| 1. |
- Franz, D, et al.
(författare)
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Towards long-term standardised carbon and greenhouse gas observations for monitoring Europe´s terrestrial ecosystems: a review
- 2018
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Ingår i: International Agrophysics. - : Walter de Gruyter GmbH. - 0236-8722 .- 2300-8725. ; 32, s. 439-455
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Tidskriftsartikel (refereegranskat)abstract
- Research infrastructures play a key role in launching a new generation of integrated long-term, geographically distributed observation programmes designed to monitor climate change, better understand its impacts on global ecosystems, and evaluate possible mitigation and adaptation strategies. The pan-European Integrated Carbon Observation System combines carbon and greenhouse gas (GHG; CO2, CH4, N2O, H2O) observations within the atmosphere, terrestrial ecosystems and oceans. High-precision measurements are obtained using standardised methodologies, are centrally processed and openly available in a traceable and verifiable fashion in combination with detailed metadata. The Integrated Carbon Observation System ecosystem station network aims to sample climate and land-cover variability across Europe. In addition to GHG flux measurements, a large set of complementary data (including management practices, vegetation and soil characteristics) is collected to support the interpretation, spatial upscaling and modelling of observed ecosystem carbon and GHG dynamics. The applied sampling design was developed and formulated in protocols by the scientific community, representing a trade-off between an ideal dataset and practical feasibility. The use of open-access, high-quality and multi-level data products by different user communities is crucial for the Integrated Carbon Observation System in order to achieve its scientific potential and societal value.
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| 2. |
- Tuovinen, EA, et al.
(författare)
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Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency
- 2020
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 40:3, s. 503-514
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Tidskriftsartikel (refereegranskat)abstract
- Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient’s clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny.
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| 3. |
- Cuni-Sanchez, Aida, et al.
(författare)
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High aboveground carbon stock of African tropical montane forests
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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| 4. |
- Rinne, J., et al.
(författare)
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Effect of the 2018 European drought on methane and carbon dioxide exchange of northern mire ecosystems
- 2020
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Ingår i: Philosophical Transactions of the Royal Society B-Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 375:1810
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Tidskriftsartikel (refereegranskat)abstract
- We analysed the effect of the 2018 European drought on greenhouse gas (GHG) exchange of five North European mire ecosystems. The low precipitation and high summer temperatures in Fennoscandia led to a lowered water table in the majority of these mires. This lowered both carbon dioxide (CO2) uptake and methane (CH4) emission during 2018, turning three out of the five mires from CO(2)sinks to sources. The calculated radiative forcing showed that the drought-induced changes in GHG fluxes first resulted in a cooling effect lasting 15-50 years, due to the lowered CH(4)emission, which was followed by warming due to the lower CO(2)uptake. This article is part of the theme issue 'Impacts of the 2018 severe drought and heatwave in Europe: from site to continental scale'.
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| 5. |
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| 6. |
- Flanagan, Sarah E, et al.
(författare)
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Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:8, s. 812-814
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Tidskriftsartikel (refereegranskat)abstract
- Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.
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| 7. |
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| 8. |
- Keskitalo, S, et al.
(författare)
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Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease
- 2019
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Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 4, s. 14-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.
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| 9. |
- Tuovinen, EA, et al.
(författare)
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Characterization of Expanded Gamma Delta T Cells from Atypical X-SCID Patient Reveals Preserved Function and IL2RG-Mediated Signaling
- 2023
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Ingår i: Journal of clinical immunology. - : Springer Science and Business Media LLC. - 1573-2592 .- 0271-9142. ; 43:2, s. 358-370
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Tidskriftsartikel (refereegranskat)abstract
- Abnormally high γδ T cell numbers among individuals with atypical SCID have been reported but detailed immunophenotyping and functional characterization of these expanded γδ T cells are limited. We have previously reported atypical SCID phenotype caused by hypomorphic IL2RG (NM_000206.3) c.172C > T;p.(Pro58Ser) variant. Here, we have further investigated the index patient’s abnormally large γδ T cell population in terms of function and phenotype by studying IL2RG cell surface expression, STAT tyrosine phosphorylation and blast formation in response to interleukin stimulation, immunophenotyping, TCRvγ sequencing, and target cell killing. In contrast to his ⍺β T cells, the patient’s γδ T cells showed normal IL2RG cell surface expression and normal or enhanced IL2RG-mediated signaling. Vδ2 + population was proportionally increased with a preponderance of memory phenotypes and high overall tendency towards perforin expression. The patient’s γδ T cells showed enhanced cytotoxicity towards A549 cancer cells. His TCRvγ repertoire was versatile but sequencing of IL2RG revealed a novel c.534C > A; p.(Phe178Leu) somatic missense variant restricted to γδ T cells. Over time this variant became predominant in γδ T cells, though initially present only in part of them. IL2RG-Pro58Ser/Phe178Leu variant showed higher cell surface expression compared to IL2RG-Pro58Ser variant in stable HEK293 cell lines, suggesting that somatic p.(Phe178Leu) variant may at least partially rescue the pathogenic effect of germline p.(Pro58Ser) variant. In conclusion, our report indicates that expansion of γδ T cells associated with atypical SCID needs further studying and cannot exclusively be deemed as a homeostatic response to low numbers of conventional T cells.
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| 10. |
- Aho, Vilma, et al.
(författare)
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Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses
- 2016
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.
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| 11. |
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| 12. |
- Carstensen, Jacob, et al.
(författare)
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Factors regulating the coastal nutrient filter in the Baltic Sea
- 2020
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Ingår i: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 49:6, s. 1194-1210
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Tidskriftsartikel (refereegranskat)abstract
- The coastal zone of the Baltic Sea is diverse with strong regional differences in the physico-chemical setting. This diversity is also reflected in the importance of different biogeochemical processes altering nutrient and organic matter fluxes on the passage from land to sea. This review investigates the most important processes for removal of nutrients and organic matter, and the factors that regulate the efficiency of the coastal filter. Nitrogen removal through denitrification is high in lagoons receiving large inputs of nitrate and organic matter. Phosphorus burial is high in archipelagos with substantial sedimentation, but the stability of different burial forms varies across the Baltic Sea. Organic matter processes are tightly linked to the nitrogen and phosphorus cycles. Moreover, these processes are strongly modulated depending on composition of vegetation and fauna. Managing coastal ecosystems to improve the effectiveness of the coastal filter can reduce eutrophication in the open Baltic Sea.
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| 13. |
- Cosens, Barbara, et al.
(författare)
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Governing complexity : Integrating science, governance, and law to manage accelerating in the commons
- 2021
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 118:36
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Tidskriftsartikel (refereegranskat)abstract
- The speed and uncertainty of environmental change in the Anthropocene challenge the capacity of coevolving social-ecological-technological systems (SETs) to adapt or transform to these changes. Formal government and legal structures further constrain the adaptive capacity of our SETs. However, new, selforganized forms of adaptive governance are emerging at multiple scales in natural resource-based SETs. Adaptive governance involves the private and public sectors as well as formal and informal institutions, self-organized to fill governance gaps in the traditional roles of states. While new governance forms are emerging, they are not yet doing so rapidly enough to match the pace of environmental change. Furthermore, they do not yet possess the legitimacy or capacity needed to address disparities between the winners and losers from change. These emergent forms of adaptive governance appear to be particularly effective in managing complexity. We explore governance and SETs as coevolving complex systems, focusing on legal systems to understand the potential pathways and obstacles to equitable adaptation. We explore how governments may facilitate the emergence of adaptive governance and promote legitimacy in both the process of governance despite the involvement of nonstate actors, and its adherence to democratic values of equity and justice. To manage the contextual nature of the results of change in complex systems, we propose the establishment of long-term study initiatives for the coproduction of knowledge, to accelerate learning and synergize interactions between science and governance and to foster public science and epistemic communities dedicated to navigating transitions to more just, sustainable, and resilient futures.
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| 14. |
- Foulds, Chris, et al.
(författare)
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An agenda for future Social Sciences and Humanities research on energy efficiency : 100 priority research questions
- 2022
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Ingår i: Humanities & Social Sciences Communications. - : Springer Nature. - 2662-9992. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Decades of techno-economic energy policymaking and research have meant evidence from the Social Sciences and Humanities (SSH)-including critical reflections on what changing a societys relation to energy (efficiency) even means-have been underutilised. In particular, (i) the SSH have too often been sidelined and/or narrowly pigeonholed by policymakers, funders, and other decision-makers when driving research agendas, and (ii) the setting of SSH-focused research agendas has not historically embedded inclusive and deliberative processes. The aim of this paper is to address these gaps through the production of a research agenda outlining future SSH research priorities for energy efficiency. A Horizon Scanning exercise was run, which sought to identify 100 priority SSH questions for energy efficiency research. This exercise included 152 researchers with prior SSH expertise on energy efficiency, who together spanned 62 (sub-)disciplines of SSH, 23 countries, and a full range of career stages. The resultant questions were inductively clustered into seven themes as follows: (1) Citizenship, engagement and knowledge exchange in relation to energy efficiency; (2) Energy efficiency in relation to equity, justice, poverty and vulnerability; (3) Energy efficiency in relation to everyday life and practices of energy consumption and production; (4) Framing, defining and measuring energy efficiency; (5) Governance, policy and political issues around energy efficiency; (6) Roles of economic systems, supply chains and financial mechanisms in improving energy efficiency; and (7) The interactions, unintended consequences and rebound effects of energy efficiency interventions. Given the consistent centrality of energy efficiency in policy programmes, this paper highlights that well-developed SSH approaches are ready to be mobilised to contribute to the development, and/or to understand the implications, of energy efficiency measures and governance solutions. Implicitly, it also emphasises the heterogeneity of SSH policy evidence that can be produced. The agenda will be of use for both (1) those new to the energy-SSH field (including policyworkers), for learnings on the capabilities and capacities of energy-SSH, and (2) established energy-SSH researchers, for insights on the collectively held futures of energy-SSH research.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
- Kallio, A, et al.
(författare)
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Role of mitochondria in tamoxifen-induced rapid death of MCF-7 breast cancer cells
- 2005
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Ingår i: Apoptosis. - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 10:6, s. 1395-1410
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Tidskriftsartikel (refereegranskat)abstract
- Tamoxifen (Tam) is widely used in chemotherapy of estrogen receptor-positive breast cancer. It inhibits proliferation and induces apoptosis of breast cancer cells by estrogen receptor-dependent modulation of gene expression, but recent reports have shown that Tam (especially at pharmacological concentrations) has also rapid nongenomic effects. Here we studied the mechanisms by which Tam exerts rapid effects on breast cancer cell viability. In serum-free medium 5-7 mu M Tam induced death of MCF-7 and MDA-MB-231 cells in a time-dependent manner in less than 60 min. This was associated with release of mitochondrial cytochrome c, a decrease of mitochondrial membrane potential and an increase in production of reactive oxygen species (ROS). This suggests that disruption of mitochondrial function has a primary role in the acute death response of the cells. Accordingly, bongkrekic acid, an inhibitor of mitochondrial permeability transition, was able to protect MCF-7 cells against Tam. Rapid cell death induction by Tam was not associated with immediate activation of caspase-9 or cleavage of poly (ADP-ribose) polymerase. It was not blocked by the caspase inhibitor z-Val-Ala-Asp-fluoromethylketone either. Diphenylene ionodium (DPI), an inhibitor of NADPH oxidase, was able to prevent Tam-induced cell death but not cytochrome c release, which suggests that ROS act distal to cytochrome c. The pure antiestrogen ICI 182780 (1 mu M) could partly oppose the effect of Tam in estrogen receptor positive MCF-7 cells, but not in estrogen receptor negative MDA-MB-231 cells. Pre-culturing MCF-7 cells in the absence of 17 beta-estradiol (E-2) or in the presence of a low Tam concentration (1 mu M) made the cells even more susceptible to rapid death induction by 5 or 7 mu M Tam. This effect was associated with decreased levels of the anti-apoptotic proteins Bcl-X-L and Bcl-2. In conclusion, our results demonstrate induction of a rapid mitochondrial cell death program in breast cancer cells at pharmacological concentrations of Tam, which are achievable in tumor tissue of Tam-treated breast cancer patients. These mechanisms may contribute to the ability of Tam therapy to induce death of breast cancer cells.
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| 22. |
- Kou, Dan, et al.
(författare)
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Peatland Heterogeneity Impacts on Regional Carbon Flux and Its Radiative Effect Within a Boreal Landscape
- 2022
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Ingår i: Journal of Geophysical Research: Biogeosciences. - 2169-8953. ; 127:9
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Tidskriftsartikel (refereegranskat)abstract
- Peatlands, with high spatial variability in ecotypes and microforms, constitute a significant part of the boreal landscape and play an important role in the global carbon (C) cycle. However, the effects of this peatland heterogeneity within the boreal landscape are rarely quantified. Here, we use field-based measurements, high-resolution land cover classification, and biogeochemical and atmospheric models to estimate the atmosphere-ecosystem C fluxes and the corresponding radiative effect (RE) for a boreal landscape (Kaamanen) in northern Finland. Our result shows that the Kaamanen catchment currently functioned as a sink of carbon dioxide (CO2) and a source of methane (CH4). Peatlands (26% of the area) contributed 22% of the total CO2 uptake and 89% of CH4 emissions; forests (61%) accounted for 78% of CO2 uptake and offset 6% of CH4 emissions; water bodies (13%) offset 7% of CO2 uptake and contributed 11% of CH4 emissions. The heterogeneity of peatlands accounted for 11%, 88%, and 75% of the area-weighted variability (deviation from the area-weighted mean among different land cover types (LCTs) within the catchment) in CO2 flux, CH4 flux, and the combined RE of CO2 and CH4 exchanges over the 25-year time horizon, respectively. Aggregating peatland LCTs or misclassifying them as nonpeatland LCTs can significantly (p < 0.05) bias the regional CH4 exchange and RE estimates, while differentiating between drier noninundated and wetter inundated peatlands can effectively reduce the bias. Current land cover products lack such details in peatland heterogeneity, which would be needed to better constrain boreal C budgets and global C-climate feedbacks.
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| 23. |
- Mathew, Alma, et al.
(författare)
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Understanding the Capacity Fade in Polyacrylonitrile Binder-based LiNi0.5Mn1.5O4 Cells
- 2022
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Ingår i: Batteries & Supercaps. - : John Wiley & Sons. - 2566-6223. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Binders are electrochemically inactive components that have a crucial impact in battery ageing although being present in only small amounts, typically 1?3?% w/w in commercial products. The electrochemical performance of a battery can be tailored via these inactive materials by optimizing the electrode integrity and surface chemistry. Polyacrylonitrile (PAN) for LiNi0.5Mn1.5O4 (LNMO) half-cells is here investigated as a binder material to enable a stable electrode-electrolyte interface. Despite being previously described in literature as an oxidatively stable polymer, it is shown that PAN degrades and develops resistive layers within the LNMO cathode. We demonstrate continuous internal resistance increase in LNMO-based cells during battery operation using intermittent current interruption (ICI) technique. Through a combination of on-line electrochemical mass spectrometry (OEMS) and X-ray photoelectron spectroscopy (XPS) characterization techniques, the degradation products can be identified as solid on the LNMO electrode surface, and no excessive gas formation seen. The increased resistance and parasitic processes are correlated to side-reactions of the PAN, possibly intramolecular cyclization, which can be identified as the main cause of the comparatively fast capacity fade.
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| 24. |
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| 25. |
- Salian, Girish D., et al.
(författare)
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Understanding the electrochemical and interfacial behaviour of sulfolane-based electrolytes in LiNi0.5Mn1.5O4-graphite full-cells
- 2023
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Ingår i: Batteries & Supercaps. - : John Wiley & Sons. - 2566-6223. ; n/a:n/a
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Tidskriftsartikel (refereegranskat)abstract
- An ethylene carbonate-free electrolyte composed of 1 M lithium bis(fluorosulfonyl) imide (LiFSI) in sulfolane (SL) is studied here for LiNi0.5Mn1.5O4-graphite full-cells. An important focus on the evaluation of the anodic stability of the SL electrolyte and the passivation layers formed on LNMO and graphite is being analysed along with intermittent current interruption (ICI) technique to observe the resistance while cycling. The results show that the sulfolane electrolyte shows more degradation at higher potentials unlike previous reports which suggested higher oxidative stability. However, the passivation layers formed due to this electrolyte degradation prevents further degradation. The resistance measurements show that major resistance arises from the cathode. The pressure evolution during the formation cycles suggests that there is lower gas evolution with sulfolane electrolyte than in the conventional electrolyte. The study opens a new outlook on the sulfolane based electrolyte especially regarding its oxidative/anodic stability.
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| 26. |
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| 27. |
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| 28. |
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| 29. |
- Vallée, Tanja C, et al.
(författare)
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Wiskott-Aldrich Syndrome: A study on 577 patients defining the genotype as a predictive biomarker for disease severity.
- 2024
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Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 143:24, s. 2504-2516
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Tidskriftsartikel (refereegranskat)abstract
- WAS is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study. Overall survival (OS) of the cohort (censored at HSCT or GT) was 82% (95% CI 78-87) at 15 years and 70% (61-80) at 30 years of age. The type of variant was predictive of outcome: patients with a missense variant in exons 1 or 2 or with the intronic hotspot variant c.559+5G>A (class I variants) had a 15-year OS of 93% (89-98) and a 30-year OS of 91% (86-97), compared to 71% (62-81) and 48% (34-68) in patients with any other variant (class II; p<0.0001). The cumulative incidence rates of disease-related complications such as severe bleeding (p=0.007), life-threatening infection (p<0.0001), and autoimmunity (p=0.004) occurred significantly later in patients with a class I variant. The cumulative incidence of malignancy (p=0.6) was not different between classes I and II. This study represents the largest cohort of WAS patients studied so far. It confirms the spectrum of disease severity and quantifies the risk for specific disease-related complications. The class of variant is a biomarker to predict the outcome for WAS patients.
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| 30. |
- Zor, K., et al.
(författare)
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A compact multifunctional microfluidic platform for exploring cellular dynamics in real-time using electrochemical detection
- 2014
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 4:109, s. 63761-63771
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Tidskriftsartikel (refereegranskat)abstract
- Downscaling of microfluidic cell culture and detection devices for electrochemical monitoring has mostly focused on miniaturization of the microfluidic chips which are often designed for specific applications and therefore lack functional flexibility. We present a compact microfluidic cell culture and electrochemical analysis platform with in-built fluid handling and detection, enabling complete cell based assays comprising on-line electrode cleaning, sterilization, surface functionalization, cell seeding, cultivation and electrochemical real-time monitoring of cellular dynamics. To demonstrate the versatility and multifunctionality of the platform, we explored amperometric monitoring of intracellular redox activity in yeast (Saccharomyces cerevisiae) and detection of exocytotically released dopamine from rat pheochromocytoma cells (PC12). Electrochemical impedance spectroscopy was used in both applications for monitoring cell sedimentation and adhesion as well as proliferation in the case of PC12 cells. The influence of flow rate on the signal amplitude in the detection of redox metabolism as well as the effect of mechanical stimulation on dopamine release were demonstrated using the programmable fluid handling capability. The here presented platform is aimed at applications utilizing cell based assays, ranging from e.g. monitoring of drug effects in pharmacological studies, characterization of neural stem cell differentiation, and screening of genetically modified microorganisms to environmental monitoring.
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