| 1. |
- Yan, C., et al.
(author)
-
Size-dependent influence of NOx on the growth rates of organic aerosol particles
- 2020
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:22
-
Journal article (peer-reviewed)abstract
- Atmospheric new-particle formation (NPF) affects climate by contributing to a large fraction of the cloud condensation nuclei (CCN). Highly oxygenated organic molecules (HOMs) drive the early particle growth and therefore substantially influence the survival of newly formed particles to CCN. Nitrogen oxide (NOx) is known to suppress the NPF driven by HOMs, but the underlying mechanism remains largely unclear. Here, we examine the response of particle growth to the changes of HOM formation caused by NOx. We show that NOx suppresses particle growth in general, but the suppression is rather nonuniform and size dependent, which can be quantitatively explained by the shifted HOM volatility after adding NOx. By illustrating how NOx affects the early growth of new particles, a critical step of CCN formation, our results help provide a refined assessment of the potential climatic effects caused by the diverse changes of NOx level in forest regions around the globe.
|
|
| 2. |
- Nitschke, S., et al.
(author)
-
Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency
- 2022
-
In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 145:7, s. 2361-2377
-
Journal article (peer-reviewed)abstract
- Longer glucan chains tend to precipitate. Glycogen, by far the largest mammalian glucan and the largest molecule in the cytosol with up to 55 000 glucoses, does not, due to a highly regularly branched spherical structure that allows it to be perfused with cytosol. Aberrant construction of glycogen leads it to precipitate, accumulate into polyglucosan bodies that resemble plant starch amylopectin and cause disease. This pathology, amylopectinosis, is caused by mutations in a series of single genes whose functions are under active study toward understanding the mechanisms of proper glycogen construction. Concurrently, we are characterizing the physicochemical particularities of glycogen and polyglucosans associated with each gene. These genes include GBE1, EPM2A and EPM2B, which respectively encode the glycogen branching enzyme, the glycogen phosphatase laforin and the laforin-interacting E3 ubiquitin ligase malin, for which an unequivocal function is not yet known. Mutations in GBE1 cause a motor neuron disease (adult polyglucosan body disease), and mutations in EPM2A or EPM2B a fatal progressive myoclonus epilepsy (Lafora disease). RBCK1 deficiency causes an amylopectinosis with fatal skeletal and cardiac myopathy (polyglucosan body myopathy 1, OMIM# 615895). RBCK1 is a component of the linear ubiquitin chain assembly complex, with unique functions including generating linear ubiquitin chains and ubiquitinating hydroxyl (versus canonical amine) residues, including of glycogen. In a mouse model we now show (i) that the amylopectinosis of RBCK1 deficiency, like in adult polyglucosan body disease and Lafora disease, affects the brain; (ii) that RBCK1 deficiency glycogen, like in adult polyglucosan body disease and Lafora disease, has overlong branches; (iii) that unlike adult polyglucosan body disease but like Lafora disease, RBCK1 deficiency glycogen is hyperphosphorylated; and finally (iv) that unlike laforin-deficient Lafora disease but like malin-deficient Lafora disease, RBCK1 deficiency's glycogen hyperphosphorylation is limited to precipitated polyglucosans. In summary, the fundamental glycogen pathology of RBCK1 deficiency recapitulates that of malin-deficient Lafora disease. Additionally, we uncover sex and genetic background effects in RBCK1 deficiency on organ-and brain-region specific amylopectinoses, and in the brain on consequent neuroinflammation and behavioural deficits. Finally, we exploit the portion of the basic glycogen pathology that is common to adult polyglucosan body disease, both forms of Lafora disease and RBCK1 deficiency, namely overlong branches, to show that a unified approach based on downregulating glycogen synthase, the enzyme that elongates glycogen branches, can rescue all four diseases.
|
|
| 3. |
|
|
| 4. |
- Castarède, Dimitri, et al.
(author)
-
Development and characterization of the Portable Ice Nucleation Chamber 2 (PINCii)
- 2023
-
In: Atmospheric Measurement Techniques. - 1867-1381. ; 16:16, s. 3881-3899
-
Journal article (peer-reviewed)abstract
- The Portable Ice Nucleation Chamber 2 (PINCii) is a newly developed continuous flow diffusion chamber (CFDC) for measuring ice nucleating particles (INPs). PINCii is a vertically oriented parallel-plate CFDC that has been engineered to improve upon the limitations of previous generations of CFDCs. This work presents a detailed description of the PINCii instrument and the upgrades that make it unique compared with other operational CFDCs. The PINCii design offers several possibilities for improved INP measurements. Notably, a specific icing procedure results in low background particle counts, which demonstrates the potential for PINCii to measure INPs at low concentrations ( < 10 L (-1)). High-spatial-resolution wall-temperature mapping enables the identification of temperature inhomogeneities on the chamber walls. This feature is used to introduce and discuss a new method for analyzing CFDC data based on the most extreme lamina conditions present within the chamber, which represent conditions most likely to trigger ice nucleation. A temperature gradient can be maintained throughout the evaporation section in addition to the main chamber, which enables PINCii to be used to study droplet activation processes or to extend ice crystal growth. A series of both liquid droplet activation and ice nucleation experiments were conducted at temperature and saturation conditions that span the spectrum of PINCii's operational conditions ( 50 <= temperature <= 15 degrees C and 100 <= relative humidity with respect to ice <= 160 %) to demonstrate the instrument's capabilities. In addition, typical sources of uncertainty in CFDCs, including particle background, particle loss, and variations in aerosol lamina temperature and relative humidity, are quantified and discussed for PINCii.
|
|
| 5. |
- Sahu, B, et al.
(author)
-
Human cell transformation by combined lineage conversion and oncogene expression
- 2021
-
In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 40:36, s. 5533-5547
-
Journal article (peer-reviewed)abstract
- Cancer is the most complex genetic disease known, with mutations implicated in more than 250 genes. However, it is still elusive which specific mutations found in human patients lead to tumorigenesis. Here we show that a combination of oncogenes that is characteristic of liver cancer (CTNNB1, TERT, MYC) induces senescence in human fibroblasts and primary hepatocytes. However, reprogramming fibroblasts to a liver progenitor fate, induced hepatocytes (iHeps), makes them sensitive to transformation by the same oncogenes. The transformed iHeps are highly proliferative, tumorigenic in nude mice, and bear gene expression signatures of liver cancer. These results show that tumorigenesis is triggered by a combination of three elements: the set of driver mutations, the cellular lineage, and the state of differentiation of the cells along the lineage. Our results provide direct support for the role of cell identity as a key determinant in transformation and establish a paradigm for studying the dynamic role of oncogenic drivers in human tumorigenesis.
|
|
| 6. |
|
|
| 7. |
- Hägglund, Gunnar, et al.
(author)
-
Treatment of spasticity in children and adolescents with cerebral palsy in Northern Europe : a CP-North registry study
- 2021
-
In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 21:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Spasticity is present in more than 80% of the population with cerebral palsy (CP). The aim of this study was to describe and compare the use of three spasticity reducing methods; Botulinum toxin-A therapy (BTX-A), Selective dorsal rhizotomy (SDR) and Intrathecal baclofen therapy (ITB) among children and adolescents with CP in six northern European countries.METHODS: This registry-based study included population-based data in children and adolescents with CP born 2002 to 2017 and recorded in the follow-up programs for CP in Sweden, Norway, Denmark, Iceland and Scotland, and a defined cohort in Finland.RESULTS: A total of 8,817 individuals were included. The proportion of individuals treated with SDR and ITB was significantly different between the countries. SDR treatment ranged from 0% ( Finland and Iceland) to 3.4% (Scotland) and ITB treatment from 2.2% (Sweden) to 3.7% (Denmark and Scotland). BTX-A treatment in the lower extremities reported 2017-2018 ranged from 8.6% in Denmark to 20% in Norway (p < 0.01). Mean age for undergoing SDR ranged from 4.5 years in Norway to 7.3 years in Denmark (p < 0.01). Mean age at ITB surgery ranged from 6.3 years in Norway to 10.1 years in Finland (p < 0.01). Mean age for BTX-A treatment ranged from 7.1 years in Denmark to 10.3 years in Iceland (p < 0.01). Treatment with SDR was most common in Gross Motor Function Classification System (GMFCS) level III, ITB in level V, and BTX-A in level I. The most common muscle treated with BTX-A was the calf muscle, with the highest proportion in GMFCS level I. BTX-A treatment of hamstring and hip muscles was most common in GMFCS levels IV-V in all countries.CONCLUSION: There were statistically significant differences between countries regarding the proportion of children and adolescents with CP treated with the three spasticity reducing methods, mean age for treatment and treatment related to GMFCS level. This is likely due to differences in the availability of these treatment methods and/or differences in preferences of treatment methods among professionals and possibly patients across countries.
|
|
| 8. |
- Matilla-Santander, N., et al.
(author)
-
COVID-19 and Precarious Employment : Consequences of the Evolving Crisis
- 2021
-
In: International Journal of Health Services. - : Sage Publications. - 0020-7314 .- 1541-4469. ; 5:2, s. 226-228
-
Journal article (peer-reviewed)abstract
- The world of work is facing an ongoing pandemic and an economic downturn with severe effects worldwide. Workers trapped in precarious employment (PE), both formal and informal, are among those most affected by the COVID-19 pandemic. Here we call attention to at least 5 critical ways that the consequences of the crisis among workers in PE will be felt globally: (a) PE will increase, (b) workers in PE will become more precarious, (c) workers in PE will face unemployment without being officially laid off, (d) workers in PE will be exposed to serious stressors and dramatic life changes that may lead to a rise in diseases of despair, and (e) PE might be a factor in deterring the control of or in generating new COVID-19 outbreaks. We conclude that what we really need is a new social contract, where the work of all workers is recognized and protected with adequate job contracts, employment security, and social protection in a new economy, both during and after the COVID-19 crisis.
|
|
| 9. |
- Milutinovic, Goran
(author)
-
Computational and Visual Tools for Geospatial Multi-Criteria Decision-Making
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Geospatial multi-criteria decision-making usually concerns quasi-continuous choice models, with the number of alternatives constrained only by the limits of the used representation model. This sets high demands on the decision-making methods used in the context. The most commonly used approach in geospatial decision-making is combining a method for assigning criteria weights with an aggregation method. As pairwise comparison of alternatives is not feasible when the number of alternatives is large, the weights are usually assigned to criteria without considering the values or the value ranges of the alternatives, an approach often criticized in the decision analysis literature. Apart from criteria weighting controversy, this approach does not allow for advanced use of interactive visualization in the choice phase of the decision-making process. In this thesis, two alternative methods for geospatial decision-making based on the even swaps method are developed. The first method relies on automation of swaps, which makes this method viable for decision problems with any number of alternatives. The second method emanates from the findings of behavioral decision theory, and combines even swaps with reduction of large data sets through quasi-satisficing, allowing for efficient use of interactive visualization in the choice phase of the decision process. Visualization frameworks for both methods are also developed in the thesis. They include both geo-specific representations, such as interactive maps, and infovis techniques such as graphs, diagrams, scatterplots and parallel coordinates. Two studies concerning the impact of interactive visualization on decision-making are presented in the thesis: a study concerning the impact of interactive visualization on geospatial decision-making, and a study concerning potential effects of visual saliency on decision-making. The results of the first study indicated positive effects of interactive visualization on coherency and consistency in performing trade-offs. The results of the second study show that visual saliency may help decision-makers make better decisions. The work presented in this thesis contributes to method development and the use of interactive visualization in the context of geospatial decision-making.
|
|
| 10. |
|
|
