Tyramine acts downstream of neuronal XBP-1s to coordinate inter-tissue UPRER activation and behavior in C. elegans

In C. elegans, expression of the UPRER transcription factor xbp-1s in neurons cell non-autonomously activates the UPRER in the intestine, leading to enhanced proteostasis and lifespan. To better understand this signaling pathway, we isolated neurons from animals expressing neuronal xbp-1s for transcriptomic analysis, revealing a striking remodeling of transcripts involved in neuronal signaling. We then identified signaling molecules required for cell non-autonomous intestinal UPRER activation, including the biogenic amine tyramine. Expression of xbp-1s in just two pairs of neurons that synthesize tyramine, the RIM and RIC interneurons, induced intestinal UPRER activation and extended longevity, and exposure to stress led to splicing and activation of xbp-1 in these neurons. In addition, we found that neuronal xbp-1s modulates feeding behavior and reproduction, dependent upon tyramine synthesis. XBP-1s therefore remodels neuronal signaling to coordinately modulate intestinal physiology and stress-responsive behavior, functioning as a global regulator of organismal responses to stress

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries(1,2). However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world(3) and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health(4,5). However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol-which is a marker of cardiovascular riskchanged from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million-4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.Peer reviewe

Contrôle du détecteur interférométrique d'ondes gravitationnelles Advanced Virgo

The first detection of a Gravitational Wave (GW) was done on September 14 th of 2015 by the LIGO-Virgo collaboration with the two LIGO detectors. It was emitted by the merger of a Binary Black Hole, providing the first direct proof of the existence of Black Holes. Advanced Virgo is the upgraded version of the Virgo interferometer and it will join the LIGO detectors in the next months. The passage of a GW on Earth induces a change on the distance between test masses (experiencing only the gravitational interaction) in a differential way. This distance variation is proportional to the amplitude of the GW however the largest displacement observable on Earth will be of the order of 10⁻¹⁹ m/sqrt(Hz). Taking this in account, a Michelson interferometer is the ideal instrument to detect this differential effect. GWs detectors will use suspended mirrors to behave as test masses. The passage of a GW will cause a change on the distance between the mirrors that will spoil the interference condition, allowing some light to leak to the detection photodiode. However, a simple Michelson interferometer does not provide enough sensitivity. For this reason the first generation of detectors added Fabry-Perot cavities in the arms, in order to increase the optical path. A second change was the addition of an extra mirror in order to recycle the light that comes back towards the laser, to increase the effective power, creating a new cavity also known as Power Recycling Cavity (PRC). Its effect is more important when the Michelson is tuned in an optimal way in a dark fringe. All the mirrors of the detector are affected by the seismic noise and so their distance is continuously changing. It is necessary to control the longitudinal and angular position of the cavities in order to keep them at resonance. During my thesis I have studied the control of Advanced Virgo using simulation and during the commissioning itself. First of all I have simulated the control strategy used in Virgo using modal simulations. The aim was to check if the same strategy could be applied to Advanced Virgo or if it needs adaptation. In Advanced Virgo the Fabry-Perot cavities have a higher finesse, which arises new dynamical problems and requires a special control strategy that I have modified to match the commissioning needs. Regarding the PRC, we have studied the impact of its stability on the performance of the interferometer. As it is very close from the instability region, the electrical field inside will be very sensitive to alignment and matching of the laser beam. We have checked using simulations its impact on the longitudinal controls, which can become unstable, and a solution has been validated. Then I have used this information during the commissioning of the Advanced Virgo detector. In this thesis the details of the commissioning of the longitudinal and angular control of the interferometer will be presented. It includes the frequency stabilization, which has a key role in the control of the interferometer, since it is the dominant noise.La première détection d'une Onde Gravitationnelle (OG) a été faite le 14 Septembre 2015 par la collaboration LIGO-Virgo avec les deux détecteurs de LIGO. Elle a été émise par la fusion de deux Trous Noirs, fournissant ainsi la première preuve directe de l’existence des Trous Noirs. Advanced Virgo est la version améliorée de l’interféromètre Virgo et il va rejoindre les détecteurs LIGO dans les mois qui suivent. Le passage d'une OG induit un changement différentiel de la distance entre masses-test (uniquement sensibles à la force gravitationnelle). Cette variation de distance est proportionnelle à l'amplitude de l'OG, néanmoins le déplacement le plus grand qui peut être observé depuis la Terre est de l'ordre de 10⁻¹⁹ m/sqrt(Hz) en terme de densité spectrale. C'est pour cela que l’interféromètre de Michelson est l'instrument idéal pour détecter cet effet différentiel. Les détecteurs d’OG utilisent des miroirs suspendus, qui se comportent comme masses-test. Le passage d'une OG va produire un changement dans la distance entre les miroirs qui va modifier la condition d’interférence et donc une variation de puissance lumineuse mesurée par la photodiode de détection. Cependant, un Michelson simple n'est pas assez sensible et des améliorations ont été ajoutées. La première génération de détecteurs a ajouté des cavités Fabry-Pérot dans les bras pour augmenter le chemin optique. De plus un nouveau miroir a été ajouté pour recirculer la lumière réfléchie vers le laser et augmenter la puissance effective, en créant une nouvelle cavité connue comme Power Recycling Cavity (PRC). Son effet est d’autant plus important que le Michelson est en fait optimalement réglé sur une frange noire. Tous les miroirs du détecteur ressentent le bruit sismique et les longueurs des cavités, entre autres, changent en permanence. Il est donc nécessaire de contrôler activement la position longitudinale et angulaire des cavités pour les maintenir en résonance. Pendant ma thèse j'ai étudié le contrôle de Advanced Virgo d’abord en simulation puis pendant le commissioning lui-même. D'abord j'ai simulé la stratégie de contrôle utilisée dans Virgo avec des simulations modales. L'objectif était de vérifier si la même stratégie pouvait être appliquée à Advanced Virgo ou s'il fallait l'adapter. Avec Advanced Virgo les cavités Fabry-Pérot ont une finesse plus grande ce qui entraîne de nouveaux effets dynamiques et qui demande une stratégie de contrôle spéciale, stratégie que j'ai modifiée pour l'adapter aux besoins du commissioning. Concernant la PRC, j’ai étudié l'impact de sa stabilité dans le fonctionnement de l’interféromètre. Comme elle est très proche de la région d’instabilité, l’onde lumineuse être très sensible à l'alignement et a l'adaptation du faisceau à la cavité. J’ai vérifié avec les simulations son impact sur les contrôles longitudinaux, qui peuvent devenir instables, et une solution a été validée. Ensuite j'ai utilisé cette information pour le commissioning d'Advanced Virgo. Dans cette thèse les détails du commissioning des contrôles longitudinal et angulaire de l’interféromètre sont présentés. La stabilisation en fréquence est aussi présentée, puisqu'elle joue un rôle très important dans le contrôle de l’interféromètre car étant le bruit dominant

Eventos adversos temporalmente asociados a VAMENGOC- BC®. Municipio La Lisa, 1998-1999

Con el objetivo de describir la frecuencia de eventos temporalmente asociados a la vacuna cubana VAMENGOC- BC®, se realizó un estudio observacional de tipo descriptivo, cuyo universo estuvo constituido por los lactantes en las edades comprendidas de tres (3549) y cinco meses (3832) de edad de las áreas de salud del Municipio La Lisa en Ciudad de La Habana. Hubo un 3,21% de niños con eventos adversos, con una mayor frecuencia después de la primera dosis; sin diferencias apreciables por sexo. La clasificación fue de un 52% de tipo sistémico, locales un 19% y no solicitados un 29%. La mayor parte de los niños afectados fue en las primeras 72 horas posteriores a la vacunación, y desaparecieron antes de 72 horas desde su comienzo. Las manifestaciones más frecuentes fueron fiebre (predominó entre todos los eventos adversos con 1,53 casos por 100 vacunados); la induración (0,31 por 100 vacunados), eritema (0,30 por 100 vacunados) y el dolor (0,136 por 100 vacunados) en el sitio de administración de la vacuna; irritabilidad (0,244 por 100 vacunados) y pérdida de apetito (0,311 por 100 vacunados). Los eventos no solicitados más frecuentes fueron la Enfermedad Respiratoria Aguda (0,637 por 100 vacunados), la Enfermedad Diarreica Aguda (0,311 por 100 vacunados) y la Otitis Media (0,176 por 100 vacunados). Los eventos adversos serios fueron infrecuentes. No hubo fallecidos y todos los casos se recuperaron en menos de diez días, sin secuelas, discapacidades ni minusvalía

Simulations for the Locking and Alignment Strategy of the DRMI Configuration of the Advanced Virgo Plus Detector

The Advanced Virgo Plus project aims to increase the sensitivity of the Virgo gravitational-wave detector, given the forthcoming O4 Observing Run. One of the major upgrades is the addition of the Signal Recycling Mirror in the optical layout. This additional mirror will provide a broadband improvement to the sensitivity curve of the instrument, but poses significant challenges in the acquisition and operation of the detector’s working point. The process which brings the main optical components from the uncontrolled state to the final working point, which ensures the best detector sensitivity, is called lock acquisition: the lock acquisition is made by moving through increasingly more complex configurations toward the full control of all the interferometer’s longitudinal degrees of freedom. This paper will focus on the control of the Dual-Recycled Michelson Interferometer (DRMI, the central part of the Virgo interferometer), presenting a comprehensive study of the optical simulations used in the design and the commissioning of this configuration. Treated topics include: the characterization of optical fields, powers, and error signals for the controls; the development of a trigger logic to be used for the lock acquisition; the study of the alignment sensing and control system. The interdependence between the three items has also been studied. Moreover, the validity of the studied techniques will be assessed by a comparison with experimental data

Temperature Control for an Intra-Mirror Etalon in Interferometric Gravitational Wave Detector Fabry–Perot Cavities

International audienceThe sensitivity of interferometric gravitational wave detectors is optimized, in part, by balanced finesse in the long Fabry–Perot arm cavities. The input test mass mirrors of Advanced Virgo feature parallel faces, which creates an etalon within the substrate, adding variability in the total mirror reflectivity, in order to correct imbalanced finesse due to manufacturing tolerances. Temperature variations in mirror substrate change the optical path length primarily through varying the index of refraction and are tuned to correct for a finesse imbalance of up to 2.8% by a full etalon fringe of 0.257 K. A negative feedback control system was designed to control the mirror temperature by using an electrical resistive heating belt actuator for a heat transfer process modeled as a two-pole plant. A zero controller filter was designed which achieves temperature control within 2.3% of the etalon fringe and recovers to within 10% of the working point within 32 hours after a step input of one etalon fringe. A preliminary unlock condition control designed to compensate when the interferometer unlocks shows that the control remains stable even after a drastic change in the plant due to the absence of the laser heating. Further improvements to the control must also consider the full heat transfer mechanisms by using modern control state space models

Vacuum-compatible low-loss Faraday isolator for efficient squeezed-light injection in laser-interferometer-based gravitational-wave detectors

International audienceIn this paper, we present, to the best of our knowledge, the first low-loss vacuum-compatible thermally controlled Faraday isolator able to retain a good isolation factor under high-vacuum working conditions. The throughput that can be obtained with the developed device is as high as 99%, retaining an isolation factor higher than 40 dB. That very high isolation ratio can be kept over long time periods independently from external temperature conditions with a few Celsius degrees of variation due to thermal active control. The mechanical and optical configuration is detailed, and the performances achieved with this device are presented

Design for interaction: Factorized Nyquist based control design applied to a Gravitational Wave detector

Gravitational Wave detectors require feedback control to control the length between the sensitive components of the detector. The degrees of freedom in the control system are inherently coupled and the level of interaction furthermore varies over time. A systematic control design approach for the feedback controllers is presented which provides a guide on how to cope with the varying levels of interaction. A new controller for one of the loops has been designed and experimental results measured on the Gravitational Wave detector Advanced Virgo show a significant reduction in the root mean square error of the loop with the new controller

Integrating H2 synthesis and dynamic error budgetting for improved gravitational wave detection

Dynamic error budgets are an essential tool in identifying opportunities for improvements in a control system for Gravitational Wave detectors, but their potential is often not fully utilized in the control design. This paper presents a model and dynamic error budget for a challenging nested control system in the Advanced Virgo detector in combination with a systematic control design framework for one of the controllers. This framework fully utilizes the dynamic error budget by using H2 synthesis to allow for fast iterations in the control design when dealing with conflicting control objectives. Simulations together with experimental results on Advanced Virgo illustrate the effectiveness of the presented framework