XLIM

Abstract Metasurface is a recently developed nanophotonics concept to manipulate the properties of light by replacing conventional bulky optical components with ultrathin (more than 10 4 times thinner) flat optical components. Since the first demonstration of metasurfaces in 2011, they have attracted tremendous interest in the consumer optics and electronics industries. Recently, metasurface‐empowered novel bioimaging and biosensing tools have emerged and been reported. Given the recent advances in metasurfaces in biomedical engineering, this review article covers the state of the art for this technology and provides a comprehensive interdisciplinary perspective on this field. The topics that we have covered include metasurfaces for chiral imaging, endoscopic optical coherence tomography, fluorescent imaging, super‐resolution imaging, magnetic resonance imaging, quantitative phase imaging, sensing of antibodies, proteins, DNAs, cells, and cancer biomarkers. Future directions are discussed in twofold: application‐specific biomedical metasurfaces and bioinspired metasurface devices. Perspectives on challenges and opportunities of metasurfaces, biophotonics, and translational biomedical devices are also provided. The objective of this review article is to inform and stimulate interdisciplinary research: firstly, by introducing the metasurface concept to the biomedical community; and secondly by assisting the metasurface community to understand the needs and realize the opportunities in the medical fields. In addition, this article provides two knowledge boxes describing the design process of a metasurface lens and the performance matrix of a biosensor, which serve as a “crash‐course” introduction to those new to both fields.

Cells are essential to understanding health and disease, yet traditional models fall short of modeling and simulating their function and behavior. Advances in AI and omics offer groundbreaking opportunities to create an AI virtual cell (AIVC), a multi-scale, multi-modal large-neural-network-based model that can represent and simulate the behavior of molecules, cells, and tissues across diverse states. This Perspective provides a vision on their design and how collaborative efforts to build AIVCs will transform biological research by allowing high-fidelity simulations, accelerating discoveries, and guiding experimental studies, offering new opportunities for understanding cellular functions and fostering interdisciplinary collaborations in open science.

This article deals with robust fixed-time stability and stabilization. First, new global robust fixed-time stability results are proposed for scalar systems by using constant and variable exponent coefficients. Then, they are applied to global robust fixed-time stabilization of a class of uncertain nonlinear second-order systems by using sliding-mode control. All the results are illustrated in simulation.

<h3>Background</h3> Oncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death and induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development as an oncolytic immunotherapy in this study as it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis and is a potent activator of both innate and adaptive immunity. HSV-1 also has a large capacity for the insertion of additional, potentially therapeutic, exogenous genes. Finally, HSV-1 has a proven safety and efficacy profile in patients with cancer, talimogene laherparepvec (T-VEC), an oncolytic HSV-1 which expresses GM-CSF, being the only oncolytic immunotherapy approach that has received FDA approval. As the clinical efficacy of oncolytic immunotherapy has been shown to be further enhanced by combination with immune checkpoint inhibitors, developing improved oncolytic platforms which can synergize with other existing immunotherapies is a high priority. In this study we sought to further optimize HSV-1 based oncolytic immunotherapy through multiple approaches to maximize: (i) the extent of tumor cell killing, augmenting the release of tumor antigens and danger-associated molecular pattern (DAMP) factors; (ii) the immunogenicity of tumor cell death; and (iii) the resulting systemic anti-tumor immune response. <h3>Methods</h3> To sample the wide diversity amongst clinical strains of HSV-1, twenty nine new clinical strains isolated from cold sores from otherwise healthy volunteers were screened across a panel of human tumor cell lines to identify the strain with the most potent tumor cell killing ability, which was then used for further development. Following deletion of the genes encoding ICP34.5 and ICP47 to provide tumor selectivity, the extent of cell killing and the immunogenicity of cell death was enhanced through insertion of a gene encoding a truncated, constitutively highly fusogenic form of the envelope glycoprotein of gibbon ape leukemia virus (GALV-GP-R⁻). A number of further armed derivatives of this virus were then constructed intended to further enhance the anti-tumor immune response which was generated following fusion-enhanced, oncolytic virus replication-mediated cell death. These viruses expressed GMCSF, an anti-CTLA-4 antibody-like molecule, CD40L, OX40L and/or 4-1BB, each of which is expected to act predominantly at the site and time of immune response initiation. Expression of these proteins was confirmed by ELISA and/or western blotting. Immunogenic cell death was assessed by measuring the levels of HMGB1 and ATP from cell free supernatants from treated cells, and by measuring the surface expression of calreticulin. GALV-GP-R⁻ mediated cell to cell fusion and killing was tested in a range of tumor cell lines in vitro. Finally, the in vivo therapeutic potential of these viruses was tested using human A549 (lung cancer) and MDA-MB-231(breast cancer) tumor nude mouse xenograft models and systemic anti-tumor effects tested using dual flank syngeneic 4434 (melanoma), A20 (lymphoma) mouse tumor models alone and in combination with a murine anti-PD1 antibody, and 9 L (gliosarcoma) tumors in rats. <h3>Results</h3> The twenty nine clinical strains of HSV-1 isolated and tested demonstrated a broad range of tumor cell killing abilities allowing the most potent strain to be identified which was then used for further development. Oncolytic ability was demonstrated to be further augmented by the expression of GALV-GP-R⁻ in a range of tumor cell lines in vitro and in mouse xenograft models in nude mice. The expression of GALV-GP-R⁻ was also demonstrated to lead to enhanced immunogenic cell death in vitro as confirmed by the increased release of HMGB1 and ATP and increased levels of calreticulin on the cell surface. Experiments using the rat 9 L syngeneic tumor model demonstrated that GALV-GP-R⁻ expression increased abscopal uninjected (anenestic) tumor responses and data using mouse 4434 tumors demonstrated that virus treatment increased CD8+ T cell levels both in the injected and uninjected tumor, and also led to increased expression of PD-L1. A combination study using varying doses of a virus expressing GALV-GP-R⁻ and mGM-CSF and an anti-murine PD1 antibody showed enhanced anti-tumor effects with the combination which was most evident at low virus doses, and also lead to immunological memory. Finally, treatment of mice with derivatives of this virus which additionally expressed anti-mCTLA-4, mCD40L, m4-1BBL, or mOX40L demonstrated enhanced activity, particularly in uninjected tumors. <h3>Conclusion</h3> The new HSV-1 based platform described provides a potent and versatile approach to developing new oncolytic immunotherapies for clinical use. Each of the modifications employed was demonstrated to aid in optimizing the potential of the virus to both directly kill tumors and to lead to systemic therapeutic benefit. For clinical use, these viruses are expected to be most effective in combination with other anti-cancer agents, in particular PD1/L1-targeted immune checkpoint blockade. The first virus from this program (expressing GALV-GP-R⁻ and hGM-CSF) has entered clinical development alone and in combination with anti-PD1 therapy in a number of tumor types (NCT03767348).

This paper presents a multi-polarization reconfigurable antenna with four dipole radiators for biomedical applications in body-centric wireless communication system (BWCS). The proposed multi-dipole antenna with switchable 0°, +45°, 90° and -45° linear polarizations is able to overcome the polarization mismatching and multi-path distortion in complex wireless channels as in BWCS. To realize this reconfigurable feature for the first time among all the reported antenna designs, we assembled four dipoles together with 45° rotated sequential arrangements. These dipoles are excited by the same feeding source provided by a ground tapered Balun. A metallic reflector is placed below the dipoles to generate a broadside radiation. By introducing eight PIN diodes as RF switches between the excitation source and the four dipoles, we can control a specific dipole to operate. As the results, 0°, +45°, 90° and -45° linear polarizations can be switched correspondingly to different operating dipoles. Experimental results agree with the simulation and show that the proposed antenna well works in all polarization modes with desirable electrical characteristics. The antenna has a wide impedance bandwidth of 34% from 2.2 to 3.1 GHz (for the reflection coefficient ≤ -10 dB) and exhibits a stable cardioid-shaped radiation pattern across the operating bandwidth with a peak gain of 5.2 dBi. To validate the effectiveness of the multi-dipole antenna for biomedical applications, we also designed a meandered PIFA as the implantable antenna. Finally, the communication link measurement shows that our proposed antenna is able to minimize the polarization mismatching and maintains the optimal communication link thanks to its polarization reconfigurability.

Motivated by applications in quantum chemistry and solid state physics, we\napply general results from approximation theory and matrix analysis to the\nstudy of the decay properties of spectral projectors associated with large and\nsparse Hermitian matrices. Our theory leads to a rigorous proof of the\nexponential off-diagonal decay ("nearsightedness") for the density matrix of\ngapped systems at zero electronic temperature in both orthogonal and\nnon-orthogonal representations, thus providing a firm theoretical basis for the\npossibility of linear scaling methods in electronic structure calculations for\nnon-metallic systems. We further discuss the case of density matrices for\nmetallic systems at positive electronic temperature. A few other possible\napplications are also discussed.\n

Since the introduction of the notion of privacy homomorphism by Rivest et al. in the late 1970s, the design of efficient and secure encryption schemes allowing the performance of general computations in the encrypted domain has been one of the holy grails of the cryptographic community. Despite numerous partial answers, the problem of designing such a powerful primitive has remained open until the theoretical breakthrough of the fully homomorphic encryption (FHE) scheme published by Gentry in the late 2000s. Since then, progress has been fast-paced, and it can now be reasonably said that practical homomorphic encryption-based computing will become a reality in the near future.

Abstract Background Gastroparesis is a functional disorder with a variety of symptoms that is characterized by delayed gastric emptying in the absence of mechanical obstruction. A recent series of retrospective studies has demonstrated that peroral endoscopic pyloromyotomy (G-POEM) is a promising endoscopic procedure for treating patients with refractory gastroparesis. The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of G-POEM. Methods 20 patients with refractory gastroparesis (10 diabetic and 10 nondiabetic) were prospectively included in the trial. Patients were treated by G-POEM after evaluation of pyloric function using an endoscopic functional luminal imaging probe. Clinical responses were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and quality of life was assessed using the Patient Assessment of Upper Gastrointestinal Disorders – Quality of Life scale and the Gastrointestinal Quality of Life Index scores. Gastric emptying was measured using 4-hour scintigraphy before G-POEM and at 3 months. Results Feasibility of the procedure was 100 %. Compared with baseline values, G-POEM significantly improved symptoms (GCSI: 1.3 vs. 3.5; P &lt; 0.001), quality of life, and gastric emptying (T½: 100 vs. 345 minutes, P &lt; 0.001; %H2: 56.0 % vs. 81.5 %, P &lt; 0.001; %H4: 15.0 % vs. 57.5 %, P = 0.003) at 3 months. The clinical success of G-POEM using the functional imaging probe inflated to 50 mL had specificity of 100 % and sensitivity of 72.2 % (P = 0.04; 95 % confidence interval 0.51 – 0.94; area under the curve 0.72) at a distensibility threshold of 9.2 mm2/mmHg. Conclusion G-POEM was efficacious and safe for treating refractory gastroparesis, especially in patients with low pyloric distensibility.

This technical note deals with a general class of discrete 2-D possibly nonlinear systems based on the Roesser model. We first motivate the introduction of Lyapunov type definitions of asymptotic and exponential stability. This will allow us to introduce and discuss several particularities that cannot be found in 1-D systems. Once this background has been carefully designed, we develop different Lyapunov theorems in order to check asymptotic and exponential stability of nonlinear 2-D systems. Finally we propose the first converse Lyapunov theorem in the case of exponential stability.

We have designed, fabricated, and experimentally verified a highly sensitive plasmonic sensing device in the terahertz frequency range. For a proof of concept of the sensing phenomenon, we have chosen the so-called fishnet structure based on circular hole array insensitive to the polarization of the incident wave. We employ the localized resonance associated with the cutoff frequency (electric plasma frequency) of the hole array to investigate its sensing capability. A thin-film overlayer deposited on the surface of the metallic apertures causes an amplitude modulation and a shift in the resonant frequency of the terahertz transmission. The frequency shift and the amplitude modulation were investigated as a function of the refractive index and the thickness of the overlayer for determining the sensing potential of the proposed structure. Measurements carried out using terahertz time-domain spectroscopy show good agreement with the numerical predictions. The results we obtained indicate that the proposed device could be very promising for enhancing the sensing capabilities of the refractive index changes involved in bio-applications, for instance.

The availability of genomic sequences of several Verticillium species triggered an explosion of genome-scale investigations of mechanisms fundamental to the Verticillium life cycle and disease process. Comparative genomics studies have revealed evolutionary mechanisms, such as hybridization and interchromosomal rearrangements, that have shaped these genomes. Functional analyses of a diverse group of genes encoding virulence factors indicate that successful host xylem colonization relies on specific Verticillium responses to various stresses, including nutrient deficiency and host defense-derived oxidative stress. Regulatory pathways that control responses to changes in nutrient availability also appear to positively control resting structure development. Conversely, resting structure development seems to be repressed by pathways, such as those involving effector secretion, which promote responses to host defenses. The genomics-enabled functional characterization of responses to the challenges presented by the xylem environment, accompanied by identification of novel virulence factors, has rapidly expanded our understanding of niche adaptation in Verticillium species.

Standard optical lithography relying on clean room and microelectronic facilities is used to fabricate a thin-flexible metamaterial absorber, designed to operate at submillimeter wavelengths over the 0.1-1 THz frequency band. Large terahertz absorption has been demonstrated numerically and through experimental measurements with a maximum level of about 80%. We put emphasis in this present work on the use of single-sized "meta-cells" to achieve multiple absorption peaks. Furthermore, the use of a thin-flexible dielectric spacer makes it promising for stealth technology applications in order to disguise objects and make them less visible to radar and other detection methods.

We investigate some open problems on almost perfect nonlinear (APN) functions over a finite field of characteristic <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$2$</tex> . We provide new characterizations of APN functions and of APN permutations by means of their component functions. We generalize some results of Nyberg (1994) and strengthen a conjecture on the upper bound of nonlinearity of APN functions. We also focus on the case of quadratic functions. We contribute to the current works on APN quadratic functions by proving that a large class of quadratic functions cannot be APN.

We present a photosensitive three-hole microstructured optical fiber specifically designed to improve the refractive index sensitivity of a standard fiber Bragg grating (FBG) sensor photowritten in the suspended Ge-doped silica core. We describe the specific photowriting procedure used to realize gratings in such a fiber. We then determine their spectral sensitivity to the refractive index changes of material filling the holes surrounding the core. The sensitivity is compared with that of standard FBGs photowritten in a six-hole fiber with a larger core diameter. We demonstrate an improvement in the sensitivity by two orders of magnitude and reach a resolution of 3 x 10(-5) and 6 x 10(-6) around mean refractive index values of 1.33 and 1.40, respectively.

In this paper, we propose two new generic attacks on the rank syndrome decoding (RSD) problem. Let C be a random [n, k] rank code over GF(q <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">m</sup> ) and let y = x + e be a received word, such that x ∈ C and rank(e) = r. The first attack, the support attack, is combinatorial and permits to recover an error e of rank weight r in min(O((n - k) <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> qr1(km/n)J, O((n - k) <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> m <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> q <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">⌈(r-1)I(((k+1)m)/n)J))⌉</sup> operations on GF(q). This new attack improves the exponent for the best generic attack for the RSD problem in the case n > m, by introducing the ratio m/n in the exponential coefficient of the previously best known attacks. The second attack, the annulator polynomial attack, is an algebraic attack based on the theory of q-polynomials introduced by Ore. We propose a new algebraic setting for the RSD problem that permits to consider equations and unknowns in the extension field GF(qm) rather than in GF(q) as it is usually the case. We consider two approaches to solve the problem in this new setting. The linearization technique shows that if n ≥ (k + 1) (r + 1) - 1 the RSD problem can be solved in polynomial time. More generally, we prove that if [(((r + 1)(k + 1)- (n + 1))/r)1 ≤ k, the RSD problem can be solved with an average complexity of O(r <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> k <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> qr <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">Γ(((r+1)(k+1)-(n+1))/r)l)⌉</sup> operations in the base field GF(q). We also consider solving with Gröbner bases for which we discuss theoretical complexity, we also consider hybrid solving with Gröbner bases on practical parameters. As an example of application, we use our new attacks on all recent cryptosystems parameters, which repair the GPT cryptosystem, we break all examples of published proposed parameters, and some parameters are broken in less than 1 s in certain cases.

BACKGROUND: Endoscopic resection of adenomas prevents colorectal cancer, but the optimal technique for larger lesions is controversial. Piecemeal endoscopic mucosal resection (EMR) has a low adverse event (AE) rate but a variable recurrence rate necessitating early follow-up. Endoscopic submucosal dissection (ESD) can reduce recurrence but may increase AEs. OBJECTIVE: To compare ESD and EMR for large colonic adenomas. DESIGN: Participant-masked, parallel-group, superiority, randomized controlled trial. (ClinicalTrials.gov: NCT03962868). SETTING: Multicenter study involving 6 French referral centers from November 2019 to February 2021. PARTICIPANTS: Patients with large (≥25 mm) benign colonic lesions referred for resection. INTERVENTION: The patients were randomly assigned by computer 1:1 (stratification by lesion location and center) to ESD or EMR. MEASUREMENTS: The primary end point was 6-month local recurrence (neoplastic tissue on endoscopic assessment and scar biopsy). The secondary end points were technical failure, en bloc R0 resection, and cumulative AEs. RESULTS: = 318 lesions in 318 patients), recurrence occurred after 1 of 161 ESDs (0.6%) and 8 of 157 EMRs (5.1%) (relative risk, 0.12 [95% CI, 0.01 to 0.96]). No recurrence occurred in R0-resected cases (90%) after ESD. The AEs occurred more often after ESD than EMR (35.6% vs. 24.5%, respectively; relative risk, 1.4 [CI, 1.0 to 2.0]). LIMITATION: Procedures were performed under general anesthesia during hospitalization in accordance with the French health system. CONCLUSION: Compared with EMR, ESD reduces the 6-month recurrence rate, obviating the need for systematic early follow-up colonoscopy at the cost of more AEs. PRIMARY FUNDING SOURCE: French Ministry of Health.

This letter investigates the impact of spatial channel correlation on the outage probability of intelligent reflecting surface (IRS)-assisted single-input single-output (SISO) communication systems. In particular, we derive a novel closed-form expression of the outage probability for arbitrary phase shifts and correlation matrices of the indirect channels. To shed light on the impact of the spatial correlation, we further attain the closed-form expressions for two common scenarios met in the literature when the large-scale fading coefficients are expressed by the loss over a propagation distance. Numerical results validate the tightness and effectiveness of the closed-form expressions. Furthermore, the spatial correlation offers significant decreases in the outage probability as the direct channel is blocked.

An original design of hollow-core photonic crystal fiber composed of a thin silica ring suspended in air by six silica struts is proposed. This structure can be viewed as a simplified Kagomé-lattice fiber reduced to one layer of air holes. By working on the core surround parameters, an efficient antiresonant air guiding was successfully demonstrated. Two large low-loss windows (visible/IR) were measured with a minimum attenuation less than 0.2 dB radicalm at yellow wavelengths, comparable with state-of-the-art designs. The curvature behavior was also studied, showing low bending loss sensitivity for the fundamental transmission band. These relevant features might open a new route to propose original hollow-core fiber designs while making their production simpler and faster than previously.

Fast CARS: The cell-death process was observed in real time at the subcellular level by coherent anti-Stokes Raman microspectroscopy, an extension of anti-Stokes Raman scattering (CARS) microscopy. Changes in the chemical contrast during the dying process can be clearly resolved (see picture).

Abstract Almost all mesh processing procedures cause some more or less visible changes in the appearance of objects represented by polygonal meshes. In many cases, such as mesh watermarking, simplification or lossy compression, the objective is to make the change in appearance negligible, or as small as possible, given some other constraints. Measuring the amount of distortion requires taking into account the final purpose of the data. In many applications, the final consumer of the data is a human observer, and therefore the perceptibility of the introduced appearance change by a human observer should be the criterion that is taken into account when designing and configuring the processing algorithms. In this review, we discuss the existing comparison metrics for static and dynamic (animated) triangle meshes. We describe the concepts used in perception‐oriented metrics used for 2D image comparison, and we show how these concepts are employed in existing 3D mesh metrics. We describe the character of subjective data used for evaluation of mesh metrics and provide comparison results identifying the advantages and drawbacks of each method. Finally, we also discuss employing the perception‐correlated metrics in perception‐oriented mesh processing algorithms.