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Recent studies have shown that microporous graphene foam (GF) exhibits photoacoustic effect when irradiated with modulated light. Inspired by this phenomenon, we fabricated a light emitting diode (LED)-induced system-level GF speaker that generates photoacoustic waves in a frequency range of 0.2–16 kHz or plays music with high fidelity when illuminated by modulated LED light. LED light modulation is realized by our specially designed driving circuit that combines the AC voltage corresponding to the audio signal (sinusoidal signal or music from a cell phone) and a DC bias. To reveal the effect of the microporous structure of GF on the photoacoustics, we simulated the thermo-acoustic process (the second process of the photoacoustic effect). We built a periodically heated model of micro-spherical air unit with a diameter of 42 μm to investigate the relationship between the heat flow absorbed by the air unit and the thermo-acoustic wave created by it. The simulated results show that in the frequency range of 0.2–16 kHz, the thermo-acoustic pressure correlates with the frequency of heat flow. Moreover, in the diameter range of 10 to 80 μm of the air unit, the thermo-acoustic pressure is directly proportional to the square of the diameter of the air unit, suggesting that the photoacoustic effect can be enhanced by increasing the size of the GF pores to a certain extent. This work demonstrates the light-induced speakers and provides theoretical support for the photoacoustic effect that occurs in materials with microporous structures.

Tunable mid-infrared emission is highly applicable in the fields of molecular spectroscopy and atmospheric monitoring. Recent studies have demonstrated that external electric fields can induce non-zero optical bandgaps of up to 250 meV in graphene materials, thereby paving the way for mid-infrared emissions (3–14 μm) to be realized. Graphene foam (GF) possesses a unique highly porous microstructure, which allows intense reflection or scattering of incident photons and gives rise to efficient interband optical absorption. Enhanced electron–phonon coupling enables free electrons in the conduction band to relax non-radiatively to the 1s-state. Mid-infrared emission is generated owing to electron–hole recombination. In this work, we demonstrate the induction of widely tunable (2.9–8.6 μm) mid-infrared emission in GF by modulated visible laser diode (LD) light with modulation frequencies ranging from 1.5 to 0.5 kHz. The peak emission wavelength correlates with the modulation frequency and is independent of the wavelength of LD light of visible range, whereas the emission intensity is related to the alternating intensity of the LD. Our findings indicate that GF is not only a novel mid-infrared emitting material, but one that promises bandgap flexibility for widely tunable mid-infrared sources.

Background: Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in hematologic malignancies but limited success in solid tumors. GCC19CART, the first clinical candidate from the CoupledCAR solid tumor platform, is designed to overcome the limitations of conventional CAR T-cells in solid tumor malignancies by pairing solid tumor CAR T-cells with CD19 targeting CAR T-cells to amplify proliferation and activation of the solid tumor CAR T component. GCC19CART targets guanylate cyclase-C (GCC) which is expressed in the metastatic lesions of 70%-80% of subjects with colorectal cancers. A Phase 1 investigator-initiated clinical trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer who have received at least 2 prior lines of therapy. Based on a data cutoff on October 20, 2022 21 subjects have been enrolled in 2 dose escalation groups at 5 hospitals in China. Methods: Subjects are screened for GCC expression by immunohistochemistry. Eligible subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of two preassigned doses: 1 × 106 or 2 × 106 CAR T-cells/kg. Endpoints are safety and preliminary evidence of efficacy as determined by CT or PET/CT per RECIST 1.1 or PERCIST 1.0. All responses were confirmed by an independent third-party imaging contract research organization (CRO). Results: 13 subjects have been enrolled to dose level 1 (1 × 106 cells/kg) and 8 subjects have been enrolled to dose level 2 (2 × 106 cells/kg). The most common adverse events were cytokine release syndrome (CRS) in 21/21 subjects (Grade 1 19/21 (90.48%) or Grade 2 2/21 (9.52%)) and diarrhea in 21/21 subjects (Grade 1 6/21 (28.57%) Grade 2 5/21 (23.81%) Grade 3 9/21 (42.86%) or Grade 4 1/21 (4.76%)). Neurotoxicity was observed in 2/21 (9.52%) subjects at Grade 3 or 4 and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 28.6% (6/21). For dose level 1, the overall response rate (ORR) per RECIST 1.1 was 15.4% (2/13). Two subjects demonstrated a partial response (PR) while 3 additional subjects had partial metabolic response (PMR) on PET/CT with stable disease (SD) or progressive disease (PD) per RECIST 1.1. For dose level 2, The ORR per RECIST 1.1 was 50% (4/8). 4 subjects demonstrated a PR (3 at month 1, 1 at month 3 after being SD at month 1) and 2 additional subjects had PMR on PET/CT with SD per RECIST 1.1. Conclusions: preliminary data show that GCC19CART has meaningful dose dependent clinical activity and an acceptable safety profile in relapsed or refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented. A Phase 1 trial of GCC19CART in the US under a cleared IND is expected to enroll patients from mid-2022. Citation Format: Naifei Chen, Chengfei Pu, Lingling Zhao, Ning Li, Chang Wang, Yusheng Huang, Suxia Luo, Xun Li, Zhenzhou Yang, Jun Bie, Ruihong Zhu, Xi Huang, Haiyang Tang, Tingting Liang, Yizhuo Wang, Beibei Jia, Dongqi Chen, Zhao Wu, Yongping Song, Victor Lu, Lei Xiao, Jiuwei Cui. A phase 1 dose escalation study of GCC19CART - a novel CoupledCAR therapy for subjects with metastatic colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1130.

Background: Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in hematologic malignancies but limited success in solid tumors. GCC19CART, the first clinical candidate from the CoupledCAR® solid tumor platform, targets guanylate cyclase-C (GCC) which is expressed in colorectal cancers. A Phase 1 investigator-initiated dose escalation trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer. Based on a data cutoff on September 10, 2021, 15 patients enrolled and 12 patients completed ≥1 evaluation of response and were evaluable. Methods: Subjects with relapsed or refractory metastatic colorectal cancer are screened for GCC expression, with 70% to 80% of subjects expected to demonstrate GCC per historical data. Subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of three doses from 1x106, or 2x106 cells/kg. Endpoints are safety and preliminary evidence of efficacy as determined by CT or PET/CT per RECIST1.1 or PERCIST 1.0. Results: 7 subjects have been enrolled to dose level 1 (1x106 cells/kg) and 5 subjects have been enrolled to dose level 2 (2x106 cells/kg) and have a 1 month post-infusion imaging study available for review. The most common adverse events were cytokine release syndrome (CRS) in 11/12 subjects (Grade 1 10/12 (83.33%) or Grade 2 1/12 (8.33%)) and diarrhea in 12/12 subjects (Grade 1 2/12 (16.67%) Grade 2 2/12 (16.67%) Grade 3 8/12 (66.67%)). Neurotoxicity was observed in 1/12 (8.33%) subjects at Grade 4 and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 41.67% (5/12). For dose level 1, the overall response rate (ORR) per RECIST 1.1 was 28.57% (2/7). Two subjects demonstrated a partial response (PR) while 2 additional subjects had partial metabolic response (PMR) on PET/CT with stable disease (SD) or progressive disease (PD) per RECIST 1.1. For dose level 2, The ORR per RECIST 1.1 was 60% (3/5). 3 subjects demonstrated a PR (2 at month 1, 1 at month 3 after being SD at month 1) and an additional subject had PMR on PET/CT with SD per RECIST 1.1. Conclusions: GCC19CART demonstrated meaningful clinical activity and an acceptable safety profile in relapsed or refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented. A United States based Phase 1 trial of GCC19CART is anticipated for early 2022. Citation Format: Naifei Chen, Chengfei Pu, Lingling Zhao, Chang Wang, Ruihong Zhu, Tingting Liang, Xi Huang, Haiyang Tang, Yizhuo Wang, Beibei Jia, Dongqi Chen, Eugene Kennedy, Zhao Wu, Lei Xiao, Jiuwei Cui. Novel coupledCAR࣪technology for treating colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2747.

One key hurdle for the CAR-T cell treatment of solid tumors is the limited accessibility of solid tumor antigens outside the tumor microenvironment, which prohibits the expansion of solid tumor-targeting CAR-T cells in patients. Here, we report the characterization of prostatic acid phosphatase (PAP) as a feasible CAR-T target for prostate cancer and a novel approach, named CoupledCAR, to expand solid tumor-targeting CAR-T cells lacking solid tumor antigens based on the observation of non-transduced T cells proliferating together with CD19 CAR-T cells during the treatment of acute lymphocyte leukemia. We demonstrated that CoupledCAR can significantly enhance the expansion and antitumor efficacy of PAP CAR-T cells both in vitro and in vivo. Furthermore, we showed that the expansion of solid tumor-targeting CAR-T cells does not depend on CAR/CD3ζ stimulation through direct antigen binding with CAR but enhances the memory status of CAR-T cells and causes little exhaustion. Since the CoupledCAR system does not rely on solid tumor antigens, we propose that it can be utilized in all CAR-T and T cell therapies for the treatment of solid tumors. Citation Format: Zhiyuan Cao, Chengfei Pu, Xianyang Jiang, Guiting Han, Yuzhe Peng, Wensheng Wang, Wei Ding, Xiaogang Shen, Dongqi chen, Beibei Jia, Xiaoqiang Xu, Zhipeng Huang, Xi Huang, Wenbi Liu, Ruihong Zhu, Lee Tian, Christopher Ballas, Victor.X Lu, Zhao Wu, Lei Xiao. Antigen-independent expansion enhances efficacy of CAR-T cells against solid tumor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2838.

The main method of fault diagnosis is to determine the fault location by extracting the fault frequency after the original signal is de-noised, but in many cases it is not enough to judge the fault location only by the fault frequency. In this paper, the correlation filtering method are combined to Morlet wavelet and power spectral entropy to judge the faults of different degrees at the same frequency based on extracting the fault frequency, and the validity of this method is verified by testing the actual bearing fault data. First, a set of wavelet groups with a high correlation coefficient and a maximum correlation coefficient of the original signal were extracted through correlation filtering method based on Morlet wavelet. Then the specific wavelet in the wavelet group was linearly superimposed. finally, the power spectral entropy of the superimposed wavelet was calculated. The power spectral entropy and periodic parameters are used to judge the bearing fault location and its severity. Result indicate that the proposed method is able to distinguish between normal and fault signals and provide a basis for judging the degree of failure.

Background: Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in hematologic malignancies but limited success in solid tumors. GCC19CART, the first clinical candidate from the CoupledCAR ® solid tumor platform, targets guanylate cyclase-C (GCC) which is expressed in colorectal cancers. A Phase 1 investigator-initiated dose escalation trial is underway in China for patients with relapsed or refractory metastatic colorectal cancer. Data presented here are from a single participating institution. Methods: Subjects with relapsed or refractory metastatic colorectal cancer are screened for GCC expression, with 70% to 80% of subjects expected to demonstrate GCC per historical data. Subjects undergo leukapheresis, a single dose of lymphodepleting chemotherapy (fludarabine 30mg/m2 and cyclophosphamide 300mg/m2) 3 days prior to infusion, and then administration of a single infusion of GCC19CART at one of three doses of 1x10 6, 2x10 6, or 3x10 6 cells/kg. Endpoints are safety and preliminary evidence of efficacy as determined by CT or PET/CT per RECIST1.1 or PERCIST 1.0. Results: 5 subjects have been enrolled to dose level 1 (1x10 6 cells/kg) and 5 subjects have been enrolled to dose level 2 (2x10 6 cells/kg) and have a 1-month post-infusion imaging study available for review. The most common adverse events were cytokine release syndrome (CRS) in 10/10 subjects (Grade 1 9/10 (90%) or Grade 2 1/10 (10%)) and diarrhea in 10/10 subjects (Grade 1 3/10 (30%) Grade 2 1/10 (10%) Grade 3 6/10 (60%)). Neurotoxicity was observed in 1/10 (10%) subjects at Grade 4 and resolved with corticosteroids. The combined overall response rate (ORR) for both dose levels was 50% (5/10). For dose level 1, the overall response rate (ORR) per RECIST 1.1 was 40% (2/5). Two subjects demonstrated a partial response (PR) while an additional subject had partial metabolic response (PMR) on PET/CT with stable disease (SD) per RECIST 1.1. For dose level 2, The ORR per RECIST 1.1 was 60% (3/5). 3 subjects demonstrated a PR (2 at month 1, 1 at month 3 after being SD at month 1) and an additional subject had PMR on PET/CT with SD per RECIST 1.1. Conclusions: GCC19CART demonstrated meaningful clinical activity and an acceptable safety profile in relapsed or refractory metastatic colorectal cancer. This trial is ongoing and updated data will be presented. A United States based Phase 1 trial of GCC19CART is anticipated for early 2022. Disclosures Pu: Innovative Cellular Therapeutics: Current Employment. Zhu: Innovative Cellular Therapeutics: Current Employment. Huang: https://www.accme.org/accreditation-rules/standards-for-integrity-independence-accredited-ce/eligibility: Current Employment. Tang: Innovative Cellular Therapeutics: Current Employment. Jia: Innovative Cellular Therapeutics: Current Employment. Chen: Innovative Cellular Therapeutics: Current Employment. Kennedy: Innovative Cellular Therapeutics: Current Employment. Wu: Innovative Cellular Therapeutics: Current Employment. Xiao: Innovative Cellular Therapeutics: Current Employment.

An uncooled infrared focal plane array (FPA) for a multiband optical imaging system monitoring small gas leakages is low in cost but limited by its frame rate and sensitivity. We propose the concept of Archimedean spiral push-broom filtering (ASPBF), where the trajectory of an Archimedean spiral over the FPA is approximated as a straight line. The ASPBF precisely matches the electronic pulse scanning of the uncooled infrared FPA row by row to improve the frame rate. We applied differential imaging to promote gas detection sensitivity. Prototype can detect 11 ml/min of ethylene gas at ΔT = 3 °C with frame rate of 8 fps.

This paper explores from the security problems about whether fix patches and selective repair of the vulnerabilities, which takes computer vulnerabilities and patches associated into comprehensive consideration. Through selecting some key factors as attributes vectors, I propose the selective vulnerability - patch associated repair model by using support vector machine (SVM) classification method in data mining, and use the Matlab to implement the simulation experiment.