| 1. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 2. |
- Dell'Amico, Alessandro, 1984-
(författare)
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On Electrohydraulic Pressure Control for Power Steering Applications : Active Steering for Road Vehicles
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis deals with the Electrohydraulic Power Steering system for road vehicles, using electronic pressure control valves. With an ever increasing demand for safer vehicles and fewer traffic accidents, steering-related active safety functions are becoming more common in modern vehicles. Future road vehicles will also evolve towards autonomous vehicles, with several safety, environmental and financial benefits. A key component in realising such solutions is active steering.The power steering system was initially developed to ease the driver's workload by assisting in turning the wheels. This is traditionally done through a passive open-centre hydraulic system and heavy trucks must still rely on fluid power, due to the heavy work forces. Since the purpose of the original system is to control the assistive pressure, one way would be to use proportional pressure control valves. Since these are electronically controlled, active steering is possible and with closed-centre, energy efficiency can be significantly improved on.In this work, such a system is analysed in detail with the purpose of investigating the possible use of the system for Boost curve control and position control for autonomous driving. Commercially available valves are investigated since they provide an attractive solution. A model-based approach is adopted, where simulation of the system is an important tool. Another important tool is hardware-in-the-loop simulation. A test rig of an electrohydraulic power steering system, is developed.This work has shown how proportional pressure control valves can be used for Boost curve control and position control and what implications this has on a system level. As it turns out, the valves add a great deal of time lag and with the high gain from the Boost curve, this creates a control challenge. The problem can be handled by tuning the Boost gain, pressure response and damping and has been effectively shown through simulation and experiments. For position control, there is greater freedom to design the controller to fit the system. The pressure response can be made fast enough for this case and the time lag is much less critical.
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| 3. |
- Evangelou, Evangelos, et al.
(författare)
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Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:10, s. 1412-1425
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Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.
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| 4. |
- Flannick, Jason, et al.
(författare)
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Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
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Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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| 5. |
- Franzoni, Federica, et al.
(författare)
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A Novel System for Combined Hydrogen Production and Power Generation
- 2009
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Ingår i: SAE Technical Papers. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. - 0148-7191 .- 2688-3627. ; , s. 1-10
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Konferensbidrag (refereegranskat)abstract
- A novel concept of combined hydrogen production andpower generation system based on the combustion ofaluminum in water is explored. The energy conversionsystem proposed is potentially able to provide fourdifferent energy sources, such us pressurized hydrogen,high temperature steam, heat, and work at thecrankshaft on demand, as well as to fully comply withthe environment sustainability requirements.Once aluminum oxide layer is removed, the purealuminum can react with water producing alumina andhydrogen while releasing a significant amount of energy.Thus, the hydrogen can be stored for further use and thesteam can be employed for energy generation or workproduction in a supplementary power system. Theprocess is proved to be self-sustained and to provide aremarkable amount of energy available as work orhydrogen. Furthermore, since the aluminum oxidation iscompletely GHG free and the alumina produced by thereaction can be recycled back to aluminum, the processhas a sustainable environmental management.A preliminary design of the combined hydrogenproduction and power generation unit based on thealuminum combustion in water is proposed and theefficiency of the process is discussed in terms of bothhydrogen production and power generation
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| 6. |
- Franzoni, Federica, et al.
(författare)
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Combined hydrogen production and power generation from aluminumcombustion with water: analysis of the concept
- 2010
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Ingår i: International Journal of Hydrogen Energy. - : Elsevier BV. - 0360-3199. ; 35:4, s. 1548-1559
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Tidskriftsartikel (refereegranskat)abstract
- In this paper the combined production of hydrogen and power based on the aluminum combustion with water isinvestigated. Furthermore, a concept system is proposed that is potentially able to provide pressurized hydrogen and hightemperature steam along with heat and work at the crankshaft. The system demonstrates high energy conversionefficiency, as well as it fully complies with environment sustainability requirements.The use of aluminum as an energy carrier or a fuel has been already studied in literature, but its application in the field ofthe energy conversion systems is currently not well explored. Once aluminum oxide layer is removed, the pure aluminumcan react with water producing alumina and hydrogen while releasing a significant amount of heat that can be used toproduce superheated steam. Both pressurized hydrogen and superheated steam can be used in a turbine power systemdeveloping electrical or mechanical power. Moreover, the hydrogen can be either stored for further usage or burned inorder to obtain a larger amount of heat for the process.From an environmental viewpoint, an energy conversion utilizing the combustion of aluminum with water is veryinteresting since the aluminum oxidation is completely GHG free and the high grade alumina produced by the reaction isharmless and can be employed in other technological processes or recycled back to aluminum.Finally, an embodiment of the concept system for the combined production of hydrogen and power based on thealuminum combustion with water is proposed and its possible applications are discussed.
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| 7. |
- Fuchsberger, Christian, et al.
(författare)
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The genetic architecture of type 2 diabetes
- 2016
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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| 8. |
- Joshi, Peter K, et al.
(författare)
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Directional dominance on stature and cognition in diverse human populations
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
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Tidskriftsartikel (refereegranskat)abstract
- Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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| 9. |
- Kimberling, William J., et al.
(författare)
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Gene mapping of Usher syndrome type IIa : localization of the gene to a 2.1-cM segment on chromosome 1q41
- 1995
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 56:1, s. 216-223
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor β2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.
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| 10. |
- Kimberling, William J., et al.
(författare)
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Localization of Usher syndrome type II to chromosome 1q
- 1990
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Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 7:2, s. 245-249
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Tidskriftsartikel (refereegranskat)abstract
- Usher syndrome is characterized by congenital hearing loss, progressive visual impairment due to retinitis pigmentosa, and variable vestibular problems. The two subtypes of Usher syndrome, types I and II, can be distinguished by the degree of hearing loss and by the presence or absence of vestibular dysfunction. Type I is characterized by a profound hearing loss and totally absent vestibular responses, while type II has a milder hearing loss and normal vestibular function. Fifty-five members of eight type II Usher syndrome families were typed for three DNA markers in the distal region of chromosome 1q: D1S65 (pEKH7.4), REN (pHRnES1.9), and D1S81 (pTHH33). Statistically significant linkage was observed for Usher syndrome type II with a maximum multipoint lod score of 6.37 at the position of the marker THH33, thus localizing the Usher type II (USH2) gene to 1q. Nine families with type I Usher syndrome failed to show linkage to the same three markers. The statistical test for heterogeneity of linkage between Usher syndrome types I and II was highly significant, thus demonstrating that they are due to mutations at different genetic loci.
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