A two-step hybrid approach for modeling the nonlinear dynamic response of piezoelectric energy harvesters

An effective hybrid computational framework is described here in order to assess the nonlinear dynamic response of piezoelectric energy harvesting devices. The proposed strategy basically consists of two steps. First, fully coupled multiphysics finite element (FE) analyses are performed to evaluate the nonlinear static response of the device. An enhanced reduced-order model is then derived, where the global dynamic response is formulated in the state-space using lumped coefficients enriched with the information derived from the FE simulations. The electromechanical response of piezoelectric beams under forced vibrations is studied by means of the proposed approach, which is also validated by comparing numerical predictions with some experimental results. Such numerical and experimental investigations have been carried out with the main aim of studying the influence of material and geometrical parameters on the global nonlinear response. The advantage of the presented approach is that the overall computational and experimental efforts are significantly reduced while preserving a satisfactory accuracy in the assessment of the global behavior

Maml1 acts cooperatively with Gli proteins to regulate Sonic hedgheog signaling pathway

Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (GCPs) and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma. The effects of Shh pathway are mediated by the Gli family of transcription factors, which controls the expression of a number of target genes, including Gli1. Here, we identify Mastermind-like 1 (Maml1) as a novel regulator of the Shh signaling since it interacts with Gli proteins, working as a potent transcriptional coactivator. Notably, Maml1 silencing results in a significant reduction of Gli target genes expression, with a negative impact on cell growth of NIH3T3 and Patched1−/− mouse embryonic fibroblasts (MEFs), bearing a constitutively active Shh signaling. Remarkably, Shh pathway activity results severely compromised both in MEFs and GCPs deriving from Maml1−/− mice with an impairment of GCPs proliferation and cerebellum development. Therefore Maml1−/− phenotype mimics aspects of Shh pathway deficiency, suggesting an intrinsic requirement for Maml1 in cerebellum development. The present study shows a new role for Maml1 as a component of Shh signaling, which plays a crucial role in both development and tumorigenesis

Modelling and parameter identification of electromechanical systems for energy harvesting and sensing

Advanced modelling of electro-mechanical systems for energy harvesting (EH) and sensing is important to develop reliable self-powered autonomous electronic devices and for structural health monitoring (SHM). In this perspective, a novel computational approach is here proposed for both real-time and off-line parameter identification (PI). The system response is governed by a set of four partial differential equations (PDE) where the three displacement components and the electrical potential are the unknowns. Firstly, the finite element (FE) method is used to reduce the PDE problem into a set of ordinary differential equations (ODE). Then, a state- space model is derived with the aim to limit the PI problem to a subset of unknowns. After that, an identification error is introduced and the Lyapunov theory is used to derive the PI algorithm. The numerical implementation is based on a sensitivity analysis feedback block. The overall proposed computational strategy is robust and results in an exponential asymptotic convergence. The accuracy of the PI method is demonstrated by analysing the time–domain response of an array of piezoelectric bimorphs subjected to low–frequency structural random vibrations. The selected case–study is an existing cable–stayed bridge, for which an extensive dynamic monitoring campaign has provided the experimental data. Once time histories of the device response are obtained through time–dependent dynamic FE simulations, the PI algorithm is used to determine the unknown lumped coefficients of the state-space model. The comparison between FE method and lumped parameters model in terms of tip displacement and output voltage demonstrates the superior predictive capability of the new PI algorithm. As a result of the sensitivity analysis, guidelines to assess the optimal array configuration are also provided

Differential Protein Expression Profiles in Glaucomatous Trabecular Meshwork: An Evaluation Study on a Small Primary Open Angle Glaucoma Population

INTRODUCTION: Primary open angle glaucoma (POAG) is a progressive optic neuropathy characterized by impaired aqueous outflow and extensive remodeling in the trabecular meshwork (TM). The aim of this study was to characterize and compare the expression patterns of selected proteins belonging to the tissue remodeling, inflammation and growth factor pathways in ex vivo glaucomatous and post-mortem TMs using protein-array analysis. METHODS: TM specimens were collected from 63 white subjects, including 40 patients with glaucoma and 23 controls. Forty POAG TMs were collected at the time of surgery and 23 post-mortem specimens were from non-glaucomatous donor sclerocorneal tissues. Protein profiles were evaluated using a chip-based array consisting of 60 literature-selected antibodies. RESULTS: A different expression of some factors was observed in POAG TMs with respect to post-mortem specimens, either in abundance (interleukin [IL]10, IL6, IL5, IL7, IL12, IL3, macrophage inflammatory protein [MIP]1δ/α, vascular endothelial growth factor [VEGF], transforming growth factor beta 1 [TGFβ1], soluble tumor necrosis factor receptor I [sTNFRI]) or in scarcity (IL16, IL18, intercellular adhesion molecule 3 [ICAM3], matrix metalloproteinase-7 [MMP7], tissue inhibitor of metalloproteinase 1 [TIMP1]). MMP2, MMP7, TGFβ1, and VEGF expressions were confirmed by Western blot, zymography, and polymerase chain reaction. No difference in protein profile expression was detected between glaucomatous subtypes. CONCLUSION: The analysis of this small TM population highlighted some proteins linked to POAG, some previously reported and others of new detection (IL7, MIPs, sTNFαRI). A larger POAG population is required to select promising disease-associated biomarker candidates. FUNDING: This study was partially supported by the Fondazione Roma, the Italian Ministry of Health and the “National 5xMille 2010 tax donation to IRCCS-G.B. Bietti Foundation”. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-016-0285-x) contains supplementary material, which is available to authorized users

What’s in the bee nest holes? A single aggregation of Megachile parietina reveals and helps to fill up Eltonian shortfalls

Megachile (Chalicodoma) parietina (Geoffroy, 1785) is a Palearctic solitary bee included in the Red List of some central European Countries. Females build durable nests, reused year after year, by mixing soil with a salivary secretion. Like for most solitary bees, the resources contained within M. parietina nests attract several other insects which exploit pollen supplies or feed on the immature brood. These associated insects have mainly been studied for mantained bees and considered for their effect on the host reproductive success.A very large nesting aggregation of M. parietina in Central Tuscany has been studied for three consecutive years. We have identified 32 associated insect species, which certainly are an underestimate of the species present. Among the identified species, only eight had been previously reported for M. parietina. All the species were classified both according to the specificity for the host taxon (Chalicodoma, Megachilidae, Anthophila, Hymenoptera, Others) and to the ecological relationship (cleptoparasites, parasitoids, predators of larvae, food commensal, scavengers, and occasional nest users).This highlighted both the richness of the ecological network within the nesting aggregation and the value of studying these nesting sites to fill Eltonian shortfalls, i.e. the deficiency in ecology knowledge, of bees and their associated fauna.Implications for insect conservation.We suggest that, besides their role in pollination, large and stable bee nesting sites increase the local insect biodiversity, and that attention should be paid to their conservation within actions aimed to support populations of wild pollinators

Digitalization and real-time control to mitigate environmental impacts along rivers: Focus on artificial barriers, hydropower systems and European priorities

Hydropower globally represents the main source of renewable energy, and provides several benefits, e.g., water storage and flexibility; on the other hand, it may cause significant impacts on the environment. Hence sustainable hydropower needs to achieve a balance between electricity generation, impacts on ecosystems and benefits on society, supporting the achievement of the Green Deal targets. The implementation of digital, information, communication and control (DICC) technologies is emerging as an effective strategy to support such a trade-off, especially in the European Union (EU), fostering both the green and the digital transitions. In this study, we show how DICC can foster the environmental integration of hydropower into the Earth spheres, with focus on the hydrosphere (e.g., on water quality and quantity, hydropeaking mitigation, environmental flow control), biosphere (e.g., improvement of riparian vegetation, fish habitat and migration), atmosphere (reduction of methane emissions and evaporation from reservoirs), lithosphere (better sediment management, reduction of seepages), and on the anthroposphere (e.g., reduction of pollution associated to combined sewer overflows, chemicals, plastics and microplastics). With reference to the abovementioned Earth spheres, the main DICC applications, case studies, challenges, Technology Readiness Level (TRL), benefits and limitations, and transversal benefits for energy generation and predictive Operation and Maintenance (O&M), are discussed. The priorities for the European Union are highlighted. Although the paper focuses primarly on hydropower, analogous considerations are valid for any artificial barrier, water reservoir and civil structure which interferes with freshwater systems.Digitalization and real-time control to mitigate environmental impacts along rivers: Focus on artificial barriers, hydropower systems and European prioritiespublishedVersio

Notch3/Jagged1 Circuitry Reinforces Notch Signaling and Sustains T-ALL

AbstractDeregulated Notch signaling has been extensively linked to T-cell acute lymphoblastic leukemia (T-ALL). Here, we show a direct relationship between Notch3 receptor and Jagged1 ligand in human cell lines and in a mouse model of T-ALL. We provide evidence that Notch-specific ligand Jagged1 is a new Notch3 signaling target gene. This essential event justifies an aberrant Notch3/Jagged1 cis-expression inside the same cell. Moreover, we demonstrate in Notch3-IC–overexpressing T lymphoma cells that Jagged1 undergoes a raft-associated constitutive processing. The proteolytic cleavage allows the Jagged1 intracellular domain to empower Notch signaling activity and to increase the transcriptional activation of Jagged1 itself (autocrine effect). On the other hand, the release of the soluble Jagged1 extracellular domain has a positive impact on activating Notch signaling in adjacent cells (paracrine effect), finally giving rise to a Notch3/Jagged1 auto-sustaining loop that supports the survival, proliferation, and invasion of lymphoma cells and contributes to the development and progression of Notch-dependent T-ALL. These observations are also supported by a study conducted on a cohort of patients in which Jagged1 expression is associated to adverse prognosis

Role of interferon lambda 4 and ALT levels in optimising treatment of HCV for patients with low-stage fibrosis

The use of new anti-HCV drugs is currently limited by high costs and dual therapy; pegylated interferon and ribavirin (peg-IFN+RBV) still represents the only affordable treatment in patients with low-stage fibrosis. We evaluated the role of Interferon lambda4 (IFNL4) polymorphisms and its combination with on-treatment alanine transaminase (ALT) modification in predicting sustained virological response (SVR) in HCV genotype 1 and 4 patients with low-stage fibrosis. We retrospectively analysed 124 patients with Metavir ≤F2, who received dual therapy at our centre. Genotyping for IFNL4 polymorphisms was assessed at baseline, as well as ALT levels (baseline and week 2, 4, 12 and 24 of therapy). Thirty patients (24%) were TT/TT, 74 (60%) TT/DG and 20 (16%) DG/DG. The SVR rate was significantly higher in TT/TT genotype compare to TT/DG and DG/DG (97% vs. 53% and 50%, respectively, p=0.001). Patients that achieved a 60% reduction of ALT baseline value after 4 weeks of therapy had a significantly higher SVR rate (94% vs. 52%, p<0.001). Factors significantly associated with SVR were TT/TT genotype (p=0.029), RVR (p=0.019) and 60% ALT reduction at 4 week of therapy (p=0.005). The absence of both TT/TT genotype and 60% ALT reduction were negative predictors of SVR (p<0.001). In conclusion, the combined use of IFNL4 polymorphisms and ALT reduction at 4 week of treatment is able to optimize candidates’ selection for peg-IFN+RBV, discriminating those that could still benefit from dual therapy from the ones that need the new regimen

Amyotrophic lateral sclerosis stratification: unveiling patterns with virome, inflammation, and metabolism molecules

Amyotrophic lateral sclerosis (ALS) is an untreatable and clinically heterogeneous condition primarily affecting motor neurons. The ongoing quest for reliable biomarkers that mirror the disease status and progression has led to investigations that extend beyond motor neurons' pathology, encompassing broader systemic factors such as metabolism, immunity, and the microbiome. Our study contributes to this effort by examining the potential role of microbiome-related components, including viral elements, such as torque tenovirus (TTV), and various inflammatory factors, in ALS. In our analysis of serum samples from 100 ALS patients and 34 healthy controls (HC), we evaluated 14 cytokines, TTV DNA load, and 18 free fatty acids (FFA). We found that the evaluated variables are effective in differentiating ALS patients from healthy controls. In addition, our research identifies four unique patient clusters, each characterized by distinct biological profiles. Intriguingly, no correlations were found with site of onset, sex, progression rate, phenotype, or C9ORF72 expansion. A remarkable aspect of our findings is the discovery of a gender-specific relationship between levels of 2-ethylhexanoic acid and patient survival. In addition to contributing to the growing body of evidence suggesting altered peripheral immune responses in ALS, our exploratory research underscores metabolic diversity challenging conventional clinical classifications. If our exploratory findings are validated by further research, they could significantly impact disease understanding and patient care customization. Identifying groups based on biological profiles might aid in clustering patients with varying responses to treatments