Proposal of a VHEE Linac for FLASH radiotherapy

Translation of electron FLASH radiotherapy in clinical practice requires the use of high energy accelerators to treat deep tumours and Very High Electron Energy (VHEE) could represent a valid technique to achieve this goal. In this scenario, a VHEE FLASH linac is under study at the University La Sapienza of Rome (Italy) in collaboration with the Italian Institute for Nuclear Research (INFN) and the Institut Curie (France). Here we present the preliminary results of a compact C-band system aiming to reach an high accelerating gradient and an high pulse current necessary to deliver high dose per pulse and ultra-high dose rate required for FLASH effect. We propose a system composed of a low energy high current injector linac followed by a modular section of high accelerating gradient structures. CST code is used to define the required LINAC’s RF parameters and beam dynamics simulations are performed using TSTEP and ASTR

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

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

Seismic characterization and reconstruction of reference ground motion at accelerometric sites of the Italian national accelerometric network (RAN)

We present a field procedure that has been extensively used in Italy to characterize local seismic response at accelerometric sites and to retrieve ground motion at reference soil conditions by deconvolution analysis. To allow a generalized application to large areas where borehole data are generally lacking or inadequate for the seismic characterization for soils down to the reference seismic bedrock, cost-effectiveness of the considered procedures is a main issue. Thus, major efforts have been devoted to optimize available information and exploit fast and cheap surface geophysical prospecting. In particular, geological/geomorphological survey and passive seismic prospecting (both in single- and multi-station configurations) were jointly considered to reconstruct seismo-stratigraphical site conditions. This information was then used to feed numerical modeling aiming at computing the local seismic response and performing a deconvolution analysis to reconstruct ground motion at reference soil conditions. Major attention was devoted to evaluate and manage uncertainty involved in the procedure and to quantify its effect on final outcomes. An application of this procedure to a set of sites included in the Italian Accelerometric Network is presented