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Identification of a new COQ4 spliceogenic variant causing severe primary coenzyme Q deficiency
No full textBackground and aims: Primary Coenzyme Q (CoQ) deficiency caused by COQ4 defects is a clinically heterogeneous mitochondrial condition characterized by reduced levels of CoQ10 in tissues. Next-generation sequencing has lately boosted the genetic diagnosis of an increasing number of patients. Still, functional validation of new variants of uncertain significance is essential for an adequate diagnosis, proper clinical management, treatment, and genetic counseling. Materials and methods: Both fibroblasts from a proband with COQ4 deficiency and a COQ4 knockout cell model have been characterized by a combination of biochemical and genetic analysis (HPLC lipid analysis, Oxygen consumption, minigene analysis, RNAseq, among others). Results: Here, we report the case of a subject harboring a new variant of the COQ4 gene in compound heterozygosis, which shows severe clinical manifestations. We present the molecular characterization of this new pathogenic variant affecting the splicing of COQ4. Conclusion: Our results highlight the importance of expanding the genetic analysis beyond the coding sequence to reduce the misdiagnosis of primary CoQ deficiency patients
Hierarchical System to Predict Human Motion and Intentions for Efficient and Safe Human-Robot Interaction in Industrial Environments
No full textFATIGUE THRESHOLDS OF ADDITIVELY MANUFACTURED AND WROUGHT METAL MATERIALS WITH NOTCH-DEFECT INTERACTION SUBJECTED TO MULTIAXIAL LOCAL STRESSES
Get PDFAmong the possibilities AM offers, lattice structures (or cellular structures, metamaterials) stand out. These structures are obtained by the periodic repetition of a Unit Cell (UC) of struts or surfaces in space. The possibility to obtain stiffness-to-weight and strength-to-weight ratios competitive with composite materials make such structures particularly suitable for the aerospace, automotive, and biomedical industries.
However, the potential of AM, especially for lattice structures, is currently limited by significant concerns related to their structural integrity due to mechanical peculiarities closely linked to the production process. These challenges underscore the urgent need for further research and standardization in this field. In particular: (i) the pronounced surface roughness and the internal defects that may favor fatigue crack initiation and growth, (ii) the intense residual stresses in As Built (AB) conditions, and (iii) the high defect sensitivity of AMed microstructures in AB conditions. These factors collectively contribute to the poor fatigue strength of AMed materials compared to their counterparts obtained by conventional processes. Moreover, the fatigue assessment is complex considering: (i) the potentially significant discrepancy between the As Designed (AD) and As Built (AB) geometry of the component, (ii) the inherently notched nature of lattice structures and the manufacturing defects leading to severe stress concentrations and local multiaxial stress fields, (iii) the unpredictability of the defect distribution based solely on process parameters and the geometry of the part, and (iv) the lack of regulations standardizing either the experimental testing of lattice structures and their fatigue assessment.
In this context, the present work aims to estimate the fatigue limit of lattice structures produced via Powder Bed Fusion (PBF) of metallic powders, assessing the effect of the AM characteristic defects and the local multiaxiality with a unified approach. The key novelty of this Ph.D. project is to consider lattice structures as defective and notched materials and to estimate the fatigue limit using non-conventional extensions of the Linear Elastic Fracture Mechanics (LEFM), starting from the mechanical properties of the base material. It will be possible to develop optimization strategies for lattice structures that are robust to the actual geometry of the lattice structure and the remote load actions since the fatigue assessment is performed locally at the scale of the UC, where the fatigue strength is included as a constraint. However, the design approach needs to be validated.
To address the intricate nature of the fatigue problem for lattice structures, this work has methodologically explored the following aspects before analyzing the fatigue strength of lattice structures: (i) the interaction between defects and notches, particularly in the presence of sharp notches, an aspect poorly documented in the literature, and (ii) the development of a unified criterion for estimating the multiaxial fatigue limit for sharp notches and defects
Is the Energy Transition of Housing Financially Viable? Unlocking the Potential of Deep Retrofits with New Business Models
Get PDFThe transition to energy-efficient buildings is a priority of the European EPBD (Energy Performance Building Directive) and requires deep retrofits to reduce consumption and emissions. However, their financial viability remains underexplored. This research assesses the financial feasibility of deep retrofit interventions through innovative business models, focusing on the Managed Energy Services Agreement (MESA), which is considered the most effective for residential buildings. Additionally, we integrate off-site production from the Energiesprong model, which optimizes costs and time through long-term contracts and industrialized retrofit technologies. The analysis targets two investment profiles—owner/tenant and developer/entrepreneur—in Italian urban contexts with different market dynamics. A static analysis evaluates retrofits based on existing costs and technologies, while a dynamic analysis considers future profitability improvements because of cost reductions enabled by off-site production. The results indicate that, under current conditions, residential retrofitting is not financially sustainable without public subsidies. However, cost reductions driven by off-site technologies improve profitability, making large-scale retrofits feasible. Moreover, real estate market characteristics affect financial sustainability: in smaller cities, deeper cost reductions are necessary for retrofit interventions to become viable
Matrice geopolimerica per materiale d'attrito
No full textBrake pads are essential component of automotive braking systems, consisting of friction material supported by a rigid backing plate. The friction generated when the pad slides against the disc converts kinetic energy into thermal energy. Brake friction materials are complex composites containing a diverse category of ingredients, including metals, ceramics, and polymers. Each component serves a specific function, such as enhancing fade resistance, controlling the friction coefficient, reducing noise, and increasing strength. Among these constituents, the resin acts as a matrix that binds the powders together. Currently, phenolic resins are predominantly used, often combined with elastomers to improve vibration damping. This binder is crucial for determining the wear resistance and fade resistance of the brake pads (a phenomenon where braking performance diminishes due to overheating from extended use). Despite its widespread use due to cost-effectiveness, mechanical properties, and strong adhesion, phenolic resin has notable drawbacks. It releases volatile organic compounds (VOCs) such as formaldehyde and polycyclic aromatic hydrocarbons (PAHs) during production, which pose health risks, including carcinogenic effects. Furthermore, phenolic resins degrade at high temperatures, reaching up to 700°C during intense braking, leading to the release of hazardous gases and decreased brake performance through fading, thus compromising vehicle safety.
This PhD project focused on replacing phenolic resin with an inorganic matrix, specifically geopolymer. Funded by ITT Italia S.r.l., a leading global producer of brake pads, the research aimed to substitute phenolic resin with geopolymer without altering existing production processes. Indeed, geopolymers, in contrast to phenolic resins, offer superior thermal stability, withstanding temperatures exceeding 1000°C without significant degradation. They do not emit VOCs, thus providing environmental benefits. The Cold Sintering Process (CSP) was utilized to produce geopolymer-based brake pads, enabling their manufacture without changes to current production lines, as requested by the company.
The study initially confirmed the feasibility of producing geopolymer matrices using CSP, achieving an ultra-dense body (total porosity below 7%), by processing potassium-based geopolymer powder at an optimal moisture content under mild isostatic pressure (70 MPa) and moderate temperature (150°C) for a brief duration (10 minutes). The resulting products demonstrated chemical stability (high resistance to boiling tests) and strong mechanical properties (flexural strength) without requiring additional thermal treatments.
Subsequent bench and vehicle tests compared geopolymer-based friction materials with traditional phenolic resin pads. In particular, the vehicle testing showed that geopolymer pads performed exceptionally well in electric vehicles, achieving perfect scores for noise and durability while significantly improving wear resistance and coefficient of friction (CoF) stability compared to traditional pads. Additionally, efforts were being made to replace phenolic resin with geopolymer in the underlayer binder, aiming to further minimize the organic content in brake pad formulations
Overall, this research demonstrated significant advancements in geopolymer brake pads, highlighting their feasibility and potential for future development and commercialization. The findings pave the way for further refinement and exploration of fully geopolymer-based brake systems, emphasizing both performance improvement and environmental sustainabilit
Boundary value problems for Choquard equations
Get PDFWe consider the following nonlinear Choquard equation −Δu+Vu=(Iα∗|u|p)|u|p−2uinΩ⊂RN, where N≥2, p∈(1,+∞), V(x) is a continuous radial function such that infx∈ΩV>0 and Iα(x) is the Riesz potential of order α∈(0,N). Assuming Neumann or Dirichlet boundary conditions, we prove existence of a positive radial solution to the corresponding boundary value problem when Ω is an annulus, or an exterior domain of the form RN∖Br(0) ̄. We also provide a nonexistence result: if p≥[Formula presented] the corresponding Dirichlet problem has no nontrivial regular solution in strictly star-shaped domains. Finally, when considering annular domains, letting α→0+ we recover existence results for the corresponding local problem with power-type nonlinearity
Comparative analysis between Reverdin-Isham Osteotomy (RIO) and minimally invasive intramedullary nail device (MIIND) in association with AKIN osteotomy for Hallux valgus correction
Get PDFBackground: Hallux valgus (HV) is a widespread condition that leads to discomfort in daily life. There are different surgical techniques for HV. This retrospective and comparative study aimed to compare the clinical and radiographic outcomes of the Reverdin-Isham osteotomy (RIO) and the Minimally Invasive Intramedullary Nail Device (MIIND) surgical techniques. Methods: One hundred ninety-six patients with mild-to-severe HV were enrolled and divided into two groups: 98 patients with mild-moderate HV and 98 with moderate-severe HV, treated with the RIO and MIIND techniques, respectively. Radiographic and clinical evaluations were assessed preoperatively at 3, 12 and 60 months after surgery. Radiologically, the Hallux Valgus Angle (HVA), Intermetatarsal Angle (IMA), Distal Metatarsal Articular Angle (DMAA) and Tibial Sesamoid Position (TSP) were evaluated. Clinically, the AOFAS hallux metatarsophalangeal-interphalangeal scale and the Numeric Rating Scale (NRS-11) for pain were assessed. A propensity score matching (PSM) model was implemented to compare the two techniques. Results: In the RIO group, the mean HVA correction from preoperative value to 60 months of follow-up was 8.69° (p < 0.0001), the mean IMA correction was 2.42° (p < 0.0001), and the mean DMAA correction was 0.09°. In the MIIND group, the mean HVA correction was 24.92° (p < 0.0001), the mean IMA correction was 8.75° (p < 0.0001), and the mean DMAA correction was 6.28° (p < 0.0001). The mean AOFAS score improved over time, and NRS-11 decreased in both groups. After PSM model application, the variables that impacted the allocation to RIO or MIIND techniques were age, preoperative HVA values and HV severity. Conclusion: Our study demonstrates the efficacy of RIO for mild-moderate HV and MIIND for moderate-severe HV. Radiographic and clinical outcomes improved in both groups, but older patients with higher HVA and severe HV should be treated with the MIIND technique to achieve satisfactory outcomes. Level of evidence: III, retrospective cohort study
Submanifolds with boundary and Stokes’ Theorem in Heisenberg groups
Get PDFWe introduce and study the notion of C^1_H-regular submanifold with boundary in sub-Riemannian Heisenberg groups. As an application, we prove a version of Stokes' Theorem for CH1-regular submanifolds with boundary that takes into account Rumin's complex of differential forms in Heisenberg groups
Defining child maltreatment for research and surveillance: an international, multi-sectoral, Delphi consensus study in 34 countries in Europe and surrounding regions
Get PDFChild maltreatment is a complex public health issue that has consequences across the life-course. Studies to quantify child maltreatment and identify interventions and services are constrained by a lack of uniform definitions. We conducted a European Delphi study to reach consensus on types and characteristics of child maltreatment for use in surveillance and research. Statements were developed following a scoping review and identification of key concepts by an international expert team (n = 19). A multidisciplinary expert panel (n = 70) from 34 countries completed three rounds of an online survey. We defined consensus as ≥70% agreement or disagreement with each statement after the final round. Consensus was reached on 26/31 statements (participant retention rate 94%). From the statements, we propose a unified definition of child maltreatment to improve measurement and surveillance in Europe. Concerted efforts are now required to test and refine the definition further prior to real-world operationalisation