Predictive Model to Identify the Long Time Survivor in Patients with Glioblastoma: A Cohort Study Integrating Machine Learning Algorithms.

We aimed to develop and validate a predictive model for identifying long-term survivors (LTS) among glioblastoma (GB) patients, defined as those with an overall survival (OS) of more than 3 years. A total of 293 GB patients from CGGA and 169 from TCGA database were assigned to training and validation cohort, respectively. The differences in expression of immune checkpoint genes (ICGs) and immune infiltration landscape were compared between LTS and short time survivor (STS) (OS<1.5 years). The differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify the genes differentially expressed between LTS and STS. Three different machine learning algorithms were employed to select the predictive genes from the overlapping region of DEGs and WGCNA to construct the nomogram. The comparison between LTS and STS revealed that STS exhibited an immune-resistant status, with higher expression of ICGs (P<0.05) and greater infiltration of immune suppression cells compared to LTS (P<0.05). Four genes, namely, OSMR, FMOD, CXCL14, and TIMP1, were identified and incorporated into the nomogram, which possessed good potential in predicting LTS probability among GB patients both in the training (C-index, 0.791; 0.772-0.817) and validation cohort (C-index, 0.770; 0.751-0.806). STS was found to be more likely to exhibit an immune-cold phenotype. The identified predictive genes were used to construct the nomogram with potential to identify LTS among GB patients.

A novel fault diagnosis method for second-order bandpass filter circuit based on TQWT-CNN.

To accurately locate faulty components in analog circuits, an analog circuit fault diagnosis method based on Tunable Q-factor Wavelet Transform(TQWT) and Convolutional Neural Network (CNN) is proposed in this paper. Firstly, the Grey Wolf algorithm (GWO) is used to improve the TQWT. The improved TQWT can adaptively determine the parameters Q-factor and decomposition level. Secondly, The signal is decomposed, and single-branch reconstruction is conducted with TQWT to facilitate adequate feature extraction. Thirdly, to capture the time-frequency features in the signal, a CNN-LSTM network is built by combining CNN and LSTM for feature extraction. Finally, CNN, which introduces Fully Convolutional Network (FCN) layers and a Batch Normalization layer, is used to fault diagnosis. The method was comprehensively evaluated with a second-order bandpass filter circuit. The experimental results illustrate that the proposed fault diagnosis method can achieve excellent fault diagnosis accuracy, and the average accuracy is 98.96%.

Weak Capacitance Detection Circuit of Micro-Hemispherical Gyroscope Based on Common-Mode Feedback Fusion Modulation and Demodulation.

As an effective capacitance signal produced by a micro-hemisphere gyro is usually below the pF level, and the capacitance reading process is susceptible to parasitic capacitance and environmental noise, it is highly difficult to acquire an effective capacitance signal. Reducing and suppressing noise in the gyro capacitance detection circuit is a key means to improve the performance of detecting the weak capacitance generated by MEMS gyros. In this paper, we propose a novel capacitance detection circuit, where three different means are utilized to achieve noise reduction. Firstly, the input common-mode feedback is applied to the circuit to solve the input common-mode voltage drift caused by both parasitic capacitance and gain capacitance. Secondly, a low-noise, high-gain amplifier is used to reduce the equivalent input noise. Thirdly, the modulator-demodulator and filter are introduced to the proposed circuit to effectively mitigate the side effects of noise; thus, the accuracy of capacitance detection can be further improved. The experimental results show that with the input voltage of 6 V, the newly designed circuit produces an output dynamic range of 102 dB and the output voltage noise of 5.69 nV/√Hz, achieving a sensitivity of 12.53 V/pF.

Design and Optimization of Hemispherical Resonators Based on PSO-BP and NSGA-II.

Although one of the poster children of high-performance MEMS (Micro Electro Mechanical Systems) gyroscopes, the MEMS hemispherical resonator gyroscope (HRG) is faced with the barrier of technical and process limits, which makes it unable to form a resonator with the best structure. How to obtain the best resonator under specific technical and process limits is a significant topic for us. In this paper, the optimization of a MEMS polysilicon hemispherical resonator, designed by patterns based on PSO-BP and NSGA-II, was introduced. Firstly, the geometric parameters that significantly contribute to the performance of the resonator were determined via a thermoelastic model and process characteristics. Variety regulation between its performance parameters and geometric characteristics was discovered preliminarily using finite element simulation under a specified range. Then, the mapping between performance parameters and structure parameters was determined and stored in the BP neural network, which was optimized via PSO. Finally, the structure parameters in a specific numerical range corresponding to the best performance were obtained via the selection, heredity, and variation of NSGAII. Additionally, it was demonstrated using commercial finite element soft analysis that the output of the NSGAII, which corresponded to the Q factor of 42,454 and frequency difference of 8539, was a better structure for the resonator (generated by polysilicon under this process within a selected range) than the original. Instead of experimental processing, this study provides an effective and economical alternative for the design and optimization of high-performance HRGs under specific technical and process limits.

Nonlinearity-Induced Multiplexed Optical Trapping and Manipulation with Femtosecond Vector Beams.

Optical trapping and manipulation of atoms, nanoparticles, and biological entities are widely employed in quantum technology, biophysics, and sensing. Single traps are typically achieved with linearly polarized light, while vortex beams form rotationally unstable symmetric traps. Here we demonstrate multiplexed optical traps reconfigurable with intensity and polarization of the trapping beam using intensity-dependent polarizability of nanoparticles. Nonlinearity combined with a longitudinal field of focused femtosecond vortex beams results in a stable optical force potential with multiple traps, in striking contrast to a linear trapping regime. The number of traps and their orientation can be controlled by the cylindrical vector beam order, polarization, and intensity. The nonlinear trapping demonstrated here on the example of plasmonic nanoparticles opens up opportunities for deterministic trapping and polarization-controlled manipulation of multiple dielectric and semiconductor particles, atoms, and biological objects since most of them exhibit a required intensity-dependent refractive index.

Quantitative study on a resampling mask method for speckle reduction with amplitude superposition.

One-shot digital holographic imaging has the advantages of high stability and low temporal cost. However, its reconstruction is degraded severely by the laser speckle. A rectangle, ellipse, and diamond resampling mask method in spatial domain for speckle reduction is proposed. The effectiveness of the method for speckle reduction is explained successfully. In the method, one hologram recorded in a certain size is divided into N=S×T sub-holograms. Angular spectrum transform is applied to the holographic reconstruction of a diffuse object. N reconstructed amplitude images are calculated from the corresponding sub-holograms. Benefitting from speckle's random distribution, superimposing these N uncorrelated amplitude images would lead to a final reconstructed image with reduced speckle. Normalized relative standard deviation values of the reconstructed image are in good agreement with the asymptotical law. The maximum relative errors between the experiment data and the theoretical values are below 7.2%. The effect of the method on the spatial resolution of the reconstructed image is also quantitatively evaluated. Experimental and simulation results prove the feasibility and effectiveness of the proposed method.

Design quadrilateral apertures in binary computer-generated holograms of large space bandwidth product.

A new approach for designing the binary computer-generated hologram (CGH) of a very large number of pixels is proposed. Diffraction of the CGH apertures is computed by the analytical Abbe transform and by considering the aperture edges as the basic diffracting elements. The computation cost is independent of the CGH size. The arbitrary-shaped polygonal apertures in the CGH consist of quadrilateral apertures, which are designed by assigning the binary phases using the parallel genetic algorithm with a local search, followed by optimizing the locations of the co-vertices with a direct search. The design results in high performance with low image reconstruction error.

Optical trapping of the anisotropic crystal nanorod.

We observed in the optical tweezers experiment that some anisotropic nanorod was stably trapped in an orientation tiled to the beam axis. We explain this trapping with the T-matrix calculation. As the vector spherical wave functions do not individually satisfy the anisotropic vector wave equation, we expand the incident and scattered fields in the isotropic buffer in terms of E→, and the internal field in the anisotropic nanoparticle in terms of D→, and use the boundary condition for the normal components of D→ to compute the T-matrix. We found that when the optical axes of an anisotropic nanorod are not aligned to the nanorod axis, the nanorod may be trapped stably at a tilted angle, under which the lateral torque equals to zero and the derivative of the torque is negative.

Effect of the object 3D shape on the viscoelastic testing in optical tweezers.

Viscoelastic testing of biological cells has been performed with the optical tweezers and stretcher. Historically, the cells were modeled by the spring-dashpot network or the power-law models, which can however characterize only the homogeneous, isotropic viscoelastic material, but not the 3D cell itself. Our mechanical and finite element analyses show that the cell elongations are different significantly for different cell 3D shapes in the creep testing. In the dynamic testing the loss tangent, which is measurable directly in the experiment, is not sensitive to the cell shape. However, the stress-strain hysteresis loop still depends on the cell 3D shape.

Mechanical analysis of the optical tweezers in time-sharing regime.

Time-sharing optical tweezers is a versatile technique to realize multiple traps for manipulating biological cells and macromolecules. It has been based on an intuitive hypothesis that the trapped viscoelastic object does not "sense" blinking of the optical beam. We present a quantitative analysis using mechanical modeling and numerical simulation, showing that the local stress and strain are jumping all the time and at all locations with the jumping amplitude independent of the recovery time of the viscoelastic material and the jumping frequency. Effects of the stress and strain jumping on the object deformation and the internal energy dissipation are analyzed.

Radiation pressure on a biconcave human Red Blood Cell and the resulting deformation in a pair of parallel optical traps.

We calculated the three-dimensional optical stress distribution and the resulting deformation on a biconcave human red blood cell (RBC) in a pair of parallel optical trap. We assumed a Gaussian intensity distribution with a spherical wavefront for each trapping beam and calculated the optical stress from the momentum transfer associated with the reflection and refraction of the incident photons at each interface. The RBC was modelled as a biconcave thin elastic membrane with uniform elasticity and a uniform thickness of 0.25 µm. The resulting cell deformation was determined from the optical stress distribution by finite element software, Comsol Structure Mechanics Module, with Young's modulus (E) as a fitting parameter in order to fit the theoretical results for cell elongation to our experimental data.

Three-dimensional light-scattering and deformation of individual biconcave human blood cells in optical tweezers.

For studying the elastic properties of a biconcave red blood cell using the dual-trap optical tweezers without attaching microbeads to the cell, we implemented a three-dimensional finite element simulation of the light scattering and cell's deformation using the coupled electromagnetic and continuum mechanics modules. We built the vector field of the trapping beams, the cell structure layout, the hyperelastic and viscoelastic cell materials, and we reinforced the constraints on the cell constant volume in the simulation. This computation model can be useful for studying the scattering and the other mechanical properties of the biological cells.

Modeling highly focused laser beam in optical tweezers with the vector Gaussian beam in the T-matrix method.

The vector Gaussian beam with high-order corrections is used to describe accurately the laser beam up to numerical aperture NA=1.20 in the optical tweezers for trapping nanoparticles. The beam is then expanded in the T-matrix method into the vector spherical wave function (VSWF) series using the point matching method with a new selection of the matching points. The errors in the beam description and in the VSWF expansion are much lower than those that occur in the paraxial Gaussian beam model.

Keratin 8/18 regulation of cell stiffness-extracellular matrix interplay through modulation of Rho-mediated actin cytoskeleton dynamics.

Cell mechanical activity generated from the interplay between the extracellular matrix (ECM) and the actin cytoskeleton is essential for the regulation of cell adhesion, spreading and migration during normal and cancer development. Keratins are the intermediate filament (IF) proteins of epithelial cells, expressed as pairs in a lineage/differentiation manner. Hepatic epithelial cell IFs are made solely of keratins 8/18 (K8/K18), hallmarks of all simple epithelia. Notably, our recent work on these epithelial cells has revealed a key regulatory function for K8/K18 IFs in adhesion/migration, through modulation of integrin interactions with ECM, actin adaptors and signaling molecules at focal adhesions. Here, using K8-knockdown rat H4 hepatoma cells and their K8/K18-containing counterparts seeded on fibronectin-coated substrata of different rigidities, we show that the K8/K18 IF-lacking cells lose their ability to spread and exhibit an altered actin fiber organization, upon seeding on a low-rigidity substratum. We also demonstrate a concomitant reduction in local cell stiffness at focal adhesions generated by fibronectin-coated microbeads attached to the dorsal cell surface. In addition, we find that this K8/K18 IF modulation of cell stiffness and actin fiber organization occurs through RhoA-ROCK signaling. Together, the results uncover a K8/K18 IF contribution to the cell stiffness-ECM rigidity interplay through a modulation of Rho-dependent actin organization and dynamics in simple epithelial cells.

Rigorous solution for optical diffraction of a sub-wavelength real-metal slit.

We present a rigorous closed-form solution of the Sommerfeld integral for the optical scattering of a metal sub-wavelength slit. The two-dimensional (2D) field solution consists of the Surface Plasmon Polariton (SPP) mode at the metal surface and the 2D scattered field, which is the cylindrical harmonic of first order emitted by the electrical dipole and convolved with the 1D transient SPP along the interface. The creeping wave or quasi-cylindrical wave detected in the previous experiment is not an extra evanescent surface wave, but is the asymptotic behavior of the 2D scattered field at the proximity of the slit. Furthermore, our solution predicts a strong resonant enhancement of the scattered field at the proximity of the slit, depending on the materials and wavelength.

Applications of Nano-optics.

As nanoscale fabrication techniques advance, nano-optics continues to offer enabling solutions to numerous practical applications for information optics. This Applied Optics feature issue focuses on the Application of Nano-optics.

Modeling and designing metallic superlens with metallic objects.

When the metallic near-field superlens is to image a planar object, which is itself metallic, such as that in the near-field lithography applications, the object nanometer features will act as the Hertzian dipole sources and launch homogeneous and evanescent waves. The imaging system can be modeled as a dielectric Fabry-Perot cavity with the two surface plasmon resonant mirrors. We show the expressions of the transfer function and optimize the imaging system configuration using the genetic algorithm. The effectiveness of the design is confirmed by the image intensity profile computed with the numerical finite difference in time domain method.

Measuring integrated cellular mechanical stress response at focal adhesions by optical tweezers.

The ability of cells to sustain mechanical stress is largely modulated by the cytoskeleton. We present a new application of optical tweezers to study cell's mechanical properties. We trap a fibronectin-coated bead attached to an adherent H4II-EC3 rat hepatoma cell in order to apply the force to the cell surface membrane. The bead position corresponding to the cell's local mechanical response at focal adhesions is measured with a quadrant detector. We assessed the cell response by tracking the evolution of the equilibrium force for 40 cells selected at random and selected a temporal window to assess the cell initial force expression at focal adhesions. The mean value of the force within this time window over 40 randomly selected bead∕cell bounds was 52.3 pN. Then, we assessed the responses of the cells with modulation of the cytoskeletons, namely the ubiquitous actin-microfilaments and microtubules, plus the differentiation-dependent keratin intermediate filaments. Notably, a destabilization of the first two networks led to around 50 and 30% reductions in the mean equilibrium forces, respectively, relative to untreated cells, whereas a loss of the third one yielded a 25% increase. The differences in the forces from untreated and treated cells are resolved by the optical tweezers experiment.

Angular and position stability of a nanorod trapped in an optical tweezers.

We analyze the trap stiffness and trapping force potential for a nano-cylinder trapped in the optical tweezers against its axial and lateral shift and tilt associated to the natural Brownian motion. We explain the physical properties of the optical trapping by computing and integrating the radiation stress distribution on the nano-cylinder surfaces using the T-matrix approach. Our computation shows that the force stiffness to the lateral shift is several times higher than that to the axial shift of the nano-cylinder, and lateral torque due to the stress on the side-face is 1-2 orders of magnitude higher than that on the end-faces of a nano-cylinder with the aspect ratio of 2 - 20. The torque due to the stress on the nano-cylinder surface is 2-3 orders of magnitude higher than the spin torque. We explain why a nano-cylinder of low aspect ratio is trapped and aligned normal to the trapping beam axis.

Dynamic deformation of red blood cell in dual-trap optical tweezers.

Three-dimensional dynamic deformation of a red blood cell in a dual-trap optical tweezers is computed with the elastic membrane theory and is compared with the experimental results. When a soft particle is trapped by a laser beam, the particle is deformed depending on the radiation stress distribution whereas the stress distribution on the particle in turn depends on the deformation of its morphological shape. We compute the stress re-distribution on the deformed cell and its subsequent deformations recursively until a final equilibrium state solution is achieved. The experiment is done with the red blood cells in suspension swollen to spherical shape. The cell membrane elasticity coefficient is obtained by fitting the theoretical prediction with the experimental data. This approach allows us to evaluate up to 20% deformation of cell's shape.