In vivo myelin water quantification using diffusion–relaxation correlation MRI: A comparison of 1D and 2D methods

Multidimensional Magnetic Resonance Imaging (MRI) is a versatile tool for microstructure mapping. We use a diffusion weighted inversion recovery spin echo (DW-IR-SE) sequence with spiral readouts at ultra-strong gradients to acquire a rich diffusion–relaxation data set with sensitivity to myelin water. We reconstruct 1D and 2D spectra with a two-step convex optimization approach and investigate a variety of multidimensional MRI methods, including 1D multi-component relaxometry, 1D multi-component diffusometry, 2D relaxation correlation imaging, and 2D diffusion-relaxation correlation spectroscopic imaging (DR-CSI), in terms of their potential to quantify tissue microstructure, including the myelin water fraction (MWF). We observe a distinct spectral peak that we attribute to myelin water in multi-component T1 relaxometry, T1-T2 correlation, T1-D correlation, and T2-D correlation imaging. Due to lower achievable echo times compared to diffusometry, MWF maps from relaxometry have higher quality. Whilst 1D multi-component T1 data allows much faster myelin mapping, 2D approaches could offer unique insights into tissue microstructure and especially myelin diffusion

The UAV-based test source as an end-to-end verification tool for aperture arrays

A UAV-mounted radio-frequency transmitter is proposed as a known reference field source to perform a set of functional tests on aperture arrays. The experimental results obtained on complete prototypes (end-to-end) and sub-assemblies provide good confidence on both amplitude and timing verification

Association of Genetic Markers with CSF Oligoclonal Bands in Multiple Sclerosis Patients

Objective:to explore the association between genetic markers and Oligoclonal Bands (OCB) in the Cerebro Spinal Fluid (CSF) of Italian Multiple Sclerosis patients.Methods:We genotyped 1115 Italian patients for HLA-DRB1*15 and HLA-A*02. In a subset of 925 patients we tested association with 52 non-HLA SNPs associated with MS susceptibility and we calculated a weighted Genetic Risk Score. Finally, we performed a Genome Wide Association Study (GWAS) with OCB status on a subset of 562 patients. The best associated SNPs of the Italian GWAS were replicated in silico in Scandinavian and Belgian populations, and meta-analyzed.Results:HLA-DRB1*15 is associated with OCB+: p = 0.03, Odds Ratio (OR) = 1.6, 95% Confidence Limits (CL) = 1.1-2.4. None of the 52 non-HLA MS susceptibility loci was associated with OCB, except one SNP (rs2546890) near IL12B gene (OR: 1.45; 1.09-1.92). The weighted Genetic Risk Score mean was significantly (p = 0.0008) higher in OCB+ (7.668) than in OCB- (7.412) patients. After meta-analysis on the three datasets (Italian, Scandinavian and Belgian) for the best associated signals resulted from the Italian GWAS, the strongest signal was a SNP (rs9320598) on chromosome 6q (p = 9.4×10-7) outside the HLA region (65 Mb).Discussion:genetic factors predispose to the development of OCB

Combining Network Modeling and Gene Expression Microarray Analysis to Explore the Dynamics of Th1 and Th2 Cell Regulation

Two T helper (Th) cell subsets, namely Th1 and Th2 cells, play an important role in inflammatory diseases. The two subsets are thought to counter-regulate each other, and alterations in their balance result in different diseases. This paradigm has been challenged by recent clinical and experimental data. Because of the large number of genes involved in regulating Th1 and Th2 cells, assessment of this paradigm by modeling or experiments is difficult. Novel algorithms based on formal methods now permit the analysis of large gene regulatory networks. By combining these algorithms with in silico knockouts and gene expression microarray data from human T cells, we examined if the results were compatible with a counter-regulatory role of Th1 and Th2 cells. We constructed a directed network model of genes regulating Th1 and Th2 cells through text mining and manual curation. We identified four attractors in the network, three of which included genes that corresponded to Th0, Th1 and Th2 cells. The fourth attractor contained a mixture of Th1 and Th2 genes. We found that neither in silico knockouts of the Th1 and Th2 attractor genes nor gene expression microarray data from patients with immunological disorders and healthy subjects supported a counter-regulatory role of Th1 and Th2 cells. By combining network modeling with transcriptomic data analysis and in silico knockouts, we have devised a practical way to help unravel complex regulatory network topology and to increase our understanding of how network actions may differ in health and disease

Developments of FPGA-based digital back-ends for low frequency antenna arrays at Medicina radio telescopes

In radio astronomy Field Programmable Gate Array (FPGA) technology is largely used for the implementation of digital signal processing techniques applied to antenna arrays. This is mainly due to the good trade-off among computing resources, power consumption and cost offered by FPGA chip compared to other technologies like ASIC, GPU and CPU. In the last years several digital backend systems based on such devices have been developed at the Medicina radio astronomical station (INAF-IRA, Bologna, Italy). Instruments like FX correlator, direct imager, beamformer, multi-beam system have been successfully designed and realized on CASPER (Collaboration for Astronomy Signal Processing and Electronics Research, https://casper.berkeley.edu) processing boards. In this paper we present the gained experience in this kind of applications

Development of a New Digital Signal Processing Platform for the Square Kilometre Array

A novel digital hardware platform has been designed for the Low Frequency Aperture Array (LFAA) component of the Square Kilometre Array (SKA). This board, called Analog Digital Unit (ADU), is a 6U board containing sixteen dual-inputs Analog to Digital Converters (ADC) and two Field Programmable Gate Array (FPGA) devices, capable of digitizing and processing 32 RF input signals. We present the main features of the board and the signal processing firmware that has been developed for LFAA. Although the ADU has been conceived mainly for the low frequency band (50-350 MHz), its use has been proved effective also for higher frequencies (375-650 MHz). In this paper we describe also the application of ADU as the digital acquisition and processing system for PHAROS2, a cryogenically cooled 4-8 GHz Phased Array Feed (PAF) demonstrator. The final part is focused on the future developments of the board

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Exploration of an innovative ranging method for bi-static radar, applied in LEO Space Debris surveying and tracking

Space Situational Awareness (SSA) is referred as one of the capacitive areas of strategic interest to be developed/completed in the future in the short and medium term, for any nation with the target of the access to the space. One of the fundamental components is the Space Surveillance and Tracking (SST) program, considered as the capability to build a spatial mapping of the objects in orbit, their classification and the exact identification of their orbital characteristics. For this reason, radar measurements are relevant, in particular to observe objects in Low Earth Orbit. The Italian National Institute of Astrophysics together with Vitrociset company and Politecnico di Milano, studied and developed a new and innovative method for the range measure applied to bi-static radars to support the European Union Space Surveillance and Tracking (EUSST) program. Several tests have been carried out using the BIRALES and BIRALET sensors for survey and tracking observations respectively. Finally, the results obtained from observations have been compared with the real positions of the targets in order to validate the system. The ranging method relies on the synchronization of the transmitting and receiving antennas and on the correlation of the echo received from the scattering of the orbiting object. To do that, the transmitting antenna emits simultaneously two different signals: a Chirp signal for range measurement and a second “Continuous Wave” (CW) for Doppler shift measurement and object track reconstruction. Overall, we simultaneously obtain time profiles for range, angular position (azimuth and elevation), and Doppler during the passage of the objects inside the sensor Field of View. By virtue of the above plethora of measurements, this method guarantees also the possibility to produce an Initial Orbital Determination (IOD) for unknown objects

Exploitation of bi-static radar architectures for LEO Space Debris surveying and tracking: The BIRALES/BlRALET project

The space debris population is continuously growing and it represents a potential issue for spacecraft. New collisions could exponentially rise the amount of debris and so the level of risk represented by these objects. The monitoring of space environment is necessary to prevent new collisions. For this reason, radar measurements are relevant, in particular to observe objects in Low Earth Orbit. Regarding the Italian contribution, there are two radars based on two different radio telescopes as receivers: the BIRALES and the BIRALET systems. We propose a detailed description of these systems, focusing on hardware and software components that permit to perform range and range rate measurement of resident space objects