Boron-Containing MOF Nanoparticles with Stable Metabolism in U87-MG Cells Combining Microdosimetry To Evaluate Relative Biological Effectiveness of Boron Neutron Capture Therapy.

Accurate prediction of the relative biological effectiveness (RBE) of boron neutron capture therapy (BNCT) is challenging. The therapy is different from other radiotherapy; the dynamic distribution of boron-containing compounds in tumor cells affects the therapeutic outcome considerably and hampers accurate measurement of the neutron-absorbed dose. Herein, we used boron-containing metal-organic framework nanoparticles (BMOFs) with high boron content to target U87-MG cells and maintain the concentration of the 10B isotope in cells. The content of boron in the cells could maintain 90% (60 ppm) within 20 min compared with that at the beginning; therefore, the accurate RBE of BNCT can be acquired. The effects of BNCT upon cells after neutron irradiation were observed, and the neutron-absorbed dose was obtained by Monte Carlo simulations. The RBE of BMOFs was 6.78, which was 4.1-fold higher than that of a small-molecule boron-containing agent (boric acid). The energy spectrum of various particles was analyzed by Monte Carlo simulations, and the RBE was verified theoretically. Our results suggested that the use of nanoparticle-based boron carriers in BNCT may have many advantages and that maintaining a stable boron distribution within cells may significantly improve the efficiency of BNCT.

Boron-peptide conjugates with angiopep-2 for boron neutron capture therapy.

Boron neutron capture therapy (BNCT) induces intracellular nuclear reaction to destroy cancer cells during thermal neutron irradiation. To selectively eliminate cancer cells but avoid harmful effects on normal tissues, novel boron-peptide conjugates with angiopep-2, namely ANG-B, were constructed and evaluated in preclinical settings. Boron-peptide conjugates were synthesized using solid-phase peptide synthesis, and the molecular mass was validated by mass spectrometry afterwards. Boron concentrations in 6 cancer cell lines and an intracranial glioma mouse model after treatments were analyzed by inductively coupled plasma atomic emission spectroscopy (ICP-AES). Phenylalanine (BPA) was tested in parallel for comparison. In vitro treatment with boron delivery peptides significantly increased boron uptake in cancer cells. BNCT with 5 mM ANG-B caused 86.5% ± 5.3% of clonogenic cell death, while BPA at the same concentration caused 73.3% ± 6.0% clonogenic cell death. The in vivo effect of ANG-B in an intracranial glioma mouse model was evaluated by PET/CT imaging at 31 days after BNCT. The mouse glioma tumours in the ANG-B-treated group were shrunk by 62.9% on average, while the BPA-treated tumours shrank by only 23.0%. Therefore, ANG-B is an efficient boron delivery agent, which has low cytotoxicity and high tumour-to-blood ratio. Based on these experimental results, we expected that ANG-B may leverage BNCT performance in clinical applications in future.

A Boronated Derivative of Temozolomide Showing Enhanced Efficacy in Boron Neutron Capture Therapy of Glioblastoma.

There is an incontestable need for improved treatment modality for glioblastoma due to its extraordinary resistance to traditional chemoradiation therapy. Boron neutron capture therapy (BNCT) may play a role in the future. We designed and synthesized a 10B-boronated derivative of temozolomide, TMZB. BNCT was carried out with a total neutron radiation fluence of 2.4 ± 0.3 × 1011 n/cm2. The effects of TMZB in BNCT were measured with a clonogenic cell survival assay in vitro and PET/CT imaging in vivo. Then, 10B-boronated phenylalanine (BPA) was tested in parallel with TMZB for comparison. The IC50 of TMZB for the cytotoxicity of clonogenic cells in HS683 was 0.208 mM, which is comparable to the IC50 of temozolomide at 0.213 mM. In BNCT treatment, 0.243 mM TMZB caused 91.2% ± 6.4% of clonogenic cell death, while 0.239 mM BPA eliminated 63.7% ± 6.3% of clonogenic cells. TMZB had a tumor-to-normal brain ratio of 2.9 ± 1.1 and a tumor-to-blood ratio of 3.8 ± 0.2 in a mouse glioblastoma model. BNCT with TMZB in this model caused 58.2% tumor shrinkage at 31 days after neutron irradiation, while the number for BPA was 35.2%. Therefore, by combining the effects of chemotherapy from temozolomide and radiotherapy with heavy charged particles from BNCT, TMZB-based BNCT exhibited promising potential for therapeutic applications in glioblastoma treatment.

Off-Grid DOA Estimation Based on Circularly Fully Convolutional Networks (CFCN) Using Space-Frequency Pseudo-Spectrum.

Low-frequency multi-source direction-of-arrival (DOA) estimation has been challenging for micro-aperture arrays. Deep learning (DL)-based models have been introduced to this problem. Generally, existing DL-based methods formulate DOA estimation as a multi-label multi-classification problem. However, the accuracy of these methods is limited by the number of grids, and the performance is overly dependent on the training data set. In this paper, we propose an off-grid DL-based DOA estimation. The backbone is based on circularly fully convolutional networks (CFCN), trained by the data set labeled by space-frequency pseudo-spectra, and provides on-grid DOA proposals. Then, the regressor is developed to estimate the precise DOAs according to corresponding proposals and features. In this framework, spatial phase features are extracted by the circular convolution calculation. The improvement in spatial resolution is converted to increasing the dimensionality of features by rotating convolutional networks. This model ensures that the DOA estimations at different sub-bands have the same interpretation ability and effectively reduce network model parameters. The simulation and semi-anechoic chamber experiment results show that CFCN-based DOA is superior to existing methods in terms of generalization ability, resolution, and accuracy.

A Robust Steered Response Power Localization Method for Wireless Acoustic Sensor Networks in an Outdoor Environment.

The localization of outdoor acoustic sources has attracted attention in wireless sensor networks. In this paper, the steered response power (SRP) localization of band-pass signal associated with steering time delay uncertainty and coarser spatial grids is considered. We propose a modified SRP-based source localization method for enhancing the localization robustness in outdoor scenarios. In particular, we derive a sufficient condition dependent on the generalized cross-correlation (GCC) waveform function for robust on-grid source localization and show that the SRP function with GCCs satisfying this condition can suppress the disturbances induced by the grid distance and the uncertain steering time delays. Then a GCC refinement procedure for band-pass GCCs is designed, which uses complex wavelet functions in multiple sub-bands to filter the GCCs and averages the envelopes of the filtered GCCs as the equivalent GCC to match the sufficient condition. Simulation results and field experiments demonstrate the excellent performance of the proposed method against the existing SRP-based methods.

The Kinetic Behaviors of H Impurities in the Li/Ta Bilayer: Application for the Accelerator-Based BNCT.

Hydrogen bubble phenomenon is one of the key issues to be solved in the development of a long-life target system for boron neutron capture therapy (BNCT). In this study, we assessed the kinetic behaviors of H impurities in the nano-composite target from the atomic level. Firstly, two kinds of Li/Ta nanolayer models were constructed, based on the calculated lattice parameters and surface energies. The H solution energy, diffusion mechanism, and hydrogen bubbles formation in the Li/Ta nanostructured bilayer were studied, through theoretical modeling and simulation. Our results show that the Li/Ta interfaces are effective sinks of H atoms because the H solution energies in the interface are lower. Meanwhile, due to the relatively low diffusion barriers, the large-scale H transport through the interface is possible. In addition, although it is more likely to form hydrogen bubbles in the Ta layer, compared with the Li layer, the anti-blistering ability of Ta is more impressive compared with most of other candidate materials. Therefore, the Ta layer is able to act as the hydrogen absorber in the Li/Ta bilayer, and relieve the hydrogen damage of the Li layer in the large-scale proton radiations.

Comparison between pupal and adult X-ray radiation, designed for the sterile insect technique for Aedes albopictus control.

Aedes albopictus is a vector of several human viral diseases, including dengue, chikungunya, and Zika. New control method for Aedes albopictus is needed to replace traditional methods such as chemical insecticides which induce resistance, environmental contamination and toxicity to human. In sterile insect technique (SIT), male mosquitoes are sterilized by γ-ray or X-ray irradiation before released. In this study, the relative effectiveness of X-ray irradiation as a mosquito SIT was investigated. Both pupal and adult Aedes albopictus were subjected to different radiation doses and their emergence, survivorship, longevity, induced sterility, and male mating competitiveness were evaluated. Relative to controls, irradiation had no significant effect on emergence and survivorship but significantly reduce adult longevity. Induced sterility were essentially same for both irradiated pupal and adult. At a dose of 40 Gy, 97% and 100% sterility was respectively achieved for males and females. Mating competitiveness was reduced both in adult males and those derived from pupae exposed to 40 Gy. However, populations can be suppressed by increasing the release ratio (sterile: normal). When the release ratio was 7:1, 74% of the wild population could be suppressed. Overall, the results of the present study showed that SIT based on X-Ray irradiation is scientific and feasible to control Aedes albopictus.

Estimation of low-altitude moving target trajectory using single acoustic array.

An acoustic-signature based method of estimating the flight trajectory of low-altitude flying aircraft that only requires a stationary microphone array is proposed. This method leverages the Doppler shifts of engine sound to estimate the closest point of approach distance, time, and speed. It also leverages the acoustic phase shift over the microphone array to estimate the direction of arrival of the target. Combining these parameters, this algorithm provides a total least square estimate of the target trajectory under the assumption of constant target height, direction, and speed. Analytical bounds of potential performance degradation due to noise are derived and the estimation error caused by signal propagation delay is analyzed, and both are verified with extensive simulation. The proposed algorithm is also validated by processing the data collected in field experiments.