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1.	Stanaway, Jeffrey D., et al. (author) Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017 2018 In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1923-1994 Journal article (peer-reviewed)abstract Background The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk-outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk-outcome pairs, and new data on risk exposure levels and risk- outcome associations. Methods We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk-outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017.
2.	Richards, Stephen, et al. (author) The genome of the model beetle and pest Tribolium castaneum. 2008 In: Nature. - 1476-4687. ; 452:7190, s. 949-55 Journal article (peer-reviewed)abstract Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
3.	Agrawal, Mridul, et al. (author) TET2-mutant clonal hematopoiesis and risk of gout 2022 In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 140:10, s. 1094-1103 Journal article (peer-reviewed)abstract Gout is a common inflammatory arthritis caused by precipitation of monosodium urate (MSU) crystals in individuals with hyperuricemia. Acute flares are accompanied by secretion of proinflammatory cytokines, including interleukin-1β (IL-1β). Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition predisposing to hematologic cancers and cardiovascular disease. CHIP is associated with elevated IL-1β, thus we investigated CHIP as a risk factor for gout. To test the clinical association between CHIP and gout, we analyzed whole exome sequencing data from 177 824 individuals in the MGB Biobank (MGBB) and UK Biobank (UKB). In both cohorts, the frequency of gout was higher among individuals with CHIP than without CHIP (MGBB, CHIP with variant allele fraction [VAF] ≥2%: odds ratio [OR], 1.69; 95% CI, 1.09-2.61; P = .0189; UKB, CHIP with VAF ≥10%: OR, 1.25; 95% CI, 1.05-1.50; P = .0133). Moreover, individuals with CHIP and a VAF ≥10% had an increased risk of incident gout (UKB: hazard ratio [HR], 1.28; 95% CI, 1.06-1.55; P = .0107). In murine models of gout pathogenesis, animals with Tet2 knockout hematopoietic cells had exaggerated IL-1β secretion and paw edema upon administration of MSU crystals. Tet2 knockout macrophages elaborated higher levels of IL-1β in response to MSU crystals in vitro, which was ameliorated through genetic and pharmacologic Nlrp3 inflammasome inhibition. These studies show that TET2-mutant CHIP is associated with an increased risk of gout in humans and that MSU crystals lead to elevated IL-1β levels in Tet2 knockout murine models. We identify CHIP as an amplifier of NLRP3-dependent inflammatory responses to MSU crystals in patients with gout.
4.	Ebert, Thomas, et al. (author) Insights in the regulation of trimetylamine N-oxide production using a comparative biomimetic approach suggest a metabolic switch in hibernating bears 2020 In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1 Journal article (peer-reviewed)abstract Experimental studies suggest involvement of trimethylamine N-oxide (TMAO) in the aetiology of cardiometabolic diseases and chronic kidney disease (CKD), in part via metabolism of ingested food. Using a comparative biomimetic approach, we have investigated circulating levels of the gut metabolites betaine, choline, and TMAO in human CKD, across animal species as well as during hibernation in two animal species. Betaine, choline, and TMAO levels were associated with renal function in humans and differed significantly across animal species. Free-ranging brown bears showed a distinct regulation pattern with an increase in betaine (422%) and choline (18%) levels during hibernation, but exhibited undetectable levels of TMAO. Free-ranging brown bears had higher betaine, lower choline, and undetectable TMAO levels compared to captive brown bears. Endogenously produced betaine may protect bears and garden dormice during the vulnerable hibernating period. Carnivorous eating habits are linked to TMAO levels in the animal kingdom. Captivity may alter the microbiota and cause a subsequent increase of TMAO production. Since free-ranging bears seems to turn on a metabolic switch that shunts choline to generate betaine instead of TMAO, characterisation and understanding of such an adaptive switch could hold clues for novel treatment options in burden of lifestyle diseases, such as CKD.
5.	Hernandez, Leah, et al. (author) Blood-brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins 2022 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1 Journal article (peer-reviewed)abstract Kidney failure and associated uraemia have implications for the cardiovascular system, brain, and blood-brain barrier (BBB). We aim to examine BBB disruption, by assessing brain-derived neurotropic factor (BDNF), neuron-specific enolase (NSE) levels, and gut-blood barrier (GBB) disruption by trimethylamine N-oxide (TMAO), in chronic kidney disease (CKD) patients. Additionally, endothelial tight-junction protein expressions and modulation via TMAO were assessed. Serum from chronic kidney disease (CKD) female and male haemodialysis (HD) patients, and controls, were used to measure BDNF and NSE by enzyme-linked immunosorbent assays, and TMAO by mass spectrometry. Immunofluorescent staining of subcutaneous fat biopsies from kidney transplant recipients, and controls, were used to measure microvascular expression of tight-junction proteins (claudin-5, occludin, JAM-1), and control microvasculature for TMAO effects. HD patients versus controls, had significantly lower and higher serum levels of BDNF and NSE, respectively. In CKD biopsies versus controls, reduced expression of claudin-5, occludin, and JAM-1 were observed. Incubation with TMAO significantly decreased expression of all tight-junction proteins in the microvasculature. Uraemia affects BBB and GBB resulting in altered levels of circulating NSE, BDNF and TMAO, respectively, and it also reduces expression of tight-junction proteins that confer BBB maintenance. TMAO serves as a potential candidate to alter BBB integrity in CKD.
6.	Lechman, Eric R, et al. (author) miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. 2016 In: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 29:2, s. 214-228 Journal article (peer-reviewed)abstract To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
7.	Andres, Beatrice, et al. (author) Strong momentum-dependent electron-magnon renormalization of a surface resonance on iron 2022 In: Applied Physics Letters. - : American Institute of Physics (AIP). - 0003-6951 .- 1077-3118. ; 120:20 Journal article (peer-reviewed)abstract The coupling of electrons to spin excitations and the generation of magnons is essential for spin mixing in the ultrafast magnetization dynamics of 3d ferromagnets. Although magnon energies are generally much larger than phonon energies, until now their electronic band renormalization effect in 3d ferromagnets suggests a significantly weaker quasiparticle interaction. Using spin- and angle-resolved photoemission, we show an extraordinarily strong renormalization leading to two-branch splitting of an iron surface resonance at ~& nbsp;200 meV. Its strong magnetic linear dichroism unveils the magnetic nature and momentum dependence of the energy renormalization. By determining the frequency- and momentum-dependent self-energy due to generic electron-boson interaction to compute the resultant electron spectral function, we suggest that the surface-state splitting can be described by strong coupling to an optical spin wave in an iron thin film.& nbsp;& nbsp;Published under an exclusive license by AIP Publishing.
8.	Anzt, Hartwig, et al. (author) An environment for sustainable research software in Germany and beyond: current state, open challenges, and call for action 2020 In: F1000 Research. - : F1000 Research Ltd. - 2046-1402. ; 9 Journal article (peer-reviewed)abstract Research software has become a central asset in academic research. It optimizes existing and enables new research methods, implements and embeds research knowledge, and constitutes an essential research product in itself. Research software must be sustainable in order to understand, replicate, reproduce, and build upon existing research or conduct new research effectively. In other words, software must be available, discoverable, usable, and adaptable to new needs, both now and in the future. Research software therefore requires an environment that supports sustainability. Hence, a change is needed in the way research software development and maintenance are currently motivated, incentivized, funded, structurally and infrastructurally supported, and legally treated. Failing to do so will threaten the quality and validity of research. In this paper, we identify challenges for research software sustainability in Germany and beyond, in terms of motivation, selection, research software engineering personnel, funding, infrastructure, and legal aspects. Besides researchers, we specifically address political and academic decision-makers to increase awareness of the importance and needs of sustainable research software practices. In particular, we recommend strategies and measures to create an environment for sustainable research software, with the ultimate goal to ensure that software-driven research is valid, reproducible and sustainable, and that software is recognized as a first class citizen in research. This paper is the outcome of two workshops run in Germany in 2019, at deRSE19 - the first International Conference of Research Software Engineers in Germany - and a dedicated DFG-supported follow-up workshop in Berlin.
9.	Azour, Farivar, et al. (author) Invasion rate and population characteristics of the round goby Neogobius melanostomus: effects of density and invasion history 2015 In: Aquatic Biology. - : Inter-Research Science Center. - 1864-7782 .- 1864-7790. ; 24:1, s. 41-52 Journal article (peer-reviewed)abstract Round goby Neogobius melanostomus is currently one of the most wide-ranging invasive fish species in Europe and North America. The present study demonstrates how the distribution of round goby has expanded from 2008 to 2013 at a rate of about 30 km yr(-1) along the Danish coastline in the western Baltic Sea. Further analyses showed that fish from an established high-density round goby population were slow-growing and displayed poorer condition (weight at age and hepatosomatic index) compared to fish sampled from recently invaded locations (i.e. at the forefront of the distribution range). The established population revealed a broad age distribution and a 1:1 gender ratio, while fish from a recently invaded site were primarily of intermediate ages with a male-biased gender ratio. Otolith analyses suggested that the oldest individuals from the recently invaded area experienced superior growth conditions only in the most recent years, suggesting immigration into the area as adults. Our results suggest that intraspecific competition for food may cause continued dispersal of the species and that population demographics likely relate to invasion history.
10.	Bhattacharya, Romit, et al. (author) Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV : a report from the REPRIEVE trial 2024 In: Blood Advances. - 2473-9529. ; 8:4, s. 959-967 Journal article (peer-reviewed)abstract Clonal hematopoiesis of indeterminate potential (CHIP), the clonal expansion of myeloid cells with leukemogenic mutations, results in increased coronary artery disease (CAD) risk. CHIP is more prevalent among people with HIV (PWH), but the risk factors are unknown. CHIP was identified among PWH in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) using whole-exome sequencing. Logistic regression was used to associate sociodemographic factors and HIV-specific factors with CHIP adjusting for age, sex, and smoking status. In the studied global cohort of 4486 PWH, mean age was 49.9 (standard deviation [SD], 6.4) years; 1650 (36.8%) were female; and 3418 (76.2%) were non-White. CHIP was identified in 223 of 4486 (4.97%) and in 38 of 373 (10.2%) among those aged ≥60 years. Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.05-1.09; P < .0001) and smoking (OR, 1.37; 95% CI, 1.14-1.66; P < .001) associated with increased odds of CHIP. Globally, participants outside of North America had lower odds of CHIP including sub- Saharan Africa (OR, 0.57; 95% CI, 0.4-0.81; P = .0019), South Asia (OR, 0.45; 95% CI, 0.23-0.80; P = .01), and Latin America/Caribbean (OR, 0.56; 95% CI, 0.34-0.87; P = .014). Hispanic/Latino ethnicity (OR, 0.38; 95% CI, 0.23-0.54; P = .002) associated with significantly lower odds of CHIP. Among HIV-specific factors, CD4 nadir <50 cells/mm3 associated with a 1.9-fold (95% CI, 1.21-3.05; P = .006) increased odds of CHIP, with the effect being significantly stronger among individuals with short duration of antiretroviral therapy (ART; OR, 4.15; 95% CI, 1.51-11.1; P = .005) (Pinteraction= .0492). Among PWH at low-to-moderate CAD risk on stable ART, smoking, CD4 nadir, North American origin, and non-Hispanic ethnicity associated with increased odds of CHIP.
11.	Björk, Jonas, et al. (author) GFR estimation based on standardized creatinine and cystatin C : A European multicenter analysis in older adults 2018 In: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1437-4331 .- 1434-6621. ; 56:3, s. 422-435 Journal article (peer-reviewed)abstract Although recommended by the Kidney Disease Improving Global Outcomes, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPICR) creatinine equation was not targeted to estimate glomerular filtration rate (eGFR) among older adults. The Berlin Initiative Study (BIS1CR) equation was specifically developed in older adults, and the Lund-Malmö revised (LMRCR) and the Full Age Spectrum (FASCR) equations have shown promising results in older adults. Our aim was to validate these four creatinine equations, including addition of cystatin C in a large multicenter cohort of Europeans ≥70 years. A total of 3226 individuals (2638 with cystatin C) underwent GFR measurement (mGFR; median, 44 mL/min/1.73 m2) using plasma iohexol clearance. Bias, precision (interquartile range [IQR]), accuracy (percent of estimates ±30% of mGFR, P30), eGFR accuracy diagrams and probability diagrams to classify mGFR<45 mL/min/1.73 m2 were compared. The overall results of BIS1CR/CKD-EPICR/FASCR/LMRCR were as follows: median bias, 1.7/3.6/0.6/-0.7 mL/min/1.73 m2; IQR, 11.6/12.3/11.1/10.5 mL/min/1.73 m2; and P30, 77.5%/76.4%/80.9%/83.5% (significantly higher for LMR, p<0.001). Substandard P30 (<75%) was noted for all equations at mGFR<30 mL/min/1.73 m2, and at body mass index values <20 and ≥35 kg/m2. LMRCR had the most stable performance across mGFR subgroups. Only LMRCR and FASCR had a relatively constant small bias across eGFR levels. Probability diagrams exhibited wide eGFR intervals for all equations where mGFR<45 could not be confidently ruled in or out. Adding cystatin C improved P30 accuracy to 85.7/86.8/85.7/88.7 for BIS2CR+CYS/CKD-EPICR+CYS/FASCR+CYS/MEANLMR+CAPA. LMRCR and FASCR seem to be attractive alternatives to CKD-EPICR in estimating GFR by creatinine-based equations in older Europeans. Addition of cystatin C leads to important improvement in estimation performance.
12.	Butt, Linus, et al. (author) A molecular mechanism explaining albuminuria in kidney disease 2020 In: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 2:5, s. 461-474 Journal article (peer-reviewed)abstract Mammalian kidneys constantly filter large amounts of liquid, with almost complete retention of albumin and other macromolecules in the plasma. Breakdown of the three-layered renal filtration barrier results in loss of albumin into urine (albuminuria) across the wall of small renal capillaries, and is a leading cause of chronic kidney disease. However, exactly how the renal filter works and why its permeability is altered in kidney diseases is poorly understood. Here we show that the permeability of the renal filter is modulated through compression of the capillary wall. We collect morphometric data prior to and after onset of albuminuria in a mouse model equivalent to a human genetic disease affecting the renal filtration barrier. Combining quantitative analyses with mathematical modelling, we demonstrate that morphological alterations of the glomerular filtration barrier lead to reduced compressive forces that counteract filtration pressure, thereby resulting in capillary dilatation, and ultimately albuminuria. Our results reveal distinct functions of the different layers of the filtration barrier and expand the molecular understanding of defective renal filtration in chronic kidney disease.
13.	Cernea, Daniel, 1983-, et al. (author) Controlling In-Vehicle Systems with a Commercial EEG Headset: Performance and Cognitive Load 2012 In: Visualization of Large and Unstructured Data Sets. - : Schloss Dagstuhl - Leibniz-Zentrum für Informatik. Conference paper (peer-reviewed)abstract Humans have dreamed for centuries to control their surroundings solely by the power of theirminds. These aspirations have been captured by multiple science fiction creations, like theNeuromancer novel by William Gibson or the Brainstorm cinematic movie, to name just a few.Nowadays these dreams are slowly becoming reality due to a variety of brain-computer interfaces(BCI) that detect neural activation patterns and support the control of devices by brain signals.An important field in which BCIs are being successfully integrated is the interaction withvehicular systems. In this paper we evaluate the performance of BCIs, more specifically a commercialelectroencephalographic (EEG) headset, in combination with vehicle dashboard systemsand highlight the advantages and limitations of this approach. Further, we investigate the cognitiveload that drivers experience when interacting with secondary in-vehicle devices via touchcontrols or a BCI headset. As in-vehicle systems are increasingly versatile and complex, it becomesvital to capture the level of distraction and errors that controlling these secondary systemsmight introduce to the primary driving process. Our results suggest that the control with theEEG headset introduces less distraction to the driver, probably as it allows the eyes of the driverto remain focused on the road. Still, the control of the vehicle dashboard by EEG is efficientonly for a limited number of functions, after which increasing the number of in-vehicle controlsamplifies the detection of false commands.
14.	Cernea, Daniel, 1983-, et al. (author) EEG-based Measurement of Subjective Parameters in Evaluations 2011 In: <em> HCI International 2011 Posters' Extended Abstracts</em>. - Berlin Heidelberg : Springer. - 9783642220944 ; , s. 279-283 Conference paper (peer-reviewed)abstract Evaluating new approaches, be it new interaction techniques, new applications or even new hardware, is an important task, which has to be done to ensure both usability and user satisfaction. The drawback of evaluating subjective parameters is that this can be relatively time consuming, and the outcome is possibly quite imprecise. Considering the recent release of cost-efficient commercial EEG headsets, we propose the utilization of electro-encephalographic (EEG) devices for evaluation purposes. The goal of our research is to evaluate if a commercial EEG headset can provide cutting-edge support during user studies and evaluations. Our results are encouraging and suggest that wireless EEG technology is a viable alternative for measuring subjectivity in evaluation scenarios.
15.	Cernea, Daniel, 1983-, et al. (author) Measuring Subjectivity : Supporting Evaluations with the Emotiv EPOC Neuroheadset 2012 In: Künstliche Intelligenz. - : Springer Berlin/Heidelberg. - 0933-1875 .- 1610-1987. ; 26:2, s. 177-182 Journal article (peer-reviewed)abstract Since the dawn of the industrial era, modern devices and interaction methods have undergone rigorous evaluations in order to ensure their functionality and quality, as well as usability. While there are many methods for measuring objective data, capturing and interpreting subjective factors—like the feelings or states of mind of the users—is still an imprecise and usually post-event process. In this paper we propose the utilization of the Emotiv EPOC commercial electroencephalographic (EEG) neuroheadset for real-time support during evaluations and user studies. We show in two evaluation scenarios that the wireless EPOC headsets can be used efficiently for supporting subjectivity measurement. Additionally, we highlight situations that may result in a lower accuracy, as well as explore possible reasons and propose solutions for improving the error rates of the device.
16.	Furukawa, Toshi A., et al. (author) Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data 2021 In: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511 Research review (peer-reviewed)abstract Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
17.	Gumuser, Esra D., et al. (author) Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease 2023 In: Journal of the American College of Cardiology. - 0735-1097. ; 81:20, s. 1996-2009 Journal article (peer-reviewed)abstract Background: Clonal hematopoiesis of indeterminate potential (CHIP)—the age-related clonal expansion of blood stem cells with leukemia-associated mutations—is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear. Objectives: This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD. Methods: Individuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression. Results: Of 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001). Conclusions: CHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP.
18.	Guo, Renjun, et al. (author) Degradation mechanisms of perovskite solar cells under vacuum and one atmosphere of nitrogen 2021 In: Nature Energy. - : Springer Nature. - 2058-7546. ; 6:10, s. 977- Journal article (peer-reviewed)abstract Extensive studies have focused on improving the operational stability of perovskite solar cells, but few have surveyed the fundamental degradation mechanisms. One aspect overlooked in earlier works is the effect of the atmosphere on device performance during operation. Here we investigate the degradation mechanisms of perovskite solar cells operated under vacuum and under a nitrogen atmosphere using synchrotron radiation-based operando grazing-incidence X-ray scattering methods. Unlike the observations described in previous reports, we find that light-induced phase segregation, lattice shrinkage and morphology deformation occur under vacuum. Under nitrogen, only lattice shrinkage appears during the operation of solar cells, resulting in better device stability. The different behaviour under nitrogen is attributed to a larger energy barrier for lattice distortion and phase segregation. Finally, we find that the migration of excessive PbI2 to the interface between the perovskite and the hole transport layer degrades the performance of devices under vacuum or under nitrogen. Understanding degradation mechanisms in perovskite solar cells is key to their development. Now, Guo et al. show a greater degradation of the perovskite structure and morphology for devices operated under vacuum than under nitrogen.
19.	Jabado, Rima W., et al. (author) Troubled waters : Threats and extinction risk of the sharks, rays and chimaeras of the Arabian Sea and adjacent waters 2018 In: Fish and Fisheries. - : Wiley-Blackwell. - 1467-2960 .- 1467-2979. ; 19:6, s. 1043-1062 Journal article (peer-reviewed)abstract The extinction risk of sharks, rays and chimaeras is higher than that for most other vertebrates due to low intrinsic population growth rates of many species and the fishing intensity they face. The Arabian Sea and adjacent waters border some of the most important chondrichthyan fishing and trading nations globally, yet there has been no previous attempt to assess the conservation status of species occurring here. Using IUCN Red List of Threatened Species Categories and Criteria and their guidelines for application at the regional level, we present the first assessment of extinction risk for 153 species of sharks, rays and chimaeras. Results indicate that this region, home to 15% of described chondrichthyans including 30 endemic species, has some of the most threatened chondrichthyan populations in the world. Seventy-eight species (50.9%) were assessed as threatened (Critically Endangered, Endangered or Vulnerable), and 27 species (17.6%) as Near Threatened. Twenty-nine species (19%) were Data Deficient with insufficient information to assess their status. Chondrichthyan populations have significantly declined due to largely uncontrolled and unregulated fisheries combined with habitat degradation. Further, there is limited political will and national and regional capacities to assess, manage, conserve or rebuild stocks. Outside the few deepsea locations that are lightly exploited, the prognosis for the recovery of most species is poor in the near-absence of management. Concerted national and regional management measures are urgently needed to ensure extinctions are avoided, the sustainability of more productive species is secured, and to avoid the continued thinning of the regional food security portfolio.
20.	Jaiswal, Siddhartha, et al. (author) Age-Related Clonal Hematopoiesis Associated with Adverse Outcomes. 2014 In: New England Journal of Medicine. - 0028-4793. ; 371:26, s. 2488-2498 Journal article (peer-reviewed)abstract Background The incidence of hematologic cancers increases with age. These cancers are associated with recurrent somatic mutations in specific genes. We hypothesized that such mutations would be detectable in the blood of some persons who are not known to have hematologic disorders. Methods We analyzed whole-exome sequencing data from DNA in the peripheral-blood cells of 17,182 persons who were unselected for hematologic phenotypes. We looked for somatic mutations by identifying previously characterized single-nucleotide variants and small insertions or deletions in 160 genes that are recurrently mutated in hematologic cancers. The presence of mutations was analyzed for an association with hematologic phenotypes, survival, and cardiovascular events. Results Detectable somatic mutations were rare in persons younger than 40 years of age but rose appreciably in frequency with age. Among persons 70 to 79 years of age, 80 to 89 years of age, and 90 to 108 years of age, these clonal mutations were observed in 9.5% (219 of 2300 persons), 11.7% (37 of 317), and 18.4% (19 of 103), respectively. The majority of the variants occurred in three genes: DNMT3A, TET2, and ASXL1. The presence of a somatic mutation was associated with an increase in the risk of hematologic cancer (hazard ratio, 11.1; 95% confidence interval [CI], 3.9 to 32.6), an increase in all-cause mortality (hazard ratio, 1.4; 95% CI, 1.1 to 1.8), and increases in the risks of incident coronary heart disease (hazard ratio, 2.0; 95% CI, 1.2 to 3.4) and ischemic stroke (hazard ratio, 2.6; 95% CI, 1.4 to 4.8). Conclusions Age-related clonal hematopoiesis is a common condition that is associated with increases in the risk of hematologic cancer and in all-cause mortality, with the latter possibly due to an increased risk of cardiovascular disease. (Funded by the National Institutes of Health and others.).
21.	Järås, Marcus, et al. (author) Csnk1a1 inhibition has p53-dependent therapeutic efficacy in acute myeloid leukemia 2014 In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 211:4, s. 605-612 Journal article (peer-reviewed)abstract Despite extensive insights into the underlying genetics and biology of acute myeloid leukemia (AML), overall survival remains poor and new therapies are needed. We found that casein kinase 1 alpha (Csnk1a1), a serine-threonine kinase, is essential for AML cell survival in vivo. Normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected by shRNA-mediated knockdown of Csnk1a1. To identify downstream mediators of Csnk1a1 critical for leukemia cells, we performed an in vivo pooled shRNA screen and gene expression profiling. We found that Csnk1a1 knockdown results in decreased Rps6 phosphorylation, increased p53 activity, and myeloid differentiation. Consistent with these observations, p53-null leukemias were insensitive to Csnk1a1 knockdown. We further evaluated whether D4476, a casein kinase 1 inhibitor, would exhibit selective antileukemic effects. Treatment of leukemia stem cells (LSCs) with D4476 showed highly selective killing of LSCs over normal HSPCs. In summary, these findings demonstrate that Csnk1a1 inhibition causes reduced Rps6 phosphorylation and activation of p53, resulting in selective elimination of leukemia cells, revealing Csnk1a1 as a potential therapeutic target for the treatment of AML.
22.	Laucyte-Cibulskiene, Agne, et al. (author) Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease : focus on sex-specific associations with vascular outcomes and all-cause mortality 2021 In: Biology of Sex Differences. - : Springer Science and Business Media LLC. - 2042-6410. ; 12:1 Journal article (peer-reviewed)abstract Background: Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods: ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results: Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02). Conclusions: In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.
23.	Lehr, Dirk, et al. (author) Occupational e-mental health : current approaches and promising perspectives for promoting mental health in workers 2016 In: Healthy at work. - Cham : Springer. - 9783319323299 - 9783319323312 ; , s. 257-281 Book chapter (peer-reviewed)abstract During the past few years, the Internet has started to change lifestyles and affect all life domains, including working life. It is also increasingly used for targeting mental health issues. The “application of information technology in mental and behavioral health” (Andersson G, Riper H, Carlbring P (2014) Editorial: Introducing Internet interventions—a new open access journal. Internet Intervent 1:1–2) is becoming common in health-care; interventions have already been incorporated into routine care in countries such as the Netherlands, Sweden, the UK, Australia, and the USA. As a next step, Internet interventions in the area of occupational health are progressively emerging. They may offer an evidence-based, cost-effective, and convenient way of promoting workers’ mental health on a large scale. Currently, Internet interventions for workers are the most promising approach in the field of occupational e-mental health. The evolution of occupational e-mental health is embedded in interdisciplinary research, practice, and policy. In the first section of this chapter, the origins of occupational e-mental health will be outlined and a definition proposed. Following this, different approaches to occupational e-mental health will be described and their potentials elucidated. A comparison between Internet interventions and traditional stress-management trainings will provide further insights into the design and characteristics of the most elaborated approach in occupational e-mental health. Subsequently, various Internet training programs will be introduced and the evidence for their efficacy summarized. Finally, important topics for further research and implementation will be outlined.
24.	Lin, Amy Erica, et al. (author) Clonal Hematopoiesis of Indeterminate Potential With Loss of Tet2 Enhances Risk for Atrial Fibrillation Through Nlrp3 Inflammasome Activation 2024 In: Circulation. - 0009-7322. ; 149:18, s. 1419-1434 Journal article (peer-reviewed)abstract BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), a common age-associated phenomenon, associates with increased risk of both hematological malignancy and cardiovascular disease. Although CHIP is known to increase the risk of myocardial infarction and heart failure, the influence of CHIP in cardiac arrhythmias, such as atrial fibrillation (AF), is less explored. METHODS: CHIP prevalence was determined in the UK Biobank, and incident AF analysis was stratified by CHIP status and clone size using Cox proportional hazard models. Lethally irradiated mice were transplanted with hematopoietic-specific loss of Tet2, hematopoietic-specific loss of Tet2 and Nlrp3, or wild-type control and fed a Western diet, compounded with or without NLRP3 (NLR [NACHT, LRR {leucine rich repeat}] family pyrin domain containing protein 3) inhibitor, NP3-361, for 6 to 9 weeks. Mice underwent in vivo invasive electrophysiology studies and ex vivo optical mapping. Cardiomyocytes from Ldlr−/− mice with hematopoietic-specific loss of Tet2 or wild-type control and fed a Western diet were isolated to evaluate calcium signaling dynamics and analysis. Cocultures of pluripotent stem cell-derived atrial cardiomyocytes were incubated with Tet2deficient bone marrow-derived macrophages, wild-type control, or cytokines IL-1β (interleukin 1β) or IL-6 (interleukin 6). RESULTS: Analysis of the UK Biobank showed individuals with CHIP, in particular TET2 CHIP, have increased incident AF. Hematopoietic-specific inactivation of Tet2 increases AF propensity in atherogenic and nonatherogenic mouse models and is associated with increased Nlrp3 expression and CaMKII (Ca2+/calmodulin-dependent protein kinase II) activation, with AF susceptibility prevented by inactivation of Nlrp3. Cardiomyocytes isolated from Ldlr−/− mice with hematopoietic inactivation of Tet2 and fed a Western diet have impaired calcium release from the sarcoplasmic reticulum into the cytosol, contributing to atrial arrhythmogenesis. Abnormal sarcoplasmic reticulum calcium release was recapitulated in cocultures of cardiomyocytes with the addition of Tet2-deficient macrophages or cytokines IL-1β or IL-6. CONCLUSIONS: We identified a modest association between CHIP, particularly TET2 CHIP, and incident AF in the UK Biobank population. In a mouse model of AF resulting from hematopoietic-specific inactivation of Tet2, we propose altered calcium handling as an arrhythmogenic mechanism, dependent on Nlrp3 inflammasome activation. Our data are in keeping with previous studies of CHIP in cardiovascular disease, and further studies into the therapeutic potential of NLRP3 inhibition for individuals with TET2 CHIP may be warranted.
25.	Olech, Peter-Scott, et al. (author) Digital Interactive Public Pinboards for Disaster and Crisis Management : Concept and Prototype Design 2012 In: Proceedings of the 2012 International Conference on Information and Knowledge Engineering (IKE '12) at the 2012 World Congress in Computer Science, Computer Engineering, and Applied Computing (WorldComp '12). - : CSREA Press. - 1601322038 Conference paper (peer-reviewed)abstract Recent natural disasters, like the earthquakesin Port-au-Prince, Haiti (2010), Christchurch, New Zealand(2011) and the Tohoku earthquake in Japan (2011), whichalso triggered a tsunami resulting in the catastrophic failureof numerous nuclear power plants, pose the question howto support first responders in providing fast and adequatehelp. When first responders arrive on-site it is crucial thatthe flow of information is ensured: important fields arelogistics, communication, personal management and the deploymentof up-to-date information. Unfortunately the eventsin the past showed that there are certain shortcomings,especially in terms of communicating information from localresponders to arriving responders. Our approach proposesthe utilization of large public displays, seizing the ideaof traditional pinboards, referred in our work as DigitalInteractive Public Pinboards (DIPP). DIPPs are set up inhot spot locations and provide fast and reliable informationto first responders as well as citizens in the area of thenatural disaster.
26.	Olech, Peter-Scott, et al. (author) V.I.P. : Supporting Digital Earth Ideas through Visualization, Interaction and Presentation Screens 2010 In: <em>Proceedings of the 7th Taipei International Digital Earth Symposium (TIDES '10). </em>. Conference paper (peer-reviewed)
27.	Pruisscher, Peter, 1988- (author) Functional genomics of diapause in two temperate butterflies 2019 Doctoral thesis (other academic/artistic)abstract Natural selection will act on a given phenotype to maximize fitness in a particular environment, even if this would result in reduced fitness in other environments. In insects some of the strongest selection pressures act on timing life cycles to seasonal variation in environmental conditions, in order to maximize growth, reproduction, and to anticipate the onset of winter. Many temperate insects survive winter by entering a pre-programmed state of developmental arrest, called diapause. The decision to induce diapause is predominantly based on measuring day length. Populations have adapted to latitudinal variation in photoperiod, thereby synchronizing with local seasonal variation. However, there is no general understanding of the genetic basis for controlling diapause induction, maintenance and termination. In this thesis I aimed to gain a better understanding of the genetic basis underlying variation in the induction decision, as well as to gain insights into gene expression changes during diapause in temperate butterflies. I started by revealing local adaptation in the photoperiodic response of two divergent populations of Pieris napi (Paper I). I found that variation in diapause induction among populations of both P. napi and Pararge aegeria showed strong sex-linked inheritance in inter-population crosses (Paper I and II). The genome-wide variation across populations was relatively low in both species. However, there was strong divergence in genomic regions containing the circadian clock genes timeless and period in P. aegeria, and period, cycle, and clock in P. napi. The genetic variation in these specific regions segregated between diapausing and direct developing individuals of inter-population crosses, showing that allelic variation at few genes with known functions in the circadian clock correlated to variation in diapause induction (Paper II and III). Furthermore, I investigated the transcriptional dynamics in two tissues (head and abdomen) during diapause (Paper IV). Already at the first day of pupal development there are on average 409 differentially expressed genes (DEG) each up and down regulated between the direct development and diapause pathways, and this increases dramatically across these formative stages to an average of 2695. Moreover, gene expression is highly dynamic during diapause, showing more than 2600 DEG’s in the first month of diapause development, but only 20 DEG’s in the third month. Moreover, gene expression is independent of environmental conditions, revealing a pre-programmed transcriptional landscape that is active during the winter. Still, adults emerging from either the direct or diapause pathways do not show large transcriptomic differences, suggesting the adult phenotype is strongly canalized. Thus, by integrating whole-genome scans with targeted genotyping and bulk-segregant analyses in population crosses, I demonstrate that adaptive variation in seasonal life cycle regulation in the two butterflies P. napi and P. aegeria both converge on genes of the circadian clock, suggesting convergent evolution in these distantly related butterflies.Moreover, the diapause program is a dynamic process with a distinct transcriptional profile in comparison to direct development, showing that on a transcriptome level diapause development and direct development are two distinct developmental strategies.
28.	Puram, Rishi V, et al. (author) Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML 2016 In: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 165:2, s. 16-303 Journal article (peer-reviewed)abstract Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.
29.	Schuermans, Art, et al. (author) Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias 2024 In: European Heart Journal. - 0195-668X. ; 45:10, s. 791-805 Journal article (peer-reviewed)abstract Background and Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutaAims tions, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias.Methods UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested. Results This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04–1.18; P = .001] and 1.13 (95% CI 1.05–1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01–1.19; P = .031) and 1.13 (95% CI 1.03–1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00–1.34; P = .049) and 1.22 (95% CI 1.03–1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07–1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR. Conclusions CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.
30.	Tan, Pepe, 1988, et al. (author) Characterizing phase change materials using the T-History method: On the factors influencing the accuracy and precision of the enthalpy-temperature curve 2018 In: Thermochimica Acta. - : Elsevier BV. - 0040-6031. ; 666, s. 212-228 Journal article (peer-reviewed)abstract While research on using the latent heat of so called phase change materials (PCMs) for thermal energy storage has gained increasing interest in the last decade, the measurement of its thermal properties are still subject to research. The T-History method has been frequently used by researchers to measure the enthalpy–temperature curve of PCMs but the factors influencing its accuracy and precision have rarely been discussed. This work provides a systematic experimental study of an organic PCM based on different insulated sample holders. It is first shown that the data evaluation method has to be adjusted against noise to improve both accuracy and precision for all experimental setups. The results moreover show that neglecting the insulation thermal mass in the experimental setup leads to systematic errors in the enthalpy results due to oversimplification of the mathematical model. This confirms a previous numerical study by the authors. It is recommended that either the mathematical model or the experimental setup are adjusted in future work to decrease this error. Until then it is generally recommended to use sample holders with a high ratio between the thermal mass of the PCM to the insulated sample holder. This is further supported by a measurement uncertainty analysis via Monte Carlo simulations.
31.	Tan, Pepe, 1988, et al. (author) Correction of the enthalpy–temperature curve of phase change materials obtained from the T-History method based on a transient heat conduction model 2017 In: International Journal of Heat and Mass Transfer. - : Elsevier BV. - 0017-9310. ; 105:February 2017, s. 573-588 Journal article (peer-reviewed)abstract Utilizing the latent heat of materials undergoing phase transitions, or so called phase change materials (PCMs), for thermal energy storage offers higher storage densities compared to purely sensible thermal energy storages. For evaluating different PCMs the T-History method has often been applied by researchers in order to determine the characteristic enthalpy versus temperature curves. In previous research many different T-History setups are described where the sample holder is insulated. The intention is to decrease internal temperature gradients inside the sample holder with PCM. However, in the mathematical model for evaluating the enthalpy curve of the PCM based on the measured temperature response, the thermal mass of the insulation around the sample holder has been neglected.In this study, a one dimensional numerical transient heat transfer model is used to show that neglecting the insulation thermal mass leads to a systematic error on the obtained enthalpy versus temperature curves. The error is caused by deviations in the transient heat flows for reference and PCM sample when both are cooled down or heated, respectively. These deviations can be corrected by introducing a correction factor.
32.	Thelen, Sebastian, et al. (author) D.I.P. – A Digital Interactive Pinboard with Support for Smart Device Interaction 2010 In: In Proceedings of the IASTED International Conference on Portable Lifestyle Devices (PLD '10). - : ACTA Press. Conference paper (peer-reviewed)abstract Smart phone devices are more popular than ever and becauseof their processing power able to deal with almost any kind of multimedia content, i.e., videos, audio, images,and text documents. Files are often shared in direct ways, for example via email, or by uploading them to one of the popular internet platforms. In this paper we present the Digital Interactive Pinboard (DIP), an alternative approach for sharing multimedia files via smart phones on large display systems. DIPs are based on the idea of traditional bulletin boards and like these set up in well visited places, so called hotspots. Systems implementing the approach do not ust act as passive public displays, but support a series of advanced interaction concepts optimized for smart phones. DIPs imply a strong social component, since physical presence is required to interact with board items that can be organized based on various group-specific criteria. We argue that a combination of physical and virtual aspects has impact on how users interact with the system and the way information is perceived. We introduce and analyze the approach from a conceptual point of view, as well as from the implementation side. We further describe two scenarios in which our approach has been employed to exchange information in well-frequented locations.
33.	Wen, Peter J., et al. (author) Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane 2016 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7 Journal article (peer-reviewed)abstract Vesicle fusion is executed via formation of an Omega-shaped structure (Omega-profile), followed by closure (kiss-and-run) or merging of the Omega-profile into the plasma membrane (full fusion). Although Omega-profile closure limits release but recycles vesicles economically, Omega-profile merging facilitates release but couples to classical endocytosis for recycling. Despite its crucial role in determining exocytosis/endocytosis modes, how Omega-profile merging is mediated is poorly understood in endocrine cells and neurons containing small similar to 30-300 nm vesicles. Here, using confocal and super-resolution STED imaging, force measurements, pharmacology and gene knockout, we show that dynamic assembly of filamentous actin, involving ATP hydrolysis, N-WASP and formin, mediates Omega-profile merging by providing sufficient plasma membrane tension to shrink the Omega-profile in neuroendocrine chromaffin cells containing similar to 300 nm vesicles. Actin-directed compounds also induce Omega-profile accumulation at lamprey synaptic active zones, suggesting that actin may mediate Omega-profile merging at synapses. These results uncover molecular and biophysical mechanisms underlying Omega-profile merging.
34.	Yu, Zhi, et al. (author) Genetic modification of inflammation- and clonal hematopoiesis-associated cardiovascular risk 2023 In: Journal of Clinical Investigation. - 0021-9738. ; 133:18 Journal article (peer-reviewed)abstract Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVDs), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. We identified CHIP using whole-exome sequencing data of blood DNA and modeled as a composite, considering all driver genes together, as well as separately for common drivers (DNMT3A, TET2, ASXL1, and JAK2). We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identified IL1RAP as a potential key molecule for CHIP-associated CVD risk across genes and increased AIM2 gene expression leading to heightened JAK2- and ASXL1-associated CVD risk. We show that CRISPR-induced Asxl1-mutated murine macrophages had a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVDprotective effect of IL10 expression in ASXL1 CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides evidence to support gene-specific strategies to address CHIP-associated CVD risk.
35.	Zekavat, Seyedeh M., et al. (author) TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease 2023 In: Nature Cardiovascular Research. - : Springer Science and Business Media LLC. - 2731-0590. ; 2:2, s. 144-158 Journal article (peer-reviewed)abstract Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP) are associated with an increased risk of hematologic malignancy, coronary artery disease and all-cause mortality. Here we analyze the relation between CHIP status and incident peripheral artery disease (PAD) and atherosclerosis, using whole-exome sequencing and clinical data from the UK Biobank and the Mass General Brigham Biobank. CHIP associated with incident PAD and atherosclerotic disease across multiple beds, with increased risk among individuals with CHIP driven by mutation in DNA damage repair (DDR) genes, such as TP53 and PPM1D. To model the effects of DDR-induced CHIP on atherosclerosis, we used a competitive bone marrow transplantation strategy and generated atherosclerosis-prone Ldlr −/− chimeric mice carrying 20% p53-deficient hematopoietic cells. The chimeric mice were analyzed 13 weeks after grafting and showed increased aortic plaque size and accumulation of macrophages within the plaque, driven by increased proliferation of p53-deficient plaque macrophages. In summary, our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system beyond the coronary arteries and provide genetic and experimental support for a direct causal contribution of TP53-mutant CHIP to atherosclerosis.

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