Unmanned Aircraft Systems (UAS) Integration in the National Airspace System (NAS) Project. NASA Contributions to the SARP WC Definition

To better inform sense and avoid research needs and to understand ongoing investigation of potential solutions that ultimately lead to the assisting the FAA with their Congressional mandate to fly UAS in the NAS

Human iPSC modelling of a familial form of atrial fibrillation reveals a gain of function of I-f and I-CaL in patient-derived cardiomyocytes

Aims: Atrial fibrillation (AF) is the most common type of cardiac arrhythmias, whose incidence is likely to increase with the aging of the population. It is considered a progressive condition, frequently observed as a complication of other cardiovascular disorders. However, recent genetic studies revealed the presence of several mutations and variants linked to AF, findings that define AF as a multifactorial disease. Due to the complex genetics and paucity of models, molecular mechanisms underlying the initiation of AF are still poorly understood. Here we investigate the pathophysiological mechanisms of a familial form of AF, with particular attention to the identification of putative triggering cellular mechanisms, using patient's derived cardiomyocytes (CMs) differentiated from induced pluripotent stem cells (iPSCs). Methods and results: Here we report the clinical case of three siblings with untreatable persistent AF whose whole-exome sequence analysis revealed several mutated genes. To understand the pathophysiology of this multifactorial form of AF we generated three iPSC clones from two of these patients and differentiated these cells towards the cardiac lineage. Electrophysiological characterization of patient-derived CMs (AF-CMs) revealed that they have higher beating rates compared to control (CTRL)-CMs. The analysis showed an increased contribution of the If and ICaL currents. No differences were observed in the repolarizing current IKr and in the sarcoplasmic reticulum calcium handling. Paced AF-CMs presented significantly prolonged action potentials and, under stressful conditions, generated both delayed after-depolarizations of bigger amplitude and more ectopic beats than CTRL cells. Conclusions: Our results demonstrate that the common genetic background of the patients induces functional alterations of If and ICaL currents leading to a cardiac substrate more prone to develop arrhythmias under demanding conditions. To our knowledge this is the first report that, using patient-derived CMs differentiated from iPSC, suggests a plausible cellular mechanism underlying this complex familial form of AF

Habitar a metrópole: os apartamentos quitinetes de Adolf Franz Heep

The restructuring of the housing market and the emergence of a new housing typology in Sao Paulo from the mid-1940s, the kitchenette apartment, coincided with changes in the parameters that guided disciplinary discourse and architectural practice in Brazil. Analyze the moment the new typology was formulated, their initial motivations and subsequent developments, allows not only to recover the trajectory of the German architect Adolf Franz Heep (1902-1978) as investigate the dialogue between European architectural avant-garde, the North-American experiences, the local architectural production and the local demands

ECMO for COVID-19 patients in Europe and Israel

Since March 15th, 2020, 177 centres from Europe and Israel have joined the study, routinely reporting on the ECMO support they provide to COVID-19 patients. The mean annual number of cases treated with ECMO in the participating centres before the pandemic (2019) was 55. The number of COVID-19 patients has increased rapidly each week reaching 1531 treated patients as of September 14th. The greatest number of cases has been reported from France (n = 385), UK (n = 193), Germany (n = 176), Spain (n = 166), and Italy (n = 136) .The mean age of treated patients was 52.6 years (range 16–80), 79% were male. The ECMO configuration used was VV in 91% of cases, VA in 5% and other in 4%. The mean PaO2 before ECMO implantation was 65 mmHg. The mean duration of ECMO support thus far has been 18 days and the mean ICU length of stay of these patients was 33 days. As of the 14th September, overall 841 patients have been weaned from ECMO support, 601 died during ECMO support, 71 died after withdrawal of ECMO, 79 are still receiving ECMO support and for 10 patients status n.a. . Our preliminary data suggest that patients placed on ECMO with severe refractory respiratory or cardiac failure secondary to COVID-19 have a reasonable (55%) chance of survival. Further extensive data analysis is expected to provide invaluable information on the demographics, severity of illness, indications and different ECMO management strategies in these patients

L’audizione della “vittima vulnerabile” tra procedimento e processo

Nel presente lavoro di ricerca ricostruiremo la tutela della vittima, attraverso un breve excursus storico, dalla sua originaria situazione di oblio fino alla sua riscoperta. Attraverseremo man mano le fasi che portano dalla nozione del termine “vittima” fino ad arrivare alle fonti europee che hanno fatto da motore trainante per una contemporanea rivalutazione della stessa. Arriveremo ad una elencazione dettagliata delle tutele garantite alla vittima dalla direttiva europea 2012/29/UE e approfondiremo la nozione stessa con le sue più ampie sfumature compresa quella importantissima della vulnerabilità. La vulnerabilità costituisce una accezione particolare legata ad una valutazione soggettiva e oggettiva (individual assestment, portato avanti dalla Direttiva 2012/29/UE, nonché il nuovo art. 90 quater c.p.p.) che rappresenta senz’altro un notevole progresso in vista della più ampia garanzia di tutela della vittima. In sintesi, l’autorità competente, nell’operare la valutazione appena richiamata, deve prendere in considerazione da un lato la natura e le circostanze del reato, e dall’altro tutte le caratteristiche fisiche e psicologiche della vittima stessa. È certo che la dichiarazione di vulnerabilità è destinata ad incidere e limitare in modo significativo il diritto di difesa dell’imputato/indagato, da qui cercheremo di analizzare il bilanciamento degli interessi in gioco. Il presente lavoro vuole verificare in che misura l’ordinamento italiano abbia recepito le indicazioni provenienti dai provvedimenti europei adottati sul tema, fino ad arrivare al tentativo di delineare quello che è stato definito lo “statuto” della vittima del reato. È traguardo preminente del seguente elaborato analizzare la figura del testimone vulnerabile e la sua disciplina normativa, le tutele ad egli riservate e le sue peculiarità e condizioni. Negli ultimi anni si è assistito ad una importante evoluzione normativa con oggetto il rafforzamento dei diritti dell’imputato e quelli della persona offesa grazie ai due decreti legislativi: decreto legislativo n. 24 del 4 marzo 2014 e il decreto legislativo n. 212 del 2015, i quali novellando alcuni articoli del codice di procedura penale hanno posto le basi per un vero e proprio statuto della prova “dichiarativa” del soggetto vulnerabile codificandolo nell’art. 398 comma 5 ter c.p.p. L'intento del legislatore è quello di tutelare il dichiarante quando questi acquisisca la qualifica di soggetto vulnerabile e di assicurarne una protezione non solo “nel processo”, ma anche “dal processo”. Scopo dell’elaborato è porre sotto la lente di ingrandimento alcune norme del codice di rito che, negli ultimi anni, hanno mutato di forma e contenuti. Vedremo, quindi, le varie questioni che si presentano prendendo in esame le norme del c.p.p. l’art.398 comma 5 ter, l’art. 392 comma 1 bis, l’art. 393 comma 2 bis, l’art. 393 comma 5 bis, l’art. 498 comma che disciplinano il quadro normativo del testimone vulnerabile a partire dalle audizioni investigative ad arrivare al dibattimento. Infine, approfondiremo le tutele di vittime di alcuni specifici reati, tra i più nuovi la tutela della vittima di violenza di genere: la legge n. 119 del 2013 (nata dal c.d. decreto femminicidio) e le vittime di usura, mafia e terrorismo

A Hybrid Nanoplatform of Graphene Oxide/Nanogold for Plasmonic Sensing and Cellular Applications at the Nanobiointerface

In this study, nanocomposites of spherical gold nanoparticles (AuNPs) and graphene oxide (GO) nanosheets were fabricated by a simple one-step reduction method. The characterisation by UV-visible spectroscopy of the plasmonic sensing properties pointed out to a strong interaction between graphene and metal nanoparticles in the hybrid GO-AuNP, as confirmed by nuclear magnetic resonance. Moreover, atomic force microscopy analyses demonstrated that the gold nanoparticles were mostly confined to the basal planes of the GO sheets. The response of the nanoassemblies at the biointerface with human neuroblastoma SH-SY5Y cell line was investigated in terms of nanotoxicity as well as of total and mitochondrial reactive oxygen species production. Confocal microscopy imaging of cellular internalization highlighted the promising potentialities of GO-AuNP nanoplatforms for theranostic (i.e., sensing/imaging + therapy) applications

Lost in HELLS: Disentangling the mystery of SALNR existence in senescence cellular models.

Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular senescence by transcriptionally and post-transcriptionally modulating the expression of many important genes involved in senescence-associated pathways and processes. Among the different lncRNAs associated to senescence, Senescence Associated Long Non-coding RNA (SALNR) was found to be down-regulated in different cellular models of senescence. Since its release in 2015, SALNR has not been annotated in any database or public repository, and no other experimental data have been published. The SALNR sequence is located on the long arm of chromosome 10, at band 10q23.33, and it overlaps the 3' end of the HELLS gene. This investigation helped to unravel the mystery of the existence of SALNR by analyzing publicly available short- and long-read RNA sequencing data sets and RT-PCR analysis in human tissues and cell lines. Additionally, the expression of HELLS has been studied in cellular models of replicative senescence, both in silico and in vitro. Our findings, while not supporting the actual existence of SALNR as an independent transcript in the analyzed experimental models, demonstrate the expression of a predicted HELLS isoform entirely covering the SALNR genomic region. Furthermore, we observed a strong down-regulation of HELLS in senescent cells versus proliferating cells, supporting its role in the senescence and aging process

Theranostic Nanoplatforms of Thiolated Reduced Graphene Oxide Nanosheets and Gold Nanoparticles

In this study, graphene oxide (GO) and reduced-thiolated GO (rGOSH) were used as 2D substrate to fabricate nanocomposites with nanoparticles of gold nanospheres (AuNS) or nanorods (AuNR), via in situ reduction of the metal salt precursor and seed-mediated growth processes. The plasmonic sensing capability of the gold-decorated nanosheets were scrutinized by UV-visible (UV-VIS) spectroscopy. Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), thermogravimetric analyses (TGA), and atomic force microscopy (AFM) were performed in order to prove the actual reduction that occurred concomitantly with the thiolation of GO, the increase in the hydrophobic character as well as the size, and preferential gathering of the gold nanoparticles onto the nanosheet substrates, respectively. Moreover, the theoretical electronic and infrared absorption (UV-VIS and IR) spectra were calculated within a time-dependent approach of density functional theory (DFT). Eventually, in vitro cellular experiments on human neuroblastoma cells (SH-SY5Y line) were carried out in order to evaluate the nanotoxicity of the nanocomposites by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium reduction (MTT) colorimetric assay. Results pointed out the promising potential of these hybrids as plasmonic theranostic platforms with different hydrophilic or hydrophobic features as well as cytotoxic effects against cancer cells