POH1/Rpn11/PSMD14: a journey from basic research in fission yeast to a prognostic marker and a druggable target in cancer cells.

POH1/Rpn11/PSMD14 is a highly conserved protein in eukaryotes from unicellular organisms to human and has a crucial role in cellular homoeostasis. It is a subunit of the regulatory particle of the proteasome, where it acts as an intrinsic deubiquitinase removing polyubiquitin chains from substrate proteins. This function is not only coupled to the translocation of substrates into the core of the proteasome and their subsequent degradation but also, in some instances, to the stabilisation of ubiquitinated proteins through their deubiquitination. POH1 was initially discovered as a functional homologue of the fission yeast gene pad1 <sup>+</sup> , which confers drug resistance when overexpressed. In translational studies, expression of POH1 has been found to be increased in several tumour types relative to normal adjacent tissue and to correlate with tumour progression, higher tumour grade, decreased sensitivity to cytotoxic drugs and poor prognosis. Proteasome inhibitors targeting the core particle of the proteasome are highly active in the treatment of myeloma, and recently developed POH1 inhibitors, such as capzimin and thiolutin, have shown promising anticancer activity in cell lines of solid tumours and leukaemia. Here we give an overview of POH1 function in the cell, of its potential role in oncogenesis and of recent progress in developing POH1-targeting drugs

Early Ceramics in Anatolia: Implications for the Production and Use of the Earliest Pottery. The Evidence from Boncuklu Höyük

Fragments of possible fired clay found at Boncuklu Höyük, central Turkey, appear to derive from rudimentary vessels, despite the later ninth- and early eighth-millennium cal. bc and thus ‘Aceramic’ dates for the site. This paper will examine the evidence for such fired clay vessels at Boncuklu and consider their implications as examples of some of the earliest pottery in Anatolia. The discussion will examine contextual evidence for the role of these fragments and consider their relative rarity at the site and the implications for the marked widespread adoption of pottery in southwest Asia c. 7000–6700 cal. bc

The ubiquitin-proteasome pathway in cancer.

Degradation by the 26S proteasome of specific proteins that have been targeted by the ubiquitin pathway is the major intracellular non-lysosomal proteolytic mechanism and is involved in a broad range of processes, such as cell cycle progression, antigen presentation and control of gene expression. Recent work, reviewed here, has shown that this pathway is often the target of cancer-related deregulation and can underlie processes, such as oncogenic transformation, tumour progression, escape from immune surveillance and drug resistance

A Novel Highly Symmetric TM01 Mode Launcher for Ultimate Brightness Applications

The R&D of high gradient radiofrequency (RF) devices is aimed to develop innovative accelerating structures based on new manufacturing techniques and materials in order to construct devices operating with the highest accelerating gradient. Recent studies have shown a large increase in the maximum sustained RF surface electric fields in copper structures operating at cryogenic temperatures. These novel approaches allow significant performance improvements of RF photoinjectors. Indeed the operation at high surface fields results in considerable increase of electron beam brilliance. This enhancement requires high field quality in the RF photoinjector and, specifically in the design of the power coupler. In this work we present a novel device for the RF photoinjector: a compact X-band TM01 mode launcher with a fourfold symmetry which minimizes both dipole and quadrupole RF components

Rotor bar pre-fault detection in the squirrel cage induction motors

The paper deals with a diagnosis technique to detect and monitor incipient faults in the rotor bars of squirrel gage induction motors. The failure mode analysis is performed monitoring the motor axial vibrations. To accomplish the task, the authors present a mathematical model that allows relating the occurrence and the severity of the faults to the presence and the magnitude of some frequency components of the axial vibration spectrum. To validate the proposed approach, the results obtained by applying the mathematical model are compared with the ones obtained by experimental tests done on both healthy and faulty motors

Electron cloud buildup and impedance effects on beam dynamics in the future circular e+e− collider and experimental characterization of thin TiZrV vacuum chamber coatings

The Future Circular Collider FCC-ee is a study toward a high luminosity electron-positron collider with a centre-of-mass energy from 91 GeV to 365 GeV. Due to the beam parameters and pipe dimensions, collective effects and electron cloud can be very critical aspects for the machine and can represent the main limitations to its performance. An estimation of the electron cloud build up in the main machine components and an impedance model are required to analyze the induced instabilities and to find solutions for their mitigation. Special attention has been given to the resistive wall impedance associated with a layer of nonevaporable getter (NEG) coating on the vacuum chamber required for electron cloud mitigation. The studies presented in this paper will show that minimizing the thickness of this coating layer is mandatory to increase the single bunch instability thresholds in the proposed lepton collider at 45.6 GeV. For this reason, NEG thin films with thicknesses below 250 nm have been investigated by means of numerical simulations to minimize the resistive wall impedance. In parallel, an extensive measurement campaign was performed at CERN to characterize these thin films, with the purpose of finding the minimum effective thickness satisfying vacuum and electron cloud requirements

The Ka-band high power klystron amplifier design program of INFN

In the framework of the Compact Light XLS project, a short ultra-high gradient linearizer working on the third harmonic of the main linac frequency is requested. Increasing gradients and reducing dimensions are requirements for XLS and all next generation linear accelerators. Actually, ultra-compact normal conducting accelerating structures, operating in the Ka-band are required to achieve ultra-high gradients for research, industrial and medical applications, with electric field ranging from 100 to 150 MV/m. To fulfill these strong requirements, the R&D of a proper Ka-band klystron with high RF power output and a high efficiency is mandatory. This contribution reports the design of a possible klystron amplifier tube operating on the 010 mode at 36 GHz, the third harmonic of the 12 GHz linac frequency, with an efficiency of 42% and a 20 MW RF power output. This contribution discusses also the high-power DC gun, the beam focusing channel and the RF beam dynamics

Progress on the hybrid gun project at UCLA

UCLA/INFN-LNF/Univ. Rome has been developing the hybrid gun which has an RF gun and a short linac for velocity bunching in one structure. After the cavity was manufactured at INFN-LNF in 2012, tests of the gun was carried out at UCLA. The field in the standing wave part was 20 % smaller than the simulation but the phase advance was fine. The cavity was commissioned successfully up to 13 MW. The beam test was performed at 11.5 MW and demonstrated the bunch compression