Percutaneous Left Atrial Appendage Occlusion

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Rail freight automation in Shift2Rail – Development of prototypes

The Shift2Rail pillar “Technologies for attractive and sustainable European Freight” (IP5) has a clear target vision, which can be summarized in two words: Digitization & Automation. The IP5 members want to speed up the digital transformation and automation of rail freight to ultimately gain market share in the competitive race with other modes of transport. In order to advance automation, multiple projects have been launched under funding. Two key technology demonstrators are presented in this paper: 1. Semi-Automated Operation with Distributed Power Systems (DPS) for efficient Master-Slave Operation, e.g. push-pull operation or in long and heavy trains up to 1,500 m 2. Automatic Train Operation (ATO) with Obstacle Detection (OD) on network sections with European Train Control System (ETCS) from Level 2 upward

Photonics based perfect secrecy cryptography : toward fully classical implementations

Funding: A.D.F. acknowledges support from UK EPSRC (EP/L017008/1).Developing an unbreakable cryptography is a longstanding question and a global challenge in the internet era. Photonics technologies are at the frontline of research, aiming at providing the ultimate system capable of ending the cybercrime industry by changing the way information is treated and protected now and in the long run. Such perspective discusses some of the current challenges as well as opportunities that classical and quantum systems open in the field of cryptography as both a science and an engineering.PostprintPeer reviewe

The HoverMesh: a deformable structure based on vacuum cells: new advances in the research of tangible user interfaces

In this paper we propose a novel attempt to develop a spatial tangible user interface (TUI) [1] based on a deformable structure, the so-called HoverMesh. It consists of a stiff cubical, whose upper wall is composed of a deformable mesh of particle filled inflatable cells. This mesh can be deformed by inflating and/or deflating the cubical while consolidating (evacuating) and/or releasing (inflating) the cells. The HoverMesh is both an input and output device and we see its major benefit in the wide interaction area. The haptic feedback modality is thus embedded as well. The first results in our early experiments sustain the concept of a mesh based on inflatable cells

Molecular Mechanisms Underlying Cell Death in Spinal Networks in Relation to Locomotor Activity After Acute Injury in vitro

Understanding the pathophysiological changes triggered by an acute spinal cord injury is a primary goal to prevent and treat chronic disability with a mechanism-based approach. After the primary phase of rapid cell death at the injury site, secondary damage occurs via autodestruction of unscathed tissue through complex cell-death mechanisms that comprise caspase-dependent and caspase-independent pathways. To devise novel neuroprotective strategies to restore locomotion, it is, therefore, necessary to focus on the death mechanisms of neurons and glia within spinal locomotor networks. To this end, the availability of in vitro preparations of the rodent spinal cord capable of expressing locomotor-like oscillatory patterns recorded electrophysiologically from motoneuron pools offers the novel opportunity to correlate locomotor network function with molecular and histological changes long after an acute experimental lesion. Distinct forms of damage to the in vitro spinal cord, namely excitotoxic stimulation or severe metabolic perturbation (with oxidative stress, hypoxia/aglycemia), can be applied with differential outcome in terms of cell types and functional loss. In either case, cell death is a delayed phenomenon developing over several hours. Neurons are more vulnerable to excitotoxicity and more resistant to metabolic perturbation, while the opposite holds true for glia. Neurons mainly die because of hyperactivation of poly(ADP-ribose) polymerase-1 (PARP-1) with subsequent DNA damage and mitochondrial energy collapse. Conversely, glial cells die predominantly by apoptosis. It is likely that early neuroprotection against acute spinal injury may require tailor-made drugs targeted to specific cell-death processes of certain cell types within the locomotor circuitry. Furthermore, comparison of network size and function before and after graded injury provides an estimate of the minimal network membership to express the locomotor program

Effects of Random Mutagenesis and In Vivo Selection on the Specificity and Stability of a Thermozyme

Factors that give enzymes stability, activity, and substrate recognition result from the combination of few weak molecular interactions, which can be difficult to study through rational protein engineering approaches. We used irrational random mutagenesis and in vivo selection to test if a β-glycosidase from the thermoacidophile Saccharolobus solfataricus (Ssβ-gly) could complement an Escherichia coli strain unable to grow on lactose. The triple mutant of Ssβ-gly (S26L, P171L, and A235V) was more active than the wild type at 85 °C, inactivated at this temperature almost 300-fold quicker, and showed a 2-fold higher kcat on galactosides. The three mutations, which were far from the active site, were analyzed to test their effect at the structural level. Improved activity on galactosides was induced by the mutations. The S26L and P171L mutations destabilized the enzyme through the removal of a hydrogen bond and increased flexibility of the peptide backbone, respectively. However, the flexibility added by S26L mutation improved the activity at T > 60 °C. This study shows that random mutagenesis and biological selection allowed the identification of residues that are critical in determining thermal activity, stability, and substrate recognitio

Nicotine Neurotoxicity Involves Low Wnt1 Signaling in Spinal Locomotor Networks of the Postnatal Rodent Spinal Cord

The postnatal rodent spinal cord in-vitro is a useful model to investigate early pathophysi-ological changes after injury. While low dose nicotine (1 µM) induces neuroprotection, how higher doses affect spinal networks is unknown. Using spinal preparations of postnatal wild-type Wistar rat and Wnt1Cre2:Rosa26Tom double-transgenic mouse, we studied the effect of nicotine (0.5–10 µM) on locomotor networks in-vitro. Nicotine 10 µM induced motoneuron depolarization, suppressed monosynaptic reflexes, and decreased fictive locomotion in rat spinal cord. Delayed fall in neuronal numbers (including motoneurons) of central and ventral regions emerged without loss of dorsal neurons. Conversely, nicotine (0.5–1 µM) preserved neurons throughout the spinal cord and strongly activated the Wnt1 signaling pathway. High-dose nicotine enhanced expression of S100 and GFAP in astrocytes indicating a stress response. Excitotoxicity induced by kainate was contrasted by nicotine (10 µM) in the dorsal area and persisted in central and ventral regions with no change in basal Wnt signaling. When combining nicotine with kainate, the activation of Wnt1 was reduced compared to kainate/sham. The present results suggest that high dose nicotine was neurotoxic to central and ventral spinal neurons as the neuroprotective role of Wnt signaling became attenuated. This also corroborates the risk of cigarette smoking for the foetus/newborn since tobacco contains nicotine.Fil: Kaur, Jaspreet. Universidad de Copenhagen; DinamarcaFil: Mazzone, Graciela Luján. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Aquino, Jorge Benjamin. Universidad Austral. Facultad de Ciencias Biomédicas. Instituto de Investigaciones en Medicina Traslacional. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones en Medicina Traslacional; ArgentinaFil: Nistri, Andrea. International School For Advanced Studies; Itali

GABAergic Mechanisms Can Redress the Tilted Balance between Excitation and Inhibition in Damaged Spinal Networks

Correct operation of neuronal networks depends on the interplay between synaptic excitation and inhibition processes leading to a dynamic state termed balanced network. In the spinal cord, balanced network activity is fundamental for the expression of locomotor patterns necessary for rhythmic activation of limb extensor and flexor muscles. After spinal cord lesion, paralysis ensues often followed by spasticity. These conditions imply that, below the damaged site, the state of balanced networks has been disrupted and that restoration might be attempted by modulating the excitability of sublesional spinal neurons. Because of the widespread expression of inhibitory GABAergic neurons in the spinal cord, their role in the early and late phases of spinal cord injury deserves full attention. Thus, an early surge in extracellular GABA might be involved in the onset of spinal shock while a relative deficit of GABAergic mechanisms may be a contributor to spasticity. We discuss the role of GABA A receptors at synaptic and extrasynaptic level to modulate network excitability and to offer a pharmacological target for symptom control. In particular, it is proposed that activation of GABA A receptors with synthetic GABA agonists may downregulate motoneuron hyperexcitability (due to enhanced persistent ionic currents) and, therefore, diminish spasticity. This approach might constitute a complementary strategy to regulate network excitability after injury so that reconstruction of damaged spinal networks with new materials or cell transplants might proceed more successfully

The Impact of the COVID-19 Pandemic on State Court Proceedings: Five Key Findings

The University of Illinois System’s Institute for Government and Public Affairs and the National Center for State Courts jointly conducted the COVID-19 and the State Courts Study between August 2020 and July 2021. The first stage of the study involved focus groups of attorneys, judges, court administrators, court staff, jurors, and litigants in four states. This report describes some results of the second stage of the study, which involved nationwide surveys of judges, court personnel, and attorneys. The surveys asked participants questions about access to courts during the pandemic and their experiences with the new strategies courts adopted to continue hearing and processing cases. This report summarizes five key findings from the surveys concerning access to the courts. • • First, early in the pandemic, most attorneys thought that litigants’ access to judicial proceedings was worse than usual. • Second, attorneys reported that litigants’ experiences in courts improved after September 2020. Over time, participants believed that some early access difficulties abated. • Third, court personnel had a more positive view than did attorneys about the ability of individuals to participate in the judicial system during the pandemic. • Fourth, attorneys with practices concentrated in landlord-tenant law and criminal law perceived somewhat greater problems than did attorneys who practice in other areas of the law. • Fifth, while participants identified many benefits to online court proceedings, they also saw drawbacks. Assessing whether and under what circumstances to conduct court proceedings online after the pandemic is over will require careful consideration of benefits and downsides and balancing some competing factors.Ope