Thermal Testing and Integration: Magnetospheric MultiScale (MMS) Observatories with Digital 1-Wire Sensors

Thermocouples require two thin wires to be routed out of the spacecraft to connect to the ground support equipment used to monitor and record the temperature data. This large number of wires that exit the observatory complicates integration and creates an undesirable heat path during testing. These wires exiting the spacecraft need to be characterized as a thermal short that will not exist during flight. To minimize complexity and reduce thermal variables from these ground support equipment (GSE) wires, MMS pursued a hybrid path for temperature monitoring, utilizing thermocouples and digital 1-wire temperature sensors. Digital 1-wire sensors can greatly reduce harness mass, length and complexity as they can be spliced together. For MMS, 350 digital 1-wire sensors were installed on the spacecraft with only 18 wires exiting as opposed to a potential 700 thermocouple wires. Digital 1-wire sensors had not been used in such a large scale at NASAGSFC prior to the MMS mission. During the MMS thermal vacuum testing a lessons learned matrix was formulated that will assist future integration of 1-wires into thermal testing and one day into flight

Thermal Integration and Testing Magnetospheric MultiScale (MMS) Observatories Using Digital 1-wire Sensors

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Autonomic responses to emotional linguistic stimuli and amplitude of low-frequency fluctuations predict outcome after severe brain injury

An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC

Excitability of the supplementary motor area in Parkinson's disease depends on subcortical damage

Background: Cortical dysfunctioning significantly contributes to the pathogenesis of motor symptoms in Parkinson's disease (PD). Objective: We aimed at testing whether an acute levodopa administration has measurable and specific cortical effects possibly related to striatal dopaminergic deficit. Methods: In thirteen PD patients, we measured the electroencephalographic responses to transcranial magnetic stimulation (TMS/EEG) of the supplementary motor area and superior parietal lobule (n = 8) before and after an acute intake of levodopa. We also performed a single-photon emission computed tomography and [123I]N-\u3c9-fluoropropyl-2\u3b2-carbomethoxy-3\u3b2-(4-iodophenyl)nortropane to identify the more affected and the less affected brain side in each patient, according to the dopaminergic innervation loss of the putamen. Cortical excitability changes before and after an acute intake of levodopa were computed and compared between the more and the less affected brain side at the single-patient as well as at the group level. Results: We found that levodopa intake induces a significant increase (P < 0.01) of cortical excitability nearby the supplementary motor area in the more affected brain side, greater (P < 0.025) than in the less affected brain side. Notably, cortical excitability changes nearby the superior parietal lobule were not statistically significant. Conclusions: These results strengthen the idea that dysfunction of specific cortico-subcortical circuits may contribute to pathophysiology of PD symptoms. Most important, they support the use of navigated TMS/EEG as a non-invasive tool to better understand the pathophysiology of PD

Complexity of multi-dimensional spontaneous EEG decreases during propofol induced general anaesthesia

Emerging neural theories of consciousness suggest a correlation between a specific type of neural dynamical complexity and the level of consciousness: When awake and aware, causal interactions between brain regions are both integrated (all regions are to a certain extent connected) and differentiated (there is inhomogeneity and variety in the interactions). In support of this, recent work by Casali et al (2013) has shown that Lempel-Ziv complexity correlates strongly with conscious level, when computed on the EEG response to transcranial magnetic stimulation. Here we investigated complexity of spontaneous high-density EEG data during propofol-induced general anaesthesia. We consider three distinct measures: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability in the constitution of the set of active channels; and (iii) the novel synchrony coalition entropy (SCE), which measures the variability in the constitution of the set of synchronous channels. After some simulations on Kuramoto oscillator models which demonstrate that these measures capture distinct ‘flavours’ of complexity, we show that there is a robustly measurable decrease in the complexity of spontaneous EEG during general anaesthesia

Stratification of unresponsive patients by an independently validated index of brain complexity.

OBJECTIVE: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs). METHODS: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]). RESULTS: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition. INTERPRETATION: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior

New steps on an old path: Novel estrogen receptor inhibitors in breast cancer

Estrogen receptor (ER) signaling represents the main driver of tumor growth and survival in hormone receptor positive (HR+) breast cancer (BC). Thus, endocrine therapy (ET) alone or in combination with targeted agents constitutes the mainstay of the treatment for this BC subtype. Despite its efficacy, intrinsic or acquired resistance to ET occurs in a large proportion of cases, mainly due to aberrant activation of ER signaling (i.e. through ligand-independent ER activation, in the presence of estrogen receptor 1 (ESR1) gene aberration or ER protein phosphorylation) and/or the upregulation of escape pathways, such as the PI3K/AKT/mTOR pathway. Therefore, the development of new ER pathway targeting agents remains essential to delay and overcome ET resistance, enhance treatment efficacy and tolerability, and ultimately prolong patient survival and improve their quality of life. Several novel ER targeting agents are currently under investigation. Among these, the oral selective ER degraders (SERDs) represent the pharmacological class at the most advanced stage of development and promise to enrich the therapeutic armamentarium of HR+ BC in the next few years, as they showed promising results in several clinical trials, either as single ET agents or in combination with targeted therapies. In this manuscript, we aim to provide a comprehensive overview on the clinical development of novel ER targeting agents, reporting the most up-to-date evidence on oral SERDs and other compounds, including new selective ER modulators (SERMs), ER proteolysis targeting chimera (PROTACs), selective ER covalent antagonists (SERCAs), complete ER antagonists (CERANs), selective human ER partial agonists (ShERPAs). Furthermore, we discuss the potential implications of introducing these novel treatment strategies in the evolving and complex therapeutic scenario of HR+ BC

Monitoramento da aquicultura em reservatórios continentais por meio do índice de estado trófico.

A aquicultura é a atividade que mais cresce dentre os setores de produção de alimentos, porém, sua prática pode causar impactos ambientais no ambiente aquático, caso não haja um plano de monitoramento eficiente. O objetivo do presente trabalho foi avaliar o grau de trofia do ambiente utilizando o Índice de Estado Trófico (IET) em uma atividade aquícola de sistema de produção em tanques-rede no reservatório do Lajeado, Palmas, Tocantins na estação seca do ano. O monitoramento foi realizado no período de maio/2017 a agosto/2017 e envolveu a coleta de amostras para análises dos seguintes parâmetros de qualidade de água: fósforo total e clorofila-a. Paralelamente, houve a realização de coleta de dados de temperatura, turbidez, oxigênio dissolvido, condutividade, pH e sólidos totais dissolvidos. Os resultados do cálculo do Índice de Estado Trófico (IET) mostraram que a área em estudo durante os meses de maio e agosto apresentou-se predominantemente em graus eutrófico e hipereutrófico. O ponto controle também apresentou alto grau de trofia, indicando que o estado trófico do lago nas proximidades da área aquícola sofre forte influência de atividades antrópicas externas. Assim, os efeitos desta atividade a médio e longo prazo são difíceis de serem previstos, havendo a necessidade constante do monitoramento e controle da qualidade da água

Circadian dynamics in measures of cortical excitation and inhibition balance

Several neuropsychiatric and neurological disorders have recently been characterized as dysfunctions arising from a ‘final common pathway’ of imbalanced excitation to inhibition within cortical networks. How the regulation of a cortical E/I ratio is affected by sleep and the circadian rhythm however, remains to be established. Here we addressed this issue through the analyses of TMS-evoked responses recorded over a 29h sleep deprivation protocol conducted in young and healthy volunteers. Spectral analyses of TMS-evoked responses in frontal cortex revealed non-linear changes in gamma band evoked oscillations, compatible with an influence of circadian timing on inhibitory interneuron activity. In silico inferences of cell-to-cell excitatory and inhibitory connectivity and GABA/Glutamate receptor time constant based on neural mass modeling within the Dynamic causal modeling framework, further suggested excitation/inhibition balance was under a strong circadian influence. These results indicate that circadian changes in EEG spectral properties, in measure of excitatory/inhibitory connectivity and in GABA/glutamate receptor function could support the maintenance of cognitive performance during a normal waking day, but also during overnight wakefulness. More generally, these findings demonstrate a slow daily regulation of cortical excitation/inhibition balance, which depends on circadian-timing and prior sleep-wake history