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Abstract: Nanoparticles are well-established carriers for targeted delivery of bioactive polymeric nanoparticles (PNPs). They have attracted significant attention from pharmaceutical scientists globally due to their wide range of applications in the medical field. The encapsulation of drugs into the nanoparticles offer several unique characteristics leading to prolonged circulation, improved drug localization, and thus enhanced drug efficacy. It also provides a better understanding of the molecular basis of the disease. Nanoparticles allow efficient maintenance of medication cycles at the target site, with less exposure to normal cells and thus decreasing the rehabilitation period. Despite extensive developments in the field of nanotechnology, specifically in drug delivery, only a few nanotechnology-based products are currently available in the market. Thus, further advanced exploration is necessary to make nanoparticles useful for the betterment of mankind. This review is focused on recent advancements in pharmaceutical nanotechnology with special emphasis on polymers used for the preparation of PNPs and their emerging applications in tumor-targeting. This manuscript also highlights on the recent patents disclosing PNPs for tumor targeting.

Printed electrical gas sensors are a low-cost, lightweight, low-power, and potentially disposable alternative to gas sensors manufactured using conventional methods such as photolithography, etching, and chemical vapor deposition. The growing interest in Internet-of-Things, smart homes, wearable devices, and point-of-need sensors has been the main driver fueling the development of new classes of printed electrical gas sensors. In this Perspective, we provide an insight into the current research related to printed electrical gas sensors including materials, methods of fabrication, and applications in monitoring food quality, air quality, diagnosis of diseases, and detection of hazardous gases. We further describe the challenges and future opportunities for this emerging technology.

The terahertz (0.1–10 THz) range represents a fast-evolving research and industrial field. The great interest for this portion of the electromagnetic spectrum, which lies between the photonics and the electronics ranges, stems from the unique and disruptive sectors where this radiation finds applications in, such as spectroscopy, quantum electronics, sensing and wireless communications beyond 5G. Engineering the propagation of terahertz light has always proved to be an intrinsically difficult task and for a long time it has been the bottleneck hindering the full exploitation of the terahertz spectrum. Amongst the different approaches that have been proposed so far for terahertz signal manipulation, the implementation of metamaterials has proved to be the most successful one, owing to the relative ease of realisation, high efficiency and spectral versatility. In this review, we present the latest developments in terahertz modulators based on metamaterials, while highlighting a few selected key applications in sensing, wireless communications and quantum electronics, which have particularly benefitted from these developments.

Glial fibrillary acidic protein (GFAP) is a discriminative blood biomarker for many neurological diseases, such as traumatic brain injury. Detection of GFAP in buffer solutions using biosensors has been demonstrated, but accurate quantification of GFAP in patient samples has not been reported, yet in urgent need. Herein, we demonstrate a robust on-chip graphene field-effect transistor (GFET) biosensing method for sensitive and ultrafast detection of GFAP in patient plasma. Patients with moderate–severe traumatic brain injuries, defined by the Mayo classification, are recruited to provide plasma samples. The binding of target GFAP with the specific antibodies that are conjugated on a monolayer GFET device triggers the shift of its Dirac point, and this signal change is correlated with the GFAP concentration in the patient plasma. The limit of detection (LOD) values of 20 fg/mL (400 aM) in buffer solution and 231 fg/mL (4 fM) in patient plasma have been achieved using this approach. In parallel, for the first time, we compare our results to the state-of-the-art single-molecule array (Simoa) technology and the classic enzyme-linked immunosorbent assay (ELISA) for reference. The GFET biosensor shows competitive LOD to Simoa (1.18 pg/mL) and faster sample-to-result time (

Microfluidics offers precise and dynamic control of microenvironments for the study of temporal cellular responses. However, recent research focusing solely on either homocellular (single-cell, population) or heterocellular response may yield insufficient output, which possibly leads to partial comprehension about the underlying mechanisms of signaling events and corresponding cellular behaviors. Here, a universal microfluidic approach is developed for integrated analysis of temporal signaling and cell migration dynamics in multiple cellular contexts (single-cell, population and coculture). This approach allows to confine the desired number or mixture of specific cell sample types in a single device. Precise single cell seeding was achieved manually with bidirectional controllability. Coupled with time-lapse imaging, temporal cellular responses can be observed with single-cell resolution. Using NIH3T3 cells stably expressing signal transducer and activator of transcription 1/2 (STAT1/2) activity biosensors, temporal STAT1/2 activation and cell migration dynamics were explored in isolated single cells, populations and cocultures stimulated with temporal inputs, such as single-pulse and continuous signals of interferon γ (IFNγ) or lipopolysaccharide (LPS). We demonstrate distinct dynamic responses of fibroblasts in different cellular contexts. Our presented approach facilitates a multi-dimensional understanding of STAT signaling and corresponding migration behaviors.

We report the first inorganic/organic hybrids that show outstanding mechanical properties (withstanding cyclic loading) and bone bioactivity. This new hybrid material may fulfil the unmet clinical need for bioactive synthetic bone grafts that can withstand cyclic loading. A SiO2/PTHF/PCL-diCOOH sol-gel hybrid system, that combined inorganic and organic co-networks at the molecular level, previously demonstrated unprecedented synergy of properties, with excellent flexibility and promoted formation of articular cartilage matrix in vitro. Here, for the first time, calcium and phosphate ions were incorporated into the inorganic component of the hybrid network, to impart osteogenic properties. Calcium methoxyethoxide and triethyl phosphate were the calcium and phosphate precursors because they allow for incorporation into the silicate network at low temperature. The hybrid network was characterised with ATR-FTIR, XRD and solid-state Nuclear Magnetic Resonance, which proved calcium and phosphate incorporation and suggested the Ca2+ ions also interacted with PCL-diCOOH through ionic bonds. This resulted in an increased strength (17–64 MPa) and modulus of toughness (2.5–14 MPa) compared to the original SiO2/PTHF/PCL-diCOOH hybrid material (which showed strength of ∼3 MPa and modulus of toughness of ∼0.35 MPa), while also maintaining the ability to withstand cyclic loading. The presence of calcium and phosphates in the silicate network resulted in a more congruent dissolution of the inorganic and organic co-networks in TRIS buffer. This was shown by the presence of silicon, calcium and phosphate ions along with PCL in the TRIS buffer after 1 week, whereas Ca-free hybrids mainly released PCL with negligible Si dissolution. The presence of calcium and phosphates also enabled deposition of hydroxycarbonate apatite following immersion in simulated body fluid, which was not seen on Ca-free hybrid. All hybrids passed cell cytotoxicity tests and supported pre-osteoblast cell attachment. The phosphate-free hybrid showed the best mechanical behaviour and supported better cell attachment, spreading and potentially differentiation of cells. Therefore, the SiO2-CaO/PTHF/PCL-diCOOH hybrid represents a promising biomaterial for use in bone regeneration.

Personalized and point-of-care (POC) diagnoses are critical for ocular physiology and disease diagnosis. Real-time monitoring and continuous sampling abilities of tear fluid and user-friendliness have become the key characteristics for the applied ophthalmic techniques. Fluorescence technologies, as one of the most popular methods that can fulfill the requirements of clinical ophthalmic applications for optical sensing, have been raised and applied for tear sensing and diagnostic platforms in recent decades. Wearable sensors in this case have been increasingly developed for ocular diagnosis. Contact lenses, as one of the commercialized and popular tools for ocular dysfunction, have been developed as a platform for fluorescence sensing in tears diagnostics and real-time monitoring. Numbers of biochemical analytes have been examined through developed fluorescent contact lens sensors, including pH values, electrolytes, glucose, and enzymes. These sensors have been proven for monitoring ocular conditions, enhancing and detecting medical treatments, and tracking efficiency of related ophthalmic surgeries at POC settings. This review summarizes the applied ophthalmic fluorescence sensing technologies in tears for ocular diagnosis and monitoring. In addition, the cooperation of fabricated fluorescent sensor with mobile phone readout devices for diagnosing ocular diseases with specific biomarkers continuously is also discussed. Further perspectives for the developments and applications of fluorescent ocular sensing and diagnosing technologies are also provided.

Coupled resonator filters implemented as microelectromechanical systems (MEMS) offer performance advantages as band-pass filters at MHz frequencies. Here new designs based on resonant cavities for acoustic slow waves are developed to allow alternative frequency responses. Derivation of the lumped element model for coupled beam systems with in-plane motion from Rayleigh–Ritz perturbation theory is first reviewed. Departures from ideal behaviour caused by mechanical and electrostatic detuning are resolved. Slow wave theory is then used to develop linear array topologies with novel responses including band-stop and comb filtering with controlled filter roll-off. A systematic procedure is developed to allow rapid identification of design parameters without the need for lengthy numerical simulation, using the lumped element, stiffness matrix and finite element methods to investigate the layout parameters of initial design concepts, detailed mechanical effects and detailed electrostatic effects, respectively. High performance is demonstrated, with good agreement between the models.

BACKGROUND: Baricitinib is approved for the treatment of rheumatoid arthritis (RA). The authors retrospectively investigated adverse events (AEs) by data-mining a self-reporting database to better understand toxicities, especially since it has been used during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A reporting odds ratio (ROR) was used to detect the risk signals from the data in the US Food and Drug Administration (FDA) adverse event reporting system database (FAERS). The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). RESULTS: The search retrieved 1,598 baricitinib-associated cases within the reporting period: 86 PTs with significant disproportionality were retained. Infections including 'herpes zoster,' 'oral herpes,' and 'herpes virus infection' were found at a similar rate to those reported in trials, and such events were rare. Reports emerged for several thrombotic adverse events, while these events were also rare. Unexpected safety signals as opportunistic infections were detected. Serious outcomes as death and life-threatening outcomes accounted for 9.76% of the reported cases. CONCLUSIONS: The incidence of these AEs does not appear above the background expected. These data are consistent with routine clinical observations and suggest the importance of pharmacovigilance.

Surface plasmons at an interface between dielectric and metal regions can in theory be made arbitrarily compact normal to the interface by introducing extreme anisotropy in the material parameters. We propose a metamaterial structure comprising a square array of gold cylinders and tune the filling factor to achieve the material parameters we seek. Theory is compared to a simulation wherein the unit cell dimensions of the metamaterial are shown to be the limiting factor in the degree of localisation achieved.

Zn-containing dense monodispersed bioactive glass nanoparticles (Zn-BAGNPs) have been developed to deliver therapeutic inorganic trace elements, including Si, Ca, Sr, and Zn, to the cells through the degradation process, as delivery carriers for stimulating bone regeneration because of their capacity to induce osteogenic differentiation. The sol–gel-derived dense silica nanoparticles (SiO2-NPs) were first synthesized using the modified Stöber method, prior to incorporating therapeutic cations through the heat treatment process. The successfully synthesized monodispersed Zn-BAGNPs (diameter of 130 ± 20 nm) were homogeneous in size with spherical morphology. Ca, Sr and Zn were incorporated through the two-step post-functionalization process, with the nominal ZnO ratio between 0 and 2 (0, 0.5, 1.0, 1.5 and 2.0). Zn-BAGNPs have the capacity for continuous degradation and simultaneous ion release in SBF and PBS solutions due to their amorphous structure. Zn-BAGNPs have no in vitro cytotoxicity on the murine pre-osteoblast cell (MC3T3-E1) and periodontal ligament stem cells (PDLSCs), up to a concentration of 250 µg/mL. Zn-BAGNPs also stimulated osteogenic differentiation on PDLSCs treated with particles, after 2 and 3 weeks in culture. Zn-BAGNPs were not toxic to the cells and have the potential to stimulate osteogenic differentiation on PDLSCs. Therefore, Zn-BAGNPs are potential vehicles for therapeutic cation delivery for applications in bone and dental regenerations.

We studied the striking effect of external irradiation of nanowires on the dynamics of their surface morphology at elevated temperatures that do not destroy their crystal lattice. Numerical experiments performed on the basis of the Monte Carlo model revealed new possibilities for controlled periodic modulation of the cross-section of quasi-one-dimensional nanostructures for opto- and nanoelectronic elements. These are related to the fact that external irradiation stimulates the surface diffusion of atoms. On the one hand, such stimulation should accelerate the development of the well-known spontaneous thermal instability of nanowires (Rayleigh instability), which leads to their disintegration into nanoclusters. On the other hand, this leads to the forced development of the well-known roughening transition (RT) effect. Under normal circumstances, this manifests itself on selected crystal faces at a temperature above the critical one. The artificial stimulation of this effect on the lateral surface of quasi-one-dimensional structures determines many unpredictable scenarios of their surface dynamics, which essentially depend on the orientation of the nanowire axis relative to its internal crystal structure. In particular, the long-wave Rayleigh breakup observed in absence of external irradiation transforms into strongly pronounced short-wave metastable modulations of the cross-section (a chain of unduloids). The effect of the self-consistent relationship between the Rayleigh instability and RT is dimensional and can be observed only at relatively small nanowire radii. The fact is analyzed that, for the manifestation of this effect, it is very important to prevent significant heating of the nanowire when surface diffusion is stimulated. A number of developed theoretical concepts have already found confirmation in real experiments with Au and Ag nanowires irradiated by electrons and Ag+ ions, respectively. This research was supported by the Swiss National Science Foundation (SNSF) (IZSEZ0_206111).

Continuous monitoring of physiological conditions and biomarkers via optical holographic sensors is an area of growing interest to facilitate the expansion of personalised medicine. Here, a facile laser-induced dual polymerization method is developed to fabricate holographic hydrogel sensors for the continuous and reversible colorimetric determination of pH variations over a physiological range in serum (pH 7–9). Readout parameters simulated through a Finite-difference time-domain Yee's algorithm retrieve the spectral response through expansion. Laser lithography of holographic hydrogel sensor fabrication is achieved via a single 355 nm laser pulse to initiate polymerization of ultrafine hydrogel fringes. Eliminating the requirement for complex processing of toxic components and streamlining the synthetic procedure provides a simpler route to mass production. Optimised pH-responsive hydrogels contain amine bearing functional co-monomers demonstrating reversible Bragg wavelength shifts of 172 nm across the entire visible wavelength range with pH variation from 7.0 to 9.0 upon illumination with broadband light. Photolithographic recording of information shows the ability to convey detailed information to users for qualitative identification of pH. Holographic sensor reversibility over 20 cycles showed minimal variation in replay wavelength supporting reliable and consistent readout, with optimised sensors showing rapid response times of

Lateral flow tests, commonly based on metal plasmonic nanoparticles, are rapid, robust, and low-cost. However, improvements in analytical sensitivity are required to allow detection of low-abundance biomarkers, for example detection of low antigen concentrations for earlier or asymptomatic diagnosis of infectious diseases. Efforts to improve sensitivity often require changes to the assay. Here, we developed optical methods to improve the sensitivity of absorption-based lateral flow tests, requiring no assay modifications to existing tests. We experimentally compared five different lock-in and subtraction-based methods, exploiting the narrow plasmonic peak of gold nanoparticles for background removal by imaging at different light wavelengths. A statistical framework and three fitting models were used to compare limits of detection, giving a 2.0-5.4-fold improvement. We then demonstrated the broad applicability of the method to an ultrasensitive assay, designing 530 nm composite nanoparticles to increase the particle volume, and therefore light absorption per particle, whilst retaining the plasmonic peak to allow background removal and without adding any assay steps. This multifaceted, modular approach gave a combined 58-fold improvement in the fundamental limit of detection using a biotin-avidin model over 50 nm gold nanoparticles with single-wavelength imaging. Applying to a sandwich assay for the detection of HIV capsid protein gave a limit of detection of 170 fM. Additionally, we developed an open-source software tool for performing the detection limit analysis used in this work.

Deep learning (DL) is a subfield of machine learning (ML), which has recently demonstrated its potency to significantly improve the quantification and classification workflows in biomedical and clinical applications. Among the end applications profoundly benefitting from DL, cellular morphology quantification is one of the pioneers. Here, we first briefly explain fundamental concepts in DL and then we review some of the emerging DL-enabled applications in cell morphology quantification in the fields of embryology, point-of-care ovulation testing, as a predictive tool for fetal heart pregnancy, cancer diagnostics via classification of cancer histology images, autosomal polycystic kidney disease, and chronic kidney diseases.

Domain walls in Cu–Cl boracite develop as a consequence of an improper ferroelastic, improper ferroelectric transition, and have attracted close interest because some are conductive and all can be mechanically written and repositioned by application of an electric field. The phase transition and its associated dynamical properties have been analysed here from the perspective of strain and elasticity. Determination of spontaneous strains from published lattice parameter data has allowed the equilibrium long-range order parameter for F 4 ̄ 3c → Pca21 to be modelled simply as being close to the order–disorder limit. High acoustic loss in the cubic phase, revealed by resonant ultrasound spectroscopy, is consistent with the presence of dynamical microdomains of the orthorhombic structure with relaxation times in the vicinity of ∼10−5–10−6 s. Low acoustic loss in the stability field of the orthorhombic structure signifies, on the other hand, that ferroelastic twin walls which develop as a consequence of the order–disorder process are immobile on this time scale. A Debye loss peak accompanied by ∼1% elastic stiffening at ∼40 K is indicative of some freezing of defects which couple with strain or of some more intrinsic freezing process. The activation energy of ⩾∼0.01–0.02 eV implies a mechanism which could involve strain relaxation clouds around local ferroelectric dipoles or freezing of polarons that determine the conductivity of twin walls.

The metallic glasses are known as amorphous and metastable materials. These materials have superior mechanical properties over crystalline materials with the same chemistry. Continuous efforts were made to improve the properties of metallic glass. The severe plastic deformation (SPD) method is used to improve the ductility of the glass. SPD causes the deformation at the atomic level in the disordered structure of the glass. Many methods are reported, such as cryogenic cycling, high-pressure torsion, and equal channel angular pressing, which are used for the SPD. In recent works on nanostructured metallic glasses, it has been evidenced that some properties, for example, mechanical, thermal, and magnetic, have improved compared to the bulk metallic glass. This paper has reviewed the recent progress in the SPD of the bulk and nanostructured metallic glasses. Different methods for the SPD have been addressed here. The effect of SPD on the properties of metallic glass is deliberated in this paper. Moreover, the challenging tasks of deformation occurrence in the glass and its characterization were considered, trying to develop a sound understanding of SPD in bulk and nanostructured metallic glasses.

The development of hematite-based electrocatalysts (EC) and photoelectrocatalysts (PEC) for oxygen evolution reaction (OER) is highly promising on account of the low-cost and favorable chemical properties. Herein, we report a unique inverse opal framework hematite-based bi-functional catalyst for both EC and PEC water oxidation in alkaline media. Under the combined action of oxygen vacancies (Vo) and gold nanostars (AuNSs) on hematite, the catalyst exhibited excellent activity and stability on both EC and PEC. The composite showed superior electrocatalytic performance for OER with a low overpotential of 281 mV at 10 mA cm−2. Density functional theory (DFT) studies reveal that the coverage of Vo controls the d-band center of surface Fe sites, and the OER activity displays a volcano relationship with the Vo coverage. The addition of gold nanoparticles on the hematite with low Vo coverage improves the adsorption strength of oxygen-containing intermediates to the optimal point and increases the OER activity. Furthermore, the as-prepared photoanode exhibits a ∼3.13 fold increase in current (1.46 mA cm−2) at 1.23 V versus RHE. It is proposed that Vo promotes bulk conductivity and surface catalysis and exhibits reduced activation energy under high light intensity. AuNSs efficiently inhibits the bulk recombination and improves carrier concentration because of the Fermi level equilibration and plasmonic resonance, and the surface catalysis compensates the deterioration of interfacial recombination of carriers induced by Vo, playing a synergistic role.

In this paper, we discuss a novel approach to chemical storage based on the physical properties of the chemicals (reactivity, solid or liquid, and volume) and the intrinsic hazards associated with a chemical as identified by the hazard statements. These are indicated on a substance’s safety data sheet (SDS), for example, oxidizing, flammability, toxicity, and compatibility with other chemicals. We introduce a flowchart to identify appropriate storage locations for each chemical in the laboratory and describe what amendments could be needed to our system if it is replicated at another institution. We describe the advantages of using a chemical inventory system and how it was integrated with our storage guidance. Finally, we provide insights and share lessons learnt on maintaining good chemical management.

Explicit treatment of electronic polarizability in empirical force fields (FFs) represents an extension over a traditional additive or pairwise FF and provides a more realistic model of the variations in electronic structure in condensed phase, macromolecular simulations. To facilitate utilization of the polarizable FF based on the classical Drude oscillator model, Drude Prepper has been developed in CHARMM-GUI. Drude Prepper ingests additive CHARMM protein structures file (PSF) and pre-equilibrated coordinates in CHARMM, PDB, or NAMD format, from which the molecular components of the system are identified. These include all residues and patches connecting those residues along with water, ions, and other solute molecules. This information is then used to construct the Drude FF-based PSF using molecular generation capabilities in CHARMM, followed by minimization and equilibration. In addition, inputs are generated for molecular dynamics (MD) simulations using CHARMM, GROMACS, NAMD, and OpenMM. Validation of the Drude Prepper protocol and inputs is performed through conversion and MD simulations of various heterogeneous systems that include proteins, nucleic acids, lipids, polysaccharides, and atomic ions using the aforementioned simulation packages. Stable simulations are obtained in all studied systems, including 5 μs simulation of ubiquitin, verifying the integrity of the generated Drude PSFs. In addition, the ability of the Drude FF to model variations in electronic structure is shown through dipole moment analysis in selected systems. The capabilities and availability of Drude Prepper in CHARMM-GUI is anticipated to greatly facilitate the application of the Drude FF to a range of condensed phase, macromolecular systems. Accepted version

The performance of millimeter wave (mmWave) line-of-sight multiple input multiple output (LOS MIMO) systems using hybrid arrays of planar subarrays was studied. We characterized the achievable maximum spatial multiplexing gain for such LOS MIMO systems by the measures of spectral efficiency and effective degree of freedom (EDoF). By proposing a joint plane-wave and spherical-wave-based general 3D channel model, we derived the optimal design parameters in the analog domain, i.e., the optimal subarray separation products, and analyzed their sensitivity on the system performance. We also gave analytical eigenvalue expressions of the equivalent LOS MIMO channel matrix, which are applicable to the case of a non-optimal design, as well as the upper and lower bounds of the EDoF for system performance evaluation. A piecewise uniform quantization codebook was further designed for quantizing phase shifter values in practical applications. The numerical and simulation results show that planar subarrays are superior to traditional arrays in terms of spectral efficiency and EDoF in Ricean fading channels because they are more robust to the change in the communication distance and the deviation from the optimal design. The use of hybrid arrays of planar subarrays effectively removes the limitation of mmWave LOS MIMO systems using traditional arrays, through which, the conventional Rayleigh distance criterion has to be satisfied to achieve the optimal performance.

Contact lenses can be functionalized to offer advanced capabilities transcending their primary applications in vision correction and cosmetics. Herein, 40 and 60 nm spherical silver nanoparticles (SNPs) are integrated within poly(2-hydroxyethyl methacrylate) (pHEMA) contact lenses toward fabrication of SNP-loaded contact lenses with excellent optical and material properties as wearables for blue-yellow color vision deficiency (CVD) patients. The morphology and optical properties of the SNPs are characterized prepolymerization using the transmission electron microscopy (TEM) and an optical spectrophotometer. Then, the transmission spectra of the SNP-loaded contact lenses at different concentrations along with the wettability and water content are measured, to demonstrate the effect of NPs’ addition on the lenses’ optical and material characteristics. Results indicate that the transmission spectra of SNP-loaded contact lenses, with optimum concentrations, filter out problematic wavelengths of visible light (485–495 nm), which will facilitate better color distinction for blue-yellow CVD patients. The contact lenses’ optical properties are analogous to the commercial colorblind glasses, indicating their effectiveness as color filtering wearables. Finally, the cytobiocompatability analysis of the contact lenses to RAW 264.7 culture of cells shows that they are biocompatible, and the cell viability remains higher than 75% after 24 h in contact with the lenses.

We ask the question 'what happens to Bloch waves in gratings synthetically moving at near the speed of light?'. First we define a constant refractive index (CRI) model in which Bloch waves remain well defined as they break the light barrier, then show their dispersion rotating through 360 degrees from negative to positive and back again. Next we introduce the effective medium approximation (EMA) then refine it into a 4-wave model which proves to be highly accurate. Finally using the Bloch waves to expand a pulse of light we demonstrate sudden inflation of pulse amplitude combined with reversal of propagation direction as a luminal grating is turned on., Comment: 11 pages, 5 figures

This paper presents an approach for the topological design of multi-material compliant mechanisms with global stress constraints. The element stacking method and the separable stress interpolation scheme are applied to calculate the element stiffness and element stress of multi-material structures. The output displacement of multi-material compliant mechanisms is maximized under the constraints of the maximum stress and the structural volume of each material. The modified P-norm method is applied to aggregate the local von Mises stress constraints for all the finite elements to a global stress constraint. The sensitivities are calculated by the adjoint method, and the method of moving asymptotes is utilized to update the optimization problem. Several numerical examples are presented to demonstrate the effectiveness of the proposed method. The appearance of the de facto hinges in the optimal mechanisms can be suppressed effectively by using the topology optimization model with global stress constraints, and the stress constraints for each material can be met.

Mixing at the microscale is of great importance for various applications ranging from biological and chemical synthesis to drug delivery. Among the numerous types of micromixers that have been developed, planar passive spiral micromixers have gained considerable interest due to their ease of fabrication and integration into complex miniaturized systems. However, less attention has been paid to non-planar spiral micromixers with various cross-sections and the effects of these cross-sections on the total performance of the micromixer. Here, mixing performance in a spiral micromixer with different channel cross-sections is evaluated experimentally and numerically in the Re range of 0.001 to 50. The accuracy of the 3D-finite element model was first verified at different flow rates by tracking the mixing index across the loops, which were directly proportional to the spiral radius and were hence also proportional to the Dean flow. It is shown that higher flow rates induce stronger vortices compared to lower flow rates; thus, fewer loops are required for efficient mixing. The numerical study revealed that a large-angle outward trapezoidal cross-section provides the highest mixing performance, reaching efficiencies of up to 95%. Moreover, the velocity/vorticity along the channel length was analyzed and discussed to evaluate channel mixing performance. A relatively low pressure drop (

Accurate, reliable, and cost-effective immunosensors are clinically important for the early diagnosis and monitoring of progressive diseases, and multiplexed sensing is a promising strategy for the next generation of diagnostics. This strategy allows for the simultaneous detection and quantification of multiple biomarkers with significantly enhanced reproducibility and reliability, whilst requiring smaller sample volumes, fewer materials, and shorter average analysis time for individual biomarkers than individual tests. In this opinionated review, we compare different techniques for the development of multiplexed immunosensors. We review the state-of-the-art approaches in the field of multiplexed immunosensors using electrical, electrochemical, and optical methods. The barriers that prevent translating this sensing strategy into clinics are outlined together with the potential solutions. We also share our vision on how multiplexed immunosensors will continue their evolution in the coming years.

Proteomic mapping of cell surfaces is an invaluable tool for drug development and clinical diagnostics. This work describes a new ‘snapshot imprinting’ method designed to obtain proteomic maps of cell surfaces, with the aim of identifying cell surface markers and epitopes for diagnostic and therapeutic applications. The analysis of two cancer cell lines, HN5 and MDA-MB-468, is described herein as a proof of concept, along with the selective targeting of three identified epitopes of epidermal growth factor receptor using molecularly imprinted polymer nanoparticles. 438 proteins were identified using this technique, with 283 considered to be transmembrane or extracellular proteins. The major advantage of the molecular imprinting approach developed here is the ability to analyse cell surface proteins without tedious fractionation, affinity separation or labelling. We believe that this system of protein analysis may provide a basic molecular diagnostics toolbox for precise, personalised treatment of cancer and other diseases.

Optical resonances arising from quasi-bound states in the continuum (QBICs) have been recently identified in nanostructured dielectrics, showing ultrahigh quality factors accompanied by very large electromagnetic field enhancements. In this work, we design a periodic array of gallium phosphide (GaP) elliptical cylinders supporting, concurrently, three spectrally separated QBIC resonances with in-plane magnetic dipole, out-of-plane magnetic dipole, and electric quadrupole characters. We numerically explore this system for second-harmonic generation and degenerate four-wave mixing, demonstrating giant per unit cell conversion efficiencies of up to ∼ 2 W−1 and ∼ 60 W−2, respectively, when considering realistic introduced asymmetries in the metasurface, compatible with current fabrication limitations. We find that this configuration outperforms by up to more than four orders of magnitude the response of low-Q Mie or anapole resonances in individual GaP nanoantennas with engineered nonlinear mode-matching conditions. Benefiting from the straight-oriented electric field of one of the examined high-Q resonances, we further propose a novel nanocavity design for enhanced spectroscopies by slotting the meta-atoms of the periodic array. We discover that the optical cavity sustains high-intensity fields homogeneously distributed inside the slot, delivering its best performance when the elliptical cylinders are cut from end to end forming a gap, which represents a convenient model for experimental investigations. When placing an electric point dipole inside the added aperture, we find that the metasurface offers ultrahigh radiative enhancements, exceeding the previously reported slotted dielectric nanodisk at the anapole excitation by more than two orders of magnitude.

The coupled light-matter modes supported by plasmonic metasurfaces can be combined with topological principles to yield subwavelength topological valley states of light. We give a systematic presentation of the topological valley states available for lattices of metallic nanoparticles: All possible lattices with hexagonal symmetry are considered, as well as valley states emerging on a square lattice. Several unique effects which have yet to be explored in plasmonics are identified, such as robust guiding, filtering and splitting of modes, as well as dual-band effects. We demonstrate these by means of scattering computations based on the coupled dipole method that encompass the full electromagnetic interactions between nanoparticles., Comment: 10 pages, 9 figures

Plasmonic nanoantennas have revolutionized the way we study and modulate light–matter interaction. Due to nanofabrication limitations, dimer-type nanoantennas always exhibit some degree of asymmetry, which is desirable in some cases. For instance, in sensing applications, asymmetry is sometimes induced by design in plasmonic nanoantennas to favor higher order nonradiative modes with sharp Fano line shapes. Regardless of the actual origin of the asymmetry, unintentional or intentional, an analytical frame that can deal with it in a seamless manner would be beneficial. We resort to conformal mapping for this task and we track the influence of the degree of asymmetry of the circular sectors composing gold bowtie nanoantennas on the nonradiative Purcell enhancement of a nearby nanoemitter. This manuscript reviews the contributions of conformal mapping to plasmonic nanoantennas and illustrates the advantages of the elegant analytical solution provided by conformal mapping to grasp physical insights, which can serve as a springboard for new plasmonic asymmetric nanoantenna designs.

A novel cost-efficient Heat Stamping (HS) process, combining Heat treatment and fast Stamping, was proposed to produce complex-shaped titanium alloy panel components with low energy consumption and short cycle time. To investigate the feasibility of the HS process for forming Ti-6Al-4V, the stress-strain behaviours of the material under step quenching treatments in HS processes were investigated and compared with those under direct heating treatments in Hot Forming (HF) processes, through uniaxial tensile tests at the temperature range of 800 - 950 °C and the strain rate range of 0.01 - 5 /s. To reduce the strain softening, step quenching treatment was designed by soaking the specimen at 950 °C and fast quenching it to 800 °C for forming. It was found that strain softening in the step quenching tests was reduced as compared to direct heating tests at the strain rate of 1 /s; strain hardening was observed in step quenching test at the strain rate of 0.1 /s, achieved by enhancing the dynamic phase transformation from β phase to secondary α (αs) during deformation. Strain rate hardening of the material under step quenching treatment was found to be higher than those under direct heating treatment at the same temperature of 800 °C. To evaluate the novel HS concept, Heat Stamping experiments under step quenching treatments were carried out by using a drawability tool set. A cup-shaped demonstrator with the drawing ratio of 1.3 was produced to prove the feasibility of HS process.

Joining of aluminum alloys through plastic deformation and short-time diffusion bonding has significant applications in a wide range of engineering sectors. It is also important in the elimination of voids and defects in casting ingots through hot rolling processes. An aluminum alloy, AA1060, was selected for the roll-bonding experimental research at vacuum conditions. Parameters including grain size and orientation, dislocation distribution, oxide film breakage, interface welding ratio were studied and analyzed at different hot rolling conditions. Analytical techniques were also developed to analyze the deformation, stress and strain states of the material at hot rolling conditions. The results show that under the condition of 580℃ and 60% deformation, the welding interfaces disappears, and the alloy matrix structure is not overburned.

The goal of this work is to find a reasonable norm to measure the area of low angle grain boundaries (LABs) using EBSD data, which is useful for the metal forming community involved in developing appropriate constitutive models for dynamic recovery. Typically, LABs are defined as the grain boundaries with misorientation between 2° and 10°. However, it is found in this study that reasonable variations of area per volume of LABs (Slab) with strain level (ε), strain rate (έ) and temperature is not be observed for AA7050 with this definition. There is a competition among different processes, including sub-grain formation and coarsening, rotation of sub-grain/cell boundary and migration of LABs and high angle grain boundaries (HABs) during recovery and continuous dynamic recrystallisation. By analysing the evolution of Kernal Angle Misorientation (KAM), it is shown that recovery has more effect on the lower angle part (< 1°) of local misorientation. If the lower limit of LABs is shift to 0.5°, the evolution of Slab with ε and έ shows clear pattern and increasing trend of Slab with temperature is consistent with temperature effect on sub-grain formation process. With such definition, we can have a better understanding of the microstructure evolution in the dynamic restoration of AA7050.

This paper focuses on the prediction of the formability limit of the stiffened panels during the loading stage and heating stage of the creep age forming (CAF) process. A set of non-linear finite element (FE) simulations has been carried out to investigate the elastic-plastic buckling behaviour of stiffened panels subjected to pure bending at the room temperature and the ageing temperature (155 ℃) for AA2050. From the non-linear FE simulations, the effects of main geometric parameters (stiffener thickness and stiffener height) on the critical buckling stress and the critical radius of the stiffened panel have been investigated at both temperatures. Increasing the stiffener thickness or decreasing the stiffener height leads to an increase of the critical buckling stress and an increase of formability limit. The critical buckling stress at the ageing temperature is smaller than that at the room temperature when the stiffened panel enters the plastic region, however, the formability increases slightly at the ageing temperature.

Sheet-metal free-form stamping technology deforms sheet-metals with simple and low costs universal tools on a working bench, which is normally an anvil. This traditional forming method is praised for its high forming flexibility but complained due to its reliance on individual experience thus low repeatability. In this paper, a python-based overall learning algorithm, which incorporates a reinforcement learning (RL) algorithm, for a designed sheet-metal free-form stamping case is developed. A neural network system, known as deep Q-network (DQN), was used to approximate the action-value function (Q function) in the Deep Q-learning algorithm. The DQN was trained using mini-batch training method, with the computational experiment data provided through Finite Element (FE) simulations. The overall learning algorithm was instantiated and evaluated by training the RL model to convergence, which is able to predict the optimal forming route to achieve the desired shape. This algorithm achieves the intellectualisation of the traditional free-form sheet-metal stamping process for the first time, without prior expertise for guidance.

INTRODUCTION: Antiretroviral and anti-tuberculosis (TB) drugs are often co-administered in people living with HIV (PLWH). Early initiation of antiretroviral therapy (ART) during TB treatment improves survival in patients with advanced HIV disease. However, safety concerns related to clinically significant changes in drug exposure resulting from drug-drug interactions; development of overlapping toxicities and specific challenges related to co-administration during pregnancy represent barriers to successful combined treatment for HIV and TB. AREAS COVERED: Pharmacokinetic interactions of different classes of ART when combined with anti-TB drugs used for sensitive-, drug-resistant (DR) and latent TB are discussed. Overlapping drug toxicities, implications of immune reconstitution inflammatory syndrome (IRIS), safety in pregnancy and research gaps are also explored. EXPERT OPINION: New antiretroviral and anti-tuberculosis drugs have been recently introduced and international guidelines updated. A number of effective molecules and clinical data are now available to build treatment regimens for PLWH with latent or active TB. Adopting a systematic approach that also takes into account the need for individualized variations based on the available evidence is the key to successfully integrate ART and TB treatment and improve treatment outcomes.

11 pags. 6 figs.-- Open Access funded by Creative Commons Atribution Licence 4.0, The existence of topologically protected edge modes is often cited as a highly desirable trait of topological insulators. However, these edge states are not always present. A realistic physical treatment of long-range hopping in a one-dimensional dipolar system can break the symmetry that protects the edge modes without affecting the bulk topological number, leading to a breakdown in bulk-edge correspondence (BEC). Hence, it is important to gain a better understanding of where and how this occurs, as well as how to measure it. Here we examine the behaviour of the bulk and edge modes in a dimerised chain of metallic nanoparticles and in a simpler non-Hermitian next-nearest-neighbour model to provide some insights into the phenomena of bulk-edge breakdown. We construct BEC phase diagrams for the simpler case and use these ideas to devise a measure of symmetry-breaking for the plasmonic system based on its bulk properties. This provides a parameter regime in which BEC is preserved in the topological plasmonic chain, as well as a framework for assessing this phenomenon in other systems., Acknowledges funding from EPSRC. PAH acknowledges the Gordon and Betty Moore Foundation. VG acknowledges the Spanish Ministerio de Economia y Competitividad for financial support through the grant NANOTOPO (FIS2017-91413-EXP) and also Consejo Superior de Investigaciones Cientficas (INTRAMURALES 201750I039). This work is supported in part by Fundação para a Ciência e a Tecnologia and by Instituto de Telecomunicações under project CEECIND/03866/2017.

Polymer electrolyte fuel cells hold great promise for a range of applications but require advances in durability for widespread commercial uptake. Corrosion of the carbon support is one of the main degradation pathways, hence, corrosion-resilient graphene has been widely suggested as an alternative to traditional carbon black. However, the performance of bulk graphene-based electrodes is typically lower than that of commercial carbon black due to their stacking effects. This article reports a simple, scalable and non-destructive method through which the pore structure and platinum utilisation of graphene-based membrane electrode assemblies can be significantly improved. Urea is incorporated into the catalyst ink before deposition, and is then simply removed from the catalyst layer after spraying by submerging the electrode in water. This additive hinders graphene restacking and increases porosity, resulting in a significant increase in Pt utilisation and current density. This technique does not require harsh template etching and it represents a pathway to significantly improve graphene-based electrodes by introducing hierarchical porosity using scalable liquid processes.

A quantitative fluorescent probe that responds to changes in temperature is highly desirable for studies of biological environments, particularly in cellulo. Here, we report new cell-permeable fluorescence probes based on the BODIPY moiety that respond to environmental temperature. The new probes were developed on the basis of a well-established BODIPY-based viscosity probe by functionalization with cyclopropyl substituents at α and β positions of the BODIPY core. In contrast to the parent BODIPY fluorophore, α-cyclopropyl-substituted fluorophore displays temperature-dependent time-resolved fluorescence decays showing greatly diminished viscosity dependence, making it an attractive sensor to be used with fluorescence lifetime imaging microscopy (FLIM). We performed theoretical calculations that help rationalize the effect of the cyclopropyl substituents on the photophysical behavior of the new BODIPYs. In summary, we designed an attractive new quantitative FLIM-based temperature probe that can be used for temperature sensing in live cells.

In recent years, significant advances in the field of medical materials have begun to emerge, especially in nanotechnology. The modern area of nanostructured implants possesses wide applications in various medical implants including their dental use. Nano-surface functions present substantial resolutions to medical obstacles through improved biomaterial proficiency, innovative dental-implant designs, and surface design procedures, such as nanoscale adhesive surfaces, bio-chemical anodization, and surface modification technique. This work covers dental implant history, nanotechnological advances, and its development that includes a description, basic properties, and the related results of composites and surface morphology, and the different types of nanomaterials used in dental implants. Significant attempts have been made over the last few decades to strengthen osteointegration and prevent bacterial attachment to the implant surfaces. The micro and nano-topography of the hierarchical surface orchestrate the biological reactions of implants and may solve the problems associated with implant-tissue issues. This research investigates the implant articles from 1964 to 2021, which offers a brief description of the nanostructured biomaterials to enhance dental implants’ performance and may open new frontiers in the advancement of implant technology.

10 pags., 4 fiigs., Topological quantum dots (TQDs) are 3D topological insulator (TI) nanoparticles, displaying symmetry-protected surface states with discretized energies. We present a theoretical proposal to harness these energy levels in a closed lasing scheme operating in the terahertz (THz) frequency range. In this scheme, a single TQD lases from its topological surface states in the THz regime when pumped with low intensity, incoherent THz frequency light. The time scales associated with the system are unusually slow, and we find that lasing occurs with a very low threshold. THz lasers are often bulky or require intricately engineered nanostructures. Topological quantum dots present a new, compact and simple platform for THz lasing. The lasing threshold is so low, we predict that the room-temperature blackbody radiation can substantially contribute to population inversion, providing a route to room-temperature THz lasing pumped via blackbody radiation., M. S. R. would like to acknowledge the financial support of the Centre for Doctoral Training on Theory and Simulation of Materials at Imperial College London funded by EPSRC Grant No. EP/L015579/1. V. G. acknowledges the Spanish Ministerio de Economia y Competitividad for financial support through the grant NANOTOPO (FIS2017-91413-EXP), and also the Ministerio de Ciencia, Innovación y Universidades through the grant MELODIA (PGC2018-095777-B-C21). V. G. thanks the “ENSEMBLE3 - Centre of Excellence for nanophotonics, advanced materials and novel crystal growth-based technologies” project (GA No. MAB/2020/14) carried out within the International Research Agendas programme of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund and the European Union’s Horizon 2020 research and innovation programme Teaming for Excellence (GA. No. 857543) for support of this work.

An endothelial-lined blood vessel model is obtained in a PDMS (Polydimethylsiloxane) microfluidic system, where vascular endothelial cells are grown under physiological shear stress, allowing -like maturation. This experimental model is employed for enhanced drug delivery studies, aimed at characterising the increase in endothelial permeability upon microbubble-enhanced ultrasound-induced (USMB) cavitation. We developed a multi-step protocol to couple the optical and the acoustic set-ups, thanks to a 3D-printed insonation chamber, provided with direct optical access and a support for the US transducer. Cavitation-induced interendothelial gap opening is then analysed using a customised code that quantifies gap area and the relative statistics. We show that exposure to US in presence of microbubbles significantly increases endothelial permeability and that tissue integrity completely recovers within 45 min upon insonation. This protocol, along with the versatility of the microfluidic platform, allows to quantitatively characterise cavitation-induced events for its potential employment in clinics.