| 11. |
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| 12. |
- Fernandez-Chacon, Macarena, et al.
(författare)
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Incongruence between transcriptional and vascular pathophysiological cell states
- 2023
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Ingår i: NATURE CARDIOVASCULAR RESEARCH. - : SPRINGERNATURE. - 2731-0590. ; 2:6, s. 530-549
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Tidskriftsartikel (refereegranskat)abstract
- The Notch pathway is a major regulator of endothelial transcriptional specification. Targeting the Notch receptors or Delta-like ligand 4 (Dll4) dysregulates angiogenesis. Here, by analyzing single and compound genetic mutants for all Notch signaling members, we find significant differences in the way ligands and receptors regulate liver vascular homeostasis. Loss of Notch receptors caused endothelial hypermitogenic cell-cycle arrest and senescence. Conversely, Dll4 loss triggered a strong Myc-driven transcriptional switch inducing endothelial proliferation and the tip-cell state. Myc loss suppressed the induction of angiogenesis in the absence of Dll4, without preventing the vascular enlargement and organ pathology. Similarly, inhibition of other pro-angiogenic pathways, including MAPK/ERK and mTOR, had no effect on the vascular expansion induced by Dll4 loss; however, anti-VEGFA treatment prevented it without fully suppressing the transcriptional and metabolic programs. This study shows incongruence between single-cell transcriptional states, vascular phenotypes and related pathophysiology. Our findings also suggest that the vascular structure abnormalization, rather than neoplasms, causes the reported anti-Dll4 antibody toxicity. Fernandez-Chacon et al. use imaging and scRNA-seq after targeting multiple Notch genes and angiogenic signaling pathways to find that the function of these pathways in vascular pathophysiology cannot be predicted by assessing transcriptional states.
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| 13. |
- Filippatos, G. S., et al.
(författare)
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Independent academic Data Monitoring Committees for clinical trials in cardiovascular and cardiometabolic diseases
- 2017
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 19:4, s. 449-456
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Tidskriftsartikel (refereegranskat)abstract
- Data Monitoring Committees (DMCs) play a crucial role in the conducting of clinical trials to ensure the safety of study participants and to maintain a trial's scientific integrity. Generally accepted standards exist for DMC composition and operational conduct. However, some relevant issues are not specifically addressed in current guidance documents, resulting in uncertainties regarding optimal approaches for communication between the DMC, steering committee, and sponsors, release of information, and liability protection for DMC members. The Heart Failure Association (HFA) of the European Society of Cardiology (ESC), in collaboration with the Clinical Trials Unit of the European Heart Agency (EHA) of the ESC convened a meeting of international experts in DMCs for cardiovascular and cardiometabolic clinical trials to identify specific issues and develop steps to resolve challenges faced by DMCs.The main recommendations from the meeting relate to methodological consistency, independence, managing conflicts of interest, liability protection, and training of future DMC members. This paper summarizes the key outcomes from this expert meeting, and describes the core set of activities that might be further developed and ultimately implemented by the ESC, HFA, and other interested ESC constituent bodies. The HFA will continue to work with stakeholders in cardiovascular and cardiometabolic clinical research to promote these goals.
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| 14. |
- Hallgren, Mikael, et al.
(författare)
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The tubed mega frame - An innovative structural system for tall buildings
- 2015
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Ingår i: Concrete - Innovation and Design. - : Technical University of Denmark. ; , s. 473-474, s. 473-474
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Konferensbidrag (refereegranskat)abstract
- The Tubed Mega Frame is a new structure concept for high-rise buildings which is developed by Tyréns in Sweden. The Tubed Mega Frame consists of large hollow vertical shafts, mega columns, and perimeter walls. In a series of in-depth structural studies, the global response of the system as well as the detailed design of the mega columns and the perimeter walls have been investigated. The studies have been performed on an 800 m high prototype building. Parallel to these studies, the feasibility of the construction process has been the objective in another investigation. The chosen structural material for the Tubed Mega Frame is reinforced high-strength concrete. The conclusions from the studies show that the Tubed Mega Frame is a potentially feasible structural system with high-efficiency for high-rise buildings.
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| 15. |
- Honkalampi-Hämäläinen, U., et al.
(författare)
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Safety evaluation of food contact paper and board using chemical tests and in vitro bioassays : Role of known and unknown substances
- 2010
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Ingår i: Food Additives and Contaminants. - : Informa UK Limited. - 0265-203X .- 1464-5122. ; 27:3, s. 406-115
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Tidskriftsartikel (refereegranskat)abstract
- In vitro toxicological tests have been proposed as an approach to complement the chemical safety assessment of food contact materials, particularly those with a complex or unknown chemical composition such as paper and board. Among the concerns raised regarding the applicability of in vitro tests are the effects of interference of the extractables on the outcome of the cytotoxicity and genotoxicity tests applied and the role of known compounds present in chemically complex materials, such as paper and board, either as constituents or contaminants. To answer these questions, a series of experiments were performed to assess the role of natural substances (wood extracts, resin acids), some additives (diisopropylnaphthalene, phthalates, acrylamide, fluorescent whitening agents) and contaminants (2,4-diaminotoluene, benzo[a]pyrene) in the toxicological profile of paper and board. These substances were individually tested or used to spike actual paper and board extracts. The toxic concentrations of diisopropylnaphthalenes and phthalates were compared with those actually detected in paper and board extracts showing conspicuous toxicity. According to the results of the spiking experiments, the extracts did not affect the toxicity of tested chemicals nor was there any significant metabolic interference in the cases where two compounds were used in tests involving xenobiotic metabolism by the target cells. While the identified substances apparently have a role in the cytotoxicity of some of the project samples, their presence does not explain the total toxicological profile of the extracts. In conclusion, in vitro toxicological testing can have a role in the safety assessment of chemically complex materials in detecting potentially harmful activities not predictable by chemical analysis alone.
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| 16. |
- Lawrenz, F., et al.
(författare)
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Morphology, mechanical stability, and protective properties of ultrathin gallium oxide coatings
- 2015
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 31:21, s. 5836-5842
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Tidskriftsartikel (refereegranskat)abstract
- Ultrathin gallium oxide layers with a thickness of 2.8 ± 0.2 nm were transferred from the surface of liquid gallium onto solid substrates, including conjugated polymer poly(3-hexylthiophene) (P3HT). The gallium oxide exhibits high mechanical stability, withstanding normal pressures of up to 1 GPa in contact mode scanning force microscopy imaging. Moreover, it lowers the rate of photodegradation of P3HT by 4 orders of magnitude, as compared to uncovered P3HT. This allows us to estimate the upper limits for oxygen and water vapor transmission rates of 0.08 cm3 m-2 day-1 and 0.06 mg m-2 day-1, respectively. Hence, similar to other highly functional coatings such as graphene, ultrathin gallium oxide layers can be regarded as promising candidates for protective layers in flexible organic (opto-)electronics and photovoltaics because they offer permeation barrier functionalities in conjunction with high optical transparency.
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| 17. |
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| 18. |
- Lundin, Daniel, et al.
(författare)
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Which sequencing depth is sufficient to describe patterns in bacterial alpha- and beta-diversity?
- 2012
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Ingår i: Environmental Microbiology Reports. - : Wiley. - 1758-2229. ; 4:3, s. 367-372
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Tidskriftsartikel (refereegranskat)abstract
- The vastness of microbial diversity implies that an almost infinite number of individuals needs to be identified to accurately describe such communities. Practical and economical constraints may therefore prevent appropriate study designs. However, for many questions in ecology it is not essential to know the actual diversity but rather the trends among samples thereof. It is, hence, important to know to what depth microbial communities need to be sampled to accurately measure trends in diversity. We used three data sets of freshwater and sediment bacteria, where diversity was explored using 454 pyrosequencing. Each data set contained 615 communities from which 15 00020 000 16S rRNA gene sequences each were obtained. These data sets were subsampled repeatedly to 10 different depths down to 200 sequences per community. Diversity estimates varied with sequencing depth, yet, trends in diversity among samples were less sensitive. We found that 1000 denoised sequences per sample explained to 90% the trends in beta-diversity (Bray-Curtis index) among samples observed for 15 00020 000 sequences. Similarly, 5000 denoised sequences were sufficient to describe trends in a-diversity (Shannon index) with the same accuracy. Further, 5000 denoised sequences captured to more than 80% the trends in Chao1 richness and Pielou's evenness.
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| 19. |
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| 20. |
- Schindler, Severin, 1987, et al.
(författare)
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Focused electron beam based direct-write fabrication of graphene and amorphous carbon from oxo-functionalized graphene on silicon dioxide
- 2017
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 19:4, s. 2683-2686
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Tidskriftsartikel (refereegranskat)abstract
- Controlled patterning of graphene is an important task towards device fabrication and thus is the focus of current research activities. Graphene oxide (GO) is a solution-processible precursor of graphene. It can be patterned by thermal processing. However, thermal processing of GO leads to decomposition and CO2 formation. Alternatively, focused electron beam induced processing (FEBIP) techniques can be used to pattern graphene with high spatial resolution. Based on this approach, we explore FEBIP of GO deposited on SiO2. Using oxo-functionalized graphene (oxo-G) with an in-plane lattice defect density of 1% we are able to image the electron beam-induced effects by scanning Raman microscopy for the first time. Depending on electron energy (2-30 keV) and doses (50-800 mC m(-2)) either reduction of GO or formation of permanent lattice defects occurs. This result reflects a step towards controlled FEBIP processing of oxo-G.
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