Guiding of Charged Particle Beams in Curved Plasma-Discharge Capillaries.

We present a new approach that demonstrates the deflection and guiding of relativistic electron beams over curved paths by means of the magnetic field generated in a plasma-discharge capillary. We experimentally prove that the guiding is much less affected by the beam chromatic dispersion with respect to a conventional bending magnet and, with the support of numerical simulations, we show that it can even be made dispersionless by employing larger discharge currents. This proof-of-principle experiment extends the use of plasma-based devices, that revolutionized the field of particle accelerators enabling the generation of GeV beams in few centimeters. Compared to state-of-the-art technology based on conventional bending magnets and quadrupole lenses, these results provide a compact and affordable solution for the development of next-generation tabletop facilities.

Stable Operation of a Free-Electron Laser Driven by a Plasma Accelerator.

The breakthrough provided by plasma-based accelerators enabled unprecedented accelerating fields by boosting electron beams to gigaelectronvolt energies within a few centimeters [1-4]. This, in turn, allows the realization of ultracompact light sources based on free-electron lasers (FELs) [5], as demonstrated by two pioneering experiments that reported the observation of self-amplified spontaneous emission (SASE) driven by plasma-accelerated beams [6,7]. However, the lack of stability and reproducibility due to the intrinsic nature of the SASE process (whose amplification starts from the shot noise of the electron beam) may hinder their effective implementation for user purposes. Here, we report a proof-of-principle experiment using plasma-accelerated beams to generate stable and reproducible FEL light seeded by an external laser. FEL radiation is emitted in the infrared range, showing the typical exponential growth of its energy over six consecutive undulators. Compared to SASE, the seeded FEL pulses have energies 2 orders of magnitude larger and stability that is 3 times higher.

Free-electron lasing with compact beam-driven plasma wakefield accelerator.

The possibility to accelerate electron beams to ultra-relativistic velocities over short distances by using plasma-based technology holds the potential for a revolution in the field of particle accelerators1-4. The compact nature of plasma-based accelerators would allow the realization of table-top machines capable of driving a free-electron laser (FEL)5, a formidable tool to investigate matter at the sub-atomic level by generating coherent light pulses with sub-ångström wavelengths and sub-femtosecond durations6,7. So far, however, the high-energy electron beams required to operate FELs had to be obtained through the use of conventional large-size radio-frequency (RF) accelerators, bound to a sizeable footprint as a result of their limited accelerating fields. Here we report the experimental evidence of FEL lasing by a compact (3-cm) particle-beam-driven plasma accelerator. The accelerated beams are completely characterized in the six-dimensional phase space and have high quality, comparable with state-of-the-art accelerators8. This allowed the observation of narrow-band amplified radiation in the infrared range with typical exponential growth of its intensity over six consecutive undulators. This proof-of-principle experiment represents a fundamental milestone in the use of plasma-based accelerators, contributing to the development of next-generation compact facilities for user-oriented applications9.

Search for Lepton Number and Flavor Violation in K

Searches for the lepton number violating K^{+}→π^{-}µ^{+}e^{+} decay and the lepton flavor violating K^{+}→π^{+}µ^{-}e^{+} and π^{0}→µ^{-}e^{+} decays are reported using data collected by the NA62 experiment at CERN in 2017-2018. No evidence for these decays is found and upper limits of the branching ratios are obtained at 90% confidence level: B(K^{+}→π^{-}µ^{+}e^{+})<4.2×10^{-11}, B(K^{+}→π^{+}µ^{-}e^{+})<6.6×10^{-11} and B(π^{0}→µ^{-}e^{+})<3.2×10^{-10}. These results improve by 1 order of magnitude over previous results for these decay modes.

Modeling and diagnostics for plasma discharge capillaries.

In this paper, we show how plasma discharge capillaries can be numerically modeled as resistors within an RLC-series discharge circuit, allowing for a simple description of these systems, while taking into account heat and radiation losses. An analytic radial model is also provided and compared to the numerical model for plasma discharge capillaries at thermal equilibrium, with corrections due to radiation losses. Finally, diagnostic techniques based on visible spectroscopy of plasma emission lines are discussed both for atomic and molecular gases, comparing experimental results with numerical simulations and theoretical calculations.

Longitudinal Phase-Space Manipulation with Beam-Driven Plasma Wakefields.

The development of compact accelerator facilities providing high-brightness beams is one of the most challenging tasks in the field of next-generation compact and cost affordable particle accelerators, to be used in many fields for industrial, medical, and research applications. The ability to shape the beam longitudinal phase space, in particular, plays a key role in achieving high-peak brightness. Here we present a new approach that allows us to tune the longitudinal phase space of a high-brightness beam by means of plasma wakefields. The electron beam passing through the plasma drives large wakefields that are used to manipulate the time-energy correlation of particles along the beam itself. We experimentally demonstrate that such a solution is highly tunable by simply adjusting the density of the plasma and can be used to imprint or remove any correlation onto the beam. This is a fundamental requirement when dealing with largely time-energy correlated beams coming from future plasma accelerators.

Focusing of High-Brightness Electron Beams with Active-Plasma Lenses.

Plasma-based technology promises a tremendous reduction in size of accelerators used for research, medical, and industrial applications, making it possible to develop tabletop machines accessible for a broader scientific community. By overcoming current limits of conventional accelerators and pushing particles to larger and larger energies, the availability of strong and tunable focusing optics is mandatory also because plasma-accelerated beams usually have large angular divergences. In this regard, active-plasma lenses represent a compact and affordable tool to generate radially symmetric magnetic fields several orders of magnitude larger than conventional quadrupoles and solenoids. However, it has been recently proved that the focusing can be highly nonlinear and induce a dramatic emittance growth. Here, we present experimental results showing how these nonlinearities can be minimized and lensing improved. These achievements represent a major breakthrough toward the miniaturization of next-generation focusing devices.

3D-printed capillary for hydrogen filled discharge for plasma based experiments in RF-based electron linac accelerator.

Plasma-based acceleration experiments require capillaries with a radius of a few hundred microns to confine plasma up to a centimeter scale capillary length. A long and controlled plasma channel allows to sustain high fields which may be used for manipulation of the electron beams or to accelerate electrons. The production of these capillaries is relatively complicated and expensive since they are usually made with hard materials whose manufacturing requires highly specialized industries. Fine variations of the capillary shape may significantly increase the cost and time needed to produce them. In this article, we demonstrate the possibility of using 3D printed polymeric capillaries to drive a hydrogen-filled plasma discharge up to 1 Hz of repetition rate in an RF based electron linac. The plasma density distribution has been measured after several shot intervals, showing the effect of the surface ablation on the plasma density distribution. This effect is almost invisible in the earlier stages of the discharge. After more than 55000 shots (corresponding to more than 16 h of working time), the effects of the ablation on the plasma density distribution are not evident and the capillary can still be used. The use of these capillaries will significantly reduce the cost and time for prototyping, allowing us to easily manipulate their geometry, laying another building block for future cheap and compact particle accelerators.

Type II CRISPR/Cas9 approach in the oncological therapy.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a prokaryotic adaptable immune mechanism used by many bacteria and archaea to protect themselves from foreign nucleic acids. This complex system can recognize and cut non-self DNA in order to provide the prokaryotic organisms a strong defense against foreign viral or plasmid attacks and make the cell immune from further assaults. Today, it has been adapted to be used in vitro and in vivo in eukaryotic cells to perform a complete and highly selective gene knockout or a specific gene editing. The ease of use and the low cost are only two features that have made it very popular among the scientific community and the possibility to be used as a clinical treatment in several genetic derived pathologies has rapidly spread its fame worldwide. However, CRISPR is still not fully understood and many efforts need to be done in order to make it a real power tool for the human clinical treatment especially for oncological patients. Indeed, since cancer originates from non-lethal genetic disorders, CRISPR discovery fuels the hope to strike tumors on their roots. More than 4000 papers regarding CRISPR were published in the last ten years and only few of them take in count the possible applications in oncology. The purpose of this review is to clarify many problematics on the CRISPR usage and highlight its potential in oncological therapy.

Endothelial Progenitor Cells in Sprouting Angiogenesis: Proteases Pave the Way.

Sprouting angiogenesis consists of the expansion and remodelling of existing vessels, where the vascular sprouts connect each other to form new vascular loops. Endothelial Progenitor Cells (EPCs) are a subtype of stem cells, with high proliferative potential, able to differentiate into mature Endothelial Cells (ECs) during the neovascularization process. In addition to this direct structural role EPCs improve neovascularization, also secreting numerous pro-angiogenic factors able to enhance the proliferation, survival and function of mature ECs, and other surrounding progenitor cells. While sprouting angiogenesis by mature ECs involves resident ECs, the vasculogenic contribution of EPCs is a high hurdle race. Bone marrowmobilized EPCs have to detach from the stem cell niche, intravasate into bone marrow vessels, reach the hypoxic area or tumour site, extravasate and incorporate into the new vessel lumen, thus complementing the resident mature ECs in sprouting angiogenesis. The goal of this review is to highlight the role of the main protease systems able to control each of these steps. The pivotal protease systems here described, involved in vascular patterning in sprouting angiogenesis, are the matrix-metalloproteinases (MMPs), the serineproteinases urokinase-type plasminogen activator (uPA) associated with its receptor (uPAR) and receptorassociated plasminogen/plasmin, the neutrophil elastase and the cathepsins. Since angiogenesis plays a critical role not only in physiological but also in pathological processes, such as in tumours, controlling the contribution of EPCs to the angiogenic process, through the regulation of the protease systems involved, could yield new opportunities for the therapeutic prospect of efficient control of pathological angiogenesis.

Note: Comparative experimental studies on the performance of 2-2 piezocomposite for medical ultrasound transducers.

The paper reports the experimental investigation of the behavior of 2-2 Lead Zirconate Titanate (PZT)-polymer composite transducers array for clinical ultrasound equipments. Several 2-2 plate composites having the same dicing pitch of 0.11 mm and different volume fractions were manufactured and investigated. Measurements were performed through different techniques such as electrical impedance, pulse-echo, and Laser Doppler Vibrometer. With the last one, maps of the surface displacement were presented relative to thickness mode and first lateral mode resonance frequencies. The transducers with volume fractions of the 40% resulted markedly inefficient, whereas the largest bandwidth and best band shape were achieved by the 50%.

Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae)

The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA A antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA A receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA A receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.

Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae).

The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA(A) antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA(A) receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA(A) receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.

Photoacoustic cell for ultrasound contrast agent characterization.

Photoacoustics has emerged as a tool for the study of liquid gel suspension behavior and has been recently employed in a number of new biomedical applications. In this paper, a photoacoustic sensor is presented which was designed and realized for analyzing photothermal signals from solutions filled with microbubbles, commonly used as ultrasound contrast agents in echographic imaging techniques. It is a closed cell device, where photothermal volume variation of an aqueous solution produces the periodic deflection of a thin membrane closing the cell at the end of a short pipe. The cell then acts as a Helmholtz resonator, where the displacement of the membrane is measured through a laser probe interferometer, whereas photoacoustic signal is generated by a laser chopped light beam impinging onto the solution through a glass window. Particularly, the microbubble shell has been modeled through an effective surface tension parameter, which has been then evaluated from experimental data through the shift of the resonance frequencies of the photoacoustic sensor. This shift of the resonance frequencies of the photoacoustic sensor caused by microbubble solutions is high enough for making such a cell a reliable tool for testing ultrasound contrast agent, particularly for bubble shell characterization.

Indentation modulus and hardness of viscoelastic thin films by atomic force microscopy: A case study.

We propose a nanoindentation technique based on atomic force microscopy (AFM) that allows one to deduce both indentation modulus and hardness of viscoelastic materials from the force versus penetration depth dependence, obtained by recording the AFM cantilever deflection as a function of the sample vertical displacement when the tip is pressed against (loading phase) and then removed from (unloading phase) the surface of the sample. Reliable quantitative measurements of both indentation modulus and hardness of the investigated sample are obtained by calibrating the technique through a set of different polymeric samples, used as reference materials, whose mechanical properties have been previously determined by standard indentation tests. By analyzing the dependence of the cantilever deflection versus time, the proposed technique allows one to evaluate and correct the effect of viscoelastic properties of the investigated materials, by adapting a post-experiment data processing procedure well-established for standard depth sensing indentation tests. The technique is described in the case of the measurement of indentation modulus and hardness of a thin film of poly(3,4-ethylenedioxythiophene) doped with poly(4-styrenesulfonate), deposited by chronoamperometry on an indium tin oxide (ITO) substrate.

Quantitative measurement of indentation hardness and modulus of compliant materials by atomic force microscopy.

An atomic force microscopy (AFM) based technique is proposed for the characterization of both indentation modulus and hardness of compliant materials. A standard AFM tip is used as an indenter to record force versus indentation curves analogous to those obtained in standard indentation tests. In order to overcome the lack of information about the apex geometry, the proposed technique requires calibration using a set of reference samples whose mechanical properties have been previously characterized by means of an independent technique, such as standard indentation. Due to the selected reference samples, the technique has been demonstrated to allow reliable measurements of indentation modulus and hardness in the range of 0.3-4.0 GPa and 15-250 MPa, respectively.

Application of the Method of Organizational Congruencies in Substituting Organic Solvents With Vegetable Agents for the Cleaning of an Offset Printing Machine.

The aim of this research is the application of the Method of Organizational Congruencies before and after the substitution of organic solvents with vegetable agents for the cleaning of an offset printing machine in order to assess the organizational changes. A solvent-free process is the goal of the Subsprint Project (Technology Transfer Program of the European Community). This study shows how human and environmental health is improved by using vegetable agents, though this change may lead to some other organizational constraints such as an increase of the time needed, monotony, and repetitiveness of the technical actions involved. The authors underline that the knowledge of the impact of the new technology on health helps a better understanding of the resistance to the change and its further amelioration.