A QFD-based method to support SMEs in benchmarking co-design tools

Efficient collaborative product design is crucial for extended enterprises willing to develop complex products pursuing a short time to market. However, successful collaborative product design depends on the ability to effectively manage and share engineering knowledge and data throughout the entire product development process. Co-design software platforms aim to facilitate cooperation in distributed teams. In the context of Small and Medium Enterprises (SMEs) the advanced co-design software implementation to support the supply chain is not a trivial task. SMEs have peculiar characteristics such as flexibility, ICT skills and financial resources, which are difficult to be integrated within a structured design network. This paper presents a method to define and evaluate a co-design platform dedicated to SMEs in the mechanical product field. System architecture is defined by applying suitable metrics based on collaborative process characteristics in order to assess functionality performance of the available tools. Benchmarking is based on different levels of collaboration recognized in the typical product development process in SMEs. Correlation between process metrics, software functionalities and specific collaboration requirements is managed by adopting Quality Function Deployment (QFD) techniques. A practical case study allows the robustness of the proposed method to be verified and the main advantages and future developments to be discussed.     

Adsorption and Release of Sulfamethizole from Mesoporous Silica Nanoparticles Functionalised with Triethylenetetramine

Mesoporous silica nanoparticles (MSN) were synthesised and functionalised with triethylenetetramine (MSN-TETA). The samples were fully characterised (transmission electron microscopy, small angle X-ray scattering, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential and nitrogen adsorption/desorption isotherms) and used as carriers for the adsorption of the antimicrobial drug sulphamethizole (SMZ). SMZ loading, quantified by UV–Vis spectroscopy, was higher on MSN-TETA (345.8 mg g⁻¹) compared with bare MSN (215.4 mg g⁻¹) even in the presence of a lower surface area (671 vs. 942 m² g⁻¹). The kinetics of SMZ adsorption on MSN and MSN-TETA followed a pseudo-second-order model. The adsorption isotherm is described better by a Langmuir model rather than a Temkin or Freundlich model. Release kinetics showed a burst release of SMZ from bare MSN samples (k₁ = 136 h⁻¹) in contrast to a slower release found with MSN-TETA (k₁ = 3.04 h⁻¹), suggesting attractive intermolecular interactions slow down SMZ release from MSN-TETA. In summary, the MSN surface area did not influence SMZ adsorption and release. On the contrary, the design of an effective drug delivery system must consider the intermolecular interactions between the adsorbent and the adsorbate.     

Block of the Mevalonate Pathway Triggers Oxidative and Inflammatory Molecular Mechanisms Modulated by Exogenous Isoprenoid Compounds

Deregulation of the mevalonate pathway is known to be involved in a number of diseases that exhibit a systemic inflammatory phenotype and often neurological involvements, as seen in patients suffering from a rare disease called mevalonate kinase deficiency (MKD). One of the molecular mechanisms underlying this pathology could depend on the shortage of isoprenoid compounds and the subsequent mitochondrial damage, leading to oxidative stress and pro-inflammatory cytokines’ release. Moreover, it has been demonstrated that cellular death results from the balance between apoptosis and pyroptosis, both driven by mitochondrial damage and the molecular platform inflammasome. In order to rescue the deregulated pathway and decrease inflammatory markers, exogenous isoprenoid compounds were administered to a biochemical model of MKD obtained treating a murine monocytic cell line with a compound able to block the mevalonate pathway, plus an inflammatory stimulus. Our results show that isoprenoids acted in different ways, mainly increasing the expression of the evaluated markers [apoptosis, mitochondrial dysfunction, nucleotide-binding oligomerization-domain protein-like receptors 3 (NALP3), cytokines and nitric oxide (NO)]. Our findings confirm the hypothesis that inflammation is triggered, at least partially, by the shortage of isoprenoids. Moreover, although further studies are necessary, the achieved results suggest a possible role for exogenous isoprenoids in the treatment of MKD.     

Preovulatory rise of NGF in ovine follicular fluid: possible involvement in the control of oocyte maturation

Since nerve growth factor (NGF) is produced in vitro by granulosa cells after gonadotropin stimulation, the present research has been designed to investigate whether this neurotropin is involved in the events triggered by the gonadotropin surge that lead the follicle to ovulate a mature oocyte. To this aim, NGF levels in follicular fluid, collected before or 20 hours after the gonadotropin surge, was measured by ELISA. To evaluate whether NGF may have a non-neurotropic effect on follicle cells, the presence of NGF receptors was investigated by immunohistochemistry and further evaluated by analysing the tyrosine-phosphorylation pattern after NGF stimulation in vitro. The effect of NGF on the degree of cumulus expansion, cumulus-oocyte metabolic coupling, and meiotic maturation was finally studied by using the culture of follicle-enclosed oocyte. The results demonstrate that GnRH causes a dramatic rise of NGF in large follicles. Immunohistochemistry revealed a discrete positivity for trkA receptors localised in cumulus cells. Tyrosine phosphorylation pattern confirms that somatic cells are capable to transduce NGF signal. By contrast, all the oocytes examined were negative for trkA and did not change the phosphorylation pattern after NGF. In vitro NGF (100 ng/ml) induced a marked cumulus expansion and a progressive cumulus-oocyte uncoupling similar to that produced by gonadotropins. The addition of NGF also caused the resumption of meiosis in more than 70% of the oocytes analysed with an effect that is only slightly less pronounced than that of gonadotropins (80%). The increase in NGF secretion following gonadotropin surge suggests that this neurotropin may be involved in the control of oocyte maturation.     

Rapid 3D Printing of Electrohydraulic (HASEL) Tentacle Actuators

A comprehensive material system is introduced for the additive manufacturing of electrohydraulic (HASEL) tentacle actuators. This material system consists of a photo‐curable, elastomeric silicone‐urethane with relatively strong dielectric properties (ε_r ≈ 8.8 at 1 kHz) in combination with ionically‐conductive hydrogel and silver paint electrodes that displace a vegetable‐based liquid dielectric under the application of an electric field. The electronic properties of the silicone material as well as the mechanical properties of the constitutive silicone and hydrogel materials are investigated. The hydraulic pressure exerted on the dielectric working fluid in these capacitive actuators is measured in order to characterize their quasi‐static behavior. Various design features enabled by 3D printing influence this behavior—decreasing the voltage at which actuation begins or increasing the force density in the system. Using a capacitance change of >35% across the actuators while powered, a demonstration of self‐sensing inherent to HASELs is shown. Antagonistic pairs of the 3D printed actuators are shown to exert a blocked force of over 400 mN. An electrohydraulic tentacle actuator is then fabricated to demonstrate the use of this material and actuation system in a synthetic hydrostat. This tentacle actuator is shown to achieve motion in a multi‐dimensional space.     

Variant Enrichment Analysis to Explore Pathways Functionality in Complex Autoinflammatory Skin Disorders through Whole Exome Sequencing Analysis

The challenge of unravelling the molecular basis of multifactorial disorders nowadays cannot rely just on association studies searching for potential causative variants shared by groups of patients and not present in healthy individuals; indeed, association studies have as a main limitation the lack of information on the interactions between the disease-causing variants. Thus, new genomic analysis tools focusing on disrupted pathways rather than associated gene variants are required to better understand the complexity of a disease. Therefore, we developed the Variant Enrichment Analysis (VEA) workflow, a tool applicable for whole exome sequencing data, able to find differences between the numbers of genetic variants in a given pathway in comparison with a reference dataset. In this study, we applied VEA to discover novel pathways altered in patients with complex autoinflammatory skin disorders, namely PASH (n = 9), 3 of whom are overlapping with SAPHO) and PAPASH (n = 3). With this approach we have been able to identify pathways related to neutrophil and endothelial cells homeostasis/activations, as disrupted in our patients. We hypothesized that unregulated neutrophil transendothelial migration could elicit increased neutrophil infiltration and tissue damage. Based on our findings, VEA, in our experimental dataset, allowed us to predict novel pathways impaired in subjects with autoinflammatory skin disorders.     

A New Paradigm for a New Field: Communicating Representations of Engineering Education Research

Based on a three‐year experience of developing, facilitating, and assessing NSF‐funded workshops on Rigorous Research in Engineering Education (RREE), the authors present four representations of engineering education scholarly work in the United States, specifically teaching and research. Many of the representations describe the relationships between engineering research, education research, teaching, and assessment. For each of the representations, assessment data are presented to evaluate which aspects resonated with workshop participants and which needed to be changed for wide acceptance by a U.S. engineering education audience. It was found that participants preferred continua to dichotomy and were more receptive to models that were introduced inductively through active learning exercises. Lessons learned, implications for the field, and future plans for further development of the paradigm are also included.