Modeling and simulation of a digital control design approach for power supply systems

Electronic designers need to model and simulate system features as close as possible to its effective behaviour. Moreover, today, electronics systems are often composed of mixed analog and digital components. The increasing complexity has led to the use of different simulation softwares, each one specific for a particular level of abstraction: mathematical, circuital, behavioural, etc. In order to simulate the entire system these softwares should work together: co-simulation is necessary for digitally controlled power electronics systems. In this paper, the modeling of a digitally controlled switching power supply system using MATLAB/Simulink, ALDEC Active-HDL and Powersys PSIM is presented. The power converter is modelled in PSIM, the digital control is described in VHDL by using Active-HDL, and the complete system is simulated in MATLAB/Simulink environment. This design approach presents all the advantages of each used software and all its features will be discussed. The comparison between simulation and experimental results of the digitally controlled step-down converter prototype are reported

Reactions to treatment debriefing among the participants of a placebo controlled trial

BACKGROUND: A significant proportion of trial participants respond to placebos for a variety of conditions. Despite the common conduct of these trials and the strong emphasis placed on informed consent, very little is known about informing participants about their individual treatment allocation at trial closure. This study aims to address this gap in the literature by exploring treatment beliefs and reactions to feedback about treatment allocation in the participants of a placebo-controlled randomized clinical trial (RCT). METHODS: Survey of trial participants using a semi-structured questionnaire including close and open-ended questions administered as telephone interviews and postal questionnaires. Trial participants were enrolled in a double-blind placebo-controlled RCT evaluating the effectiveness of corticosteroid for heel pain (ISRCTN36539116). The trial had closed and participants remained blind to treatment allocation. We assessed treatment expectations, the percentage of participants who wanted to be informed about their treatment allocation, their ability to guess and reactions to debriefing. RESULTS: Forty-six (73%) contactable participants responded to our survey. Forty-two were eligible (four participants with bilateral disease were excluded as they had received both treatments). Most (79%) participants did not have any expectations prior to receiving treatment, but many 'hoped' that something would help. Reasons for not having high expectations included the experimental nature of their care and possibility that they may get a placebo. Participants were hopeful because their pain was so severe and because they trusted the staff and services. Most (83%) wanted to be informed about their treatment allocation and study results. Over half (55%) said they could not guess which treatment they had been randomized to, and many of those who attempted a guess were incorrect. Reactions to treatment debriefing were generally positive, including in placebo responders. CONCLUSION: Our study suggests that most trial participants want to be informed about their treatment allocation and trial results. Further research is required to develop measure of hope and expectancy and to rigorously evaluate the effects of debriefing prospectively

Fine characterization of immunological mechanisms mediated by the major allergens of Parietaria judaica and hypoallergenic hybrid, rPjEDcys

Purpose: Allergy is a hypersensitivity disease IgE-mediated, affecting more than 25% of the population. The symptoms of IgE-mediated allergies reactions can be transiently ameliorated pharmacologically, but the only curative treatment of allergies is Allergen-Specific Immunotherapy (SIT). Recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during SIT. Parietaria judaica (Pj) pollen contains two major allergens belonging to the family of Lipid Tranfer Proteins (Par j 1 and Par j 2). By means of DNA recombinant technology, a hybrid hypoallergenic (PjEDcys), expressing disulphide bond variants of Par j 1 and Par j 2, was generated. The aim of this research project is to study the immunological mechanisms activated by the major allergens of Parietaria judaica, Par j 1 and Par j 2, and hypoallergenic hybrid rPjEDcys. Moreover, the project I am involved is trying to address the question whether this engineered hypoallergenic derivative can be a potential products for safer Allergen Specific Immunotherapy (SIT). Methods: Par j 1, Par j 2 and PjEDcys were produced as recombinant proteins. Human Peripheral Blood Mononuclear Cell (PBMC) from P. judaica allergic patients were stimulated in vitro with wild-type recombinant allergens and hybrid. PBMC proliferation assay, cytokine secretion assay, magnetic cell sorting of different subset of regulatory T cells, multiparametric flow cytometric analysis and molecular characterization using Real Time-PCR on sorted cells allow to study the biological properties of wild-type recombinant allergens and hybrid hypoallergenic derivate. Results: In vitro analysis suggested that PjEDcys have a reduced allergenity and maintained T cells reactivity. PBMC of P. judaica allergic patients stimulated in vitro with the hybrid and the wild-type recombinant allergens scored a percentage of proliferating CD4+ and CD56+ cell higher than unstimulated sample. Consistent with these data, cytokine secretion assay on CD4+ cells demonstrated that PBMC stimulation with rPjEDcys showed a percentage of IL-5 and IL-13 secreting T CD4+ cells lower than the wild-type allergens. Both rPjEDcys and wild-type stimulation promote the secretion of IFN- \u3b3 and IL-10 by T CD4+ cells. Finally whit the aim to study which subset of regulatory cells respond to wild-tipe allergens and hypoallergenic hybrid new experiment are setting. Discussion: In this experimental setting, the use of the major allergens of Pj and the hybrid polypeptides, rPjEDcys allows me to study the immunological mechanisms activated by the two different antigen stimulation and to investigate differences between the wild-type allergen and the hypoallergenic mutant rPjEDcys. Our data showed that CD4+ cells are clearly the predominant cell population proliferating in response to mixture of Par j 1 and Par j 2 allergens. The hypoallergenic derivate rPjEDcys retain the ability to stimulate CD4+ cells proliferation like the mixture of allergens (rPar j 1 and rPar j 2). Moreover these results highlighted a particular interesting datum; the mixture of allergens and the rPjEDcys hybrid showed the ability to stimulate an innate immune response, inducing CD56+ cells proliferative response. Cytokine secretion assay demonstrate that rPjEDcys reduce the secretion of IL-5 and IL-13, Th2 cytokines with a critical role in the development of allergy, compared to wild-type allergens. This may reflect the different biological function exerted by rPjEDcys. Conclusion: Collectivelly, our findings demonstrate that PjEDcys show a reduced allergenicity but maintained its immunogenicity and maybe it is also capable to regulate and redirect the immune response. These results suggest that PjEDcys represent a useful approach for immunotherapy of allergic disease

Secondary Cosmic Ray Nuclei from Supernova Remnants and Constraints to the Propagation Parameters

The secondary-to-primary B/C ratio is widely used to study the cosmic ray (CR) propagation processes in the Galaxy. It is usually assumed that secondary nuclei such as Li-Be-B are entirely generated by collisions of heavier CR nuclei with the interstellar medium (ISM). We study the CR propagation under a scenario where secondary nuclei can also be produced or accelerated from galactic sources. We consider the processes of hadronic interactions inside supernova remnants (SNRs) and re-acceleration of background CRs in strong shocks. Thus, we investigate their impact in the propagation parameter determination within present and future data. The spectra of Li-Be-B nuclei emitted from SNRs are harder than those due to CR collisions with the ISM. The secondary-to-primary ratios flatten significantly at ~TeV/n energies, both from spallation and re-acceleration in the sources. The two mechanisms are complementary to each other and depend on the properties of the local ISM around the expanding remnants. The secondary production in SNRs is significant for dense background media, n ~1 cm^-3, while the amount of re-accelerated CRs is relevant for SNRs expanding into rarefied media, n ~0.1 cm-3. Due to these effects, the the diffusion parameter 'delta' may be misunderstood by a factor of ~5-15%. Our estimations indicate that an experiment of the AMS-02 caliber can constrain the key propagation parameters while breaking the source-transport degeneracy, for a wide class of B/C-consistent models. Given the precision of the data expected from on-going experiments, the SNR production/acceleration of secondary nuclei should be considered, if any, to prevent a possible mis-determination of the CR transport parameters.Comment: 13 pages, 9 figures; matches the published versio

Study of uptake mechanisms of halloysite nanotubes in different cell lines

Purpose: Halloysite nanotubes (HNTs) are a natural aluminosilicate clay with a chemical formula of Al2Si2O5(OH)4×nH2O and a hollow tubular structure. Due to their peculiar structure, HNTs can play an important role as a drug carrier system. Currently, the mechanism by which HNTs are internalized into living cells, and what is the transport pathway, is still unclear. Therefore, this study aimed at establishing the in vitro mechanism by which halloysite nanotubes could be internalized, using phagocytic and non-phagocytic cell lines as models. Methods: The HNT/CURBO hybrid system, where a fluorescent probe (CURBO) is confined in the HNT lumen, has been used as a model to study the transport pathway mechanisms of HNTs. The cytocompatibility of HNT/CURBO on cell lines model was investigated by MTS assay. In order to identify the internalization pathway involved in the cellular uptake, we performed various endocytosis-inhibiting studies, and we used fluorescence microscopy to verify the nanomaterial internalization by cells. We evaluated the haemolytic effect of HNT/CURBO placed in contact with human red blood cells (HRBCs), by reading the absorbance value of the supernatant at 570 nm. Results: The HNT/CURBO is highly biocompatible and does not have an appreciable haemolytic effect. The results of the inhibition tests have shown that the internalization process of nanotubes occurs in an energy-dependent manner in both the investigated cell lines, although they have different characteristics. In particular, in non-phagocytic cells, clathrin-dependent and independent endocytosis are involved. In phagocytic cells, in addition to phagocytosis and clathrin-dependent endocytosis, microtubules also participate in the halloysite cellular trafficking. Upon internalization by cells, HNT/CURBO is localized in the cytoplasmic area, particularly in the perinuclear region. Conclusion: Understanding the cellular transport pathways of HNTs can help in the rational design of novel drug delivery systems and can be of great value for their applications in biotechnology

Hybrid supramolecular gels of Fmoc-F/halloysite nanotubes: systems for sustained release of camptothecin

Supramolecular gel hybrids obtained by self-assembly of Fmoc-L-phenylalanine (Fmoc-F) in the presence of functionalized halloysite nanotubes (f-HNT) were obtained in biocompatible solvents and employed as carriers for the delivery of camptothecin (CPT) molecules. The synthesis of the new f-HNT material as well as its characterization are described. The properties of the hybrid hydrogels and organogels were analyzed by several techniques. The presence of small amounts of f-HNT allows good dispersion of the tubes and the subsequent formation of homogeneous gels. The experimental results show that f-HNT functions only as an additive in the hybrid gels and does not demonstrate gelator behavior. The in vitro kinetic release from both f-HNT/CPT and Fmoc-F/f-HNT/CPT was studied in media that imitates physiological conditions, and the factors controlling the release process were determined and discussed. Furthermore, the antiproliferative in vitro activities of the gels were evaluated towards human cervical cancer HeLa cells. A comparison of data collected in both systems shows the synergistic action of f-HNT and the gel matrix in controlling the release of CPT in the media and maintaining the drug in its active form. Finally, a comparison with pristine HNT is also reported. This study suggests a suitable strategy to obtain two-component gel hybrids based on nanocarriers with controlled drug carrier capacity for biomedical applications

Dark Matter detection via lepton cosmic rays

Recent observations of lepton cosmic rays, coming from the PAMELA and FERMI experiments, have pushed our understanding of the interstellar medium and cosmic rays sources to unprecedented levels. The imprint of dark matter on lepton cosmic rays is the most exciting explanation of both PAMELA's positron excess and FERMI's total flux of electrons. Alternatively, supernovae are astrophysical objects with the same potential to explain these observations. In this work, we present an updated study of the astrophysical sources of lepton cosmic rays and the possible trace of a dark matter signal on the positron excess and total flux of electrons.Comment: 6 pages and 3 figures. Proceedings for PASCOS 2010, Valencia, Spai

A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19

Inflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorticoid receptor and is expressed in the liver of patients with hepatic cirrhosis and hepatocellular carcinoma (HCC). Furthermore, we have quantified the gene expression level of p65 and p65 iso5 in the PBMC of patients affected by SARS-CoV-2 disease. The results showed that in these patients the p65 and p65 iso5 mRNA levels are higher than in healthy subjects. The ability of p65 iso5 to bind dexamethasone and the regulation of the glucocorticoid (GC) response in the opposite way of the wild type improves our knowledge and understanding of the anti-inflammatory response and identifies it as a new therapeutic target to control inflammation and related diseases