in conjunction with total column measurements from nadir-viewing instruments as well as data assimilation systems in order to better monitor and forecast air quality. Also, the heritage of these instruments implies the ALISS measurements will be extremely valuable in the continuation of climate-quality time series of important constituents such as stratospheric aerosols, water vapour, and ozone. Continuity of these vertically resolved data records is currently threatened by a looming gap in satellite-based limb sounders. This talk will outline the ALISS concept and the utility of the measurements.
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| 8. |
- Besjakov, Jack, et al.
(author)
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Grading scale of radiographic findings in the pubic bone and symphysis in athletes.
- 2003
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In: Acta Radiologica. - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 44:1, s. 79-83
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Journal article (peer-reviewed)abstract
- Purpose: Radiographic abnormalities in the pubic bone and symphysis are often seen in athletes with groin pain. The aim was to create a grading scale of such radiologic changes. Material and Methods: Plain radiography of the pelvic ring including the pubic bone and the symphysis was performed in 20 male athletes, age 19-35, with long-standing uni- or bilateral groin pain. We used two control groups: Control group 1: 20 healthy age-matched men who had undergone radiologic examination of the pelvis due to trauma. Control group 2: 120 adults (66 men and 54 women) in 9 age groups between 15 and 90 years of age. These examinations were also evaluated for interobserver variance. Results and Conclusion: The grading scale was based on the type and the amount of the different changes, which were classified as follows: No bone changes (grade 0), slight bone changes (grade 1), intermediate changes (grade 2), and advanced changes (grade 3). The grading scale is easy to interpret and an otherwise troublesome communication between the radiologist and the physician was avoided. There was a high interobserver agreement with a high kappa value (0.8707). Male athletes with long-standing groin pain had abnormal bone changes in the symphysis significantly more frequently and more severely (p>0.001) than their age-matched references. In asymptomatic individuals such abnormalities increased in frequency with age both in men and women.
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| 9. |
- Franks, P. W., et al.
(author)
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Genomic variants at the PINK1 locus are associated with transcript abundance and plasma nonesterified fatty acid concentrations in European whites
- 2008
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In: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 22:9, s. 3135-3145
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Journal article (peer-reviewed)abstract
- The purpose of this study was to characterize associations between PINK1 genotypes, PINK1 transcript levels, and metabolic phenotypes in healthy adults and those with type 2 diabetes (T2D). We measured PINK1 skeletal muscle transcript levels and 8 independent PINK1 single nucleotide polymorphisms (SNPs) in a cohort of 208 Danish whites and in a cohort of 1701 British whites (SNPs and metabolic phenotypes only). Furthermore, we assessed the effects of PINK1 transcript ablation in primary adipocytes using RNA interference (RNAi). Six PINK1 SNPs were associated with PINK1 transcript levels (P < 0.04 to P < 0.0001). Obesity modified the association between PINK1 transcript levels and T2D risk (interaction P=0.005); transcript levels were inversely related with T2D in obese (n=105) [odds ratio (OR) per SD increase in expression levels=0.44; 95% confidence interval (CI): 0.23, 0.84; P=0.013] but not in nonobese (n=103) (OR=1.20; 95% CI: 0.82, 1.76; P=0.34) individuals. In the British cohort, several PINK1 SNPs were associated with plasma nonesterified fatty acid concentrations. Nominal genotype associations were also observed for fasting glucose, 2-h glucose, and maximal oxygen consumption, although these were not statistically significant after correcting for multiple testing. In primary adipocytes, Pink1 knockdown affected fatty acid binding protein 4 (Fabp4) expression, indicating that PINK1 may influence substrate metabolism. We demonstrate that PINK1 polymorphisms are associated with PINK1 transcript levels and measures of fatty acid metabolism in a concordant manner, whereas our RNAi data imply that PINK1 may indirectly influence lipid metabolism.
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| 10. |
- Gnad, T., et al.
(author)
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Adenosine activates brown adipose tissue and recruits beige adipocytes via A(2A) receptors
- 2014
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 516:7531
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Journal article (peer-reviewed)abstract
- Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies(1-5). Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of beta-adrenergic receptors(1-5). Because BAT therapies based on cold exposureor beta-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat(6-8). However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A(2A) receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A(2A) receptors in mice causes adecrease in BAT-dependent thermogenesis, whereas treatment with A(2A) agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A(2A) receptors or injection of lentiviral vectors expressing the A(2A) receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A(2A) agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A(2A) signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.
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| 11. |
- Gustavsson, P, et al.
(author)
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A population-based case-referent study of myocardial infarction and occupational exposure to motor exhaust, other combustion products, organic solvents, lead, and dynamite. Stockholm Heart Epidemiology Program (SHEEP) Study Group.
- 2001
-
In: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983 .- 1531-5487. ; 12:2, s. 222-8
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Journal article (peer-reviewed)abstract
- This case-referent study investigated the risk of myocardial infarction from occupational exposure to motor exhaust, other combustion products, organic solvents, lead, and dynamite. We identified first-time, nonfatal myocardial infarctions among men and women 45-70 years of age in Stockholm County from 1992 through 1994. We selected referent subjects from the population to match the demographic characteristics of the cases. A lifetime history of occupations was obtained by questionnaire. The response rate was 81% for the cases and 74% for the referents, with 1,335 cases and 1,658 referents included in the study. An occupational hygienist assessed occupational exposures, coding the intensity and probability of exposure for each subject. We adjusted relative risk estimates for tobacco smoking, alcohol drinking, hypertension, diabetes mellitus, overweight, and physical inactivity at leisure time. The relative risk of myocardial infarction was 2.11 (95% confidence interval = 1.23-3.60) among those who were highly exposed and 1.42 (95% confidence interval = 1.05-1.92) among those who were intermediately exposed to combustion products from organic material. We observed an exposure-response pattern, in terms of both maximum exposure intensity and cumulative dose. Exposure to dynamite and organic solvents was possibly associated with an increased risk. The other exposures were not consistently associated with myocardial infarction.
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| 12. |
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| 13. |
- Larsson, B., et al.
(author)
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First NH3 detection of the Orion Bar
- 2003
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L69-L72
-
Journal article (peer-reviewed)abstract
- Odin has successfully observed three regions in the Orion A cloud, i.e. Ori KL, Ori S and the Orion Bar, in the 572.5 GHz rotational ground state line of ammonia, ortho-NH3 (J,K) = (1,0) -> (0,0), and the result for the Orion Bar represents the first detection in an ammonia line. Several velocity components are present in the data. Specifically, the observed line profile from the Orion Bar can be decomposed into two components, which are in agreement with observations in high-J CO lines by Wilson et al. (\cite{wilson01}). Using the source model for the Orion Bar by these authors, our Odin observation implies a total ammonia abundance of NH3/H2 = 5x 10-9. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation has been the industrial prime contractor.
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| 14. |
- Liseau, R., et al.
(author)
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First detection of NH3 (10 -> 00) from a low mass cloud core. On the low ammonia abundance of the rho Oph A core
- 2003
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L73-L76
-
Journal article (peer-reviewed)abstract
- Odin has successfully observed the molecular core rho Oph A in the 572.5 GHz rotational ground state line of ammonia, NH3 (JK = 10 -> 00). The interpretation of this result makes use of complementary molecular line data obtained from the ground (C17O and CH3OH) as part of the Odin preparatory work. Comparison of these observations with theoretical model calculations of line excitation and transfer yields a quite ordinary abundance of methanol, X(CH3OH)= 3 x 10-9. Unless NH3 is not entirely segregated from C17O and CH3OH, ammonia is found to be significantly underabundant with respect to typical dense core values, viz. X(NH3) = 8 x 10-10. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation has been the industrial prime contractor. and based on observations collected with the Swedish ESO Submillimeter Telescope, SEST, in La Silla, Chile.
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| 15. |
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| 16. |
- Olofsson, Henrik, 1972, et al.
(author)
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Odin water mapping in the Orion KL region
- 2003
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L47-L54
-
Journal article (peer-reviewed)abstract
- New results from water mapping observations of the Orion KL region using the submm/mm wave satellite Odin (2.1\arcmin beam size at 557 GHz), are presented. The ortho-H2O \jkktrans{1}{1}{0}{1}{0}{1} ground state transition was observed in a 7arcminx 7arcmin rectangular grid with a spacing of 1\arcmin, while the same line of H218O was measured in two positions, Orion KL itself and 2\arcmin south of Orion KL. In the main water species, the KL molecular outflow is largely resolved from the ambient cloud and it is found to have an extension of 60\arcsec-110\arcsec. The H2O outflow profile exhibits a rather striking absorption-like asymmetry at the line centre. Self-absorption in the near (or ``blue'') part of the outflow (and possibly in foreground quiescent halo gas) is tentatively suggested to play a role here. We argue that the dominant part of the KL H218O outflow emission emanates from the compact (size ~ 15\arcsec) low-velocity flow and here estimate an H2O abundance of circa 10-5 compared to all H2 in the flow - an order of magnitude below earlier estimates of the H2O abundance in the shocked gas of the high-velocity flow. The narrow ambient cloud lines show weak velocity trends, both in the N-S and E-W directions. H218O is detected for the first time in the southern position at a level of ~ 0.15 K and we here estimate an H2O abundance of (1-8) x 10-8. Odin is a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and the Centre National d'Études Spatiales (CNES, France). The Swedish Space Corporation (SSC) was the industrial prime contractor and is also responsible for the satellite operation.
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| 17. |
- Pagani, L., et al.
(author)
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Low upper limits on the O2 abundance from the Odin satellite
- 2003
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L77-L81
-
Journal article (peer-reviewed)abstract
- For the first time, a search has been conducted in our Galaxy for the 119 GHz transition connecting to the ground state of O2, using the Odin satellite. Equipped with a sensitive 3 mm receiver (Tsys(SSB) = 600 K), Odin has reached unprecedented upper limits on the abundance of O2, especially in cold dark clouds where the excited state levels involved in the 487 GHz transition are not expected to be significantly populated. Here we report upper limits for a dozen sources. In cold dark clouds we improve upon the published SWAS upper limits by more than an order of magnitude, reaching N(O2)/N(H2) <= 10-7 in half of the sources. While standard chemical models are definitively ruled out by these new limits, our results are compatible with several recent studies that derive lower O2 abundances. Goldsmith et al. (\cite{SWAS2002}) recently reported a SWAS tentative detection of the 487 GHz transition of O2 in an outflow wing towards rho Oph A in a combination of 7 beams covering approximately 10arcmin x 14arcmin . In a brief (1.3 hour integration time) and partial covering of the SWAS region (~65% if we exclude their central position), we did not detect the corresponding 119 GHz line. Our 3 sigma upper limit on the O2 column density is 7.3x 1015 cm-2. We presently cannot exclude the possibility that the SWAS signal lies mostly outside of the 9\arcmin Odin beam and has escaped our sensitive detector. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is operating Odin.
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| 18. |
- Sandqvist, Aa., et al.
(author)
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Odin observations of H2O in the Galactic Centre
- 2003
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L63-L67
-
Journal article (peer-reviewed)abstract
- The Odin satellite has been used to detect emission and absorption in the 557-GHz H216O line in the Galactic Centre towards the Sgr Astar Circumnuclear Disk (CND), and the Sgr A +20 km s-1 and +50 km s-1 molecular clouds. Strong broad H2O emission lines have been detected in all three objects. Narrow H2O absorption lines are present at all three positions and originate along the lines of sight in the 3-kpc Spiral Arm, the -30 km s-1 Spiral Arm and the Local Sgr Spiral Arm. Broad H2O absorption lines near -130 km s-1 are also observed, originating in the Expanding Molecular Ring. A new molecular feature (the ``High Positive Velocity Gas'' - HPVG) has been identified in the positive velocity range of ~+120 to +220 km s-1, seen definitely in absorption against the stronger dust continuum emission from the +20 km s-1 and +50 km s-1 clouds and possibly in emission towards the position of Sgr Astar CND. The 548-GHz H218O isotope line towards the CND is not detected at the 0.02 K (rms) level. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes) and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is also responsible for the satellite operation.
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| 19. |
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| 20. |
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| 21. |
- Wilson, C. D., et al.
(author)
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Submillimeter emission from water in the W3 region
- 2003
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 402, s. L59-L62
-
Journal article (peer-reviewed)abstract
- Using the Odin satellite, we have mapped the submillimeter emission from the 110-101 transition of ortho-water in the W3 star-forming region. A 5arcminx 5arcmin map of the W3 IRS4 and W3 IRS5 region reveals strong water lines at half the positions in the map. The relative strength of the Odin lines compared to previous observations by SWAS suggests that we are seeing water emission from an extended region. Across much of the map the lines are double-peaked, with an absorption feature at -39 km s-1; however, some positions in the map show a single strong line at -43 km s-1. We interpret the double-peaked lines as arising from optically thick, self-absorbed water emission near the W3 IRS5, while the narrower blue-shifted lines originate in emission near W3 IRS4. In this model, the unusual appearance of the spectral lines across the map results from a coincidental agreement in velocity between the emission near W3 IRS4 and the blue peak of the more complex lines near W3 IRS5. The strength of the water lines near W3 IRS4 suggests we may be seeing water emission enhanced in a photon-dominated region. Based on observations with Odin, a Swedish-led satellite project funded jointly by the Swedish National Space Board (SNSB), the Canadian Space Agency (CSA), the National Technology Agency of Finland (Tekes), and Centre National d'Études Spatiales (CNES). The Swedish Space Corporation was the industrial prime contractor and is also responsible for the satellite operation.
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| 22. |
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| 23. |
- Filla, Reno, et al.
(author)
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A Case Study on Quantifying the Workload of Working Machine Operators by Means of Psychophysiological Measurements
-
Other publication (other academic/artistic)abstract
- In this study of eighteen wheel loader operators, test-driving a machine in three different traction force settings, we examine if a workload index derived from psychophysiological measurements of heart rate, finger temperature, skin conductance, respiration rate and end-tidal CO2-concentration in exhaled air can be used to assess operator workload in sufficient detail to use it as a complement to traditional subjective evaluations, and also to use such measurements in a workload-adaptive operator assistance system in a longer perspective.
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| 24. |
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| 25. |
- Henriksen, T. I., et al.
(author)
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Dysregulated autophagy in muscle precursor cells from humans with type 2 diabetes
- 2019
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- Autophagy is active during cellular remodeling including muscle differentiation. Muscle differentiation is dysregulated in type 2 diabetes and we therefore hypothesize that muscle precursor cells from people with type 2 diabetes (T2DM) have a dysregulation of their autophagy leading to impaired myogenesis. Muscle precursor cells were isolated from people with T2DM or healthy controls and differentiated in vitro. Autophagy marker levels were assessed by immunoblotting. Differentially expressed autophagy-related genes between healthy and T2DM groups were identified based on a previously published RNA-sequencing data-set, which we verified by RT-qPCR. siRNA was used to assess the function of differentially expressed autophagy genes. Basal autophagy increases during human muscle differentiation, while T2DM muscle cells have reduced levels of autophagy marker ATG7 and show a blunted response to starvation. Moreover, we demonstrate that the 3 non-canonical autophagy genes DRAM1, VAMP8 and TP53INP1 as differentially expressed between healthy and T2DM groups during myoblast differentiation, and that T53INP1 knock-down alters expression of both pro-and anti-apoptotic genes. In vitro differentiated T2DM muscle cells show differential expression of autophagy-related genes. These genes do not regulate myogenic transcription factors but may rather be involved in p53-associated myoblast apoptosis during early myogenesis.
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| 26. |
- Kylhammar, D., et al.
(author)
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Angiogenic and inflammatory biomarkers for screening and follow-up in patients with pulmonary arterial hypertension
- 2018
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In: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 47:4, s. 319-324
-
Journal article (peer-reviewed)abstract
- Objective: To identify circulating angiogenic and inflammatory biomarkers with potential in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc), and in early diagnosis and determination of treatment response in PAH. Method: Plasma samples were taken at the time of PAH diagnosis and at treatment follow-up after a median (interquartile range) of 4 months (3–9.8 months) in idiopathic (n = 9) and SSc-associated PAH (n = 11). In patients with SSc-associated PAH, plasma samples had also been gathered a median of 2 years (0.8–3 years) before PAH diagnosis (n = 10). Additional plasma samples were retrieved at two time-points separated by a median of 12 years (10–13 years) from SSc patients who did not develop PAH (n = 10) and from controls (n = 8). Angiogenic and inflammatory biomarkers were analysed by multiplex immunoassays. Results: Plasma levels of placenta growth factor (PlGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), and tumour necrosis factor-α (TNF-α) were higher (p < 0.05) in SSc patients who later developed PAH than in those who did not. Plasma vascular endothelial growth factor (VEGF)-D increased (p < 0.05) in SSc patients as PAH developed. Plasma levels of PlGF, VEGF-A, VEGF-D, sVEGFR-1, interleukin-6, and TNF-α were higher (p < 0.05) in PAH than controls. There were no significant differences in circulating biomarkers between idiopathic and SSc-associated PAH. Plasma sVEGFR-1 decreased (p < 0.05) after initiating PAH-targeted treatments. Conclusions: Plasma levels of PlGF, sVEGFR-1, TNF-α, and VEGF-D have potential in screening for SSc-associated PAH. Plasma sVEGFR-1 may be a biomarker of treatment response.
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| 27. |
- Lavery, Tyrone H., et al.
(author)
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Impact Indicators for Biodiversity Conservation Research : Measuring Influence within and beyond Academia
- 2021
-
In: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 71:4, s. 383-395
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Journal article (peer-reviewed)abstract
- Measuring, reporting and forecasting research impact beyond academia has become increasingly important to demonstrate and understand real-world benefits. This is arguably most important in crisis disciplines such as medicine, environmental sustainability and biodiversity conservation, where application of new knowledge is urgently needed to improve health and environmental outcomes. Increasing focus on impact has prompted the development of theoretical guidance and practical tools tailored to a range of disciplines, but commensurate development of tools for conservation is still needed. In the present article, we review available tools for evaluating research impact applicable to conservation research. From these, and via a survey of conservation professionals, we compiled and ranked a list of 96 impact indicators useful for conservation science. Our indicators apply to a logic chain of inputs, processes, outputs, outcomes, and impacts. We suggest the list can act as a clear guide to realize and measure potential impacts from conservation research within and beyond academia.
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| 28. |
- Masche, J. Gowert, et al.
(author)
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Influences between parents and adolescents during the transition from middle school to the next stage of school or professional education
- 2003
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In: Psychologie in Erziehung und Unterricht. - 0342-183X. ; 50:2, s. 152-167
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Journal article (peer-reviewed)abstract
- According to individuation theory of parent-adolescent relationships, the primary parent-child hierarchy is gradually replaced by a peer-like reciprocity of parents and adolescents. However, it is questioned whether a peer-like relationship is the aim of development. Within a time span of about half a year, 41 families with school leavers after 10th grade of non college-bound school track were interrogated three times, regarding their mutual influences. Between-subject factors were the kind of educational transition (into professional training vs. to a different school track) and. the existence of younger and of older siblings. According to the family members' statements, parental influences prevailed at all time points. Both generations influenced each other for the adolescents' benefit, especially concerning school and career. Further results indicated that greater mutuality in the parent-child relationship was more intensively pursued by the parents rather than by the adolescents.
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| 29. |
- Nilsson, Emma A, et al.
(author)
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Altered DNA Methylation and Differential Expression of Genes Influencing Metabolism and Inflammation in Adipose Tissue From Subjects With Type 2 Diabetes
- 2014
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 63:9, s. 2962-2976
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Journal article (peer-reviewed)abstract
- Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts. In adipose tissue from diabetic twins, we found decreased expression of genes involved in oxidative phosphorylation; carbohydrate, amino acid, and lipid metabolism; and increased expression of genes involved in inflammation and glycan degradation. The most differentially expressed genes included ELOVL6, GYS2, FADS1, SPP1 (OPN), CCL18, and IL1RN. We replicated these results in adipose tissue from an independent case-control cohort. Several candidate genes for obesity and T2D (e.g., IRS1 and VEGFA) were differentially expressed in discordant twins. We found a heritable contribution to the genome-wide DNA methylation variability in twins. Differences in methylation between monozygotic twin pairs discordant for T2D were subsequently modest. However, 15,627 sites, representing 7,046 genes including PPARG, KCNQ1, TCF7L2, and IRS1, showed differential DNA methylation in adipose tissue from unrelated subjects with T2D compared with control subjects. A total of 1,410 of these sites also showed differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified copy number variants (CNVs) in monozygotic twin pairs discordant for T2D. Taken together, subjects with T2D exhibit multiple transcriptional and epigenetic changes in adipose tissue relevant to the development of the disease.
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- Timmons, James A., et al.
(author)
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Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans
- 2010
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In: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 108:6, s. 1487-1496
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Journal article (peer-reviewed)abstract
- Timmons JA, Knudsen S, Rankinen T, Koch LG, Sarzynski M, Jensen T, Keller P, Scheele C, Vollaard NB, Nielsen S, Akerstrom T, MacDougald OA, Jansson E, Greenhaff PL, Tarnopolsky MA, van Loon LJ, Pedersen BK, Sundberg CJ, Wahlestedt C, Britton SL, Bouchard C. Using molecular classification to predict gains in maximal aerobic capacity following endurance exercise training in humans. J Appl Physiol 108: 1487-1496, 2010. First published February 4, 2010; doi:10.1152/japplphysiol.01295.2009.-A low maximal oxygen consumption ((V) over dotO(2max)) is a strong risk factor for premature mortality. Supervised endurance exercise training increases (V) over dotO(2max) with a very wide range of effectiveness in humans. Discovering the DNA variants that contribute to this heterogeneity typically requires substantial sample sizes. In the present study, we first use RNA expression profiling to produce a molecular classifier that predicts (V) over dotO(2max) training response. We then hypothesized that the classifier genes would harbor DNA variants that contributed to the heterogeneous (V) over dotO(2max) response. Two independent preintervention RNA expression data sets were generated (n = 41 gene chips) from subjects that underwent supervised endurance training: one identified and the second blindly validated an RNA expression signature that predicted change in (V) over dotO(2max) (""predictor"" genes). The HERITAGE Family Study (n = 473) was used for genotyping. We discovered a 29-RNA signature that predicted (V) over dotO(2max) training response on a continuous scale; these genes contained similar to 6 new single-nucleotide polymorphisms associated with gains in (V) over dotO(2max) in the HERITAGE Family Study. Three of four novel candidate genes from the HERITAGE Family Study were confirmed as RNA predictor genes (i.e., ""reciprocal"" RNA validation of a quantitative trait locus genotype), enhancing the performance of the 29-RNA-based predictor. Notably, RNA abundance for the predictor genes was unchanged by exercise training, supporting the idea that expression was preset by genetic variation. Regression analysis yielded a model where 11 single-nucleotide polymorphisms explained 23% of the variance in gains in (V) over dotO(2max), corresponding to similar to 50% of the estimated genetic variance for (V) over dotO(2max). In conclusion, combining RNA profiling with single-gene DNA marker association analysis yields a strongly validated molecular predictor with meaningful explanatory power. (V) over dotO(2max) responses to endurance training can be predicted by measuring a similar to 30-gene RNA expression signature in muscle prior to training. The general approach taken could accelerate the discovery of genetic biomarkers, sufficiently discrete for diagnostic purposes, for a range of physiological and pharmacological phenotypes in humans.
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