1,364 research outputs found

    Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice

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    Astrocytes act as a dynamic Cl− reservoir regulating Cl− homeostasis in the CNS. Astrocytic Cl− is high and stable during sleep, it is lower during wakefulness and fluctuates in response to sensory input and motor activity. Efflux of Cl− from astrocytes supports inhibitory transmission in the CNS

    Test beam performance of a CBC3-based mini-module for the Phase-2 CMS Outer Tracker before and after neutron irradiation

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    Glymphatic-assisted perivascular brain delivery of intrathecal small gold nanoparticles

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    Nanoparticles are ultrafine particulate matter having considerable potential for treatment of central nervous system (CNS) disorders. Despite their tiny size, the blood-brain barrier (BBB) restricts their access to the CNS. Their direct cerebrospinal fluid (CSF) administration bypasses the BBB endothelium, but still fails to give adequate brain uptake. We present a novel approach for efficient CNS delivery of 111In-radiolabelled gold nanoparticles (AuNPs; 10-15 nm) via intra-cisterna magna administration, with tracking by SPECT imaging. To accelerate CSF brain influx, we administered AuNPs intracisternally in conjunction with systemic hypertonic saline, which dramatically increased the parenchymal AuNP uptake, especially in deep brain regions. AuNPs entered the CNS along periarterial spaces as visualized by MRI of gadolinium-labelled AuNPs and were cleared from brain within 24 h and excreted through the kidneys. Thus, the glymphatic-assisted perivascular network augment by systemic hypertonic saline is a pathway for highly efficient brain-wide distribution of small AuNPs.Peer reviewe

    Evaluation of HPK n+n^+-pp planar pixel sensors for the CMS Phase-2 upgrade

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    International audienceTo cope with the challenging environment of the planned high luminosity upgrade of the Large Hadron Collider (HL-LHC), sched-uled to start operation in 2029, CMS will replace its entire tracking system. The requirements for the tracker are largely determinedby the long operation time of 10 years with an instantaneous peak luminosity of up to 7.5 × 1034 cm−2 s−1 in the ultimate perfor-mance scenario. Depending on the radial distance from the interaction point, the silicon sensors will receive a particle fluencecorresponding to a non-ionizing energy loss of up to Ίeq = 3.5 × 1016 cm−2. This paper focuses on planar pixel sensor design andqualification up to a fluence of Ίeq = 1.4 × 1016 cm−2.For the development of appropriate planar pixel sensors an R&D program was initiated, which includes n+-p sensors on 150 mm(6”) wafers with an active thickness of 150 ÎŒm with pixel sizes of 100 × 25 ÎŒm2 and 50 × 50 ÎŒm2 manufactured by Hamamatsu.Single chip modules with ROC4Sens and RD53A readout chips were made. Irradiation with protons and neutrons, as well was anextensive test beam campaign at DESY were carried out. This paper presents the investigation of various assemblies mainly withROC4Sens readout chips. It demonstrates that multiple designs fulfill the requirements in terms of breakdown voltage, leakagecurrent and efficiency. The single point resolution for 50 × 50 ÎŒm2 pixels is measured as 4.0 ÎŒm for non-irradiated samples, and6.3 ÎŒm after irradiation to Ίeq = 7.2 × 1015 cm−2

    Electrocardiography Assessment of Sympatico–Vagal Balance during Resting and Pain Using the Texas Instruments ADS1299

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    Sympatico–vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico–vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico–vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico–vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly (p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers

    Electrocardiography Assessment of Sympatico–Vagal Balance during Resting and Pain using the Texas Instruments ADS1299

    No full text
    Sympatico–vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico–vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico–vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico–vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly (p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers

    Test beam performance of a CBC3-based mini-module for the Phase-2 CMS Outer Tracker before and after neutron irradiation

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    Test beam performance of a CBC3-based mini-module for the Phase-2 CMS Outer Tracker before and after neutron irradiation

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    The Large Hadron Collider (LHC) at CERN will undergo major upgrades to increase the instantaneous luminosity up to 5–7.5×1034^{34} cm−2^{-2}s−1^{-1}. This High Luminosity upgrade of the LHC (HL-LHC) will deliver a total of 3000–4000 fb-1 of proton-proton collisions at a center-of-mass energy of 13–14 TeV. To cope with these challenging environmental conditions, the strip tracker of the CMS experiment will be upgraded using modules with two closely-spaced silicon sensors to provide information to include tracking in the Level-1 trigger selection. This paper describes the performance, in a test beam experiment, of the first prototype module based on the final version of the CMS Binary Chip front-end ASIC before and after the module was irradiated with neutrons. Results demonstrate that the prototype module satisfies the requirements, providing efficient tracking information, after being irradiated with a total fluence comparable to the one expected through the lifetime of the experiment

    Sizes and shapes of perivascular spaces surrounding murine pial arteries

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    Abstract Background Flow of cerebrospinal fluid (CSF) through brain perivascular spaces (PVSs) is essential for the clearance of interstitial metabolic waste products whose accumulation and aggregation is a key mechanism of pathogenesis in many diseases. The PVS geometry has important implications for CSF flow as it affects CSF and solute transport rates. Thus, the size and shape of the perivascular spaces are essential parameters for models of CSF transport in the brain and require accurate quantification. Methods We segmented two-photon images of pial (surface) PVSs and the adjacent arteries and characterized their sizes and shapes of cross sections from 14 PVS segments in 9 mice. Based on the analysis, we propose an idealized model that approximates the cross-sectional size and shape of pial PVSs, closely matching their area ratios and hydraulic resistances. Results The ratio of PVS-to-vessel area varies widely across the cross sections analyzed. The hydraulic resistance per unit length of the PVS scales with the PVS cross-sectional area, and we found a power-law fit that predicts resistance as a function of the area. Three idealized geometric models were compared to PVSs imaged in vivo, and their accuracy in reproducing hydraulic resistances and PVS-to-vessel area ratios were evaluated. The area ratio was obtained across different cross sections, and we found that the distribution peaks for the original PVS and its closest idealized fit (polynomial fit) were 1.12 and 1.21, respectively. The peak of the hydraulic resistance distribution is 1.73×10151.73\times 10^{15} 1.73 × 10 15  Pa  s/m 5^{5} 5 and 1.44×10151.44\times 10^{15} 1.44 × 10 15  Pa s/m 5^{5} 5 for the segmentation and its closest idealized fit, respectively. Conclusions PVS hydraulic resistance can be reasonably predicted as a function of the PVS area. The proposed polynomial-based fit most closely captures the shape of the PVS with respect to area ratio and hydraulic resistance. Idealized PVS shapes are convenient for modeling, which can be used to better understand how anatomical variations affect clearance and drug transport
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