The low-temperature energy calibration system for the CUORE bolometer array

The CUORE experiment will search for neutrinoless double beta decay (0nDBD) of 130Te using an array of 988 TeO_2 bolometers operated at 10 mK in the Laboratori Nazionali del Gran Sasso (Italy). The detector is housed in a large cryogen-free cryostat cooled by pulse tubes and a high-power dilution refrigerator. The TeO_2 bolometers measure the event energies, and a precise and reliable energy calibration is critical for the successful identification of candidate 0nDBD and background events. The detector calibration system under development is based on the insertion of 12 gamma-sources that are able to move under their own weight through a set of guide tubes that route them from deployment boxes on the 300K flange down into position in the detector region inside the cryostat. The CUORE experiment poses stringent requirements on the maximum heat load on the cryostat, material radiopurity, contamination risk and the ability to fully retract the sources during normal data taking. Together with the integration into a unique cryostat, this requires careful design and unconventional solutions. We present the design, challenges, and expected performance of this low-temperature energy calibration system.Comment: To be published in the proceedings of the 13th International Workshop on Low Temperature Detectors (LTD), Stanford, CA, July 20-24, 200

Heart rate detection by Fitbit ChargeHR™: A validation study versus portable polysomnography

Consumer "Smartbands" can collect physiological parameters, such as heart rate (HR), continuously across the sleep-wake cycle. Nevertheless, the quality of HR data detected by such devices and their place in the research and clinical field is debatable, as they are rarely rigorously validated. The objective of the present study was to investigate the reliability of pulse photoplethysmographic detection by the Fitbit ChargeHR (FBCHR, Fitbit Inc.) in a natural setting of continuous recording across vigilance states. To fulfil this aim, concurrent portable polysomnographic (pPSG) and the Fitbit's photoplethysmographic data were collected from a group of 25 healthy young adults, for ≥12hr. The pPSG-derived HR was automatically computed and visually verified for each 1-min epoch, while the FBCHR HR measurements were downloaded from the application programming interface provided by the manufacturer. The FBCHR was generally accurate in estimating the HR, with a mean (SD) difference of -0.66(0.04)beats/min (bpm) versus the pPSG-derived HR reference, and an overall Pearson's correlation coefficient (r) of 0.93 (average per participant r=0.85±0.11), regardless of vigilance state. The correlation coefficients were larger during all sleep phases (rapid eye movement, r=0.9662; N1, r=0.9918; N2, r=0.9793; N3, r=0.9849) than in wakefulness (r=0.8432). Moreover, the correlation coefficient was lower for HRs of >100bpm (r=0.374) than for HRs of <100bpm (r=0.84). Consistently, Bland-Altman analysis supports the overall higher accuracy in the detection of HR during sleep. The relatively high accuracy of FBCHR pulse rate detection during sleep makes this device suitable for sleep-related research applications in healthy participants, under free-living conditions

Sensory Processing Across Conscious and Nonconscious Brain States: From Single Neurons to Distributed Networks for Inferential Representation

Neuronal activity is markedly different across brain states: it varies from desynchronized activity during wakefulness to the synchronous alternation between active and silent states characteristic of deep sleep. Surprisingly, limited attention has been paid to investigating how brain states affect sensory processing. While it was long assumed that the brain was mostly disconnected from external stimuli during sleep, an increasing number of studies indicates that sensory stimuli continue to be processed across all brain states—albeit differently. In this review article, we first discuss what constitutes a brain state. We argue that—next to global, behavioral states such as wakefulness and sleep—there is a concomitant need to distinguish bouts of oscillatory dynamics with specific global/local activity patterns and lasting for a few hundreds of milliseconds, as these can lead to the same sensory stimulus being either perceived or not. We define these short-lasting bouts as micro-states. We proceed to characterize how sensory-evoked neural responses vary between conscious and nonconscious states. We focus on two complementary aspects: neuronal ensembles and inter-areal communication. First, we review which features of ensemble activity are conducive to perception, and how these features vary across brain states. Properties such as heterogeneity, sparsity and synchronicity in neuronal ensembles will especially be considered as essential correlates of conscious processing. Second, we discuss how inter-areal communication varies across brain states and how this may affect brain operations and sensory processing. Finally, we discuss predictive coding (PC) and the concept of multi-level representations as a key framework for understanding conscious sensory processing. In this framework the brain implements conscious representations as inferences about world states across multiple representational levels. In this representational hierarchy, low-level inference may be carried out nonconsciously, whereas high levels integrate across different sensory modalities and larger spatial scales, correlating with conscious processing. This inferential framework is used to interpret several cellular and population-level findings in the context of brain states, and we briefly compare its implications to two other theories of consciousness. In conclusion, this review article, provides foundations to guide future studies aiming to uncover the mechanisms of sensory processing and perception across brain states

Consciousness Regained: Disentangling Mechanisms, Brain Systems, and Behavioral Responses

How consciousness (experience) arises from and relates to material brain processes (the "mind-body problem") has been pondered by thinkers for centuries, and is regarded as among the deepest unsolved problems in science, with wide-ranging theoretical, clinical, and ethical implications. Until the last few decades, this was largely seen as a philosophical topic, but not widely accepted in mainstream neuroscience. Since the 1980s, however, novel methods and theoretical advances have yielded remarkable results, opening up the field for scientific and clinical progress. Since a seminal paper by Crick and Koch (1998) claimed that a science of consciousness should first search for its neural correlates (NCC), a variety of correlates have been suggested, including both content-specific NCCs, determining particular phenomenal components within an experience, and the full NCC, the neural substrates supporting entire conscious experiences. In this review, we present recent progress on theoretical, experimental, and clinical issues. Specifically, we (1) review methodological advances that are important for dissociating conscious experience from related enabling and executive functions, (2) suggest how critically reconsidering the role of the frontal cortex may further delineate NCCs, (3) advocate the need for general, objective, brain-based measures of the capacity for consciousness that are independent of sensory processing and executive functions, and (4) show how animal studies can reveal population and network phenomena of relevance for understanding mechanisms of consciousness.European Union's Horizon 2020 Research and Innovation ProgrammeHermann and Lilly Schilling FoundationGerman Research FoundationCenter for Nanoscale Microscopy and Molecular Physiology of the BrainNational Institutes of Health/National Institute of Neurological Disorders and StrokeSao Paulo Research FoundationJames S. McDonnell Foundation Scholar AwardEU Grant H2020-FETOPENCanadian Institute for Advanced ResearchAzrieli Program in Brain, Mind and ConsciousnessFLAG-ERA JTC project CANONNorwegian Research CouncilNetherlands Organization for Scientific ResearchUniv Oslo, Inst Basal Med Sci, Div Physiol, Dept Mol Med, POB 1103 Blindern, N-0317 Oslo, NorwayUniv Wisconsin, Dept Neurol, Madison, WI 53705 USAUniv Wisconsin, Dept Psychiat, Madison, WI 53719 USAUniv Fed Sao Paulo, Inst Sci & Technol, BR-12231280 Sao Jose Dos Campos, SP, BrazilUniv Milan, Dept Biomed & Clin Sci Luigi Sacco, I-20157 Milan, ItalyFdn Don Carlo Gnocchi ONLUS, Ist Ricovero & Cura Carattere Sci, I-20162 Milan, ItalyUniv Amsterdam, Swammerdam Inst Life Sci, Cognit & Syst Neurosci Grp, NL-1098 XH Amsterdam, NetherlandsUniv Amsterdam, Res Prior Program Brain & Cognit, NL-1098 XH Amsterdam, NetherlandsUniv Med Goettingen, Dept Cognit Neurol, D-37075 Gottingen, GermanyLeibniz Inst Primate Res, German Primate Ctr, D-37077 Gottingen, GermanyLeibniz Sci Campus Primate Cognit, D-37077 Gottingen, GermanyUniv Fed Sao Paulo, Inst Sci & Technol, BR-12231280 Sao Jose Dos Campos, SP, BrazilEuropean Union's Horizon 2020 Research and Innovation Programme: 720270German Research Foundation: WI 4046/1-1National Institutes of Health/National Institute of Neurological Disorders and Stroke: 1R03NS096379FAPESP: 2016/08263-9EU Grant H2020-FETOPEN: RIA 686764Web of Scienc

Mode shift of the voltage sensors in Shaker K+ channels is caused by energetic coupling to the pore domain

The voltage sensors of voltage-gated ion channels undergo a conformational change upon depolarization of the membrane that leads to pore opening. This conformational change can be measured as gating currents and is thought to be transferred to the pore domain via an annealing of the covalent link between voltage sensor and pore (S4-S5 linker) and the C terminus of the pore domain (S6). Upon prolonged depolarizations, the voltage dependence of the charge movement shifts to more hyperpolarized potentials. This mode shift had been linked to C-type inactivation but has recently been suggested to be caused by a relaxation of the voltage sensor itself. In this study, we identified two ShakerIR mutations in the S4-S5 linker (I384N) and S6 (F484G) that, when mutated, completely uncouple voltage sensor movement from pore opening. Using these mutants, we show that the pore transfers energy onto the voltage sensor and that uncoupling the pore from the voltage sensor leads the voltage sensors to be activated at more negative potentials. This uncoupling also eliminates the mode shift occurring during prolonged depolarizations, indicating that the pore influences entry into the mode shift. Using voltage-clamp fluorometry, we identified that the slow conformational change of the S4 previously correlated with the mode shift disappears when uncoupling the pore. The effects can be explained by a mechanical load that is imposed upon the voltage sensors by the pore domain and allosterically modulates its conformation. Mode shift is caused by the stabilization of the open state but leads to a conformational change in the voltage sensor

Mutational screening of the TPO and DUOX2 genes in Argentinian children with congenital hypothyroidism due to thyroid dyshormonogenesis

[Purpose]: Primary congenital hypothyroidism (CH) is the most common endocrine disease in children and one of the preventable causes of both cognitive and motor deficits. We present a genetic and bioinformatics investigation of rational clinical design in 17 Argentine patients suspected of CH due to thyroid dyshormonogenesis (TDH). [Methods]: Next-Generation Sequencing approach was used to identify variants in Thyroid Peroxidase (TPO) and Dual Oxidase 2 (DUOX2) genes. A custom panel targeting 7 genes associated with TDH [(TPO), Iodothyrosine Deiodinase I (IYD), Solute Carrier Family 26 Member 4 (SLC26A4), Thyroglobulin (TG), DUOX2, Dual Oxidase Maturation Factor 2 (DUOXA2), Solute Carrier Family 5 Member 5 (SLC5A5)] and 4 associated with thyroid dysembryogenesis [PAX8, FOXE1, NKX2-1, Thyroid Stimulating Hormone Receptor (TSHR)] has been designed. Additionally, bioinformatic analysis and structural modeling were carried out to predict the disease-causing potential variants. [Results]: Four novel variants have been identified, two in TPO: c.2749-2 A > C and c.2752_2753delAG, [p.Ser918Cysfs*62] and two variants in DUOX2 gene: c.425 C > G [p.Pro142Arg] and c.2695delC [p.Gln899Serfs*21]. Eighteen identified TPO, DUOX2 and IYD variants were previously described. We identified potentially pahogenic biallelic variants in TPO and DUOX2 in 7 and 2 patients, respectively. We also detected a potentially pathogenic monoallelic variant in TPO and DUOX2 in 7 and 1 patients respectively. [Conclusions]: 22 variants have been identified associated with TDH. All described novel mutations occur in domains important for protein structure and function, predicting the TDH phenotype.This study was funded by grants from the Fondo para la Investigación Científica y Tecnológica (FONCyT-ANPCyT-MINCyT, PICT 2014-1193 to CMR, PICT 2015-1811 and PICT-2018-02146 to H.M.T.), CONICET (PIP 2015-11220150100499 to C.M.R.), Universidad de Buenos Aires (UBACyT 2016-20020150100099BA and 2020-20020190100050BA to C.M.R.) and Fondo de Investigación Sanitaria/FEDER (PI16/01920 and PI20/01589 to R.G.-S.)

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal