Lifetime of the superconductive state in short and long Josephson junctions

We study the transient statistical properties of short and long Josephson junctions under the influence of thermal and correlated fluctuations. In particular, we investigate the lifetime of the superconductive metastable state finding the presence of noise induced phenomena. For short Josephson junctions we investigate the lifetime as a function both of the frequency of the current driving signal and the noise intensity and we find how these noise-induced effects are modified by the presence of a correlated noise source. For long Josephson junctions we integrate numerically the sine-Gordon equation calculating the lifetime as a function of the length of the junction both for inhomogeneous and homogeneous bias current distributions. We obtain a nonmonotonic behavior of the lifetime as a function of the frequency of the current driving signal and the correlation time of the noise. Moreover we find two maxima in the nonmonotonic behaviour of the mean escape time as a function of the correlated noise intensity.Comment: 12 pages, 9 figure

Moral Mediators in the Metaverse: Exploring Artificial Morality through a Talking Cricket Paradigm

As technological innovations continue to shape our social interactions, the Metaverse introduces immersive experiences that reflect real-life practices, accessible by users through their avatars. However, these interactions also bring forth potential negative aspects, including discrimination and cyberbullying. While current automatic detection systems exist, educating users on appropriate behaviour remains crucial. Leveraging recent advancements in Artificial Intelligence, the paper focuses on creating virtual AI-controlled moral agents within the Metaverse to guide users in dealing with moral dilemmas. The research aims to understand how such agents impact users' perceptions and behaviours in ethically challenging virtual environments

Mannheim Peritonitis Index (MPI) and elderly population: Prognostic evaluation in acute secondary peritonitis

Introduction. Acute Secondary Peritonitis due to abdominal visceral perforation is characterized by high mortality and morbidity risk. Risk stratification allows prognosis prediction to adopt the best surgical treatment and clinical care support therapy. In Western countries elderly people represent a significant percentage of population Aim. Evaluation of Mannheim Peritonitis Index (MPI) and consideration upon old people. Patients and methods. Retrospective study on 104 patients admitted and operated for \ue2\u80\u9cAcute Secondary Peritonitis due to visceral perforation\ue2\u80\u9d. MPI was scored. In our study we want to demonstrate efficacy of MPI and the possibility to consider older age an independent prognostic factor. Results. Mortality was 25.96%. Greatest sensitivity and specificity for the MPI score as a predictor of mortality was at the score of 20. MPI score of 22. Patients with MPI score 17-21 had 0.46 times lower risk of mortality compared to patients with MPI score >21. In the group of patients with MPI score of >20 the mortality rate was 48.5% for patients older than 80 years old and 12.1% for younger patients (p < 0.005); in the group with MPI score of < 20 mortality rate was respectively 8.4% and 1.4% (p < 0.005). Discussion and conclusions. Data confirm the accuracy of the test. MPI score and age over 80 years old resulted independent predictors of mortality at multivariate analysis

Potential uses of olive oil secoiridoids for the prevention and treatment of cancer: A narrative review of preclinical studies

The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and char-acterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed

Gut-dependent inflammation and alterations of the intestinal microbiota in individuals with perinatal HIV exposure and different HIV serostatus

Objective: HIV-exposed infected (HEI) and uninfected (HEU) children represent the two possible outcomes of maternal HIV infection. Modifications of the intestinal microbiome have been linked to clinical vulnerability in both settings, yet whether HEI and HEU differ in terms of gut impairment and peripheral inflammation/activation is unknown. Design: We performed a cross-sectional, pilot study on fecal and plasma microbiome as well as plasma markers of gut damage, microbial translocation, inflammation and immune activation in HIV-infected and uninfected children born from an HIV-infected mother. Methods: Fecal and plasma microbiome were determined by means of 16S rDNA amplification with subsequent qPCR quantification. Plasma markers were quantified via ELISA. Results: Forty-seven HEI and 33 HEU children were consecutively enrolled. The two groups displayed differences in fecal beta-diversity and relative abundance, yet similar microbiome profiles in plasma as well as comparable gut damage and microbial translocation. In contrast, monocyte activation (sCD14) and systemic inflammation (IL-6) were significantly higher in HEI than HEU. Conclusion: In the setting of perinatal HIV infection, enduring immune activation and inflammation do not appear to be linked to alterations within the gut. Given that markers of activation and inflammation are independent predictors of HIV disease progression, future studies are needed to understand the underlying mechanisms of such processes and elaborate adjuvant therapies to reduce the clinical risk in individuals with perinatal HIV infection

HDAC6 mediates the acetylation of TRIM50

The E3 Ubiquitin ligase TRIM50 promotes the formation and clearance of aggresome-associated polyubiquitinated proteins through HDAC6 interaction, a tubulin specific deacetylase that regulates microtubule-dependent aggresome formation. In this report we showed that TRIM50 is a target of HDAC6 with Lys-372 as a critical residue for acetylation. We identified p300 and PCAF as two TRIM50 acetyltransferases and we further showed that a balance between ubiquitination and acetylation regulates TRIM50 degradatio

The two-step treatment for giant hepatic hemangiomas

The aim of the present study is to analyze the feasibility and the impact of a two-step approach in the treatment of giant hemangiomas (GH) i.e., exceeding 10 cm in maximum diameter, con-sisting of transarterial embolization (TAE) followed by laparoscopic liver resection (LLR). Ten patients with 11 GH were treated with TAE and subsequent LLR between 2017 and 2020 (Group A). A matched cohort of 10 patients with GH treated with upfront LLR between 2014 and 2017 was identified for comparison (Group B). Data were analyzed regarding intraoperative and postoperative outcomes, including successful completion of LLR, morbidity, and mortality. Successful microparticle emboliza-tion of the GH-feeding arteries was performed in all patients in group A. In three cases a liquid embolic agent (Squid-18) was also injected to obtain complete embolization. No complications were observed after TAE. Successful surgery was performed after a mean time interval of 2.2 days from TAE without any case of conversion to laparotomy. Statistically significant differences between group A and group B were found in intraoperative blood loss (250 \ub1 200 vs. 400 \ub1 300 mL, p = 0.039), operative time (245 \ub1 60 vs. 420 \ub1 60 min, p = 0.027), and length of stay (5 \ub1 1 vs. 8 \ub1 2 days, p = 0.046). Our data suggest that two-step TAE + LLR might be a safe and effective option for surgical treatment of GH &gt;10 cm

Consequence of the tumor-associated conversion to cyclin D1b.

Clinical evidence suggests that cyclin D1b, a variant of cyclin D1, is associated with tumor progression and poor outcome. However, the underlying molecular basis was unknown. Here, novel models were created to generate a genetic switch from cyclin D1 to cyclin D1b. Extensive analyses uncovered overlapping but non-redundant functions of cyclin D1b compared to cyclin D1 on developmental phenotypes, and illustrated the importance of the transcriptional regulatory functions of cyclin D1b in vivo. Data obtained identify cyclin D1b as an oncogene, wherein cyclin D1b expression under the endogenous promoter induced cellular transformation and further cooperated with known oncogenes to promote tumor growth in vivo. Further molecular interrogation uncovered unexpected links between cyclin D1b and the DNA damage/PARP1 regulatory networks, which could be exploited to suppress cyclin D1b-driven tumors. Collectively, these data are the first to define the consequence of cyclin D1b expression on normal cellular function, present evidence for cyclin D1b as an oncogene, and provide pre-clinical evidence of effective methods to thwart growth of cells dependent upon this oncogenic variant

Spontaneous Isomerization of Long-Lived Proteins Provides a Molecular Mechanism for the Lysosomal Failure Observed in Alzheimer's Disease.

Proteinaceous aggregation is a well-known observable in Alzheimer's disease (AD), but failure and storage of lysosomal bodies within neurons is equally ubiquitous and actually precedes bulk accumulation of extracellular amyloid plaque. In fact, AD shares many similarities with certain lysosomal storage disorders though establishing a biochemical connection has proven difficult. Herein, we demonstrate that isomerization and epimerization, which are spontaneous chemical modifications that occur in long-lived proteins, prevent digestion by the proteases in the lysosome (namely, the cathepsins). For example, isomerization of aspartic acid into l-isoAsp prevents digestion of the N-terminal portion of Aβ by cathepsin L, one of the most aggressive lysosomal proteases. Similar results were obtained after examination of various target peptides with a full series of cathepsins, including endo-, amino-, and carboxy-peptidases. In all cases peptide fragments too long for transporter recognition or release from the lysosome persisted after treatment, providing a mechanism for eventual lysosomal storage and bridging the gap between AD and lysosomal storage disorders. Additional experiments with microglial cells confirmed that isomerization disrupts proteolysis in active lysosomes. These results are easily rationalized in terms of protease active sites, which are engineered to precisely orient the peptide backbone and cannot accommodate the backbone shift caused by isoaspartic acid or side chain dislocation resulting from epimerization. Although Aβ is known to be isomerized and epimerized in plaques present in AD brains, we further establish that the rates of modification for aspartic acid in positions 1 and 7 are fast and could accrue prior to plaque formation. Spontaneous chemistry can therefore provide modified substrates capable of inducing gradual lysosomal failure, which may play an important role in the cascade of events leading to the disrupted proteostasis, amyloid formation, and tauopathies associated with AD