| 31. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 32. |
- Nyberg, Martin, et al.
(författare)
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PCA3 as a diagnostic marker for prostate cancer: A validation study on a Swedish patient population.
- 2010
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Ingår i: Scandinavian Journal of Urology and Nephrology. - : Informa UK Limited. - 1651-2065 .- 0036-5599. ; 44, s. 378-383
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objective. Prostate cancer antigen 3 in urine (uPCA3) has been shown to perform better than total prostate-specific antigen in serum (tPSA) to predict prostate cancer (PCa) detection. The aim of this study was to validate the diagnostic precision of uPCA3 in a mixed set of patients with no previous history of PCa, including patients with previous negative biopsies. Material and methods. The study included 62 men scheduled for prostate biopsy at Skåne University Hospital Malmö, Sweden. Urine samples were obtained according to the Progensa™ uPCA3 assay. Logistic regression and receiver operating characteristic curves were used to test associations between levels of biomarkers and prostate cancer. Results. According to pathological examination of core needle biopsies, PCa was found in 18 out of 62 patients. A one-step increase in uPCA3 was associated with an increase in the odds of cancer of 1.026 (p = 0.005). Differences in the odds ratio between uPCA3 and tPSA were not statistically significant. A model using both markers did not increase prediction of event. Areas under the curve for uPCA3, tPSA and a model combining uPCA3 and tPSA did not differ significantly. No significant correlation was found between uPCA3 and tPSA or prostate volume. Conclusion. In this small set of mixed patients uPCA3 alone and tPSA performed equally well as diagnostic markers for PCa. A combination of the two markers did not improve the diagnostic performance. This study does not support a role for the uPCA3 urine test to replace or be added to tPSA in PCa detection.
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| 33. |
- Ortegren, J., et al.
(författare)
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Improved thermal stability of pyroelectric polymers by crosslinking of ferroelectric liquid crystals
- 2001
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1089-5647 .- 1520-6106 .- 1520-5207. ; 105:42, s. 10223-10227
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Tidskriftsartikel (refereegranskat)abstract
- Monofunctional ferroelectric liquid crystalline monomers and a blend of monofunctional/lbifunctional ferroelectric liquid crystalline monomers were photopolymerized, yielding a side-chain liquid crystalline polymer and a cross-linked polymer, respectively. The cross-linked polymer exhibited higher thermal stability than the side-chain liquid crystalline polymer and was pyroelectric up to 170 degreesC, whereas the side-chain liquid crystalline polymer lost most of its pyroelectricity at 38 degreesC. It is shown by electrooptic and birefringence measurements that cross-linking in the unwound SmC* phase prevented the reoccurrence of the helical superstructure.
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| 34. |
- Plan, Anders, et al.
(författare)
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Exceptional preservation of reidite in the Rochechouart impact structure, France: New insights into shock deformation and phase transition of zircon
- 2021
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Ingår i: Meteoritics and Planetary Science. - : Wiley. - 1086-9379 .- 1945-5100. ; 56:10, s. 1795-1828
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Tidskriftsartikel (refereegranskat)abstract
- Reidite, the high-pressure zircon (ZrSiO4) polymorph, is a diagnostic indicator of impact events. Natural records of reidite are, however, scarce, occurring mainly as micrometer-sized lamellae, granules, and dendrites. Here, we present a unique sequence of shocked zircon grains found within a clast from the Chassenon suevitic breccia (shock stageIII) from the ~200 Ma, 20–50 km wide Rochechouart impact structure in France. Our study comprises detailed characterization with scanning electron microscopy coupled with electron backscatter diffraction with the goal of investigating the stability and response of ZrSiO4 under extreme P–T conditions. The shocked zircon grains have preserved various amounts of reidite ranging from 4% up to complete conversion. The grains contain various variants of reidite, including the common habits: lamellae and granular reidite. In addition, three novel variants have been identified: blade, wedge, and massive domains. Several of these crosscut and offset each other, revealing that reidite can form at multiple stages during an impact event. Our data provide evidence that reidite can be preserved in impactites to a much greater extent than previously documented. We have further characterized reversion products of reidite in the form of fully recrystallized granular zircon grains and minute domains of granular zircon in reidite-bearing grains that occur in close relationship to reidite. Neoblasts in these grains have a distinct crystallography that is the result of systematic inheritance of reidite. We interpret that the fully granular grains have formed from prolonged exposure of temperatures in excess of 1200 °C. Reidite-bearing grains with granular domains might signify swift quenching from temperatures close to 1200 °C. Grains subjected to these specific conditions therefore underwent partial zircon-to-reidite reversion, instead of full grain recrystallization. Based on our ZrSiO4 microstructural constraints, we decipher the grains evolution at specific P–T conditions related to different impact stages, offering further understanding of the behavior of ZrSiO4 during shock.
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| 35. |
- Scott, Robert A., et al.
(författare)
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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
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Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
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| 36. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
-
Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 37. |
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| 38. |
- Syed Khaja, Azharuddin Sajid, et al.
(författare)
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Elevated level of wnt5a protein in localized prostate cancer tissue is associated with better outcome.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10
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Tidskriftsartikel (refereegranskat)abstract
- Wnt5a is a non-canonical secreted glycoprotein of the Wnt family that plays an important role in cancer development and progression. Previous studies report that Wnt5a is upregulated in prostate cancer and suggested that Wnt5a affects migration and invasion of prostate tumor cell. This study aimed to evaluate the prognostic value of Wnt5a protein expression in prostate cancer tissue and its potential to predict outcome after radical prostatectomy in patients with localized prostate cancer.
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| 39. |
- Twine, Susan, et al.
(författare)
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A mutant of Francisella tularensis strain SCHU S4 lacking the ability to express a 58-kilodalton protein is attenuated for virulence and is an effective live vaccine
- 2005
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 73:12, s. 8345-8352
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Tidskriftsartikel (refereegranskat)abstract
- Francisella tularensis subsp. tularensis (type A) strain SCHU S4 is a prototypic strain of the pathogen that is highly virulent for humans and other mammals. Its intradermal (i.d.) 50% lethal dose (LD50) for mice is <10 CFU. We discovered a spontaneous mutant, designated FSC043, of SCHU S4 with an i.d. LD50 of >10(8) CFU. FSC043 effectively vaccinated mice against challenge with a highly virulent type A strain, and the protective efficacy was at least as good as that of F. tularensis LVS, an empirically attenuated strain which has been used as an efficacious human vaccine. Comparative proteomics was used to identify two proteins of unknown function that were identified as defective in LVS and FSC043, and deletion mutants of SCHU S4 were created for each of the two encoding genes. One mutant, the DeltaFTT0918 strain, failed to express a 58-kDa protein, had an i.d. LD50 of approximately 10(5) CFU, and was found to be less capable than SCHU S4 of growing in peritoneal mouse macrophages. Mice that recovered from sublethal infection with the DeltaFTT0918 mutant survived when challenged 2 months later with >100 LD50s of the highly virulent type A strain FSC033. This is the first report of the generation of defined mutants of F. tularensis subsp. tularensis and their use as live vaccines.
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| 40. |
- Williamsson, Ia
(författare)
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Establishment Patterns of Model Diffusion Theory
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Information technology is now part of almost every product and service, and the ever-increasing rate of technology and software development demands an appropriate software development process model. The model, whichdescribes the software development process, plays a crucial role for success in software projects. Models are constantly produced and refined in academia and practice, but models from academia tend to remain unused in practice, or take a long time to reach practice. Currently there is a lack of knowledge on how models are transferred or diffused in and between academia and practice, which is the knowledge gap that this study aims to investigate.The research purpose has thus been to investigate and ground a theory about the diffusion of software process models in and between academia and practice. The study is based on data collected from 31 informants, from both academia and practice, and analyzed with a grounded theory method approach. The Diffusion of Innovation theory was consulted during theory development, and the perceived model characteristics, complexity, ando bservability are seen as distinguishing differences between the theories.The resulting grounded theory, “Establishment Patterns of Model Diffusion” describes four important areas, and how they affect each other ina model diffusion situation. The areas are: Motivation; Establishment; Usage; and Quality. How model diffusion takes place depends on the are as themselves, on the prevailing conditions, on the knowledge at hand and on how the areas are evaluated. This shows multi-faceted, time-dependent, and unpredictable patterns for model diffusion. The patterns include experience of model use, the past and future context of use, the characteristics of the model, requirements in the working process, individuals’ empowerment, availability of multiple models, composition of project groups, and the group members’ private and business networks.The findings have several implications. For academia, the benefits may be in the awareness of the multiple patterns for model diffusion and software process improvements, which cannot be separated from each other. Models are constantly adopted and simultaneously modified in practice. Practice may benefit from an awareness of the multiple patterns for model diffusionand sources of experience and knowledge, and how to make use of the existing knowledge capital strategically. Both academia and practice may also benefit from increased cooperation, each contributing their unique experience, and consequently increasing relevance for practice in the diffusion of models, and in developing and receiving research results in a useful format.
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