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One of the options currently taken into account for the realization of the first DEMO reactor is the “water-cooled lanket”. This option implies an irradiation temperature for the blanket material in the range of 280–350 °C. Therefore, in light of the under irradiation behaviour of EUROFER, namely of the DBTT shift toward high temperature due to the low irradiation temperature embrittlement, the target of the hereby reported activities is the development of much tougher alloys, to try to tolerate the embrittlement due to the low irradiation temperature. We report in this paper the work done to optimize the toughness of Eurofer 97, increasing the normalizing temperature and maintaining a small grain size using multiple normalizing treatments. We report also the mechanical behaviour of two 9Cr1WTa type alloys, produced and tested with the same aim to find alloys more resistant to embrittlement at low irradiation temperature. Keywords: EUROFER 97, RAFM steels, Microstructure, Heat treatment, Tensile, Charpy, KLST

The contribution of ENEA together with Rina-CSM to the Eurofusion programme “WPMAT-Advanced Seels” deals with the development of innovative RAFM steels able to withstand the critical temperatures typical of the different operational environments foreseen for the blanket of the first DEMO reactor. The optimization of the chemical composition and the Thermo Mechanical Treatment for these materials should be done according to the blanket operating temperatures that are related to two possible working conditions: the WCLL-BB (Water Cooled Lead Lithium Breeding Blanket) or the H(D)CLL-BB (Helium (Dual) Cooled Lead Lithium Breeding Blanket). On the one hand the “water-cooling” option implies a minimum irradiation temperature for the blanket material in the range of 280–350 °C. On the other hand, the “helium-cooled” and the “dual-coolant” solutions imply an operating temperature for the blanket material in the range of 650 °C. Therefore in the first case the target is the improvement of the toughness of the martensitic alloys; whilst concerning the second scenario the target is the development of more creep resistant martensitic steels, suitable to tolerate such a high operating temperature. In both the cases the Tungsten content plays a key role, both in terms of solid solution hardening and influence on the DBTT. Two alloys aimed at fulfilling the specifications for the two DEMO operating conditions, both with increased Tungsten content respect to Eurofer, have been produced and characterized. The mechanical properties of these two alloys are hereby reported and discussed.

Small-angle neutron scattering (SANS) and neutron diffraction have been utilized for micro-structural characterization of Eurofer97/2 heats submitted to thermo-mechanical treatments, with the aim to investigate macroscopic material volumes and to complete the local information provided by scanning electron microscopy. The measurements were carried out at MLZ in Garching, utilizing for SANS also a polarized neutron beam. The investigated samples had been submitted to austenitization and tempering at different temperatures, as well as to double austenitization and to “ausforming”, that is austenitization followed by hot rolling. For most of the examined treatments, nearly identical SANS cross-sections were measured, close to the one of Eurofer97/1. In the ausformed sample the nuclear SANS cross-section is also nearly identical to the other samples but the magnetic one is one order of magnitude higher. Furthermore, over a wide experimental interval its nuclear-magnetic interference, measured by polarized SANS, is of opposite sign with respect to the non-ausformed samples. Neutron diffraction measurements provided strong evidence that the origin of such effects is due to the presence of the non-magnetic austenite phase in the ausformed sample, with an estimated volume fraction of 0.17 ± 0.02; within the experimental resolution, it disappears after subsequent tempering.

One of the options currently taken into account for the realization of the first DEMO reactor is the “water-cooled blanket”. This option implies a minimum irradiation temperature for the blanket material in the range of 280–350 °C. In addition to the DBTT (Ductile to Brittle Transition Temperature) shift due to the DPA (displacement per atom) damage under irradiation, also the issue of the increased embrittlement due to He production must be taken into account. This issue appears even more detrimental and less manageable because the DBBT shift due to the Helium production does not saturate with the dose, as it results from previous works reported in literature. The experimental results and the difference in behaviour between ODS (Oxide Dispersion Strengthened Steels) RAFM (Reduced Activation Ferritic Martensitic) and other FM (Ferritic Martensitic) alloys (EM10, P91) showed that it is possible to improve the resistance to He embrittlement by both intra-granular precipitation of Y-Ti oxides and by decreasing the grain size at the same time. Nevertheless, anyway, the multiplication of the grain boundaries increases the dilution of He on grain surface, delaying the formation of He bubbles on grain boundaries and, therefore, the susceptibility to the He embrittlement. Several grain size reduction strategies have then been investigated on EUROFER both at the austenitization stage, on the PAGS (Prior Austenite Grain Size), and at the tempering stage, on the tempered martensite. The microstructural observations have been carried out by means of SEM (Scanning Electron Microscopy). Also the effect of grain size reduction on the toughness of the material will be taken into account; The DBTTs resulting from impact tests on KLST specimens will be shown. The outcomes of the microstructural observations, as well as the preliminary mechanical characterization (impact tests) will be discussed in this paper. Keywords: EUROFER 97, RAFM steels, Microstructure, Multiple normalization, Asymmetric rolling, Recrystallization, KLST

Among the options currently taken into account for the realization of the first DEMO reactor there are the “helium-cooled” and the “dual coolant” breeding blanket. Therefore the high temperature (650 °C) behavior of the proposed innovative martensitic alloys should be improved, namely the frame of the hereby reported activities is the development of martensitic alloys more resistant to creep, suitable to tolerate such a high operating temperature. In order to improve the high temperature mechanical properties, concerning the alloy design strategies, two alternative routes are proposed; the effect of Nitrogen and Tungsten increase are taken into account as well as the addition of carbo-nitride forming elements, like Vanadium, combined with the “ausforming” thermo-mechanical treatments. Two alloys have been designed and a special thermo-mechanical treatment on Eurofer 97-2 is proposed. The “ausforming” treatment, consisting in a sort of hot-working at a lower temperature with respect to the austenitization one after the austenitization stage, is aimed at the achievement of a beneficial dislocation “pinning” at high temperature due to carbide precipitation. Generally the improvement of tensile properties is associated to the hardening of the steel due to dislocation network and precipitation effects. This hardening is accompanied by a DBTT increase to markedly higher values with respect to Standard Eurofer. The proposed materials should be, in any case, at least room temperature ductile in order to undergo safe manufacturing and assembling processes. Therefore the issue of the DBTT increase has been taken into account by tuning the tempering temperature adequately. The two variations from chemical composition of Eurofer 97 have been casted and the thermo-mechanical treatments have been selected by means of SEM and hardness measurements to tune grain size and precipitation of carbides. The outcomes of the preliminary mechanical characterization (tensile, creep and impact tests) will be discussed in this paper. Keywords: EUROFER 97, RAFM steels, Thermo-mechanical treatment, Ausforming, Tensile, Creep, Charpy

The clinical and morphological picture of Merkel cell carcinoma (MCC) may be rather challenging; therefore, the immunohistochemical profile plays a relevant role in confirming the microscopic diagnosis. A panel of antibodies including cytokeratins 20, 7 and epithelial membrane antigen, and neuronspecific enolase is used in confirming the morphological diagnosis of MCC. The majority of MCCs express CK20 and are CK7-negative. Herein, we present a case of primary cutaneous neuroendocrine carcinoma with an atypical immunohistochemical pattern. A 83-years old woman presented with a painless plaque, red to violaceous in colour, located in the leg. The skin tumor was excided, formalin-fixed and paraffinembedded. Tissue sections were immunostained with a panel of antibodies routinely utilized in complex primary skin tumors for evidencing epithelial and neuroendocrine differentiation of tumor cells. The neuroendocrine differentiation of tumor cells was evidenced by their immunoreactivity for synaptophysin, chromograninA and neuron-specific enolase. Tumor cells also showed diffuse cytoplasmic staining for CK7. No immunoreactivity was detected for CK20 and thyroid transcription factor-1. Our data, together with previous rare reports of CK20-/CK7+ MCCs, lay stress on the importance of routinely utilizing a panel of antibodies in the differential diagnosis of complex primary carcinomas of the skin and may have important implications in expanding the differential diagnosis of skin tumors. In particular, caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of reactivity of tumor cells for CK20, favouring the wrong diagnosis of less aggressive skin tumors.

Chemical Vapour Infiltration (CVI) technique has been long used to produce carbon/carbon composites. The Pyrolytic Carbon (Py-C) matrix infiltrated by CVI could have different microstructures, i.e. Rough Laminar (RL), Smooth Laminar (SL) or Isotropic (ISO). These matrix microstructures, characterized by different properties, influence the mechanical behaviour of the obtained composites. Tailoring the process parameters, it is possible to direct the infiltration towards a specific Py-C type. However, the factors, influencing the production of a specific matrix microstructure, are numerous and interconnected, e.g. temperature, pressure, flow rates etc. Due to the complexity of the physical and chemical phenomena involved in CVI process, up to now it has not been possible to obtain a general correlation between CVI process parameters and Py–C microstructure. This study is aimed at investigating the relationship between infiltration temperature and the microstructure of obtained Py-C, for a pilot - sized CVI/CVD reactor. Fixing the other process parameters and varying only the temperature, from 1100°C to 1300°C, the Py-C infiltration was performed on fibrous preforms. Polarized light microscopy, with quantitative measurements of average extinction angle (Ae), and Raman spectroscopy were used to characterize the obtained Py-C microstructures.

The protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. The purpose of this study is to compare IMP3 immunostaining in squamous cellular skin tumor and determine whether IMP3 can aid in the differential diagnosis of these lesions. To our knowledge, IMP3 expression has not been investigated in skin squamous cell proliferations thus far. Immunohistochemical staining for IMP3 was performed on slides organized by samples from 67 patients, 34 with keratoacanthoma and 33 with primary squamous cell carcinoma (16 invasive and 17 in situ). The majority of our KAs (25/34) were negative for IMP-3 staining. The majority of SCCs (19/33) are positive for IMP3 staining. The percentage of IMP3 positive cells increases significantly in group SCC (p=0.0111), and in particular in the SCC in situ group (p=0.0021) with respect to the KA group. IMP3 intensity staining increases significantly in SCCs (p=0.0213), and particularly in SCCs (p=0.008) with respect to KA. Our data show that IMP3 expression is different in keratoacanthomas with respect to squamous cell carcinoma. IMP3 assessment and staining pattern, together with a careful histological study, can be useful in the differential diagnosis between KA e SCC.

C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intradermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing melanoma from melanocytic nevi, if we consider c-Kit expression in intraepidermal proliferating cells. The c-Kit expression in proliferating melanocytes in the dermis could help in the differential diagnosis between a superficial spreading melanoma (with dermis invasion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma.

The clinical and morphological picture of Merkel cell carcinoma (MCC) may be rather challenging; therefore, the immunohistochemical profile plays a relevant role in confirming the microscopic diagnosis. A panel of antibodies including cytokeratins 20, 7 and epithelial membrane antigen, and neuronspecific enolase is used in confirming the morphological diagnosis of MCC. The majority of MCCs express CK20 and are CK7-negative. Herein, we present a case of primary cutaneous neuroendocrine carcinoma with an atypical immunohistochemical pattern. A 83-years old woman presented with a painless plaque, red to violaceous in colour, located in the leg. The skin tumor was excided, formalin-fixed and paraffinembedded. Tissue sections were immunostained with a panel of antibodies routinely utilized in complex primary skin tumors for evidencing epithelial and neuroendocrine differentiation of tumor cells. The neuroendocrine differentiation of tumor cells was evidenced by their immunoreactivity for synaptophysin, chromograninA and neuron-specific enolase. Tumor cells also showed diffuse cytoplasmic staining for CK7. No immunoreactivity was detected for CK20 and thyroid transcription factor-1. Our data, together with previous rare reports of CK20-/CK7+ MCCs, lay stress on the importance of routinely utilizing a panel of antibodies in the differential diagnosis of complex primary carcinomas of the skin and may have important implications in expanding the differential diagnosis of skin tumors. In particular, caution should be taken in excluding the diagnosis of MCC only on the basis of the absence of reactivity of tumor cells for CK20, favouring the wrong diagnosis of less aggressive skin tumors.

Y-TZP ball heads were introduced into the market in 1985. Since then these components have had wide diffusion in hip replacements, due to their good mechanical performance and reliability. Namely, only a few papers were published up to year 2000 reporting failures of Y-TZP ball heads. The worldwide recall in August 2001 of some Y-TZP batches changed this situation. This paper analyse the material of a ceramic ball head that fractured in vivo 34 months after surgery. The retrieved fragments were submitted for visual inspection, fractographic analysis by optical microscopy, X-ray diffractometry, and FEG-SEM ceramography analysis. The results obtained show that the hydrothermal stability of the material had only a secondary role in the fracture. The literature reporting on failures of THR making use of Y-TZP ball heads is discussed. [ABSTRACT FROM AUTHOR]

Highly conductive and transparent NiOx films can be very useful as buffer layers for the optimization of the p-type contacts of optoelectronic devices. Thin NiOx films were fabricated by reactive radio frequency (RF) sputtering at room temperature starting from a Ni target. A systematic study of the influence of oxygen partial pressure, RF power and sputtering gas pressure on the films’ properties was carried out. The structural, microstructural, optical and electrical properties were affected differently by the sputtering parameters. Resistivity decreased by increasing the oxygen partial pressure and the sputtering total pressure and by decreasing the RF power, while transmittance increased by decreasing the oxygen partial pressure and by increasing the RF power and sputtering pressure. Minimum resistivity of 1.6 × 10−2 Ωcm and a visible transmittance of 40% were achieved for a film grown in a pure oxygen atmosphere, while a higher transmittance of 54% and a resistivity of ρ = 1.1 × 10−1 Ωcm were obtained for a film grown at 30% oxygen partial pressure. The trends of transmittance and resistivity as a function of the oxygen pressure during the sputtering process can be explained in terms of the amount of Ni3+ defects deduced by x-ray photoelectron spectroscopy (XPS) measurements. The full interpretation of the other results is less straightforward and highlights the relevance of the samples’ structural properties. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is a very common malignant skin tumor that rarely metastatizes, but is often locally aggressive. Several factors, like large size (more than 3 cm), exposure to ultraviolet rays, histological variants, level of infiltration and perineural or perivascular invasion, are associated with a more aggressive clinical course. These morphological features seem to be more determinant in mideface localized BCC, which frequently show a significantly higher recurrence rate. An immunohistochemical profile, characterized by reactivity of tumor cells for p53, Ki67 and alpha-SMA has been associated with a more aggressive behaviour in large BCCs. The aim of this study was to verify if also little (less than 3 cm) basal cell carcinomas can express immunohistochemical markers typical for an aggressive behaviour.

ATP7B is a copper transporting P-type ATPase, also known as Wilson disease protein, which plays a key role in copper distribution inside cells. Recent experimental data in cell culture have shown that ATP7B putatively serves a dual function in hepatocytes: when localized to the Golgi apparatus, it has a biosynthetic role, delivering copper atoms to apoceruloplasmin; when the hepatocytes are under copper stress, ATP7B translocates to the biliary pole to transport excess copper out of the cell and into the bile canaliculus for subsequent excretion from the body via the bile. The above data on ATP7B localization have been mainly obtained in tumor cell systems in vitro. The aim of the present work was to assess the presence and localization of the Wilson disease protein in the human liver. We tested immunoreactivity for ATP7B in 10 human liver biopsies, in which no significant pathological lesion was found using a polyclonal antiserum specific for ATP7B. In the normal liver, immunoreactivity for ATP7B was observed in hepatocytes and in biliary cells. In the hepatocytes, immunoreactivity for ATP7B was observed close to the plasma membrane, both at the sinusoidal and at the biliary pole. In the biliary cells, ATP7B was localized close to the cell membrane, mainly concentrated at the basal pole of the cells. The data suggest that, in human liver, ATP7B is localized to the plasma membrane of both hepatocytes and biliary epithelial cells.

Basal cell carcinoma (BCC) is a very common malignant skin tumor that rarely metastatizes, but is often locally aggressive. Several factors, like large size (more than 3 cm), exposure to ultraviolet rays, histological variants, level of infiltration and perineural or perivascular invasion, are associated with a more aggressive clinical course. These morphological features seem to be more determinant in mideface localized BCC, which frequently show a significantly higher recurrence rate. An immunohistochemical profile, characterized by reactivity of tumor cells for p53, Ki67 and alpha-SMA has been associated with a more aggressive behaviour in large BCCs. The aim of this study was to verify if also little (less than 3 cm) basal cell carcinomas can express immunohistochemical markers typical for an aggressive behaviour.

Silver thiolate nanoclusters (Ag NCs) show distinctive optical properties resulting from their hybrid nature, metallic and molecular, exhibiting size-, structure-, and surface-dependent photoluminescence, thus enabling the exploitation of Ag NCs for potential applications in nanobiotechnology, catalysis, and biomedicine. However, tailoring Ag NCs for specific applications requires achieving long-term stability and may involve modifying surface chemistry, fine-tuning ligand composition, or adding functional groups. In this study, we report the synthesis of novel Ag NCs using 2-ethanephenylthiolate (SR) as a ligand, highlight critical points addressing stability, and characterize their optical and structural properties. A preliminary electrical characterization revealed high anisotropy, well suited for potential use in electronics/sensing applications. We also present the synthesis and characterization of Ag NCs using 10-carboxylic 2-ol thiolate (SR'COOH) having a terminal carboxylic group for conjugation with amine-containing molecules. We present a preliminary assessment of its bioconjugation capability using bovine serum albumin as a model protein indicating its prospective application as a biomolecule support.

Background: Basal cell carcinoma (BCC) is the most common malignant skin tumor. Although it rarely evolves into a metastatic disease, BCC can lead to a significant morbidity due to local invasion. The risk of lesion recurrence depends on clinical and histopathological factors as described by the Nation Comprehensive Cancer Network (NCCN). The surgical excision margins have a well-known role: there is a close relationship between high recurrence rate of BCC and the tumor proximity to the surgical margins. Aim of our study was to assess whether there is a significative correlation between recurring BCC and volume ratio (VRb/t), defined as ratio between excisional biopsy volume and tumor volume, and if VRb/t is a useful parameter to assess the risk of recurrence of BCC., Methods: Retrospective case-control study in 80 patients with history of recurrent basal cell carcinoma of the nose (cases), and 43 patients with history of basal cell carcinoma of the nose with no evidence of relapse (controls) in the following 8 years., Results: Surgical excision margins, histological subtype, ulceration, depth of invasion and volume ratio (VRb/t) were evaluated in case and controls. The evaluation of VRb/t evidenced a significant difference between recurrent BCC and non-recurrent BCC. The mean values of VRb/t were 6.17 for cases and 11.94 for controls. The Binomial Logistic Regression has displayed, for values of VRb/t around 7, a probability of 75% to identify BCCs belonging to the recurrent group., Conclusions: Our data show a significant correlation between recurrent BCCs and VRb/t. VRb/t can help in the assessment of recurrence risk, used together with others prognostic factor. For values of VRb/t close to 7 it should be recommended a close follow-up to promptly identify a possible recurrence.

The role of human oncoviruses in melanoma has been poorly investigated. The aim of this study was to investigate the association between oncoviruses and melanomas searching for human papillomavirus (HPV), Epstein Barr virus (EBV), and human herpesvirus 8DNA in melanoma specimens. Formalin-fixed and paraffin-embedded tissue specimens of cutaneous, mucosal, and ocular melanomas (OM) were selected from the Pathology Departments of the Galliera Hospital (Genoa) and the University Hospitals of Turin and Cagliari. Cutaneous and mucosal nevi have been collected as controls. The oncoviruses search has been performed with different polymerase chain reaction reagent kits. Fifty-four melanomas (25 mucosal, 12 ocular, and 17 cutaneous) and 26 nevi (15 cutaneous and 11 mucosal) specimens were selected. The detection rate for one of the investigated oncoviruses was 17% in mucosal, 20% in ocular, and 0% in cutaneous melanomas (CMs). Despite the differences between groups seeming remarkable, there was no statistical significance (p > 0.5). Our data do not support a primary role of oncoviruses in melanoma carcinogenesis; however, the finding of HPV and EBV DNA in a considerable fraction of mucosal and OMs suggests that these viruses may act as cofactors in the development of extra-CMs., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Silver thiolate nanoclusters have been functionalized with a chiral amino alcohol ligand that has previously shown high catalytic efficiency in different asymmetric reactions. The as-developed nanostructured catalyst, which can be easily recovered by simple centrifugation, has been tested in the addition of nitromethane to aromatic aldehydes, showing the same catalytic activity as the homogeneous ligand. Moreover, it was reused for two further recycling cycles without loss of efficiency. To the best of our knowledge, this is the first example of silver nanoclusters employed as a support for chiral ligands for heterogeneous phase asymmetric catalysis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Primary localized cutaneous nodular amyloidosis (PLCNA) is a rare condition due to the plasma cell proliferation and skin deposition of immunoglobulin light chains, without systemic amyloidosis or hematological dyscrasias. The association with autoimmune connective tissue diseases has been reported, especially with Sjogren's syndrome, and in a few cases with systemic sclerosis. Herein, we describe three cases of PLCNA occurring in women with a diagnosis of limited cutaneous systemic sclerosis and review the literature on the topic to highlight a stereotypical presentation. Moreover, we support the usefulness of dermoscopy, characterized by a yellow-orange waxy pattern surrounded by telangiectasias, for a rapid and non-invasive diagnostic assessment. Thus, when asymptomatic nodules occur on lower limbs of women affected with limited systemic sclerosis, and dermoscopy identifies yellow-orange blotches, a diagnosis of PLCNA can be considered and further confirmed by histopathology. Monitoring for systemic amyloidosis development is advisable, although the risk of progression is considered very low.

Emergent pathogen as Purpureocillium lilacinum are becoming cause of morbidity and mortality in our population, especially in immunocompromised patients. We describe a case of hyalohyphomycosis in a diabetic man under systemic steroid treatment for a bullous pemphigoid. Treatment with different antimycotic drugs were ineffective and infection spread diffusely, leading to deterioration of general conditions and ultimately death. The aim of this article is to increase awareness of clinicians about this uncommon, but frequently fatal refractory mycotic infection.