| 21. |
- Flannick, Jason, et al.
(författare)
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Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.
- 2014
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 46:4, s. 357-357
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Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ∼150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.
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| 22. |
- Hirao, Yuki, et al.
(författare)
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OGLE-2017-BLG-0406 : Spitzer Microlens Parallax Reveals Saturn-mass Planet Orbiting M-dwarf Host in the Inner Galactic Disk
- 2020
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Ingår i: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 160:2
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and analysis of the planetary microlensing event OGLE-2017-BLG-0406, which was observed both from the ground and by the Spitzer satellite in a solar orbit. At high magnification, the anomaly in the light curve was densely observed by ground-based-survey and follow-up groups, and it was found to be explained by a planetary lens with a planet/host mass ratio of q = 7.0 x 10(-4) from the light-curve modeling. The ground-only and Spitzer-only data each provide very strong one-dimensional (1D) constraints on the 2D microlens parallax vector pi(E). When combined, these yield a precise measurement of pi(E) and of the masses of the host M-host = 0.56 +/- 0.07 M-circle dot and planet M-planet = 0.41 +/- 0.05 M-Jup. The system lies at a distance D-L = 5.2 +/- 0.5 kpc from the Sun toward the Galactic bulge, and the host is more likely to be a disk population star according to the kinematics of the lens. The projected separation of the planet from the host is a(perpendicular to) = 3.5 +/- 0.3 au (i.e., just over twice the snow line). The Galactic-disk kinematics are established in part from a precise measurement of the source proper motion based on OGLE-IV data. By contrast, the Gaia proper-motion measurement of the source suffers from a catastrophic 10 sigma error.
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| 23. |
- Katsoulis, M, et al.
(författare)
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Excess mortality after hip fracture in elderly persons from Europe and the USA : the CHANCES project.
- 2017
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 281:3, s. 300-310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hip fractures are associated with diminished quality of life and survival especially amongst the elderly.OBJECTIVE: All-cause mortality after hip fracture was investigated to assess its magnitude.METHODS: A total of 122 808 participants from eight cohorts in Europe and the USA were followed up for a mean of 12.6 years, accumulating 4273 incident hip fractures and 27 999 deaths. Incident hip fractures were assessed through telephone interviews/questionnaires or national inpatient/fracture registries, and causes of death were verified with death certificates. Cox proportional hazards models and the time-dependent variable methodology were used to assess the association between hip fracture and mortality and its magnitude at different time intervals after the injury in each cohort. We obtained the effect estimates through a random-effects meta-analysis.RESULTS: Hip fracture was positively associated with increased all-cause mortality; the hazard ratio (HR) in the fully adjusted model was 2.12, 95% confidence interval (CI) 1.76-2.57, after adjusting for potential confounders. This association was stronger amongst men [HR: 2.39, 95% CI: 1.72-3.31] than amongst women [HR: 1.92, 95% CI: 1.54-2.39], although this difference was not significant. Mortality was higher during the first year after the hip fracture [HR: 2.78, 95% CI: 2.12-3.64], but it remained elevated without major fluctuations after longer time since hip fracture [HR (95% CI): 1.89 (1.50-2.37) after 1-4 years; 2.15 (1.81-2.55) after 4-8 years; 1.79 (1.57-2.05) after 8 or more years].CONCLUSION: In this large population-based sample of older persons across eight cohorts, hip fracture was associated with excess short- and long-term all-cause mortality in both sexes.
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| 24. |
- Mancini, L., et al.
(författare)
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Physical properties and transmission spectrum of the WASP-74 planetary system from multiband photometry
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 485:4, s. 5168-5179
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Tidskriftsartikel (refereegranskat)abstract
- We present broad-band photometry of 11 planetary transits of the hot Jupiter WASP-74 b, using three medium-class telescopes and employing the telescope-defocusing technique. Most of the transits were monitored through I filters and one was simultaneously observed in five optical (U, g', r', i', z') and three near-infrared (J, H, K) passbands, for a total of 18 light curves. We also obtained new high-resolution spectra of the host star. We used these new data to review the orbital and physical properties of the WASP-74 planetary system. We were able to better constrain the main system characteristics, measuring smaller radius and mass for both the hot Jupiter and its host star than previously reported in the literature. Joining our optical data with those taken with the HST in the near infrared, we built up an observational transmission spectrum of the planet, which suggests the presence of strong optical absorbers, as TiO and VO gases, in its atmosphere.
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| 25. |
- Manigand, S., et al.
(författare)
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The ALMA-PILS survey: First detection of the unsaturated 3-carbon molecules Propenal (C2H3CHO) and Propylene (C3H6) towards IRAS 16293-2422 B
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
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Tidskriftsartikel (refereegranskat)abstract
- Context. Complex organic molecules with three carbon atoms are found in the earliest stages of star formation. In particular, propenal (C2H3CHO) is a species of interest due to its implication in the formation of more complex species and even biotic molecules. Aims. This study aims to search for the presence of C2H3CHO and other three-carbon species such as propylene (C3H6) in the hot corino region of the low-mass protostellar binary IRAS 16293-2422 to understand their formation pathways. Methods. We use ALMA observations in Band 6 and 7 from various surveys to search for the presence of C3H6 and C2H3CHO towards the protostar IRAS 16293-2422 B (IRAS 16293B). The identification of the species and the estimates of the column densities and excitation temperatures are carried out by modeling the observed spectrum under the assumption of local thermodynamical equilibrium. Results. We report the detection of both C3H6 and C2H3CHO towards IRAS 16293B, however, no unblended lines were found towards the other component of the binary system, IRAS 16293A. We derive column density upper limits for C3H8, HCCCHO, n-C3H7OH, i-C3H7OH, C3O, and cis-HC(O)CHO towards IRAS 16293B. We then use a three-phase chemical model to simulate the formation of these species in a typical prestellar environment followed by its hydrodynamical collapse until the birth of the central protostar. Different formation paths, such as successive hydrogenation and radical-radical additions on grain surfaces, are tested and compared to the observational results in a number of different simulations, to assess which are the dominant formation mechanisms in the most embedded region of the protostar. Conclusions. The simulations reproduce the abundances within one order of magnitude from those observed towards IRAS 16293B, with the best agreement found for a rate of 10-12 cm3 s-1 for the gas-phase reaction C3 + O → C2 + CO. Successive hydrogenations of C3, HC(O)CHO, and CH3OCHO on grain surfaces are a major and crucial formation route of complex organics molecules, whereas both successive hydrogenation pathways and radical-radical addition reactions contribute to the formation of C2H5CHO.
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| 26. |
- Manigand, S., et al.
(författare)
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The ALMA-PILS survey: The first detection of doubly-deuterated methyl formate (CHD2OCHO) in the ISM
- 2019
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746.
-
Tidskriftsartikel (refereegranskat)abstract
- Studies of deuterated isotopologues of complex organic molecules can provide important constraints on their origin in regions of star formation. In particular, the abundances of deuterated species are very sensitive to the physical conditions in the environment where they form. Due to the low temperatures in regions of star formation, these isotopologues are enhanced to significant levels, making detections of multiply-deuterated species possible. However, for complex organic species, only the multiply-deuterated variants of methanol and methyl cyanide have been reported so far. The aim of this paper is to initiate the characterisation of multiply-deuterated variants of complex organic species with the first detection of doubly-deuterated methyl formate, CHD2OCHO. We use ALMA observations from the Protostellar Interferometric Line Survey (PILS) of the protostellar binary IRAS 16293-2422, in the spectral range of 329.1 GHz to 362.9 GHz. We report the first detection of doubly-deuterated methyl formate CHD2OCHO in the ISM. The D/H ratio of CHD2OCHO is found to be 2-3 times higher than the D/H ratio of CH2DOCHO for both sources, similar to the results for formaldehyde from the same dataset. The observations are compared to a gas-grain chemical network coupled to a dynamical physical model, tracing the evolution of a molecular cloud until the end of the Class 0 protostellar stage. The overall D/H ratio enhancements found in the observations are of the same order of magnitude as the predictions from the model for the early stages of Class 0 protostars. However, the higher D/H ratio of CHD2OCHO compared to the D/H ratio of CH2DOCHO is still not predicted by the model. This suggests that a mechanism is enhancing the D/H ratio of singly- and doubly-deuterated methyl formate that is not in the model, e.g. mechanisms for H-D substitutions.
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| 27. |
- Persson, Magnus V., 1983, et al.
(författare)
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The ALMA-PILS Survey: Formaldehyde deuteration in warm gas on small scales toward IRAS 16293-2422 B
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 610
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Tidskriftsartikel (refereegranskat)abstract
- Context. The enhanced degrees of deuterium fractionation observed in envelopes around protostars demonstrate the importance of chemistry at low temperatures, relevant in pre- and protostellar cores. Formaldehyde is an important species in the formation of methanol and more complex molecules. Aims. Here, we aim to present the first study of formaldehyde deuteration on small scales around the prototypical low-mass protostar IRAS 16293-2422 using high spatial and spectral resolution Atacama Large Millimeter/submillimeter Array (ALMA) observations. We determine the excitation temperature, abundances and fractionation level of several formaldehyde isotopologues, including its deuterated forms. Methods. Excitation temperature and column densities of formaldehyde in the gas close to one of the components of the binary were constrained through modeling of optically thin lines assuming local thermodynamical equilibrium. The abundance ratios were compared to results from previous single dish observations, astrochemical models and local ISM values. Results. Numerous isotopologues of formaldehyde are detected, among them H 2 C 17 O, and D 2 13 CO for the first time in the ISM. The large range of upper energy levels covered by the HDCO lines help constrain the excitation temperature to 106 ± 13 K. Using the derived column densities, formaldehyde shows a deuterium fractionation of HDCO/H 2 CO = 6.5 ± 1%, D 2 CO/HDCO = 12.8 -4.1 +3.3 %, and D 2 CO/H 2 CO = 0.6(4) ± 0.1%. The isotopic ratios derived are 16 O/ 18 O = 805 -79 +43 , 18 O/ 17 O = 3.2 -0.3 +0.2 , and 12 C/ 13 C = 56 -11 +8 . Conclusions. The HDCO/H 2 CO ratio is lower than that found in previous studies, highlighting the uncertainties involved in interpreting single dish observations of the inner warm regions. The D 2 CO/HDCO ratio is only slightly larger than the HDCO/H 2 CO ratio. This is consistent with formaldehyde forming in the ice as soon as CO has frozen onto the grains, with most of the deuteration happening toward the end of the prestellar core phase. A comparison with available time-dependent chemical models indicates that the source is in the early Class 0 stage.
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| 28. |
- Sperling, L., et al.
(författare)
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Detection of chromosomal abnormalities, congenital abnormalities and transfusion syndrome in twins
- 2007
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Ingår i: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 29:5, s. 517-526
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Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate the outcome of screening for structural malformations in twins and the outcome of screening for twin-twin transfusion syndrome (TTTS) among monochorionic twins through a number of ultrasound scans from 12 weeks' gestation. Methods Enrolled into this prospective multicenter observational study were women with twin pregnancies diagnosed before 14 + 6 gestational weeks. The monochorionic pregnancies were scanned every second week until 23 weeks in order to rule out early TTTS. All pregnancies had an anomaly scan in week 19 and fetal echocardiography in week 21 that was performed by specialists in fetal echocardiography. Zygosity was determined by DNA analysis in all twin pairs with the same sex. Results Among the 495 pregnancies the prenatal detection rate for severe structural abnormalities including chromosomal aneuploidies was 83% by the combination of a first-trimester nuchal translucency scan and the anomaly scan in week 19. The incidence of severe structural abnormalities was 2.6% and two-thirds of these anomalies were cardiac. There was no significant difference between the incidence in monozygotic and dizygotic twins, nor between twins conceived naturally or those conceived by assisted reproduction. The incidence of TTTS was 23% from 12 weeks until delivery, and all those monochorionic twin pregnancies that miscarried had signs of TTTS. Conclusion Twin pregnancies have an increased risk of congenital malformations and one out of four monochorionic pregnancies develops TTTS. Ultrasound screening to assess chorionicity and follow-up of monochorionic pregnancies to detect signs of TTTS, as well as malformation screening, are therefore essential in the antenatal care of twin pregnancies. Copyright (c) 2007 IS UOG. Published by John Wiley & Sons, Ltd.
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| 29. |
- Stacey, Simon N, et al.
(författare)
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A germline variant in the TP53 polyadenylation signal confers cancer susceptibility.
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:11, s. 1098-103
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Tidskriftsartikel (refereegranskat)abstract
- To identify new risk variants for cutaneous basal cell carcinoma, we performed a genome-wide association study of 16 million SNPs identified through whole-genome sequencing of 457 Icelanders. We imputed genotypes for 41,675 Illumina SNP chip-typed Icelanders and their relatives. In the discovery phase, the strongest signal came from rs78378222[C] (odds ratio (OR) = 2.36, P = 5.2 × 10(-17)), which has a frequency of 0.0192 in the Icelandic population. We then confirmed this association in non-Icelandic samples (OR = 1.75, P = 0.0060; overall OR = 2.16, P = 2.2 × 10(-20)). rs78378222 is in the 3' untranslated region of TP53 and changes the AATAAA polyadenylation signal to AATACA, resulting in impaired 3'-end processing of TP53 mRNA. Investigation of other tumor types identified associations of this SNP with prostate cancer (OR = 1.44, P = 2.4 × 10(-6)), glioma (OR = 2.35, P = 1.0 × 10(-5)) and colorectal adenoma (OR = 1.39, P = 1.6 × 10(-4)). However, we observed no effect for breast cancer, a common Li-Fraumeni syndrome tumor (OR = 1.06, P = 0.57, 95% confidence interval 0.88-1.27).
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| 30. |
- Taquet, V., et al.
(författare)
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Linking interstellar and cometary O2: A deep search for 16O18O in the solar-Type protostar IRAS 16293b-2422
- 2018
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 618
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Tidskriftsartikel (refereegranskat)abstract
- Recent measurements carried out at comet 67P/Churyumov-Gerasimenko (67P) with the Rosetta probe revealed that molecular oxygen, O2, is the fourth most abundant molecule in comets. Models show that O2 is likely of primordial nature, coming from the interstellar cloud from which our solar system was formed. However, gaseous O2 is an elusive molecule in the interstellar medium with only one detection towards quiescent molecular clouds, in the ρ Oph A core. We perform a deep search for molecular oxygen, through the 21-01 rotational transition at 234 GHz of its 16O18O isotopologue, towards the warm compact gas surrounding the nearby Class 0 protostar IRAS 16293-2422 B with the ALMA interferometer. We also look for the chemical daughters of O2, HO2, and H2O2. Unfortunately, the H2O2 rotational transition is dominated by ethylene oxide c-C2H4O while HO2 is not detected. The targeted 16O18O transition is surrounded by two brighter transitions at ± 1 km s-1 relative to the expected 16O18O transition frequency. After subtraction of these two transitions, residual emission at a 3σ level remains, but with a velocity offset of 0.3-0.5 km s-1 relative to the source velocity, rendering the detection "tentative". We derive the O2 column density for two excitation temperatures Tex of 125 and 300 K, as indicated by other molecules, in order to compare the O2 abundance between IRAS 16293 and comet 67P. Assuming that 16O18O is not detected and using methanol CH3OH as a reference species, we obtain a [O2]/[CH3OH] abundance ratio lower than 2-5, depending on the assumed Tex, a three to four times lower abundance than the [O2]/[CH3OH] ratio of 5-15 found in comet 67P. Such a low O2 abundance could be explained by the lower temperature of the dense cloud precursor of IRAS 16293 with respect to the one at the origin of our solar system that prevented efficient formation of O2 in interstellar ices.
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