Search Results (41)

Design for excellence (DfX) comprises a broad family of product design methodologies aimed at addressing the often-competing requirements of multiple stakeholders throughout the product life cycle. Among the most pressing contemporary challenges in DfX is integrating environmental considerations into product design systematically and comprehensively. The circular economy (CE) is implemented through various R strategies (e.g., 3R: reduce, reuse, recycle), providing a normative framework intended to guide pro-environmental design decisions and life cycle thinking. This study conducts a systematic literature review focused on product development and its alignment with DfX methods in the context of circular economy practices (CEPs) to identify prevailing research trends and structural gaps in this area. Both quantitative and qualitative analyses of the literature are performed and interpreted through the lens of the circular economy butterfly diagram proposed by the Ellen MacArthur Foundation. The results reveal a pronounced asymmetry in the distribution of CE practices within product design research. Recycling and remanufacturing dominate the literature despite being positioned in the CE framework as less desirable than resource-preserving strategies such as reuse, repair, and life extension. This imbalance suggests that current research and design practices remain largely anchored in end-of-life (EoL) and resource-intensive solutions rather than prioritizing strategies that slow material and product flows. These findings highlight a critical need to intensify research on product circularity at the design stage, with greater emphasis on life-extension-oriented strategies and their integration within DfX methodologies and practices. The study provides a structured foundation for future research on circular product design and contributes to ongoing discussions on aligning design practice more closely with the fundamental principles of the circular economy. Full article

The concept of maintenance has undergone a significant evolution, adapting to the changing demands of industry over time. Initially limited to corrective actions during the Industrial Revolution—often performed without specialized personnel or dedicated departments—modern maintenance now incorporates advanced design considerations such as reliability, maintainability, safety, sustainability, and performance. This research presents a novel methodology aimed at integrating maintainability into the early stages of equipment and system design. Centered on continuous improvement, the approach prioritizes design variables that facilitate efficient maintenance throughout the asset’s lifecycle. Grounded in the UNE 151001 standard and employing the Quality Function Deployment (QFD) technique, the proposed methodology introduces the “House of Maintainability”—a structured tool that supports maintainability-oriented design and allows for diagnostic assessments of existing systems. By capturing stakeholder requirements and maintenance experience across various systems and contexts, the tool systematically translates these inputs into design criteria, ensuring compliance with maintainability standards. The methodology is validated through a real-world case study, confirming its practical applicability and effectiveness in enhancing industrial design processes with a focus on maintainability. Full article

This study introduces an energy-aware hybrid security framework that safeguards embedded systems against code theft, closing a critical gap. The approach integrates bitstream encryption, dynamic key generation, and Dynamic Function eXchange (DFX)-based memory obfuscation, yielding a layered hardware–software countermeasure to Read-Only Memory (ROM) scraping, side-channel attacks, and Man-in-the-Middle (MITM) intrusions by eavesdropping on communications on pins, cables, or Printed Circuit Board (PCB) routes. Prototyped on a Xilinx Zynq-7020 System-on-Chip (SoC) and applicable to MicroBlaze-based designs, it derives a fresh Authenticated Encryption with Associated Data (AEAD) key for each record via an Ascon-eXtendable-Output Function (XOF)–based Key Derivation Function (KDF) bound to a device identifier and a rotating slice from a secret pool, while relocating both the pool and selected Block RAM (BRAM)-resident code pages via Dynamic Function eXchange (DFX). This moving-target strategy frustrates ROM scraping, probing, and communication-line eavesdropping, while cryptographic confidentiality and integrity are provided by a lightweight AEAD (Ascon). Hardware evaluation reports cycles/byte, end-to-end latency, and per-packet energy under identical conditions across lightweight AEAD baselines; the framework’s key-derivation and DFX layers are orthogonal to the chosen AEAD. The threat model, field layouts (Nonce/AAD), receiver-side acceptance checks, and quantitative bounds are specified to enable reproducibility. By avoiding online key exchange and keeping long-lived secrets off Programmable Logic (PL)-based external memories while continuously relocating their physical locus, the framework provides a deployable, energy-aware defense in depth against code-theft vectors in FPGA-based systems. Overall, the work provides an original and deployable solution for strengthening the security of commercial products against code theft in embedded environments. Full article

Deferasirox (DFX) is an oral iron chelator for thalassemia patients with iron overload. DFX was FDA-approved as a first-line treatment for chronic iron overload. In Thailand, DFX was indicated as second-line therapy for patients unresponsive to deferiprone. Objectives: This study aimed to investigate the efficacy and safety of DFX monotherapy. Methods: All transfusion-dependent thalassemia patients who received second-line DFX monotherapy were identified from the thalassemia registry between May 2007 and May 2022. The primary endpoint was the change in body iron stores, measured by serum ferritin at week 24. At treatment end, patients with a serum ferritin (SF) level < 1000 ng/mL in transfusion-dependent thalassemia (TDT) were categorized as the ferritin response group. Multivariate analysis identified factors driving group differences. Results: Forty-two patients were enrolled with a mean age of 35.5 (13–57) years. Of these, 73.81% had beta-thalassemia. The median initial DFX dose was 20.26 (17.85–22.22) mg/kg/day, with a median treatment follow-up of 2 (1.80–2.45) years. Median SF was decreased from 2516 (1712 to 3065) ng/mL to 1027.5 (598–1867) ng/mL (p < 0.001). Of 21 (50%) patients in the ferritin response group, independent factors were age > 15 years and lower initial SF, with OR = 7.13 (95% CI 1.05–48.49, p = 0.045) and OR = 0.93 (95% CI 0.87–1.00, p = 0.039). The most common adverse events were gastric irritation symptoms (11.90%). Conclusions: Deferasirox is an effective oral iron chelator for thalassemia, with manageable side effects. Half of patients reached target SF levels. Adults (>15 years) with lower initial SF levels had a better response to DFX. Full article

Intracerebral hemorrhage (ICH), a severe stroke subtype common in the elderly, often results in high morbidity and mortality, with limited treatment options for long-term recovery. While glial scar formation is increasingly recognized as key to central nervous system (CNS) repair, its role and characteristics in the aging brain post-ICH remain unclear. This study investigated glial scar formation after ICH (100 μL autologous blood injected into the right basal ganglia model) in aged Fischer 344 rats and assessed the effects of deferoxamine (DFX) treatment. Histological and immunohistochemical analyses were conducted on days 7, 28, and 60 post-ICH using cell-specific and iron-related markers, with DFX administered at 100 mg/kg daily for 14 days in separate groups. Over time, the lesion core showed increased hemosiderin accumulation and astrogliosis. By day 60, the area of astrogliosis corresponded to an area with persistent neuronal loss (DARPP-32-negative). Glial composition shifted from microglia dominance on day 28 to astrocyte predominance by day 60. DFX treatment reduced iron deposition, astrogliosis, and DARPP-32-negative regions while enhancing oligodendrocyte presence. Iron-related markers (HO-1, ferritin, Perls’ staining) and PDGFRβ-positive fibrotic cells were concentrated in the scar core. These findings provide novel insights into scar formation after ICH in aged rats and suggest DFX as a potential therapy to improve outcomes in elderly stroke patients. Full article

The growing accumulation of solid waste from consumerism and the traditional linear economy poses significant risks to environmental sustainability and human health, increasing pressure on manufacturers to design more recyclable products. Design for Recycling (DfR), a key subset of Design for X (DfX), offers a promising strategy to enhance product recyclability. However, its implementation is hindered by ambiguous definitions, insufficient data, and a lack of robust methodologies and tools. This review clarifies the concept of DfR in engineering, identifies three critical research gaps, and proposes future research directions based on 89 papers: (1) the development of a comprehensive DfR knowledge base, (2) the creation of standardized recyclability evaluation indicators, and (3) the establishment of an automated, data-driven design generation system. These advancements aim to support the automated creation of highly recyclable products by leveraging accurate data, precise evaluations and minimized human bias. This review not only highlights existing research gaps but also provides valuable insights to guide future DfR studies and the development of more effective tools and methods. Furthermore, it emphasizes that the successful implementation of DfR requires active participation and commitment from the entire industrial chain and society. Full article

Background: Invasive aspergillosis (IA) is a deadly fungal lung infection. Antifungal resistance and treatment side effects are major concerns. Iron chelators are vital for IA management, but systemic use can cause side effects. We developed nanoparticles (NPs) to selectively deliver the iron chelator deferasirox (DFX) for IA treatment. Methods: DFX was encapsulated in poly(lactic-co-glycolic acid) (PLGA) NPs using a single emulsion solvent evaporation method. The NPs were characterized by light scattering and electron microscopy. DFX loading efficiency and release were assessed spectrophotometrically. Toxicity was evaluated using SRB, luciferase, and XTT assays. Therapeutic efficacy was tested in an IA mouse model, assessing fungal burden by qPCR and biodistribution via imaging. Results: DFX-NPs had a size of ~50 nm and a charge of ~−30 mV, with a loading efficiency of ~80%. Release kinetics showed DFX release via diffusion and bioerosion. The EC50 of DFX-NPs was significantly lower (p < 0.001) than the free drug, and they were significantly less toxic (p < 0.0001) in mammalian cell cultures. In vivo, NP treatment significantly reduced Af burden (p < 0.05). Conclusion: The designed DFX-NPs effectively target and kill Af with minimal toxicity to mammalian cells. The significant in vivo therapeutic efficacy suggests these NPs could be a safe and effective treatment for IA. Full article

This study focuses on the development of an integrated smart manufacturing system (ISMS) that centers on custom design experiences, utilizing virtual reality (VR) and cloud integration to enhance operational value. Through a Design for Excellence (DFX) approach, this system aims to seamlessly incorporate customer-specific designs into the manufacturing process, thus aligning closely with consumer needs. The research contributes significantly by (1) implementing a customer-focused design system that enhances sales benefits, (2) enabling a smooth transition from design drawings to automated production, thereby increasing manufacturing efficiency, and (3) establishing a digital transformation framework that integrates design, production, and marketing to boost overall business value. Full article

The uptake of a circular economy (CE) in the building sector is challenging, primarily due to the complexity associated with the design process and the dynamic interaction among architects, engineers, and construction (AEC) stakeholders. The standard and typical design process and construction methods raise concerns about building life cycles. Buildings should not only fulfill current needs, but one also needs to consider how they will function in the future and throughout their lifetime. To address these complexities, early planning is required to guide designers in holistically applying systems thinking to deliver CE outcomes. This paper outlines a critical review of CE implementation in buildings, with a proposed trifecta of approaches that significantly contribute to the development of circular buildings (CBs). The findings outline a proposed visualized framework with a conceptual formula that integrates CE design strategies to simplify and enhance AEC stakeholders’ perception of the circularity sequence in buildings. By strategically integrating loop-based strategies with the value retention process (VRP) and design for X (DFX) strategies, along with efficient assessment tools and technologies, it becomes feasible to embrace a CE during the design phase. The outcome of this review informs AEC stakeholders to systematically and strategically integrate the critical dimensions of a CE throughout the building life cycle, striking a balance between environmental concern, economic value, and future needs. Full article

Glioblastoma multiforme (GBM) represents the deadliest tumor among brain cancers. It is a solid tumor characterized by uncontrolled cell proliferation generating the hypoxic niches in the cancer core. By inducing the transcription of hypoxic inducible factor (HIF), hypoxia triggers many signaling cascades responsible for cancer progression and aggressiveness, including enhanced expression of vascular endothelial growth factor (VEGF) or antioxidant enzymes, such as heme oxygenase-1 (HO-1). The present work aimed to investigate the link between HO-1 expression and the hypoxic microenvironment of GBM by culturing two human glioblastoma cell lines (U87MG and A172) in the presence of a hypoxic mimetic agent, deferoxamine (DFX). By targeting hypoxia-induced HO-1, we have tested the effect of a novel acetamide-based HO-1 inhibitor (VP18/58) on GBM progression. Results have demonstrated that hypoxic conditions induced upregulation and nuclear expression of HO-1 in a cell-dependent manner related to malignant phenotype. Moreover, our data demonstrated that the HO-1 inhibitor counteracted GBM progression by modulating the HIFα/HO-1/VEGF signaling cascade in cancer cells bearing more malignant phenotypes. Full article

Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions and chemotherapy potentially has a negative impact on treatment outcomes and prognosis in patients with ALL. Therefore, initiating early iron chelation therapy during ALL treatment is a logical approach. Ideally, the selected iron chelator should also possess anti-leukaemia properties. The aim of the present study was to explore the potential impact and underlying mechanism of deferasirox (DFX) in ALL therapy. This study proved that DFX, an iron chelator, is capable of inducing leukaemia cell death through ferroptosis, which is achievable by increasing the expression of acetylated nuclear factor erythroid 2-related factor 2 (NRF2). More specifically, NRF2 acetylation on Lys599 was facilitated by acetyltransferase-p300/CBP. These findings indicate that DFX could serve as a potent adjunctive medication for patients with ALL. Moreover, DFX may offer dual benefits in ALL treatment, functioning as both an iron chelator and NRF2-modulating agent. Further research and clinical trials are necessary to fully elucidate the therapeutic potential of DFX in patients with ALL and incorporate it into treatment protocols. Full article

Plastic packaging, in the form of films, brought several advantages to the commercialization of products given its lightness and durability. It provided better ergonomics, ease of transport, increased shelf life, and easy handling and use. Despite that, plastic packaging is facing enormous sustainability concerns associated with the traditional practice of linear economy, combined with commonplace irresponsible handling by citizens since it is almost exclusively designed for single-use and its end-of-life (EOL) management is not planned for. To mitigate that, the circularity of plastic packaging must be more clearly studied and evaluated through approaches such as micro-level circular economy (CE) indicators. This paper focuses on the selection of relevant CE micro-indicators specifically for the plastic packaging sector among the plethora of indicators available. Relations are also established between CE micro-indicators and CE guiding principles, as well as the most prevalent Design for X (DfX) approaches, providing new insights into how these different aspects of sustainability can be linked together. Results show three micro-level indicators as the most relevant for circularity calculation in packaging, namely those termed ‘MCI’, ‘VRE’, and ‘CEIP’, because their methodology and approach address most of the CE guiding principles and DfX approaches relevant for the packaging sector. Finally, guidelines and good practices to promote circularity adoption in the plastic packaging sector are highlighted. This work can guide companies aiming to adopt CE micro-indicators in their practical implementation, overcoming the significant knowledge barrier that currently exists. Full article

Product engineering involves the design and development of new products or the improvement of existing products to efficiently meet market needs and ensure high quality. Design for Excellence (DfX) concepts, such as Design for Manufacturing, Design for Assembly, Design for Reliability, Design for User Experience, Design for Testability, and Design for Security, are essential in product engineering. These concepts enhance manufacturability, ease of assembly, and serviceability, thereby improving overall product performance and user experience. Integrating sustainability principles into product engineering practices is crucial due to growing concerns about environmental sustainability. Sustainability involves responsible resource use, waste and emission reduction, and consideration of social and economic impacts. Adopting sustainable practices is essential for addressing global challenges like climate change, resource depletion, and pollution. Consequently, sustainability has become a significant factor for businesses and government policies worldwide. Product engineering possesses significant potential for contributing to sustainability goals. In this view, this paper discusses a new approach called “Design for Sustainability (DfS)” that focuses on developing sustainable products. The paper discusses the various steps involved in implementing DfS in the product engineering process, highlighting its importance and benefits. By implementing DfS practices, businesses can create innovative and marketable products that minimize environmental impact while meeting consumer demands. Full article

Latent infection of Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cell cancers, including 10% of gastric carcinomas. We previously reported that hypoxia inducible factor-1α (HIF-1α) induces EBV’s latent-to-lytic switch and identified several HIF-1α-stabilizing drugs that induce this viral reactivation. Here, we tested three classes of these drugs for preferential killing of the EBV-positive gastric cancer AGS-Akata cell line compared to its matched EBV-negative AGS control. We observed preferential killing with iron chelators [Deferoxamine (DFO); Deferasirox (DFX)] and a prolyl hydroxylase inhibitor (BAY 85-3934 (Molidustat)), but not with a neddylation inhibitor [MLN4924 (Pevonedistat)]. DFO and DFX also induced preferential killing of the EBV-positive gastric cancer AGS-BDneo and SNU-719 cell lines. Preferential killing was enhanced when low-dose DFX (10 μM) was combined with the antiviral prodrug ganciclovir. DFO and DFX induced lytic EBV reactivation in approximately 10% of SNU-719 and 20-30% of AGS-Akata and AGS-BDneo cells. However, neither DFO nor DFX significantly induced synthesis of lytic EBV proteins in xenografts grown in NSG mice from AGS-Akata cells above the level observed in control-treated mice. Therefore, these FDA-approved iron chelators are less effective than gemcitabine at promoting EBV reactivation in vivo despite their high specificity and efficiency in vitro. Full article

Excess iron is known to be a risk factor of carcinogenesis. Although iron chelators show anti-cancer effects, they have not been used successfully to treat cancer patients. Triple-negative breast cancer (TNBC) is a disease with poor prognosis without effective treatments. Thus, we aimed to evaluate a possibility of iron chelators as a therapy for TNBC. Deferasirox (DFX), an iron chelator, suppressed the growth of 4T1 murine TNBC cell line cells in vitro and in vivo. Lung metastasis was further significantly reduced, leading to the hypothesis that iron metabolism between metastatic and non-metastatic cells may be different. An analysis of existing database demonstrated that the expression of iron-uptake genes was significantly suppressed in TNBC cells that metastasized to lymph nodes or lungs compared to those in primary tumors. A highly metastatic clone of the murine 4T1 TNBC cells (4T1-HM) did not proliferate well under iron-rich or iron-depleted conditions by iron chelators compared to a low-metastatic clone (4T1-LM). Bulk RNA-seq analysis of RNA from 4T1-HM and 4T1-LM cells suggested that the PI3K-AKT pathway might be responsible for this difference. Indeed, DFX suppressed the proliferation via the AKT-mTOR pathway in 4T1-HM and the human MDA-MB-231 cells, a human mesenchymal-like TNBC cell line. DFX also suppressed the growth of 4T1-HM tumors in comparison to 4T1-LM tumors, and reduced lung metastases after surgical resection of primary 4T1 tumors. These results indicated, for the first time, that highly metastatic TNBC cells have limited iron metabolism, and they can be more effectively targeted by iron chelators. Full article