| 1. |
- Mer, Arvind Singh, et al.
(författare)
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Study design requirements for RNA sequencing-based breast cancer diagnostics
- 2016
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Ingår i: Scientific Reports. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2045-2322.
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Tidskriftsartikel (refereegranskat)abstract
- Sequencing-based molecular characterization of tumors provides information required for individualized cancer treatment. There are well-defined molecular subtypes of breast cancer that provide improved prognostication compared to routine biomarkers. However, molecular subtyping is not yet implemented in routine breast cancer care. Clinical translation is dependent on subtype prediction models providing high sensitivity and specificity. In this study we evaluate sample size and RNA-sequencing read requirements for breast cancer subtyping to facilitate rational design of translational studies. We applied subsampling to ascertain the effect of training sample size and the number of RNA sequencing reads on classification accuracy of molecular subtype and routine biomarker prediction models (unsupervised and supervised). Subtype classification accuracy improved with increasing sample size up to N = 750 (accuracy = 0.93), although with a modest improvement beyond N = 350 (accuracy = 0.92). Prediction of routine biomarkers achieved accuracy of 0.94 (ER) and 0.92 (Her2) at N = 200. Subtype classification improved with RNA-sequencing library size up to 5 million reads. Development of molecular subtyping models for cancer diagnostics requires well-designed studies. Sample size and the number of RNA sequencing reads directly influence accuracy of molecular subtyping. Results in this study provide key information for rational design of translational studies aiming to bring sequencing-based diagnostics to the clinic.
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| 2. |
- Rantalainen, Mattias, et al.
(författare)
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Sequencing-based breast cancer diagnostics as an alternative to routine biomarkers
- 2016
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Ingår i: Scientific Reports. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 2045-2322.
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Tidskriftsartikel (refereegranskat)abstract
- Sequencing-based breast cancer diagnostics have the potential to replace routine biomarkers and provide molecular characterization that enable personalized precision medicine. Here we investigate the concordance between sequencing-based and routine diagnostic biomarkers and to what extent tumor sequencing contributes clinically actionable information. We applied DNA- and RNA-sequencing to characterize tumors from 307 breast cancer patients with replication in up to 739 patients. We developed models to predict status of routine biomarkers (ER, HER2,Ki-67, histological grade) from sequencing data. Non-routine biomarkers, including mutations in BRCA1, BRCA2 and ERBB2(HER2), and additional clinically actionable somatic alterations were also investigated. Concordance with routine diagnostic biomarkers was high for ER status (AUC = 0.95;AUC(replication) = 0.97) and HER2 status (AUC = 0.97;AUC(replication) = 0.92). The transcriptomic grade model enabled classification of histological grade 1 and histological grade 3 tumors with high accuracy (AUC = 0.98;AUC(replication) = 0.94). Clinically actionable mutations in BRCA1, BRCA2 and ERBB2(HER2) were detected in 5.5% of patients, while 53% had genomic alterations matching ongoing or concluded breast cancer studies. Sequencing-based molecular profiling can be applied as an alternative to histopathology to determine ER and HER2 status, in addition to providing improved tumor grading and clinically actionable mutations and molecular subtypes. Our results suggest that sequencing-based breast cancer diagnostics in a near future can replace routine biomarkers
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| 3. |
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| 4. |
- Abdollahi Sani, Negar, et al.
(författare)
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Flexible lamination-fabricated ultra-high frequency diodes based on self-supporting semiconducting composite film of silicon micro-particles and nano-fibrillated cellulose
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Low cost and flexible devices such as wearable electronics, e-labels and distributed sensors will make the future "internet of things" viable. To power and communicate with such systems, high frequency rectifiers are crucial components. We present a simple method to manufacture flexible diodes, operating at GHz frequencies, based on self-adhesive composite films of silicon micro-particles (Si-ΌPs) and glycerol dispersed in nanofibrillated cellulose (NFC). NFC, Si-ΌPs and glycerol are mixed in a water suspension, forming a self-supporting nanocellulose-silicon composite film after drying. This film is cut and laminated between a flexible pre-patterned Al bottom electrode and a conductive Ni-coated carbon tape top contact. A Schottky junction is established between the Al electrode and the Si-ΌPs. The resulting flexible diodes show current levels on the order of mA for an area of 2 mm2, a current rectification ratio up to 4 × 103 between 1 and 2 V bias and a cut-off frequency of 1.8 GHz. Energy harvesting experiments have been demonstrated using resistors as the load at 900 MHz and 1.8 GHz. The diode stack can be delaminated away from the Al electrode and then later on be transferred and reconfigured to another substrate. This provides us with reconfigurable GHz-operating diode circuits.
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| 5. |
- Abramavicius, V., et al.
(författare)
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Role of coherence and delocalization in photo-induced electron transfer at organic interfaces
- 2016
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6:32914
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Tidskriftsartikel (refereegranskat)abstract
- Photo-induced charge transfer at molecular heterojunctions has gained particular interest due to the development of organic solar cells (OSC) based on blends of electron donating and accepting materials. While charge transfer between donor and acceptor molecules can be described by Marcus theory, additional carrier delocalization and coherent propagation might play the dominant role. Here, we describe ultrafast charge separation at the interface of a conjugated polymer and an aggregate of the fullerene derivative PCBM using the stochastic Schrodinger equation (SSE) and reveal the complex time evolution of electron transfer, mediated by electronic coherence and delocalization. By fitting the model to ultrafast charge separation experiments, we estimate the extent of electron delocalization and establish the transition from coherent electron propagation to incoherent hopping. Our results indicate that even a relatively weak coupling between PCBM molecules is sufficient to facilitate electron delocalization and efficient charge separation at organic interfaces.
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| 6. |
- Adamik, Peter, et al.
(författare)
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Barrier crossing in small avian migrants : individual tracking reveals prolonged nocturnal flights into the day as a common migratory strategy
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Over decades it has been unclear how individual migratory songbirds cross large ecological barriers such as seas or deserts. By deploying light-level geolocators on four songbird species weighing only about 12 g, we found that these otherwise mainly nocturnal migrants seem to regularly extend their nocturnal flights into the day when crossing the Sahara Desert and the Mediterranean Sea. The proportion of the proposed diurnally flying birds gradually declined over the day with similar landing patterns in autumn and spring. The prolonged flights were slightly more frequent in spring than in autumn, suggesting tighter migratory schedules when returning to breeding sites. Often we found several patterns for barrier crossing for the same individual in autumn compared to the spring journey. As only a small proportion of the birds flew strictly during the night and even some individuals might have flown non-stop, we suggest that prolonged endurance flights are not an exception even in small migratory species. We emphasise an individual’s ability to perform both diurnal and nocturnal migration when facing the challenge of crossing a large ecological barrier to successfully complete a migratory journey.
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| 7. |
- Aguirre-Gutiérrez, Jesús, et al.
(författare)
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Functional traits help to explain half-century long shifts in pollinator distributions
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Changes in climate and land use can have important impacts on biodiversity. Species respond to such environmental modifications by adapting to new conditions or by shifting their geographic distributions towards more suitable areas. The latter might be constrained by species’ functional traits that influence their ability to move, reproduce or establish. Here, we show that functional traits related to dispersal, reproduction, habitat use and diet have influenced how three pollinator groups (bees, butterflies and hoverflies) responded to changes in climate and land-use in the Netherlands since 1950. Across the three pollinator groups, we found pronounced areal range expansions (>53%) and modelled range shifts towards the north (all taxa: 17–22 km), west (bees: 14 km) and east (butterflies: 11 km). The importance of specific functional traits for explaining distributional changes varied among pollinator groups. Larval diet preferences (i.e. carnivorous vs. herbivorous/detritivorous and nitrogen values of host plants, respectively) were important for hoverflies and butterflies, adult body size for hoverflies, and flight period length for all groups. Moreover, interactions among multiple traits were important to explain species’ geographic range shifts, suggesting that taxon-specific multi-trait analyses are needed to predict how global change will affect biodiversity and ecosystem services.
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| 8. |
- 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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| 9. |
- Alatalo, J. M., et al.
(författare)
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Impacts of different climate change regimes and extreme climatic events on an alpine meadow community
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Climate variability is expected to increase in future but there exist very few experimental studies that apply different warming regimes on plant communities over several years. We studied an alpine meadow community under three warming regimes over three years. Treatments consisted of (a) a constant level of warming with open-top chambers (ca. 1.9 degrees C above ambient), (b) yearly stepwise increases in warming (increases of ca. 1.0, 1.9 and 3.5 degrees C), and (c) pulse warming, a single first-year pulse event of warming (increase of ca. 3.5 degrees C). Pulse warming and stepwise warming was hypothesised to cause distinct first-year and third-year effects, respectively. We found support for both hypotheses; however, the responses varied among measurement levels (whole community, canopy, bottom layer, and plant functional groups), treatments, and time. Our study revealed complex responses of the alpine plant community to the different experimentally imposed climate warming regimes. Plant cover, height and biomass frequently responded distinctly to the constant level of warming, the stepwise increase in warming and the extreme pulse-warming event. Notably, we found that stepwise warming had an accumulating effect on biomass, the responses to the different warming regimes varied among functional groups, and the short-term perturbations had negative effect on species richness and diversity
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| 10. |
- Alene Asres, Georgies, et al.
(författare)
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A novel WS2 nanowire-nanoflake hybrid material synthesized from WO3 nanowires in sulfur vapor
- 2016
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 6:25610
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Tidskriftsartikel (refereegranskat)abstract
- In this work, WS2 nanowire-nanoflake hybrids are synthesized by the sulfurization of hydrothermally grown WO3 nanowires. The influence of temperature on the formation of products is optimized to grow WS2 nanowires covered with nanoflakes. Current-voltage and resistance-temperature measurements carried out on random networks of the nanostructures show nonlinear characteristics and negative temperature coefficient of resistance indicating that the hybrids are of semiconducting nature. Bottom gated field effect transistor structures based on random networks of the hybrids show only minor modulation of the channel conductance upon applied gate voltage, which indicates poor electrical transport between the nanowires in the random films. On the other hand, the photo response of channel current holds promise for cost-efficient solution process fabrication of photodetector devices working in the visible spectral range.
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