E-PVT: enhanced position-velocity-time scheduler for computer-controlled optical finishing with comprehensive considerations of dynamics constraints, continuity and efficiency.

Deterministic computer-controlled optical finishing is an essential approach for achieving high-quality optical surfaces. Its determinism and convergence rely heavily on precise and smooth motion control to guide the machine tool over an optical surface to correct residual errors. One widely supported and smooth motion control model is position-velocity-time (PVT), which employs piecewise cubic polynomials to describe positions. Our prior research introduced a PVT-based velocity scheduling method, demonstrating sub-nanometer level convergence in ion beam figuring (IBF) processes. However, three challenges remained. Firstly, this method relies on quadratic programming, resulting in computational intensiveness for dense tool paths. Secondly, the dynamics constraints and velocity and acceleration continuities are not comprehensively considered, limiting the full potential of PVT-based control. Thirdly, no compensation mechanism existed when dynamics constraints are exceeded. In this study, in response to these challenges, we proposed the Enhanced PVT (E-PVT) method, reducing the time complexity from O(n3) to O(n) while fully addressing dynamics constraints and continuities. A novel compensation method utilizing particle swarm optimization was proposed to address situations where dynamics constraints might be exceeded while maintaining the overall processing efficiency. Validation through simulation and experimentation confirmed the improved performance of E-PVT.

Hybrid height and slope figuring method for grazing-incidence reflective optics.

Grazing-incidence reflective optics are commonly used in synchrotron radiation and free-electron laser facilities to transport and focus the emitted X-ray beams. To preserve the imaging capability at the diffraction limit, the fabrication of these optics requires precise control of both the residual height and slope errors. However, all the surface figuring methods are height based, lacking the explicit control of surface slopes. Although our preliminary work demonstrated a one-dimensional (1D) slope-based figuring model, its 2D extension is not straightforward. In this study, a novel 2D slope-based figuring method is proposed, which employs an alternating objective optimization on the slopes in the x- and y-directions directly. An analytical simulation revealed that the slope-based method achieved smaller residual slope errors than the height-based method, while the height-based method achieved smaller residual height errors than the slope-based method. Therefore, a hybrid height and slope figuring method was proposed to further enable explicit control of both the height and slopes according to the final mirror specifications. An experiment to finish an elliptical-cylindrical mirror using the hybrid method with ion beam figuring was then performed. Both the residual height and slope errors converged below the specified threshold values, which verified the feasibility and effectiveness of the proposed ideas.

Digital filtering of ghost signal in phase measuring deflectometry.

We introduce a method of geometric screen modification to remove ghost reflections commonly observed in deflectometry optical testing. The proposed method modifies the optical layout and illumination source area to bypass the generation of reflected rays from the undesired surface. The layout flexibility of deflectometry allows us to design specific system layouts that avoid the generation of interrupting secondary rays. The proposed method is supported by optical raytrace simulations, and experimental results are demonstrated with convex and concave lens case studies. Finally, the limitations of the digital masking method are discussed.

Cancer Target Gene Screening: a web application for breast cancer target gene screening using multi-omics data analysis.

Breast cancer comprises several molecular subtypes with distinct clinical features and treatment responses, and a substantial portion of each subtype remains incurable. A comprehensive analysis of multi-omics data and clinical profiles is required in order to better understand the biological complexity of this cancer type and to identify new prognostic and therapeutic markers. Thus, there arises a need for useful analytical tools to assist in the investigation and clinical management of the disease. We developed Cancer Target Gene Screening (CTGS), a web application that provides rapid and user-friendly analysis of multi-omics data sets from a large number of primary breast tumors. It allows the investigation of genomic and epigenomic aberrations, evaluation of transcriptomic profiles and performance of survival analyses and of bivariate correlations between layers of omics data. Notably, the genome-wide screening function of CTGS prioritizes candidate genes of clinical and biological significance among genes with copy number alteration, DNA methylation and dysregulated expression by the integrative analysis of different types of omics data in customized subgroups of breast cancer patients. These features may help in the identification of druggable cancer driver genes in a specific subtype or the clinical condition of human breast cancer. CTGS is available at http://ctgs.biohackers.net.

Genetic algorithm-powered non-sequential dwell time optimization for large optics fabrication.

Computer Controlled Optical Surfacing (CCOS) is widely applied for fabricating large aspheric optical surfaces. For large optics fabrication, various sizes of polishing tools are used sequentially. This raises the importance of efficient and globally optimized dwell time map of each tool. In this study, we propose a GEnetic Algorithm-powered Non-Sequential (GEANS) optimization technique to improve the feasibility of the conventional non-sequential optimization technique. GEANS consists of two interdependent parts: i) compose an influence matrix by imposing constraints on adjacent dwell points and ii) induce the desired dwell time map through the genetic algorithm. CCOS simulation results show that GEANS generates a preferable dwell time map that provides high figuring efficiency and structural similarity with the shape of target removal map, while improving computational efficiency more than 1000 times over the conventional non-sequential optimization method. The practicability of GEANS is demonstrated through error analyses. Random tool positioning error and tool influence function errors are imposed on dwell time maps. Compared to the conventional non-sequential optimization method, the power spectral density values of residual surface error from GEANS remain stable. GEANS also shows superior applicability when the maximum acceleration of a tool is applied.

Multi-tool optimization for computer controlled optical surfacing.

With the rapid development of precision technologies, the demand of high-precision optical surfaces has drastically increased. These optical surfaces are mainly fabricated with computer controlled optical surfacing (CCOS). In a CCOS process, a target surface removal profile is achieved by scheduling the dwell time for a set of machine tools. The optimized dwell time should be positive and smooth to ensure convergence to the target while considering CNC dynamics. The total run time of each machine tool is also expected to be balanced to improve the overall processing efficiency. In the past few decades, dwell time optimization for a single machine tool has been extensively developed. While the methods are applicable to multi-tool scenarios, they fail to consider the overall contributions of multiple tools simultaneously. In this paper, we conduct a systematic study on the strategies for multi-tool dwell time optimization and propose an innovative method for simultaneously scheduling dwell time for multiple tools for the first time. First, the influential factors to the positiveness and smoothness of dwell time solutions for a single machine tool are analyzed. The compensation strategies that minimize the residual while considering the CNC dynamics limit are then proposed. Afterwards, these strategies are extended to the proposed multi-tool optimization that further balances the run time of machine tools. Finally, the superiority of each strategy is carefully studied via simulation and experiment. The experiment is performed by bonnet polishing a 60 mm × 60 mm mirror with three tools of different diameters (i.e., 12 mm, 8 mm, and 5 mm). The figure error of the mirror is reduced from 45.42 nm to 11.18 nm root mean square in 13.28 min. Moreover, the measured polishing result well coincides with the estimation, which proves the effectiveness of the proposed method.

Modeling and characterization of OASIS inflatable primary antenna by dual modality metrology.

OASIS (Orbiting Astronomical Satellite for Investigating Stellar Systems) is a space-based observatory with a 14 m diameter inflatable primary antenna that will perform high spectral resolution observations at terahertz frequencies. The large inflatable aperture, non-traditional surface configuration, and the double layered membrane structure afford unique challenges to the modeling and testing of the primary antenna. A 1-meter prototype of the primary antenna (A1) was built to validate our technical approach. A laser radar coordinate measuring system was adopted to measure the shape of A1. In addition, deflectometry was performed to monitor the stability of A1 during the radar measurement. Test cases pertaining to specific operational conditions expected for the 14 m OASIS primary were explored. The measured data were then compared to the Fichter model and Finite-element Analyzer for Inflatable Membranes (FAIM).

Random adaptive tool path for zonal optics fabrication.

Deterministic optics fabrication using sub-aperture tools has been vital for manufacturing precision optical surfaces. The fabrication process requires the tool influence function and the tool path to calculate the dwell time that guides the tool to bring surface quality within tight design tolerances. Widely used spiral and raster paths may leave excess waviness from the tool path, and the unavoidable constant removal layer is added to obtain positive dwell time. This waviness can be removed by either using smaller tools sequentially or randomizing the tool path. However, the existing tool-path solutions can hardly adapt to different surface aperture shapes and localized surface errors. Process efficiency and accuracy are also not well considered in tool-path planning. We propose an innovative zonal Random Adaptive Path (RAP) to solve these problems in this study. Firstly, RAP can be flexibly adapted to different surface aperture shapes by introducing part boundary. Secondly, an average threshold strategy is used in the RAP planning to improve efficiency, enabling the surface errors to be selectively corrected. Finally, the threshold is performed in several passes within one processing cycle, each with its RAP, until the desired residual is achieved. The performance of the proposed RAP is studied by comparing it with the conventional tool paths. The results demonstrated that RAP takes the least processing time and achieves the best surface quality, which verifies the effectiveness of RAP in deterministic optics fabrication.

Non-planar illumination deflectometry for axicon metrology.

We introduce an on-axis deflectometry test configuration for axicon metrology. Axicons are challenging to measure due to their characteristically steep, convex geometry. However, if an axicon is coaxially aligned with a camera and a surrounding cylindrical illumination source, high-resolution surface measurements can be obtained via the principle of deflectometry. Emitted from the temporally modulated source, light deflects at the conical surface and into the entrance pupil of a camera, illuminating the full axicon aperture except the ø 0.5-mm rounded tip. Deflectometry measurements of a 100° and 140° axicon show holistic cone angle agreement within 0.035° against touch probe data and up to 7.93 root µm mean square difference from a best-fit cone. We discuss the non-planar illumination architecture, sensitivity, and experimental results of arbitrary apex angle axicons.

RISE: robust iterative surface extension for sub-nanometer X-ray mirror fabrication.

Precision optics have been widely required in many advanced technological applications. X-ray mirrors, as an example, serve as the key optical components at synchrotron radiation and free electron laser facilities. They are rectangular silicon or glass substrates where a rectangular Clear Aperture (CA) needs to be polished to sub-nanometer Root Mean Squared (RMS) to keep the imaging capability of the incoming X-ray wavefront at the diffraction limit. The convolutional polishing model requires a CA to be extended with extra data, from which the dwell time is calculated via deconvolution. However, since deconvolution is very sensitive to boundary errors and noise, the existing surface extension methods can hardly fulfill the sub-nanometer requirement. On one hand, the figure errors in a CA were improperly modeled during the extension, leading to continuity issues along the boundary. On the other hand, uncorrectable high-frequency errors and noise were also extended. In this study, we propose a novel Robust Iterative Surface Extension (RISE) method that resolves these problems with a data fitting strategy. RISE models the figure errors in a CA with orthogonal polynomials and ensures that only correctable errors are fit and extended. Combined with boundary conditions, an iterative refinement of dwell time is then proposed to compensate the errors brought by the extension and deconvolution, which drastically reduces the estimated figure error residuals in a CA while the increase of total dwell time is negligible. To our best knowledge, RISE is the first data fitting-based surface extension method and is the first to optimize dwell time based on iterative extension. An experimental verification of RISE is given by fabricating two elliptic cylinders (10 mm × 80 mm CAs) starting from a sphere with a radius of curvature around 173 m using ion beam figuring. The figure errors in the two CAs greatly improved from 204.96 nm RMS and 190.28 nm RMS to 0.62 nm RMS and 0.71 nm RMS, respectively, which proves that RISE is an effective method for sub-nanometer level X-ray mirror fabrication.

Universal dwell time optimization for deterministic optics fabrication.

Computer-Controlled Optical Surfacing (CCOS) has been greatly developed and widely used for precision optical fabrication in the past three decades. It relies on robust dwell time solutions to determine how long the polishing tools must dwell at certain points over the surfaces to achieve the expected forms. However, as dwell time calculations are modeled as ill-posed deconvolution, it is always non-trivial to reach a reliable solution that 1) is non-negative, since CCOS systems are not capable of adding materials, 2) minimizes the residual in the clear aperture 3) minimizes the total dwell time to guarantee the stability and efficiency of CCOS processes, 4) can be flexibly adapted to different tool paths, 5) the parameter tuning of the algorithm is simple, and 6) the computational cost is reasonable. In this study, we propose a novel Universal Dwell time Optimization (UDO) model that universally satisfies these criteria. First, the matrix-based discretization of the convolutional polishing model is employed so that dwell time can be flexibly calculated for arbitrary dwell points. Second, UDO simplifies the inverse deconvolution as a forward scalar optimization for the first time, which drastically increases the solution stability and the computational efficiency. Finally, the dwell time solution is improved by a robust iterative refinement and a total dwell time reduction scheme. The superiority and general applicability of the proposed algorithm are verified on the simulations of different CCOS processes. A real application of UDO in improving a synchrotron X-ray mirror using Ion Beam Figuring (IBF) is then demonstrated. The simulation indicates that the estimated residual in the 92.3 mm × 15.7 mm CA can be reduced from 6.32 nm Root Mean Square (RMS) to 0.20 nm RMS in 3.37 min. After one IBF process, the measured residual in the CA converges to 0.19 nm RMS, which coincides with the simulation.

Computational vector fiducial for deflectometry system alignment.

One of deflectometry's cardinal strengths is its ability to measure highly dynamically sloped optics without needing physical null references. Accurate surface measurements using deflectometry, however, require precise calibration processes. In this Letter, we introduce an alignment technique using a computational fiducial to align a deflectometry system without additional hardware equipment (i.e., algorithmic innovation). Using the ray tracing program, we build relationships between the plane of the screen and detector and algorithmically generate a fiducial pattern for the deflectometry configuration. Since the fiducial pattern is based on ideal system geometry, misalignment of the unit under test with its target position causes a discrepancy between the actual image on the camera detector and the ideal fiducial image. We leverage G and C vector polynomials to quantify misalignment and estimate the alignment status through a reverse optimization method. Simulation and experimental results demonstrate that the proposed algorithm can align the 195mm×80mm of a rectangular aperture freeform optic within 10 µm of peak-to-valley accuracy. The computational fiducial-based alignment algorithm is simple to apply and can be an essential procedure for conventional methods of deflectometry system alignment.

CDK12 drives breast tumor initiation and trastuzumab resistance via WNT and IRS1-ErbB-PI3K signaling.

Cyclin-dependent kinase 12 (CDK12) has emerged as an effective therapeutic target due to its ability to regulate DNA damage repair in human cancers, but little is known about the role of CDK12 in driving tumorigenesis. Here, we demonstrate that CDK12 promotes tumor initiation as a novel regulator of cancer stem cells (CSCs) and induces anti-HER2 therapy resistance in human breast cancer. High CDK12 expression caused by concurrent amplification of CDK12 and HER2 in breast cancer patients is associated with disease recurrence and poor survival. CDK12 induces self-renewal of breast CSCs and in vivo tumor-initiating ability, and also reduces susceptibility to trastuzumab. Furthermore, CDK12 kinase activity inhibition facilitates anticancer efficacy of trastuzumab in HER2+ tumors, and mice bearing trastuzumab-resistant HER2+ tumor show sensitivity to an inhibitor of CDK12. Mechanistically, the catalytic activity of CDK12 is required for the expression of genes involved in the activation of ErbB-PI3K-AKT or WNT-signaling cascades. These results suggest that CDK12 is a major oncogenic driver and an actionable target for HER2+ breast cancer to replace or augment current anti-HER2 therapies.

Dual-tool multiplexing model of parallel computer controlled optical surfacing.

Fabrication of large optics is a time-consuming process and requires a vast investment in manpower and financial resources. Increasing the material removal rate of polishing tools and minimizing dwell time are two common ways of reducing the processing time. Indeed, the polishing efficiency can be further improved if multiple tools are used at the same time. In this Letter, we propose a dual-tool deterministic polishing model, which multiplexes the dwell time and optimizes the run parameters of two polishing tools simultaneously. The run velocities of the two tools are coordinated by boundary conditions with a velocity adjustment algorithm, and the corresponding polishing paths are studied. We demonstrate this model with a simulation of polishing one segment of the Giant Magellan Telescope, where, with the proposed dual-tool multiplexing, the processing time of an ø8.4 m mirror has been reduced by 50.54% compared with that using two tools in a sequential schedule.

Interference of two diverging beams reflected from a plane parallel plate: stationary fringes with characteristic stable period.

We investigated interference fringes due to superposition of diverging light waves reflected from the two sides of a plane parallel plate. A non-localized fringe pattern of high contrast was obtained as a function of incident angle when we used a coherent diverging beam. We found that the fringe density increased to a certain angle and then decreased thereafter, against the common belief that the fringe density increases monotonically with the angle of incidence. Because the fringe density is maximum at this angle and does not change rapidly in the vicinity, we could employ Fourier analysis to estimate interferometric parameters, such as thickness, refractive index, and wavelength, that determine the characteristic stationary fringe density.

Development of a position-velocity-time-modulated two-dimensional ion beam figuring system for synchrotron x-ray mirror fabrication.

With the rapid evolution of synchrotron x-ray sources, the demand for high-quality precision x-ray mirrors has greatly increased. Single nanometer shape accuracy is required to keep imaging capabilities at the diffraction limit. Ion beam figuring (IBF) has been used frequently for ultra-precision finishing of mirrors, but achieving the ultimate accuracy depends on three important points: careful alignment, accurate dwell time calculation and implementation, and accurate optical metrology. The Optical Metrology Group at National Synchrotron Light Source II has designed and built a position-velocity-time-modulated two-dimensional IBF system (PVT-IBF) with three novel characteristics: (1) a beam footprint on the mirror was used as a reference to align the coordinate systems between the metrology and the IBF hardware; (2) the robust iterative Fourier transform-based dwell time algorithm proposed by our group was applied to obtain an accurate dwell time map; and (3) the dwell time was then transformed to velocities and implemented with the PVT motion scheme. In this study, the technical aspects of the PVT-IBF systems are described in detail, followed by an experimental demonstration of the figuring results. In our first experiment, the 2D RMS in a $ 50\;{\rm mm} \times 5\;{\rm mm} $50mm×5mm clear aperture was reduced from 3.4 to 1.1 nm after one IBF run. In our second experiment, due to a 5 mm pinhole installed in front of the source, the 2D RMS in a $ 50\;{\rm mm} \times 5\;{\rm mm} $50mm×5mm clear aperture was reduced from 39.1 to 1.9 nm after three IBF runs, demonstrating that our PVT-IBF solution is an effective and deterministic figuring process.

Adaptive Shack-Hartmann wavefront sensor accommodating large wavefront variations.

Shack-Hartmann wavefront sensors (SHWFSs) usually have fixed subaperture areas on the detector, in order to fix the minimum and maximum amounts of wavefront departure, or the dynamic range of measurement. We introduce an active approach, named Adaptive Shack Hartmann Wavefront Sensor (A-SHWFS). A-SHWFS is used to reconfigure detection subaperture areas by either blocking or unblocking desired lenslets by using an electronically modulated mask. This mask either increases or decreases the measurable aberration magnitude by placing a liquid crystal display (LCD) panel in front of the lenslet array. Depending on which control signal that is sent to the LCD, the variable, application-dependent blocking pattern (horizontal, vertical, diagonal, uneven) makes this an adaptive and efficient sensor with a variable dynamic range of measurement. This scheme is also useful for regional blocking, which occurs when the wavefront is severely aberrated in a limited region.

Model-free deflectometry for freeform optics measurement using an iterative reconstruction technique.

We present a novel model-free iterative data-processing approach that improves surface reconstruction accuracy for deflectometry tests of unknown surfaces. This new processing method iteratively reconstructs the surface, leading to reduced error in the final reconstructed surface. The method was implemented in a deflectometry system, and a freeform surface was tested and compared to interferometric test results. The reconstructed departure from interferometric results was reduced from 15.80 µm RMS with model-based deflectometry down to 5.20 µm RMS with the iterative technique reported here.

Simultaneous multi-segmented mirror orientation test system using a digital aperture based on sheared Fourier analysis.

This paper presents a simultaneous multi-segmented mirror orientation test system (SMOTS) using localized sheared images. A CMOS camera captures images of reflected 2D sinusoidal patterns from the test mirrors as their orientation changes. Surface orientation is measured to within 0.8 µrad (0.16 arcseconds) for a flat mirror. In addition, we measure the variation of seven mirror segments simultaneously. Furthermore, SMOTS is applied to measure the orientation of two concave mirrors with an accuracy of 2.7 µrad (0.56 arcseconds). The measurement time for seven segments is 0.07 s. This technique can monitor the mirror segment orientation in an open/closed-loop for various optical setups.

UTX inhibits EMT-induced breast CSC properties by epigenetic repression of EMT genes in cooperation with LSD1 and HDAC1.

The histone H3K27 demethylase, UTX, is a known component of the H3K4 methyltransferase MLL complex, but its functional association with H3K4 methylation in human cancers remains largely unknown. Here we demonstrate that UTX loss induces epithelial-mesenchymal transition (EMT)-mediated breast cancer stem cell (CSC) properties by increasing the expression of the SNAIL, ZEB1 and ZEB2 EMT transcription factors (EMT-TFs) and of the transcriptional repressor CDH1. UTX facilitates the epigenetic silencing of EMT-TFs by inducing competition between MLL4 and the H3K4 demethylase LSD1. EMT-TF promoters are occupied by c-Myc and MLL4, and UTX recognizes these proteins, interrupting their transcriptional activation function. UTX decreases H3K4me2 and H3 acetylation at these promoters by forming a transcriptional repressive complex with LSD1, HDAC1 and DNMT1. Taken together, our findings indicate that UTX is a prominent tumour suppressor that functions as a negative regulator of EMT-induced CSC-like properties by epigenetically repressing EMT-TFs.