| 1. |
- Aquila, Andrew, et al.
(författare)
-
Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
-
Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
-
Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
|
|
| 2. |
- Arnlund, David, et al.
(författare)
-
Visualizing a protein quake with time-resolved X-ray scattering at a free-electron laser
- 2014
-
Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:9, s. 923-926
-
Tidskriftsartikel (refereegranskat)abstract
- We describe a method to measure ultrafast protein structural changes using time-resolved wide-angle X-ray scattering at an X-ray free-electron laser. We demonstrated this approach using multiphoton excitation of the Blastochloris viridis photosynthetic reaction center, observing an ultrafast global conformational change that arises within picoseconds and precedes the propagation of heat through the protein. This provides direct structural evidence for a 'protein quake': the hypothesis that proteins rapidly dissipate energy through quake-like structural motions.
|
|
| 3. |
- Barty, A., et al.
(författare)
-
Self-terminating diffraction gates femtosecond X-ray nanocrystallography measurements
- 2012
-
Ingår i: Nature Photonics. - 1749-4885 .- 1749-4893. ; 6:1, s. 35-40
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray free-electron lasers have enabled new approaches to the structural determination of protein crystals that are too small or radiation-sensitive for conventional analysis1. For sufficiently short pulses, diffraction is collected before significant changes occur to the sample, and it has been predicted that pulses as short as 10 fs may be required to acquire atomic-resolution structural information1, 2, 3, 4. Here, we describe a mechanism unique to ultrafast, ultra-intense X-ray experiments that allows structural information to be collected from crystalline samples using high radiation doses without the requirement for the pulse to terminate before the onset of sample damage. Instead, the diffracted X-rays are gated by a rapid loss of crystalline periodicity, producing apparent pulse lengths significantly shorter than the duration of the incident pulse. The shortest apparent pulse lengths occur at the highest resolution, and our measurements indicate that current X-ray free-electron laser technology5 should enable structural determination from submicrometre protein crystals with atomic resolution.
|
|
| 4. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
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.
|
|
| 5. |
|
|
| 6. |
- Ekelund Axelson, Lena, et al.
(författare)
-
Communicating GHG mitigating food consumption in-store An observational study of food retailers in five European countries
- 2014
-
Ingår i: British Food Journal. - 0007-070X .- 1758-4108. ; 116, s. 1618-1635
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose - Current food consumption patterns contribute negatively to greenhouse gas (GHG) emissions and climate change. Positioned at the interface between producers and consumers, retailers have the potential to reduce this problem through informing their customers on the consequences of their actions. The purpose of this paper is to understand the variety of ways European retailers go about informing their customers on the linkage between food choice and climate change as well as which actions they advocate in-store to reduce the problem.Design/methodology/approach - In-store walkthroughs lasting between 40 minutes and 1.5 hours were carried out at 30 grocery stores in five European countries to identify climate mitigating communications. The observations targeted any message produced and transmitted by the retailer where links between food and climate change were drawn.Findings - The diversity in climate mitigating food communication we expected to find across Europe did not materialize. Only four out of the 30 retailers visited transmitted to their customers any information showing a direct link between food consumption and climate change. Indirectly, the authors found some retailers communicating food choices believed to lead to GHG reduction without linking them to climate change. Finally the authors found several retailers communicating what the authors argue are ambiguous messages to their customers where sustainability issues were confounded with climate ones. The dearth of climate mitigating food communications reveals the complexity in informing customers on such issues but also a possible lack of interest on the part of both parties.Originality/value - This research contributes empirically to knowledge of how retailers communicate climate mitigating food consumption to consumers.
|
|
| 7. |
- Elks, Cathy E, et al.
(författare)
-
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
-
Tidskriftsartikel (refereegranskat)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
|
|
| 8. |
- Fernqvist, Fredrik, et al.
(författare)
-
Who's to Blame for Tasteless Tomatoes? The Effect of Tomato Chilling on Consumers' Taste Perceptions
- 2012
-
Ingår i: European Journal of Horticultural Science. - 1611-4426 .- 1611-4434. ; 77, s. 193-198
-
Tidskriftsartikel (refereegranskat)abstract
- The most common stated reason to consumer dissatisfaction with tomatoes is lack of flavour. It has been shown that a common storage practice among consumer households is to store tomatoes in the refrigerator, which have a negative impact on tomato taste. Thus, consumer postharvest treatment in home may be a reason to diminishing taste. In a Swedish consumer survey we find that 53 % are dissatisfied with tomato taste and that 74 % store their tomatoes after purchase in a temperature below recommendations. Research done on the effect of tomato storage has led to the suggestion that growers should educate consumers on handling practices in order to remove the negative effect chilling has on taste experience. However, past research has been conducted on samples that potentially do not represent the target consumer, as trained sensory panels do not perceive taste as untrained consumers do. Based on previous empirical studies using expert panels, we hypothesise that panels consisting of ordinary consumers will prefer tomatoes stored in room temperature to those chilled under ordinary refrigerated conditions (i.e. 7 degrees C) regardless of variety. Thus, we replicate and challenge past findings and normative recommendations through the use of two experiments involving consumer panels evaluating two varieties of tomatoes, 'Arvento' and 'Tiesto', stored two days in refrigerator (7 degrees C) and room temperature (21 degrees C) respectively. We found a significant difference in consumer liking for 'Arvento' that were unchilled (M=6.443, SD=+/- 1.765) and chilled (M=5.849, SD=+/- 1.894), t(351)=4.270, p<0.001 (two tailed), albeit with a small effect size (eta squared statistic (.049)). No significant difference in liking was found for the 'Tiesto' variety. We find, contrary to previous research, that storage temperature has no or only a marginal effect on perceived taste among respondents in untrained consumer panels for the two varieties in our trial. Theoretical and practical implications are discussed.
|
|
| 9. |
- Ganesh, Santhi K., et al.
(författare)
-
Loci influencing blood pressure identified using a cardiovascular gene-centric array
- 2013
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 22:8, s. 1663-1678
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped 50 000 single-nucleotide polymorphisms (SNPs) that capture variation in 2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P 2.4 10(6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.
|
|
| 10. |
- Heid, Iris M, et al.
(författare)
-
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
-
Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
|
|
| 11. |
- Hunter, Erik
(författare)
-
Entrepreneurial ties and innovativeness in the start-up decision
- 2012
-
Ingår i: International Journal of Entrepreneurship and Innovation. - : SAGE Publications. - 1465-7503 .- 2043-6882. ; 13, s. 153-163
-
Tidskriftsartikel (refereegranskat)abstract
- Do entrepreneurial ties increase innovativeness during the start-up process? Based on data collected from 45 countries and 7,067 nascent entrepreneurs, the authors' results indicate that knowing someone who has started a business within the last two years (entrepreneurial ties) has a significant impact on the intended level of innovativeness during the start-up process. Specifically, entrepreneurial ties have a positive impact on the expected level of competition, intended newness to customers, newness of technology and the intended level of exports and growth. This study contributes to the entrepreneurial network literature by changing the focus from the influence of ties on the start-up decision per se to their influence on the innovative nature of the start-up process.
|
|
| 12. |
- Isgren, Ellinor, et al.
(författare)
-
Alternativa försäljningskanaler för nöt- och lammkött : kartläggning och analys
- 2012
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Den här rapporten syftar till att kartlägga de alternativa försäljningskanaler för nöt-och lammkött som finns i Sverige (dvs. verksamheter utöver dagligvaruhandeln som säljer nöt- och/eller lammkött direkt till slutkonsument), samt att genom en kvalitativ intervjustudie få en djupare förståelse för verksamhetskategorierna identifierade genom kartläggningen. Kartläggningen utfördes med internet som verktyg och identifierade 395 olika verksamheter i tre huvudkategorier; gårdsbutiker (95), försäljning av köttlådor (200) och köttbutiker (100). Gårdsbutiker säljer ofta kött tillsammans med andra typer av produkter. Köttlådor säljs framför allt från enskilda producenter men det finns även företag och föreningar som gemensamt säljer och marknadsför sina produkter. Köttbutiker ligger ofta i tätorter och har ibland även egen produktion knuten till sig. Någon typ av verksamhet har identifierats i de flesta av Sveriges landskap, men antalet identifierade verksamheter varierar från inga alls i Lappland och Härjedalen till över 60 i Uppland, Västergötland och Uppland, med en genomsnittlig koncentration på en verksamhet per 24 000 invånare. Befolknings- och djurhållningstäthet är troligen en stor del av förklaringen till variationen, men det kan även finnas andra faktorer, till exempel att en verksamhet ger upphov till fler, tillgång till slakterier som kan samarbeta med småskaliga aktörer, och turism. Intervjustudien utfördes med 5 verksamheter från varje huvudkategori, dvs. totalt 15 verksamheter via telefon eller personligt möte. Alla intervjuade verksamheter sålde kött från egen produktion och/eller svenskt och så närproducerat som möjligt (detta är dock inte nödvändigtvis fallet då det finns ett mindre antal köttbutiker identifierade genom kartläggningen som även eller endast säljer importerat kött). Personerna bakom verksamheterna var i varierande åldrar men hade gemensamt att man ofta sen länge hade en koppling till orten eller regionen man var verksam i samt att det fanns ett stort personligt intresse för hållbarhet, djurvälfärd och köttkvalitet. Man var överlag positivt inställd till verksamhetens framtidsutsikter då man såg ett ökande intresse och kunskap bland konsumenterna rörande köttets ursprung, kvalitet och hälsoaspekter, detta trots att producenterna i studien ofta såg en blygsam lönsamhet och en stor arbetsinsats (köttbutiksinnehavarna tycktes uppfatta lönsamheten som relativt god, ibland över förväntan). Det finns tecken, utöver verksamhetsutövarnas intryck, som tyder på att de alternativa försäljningskanalerna är på frammarsch då många verksamheter (både inom intervjustudien och kartläggningen i stort) startats inom 1-2 år; däremot är det okänt hur många verksamheter som lagts ned under samma period. Verksamheternas erfarenheter är dock inte odelat positiva. Det finns bland en del en viss skepticism då intresset förvisso har ökat men att de allra flesta konsumenter fortfarande endast är intresserade av köttets pris och har vant sig vid dagligvaruhandelns billiga livsmedel. En producent upplever också att andra producenter säljer till orimligt låga priser vilket försvårar möjligheterna till lönsamhet. Prisvariationen för vissa produkter är stor och tycks inte endast kunna förklaras av skillnader i kvalitet och styckning. Andra problem inkluderar bristande kunskap bland konsumenterna rörande de mindre ädla detaljerna, krånglig byråkrati, och en s.k. ”inflation” i vagt definierade begrepp som närproducerat. Just detta att köttet är närproducerat eller kanske framför allt att man vet var köttet kommer ifrån och hur djuren haft det tror verksamhetsutövarna är viktiga mervärden för kunderna, liksom att köttet håller en hög kvalitet. Förbättrad lönsamhet för producenter med egen försäljning, hur man som verksamhet utmärker och marknadsför sig när det finns fler och fler som erbjuder samma eller liknande mervärden, utbyte av kunskap och erfarenheter och samverkan med olika typer av aktörer är viktiga frågor inför framtiden.
|
|
| 13. |
- Isgren, Ellinor, et al.
(författare)
-
Strukturer och strategier för lönsam produktion och säker tillförsel av inhemskt nötkött : Lärdomar från McDonald’s europeiska leverantörskedjor
- 2013
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I den här rapporten presenteras resultatet från ett forskningsprojekt utfört vid Sveriges Lantbruksuniversitet i samarbete med McDonald’s Sverige, Sveriges Nötköttsproducenter och LRF. Syftet var att dra lärdomar från några av McDonald’s europeiska motsvarigheter och deras leverantörskedja, kring hur olika strukturer och strategier i kedjan kan hjälpa till att stimulera och stärka produktionen av inhemskt nötkött och därmed också säkra tillgången. Efter litteraturstudier intervjuades personer inom leverantörskedjan i Österrike, Irland och Storbritannien under våren 2013. Materialet kompletterades sedan med intervjuer med personer inom den svenska nötköttskedjan. Rapportens resultatdel inleds med en översikt över nötköttsproduktion och -marknad i de fyra länderna. Skillnader och likheter diskuteras, och både i skillnaderna och i likheterna god potential till kunskapsöverföring mellan länderna – även om det måste göras med viss försiktighet. När vi tittar närmre på de kedjor som kan sägas utgöra vår ”fallstudie” har vi identifierat ett antal faktorer som kan kunna ligga till grund för rekommendationer för svenska nötköttskedjor. En är hur man inom producentledet organiserar sig i form av olika typer av producentföreningar och -grupper. Vi uppmuntrar utvecklingen mot mer organisation av olika typer inom det svenska producentledet. Vi såg också ett ökat fokus på samarbete mellan olika nivåer i kedjan, och flera exempel visas upp i rapporten, såsom gemensamma satsningar på kunskapsöverföring och utveckling av kvalitetssäkringssystem. Det råder en stor tilltro till att samarbete och god kommunikation genom hela kedjan är en nödvändig och framgångsrik strategi för nötköttssektorn. Alla tre kedjor använder sig av de omfattande kvalitetssäkringssystem som utvecklats för inhemskt nötkött. Systemen har växt fram utifrån konsumenternas efterfrågan och krav, vilket kanske är den största anledningen till att de ses som en nödvändig och generellt positiv utveckling. Ett annorlunda utgångsläge i Sverige gör att vi ställer oss tveksamma till att försöka efterlikna dessa länder på den här punkten. I Österrikes kedja har man dock även utvecklat ett system specifikt för McDonald’s kedja. I utbyte för att uppfylla företagets krav får producenter en merbetalning per kg av slaktvikten. På så sätt vill man bidra på ett mer direkt sätt till den inhemska produktionen av en viss sorts nötkött. I alla fyra länder är det köparna, såsom dagligvaruhandeln, som uppfattas ha makten i kedjan - vilket ses som problematiskt. Det här behöver angripas från två håll; dels behöver producenterna göra vad de kan för att skapa en bättre position genom till exempel organisation, och dessutom utnyttja sin befintliga förhandlingskraft bättre. Dels behöver köpare som månar om att kunna köpa inhemskt nötkött även i framtiden anamma mer långsiktiga strategier, där man tar hänsyn till vad som händer i hela kedjan och inte bara i transaktionen med den direkta leverantören. Rapporten avslutas med våra slutsatser och rekommendationer som riktar sig mot producenter såväl som förädlingsledet och köpare, samt några mot sektorn som helhet.
|
|
| 14. |
|
|
| 15. |
- Johansson, Linda C, 1983, et al.
(författare)
-
Lipidic phase membrane protein serial femtosecond crystallography.
- 2012
-
Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 9:3, s. 263-265
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray free electron laser (X-FEL)-based serial femtosecond crystallography is an emerging method with potential to rapidly advance the challenging field of membrane protein structural biology. Here we recorded interpretable diffraction data from micrometer-sized lipidic sponge phase crystals of the Blastochloris viridis photosynthetic reaction center delivered into an X-FEL beam using a sponge phase micro-jet.
|
|
| 16. |
- Johansson, Linda C, 1983, et al.
(författare)
-
Structure of a photosynthetic reaction centre determined by serial femtosecond crystallography.
- 2013
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- Serial femtosecond crystallography is an X-ray free-electron-laser-based method with considerable potential to have an impact on challenging problems in structural biology. Here we present X-ray diffraction data recorded from microcrystals of the Blastochloris viridis photosynthetic reaction centre to 2.8Å resolution and determine its serial femtosecond crystallography structure to 3.5Å resolution. Although every microcrystal is exposed to a dose of 33MGy, no signs of X-ray-induced radiation damage are visible in this integral membrane protein structure.
|
|
| 17. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
|
|
| 18. |
|
|
| 19. |
- Mandt, Kathleen E., et al.
(författare)
-
Ion densities and composition of Titan's upper atmosphere derived from the Cassini Ion Neutral Mass Spectrometer : Analysis methods and comparison of measured ion densities to photochemical model simulations
- 2012
-
Ingår i: Journal of Geophysical Research. - 0148-0227 .- 2156-2202. ; 117, s. E10006-
-
Tidskriftsartikel (refereegranskat)abstract
- The Cassini Ion Neutral Mass Spectrometer (INMS) has measured both neutral and ion species in Titan's upper atmosphere and ionosphere and the Enceladus plumes. Ion densities derived from INMS measurements are essential data for constraining photochemical models of Titan's ionosphere. The objective of this paper is to present an optimized method for converting raw data measured by INMS to ion densities. To do this, we conduct a detailed analysis of ground and in-flight calibration to constrain the instrument response to ion energy, the critical parameter on which the calibration is based. Data taken by the Cassini Radio Plasma Wave Science Langmuir Probe and the Cassini Plasma Spectrometer Ion Beam Spectrometer are used as independent measurement constraints in this analysis. Total ion densities derived with this method show good agreement with these data sets in the altitude region (similar to 1100-1400 km) where ion drift velocities are low and the mass of the ions is within the measurement range of the INMS (1-99 Daltons). Although ion densities calculated by the method presented here differ slightly from those presented in previous INMS publications, we find that the implications for the science presented in previous publications is mostly negligible. We demonstrate the role of the INMS ion densities in constraining photochemical models and find that (1) cross sections having high resolution as a function of wavelength are necessary for calculating the initial photoionization products and (2) there are disagreements between the measured ion densities representative of the initial steps in Titan photochemistry that require further investigation.
|
|
| 20. |
- Palmer, Nicholette D, et al.
(författare)
-
A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
-
Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
-
Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
|
|
| 21. |
|
|
| 22. |
- Speliotes, Elizabeth K., et al.
(författare)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
| 23. |
- Stolk, Lisette, et al.
(författare)
-
Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
-
Tidskriftsartikel (refereegranskat)abstract
- To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
|
|
| 24. |
- Tragante, Vinicius, et al.
(författare)
-
Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.
- 2014
-
Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:3, s. 349-360
-
Tidskriftsartikel (refereegranskat)abstract
- Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
|
|
| 25. |
|
|
