In-vivo multilaboratory investigation of the optical properties of the human head

The in-vivo optical properties of the human head are investigated in the 600–1100 nm range on different subjects using continuous wave and time domain diffuse optical spectroscopy. The work was performed in collaboration with different research groups and the different techniques were applied to the same subject. Data analysis was carried out using homogeneous and layered models and final results were also confirmed by Monte Carlo simulations. The depth sensitivity of each technique was investigated and related to the probed region of the cerebral tissue. This work, based on different validated instruments, is a contribution to fill the existing gap between the present knowledge and the actual in-vivo values of the head optical properties

Frataxin deficiency shifts metabolism to promote reactive microglia via glucose catabolism

Immunometabolism investigates the intricate relationship between the immune system and cellular metabolism. This study delves into the consequences of mitochondrial frataxin (FXN) depletion, the primary cause of Friedreich's ataxia (FRDA), a debilitating neurodegenerative condition characterized by impaired coordination and muscle control. By using single-cell RNA sequencing, we have identified distinct cellular clusters within the cerebellum of an FRDA mouse model, emphasizing a significant loss in the homeostatic response of microglial cells lacking FXN. Remarkably, these microglia deficient in FXN display heightened reactive responses to inflammatory stimuli. Furthermore, our metabolomic analyses reveal a shift towards glycolysis and itaconate production in these cells. Remarkably, treatment with butyrate counteracts these immunometabolic changes, triggering an antioxidant response via the itaconate-Nrf2-GSH pathways and suppressing the expression of inflammatory genes. Furthermore, we identify Hcar2 (GPR109A) as a mediator involved in restoring the homeostasis of microglia without FXN. Motor function tests conducted on FRDA mice underscore the neuroprotective attributes of butyrate supplementation, enhancing neuromotor performance. In conclusion, our findings elucidate the role of disrupted homeostatic function in cerebellar microglia in the pathogenesis of FRDA. Moreover, they underscore the potential of butyrate to mitigate inflammatory gene expression, correct metabolic imbalances, and improve neuromotor capabilities in FRDA

Lipocalin-2 promotes adipose-macrophage interactions to shape peripheral and central inflammatory responses in experimental autoimmune encephalomyelitis

Objective: Accumulating evidence suggests that dysfunctional adipose tissue (AT) plays a major role in the risk of developing multiple sclerosis (MS), the most common immune-mediated and demyelinating disease of the central nervous system. However, the contribution of adipose tissue to the etiology and progression of MS is still obscure. This study aimed at deciphering the responses of AT in experimental autoimmune encephalomyelitis (EAE), the best characterized animal model of MS. Results and methods: We observed a significant AT loss in EAE mice at the onset of disease, with a significant infiltration of M1-like macrophages and fibrosis in the AT, resembling a cachectic phenotype. Through an integrative and multilayered approach, we identified lipocalin2 (LCN2) as the key molecule released by dysfunctional adipocytes through redox-dependent mechanism. Adipose-derived LCN2 shapes the pro-inflammatory macrophage phenotype, and the genetic deficiency of LCN2 specifically in AT reduced weight loss as well as inflammatory macrophage infiltration in spinal cord in EAE mice. Mature adipocytes downregulating LCN2 reduced lipolytic response to inflammatory stimuli (e.g. TNFα) through an ATGL-mediated mechanism. Conclusions: Overall data highlighted a role LCN2 in exacerbating inflammatory phenotype in EAE model, suggesting a pathogenic role of dysfunctional AT in MS

Status of a C-band Phased Array Feed with RFSoC digital beamformer

In this paper, we describe the design and development status of a room-temperature C-band Phased Array Feed (PAF) demonstrator, based on Radio Frequency System-on-Chip (RFSoC) for radio astronomy application, to be installed on the Sardinia Radio Telescope. The instrument is optimized to work across the 4.75-6.00 GHz radio frequency (RF) band. The project of the front-end includes a compact RF module based on an 8×8 array of linear dual-polarization antenna elements integrated with Monolithic Microwave Integrated Circuit (MMIC) Low Noise Amplifiers (LNAs). In the preliminary version of the front-end project, which considers only one linear polarization, a subset of 32 elements are connected to the LNAs, while the rest of them are terminated to 50 Ohm matched loads. A dedicated signal acquisition chain of microwave components, based on two stages of filtering and signal conditioning, permits the injection of the 32 RF signals to the two commercial back-ends based on RFSoC digital boards. Each board is equipped with 16 inputs, with 1.25 GHz instantaneous bandwidth, and performs the frequency channelization, the partial and final beamforming of at least four independent beams (the number of beams may vary depending on the observation requirements). A general description of the front-end design, the back-end hardware, firmware and software development and an optimizer for the whole system performances evaluation, is presented

Test-Driven Design of an Active Dual-Polarized Log-Periodic Antenna for the Square Kilometre Array

An active dual-polarized Log-Periodic antenna has been designed to meet the requirements of the low-frequency (50-350 MHz) radio telescope of the Square Kilometre Array (SKA). The integration of antenna and low noise amplifier has been conceived in order to achieve a high degree of testability. This aspect has been found to be crucial to obtain a smooth frequency response compatible with the SKA science cases. The design has also been driven by other factors such as the large-volume production (more than 130 000 antennas will be built) and the environmental conditions of the harsh Australian desert. A specific verification approach based on both wideband radiometric spectral and spatial measurements in relevant laboratory and in-situ conditions has been developed. Electromagnetic analyses and experimental results exhibit a very good agreement. In December 2019, this antenna was part of the reference solution for the System Critical Design Review of the SKA

Architecture of C-band Phased Array Feed with RFSoC digital beamformer

We describe the architecture of a room-temperature C-band Phased Array Feed (PAF) demonstrator based on Radio Frequency System-on-Chip (RFSoC) for radio astronomy application. The instrument operates across the 4.75-6.00 GHz RF band (C-band). The RF section includes a compact module based on an 8×8 array of dual-polarization antennas integrated with MMIC (Monolithic Microwave Integrated Circuit) Low Noise Amplifiers (LNAs). A subset of 32 elements of one of the two polarization channels of the 128 antennas are connected to the LNAs, while the rest are terminated into internal loads. Following two stages of filtering and signal conditioning, the 32 RF signals are injected in two commercial RFSoC digital boards, each accepting 16 inputs with 1.25 GHz bandwidth, that will perform the frequency channelization, the partial and final beamforming of four independent beams with 1.25 GHz instantaneous bandwidth

Electrocardiographic findings in patients with arrhythmogenic cardiomyopathy and right bundle branch block ventricular tachycardia

AIMS: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data. METHODS AND RESULTS: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available.  Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV. CONCLUSIONS: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants

Characterization of the SKA1-Low prototype station Aperture Array Verification System 2

The low frequency component of the Square Kilometre Array (SKA1-Low) will be an aperture phased array located at the Murchison Radio-astronomy Observatory (MRO) site in Western Australia. It will be composed of 512 stations, each consisting of 256 log-periodic dual-polarized antennas, and will operate in the low frequency range (50 to 350 MHz) of the SKA bandwidth. The Aperture Array Verification System 2 (AAVS2), operational since late 2019, is the last full-size engineering prototype station deployed at the MRO site before the start of the SKA1-Low construction phase. The aim of this paper is to characterize the station performance through commissioning observations at six different frequencies (55, 70, 110, 160, 230, and 320 MHz) collected during its first year of activities. We describe the calibration procedure, present the resulting all-sky images and their analysis, and discuss the station calibratability and system stability. Using the difference imaging method, we also derive estimates of the SKA1-Low sensitivity for the same frequencies and compare them with those obtained through electromagnetic simulations across the entire telescope bandwidth, finding good agreement (within 13%). Moreover, our estimates exceed the SKA1-Low requirements at all considered frequencies by up to a factor of ∼2.3. Our results are very promising and allow for an initial validation of the AAVS2 prototype station performance, which is an important step toward the coming SKA1-Low telescope construction and science

Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable

Sex differences in brain and plasma beta-endorphin content following testosterone, dihydrotestosterone and estradiol administration to gonadectomized rats

The present study aims at evaluating the effect of a 2-week treatment with testosterone (T), dihydrotestosterone (DHT) and estradiol valerate (E(2)V) on brain and plasma beta-endorphin (beta-END) concentrations in gonadectomized rats of both sexes. METHODS: Eight groups of female and 8 groups of male Wistar rats were included. For each sex, 1 group of gonad-intact and 1 group of gonadectomized rats were employed as controls (placebo). The other groups received subcutaneous T at the doses of 10 and 100 microg/kg/day (female rats) or 1 and 5 mg/kg/day (male rats). Subcutaneous DHT was administered at the doses of 1, 10, 100 microg/kg/day (female rats) or 0.1, 1 and 5 mg/kg/day (male rats). E(2)V was administered subcutaneously at 0.05 mg/kg/day. beta-END levels were measured in different brain areas and plasma. RESULTS: Ovariectomy (OVX) induced a significant decrease in beta-END in all brain areas analyzed as well as in plasma. Orchidectomy (OCX) reduced opioid concentration in the hypothalamus, anterior pituitary and neurointermediate lobe. In OVX rats, T replacement as well as E(2)V significantly increased beta-END concentration in all brain areas and in plasma. In the OCX group, T and E(2)V did not influence beta-END concentrations in different hypothalamic areas. However, they produced a significant rise in beta-END levels in the hypothalamus, neurointermediate lobe, anterior pituitary and plasma. Conversely, DHT replacement did not affect beta-END levels at any dose administered, either in males or females. CONCLUSIONS: The sensitivity of the endogenous opiatergic system to T administration seems to be sex-related. This effect is particularly evident in the brains of female animals where this endogenous endorphin elicits a much greater response than it does in males that have undergone gonadal steroid depletion and subsequent T replacement