| 1. |
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| 2. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 9. |
- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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| 12. |
- Bao, Qinye, 1985-
(författare)
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Interface Phenomena in Organic Electronics
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic electronics based on organic semiconductors offer tremendous advantages compared to traditional inorganic counterparts such as low temperature processing, light weight, low manufacturing cost, high throughput and mechanical flexibility. Many key electronic processes in organic electronic devices, e.g. charge injection/extraction, charge recombination and exciton dissociation, occur at interfaces, significantly controlling performance and function. Understanding/modeling the interface energetics at organic-electrode/organic-organic heterojunctions is one of the crucial issues for organic electronic technologies to provide a route for improving device efficiency, which is the aim of the research presented in this thesis.Integer charge transfer (ICT) states pre-existed in the dark and created as a consequence of Fermi level equilibrium at donor-acceptor interface have a profound effect on open circuit voltage in organic bulk heterojunction photovoltaics. ICT state formation causes vacuum level misalignment that yields a roughly constant effective donor ionization potential to acceptor electron affinity energy difference at the donor-acceptor interface, even though there is a large variation in electron affinity for the fullerene series. The large variation in open circuit voltage for the corresponding device series instead is found to be a consequence of trap-assisted recombination via integer charge transfer states. Based on the results, novel design rules for optimizing open circuit voltage and performance of organic bulk heterojunction solar cells are proposed.Doping and insertion of interlayer are two established methods for enhancing charge injection/extraction properties at organic-electrode interface. By studying the energy level alignment behavior at low to intermediate doping levels for molecule-doped conjugated polymer/electrode interfaces, we deduce that two combined processes govern the interface energetics: (i) equilibration of the Fermi level due to oxidation (or reduction) of polymer sites at the interface as per the ICT model and (ii) a double dipole step induced by image charge from the dopant-polymer charge transfer complex that causes a shift of the work function. Such behavior is expected to hold in general for low to intermediate level doped organic semiconductor systems. The unified model is further extended to be suitable for conjugated electrolyte/electrode interfaces, revealing the design rules for achieving the smallest charge injection/extraction barrier for both thin tunneling and thick charge transporting conjugated electrolyte interlayers.To probe into the energy level spatial extension at interfaces, we employ the original approach of building and characterizing multilayers composed of a well-defined number of polymer monolayers with the Langmuir-Shäfer method to control polymer film uniformity and thicknesses, avoiding the problems associated with spin-coating ultrathin films. The disordered/amorphous films feature smaller, and in fact negligible, energy level bending compared to the more well-ordered films, in contradiction with existing models. It is found that that energy level bending depends on the ICT state distribution rather than the density of states of the neutral polymer chains in relation to the Fermi energy, thus taking into account the Coulomb energy associated with charging the polymer chain and transferring a charge across the interface. Based on this work, a general model for energy level bending in absence of significant doping of conjugated polymer films is proposed.Organic semiconductors are sensitive to ambient atmosphere that can influence the energetics. The degradation effects of common PCBM film induced by oxygen and water are found to be completely different. Upon exposure to oxygen, the work function is down-shifted by ~ 0.15 eV compared to the ICT curve of the pristine PCBM film, originating from the weak interaction between the fullerene part of PCBM and oxygen, and this can be reversed by thermal treatment in vacuum. The down-shift in energetics will cause a loss in open circuit voltage at electrode interface, but aids free charge generation at donor-acceptor interface. Upon exposure to water, there is irreversible extensive broadening and bleaching of the valence electronic structure features as well as a substantial decrease of work function and ionization potential, severely degrading the transport properties.Overall, the research results in this thesis thus give a deeper understanding of interface phenomena in organic electronics, especially regard to organic solar cells, aimed to further improve the device operation efficiency and lifetime.
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| 13. |
- Bombarda, F., et al.
(författare)
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Runaway electron beam control
- 2019
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
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Tidskriftsartikel (refereegranskat)
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| 14. |
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| 15. |
- Kilpelainen, TO, et al.
(författare)
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Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
- 2019
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Ingår i: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
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Tidskriftsartikel (refereegranskat)abstract
- Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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| 17. |
- Liu, Hangning, et al.
(författare)
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Cobalt Oxide Arrays Anchored to Copper Foam as Efficient Binder‐free Anode for Lithium Ion Batteries
- 2023
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Ingår i: ChemPhysChem. - : Wiley-VCH Verlagsgesellschaft. - 1439-4235 .- 1439-7641. ; 24:17
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Tidskriftsartikel (refereegranskat)abstract
- The development of lithium-ion batteries with simplified assembling steps and fast charge capability is crucial for current battery applications. In this study, we propose a simple in-situ strategy for the construction of high-dispersive cobalt oxide (CoO) nanoneedle arrays, which grow vertically on a copper foam substrate. It is demonstrated that this nanoneedle CoO electrodes provide abundant electrochemical surface area. The resulting CoO arrays directly act as binder-free anodes in lithium-ion batteries with the copper foam functioning as the current collector. The highly-dispersed feature of the nanoneedle arrays enhances the effectiveness of active materials, leading to outstanding rate capability and superior long-term cycling stability. These impressive electrochemical properties are attributed to the highly-dispersed self-standing nanoarrays, the advantages of binder-free constituent, and the high exposed surface area of the copper foam substrate compared to copper foil, which enrich active surface area and facilitate charge transfer. The proposed approach to prepare binder-free lithium-ion battery anodes streamlines the electrode fabrication steps and holds significant promise for the future development of the battery industry.
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| 21. |
- Xu, Weidong, 1988-, et al.
(författare)
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Rational molecular passivation for high-performance perovskite light-emitting diodes
- 2019
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Ingår i: Nature Photonics. - : Springer Nature Publishing AG. - 1749-4885 .- 1749-4893. ; 13:6, s. 418-424
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Tidskriftsartikel (refereegranskat)abstract
- A major efficiency limit for solution-processed perovskite optoelectronic devices, for example light-emitting diodes, is trap-mediated non-radiative losses. Defect passivation using organic molecules has been identified as an attractive approach to tackle this issue. However, implementation of this approach has been hindered by a lack of deep understanding of how the molecular structures influence the effectiveness of passivation. We show that the so far largely ignored hydrogen bonds play a critical role in affecting the passivation. By weakening the hydrogen bonding between the passivating functional moieties and the organic cation featuring in the perovskite, we significantly enhance the interaction with defect sites and minimize non-radiative recombination losses. Consequently, we achieve exceptionally high-performance near-infrared perovskite light-emitting diodes with a record external quantum efficiency of 21.6%. In addition, our passivated perovskite light-emitting diodes maintain a high external quantum efficiency of 20.1% and a wall-plug efficiency of 11.0% at a high current density of 200 mA cm−2, making them more attractive than the most efficient organic and quantum-dot light-emitting diodes at high excitations.
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| 22. |
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- 2018
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:1
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Forskningsöversikt (refereegranskat)
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| 30. |
- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 31. |
- Cheung, BB, et al.
(författare)
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A novel combination therapy targeting ubiquitin-specific protease 5 in MYCN-driven neuroblastoma
- 2021
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 40:13, s. 2367-2381
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Tidskriftsartikel (refereegranskat)abstract
- Histone deacetylase (HDAC) inhibitors are effective in MYCN-driven cancers, because of a unique need for HDAC recruitment by the MYCN oncogenic signal. However, HDAC inhibitors are much more effective in combination with other anti-cancer agents. To identify novel compounds which act synergistically with HDAC inhibitor, such as suberanoyl hydroxamic acid (SAHA), we performed a cell-based, high-throughput drug screen of 10,560 small molecule compounds from a drug-like diversity library and identified a small molecule compound (SE486-11) which synergistically enhanced the cytotoxic effects of SAHA. Effects of drug combinations on cell viability, proliferation, apoptosis and colony forming were assessed in a panel of neuroblastoma cell lines. Treatment with SAHA and SE486-11 increased MYCN ubiquitination and degradation, and markedly inhibited tumorigenesis in neuroblastoma xenografts, and, MYCN transgenic zebrafish and mice. The combination reduced ubiquitin-specific protease 5 (USP5) levels and increased unanchored polyubiquitin chains. Overexpression of USP5 rescued neuroblastoma cells from the cytopathic effects of the combination and reduced unanchored polyubiquitin, suggesting USP5 is a therapeutic target of the combination. SAHA and SE486-11 directly bound to USP5 and the drug combination exhibited a 100-fold higher binding to USP5 than individual drugs alone in microscale thermophoresis assays. MYCN bound to the USP5 promoter and induced USP5 gene expression suggesting that USP5 and MYCN expression created a forward positive feedback loop in neuroblastoma cells. Thus, USP5 acts as an oncogenic cofactor with MYCN in neuroblastoma and the novel combination of HDAC inhibitor with SE486-11 represents a novel therapeutic approach for the treatment of MYCN-driven neuroblastoma.
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| 32. |
- Clark, DW, et al.
(författare)
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Associations of autozygosity with a broad range of human phenotypes
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
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Tidskriftsartikel (refereegranskat)abstract
- In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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| 42. |
- Guan, Qingxia, et al.
(författare)
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Isopropylated and tert-butylated triarylphosphate isomers in house dust from South China and Midwestern United States
- 2019
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Ingår i: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 686, s. 1113-1119
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we determined the concentrations and compositions of a suite of isopropylated and tert-butylated triarylphosphate ester (ITP and TBPP) isomers in house dust from the city of Guangzhou located in South China and the city of Carbondale in Midwestern United States. These two groups of organophosphate esters (OPE) are structurally analogous to triphenyl phosphate (TPHP), but have rarely been investigated for environmental occurrences and human exposure risks. The majority of target ITP and TBPP isomers were 100% detected in house dust from the two locations. Median concentrations of Sigma ITPs (including all ITP isomers) and Sigma TBPPs (including all TBPP isomers) were 63.4 ng/g (range: 16.0-500 ng/g) and 35.4 ng/g (8.1-198 ng/g) in South China house dust, respectively, compared with 476 ng/g (140-1610 ng/g) for Sigma ITPs and 81.3 ng/g (352-800 ng/g) for Sigma TBPPs in Midwestern US. dust. The profiles of ITP or TBPP isomers were similar between the two locations and were dominated by 2-isopropylphenyl diphenyl phosphate (2IPPDPP) and 4-tertbutylphenyl diphenyl phosphate (4tBPDPP), respectively. Although the levels of Sigma ITPs and Sigma TBPPs were generally one order of magnitude lower than those of TPHP in the same dust samples, the broad occurrences of most of these isomers in house dust from the two locations likely suggest their wide applications in household consumer products. Estimated intakes of Sigma ITPs and Sigma ITBPPs via dust ingestion were generally three orders of magnitude lower than the reference dose proposed for TPHP. However, these emerging OPE chemicals merit continuous environmental surveillance, given their possible applications as specific commercial mixtures or as components/impurities in other flame retardant/plasticizer mixtures. (C) 2019 Published by Elsevier B.V.
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| 45. |
- Jagarlamudi, Krishna Rao, 1980-
(författare)
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The functional roles of the intra-oocyte phosphatidylinositol 3-kinase (PI3K) signaling in controlling follicular development in mice
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The key functions of the mammalian ovary are the production of fertilizable oocytes and thesecretion of steroid hormones. At the time of birth the human ovary is composed of basic unitstermed primordial follicles. Primordial follicles are long-lived structures in the ovary and some ofthem last until the woman reaches menopause. However, the intra-oocyte signaling pathways thatactivate primordial follicles and early follicular development are largely unknown. In this thesis, the functional roles that the phosphatidylinositol 3-kinase (PI3K) signaling pathwayplays in follicular development were investigated. In vivo approaches using genetically modifiedmouse models were used to determine the functions of several members of the PI3K signalingpathway in oocytes and in follicles. The function of Foxo3a, a substrate of Akt, was investigatedby expressing Foxo3a constitutively in oocytes of primary follicles. We found that continuouslyactive Foxo3a in mouse oocytes caused retardation of oocyte growth, resulting in arrest offollicular development. The functions of p27kip1 (p27) were studied using p27-deficient (p27-/-)mice. It was found that p27 suppresses follicle endowment/formation and activation, and that itinduces follicle atresia. The functions of PI3K signaling in oocytes during follicular activationwere also investigated using conditional mutant mice, by disrupting the Pten in oocytes ofprimordial follicles. We found that, all primordial follicles were prematurely activated due toovergrowth of oocytes and these follicles were depleted in young adulthood, causing prematureovarian failure (POF). At the same time, disruption of the Pten from oocytes of primary follicleshad no effect on activation of primordial follicles, and the follicles developed and maturednormally. The results clearly show that the PI3K pathway in the mammalian oocyte plays a keyrole in follicular activation through control of initiation of oocyte growth and folliculardevelopment.
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| 46. |
- Jansson, Emil
(författare)
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Challenges with Driverless and Unattended Train Operations
- 2023
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Demand for transportation continues to increase, for both freight and passenger services. One of the most energy-efficient modes of transportation is rail. One solution to increase the attractiveness of rail transport is to introduce automatic train operation (ATO) with a high grade of automation (GoA). Driverless and unattended train operation could entail positive effects but would also bring challenges when removing the train driver. Thus, there is a need to understand the role of train drivers, especially in unplanned events. The main research objectiveis to understand the train driver roles during unplanned events and the frequency of such events. This thesis includes three papers to fulfill the research objective.This thesis studied delay logs and trackside sensor logs. A qualitative method, thematic analysis, was used to identify themes of the roles performed by train driver from the delay logs. The chi-square test statistical method was used to analyze these trackside sensor logs.Six main categories of tasks for train drivers were identified for unplanned events. Detect, Report, Inspect, Adjust, Manage passengers, and Respond to train orders. Each category was analyzed for each grade of automation by giving the responsibility for each category. The results highlight in a novel way the varied challenges between grade of automation in mainline systems. Detecting abnormalities was the most common task train drivers performed during unplanned events. Train drivers use four human senses to detect abnormalities: sight, hearing, touch, and smell. This indicates the need for onboard sensors. However, the real challenge is in processing all sensor data to gain anaccurate evaluation of any fault. One specific type of unplanned event in which the train driver is needed involves trackside sensor alarms. Freight trains are ten times more likely to trip an alarm than passenger trains. Alarms are more frequent in colder climate zones during winter months. These differences are statistically significant and indicate that not all lines and train types might be suitable for a high grade of automation.If driverless or unattended train operation will become a reality in future, many challenges must be met. This thesis gives deeper understanding of these challenges using a novel way to identify and quantify train driver tasks during unplanned events.
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| 47. |
- Kerrebrouck, Joris Van, et al.
(författare)
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726.7-Gb/s 1.5-μm single-mode VCSEL discrete multi-tone transmission over 2.5-km multicore fiber
- 2018
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Ingår i: 2018 Optical Fiber Communications Conference and Exposition, OFC 2018 - Proceedings. - : Institute of Electrical and Electronics Engineers Inc.. - 9781943580385 ; , s. 1-3
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Konferensbidrag (refereegranskat)abstract
- A 107Gb/s net-rate DMT optical signal was generated using a single-mode long-wavelength VCSEL with a modulation bandwidth of 23 GHz. We experimentally demonstrated a total net-rate up to 726.7Gb/s at 1.5μm over 2.5km 7-core dispersion-uncompensated MCF.
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