| 1. |
- Ahmad, Shafqat, et al.
(författare)
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Gene × physical activity interactions in obesity: combined analysis of 111,421 individuals of European ancestry. : combined analysis of 111,421 individuals of European ancestry
- 2013
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 9:7, s. 1003607-1003607
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Tidskriftsartikel (refereegranskat)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS × physical activity interaction effect estimate (Pinteraction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, Pinteraction = 0.014 vs. n = 71,611, Pinteraction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (Pinteraction = 0.003) and the SEC16B rs10913469 (Pinteraction = 0.025) variants showed evidence of SNP × physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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| 2. |
- Ahmad, Shafqat, et al.
(författare)
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Gene x physical activity interactions in obesity : combined analysis of 111,421 individuals of European ancestry
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science. - 1553-7390 .- 1553-7404. ; 9:7, s. e1003607-
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Tidskriftsartikel (refereegranskat)abstract
- Numerous obesity loci have been identified using genome-wide association studies. A UK study indicated that physical activity may attenuate the cumulative effect of 12 of these loci, but replication studies are lacking. Therefore, we tested whether the aggregate effect of these loci is diminished in adults of European ancestry reporting high levels of physical activity. Twelve obesity-susceptibility loci were genotyped or imputed in 111,421 participants. A genetic risk score (GRS) was calculated by summing the BMI-associated alleles of each genetic variant. Physical activity was assessed using self-administered questionnaires. Multiplicative interactions between the GRS and physical activity on BMI were tested in linear and logistic regression models in each cohort, with adjustment for age, age(2), sex, study center (for multicenter studies), and the marginal terms for physical activity and the GRS. These results were combined using meta-analysis weighted by cohort sample size. The meta-analysis yielded a statistically significant GRS x physical activity interaction effect estimate (P-interaction = 0.015). However, a statistically significant interaction effect was only apparent in North American cohorts (n = 39,810, P-interaction = 0.014 vs. n = 71,611, P-interaction = 0.275 for Europeans). In secondary analyses, both the FTO rs1121980 (P-interaction = 0.003) and the SEC16B rs10913469 (P-interaction = 0.025) variants showed evidence of SNP x physical activity interactions. This meta-analysis of 111,421 individuals provides further support for an interaction between physical activity and a GRS in obesity disposition, although these findings hinge on the inclusion of cohorts from North America, indicating that these results are either population-specific or non-causal.
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| 3. |
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| 4. |
- Dahl Jensen, Lasse, et al.
(författare)
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Opposing Effects of Circadian Clock Genes Bmal1 and Period2 in Regulation of VEGF-Dependent Angiogenesis in Developing Zebrafish
- 2012
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Ingår i: Cell Reports. - : Elsevier (Cell Press). - 2211-1247. ; 2:2, s. 231-241
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mechanisms underlying circadian-regulated physiological processes remain largely unknown. Here, we show that disruption of the circadian clock by both constant exposure to light and genetic manipulation of key genes in zebrafish led to impaired developmental angiogenesis. A bmal1-specific morpholino inhibited developmental angiogenesis in zebrafish embryos without causing obvious nonvascular phenotypes. Conversely, a period2 morpholino accelerated angiogenic vessel growth, suggesting that Bmal1 and Period2 display opposing angiogenic effects. Using a promoter-reporter system consisting of various deleted vegf-promoter mutants, we show that Bmal1 directly binds to and activates the vegf promoter via E-boxes. Additionally, we provide evidence that knockdown of Bmal1 leads to impaired Notch-inhibition-induced vascular sprouting. These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis.
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| 5. |
- Fleischer, Siegfried, 1938-, et al.
(författare)
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Dark oxidation of water in soils
- 2013
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - Hoboken, NJ : Wiley-Blackwell. - 0280-6509 .- 1600-0889. ; 65:1
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Tidskriftsartikel (refereegranskat)abstract
- We report the release of oxygen (O2) under dark conditions in aerobic soils. This unexpected process is hidden by respiration which constitutes the dominating reversal O2 flux. By using H218O in different soils, we confirmed that 16O18O and 18O2 released under dark soil conditions originated from added H218O. Water is the only large-scale source of electrons for reduction of CO2 in soils, but it has not been considered as an electron donor because of the very strong oxidation system needed. A high share of soil inorganic material seems to favor the release of O2. © 2013 S. Fleischer et al.
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| 6. |
- Hosaka, Kayoko, et al.
(författare)
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Tumour PDGF-BB expression levels determine dual effects of anti-PDGF drugs on vascular remodelling and metastasis
- 2013
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Ingår i: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:2129
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Tidskriftsartikel (refereegranskat)abstract
- Anti-platelet-derived growth factor (PDGF) drugs are routinely used in front-line therapy for the treatment of various cancers, but the molecular mechanism underlying their dose-dependent impact on vascular remodelling remains poorly understood. Here we show that anti-PDGF drugs significantly inhibit tumour growth and metastasis in high PDGF-BB-producing tumours by preventing pericyte loss and vascular permeability, whereas they promote tumour cell dissemination and metastasis in PDGF-BB-low-producing or PDGF-BB-negative tumours by ablating pericytes from tumour vessels. We show that this opposing effect is due to PDGF-beta signalling in pericytes. Persistent exposure of pericytes to PDGF-BB markedly downregulates PDGF-beta and inactivation of the PDGF-beta signalling decreases integrin alpha 1 beta 1 levels, which impairs pericyte adhesion to extracellular matrix components in blood vessels. Our data suggest that tumour PDGF-BB levels may serve as a biomarker for selection of tumour-bearing hosts for anti-PDGF therapy and unsupervised use of anti-PDGF drugs could potentially promote tumour invasion and metastasis.
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| 7. |
- Jansson, Gustav, et al.
(författare)
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Modularization in a housing platform for mass customization
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The problem of combining production efficiency with flexible product offers in housing design is well known. The platform concept is applied in housing to support design and production with predefined solutions. Modularization can be useful to meet both client demands on flexibility and production requirements on standardisation. To identify the module drivers in housing, ten projects at one off-site housing company were analysed. Furthermore, the cycle time for the modules was recorded. Client, design, purchasing, production and suppliers have different module drivers. When module drivers concur, modules are identified by; identifying clear and few interfaces, the availability of a supplier, and the cycle time for the design and production of the module in relation to the production pace. The results from the case study further show that fixed geometry on modules is a less successful concept than parameterised modules in housing. The ability to outsource technical solutions increased, when the module drivers were combined with a long term relationship with the supplier. Variant modules were successfully applied in the studied company to respond to client demands. Further research is needed on how to configure generic modules.
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| 8. |
- Jensen, Laura, et al.
(författare)
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Cell transplantation in Parkinson's disease: problems and perspectives.
- 2010
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Ingår i: Current Opinion in Neurology. - 1473-6551. ; 23, s. 426-432
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: We review recent experiments conducted using embryonic tissue and stem cell transplants in experimental models of Parkinson's disease. We also highlight the challenges which remain to be met in order for cell therapy to become clinically effective and safe. RECENT FINDINGS: The outcome of previous clinical transplantation trials was variable in terms of motor recovery. We discuss whether transplants can mitigate L-3,4-dihydroxyphenylalanine (L-DOPA)-induced dyskinesias and consider the risk factors which predispose to graft-induced dyskinesias. In addition, we introduce Transeuro, a new European Union-funded multicenter consortium which plans to perform transplantation trials.Stem cells have emerged as an alternative source for the generation of dopaminergic precursors. We briefly outline progress made in the use of human embryonic stem cells and focus predominantly on the emerging field of induced pluripotency. We conclude by introducing the exciting and novel method of direct reprogramming which involves the conversion of fibroblasts to neurons without inducing a pluripotent state. SUMMARY: The area of cell transplantation has been revitalized by the identification of parameters which predispose patients to graft-induced dyskinesias and by the emergence of novel methods of generating dopaminergic neurons. Hopefully, the Transeuro clinical trials will give further impetus and act as a stepping stone to future trials employing stem-cell-derived neurons.
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| 9. |
- Jensen, Patrik, et al.
(författare)
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Applying products in product platforms in the AEC firm
- 2014
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Ingår i: Computing in civil and building engineering. - Reston, VA : American Society of Civil Engineers (ASCE). - 9780784413616 ; , s. 1062-1069
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Konferensbidrag (refereegranskat)abstract
- A 5 step method for developing configurable “products in product” platforms to be used in an engineer-to-order (ETO) design process is proposed. The idea is based on the transformation of typical product architectures into modular design platforms where standard and variant modules are identified and developed. The platform modules can then be configured and combined with traditional design methods to meet the project specific requirements in the design process. Based on 1193 project designs, several configurable “products in product” were identified and developed in a real case study using the proposed method.
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| 10. |
- Jensen, Patrik
(författare)
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Configuration of modularised building systems
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Swedish building industry is mainly project-oriented where the design process is sequential involving various disciplines separated both in time and space. During the last decades the industry has been criticised and accused of having problems with quality and low productivity. One cause is believed to be deficiencies in information transfer between different functional teams in the project organisation. A more product-oriented approach has been proposed by some as one solution that can improve quality and productivity. Several construction companies have started to develop platforms consisting of standardized technical solutions and processes that can be adapted and used in specific projects. However, the current practice of involved disciplines need to adapt to new methods and processes and the question is; Is it possible to apply principles based on mass customisation in the one-of-a kind project dominated construction industry?In the shift to mass customization, the manufacturing industry is developing product platforms from which customized products can be configured in a so called configuration process. A product platform in the manufacturing industry consists of modules that can be combined into customized products using a configuration system. Modularization is the method used to organize the components of a product family with the aim to simplify and minimize the number of component variants to improve customization without compromising the productivity of the manufacturing process. Erixon (1998) defines modularization as; "Decomposition of a product into building blocks (modules) with specified interfaces, driven by company specific reasons". The aim of the thesis is to study and propose solutions of the integration between architectural design, engineering and production using mass customisation principles without changing the traditional structure of the AEC industry. The author's background as practising structural design engineer in an AEC consultancy company has made it possible to study, propose and apply methods in two real-life industrial cases and in one development project of a building system for multi-storey wooden houses. The research performed mainly relies on qualitative research methods combined with action research. The result of the thesis is a configuration demonstration, in which four product views been identified; the customer, the engineering, the production and the assembly view. Constraints and rules of the building system is transferred upstream while design information is transferred downstream the value chain using design automation and design guides embedded in the different disciplines CAD applications. The process has been illustrated for a cut-to-fit configurable wooden slab module in which a design guide is used in the architect tool transferring dimensional information via XML to the knowledge based engineering tool where the detailed design is automated. The result, including shop floor drawings, bill of quantities and CNC files is then used in the prefabrication of the customized floor slab module. The knowledge based engineering tool used in the demonstration is a product configurator integrated into a 3D CAD system mainly used in the mechanical industry. To implement configuration processes in the construction industry it is evident that constraints and rules of the building system needs to be transferred upstream to disciplines working early in the specification process. Otherwise the risk is high that "ad-hoc" solutions violating the rules of the building system will be transferred downstream to engineering and production causing quality issues and lower productivity as a result. Implementing configuration processes will also require new business models. AEC consultants with competence in engineering and advanced design tools can develop new modularised building systems and configuration tools rather than selling engineering hours in design of specific buildings. This can also foster the development of more open and flexible building systems on the market.
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