407 research outputs found

    Weight-Constrained Reliability Allocation for All Electric Aircraft Powertrains

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    The shift towards electric aircraft poses significant challenges in balancing lightweight design and high reliability of powertrains. Typically, improving reliability requires redundancy, which adds weight, while lightweight designs often compromise reliability. In this paper, we propose a weight-constrained reliability allocation model for the powertrain design of electric aircraft. The relationship between reliability and weight for each component, including battery, inverter, and electric motor is analytically and linearly expressed using universal generating functions (UGF) and McCormick envelope technique. Our model considers variable operating conditions that impact component reliability, such as changes in core temperature caused by high-attitude and variable thrust power caused by wind speed and direction. Our approach enhances the overall performance of electric powertrains systems for aircraft. Using the " Spirit of Innovation " electric aircraft as a case study, the proposed method can improve the powertrain reliability from 0.9786 to 0.9870 through reasonable allocation without adding extra weight. Alternatively, it can reduce the weight by 3.1% without compromising the reliability of the powertrain.</p

    Cryo-XPS for Surface Characterization of Nanomedicines

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    Nanoparticles used for medical applications commonly possess coatings or surface functionalities intended to provide specific behavior in vivo, for example, the use of PEG to provide stealth properties. Direct, quantitative measurement of the surface chemistry and composition of such systems in a hydrated environment has thus far not been demonstrated, yet such measurements are of great importance for the development of nanomedicine systems. Here we demonstrate the first use of cryo-XPS for the measurement of two PEG-functionalized nanomedicines: a polymeric drug delivery system and a lipid nanoparticle mRNA carrier. The observed differences between cryo-XPS and standard XPS measurements indicate the potential of cryo-XPS for providing quantitative measurements of such nanoparticle systems in hydrated conditions.acceptedVersio

    Nanoparticle isolation from biological media for protein corona analysis : the impact of incubation and recovery protocols on nanoparticle properties

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    Nanoparticles are increasingly implemented in biomedical applications, including the diagnosis and treatment of disease. When exposed to complex biological media, nanoparticles spontaneously interact with their surrounding environment, leading to the surface-adsorption of small and bio- macromolecules- termed the "corona". Corona composition is governed by nanoparticle properties and incubation parameters. While the focus of most studies is on the protein signature of the nanoparticle corona, the impact of experimental protocols on nanoparticle size in the presence of complex biological media, and the impact of nanoparticle recovery from biological media has not yet been reported. Here using a non-degradable robust model, we show how centrifugation-resuspension protocols used for the isolation of nanoparticles from incubation media, incubation duration and shear flow conditions alter nanoparticle parameters including particle size, zeta potential and total protein content. Our results show significant changes in nanoparticle size following exposure to media containing protein under different flow conditions, which also altered the composition of surface-adsorbed proteins profiled by SDS-PAGE. Our in situ analysis of nanoparticle size in media containing protein using particle tracking analysis highlights that centrifugation-resuspension is disruptive to agglomerates that are spontaneously formed in protein containing media, highlighting the need for in situ analytical methods that do not alter the intermediates formed following nanoparticle exposure to biological media. Nanomedicines are mostly intended for parenteral administration, and our findings show that parameters such as shear flow can significantly alter nanoparticle physicochemical parameters. Overall, we show that the centrifugation-resuspension isolation of nanoparticles from media significantly alters particle parameters in addition to the overall protein composition of surface-adsorbed proteins. We recommend that nanoparticle characterization pipelines studying bio-nano interactions during early nanomedicine development consider biologically-relevant shear flow conditions and media composition that can significantly alter particle physical parameters and subsequent conclusions from these studies

    Evaluating the impact of experimental shear flow parameters on nanoparticle protein corona formation

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    The use of nanoparticles has increasingly been implemented in biomedical applications including the diagnosis and treatment of disease. When administered to a biological system, nanoparticles spontaneously interact with their surrounding environment, leading to the surface-adsorption of small molecules and biomacromolecules. The protein component of the surface-adsorbed species, is often referred to as the "protein corona". The composition of the protein corona is governed by nanoparticle properties, incubation media and parameters related to the environment in which nanoparticle incubations are performed. In this study, we investigated the formation of protein corona on polystyrene nanoparticles which have different surface chemistries and the impact of experimental incubation parameters, including centrifugation-resuspension protocols, incubation duration and shear flow rate conditions. The particle characteristics measured include size distribution, zeta potential and total protein content. Our findings show significant differences in nanoparticle size following exposure to media containing proteins across the three different nanoparticle surface chemistries. These findings were also confirmed by total protein concentration measurements performed on nanoparticles recovered from bulk media, and measurements of the composition of surface-adsorbed proteins by gel electrophoresis. We also found that exposure to different shear flow conditions alters both the thickness and the composition of surface-adsorbed protein coronas. In parallel to analysis of nanoparticles isolated using the centrifugation-resuspension protocol, we performed in situ analysis of nanoparticle size in media containing proteins. Results obtained from these measurements highlight that the recovery procedure is disruptive to the protein corona and therefore the need for investigative methods that do not alter the properties of the nanoparticle coronas. Nanomedicines are generally intended for administration via injection, and our findings show that parameters such as shear flow and media composition can significantly alter nanoparticle physicochemical parameters. Overall, we show that the recovery protocol can significantly alter particle parameters in addition to the overall protein composition of surface-adsorbed proteins. We recommend that nanoparticle characterization pipelines studying bio-nano interactions during early nanomedicine development consider experimental design in the context of biologically-relevant shear flow conditions and media composition because these parameters can significantly alter particle physical parameters and the subsequent conclusions drawn from such studies

    Biomechanical and histological changes associated with riboflavin ultraviolet-A-induced CXL with different irradiances in young human corneal stroma.

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    Keratoconus (KC) is a degenerative condition affecting the cornea, characterized by progressive thinning and bulging, which can ultimately result in serious visual impairment. The onset and progression of KC are closely tied to the gradual weakening of the cornea's biomechanical properties. KC progression can be prevented with corneal cross-linking (CXL), but this treatment has shortcomings, and evaluating its tissue stiffening effect is important for determining its efficacy. In this field, the shortage of human corneas has made it necessary for most previous studies to rely on animal corneas, which have different microstructure and may be affected differently from human corneas. In this research, we have used the lenticules obtained through small incision lenticule extraction (SMILE) surgeries as a source of human tissue to assess CXL. And to further improve the results' reliability, we used inflation testing, personalized finite element modeling, numerical optimization and histology microstructure analysis. These methods enabled determining the biomechanical and histological effects of CXL protocols involving different irradiation intensities of 3, 9, 18, and 30 mW/cm2, all delivering the same total energy dose of 5.4 J/cm2. The results showed that the CXL effect did not vary significantly with protocols using 3-18 mW/cm2 irradiance, but there was a significant efficacy drop with 30 mW/cm2 irradiance. This study validated the updated algorithm and provided guidance for corneal lenticule reuse and the effects of different CXL protocols on the biomechanical properties of the human corneal stroma

    Perceived Roles and Barriers in Delivering Community-Based Care: A Qualitative Study of Health and Social Care Professionals

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    Introduction: As healthcare systems increasingly embrace population health management, the integration of health and social care to improve the health and well-being of individuals is crucial. Thus, we conducted a qualitative study in Singapore to understand health and social care professionals’ (HCPs and SCPs) perception of the roles they played in delivering community-based care. Methods: A descriptive phenomenological research design was adopted. HCPs and SCPs (n = 53) providing services in community settings were recruited purposefully and interviewed through eleven focus group discussions. Each session was recorded and transcribed. Thematic analysis was applied. Results: Our results revealed eight themes in three main categories describing the roles played by HCPs and SCPs, including: (1) delivering needs-based care in community settings; (2) activating and empowering clients in health care, and (3) fostering community-based sustainable support networks. Six barriers encountered while performing these roles were also identified. Discussion and Conclusion: Our results highlight that the roles of HCPs and SCPs go beyond the provision of direct medical and social care. They were involved in activating and empowering clients to take care of their health, and importantly, fostering community-based sustainable support networks to better empower individuals in coping with health challenges. The identified barriers shed light on areas for potential improvements for integrated community care

    Hydrophobically Modified Sulfobetaine Copolymers with Tunable Aqueous UCST through Postpolymerization Modification of Poly(pentafluorophenyl acrylate)

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    Polysulfobetaines, polymers carrying highly polar zwitterionic side chains, present a promising research field by virtue of their antifouling properties, hemocompatibility, and stimulus-responsive behavior. However, limited synthetic approaches exist to produce sulfobetaine copolymers comprising hydrophobic components. Postpolymerization modification of an activated ester precursor, poly(pentafluorophenyl acrylate), employing a zwitterionic amine, 3-((3-aminopropyl)dimethylammonio)propane-1-sulfonate, ADPS, is presented as a novel, one-step synthetic concept toward sulfobetaine (co)polymers. Modifications were performed in homogeneous solution using propylene carbonate as solvent with mixtures of ADPS and pentylamine, benzylamine, and dodecylamine producing a series of well-defined statistical acrylamido sulfobetaine copolymers containing hydrophobic pentyl, benzyl, or dodecylacrylamide comonomers with well-controllable molar composition as evidenced by NMR and FT-IR spectroscopy and size exclusion chromatography.This synthetic strategy was exploited to investigate, for the first time, the influence of hydrophobic modification on the upper critical solution temperature (UCST) of sulfobetaine copolymers in aqueous solution. Surprisingly, incorporation of pentyl groups was found to increase solubility over a wide composition range, whereas benzyl groups decreased solubility—an effect attributed to different entropic and enthalpic contributions of both functional groups. While UCST transitions of polysulfobetaines are typically limited to higher molar mass samples, incorporation of 0–65 mol % of benzyl groups into copolymers with molar masses of 25.5–34.5 kg/mol enabled sharp, reversible transitions from 6 to 82 °C in solutions containing up to 76 mM NaCl, as observed by optical transmittance and dynamic light scattering. Both synthesis and systematic UCST increase of sulfobetaine copolymers presented here are expected to expand the scope and applicability of these smart materials

    Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

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    A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

    Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

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    A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV

    Probing effective field theory operators in the associated production of top quarks with a Z boson in multilepton final states at root s=13 TeV

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