A. R. Rossi

Electron Linac design to drive bright Compton back-scattering gamma-ray sources

The technological development in the field of high brightness linear accelerators and high energy/high quality lasers enables today designing high brilliance Compton-X and Gamma-photon beams suitable for a wide range of applications in the innovative field of nuclear photonics. The challenging requirements of this kind of source comprise: tunable energy (1–20 MeV), very narrow bandwidth (0.3%), and high spectral density (104 photons/s/eV). We present here a study focused on the design and the optimization of an electron Linac aimed to meet the source specifications of the European Extreme Light Infrastructure—Nuclear Physics project, currently funded and seeking for an innovative machine design in order to outperform state-of-the-art facilities. We show that the phase space density of the electron beam, at the collision point against the laser pulse, is the main quality factor characterizing the Linac.

The SPARC linear accelerator based terahertz source

Ultra-short electron beams, produced through the velocity bunching compression technique, are used to drive the SPARC linear accelerator based source, which relies on the emission of coherent transition radiation in the terahertz range. This paper reports on the main features of this radiation, as terahertz source, with spectral coverage up to 5 THz and pulse duration down to 200 fs, with an energy per pulse of the order of several micro-joule, and as electron beam longitudinal diagnostics.

Persistence of mucosal and systemic immune responses following sublingual immunization

The development of mucosal vaccines for prevention of infectious diseases caused by pathogens entering through the mucosal surfaces is an important and challenging objective. To this purpose, we evaluated the efficacy and durability of immune response induced by sublingual immunization with tetanus toxoid (TT) as an antigen in the presence of mucosal adjuvants, such as E. coli Heat-Labile enterotoxin (LT) or the mutant of LT lacking ADP ribosyltransferase activity (LTK63). Both serum anti-TT IgG and mucosal anti-TT IgA antibodies reached a peak after four immunizations and decreased over time, maintaining detectable titers up to 4 months after the last immunization. Similarly, antigen-specific antibody secreting cells in bone marrow and TT-specific CD4+ and CD8+ T cells in draining lymph nodes and spleen were present up to 4 months from the last immunization. Overall, LT-treated mice showed significantly higher responses compared to LTK63 immunized mice. The efficacy and persistence of the immune response induced by sublingual immunization with different adjuvants strongly suggest that this route represents an appealing and promising alternative to the other mucosal routes of vaccine delivery.

Successful therapeutic vaccination with integrase defective lentiviral vector expressing nononcogenic human papillomavirus E7 protein.

Persistent infection with high risk genotypes of human papillomavirus (HPV) is the cause of cervical cancer, one of most common cancer among woman worldwide, and represents an important risk factor associated with other anogenital and oropharyngeal cancers in men and women. Here, we designed a therapeutic vaccine based on integrase defective lentiviral vector (IDLV) to deliver a mutated nononcogenic form of HPV16 E7 protein, considered as a tumor specific antigen for immunotherapy of HPV‐associated cervical cancer, fused to calreticulin (CRT), a protein able to enhance major histocompatibility complex class I antigen presentation (IDLV‐CRT/E7). Vaccination with IDLV‐CRT/E7 induced a potent and persistent E7‐specific T cell response up to 1 year after a single immunization. Importantly, a single immunization with IDLV‐CRT/E7 was able to prevent growth of E7‐expressing TC‐1 tumor cells and to eradicate established tumors in mice. The strong therapeutic effect induced by the IDLV‐based vaccine in this preclinical model suggests that this strategy may be further exploited as a safe and attractive anticancer immunotherapeutic vaccine in humans.

Integrase-defective lentiviral- vector-based vaccine: a new vector for induction of T cell immunity

Introduction: The development of new strategies for the induction of potent and broad immune responses is of high priority in the vaccine field. In this setting, integrase-defective lentiviral vectors (IDLV) represent a new and promising delivery system for immunization purposes. Areas covered: In this review we describe the development and application of IDLV for vaccination. IDLV are turning out to be a new class of vectors endowed with peculiar characteristics, setting them apart from the parental integration-competent lentiviral vectors. Recent data suggest that IDLV are able to induce strong antigen-specific immune responses in terms of quantity, persistence and quality of CD8+ T cell response following a single immunization in mice. Expert opinion: IDLV are a recent acquisition in the field of genetic immunization, thus allowing for the opportunity of further upgrading, including increasing antigen expression and potency of immune response. Based on recent reports showing the potential of IDLV for immunization in mouse models, further development and validation of IDLV, including comparison with other vaccine protocols and use in non-human primate models, are warranted.

Experimental characterization of active plasma lensing for electron beams

The active plasma lens represents a compact and affordable tool with radially symmetric focusing and field gradients up to several kT/m. In order to be used as a focusing device, its effects on the particle beam distribution must be well characterized. Here, we present the experimental results obtained by focusing an high-brightness electron beam by means of a 3 cm-long discharge-capillary pre-filled with Hydrogen gas. We achieved minimum spot sizes of 24 μ m (rms) showing that, during plasma lensing, the beam emittance increases due to nonlinearities in the focusing field. The results have been cross-checked with numerical simulations, showing an excellent agreement.

Experimental characterization of the effects induced by passive plasma lens on high brightness electron bunches

We report on the experimental characterization of the effect that a passive plasma lens in the overdense regime has on high-brightness bunch quality by means of 6D phase-space analysis. The passive lens is generated by confining hydrogen gas with a capillary tube pre-ionized with a high-voltage discharge. We observed that the optimum condition is retrieved at the end of the overdense regime with almost no effect on bunch brightness. The presence of gas jets, leaking from the hollow capillary end-points, extends the lens effects also outside of the capillary, resulting in longer focusing channels. Experimental results are supported with numerical simulations of the complete accelerator line together with the plasma channel section.

Simian immunodeficiency virus-Vpx for improving integrase defective lentiviral vector-based vaccines

BackgroundIntegrase defective lentiviral vectors (IDLV) represent a promising delivery system for immunization purposes. Human dendritic cells (DC) are the main cell types mediating the immune response and are readily transduced by IDLV, allowing effective triggering of in vitro expansion of antigen-specific primed CD8+ T cells. However, IDLV expression in transduced DC is at lower levels than those of the integrase (IN) competent counterpart, thus requiring further improvement of IDLV for future use in the clinic.ResultsIn this paper we show that the addition of simian immunodeficiency (SIV)-Vpx protein in the vector preparation greatly improves transduction of human and simian DC, but not of murine DC, thus increasing the ability of transduced DC to act as functional antigen presenting cells, in the absence of integrated vector sequences. Importantly, the presence of SIV-Vpx allows for using lower dose of input IDLV during in vitro transduction, thus further improving the IDLV safety profile.ConclusionsThese results have significant implications for the development of IDLV-based vaccines.

Time-domain measurement of a self-amplified spontaneous emission free-electron laser with an energy-chirped electron beam and undulator tapering

We report the first experimental implementation of a method based on simultaneous use of an energy chirp in the electron beam and a tapered undulator, for the generation of ultrashort pulses in a self-amplified spontaneous emission mode free-electron laser (SASE FEL). The experiment, performed at the SPARC FEL test facility, demonstrates the possibility of compensating the nominally detrimental effect of the chirp by a proper taper of the undulator gaps. An increase of more than 1 order of magnitude in the pulse energy is observed in comparison to the untapered case, accompanied by FEL spectra where the typical SASE spiking is suppressed.

The Italian health surveillance (SiVeAS) prioritization approach to reduce chronic disease risk factors

ObjectiveBecause public health funds are limited, programs need to be prioritized.MethodsWe used data on 15 risk factors from Italy’s public health surveillance to inform prioritization of programs. We ranked risk factors using a score based on the product of six criteria: deaths attributable to risk factors; prevalence of risk factors; risk factor prevalence trend; disparity based on the ratio of risk factor prevalence between low and high education attainment; level of intervention effectiveness; and cost of the intervention.ResultsWe identified seven priorities: physical inactivity; cigarette smoking (current smoking); ever told had hypertension; not having blood pressure screening; ever told had high cholesterol; alcohol (heavy drinking); not eating five fruits and vegetables a day; and not having a fecal occult blood test.ConclusionsThis prioritization method should be used as a tool for planning and decision making.