Generation of an induced pluripotent stem cell line, CSSi011-A (6534), from an Amyotrophic lateral sclerosis patient with heterozygous L145F mutation in SOD1 gene

Among the known causative genes of familial ALS, SOD1 mutation is one of the most common. It encodes for the ubiquitous detoxifying copper/zinc binding SOD1 enzyme, whose mutations selectively cause motor neuron death, although the mechanisms are not as yet clear. What is known is that mutant-mediated toxicity is not caused by loss of its detoxifying activity but by a gain-of-function. In order to better understand the pathogenic mechanisms of SOD1 mutation, a human induced pluripotent stem cell (hiPSC) line was generated from the somatic cells of a female patient carrying a missense variation in SOD1 (L145F)

Detection chain and electronic readout of the QUBIC instrument

The Q and U Bolometric Interferometer for Cosmology (QUBIC) Technical Demonstrator (TD) aiming to shows the feasibility of the combination of interferometry and bolometric detection. The electronic readout system is based on an array of 128 NbSi Transition Edge Sensors cooled at 350mK readout with 128 SQUIDs at 1K controlled and amplified by an Application Specific Integrated Circuit at 40K. This readout design allows a 128:1 Time Domain Multiplexing. We report the design and the performance of the detection chain in this paper. The technological demonstrator unwent a campaign of test in the lab. Evaluation of the QUBIC bolometers and readout electronics includes the measurement of I-V curves, time constant and the Noise Equivalent Power. Currently the mean Noise Equivalent Power is ~ 2 x 10⁻¹⁶ W/√Hz

Detection chain and electronic readout of the QUBIC instrument

The Q and U Bolometric Interferometer for Cosmology (QUBIC) Technical Demonstrator (TD) aiming to shows the feasibility of the combination of interferometry and bolometric detection. The electronic readout system is based on an array of 128 NbSi Transition Edge Sensors cooled at 350mK readout with 128 SQUIDs at 1K controlled and amplified by an Application Specific Integrated Circuit at 40K. This readout design allows a 128:1 Time Domain Multiplexing. We report the design and the performance of the detection chain in this paper. The technological demonstrator unwent a campaign of test in the lab. Evaluation of the QUBIC bolometers and readout electronics includes the measurement of I-V curves, time constant and the Noise Equivalent Power. Currently the mean Noise Equivalent Power is ~ 2 x 10⁻¹⁶ W/√Hz

Production of CSSi013-A (9360) iPSC line from an asymptomatic subject carrying an heterozygous mutation in TDP-43 protein

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease affecting both upper and lower motoneurons. The transactive response DNA binding protein (TARDBP) gene, encoding for TDP-43, is one of the most commonly mutated gene associated with familial cases of ALS (10%). We generated a human induced pluripotent stem cell (hiPSC) line from the fibroblasts of an asymptomatic subject carrying the TARDBP p.G376D mutation. This mutation is very rare and was described in a large Apulian family, in which all ALS affected members are carriers of the mutation. The subject here described is the first identified asymptomatic carrier of the mutation

Small scale Suspended Interferometer for Ponderomotive Squeezing (SIPS) as test bench of the EPR squeezer for Advanced Virgo

We are developing a small-scale interferometer with monolithic suspension of test masses (SIPS), that will be sensitive to the quantum radiation pressure noise in the audio frequency band of gravitational wave detectors. In the same time, a table-top experiment for the frequency dependent squeezing generation, through the Einstein Podolsky Rosen (EPR) principle, is under construction. SIPS interferometer, being designed to achieve the quantum radiation pressure noise limit exploiting high finesse optical cavities, turns out to be a suitable test bench for the EPR technique, before a possible integration in Virgo for broadband quantum noise reduction. In this work, we describe the concept of the SIPS experiment, the most important noises affecting this setup, and we briefly present the current status and the plan for the integration with the EPR squeezing experiment

Characterization of the p.L145F and p.S135N Mutations in SOD1: Impact on the Metabolism of Fibroblasts Derived from Amyotrophic Lateral Sclerosis Patients

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of the upper and lower motor neurons (MNs). About 10% of patients have a family history (familial, fALS); however, most patients seem to develop the sporadic form of the disease (sALS). SOD1 (Cu/Zn superoxide dismutase-1) is the first studied gene among the ones related to ALS. Mutant SOD1 can adopt multiple misfolded conformation, lose the correct coordination of metal binding, decrease structural stability, and form aggregates. For all these reasons, it is complicated to characterize the conformational alterations of the ALS-associated mutant SOD1, and how they relate to toxicity. In this work, we performed a multilayered study on fibroblasts derived from two ALS patients, namely SOD1L145F and SOD1S135N, carrying the p.L145F and the p.S135N missense variants, respectively. The patients showed diverse symptoms and disease progression in accordance with our bioinformatic analysis, which predicted the different effects of the two mutations in terms of protein structure. Interestingly, both mutations had an effect on the fibroblast energy metabolisms. However, while the SOD1L145F fibroblasts still relied more on oxidative phosphorylation, the SOD1S135N fibroblasts showed a metabolic shift toward glycolysis. Our study suggests that SOD1 mutations might lead to alterations in the energy metabolism

Progress in a Vacuum Weight Search Experiment

International audienceWe present the status of the art of the Archimedes experiment, devoted to measuring the debated interaction of quantum vacuum fluctuations and gravity. The method is essentially the weighing of the transition energy of a layered superconductor where the contribution of vacuum energy to the transition energy is expected to be relevant. The transition is obtained by modulating the temperature of the superconducting sample at a frequency of about 10 mHz and the expected change of weight is measured with a suitably designed high sensitivity cryogenic beam balance. In this paper, we present an overview of the experiment, discussing the expected signal to be measured, and presenting in particular the result of a prototype balance operated in our present laboratory. In the frequency range of the measurement, the sensitivity is affected mainly by seismic, thermal, sensor, and control noise. We discuss these points showing in particular the design of the cryogenic apparatus, the final balance, and the quiet seismic site that will host the final measurement

Picoradiant tiltmeter and direct ground tilt measurements at the Sos Enattos site

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Casimir energy for N superconducting cavities: a model for the YBCO (GdBCO) sample to be used in the Archimedes experiment

International audienceAbstract In this paper we study the Casimir energy of a sample made by N cavities, with $$N\gg 1$$ N ≫ 1 , across the transition from the metallic to the superconducting phase of the constituting plates. After having characterised the energy for the configuration in which the layers constituting the cavities are made by dielectric and for the configuration in which the layers are made by plasma sheets, we concentrate our analysis on the latter. It represents the final step towards the macroscopical characterisation of a “multi-cavity” (with N large) necessary to fully understand the behaviour of the Casimir energy of a YBCO (or a GdBCO) sample across the transition. Our analysis is especially useful to the Archimedes experiment, aimed at measuring the interaction of the electromagnetic vacuum energy with a gravitational field. To this purpose, we aim at modulating the Casimir energy of a layered structure, the multi-cavity, by inducing a transition from the metallic to the superconducting phase. After having characterised the Casimir energy of such a structure for both the metallic and the superconducting phase, we give an estimate of the modulation of the energy across the transition