Enhancing the accuracy of engine calibration through a computer aided calibration algorithm

Abstract This paper addresses a novel Computer Aided Calibration software developed by the authors to overcome a critical issue of the traditional calibration process: improve the calibration accuracy. The algorithm includes some innovative features aimed at error minimization through a complete parametric analysis of a target ECU functions. Therefore, it is possible to assess if further quantities that are not considered as calibration parameters within the current ECU function model actually affect the quantity estimated by the function itself. If so, a more accurate physical model can be implemented within the ECU function to increase the accuracy of the calibration process

Effects of Oestrogen on MicroRNA Expression in Hormone-Responsive Breast Cancer Cells

Oestrogen receptor alpha (ERα) is a ligand-dependent transcription factor that mediates oestrogen effects in hormone-responsive cells. Following oestrogenic activation, ERα directly regulates the transcription of target genes via DNA binding. MicroRNAs (miRNAs) represent a class of small noncoding RNAs that function as negative regulators of protein-coding gene expression. They are found aberrantly expressed or mutated in cancer, suggesting their crucial role as either oncogenes or tumour suppressor genes. Here, we analysed changes in miRNA expression in response to oestrogen in hormone-responsive breast cancer MCF-7 and ZR-75.1 cells by microarray-mediated expression profiling. This led to the identification of 172 miRNAs up- or down-regulated by ERα in response to 17β-oestradiol, of which 52 are similarly regulated by the hormone in the two cell models investigated. To identify mechanisms by which ERα exerts its effects on oestrogen-responsive miRNA genes, the oestrogen-dependent miRNA expression profiles were integrated with global in vivo ERα binding site mapping in the genome by ChIP-Seq. In addition, data from miRNA and messenger RNA (mRNA) expression profiles obtained under identical experimental conditions were compared to identify relevant miRNA target transcripts. Results show that miRNAs modulated by ERα represent a novel genomic pathway to impact oestrogen-dependent processes that affect hormone-responsive breast cancer cell behaviour. MiRNome analysis in tumour tissues from breast cancer patients confirmed a strong association between expression of these small RNAs and clinical outcome of the disease, although this appears to involve only marginally the oestrogen-regulated miRNAs identified in this study

Direct regulation of microRNA biogenesis and expression by estrogen receptor beta in hormone-responsive breast cancer.

Estrogen effects on mammary epithelial and breast cancer (BC) cells are mediated by the nuclear receptors ERα and ERβ, transcription factors that display functional antagonism with each other, with ERβ acting as oncosuppressor and interfering with the effects of ERα on cell proliferation, tumor promotion and progression. Indeed, hormone-responsive, ERα+ BC cells often lack ERβ, which when present associates with a less aggressive clinical phenotype of the disease. Recent evidences point to a significant role of microRNAs (miRNAs) in BC, where specific miRNA expression profiles associate with distinct clinical and biological phenotypes of the lesion. Considering the possibility that ERβ might influence BC cell behavior via miRNAs, we compared miRNome expression in ERβ+ vs ERβ- hormone-responsive BC cells and found a widespread effect of this ER subtype on the expression pattern of these non-coding RNAs. More importantly, the expression pattern of 67 miRNAs, including 10 regulated by ERβ in BC cells, clearly distinguishes ERβ+, node-negative, from ERβ-, metastatic, mammary tumors. Molecular dissection of miRNA biogenesis revealed multiple mechanisms for direct regulation of this process by ERβ+ in BC cell nuclei. In particular, ERβ downregulates miR-30a by binding to two specific sites proximal to the gene and thereby inhibiting pri-miR synthesis. On the other hand, the receptor promotes miR-23b, -27b and 24-1 accumulation in the cell by binding in close proximity of the corresponding gene cluster and preventing in situ the inhibitory effects of ERα on pri-miR maturation by the p68/DDX5-Drosha microprocessor complex. These results indicate that cell autonomous regulation of miRNA expression is part of the mechanism of action of ERβ in BC cells and could contribute to establishment or maintenance of a less aggressive tumor phenotype mediated by this nuclear receptor

Design and validation of a human brain endothelial microvessel-on-a-chip open microfluidic model enabling advanced optical imaging

We describe here the design and implementation of an in vitro microvascular open model system using human brain microvascular endothelial cells. The design has several advantages over other traditional closed microfluidic platforms: (1) it enables controlled unidirectional flow of media at physiological rates to support vascular function, (2) it allows for very small volumes which makes the device ideal for studies involving biotherapeutics, (3) it is amenable for multiple high resolution imaging modalities such as transmission electron microscopy (TEM), 3D live fluorescence imaging using traditional spinning disk confocal microscopy, and advanced lattice light sheet microscopy (LLSM). Importantly, we miniaturized the design, so it can fit within the physical constraints of LLSM, with the objective to study physiology in live cells at subcellular level. We validated barrier function of our brain microvessel-on-a-chip by measuring permeability of fluorescent dextran and a human monoclonal antibody. One potential application is to investigate mechanisms of transcytosis across the brain microvessel-like barrier of fluorescently-tagged biologics, viruses or nanoparticles

Dupilumab in the treatment of severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP): A multicentric observational Phase IV real-life study (DUPIREAL)

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with significant morbidity and reduced health-related quality of life. Findings from clinical trials have demonstrated the effectiveness of dupilumab in CRSwNP, although real-world evidence is still limited. Methods This Phase IV real-life, observational, multicenter study assessed the effectiveness and safety of dupilumab in patients with severe uncontrolled CRSwNP (n = 648) over the first year of treatment. We collected data at baseline and after 1, 3, 6, 9, and 12 months of follow-up. We focused on nasal polyps score (NPS), symptoms, and olfactory function. We stratified outcomes by comorbidities, previous surgery, and adherence to intranasal corticosteroids, and examined the success rates based on current guidelines, as well as potential predictors of response at each timepoint. Results We observed a significant decrease in NPS from a median value of 6 (IQR 5–6) at baseline to 1.0 (IQR 0.0–2.0) at 12 months (p < .001), and a significant decrease in Sino-Nasal Outcomes Test-22 (SNOT-22) from a median score of 58 (IQR 49–70) at baseline to 11 (IQR 6–21; p < .001) at 12 months. Sniffin' Sticks scores showed a significant increase over 12 months (p < .001) compared to baseline. The results were unaffected by concomitant diseases, number of previous surgeries, and adherence to topical steroids, except for minor differences in rapidity of action. An excellent-moderate response was observed in 96.9% of patients at 12 months based on EPOS 2020 criteria. Conclusions Our findings from this large-scale real-life study support the effectiveness of dupilumab as an add-on therapy in patients with severe uncontrolled CRSwNP in reducing polyp size and improving the quality of life, severity of symptoms, nasal congestion, and smell

Engine Valvetrain Lift Prediction Using a Physic-based Model for The Electronic Control Unit Calibration

The electronic control has an increasingly important role in the evolution of the internal combustion engine (ICE) and the vehicle. Research in the automotive sector, in this historical period, is dictated by three main guidelines: reducing polluting emissions and fuel consumption while maintaining high performance. The Electronic Control Unit (ECU) has made it possible, complicating the engine both in terms of architecture and in terms of strategies, controlling, through simplified functions, physical phenomena in an ever more precise way. The ECU functions are experimentally calibrated, reducing the error between the quantity estimated by the function and the experimental quantity over the entire operating range of the engine, developing extensive experimental campaigns. The calibration process of the ECU functions is one of the longest and most expensive processes in the development of a new vehicle. Some lines of research have been explored to reduce the experimental tests to be carried out on the test bench. The use of neural networks (NN) has proven to be effective, leading to a reduction in experimental tests from 40 to 60%. Another methodology consists in the use of 1D/0D Thermo-fluid dynamic models of the ICE. These models are used as virtual test benches and through them it is possible to carry out the experimental campaigns necessary for the calibration of the control unit functions. At the real test bench, only the few experimental tests necessary for the validation of the model must be carried out. One of the simplifications that is usually made in the 1D/0D ICE models consists in assigning a single intake and exhaust valve lift, without taking into account the effect of the engine speed on the valve lift in early intake valve closure (EIVC) mode for engines equipped with VVA. This phenomenon has a not negligible effect on engine performance, especially at high engine speeds. In the case of engine models equipped with VVA, the valve lift cannot be imposed, since it is unique for each closing angle at each engine speed. Indeed, in order to assign the correct valve lift for a given engine speed and EIVC, numerous experimental tests should be carried out, making vain the beneficial effects of the method. In this work, the authors propose the use of a 0D/1D CFD model of the entire electro-hydraulic valvetrain VVA module, coupled with 1D lumped mass for reproducing the linear displacements of the intake valve, and for simulating the interactions between flow and mechanical systems of the solenoid hydro-mechanical valve. Thus, model simulations allow to predict the valve lift in all the necessary conditions in the experimental campaigns for the calibration of the control unit functions. Starting from geometric valvetrain data, the model has been validated with a parametric analysis of some variables on which there was greater uncertainty, by comparing the valve lift obtained by the model with the experimental ones in certain engine speeds. Subsequently, the authors have obtained the valve lifts in conditions not used for model validation, comparing them with their respective experimental lifts. The model has proven to be sensitive to the effect of the variation of the engine speed, reproducing the valve lift with a low error. In this way it is possible to reduce the experimental effort aimed to the calibration process considering that the virtual experimental campaign has proven to be reliable

L'orecchio controlaterale nei pazienti affetti da otite cronica con e senza colesteatoma La nuova Clinica Otorinolaringoiatrica, supp 5 vol XLIX , pp 414-418,1997

in "Otite media : opinioni a confronto

L'orecchio controlaterale nei pazienti affetti da otite cronica con e senza colesteatoma

Comunicazione -Abstrac

Anchored myringoplasty for total perforation with malleus adhesion to the promontory

[No abstract available