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Previously, we demonstrated that the 177Lu-labeled single-chain variable fragment of an anti-prostate-specific membrane antigen (PSMA) IgG D2B antibody (scFvD2B) showed higher prostate cancer (PCa) cell uptake and tumor radiation doses compared to 177Lu-labeled Glu-ureide-based PSMA inhibitory peptides. To obtain a 99mTc-/177Lu-scFvD2B theranostic pair, this research aimed to synthesize and biochemically characterize a novel 99mTc-scFvD2B radiotracer. The scFvD2B-Tag and scFvD2B antibody fragments were produced and purified. Then, two HYNIC derivatives, HYNIC-Gly-Gly-Cys-NH2 (HYNIC-GGC) and succinimidyl-HYNIC (S-HYNIC), were used to conjugate the scFvD2B-Tag and scFvD2B isoforms, respectively. Subsequently, chemical characterization, immunoreactivity tests (affinity and specificity), radiochemical purity tests, stability tests in human serum, cellular uptake and internalization in LNCaP(+), PC3-PIP(++) or PC3(−) PCa cells of the resulting unlabeled HYNIC-scFvD2B conjugates (HscFv) and 99mTc-HscFv agents were performed. The results showed that incorporating HYNIC as a chelator did not affect the affinity, specificity or stability of scFvD2B. After purification, the radiochemical purity of 99mTc-HscFv radiotracers was greater than 95%. A two-sample t-test of 99mTc-HscFv1 and 99mTc-HscFv1 uptake in PC3-PIP vs. PC3 showed a p-value < 0.001, indicating that the PSMA receptor interaction of 99mTc-HscFv agents was statistically significantly higher in PSMA-positive cells than in the negative controls. In conclusion, the results of this research warrant further preclinical studies to determine whether the in vivo pharmacokinetics and tumor uptake of 99mTc-HscFv still offer sufficient advantages over HYNIC-conjugated peptides to be considered for SPECT/PSMA imaging.

Despite advances in chemotherapeutic drugs used against cervical cancer, available chemotherapy treatments adversely affect the patient’s quality of life. For this reason, new molecules from natural sources with antitumor potential and few side effects are required. In previous research, Pllans−II, a phospholipase A2 type-Asp49 from Porthidium lansbergii lansbergii snake venom, has shown selective attack against the HeLa and Ca Ski cervical cancer cell lines. This work suggests that the cytotoxic effect generated by Pllans−II on HeLa cells is triggered without affecting the integrity of the cytoplasmic membrane or depolarizing the mitochondrial membranes. The results allow us to establish that cell death in HeLa is related to the junction blockage between α5β1 integrins and fibronectin of the extracellular matrix. Pllans−II reduces the cells’ ability of adhesion and affects survival and proliferation pathways mediated by intracellular communication with the external environment. Our findings confirmed Pllans−II as a potential prototype for developing a selective chemotherapeutic drug against cervical cancer.

This review was devoted to outlining the use and potential increasing application of the Design of Experiment (DoE) approach to the rational and planned synthesis of inorganic nanomaterials, with a particular focus on polycrystalline nanostructures (metal and alloys, oxides, chalcogenides, halogenides, etc.) produced by sustainable wet chemistry routes based on a multi-parameter experimental landscape. After having contextualised the stringent need for a rational approach to inorganic materials’ synthesis, a concise theoretical background on DoE is provided, focusing on its statistical basis, shortly describing the different sub-methodologies, and outlining the pros and cons of each. In the second part of the review, a wider section is dedicated to the application of DoE to the rational synthesis of different kinds of chemical systems, with a specific focus on inorganic materials.

Hot spots and bright patterns on plasma-facing components (PFC) in visible light are observed in electron cyclotron resonance heated (ECRH) plasmas at low densities in the stellarator Wendelstein 7-X. The events are often located far outside of any convective plasma loads and led in some cases to damages of diagnostic components, where the interaction zones qualitatively agree with fast particle loss simulations. Reciprocating electric probes indicate that this phenomenon is related to a non-thermal electron population that can have a beam like character, being directed in one parallel direction. Further, the electrons can be trapped on rational flux surfaces and be used to map magnetic islands.

Peterle et al. show that a subtilisin like serine protease secreted from gut microbiota Bacillus subtilis cleaves the wild-type human transthyretin (hTTR) to generate an amyloidogenic peptide. High propensity of the hTTR fragment to form pathogenic protein aggregates implicates the serine protease in the pathogenesis of acquired senile systemic amyloidosis.

SPIDER is the 100 keV full-size Negative Ion Source prototype of the ITER Neutral Beam Injector, operating at Consorzio RFX in Padova, Italy. The largest Negative Ion Source in the world, SPIDER generates an RF driven plasma from which Deuterium or Hydrogen negative ions are produced and extracted. At the end of 2021, a scheduled long-term shutdown started to introduce major modifications and improvements aiming to solve issues and drawbacks identified during the first three years of SPIDER operations. The first action of the shutdown period was the disassembly and characterization of the SPIDER beam source after removal from the vacuum vessel and its placement inside the clean room. Each component was carefully assessed and catalogued, following a documented procedure. Some source components, i.e., the Plasma Grid, Extraction Grid and Bias Plate, revealed the presence of different and non-uniform red, white and green coatings that might be correlated to back-streaming positive ions impinging on grid surfaces, electrical discharges and caesium evaporation. Thus, several analyses have been carried out to understand the nature of such coatings, with the study still ongoing. The evidence of caesium evaporation and deposition on molybdenum-coated SPIDER components, such as the formation of oxides and hydroxides, is demonstrated through surface characterization analyses with the use of the Scanning Electron Microscope (SEM), X-ray Diffraction (XRD) and X-ray Photoelectron Spectroscopy (XPS).

Background: Recent studies have shown that patients diagnosed with coronarivus disease 2019 (COVID-19) and also with previous cardiovascular diseases have a higher mortality due to worsening heart disease. At the same time, patients without previous cardiovascular disease may also have cardiac complications. The aim of this multicenter study was to assess high sensitivity cardiac troponin T (hs-cTnT) in patients with COVID-19 and to evaluate the incidence of myocardial injury. Methods: In this multicenter study we enrolled 543 patients, 57.8% males, median age 63 years (range 18–99) from three selected hospitals: University Hospital Tor Vergata in Rome, Fondazione IRCCS Ca 'Granda Ospedale Maggiore Policlinico, in Milan, S Chiara Hospital in Trento. We measured hs-cTnT in all patients to assess myocardial injury and correlations with patient’s age, symptoms and disease course. Results: The data showed that, among the 543 patients studied, 257 patients (47.3%) had hs-cTnT values higher than the upper reference limit (URL) of 14 ng/L. Patients with high hs-cTnT had more frequently fever (p

In this paper we present our studies about the choices of anode design and operational regime in order to get high efficiency glow discharge cleaning of the first wall of a fusion device. We analyzed a database of toroidal and poloidal profiles of the ion current density at the wall, measured by electrostatic probes embedded in RFX-mod first wall tiles, taken in different configurations. The ion current at the wall, both global and local, is in fact strictly connected to the cleaning efficiency, since during glow discharge the wall is physically sputtered by the ions. We found that small size anodes and high in-vessel pressure lead to the peaking of the current profile around the anodes locations, and we experimentally characterized this effect. Instead, we found that anode radial position in the poloidal section has negligible effect on current density profile, even when the anodes are placed at the first wall. Finally, the most convenient operational regime, in terms of pressure and current, has been proposed. Keywords: RFX-mod, Glow discharge, Wall cleaning, Ion current profile, Anode design

A simple analytic model for the repartition of the Scrape-Off Layer (SOL) exhaust power between the inner and outer divertors in a diverted low-density tokamak plasma is introduced. Electron heat conduction is assumed to dominate the heat transport, from the outboard mid-plane to the divertor targets, with no heat sinks or sources in the SOL. Both divertor channels are in the attached, high-recycling regime. The model is in reasonable qualitative agreement with recent TCV experimental data and EMC3-Eirene simulations. For the Single Null divertor, it reproduces the experimentally observed increase in the power ratio between the inner and outer divertor plates of TCV, Pin/Pout, with increasing the outer divertor leg length or the outer target flux expansion. For the Snowflake Minus configuration, it reproduces the observed variation of Pin/Pout with X-point separation, although only for the reversed magnetic field direction. Within the model limitations, it provides a basic understanding of the power sharing in alternative divertor geometries. Keywords: Heat exhaust, SOL transport, Long-legged Single Null Divertor, Snowflake Divertor, In-out power sharing, TCV

In fusion devices strong interest is deserved to the edge filament transport both related to turbulent and ELMy structures, because they are believed to provide important interaction with the plasma facing components and divertor plates. Among their features also the electromagnetic (EM) properties are expected to play an important role and in particular for the high beta regimes expected in future devices. The presence of ELM and inter-ELM electromagnetic filaments were detected during H-mode discharges in COMPASS device Scrape-Off Layer, where a new probe head was recently developed and commissioned. The diagnostic allows the simultaneous measurements of electrostatic and magnetic fluctuations with high time resolution, suitable for the identification of EM features of filaments. The method allows in particular the direct measurement of the current density associated to filaments. Detailed electrostatic and electromagnetic features analysis revealed a complex and fragmented structure within a single ELM and strong peaks in parallel current density Jtor are observed to characterize the ELM bunch. Analogous EM structures are observed also in inter-ELM phase, but with more than one order of magnitude lower intensity and time scale. Keywords: Electromagnetic filaments, ELMs, Scrape-Off Layer, Magnetic fluctuations, Current density

The edge of the RFX-mod (R=2m, a=0.46m) Reversed Field Pinch device is characterized by weak magnetic chaos affecting ion and electron diffusion. Edge particle transport is strongly influenced by a toroidal and poloidal asymmetry caused by magnetic islands and an ambipolar radial electric field ensures local neutrality. At higher plasma current (Iϕ>1MA) a spontaneous resonant dominant mode m/n=1/7, slowly rotating, develops in the inner region. The edge electron pressure Pe and floating potential Vf show a shape of the Plasma Wall Interaction (PWI) with the same toroidal periodicity, which follows the edge local ideal magnetic displacement Δ1,7.Detailed measurements along the poloidal direction of Pe and Vf have been undertaken newly, their time behavior present respect to Δ1,7 a time lag, which depends on the poloidal angle θ. The mode analysis in terms of helical angle reveals a role of the 0/7 mode in determining a poloidal phase lag respect to Δ1,7 of Pe and Vf. Since the 0/7 is the largest toroidal sideband of the 1/7 mode, this work suggests a role of toroidal coupling in determining the plasma response to a MP. Keywords: RFX, RFP, PWI, THB, MPs, Stochastic layers, Magnetic chaos

Site-specific conjugation of proteins is currently required to produce homogenous derivatives for medicine applications. Proteins derivatized at specific positions of the polypeptide chain can actually show higher stability, superior pharmacokinetics, and activity in vivo, as compared with conjugates modified at heterogeneous sites. Moreover, they can be better characterized regarding the composition of the derivatization sites as well as the conformational and activity properties. To this aim, several site-specific derivatization approaches have been developed. Among these, enzymes are powerful tools that efficiently allow the generation of homogenous protein–drug conjugates under physiological conditions, thus preserving their native structure and activity. This review will summarize the progress made over the last decade on the use of enzymatic-based methodologies for the production of site-specific labeled immunoconjugates of interest for nuclear medicine. Enzymes used in this field, including microbial transglutaminase, sortase, galactosyltransferase, and lipoic acid ligase, will be overviewed and their recent applications in the radiopharmaceutical field will be described. Since nuclear medicine can benefit greatly from the production of homogenous derivatives, we hope that this review will aid the use of enzymes for the development of better radio-conjugates for diagnostic and therapeutic purposes.

The next generation of 4π arrays for high-precision γ-ray spectroscopy AGATA will consist of γ-ray tracking detectors. They represent high-fold segmented Ge detectors and a front-end electronics, based on digital signal processing techniques, which allows to extract energy, timing and spatial information on the interactions of a γ-ray in the Ge detector by pulse shape analysis of its signals. Utilizing the information on the positions of the interaction points and the energies released at each point the tracks of the γ-rays in a Ge shell can be reconstructed in three dimensions on the basis of the Compton-scattering formula.

For the first time, material analysis techniques have been applied to study the effect of ion cyclotron wall conditioning (ICWC) on probe surfaces in a metal-wall machine. ICWC is a technique envisaged to contribute to the removal of fuel and impurities from the first wall of ITER. The objective of this work was to assess impurity migration under ICWC operation. Tungsten probes were exposed in ASDEX Upgrade to discharges in helium. After wall conditioning, the probes were covered with a co-deposited layer containing D, B, C, N, O and relatively high amount of He. The concentration ratio He/C+B was 0.7. The formation of the co-deposited layer indicates that a fraction of the impurities desorbed from the wall under ICWC operation are transported by plasma and deposited away from their original location. Keywords: ICWC, Erosion-deposition, Fuel removal, Ion beam analysis, ASDEX Upgrade

The objective of the present study was to evaluate the presence of Salmonella sp. serovars in mesenteric lymph nodes of swine as well as the spread potential of the agent during slaughter and inspection activities. Animals were bred in confinement and slaughtered in officially inspected facilities in western Parana, Brazil. Thefollowing samples were collected in five replications, at different moments of the slaughter process: 30 chains of mesenteric lymph nodes; 12 swabs of white viscera inspection tables; eight swabs of knives used in lymph nodes inspection; and four swabs of gloves of theinspection staff. Microbiological analysis of the lymph nodes of 150 animals showed Salmonella sp in 17.3% (26/150) of them. The agent was also isolated in 5.0% (2/40) of the knives, and in 28.3% (17/60) of the white viscera inspection tables. None of the gloves was positive(0/20). In conclusion, Salmonella serovars from mesenteric lymph nodes and different surfaces that get in contact with slaughtered animals show the agent´s spread potential and consequently cross-contamination during the slaughter process.