Study of 13CR-4NI-(MO) (F6NM) steel grade heat treatment for maximum hardness control in industrial heats

The standard NACE MR0175 (ISO 15156) requires a maximum hardness value of 23 HRC for 13Cr-4Ni-(Mo) steel grade for sour service, requiring a double tempering heat treatment at temperature in the range 648–691°C for the first tempering and 593–621°C for the second tempering. Difficulties in limiting alloy hardness after the tempering of forged mechanical components (F6NM) are often faced. Variables affecting the thermal behavior of 13Cr-4Ni-(Mo) during single and double tempering treatments have been studied by means of transmission electron microscopy (TEM) observations, X-ray diffraction measurements, dilatometry, and thermo-mechanical simulations. It has been found that relatively low Ac1 temperatures in this alloy induce the formation of austenite phase above 600°C during tempering, and that the formed, reverted austenite tends to be unstable upon cooling, thus contributing to the increase of final hardness via transformation to virgin martensite. Therefore, it is necessary to increase the Ac1 temperature as much as possible to allow the tempering of martensite at the temperature range required by NACE without the detrimental formation of virgin martensite upon final cooling. Attempts to do so have been carried out by reducing both carbon (<0.02% C) and nitrogen (<100 ppm) levels. Results obtained herein show final hardness below NACE limits without an unacceptable loss of mechanical strength

Folgoration as an Example of Pathergy in a Patient Affected by Pyoderma Gangrenosum and Takayasu's Arteritis

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. Clinical manifestations of PG are characterized by destructive, necrotizing, and noninfective ulceration of the skin. 20–30% of cases are initiated and aggravated by minor trauma or surgery, a phenomenon named pathergy. PG is related to several autoimmune diseases including ulcerative colitis, Crohn's disease, rheumatoid arthritis, and monoclonal gammopathy. The association with Takayasu's arteritis (TA), a chronic inflammatory and stenotic disease of large and medium-sized arteries, is instead less common. We report a case of PG associated with TA that was induced by an accident with folgoration of the skin; in this case the folgoration can be considered as an exemple of Pathergy, that is, a characteristic feature of PG

Spesolimab in patients with flare of generalized pustular psoriasis: A multicentre case-series

Dear Editor,Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening, chronic inf lammatory disease character-ized by acute f lares of pustular eruptions that can be accom-panied by systemic inf lammation. GPP can be associated with chronic plaque psoriasi

Paradoxical psoriasis induced by Anti-TNFα treatment: Evaluation of disease-specific clinical and genetic markers

Paradoxical psoriasis (PP) may occur during treatment with anti-tumor necrosis factor-alpha (TNF-α) drugs in various chronic immune-mediated diseases, mainly inflammatory bowel diseases (IBD) and psoriasis. In this study, clinical and genetic characteristics of PP arising in IBD and psoriatic patients were investigated to identify disease-specific markers of the paradoxical effect. A total of 161 IBD and psoriatic patients treated with anti-TNF-α drugs were included in the study. Of these patients, 39 developed PP. All patients were characterized for the main clinical– pathologic characteristics and genotyped for six candidate single nucleotide polymorphisms (SNPs) selected for their possible role in PP susceptibility. In IBD patients, the onset of PP was associated with female sex, presence of comorbidities, and use of adalimumab. IBD patients with PP had a higher frequency of the TNF-α rs1799964 rare allele (p= 0.006) compared with cases without the paradoxical effect, and a lower frequency of the human leucocyte antigen (HLA)-Cw06 rs10484554 rare allele (p= 0.03) compared with psoriatic patients with PP. Overall, these findings point to specific clinical and genetic characteristics of IBD patients with PP and provide data showing that genetic variability may be related to the paradoxical effect of anti-TNF-α drugs with possible implications into clinical practice

Study of shock waves generation, hot electron production and role of parametric instabilities in an intensity regime relevant for the shock ignition

We present experimental results at intensities relevant to Shock Ignition obtained at the sub-ns Prague Asterix Laser System in 2012 . We studied shock waves produced by laser-matter interaction in presence of a pre-plasma. We used a first beam at 1ω (1315 nm) at 7 × 10 13 W/cm 2 to create a pre-plasma on the front side of the target and a second at 3ω (438 nm) at ∼ 10 16 W/cm 2 to create the shock wave. Multilayer targets composed of 25 (or 40 μm) of plastic (doped with Cl), 5 μm of Cu (for Kα diagnostics) and 20 μm of Al for shock measurement were used. We used X-ray spectroscopy of Cl to evaluate the plasma temperature, Kα imaging and spectroscopy to evaluate spatial and spectral properties of the fast electrons and a streak camera for shock breakout measurements. Parametric instabilities (Stimulated Raman Scattering, Stimulated Brillouin Scattering and Two Plasmon Decay) were studied by collecting the back scattered light and analysing its spectrum. Back scattered energy was measured with calorimeters. To evaluate the maximum pressure reached in our experiment we performed hydro simulations with CHIC and DUED codes. The maximum shock pressure generated in our experiment at the front side of the target during laser-interaction is 90 Mbar. The conversion efficiency into hot electrons was estimated to be of the order of ∼ 0.1% and their mean energy in the order ∼50 keV. Content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distributio

Effectiveness and safety of bimekizumab for the treatment of plaque psoriasis. a real-life multicenter study—IL PSO (Italian landscape psoriasis)

Introduction: Bimekizumab is a monoclonal antibody that targets Interleukin-17 A and F, approved for the treatment of moderate-to-severe plaque psoriasis. While bimekizumab has been evaluated in several phase-III clinical trials, real-world evidence is still very limited. Method: This multicenter retrospective study included patients affected by plaque psoriasis treated with bimekizumab from May 1, 2022 to April 30, 2023, at 19 Italian referral hospitals. Patients affected by moderate-to-severe plaque psoriasis eligible for systemic treatments were included. The effectiveness of bimekizumab was evaluated in terms of reduction in psoriasis area and severity index (PASI) compared with baseline at weeks 4 and 16. The main outcomes were the percentages of patients achieving an improvement of at least 75% (PASI75), 90% (PASI90) and 100% (PASI100) in PASI score. Results: The study included 237 patients who received at least one injection of bimekizumab. One hundred and seventy-one patients and 114 reached four and 16 weeks of follow-up, respectively. Complete skin clearance was achieved by 43.3% and 75.4% of patients at weeks 4 and 16, respectively. At week 16, 86.8% of patients reported no impact on their quality of life. At week 16, there were no significant differences between bio-naïve and bio-experienced patients in terms of PASI75, PASI90 and PASI100. The most commonly reported adverse events (AEs) were oral candidiasis (10.1%). No severe AEs or AEs leading to discontinuation were observed throughout the study. Conclusion: Our experience supports the effectiveness and tolerability of bimekizumab in a real-world setting with similar results compared with phase-III clinical trials

Microsatellite instability in thyroid tumours and tumour-like lesions

Fifty-one thyroid tumours and tumour-like lesions were analysed for instability at ten dinucleotide microsatellite loci and at two coding mononucleotide repeats within the transforming growth factor β (TGF-β) type II receptor (TβRII) and insulin-like growth factor II (IGF-II) receptor (IGFIIR) genes respectively. Microsatellite instability (MI) was detected in 11 out of 51 cases (21.5%), including six (11.7%) with MI at one or two loci and five (9.8%) with Ml at three or more loci (RER+ phenotype). No mutations in the TβRII and IGFIIR repeats were observed. The overall frequency of MI did not significantly vary in relation to age, gender, benign versus malignant status and tumour size. However, widespread MI was significantly more frequent in follicular adenomas and carcinomas than in papillary and Hürthle cell tumours: three out of nine tumours of follicular type (33.3%) resulted in replication error positive (RER+), versus 1 out of 29 papillary carcinomas (3.4%, P = 0.01), and zero out of eight Hürthle cell neoplasms. Regional lymph node metastases were present in five MI-negative primary cancers and resulted in MI-positive in two cases. © 1999 Cancer Research Campaig

x ray imaging of bio medical samples using laser plasma based x ray sources and lif detector

This contribution to ECPD2019 is dedicated to the memory of Anatoly Faenov. During a period of approximately thirteen years 1994–2006, Anatoly and his wife Tatiana Pikuz (simply "Tania" for friends), accepting the frequent invitations of the National Institute for Nuclear Physics (INFN) and of the Italian National Agency for New Technologies, Energy and Sustainable Economic Development (ENEA), cooperated with many Italian research laboratories dedicated to EUV and soft X-ray generation, spread in different towns (L'Aquila, Frascati, Milano, Padova, Pisa, Roma, etc.). In spite of the fact that they could stay in Italy only about one or two months per year, their activity was so intense that more than 50 peer- reviewed publications were generated from their experimental and theoretical work (just considering only the results obtained at L'Aquila and Tor Vergata—Rome Universities and at the ENEA Research Center of Frascati), without mentioning the cultural atmosphere that they stimulated in the field of Science and Humanity. The numerous experimental spectra obtained at ENEA by means of their spherically bent mica spectrometers, together with the corresponding theoretical simulations performed in Moscow, allowed to study the changing role of different excitations mechanisms for various plasma conditions, and to characterize at best the ENEA laser-plasma source for different applications: polychromatic and monochromatic micro-radiography of dried biological samples at 1 keV, soft X-ray contact microscopy (SXCM) of living cells in the water-window spectral region, spectroscopy of hollow atoms, etc. In this memorial paper, the main results of biological samples imaging on lithium fluoride (LiF) detectors, obtained with the ENEA and Tor Vergata University laser-plasma sources, are presented. In particular, the improvement of the micro-radiography and of the SXCM techniques obtained after moving from photoresist detectors and photographic films to lithium fluoride (LiF) detectors are discussed, for both dried and wet biological samples

IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network

Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field