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In NIO1, a compact H - ion source installed at RFX operated in continuous mode, gas conditioning was needed to improve results in Cs-free regimes (up to a current density about 25 or 30 A/m 2 ). Installation of a cesium oven gave an additional increase of current, progressively limited also by a rapid overcesiation: we observed an average density about 50 A/m 2 (with a peak of 67 A/m 2 ). Obtained beam optics is briefly compared with simulations and previous results in the Cs-free regime in similar conditions (as source voltage, often set below or equal 11 kV). In both regimes, central beamlet apparent density is larger, possibly because of a narrow bias plate mask, now enlarged. Further improvements for Cs-based regime include a moderate oven reservoir temperature, careful tuning and a substantial increase of beam voltage, and power handling capability.

The experimental fusion reactor ITER will feature two (or three) heating neutral beam injectors (NBI) capable of delivering 33(or 50) MW of power into the plasma. A NBI consists of a plasma source for production of negative ions (extracted negative ion current up to 329 A/m 2 in H and 285 A/m 2 in D) then accelerated up to 1 MeV for one hour. The negative ion beam is neutralized, and the residual ions are electrostatically removed before injection. The beamline was designed for a beam divergence between 3 and 7 mrad. The ion source in ITER NBIs relies on RF-driven, Inductively-Coupled Plasmas (ICP), based on the prototypes developed at IPP Garching; RF-driven negative-ion beam sources have never been employed in fusion devices up to now. The recent results of SPIDER, the full size ITER NBI ion source operating at NBTF in Consorzio RFX, Padova, measure a beamlet divergence minimum of 12mrad and highlighted beam spatial non-uniformity. SPIDER results confirmed the experimental divergence found in smaller prototype sources, which is larger compared to filament-arc ion sources. Although prototype experiments have shown that the extracted current requirement can be achieved with minor design improvements, the beamlet divergence is expected to marginally achieve the design value of 7 mrad, which in multi-grid long accelerators results in unexpected heat loads over the accelerator grids. A contributor to the beam divergence is the energy/temperature of the extracted negative ions, so it is believed that plasma differences between the two source types play a role. Research is focused on the plasma parameters in the ion source. One RF driver, identical to the ones used in SPIDER, installed in a relatively small-scale experimental set-up, inherently more flexible than large devices, is starting operations devoted to the investigation of the properties of RF-generated plasmas, so as to contribute to the assessment of negative ion precursors, and of their relationship with the plasma parameters, particularly when enhancing plasma confinement. The scientific questions, that have arisen from the preliminary results of SPIDER, guided the design of the test stand, which are described in this contribution, together with the diagnostic systems and related simulation tools. The test stand, which shares with the larger experiment all the geometrical features and constraints, will allow technological developments and optimized engineering solutions related to the ICP design for the ITER NBIs.

There are clinical challenges related to adjuvant treatment in colorectal cancer (CRC) and novel molecular markers are needed for better risk stratification of patients. Our aim was to integrate our previously reported clinical-genetic prognostic score with new immunogenetic markers of 5-year disease-free survival (DFS) to evaluate the recurrence risk stratification before fluoropyrimidine (FL)-based adjuvant therapy. The study population included a total of 270 stage II-III CRC patients treated with adjuvant FL with (FL + OXA, = 119) or without oxaliplatin (FL, = 151). Patients were genotyped for a panel of 192 tagging polymorphisms in 34 immune-related genes. The -rs1861494 polymorphism was associated with worse DFS in the FL + OXA (HR = 2.14, 95%CI 1.13-4.08; = 0.020, -value = 0.249) and FL (HR = 1.97, 95%CI 1.00-3.86; = 0.049) cohorts, according to a dominant model. The integration of -rs1861494 in our previous clinical genetic multiparametric score of DFS improved the patients' risk stratification (Log-rank = 0.0026 in the pooled population). These findings could improve the discrimination of patients who would benefit from adjuvant treatment. In addition, the results may help better elucidate the interplay between the immune system and chemotherapeutics and help determine the efficacy of anti-tumor strategies.

We present a detailed study of an adiabatic state preparation in an effective three-level quantum system. States can be prepared with high speed and fidelity by adding a counterdiabatic (CD) quantum control protocol. As a second step, we invert the preparation protocol to get back to the initial state. This describes an overall cyclic evolution in state space. Using counterdiabatic terms, the resulting composed fast evolution can be repeated many times. We then analyze the control of Berry's phase along the adiabatic cyclic path and show that Berry's phase can act as a sensitive detector of non-perfect state transfer.

Consorzio RFX and INFN-LNL have designed, built and operated the compact radiofrequency negative ion source NIO1 (Negative Ion Optimization phase 1) with the aim of studying the production and acceleration of H- ions. In particular, NIO1 was designed to keep plasma generation and beam extraction continuously active for several hours. Since 2020 the production of negative ions at the plasma grid (the first grid of the acceleration system) has been enhanced by a Cs layer, deposited though active Cs evaporation in the source volume. For the negative ion sources applied to fusion neutral beam injectors, it is essential to keep the beam current and the fraction of co-extracted electrons stable for at least 1 h, against the consequences of Cs sputtering and redistribution operated by the plasma. The paper presents the latest results of the NIO1 source, in terms of caesiation process and beam performances during continuous (6{\\div}7 h) plasma pulses. Due to the small dimensions of the NIO1 source (20 x (diam.)10 cm), the Cs density in the volume is high (10^15 \\div 10^16 m^-3) and dominated by plasma-wall interaction. The maximum beam current density and minimum fraction of co-extracted electrons were respectively about 30 A/m^2 and 2. Similarly to what done in other negative ion sources, the plasma grid temperature in NIO1 was raised for the first time, up to 80 {\\deg}C, although this led to a minimal improvement of the beam current and to an increase of the co-extracted electron current.

The Major Atmospheric Gamma Imaging Cherenkov (MAGIC) telescope system consists of two imaging atmospheric Cherenkov telescopes (IACTs) and is located on the Canary island of La Palma. IACTs are excellent tools to inspect the very-high-energy (few tens of GeV and above) gamma-ray sky by capturing images of the air showers, originated by the absorption of gamma rays and cosmic rays by the atmosphere, through the detection of Cherenkov photons emitted in the shower. One of the main factors determining the sensitivity of IACTs to gamma-ray sources, in general, is how well reconstructed the properties (type, energy, and incoming direction) of the primary particle triggering the air shower are. We present how deep convolutional neural networks (CNNs) are being explored as a promising method for IACT full-event reconstruction. The performance of the method is evaluated on observational data using the standard MAGIC Analysis and Reconstruction Software, MARS, and CTLearn, a package for IACT event reconstruction through deep learning.

AimsDiabetes is associated with an excess release of neutrophil extracellular traps (NETs) and an enhanced NETosis, a neutrophil cell death programme instrumental to anti-microbial defences, but also involved in tissue damage. We herein investigated whether the antidiabetic drug metformin protects against NETosis.MethodsWe measured NET components in the plasma of patients with pre-diabetes who were randomized to receive metformin or placebo for 2 months. To control for the effect on glucose, we also measured NET components in the plasma of patients with type 2 diabetes before and after treatment with insulin or dapagliflozin. In vitro, we used static and dynamic imaging with advanced live confocal two-photon microscopy to evaluate the effects of metformin on cellular events during NETosis. We examined putative molecular mechanisms by monitoring chromatin decondensation and DNA release in vitro.ResultsMetformin, as compared to placebo, significantly reduced the concentrations of NET components elastase, proteinase-3, histones and double strand DNA, whereas glucose control with insulin or dapagliflozin exerted no significant effect. In vitro, metformin prevented pathologic changes in nuclear dynamics and DNA release, resulting in a blunted NETosis in response to phorbol myristate acetate and calcium influx. Metformin prevented membrane translocation of PKC-βII and activation of NADPH oxidase in neutrophils, both of which diminished the NETosis response.ConclusionsMetformin treatment reduced the concentrations of NET components independently from glucose control. This effect was reproducible in vitro and was related to the inhibitory effect exerted by metformin on the PKC-NADPH oxidase pathway.

PurposeCurrently, assisted reproduction clinics employ various sperm selection techniques to identify the best sperm for fertilization. However, these techniques may not assess crucial sperm traits that can substantially impact embryonic quality. To address this, we propose analyzing diverse histone modifications as potential markers of sperm functionality and success in assisted reproduction techniques.MethodsCross-sectional pilot study including infertile male patients attending an infertility clinic in CABA, Argentina between April and August 2019 was performed. We used immunofluorescence techniques to evaluate post-translational modifications of histones in sperm and established correlations with in vitro fertilization outcome and embryo quality.ResultsOur findings indicate a negative correlation between H3K4me3 and H3K4me2 marks and fertilization rate and showed a positive correlation of this parameter with H3K9me mark. In addition, there was a positive correlation between H3K27me3 and good embryo quality.ConclusionsThis pilot study proposes a non-invasive strategy to predict embryo quality by analyzing spermatozoa prior to fertilization. The assessment of histone post-translational modifications in sperm samples could provide useful information for the recognition of epigenetic marks that could predict the health of the embryo of an assisted fertilization treatment.

Axial disorders, including postural deformities, postural instability, and gait disturbances, are among the most disabling symptoms of Parkinson’s disease (PD). Equistasi®, a wearable proprioceptive stabilizer device, has been proposed as neurological rehabilitative device for this set of symptoms. To investigate the effects of the device on gait and balance, 24 participants affected by PD were enrolled in this crossover double-dummy, randomized, controlled study. Subjects were assessed four times before and after 8 weeks treatment with either active or placebo device; one-month wash-out was taken between treatments, in a 20-week timeframe. Gait analysis and instrumented Romberg test were performed with the aid of a sterofotogrammetric system and two force plates. Joint kinematics, spatiotemporal parameters of gait and center of pressure parameters were extracted. Paired T-test (p < 0.05) was adopted after evidence of normality to compare the variables across different acquisition sessions; Wilcoxon was adopted for non-normal distributions. Before and after the treatment with the active device, statistically significant improvements were observed in trunk flexion extension and in the ankle dorsi-plantarflexion. Regarding balance assessment, significant improvements were reported at the frequencies corresponding to vestibular system. These findings may open new possibilities on PD’s rehabilitative interventions.

Bioprobes immobilization methods that elevate the probes from the substrate are generally preferred in microarray technology because they prevent steric limitations during the hybridization of the target to probes. A versatile approach to control the thickness of a polymeric coating based on click chemistry to obtain covalently linked layer-by-layer coatings for surface functionalization is presented. By alternating cycles of coating using copolymers bearing click groups, the thickness of the film increases, while remaining functional and stable. Click chemistry reactions provide numerous advantages over standard conjugation procedures typically used in microarrays. They include: quantitative yields and insensitivity of the reaction to pH and hydrolysis. Moreover, click reactions do not interfere with organic groups naturally present in DNA, proteins and peptides such as amino and carboxyl groups allowing orthogonal and chemoselective probe immobilization. In addition to the formation of multilayers, click reactions allow to bind biomolecules to polymer chains generating so-called polymeric probes, which are then immobilized on microarray supports. In a microarray assay of clinical relevance, this methodology provides a miniaturized, tri-dimensional multilayer with higher density of capture probe, improved hybridization efficiency and sensitivity.