Identification of bolted joint properties through substructure decoupling

Substructure decoupling techniques, defined in the frame of Frequency Based Substructuring, allow to identify the dynamic behaviour of a structural subsystem starting from the known dynamics of the coupled system and from information about the remaining components. The problem of joint identification can be approached in the substructuring framework by decoupling jointed substructures from the assembled system. In this case, information about the coupling DoFs of the assembled structure is necessary and this could be a problem if the interface is inaccessible for measurements. Expansion techniques can be used to obtain the dynamics on inaccessible (interface) DoFs starting from accessible (internal) DoFs. A promising technique is the System Equivalent Model Mixing (SEMM) that combines numerical and experimental models of the same component to obtain a hybrid model. This technique has been already used in an iterative coupling–decoupling procedure to identify the linear dynamic behaviour of a joint, with a Virtual Point description of the interface. In this work, a similar identification procedure is applied to the Brake Reus Beam benchmark to identify the linear dynamic behaviour of a three bolted connection at low levels of excitation. The joint is considered as a third independent substructure that accounts for the mass and stiffness properties of the three bolts, thus avoiding singularity in the decoupling process. Instead of using the Virtual Point Transformation, the interface is modelled by performing a modal condensation on remote points allowing deformation of the connecting surfaces between subcomponents. The purpose of the study is to highlight numerical and ill-conditioning problems that may arise in this kind of identification

Proof-of-Concept Study on the Use of Tangerine-Derived Nanovesicles as siRNA Delivery Vehicles toward Colorectal Cancer Cell Line SW480

In the last years, the field of nanomedicine and drug delivery has grown exponentially, providing new platforms to carry therapeutic agents into the target sites. Extracellular vesicles (EVs) are ready-to-use, biocompatible, and non-toxic nanoparticles that are revolutionizing the field of drug delivery. EVs are involved in cell-cell communication and mediate many physiological and pathological processes by transferring their bioactive cargo to target cells. Recently, nanovesicles from plants (PDNVs) are raising the interest of the scientific community due to their high yield and biocompatibility. This study aims to evaluate whether PDNVs may be used as drug delivery systems. We isolated and characterized nanovesicles from tangerine juice (TNVs) that were comparable to mammalian EVs in size and morphology. TNVs carry the traditional EV marker HSP70 and, as demonstrated by metabolomic analysis, contain flavonoids, organic acids, and limonoids. TNVs were loaded with DDHD1-siRNA through electroporation, obtaining a loading efficiency of 13%. We found that the DDHD1-siRNA complex TNVs were able to deliver DDHD1-siRNA to human colorectal cancer cells, inhibiting the target expression by about 60%. This study represents a proof of concept for the use of PDNVs as vehicles of RNA interference (RNAi) toward mammalian cells

Usefulness of Stress Echocardiography in the Management of Patients Treated with Anticancer Drugs

In recent years, the survival of patients with cancer has improved thanks to advances in antineoplastic therapeutic protocols. This has led to an increasing burden of cardiovascular complications related to cancer treatment. Therefore, a new branch of cardiology has been created, ``cardio-oncology,'' with the aims of preventing cardiovascular complications related to antineoplastic treatment, achieving early diagnosis and treatment of any complications, and allowing completion of the expected antineoplastic treatment. Stress echocardiography has a pivotal role in achieving a timely diagnosis of coronary artery disease and thus is the best management approach in this clinical setting. Atherosclerotic processes can be exacerbated by both chemotherapy and chest irradiation in patients with cancer, even several years after anticancer treatment completion. Moreover, stress echocardiography has many other potential applications, such as in the evaluation of subclinical left ventricular dysfunction and contractile reserve in patients treated with anticancer drugs that have the potential to induce myocardial damage, as well as evaluating valve disease. The objective of this review is to delineate the role of stress echocardiography in cardio-oncology

Humoral and cellular response following vaccination with the BNT162b2 mRNA COVID-19 vaccine in patients affected by primary immunodeficiencies

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells