Direction Specific Analysis of Psychoacoustics Parameters inside Car Cockpit: A Novel Tool for NVH and Sound Quality

Psychoacoustics parameters are widely employed in automotive field for objective evaluation of Sound Quality (SQ) of vehicle cabins and their components. The standard approach relies on binaural recordings from which numerical values and curves are calculated. In addition, head-locked binaural listening playback can be performed. The Virtual Reality (VR) technology recently started to diffuse also in automotive field, bringing new possibilities for enhanced and immersive listening sessions, thanks to the usage of massive microphone arrays instead of binaural microphones. In this paper, we combine both solutions: the principal SQ parameters are derived from multichannel recordings. This allows computing a map of direction-dependent values of SQ parameters. The acquisition system consists in a spherical microphone array with 32 capsules and a multiple-lens camera for capturing a panoramic equirectangular background image. The audio recording is encoded into High Order Ambisonics (HOA) format for being compared with a classic omnidirectional microphone and into Spatial PCM Sampling (SPS) format for producing 360° equirectangular color maps. The SPS encoding is used to plot over the background image the distribution of SPL values in dB (A) and of the SQ parameters: by adding to them the directional information, it results into a novel 360° diagnostic tool for localizing the most annoying sources. Furthermore, the playback of the HOA soundtrack can be performed both on a loudspeaker rig inside an Ambisonics listening room or on binaural headphones attached to a Head Mounted Display (HMD), benefiting from head-tracking and personalized Head Related Transfer Functions (HRTFs), allowing to make quick subjective evaluations with a degree of realism unattainable with the older static binaural approach

Defective dystrophic thymus determines degenerative changes in skeletal muscle.

In Duchenne muscular dystrophy (DMD), sarcolemma fragility and myofiber necrosis produce cellular debris that attract inflammatory cells. Macrophages and T-lymphocytes infiltrate muscles in response to damage-associated molecular pattern signalling and the release of TNF-α, TGF-β and interleukins prevent skeletal muscle improvement from the inflammation. This immunological scenario was extended by the discovery of a specific response to muscle antigens and a role for regulatory T cells (Tregs) in muscle regeneration. Normally, autoimmunity is avoided by autoreactive T-lymphocyte deletion within thymus, while in the periphery Tregs monitor effector T-cells escaping from central regulatory control. Here, we report impairment of thymus architecture of mdx mice together with decreased expression of ghrelin, autophagy dysfunction and AIRE down-regulation. Transplantation of dystrophic thymus in recipient nude mice determine the up-regulation of inflammatory/fibrotic markers, marked metabolic breakdown that leads to muscle atrophy and loss of force. These results indicate that involution of dystrophic thymus exacerbates muscular dystrophy by altering central immune tolerance

Induction of neurotrophin expression via human adult mesenchymal stem cells: implication for cell therapy in neurodegenerative diseases.

In animal models of neurological disorders for cerebral ischemia, Parkinson's disease, and spinal cord lesions, transplantation of mesenchymal stem cells (MSCs) has been reported to improve functional outcome. Three mechanisms have been suggested for the effects of the MSCs: transdifferentiation of the grafted cells with replacement of degenerating neural cells, cell fusion, and neuroprotection of the dying cells. Here we demonstrate that a restricted number of cells with differentiated astroglial features can be obtained from human adult MSCs (hMSCs) both in vitro using different induction protocols and in vivo after transplantation into the developing mouse brain. We then examined the in vitro differentiation capacity of the hMSCs in coculture with slices of neonatal brain cortex. In this condition the hMSCs did not show any neuronal transdifferentiation but expressed neurotrophin low-affinity (NGFRp75) and high-affinity (trkC) receptors and released nerve growth factor (NGF) and neurotrophin-3 (NT-3). The same neurotrophin's expression was demonstrated 45 days after the intracerebral transplantation of hMSCs into nude mice with surviving astroglial cells. These data further confirm the limited capability of adult hMSC to differentiate into neurons whereas they differentiated in astroglial cells. Moreover, the secretion of neurotrophic factors combined with activation of the specific receptors of transplanted hMSCs demonstrated an alternative mechanism for neuroprotection of degenerating neurons. hMSCs are further defined in their transplantation potential for treating neurological disorders

Generation of the Becker muscular dystrophy patient derived induced pluripotent stem cell line carrying the DMD splicing mutation c.1705-8 T>C

Becker Muscular dystrophy (BMD) is an X-linked syndrome characterized by progressive muscle weakness. BMD is generally less severe than Duchenne Muscular Dystrophy. BMD is caused by mutations in the dystrophin gene that normally give rise to the production of a truncated but partially functional dystrophin protein. We generated an induced pluripotent cell line from dermal fibroblasts of a BMD patient carrying a splice mutation in the dystrophin gene (c.1705-8 T>C). The iPSC cell-line displayed the characteristic pluripotent-like morphology, expressed pluripotency markers, differentiated into cells of the three germ layers and had a normal karyotype

Effect of human skin-derived stem cells on vessel architecture, tumor growth, and tumor invasion in brain tumor animal models

Glioblastomas represent an important cause of cancer-related mortality with poor survival. Despite many advances, the mean survival time has not significantly improved in the last decades. New experimental approaches have shown tumor regression after the grafting of neural stem cells and human mesenchymal stem cells into experimental intracranial gliomas of adult rodents. However, the cell source seems to be an important limitation for autologous transplantation in glioblastoma. In the present study, we evaluated the tumor targeting and antitumor activity of human skin-derived stem cells (hSDSCs) in human brain tumor models. The hSDSCs exhibit tumor targeting characteristics in vivo when injected into the controlateral hemisphere or into the tail vein of mice. When implanted directly into glioblastomas, hSDSCs distributed themselves extensively throughout the tumor mass, reduced tumor vessel density, and decreased angiogenic sprouts. In addition, transplanted hSDSCs differentiate into pericyte cell and release high amounts of human transforming growth factor-beta1 with low expression of vascular endothelial growth factor, which may contribute to the decreased tumor cell invasion and number of tumor vessels. In long-term experiments, the hSDSCs were also able to significantly inhibit tumor growth and to prolong animal survival. Similar behavior was seen when hSDSCs were implanted into two different tumor models, the chicken embryo experimental glioma model and the transgenic Tyrp1-Tag mice. Taken together, these data validate the use of hSDSCs for targeting human brain tumors. They may represent therapeutically effective cells for the treatment of intracranial tumors after autologous transplantation

Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles.

Fibrosis and fat replacement in skeletal muscle are major complications that lead to a loss of mobility in chronic muscle disorders, such as muscular dystrophy. However, the in vivo properties of adipogenic stem and precursor cells remain unclear, mainly due to the high cell heterogeneity in skeletal muscles. Here, we use single-cell RNA sequencing to decomplexify interstitial cell populations in healthy and dystrophic skeletal muscles. We identify an interstitial CD142-positive cell population in mice and humans that is responsible for the inhibition of adipogenesis through GDF10 secretion. Furthermore, we show that the interstitial cell composition is completely altered in muscular dystrophy, with a near absence of CD142-positive cells. The identification of these adipo-regulatory cells in the skeletal muscle aids our understanding of the aberrant fat deposition in muscular dystrophy, paving the way for treatments that could counteract degeneration in patients with muscular dystrophy

Formation of laser plasma channels in a stationary gas

The formation of plasma channels with nonuniformity of about +- 3.5% has been demonstrated. The channels had a density of 1.2x10^19 cm-3 with a radius of 15 um and with length >= 2.5 mm. The channels were formed by 0.3 J, 100 ps laser pulses in a nonflowing gas, contained in a cylindrical chamber. The laser beam passed through the chamber along its axis via pinholes in the chamber walls. A plasma channel with an electron density on the order of 10^18 - 10^19 cm-3 was formed in pure He, N2, Ar, and Xe. A uniform channel forms at proper time delays and in optimal pressure ranges, which depend on the sort of gas. The influence of the interaction of the laser beam with the gas leaking out of the chamber through the pinholes was found insignificant. However, the formation of an ablative plasma on the walls of the pinholes by the wings of the radial profile of the laser beam plays an important role in the plasma channel formation and its uniformity. A low current glow discharge initiated in the chamber slightly improves the uniformity of the plasma channel, while a high current arc discharge leads to the formation of overdense plasma near the front pinhole and further refraction of the laser beam. The obtained results show the feasibility of creating uniform plasma channels in non-flowing gas targets.Comment: 15 pages, 7 figures, submitted to Physics of Plasma

Preliminary evidences of safety and efficacy of flavonoids- and omega 3-based compound for muscular dystrophies treatment: a randomized double-blind placebo controlled pilot clinical trial.

Background: Nutritional compounds can exert both anti-inflammatory and anti-oxidant effects. Since these events exacerbate the pathophysiology of muscular dystrophies, we investigated nutraceutical supplementation as an adjuvant therapy in dystrophic patients, to low costs and easy route of administration. Moreover, this treatment could represent an alternative therapeutic strategy for dystrophic patients who do not respond to corticosteroid treatment. Objective: A 24 weeks randomized double-blind placebo-controlled clinical study was aimed at evaluating the safety and efficacy of daily oral administration of flavonoidsand omega3-based natural supplement (FLAVOMEGA) in patients affected by muscular dystrophy with recognized muscle inflammation. Design: We screened 60 patients diagnosed for Duchenne (DMD), Facioscapulohumeral (FSHD), and Limb Girdle Muscular Dystrophy (LGMD). Using a computer-generated random allocation sequence, we stratified patients in a 2:1:1 ratio (DMD:FSHD:LGMD) to one of two treatment groups: continuous FLAVOMEGA, continuous placebo. Of 29 patients included, only 24 completed the study: 15 were given FLAVOMEGA, 14 placebo. Results: FLAVOMEGA was well tolerated with no reported adverse events. Significant treatment differences in the change from baseline in 6 min walk distance (6MWD; secondary efficacy endpoint) (P = 0.033) and in isokinetic knee extension (P = 0.039) (primary efficacy endpoint) were observed in LGMD and FSHD subjects. Serum CK levels (secondary efficacy endpoint) decreased in all FLAVOMEGA treated groups with significant difference in DMD subjects (P = 0.039). Conclusions: Although the small number of patients and the wide range of disease severity among patients reduced statistical significance, we obtained an optimal profile of safety and tolerability for the compound, showing valuable data of efficacy in primary and secondary endpoints

Blockade of IGF2R improves muscle regeneration and ameliorates Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a debilitating fatal X-linked muscle disorder. Recent findings indicate that IGFs play a central role in skeletal muscle regeneration and development. Among IGFs, insulinlike growth factor 2 (IGF2) is a key regulator of cell growth, survival, migration and differentiation. The type 2 IGF receptor (IGF2R) modulates circulating and tissue levels of IGF2 by targeting it to lysosomes for degradation. We found that IGF2R and the store-operated Ca2+ channel CD20 share a common hydrophobic binding motif that stabilizes their association. Silencing CD20 decreased myoblast differentiation, whereas blockade of IGF2R increased proliferation and differentiation in myoblasts via the calmodulin/calcineurin/NFAT pathway. Remarkably, anti-IGF2R induced CD20 phosphorylation, leading to the activation of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) and removal of intracellular Ca2+. Interestingly, we found that IGF2R expression was increased in dystrophic skeletal muscle of human DMD patients and mdx mice. Blockade of IGF2R by neutralizing antibodies stimulated muscle regeneration, induced force recovery and normalized capillary architecture in dystrophic mdx mice representing an encouraging starting point for the development of new biological therapies for DMD