On forward and inverse uncertainty quantification for models involving hysteresis operators

Parameters within hysteresis operators modeling real world objects have to be identified from measurements and are therefore subject to corresponding errors. To investigate the influence of these errors, the methods of Uncertainty Quantification (UQ) are applied. Results of forward UQ for a play operator with a stochastic yield limit are presented. Moreover, inverse UQ is performed to identify the parameters in the weight function in a Prandtl-Ishlinskiĭ operator and the uncertainties of these parameters

A simple scheme for the inversion of a Preisach like hysteresis operator in saturation conditions

A class of operators based on a Prandtl-Ishilinskii operator with inverse in a closed form is presented. Conversely to those considered in the past, they describe the B - H constitutive equation and not the usual J - H link. This allows its application in numerical schemes for the description of nonlinear dynamic circuits in transient conditions, with low formulation effort and computational weight, with respect to the standard inversion of the operator. The model has been implemented into a numerical scheme describing a RL nonlinear and hysteretic circuit, outlining the effects of residual magnetization and coercive field on the global current dynamics. The model performances are preliminary compared to numerical model based on the standard numerical inversion of the operator, along with the experimental results of transient current analysis

Proof of principle of a fuel injector based on a magnetostrictive actuator

One of the goals of modern internal combustion engines is the NOx-soot trade-off, and this would be better achieved by a better control of the fuel injection. Moreover, this feature can be also useful for high-performance hydraulic systems. Actual fuel injection technology either allows only the control of the injection time or it is based on very complex mechanical-hydraulic systems, as in the case of piezo-actuators. This work describes the basic steps that brought the authors to the realization of a concept fuel injector based on a Terfenol-D magnetostrictive actuator that could overcome the previous issues, being both simple and controllable. The study provides the design, development, and a feasibility analysis of a magnetostrictive actuator for fuel injection, by providing a basic magneto-static analysis of the actuator, the adaptation of a suitable standard fuel injector, and its experimental testing in a lab environment, with different shapes and amplitude of the reference signal to follow

Regulation of miR-483-3p by the O-linked N-acetylglucosamine transferase links chemosensitivity to glucose metabolism in liver cancer cells

The miR-483-3p is upregulated in several tumors, including liver tumors, where it inhibits TP53-dependent apoptosis by targeting the pro-apoptotic gene BBC3/PUMA. The transcriptional regulation of the miR-483-3p could be driven by the β-catenin/USF1 complex, independently from its host gene IGF2, and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type TP53 the upregulation of the miR-483-3p overcomes the antitumoral effects of the tumor-suppressor miR-145-5p by a mechanism involving cellular glucose availability. Here we demonstrate that in HepG2 cells, the molecular link between glucose concentration and miR-483-3p expression entails the O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT), which stabilizes the transcriptional complex at the miR-483 promoter. HepG2 cells showed reduced miR-483-3p expression and increased susceptibility to 5-fluorouracil (5-FU)-induced apoptosis in presence of the inhibitor of glycolysis 2-deoxy-D-glucose (2-DG). However, in vivo experiments showed that HepG2 cells with higher miR-483-3p expression were selected during tumor progression regardless of 5-FU treatment. Furthermore, treatment with 2-DG alone did not significantly reduce HepG2 xenograft load in immunodeficient mice. In conclusion, we show that in HepG2 cells glucose uptake increases the expression of the oncogenic miR-483-3p through the OGT pathway. This suggests that depletion of the miR-483-3p may be a valuable therapeutic approach in liver cancer patients, but the use of inhibitors of glycolysis to achieve this purpose could accelerate the selection of resistant neoplastic cell clones

Three-dimensional simulation of clouds of multi-disperse evaporating saliva droplets in a train cabin

In line with recent ongoing efforts to collect crucial information about the mechanisms of virus diffusion and put them in relation to the effective complexity of the several natural or artificial environments where human beings leave and operate, the present study deals with the dispersion of evaporating saliva droplets in the cabin of an interregional train. A relevant physical model is constructed taking into account the state of the art in terms of existing paradigms and their ability to represent some fundamental aspects related to the evolution in time of a cloud of multi-disperse droplets. Conveniently, such a theoretical framework is turned into a computational one that relies on low Mach-number asymptotics and can therefore take advantage of the typical benefits (relatively low computational cost) associated with pressure-based methods. Numerical simulations are used to predict the flow established in the cabin as a result of the ventilation systems and related settings dictated by considerations on passenger comfort. The solution of two-way coupled Lagrangian evolution equations is used to capture the associated dynamics of the dispersed phase and predict its transport in conjunction with the peculiar topology of the considered flow and morphology of solid surfaces, which bound it (including the human beings). Typical physiological processes such as talking or coughing are considered. An analysis on the impact of the multiplicity of droplet sources is also conducted, thereby providing some indications in terms of potential risks for the cabin occupants

UCbase & miRfunc: a database of ultraconserved sequences and microRNA function

Four hundred and eighty-one ultraconserved sequences (UCRs) longer than 200 bases were discovered in the genomes of human, mouse and rat. These are DNA sequences showing 100% identity among the three species. UCRs are frequently located at genomic regions involved in cancer, differentially expressed in human leukemias and carcinomas and in some instances regulated by microRNAs (miRNAs). Here we present UCbase & miRfunc, the first database which provides ultraconserved sequences data and shows miRNA function. Also, it links UCRs and miRNAs with the related human disorders and genomic properties. The current release contains over 2000 sequences from three species (human, mouse and rat). As a web application, UCbase & miRfunc is platform independent and it is accessible at http://microrna.osu.edu/.UCbase4

A method to generate perfusable physiologic-like vascular channels within a liver-on-chip model

Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.Supplementary Material: Further data on collagen–fibrin gel characterization, immunofluorescent staining of peculiar endothelial markers, rocker platform setup, and an upgraded version of the current ECM-mediated-contact platform are presented in the supplementary material available online at: https://pubs.aip.org/bmf/article-supplement/2925768/zip/064103_1_5.0170606.suppl_material/ (zip file).Copyright © 2023 Author(s). The human vasculature is essential in organs and tissues for the transport of nutrients, metabolic waste products, and the maintenance of homeostasis. The integration of vessels in in vitro organs-on-chip may, therefore, improve the similarity to the native organ microenvironment, ensuring proper physiological functions and reducing the gap between experimental research and clinical outcomes. This gap is particularly evident in drug testing and the use of vascularized models may provide more realistic insights into human responses to drugs in the pre-clinical phases of the drug development pipeline. In this context, different vascularized liver models have been developed to recapitulate the architecture of the hepatic sinusoid, exploiting either porous membranes or bioprinting techniques. In this work, we developed a method to generate perfusable vascular channels with a circular cross section within organs-on-chip without any interposing material between the parenchyma and the surrounding environment. Through this technique, vascularized liver sinusoid-on-chip systems with and without the inclusion of the space of Disse were designed and developed. The recapitulation of the Disse layer, therefore, a gap between hepatocytes and endothelial cells physiologically present in the native liver milieu, seems to enhance hepatic functionality (e.g., albumin production) compared to when hepatocytes are in close contact with endothelial cells. These findings pave the way to numerous further uses of microfluidic technologies coupled with vascularized tissue models (e.g., immune system perfusion) as well as the integration within multiorgan-on-chip settings.This work was partially financed by the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No 800924 (International Cancer Research Fellowships-2 [iCARE-2])

Induction of microRNAs, mir-155, mir-222, mir-424 and mir-503, promotes monocytic differentiation through combinatorial regulation

Acute myeloid leukemia (AML) involves a block in terminal differentiation of the myeloid lineage and uncontrolled proliferation of a progenitor state. Using phorbol myristate acetate (PMA), it is possible to overcome this block in THP-1 cells (an M5-AML containing the MLL-MLLT3 fusion), resulting in differentiation to an adherent monocytic phenotype. As part of FANTOM4, we used microarrays to identify 23 microRNAs that are regulated by PMA. We identify four PMA-induced micro- RNAs (mir-155, mir-222, mir-424 and mir-503) that when overexpressed cause cell-cycle arrest and partial differentiation and when used in combination induce additional changes not seen by any individual microRNA. We further characterize these prodifferentiative microRNAs and show that mir-155 and mir-222 induce G2 arrest and apoptosis, respectively. We find mir-424 and mir-503 are derived from a polycistronic precursor mir-424-503 that is under repression by the MLL-MLLT3 leukemogenic fusion. Both of these microRNAs directly target cell-cycle regulators and induce G1 cell-cycle arrest when overexpressed in THP-1. We also find that the pro-differentiative mir-424 and mir-503 downregulate the anti-differentiative mir-9 by targeting a site in its primary transcript. Our study highlights the combinatorial effects of multiple microRNAs within cellular systems.Comment: 45 pages 5 figure

Genetic dynamics in untreated CLL patients with either stable or progressive disease: A longitudinal study

Clonal evolution of chronic lymphocytic leukemia (CLL) often follows chemotherapy and is associated with adverse outcome, but also occurs in untreated patients, in which case its predictive role is debated. We investigated whether the selection and expansion of CLL clone(s) precede an aggressive disease shift. We found that clonal evolution occurs in all CLL patients, irrespective of the clinical outcome, but is faster during disease progression. In particular, changes in the frequency of nucleotide variants (NVs) in specific CLL-related genes may represent an indicator of poor clinical outcome

MicroRNA-221 Modulates RSV Replication in Human Bronchial Epithelium by Targeting NGF Expression

Background: Early-life infection by respiratory syncytial virus (RSV) is associated with aberrant expression of the prototypical neurotrophin nerve growth factor (NGF) and its cognate receptors in human bronchial epithelium. However, the chain of events leading to this outcome, and its functional implications for the progression of the viral infection, has not been elucidated. This study sought to test the hypothesis that RSV infection modulates neurotrophic pathways in human airways by silencing the expression of specific microRNAs (miRNAs), and that this effect favors viral growth by interfering with programmed death of infected cells. Methodology: Human bronchial epithelial cells infected with green fluorescent protein-expressing RSV (rgRSV) were screened with multiplex qPCR arrays, and miRNAs significantly affected by the virus were analyzed for homology with mRNAs encoding neurotrophic factors or receptors. Mimic sequences of selected miRNAs were transfected into noninfected bronchial cells to confirm the role of each of them in regulating neurotrophins expression at the gene and protein level, and to study their influence on cell cycle and viral replication. Principal Findings: RSV caused downregulation of 24 miRNAs and upregulation of 2 (p,0.01). Homology analysis of microarray data revealed that 6 of those miRNAs exhibited a high degree of complementarity to NGF and/or one of its cognate receptors TrKA and p75 NTR. Among the selected miRNAs, miR-221 was significantly downregulated by RSV and it