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Methylome-wide association studies and epigenetic biomarker development for 133 mass spectrometry-assessed circulating proteins in 14,671 Generation Scotland participants
No full textBackground: DNA methylation (DNAm) can regulate gene expression, and its genome-wide patterns (epigenetic scores or EpiScores) can act as biomarkers for complex traits. The relative stability of methylation profiles may enable better assessment of chronic exposures compared to single time-point protein measures. We present the first large-scale epigenetic study of the highly-abundant serum proteome measured via ultra-high throughput mass spectrometry in 14,671 samples from the Generation Scotland cohort. We further demonstrate the first large-scale comparison of protein EpiScores and their respective proteins as predictors of incident cardiovascular disease.
Results: Marginal epigenome-wide association models, adjusting for age, sex, measurement batch, estimated white cell proportions, BMI, smoking and methylation principal components, reveal 15,855 significant CpG – protein associations across 125 of 133 proteins PBonferroni 0.95). 112 protein EpiScores correlate significantly with their respective protein in a holdout test-set. Of these, sixteen associate significantly with incident all-cause cardiovascular disease (Nevents=191) compared to one measured protein.
Conclusions: We highlight a complex interplay between the blood-based methylome and proteome. Importantly, we show that protein EpiScores correlate with measured proteins and demonstrate that the, as-yet understudied, high-abundance proteome may yield clinically relevant biomarkers. The protein EpiScores demonstrate more significant associations with cardiovascular disease than directly measured proteins, suggesting their potential as clinical biomarkers for monitoring or predicting disease risk. We suggest that biomarker development could be enhanced by the consideration of protein EpiScores alongside measured proteins
Boundary representations of intermediate forms between a regular Dirichlet form and its active main part
No full textWe characterize all semigroups sandwiched between the semigroup of a Dirichlet form and the semigroup of its active main part. In case the Dirichlet form is regular, we give a more explicit description of the quadratic forms of the sandwiched semigroups in terms of pairs consisting of an open set and a measure on an abstract boundary
Rolling at right angles: Magnetic anisotropy enables dual-anisotropic active matter
No full textWe report on an experimental active matter system with motion restricted to four cardinal directions. Our particles are magnetite-doped colloidal spheres driven by the Quincke electrorotational instability. The absence of a magnetic field (||=0) leads to circular trajectories interspersed with short spontaneous runs. Intermediate fields (||≲20mT) linearize the motion along the axis perpendicular to . At high magnetic fields, we observe the surprising emergence of a second, distinct linearization along the axis parallel to . With numerical simulations, we show that this behavior can be explained by anisotropic magnetic susceptibility
LNCS
No full textCVRFs are PRFs that unify the properties of verifiable and constrained PRFs. Since they were introduced concurrently by Fuchsbauer and Chandran-Raghuraman-Vinayagamurthy in 2014, it has been an open problem to construct CVRFs without using heavy machinery such as multilinear maps, obfuscation or functional encryption.
We solve this problem by constructing a prefix-constrained verifiable PRF that does not rely on the aforementioned assumptions. Essentially, our construction is a verifiable version of the Goldreich-Goldwasser-Micali PRF. To achieve verifiability we leverage degree-2 algebraic PRGs and bilinear groups. In short, proofs consist of intermediate values of the Goldreich-Goldwasser-Micali PRF raised to the exponents of group elements. These outputs can be verified using pairings since the underlying PRG is of degree 2.
We prove the selective security of our construction under the Decisional Square Diffie-Hellman (DSDH) assumption and a new assumption, which we dub recursive Decisional Diffie-Hellman (recursive DDH).
We prove the soundness of recursive DDH in the generic group model assuming the hardness of the Multivariate Quadratic (MQ) problem and a new variant thereof, which we call MQ+.
Last, in terms of applications, we observe that our CVRF is also an exponent (C)VRF in the plain model. Exponent VRFs were recently introduced by Boneh et al. (Eurocrypt’25) with various applications to threshold cryptography in mind. In addition to that, we give further applications for prefix-CVRFs in the blockchain setting, namely, stake-pooling and compressible randomness beacons
Reduction of neuronal activity mediated by blood-vessel regression in the brain
No full textThe brain vasculature supplies neurons with glucose and oxygen, but little is known about how vascular plasticity contributes to brain function. Using longitudinal in vivo imaging, we report that a substantial proportion of blood vessels in the adult mouse brain sporadically occlude and regress. Their regression proceeds through sequential stages of blood-flow occlusion, endothelial cell collapse, relocation or loss of pericytes, and retraction of glial endfeet. Regressing vessels are found to be widespread in mouse, monkey and human brains. We further reveal that blood vessel regression cause a reduction of neuronal activity due to a dysfunction in mitochondrial metabolism and glutamate production. Our results elucidate the mechanism of vessel regression and its role in neuronal function in the adult brain
Efficient formation of a massive quiescent galaxy at redshift 4.9
No full textWithin the established framework of structure formation, galaxies start as systems of low stellar mass and gradually grow into far more massive galaxies. The existence of massive galaxies in the first billion years of the Universe, as suggested by recent observations, seems to challenge this model, as such galaxies would require highly efficient conversion of baryons into stars. An even greater challenge in this epoch is the existence of massive galaxies that have already ceased forming stars. However, robust detections of early massive quiescent galaxies have been challenging due to the coarse wavelength sampling of photometric surveys. Here we report the spectroscopic confirmation with the James Webb Space Telescope of the quiescent galaxy RUBIES-EGS-QG-1 at redshift z = 4.90, 1.2 billion years after the Big Bang. Deep stellar absorption features in the spectrum reveal that the stellar mass of the galaxy of 1011 M⊙ formed in a short 200 Myr burst of star formation, after which star formation activity dropped rapidly and persistently. According to current galaxy formation models, systems with such rapid stellar mass growth and early quenching are too rare to plausibly occur in the small area probed spectroscopically with JWST. Instead, the discovery of RUBIES-EGS-QG-1 implies that early massive quiescent galaxies can be quenched earlier or exhaust gas available for star formation more efficiently than assumed at present
Ab initio Auger spectrum of the ultrafast dissociating 2p3/2−1σ* resonance in HCl
No full textWe present an ab initio theoretical method to calculate the resonant Auger spectrum in the presence of ultrafast dissociation. The method is demonstrated by deriving the L-VV resonant Auger spectrum mediated by the 2p3/2−1σ* resonance in HCl, where the electronic Auger decay and nuclear dissociation occur on the same time scale. The Auger decay rates are calculated within the one-center approximation and are shown to vary significantly with the inter-nuclear distance. A quantum-mechanical description of dissociation is effectuated by propagating the corresponding Franck–Condon factors. The calculated profiles of Auger spectral lines resemble those of atomic Auger decay but here the characteristic tails extend towards lower electron kinetic energies, which reflect specific features of the potential energy curves. The presented method can describe the resonant Auger spectrum for an arbitrary speed of dissociation and simplifies to known approximations in the limiting cases
Order-2 Delaunay triangulations optimize angles
No full textThe local angle property of the (order-1) Delaunay triangulations of a generic set in R2
asserts that the sum of two angles opposite a common edge is less than π. This paper extends this property to higher order and uses it to generalize two classic properties from order-1 to order-2: (1) among the complete level-2 hypertriangulations of a generic point set in R2, the order-2 Delaunay triangulation lexicographically maximizes the sorted angle vector; (2) among the maximal level-2 hypertriangulations of a generic point set in R2, the order-2 Delaunay triangulation is the only one that has the local angle property. We also use our method of establishing (2) to give a new short proof of the angle vector optimality for the (order-1) Delaunay triangulation. For order-1, both properties have been instrumental in numerous applications of Delaunay triangulations, and we expect that their generalization will make order-2 Delaunay triangulations more attractive to applications as well
Supernova shocks cannot explain the inflated state of hypervelocity runaways from white dwarf binaries
No full textRecent observations have found a growing number of hypervelocity stars with speeds of ≈1500 − 2500 km s−1 that could have only been produced through thermonuclear supernovae in white dwarf binaries. Most of the observed hypervelocity runaways in this class display a surprising inflated structure: their current radii are roughly an order of magnitude greater than they would have been as white dwarfs filling their Roche lobe. While many simulations exist studying the dynamical phase leading to supernova detonation in these systems, no detailed calculations of the long-term structure of the runaways have yet been performed. We used an existing AREPO hydrodynamical simulation of a supernova in a white dwarf binary as a starting point for the evolution of these stars with the one-dimensional stellar evolution code MESA. We show that the supernova shock is not energetic enough to inflate the white dwarf over timescales longer than a few thousand years, significantly shorter than the 105 − 6 year lifetimes inferred for observed hypervelocity runaways. Although they experience a shock from a supernova less than ≈0.02 R⊙ away, our models do not experience significant interior heating, and all contract back to radii of around 0.01 R⊙ within about 104 years. Explaining the observed inflated states requires either an additional source of significant heating or some other physics that is not yet accounted for in the subsequent evolution
2025_SCACCHI_JCIS
No full textThis data set contains the simulation input files, scripts, and figures data belonging to the publication
Alberto Scacchi, Carlo Rigoni, Mikko P. Haataja, Jakko V. I. Timonen, and Maria Sammalkorpi, "A Coarse-grained Model for Aqueous Two-phase Systems: Application to Ferrofluids", Journal of Colloids and Interface Science (2025). https://doi.org/10.1016/j.jcis.2025.01.256