SwePub - search: WFRF:(Winkler Martin Wolfgang)

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1.	Lango Allen, Hana, et al. (author) Hundreds of variants clustered in genomic loci and biological pathways affect human height. 2010 In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8 Journal article (peer-reviewed)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.
2.	Berndt, Sonja I., et al. (author) Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture 2013 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69 Journal article (peer-reviewed)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.
3.	Kanoni, Stavroula, et al. (author) Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis. 2022 In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1 Journal article (peer-reviewed)abstract Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
4.	Locke, Adam E, et al. (author) Genetic studies of body mass index yield new insights for obesity biology. 2015 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401 Journal article (peer-reviewed)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.
5.	Shungin, Dmitry, et al. (author) New genetic loci link adipose and insulin biology to body fat distribution. 2015 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378 Journal article (peer-reviewed)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.
6.	Gorski, Mathias, et al. (author) Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies 2022 In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639 Journal article (peer-reviewed)abstract Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
7.	Gorski, Mathias, et al. (author) Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline 2021 In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 99:4, s. 926-939 Journal article (peer-reviewed)abstract Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m2/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m2 at follow-up among those with eGFRcrea 60 mL/min/1.73m2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
8.	Schmidt, Sebastian, et al. (author) A reversible state of hypometabolism in a human cellular model of sporadic Parkinson's disease 2023 In: Nature Communications. - 2041-1723. ; 14:1 Journal article (peer-reviewed)abstract Sporadic Parkinson's Disease (sPD) is a progressive neurodegenerative disorder caused by multiple genetic and environmental factors. Mitochondrial dysfunction is one contributing factor, but its role at different stages of disease progression is not fully understood. Here, we showed that neural precursor cells and dopaminergic neurons derived from induced pluripotent stem cells (hiPSCs) from sPD patients exhibited a hypometabolism. Further analysis based on transcriptomics, proteomics, and metabolomics identified the citric acid cycle, specifically the alpha-ketoglutarate dehydrogenase complex (OGDHC), as bottleneck in sPD metabolism. A follow-up study of the patients approximately 10 years after initial biopsy demonstrated a correlation between OGDHC activity in our cellular model and the disease progression. In addition, the alterations in cellular metabolism observed in our cellular model were restored by interfering with the enhanced SHH signal transduction in sPD. Thus, inhibiting overactive SHH signaling may have potential as neuroprotective therapy during early stages of sPD. Mitochondrial dysfunction is a contributing factor in Parkinson's disease. Here the authors carry out a multilayered omics analysis of Parkinson's disease patient-derived neuronal cells, which reveals a reversible hypometabolism mediated by alpha-ketoglutarate dehydrogenase deficiency, which is correlated with disease progression in the donating patients.
9.	Anchordoqui, Luis A., et al. (author) The Forward Physics Facility : Sites, experiments, and physics potential 2022 In: Physics reports. - : Elsevier. - 0370-1573 .- 1873-6270. ; 968, s. 1-50 Journal article (peer-reviewed)abstract The Forward Physics Facility (FPF) is a proposal to create a cavern with the space and infrastructure to support a suite of far-forward experiments at the Large Hadron Collider during the High Luminosity era. Located along the beam collision axis and shielded from the interaction point by at least 100 m of concrete and rock, the FPF will house experiments that will detect particles outside the acceptance of the existing large LHC experiments and will observe rare and exotic processes in an extremely low-background environment. In this work, we summarize the current status of plans for the FPF, including recent progress in civil engineering in identifying promising sites for the FPF and the experiments currently envisioned to realize the FPF's physics potential. We then review the many Standard Model and new physics topics that will be advanced by the FPF, including searches for long-lived particles, probes of dark matter and dark sectors, high-statistics studies of TeV neutrinos of all three flavors, aspects of perturbative and non-perturbative QCD, and high-energy astroparticle physics.
10.	Di Mauro, Mattia, et al. (author) Multimessenger constraints on the dark matter interpretation of the Fermi-LAT Galactic Center excess 2021 In: Physical Review D. - 2470-0010 .- 2470-0029. ; 103:12 Journal article (peer-reviewed)abstract An excess of gamma rays in the data measured by the Fermi Large Area Telescope in the direction of the Galactic Center has been reported in several publications. This excess, labeled as the Galactic Center excess (GCE), is detected analyzing the data with different interstellar emission models, point source catalogs and analysis techniques. The characteristics of the GCE, recently measured with unprecedented precision, are all compatible with dark matter particles (DM) annihilating in the main halo of our Galaxy, even if other interpretations are still not excluded. We investigate the DM candidates that fit the observed GCE spectrum and spatial morphology. We assume a simple scenario with DM annihilating into a single channel but we inspect also more complicated models with two and three channels. We perform a search for a gamma-ray flux from a list of 48 Milky Way dwarf spheroidal galaxies (dSphs) using state-of-the-art estimation of the DM density in these objects. Since we do not find any significant signal from the dSphs, we put upper limits on the annihilation cross section that result to be compatible with the DM candidate that fits the GCE. However, we find that the GCE DM signal is excluded at the 95% confidence level by the AMS-02 (p) over bar flux data for all purely hadronic (semihadronic) channels unless the diffusive halo size L is smaller than 1.7 kpc (2.6 kpc). Such a small diffusion halo is at the 2 sigma significance lower limit for the results inferred from fluxes of radioactive cosmic rays and is in some tension with results from analyses performed with radio and gamma-ray data. Furthermore, AMS-02 e(+) data rule out the GCE DM interpretation with pure or partial annihilation into e(+)e(-). The only DM candidate that fits the GCE spectrum and fulfills all constraints obtained with the combined dSphs analysis and the AMS-02 (p) over bar and e(+) data annihilates purely (or very dominantly) into mu(+)mu(-), has a mass of similar to 60 GeV and roughly a thermal cross section.
11.	Freese, Katherine, et al. (author) Chain early dark energy : A Proposal for solving the Hubble tension and explaining today's dark energy 2021 In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 104:8 Journal article (peer-reviewed)abstract We propose a new model of early dark energy (EDE) as a possible solution to the Hubble tension in cosmology, the apparent discrepancy between local measurements of the Hubble constant H-0 similar or equal to 74 km s(-1) Mpc(-1) and H-0 similar or equal to 67 km s(-1) Mpc(-1) inferred from the cosmic microwave background (CMB). In chain EDE, the universe undergoes a series of first order phase transitions, starting at a high energy vacuum in a potential, and tunneling down through a chain of every lower energy metastable minima. As in all EDE models, the contribution of the vacuum energy to the total energy density of the universe is initially negligible, but reaches similar to 10% around matter-radiation equality, before cosmological data require it to redshift away quickly-at least as fast as radiation. We indeed obtain this required behavior with a series of N tunneling events, and show that for N > 600 the phase transitions are rapid enough to allow fast percolation and thereby avoid large scale anisotropies in the CMB. We construct a specific example of chain EDE featuring a scalar field in a quasiperiodic potential (a tilted cosine), which is ubiquitous in axion physics and, therefore, carries strong theoretical motivation. Interestingly, the energy difference between vacua can be roughly the size of today's dark energy (milli-electron-volt scale). Therefore, the end result of chain EDE could provide a natural explanation of dark energy, if the tunneling becomes extremely slow in the final step before the field reaches zero (or negative) energy. We discuss a simple mechanism which can stop the scalar field in the desired minimum. Thus chain EDE offers the exciting prospect to explain EDE and dark energy by the same scalar field.
12.	Freese, Katherine, 1957-, et al. (author) Dark matter and gravitational waves from a dark big bang 2023 In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 107:8 Journal article (peer-reviewed)abstract The hot big bang is often considered as the origin of all matter and radiation in the Universe. Primordial nucleosynthesis provides strong evidence that the early Universe contained a hot plasma of photons and baryons with a temperature T>MeV. However, the earliest probes of dark matter originate from much later times around the epoch of structure formation. In this work we describe a scenario in which dark matter (and possibly dark radiation) can be formed around or even after primordial nucleosynthesis in a second big bang, which we dub the “dark big bang.” The latter occurs through a phase transition in the dark sector that transforms dark vacuum energy into a hot dark plasma of particles; in this paper we focus on a first-order phase transition for the dark big bang. The correct dark matter abundance can be set by dark matter cannibalism or by pair annihilation within the dark sector followed by a thermal freeze-out. Alternatively ultraheavy “dark-zilla” dark matter can originate directly from bubble collisions during the dark big bang. We will show that the dark big bang is consistent with constraints from structure formation and the cosmic microwave background if it occurred when the Universe was less than one month old, corresponding to a temperature in the visible sector above O(keV). While the dark matter evades direct and indirect detection, the dark big bang gives rise to striking gravity wave signatures to be tested at pulsar timing array experiments. Furthermore, the dark big bang allows for realizations of self-interacting and/or warm dark matter, which suggest exciting discovery potential in future small-scale structure observations.
13.	Freese, Katherine, et al. (author) Have pulsar timing arrays detected the hot big bang: Gravitational waves from strong first order phase transitions in the early Universe 2022 In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 106:10 Journal article (peer-reviewed)abstract The origins of matter and radiation in the universe lie in a hot big bang. We present a number of well-motivated cosmologies in which the big bang occurs through a strong first-order phase transition - either at the end of inflation, after a period of kination ("kination-induced big bang"), or after a second period of vacuum domination in the early Universe ("supercooled big bang"); we also propose a "dark big bang"where only the dark matter in the Universe is created in a first-order phase transition much after inflation. In all of these scenarios, the resulting gravitational radiation can explain the tentative signals reported by the NANOGrav, Parkes, and European Pulsar Timing Array experiments if the reheating temperature of the hot big bang, and correspondingly the energy scale of the false vacuum, falls in the range T∗∼ρvac1/4=MeV-100 GeV. All of the same models at higher reheating temperatures will be of interest to upcoming ground- and space-based interferometer searches for gravitational waves at larger frequency.
14.	Freese, Katherine, et al. (author) Natural Chain Inflation 2022 In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 829 Journal article (peer-reviewed)abstract In Chain Inflation the universe tunnels along a series of false vacua of ever-decreasing energy. The main goal of this paper is to embed Chain Inflation in high energy fundamental physics. We begin by illustrating a simple effective formalism for calculating Cosmic Microwave Background (CMB) observables in Chain Inflation. Density perturbations seeding the anisotropies emerge from the probabilistic nature of tunneling (rather than from quantum fluctuations of the inflation). To obtain the correct normalization of the scalar power spectrum and the scalar spectral index, we find an upper limit on the scale of inflation at horizon crossing of CMB scales, V-*(1/4) < 10(12) GeV. We then provide an explicit realization of chain inflation, in which the inflaton is identified with an axion in supergravity. The axion enjoys a perturbative shift symmetry which is broken to a discrete remnant by instantons. The model, which we dub 'natural chain inflation' satisfies all cosmological constraints and can be embedded into a standard Lambda CDM cosmology. Our work provides a major step towards the ultraviolet completion of chain inflation in string theory.
15.	Freese, Katherine, 1957-, et al. (author) The Gravitational Wave Spectrum of Chain Inflation Other publication (other academic/artistic)abstract Chain inflation is an alternative to slow-roll inflation in which the inflaton tunnels along a large number of consecutive minima in its potential. In this work we perform the first comprehensive calculation of the gravitational wave spectrum of chain inflation. In contrast to slow-roll inflation the latter does not stem from quantum fluctuations of the gravitational field during inflation, but rather from the bubble collisions during the first-order phase transitions associated with vacuum tunneling. Our calculation is performed within an effective theory of chain inflation which builds on an expansion of the tunneling rate capturing most of the available model space. The effective theory can be seen as chain inflation's analogue of the slow-roll expansion in rolling models of inflation. We show that chain inflation produces a very characteristic double-peak spectrum: a faint high-frequency peak associated with the gravitational radiation emitted during inflation, and a strong low-frequency peak associated with the graceful exit from chain inflation (marking the transition to the radiation-dominated epoch). There exist very exciting prospects to test the gravitational wave signal from chain inflation at the aLIGO-aVIRGO-KAGRA network, at LISA and /or at pulsar timing array experiments. A particularly intriguing possibility we point out is that chain inflation could be the source of the stochastic gravitational wave background recently detected by NANOGrav, PPTA, EPTA and CPTA. We also show that the gravitational wave signal of chain inflation is often accompanied by running/ higher running of the scalar spectral index to be tested at future Cosmic Microwave Background experiments.
16.	Geilhufe, R. Matthias, et al. (author) Dirac materials for sub-MeV dark matter detection : New targets and improved formalism 2020 In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 101:5 Journal article (peer-reviewed)abstract Because of their tiny band gaps Dirac materials promise to improve the sensitivity for dark matter particles in the sub-MeV mass range by many orders of magnitude. We study several candidate materials and calculate the expected rates for dark matter scattering via light and heavy dark photons as well as for dark photon absorption. A particular emphasis is placed on how to distinguish a dark matter signal from background by searching for the characteristic daily modulation of the signal, which arises from the directional sensitivity of anisotropic materials in combination with the rotation of Earth. We revisit and improve previous calculations and propose two new candidate Dirac materials: bis(naphthoquinone)tetrathiafulvalene (BNQ-TTF) and Yb3PbO. We perform detailed calculations of the band structures of these materials and of ZrTe5 based on density functional theory and determine the band gap, the Fermi velocities, and the dielectric tensor. We show that in both ZrTe5 and BNQ-TTF the amplitude of the daily modulation can be larger than 10% of the total rate, allowing us to probe the preferred regions of parameter space even in the presence of sizable backgrounds. BNQ-TTF is found to be particularly sensitive to small dark matter masses (below 100 keV for scattering and below 50 meV for absorption), while Yb3PbO performs best for heavier particles.
17.	Heisig, Jan, et al. (author) Dark matter or correlated errors : Systematics of the AMS-02 antiproton excess 2020 In: Physical Review Research. - 2643-1564. ; 2:4 Journal article (peer-reviewed)abstract Several studies have pointed out an excess in the AMS-02 antiproton spectrum at rigidities of 10–20 GV. Its spectral properties were found to be consistent with a dark-matter particle of mass 50–100 GeV which annihilates hadronically at roughly the thermal rate. In this paper, we reinvestigate the antiproton excess, including all relevant sources of systematic errors. Most importantly, we perform a realistic estimate of the correlations in the AMS-02 systematic error which could potentially “fake” a dark-matter signal. The dominant systematics in the relevant rigidity range originate from uncertainties in the cross sections for absorption of cosmic rays within the detector material. We calculate their correlations within the Glauber-Gribov theory of inelastic scattering. The AMS-02 correlations enter our spectral search for dark matter in the form of covariance matrices, which we make publicly available for the cosmic-ray community. We find that the global significance of the antiproton excess is reduced to below 1 σ once all systematics, including the derived AMS-02 error correlations, are taken into account. No significant preference for a dark-matter signal in the AMS-02 antiproton data is found in the mass range 10–10 000 GeV.
18.	Hibar, Derrek P., et al. (author) Novel genetic loci associated with hippocampal volume 2017 In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8 Journal article (peer-reviewed)abstract The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
19.	Kane, Gordon, et al. (author) Baryogenesis from a modulus dominated universe 2020 In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :02 Journal article (peer-reviewed)abstract String/ M-theory compactifications predict the existence of a modulus field with a mass of 100-10000TeV. Its decay at MeV-temperatures generates large amounts of entropy and washes out any previously produced baryon asymmetry. We describe how the baryon asymmetry can be (re)generated by the modulus decay. The mechanism relates the smallness of the asymmetry to the hierarchy between the Planck- and the Fermi-scale.
20.	Kane, Gordon, et al. (author) Deriving the inflaton in compactified M-theory with a de Sitter vacuum 2019 In: Physical Review D. - 2470-0010 .- 2470-0029. ; 100:6 Journal article (peer-reviewed)abstract Compactifying M-theory on a manifold of G2 holonomy gives a UV complete 4D theory. It is supersymmetric, with soft supersymmetry breaking via gaugino condensation that simultaneously stabilizes all moduli and generates a hierarchy between the Planck and the Fermi scale. It generically has gauge matter, chiral fermions, and several other important features of our world. Here we show that the theory also contains a successful inflaton, which is a linear combination of moduli closely aligned with the overall volume modulus of the compactified G2 manifold. The scheme does not rely on ad hoc assumptions, but derives from an effective quantum theory of gravity. Inflation arises near an inflection point in the potential which can be deformed into a local minimum. This implies that a de Sitter vacuum can occur in the moduli potential even without uplifting. Generically present charged hidden sector matter generates a de Sitter vacuum as well.
21.	Mauritsen, Thorsten, et al. (author) Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO2 2019 In: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:4, s. 998-1038 Journal article (peer-reviewed)abstract A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO2 over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO2 forcing, which nonetheless can be represented by a simple two-layer model.
22.	Reinert, Annika, et al. (author) A precision search for WIMPs with charged cosmic rays 2018 In: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics Publishing (IOPP). - 1475-7516. ; :1 Journal article (peer-reviewed)abstract AMS-02 has reached the sensitivity to probe canonical thermal WIMPs by their annihilation into antiprotons. Due to the high precision of the data, uncertainties in the astrophysical background have become the most limiting factor for indirect dark matter detection. In this work we systematically quantify and where possible reduce uncertainties in the antiproton background. We constrain the propagation of charged cosmic rays through the combination of antiproton, BBC and positron data. Cross section uncertainties are determined from a wide collection of accelerator data and are for the first time ever fully taken into account. This allows us to robustly constrain even subdominant dark matter signals through their spectral properties. For a standard NFW dark matter profile we are able to exclude thermal WIMPs with masses up to 570 GeV which annihilate into bottom quarks. While we confirm a reported excess compatible with dark matter of mass around 80 GeV, its local (global) significance only reaches 2.2 sigma (1.1 sigma) in our analysis.
23.	Winkler, Martin Wolfgang (author) Cosmic ray antiprotons at high energies 2017 In: Journal of Cosmology and Astroparticle Physics. - : Institute of Physics (IOP). - 1475-7516. ; :2 Journal article (peer-reviewed)abstract Cosmic ray antiprotons provide a powerful tool to probe dark matter annihilations in our galaxy. The sensitivity of this important channel is, however, diluted by sizable uncertainties in the secondary antiproton background. In this work, we improve the calculation of secondary antiproton production with a particular focus on the high energy regime. We employ the most recent collider data and identify a substantial increase of antiproton cross sections with energy. This increase is driven by the violation of Feynman scaling as well as by an enhanced strange hyperon production. The updated antiproton production cross sections are made publicly available for independent use in cosmic ray studies. In addition, we provide the correlation matrix of cross section uncertainties for the AMS-02 experiment. At high energies, the new cross sections improve the compatibility of the AMS-02 data with a pure secondary origin of antiprotons in cosmic rays.
24.	Winkler, Martin Wolfgang, et al. (author) Dark Matter Annihilation Can Produce a Detectable Antihelium Flux through (Lambda)over-bar(b) Decays 2021 In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 126:10 Journal article (peer-reviewed)abstract Recent observations by the Alpha Magnetic Spectrometer (AMS-02) have tentatively detected a handful of cosmic-ray antihelium events. Such events have long been considered as smoking-gun evidence for new physics, because astrophysical antihelium production is expected to be negligible. However, the darkmatter-induced antihelium flux is also expected to fall below current sensitivities, particularly in light of existing antiproton constraints. Here, we demonstrate that a previously neglected standard model process-the production of antihelium through the displaced-vertex decay of (Lambda) over bar (b)-baryons-can significantly boost the dark matter induced antihelium flux. This process can entirely dominate the production of high-energy antihelium nuclei, increasing the rate of detectable AMS-02 events by 2 orders of magnitude.
25.	Winkler, Martin Wolfgang (author) Decay and detection of a light scalar boson mixing with the Higgs boson 2019 In: Physical Review D. - : American Physical Society. - 2470-0010 .- 2470-0029. ; 99:1 Journal article (peer-reviewed)abstract The simplest extension of the standard model consists in adding one singlet scalar field which mixes with the Higgs boson. O(GeV) masses of the new scalar carry strong motivation from relaxion, dark matter and inflation models. The decay of a GeV scalar is, however, notoriously difficult to address since, at this mass scale, the chiral expansion breaks down and perturbative QCD does not apply. Existing estimates of the GeV scalar decay rate disagree by several orders of magnitude. In this work, we perform a new dispersive analysis in order to strongly reduce these uncertainties and to address discrepancies in earlier results. We will update existing limits on light scalars and future experimental sensitivities which are in some cases strongly affected by the new-found decay rates. The meson form factors provided in this work, can be used to generalize our findings to non-universally coupled light scalars.
26.	Winkler, Martin Wolfgang, et al. (author) Power spectrum of density perturbations in chain inflation 2021 In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 103:4 Journal article (peer-reviewed)abstract Chain inflation is an alternative to slow roll inflation in which the Universe undergoes a series of transitions between different vacua. The density perturbations (studied in this paper) are seeded by the probabilistic nature of tunneling rather than quantum fluctuations of the inflaton. We find the scalar power spectrum of chain inflation and show that it is fully consistent with a Lambda CDM cosmology. In agreement with some of the previous literature (and disagreement with others), we show that 10(4) phase transitions per e-fold are required in order to agree with the amplitude of cosmic microwave background anisotropies within the observed range of scales. Interestingly, the amplitude of perturbations constrains chain inflation to a regime of highly unstable de Sitter spaces, which may be favorable from a quantum gravity perspective since the swampland conjecture on trans-Planckian censorship is automatically satisfied. We provide new analytic estimates for the bounce action and the tunneling rate in periodic potentials which replace the thin-wall approximation in the regime of fast tunneling. Finally, we study model implications and derive an upper limit of similar to 10(10) GeV on the axion decay constant in viable chain inflation with axions.
27.	Winkler, Martin Wolfgang, et al. (author) Probing the weak gravity conjecture in the cosmic microwave background 2020 In: Physical Review D. - 2470-0010 .- 2470-0029. ; 101:8 Journal article (peer-reviewed)abstract The weak gravity conjecture imposes severe constraints on natural inflation. A trans-Planckian axion decay constant can be realized only if the potential exhibits an additional (subdominant) modulation with sub-Planckian periodicity. The resulting wiggles in the axion potential generate a characteristic modulation in the scalar power spectrum of inflation which is logarithmic in the angular scale. The compatibility of this modulation is tested against the most recent cosmic microwave background (CMB) data by Planck and BICEP/Keck. Intriguingly, we find that the modulation completely resolves the tension of natural inflation with the CMB. A Bayesian model comparison reveals that natural inflation with modulations describes all existing data equally well as the cosmological standard model ACDM. In addition, the bound of a tensor-to-scalar ratio r > 0.002 correlated with a striking small-scale suppression of the scalar power spectrum occurs. Future CMB experiments could directly probe the modulation through their improved sensitivity to smaller angular scales and possibly the measurement of spectral distortions. They could, thus, verify a key prediction of the weak gravity conjecture and provide dramatic new insights into the theory of quantum gravity.
28.	Zhang, Rong, et al. (author) ISL1 is a major susceptibility gene for classic bladder exstrophy and a regulator of urinary tract development 2017 In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7 Journal article (peer-reviewed)abstract Previously genome-wide association methods in patients with classic bladder exstrophy (CBE) found association with ISL1, a master control gene expressed in pericloacal mesenchyme. This study sought to further explore the genetics in a larger set of patients following-up on the most promising genomic regions previously reported. Genotypes of 12 markers obtained from 268 CBE patients of Australian, British, German Italian, Spanish and Swedish origin and 1,354 ethnically matched controls and from 92 CBE case-parent trios from North America were analysed. Only marker rs6874700 at the ISL1 locus showed association (p = 2.22 x 10(-08)). A meta-analysis of rs6874700 of our previous and present study showed a p value of 9.2 x 10(-19). Developmental biology models were used to clarify the location of ISL1 activity in the forming urinary tract. Genetic lineage analysis of Isl1-expressing cells by the lineage tracer mouse model showed Isl1-expressing cells in the urinary tract of mouse embryos at E10.5 and distributed in the bladder at E15.5. Expression of isl1 in zebrafish larvae staged 48 hpf was detected in a small region of the developing pronephros. Our study supports ISL1 as a major susceptibility gene for CBE and as a regulator of urinary tract development.

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