For modern switching power supplies, current bulk magnetic materials, such as ferrites or magnetic metal alloys, cannot provide both low loss and high magnetic saturation to function with both high power density and high efficiency at high frequencies (10-100 MHz). Magnetic nanocomposites comprised of a ferrite and magnetic metal alloy provide the opportunity to achieve these desired magnetic properties, but previously investigated thin-film fabrication techniques have difficulty achieving multi-micrometer film thicknesses which are necessary to provide practical magnetic energy storage and power handling. Here, we present a versatile technique to fabricate thick magnetic nanocomposites via a two-step process, consisting of the electrophoretic deposition of an iron oxide nanoparticle phase into a mold on a substrate, followed by electro-infiltration of a nickel matrix. The deposited films are imaged via scanning electron microscopy and energy dispersive X-ray spectroscopy to identify the presence of iron and nickel, confirming the infiltration of the nickel between the iron oxide nanoparticles. A film thickness of ∼7 μm was measured via stylus profilometry. Further confirmation of successful composite formation is obtained with vibrating sample magnetometry, showing the saturation magnetization value of the composite (473 kA/m) falls between that of the iron oxide nanoparticles (280 kA/m) and the nickel matrix (555 kA/m). These results demonstrate the potential of electrophoretic deposition coupled with electro-infiltration to fabricate magnetic nanocomposite films.
IntroductionMentorship is essential for students considering a future in academic medicine. Mentoring is recognized as one of the most important factors in determining career success through enhancing trainees' goals and productivity. An effective mentoring relationship can drive trainees' goals to fruition by providing support so that opportunistic risk can be taken and failures can be reevaluated into learning experiences. Mentorship has such importance that it was deemed mandatory in education by the Liaison Committee on Medical Education and the Accreditation Council for Graduate Medical Education. Moreover, mentoring can play a significant role in helping to diversify the academic medicine workforce.MethodsThis 60-minute workshop utilizes a didactic PowerPoint presentation and small-group role-play exercise to introduce participants to the importance of mentoring in the development of academic medicine careers and to provide instruction on establishing effective meetings with prospective mentors. Faculty facilitated the workshop at nine regional academic medicine conferences held across the country.ResultsEighty-seven diverse participants completed an evaluation form. In comparing pre- and postworkshop responses, there was a statistically significant increase in confidence to “Find a mentor for a career in academic medicine” (2.29 vs. 3.26, p < .001) and “Have a successful relationship with an academic medicine mentor” (2.52 vs. 3.38, p < .001). Moreover, more than 85% agreed or strongly agreed that the workshop's learning objectives were met.DiscussionTrainees from diverse backgrounds gained crucial insight into the importance of mentorship and techniques on how to establish and maintain mentors while pursuing an academic medicine career.
T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve response rates compared with monotherapy PD-1/L1 blockade in checkpoint naive nonsmall cell lung cancer with PD-L1 expression >50%. TIGIT mAbs with an effector-competent Fc can induce myeloid cell activation, and some have demonstrated effector T cell depletion, which carries a clinical liability of unknown significance. TIGIT Ab blockade translates to antitumor activity by enabling PVR signaling through CD226 (DNAM-1), which can be directly inhibited by PD-1. Furthermore, DNAM-1 is downregulated on tumor-infiltrating lymphocytes (TILs) in advanced and checkpoint inhibitionresistant cancers. Therefore, broadening clinical responses from TIGIT blockade into PD-L1 low or checkpoint inhibitionresistant tumors, may be induced by immune costimulation that operates independently from PD-1/L1 inhibition. TNFSF14 (LIGHT) was identified through genomic screens, in vitro functional analysis, and immune profiling of TILs as a TNF ligand that could provide broad immune activation. Accordingly, murine and human bifunctional fusion proteins were engineered linking the extracellular domain of TIGIT to the extracellular domain of LIGHT, yielding TIGIT-Fc-LIGHT. TIGIT competitively inhibited binding to all PVR ligands. LIGHT directly activated myeloid cells through interactions with LTbR (lymphotoxin b receptor), without the requirement for a competent Fc domain to engage Fcg receptors. LIGHT costimulated CD8 + T and NK cells through HVEM (herpes virus entry mediator A). Importantly, HVEM was more widely expressed than DNAM-1 on T memory stem cells and TILs across a range of tumor types. Taken together, the mechanisms of TIGIT-Fc-LIGHT promoted strong antitumor activity in preclinical tumor models of primary and acquired resistance to PD-1 blockade, suggesting that immune costimulation mediated by LIGHT may broaden the clinical utility of TIGIT blockade.
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