Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes

Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interac- tions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin g1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs

Beam dynamics optimization of EuPRAXIA@SPARCLAB RF injector

At EuPRAXIA@SPARCLAB an X-ray FEL user facility is driven by a plasma accelerator in the particle-driven configuration where an ultra-relativistic beam, the driver, through a plasma generates a wake of charge density useful for accelerating a witness beam. The electron bunches are generated through the so-called comb technique in an RF injector that consists of a 1.6-cell S-band gun followed by four S-band TW accelerating structures. The main working point foresees a 30pC witness and a 200pC driver longitudinally compressed in the first accelerating structure operated in the velocity-bunching regime, which allows to accelerate and manipulate the beam to reach proper transverse and longitudinal parameters. The optimization of the witness emittance is performed with additional magnetic field around the gun and the velocity bunching S-band structures and by shaping the laser pulse at the cathode. The paper reports on beam dynamics studies performed also with the insertion of an X-band RF cavity after the gun that is proposed to shape the beam current distribution and stabilize it with respect to RF jitters

On the betatron radiation in cylindrically symmetric plasma-ion channels

The relativistic interaction of short pulsed lasers or electrons with plasma has recently led to the birth of a new generation of femtosecond X-ray sources. Radiations with properties similar to those that can be observed from a wiggler or undulator, can be generated by the oscillations induced in the exited plasma by electrons (PWFA) or by lasers (LWFA), making plasma an interesting medium both for the acceleration as well as for the radiation source, whit properties of being compact, providing collimated, incoherent, femtosecond radiation, and a lot of effort is being made to understand and improve this new source to make it really competitive. This paper summarizes and shows some theoretical results and numerical simulation of a simplified model called plasma ion column, using as a starting point the parameters expected for EuPRAXIA@SPARC_LAB facility, highlighting strengths, limitations and scaling laws, which allow for a comparison with other types of more consolidated sources of light as Compton, Synchrotron and Free electron lasers

Beam dynamics optimization for high gradient beam driven plasma wakefield acceleration at SPARC-LAB

The SPARCLAB test facility at the LNF (Laboratori Nazionali di Frascati, Rome) holds a high brightness photo-injector used to investigate advanced beam manipulation techniques. High brightness electron bunch trains (so-called comb beams) can be generated striking on the photo-cathode of a Radio Frequency (RF) photo-injector with a ultra-short UV laser pulse train in tandem with the velocity bunching technique. Beam dynamics studies have been performed with the aim of optimizing the dynamics of the double beam (driver and witness) used to perform particle driven plasma wake field acceleration (PWFA). In this scenario different scans on beam parameters were carried on adopting the ASTRA simulation code, in order to optimize the witness beam quality and improve the plasma booster stage performances. A benchmark of the simulations has been then performed, reproducing the experimental data obtained from the optimization of machine performances, and a good agreement was found

SAFEST. A compact C-band linear accelerator for VHEE-FLASH radiotherapy

FLASH Radiotherapy is a revolutionary new technique in the cancer cure. Several pre-clinical studies have demonstrated that treatment with electron radiation delivered with mean dose rates above 100Gy/s, an ultra-high instantaneous dose rate > 106Gy/s, and total irradiation time < 100ms, significantly decreases the toxicity in the healthy tissue while keeping the same efficacy in cancer treatment. Although recent studies shed some light on the biological mechanisms and on the effects of FLASH electron beams on tissues and organs of small animals, more research investigation is necessary before the FLASH technique can be translated into clinical applications. Researchers also aim to explore the radio-therapeutic effects of high-dose beams delivered at Very High Electron Energy (VHEE), in the range 50-250 MeV, suitable for treating deep-seated tumors. We describe the project SAFEST, carried out at La Sapienza University in collaboration with INFN for the realization of a compact C-band electron linac VHEE at the energy of 60-150 MeV, able to deliver the high current up to 200mA and the very high dose rates required by the FLASH regime, and suitable for a hospital environment

A new national survey of centers for cognitive disorders and dementias in Italy

IntroductionA new national survey has been carried out by the Italian Centers for Cognitive Disorders and Dementias (CCDDs). The aim of this new national survey is to provide a comprehensive description of the characteristics, organizational aspects of the CCDDs, and experiences during the COVID-19 pandemic.MethodsA list of all national CCDDs was requested from the delegates of each Italian region. The online questionnaire is divided in two main sections: a profile section, containing information on location and accessibility, and a data collection form covering organization, services, treatments, activities, and any service interruptions caused by the COVID-19 outbreak.ResultsIn total, 511 out of 534 (96%) facilities completed the profile section, while 450 out of 534 (84%) CCDDs also completed the data collection form. Almost half of the CCDDs (55.1%) operated for 3 or fewer days a week. About one-third of the facilities had at least two professional figures among neurologists, geriatricians and psychiatrists. In 2020, only a third of facilities were open all the time, but in 2021, two-thirds of the facilities were open.ConclusionThis paper provides an update on the current status of CCDDs in Italy, which still shows considerable heterogeneity. The survey revealed a modest improvement in the functioning of CCDDs, although substantial efforts are still required to ensure the diagnosis and care of patients with dementia

Sparticle mass hierarchies, simplified models from SUGRA unification, and benchmarks for LHC Run-II SUSY searches

Sparticle mass hierarchies contain significant information regarding the origin and nature of supersymmetry breaking. The hierarchical patterns are severely constrained by electroweak symmetry breaking as well as by the astrophysical and particle physics data. They are further constrained by the Higgs boson mass measurement. The sparticle mass hierarchies can be used to generate simplified models consistent with the high scale models. In this work we consider supergravity models with universal boundary conditions for soft parameters at the unification scale as well as supergravity models with nonuniversalities and delineate the list of sparticle mass hierarchies for the five lightest sparticles. Simplified models can be obtained by a truncation of these, retaining a smaller set of lightest particles. The mass hierarchies and their truncated versions enlarge significantly the list of simplified models currently being used in the literature. Benchmarks for a variety of supergravity unified models appropriate for SUSY searches at future colliders are also presented. The signature analysis of two benchmark models has been carried out and a discussion of the searches needed for their discovery at LHC RUN-II is given. An analysis of the spin independent neutralino-proton cross section exhibiting the Higgs boson mass dependence and the hierarchical patterns is also carried out. It is seen that a knowledge of the spin independent neutralino-proton cross section and the neutralino mass will narrow down the list of the allowed sparticle mass hierarchies. Thus dark matter experiments along with analyses for the LHC Run-II will provide strong clues to the nature of symmetry breaking at the unification scale.Comment: To appear in JHEP; 37 pages, 11 tables, 11 figure

Nanotechnology intervention of the microbiome for cancer therapy

The microbiome is emerging as a key player and driver of cancer. Traditional modalities to manipulate the microbiome (for example, antibiotics, probiotics and microbiota transplants) have been shown to improve efficacy of cancer therapies in some cases, but issues such as collateral damage to the commensal microbiota and consistency of these approaches motivates efforts towards developing new technologies specifically designed for the microbiome–cancer interface. Considering the success of nanotechnology in transforming cancer diagnostics and treatment, nanotechnologies capable of manipulating interactions that occur across microscopic and molecular length scales in the microbiome and the tumour microenvironment have the potential to provide innovative strategies for cancer treatment. As such, opportunities at the intersection of nanotechnology, the microbiome and cancer are massive. In this Review, we highlight key opportunistic areas for applying nanotechnologies towards manipulating the microbiome for the treatment of cancer, give an overview of seminal work and discuss future challenges and our perspective on this emerging area