A segmentation clock patterns cellular differentiation in a bacterial biofilm.

Contrary to multicellular organisms that display segmentation during development, communities of unicellular organisms are believed to be devoid of such sophisticated patterning. Unexpectedly, we find that the gene expression underlying the nitrogen stress response of a developing Bacillus subtilis biofilm becomes organized into a ring-like pattern. Mathematical modeling and genetic probing of the underlying circuit indicate that this patterning is generated by a clock and wavefront mechanism, similar to that driving vertebrate somitogenesis. We experimentally validated this hypothesis by showing that predicted nutrient conditions can even lead to multiple concentric rings, resembling segments. We additionally confirmed that this patterning mechanism is driven by cell-autonomous oscillations. Importantly, we show that the clock and wavefront process also spatially patterns sporulation within the biofilm. Together, these findings reveal a biofilm segmentation clock that organizes cellular differentiation in space and time, thereby challenging the paradigm that such patterning mechanisms are exclusive to plant and animal development.

Temporal control of RNAi reveals both robust and labile feedback loops in the segmentation clock of the red flour beetle.

Animals from all major clades have evolved a segmented trunk, reflected in the human spine or the insect segments. These units emerge during embryogenesis from a posterior segment addition zone (SAZ), where repetitive gene activity is regulated by a mechanism described by the clock and wavefront/speed gradient model. In the red flour beetle Tribolium castaneum, RNA interference (RNAi) has been used to continuously knock down the function of primary pair-rule genes (pPRGs), caudal or Wnt pathway components, which has led to the complete breakdown of segmentation. However, it has remained untested, if this breakdown was reversible by bringing the missing gene function back to the system. To fill this gap, we established a transgenic system in T. castaneum, which allows blocking an ongoing RNAi effect with temporal control by expressing a viral inhibitor of RNAi via heat shock. We show that the T. castaneum segmentation machinery was able to reestablish after RNAi targeting the pPRGs Tc-eve, Tc-odd, and Tc-runt was blocked. However, we observed no rescue after blocking RNAi targeting Wnt pathway components. We conclude that the insect segmentation system contains both robust feedback loops that can reestablish and labile feedback loops that break down irreversibly. This combination may reconcile conflicting needs of the system: Labile systems controlling initiation and maintenance of the SAZ ensure that only one SAZ is formed. Robust feedback loops confer developmental robustness toward external disturbances.

A distinct transcriptome characterizes neural crest-derived cells at the migratory wavefront during enteric nervous system development.

Enteric nervous system development relies on intestinal colonization by enteric neural crest-derived cells (ENCDCs). This is driven by a population of highly migratory and proliferative ENCDCs at the wavefront, but the molecular characteristics of these cells are unknown. ENCDCs from the wavefront and the trailing region were isolated and subjected to RNA-seq. Wavefront-ENCDCs were transcriptionally distinct from trailing ENCDCs, and temporal modelling confirmed their relative immaturity. This population of ENCDCs exhibited altered expression of ECM and cytoskeletal genes, consistent with a migratory phenotype. Unlike trailing ENCDCs, the wavefront lacked expression of genes related to neuronal or glial maturation. As wavefront ENCDC genes were associated with migration and developmental immaturity, the genes that remain expressed in later progenitor populations may be particularly pertinent to understanding the maintenance of ENCDC progenitor characteristics. Dusp6 expression was specifically upregulated at the wavefront. Inhibiting DUSP6 activity prevented wavefront colonization of the hindgut, and inhibited the migratory ability of post-colonized ENCDCs from midgut and postnatal neurospheres. These effects were reversed by simultaneous inhibition of ERK signaling, indicating that DUSP6-mediated ERK inhibition is required for ENCDC migration in mouse and chick.

Fast wavefront shaping for two-photon brain imaging with multipatch correction.

Nonlinear fluorescence microscopy promotes in-vivo optical imaging of cellular structure at diffraction-limited resolution deep inside scattering biological tissues. Active compensation of tissue-induced aberrations and light scattering through adaptive wavefront correction further extends the accessible depth by restoring high resolution at large depth. However, those corrections are only valid over a very limited field of view within the angular memory effect. To overcome this limitation, we introduce an acousto-optic light modulation technique for fluorescence imaging with simultaneous wavefront correction at pixel scan speed. Biaxial wavefront corrections are first learned by adaptive optimization at multiple locations in the image field. During image acquisition, the learned corrections are then switched on the fly according to the position of the excitation focus during the raster scan. The proposed microscope is applied to in vivo transcranial neuron imaging and demonstrates multi-patch correction of thinned skull-induced aberrations and scattering at 40-kHz data acquisition speed.

Coherent enhancement of optical remission in diffusive media.

Remitted waves are used for sensing and imaging in diverse diffusive media from the Earth's crust to the human brain. Separating the source and detector increases the penetration depth of light, but the signal strength decreases rapidly, leading to a poor signal-to-noise ratio. Here, we show, experimentally and numerically, that wavefront shaping a laser beam incident on a diffusive sample enables an enhancement of remission by an order of magnitude at depths of up to 10 transport mean free paths. We develop a theoretical model which predicts the maximal remission enhancement. Our analysis reveals a significant improvement in the sensitivity of remitted waves to local changes of absorption deep inside diffusive media. This work illustrates the potential of coherent wavefront control for noninvasive diffuse wave imaging applications, such as diffuse optical tomography and functional near-infrared spectroscopy.

Polariton Microfluidics for Nonreciprocal Dragging and Reconfigurable Shaping of Polaritons.

Dielectric environment engineering is an efficient and general approach to manipulating polaritons. Liquids serving as the surrounding media of polaritons have been used to shift polariton dispersions and tailor polariton wavefronts. However, those liquid-based methods have so far been limited to their static states, not fully unleashing the promise offered by the mobility of liquids. Here, we propose a microfluidic strategy for polariton manipulation by merging polaritonics with microfluidics. The diffusion of fluids causes gradient refractive indices over microchannels, which breaks the symmetry of polariton dispersions and realizes the microfluidic analogue to nonreciprocal polariton dragging. Based on polariton microfluidics, we also designed a set of on-chip polaritonic elements to actively shape polaritons, including planar lenses, off-axis lenses, Janus lenses, bends, and splitters. Our strategy expands the toolkit for the manipulation of polaritons at the subwavelength scale and possesses potential in the fields of polariton biochemistry and molecular sensing.

Dynamic and Polarization-Independent Wavefront Control Based on Hybrid Topological Metasurfaces.

Exceptional points (EPs), known as non-Hermitian singularities, have been observed and investigated in parity-time symmetric metasurfaces. However, the chirality and tunability in non-Hermitian metasurfaces still need to be explored. Here, we propose a dynamic topological metasurface with the meta-atom consisting of two orthogonally oriented nanorods, which are placed on the phase change material Ge2Sb2Te5 (GST) and SiO2 dielectric layer, respectively. When GST is converted from the amorphous state (a-GST) to the crystalline state (c-GST), an EP can be dynamically switched from the "ON" state to the "OFF" state in a parameter space. Moreover, based on the topologically protected phase and amplitude modulations of the cross-polarization component, the phase-only hologram and amplitude-only hologram are engineered in the a-GST case and concealed in the c-GST case. Finally, we explore the 2D-chiral symmetry of meta-atoms and further propose two spin-selective meta-deflectors and a hybrid meta-deflector operating with arbitrary polarizations. The GST-based hybrid metasurface offers richer possibilities to realize various wavefront controls.

Temperature-Dependent Excitonic Light Manipulation with Atomically Thin Optical Elements.

Monolayer 2D semiconductors, such as WS2, exhibit uniquely strong light-matter interactions due to exciton resonances that enable atomically thin optical elements. Similar to geometry-dependent plasmon and Mie resonances, these intrinsic material resonances offer coherent and tunable light scattering. Thus far, the impact of the excitons' temporal dynamics on the performance of such excitonic metasurfaces remains unexplored. Here, we show how the excitonic decay rates dictate the focusing efficiency of an atomically thin lens carved directly out of exfoliated monolayer WS2. By isolating the coherent exciton radiation from the incoherent background in the focus of the lens, we obtain a direct measure of the role of exciton radiation in wavefront shaping. Furthermore, we investigate the influence of exciton-phonon scattering by characterizing the focusing efficiency as a function of temperature, demonstrating an increased optical efficiency at cryogenic temperatures. Our results provide valuable insights into the role of excitonic light scattering in 2D nanophotonic devices.

Wavefront analysis and phase correctors design using SHADOW.

Knife-edge imaging is a successful method for determining the wavefront distortion of focusing optics such as Kirkpatrick-Baez mirrors or compound refractive lenses. In this study, the wavefront error of an imperfect elliptical mirror is predicted by developing a knife-edge program using the SHADOW/OASYS platform. It is shown that the focusing optics can be aligned perfectly by minimizing the parabolic and cubic coefficients of the wavefront error. The residual wavefront error provides precise information about the figure/height errors of the focusing optics suggesting it as an accurate method for in situ optical metrology. A Python program is developed to design a customized wavefront refractive corrector to minimize the residual wavefront error. Uniform beam at and out of focus and higher peak intensity are achieved by the wavefront correction in comparison with ideal focusing. The developed code provides a quick way for wavefront error analysis and corrector design for non-ideal optics especially for the new-generation diffraction-limited sources, and saves considerable experimental time and effort.

The effect of transport apertures on relay-imaged, sharp-edged laser profiles in photoinjectors and the impact on electron beam properties.

In a photoinjector electron source, the initial transverse electron bunch properties are determined by the spatial properties of the laser beam on the photocathode. Spatial shaping of the laser is commonly achieved by relay imaging an illuminated circular mask onto the photocathode. However, the Gibbs phenomenon shows that recreating the sharp edge and discontinuity of the cut profile at the mask on the cathode is not possible with an optical relay of finite aperture. Furthermore, the practical injection of the laser into the photoinjector results in the beam passing through small or asymmetrically positioned apertures. This work uses wavefront propagation to show how the transport apertures cause ripple structures to appear in the transverse laser profile even when effectively the full laser power is transmitted. The impact of these structures on the propagated electron bunch has also been studied with electron bunches of high and low charge density. With high charge density, the ripples in the initial charge distribution rapidly wash-out through space charge effects. However, for bunches with low charge density, the ripples can persist through the bunch transport. Although statistical properties of the electron bunch in the cases studied are not greatly affected, there is the potential for the distorted electron bunch to negatively impact machine performance. Therefore, these effects should be considered in the design phase of accelerators using photoinjectors.

Soft X-ray wavefront sensing at an ellipsoidal mirror shell.

A reliable `in situ' method for wavefront sensing in the soft X-ray domain is reported, developed for the characterization of rotationally symmetric optical elements, like an ellipsoidal mirror shell. In a laboratory setup, the mirror sample is irradiated by an electron-excited (4.4 keV), micrometre-sized (∼2 µm) fluorescence source (carbon Kα, 277 eV). Substantially, the three-dimensional intensity distribution I(r) is recorded by a CCD camera (2048 × 512 pixels of 13.5 µm) at two positions along the optical axis, symmetrically displaced by ±21-25% from the focus. The transport-of-intensity equation is interpreted in a geometrical sense from plane to plane and implemented as a ray tracing code, to retrieve the phase Φ(r) from the radial intensity gradient on a sub-pixel scale. For reasons of statistical reliability, five intra-/extra-focal CCD image pairs are evaluated and averaged to an annular two-dimensional map of the wavefront error {\cal W}. In units of the test wavelength (C Kα), an r.m.s. value \sigma_{\cal{W}} = ±10.9λ0 and a peak-to-valley amplitude of ±31.3λ0 are obtained. By means of the wavefront, the focus is first reconstructed with a result for its diameter of 38.4 µm, close to the direct experimental observation of 39.4 µm (FWHM). Secondly, figure and slope errors of the ellipsoid are characterized with an average of ±1.14 µm and ±8.8 arcsec (r.m.s.), respectively, the latter in reasonable agreement with the measured focal intensity distribution. The findings enable, amongst others, the precise alignment of axisymmetric X-ray mirrors or the design of a wavefront corrector for high-resolution X-ray science.

Evaluation of the X-ray/EUV Nanolithography Facility at AS through wavefront propagation simulations.

Synchrotron light sources can provide the required spatial coherence, stability and control to support the development of advanced lithography at the extreme ultraviolet and soft X-ray wavelengths that are relevant to current and future fabricating technologies. Here an evaluation of the optical performance of the soft X-ray (SXR) beamline of the Australian Synchrotron (AS) and its suitability for developing interference lithography using radiation in the 91.8 eV (13.5 nm) to 300 eV (4.13 nm) range are presented. A comprehensive physical optics model of the APPLE-II undulator source and SXR beamline was constructed to simulate the properties of the illumination at the proposed location of a photomask, as a function of photon energy, collimation and monochromator parameters. The model is validated using a combination of experimental measurements of the photon intensity distribution of the undulator harmonics. It is shown that the undulator harmonics intensity ratio can be accurately measured using an imaging detector and controlled using beamline optics. Finally, the photomask geometric constraints and achievable performance for the limiting case of fully spatially coherent illumination are evaluated.

Accuracy of intraoperative aberrometry versus modern preoperative methods in post-myopic laser vision correction eyes undergoing cataract surgery with capsular tension ring placement.

PURPOSE: To assess the accuracy of intraoperative wavefront aberrometry (IWA) versus modern intraocular lens formulas in post-myopic laser vision correction (LVC) patients undergoing cataract surgery with capsular tension ring placement. METHODS: This is a retrospective chart review conducted at an academic outpatient center. All post-myopic LVC eyes undergoing cataract surgery with IWA from a single surgeon from 05/2017 to 12/2019 were included. All patients received a capsular tension ring (CTR). Mean numerical error (MNE), median numerical error (MedNE), and percentages of prediction error within 0.50D, 0.75D, and 1.00D were calculated for the above formulas. RESULTS: Twenty-seven post-myopic LVC eyes from 18 patients were included. In post-myopic LVC, MNE with Optiwave Refractive Analysis (ORA), Barrett True K (BTK), Haigis, Haigis-L, Shammas, SRK/T, Hill-RBF v3.0, and W-K AL-adjusted Holladay 1 were + 0.224, - 0.094, + 0.193, - 0.231, - 0.372, + 1.013, + 0.860, and + 0.630 (F = 8.49, p < 0.001). MedNE were + 0.125, - 0.145, + 0.175, + 0.333, + 0.333, + 1.100, + 0.880, and + 0.765 (F = 7.89, p < 0.001), respectively. BTK provided improved accuracy in both MNE (p < 0.001) and MedNE (p = .033) when compared to ORA in pairwise analysis. If the ORA vs. BTK-suggested IOL power were routinely selected, 30% and 15% of eyes would have projected hyperopic outcomes, respectively (p = 0.09). CONCLUSIONS: Our study suggests that in post-myopic LVC eyes undergoing cataract surgery with CTRs, BTK performed more accurately than ORA with regard to accuracy and yielded a lower percentage of eyes with hyperopic outcomes. Haigis, Haigis-L, and Shammas yielded similar results to ORA with regard to accuracy and percentage of eyes with hyperopic outcomes. On average, Shammas and Haigis-L suggested IOLs that would yield outcomes more myopic than expected when compared to BTK.

Allowable movement of wavefront-guided contact lens corrections in normal and keratoconic eyes.

PURPOSE: The goal was to use SyntEyes modelling to estimate the allowable alignment error of wavefront-guided rigid contact lens corrections for a range of normal and keratoconic eye aberration structures to keep objectively measured visual image quality at or above average levels of well-corrected normal eyes. Secondary purposes included determining the required radial order of correction, whether increased radial order of the corrections further constrained the allowable alignment error and how alignment constraints vary with keratoconus severity. METHODS: Building on previous work, 20 normal SyntEyes and 20 keratoconic SyntEyes were fitted with optimised wavefront-guided rigid contact lens corrections targeting between three and eight radial orders that drove visual image quality, as measured objectively by the visual Strehl ratio, to near 1 (best possible) over a 5-mm pupil for the aligned position. The resulting wavefront-guided contact lens was then allowed to translate up to ±1 mm in the x- and y-directions and rotate up ±15°. RESULTS: Allowable alignment error changed as a function of the magnitude of aberration structure to be corrected, which depends on keratoconus severity. This alignment error varied only slightly with the radial order of correction above the fourth radial order. To return the keratoconic SyntEyes to average levels of visual image quality depended on maximum anterior corneal curvature (Kmax). Acceptable tolerances for misalignment that returned keratoconic visual image quality to average normal levels varied between 0.29 and 0.63 mm for translation and approximately ±6.5° for rotation, depending on the magnitude of the aberration structure being corrected. CONCLUSIONS: Allowable alignment errors vary as a function of the aberration structure being corrected, the desired goal for visual image quality and as a function of keratoconus severity.

Large-Dynamic-Range Ocular Aberration Measurement Based on Deep Learning with a Shack-Hartmann Wavefront Sensor.

The Shack-Hartmann wavefront sensor (SHWFS) is widely utilized for ocular aberration measurement. However, large ocular aberrations caused by individual differences can easily make the spot move out of the range of the corresponding sub-aperture in SHWFS, rendering the traditional centroiding method ineffective. This study applied a novel convolutional neural network (CNN) model to wavefront sensing for large dynamic ocular aberration measurement. The simulation results demonstrate that, compared to the modal method, the dynamic range of our method for main low-order aberrations in ocular system is increased by 1.86 to 43.88 times in variety. Meanwhile, the proposed method also has the best measurement accuracy, and the statistical root mean square (RMS) of the residual wavefronts is 0.0082 ± 0.0185 λ (mean ± standard deviation). The proposed method generally has a higher accuracy while having a similar or even better dynamic range as compared to traditional large-dynamic schemes. On the other hand, compared with recently developed deep learning methods, the proposed method has a much larger dynamic range and better measurement accuracy.

Wavefront Changes during a Sustained Reading Task in Presbyopic Eyes.

The objective of this study was to assess the effect of sustained reading on the temporal changes in the wavefront error in the presbyopic eye. The wavefront aberration of the eyes was measured using an IRX3 Shack-Hartmann aberrometer before and after (immediately, 5 min, and 10 min after) a reading task. Temporal changes in C20, C40, and C3-1 coefficient values of the eyes were plotted, showing a predominant number of V-shaped patterns (for C40 and C3-1) and inverse V-shaped patterns (for C20) among the study group, and the percentages (between 27 and 73%) were reported. The median of the total RMS of aberrations and the RMS of HOA (higher-order aberrations), which included comatic (3rd order) and spherical-like aberrations (4th and 6th order), increased immediately after finishing the near-vision reading task and then decreased. The median of RMS of comatic aberrations had a similar pattern of variations, while the median of RMS of spherical-like aberrations displayed an opposite pattern. Simulating the aberration changes due to lens decentration caused by relaxed zonules during 4 D accommodation in an eye model demonstrated that the expected range of changes for the vertical coma and spherical aberrations are in the order of 0.001 and 0.01 µm, respectively, which could justify why the observed changes were not statistically significant. The observed dynamic changes in HOA might be linked to the biomechanical characteristics and alterations in the displacement of the crystalline lens following prolonged near-vision tasks in presbyopic people. Although some predominant patterns under some conditions were shown, they exhibit considerable inter-subject and inter-ocular variability. This might be due to slight misalignments while fixating on the internal extended object in the aberrometer.

Exploring Wavefront Detection in Imaging Systems with Rectangular Apertures Using Phase Diversity.

The attainment of a substantial aperture in the rotating synthetic aperture imaging system involves the rotation of a slender rectangular primary mirror. This constitutes a pivotal avenue of exploration in space telescope research. Due to the considerable aspect ratio of the primary mirror, environmental disturbances can significantly impact its surface shape. Active optical technology can rectify surface shape irregularities through the detection of wavefront information. The Phase Diversity (PD) method utilizes images captured by the imaging system to compute wavefront information. In this study, the PD method is applied to rotating synthetic and other rectangular aperture imaging systems, employing Legendre polynomials to model the wavefront. The study delved into the ramifications stemming from the aperture aspect ratio and aberration size.

Statistical optimal parameters obtained by using clinical human ocular aberrations for high-precision aberration measurement.

PURPOSE: Compared to Shack-Hartmann wavefront sensor (SHWS), the parameters of virtual SHWS (vSHWS) can be easily adjusted to obtain the optimal performance of aberration measurement. Its current optimal parameters are obtained with only a set of statistical aberrations and not statistically significant. Whether the above parameters are consistent with the statistical results of the optimal parameters corresponding to each set of aberrations, and which performance is better if not? The purpose of this study was to answer these questions. METHODS: The optimal parameters to reconstruct 624 sets of clinical ocular aberrations in the highest accuracy, including the numbers of sub-apertures (NSAs) and the expansion ratios (ERs) of electric field zero-padding, were determined sequentially in this work. By using wavefront-reconstruction accuracy as an evaluation index, the statistical optimal parameter configuration was selected from some possible configurations determined by the optimal NSAs and ERs. RESULTS: The statistical optimal parameters are consistent for normal and abnormal eyes. They are different from the optimal parameters obtained with a set of statistical aberrations from the same 624 sets of aberrations, and the performance using the former is better than that using the latter. The performance using a fixed set of statistical optimal parameters is even close to that using the respective optimal parameters corresponding to each set of aberrations. CONCLUSION: The vSHWS configured with a fixed set of statistical optimal parameters can be used for high-precision aberration measurement of both normal and abnormal eyes. The statistical optimal parameters are more suitable for vSHWS than the parameters obtained with a set of statistical aberrations. These conclusions are significant for the designs of vSHWS and also SHWS.

The visual impact of higher-order aberrations in patients with pediatric blepharokeratoconjunctivitis.

PURPOSE: To analyze higher-order aberrations (HOAs) and their visual impact in a pediatric blepharokeratoconjunctivitis (PBKC) cohort compared with healthy controls. METHODS: Prospective case-control study of pediatric patients (≤ 16 years old). Subjects underwent wavefront aberrometry analysis to compare HOAs and their impact on visual quality. RESULTS: A total of 150 eyes from 76 patients were included in the analysis. The PBKC group consisted of 50 eyes and the control group of 100 healthy eyes. Mean age was 10.39 ± 3.81 years for the PBKC group and 10.80 ± 3.61 years for the controls. Mean corrected-distance visual acuity (CDVA) was 0.24 ± 0.21 logMAR in the PBKC group and 0.07 ± 0.1 in the controls (P < 0.001). Mean astigmatism was 1.6 ± 1.98D in the PBKC group vs. 0.67 ± 0.76D in the control group (P = 0.01). Mean RMS of HOAs was 1.05 ± 1.7mm in the PBKC group and 0.41 ± 0.18mm in the controls (P < 0.001). The mean modulation transfer function (MTF) in the PBKC group was significantly lower (16.37 ± 16.32) than controls (30.3 ± 23.57) (P < 0.001). Corneal leukomas, stromal vascularization, peripheral nummular subepithelial scars, and pannus formation are associated with increased HOAs. CONCLUSIONS: There was a significant increase in total HOAs of eyes with PBKC compared to healthy controls. Corneal opacity, vascularization, and scarring are associated with increased HOAs. The PBKC eye aberration profile: coma, secondary astigmatism, quadrafoil, and pentafoil, were associated with decreased CDVA and visual quality (PSF and MTF).

Higher order aberrations in keratoconus .

INTRODUCTION: Keratoconus is a progressive disorder of the cornea that causes thinning (Sedaghat et al. in Sci Rep 11(1):11971, 2021), ectasia, and irregular astigmatism, resulting in poor visual acuity that cannot be corrected with standard sphero-cylindrical spectacle lenses. One feature distinguishing keratoconic corneas is ocular aberrations, manifesting up to five or six times the amount of higher-order aberrations than a normal, healthy eye. These aberrations can cause visual disturbances even at the very early stages of the disease. METHODS: In the past, a diagnosis was derived from clinical symptoms, but technological advances have revealed multiple pre-clinical features, allowing for the differentiation between keratoconic and normal eyes at a much earlier stage. These include anterior and posterior corneal surface elevations, the corneal pachymetry profile, corneal epithelial patterns, wavefront aberration metrics, and corneal biomechanics (Sedaghat et al. in Sci Rep 11(1):11971, 2021).This review discusses the aberrations associated with keratoconus, how to measure them, and treatment methods to minimize their negative influence. CONCLUSIONS: Early diagnosis can lead to early treatment and may allow for arresting progression, thereby improving the long-term prognosis. With the acceleration of refractive surgery, it is important to identify patients with keratoconus, as they are usually contraindicated for refractive surgery.