Large deviation principle for Benedicks-Carleson quadratic maps

Since the pioneering works of Jakobson and Benedicks & Carleson and others, it has been known that a positive measure set of quadratic maps admit invariant probability measures absolutely continuous with respect to Lebesgue. These measures allow one to statistically predict the asymptotic fate of Lebesgue almost every initial condition. Estimating fluctuations of empirical distributions before they settle to equilibrium requires a fairly good control over large parts of the phase space. We use the sub-exponential slow recurrence condition of Benedicks & Carleson to build induced Markov maps of arbitrarily small scale and associated towers, to which the absolutely continuous measures can be lifted. These various lifts together enable us to obtain a control of recurrence that is sufficient to establish a level 2 large deviation principle, for the absolutely continuous measures. This result encompasses dynamics far from equilibrium, and thus significantly extends presently known local large deviations results for quadratic maps.Comment: 23 pages, no figure, former title: Full large deviation principle for Benedicks-Carleson quadratic map

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Diverse cellular and physiological roles of phospholipase C-??1

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A Study on PbMoO4 Phonon-Scintillation Detection with MMC Readouts for a Neutrinoless Double Beta Decay Search

The advanced Mo-based rare process experiment (AMoRE) is an international project searching for the neutrinoless double beta (0 nu beta beta) decay of Mo-100 using low-temperature calorimetric detection of heat and light signals based on magnetic microcalorimeter (MMC) readouts. Li2MoO4 crystals have been considered as the main target crystals for the second phase of the AMoRE project, which aims to use 100 kg of Mo-100. However, the hygroscopicity of Li2MoO4 requires moistureless processes during surface treatment, storage, detector assembly, and installation. Li2MoO4 crystals are nonhygroscopic and exhibit high scintillation efficiency, often leading to high particle discrimination power in the phonon channel via pulse-shape analysis and light/heat ratio variation. A low-temperature detector setup with a 1 cm 3 cubic crystal of Li2MoO4 was prepared for simultaneous heat and light detection based on MMC readouts. After study of internal background control using archeological Pb, Li2MoO4 crystal can be a promising candidate crystal. We present a feasibility study of Li2MoO4 crystals for a 0 nu beta beta experiment.11Nsciescopu

RGS2 promotes formation of neurites by stimulating microtubule polymerization

Regulator of G-protein signaling (RGS) proteins interact with ?? subunits of heterotrimeric G-proteins via the RGS domain and attenuate their activity by accelerating GTPase activity. RGS2, a member of the RGS family, regulates synaptic development via hereto unknown mechanism. In this study, we found that RGS2 directly interacted with tubulin via a short region at the N-terminus: amino acids 41-60. RGS2 enhanced microtubule polymerization in vitro, and the tubulin binding region was necessary and sufficient for this activity. In Vero cells, polymerization of microtubule was stimulated when peptides containing the tubulin binding region were microinjected. Immunocytochemical analysis showed that endogenous RGS2 was localized at the termini of neurites in differentiated PC12 cells. Over-expression of RGS2 enhanced the nerve growth factor-induced neurite outgrowth in PC12 cells, while specific knock-down of endogenous RGS2 suppressed the neurite outgrowth. These findings demonstrate that RGS2 contributes to the neuronal cell differentiation via regulation of microtubule dynamics.close292