Cosmic Bell Test: Measurement Settings from Milky Way Stars

Bell’s theorem states that some predictions of quantum mechanics cannot be reproduced by a local-realist theory. That conflict is expressed by Bell’s inequality, which is usually derived under the assumption that there are no statistical correlations between the choices of measurement settings and anything else that can causally affect the measurement outcomes. In previous experiments, this “freedom of choice” was addressed by ensuring that selection of measurement settings via conventional “quantum random number generators” was spacelike separated from the entangled particle creation. This, however, left open the possibility that an unknown cause affected both the setting choices and measurement outcomes as recently as mere microseconds before each experimental trial. Here we report on a new experimental test of Bell’s inequality that, for the first time, uses distant astronomical sources as “cosmic setting generators.” In our tests with polarization-entangled photons, measurement settings were chosen using real-time observations of Milky Way stars while simultaneously ensuring locality. Assuming fair sampling for all detected photons, and that each stellar photon’s color was set at emission, we observe statistically significant ≳7.31σ and ≳11.93σ violations of Bell’s inequality with estimated p values of ≲1.8×10[superscript -13] and ≲4.0×10[superscript -33], respectively, thereby pushing back by ∼600  years the most recent time by which any local-realist influences could have engineered the observed Bell violation.Austrian Academy of SciencesAustrian Science Fund (Projects SFB F40 (FOQUS) and CoQuS W1210-N16)Austria. Federal Ministry of Science, Research, and EconomyNational Science Foundation (U.S.) (INSPIRE Grant PHY-1541160 and SES-1056580)Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra

Quantitative Interaction Proteomics of Neurodegenerative Disease Proteins

Several proteins have been linked to neurodegenerative disorders (NDDs), but their molecular function is not completely understood. Here, we used quantitative interaction proteomics to identify binding partners of Amyloid beta precursor protein (APP) and Presenilin-1 (PSEN1) for Alzheimer's disease (AD), Huntingtin (HTT) for Huntington's disease, Parkin (PARK2) for Parkinson's disease, and Ataxin-1 (ATXN1) for spinocerebellar ataxia type 1. Our network reveals common signatures of protein degradation and misfolding and recapitulates known biology. Toxicity modifier screens and comparison to genome-wide association studies show that interaction partners are significantly linked to disease phenotypes in vivo. Direct comparison of wild-type proteins and disease-associated variants identified binders involved in pathogenesis, highlighting the value of differential interactome mapping. Finally, we show that the mitochondrial protein LRPPRC interacts preferentially with an early-onset AD variant of APP. This interaction appears to induce mitochondrial dysfunction, which is an early phenotype of AD.Peer reviewe

Involvement of insulin-like growth factor-I in inner ear organogenesis and regeneration

The verterbrate inner ear is an excellent model system to study signalling mechanisms in embryonic development. During the last years, insulin-like growth factor-I (IGF-I) has attracted attention in relation to the regulation of inner ear ontogenesis. IGF-I and its high-affinity tyrosine-kinase receptor are expressed during early stages of inner ear development. IGF-I is a powerful mitogen for the otic vesicle, where it stimulates cell-division and mitogenic signalling cascades. Later in development, IGF-I also promotes survival and neurogenesis of the otic neurones in the cochleovestibular ganglion (CVG). The actions of IGF-I are associated with the generation of lipidic messengers and the activation of Raf kinase, which results in the rapid induction of the expression of the proliferative celt nuclear antigen (PCNA) and the nuclear proto-oncogenes c- fos and c-jun. Regulation of organogenesis involves a dynamic balance of the mechanisms regulating cell division, differentiation and death. A model is proposed where this balance is the consequence of the action of IGF-I and NGF, which converge in Raf activation or suppression. The combinatorial expression of Jun and Fos family members in particular domains of the otic vesicle would be the final result of such cascade. Some of these mechanisms may be also implicated in otic regeneration.Peer Reviewe