RESUMO
This study endeavors to comprehensively explore and elucidate the seamless integration of NiTi shape memory alloys (SMAs) into multifaceted applications through the utilization of novel joining techniques. The primary focus lies in the utilization of wire arc additive manufacturing (WAAM) to deposit Nitinol (NiTi) onto Copper (Cu), thereby introducing a transformative approach for their integration into electro-mechanical systems and beyond. Through a detailed examination of the NiTi/Cu bimetallic junction, using advanced analytical techniques including SEM, XRD, and DSC analyses, this research aims to unravel the intricate complexities inherent within the interface. The SEM images and X-ray patterns obtained reveal a complex and nuanced interface characterized by a broad mixed zone comprising various constituents, including Ti(Ni,Cu)2, pure Cu, Ti2(Ni,Cu)3 precipitates, and Ni-rich NiTi precipitates. The DSC results, showcasing low-intensity broad peaks during thermal cycling, underscore the inherent challenges in demonstrating functional properties within the NiTi/Cu system. Recognizing the critical importance of an enhanced martensitic transformation, this study delves into the effects of heat treatment. Calorimetric curves post-annealing at 500 °C exhibit distinct transformation peaks, shedding light on the intricate influence of NiTi layer distribution within the junction. The optimal heat treatment parameters for NiTi/Cu junction restoration are meticulously explored and determined at 500 °C for a duration of 12 h. Furthermore, the study offers valuable insights into optimizing NiTi-Cu joints, with micro-hardness values reaching 485 HV and compressive strength scaling up to 650 MPa. These significant findings not only hold promise for diverse applications across various industries but also pave the way for further research directions and explorations into the realm of SMA integration and advanced joining methodologies.
RESUMO
Studies have shown that some peptides and small molecules can induce non IgE-mediated anaphylactoid reactions through mast cell activation. Upon activation, mast cells degranulate and release vasoactive and proinflammatory mediators, from cytoplasmic granules into the extracellular environment which can induce a cascade of severe adverse reactions. This study describes a lead optimization strategy to select NaV1.7 inhibitor peptides that minimize acute mast cell degranulation (MCD) toxicities. Various in vitro, in vivo, and PKPD models were used to screen candidates and guide peptide chemical modifications to mitigate this risk. Anesthetized rats dosed with peptides demonstrated treatment-related decreases in blood pressure and increases in plasma histamine concentrations which were reversible with a mast cell stabilizer, supporting the MCD mechanism. In vitro testing in rat mast cells with NaV1.7 peptides demonstrated a concentration-dependent increase in histamine. Pharmacodynamic modeling facilitated establishing an in vitro to in vivo correlation for histamine as a biomarker for blood pressure decline via the MCD mechanism. These models enabled assessment of structure-activity relationship (SAR) to identify substructures that contribute to peptide-mediated MCD. Peptides with hydrophobic and cationic characteristics were determined to have an elevated risk for MCD, which could be reduced or avoided by incorporating anionic residues into the protoxin II scaffold. Our analyses support that in vitro MCD assessment in combination with PKPD modeling can guide SAR to improve peptide lead optimization and ensure an acceptable early in vivo tolerability profile with reduced resources, cycle time, and animal use.
