Objective Of Phase Research Articles

Transport-of-intensity differential phase contrast imaging: defying weak object approximation and matched-illumination condition

Quantitative phase imaging (QPI) has emerged as a promising label-free imaging technique with growing importance in biomedical research, optical metrology, materials science, and other fields. Partially coherent illumination provides resolution twice that of the coherent diffraction limit, along with improved robustness and signal-to-noise ratio, making it an increasingly significant area of study in QPI. Partially coherent QPI, represented by differential phase contrast (DPC), linearizes the phase-to-intensity transfer process under the weak object approximation (WOA). However, the nonlinear errors caused by WOA in DPC can lead to phase underestimation. Additionally, DPC requires strict matching of the illumination numerical aperture (NA) to ensure the complete transmission of low-frequency information. This necessitates precise alignment of the optical system and limits the flexible use of objective and illumination. In this study, the applicability of the WOA under different coherence parameters is explored, and a method to defy WOA by reducing the illumination NA is proposed. The proposed method uses the transport-of-intensity equation through an additional defocused intensity image to recover the lost low-frequency information due to illumination mismatch, without requiring any iterative procedure. This method overcomes the limitations of DPC being unable to recover large phase objects and does not require the strict illumination matching conditions. The accurate quantitative morphological characterization of customized artifact and microlens arrays that do not satisfy WOA under non-matched-illumination conditions demonstrated the precise quantitative capability of the proposed method and its excellent performance in the field of measurement. Meanwhile, the phase retrieval of tongue slices and oral epithelial cells demonstrated its application potential in the biomedical field. The ability to accurately recover phase under a concise and implementable optical setup makes it a promising solution for widespread application in various label-free imaging domains.

A phase 2, randomized, double-blind, placebo-controlled study to assess the tolerability and pharmacodynamic effects of CRD-740, a PDE9 inhibitor, in participants with chronic heart failure

Abstract Background Natriuretic peptide (NP) receptor activation has a beneficial role in the treatment of heart failure (HF). The enzyme phosphodiesterase (PDE) 9 breaks down cGMP, the second messenger stimulated by natriuretic peptides. PDE9 inhibition may increase intracellular cGMP signaling and, potentially, have beneficial effects in HF. We examined the effects of the selective PDE9 inhibitor CRD-740 on the NP signaling pathway in HF. Purpose The objectives of this early phase 2 trial were to assess the tolerability of CRD-740 and its effects on plasma and urinary cGMP (markers of potential clinical effiacy) in patients with HFrEF, including those receving background treatment with sacubitril/valsartan. Methods Key inclusion criteria were patients with a history of HFrEF of > 6 mos, NYHA II or III, EF < 40% and NT-proBNP ≥600 pg/ml at screening (≥1000 pg/mL if in atrial fibrillation), on treatment with stable guideline-directed therapy for a minimum of 4 weeks. Patients were randomized 2:1 double-blind to CRD-740 (10mg twice daily for 2 weeks, then 25mg twice daily for 10 weeks) or placebo. Tolerability and safety were assessed. The primary pharmacodynamic endpoint was the between-group change from baseline in plasma cGMP at Week 4. Exploratory endpoints included urine cGMP levels, KCCQ and biomarkers. Results 60 patients were randomized to CRD-740 (n=40) or placebo (n=20). Baseline characteristics included age 67+13 yrs, 85% men, EF 28+7%, BMI 30+10, with 73% of patients taking sacubitril/valsartan, and 47% on SGLT2 inhibitors. The primary endpoint was positive, with placebo-corrected change in plasma cGMP significantly increased at all time points at week 4 in those treated with CRD-740 (see Table). cGMP levels were also increased on day 1 (Table) and week 2. A significant increase in urinary cGMP also was observed with CRD-740 vs placebo (Figure) in 6-hour collections at day 1 (p=0.012) and week 2 (p=0.014). In this small study, not powered for exploratory endpoints, directionally favorable placebo-corrected, baseline-adjusted changes also were seen in the KCCQ Clinical (+7.1 [95%CI, -1.6, +15.7], p=0.11) and Overall Summary Scores (+7.4 [-0.8, +15.5], p=0.075) for patients on CRD-740. No significant changes in NT-proBNP were observed between treatment groups. Adverse events (AEs) were observed in 62% and 50% of CRD-740 and placebo-treated patients, with discontinuation in 5% and 10% respectively, with no between-group difference in change in BP. There were no hypotension AEs, and no treatment-related serious adverse events. Conclusions In this early phase 2 trial, PDE9 inhibition with CRD-740 was well-tolerated and resulted in substantial elevations of plasma and urinary cGMP on top of standard care, including sacubitril/valsartan. These results support the potential of PDE9 inhibition to further activate the beneficial effects of the NP receptor-cGMP pathway incrementally to that achieved by existing HF treatments.Changes in Plasma cGMP over Time (ng/mL)Changes in Urinary cGMP over Time

Criteria for objects suitable for reconstruction from holograms and diffraction patterns

In this study, quantitative criteria for reconstruction of objects from their hologram and diffraction patterns, and in particular for the phase objects in digital holography, are derived. The criteria that allow distinguishing the hologram and diffraction pattern are outlined. Gabor derived his criterion for objects suitable for holography based on the condition that the background in the reconstructed object’s distribution should be nearly flat so that its intensity contrast does not exceed 0.05. According to Gabor, an opaque object is suitable for holographic reconstruction if it occupies no more than 1% of the imaged area, and a phase-shifting object cannot be reconstructed in principle. We revisit these criteria and show that both amplitude-only and phase-only objects can be reconstructed when the object occupies less than 1% of the total illuminated area. In addition, a simplified derivation of the criteria is provided that is based on Parseval’s theorem. It is shown that for objects (including amplitude-only and phase-only) reconstructed from their holograms and the twin image treated as noise, a signal-to-noise ratio of 10 or higher can be achieved provided the object occupies less than 0.5% of the total illuminated area. When a hologram is reconstructed by applying iterative algorithms, the requirement for the object size is much more generous and identical to that applied in coherent diffraction imaging: any type of object (amplitude-only, phase-only, or amplitude-and-phase mixed properties) is suitable for holography when the object’s size in each dimension is less than half of the probed region’s extent (or the field of view).

First-in-Human Phase I Clinical Trial of the Adenosine A1R/A3R Agonist AST-004 in Healthy Subjects.

AST-004 is a small-molecule adenosine A1/A3 receptor agonist that has exhibited significant cerebroprotective efficacy in preclinical models of acute ischemic stroke and traumatic brain injury. The primary objectives of this clinical phase I first-in-human study were to evaluate the safety and tolerability profile of single ascending intravenous doses in healthy subjects. The secondary objectives were to characterize the single-dose pharmacokinetic profiles in plasma, cerebrospinal fluid (CSF), and urine. In part 1 of the study, AST-004 was administered in ascending dose cohorts of 5, 25, 50, 75, and 100 mg, with 6 subjects in each cohort receiving the study drug and 2 receiving placebo. In part 2, all 12 subjects received a 100 mg IV infusion of the study drug followed by a single CSF collection per subject via lumbar puncture at 20, 40, or 60 minutes after infusion. A total of 42 subjects received AST-004, with no severe or serious adverse events observed. Twelve of these subjects experienced a treatment-emergent adverse event, the most frequent across groups being headache. In part 2, pharmacokinetic analyses confirmed that AST-004 was distributed in the CSF, with the CSF-to-plasma ratio increasing over the 3 timepoints sampled. The mean half-life was 1.1 to 1.4 hours for doses of 25 to 100 mg, and the geometric mean maximum plasma concentration obtained in the highest dosing cohort (100 mg) was 2232±428 ng/mL. AST-004 was safe and well-tolerated at plasma concentrations 3 to 8× higher than those associated with significant efficacy in astrocyte's preclinical primate stroke efficacy studies, with CSF concentrations highest at the 60-minute collection timepoint, the last timepoint tested. This study supports additional clinical investigations, including evaluation of an extended infusion to support the phase 2 program in stroke and traumatic brain injury.

P13.01.A 11C-METHIONIN PET FOR RADIOTHERAPY TREATMENT PLANNING IN PATIENTS WITH RAPID EARLY PROGRESSION AFTER GLIOBLASTOMA SURGERY: PROSPECTIVE PHASE II TRIAL

Abstract BACKGROUND Radiotherapy (RT) is a standard treatment for nearly all glioblastoma patients following initial surgery. Few retrospective studies indicate negative prognostic instances of progression during the planning magnetic resonance (MR) (up to 1 week before initiating RT), termed Rapid Early Progression (REP). The optimal RT management for REP patients remains uncertain. The objective of this prospective phase II trial (NCT05608395) is to assess impact of 11C-Methionine PET used for RT planning in REP glioblastoma patients. It is one of the first prospective clinical interventional trials focused on this specific cohort of patients. MATERIAL AND METHODS We enrolled glioblastoma, IDHwt, or Astrocytoma, IDHmt, WHO grade IV patients, who developed REP characterized by 1) increase in postoperative residuum by ≥ 25%, 2) appearance of new contras enhancing lesion, 3) unequivocal progression of the unresected satelite. Patients received treatment based on the Stupp or Perry protocol. Treatment response was evaluated using RANO criteria. RT target volumes were delineated as follows: Gross tumor volume included tumor cavity, enhancing lesion and 11C-MET PET (1.3 tumor-to-background ratio). The clinical target volume was GTV plus a modified 2cm margin reflecting surrounding organs at risk. Volumetric analyses of different radiotherapy target volume were performed using EclipseTM software including patterns of failure. RESULTS During 12/2020 - 12/2023, total of 31 patients were enrolled (16 treated via abbreviated RT course); median age 60 years, ECOG 0-1 in 28 patients, median follow up 20 months. No effect of 11C-MET PET - based radiotherapy treatment planning of GBM patients with REP was observed on PFS (median 3.4 months comparing to 4.9 in historical control cohort) and OS (12.3 months comparing to 15.7 months). Median MET volume was 7.3cm3 (43% of MRI volume), MET avidity was presented in 7 patients et least 1cm beyond MRI volume. Central recurrence was presented in 87% patients. CONCLUSION The optimal treatment of patients with REP is unknown and needs to be studied in more details including dose escalation studies with reduced target margins potentialy directed also by aminoacid PET examination. Adjustment of target radiotherapy volumes using 11C-MET PET did not lead to improved PFS or OS. Supported by NU20-03-00148.

Quantitative phase analysis of transparent phase objects in a radial shearing interferometer incorporating a wire-grid polarizer

Quantitative phase analysis of transparent phase objects in a radial shearing interferometer incorporating a wire-grid polarizer

Geometric characteristics of stromal collagen fibres in breast cancer using differential interference contrast microscopy.

Breast cancer (BC) is characterised by a high level of heterogeneity, which is influenced by the interaction of neoplastic cells with the tumour microenvironment. The diagnostic and prognostic role of the tumour stroma in BC remains to be defined. Differential interference contrast (DIC) microscopy is a label-free imaging technique well suited to visualise weak optical phase objects such as cells and tissue. This study aims to compare stromal collagen fibre characteristics between in situ and invasive breast tumours using DIC microscopy and investigate the prognostic value of collagen parameters in BC. A tissue microarray was generated from 200 cases, comprising ductal carcinoma in situ (DCIS; n=100) and invasive tumours (n=100) with an extra 50 (25 invasive BC and 25 DCIS) cases for validation was utilised. Two sections per case were used: one stained with haematoxylin and eosin (H&E) stain for histological review and one unstained for examination using DIC microscopy. Collagen fibre parameters including orientation angle, fibre alignment, fibre density, fibre width, fibre length and fibre straightness were measured. Collagen fibre density was higher in the stroma of invasive BC (161.68±11.2fibre/µm2) compared to DCIS (p<0.0001). The collagen fibres were thinner (13.78±1.08µm), straighter (0.96±0.006, on a scale of 0-1), more disorganised (95.07°±11.39°) and less aligned (0.20±0.09, on a 0-1 scale) in the invasive BC compared to DCIS (all p<0.0001). A model considering these features was developed that could distinguish between DCIS and invasive tumours with 94% accuracy. There were strong correlations between fibre characteristics and clinicopathological parameters in both groups. A statistically significant association between fibre characteristics and patients' outcomes (breast cancer specific survival, and recurrence free survival) was observed in the invasive group but not in DCIS. Although invasive BC and DCIS were both associated with stromal reaction, the structural features of collagen fibres were significantly different in the two disease stages. Analysis of the stroma fibre characteristics in the preoperative core biopsy specimen may help to differentiate pure DCIS from those associated with invasion.

Cell classification with phase-imaging meta-sensors.

The development of photonic technologies for machine learning is a promising avenue toward reducing the computational cost of image classification tasks. Here we investigate a convolutional neural network (CNN) where the first layer is replaced by an image sensor array consisting of recently developed angle-sensitive metasurface photodetectors. This array can visualize transparent phase objects directly by recording multiple anisotropic edge-enhanced images, analogous to the feature maps computed by the first convolutional layer of a CNN. The resulting classification performance is evaluated for a realistic task (the identification of transparent cancer cells from seven different lines) through computational-imaging simulations based on the measured angular characteristics of prototype devices. Our results show that this hybrid optoelectronic network can provide accurate classification (>90%) similar to its fully digital baseline CNN but with an order-of-magnitude reduction in the number of calculations.

Quantitative phase imaging with two in-line holograms.

Quantitative phase imaging (QPI) has emerged as a practical technique for acquiring structural information from phase objects. Digital holography can realize phase detection, but it is limited by a spatial bandwidth product or affected by the overlap of conjugate images. The phase retrieval algorithm serves as an effective tool for QPI dealing with intensity patterns. Traditional phase retrieval algorithms heavily rely on strong support constraints or high data redundancy to accurately reconstruct the sample image. However, in single-frame phase retrieval algorithms, the precise acquisition of support constraints is notably challenging. The multiple-measurement spends much time on data acquisition and is unsuitable for dynamic sample observation. In this paper, we propose a novel, to the best of our knowledge, quantitative phase imaging method that utilizes only two in-line holograms. We have developed a phase retrieval algorithm based on ptychography, which eliminates twin-image and separates illumination background. The proposed method achieves high data utilization efficiency and can be employed for dynamic imaging.

Dynamic phase measurement based on two-step phase-shifting interferometry with geometric phase grating

Abstract This paper proposes a novel dynamic 2-step phase-shifting interferometry method with a geometric phase grating and direct aberration-free object phase recovery algorithm. By exploring the amplitude-phase modulation property of the geometric phase grating, two-step phase-shifting interferograms with π / 2 phase shift can be obtained in a single shot through two kinds of spatial-multiplexing arrangements. Then the restriction on the background uniformity of the 2-step phase-shifting algorithms and the system aberration can be avoided simultaneously, based on the presented direct and fast object phase demodulation strategy with an object-free state recorded in advance, so an accurate object measurement result can be guaranteed. Accordingly, a detailed analysis of the theoretical model of error sources is conducted by taking the depolarization error of geometric phase grating and phase measurement model error into consideration, with a Least Squares Iteration optimization strategy established to further improve the measurement accuracy. Experiments on various types of phase objects, such as a photo-etched quartz substrate, the spatial light modulator, and a silicon chip, validate the effectiveness and accuracy of our method when compared with the reference phase obtained from 4-step temporal phase-shifting method. The dynamic phase measurement capability is demonstrated by exhibiting the evaporation process of alcohol droplet.

When Diapers are Erotic: Investigation of 197 People with Adult-Baby-Syndrome (Autonepophilia)

Goal: Autonepophilia is a behaviour of adults in which people behave like toddlers. They wear diapers, suck on pacifiers and love it to be cared for from other people. Often an erotic component is involved and urinating into the diaper is connected with sexual arousal. Currently only a small number of studies exist about the AB/DL-syndrome (adult baby / diaper lovers). This study aimed to characterize causes in the development and typical behaviours of affected persons. Method: Data were collected in social networks and online communities for adult baby / diaper lovers. A sample of 184 male and 13 female participants with AB/DL behaviour was recruited and compared with a not-affected control group (158 male and 13 female). Primarily a questionnaire was used, which was developed to collect data about this syndrome by the authors. In addition the elements of the „Giessen-Test-II“ (GT-II, Beckmann et al.) and the „Need Inventory of Sensation Seeking“ (NISS, Hamelstein et al.) were used. Results: Data support a psychodynamic, behavioural and biopsychological explanation for AB/DL behaviour. Predisposing factors were the absence of a secure attachment object, lower stimulation in the anal stage, associations between infant care and first sexual arousal, enuresis and testosterone deficiency. The main motive was the reduction of stress and tensions. In contrast to the short excitement, in a long term practicing of AB/DL led to strong feelings of humiliation and shame. Moreover, AB/DL affected individuals had fewer, shorter and poorer-qualities of partnerships compared to the control group. No significant differences were found with respect to the expression of docility or sensation seeking. Conclusion: The study shows evidence of a psychodynamic explanation for the Adult Baby Syndrome. The absence of a safe attachment object and understimulation in the anal phase of development were identified as possible predisposing factors. In combination with the fact, that AB/DL sufferers more often come from divorced and adoptive families, it can be assumed that the origin of this behaviour is in the external circumstances of childhood and youth.

Hiding Images in Quantum Correlations.

Photon-pair correlations in spontaneous parametric down-conversion are ubiquitous in quantum photonics. The ability to engineer their properties for optimizing a specific task is essential, but often challenging in practice. We demonstrate the shaping of spatial correlations between entangled photons in the form of arbitrary amplitude and phase objects. By doing this, we encode image information within the pair correlations, making it undetectable by conventional intensity measurements. It enables the transmission of complex, high-dimensional information using quantum correlations of photons, which can be useful for developing quantum communication and imaging protocols.

Differential phase contrast from electrons that cause inner shell ionization

Differential Phase Contrast (DPC) imaging, in which deviations in the bright field beam are in proportion to the electric field, has been extensively studied in the context of pure elastic scattering. Here we discuss differential phase contrast formed from core-loss scattered electrons, i.e. those that have caused inner shell ionization of atoms in the specimen, using a transition potential approach for which we study the number of final states needed for a converged calculation. In the phase object approximation, we show formally that differential phase contrast formed from core-loss scattered electrons is mainly a result of preservation of elastic contrast. Through simulation we demonstrate that whether the inelastic DPC images show element selective contrast depends on the spatial range of the ionization interaction, and specifically that when the energy loss is low the delocalisation can lead to contributions to the contrast from atoms other than that ionized. We further show that inelastic DPC images remain robustly interpretable to larger thicknesses than is the case for elastic DPC images, owing to the incoherence of the inelastic wavefields, though subtleties due to channelling remain. Lastly, we show that while a very high dose will be needed for sufficient counting statistics to discern differential phase contrast from core-loss scattered electrons, there is some enhancement of the signal-to-noise ratio with thickness that makes inelastic DPC imaging more achievable for thicker samples.

Thermal vibrations in the inversion of dynamical electron scattering

Relativistic forward scattering of electrons at finite temperature involves the incoherent superposition of diffraction patterns formed by different snapshots of thermal atomic displacements. In experiments, thermal vibrations lead to thermal diffuse scattering (TDS), partly dominating diffraction patterns of thick specimens. This study sheds light on the effects of TDS on solutions to the inverse scattering problem using combined real- and diffraction-space information acquired in a scanning transmission electron microscope (STEM) to retrieve the object's phase. Using frozen phonon multislice within the Einstein approximation, realistic ground truth data of 20-nm-thick SrTiO3 is generated and subjected to contemporary inverse multislice schemes to retrieve the projected Coulomb potential slicewise. We first classify phase retrieval algorithms as to their assumptions on periodicity along the incident beam direction, as well as pixelwise and parametrized reconstruction methods. It is found that pixelwise object reconstructions are capable of retrieving structural details qualitatively while being prone to contain TDS-related artifacts which can result in unphysical potentials. For pixelwise reconstructions of multiple independent specimen slices, we observe that the origin of TDS, i.e., thermal atomic displacements, starts to emerge naturally. However, the quantitative assessment tends to too small mean squared thermal displacements, also when reconstructing multiple object modes. Using an atomistically parametrized inversion strategy which exploits the explicit separation of thermal vibrations and potentials, temperature and chemistry of the specimen can be retrieved quantitatively with high accuracy. Published by the American Physical Society 2024

Strategies for successful dose optimization in oncology drug development: a practical guide

ABSTRACT Dose optimization is a critical challenge in drug development. Historically, dose determination in oncology has followed a divergent path from other non-oncology therapeutic areas due to the unique characteristics and requirements in Oncology. However, with the emergence of new drug modalities and mechanisms of drugs in oncology, such as immune therapies, radiopharmaceuticals, targeted therapies, cytostatic agents, and others, the dose-response relationship for efficacy and toxicity could be vastly varied compared to the cytotoxic chemotherapies. The doses below the MTD may demonstrate similar efficacy to the MTD with an improved tolerability profile, resembling what is commonly observed in non-oncology treatments. Hence, alternate strategies for dose optimization are required for new modalities in oncology drug development. This paper delves into the historical evolution of dose finding methods from non-oncology to oncology, highlighting examples and summarizing the underlying drivers of change. Subsequently, a practical framework and guidance are provided to illustrate how dose optimization can be incorporated into various stages of the development program. We provide the following general recommendations: 1) The objective for phase I is to identify a dose range rather than a single MTD dose for subsequent development to better characterize the safety and tolerability profile within the dose range. 2) At least two doses separable by PK are recommended for dose optimization in phase II. 3) Ideally, dose optimization should be performed before launching the confirmatory study. Nevertheless, innovative designs such as seamless II/III design can be implemented for dose selection and may accelerate the drug development program.

Development &amp; Validation of a Packed Bed Thermal Energy Storage Model

The rapid growth of economies and population around the world have exponentially increased the demand for energy. This demand has invoked increased annual global CO2 emissions and necessitated a transition to clean energy technologies. Reliable and affordable energy storage technologies are paramount for increasing renewable energy penetration onto the grid, supporting periods with reduced or no renewable energy generation. This project is aimed at developing a Thermal Energy Storage (TES) solution that can deliver heat to a heat engine for power production or to an industrial process for prolonged periods. TES long duration energy storage (LDES) presents many potential benefits, including 1) Low Cost 2) scalability 3) high energy density 4) low carbon footprint and 5) resiliency via ability to produce synchronous power (i.e., spinning turbomachinery). The broader objective of this project is to build, test, and model the TES concept at a 2 MWh scale to determine the economic and physics-based practicality of the system. The work presented here describes the first phase objectives of the project, including benchtop scale testing, model development, and Model Validation.

Innovative spoke design for non-pneumatic tyres with enhanced load-bearing capacity and customizability for all vehicles

For over a century, pneumatic tyres have been a crucial part of automobiles. Recently, non-pneumatic (airless) tyres have emerged, offering innovation but facing challenges in complexity, vehicle safety, adaptability, and load-bearing capacity. This research introduces a new spoke design for non-pneumatic tyres that outperforms conventional honeycomb and diamond spokes tyres in load-bearing capacity, while being less complex and customizable for various vehicles, including public transport. The study is structured into two phases. In Phase 1, the spoke design is selected from various CAD models using SolidWorks. This involves comparing the parabola design against prior design studies and honeycomb and diamond spokes concerning total deformation, maximum shear stress, equivalent (von Mises) stress, and maximum principal elastic strain with the help of FEA software Ansys. Results show that the Parabola design surpasses the pneumatic tyres in terms of load-bearing capacity, The parabola spoke design shows a consistent vertical stiffness under varying loads, ranging from 1500 N to 4500 N, with no sudden spikes or drops indicating structural instability. The objective is to identify the spoke design that best meets the performance objectives for phase 2 analysis. In Phase 2, the material selection and analysis are conducted. The goal is to determine the optimal polyurethane durometer rating for bus tyres. In this phase, the insights from Phase 1 are applied to scale up the design and choose suitable materials, showcasing the design’s adaptability from car tyres to bus tyres. Ansys will be used for analysing the total deformation of the tyre under a force of 40,000N, simulating the extreme operating conditions for bus tyres. This paper provides valuable data on non-pneumatic tyre spoke design, material selection, deformation analysis, design optimization, and standardization, enhancing vehicle safety and performance in public transport.

Spin–orbit optical broadband achromatic spatial differentiation imaging

Spatial optical analog differentiation allows ultrahigh-speed and low-power-consumption of image processing, as well as label-free imaging of transparent biological objects. Optical analog differentiation with broadband and incoherent sources is appealing for its multi-channels and multi-task information processing, as well as the high-quality differentiation imaging. Currently, broadband and incoherent optical differentiation is still challenging. Here, a compact and broadband achromatic optical spatial differentiator is demonstrated based on the intrinsic spin–orbit coupling in a natural thin crystal. By inserting a uniaxial crystal just before the camera of a conventional microscope, the spin to orbit conversion will embed an optical vortex to the image field and make a second-order topological spatial differentiation to the field, thus an isotropic differential image will be captured by the camera. The wavelength-independent property of the intrinsic spin–orbit coupling effect allows us to achieve broadband analog computing and achromatic spatial differentiation imaging. With this differentiation imaging method, both amplitude and pure phase objects are detected with high contrast. Transparent living cells and biological tissues are imaged with their edge contours and intracellular details protruded in the edge detection mode and edge enhancement mode, respectively. These findings pave the way for optical analog computing with broadband incoherent light sources and concurrently drive the advancement of high-performance and cost-effective phase contrast imaging.

Digitalisation of the Preliminary Investigation Phase, Fundamental and Human Rights and the Principle of Openness - Balancing Conflicting Interests in the Review of Large Data Sets

The EU courts have divided an investigation into two distinct stages with different aims: the preliminary investigation phase and the contradictory phase. This paper examines issues related to the digitalisation of the preliminary investigation phase, from screening and open source intelligence to data processing during unannounced inspections or dawn raids. The question is how rights of defence are secured without jeopardising an investigation where data sets have grown beyond anything previously known. Within the context of the principle of openness of government activities in Finland and Sweden, the author sets out to find how the main rule of openness is balanced with the objectives of the preliminary investigation phase. The article examines case-law and literature, complemented with public statements from competition authorities, to find that a fair balance between conflicting interests has been achieved thus far. Examples of open questions currently subject to debate do, nonetheless, range from using personal apps for detection to whether national identity as per Article 4(2) of the Treaty on European Union can tip the balance between confidentiality of correspondence and cartel enforcement categorically in favour of the former. The Court of Justice will likely have to address the issue of national identity in the ongoing Ronos case.

Neural-field-assisted transport-of-intensity phase microscopy: partially coherent quantitative phase imaging under unknown defocus distance

The transport-of-intensity equation (TIE) enables quantitative phase imaging (QPI) under partially coherent illumination by measuring the through-focus intensities combined with a linearized inverse reconstruction algorithm. However, overcoming its sensitivity to imaging settings remains a challenging problem because of the difficulty in tuning the optical parameters of the imaging system accurately and because of the instability to long-time measurements. To address these limitations, we propose and experimentally validate a solution called neural-field-assisted transport-of-intensity phase microscopy (NFTPM) by introducing a tunable defocus parameter into neural field. Without weak object approximation, NFTPM incorporates the physical prior of partially coherent image formation to constrain the neural field and learns the continuous representation of phase object without the need for training. Simulation and experimental results of HeLa cells demonstrate that NFTPM can achieve accurate, partially coherent QPI under unknown defocus distances, providing new possibilities for extending applications in live cell biology.