Isomeric fluorescence sensors for wide range detection of ionizing radiations

In order to achieve a wider range of ionizing radiations detection,novel fluorescence sensing materials have been developed that utilize the fluorescence enhancement phenomenon caused by the intramolecular photoinduced electron transfer(PET)effect.Two perylene diimide isomers PDI-P and PDI-B were designed and synthesized,and their molecular structures were characterized by high-resolution Fourier transform mass spectrometry(HRMS),nuclear magnetic resonance hydrogen and carbon spectroscopy(~1H and~(13)C NMR).The interaction between ionizing radiation and fluorescent molecules was simulated by HCl titration.The results show that combining PDIs and HCl can improve fluorescence through the retro-PET process.Despite the similarities in chemical structures,the fluorescent enhancement multiple of PDI-B with aromatic amine as electron donor is much higher than that of PDI-P with alkyl amine.In the direct irradiation experiments of ionizing radiation,the emission enhancement multiples of PDI-P and PDI-B are 2.01 and 45.4,respectively.Furthermore,density functional theory(DFT)and time-dependent density functional theory(TDDFT)calculations indicate that the HOMO and HOMO-1 energy ranges of PDI-P and PDI-B are 0.54 e V and 1.13 e V,respectively.A wider energy range has a stronger driving force on electrons,which is conducive to fluorescence quenching.Both femtosecond transient absorption spectroscopy(fs-TAS)and transient fluorescence spectroscopy(TFS)tests show that PDI-B has shorter charge separation lifetime and higher electron transfer rate constant.Although both isomers can significantly reduce LOD during PET process,PDI-B with aromatic amine has a wider detection range of 0.118—240 Gy due to its larger emission enhancement,which is a leap of three orders of magnitude.It breaks through the detection range of gamma radiation reported in existing studies,and provides theoretical support for the further study of sensitive and effective new materials for ionizing radiation detection.

Total ionizing dose effect modeling method for CMOS digital-integrated circuit

Simulating the total ionizing dose(TID)of an electrical system using transistor-level models can be difficult and expensive,particularly for digital-integrated circuits(ICs).In this study,a method for modeling TID effects in complementary metaloxide semiconductor(CMOS)digital ICs based on the input/output buffer information specification(IBIS)was proposed.The digital IC was first divided into three parts based on its internal structure:the input buffer,output buffer,and functional area.Each of these three parts was separately modeled.Using the IBIS model,the transistor V-I characteristic curves of the buffers were processed,and the physical parameters were extracted and modeled using VHDL-AMS.In the functional area,logic functions were modeled in VHDL according to the data sheet.A golden digital IC model was developed by combining the input buffer,output buffer,and functional area models.Furthermore,the golden ratio was reconstructed based on TID experimental data,enabling the assessment of TID effects on the threshold voltage,carrier mobility,and time series of the digital IC.TID experiments were conducted using a CMOS non-inverting multiplexer,NC7SZ157,and the results were compared with the simulation results,which showed that the relative errors were less than 2%at each dose point.This confirms the practicality and accuracy of the proposed modeling method.The TID effect model for digital ICs developed using this modeling technique includes both the logical function of the IC and changes in electrical properties and functional degradation impacted by TID,which has potential applications in the design of radiation-hardening tolerance in digital ICs.

Total Ionizing Dose Radiation Effects on MOS Transistors with Different Layouts

Both nMOS and pMOS transistors with two-edged and multi-finger layouts are fabricated in a standard commercial 0.6μm CMOS/bulk process to study their total ionizing dose （TID） radiation effects. The leakage current, threshold voltage shift, and transconductance of the devices are monitored before and after T-ray irradiation. Different device bias conditions are used during irradiation. The experiment results show that TID radiation effects on nMOS devices are very sensitive to their layout structures. The impact of the layout on TID effects on pMOS devices is slight and can be neglected.

Ionizing and non-ionizing kerma factors in silicon for China Spallation Neutron Source neutron spectrum

The quantification of ionizing energy deposition and non-ionizing energy deposition plays a critical role in precision neutron dosimetry and in the separation of the displacement damage effects and ionizing effects induced by neutron radiation on semiconductor devices. In this report, neutrons generated by the newly built China Spallation Neutron Source (CSNS) are simulated by Geant4 in semiconductor material silicon to calculate the ionizing and non-ionizing kerma factors. Furthermore, the integral method is applied to calculate neutron-induced ionizing at the CSNS and non-ionizing kerma factors according to the standard neutron nuclear database and the incident neutron spectrum. In addition, thermoluminescence dosimeters are utilized to measure the ionizing energy deposition and six series of bipolar junction transistors are used to measure the non-ionizing energy deposition based on their neutron damage constants. The calibrated kerma factors that were experimentally measured agreed well with the simulation and integral calculation results. This report describes a complete set of methods and fundamental data for the analysis of neutron-induced radiation effects at the CSNS on silicon-based semiconductor devices.

Combination of genistein with ionizing radiation on andro-gen-independent prostate cancer cells

Aim: To study the effect of the combined use of genistein and ionizing radiation (IR) on prostate DU145 cancer cells. Methods: DU145, an androgen-independent human prostate cancer cell line, was used in the experiment. Clonogenic assay was used to compare the survival of DU145 cells after treatments with genistein alone and in combination with graded IR. Apoptosis was assayed by DNA ladder and TUNEL stain. Cell cycle alterations were observed by flow cytometry and related protein expressions by immunoblotting. Results: Clonogenic assay demonstrated that genistein, even at low to medium concentrations, enhanced the radiosensitivity of DU145 cells. Twenty-four hours after treatment with IR and/or genistein, apoptosis was mainly seen with genistein at high concentrations and was minimally related to IR. At 72 h, apoptosis also occurred in treatment with lower concentration of genistein, especially when combined with IR. While both IR and genistein led to G2/M cell cycle arrest, combination of them further increased the DU145 cells at G2/M phase. This Gz/M arrest was largely maintained at 72 h, accompanied by increasing apoptosis and hyperdiploid cell population. Cell-cycle related protein analysis disclosed biphasic changes in cyclin B1 and less dramatically cdc-2, but stably elevated p21cipl levels with increasing genistein concentrations. Conclusion: Genistein enhanced the radiosensitivity of DU145 prostate cancer cells. The mechanisms might be involved in the increased apoptosis, prolonged cell cycle arrest and impaired damage repair.

Effect of Ionizing Radiation on the Expression of p16, CyclinDI and CDK4 in Mouse Thymocytes and Splenocytes

Objective To investigate the effect of ionizing radiation on the expression of p16, CyclinDl, and CDK4 in mouse thymocytes and splenocytes. Methods Fluorescent staining and flow cytometry analysis were employed for the measurement of protein expression. Results In time course experiments, it was found that the expression of p16 protein was significantly increased at 8, 24, and 48 h for thymocytes (P<0.05, P<0.01, and P<0.05, respectively) and at 24 h for splenocytes (P<0.05) after whole body irradiation (WBI) with 2.0 Gy X-rays. However, the expression of CDK4 protein was significantly decreased from 8 h to 24 h for thymocytes (P<0.05,P<0.01) and from 8 h to 72 h for splenocytes (P<0.05-P<0.01). In dose effect experiments, it was found that the expression of p16 protein in thymocytes and splenocytes was significantly increased at 24 h after WBI with 1.0, 2.0, and 4.0 Gy (P<0.05-P<0.01), whereas the expression of CDK4 protein was significantly decreased with 2.0Gy for thymocytes (P<0.05) and 0.5-6.0 Gy for splenocytes (P<0.05-P<0.01). Results also showed that the expression of CyclinDl protein decreased markedly in both thymocytes and splenocytes after exposure. Conclusion The results indicate that the expression of p 16 protein in thymocytes and splenocytes can be induced by ionizing radiation, and the p16-CyclinD1/CDK4 pathway may play an important role for G1 arrest of thymocytes induced by X-rays.

New Method of Total Ionizing Dose Compact Modeling in Partially Depleted Silicon-on-Insulator MOSFETs

On the basis of a detailed discussion of the development of total ionizing dose （TID） effect model, a new commercial-model-independent TID modeling approach for partially depleted silicon-on-insulator metal-oxide- semiconductor field effect transistors is developed. An exponential approximation is proposed to simplify the trap charge calculation. Irradiation experiments with 60Co gamma rays for IO and core devices are performed to validate the simulation results. An excellent agreement of measurement with the simulation results is observed.

Machine learning-based analyses for total ionizing dose effects in bipolar junction transistors

Machine learning methods have proven to be powerful in various research fields.In this paper,we show that research on radiation effects could benefit from such methods and present a machine learning-based scientific discovery approach.The total ionizing dose(TID)effects usually cause gain degradation of bipolar junction transistors(BJTs),leading to functional failures of bipolar integrated circuits.Currently,many experiments of TID effects on BJTs have been conducted at different laboratories worldwide,producing a large amount of experimental data which provides a wealth of information.However,it is difficult to utilize these data effectively.In this study,we proposed a new artificial neural network(ANN)approach to analyze the experimental data of TID effects on BJTs An ANN model was built and trained using data collected from different experiments.The results indicate that the proposed ANN model has advantages in capturing nonlinear correlations and predicting the data.The trained ANN model suggests that the TID hardness of a BJT tends to increase with base current I.A possible cause for this finding was analyzed and confirmed through irradiation experiments.

Effect of ionizing radiation on transcription of colorectal cancer MDR1 gene of HCT-8 cells

Objective:To discuss effect of ionizing radiation on transcription of colorectal cancer multidrug resistance(MDR) 1 gene of HCT-8 cells.Methods:Total RNA was extracted by guanidine thiocyanate one-step method.Northern blot was applied to detect transcription level of MDR1 gene.The expression of P-gp protein was detected by flow cytometry.Results:The expression of MDRl of normal colorectal cancer HCT-8 cells was low.It was increased by 8.35 times under stimulus with 2 Gy.When treated with low doses in advance,high expressed MDR was decreased significantly under 0.05,0.1 Gy,which was 69.00%,62.89%in 2 Cy group and 5.77 times,5.25 times in sham irradiation group.No obvious difference was detected between(0.2+2) Gy group and 2 Gy group.Compared with sham irradiation group,the percentage of P-gp positive cells after radiation of a high 2 Gy dose was increased significantly(P【0.01).When treated with high radiation dose following low radiation dose(0.05 Gy,0.1 Gy) in advance,the percentage of P-gp positive cells were also increased significantly.The percentage of P-gp positive cells were increased obviously in 0.2 Gy and 2 Gy groups.Compared with simple high radiation 2 Gy group,the percentage of P-gp positive cells was decreased significantly(P【0.05).Conclusions: Low radiation dose can reverse multidrug resistance of colorectal cancer cells caused by high radiation dose.

Autophagic cell death induced by reactive oxygen species is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells

AIM To investigate whether autophagic cell death is involved in hyperthermic sensitization to ionizing radiation in human hepatocellular carcinoma cells, and to explore the underlying mechanism.METHODS Human hepatocellular carcinoma cells were treated with hyperthermia and ionizing radiation. MTT and clonogenic assays were performed to determine cell survival. Cell autophagy was detected using acridine orange staining and flow cytometric analysis, and the expression of autophagy-associated proteins, LC3 and p62, was determined by Western blot analysis. Intracellular reactive oxygen species(ROS) were quantified using the fluorescent probe DCFH-DA.RESULTS Treatment with hyperthermia and ionizing radiation significantly decreased cell viability and surviving fraction as compared with hyperthermia or ionizing radiation alone. Cell autophagy was significantly increased after ionizing radiation combined with hyperthermia treatment, as evidenced by increased formation of acidic vesicular organelles, increased expression of LC3 II and decreased expression of p62. Intracellular ROS were also increased after combined treatment with hyperthermia and ionizing radiation. Pretreatment with N-acetylcysteine, an ROS scavenger, markedly inhibited the cytotoxicity and cell autophagy induced by hyperthermia and ionizing radiation.CONCLUSION Autophagic cell death is involved in hyperthermic sensitization of cancer cells to ionizing radiation, and its induction may be due to the increased intracellular ROS.

Total ionizing radiation-induced read bit-errors in toggle magnetoresistive random-access memory devices

The 1-Mb and 4-Mb commercial toggle magnetoresistive random-access memories（MRAMs） with 0.13 μm and 0.18-μm complementary metal–oxide–semiconductor（CMOS） process respectively and different magnetic tunneling junctions（MTJs） are irradiated with a Cobalt-60 gamma source. The electrical functions of devices during the irradiation and the room temperature annealing behavior are measured. Electrical failures are observed until the dose accumulates to 120-krad（Si） in 4-Mb MRAM while the 1-Mb MRAM keeps normal. Thus, the 0.13-μm process circuit exhibits better radiation tolerance than the 0.18-μm process circuit. However, a small quantity of read bit-errors randomly occurs only in 1-Mb MRAM during the irradiation while their electrical function is normal. It indicates that the store states of MTJ may be influenced by gamma radiation, although the electrical transport and magnetic properties are inherently immune to the radiation. We propose that the magnetic Compton scattering in the interaction of gamma ray with magnetic free layer may be the origin of the read bit-errors. Our results are useful for MRAM toward space application.

Synergistic effects of total ionizing dose and radiated electromagnetic interference on analog-to-digital converter

The influence of combined total ionization dose(TID)and radiated electromagnetic interference(EMI)in a commercial analog-to-digital converter(ADC)was studied.The degradation of the direct-current response,the static parameters,and the dynamic parameters caused by the TID and EMI separately and synergistically is presented.The experimental results demonstrate that the increase in TID intensifies data error and the signal-tonoise ratio(SNR)degradation caused by radiated EMI.The cumulative distribution function of EMI failure with respect to data error and SNR with different TIDs was extracted.The decreasing trend of the threshold was acquired with a small sample size of five for each TID group.The result indicates that the ADC is more sensitive in a compound radiation environment.

Synergistic effect of total ionizing dose on single event effect induced by pulsed laser microbeam on SiGe heterojunction bipolar transistor

The synergistic effect of total ionizing dose（TID） on single event effect（SEE） in SiGe heterojunction bipolar transistor（HBT） is investigated in a series of experiments. The SiGe HBTs after being exposed to 60 Co g irradiation are struck by pulsed laser to simulate SEE. The SEE transient currents and collected charges of the un-irradiated device are compared with those of the devices which are irradiated at high and low dose rate with various biases. The results show that the SEE damage to un-irradiated device is more serious than that to irradiated SiGe HBT at a low applied voltage of laser test. In addition, the g irradiations at forward and all-grounded bias have an obvious influence on SEE in the SiGe HBT, but the synergistic effect after cutting off the g irradiation is not significant. The influence of positive oxide-trap charges induced by TID on the distortion of electric field in SEE is the major factor of the synergistic effect. Moreover, the recombination of interface traps also plays a role in charge collection.

Surveying ionizing radiations in real time using a smartphone

Surveying ionizing radiations of the surrounding with a smartphone provides a low-cost and convenient utility for the general public. We developed a smartphone application(App) that uses the built-in camera with a CMOS sensor and a radiation signal extraction algorithm.After a calibration through a series of radiation exposures,the App could display radiation dose rate and cumulative dose in real time without requiring covering the camera lens. A smartphone with this App can be used as a fast survey tool for ionizing radiations.

Inhibition of Ciliogenesis Enhances the Cellular Sensitivity to Temozolomide and Ionizing Radiation in Human Glioblastoma Cells

Objective To investigate the function of primary cilia in regulating the cellular response to temozolomide(TMZ)and ionizing radiation(IR)in glioblastoma(GBM).Methods GBM cells were treated with TMZ or X-ray/carbon ion.The primary cilia were examined by immunostaining with Arl13 b andγ-tubulin,and the cellular resistance ability was measured by cell viability assay or survival fraction assay.Combining with cilia ablation by IFT88 depletion or chloral hydrate and induction by lithium chloride,the autophagy was measured by acridine orange staining assay.The DNA damage repair ability was estimated by the kinetic curve ofγH2 AX foci,and the DNAdependent protein kinase(DNA-PK)activation was detected by immunostaining assay.Results Primary cilia were frequently preserved in GBM,and the induction of ciliogenesis decreased cell proliferation.TMZ and IR promoted ciliogenesis in dose-and time-dependent manners,and the suppression of ciliogenesis significantly enhanced the cellular sensitivity to TMZ and IR.The inhibition of ciliogenesis elevated the lethal effects of TMZ and IR via the impairment of autophagy and DNA damage repair.The interference of ciliogenesis reduced DNA-PK activation,and the knockdown of DNA-PK led to cilium formation and elongation.Conclusion Primary cilia play a vital role in regulating the cellular sensitivity to TMZ and IR in GBM cells through mediating autophagy and DNA damage repair.

Identification of Two Novel Mitochondrial DNA Deletions Induced by Ionizing Radiation

Abstract Objective We identify ionizing radiation-induced mitochondrial DNA （mtDNA） deletions in human lymphocytes and their distribution in normal populations. Methods Long-range polymerase chain reactions （PCR） using two pairs of primers specific for the human mitochondrial genome were used to analyze the lymphoblastoid cell line following exposure to 10 Gy 6~Co y-rays. Limited-condition PCR, cloning and sequencing techniques were applied to verify the mtDNA deletions detected with long-range PCR. Human peripheral blood samples were irradiated with 0, 2 and 6 Gy ^60Co y-rays, and real-time PCR analysis was performed to validate the mtDNA deletions. In order to know the distribution of mtDNA deletions in normal population, 222 healthy Chinese adults were also investigated. Results Two mtDNA deletions, a 7455-bp deletion （nt475-nt7929 in heavy strand） and a 9225-bp deletion （nt7714 -nt369 in heavy strand）, occurring between two 8-bp direct repeats, were identified in lymphoblastoid cells using long-range PCR, limited-condition PCR and sequencing. These results were also observed for ^60Co y-rays irradiated human peripheral blood cells. Conclusion Two novel mtDNA deletions, a 7455-bp deletion and a 9225-bp deletion, were induced by ionizing radiation. The rate of the mtDNA deletions within a normal population was related to the donors＇ age, but was independent of gender.

p21 is Responsible for Ionizing Radiation-induced Bypass of Mitosis

Objective To explore the role of p21 in ionizing radiation-induced changes in protein levels during the G2/M transition and long-term G2 arrest.Methods Protein expression levels were assessed by western blot in the human uveal melanoma 92-1 cells after treatment with ionizing radiation.Depletion of p21 was carried out by employing the siR NA technique.Cell cycle distribution was determined by flow cytometry combined with histone H3 phosphorylation at Ser28,an M-phase marker.Senescence was assessed by senescenceassociated-β-galactosidase（SA-β-gal） staining combined with Ki67 staining,a cell proliferation marker.Results Accompanying increased p21,the protein levels of G2/M transition genes declined significantly in 92-1 cells irradiated with 5 Gy of X-rays.Furthermore,these irradiated cells were blocked at the G2 phase followed by cellular senescence.Depletion of p21 rescued radiation-induced G2 arrest as demonstrated by the upregulation of G2/M transition kinases,as well as the high expression of histone H3 phosphorylated at Ser28.Knockdown of p21 resulted in entry into mitosis of irradiated 92-1 cells.However,cells with serious DNA damage failed to undergo cytokinesis,leading to the accumulation of multinucleated cells.Conclusion Our results indicated that p21 was responsible for the downregulation of G2/M transition regulatory proteins and the bypass of mitosis induced by irradiation.Downregulation of p21 by siR NA resulted in G2-arrested cells entering into mitosis with serious DNA damage.This is the first report on elucidating the role of p21 in the bypass of mitosis.

Suppressing the hot carrier injection degradation rate in total ionizing dose effect hardened nMOSFETs

Annular gate nMOSFETs are frequently used in spaceborne integrated circuits due to their intrinsic good capability of resisting total ionizing dose （TID） effect. However, their capability of resisting the hot carrier effect （HCE） has also been proven to be very weak. In this paper, the reason why the annular gate nMOSFETs have good TID but bad HCE resistance is discussed in detail, and an improved design to locate the source contacts only along one side of the annular gate is used to weaken the HCE degradation. The good TID and HCE hardened capability of the design are verified by the experiments for I/O and core nMOSFETs in a 0.18 μm bulk CMOS technology. In addition, the shortcoming of this design is also discussed and the TID and the HCE characteristics of the replacers （the annular source nMOSFETs） are also studied to provide a possible alternative for the designers.

An investigation of ionizing radiation damage in different SiGe processes

Different SiGe processes and device designs are the critical influences of ionizing radiation damage. Based on the different ionizing radiation damage in SiGe HBTs fabricated by Huajie and an IBM SiGe process, quantitatively numerical simulation of ionizing radiation damage was carried out to explicate the distribution of radiation-induced charges buildup in KT9041 and IBM SiGe HBTs. The sensitive areas of the EB-spacer and isolation oxide of KT9041 are much larger than those of the IBM SiGe HBT, and the distribution of charge buildup in KT9041 is several orders of magnitude greater than that of the IBM SiGe HBT. The result suggests that the simulations are consistent with the experiment, and indicates that the geometry of the EB-spacer, the area of the Si/SiO2 interface and the isolation structure could be contributing to the different ionizing radiation damage.

Ionizing Radiation-Induced RPL23a Reduction Regulates Apoptosis via RPL11-MDM2-p53 Pathway in Mouse Spermatogonia

Objective The expression patterns of ribosomal large subunit protein 23 a(RPL23 a)in mouse testes and GC-1 cells were analyzed to investigate the potential relationship between RPL23 a expression and spermatogonia apoptosis upon exposure to X-ray.Methods Male mice and GC-1 cells were irradiated with X-ray,terminal dUTP nick end-labelling(TUNEL)was performed to detect apoptotic spermatogonia in vivo.Apoptotic rate and cell cycle phase of GC-1 cells were analyzed with flow cytometry.Protein interactions were detected by Immunoprecipitation and protein localization as studied by immunofluorescence.Immunoblotting and real-time PCR were applied to analyze to protein and gene expression.Results Ionizing radiation(IR)increased spermatogonia apoptosis,the expression of RPL11,MDM2 and p53,and decreased RPL23 a expression in mice spermatogonia in vivo and in vitro.RPL23 a knockdown weakened the interaction between RPL23 a and RPL11,leading to p53 accumulation.Moreover,knockdown and IR decreased RPL23 a that induces spermatogonia apoptosis via RPL23 a-RPL11-MDM2-p53 pathway in GC-1 cells.Conclusion These results suggested that IR reduced RPL23 a expression,leading to weakened the RPL23 a-RPL11 interactions,which may have activated p53,resulting in spermatogonia apoptosis.These results provide insights into environmental and clinical risks of radiotherapy following exposure to IR in male fertility.The graphical abstract was available in the web of www.besjournal.com.