Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val ...substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG.
The use of plastics can be dangerous due to the numerous industrial chemicals they contain. Di(2‐ethylhexyl) phthalate (DEHP), bisphenol A (BPA), and bisphenol S (BPS) are three detrimental organic ...chemicals that are used in the plastic industry. In this work, a highly sensitive photonic crystal (PCL) sensor is theoretically proposed and numerically simulated as a detector for DEHP, BPA, and BPS organic chemicals. The proposed PCL is a 1D that has the structure (GaAs/Si
3
N
4
/TiN)
N
/cavity layer/(GaAs/Si
3
N
4
/TiN)
N
, where
N
is the number of unit cells (UCs). The DEHP, BPA, and BPS analytes are assumed to be separately infiltrated into the cavity layer between two equal numbers of the UCs. The transmission spectra of the PCL are studied using the transfer matrix (TrMx) technique. The most important performance parameter is sensitivity so we have focused on it. A considerable sensitivity enhancement is obtained by raising the defect layer thickness and incidence angle. High sensitivities of 2350.51, 2168.45, and 2042.08 nm RIU
−1
are obtained for DEHP, BPA, and BPS, respectively. In the results obtained, the way can be paved for a simple technique to detect chemical compounds.
The scientific community works hard on developing reliable, rapid, highly sensitive, and low‐cost techniques to detect severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). The current ...techniques can occasionally produce false‐positive results. The development of novel approaches for the identification of SARS‐CoV‐2 is a significant area of research because of the limitations of current methods. A biosensor based on a defective binary photonic crystal (PCL) is proposed to detect SARS‐CoV‐2 concentration herein. The model of pathogen concentration‐dependent refractive index of the analyte is taken into consideration. The concept of operation of the PCL sensor is based on the defect mode shift when any change in the refractive index of the defect layer occurs. The transmission spectra of the PCL are plotted and studied. An optimum incident angle of 80° and a defect layer thickness of 5 μm are found. The relationship between the defect mode's wavelength and the concentration of SARS‐CoV‐2 is investigated and a sensitivity of 2648.3 nm RIU
−1
is attained.
To construct photodetector and photovoltaic devices, light absorption is crucial. Herein, the absorption properties of a photonic crystal (PhC) consisting of high‐ and low‐index dielectric materials ...and a metamaterial defect layer are investigated. Two graphene sheets are assumed to surround the metamaterial layer. The study is theoretically investigated and numerically simulated in the gigahertz region. The metamaterial negative permittivity and permeability are assumed to follow the Drude model. The number of unit cells, graphene chemical potential (GCP), graphene phenomenological scattering rate (GPSR), and the metamaterial layer thickness are varied to examine the PhC tunable absorption properties. The following points are demonstrated: 1) the number of absorbance peaks increases as the number of unit cells increases; 2) when the GCP increases, the absorbance peaks dramatically decay; 3) the number of absorbance peaks in the absorption spectrum is independent of the GCP and GPSR; and 4) the absorbance peaks exhibit a significant enhancement with increasing GPSR. The proposed PhC can be used to design optical devices based on graphene and metamaterials, such as sensors, filters, and absorbers in the GHz range.
A novel absorber consisting of a photonic crystal with a left‐handed material defect layer is proposed. Two graphene sheets are assumed to surround the left‐handed material layer. The following findings are observed. The number of absorbance peaks increases as the number of unit cells increases. When the graphene chemical potential increases, the absorbance peaks dramatically decay.
To ensure good water quality, microbiological contamination in water must be detected. This process is made easier and more distinctive using a photonic crystal fiber (PCF), which offers outstanding ...optical sensing capabilities. Herein, a PCF sensor model is proposed for detecting two types of waterborne bacteria, namely, Vibrio cholera and Escherichia coli bacteria. The core region of the proposed PCF sensor is made up of a single rectangle and the cladding region has 32 rectangular air holes that have the same height and width as the core rectangle. Zeonex is employed as the fiber material. Using Comsol 5.6 which is based on the finite‐element method, the model is numerically analyzed and structured. The simulation verifies the effectiveness of the proposed PCF to detect the analyte samples. Numerous performance indicators are calculated at an operating 2.8 THz. Simulation results show that the proposed PCF sensor is promising. Extremely high relative sensitivity (97.996%), lower effective area (6.3575 × 104 μm2), higher numerical aperture (0.23319), lower effective material loss (0.0034 cm−1), and lower confinement loss (0.1 × 10−14) are obtained which indicate an efficient PCF sensor. Additionally, the simplicity of the PCF design ensures the fabrication possibilities of the proposed sensor.
A photonic crystal fiber sensor is proposed for detecting two types of waterborne bacteria. The core region is made up of a single rectangle and the cladding has 32 rectangular air holes. Zeonex is employed as the fiber material. Using Comsol 5.6, the model is numerically analyzed and structured. A sensitivity (97.996%) is obtained which indicate an efficient sensor.
Numerous therapies aimed at driving an effective anti-glioma response have been employed over the last decade; nevertheless, survival outcomes for patients remain dismal. This may be due to the ...expression of immune-checkpoint ligands such as PD-L1 by glioblastoma (GBM) cells which interact with their respective receptors on tumor-infiltrating effector T cells curtailing the activation of anti-GBM CD8
+
T cell-mediated responses. Therefore, a combinatorial regimen to abolish immunosuppression would provide a powerful therapeutic approach against GBM. We developed a peptide ligand (CD200AR-L) that binds an uncharacterized CD200 immune-checkpoint activation receptor (CD200AR). We sought to test the hypothesis that CD200AR-L/CD200AR binding signals via he DAP10&12 pathways through
in vitro
studies by analyzing transcription, protein, and phosphorylation, and
in vivo
loss of function studies using inhibitors to select signaling molecules. We report that CD200AR-L/CD200AR binding induces an initial activation of the DAP10&12 pathways followed by a decrease in activity within 30 min, followed by reactivation via a positive feedback loop. Further
in vivo
studies using DAP10&12KO mice revealed that DAP10, but not DAP12, is required for tumor control. When we combined CD200AR-L with an immune-stimulatory gene therapy, in an intracranial GBM model
in vivo
, we observed increased median survival, and long-term survivors. These studies are the first to characterize the signaling pathway used by the CD200AR, demonstrating a novel strategy for modulating immune checkpoints for immunotherapy currently being analyzed in a phase I adult trial.
This paper presents a metamaterial-based flexible wearable ultra-wideband (UWB) antenna for breast imaging and wireless body area network (WBAN) applications. The wearable antenna is required to be a ...planar and low-profile structure using flexible materials. The proposed antenna comprises two layers of denim (10 × 10 mm2) and felt (10 × 15 mm2). The antenna was integrated with six metamaterial unit cells using a modified grain rice shape within a split ring resonator to enhance the bandwidth, gain, and directivity and reduce the specific absorption rate value to less than 2 W/kg. The proposed antenna operates within a broad bandwidth range (6.5 GHz–35 GHz) with the maximum gain and directivity of 8.85 dBi and 10 dBi, respectively, and a radiation efficiency of more than 70% over its operating frequency band. The results verified good agreement between the simulation and measurement of the proposed technique in detecting an existing tumor with a diameter of 4 mm from any location inside the breast. The results convincingly proved the capability of the proposed wearable UWB antenna system for both WBAN and breast imaging applications.
To improve the functionality and efficiency of electric vehicles (EVs), the smart battery management system (BMS) is essential. The accurate estimation of the state of health (SOH) and remaining ...useful life (RUL) in BMS enhance battery safety, longevity, and reliability, which enhances EV performance and efficiency. However, the accurate estimation of SOH and RUL is challenging because of capacity degradation during charging and discharging operations. The conventional research to estimate the SOH and RUL of lithium-ion battery (LIB) is based on the single model framework. However, the single model for SOH and RUL estimation may not deliver accurate outcomes due to the complex internal LIB mechanism and varying external conditions. In recent times, the application of expert hybrid techniques (combining two or more models) has drawn huge attention from the research community due to their high accuracy and robustness under varying environmental conditions. Nonetheless, the implementation of hybrid techniques for SOH and RUL estimation for BMS in EVs is currently limited. Therefore, the originality of this work is to provide a thorough review of hybrid methods for SOH and RUL estimation in LIB with an emphasis on methodologies, executions, advantages, disadvantages, accuracy, and contributions. Additionally, the co-estimation of SOH and RUL utilizing the same model is gaining global popularity among researchers. Henceforth, the presented review work also investigates various techniques utilized to co-estimate the SOH and RUL simultaneously. Furthermore, some critical operation factors associated with SOH and RUL estimation framework are analyzed related to the dataset, model execution, battery parameters and their features. The applicability of the reviewed hybrid SOH and RUL estimation techniques are discussed along with current issues and limitations. Lastly, selected future suggestions are provided to guide the automobile sector to develop a reliable and accurate framework utilizing the hybrid and co-estimation framework to estimate the SOH and RUL in LIB.
Organic compound-based sensors are used in a variety of significant fields, including medical research, azeotropic calibration, vegetable oil extraction, the shoe industry and geothermal power ...plants. Here, a high-performance, two-dimensional material-based organic compound sensor has been proposed using a surface plasmon resonance (SPR) nanostructure consisting of a BK7 glass prism, Ag, BaTiO
3
, Ag, graphene and sensing layer. The reflectivity curves of the SPR device have been investigated when the sensing media are Pentane, n-Hexane, n-Heptane and n-Octane. The thickness of the BaTiO
3
layer and the number of graphene sheets have been optimized to maximize the sensitivity. The highest sensitivity attained is 220.83 deg/RIU for n-Octane with 45 nm silver/10 nm BaTiO
3
/8 nm silver and four layers of graphene. We believe that the SPR-based sensors are simple and can replace the spectrometry, chromatography and electrochemical based sensors. The proposed design is extremely effective for diverse applications in biological, industrial and chemical detection because of its simple structure and great performance.
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