Terrestrial Very-Long-Baseline Atom Interferometry:Workshop Summary

This document presents a summary of the 2023 Terrestrial Very-Long-Baseline Atom Interferometry Workshop hosted by CERN. The workshop brought together experts from around the world to discuss the exciting developments in large-scale atom interferometer (AI) prototypes and their potential for detecting ultralight dark matter and gravitational waves. The primary objective of the workshop was to lay the groundwork for an international TVLBAI proto-collaboration. This collaboration aims to unite researchers from different institutions to strategize and secure funding for terrestrial large-scale AI projects. The ultimate goal is to create a roadmap detailing the design and technology choices for one or more km-scale detectors, which will be operational in the mid-2030s. The key sections of this report present the physics case and technical challenges, together with a comprehensive overview of the discussions at the workshop together with the main conclusions

Genetically dissecting P2rx7 expression within the central nervous system using conditional humanized mice

The purinergic P2X7 receptor (P2X7R) has attracted considerable interest as a potential target for various central nervous system (CNS) pathologies including affective and neurodegenerative disorders. To date, the distribution and cellular localization of the P2X7R in the brain are not fully resolved and a matter of debate mainly due to the limitations of existing tools. However, this knowledge should be a prerequisite for understanding the contribution of the P2X7R to brain disease. Here, we generated a genetic mouse model by humanizing the P2X7R in the mouse as mammalian model organism. We demonstrated its functionality and revealed species-specific characteristics of the humanized receptor, compared to the murine ortholog, regarding its receptivity to activation and modulation by 2′,3′-O-(benzoyl-4-benzoyl)-adenosine 5′-triphosphate (BzATP) and trifluoperazine (TFP). This humanized P2rx7 allele is accessible to spatially and temporally controlled Cre recombinase-mediated inactivation. In contrast to previously generated knockout (KO) mice, none of the described P2rx7 splice variants evade this null allele. By selective disruption and assessment of human P2RX7 expression in different brain regions and cell types, we were able to demonstrate that the P2X7R is specifically expressed in glutamatergic pyramidal neurons of the hippocampus. Also, P2X7R is expressed in major non-neuronal lineages throughout the brain, i.e., astrocytes, oligodendrocytes, and microglia. In conclusion, this humanized mouse model provides the means for detailed assessment of human P2X7R function in vivo including evaluation of agonists or antagonists. In addition, this conditional allele will enable future loss-of-function studies in conjunction with mouse models for CNS disorders.Fil: Metzger, Michael W.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Walser, Sandra M.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Aprile García, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Dedic, Nina. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Chen, Alon. Helmholtz Center Munich German Research Center For Environmental Health; Alemania. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Holsboer, Florian. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Wurst, Wolfgang. Ludwig Maximilians Universitat; Alemania. Weizmann Institute Of Science Israel; Israel. Universitat Technical Zu Munich; AlemaniaFil: Deussing, Jan M.. Max Planck Institut Fur Psychiatrie; Alemani

Audiometric notch and extended high-frequency hearing threshold shift in relation to total leisure noise exposure: An exploratory analysis

Background: Studies investigating leisure noise effect on extended high frequency hearing are insufficient and they have inconsistent results. The aim of this study was to investigate if extended high-frequency hearing threshold shift is related to audiometric notch, and if total leisure noise exposure is associated with extended high-frequency hearing threshold shift. Materials and Methods: A questionnaire of the Ohrkan cohort study was used to collect information on demographics and leisure time activities. Conventional and extended high-frequency audiometry was performed. We did logistic regression between extended high-frequency hearing threshold shift and audiometric notch as well as between total leisure noise exposure and extended high-frequency hearing threshold shift. Potential confounders (sex, school type, and firecrackers) were included. Results: Data from 278 participants (aged 18–23 years, 53.2% female) were analyzed. Associations between hearing threshold shift at 10, 11.2, 12.5, and 14 kHz with audiometric notch were observed with a higher prevalence of threshold shift at the four frequencies, compared to the notch. However, we found no associations between total leisure noise exposure and hearing threshold shift at any extended high frequency. Conclusion: This exploratory analysis suggests that while extended high-frequency hearing threshold shifts are not related to total leisure noise exposure, they are strongly associated with audiometric notch. This leads us to further explore the hypothesis that extended high-frequency threshold shift might be indicative of the appearance of audiometric notch at a later time point, which can be investigated in the future follow-ups of the Ohrkan cohort

The Relevance of Leisure Noise to Hearing Threshold Shifts: A Longitudinal Analysis Among Adolescents

Purpose: The aim of this study was to analyze the association of total leisure noise exposure and hearing threshold shifts over 5 years among adolescents enrolled in the Ohrkan cohort study. Method: The Ohrkan cohort of 2,148 students aged 13-19 years was recruited from 2009 to 2011 and followed up 5 years later. Complete baseline and follow-up reports on exposure and outcome were available for 989 participants. Leisure noise expo -sure was assessed by questionnaires, and clinical audiometric examinations were performed. Two outcomes were defined: occurrence of the Niskar notch pattern and audiometry showing maximum hearing threshold values at 3, 4, and 6 kHz (both ears). Longitudinal analysis using generalized estimating equations was performed. Results: High total leisure noise exposure, defined as an energy equivalent of a 40-hr week of > 85 dBA, was estimated for 32.7% of students at baseline and 63.8% at follow-up. A noise notch was observed in 1.1% of adolescents at baseline and 3.3% at follow-up. At baseline, the maximum measured threshold shift was 55 dB, which increased to 85 dB at the follow-up. Longitudinal analy-sis did not reveal an association between leisure noise exposure and hearing thresholds. Hearing threshold shifts or noise notches were associated with sex, school type, and time point of measurement. Conclusions: No relationship was found between leisure noise and hearing thresh-olds. Male adolescents and those attending secondary general schools, with gradua-tion following completion of ninth or 10th grade, had a greater likelihood of developing hearing threshold shifts. Prevention programs should focus on these risk groups

Heterozygosity for the Mood Disorder-Associated Variant Gln460Arg Alters P2X7 Receptor Function and Sleep Quality

A single nucleotide polymorphism substitution from glutamine (Gln, Q) to arginine (Arg, R) at codon 460 of the purinergic P2X7 receptor (P2X7R) has repeatedly been associated with mood disorders. The P2X7R-Gln460Arg variant per se is not compromised in its function. However, heterologous expression of P2X7R-Gln460Arg together with wild-type P2X7R has recently been demonstrated to impair receptor function. Here we show that this also applies to humanized mice coexpressing both human P2X7R variants. Primary hippocampal cells derived from heterozygous mice showed an attenuated calcium uptake upon agonist stimulation. While humanized mice were unaffected in their behavioral repertoire under basal housing conditions, mice that harbor both P2X7R variants showed alterations in their sleep quality resembling signs of a prodromal disease stage. Also healthy heterozygous human subjects showed mild changes in sleep parameters. These results indicate that heterozygosity for the wild-type P2X7R and its mood disorder-associated variant P2X7R-Gln460Arg represents a genetic risk factor, which is potentially able to convey susceptibility to mood disorders.Fil: Metzger, Michael W.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Walser, Sandra M.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Dedic, Nina. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Aprile García, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Jakubcakova, Vladimira. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Adamczyk, Marek. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Webb, Katharine J.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Uhr, Manfred. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Refojo, Damian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Schmidt, Mathias V.. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Friess, Elisabeth. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Steiger, Axel. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Kimura, Mayumi. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Chen, Alon. Max Planck Institut Fur Psychiatrie; Alemania. Weizmann Institute of Science; IsraelFil: Holsboer, Florian. Max Planck Institut Fur Psychiatrie; AlemaniaFil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Wurst, Wolfgang. Institute of Developmental Genetics; Alemania. Technische Universität München-Weihenstephan; Alemania. German Center for Neurodegenerative Diseases; Alemania. Universität München; AlemaniaFil: Deussing, Jan M.. Max Planck Institut Fur Psychiatrie; Alemani

ACRIDICON–CHUVA Campaign: Studying Tropical Deep Convective Clouds and Precipitation over Amazonia Using the New German Research Aircraft HALO

Between 1 September and 4 October 2014, a combined airborne and ground-based measurement campaign was conducted to study tropical deep convective clouds over the Brazilian Amazon rain forest. The new German research aircraft, High Altitude and Long Range Research Aircraft (HALO), a modified Gulfstream G550, and extensive ground-based instrumentation were deployed in and near Manaus (State of Amazonas). The campaign was part of the German–Brazilian Aerosol, Cloud, Precipitation, and Radiation Interactions and Dynamics of Convective Cloud Systems–Cloud Processes of the Main Precipitation Systems in Brazil: A Contribution to Cloud Resolving Modeling and to the GPM (Global Precipitation Measurement) (ACRIDICON– CHUVA) venture to quantify aerosol–cloud–precipitation interactions and their thermodynamic, dynamic, and radiative effects by in situ and remote sensing measurements over Amazonia. The ACRIDICON–CHUVA field observations were carried out in cooperation with the second intensive operating period of Green Ocean Amazon 2014/15 (GoAmazon2014/5). In this paper we focus on the airborne data measured on HALO, which was equipped with about 30 in situ and remote sensing instruments for meteorological, trace gas, aerosol, cloud, precipitation, and spectral solar radiation measurements