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Sökning: WFRF:(Lee Andrew)

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311.
  • Lee, Natuschka N, et al. (författare)
  • The extreme biology of meteorites : their role in understanding the origin and distribution of life on earth and in the Universe
  • 2017. - 2
  • Ingår i: Adaption of microbial life to environmental extremes. - Cham : Springer Publishing Company. - 9783319483252 - 9783319483276 ; , s. 283-325
  • Bokkapitel (refereegranskat)abstract
    • Meteorites have captured our fascination since our early history – they have evoked awe, fear, an irresistible curiosity, and numerous lively debates. Former historians have indicated that many of the ancient cultures and civilizations in Europe, Africa, Asia, the Inuit, and the native Indians in America regarded both the meteorite and the location of their fall as sacred. Thus, they used the meteorites as religious objects or for craft design like jewelry, weapons, or even practical things like tools and horse shoes. Today, meteorites continue to capture our fascination through popular cultural formats such as science fiction and also as a scientific window that reveals the secrets of the Solar System formation. Within academia, meteorites have always fomented keen scientific debate. It was not until the early nineteenth century that the cosmic origin of meteorites, i.e., being truly not tellurian, was approved by the scientific community after the late eighteenth-century work of Ernst F. Chladni (1794). This implied for the first time that there are other smaller bodies in the sky besides the Moon. After this, several other lively debates followed on controversial findings and hypotheses around the role of meteorites in the universe and for the evolutionary course of life on Earth, often in connection with the profound difficulties to approach this subject in an adequate scientific way. Principally the different types of meteorites (asteroids, meteors, etc.) can be viewed as a most extreme or exotic substrate, habitat, and transport mode of chemicals and possibly even of cell-based life forms for several reasons:(i)They have experienced a remarkable history since their origin as condensates from the Solar Nebula, more or less metamorphosed or molten fragments of asteroids, or rocks from Mars or our Moon.(ii)The meteorites have been exposed to multiple extreme conditions ranging from milliseconds to billions of years duration when traveling through the interplanetary space, until they fell down on an astronomical body like Earth.(iii)Once on Earth, the meteorites get exposed to different weathering conditions, which often makes it a challenge to retrieve their former history in an unambiguous way.
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312.
  • Lee, Roger, et al. (författare)
  • Genetic studies on the functional relevance of the protein prenyltransferases in skin keratinocytes
  • 2010
  • Ingår i: Oxford Journals About the Journal Human Molecular Genetics. - 0964-6906. ; 19:8, s. 1603-1617
  • Tidskriftsartikel (refereegranskat)abstract
    • The modification of proteins with farnesyl or geranylgeranyl lipids, a process called protein prenylation, facilitates interactions of proteins with membrane surfaces. Protein prenylation is carried out by a pair of cytosolic enzymes, protein farnesyltransferase (FTase) and protein geranylgeranyltransferase type I (GGTase-I). FTase and GGTase-I have attracted interest as therapeutic targets for both cancer and progeria, but very little information exists on the importance of these enzymes for homeostasis of normal tissues. One study actually suggested that FTase is entirely dispensable. To explore the importance of the protein prenyltransferases for normal tissues, we used conditional knockout alleles for Fntb and Pggt1b (which encode the beta-subunits of FTase and GGTase-I, respectively) and a keratin 14-Cre transgene to create mice lacking FTase or GGTase-I in skin keratinocytes. Keratinocyte-specific Fntb knockout mice were viable but developed severe alopecia. Although hair follicles appeared normal during development, they were morphologically abnormal after birth, and ultrastructural and immunohistochemical studies revealed many apoptotic cells. The interfollicular epidermis of Fntb-deficient mice appeared normal; however, keratinocytes from these mice could not proliferate in culture. As expected, non-farnesylated prelamin A and non-farnesylated DNAJA1 accumulated in Fntb-deficient keratinocytes. Keratinocyte-specific Pggt1b knockout mice survived development but died shortly after birth. Like Fntb-deficient keratinocytes, Pggt1b-deficient keratinocytes did not proliferate in culture. Thus, both FTase and GGTase-I are required for the homeostasis of skin keratinocytes.
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313.
  • Leidö, Jan, 1983- (författare)
  • Realizing the Single Software Market : Cross-National Validity of Software License Agreements
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The Internet has revolutionized the software industry, one of the world’s largest businesses. A single software market is emerging, independent of national borders, where products and services are digitally distributed. But the legal framework for software transfers is not geographically independent; relevant underlying law varies substantially between different legal systems.In this doctoral thesis, cross-national validity of certain standard software license agreements is examined as a solution to overcome national differences and improve the emerging single software market. Cross-national validity is mapped, explained, and improved under American and German law. The United States and the European Union collectively dominate the single software market. Within the EU, Germany is the most relevant legal system, and many conclusions reached under German law can be extended to the entire EU.The study identifies many current issues, caused by inter alia inherent limits of law, fundamental differences between German and American law, and problematic transferor choices. Current issues exist regarding formation, substantive content, and interpretation of software license agreements on a cross-national level. This leads to increasing legal and practical problems for the industry and individual transferors.Major and minor improvements in software license agreements and business models are suggested to achieve cross-national validity. Simple advice includes better assent mechanisms, prior disclosure, clear notice, and translating software license agreements. More comprehensive advice includes focusing on provisions that are essential from a business or technical perspective, rethinking certain business and technical choices that might lead to legal problems, making compromises over certain provisions that have only minor legal advantages but clear legal disadvantages, and choosing a way to bridge or avoid national differences regarding central provisions and practices from among available suggestions adapted to different business models.Making such improvements is becoming increasingly important as lawmakers and consumer associations in different countries become ever more active, and as developing countries become increasingly important. Improving cross-national validity will enhance legal certainty and bring us one step closer to realizing the single software market.
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314.
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315.
  • Lindgren, Johan, et al. (författare)
  • Microspectroscopic evidence of cretaceous bone proteins.
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Low concentrations of the structural protein collagen have recently been reported in dinosaur fossils based primarily on mass spectrometric analyses of whole bone extracts. However, direct spectroscopic characterization of isolated fibrous bone tissues, a crucial test of hypotheses of biomolecular preservation over deep time, has not been performed. Here, we demonstrate that endogenous proteinaceous molecules are retained in a humerus from a Late Cretaceous mosasaur (an extinct giant marine lizard). In situ immunofluorescence of demineralized bone extracts shows reactivity to antibodies raised against type I collagen, and amino acid analyses of soluble proteins extracted from the bone exhibit a composition indicative of structural proteins or their breakdown products. These data are corroborated by synchrotron radiation-based infrared microspectroscopic studies demonstrating that amino acid containing matter is located in bone matrix fibrils that express imprints of the characteristic 67 nm D-periodicity typical of collagen. Moreover, the fibrils differ significantly in spectral signature from those of potential modern bacterial contaminants, such as biofilms and collagen-like proteins. Thus, the preservation of primary soft tissues and biomolecules is not limited to large-sized bones buried in fluvial sandstone environments, but also occurs in relatively small-sized skeletal elements deposited in marine sediments.
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316.
  • Llop-Sayson, Jorge, et al. (författare)
  • Constraining the Orbit and Mass of epsilon Eridani b with Radial Velocities, Hipparcos IAD-Gaia DR2 Astrometry, and Multiepoch Vortex Coronagraphy Upper Limits
  • 2021
  • Ingår i: Astronomical Journal. - : Institute of Physics Publishing (IOPP). - 0004-6256 .- 1538-3881. ; 162:5
  • Tidskriftsartikel (refereegranskat)abstract
    • epsilon Eridani is a young planetary system hosting a complex multibelt debris disk and a confirmed Jupiter-like planet orbiting at 3.48 au from its host star. Its age and architecture are thus reminiscent of the early Solar System. The most recent study of Mawet et al., which combined radial-velocity data and Ms-band direct imaging upper limits, started to constrain the planet's orbital parameters and mass, but are still affected by large error bars and degeneracies. Here we make use of the most recent data compilation from three different techniques to further refine epsilon Eridani b's properties: RVs, absolute astrometry measurements from the Hipparcos and Gaia missions, and new Keck/NIRC2 Ms-band vortex coronagraph images. We combine this data in a Bayesian framework. We find a new mass, M-b = 0.66(-0.09)(+0.12) M-Jup, and inclination, i = 78.81(-22.41 degrees)(+29.34), with at least a factor 2 of improvement over previous uncertainties. We also report updated constraints on the longitude of the ascending node, the argument of the periastron, and the time of periastron passage. With these updated parameters, we can better predict the position of the planet at any past and future epoch, which can greatly help define the strategy and planning of future observations and with subsequent data analysis. In particular, these results can assist the search for a direct detection with JWST and the Nancy Grace Roman Space Telescope's coronagraph instrument.
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317.
  • Loth, Daan W, et al. (författare)
  • Genome-wide association analysis identifies six new loci associated with forced vital capacity
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46, s. 669-677
  • Tidskriftsartikel (refereegranskat)abstract
    • Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.
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318.
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319.
  • Luke Marinovich, M., et al. (författare)
  • Artificial intelligence (AI) to enhance breast cancer screening : protocol for population-based cohort study of cancer detection
  • 2022
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Artifi cial intelligence (AI) algorithms for interpreting mammograms have the potential to improve the effectiveness of population breast cancer screening programmes if they can detect cancers, including interval cancers, without contributing substantially to overdiagnosis. Studies suggesting that AI has comparable or greater accuracy than radiologists commonly employ € enriched' datasets in which cancer prevalence is higher than in population screening. Routine screening outcome metrics (cancer detection and recall rates) cannot be estimated from these datasets, and accuracy estimates may be subject to spectrum bias which limits generalisabilty to real-world screening. We aim to address these limitations by comparing the accuracy of AI and radiologists in a cohort of consecutive of women attending a real-world population breast cancer screening programme. Methods and analysis A retrospective, consecutive cohort of digital mammography screens from 109 000 distinct women was assembled from BreastScreen WA (BSWA), Western Australia's biennial population screening programme, from November 2016 to December 2017. The cohort includes 761 screen-detected and 235 interval cancers. Descriptive characteristics and results of radiologist double-reading will be extracted from BSWA outcomes data collection. Mammograms will be reinterpreted by a commercial AI algorithm (DeepHealth). AI accuracy will be compared with that of radiologist single-reading based on the di €erence in the area under the receiver operating characteristic curve. Cancer detection and recall rates for combined AI-radiologist reading will be estimated by pairing the first radiologist read per screen with the AI algorithm, and compared with estimates for radiologist double-reading. Ethics and dissemination This study has ethical approval from the Women and Newborn Health Service Ethics Committee (EC00350) and the Curtin University Human Research Ethics Committee (HRE2020-0316). Findings will be published in peer-reviewed journals and presented at national and international conferences. Results will also be disseminated to stakeholders in Australian breast cancer screening programmes and policy makers in population screening.
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320.
  • MacDonald, Amy M., et al. (författare)
  • Maternal and child biomonitoring strategies and levels of exposure in western Canada during the past seventeen years : The Alberta Biomonitoring Program
  • 2022
  • Ingår i: International journal of hygiene and environmental health (Print). - : Elsevier BV. - 1438-4639 .- 1618-131X. ; 244
  • Tidskriftsartikel (refereegranskat)abstract
    • The Alberta Biomonitoring Program (ABP) was created in 2005 with the initial goal of establishing baseline levels of exposure to environmental chemicals in specific populations in the province of Alberta, Canada, and was later expanded to include multiple phases. The first two phases focused on evaluating exposure in pregnant women (Phase One, 2005) and children (Phase Two, 2004–2006) by analyzing residual serum specimens. Phase Three (2013–2016) employed active recruitment techniques to evaluate environmental exposures using a revised list of chemicals in paired serum pools from pregnant women and umbilical cord blood. These three phases of the program monitored a total of 226 chemicals in 285 pooled serum samples representing 31,529 individuals. Phase Four (2017–2020) of the ABP has taken a more targeted approach, focusing on the impact of the federal legalization of cannabis on the exposure of pregnant women in Alberta to cannabis, as well as tobacco and alcohol using residual prenatal screening serum specimens. Chemicals monitored in the first three phases include herbicides, neutral pesticides, metals, metalloids, and micronutrients, methylmercury, organochlorine pesticides, organophosphate pesticides, parabens, phthalate metabolites, perfluoroalkyl substances (PFAS), phenols, phytoestrogens, polybrominated compounds, polychlorinated biphenyls (PCBs), dioxins and furans, polycyclic aromatic hydrocarbons (PAHs), and tobacco biomarkers. Phase Four monitored six biomarkers of tobacco, alcohol, and cannabis. All serum samples were pooled. Mean concentrations and 95% confidence intervals (CIs) were calculated for the chemicals detected in ≥25% of the sample pools. cross the first three phases, the data from the ABP has provided baseline exposure levels for the chemicals in pregnant women, children, and newborns across the province. Comparison within and among the phases has highlighted differences in exposure levels with age, geography, seasonality, sample type, and time. The strategies employed throughout the program phases have been demonstrated to provide effective models for population biomonitoring.
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