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In this paper, we present a metal-only transmission metasurface adopting dual-layer elements with I-shaped grooves etched on each layer, which is designed for orbital angular momentum (OAM) generation. The special arrangement of the grooves on the elements results in a wider phase compensation range, and by varying the length of the grooves, a full 360 ° phase coverage with a transmission amplitude of more than − 2 dB can be achieved at 10 GHz. As a proof of concept, a metal-only transmission metasurface composed of 400 elements is designed, fabricated, and measured. The simulated and measured results suggest that the OAM transmitted waves with the mode l = − 1 can be efficiently generated by a double-layer metal-only metasurface at around 10 GHz. Compared with conventional configurations of OAM transmitted beam generation, this configuration has great potential for high power microwave and space environment applications. [ABSTRACT FROM AUTHOR]

We propose an estimator that allows us to calculate the value of a simple system's partition function using finite sampling. The core idea is to neglect the contribution from high energy microstates, which are difficult to be sampled properly, and then calculate a volume correction term to compensate for this. As a proof of concept, the estimator is applied to calculate the partition function for several model systems, ranging from a simple harmonic oscillator to a Lennard-Jones fluid with hundreds of particles. Our results agree well with the numerically exact solutions or reference data, demonstrating that efficiently estimating partition functions for the studied example cases is possible and computationally affordable. [ABSTRACT FROM AUTHOR]

Utilizing the sparsity of the electronic structure problem, fragmentation methods have been researched for decades with great success, pushing the limits of ab initio quantum chemistry ever further. Recently, this set of methods has been expanded to include a fundamentally different approach called excitonic renormalization, providing promising initial results. It builds a supersystem Hamiltonian in a second-quantized-like representation from transition-density tensors of isolated fragments, contracted with biorthogonalized molecular integrals. This makes the method fully modular in terms of the quantum chemical methods applied to each fragment and enables massive truncation of the state-space required. Proof-of-principle tests have previously shown that an excitonically renormalized Hamiltonian can efficiently scale to hundreds of fragments, but the ad hoc approach to building the Hamiltonian was not scalable to larger fragments. On the other hand, initial tests of the originally proposed modular Hamiltonian build, presented here, show the accuracy to be poor on account of its non-Hermitian character. In this study, we bridge the gap between these with an operator expansion that is shown to converge rapidly, tending toward a Hermitian Hamiltonian while retaining the modularity, yielding an accurate, scalable method. The accuracy is tested here for a beryllium dimer. At distances near equilibrium and longer, the zeroth-order method is comparable to coupled-cluster singles, doubles, and perturbative triples and the first-order method is comparable to full configuration interaction (FCI). The second-order method agrees with FCI for distances well up the inner repulsive wall of the potential. Deviations occurring at shorter bond distances are discussed along with approaches to scaling to larger fragments. [ABSTRACT FROM AUTHOR]

Flexible and broadband microwave-absorbing structures have attracted significant attention in electromagnetic (EM) science. Although previous studies have demonstrated the potential of flexible microwave-absorbing structures using thin dielectric substrates or flexible materials, the need for broadband and flexible microwave-absorbing structures remains largely unmet, especially those that can be stretched to adapt to complex surfaces. In this article, a novel design concept of a stretchable meta-substrate comprising rigid pyramidal substrates and soft hinges is proposed, which operates as a dielectric substrate and a structural support for the metastructure. The proposed flexible and broadband microwave-absorbing metastructure is composed of a pyramidal microwave-absorbing unit and a stretchable meta-substrate, which exhibits a reflection coefficient lower than −20 dB from 2.2 to 20 GHz under normal incidence. By overcoming the mechanical and electromagnetic limitations of previous efforts with a soft material-based microwave-absorbing structure, the proposed metastructure can be stretched under 40% strain, while the −10 dB reflection coefficient spectrum only shifts by 1.1 GHz. Furthermore, the proposed metastructure exhibits stable absorption properties for EM wave irradiation with both transverse electric and transverse magnetic polarizations, even at an oblique incident angle of up to 70°. As a proof of concept, the proposed metastructure is conformally pasted on the unmanned aerial vehicle surface, and the maximum radar cross section reduction of the proposed metastructure is 30.5 dB larger than that of a conventional device. The fabricated sample can be readily applied for carrying and deployment, with potential applications in the fields of EM stealth as well as EM anti-interference. [ABSTRACT FROM AUTHOR]

We propose a modified difference weak measurement scheme that permits precise measurements of the magneto-optical Faraday effect. By making normalized difference processing for a set of post-selected light intensity, a linear-response regime with a significant weak-value amplification effect is established. In the proof-of-principle experiment, we measure the magnetic intensity using the polarization system and achieve precision at the order of ∼ 10 − 7 T. Our scheme can be applied to measure other magneto-optical effects, providing a method for future ultra-sensitive sensing and metrology in magnetic physics. [ABSTRACT FROM AUTHOR]

We present a Lagrangian-based implementation of Ehrenfest dynamics with nuclear–electronic orbital (NEO) theory and real-time time-dependent density functional theory for extended periodic systems. In addition to a quantum dynamical treatment of electrons and selected protons, this approach allows for the classical movement of all other nuclei to be taken into account in simulations of condensed matter systems. Furthermore, we introduce a Lagrangian formulation for the traveling proton basis approach and propose new schemes to enhance its application for extended periodic systems. Validation and proof-of-principle applications are performed on electronically excited proton transfer in the o-hydroxybenzaldehyde molecule with explicit solvating water molecules. These simulations demonstrate the importance of solvation dynamics and a quantum treatment of transferring protons. This work broadens the applicability of the NEO Ehrenfest dynamics approach for studying complex heterogeneous systems in the condensed phase. [ABSTRACT FROM AUTHOR]

Sub-diffraction needle beams with high intensity, sub-diffraction focal size, and long depth of focus (DOF) have attracted many researchers' attention. However, the traditional methods for needle beam generation typically require many devices, such as phase elements, amplitude filters, and lens, which leads to a complex and bulky system and unfavorable for their integration. To address these challenges, we use a single multifunctional transmissive metasurface to convert a linearly polarized plane wave into a needle beam in the microwave range. The guided wave inspired unit cells of the proposed metasurface is designed to simultaneously and independently modulate the polarization and phase of transmitted waves. By imposing the desired polarization and phase distributions on the metasurface, the proposed multifunctional transmissive metasurface can efficiently generate a needle beam with subdiffraction size and extended DOF at 10 GHz when it is illuminated by an x-polarized wave. The proposed metasurface is fabricated, and a sub-diffraction needle beam with good performance is obtained in our measurements. In addition, a proof-of-concept of a high-resolution nondestructive testing experiment based on our designed metasurface is accomplished. Our work is expected to have potential applications in nondestructive testing of materials and structures. [ABSTRACT FROM AUTHOR]

An important class of methods for modeling dynamics in open quantum systems is based on the well-known influence functional (IF) approach to solving path-integral equations of motion. Within this paradigm, path-filtering schemes based on the removal of IF elements that fall below a certain threshold aim to reduce the effort needed to calculate and store the influence functional, making very challenging simulations possible. A filtering protocol of this type is considered acceptable as long as the simulation remains mathematically stable. This, however, does not guarantee that the approximated dynamics preserve the physics of the simulated process. In this paper, we explore the possibility of training Generative Flow Networks (GFlowNets) to produce filtering protocols while optimizing for mathematical stability and for physical accuracy. Trained using the trajectory balance objective, the model produces sets of paths to be added to a truncated initial set; it is rewarded if the combined set of paths gives rise to solutions in which the trace of the density matrix is conserved, the populations remain real, and the dynamics approach the exact reference. Using a simple two-level system coupled to a dissipative reservoir, we perform proof-of-concept simulations and demonstrate the elegant and surprising filtering solutions proposed by the GFlowNet. [ABSTRACT FROM AUTHOR]

This second paper in a series of two describes the chirped-pulse ice apparatus that permits the detection of buffer gas cooled molecules desorbed from an energetically processed ice using broadband mm-wave rotational spectroscopy. Here, we detail the lower ice stage developed to generate ices at 4 K, which can then undergo energetic processing via UV/VUV photons or high-energy electrons and which ultimately enter the gas phase via temperature-programmed desorption (TPD). Over the course of TPD, the lower ice stage is interfaced with a buffer gas cooling cell that allows for sensitive detection via chirped-pulse rotational spectroscopy in the 60–90 GHz regime. In addition to a detailed description of the ice component of this apparatus, we show proof-of-principle experiments demonstrating the detection of H2CO products formed through irradiation of neat methanol ices or 1:1 CO + CH4 mixed ices. [ABSTRACT FROM AUTHOR]

We derive a coupled-mode theory (CMT) formulation for the fast analysis of periodic multi-element metasurfaces in the presence of radiation losses. Full-wave simulations of periodic multi-element metasurfaces are very time- and memory-consuming, especially as the size and complexity of the metasurface increase. The CMT formulation provides a considerably faster and efficient alternative. It results in a small system of equations with size equal to the number of supported resonator modes in the frequency range of interest, allowing to calculate the resonator mode amplitudes and, consequently, the metasurface response. Subsequently, we systematically derive analytical closed-form expressions for the coupling coefficients between two weakly coupled resonators in the presence of radiation losses and incorporate them into the CMT model, which is found important for the accurate description of the metasurface, while also providing insight into the underlying physics of complex metasurfaces. We validate the proposed formulation on benchmark examples of both metal- and dielectric-based metasurface absorbers (MSAs) by comparing the CMT results to spectral FEM simulations of the composing supercell. To further demonstrate the potential of the proposed formulation, as a proof of concept, we use the CMT to synthesize a larger optimized periodic multi-element MSA. A comprehensive comparison to full-wave FEM simulations of the composing supercell is included in terms of time and computational requirements, which shows that our method provides a valuable and efficient alternative solver for synthesizing complex metasurfaces. [ABSTRACT FROM AUTHOR]

Mobile technology has been recognized as a tool in reducing the inequality gap, especially for those in developing communities. With a Gini score of 63 in 2014, South Africa is regarded as one of the most unequal countries in the world. Furthermore, 86% of total wealth is controlled by 10% of the population with 7% of the wealth shared by 60% of the citizens. In 2017 Urglobal initiated a concept of driving technology training for rural schools and communities using mobility. In this paper we contribute to the debate by exploring the question of how providing access to technology for rural communities can lead to inclusion and social justice. Pre- and post-training surveys together with dialogue sessions were held with the pertinent respondents to explore this question. Empirical findings reflect that driving technology training on a mobile basis can be an entry point for rural communities in achieving social justice. The study is significant in that it provides a citizen-centred design for technology training and substantiates that mobility does ensure societal access regardless of geography. The study contributes to the body of knowledge by providing proof of concept that can be used for the integration of technology into rural schools and communities. [ABSTRACT FROM AUTHOR]

Determination of free cyanide (fCN) is required for various industrial, environmental, food, and clinical samples. Enzymatic methods are not widely used in this field despite their selectivity and mild conditions. Therefore, we present here a proof of concept for new spectrophotometric enzymatic assays of fCN. These are based on the hydrolysis of fCN affording the readily detectable NADH. fCN is hydrolyzed either in one step by cyanide dihydratase (CynD) or in two steps by cyanide hydratase (CynH) and formamidase (AmiF). An advantage of the latter route is the higher activity of CynH and AmiF compared to CynD. In both cases, the resulting formate is then transformed by an NAD-dependent formate dehydrogenase (FDH). The NADH thus formed is quantified colorimetrically using a known method based on a reduction of a tetrazolium salt (WST-8) with NADH. The developed assays of fCN are selective except for formic acid interference, proceed under mild conditions, and, moreover, fCN is detoxified during the reactions. The assays proceeded in a microtiter plate format. The limit of detection (LOD) and the limit of quantification (LOQ) were lower for the three-enzyme (CynH-AmiF-FDH) method (7.00 and 21.2 µmol/L, respectively) than for the two-enzyme (CynD-FDH) method (10.7 and 32.4 µmol/L, respectively). In conclusion, the new fCN assays presented in this work are selective, high-throughput, do not require harsh conditions, and use only small amounts of chemicals and enzymes. [ABSTRACT FROM AUTHOR]

Participatory plant breeding (PPB) has the potential to be an alternative to a centralized breeding model for niche markets that are historically underserved. Our objectives were to evaluate the performance of two parental cultivars from a Canadian PPB program: a modern spring wheat (Triticum aestivum L.) cultivar (5602HR) and a landrace (Red Fife)—with the progeny of the cross when selected by two farmers located 1800 km apart (denoted Farm1 and Farm2) and evaluate progeny differences from each other under organic conditions. Red Fife was 18 cm taller, matured 5 days later, and had greater lodging susceptibility, greater seed mass, and 3.5% lower protein concentration than 5602HR. Farmer genotypes were similar to 5602HR in protein concentration and lodging severity, and similar to Red Fife in plant height (14 cm taller than 5602HR) and seed mass. Farmer genotypes did not yield differently from either parent. Farmer genotypes did not differ from each other in most parameters measured; however, Farm1 had greater lodging resistance under high fertility conditions than Farm2 despite similar plant height. This research provides a proof of concept for the role that farmer selectors can play in selecting for positive traits for organic production and provide insight into organic farmers' preferences. The research also demonstrated that using an older landrace (i.e., Red Fife) allowed positive features such as tall stature to be incorporated into the resulting progeny. [ABSTRACT FROM AUTHOR]

This paper presents a novel perspective on portfolio optimization by recognizing that prices can be expressed as a scaled likelihood ratio of state price densities. This insight leads to the immediate conclusion that the optimal portfolio has a simple representation in terms of the likelihood ratio between the agent-defined physical measure and the risk-neutral measure, eliminating the need for utility maximization. The agent only needs to specify her choice of the physical measure, and we demonstrate both frequentist and Bayesian approaches for this selection. Utility maximization can be seen as a specific method for choosing the physical measure. The resulting likelihood ratio is log-utility optimal with respect to all benchmarks, aligning our approach with finding the growth optimal portfolio described in the literature. Notably, the expected log return corresponds to the relative entropy between the physical and risk-neutral measures, establishing a fundamental link to information theory. As a proof of concept, we explore previously unexplored territory in portfolio optimization, specifically addressing perceived mean reversion in specific driftless markets, such as foreign exchange (FX) markets. [ABSTRACT FROM AUTHOR]

Diffusion MRI is a leading method to non-invasively characterise brain tissue microstructure across multiple domains and scales. Diffusion-weighted steady-state free precession (DW-SSFP) is an established imaging sequence for post-mortem MRI, addressing the challenging imaging environment of fixed tissue with short T2 and low diffusivities. However, a current limitation of DW-SSFP is signal interpretation: it is not clear what diffusion 'regime' the sequence probes and therefore its potential to characterise tissue microstructure. Building on Extended Phase Graphs (EPG), I establish two alternative representations of the DW-SSFP signal in terms of (1) conventional b-values (time-independent diffusion) and (2) encoding power-spectra (time-dependent diffusion). The proposed representations provide insights into how different parameter regimes and gradient waveforms impact the diffusion sensitivity of DW-SSFP. I subsequently introduce an approach to incorporate existing biophysical models into DW-SSFP without the requirement of extensive derivations, with time dependence estimated via a Gaussian phase approximation representation of the DW-SSFP signal. Investigations incorporating free-diffusion and tissue-relevant microscopic restrictions (cylinder of varying radius) give excellent agreement to complementary analytical models and Monte Carlo simulations. Experimentally, the time-independent representation is used to derive Tensor and proof-of-principle NODDI estimates in a whole human post-mortem brain. A final SNR-efficiency investigation demonstrates the theoretical potential of DW-SSFP for ultra-high field microstructural imaging. [ABSTRACT FROM AUTHOR]

Many HIV clinics with poor IT-infrastructure are unable to report data on individuals in care with HIV, on antiretroviral treatment (ART) and virologically suppressed (VS), with the aim of monitoring the HIV Continuum of Care to estimate efficacy of HIV treatment programmes. We developed an estimation-tool, ESTIHIV, and determined the minimal data required for a random sample, to produce representative estimates, with a specified level of precision, of people with HIV on ART and VS. For proof of concept, 8852 HIV positive persons from seven clinics in seven different countries, with a follow-up visit during 2017, were included. Of those, 93.8% were on ART (95% CI 93.3–94.2) and 76.7% were VS (95% CI 75.8–77.6). In 2022, we tested the tool in the RESPOND Cohort for all countries with more than 100 participants under follow-up in 2019. We included 26,426 HIV positive persons from clinics in 27 countries, 97.8% (95% CI 97.6-98.0) were on ART and 91.5% were VS (95% CI 91.2-91.8%). There was good agreement between the RESPOND country estimates of ART and VS and the estimations using a random sample calculated in ESTIHIV. With ESTIHIV, clinics can produce a reliable estimate in figures for reporting and for monitoring the effectiveness of care in their clinics. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusions\nIMPLICATIONS FOR REHABILITATIONFalls cost the NHS over £2 billion a year, with incidence increasing rapidly with age. Design of indoor walking frames remains limited, often needing to be lifted and not supporting sit-to-stand and turning manoeuvres, which can lead to falling. This study explored aspects of safety and satisfaction and potential for clinical use of a novel prototype walking frame.Within a proof-of-concept design study, between April and November 2023 nine healthcare professionals (HCPs) [3 male 13.4 mean years clinical experience] assessed 10 in-patients and 8 community-based patients [9 male, mean ± SD age 81 ± 9.98]. Patient participants performed mobility activities with the prototype frame and a standard frame. Professionals then completed a questionnaire on safety and satisfaction when using the devices with free text options. Data were analysed using frequency and descriptive statistics and paired comparisons for ranked data, with open comments analysed using thematic analysis.HCPs reported the prototype as safe in 100% assessments (18/18), with 17/18 stating they would have prescribed it immediately if available (“Not as safe with a standard frame as she was with the prototype”.). HCP satisfaction was greater for the prototype regarding dimensions (p = 0.006; “Good ability to personalize to individual”.), safety and security (p = 0.003), ease of use (p = 0.005; “Automatically started to use it”.), and effectiveness (p = 0.003; “Turns well, minimise lifting, glides but still grips”).This study demonstrates significantly better satisfaction of HCPs with the new design regarding ease of use and safety, in inpatient and community settings, and a strong desire to prescribe it.Multidisciplinary collaboration including implementation of stakeholder feedback in the evaluation and final design of walking aids is important to produce a product that is safe, easy to use and satisfies users and healthcare professionalsNew frame design can overcome the significant safety limitations of the traditional walking frame that has not changed for decades—removing the need to lift when turning and improving movement over thresholds and different floor surfaces through innovative design of wheels and feetDesign changes to the overall shape of an indoor walking frame offers solutions for different sized users and environmentsMultidisciplinary collaboration including implementation of stakeholder feedback in the evaluation and final design of walking aids is important to produce a product that is safe, easy to use and satisfies users and healthcare professionalsNew frame design can overcome the significant safety limitations of the traditional walking frame that has not changed for decades—removing the need to lift when turning and improving movement over thresholds and different floor surfaces through innovative design of wheels and feetDesign changes to the overall shape of an indoor walking frame offers solutions for different sized users and environments [ABSTRACT FROM AUTHOR]

We explore how Proof-of-Concept (PoC) programs, as Open Innovation (OI) instruments, are implemented differently by public and private organisations in technology valorisation processes. PoC programs, traditionally employed in public institutions, are also gaining relevance in private companies to reduce uncertainty and increase market readiness of early-stage technologies. Through a multiple case study of 12 PoC programs, in this research, we compare their implementation in universities, national research centres, firms, and venture funds. We contribute to the OI and technology transfer literature by proposing four distinct PoC models and discussing how they facilitate OI practices differently across sectors. [ABSTRACT FROM AUTHOR]

To address the challenges of biopsy and intratumoral drug delivery using microdevices, a miniature multifunctional tethered device that has tissue cutting, biopsy and drug delivery capabilities is presented in this paper. The cutting module in the prototype is hydraulically powered and has an outside diameter (OD) of 2 mm at the tip and a cutter attached to 500 µm drive shaft. The hydraulic micromotor prototype was fabricated using micro additive manufacturing. It was tested using a benchtop set-up and had an average speed greater than 100,000 RPM at a water flowrate of 45 mL/min and a speed of about 34,000 RPM at 15 mL/min flowrate. This micromotor design was numerically modeled using 3D-transient simulations in ANSYS CFX to determine its performance characteristics and internal resistance. Preliminary testing was performed using cutting modules with five cutter geometries on agar tissue phantoms of different concentrations and other biological materials. The dissection ability of the cutting module, its ability to deliver particles, and collect biopsy samples were successfully demonstrated. Scaling the 2 mm OD device further, a 1 mm OD micromotor, with a nominal output shaft diameter of 250 µm, was fabricated and operated with air establishing the proof of concept. [ABSTRACT FROM AUTHOR]

Introduction: Posttraumatic stress disorder (PTSD) is a debilitating disorder characterized by intrusive memories, avoidance, negative thoughts and moods, and heightened arousal. Many patients also report gastrointestinal symptoms. Cognitive behavioral therapy (CBT) is an evidence-based treatment approach for PTSD that successfully reduces symptoms. However, many patients still meet criteria for PTSD after treatment or continue to have symptoms indicating the need for new treatment strategies for PTSD. Patients with PTSD have a disrupted intestinal microbiome (i.e., dysbiosis) which can promote neuroinflammation; thus, modulation of the microbiome could be an alternative or adjunct treatment approach for PTSD. Methods: The current study was a 12-week, double-blind, placebo-controlled trial seeking to understand if CBT combined with a microbiota-modifying, prebiotic fiber intervention would beneficially impact clinical outcomes in veterans with PTSD (n = 70). This proof-of-concept, pilot trial was designed to assess: (1) the relationship between severity of PTSD symptoms and microbiota composition and SCFA levels (i.e., acetate, propionate, butyrate), (2) if CBT treatment with a concomitant prebiotic fiber intervention would beneficially impact clinical outcomes in veterans with PTSD, (3) evaluate the feasibility and acceptability of a prebiotic intervention as an adjunct treatment to CBT, and (4) assess the impact of treatment on the intestinal microbiota and stool SCFA (i.e., mechanism). Results: This study found that PTSD severity may be associated with reduced abundance of taxa capable of producing the SCFA propionate, and that a subset of individuals with PTSD may benefit from a microbiota-modifying prebiotic intervention. Conclusion: This study suggests that targeting the intestinal microbiome through prebiotic supplementation could represent a promising avenue for enhancing treatment outcomes in some individuals with PTSD. Clinical trial registration: https://clinicaltrials.gov/ , identifier NCT05424146. [ABSTRACT FROM AUTHOR]

The existing quantitative geography literature contains a dearth of articles that span spatial autocorrelation (SA), a fundamental property of georeferenced data, and spatial optimization, a popular form of geographic analysis. The well-known location–allocation problem illustrates this state of affairs, although its empirical geographic distribution of demand virtually always exhibits positive SA. This latent redundant attribute information alludes to other tools that may well help to solve such spatial optimization problems in an improved, if not better than, heuristic way. Within a proof-of-concept perspective, this paper articulates connections between extensions of the renowned Majority Theorem of the minisum problem and especially the local indices of SA (LISA). The relationship articulation outlined here extends to the p = 2 setting linkages already established for the p = 1 spatial median problem. In addition, this paper presents the foundation for a novel extremely efficient p = 2 algorithm whose formulation demonstratively exploits spatial autocorrelation. [ABSTRACT FROM AUTHOR]

This study includes musculoskeletal disorder (MSD) risk evaluation based on the IMU sensor data gathered from patient-lifting movement performed by healthcare specialists. This is a continuation of previous research focusing on a novel multicriteria statistical model integrating experimental and large-scale statistical datasets. The proposed model estimates MSD probabilities over 5, 10, and 15 years for the neck (0.537 ± 0.156), shoulder (0.449 ± 0.084), and elbows (0.277 ± 0.221). The model enables individual risk profiling, influenced by dynamic parameters that can reduce the long-term risk by up to 70.49%. The model is in its early development stages, i.e., it is the proof of concept that offers a new approach to assessing MSD risk at work using motion tracking data in combination with statistics. Further studies with larger sample sizes and validated criterion weights are needed to refine and validate this approach. [ABSTRACT FROM AUTHOR]

Violence has been analysed in silo due to difficulties in accessing data and concerns for the safety of those exposed. While there is some literature on violence and its associations using individual datasets, analyses using combined sources of data are very limited. Ideally data from the same individuals would enable linkage and a longitudinal understanding of experiences of violence and their (health) impacts and consequences. This paper aims to provide proof of concept to create a synthetic dataset by combining data from the Crime Survey for England and Wales (CSEW) and administrative data from Rape Crisis England and Wales (RCEW), pertaining to victim-survivors of sexual violence in adulthood. Intuitively, the idea was to impute missing information from one dataset by borrowing the distribution from the other. In our analyses, we borrowed information from CSEW to impute missing data in the RCEW administrative dataset, creating a combined synthetic RCEW-CSEW dataset. Using look-alike modelling principles, we provide an innovative and cost-effective approach to exploring patterns and associations in violence-related research in a multi-sectorial setting. Methodologically, we approached data integration as a missing data problem to create a synthetic combined dataset. Multiple imputation with chained equations were employed to collate/impute data from the two different sources. To test whether this procedure was effective, we compared regressions analyses for the individual and combined synthetic datasets on binary, continuous and categorical variables. We extended our testing to an outcome measure and, finally, applied the technique to a variable fully missing in one data source. Our results show that the effect sizes for the combined dataset reflect those from the dataset used for imputation. The variance is higher, resulting in fewer statistically significant estimates. Our approach reinforces the possibility of combining administrative with survey datasets using look-alike methods to overcome existing barriers to data linkage. [ABSTRACT FROM AUTHOR]

Background: Senescence classification is an acknowledged challenge within the field, as markers are cell-type and context dependent. Currently, multiple morphological and immunofluorescence markers are required. However, emerging scRNA-seq datasets have enabled an increased understanding of senescent cell heterogeneity. Methods: Here we present SenPred, a machine-learning pipeline which identifies fibroblast senescence based on single-cell transcriptomics from fibroblasts grown in 2D and 3D. Results: Using scRNA-seq of both 2D and 3D deeply senescent fibroblasts, the model predicts intra-experimental fibroblast senescence to a high degree of accuracy (> 99% true positives). Applying SenPred to in vivo whole skin scRNA-seq datasets reveals that cells grown in 2D cannot accurately detect fibroblast senescence in vivo. Importantly, utilising scRNA-seq from 3D deeply senescent fibroblasts refines our ML model leading to improved detection of senescent cells in vivo. This is context specific, with the SenPred pipeline proving effective when detecting senescent human dermal fibroblasts in vivo, but not the senescence of lung fibroblasts or whole skin. Conclusions: We position this as a proof-of-concept study based on currently available scRNA-seq datasets, with the intention to build a holistic model to detect multiple senescent triggers using future emerging datasets. The development of SenPred has allowed for the detection of an in vivo senescent fibroblast burden in human skin, which could have broader implications for the treatment of age-related morbidities. All code for the SenPred pipeline is available at the following URL: https://github.com/bethk-h/SenPred_HDF. [ABSTRACT FROM AUTHOR]

In this work, a unified design methodology for front-end RF/mmWave receivers is presented, aiming to significantly accelerate the design procedure of the front-end RF blocks in complex RX/TX chain implementations. The proposed design methodology is based on optimization loops with well-defined cost functions so as to minimize the design iterations that may be encountered during specification tuning. As proof of concept, two essential RF blocks widely used in RF receivers, a low-noise amplifier (LNA) and a voltage-controlled oscillator (VCO), were designed using the proposed unified methodology with a 65 nm RF-CMOS processing node. Finally, the derived designs were compared to similar designs in the literature, proving that the proposed unified methodology is capable of synthesizing RF/mmWave LNAs and VCOs with industry-standard specifications within a significantly faster time frame. [ABSTRACT FROM AUTHOR]

Visible-light communication (VLC) has emerged as a promising technology to provide the very high-throughput wireless communications demanded by beyond-fifth-generation (B5G) applications. However, few works are found in the literature regarding the integration of VLC systems with other wireless communications technologies and with access networks. In this context, and as a proof of concept, we implement and experimentally evaluate a hybrid network architecture based on VLC, radio-over-fiber (RoF), free space optics (FSO), fiber-wireless (FiWi), and millimeter-waves (mm-waves) for B5G applications. Such optical networks make use of fiber-optic links based on RoF technology as backhauls, whereas their fronthauls might be either by FSO or RoF. Finally, a triple-wireless-access network is ensured by VLC, FiWi, and mm-wave links. The latter use a real 5G new radio (5G NR) signal. The system performance is evaluated in terms of a root mean square error vector magnitude (EVMRMS) parameter in accordance with the 3rd-Generation Partnership Project (3GPP) requirements. The experimental results demonstrate a total maximal theoretical throughput of approximately 1.66 Gbps, aligning with the digital performance requirements set by 3GPP. [ABSTRACT FROM AUTHOR]

Lipids are major constituents of food but are also highly relevant substructures of drugs and are increasingly applied for the development of lipid-based drug delivery systems. Lipids are prone to oxidative degradation, thus affecting the quality of food or medicines. Therefore, analytical methods or tools that enable the degree of lipid oxidation to be assessed are of utmost importance to guarantee food and drug safety. Herein, we report the design, synthesis and application of the first-in-class fluorogenic triacylglycerols that enable dynamic monitoring of lipid oxidation via straightforward fluorescence readout. Our fluorogenic triacylglycerols can be used in both aqueous and lipid-based environments. Furthermore, we showed that the sensitivity of our fluorescent tracers towards oxidation could be tuned by incorporating either saturated or unsaturated acyl chains in their triacylglycerol core structure. With this, we provide a first proof of principle for the applicability of fluorescently labelled triacylglycerols as tracers to monitor the dynamics of lipid oxidation, thus paving the way for novel discoveries in the area of lipid analytics. [ABSTRACT FROM AUTHOR]

Although commonly applied in various reactions, Shvo’s catalyst has not been modified towards solubility in highly polar solvents until now. Here, we report the straightforward synthesis of a disulfonate derivative of the complex, which allows to (transfer) (de-)hydrogenate aldehydes and ketones in aqueous solutions. A proof of principle for the recycling of the catalyst is also provided. [ABSTRACT FROM AUTHOR]

Developing switchable and multifunctional metasurfaces is essential for high-integration photonics. However, most previous studies encountered challenges such as limited degrees of freedom, simple tuning of predefined functionality, and complicated control systems. Here, we develop a general strategy to construct switchable and multifunctional metasurfaces. Two spin-modulated wave-controls are enabled by the proposed high-efficiency metasurface, which is designed using both resonant and geometric phases. Furthermore, the switchable wavefront tailoring can also be achieved by flexibly altering the lattice constant and reforming the phase retardation of the metasurfaces based on the "rotating square" (RS) kirigami technique. As a proof of concept, a kirigami metasurface is designed that successfully demonstrates dynamic controls of three-channel beam steering. In addition, another kirigami metasurface is built for realizing tri-channel complex wavefront engineering, including straight beam focusing, tilted beam focusing, and anomalous reflection. By altering the polarization of input waves as well as transformation states, the functionality of the metadevice can be switched flexibly among three different channels. Microwave experiments show good agreement with full-wave simulations, clearly demonstrating the performance of the metadevices. This strategy exhibits advantages such as flexible control, low cost, and multiple and switchable functionalities, providing a new pathway for achieving switchable wavefront engineering. [ABSTRACT FROM AUTHOR]

Introduction: The number of incidental renal lesions identified in CT scans of the abdomen is increasing. Objective: The aim of this study was to determine whether hyperdense renal lesions without solid components in a portal venous CT scan can be clearly classified as vascular or non-vascular by material decomposition into iodine and water. Methods: This retrospective single-center study included 26 patients (mean age 72 years ± 9; 16 male) with 42 hyperdense renal lesions (>20 HU) in a contrast-enhanced Photon-Counting Detector CT scan (PCD-CT) between May and December 2022. Spectral decomposition into virtual non-contrast (VNC) images and iodine quantification maps was performed, and HU values were quantified within the lesions. Further imaging and histopathological reports served as reference standards. Results: Mean VNC values were 55.7 (±24.2) HU for non-vascular and 32.2 (±11.1) HU for vascular renal lesions. Mean values in the iodine maps were 5.7 (±7.8) HU for non-vascular and 33.3 (±19.0) HU for vascular renal lesions. Using a threshold of >20.3 HU in iodine maps, a total of 7/8 (87.5%) vascular lesions were correctly identified. Conclusion: This proof-of-principle study suggests that the routine use of spectral information acquired in PCD-CT scans might be able to reduce the necessary workup for hyperdense renal lesions without solid components. Further studies with larger patient cohorts are necessary to validate the results of this study and to determine the usefulness of this method in clinical routine. [ABSTRACT FROM AUTHOR]

This paper presents a proof-of-concept of a versatile Power Quality (PQ) analyser for tracking the voltage supply in industrial and residential sectors. It implements 2D Higher-Order Statistics (HOS) to assess voltage quality, based more on the sinusoidal waveform than on power fluctuations. Beyond the second-order parameters and permissible deviations regulated by the norm, EN 50160, the two-dimensional traces and probability density functions, along with a previously studied differential index, manage to identify different states of the electrical grid. Waveforms were measured in the wall plugs of a public building. In regard to analysing reliability and voltage waveform, the results corroborate that incorporating skewness and kurtosis indicators improves the characterisation, as well as extracting the customers' supply behaviour under normal and anomalous operations. The instrument showed good behaviour in site characterisation, and the implemented method was considered as a probabilistic approach for the risk assessment of an installation. The prototype was tested in the facilities of a public building of the university, being able to detect deviations in 10 s traces of 3.9% in variance and 0.6% in kurtosis. [ABSTRACT FROM AUTHOR]

This study aimed to create a new recombinant virus by modifying the EV-A71 capsid protein, serving as a useful tool and model for studying human Enteroviruses. We developed a new screening method using EV-A71 pseudovirus particles to systematically identify suitable insertion sites and tag types in the VP1 capsid protein. The pseudovirus's infectivity and replication can be assessed by measuring postinfection luciferase signals. We reported that the site after the 100th amino acid within the VP1 BC loop of EV-A71 is particularly permissive for the insertion of various tags. Notably, the introduction of S and V5 tags at this position had minimal effect on the fitness of the tagged pseudovirus. Furthermore, recombinant infectious EV-A71 strains tagged with S and V5 epitopes were successfully rescued, and the stability of these tags was verified. Computational analysis suggested that viable insertions should be compatible with capsid assembly and receptor binding, whereas non-viable insertions could potentially disrupt the capsid's binding with heparan sulfate. We expect the tagged recombinant EV-A71 to be a useful tool for studying the various stages of the enterovirus life cycle and for virus purification, immunoprecipitation, and research in immunology and vaccine development. Furthermore, this study serves as a proof of principle and may help develop similar tags in enteroviruses, for which there are fewer available tools. [ABSTRACT FROM AUTHOR]

This work presents the design of a novel fully canonical triple-mode filter with source–load coupling for 5G applications, exploiting its very compact size for the FR1 band. The design is carried out using circular waveguide technology to attain power handling and low insertion losses. The fully canonical topology allows for increasing the selectivity of the filter since the number of finite transmission zeros is equal to the order of the filter. Given that this topology needs a source–load coupling level that is not possible to achieve with the classical iris ports, coaxial probes are used as input–output ports. A systematic procedure is developed to obtain the initial geometry before the full-wave optimization. The proof of concept is verified by a manufactured prototype at 3.7 GHz with 1.1% relative bandwidth for high coverage of 5G base stations. The results show an excellent agreement between the simulation and the measurement, validating the triple-mode filter and its underlying design process. [ABSTRACT FROM AUTHOR]

An ultrafast microwave ranging method based on optically generated frequency-modulated microwave pulses is proposed in this study. The theoretical analysis demonstrated that nanosecond-scale linear frequency modulation microwave pulse can be obtained by femtosecond laser interference under the condition of unbalanced dispersion, which can be used to achieve a high temporal resolution of the displacement change in the measurement by the principle of frequency modulation continuous wave (FMCW) radar. The proof-of-principle experiment successfully measured the displacement change with an error of 2.5 mm and a range of 0.6 m, with a response time of 468 ns. Compared to existing microwave ranging technologies, the temporal resolution was improved by two orders of magnitude, which greatly improves the temporal resolution of distance measurement in the field of microwave FMCW radar. [ABSTRACT FROM AUTHOR]

The practical deployment of Zn‐ion batteries faces challenges such as dendrite growth, side reactions and cathode dissolution in traditional electrolytes. Here, we develop a highly conductive and dynamically ion‐sieved electrolyte to simultaneously enhance the Zn metal reversibility and suppress the cathode dissolution. The dynamic ion screen at the electrode/electrolyte interface is achieved by numerous pyrane rings with a radius of 3.69 Å, which can selectively facilitate the plating/stripping and insertion/extraction process of [Zn(H2O)6]2+ and Zn2+ on the anode and cathode surfaces. As a proof of concept, Zn//Zn symmetric cells deliver exceptional cyclic stability for over 6,800 h and ultrahigh cumulative plated capacity of 1.95 Ah cm−2. Zn//Na2Mn3O7 cells exhibit satisfactory cycling performance with capacity retention of 82.7 % after 4,000 cycles, and the assembled pouch cells achieve excellent stability and durability. This work provides valuable insights into the development of electrolytes aimed at enhancing the interface stability of aqueous batteries. [ABSTRACT FROM AUTHOR]

• Emotion understanding (EU) is linked to important developmental outcomes. • Scale-up of existing EU programs is challenging due to required time and resources. • Mission FEEL! is a two-session, fully automated EU intervention for preschoolers. • Findings indicate Mission FEEL! is acceptable, feasible, and clinically meaningful. • Mission FEEL! should advance to the next phase of intervention development testing. Emotion understanding is an important competency that children begin to develop during the first years of life and serves as an essential building block for lifelong learning. Emotion understanding is linked to developmental outcomes including academic, cognitive, and social-emotional skills. Not surprisingly, efficacious interventions to promote children's social emotional skills have been developed. Scale-up of these interventions is challenging because they are time and resource intensive. Brief, fully automated interventions are promising alternatives to overcome implementation barriers. Mission FEEL! is a two-session, fully automated intervention grounded in cognitive-behavioral theory aimed at promoting emotion understanding among preschoolers. This proof-of-concept study examined the acceptability and feasibility of Mission FEEL!. We recruited 52 preschool children and their parents/guardians across Florida. Participants completed four virtual study visits: a baseline emotion understanding assessment, two intervention sessions, and a one-month follow-up emotion understanding assessment. We established a priori benchmarks to determine feasibility, acceptability, and clinical meaningfulness. The results indicated that Mission FEEL! is both feasible and acceptable. All outcomes, except two that were in the acceptable range, met the benchmarks for good or excellent. The clinical meaningfulness of the intervention was supported by parental perceptions of the program's influence on emotion-related parent-child interactions, perceived value of the program in children's daily lives, and observed difference in emotion understanding scores between baseline and follow-up. The ease of scale-up, low cost, and potential practical implications also contributed to the clinical meaningfulness. Findings from this proof-of-concept study suggest that Mission FEEL! merits advancing to the next phase of intervention development testing. [ABSTRACT FROM AUTHOR]

The present study aims to develop and present a proof-of-concept for a stop signal task with effector-specificity and higher complexity. Sixteen participants performed a stop signal task developed for lower extremities using Fitlight System™. The effect of four different delays and two sessions on response time, stop signal reaction time and accuracy was assessed using two-way repeated-measures ANOVA. The reliability of outcomes was assessed using intraclass correlation coefficients. There was a significant main effect of delay on all outcomes and an interaction of delay and session on accuracy. The reliability of outcomes was substantial with dependency on delays. Our preliminary findings suggest the feasibility of stop signal principles within more complex movements and provide an example for the development of further tests in sports context. [ABSTRACT FROM AUTHOR]

Surface‐enhanced Raman spectroscopy (SERS) was utilized to measure low‐level fentanyl concentrations mixed in common cutting agents, cocaine, 3,4‐methylenedioxymethamphetamine (MDMA), methamphetamine, and caffeine. Mixtures were prepared with a fentanyl concentration range of 0–339 μM. Data was initially analyzed by plotting the area of a diagnostic peak (1026 cm−1) against concentration to generate a calibration model. This method was successful with fentanyl/MDMA samples (LOD 0.04 μM) but not for the other mixtures. A chemometric approach was then employed. The data was evaluated using principal component analysis (PCA), partial least squares (PLS1) regression, and linear discriminant analysis (LDA). The LDA model was used to classify samples into one of three designated concentration ranges, low = 0–0.4 mM, medium = 0.4–14 mM, or high >14 mM, with fentanyl concentrations correctly classified with greater than 85% accuracy. This model was then validated using a series of "blind" fentanyl mixtures and these unknown samples were assigned to the correct concentration range with an accuracy >95%. The PLS1 model failed to provide accurate quantitative assignments for the samples but did provide an accurate prediction for the presence or absence of fentanyl. The combination of the two models enabled accurate quantitative assignment of fentanyl in binary mixtures. This work establishes a proof of concept, indicating a larger sample size could generate a more accurate model. It demonstrates that samples, containing variable, low concentrations of fentanyl, can be accurately quantified, using SERS. [ABSTRACT FROM AUTHOR]

Looking at caregivers' faces is important for early social development, and there is a concomitant increase in neural correlates of attention to familiar versus novel faces in the first 6 months. However, by 12 months of age brain responses may not differentiate between familiar and unfamiliar faces. Traditional group‐based analyses do not examine whether these 'null' findings stem from a true lack of preference within individual infants, or whether groups of infants show individually strong but heterogeneous preferences for familiar versus unfamiliar faces. In a preregistered proof‐of‐principle study, we applied Neuroadaptive Bayesian Optimisation (NBO) to test how individual infants' neural responses vary across faces differing in familiarity. Sixty‐one 5–12‐month‐olds viewed faces resulting from gradually morphing a familiar (primary caregiver) into an unfamiliar face. Electroencephalography (EEG) data from fronto‐central channels were analysed in real‐time. After the presentation of each face, the Negative central (Nc) event‐related potential (ERP) amplitude was calculated. A Bayesian Optimisation algorithm iteratively selected the next stimulus until it identified the stimulus eliciting the strongest Nc for that infant. Attrition (15%) was lower than in traditional studies (22%). Although there was no group‐level Nc‐difference between familiar versus unfamiliar faces, an optimum was predicted in 85% of the children, indicating individual‐level attentional preferences. Traditional analyses based on infants' predicted optimum confirmed NBO can identify subgroups based on brain activation. Optima were not related to age and social behaviour. NBO suggests the lack of overall familiar/unfamiliar‐face attentional preference in middle infancy is explained by heterogeneous preferences, rather than a lack of preference within individual infants. [ABSTRACT FROM AUTHOR]

Two-dimensional correlation spectroscopy is used to investigate the intermolecular interaction between two substances dissolved in the same solutions, where the intermolecular interaction is described by two reversible reactions producing two supramolecular aggregates. The severe overlappings expected among the characteristic peaks of the original solute and aggregates make conventional one-dimensional spectra difficult to accurately reflect the physiochemical nature of the intermolecular interaction. The double asynchronous orthogonal sample design (DAOSD) approach is utilized to analyze the simulated data for proof-of-principle demonstration. The patterns of cross-peaks are much more complex compared with the intermolecular interaction described by only a single reaction. Four major groups of cross-peaks with characteristic patterns observed in the pair of DAOSD asynchronous spectra are systematically analyzed and classified. Further analysis of the spectral feature of the cross-peaks of the DAOSD asynchronous spectra is helpful to exact additional information concerning the variation of the peak position and peak width of the aggregates compared with those of the original solute. The result is important to reveal the physicochemical nature of intermolecular interaction between the solutes (e.g., changes in conformation, dynamical behavior, etc.). The pattern of cross-peaks in the corresponding 2D asynchronous spectra may become rather complex when the peak position, peak width, and peak intensity of two supramolecular aggregates change simultaneously. Further work using artificial intelligence techniques to interpret the complex cross-peaks is still being carried out. [ABSTRACT FROM AUTHOR]

Chalcogenide phase-change materials (PCMs) offer a promising approach to programmable photonics thanks to their nonvolatile, reversible phase transitions and high refractive index contrast. However, conventional designs are limited by global phase control over entire PCM thin films between fully amorphous and fully crystalline states, which restricts device functionality and confines design flexibility and programmability. In this work, we present a novel approach that leverages pixel-level control of PCM in inverse-designed photonic devices, enabling highly reconfigurable, multi-functional operations. We integrate low-loss Sb2Se3 onto a multi-mode interferometer and achieve precise, localized phase manipulation through direct laser writing. This technique allows for flexible programming of the photonic device by adjusting the PCM phase pattern rather than relying on global phase states, thereby enhancing device adaptability. As a proof of concept, we programmed the device as a wavelength-division multiplexer and subsequently reconfigured it into a mode-division multiplexer. Our results underscore the potential of combining inverse design with pixel-wise tuning for next-generation programmable phase-change photonic systems. [ABSTRACT FROM AUTHOR]

The metal bipolar plate is a critical component of the hydrogen fuel cell stack used in proton exchange membrane fuel cells. Bipolar plates must have high accuracy micro-channels with a high aspect ratio (AR) between the channel depth and the half periodic width to achieve optimal cell performance. Conventional forming methods, such as micro-stamping, hydroforming, and rubber pad forming, cannot achieve these high ARs given that in these processes, material deformation is dominated by stretch deformation. In micro-roll forming the major deformation mode is bending, and this enables production of channels with higher ARs than is currently possible. However, micro-roll forming uses multiple sets of forming roll stands to form the part and this leads to technological challenges related to tool alignment and roll tool precision that must be overcome before widespread application can be achieved. This study presents a new methodology to achieve tight tool tolerances when producing micro-roll tooling by utilizing wire-EDM and micro-turning techniques. This is combined with a new micro-roll former design that enables high-precision tool alignment across multiple roll stations. Proof of concept is provided through micro-roll forming trials performed on ultra-thin titanium sheets that show that the proposed technology can achieve tight dimensional tolerances in the sub-millimeter scale that suits bipolar plate applications. [ABSTRACT FROM AUTHOR]

This article re-examines claims made around nanotechnology early in its conception in order to retrospectively highlight questions at the core of that discourse that remain relevant today. Early nanotechnology rhetoric paradoxically invokes the capacities of microbes as proof of concept, even as nanoscientists dream of creating far more complex modes of building and intervention at the nanoscale. This article traces this contradictory trope through the history of nanotechnology, including a reading of Drexler's Engines of Creation , Feynman's "There's Plenty of Room at the Bottom," the Drexler–Smalley debate, and the idea of "self-assembly." I demonstrate how microbial capacities bring into view but also cover over questions about the nature of technological control, how we define life, and what is possible at the nanoscale. Throughout, the dreams of precise control at the nanoscale are contrasted to an alternative vision presented by Lynn Margulis and Dorion Sagan that also situates microbes as technological but does so to present a vision that reworks or even displaces human control. [ABSTRACT FROM AUTHOR]

The growing concern over microplastic (MP) pollution has catalyzed extensive research efforts to comprehensively understand its environmental distribution and impact. Despite the growing number of studies documenting MP presence, the development of a standardized analytical protocol, particularly focusing on precise analytical method validation, remains a challenge. This gap arises from the complex nature of sample matrices and the diverse combinations of sample pretreatment and detection methodologies employed. Consequently, inconsistencies in detected quantities, attributed to overlooked recovery and blank measurements, persist, undermining data reliability and comparability. In this context, this study proposes an innovative solution to enhance the analytical precision for validation and evaluation of MP analysis. Leveraging Fourier Transform Infrared (FT-IR) and Quantum-cascade laser (QCL) imaging, we introduce a method that utilizes potassium bromide (KBr) pellets embedded with microplastics (MPs), facilitating exact particle number determination for method validation and quality control (QC) using FT-IR imaging of formed potassium bromide (KBr) pellets. KBr exhibits optimal properties as a matrix for MP-immobilization due to its excellent water solubility and infrared transparency. Through detailed validation, encompassing recovery, precision, and accuracy parameters, our approach represents a proof of concept that enables robust and reliable MP validation and quality control, addressing critical gaps in current methodologies. Achieved recovery rates for different polymer types and shapes, including LDPE and PVC fragments, as well as, spherical PS beads were all above the 95% mark, demonstrating high accuracy. This method serves to monitor and mitigate potential losses during sample preparation, ensuring greater accuracy and precision in microplastic analysis. By incorporating a custom synthesized polymer with a thione functionality as an internal standard alongside conventional MP polymers, we demonstrate the ability of this approach for comprehensive method validation, evaluation and quality control on a particle-based approach. [ABSTRACT FROM AUTHOR]

The compact and broadband optical switch with a large port count is demanded with the increasing communication capacity. In this article, a universal method for modeling the 1 × N switch using multimode interferometer (MMI) through transmission matrixes is proposed. Herein, the reasons for the narrowing of the operating bandwidth switch are analyzed. As a proof of concept, a wide bandwidth 1 × 4 switch, which has an insertion loss lower than 23.7 dB, and a cross talk better than −10 dB at 1550 nm are simulated, designed, and fabricated. The cross talk throughout the C band is lower than −8.5 dB. According to the experimental result, the 1 × 4 switch with four‐equal‐length modulating arms shows a 32 nm bandwidth for −10 dB cross talk which is 13 times larger than traditional switch. The switch realizes a multi‐port logic optical switch by modulation. The 1 × N switch based on the generalized Mach–Zehnder interferometer (GMZI) structure reduce the footprint significantly compared with the 1 × N switch consisting of a 1 × 2 switch cascade. It is believed that 1 × N switch based on GMZI structures is a promising solution to increase integration density. [ABSTRACT FROM AUTHOR]

Discovering antigen-reactive T cell receptors (TCRs) is central to developing effective engineered T cell immunotherapies. However, the conventional technologies for isolating antigen-reactive TCRs (i.e., major histocompatibility complex (MHC) multimer staining) focus on high-affinity interactions between the TCR and MHC-antigen complex, and may fail to identify TCRs with high efficacy for activating T cells. Here, we develop a microfluidic single-cell screening method for antigen-reactive T cells named ATLAS-seq (Aptamer-based T Lymphocyte Activity Screening and SEQuencing). This technology isolates and characterizes activated T cells via an aptamer-based fluorescent molecular sensor, which monitors the cytotoxic cytokine IFNγ secretion from single T cells upon antigen stimulation, followed by single-cell RNA and single-cell TCR sequencing. We use ATLAS-seq to screen TCRs reactive to cytomegalovirus (CMV) or prostate specific antigen (PSA) from peripheral blood mononuclear cells (PBMCs). ATLAS-seq identifies distinct TCR clonotype populations with higher T cell activation levels compared to TCRs recovered by MHC multimer staining. Select TCR clonotypes from ATLAS-seq are more efficient in target cell killing than those from MHC multimer staining. Collectively, ATLAS-seq provides an efficient and broadly applicable technology to screen antigen-reactive TCRs for engineered T cell immunotherapy. Isolation of antigen-reactive T cell receptors (TCRs) to cancer epitopes is important for engineered T cell immunotherapies. Here the authors show an aptamer-based microfluidic single-cell method to isolate antigen-reactive TCRs and show proof of principle isolations for cytomegalovirus and prostate specific antigen. [ABSTRACT FROM AUTHOR]

T‐cell‐engaging bispecific antibodies (TCEs) that target tumor antigens and T cells have shown great promise in treating cancer, particularly in hematological indications. The clinical development of TCEs often involves a lengthy first‐in‐human (FIH) trial with many dose‐escalation cohorts leading up to an early proof of concept (POC), enabling either a no‐go decision or dose selection for further clinical development. Multiple factors related to the target, product, disease, and patient population influence the efficacy and safety of TCEs. The intricate mechanism of action limits the translatability of preclinical models to the clinic, thereby posing challenges to streamline clinical development. In addition, unlike traditional chemotherapy, the top dose and recommended phase II doses (RP2Ds) for TCEs in the clinic are often not guided by the maximum tolerated dose (MTD), but rather based on the integrated dose–response assessment of the benefit/risk profile. These uncertainties pose complex challenges for translational and clinical pharmacologists (PK/PD scientists), as well as clinicians, to design an efficient clinical study that guides development. To that end, experts in the field, under the umbrella of the American Association of Pharmaceutical Scientists, have reviewed learnings from published literature and currently marketed products to share perspectives on the FIH and clinical pharmacology strategies to support early clinical development of TCEs. [ABSTRACT FROM AUTHOR]

Understanding antigen‐specific T‐cell responses is crucial for advancing immunotherapies and vaccine development. This study proposes a novel approach combining two complementary assays: the 5‐ethynyl‐2′‐deoxyuridine (EdU) incorporation assay (tracking proliferation over 0–48 h) and the VPD450 dye dilution assay (tracking proliferation over 4–6 days). Integrating these techniques provides additional insights into T‐cell proliferation kinetics. Both assays were independently optimized using anti‐CD3 and anti‐CD28 polyclonal T cell stimulation. 1 μM VPD450 is suitable for assessing T‐cell proliferation. The EdU concentration should match the stimulation strength, requiring higher concentrations to efficiently track DNA replication detection during increased cellular division. Day 5 was the optimal read‐out day for the EdU incorporation assay. We then combined the VPD450 dye dilution and EdU incorporation assays. As a proof of principle, we stimulated PBMCs from healthy donors with tetanus toxoid to assess antigen‐specific T‐cell responses. Additionally, we demonstrated the assay's application in drug research by evaluating proliferation in a mixed lymphocyte reaction with abatacept, an agonistic anti‐CTLA‐4 antibody. This combined approach offers qualitative insights into T‐cell proliferation kinetics, beneficial for assessing novel vaccine efficiency or for designing new treatments targeting T cell proliferation, such as in autoimmune settings. [ABSTRACT FROM AUTHOR]