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Sökning: WFRF:(Sage A)

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2.
  • Hudson, Thomas J., et al. (författare)
  • International network of cancer genome projects
  • 2010
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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3.
  • Leebens-Mack, James H., et al. (författare)
  • One thousand plant transcriptomes and the phylogenomics of green plants
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
  • Tidskriftsartikel (refereegranskat)abstract
    • Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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  • George, Julie, et al. (författare)
  • Comprehensive genomic profiles of small cell lung cancer
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 524:7563, s. 47-U73
  • Tidskriftsartikel (refereegranskat)abstract
    • We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
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  • Ali, M, et al. (författare)
  • Protocol for the development of the international population registry for aphasia after stroke (I-PRAISE)
  • 2022
  • Ingår i: Aphasiology. - : Informa UK Limited. - 0268-7038 .- 1464-5041. ; 36:4, s. 534-554
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We require high-quality information on the current burden, the types of therapy and resources available, methods of delivery, care pathways and long-term outcomes for people with aphasia.Aim: To document and inform international delivery of post-stroke aphasia treatment, to optimise recovery and reintegration of people with aphasia.Methods & Procedures: Multi-centre, prospective, non-randomised, open study, employing blinded outcome assessment, where appropriate, including people with post-stroke aphasia, able to attend for 30 minutes during the initial language assessment, at first contact with a speech and language therapist for assessment of aphasia at participating sites. There is no study-mandated intervention. Assessments will occur at baseline (first contact with a speech and language therapist for aphasia assessment), discharge from Speech and Language Therapy (SLT), 6 and 12-months post-stroke. Our primary outcome is changed from baseline in the Amsterdam Nijmegen Everyday Language Test (ANELT/Scenario Test for participants with severe verbal impairments) at 12-months post-stroke. Secondary outcomes at 6 and 12 months include the Therapy Outcome Measure (TOMS), Subjective Index of Physical and Social Outcome (SIPSO), Aphasia Severity Rating Scale (ASRS), Western Aphasia Battery Aphasia Quotient (WAB-AQ), stroke and aphasia quality of life scale (SAQoL-39), European Quality of Life Scale (EQ-5D), lesion description, General Health Questionnaire (GHQ-12), resource use, and satisfaction with therapy provision and success. We will collect demography, clinical data, and therapy content. Routine neuroimaging and medication administration records will be accessed where possible; imaging will be pseudonymised and transferred to a central reading centre. Data will be collected in a central registry. We will describe demography, stroke and aphasia profiles and therapies available. International individual participant data (IPD) meta-analyses will examine treatment responder rates based on minimal detectable change & clinically important changes from baseline for primary and secondary outcomes at 6 and 12 months. Multivariable meta-analyses will examine associations between demography, therapy, medication use and outcomes, considering service characteristics. Where feasible, costs associated with treatment will be reported. Where available, we will detail brain lesion size and site, and examine correlations with SLT and language outcome at 12 months.Conclusion: International differences in care, resource utilisation and outcomes will highlight avenues for further aphasia research, promote knowledge sharing and optimise aphasia rehabilitation delivery. IPD meta-analyses will enhance and expand understanding, identifying cost-effective and promising approaches to optimise rehabilitation to benefit people with aphasia.
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8.
  • Fernie, A. R., et al. (författare)
  • Perspectives on plant photorespiratory metabolism
  • 2013
  • Ingår i: Plant Biology. - : Wiley-Blackwell. - 1435-8603 .- 1438-8677. ; 15:4, s. 748-753
  • Forskningsöversikt (refereegranskat)abstract
    • Being intimately intertwined with (C3) photosynthesis, photorespiration is an incredibly high flux-bearing pathway. Traditionally, the photorespiratory cycle was viewed as closed pathway to refill the Calvin-Benson cycle with organic carbon. However, given the network nature of metabolism, it hence follows that photorespiration will interact with many other pathways. In this article, we review current understanding of these interactions and attempt to define key priorities for future research, which will allow us greater fundamental comprehension of general metabolic and developmental consequences of perturbation of this crucial metabolic process.
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  • Betti, Marco, et al. (författare)
  • Manipulating photorespiration to increase plant productivity : recent advances and perspectives for crop improvement
  • 2016
  • Ingår i: Journal of Experimental Botany. - : Oxford University Press (OUP). - 0022-0957 .- 1460-2431. ; 67:10, s. 2977-2988
  • Forskningsöversikt (refereegranskat)abstract
    • Recycling of the 2-phosphoglycolate generated by the oxygenase reaction of Rubisco requires a complex and energy-consuming set of reactions collectively known as the photorespiratory cycle. Several approaches aimed at reducing the rates of photorespiratory energy or carbon loss have been proposed, based either on screening for natural variation or by means of genetic engineering. Recent work indicates that plant yield can be substantially improved by the alteration of photorespiratory fluxes or by engineering artificial bypasses to photorespiration. However, there is also evidence indicating that, under certain environmental and/or nutritional conditions, reduced photorespiratory capacity may be detrimental to plant performance. Here we summarize recent advances obtained in photorespiratory engineering and discuss prospects for these advances to be transferred to major crops to help address the globally increasing demand for food and biomass production.
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  • Kirschbaum, Miko U.F., et al. (författare)
  • Is tree planting an effective strategy for climate change mitigation?
  • 2024
  • Ingår i: Science of the Total Environment. - : Elsevier B.V.. - 0048-9697 .- 1879-1026. ; 909
  • Tidskriftsartikel (refereegranskat)abstract
    • The world's forests store large amounts of carbon (C), and growing forests can reduce atmospheric CO2 by storing C in their biomass. This has provided the impetus for world-wide tree planting initiatives to offset fossil-fuel emissions. However, forests interact with their environment in complex and multifaceted ways that must be considered for a balanced assessment of the value of planting trees. First, one needs to consider the potential reversibility of C sequestration in trees through either harvesting or tree death from natural factors. If carbon storage is only temporary, future temperatures will actually be higher than without tree plantings, but cumulative warming will be reduced, contributing both positively and negatively to future climate-change impacts. Alternatively, forests could be used for bioenergy or wood products to replace fossil-fuel use which would obviate the need to consider the possible reversibility of any benefits. Forests also affect the Earth's energy balance through either absorbing or reflecting incoming solar radiation. As forests generally absorb more incoming radiation than bare ground or grasslands, this constitutes an important warming effect that substantially reduces the benefit of C storage, especially in snow-covered regions. Forests also affect other local ecosystem services, such as conserving biodiversity, modifying water and nutrient cycles, and preventing erosion that could be either beneficial or harmful depending on specific circumstances. Considering all these factors, tree plantings may be beneficial or detrimental for mitigating climate-change impacts, but the range of possibilities makes generalisations difficult. Their net benefit depends on many factors that differ between specific circumstances. One can, therefore, neither uncritically endorse tree planting everywhere, nor condemn it as counter-productive. Our aim is to provide key information to enable appropriate assessments to be made under specific circumstances. We conclude our discussion by providing a step-by-step guide for assessing the merit of tree plantings under specific circumstances.
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  • Fragopoulou, A., et al. (författare)
  • Scientific panel on electromagnetic field health risks : Consensus points, recommendations, and rationales
  • 2010
  • Ingår i: Reviews on Environmental Health. - 0048-7554. ; 25:4, s. 307-317
  • Tidskriftsartikel (refereegranskat)abstract
    • In November, 2009, a scientific panel met in Seletun, Norway, for three days of intensive discussion on existing scientific evidence and public health implications of the unprecedented global exposures to artificial electromagnetic fields (EMF). EMF exposures (static to 300 GHz) result from the use of electric power and from wireless telecommunications technologies for voice and data transmission, energy, security, military and radar use in weather and transportation. The Scientific Panel recognizes that the body of evidence on EMF requires a new approach to protection of public health; the growth and development of the fetus, and of children; and argues for strong preventative actions. New, biologically-based public exposure standards are urgently needed to protect public health worldwide.
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  • Frohlich, Michael W., et al. (författare)
  • Molecular phylogenetics of Euploca (Boraginaceae) : homoplasy in many characters, including the C-4 photosynthetic pathway
  • 2022
  • Ingår i: Botanical journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4074 .- 1095-8339. ; 199:2, s. 497-537
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a phylogenetic analysis using plastid (matK, rbcL) and nuclear (nrITS) DNA for diverse Euploca spp. (formerly Heliotropium section Orthostachys) from the worldwide distribution of a genus and including species encompassing the wide physiological and morphological diversity of the genus. Our results indicate that some remarkably complex features arose multiple times in parallel in Euploca, including attributes of its subsections under section Orthostachys, notably plants that, above ground, consist almost entirely of inflorescences. To elucidate in greater detail the distribution of C-4 species in Euploca and Heliotropium s.s., we made > 800 delta C-13 determinations, including some from the traditional genus Tournefortia. We greatly increase the number of proven C-4 species in Euploca, but found none outside Euploca. Of the tested Euploca spp., c. 28% are C-3 or intermediate in carbon fixation pathway. Our phylogenetic results indicate four parallel/convergent acquisitions of C-4 photosynthesis or fewer origins with subsequent loss in some species.
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13.
  • Gómez-de-Mariscal, E., et al. (författare)
  • DeepImageJ : A user-friendly environment to run deep learning models in ImageJ
  • 2021
  • Ingår i: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 18:10, s. 1192-1195
  • Tidskriftsartikel (refereegranskat)abstract
    • DeepImageJ is a user-friendly solution that enables the generic use of pre-trained deep learning models for biomedical image analysis in ImageJ. The deepImageJ environment gives access to the largest bioimage repository of pre-trained deep learning models (BioImage Model Zoo). Hence, nonexperts can easily perform common image processing tasks in life-science research with deep learning-based tools including pixel and object classification, instance segmentation, denoising or virtual staining. DeepImageJ is compatible with existing state of the art solutions and it is equipped with utility tools for developers to include new models. Very recently, several training frameworks have adopted the deepImageJ format to deploy their work in one of the most used softwares in the field (ImageJ). Beyond its direct use, we expect deepImageJ to contribute to the broader dissemination and reuse of deep learning models in life sciences applications and bioimage informatics.
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  • Kabosova, Andrea, et al. (författare)
  • Compositional differences between infant and adult human corneal basement membranes
  • 2007
  • Ingår i: Investigative Ophthalmology & Visual Science. - : Association for Research in Vision and Ophthalmology (ARVO). - 1552-5783. ; 48:11, s. 4989-4999
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE. Adult human corneal epithelial basement membrane ( EBM) and Descemet's membrane ( DM) components exhibit heterogeneous distribution. The purpose of the study was to identify changes of these components during postnatal corneal development. METHODS. Thirty healthy adult corneas and 10 corneas from 12-day- to 3-year-old children were studied by immunofluorescence with antibodies against BM components. RESULTS. Type IV collagen composition of infant corneal central EBM over Bowman's layer changed from alpha 1-alpha 2 to alpha 3-alpha 4 chains after 3 years of life; in the adult, alpha 1-alpha 2 chains were retained only in the limbal BM. Laminin alpha 2 and beta 2 chains were present in the adult limbal BM where epithelial stem cells are located. By 3 years of age, beta 2 chain appeared in the limbal BM. In all corneas, limbal BM contained laminin gamma 3 chain. In the infant DM, type IV collagen alpha 1-alpha 6 chains, perlecan, nidogen-1, nidogen-2, and netrin-4 were found on both faces, but they remained only on the endothelial face of the adult DM. The stromal face of the infant but not the adult DM was positive for tenascin-C, fibrillin-1, SPARC, and laminin-332. Type VIII collagen shifted from the endothelial face of infant DM to its stromal face in the adult. Matrilin-4 largely disappeared after the age of 3 years. CONCLUSIONS. The distribution of laminin gamma 3 chain, nidogen-2, netrin-4, matrilin-2, and matrilin-4 is described in the cornea for the first time. The observed differences between adult and infant corneal BMs may relate to changes in their mechanical strength, corneal cell adhesion and differentiation in the process of postnatal corneal maturation.
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  • Kokjohn, Sage L., et al. (författare)
  • Modeling Charge Preparation And Combustion In Diesel Fuel, Ethanol, And Dual-Fuel PCCI Engines
  • 2011
  • Ingår i: Atomization and Sprays. - 1936-2684. ; 21:2, s. 107-119
  • Tidskriftsartikel (refereegranskat)abstract
    • In this work, multi-dimensional computational fluid dynamics modeling predictions are compared for three different methods of achieving high-efficiency, low NOT, and soot premixed charge compression ignition (PCCI) combustion. The first method is early injection, highly dilute (i.e., low oxygen concentration), diesel fuel PCCI operation. In this method, the oxygen concentration is reduced to extend the ignition delay to allow adequate time for mixing prior to autoignition. The second method is early injection PCCI operation using neat ethanol. In this method, the fuel reactivity is sufficiently low such that PCCI combustion can be achieved without using external dilution. The final method, dual-fuel reactivity controlled compression ignition (RCCI) combustion, blends fuels with different ignition qualities in the combustion chamber to tailor the auto-ignition properties of the mixture for the specific operating condition. In this study, RCCI operation was investigated using in-cylinder fuel blending of diesel fuel and gasoline as well as diesel fuel and an E85 blend (i.e., 85% ethanol and 15% gasoline). It was found that the modeling approach used in this work is capable of capturing the bulk combustion characteristics (e.g., cylinder pressure) as well as the details of the injection event (e.g., liquid penetration) and ignition processes. The simulations were shown to provide accurate predictions of the differences in combustion characteristics of diesel fuel, ethanol, and fuel blends (i.e., gasoline + diesel fuel and E85 + diesel fuel). It was found that the ethanol PCCI and dual-fuel (gasoline + diesel fuel and E85 + diesel fuel) RCCI cases have significantly reduced rates of energy release compared to neat diesel fuel PCCI operation. The reduced energy release rates of the ethanol PCCI and dual-fuel RCCI cases may allow these modes of PCCI combustion to achieve higher engine loads than that of neat diesel PCCI.
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17.
  • Peterhansel, C., et al. (författare)
  • Engineering photorespiration : current state and future possibilities
  • 2013
  • Ingår i: Plant Biology. - : Wiley-Blackwell. - 1435-8603 .- 1438-8677. ; 15:4, s. 754-758
  • Forskningsöversikt (refereegranskat)abstract
    • Reduction of flux through photorespiration has been viewed as a major way to improve crop carbon fixation and yield since the energy-consuming reactions associated with this pathway were discovered. This view has been supported by the biomasses increases observed in model species that expressed artificial bypass reactions to photorespiration. Here, we present an overview about the major current attempts to reduce photorespiratory losses in crop species and provide suggestions for future research priorities.
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  • Wallace, SJ, et al. (författare)
  • A core outcome set for aphasia treatment research: The ROMA consensus statement
  • 2019
  • Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:2, s. 180-185
  • Tidskriftsartikel (refereegranskat)abstract
    • A core outcome set (COS; an agreed, minimum set of outcomes) was needed to address the heterogeneous measurement of outcomes in aphasia treatment research and to facilitate the production of transparent, meaningful, and efficient outcome data. Objective The Research Outcome Measurement in Aphasia (ROMA) consensus statement provides evidence-based recommendations for the measurement of outcomes for adults with post-stroke aphasia within phases I–IV aphasia treatment studies. Methods This statement was informed by a four-year program of research, which comprised investigation of stakeholder-important outcomes using consensus processes, a scoping review of aphasia outcome measurement instruments, and an international consensus meeting. This paper provides an overview of this process and presents the results and recommendations arising from the international consensus meeting. Results Five essential outcome constructs were identified: Language, communication, patient-reported satisfaction with treatment and impact of treatment, emotional wellbeing, and quality of life. Consensus was reached for the following measurement instruments: Language: The Western Aphasia Battery Revised (WAB-R) (74% consensus); emotional wellbeing: General Health Questionnaire (GHQ)-12 (83% consensus); quality of life: Stroke and Aphasia Quality of Life Scale (SAQOL-39) (96% consensus). Consensus was unable to be reached for measures of communication (where multiple measures exist) or patient-reported satisfaction with treatment or impact of treatment (where no measures exist). Discussion Harmonization of the ROMA COS with other core outcome initiatives in stroke rehabilitation is discussed. Ongoing research and consensus processes are outlined. Conclusion The WAB-R, GHQ-12, and SAQOL-39 are recommended to be routinely included within phases I–IV aphasia treatment studies. This consensus statement has been endorsed by the Collaboration of Aphasia Trialists, the British Aphasiology Society, the German Society for Aphasia Research and Therapy, and the Royal College of Speech Language Therapists.
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