Light Ion Accelerating Line (L3IA): Test Experiment at ILIL-PW

The construction of a novel Laser driven Light Ions Acceleration Line(L3IA) is progressing rapidly towards the operation, following the recent upgrade of the ILIL-PW laser facility. The Line was designed following the pilot experimental activity carried out earlier at the same facility to define design parameters and to identify main components including target control and diagnostic equipment, also in combination with the numerical simulations for the optimization of laser and target parameters. A preliminary set of data was acquired following the successful commissioning of the laser system >100 TW upgrade. Data include output from a range of different ion detectors and optical diagnostics installed for qualification of the laser-target interaction. An overview of the results is given along with a description of the relevant upgraded laser facility and features.Comment: 6 pages, 7 figures, 18 references, presented at the EAAC 201

Low-frequency modes in the Raman spectrum of sp-sp2 nanostructured carbon

A novel form of amorphous carbon with sp-sp2 hybridization has been recently produced by supersonic cluster beam deposition showing the presence in the film of both polyynic and cumulenic species [L. Ravagnan et al. Phys. Rev. Lett. 98, 216103 (2007)]. Here we present a in situ Raman characterization of the low frequency vibrational region (400-800 cm-1) of sp-sp2 films at different temperatures. We report the presence of two peaks at 450 cm-1 and 720 cm-1. The lower frequency peak shows an evolution with the variation of the sp content and it can be attributed, with the support of density functional theory (DFT) simulations, to bending modes of sp linear structures. The peak at 720 cm-1 does not vary with the sp content and it can be attributed to a feature in the vibrational density of states activated by the disorder of the sp2 phase.Comment: 15 pages, 5 figures, 1 tabl

Stable and Solution-Processable Cumulenic sp-Carbon Wires: A New Paradigm for Organic Electronics

open12siAcknowledgements. E.G.F. acknowledges the support through the EU Horizon 2020 research and innovation program, H2020-FETOPEN-01-2018-2020 (FET-Open Challenging Current Thinking), “LION-HEARTED”, grant agreement no. 828984. C.S.C. acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program ERC-Consolidator Grant (ERC CoG 2016 EspLORE grant agreement no. 724610, website: www.esplore.polimi.it). R.R.T. acknowledges funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canada Foundation for Innovation (CFI). This work was partially supported by the European Union's H2020-EU.4.b. – Twinning of research institutions “GREENELIT”, grant agreement number 951747. GIWAXS experiments were performed at BL11 NCD-SWEET beamline at ALBA Synchrotron (Spain) with the collaboration of ALBA staff. This work was in part carried out at Polifab, the micro- and nanotechnology centre of the Politecnico di Milano. Open access funding provided by Istituto Italiano di Tecnologia within the CRUI-CARE Agreement.Solution-processed, large-area, and flexible electronics largely relies on the excellent electronic properties of sp2-hybridized carbon molecules, either in the form of π-conjugated small molecules and polymers or graphene and carbon nanotubes. Carbon with sp-hybridization, the foundation of the elusive allotrope carbyne, offers vast opportunities for functionalized molecules in the form of linear carbon atomic wires (CAWs), with intriguing and even superior predicted electronic properties. While CAWs represent a vibrant field of research, to date, they have only been applied sparingly to molecular devices. The recent observation of the field-effect in microcrystalline cumulenes suggests their potential applications in solution-processed thin-film transistors but concerns surrounding the stability and electronic performance have precluded developments in this direction. In the present study, ideal field-effect characteristics are demonstrated for solution-processed thin films of tetraphenyl[3]cumulene, the shortest semiconducting CAW. Films are deposited through a scalable, large-area, meniscus-coating technique, providing transistors with hole mobilities in excess of 0.1 cm2V−1s−1, as well as promising operational stability under dark conditions. These results offer a solid foundation for the exploitation of a vast class of molecular semiconductors for organic electronics based on sp-hybridized carbon systems and create a previously unexplored paradigm.openPecorario S.; Scaccabarozzi A.D.; Fazzi D.; Gutierrez-Fernandez E.; Vurro V.; Maserati L.; Jiang M.; Losi T.; Sun B.; Tykwinski R.R.; Casari C.S.; Caironi M.Pecorario S.; Scaccabarozzi A.D.; Fazzi D.; Gutierrez-Fernandez E.; Vurro V.; Maserati L.; Jiang M.; Losi T.; Sun B.; Tykwinski R.R.; Casari C.S.; Caironi M

Membrane Environment Enables Ultrafast Isomerization of Amphiphilic Azobenzene

G.M.P. and E.C. contributed equally to this work. G.M.P. acknowledges the financial support from Fondazione Cariplo, grant no. 2018-0979. The authors thank the financial support from the EU Horizon 2020 Research and Innovation Programme under Grant Agreement No. 643238 (SYNCHRONICS). The authors also thank Dr. Daniele Viola for helping with the analysis of the TA data.The non‐covalent affinity of photoresponsive molecules to biotargets represents an attractive tool for achieving effective cell photo‐stimulation. Here, an amphiphilic azobenzene that preferentially dwells within the plasma membrane is studied. In particular, its isomerization dynamics in different media is investigated. It is found that in molecular aggregates formed in water, the isomerization reaction is hindered, while radiative deactivation is favored. However, once protected by a lipid shell, the photochromic molecule reacquires its ultrafast photoisomerization capacity. This behavior is explained considering collective excited states that may form in aggregates, locking the conformational dynamics and redistributing the oscillator strength. By applying the pump probe technique in different media, an isomerization time in the order of 10 ps is identified and the deactivation in the aggregate in water is also characterized. Finally, it is demonstrated that the reversible modulation of membrane potential of HEK293 cells via illumination with visible light can be indeed related to the recovered trans→cis photoreaction in lipid membrane. These data fully account for the recently reported experiments in neurons, showing that the amphiphilic azobenzenes, once partitioned in the cell membrane, are effective light actuators for the modification of the electrical state of the membrane.Fondazione Cariplo. Grant Number: 2018‐0979EU Horizon 2020 Research and Innovation Programme. Grant Number: 64323

Mesodermal Progenitor Cells (MPCs) Differentiate into Mesenchymal Stromal Cells (MSCs) by Activation of Wnt5/Calmodulin Signalling Pathway

Mesenchymal Stromal Cells (MSCs) remain poorly characterized because of the absence of manifest physical, phenotypic, and functional properties in cultured cell populations. Despite considerable research on MSCs and their clinical application, the biology of these cells is not fully clarified and data on signalling activation during mesenchymal differentiation and proliferation are controversial. The role of Wnt pathways is still debated, partly due to culture heterogeneity and methodological inconsistencies. Recently, we described a new bone marrow cell population isolated from MSC cultures that we named Mesodermal Progenitor Cells (MPCs) for their mesenchymal and endothelial differentiation potential. An optimized culture method allowed the isolation from human adult bone marrow of a highly pure population of MPCs (more than 97%), that showed the distinctive SSEA-4+CD105+CD90(neg) phenotype and not expressing MSCA-1 antigen. Under these selective culture conditions the percentage of MSCs (SSEA-4(neg)CD105+CD90(bright) and MSCA-1+), in the primary cultures, resulted lower than 2%.We demonstrate that MPCs differentiate to MSCs through an SSEA-4+CD105+CD90(bright) early intermediate precursor. Differentiation paralleled the activation of Wnt5/Calmodulin signalling by autocrine/paracrine intense secretion of Wnt5a and Wnt5b (p<0.05 vs uncondictioned media), which was later silenced in late MSCs (SSEA-4(neg)). We found the inhibition of this pathway by calmidazolium chloride specifically blocked mesenchymal induction (ID₅₀ =  0.5 µM, p<0.01), while endothelial differentiation was unaffected.The present study describes two different putative progenitors (early and late MSCs) that, together with already described MPCs, could be co-isolated and expanded in different percentages depending on the culture conditions. These results suggest that some modifications to the widely accepted MSC nomenclature are required

Genetic and phenotypic spectrum associated with IFIH1 gain-of-function

IFIH1 gain‐of‐function has been reported as a cause of a type I interferonopathy encompassing a spectrum of autoinflammatory phenotypes including Aicardi–Goutières syndrome and Singleton Merten syndrome. Ascertaining patients through a European and North American collaboration, we set out to describe the molecular, clinical and interferon status of a cohort of individuals with pathogenic heterozygous mutations in IFIH1. We identified 74 individuals from 51 families segregating a total of 27 likely pathogenic mutations in IFIH1. Ten adult individuals, 13.5% of all mutation carriers, were clinically asymptomatic (with seven of these aged over 50 years). All mutations were associated with enhanced type I interferon signaling, including six variants (22%) which were predicted as benign according to multiple in silico pathogenicity programs. The identified mutations cluster close to the ATP binding region of the protein. These data confirm variable expression and nonpenetrance as important characteristics of the IFIH1 genotype, a consistent association with enhanced type I interferon signaling, and a common mutational mechanism involving increased RNA binding affinity or decreased efficiency of ATP hydrolysis and filament disassembly rate

Waiting times for diagnosis of attention-deficit hyperactivity disorder in children and adolescents referred to Italian ADHD centers must be reduced

BACKGROUND: To investigate timely access to and the time needed to complete the diagnostic path of children and adolescents with suspected attention deficit hyperactivity disorder (ADHD) in the 18 Italian Lombardy Region ADHD reference centers. METHODS: Data of children and adolescents enrolled in the Regional ADHD disease-oriented Registry for suspected ADHD who requested their first visit in 2013-2017 were analyzed. RESULTS: The sample comprised 2262 children and adolescents aged 5-17\u2009years who accessed the ADHD centers for diagnostic classification and management. The median waiting time was of 177\u2009days (range 66-375) from the request for the initial appointment to the completion of the diagnostic path, with a three - fold difference between centers. In addition to the center, the strongest significant predictors of long waiting times were age comorbidities, the severity of the disorder, and having already completed some diagnostic procedures provided by the common standard path. CONCLUSIONS: To guarantee an equal standard of care in ADHD centers for all children and adolescents there is a pressing need to reduce the times to complete the diagnostic path. It is the task of both policymakers and each center to optimize the quality of the service and of the care delivered

Candidate biomarkers from the integration of methylation and gene expression in discordant autistic sibling pairs

While the genetics of autism spectrum disorders (ASD) has been intensively studied, resulting in the identification of over 100 putative risk genes, the epigenetics of ASD has received less attention, and results have been inconsistent across studies. We aimed to investigate the contribution of DNA methylation (DNAm) to the risk of ASD and identify candidate biomarkers arising from the interaction of epigenetic mechanisms with genotype, gene expression, and cellular proportions. We performed DNAm differential analysis using whole blood samples from 75 discordant sibling pairs of the Italian Autism Network collection and estimated their cellular composition. We studied the correlation between DNAm and gene expression accounting for the potential effects of different genotypes on DNAm. We showed that the proportion of NK cells was significantly reduced in ASD siblings suggesting an imbalance in their immune system. We identified differentially methylated regions (DMRs) involved in neurogenesis and synaptic organization. Among candidate loci for ASD, we detected a DMR mapping to CLEC11A (neighboring SHANK1) where DNAm and gene expression were significantly and negatively correlated, independently from genotype effects. As reported in previous studies, we confirmed the involvement of immune functions in the pathophysiology of ASD. Notwithstanding the complexity of the disorder, suitable biomarkers such as CLEC11A and its neighbor SHANK1 can be discovered using integrative analyses even with peripheral tissues

MKS3/TMEM67 mutations are a major cause of COACH syndrome, a joubert syndrome related disorder with liver involvement

The acronym COACH defines an autosomal recessive condition of Cerebellar vermis hypo/ aplasia, Oligophrenia, congenital Ataxia, Coloboma and Hepatic fibrosis. Patients present the “molar tooth sign”, a midbrain-hindbrain malformation pathognomonic for Joubert Syndrome (JS) and Related Disorders (JSRDs). The main feature of COACH is congenital hepatic fibrosis (CHF), resulting from malformation of the embryonic ductal plate. CHF is invariably found also in Meckel syndrome (MS), a lethal ciliopathy already found to be allelic with JSRDs at the CEP290 and RPGRIP1L genes. Recently, mutations in the MKS3 gene (approved symbol TMEM67), causative of about 7% MS cases, have been detected in few Meckel-like and pure JS patients. Analysis of MKS3 in 14 COACH families identified mutations in 8 (57%). Features such as colobomas and nephronophthisis were found only in a subset of mutated cases. These data confirm COACH as a distinct JSRD subgroup with core features of JS plus CHF, which major gene is MKS3, and further strengthen gene-phenotype correlates in JSRDs