Phase Profile Research Articles

Generation of Orbital Angular Momentum Light by Patterning Azopolymer Thin Films

Orbital angular momentum (OAM) encoding is a promising technique to boost data transmission capacity in optical communications. Most recently, azobenzene films have gained attention as a versatile tool for creating and altering OAM-carrying beams. Unique features of azobenzene films make it possible to control molecular alignment through light-induced isomerization about the azo bond. This feature enables the fabrication of diffractive optical devices such as spiral phase plates and holograms by accurately imprinting a phase profile on the incident light. By forming azobenzene sheets into diffractive optical elements, such as spiral phase plates, one can selectively create OAM-carrying beams. Due to the helical wavefront and phase variation shown by these beams, multiple distinct channels can be encoded within a single optical beam. This can significantly increase the data transmission capacity of optical communication systems with this OAM multiplexing technique. Additionally, holographic optical components made from azobenzene films can be used to build and reconstruct intricate wavefronts. It is possible to create OAM-based holograms by imprinting holographic designs on azobenzene films, which makes it simpler to control and shape optical beams for specific communication requirements. In addition, azobenzene-based materials can then be suitable for integration into optical communication devices because of their reconfigurability, compactness, and infrastructure compatibility, which are the main future perspectives for achieving OAM-based technologies for the next generation, among other factors. In this paper, we see the possible use of azobenzene films in the generation and modification of OAM beams for optical communications through light-induced isomerization. In addition, the potential role of azobenzene films in the development of novel OAM-based devices that paves the way for the realization of high-capacity, OAM-enabled optical communication networks are discussed.

A Multicenter, Open-Label, Single-Arm, Phase Ib Clinical Trial of HH2853 in the Treatment of Patients with Relapsed and/or Refractory Peripheral T-Cell Lymphoma

Introduction Peripheral T cell lymphoma (PTCL) is an aggressive tumor type with poor survival, whereas treatment options for relapsed and/or refractory (r/r) disease are very limited. Standard treatments have a median progression free survival (PFS) of only 3-4 months. HH2853, the novel, potent and selective dual inhibitor of Enhancer of Zeste Homolog 1 and 2 (EZH1/2), has demonstrated a clinical benefit with a favorable safety profile in Phase 1 and Phase 2 trials in solid tumors and R/R non-Hodgkin's lymphoma (NHL) previously. Here we report the efficacy and safety data from phase 1b trial of HH2853 in r/r PTCL. Methods The Phase 1b clinical trial in PTCL (CTR20221416) was conducted from July, 2022 to June 15, 2023 at 15 sites in China. This study consisted of two parts. In part 1, 3+3 dose-escalation design with three dose levels of HH2853 (300mg, 400mg, 600mg BID) was used to identify the MTD and recommended Phase II dosage (RP2D) of HH2853. Part 2 was dose expansion at two dose groups (300mg and 400mg BID). HH2853 was orally dosed until disease progression, intolerable toxicity or withdrawal from the study. Safety was evaluated according to CTCAE v5.0. Tumor assessments were performed according to LUGANO 2014 every 2 treatment cycles (28-day/cycle). A final data cut off (DCO) on June 15, 2023 was conducted for safety and efficacy assessments. To that date, there were still 25 pts (73.5%) remained on HH2853 treatment. Results In this study in r/r PTCL, 34 pts enrolled with different PTCL histology types, including AITL (14 pts, 41.2%), PTCL-NOS (11 pts, 32.4%), ALK -ALCL (4 pts,11.8%), NKT (2 pts, 5.9%), TFH (2 pts, 5.9%), SKIN-PTCL (1 pt, 2.9%). Pts were a median age of 58 years (range: 34 to 79), ECOG 0-1 (ECOG 0, 9 pts, 26.5%, ECOG 1, 25 pts, 73.5%), had a median of 2 lines (range 1 to 5) prior systemic therapies, 6 pts (17.6%) had bone marrow involvement at the baseline. With 30 pts (88.2%) having prior CHOP or CHOP-like therapy，with 14 pts (41.2%) were refractory to their last treatment. 1pts (2.9%) had undergone hematopoietic stem cell transplantation. 32 patients (92.1%) had experienced a treatment related adverse event (TRAE), 7 pts (20.6%) experienced grade ≥3 TRAE. The most common TRAEs (≥10%) were PLT decreased (14 pts, 41.2%) , anaemia (13 pts, 38.2%)，and diarrhoea (11 pts, 32.4%). The frequently reported TRAEs of grade ≥3 with an incidence of ≥10% were PLT decreased (5 pts, 14.7%) and neutrophil count decreased (4 pts, 11.8%). 8 pts (23.5%) had dose interrupted due to TRAE. 3 pts (8.8%) had dose reductions due to TRAE from 600 to 400 mg BID, 1 pts (6.3%) had dose reductions from 400 to 200 mg BID, and 1 pts (2.9%) discontinued from the study due to TRAEs. The safety profile was consistent to that had been observed in HH2853 studies. 1 pt (2.9%) at 600mg BID experienced dose limiting toxicity (DLT)due to grade 4 PLT decreased. The majority of TRAEs were reversible or clinically manageable. Among the 34 enrolled pts, 28 patients had the evaluated response, the Overall Response Rate (ORR) was 60.7% (17 pts), including 21.4% (6 pts) Complete Responses (CR), 39.3% (11 pts) Partial Responses (PR) and 14.3% (4 pts) Stable Disease (SD), contributing to an 75.0% (21 pts) Disease Control Rate (DCR). The median time to response (mTTR) was 1.87 months (95% CI: 1.77, 2.17). At DCO the median follow up of the pts in the study was 2.79 month (IQR: 1.94, 5.88). The median Duration of Response (mDOR), the median Progression Free Survival (mPFS) and the median OS (mOS) had not reached. The 3-month PFS rate was 74.44% (95%CI:53.62%,86.95%). The 6-month OS rates was 91.97% (95%CI: 71.50%, 97.93%). Conclusions The selective EZH1/2 dual inhibitor HH2853 demonstrated good safety and promising efficacy in r/r PTCL patients, indicating its potential as a therapeutic option for this difficult to treat patient population.

Repurposing GSK3B Small Molecule Inhibitors for Refractory Lymphoid Malignancies

Background: Small molecule GSK3B inhibitors were developed for solid tumors and neurological conditions, including Alzheimer's and Parkinson disease. Five GSK3B inhibitors achieved favorable safety and PK/PD profiles in a total of 22 Phase 1 and 2 clinical trials but no clinical response for any of these indications. GSK3B is the kinase that phosphorylates β-catenin to initiate its degradation, hence GSK3B small molecule inhibition results in rapid nuclear accumulation of β-catenin protein. Significance: Activating mutations in the Wnt/β-catenin pathway are common oncogenic drivers throughout all main types of cancer (n=64,812) but not found in B- and T-lymphoid malignancies (n=2,137). Studying tissue microarrays by β-catenin immunohistochemistry, lung, colon, breast, and melanoma specimen (n=57) showed consistently high levels of nuclear β-catenin, whereas B- and T-cell lymphomas (n=84) lacked β-catenin signal. Despite comparable mRNA levels, proteomic analyses revealed 60-400-fold lower β-catenin levels in lymphoid compared to epithelial tumors (n=1,389) suggesting that lymphoid malignancies rely on powerful mechanisms for β-catenin degradation, e.g. by GSK3B. Results: To study the effects of β-catenin activation in human cells, we induced expression of stabilized form of β-catenin in 18 lymphoid (B- and T-ALL, MCL, DLBCL, PTCL) and four myeloid leukemia cell lines. In B- and T-lymphoid cells, β-catenin accumulation compromised clonal fitness, colony formation and induced cell death, but increased competitive fitness and colony formation in myeloid leukemia cells. CEBPα-mediated reprogramming of B-ALL cells into a myeloid phenotype reversed the deleterious effects highlighting that effects of β-catenin-accumulation strictly depend on lymphoid lineage-identity. RNA-seq studies upon inducible activation of β-catenin in lymphoid cells, revealed transcriptional repression of Myc and Myc target genes as principal gene expression change. Unlike activating β-catenin:TCF7 complexes in epithelial cells, our global interactome studies in B- and T-ALL and lymphoma cells identified repressive β-catenin complexes with lymphoid-specific Ikaros zinc finger (IKZF1/2/3) proteins and several components of the NuRD complex including Mta1/2, Gatad2a/b, Chd4, HDAC1/2. Interactome and ChIP-seq analyses revealed that β-catenin together with lymphoid-specific Ikaros factors recruited repressive NuRD complex members to deacetylate H3K27 and repress MYC superenhancer (SE) regions. Genetic deletion of both IKZF1 and IKZF3 or HDRT-based mutation of Ikaros binding motifs within the Myc-SE enabled resistance to β-catenin accumulation. To leverage this previously unrecognized vulnerability of lymphoid malignancies, we examined five clinically approved GSK3B small molecule inhibitors that achieved favorable safety profiles at micromolar plasma concentrations in clinical trials for neurological disorders and solid tumors. Strikingly, LY2090314 and CHIR99021 were effective at low nanomolar concentrations in B- and T-cell malignancies that expressed lymphoid Ikaros factors. At IC50 concentrations of <5 nM, GSK3B-inhibitors induced massive accumulation of β-catenin, repression of MYC and acute cell death. In B-ALL cells with IKZF1-deletion, expression of the remaining IKZF3 factor was sufficient to retain full sensitivity to GSK3B-inhibition. Deletion of β-catenin, however, abolished the effects of GSK3B inhibitors and relieved suppression of MYC, demonstrating accumulation of β-catenin represents as central mechanism of action. Preclinical in vivo treatment experiments of refractory B-ALL and mantle cell lymphoma PDX validated small molecule GSK3B-inhibition as strategy to overcome conventional mechanisms of drug-resistance. Conclusions: B- and T-lymphoid malignancies not only lacked expression of β-catenin but critically depend on GSK3B for effective β-catenin degradation. Our interactome studies in lymphoid tumors revealed that β-catenin formed repressive complexes with lymphoid-specific Ikaros and NuRD complex factors. Strikingly, GSK3B small molecule inhibitors engage this new pathway at low nanomolar concentrations and demonstrated favorable safety profiles in Phase 1 and Phase 2 trials. Safety and efficacy of GSK3B-inhibitors opens up an immediate path for repurposing these agents towards refractory B-cell malignancies.

A Multicenter Phase2 Trial of Linperlisib in Relapsed or Refractory Peripheral T/NK Cell Lymphomas

Introduction Peripheral T/NK cell lymphomas (PTCLs) are a group of aggressive heterogeneous non-Hodgkin's lymphomas where in relapsed or refractory (r/r) disease, the approved standard therapies are limited with a median progression free survival (mPFS) of only 3-4 months. PI3Kdelta inhibitors have demonstrated clinical activities in T-cell and B-cell lymphomas, owing to the multiple cellular activities in the T, B, and myeloid cell tumor microenvironment. However, application of these agents has been hampered by poor tolerabilities, particularly with toxicities such as diarrhea/colitis, hepatotoxicity, pneumonitis, hyperglycemia, and rash. As a new PI3Kdelta-selective oral agent, linperlisib was shown to be efficacious and indicated a favorable safety profile in phase 1 and 2 clinical trials in r/r Follicular Lymphoma (FL) and PTCL. Linperlisib received marketing approval in China in 2022 for r/r FL patients (pts) with 2 prior systemic therapies. Here we report the efficacy and safety findings for linperlisib in a pivotal phase 2 trial in r/r PTCL. Methods Ninety-eight pts were enrolled in the open-label phase 2 registration trial (CTR20210333) from May 2021 to October 2022 at 25 sites in China. The trial had a representation of different PTCL subtypes: AITL (48 pts), PTCL-NOS (24 pts), NKT (8 pts), ALCL (2 pts), MEITL (2 pts), Other (4 pts), and 10pt did not qualify as PTCL confirmed by independent pathology review, yielding a Full Analysis Set (FAS) of 88 pts for efficacy evaluation. Linperlisib was orally dosed at 80 mg QD (RP2D) continuously until disease progression, intolerable toxicity, or study withdrawal. Tumor assessments performed every 2 treatment cycles (28-day cycle) were evaluated with Lugano 2014 criteria by an Independent Review Committee. Safety was evaluated according to CTCAE v5.0. Results In this phase 2 study, the median age was 57 years, ECOG 0-1 (100%). Most patients were diagnosed with Lugano 2014 Stage III (29 pts, 33%), or IV (49pts, 56%) diseases, and were refractory or relapsed to a median of 2 prior systemic therapies. Sixty-four pts (73%) had refractory diseases, 59 pts (67%) had relapsed diseases, and 35 pts (40%) were with both r/r. Treatment related adverse events (TRAE) were observed in 94 pts (95.9%) , with the most common TRAEs (≥10%) being neutropenia (59%), leukopenia (47%), thrombocytopenia (32%), anaemia (24%), elevated alanine aminotransferase (23%), elevated aspartate aminotransferase (20%), pneumonia (20%), lymphocytopenia (17%), hypertriglyceridemia (15%), fever (15%), diarrhea (14%), elevated lipase (13%), hyperuricemia (13%), rash (13%), hypercholesterolemia (12%), hyponatremia (11%), elevated lactate dehydrogenase (10%), elevated creatinine (10%). AEs of ≥Grade 3 (≥5%) were neutropenia (32%), pneumonia (14%), leukopenia (10%), anaemia (6%), thrombocytopenia (5%), upper respiratory tract infection (5%) and lymphocytopenia (5%). The most frequent Serious Adverse Event (drug-related) was pneumonia (11%). Twenty-two pts (22.4%) had dose reductions, and 9 pts (9.2%) discontinued from the study due to AEs. The safety profile was consistent with all previously reported in linperlisib clinical studies. Among the 88 FAS pts, the objective response rate (ORR) was 48%, including 30% (26 pts) complete response, 18% (16 pts) partial response, and 20% (18 pts) stable disease. The disease control rate was 68%. Responses were demonstrated in all subtypes, including AITL, PTCL-NOS, NKT, and others. As of April 24, 2023, the median duration of response had not been reached (95%CI: 7.8, NR), and mPFS was 5.5 months (95%CI: 3.5, 15.6). All pts had ≥6 months of follow-up as of the safety and efficacy analysis data cut off (April 24, 2023); median follow-up was 13.9 months. The 6-month OS rate was 75% (95% CI: 64.51%, 82.74%), the median OS was 14.2 months (95%CI: 7.9, NR), 16 pts continued to receive linperlisib treatment. Conclusions Linperlisib, as a new PI3Kdelta-selective oral agent, showed a well-tolerated safety profile with low levels of severe gastrointestinal and liver toxicities seen with other PI3K agents. In r/r PTCL, linperlisib had promising durable efficacies, with 48% ORR (30% CR) and a median duration of response that was not reached. As in previous lymphoma studies with linperlisib, a high proportion of responses were CRs, and responses were observed across almost all PTCL subtypes. A phase 2 r/r PTCL and CTCL trial in the US/EU is ongoing.

DA-EPOCH-R for High Grade B-Cell Lymphoma Patients with MYC and BCL2 and/or BCL6 Rearrangements: Clinical Results of the Induction Phase of the HOVON-152 Trial

Introduction Patients (pts) with high grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 gene rearrangements (double hit and triple hit (DH/TH)) have poor outcomes to standard R-CHOP. Retrospective studies reported improved disease-free survival (DFS) through intensification with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). This regimen was studied in a small prospective trial including 24 DH/TH and 19 single MYC rearranged (SH) lymphomas (Dunleavy, Lancet Haematol 2019). No prospective studies evaluating DA-EPOCH-R exclusively for pts with DH/TH HGBL have been reported. The HOVON-152 trial aimed to improve outcomes in untreated DH/TH HGBL pts by investigating the efficacy of the immune checkpoint inhibitor nivolumab as consolidation treatment in pts achieving complete metabolic response (CMR) after DA-EPOCH-R induction. Here, we present the efficacy and safety profile of the induction phase with DA-EPOCH-R. Methods HOVON-152 is a prospective, multi-center, single arm phase II trial. Inclusion criteria were pts with newly diagnosed HGBL-DH/TH (according to the WHO 2016 classification), age ≥ 18 years, WHO performance status (PS) 0-3 and Ann Arbor stage II-IV. During the screening period for rearrangement status, pts could receive 1 cycle of R-CHOP or DA-EPOCH-R, followed by 5 cycles of DA-EPOCH-R. All pts received intrathecal CNS prophylaxis. All diagnostic lymphoma samples were centrally reviewed. PET-CT scans were performed at diagnosis, after 3 cycles and at end-of-induction (local review, central review will be reported at the conference). Pts in CMR after induction treatment (Deauville 1-3 or a negative lymphoma biopsy in case of Deauville 4) proceeded to nivolumab consolidation (480 mg every 4 weeks for one year). The HOVON-152 aimed to improve 12 months DFS of pts in CMR after induction from an expected 70% to 85% with nivolumab consolidation. Secondary objectives included evaluation of response rates, overall survival (OS) and safety. With a power of 0.90 a sample size of 97 pts was calculated. Here, we report efficacy (CMR rate) and safety of DA-EPOCH-R induction treatment. Logistic univariate analysis is used to analyze baseline characteristics associated with response. Adverse events (AEs) were defined according to the common terminology criteria for adverse events (CTC AE 5.0), counted by the highest grade per system organ class per patient. Results From August 2018 - March 2022, 97 pts have been enrolled (study inclusion completed). One patient was excluded due to CNS localization. The median age was 62 years (range 35-79); 90 (83%) pts had stage III-IV disease and 52 (54%) had (intermediate-)high international prognostic index (IPI) (Table 1). Central pathology review confirmed DH/TH in all pts. 65 pts (67%) had a BCL2 DH, 11 (12%) a BCL6 DH and 16 (17%) a TH. Dose adjustments were performed conform protocol. The maximum dose-level (DL) achieved was DL1 in 41 (43%), DL2 in 22 (23%), DL3 in 25 (25%), DL4 in 7 (7%) and DL5 in 1 (1%) of the pts. Vincristine dose was reduced in 28/81 (35%) pts. After DA-EPOCH-R induction, 63/96 (66%, 95% CI 55-75%) pts achieved CMR. WHO PS 2-3 (odds ratio (OR) 0.15, 95% CI 0.03-0.85, p=0.03), elevated LDH (OR 0.24, 95%CI 0.10-0.59, p=0.002) and bulky disease defined as ≥10 cm mass (OR 0.23, 95%CI 0.09-0.56, p=0.001), were significantly associated with a lower chance of achieving CMR. During treatment, 7 (7%) pts experienced a grade 5 AE (ileus, intestinal perforation, multi-organ failure/sepsis). Thereof, 4 patients died during DA-EPOCH-R and 3 patients died after DA-EPOCH-R. 31 (32%) experienced a grade 4 AE (e.g. sepsis, perforation, hemorrhage, thrombocytopenia and neutropenia), 21 (22%) a grade 3 AE (e.g. anemia, mucositis, infections and electrolyte disturbances) and 16 (17%) pts a grade 2 AE. Conclusion We report the largest prospective series of DH/TH HGBL patients treated with DA-EPOCH-R. DA-EPOCH-R induction was feasible, with toxicity and dose adjustments as previously described. The observed CMR rate of 66% was lower than previously reported in a prospective cohort of mixed DH/TH and SH patients (74%). For patients achieving CMR, the nivolumab consolidation phase is ongoing. Translational side studies investigating predictive factors to identify patients not achieving CMR are ongoing. For these patients, novel strategies to improve first-line treatment are warranted.

Binary coding metasurface for broadband and flexible generation of acoustic vortex beams

Considerable efforts have recently focused on sound vortices imprinted with orbital angular momentum (OAM) yet whose generation generally relies on sophisticated phase modulation, whether through traditional phased arrays or emerging metamaterial methods. Here, we propose and numerically demonstrate a mechanism for broadband generation of acoustic vortices in a simple, flexible, and high-efficiency way through binary-phase-based chirality modulation enabled by building a binary coding metasurface. The metasurface with a theoretically derived phase profile that is implemented with two types of meta-structures is capable of twisting the incident plane wave into a vortex beam with a desired order in a broad band and at the same time enables steering the vortices' propagation direction freewheelingly. The effectiveness of our proposed mechanism is verified by numerically demonstrating the broadband generation of vortex beams carrying different OAMs through a monolayered binary coding metasurface. We further demonstrate the generality and flexibility of our mechanism for generating the multiplexed vortex beams as well as modulating the propagation direction of the output beam by judiciously designing the 1-bit coding sequences of the metasurface. We anticipate our design with capability and simplicity to have far-reaching implications in OAM-enabled applications ranging from high-capacity acoustic communication to contactless particle manipulation.

Method for increasing the utilization rate of birefringence in liquid crystal lenses.

We propose a method to increase the utilization rate of birefringence in liquid crystal (LC) lenses. The method involves designing electrode patterns based on the phase response curve of the LC material, enabling the lenses to operate across a wide range of driving voltages while generating the desired phase profile. The underlying principle of this technique is discussed in detail. Electrode patterns have been successfully designed for positive and negative cylindrical LC lenses. The experimental results demonstrate that the designed lenses generate a parabolic phase profile even when the driving voltage exceeds the linear response region. The utilization rate of LC birefringence for the positive lens has increased from 41.3% to 69.7%, indicating a 68.8% increase from the original. For the negative lens, the utilization rate has risen from 41.8% to 68.7%, representing a 64.4% increase from the original.

Dual Antenna-Based Line Crossing Detection with UHF RFID

Line crossing detection is to check whether people or objects go across a given barrier line, which is quite common and important in our daily life, such as the electronic article surveillance (EAS) checkpoint in a retail store or the finish line in track and field. Although existing solutions to line crossing detection have achieved great advancement, they do not function well when multiple objects or people cross the line at the same time. In this paper, we propose a new radio frequency identification (RFID)-based solution called RF-Line to line crossing detection, especially for multiobject scenarios. The biggest challenge is that the RFID reader’s coverage zone is invisible and irregular; we cannot roughly take the time when a tag is seen by the reader for the first time as the time when line crossing occurs. In RF-Line, we deploy two antennas opposite to each other and collect the RF phase profiles of two antennas at the same time. By a series of geometric transformations and mathematical derivations, we find that summing up the two phase profiles will get a new phase curve, in which the inflection point of the curve is the time of line crossing. In addition, we address the problem of turning back or long stay on the barrier line. We implement RF-Line with commodity RFID systems. Extensive experiments show that RF-Line can achieve accurate line crossing detection with a small error of 6.1 cm, with no need for any system calibration or complicated deployment.

Structured illumination contrast transfer function for high resolution quantitative phase imaging.

We report a sub-diffraction resolution imaging of non-fluorescent samples through quantitative phase imaging. This is achieved through a novel application of structured illumination microscopy (SIM), a super-resolution imaging technique established primarily for fluorescence microscopy. Utilizing our contrast transfer function formalism with SIM, we extract the high spatial frequency components of the phase profile from the defocused intensity images, enabling the reconstruction of a quantitative phase image with a frequency spectrum that surpasses the diffraction limit imposed by the imaging system. Our approach offers several advantages including a deterministic, phase-unwrapping-free algorithm and an easily implementable, non-interferometric setup. We validate the proposed technique for high-resolution phase imaging through both simulation and experimental results, demonstrating a two-fold enhancement in resolution. A lateral resolution of 0.814 µm is achieved for the phase imaging of human cheek cells using a 0.42 NA objective lens and an illumination wavelength of 660 nm, highlighting the efficacy of our approach for high-resolution quantitative phase imaging.

Generation of spatiotemporal vortices in nonlinear photonic crystals

Spatiotemporal vortices (STOVs) are a new, to the best of our knowledge, type of structured light in which the optical phase circulates in space–time. In this work, we propose to generate STOVs via second harmonic generation in lithium niobate nonlinear photonic crystals (NPCs) with a linearly chirped Gaussian pulse as the fundamental wave. The structural function of the NPC is derived by the inverse design method. Numerical simulations of the intensity and phase profiles of the generated second harmonic waves are performed with both the amplitude-phase-modulated and the simplified binary-phase-modulated NPCs. We anticipate our study will be valuable for the experimental generation and manipulation of STOVs in NPCs.

Hybrid cubic-chessboard metasurfaces for wideband angle-independent diffusive scattering and enhanced stealth.

Because of the shortcomings associated with their scattering patterns, both the chessboard and cubic phased metasurfaces show non-perfect diffusion and hence sub-optimal radar cross section reduction (RCSR) properties. This paper presents a novel and powerful hybrid RCSR design approach for diffusive scattering by combining the unique attributes of cubic phase and chessboard phase profiles. The hybrid phase distribution is achieved by simultaneously imposing two distinct phase profiles (chessboard and cubic) on the hybrid metasurface area with the aid of geometric phase theory to further enhance the diffusive scattering and RCSR. It is shown in this paper that through the integration of cubic and chessboard phase profiles, a metasurface with the hybrid phase mask successfully overcomes all the above issues and shortcomings related to the RCSR of both chessboard and cubic metasurfaces. In addition, the proposed design leverages the unique scattering properties offered by these distinct phase profiles to achieve enhanced stealth capabilities over wide frequency ranges and for large incidence angles. Simulation and measurement results show that the designed hybrid metasurfaces using the proposed strategy achieved RCSR and low-level diffused scattering patterns from 12-28 GHz (80%) for normal incidence of a far-field CP radar plane wave. The hybrid metasurface shows a stable angular diffusion and RCSR performance when the azimuthal and elevation incidence angles are in the range of 0° → ± 75° which is wider than other designs in the literature. Therefore, this work can make objects significantly less detectable in complex radar environments when enhanced stealth is required.

Terahertz polarization detection based on the mode analysis of longitudinally polarized vortices

Polarization detection of terahertz waves is essential for applications of terahertz waves in communication, imaging, and other fields. Here, we propose a novel terahertz polarization detection approach via the mode analysis of transmitted longitudinally polarized vortex field. By finely designing the phase profiles of the proposed all-silicon metasurface, we establish a connection between the generated longitudinally polarized vortices and the polarization parameters of the incident field. Complete polarization parameters are obtained by analyzing the intensity, phase, and mode purity of the longitudinally polarized vortex field. The comparisons between the detected polarization states and the incident states prove the accuracy of the proposed metasurface for polarization detection. Such metasurface polarization detection scheme may further promote the application of terahertz technology.

All-dielectric terahertz metasurfaces for arbitrary linear polarization detection

The polarization state, an intrinsic property of electromagnetic waves, plays a key role in determining the mechanism of light–matter interactions. Recently, the bulky elements for evaluating polarization states have been miniaturized by using metasurfaces. However, determining arbitrary linear polarization (LP) states from vortex beams generated by metasurfaces is quite challenging. Here, a general design of all-silicon quasi-periodic arrays based on polarization multiplexing technology is proposed, which can be used for the detection of arbitrary incident LP state. By embedding independent helical phase profiles in two orthogonal LP channels, the generated interference spot at the predesigned focal plane is resolvable in a proper polarized direction. Benefiting from the establishment of a parametric theoretical model, the evolution of the incident polarization can be determined using key parameters defined on the pixelated focal plane. The proposed method can flexibly determine the polarization state of incident terahertz waves, which has great potential in remote sensing, high-resolution imaging, and data communication.

Label‐Free Imaging Flow Cytometry for Cell Classification Based on Multiple Interferometric Projections Using Deep Learning

A new label‐free imaging flow cytometry method for noninvasive and automated biological cell classification is presented. Each cell is rolled during flow, and its off‐axis holograms from multiple viewpoints are acquired. Using the reconstructed quantitative phase profiles of the cell projections, highly discriminating features, enabling cell detection, classification, and differentiation, are extracted via a modified ResNet‐18 deep convolutional neural network architecture. The model is first validated by classifying metastatic breast carcinoma cells (MCF‐7) and normal human mammary epithelial cells (MCF‐10A). An increase in classification accuracy by 1% is achieved when processing five interferometric projections versus processing a single interferometric projection. This model is further tested on four types of white blood cells and exhibits an accuracy increase of 5% when processing 12 interferometric projections versus processing a single interferometric projection. This approach is shown to be superior to that of using conventional 2D‐rotation augmentation, and can be used to decrease substantially the number of cell examples needed for training the classification model without impairing the results. This novel concept has great potential to be incorporated into label‐free imaging flow cytometry and improve cell classification, and be used to detect various types of medical conditions and diseases.

Golcadomide (GOLCA; CC-99282), a Novel CELMoD Agent, Plus R-CHOP in Patients (pts) with Previously Untreated Aggressive B-Cell Lymphoma (a-BCL): Safety and Efficacy Results from Phase 1b Dose Expansion

Introduction Up to 40% of pts with diffuse large B-cell lymphoma (DLBCL) relapse after first-line chemo-immunotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). CELMoD agents such as GOLCA potently degrade target proteins Ikaros/Aiolos, resulting in antiproliferative, apoptotic, and immunomodulatory activity. GOLCA preferentially distributes to tissues and lymphoid organs. In a phase 1 study, GOLCA demonstrated a manageable safety profile with promising clinical activity as monotherapy in relapsed/refractory non-Hodgkin lymphoma (Michot et al. Blood 2021). CC-220-DLBCL-001 (NCT04884035) is an ongoing open-label, multicenter, dose escalation and expansion trial to assess safety and preliminary efficacy of CELMoD agents + R-CHOP for untreated a-BCL. GOLCA demonstrated a manageable safety profile in the dose escalation phase (Munoz et al. ICML 2023 abstract 438); we report combined results from the GOLCA dose escalation and expansion phases. Methods Eligible pts were ≥ 18 years, had untreated a-BCL with measurable disease (Lugano 2014), ECOG performance status ≤ 2 and International Prognostic Index (IPI) score 0-5 (2-5 in dose expansion). Pts were treated with R-CHOP plus GOLCA in 21-day (D) cycles (C) for up to 6C, or until disease progression/unacceptable toxicity/study withdrawal/physician decision. During dose escalation, pts received GOLCA at dose levels (DL): 0.2 mg D1-7 (DL-1), 0.4 mg D1-7 (DL1), and 0.4 mg D1-10 (DL2). DL2 met the dose-limiting toxicity threshold and was not continued in the expansion phase. During dose expansion, pts were randomized 1:1 to R-CHOP plus GOLCA at DL-1 or DL1. The primary endpoint for the expansion phase was safety of GOLCA at the recommended phase 2 dose (DL1) (based on adverse events [AEs]); secondary endpoints included overall response rate (ORR) and complete metabolic response (CMR) rate (assessed at end of treatment [EoT] by PET-CT [Lugano 2014]). Circulating tumor DNA (ctDNA) was measured at C1D1, C2D1, C3D1, and EoT using the PhasED-Seq assay. Results Across escalation and expansion, 78 pts were treated (DL-1, n = 35; DL1, n = 37; DL2, n = 6). Median age was 63.0 years, 56.4% were male, most had high-intermediate/high IPI (3-5) score at diagnosis (64.1%), Ann Arbor stage III-IV disease (83.3%), and germinal center B cell as cell of origin (51.3%); 83.3% pts had DLBCL histology. At data extraction (May 25, 2023), across escalation and expansion, 38 pts had treatment ongoing, 31 completed treatment, and 35 continued to follow-up. A total of 3 pts discontinued due to AEs, 1 each at DL-1, DL1, and DL2. In the safety population (n = 78), median GOLCA relative dose intensity (RDI) was 99.4%; 82.1% of pts received RDI ≥ 85%. RDI for CHOP components was > 90%. A total of 73 (93.6%) pts had ≥ 1 treatment-emergent AE (TEAE); 70 (89.7%) pts had ≥ 1 TEAE considered related to GOLCA; 65 (83.3%) pts had ≥ 1 grade 3/4 TEAE, 62 (79.5%) pts had ≥ 1 grade 3/4 TEAE considered related to GOLCA. The most frequently occurring grade 3/4 TEAEs were neutropenia (76.9%) and thrombocytopenia (32.1%) ( Table). A total of 30 (38.5%) pts had serious TEAEs, most frequently febrile neutropenia (preferred term: 11 pts, 14.1%); 12 (15.4%) pts had serious TEAEs of infection or infestation (system organ class); 6 pts (7.7%) had venous thromboembolisms considered related to GOLCA (4 deep vein thrombosis, 1 superficial thrombosis, 1 pulmonary embolism). Treatment-related AEs leading to GOLCA dose reduction or discontinuation occurred in 11 (14.1%) pts and 6 (7.7%) pts, respectively. After a median follow-up time of 4.1 months (range 0.3-12.3) and among all treated pts with EoT response available, 21/25 had CMR; together, 14/14 pts who received GOLCA 0.4 mg (DL1 and DL2) achieved CMR at EoT ( Figure). Among efficacy-evaluable pts (n = 56), ORR was 91.1% (95% CI 80.4-97.0). Pts treated with GOLCA at DL-1 and DL1 who were ctDNA high-risk (≥ 2.5 log hGE/mL) responded to study treatment (CMR-PMR) and had early decreases in ctDNA (Kaplan et al. ASH 2023). Conclusions GOLCA demonstrated a manageable safety profile, showed good combinability with R-CHOP, and did not compromise delivery of curative treatment. Efficacy results and substantial ctDNA decrease indicate robust clinical activity in frontline DLBCL, with a high CMR rate at EoT, particularly among patients treated at DL1. Study support Bristol Myers Squibb.

Control of magnon-magnon coupling in Ni80Fe20 nanocross arrays through system dimensions

Hybrid magnonics, founded on the coherent interplay between magnons and various quasiparticles, provides avenues for quantum transduction and the seamless transmission of coherent information. Magnon-magnon coupling, which exhibits remarkable coupling strength advantages over light-matter interactions, has emerged as a promising field. This research investigates magnon-magnon coupling in Ni80Fe20 nanocross arrays, with a focus on controlling the anticrossing phenomenon. Through a methodical adjustment of the nanocross arm length, it becomes possible to fine-tune the strength of coupling. The significance of the observed effect becomes evident when examining the power and phase profiles of distinct spin-wave (SW) modes in close proximity to and at a considerable distance from the anticrossing point. The research contributes to bridging the gap in hybrid quasi-particle interactions and offers insights into magnon-magnon coupling control. The findings open avenues for efficient magnon-based technologies and systems enabling efficient control of SW propagation characteristics and coupling, with implications for efficient quantum information processing architectures.

Metasurfaces for generating higher-order Poincaré beams by polarization-selective focusing and overall elimination of co-polarization components.

Focused higher-order Poincaré (HOP) beams are of particular interest because they facilitate understanding the exotic properties of structured light and their applications in classical physics and quantum information. However, generating focused HOP beams using metasurfaces is challenging. In this study, we proposed a metasurface design comprising two sets of metal nanoslits for generating coaxially focused HOP beams. The nanoslits were interleaved on equispaced alternating rings. The initial rings started at the two adjacent Fresnel zones to provide opposite propagation phases for overall elimination of the co-polarization components. With the designed hyperbolic and helical profiles of the geometric phases, the two vortices of the opposite cross-circular-polarizations were formed and selectively focused, realizing HOP beams of improved quality. Simulations and experimental results demonstrated the feasibility of the proposed metasurface design. This study is of significance in the integration of miniaturized optical devices and enriches the application areas of metasurfaces.

Метод Гаусса-Ньютона в задаче оптимизации расчёта осесимметричной фазовой функции по данным гильберт-диагностики

A method for reconstructing phase disturbances of a probing light field using the iterative Gauss-Newton algorithm is discussed as part of the Hilbert diagnostics development of gaseous, condensed and reacting media. In this case, the need to determine second derivatives is eliminated, which simplifies the calculations. The method consists of selecting a phase profile, which is specified by a Bezier curve, and hilbertogram calculating. The coincidence of the reference and reconstructed hilbertograms serves as a criterion for the results reliability. The Jacobian matrix for the nonlinear integral operator of Hilbert visualization is obtained. The algorithm is analyzed using a test function. The method development is associated with the algorithm application to the processing of experimental results, including the reconstruction of complex structures in which the phase function is described by several Bezier polynomials.

Liquid crystal anisotropic axicon for the generation of non-diffracting Bessel beams with longitudinally varying polarization

In this work we demonstrate a tunable liquid–crystal element of linear phase profile along the radial coordinate. In combination with a regular refractive axicon, it behaves as an anisotropic axicon, generating the collinear superposition of two orthogonally polarized Bessel beams with different propagation constant. This superposition results in a Bessel beam where the state of polarization (SOP) varies periodically along propagation. Experimental results probe the voltage control of the SOP oscillating period, which agree well with theory. This compound axicon is a very compact and efficient way of generating Bessel beams with polarization modulation, thus representing a significant advantage over other methods reported in the literature that require bulk optical systems based on spatial light modulators.

Comparative analysis between 2D and 3D colorectal cancer culture models for insights into cellular morphological and transcriptomic variations

Drug development is a time-consuming and expensive process, given the low success rate of clinical trials. Now, anticancer drug developments have shifted to three-dimensional (3D) models which are more likely to mimic tumor behavior compared to traditional two-dimensional (2D) cultures. A comparative study among different aspects was conducted between 2D and 3D cultures using colorectal cancer (CRC) cell lines, in addition, Formalin-Fixed Paraffin-Embedded (FFPE) block samples of patients with CRC were used for evaluation. Compared to the 2D culture, cells grown in 3D displayed significant (p < 0.01) differences in the pattern of cell proliferation over time, cell death phase profile, expression of tumorgenicity-related genes, and responsiveness to 5-fluorouracil, cisplatin, and doxorubicin. Epigenetically, 3D cultures and FFPE shared the same methylation pattern and microRNA expression, while 2D cells showed elevation in methylation rate and altered microRNA expression. Lastly, transcriptomic study depending on RNA sequencing and thorough bioinformatic analyses showed significant (p-adj < 0.05) dissimilarity in gene expression profile between 2D and 3D cultures involving thousands of genes (up/down-regulated) of multiple pathways for each cell line. Taken together, the study provides insights into variations in cellular morphologies between cells cultured in 2D and 3D models.