Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

Hot-Carrier Effects on Total Dose Irradiated 65 nm n-Type Metal-Oxide-Semiconductor Field-Effect Transistors

The influence of total dose irradiation on hot-carrier reliability of 65 nm n-type metal-oxide-semiconductor field- effect transistors （nMOSFETs） is investigated. Experimental results show that hot-carrier degradations on ir- radiated narrow channel nMOSFETs are greater than those without irradiation. The reason is attributed to radiation-induced charge trapping in shallow trench isolation （STI）. The electric field in the pinch-off region of the nMOSFET is enhanced by radiation-induced charge trapping in STI, resulting in a more severe hot-carrier effect.

Effects of low dose pre-irradiation on the toxicity of cyclophosphamide

Objective:The aim of the study was to investigate the effects as well as the possible mechanisms of low dose γ-ray pre-irradiation on hepatic damage,DNA damage of peripheral lymphocytes and genetic material damage caused by high dosage of cyclophosphamide(CTX).Methods:Kunming strain male mice were randomly divided into five groups:control group,sham-irradiated group,low dose irradiation group(LDR group),cyclophosphamide chemotherapy group(CTX group) and low dose irradiation combined with chemotherapy group(LDR + CTX group).Having being raised for one week,all the mice were implanted subcutaneously with S180 cells in the left inguen(control group excluded).On days 8 and 11,mice of LDR and LDR + CTX groups were given 75 mGy whole-body γ-irradiation,30 h later mice of CTX and LDR + CTX groups were injected i.p.3.0 mg cyclophosphamide.All the mice were sacrificed on day 13.DNA damage of the peripheral lymphocytes was analyzed using single cell gel electrophoresis(SCGE);ALT activity,total protein(TP) and albumin(ALB) of the plasma were analyzed using automatic biochemistry analyzer;MDA content,SOD and GSH-PX activity of the hepatic homogenate were analyzed using chromometry;genetic material damage was analyzed using micronucleus frequency(MNF) of polychromatoerythrocytes(PCE) in bone marrow.Results:1.Differences of MDA contents,SOD and GSH-PX activity of hepatic homogenate between 5 groups had notable statistical significance(P < 0.01);in control group MDA content was the lowest,SOD and GSH-PX activity were the highest,while in CTX group MDA content was the highest,SOD and GSH-PX activity were the lowest;compared with CTX group MDA content decreased significantly(P < 0.01) and SOD and GSH-PX activity increased significantly(P < 0.05) in LDR + CTX group.2.Differences of ALT activity of plasma between 5 groups had no statistical significance(F = 1.262,P > 0.05).Differences of TP and ALB of plasma between 5 groups had statistical significance(F = 12.879 and 6.336 respectively,P < 0.01);TP and ALB in control group were higher than those of other groups and compared with sham-irradiated group,TP and ALB in LDR group elevated significantly(P < 0.05).3.Differences of DNA damage of peripheral lymphocytes had notable statistical significance(F = 6.383,P < 0.01);DNA damage in control group was the lightest,while DNA damage in CTX group was the severest;compared with CTX group,DNA damage in LDR + CTX group was much lighter(P < 0.05).4.MNF of PCE between 5 groups had remarkable significance(F = 179.652,P < 0.01);compared with control group and sham-irradiated group,MNF in CTX group increased significantly(P < 0.01);compared with CTX group,MNF in LDR + CTX group had a tendency of decline,which had no statistical significance(P > 0.05).Conclusion:1.CTX can damage the hepatic tissue through oxidative stress;75 mGy γ-irradiation before CTX chemotherapy can induce activities of anti-oxidative enzymes,promote elimination of free radicals,so as to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose chemotherapy.2.A 75 mGy γ-irradiation before CTX chemotherapy has no obvious effect on ALT activity of plasma,but may have protective effect on the protein synthesis function of liver.3.High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes;75 mGy γ-irradiation before chemotherapy may have certain protective effect on DNA damage.4.CTX has potent mutagenic effect,can cause significant increase of MNF of PCE;75 mGy γ-ray pre-irradiation did not show obvious protection against genetic toxicity of high-dose CTX chemotherapy.

Microdosimetric Evaluation on the Metallic Nanoparticle-Mediated Dose Enhancement in Radiotherapeutic Proton Irradiation

Monte Carlo simulations are performed on the dosimetric effect of metallic nanoparticles in a clinical proton irradiation.With an in-water hitting model of a single nanoparticle,the secondar.y electrons dose,deposited around the particle surface,is calculated for the proton irradiations in a typical spread-out Bragg peak.The dose enhancement,as the ratio of electron doses from the target particle and background water,is evaluated for the dependence on the depth of hitting,particle size,elements,coating material and thickness.The results indicate a significant dose enhancement on the particle surface within-200 nm,but a fast decay in further distance.The dose enhancement presents a consistency along the spread-out Bragg peak,a positive dependence on both the particle size and electron density,but a strong attenuation by surface coating.Particle cluster may increase the incdividual dose enhajncement by electron crossfire,but is only noticeable in a compact case.The dose enhancement potentiates a radiosensitization use of metallic nanoparticles in clinical proton therapy,but challenqging meanwhile with the narrow ranqge of enhancement effect.

Pattern imprinting in deep sub-micron static random access memories induced by total dose irradiation

Pattem imprinting in deep sub-micron static random access memories （SRAMs） during total dose irradiation is inves- tigated in detail. As the dose accumulates, the data pattern of memory cells loading during irradiation is gradually imprinted on their background data pattern. We build a relationship between the memory cell＇s static noise margin （SNM） and the background data, and study the influence of irradiation on the probability density function of ASNM, which is the difference between two data sides＇ SNMs, to discuss the reason for pattern imprinting. Finally, we demonstrate that, for micron and deep sub-micron devices, the mechanism of pattern imprinting is the bias-dependent threshold shift of the transistor, but for a deep sub-micron device the shift results from charge trapping in the shallow trench isolation （STI） oxide rather than from the gate oxide of the micron-device.

Analysis of functional failure mode of commercial deep sub-micron SRAM induced by total dose irradiation

Functional failure mode of commercial deep sub-micron static random access memory（SRAM） induced by total dose irradiation is experimentally analyzed and verified by circuit simulation. We extensively characterize the functional failure mode of the device by testing its electrical parameters and function with test patterns covering different functional failure modes. Experimental results reveal that the functional failure mode of the device is a temporary function interruption caused by peripheral circuits being sensitive to the standby current rising. By including radiation-induced threshold shift and off-state leakage current in memory cell transistors, we simulate the influence of radiation on the functionality of the memory cell. Simulation results reveal that the memory cell is tolerant to irradiation due to its high stability, which agrees with our experimental result.

Influence of Total Ionizing Dose Irradiation on Low-Frequency Noise Responses in Partially Depleted SOI nMOSFETs

Total ionizing dose effect induced low frequency degradations in 130nm partially depleted silicon-on-insulator （SOI） technology are studied by ^60Co γ -ray irradiation. The experimental results show that the flicker noise at the front gate is not affected by the radiation since the radiation induced trapped charge in the thin gate oxide can be ignored. However, both the Lorenz spectrum noise, which is related to the linear kink effect （LKE） at the front gate, and the flicker noise at the back gate are sensitive to radiation. The radiation induced trapped charge in shallow trench isolation and the buried oxide can deplete the nearby body region and can activate the traps which reside in the depletion region. These traps act as a GR center and accelerate the consumption of the accumulated holes in the floating body. It results in the attenuation of the LKE and the increase of the Lorenz spectrum noise. Simultaneously, the radiation induced trapped charge in the buried oxide can directly lead to an enhanced flicker noise at the back gate. The trapped charge density in the buried oxide is extracted to increase from 2.21×10^18 eV^-1 cm^-3 to 3.59×10^18？eV^-1 cm^-3 after irradiation.

Concurrent chemotherapy and reduced - dose cranial spinal irradiation followed by conformal posterior fossa tumor bed boost for average - risk medulloblastoma: efficacy and patterns of failure

PURPOSE:To review the efficacy and patterns of failure in average-risk medulloblastoma patients treated withconcurrent chemotherapy and reduced-dose cranial spinal irradiation and a conformal tumor bed boost.METH-ODS AND MATERIALS:Thirty-three patients with average risk(defined as<==1.5 cm(2)of residual tumorafter resection,age>3 years,and no involvement of the cerebrospinal fluid or spine)medulloblastoma werediagnosed at our institution between January 1994 and December 2001.They were enrolled in an institutional

The Best Dose for Sterilisation of Greenhouse Whitefly, Trialeurodes vaporariorum （Westwood） （Hem.： Aleyrodidae） by Gamma Radiation

Greenhouse whitefly （GHWF）, Trialeurodes vaporariorum （Westwood） is a very important pest of greenhouse plants, but its resistance to pesticides has rendered it difficult to control by chemical methods in recent years. Sterile insect technique （SIT） is a biological control method which has been used in Area Wide Integrated Pest Management （AWIPM）. This study conducted the possibility of sterilising GHWF adults by gamma radiations emitted from cobalt 60. Longevity of the adults, and the amount of egg laying and sterilisation of eggs were determined under the influence of 50, 60, 70, 80, 90 Gy doses under controlled conditions （65 ± 5% RH, 25 ± 2 ℃, L/D = 16/8）. Normal insects were considered as control （0 dose）. The best combination for mating of normal and sterile adults （normal male × normal female as control, normal male and irradiated female, irradiated male × normal female, and irradiated male × irradiated female） was studied using a factorial design （n = 4）. Results showed that the best irradiating doses were 70 and 80 Gy for females and males respectively. Longevity of irradiated males and females was not significantly different from that of non-irradiated specimens. The best mating model was irradiated males and females.

Total dose irradiation and hot-carrier effects of sub-micro NMOSFETs

Total dose irradiation and the hot-carrier effects of sub-micro NMOSFETs are studied. The results show that the manifestations of damage caused by these two effects are quite different, though the principles of damage formation are somewhat similar. For the total dose irradiation effect, the most notable damage lies in the great increase of the off-state leakage current. As to the hot-carrier effect, most changes come from the decrease of the output characteristics curves as well as the decrease of trans-conductance. It is considered that the oxide-trapped and interface-trapped charges related to STI increase the current during irradiation, while the negative charges generated in the gate oxide, as well as the interface-trapped charges at the gate interface, cause the degradation of the hot-carrier effect. Different aspects should be considered when the device is generally hardened against these two effects.

A novel terminal structure for total dose irradiation hardened of a P-VDMOS

Using positive surface charge instead of traditional γ-ray total dose irradiation, the electric field distribution of a P-channel VDMOS terminal has been analyzed. A novel terminal structure for improving the total dose irradiation hardened of P-channel VDMOS has been proposed, and the structure is simulated and demonstrated with a -150 V P-channel VDMOS. The results show that the peak current density is reduced from 5.51 × 10^3 A/cm^2 to 2.01 × 10^3 A/cm^2, and the changed value of the breakdown voltage is 2.5 V at 500 krad（Si）. Especially, using 60Co and X-ray to validate the results, which strictly match with the simulated values, there is not any added mask or process to fabricate the novel structure, of which the process is compatible with common P-channel VDMOS processes. The novel terminal structure can be widely used in total irradiation hardened P-channel VDMOS design and fabrication, which holds a great potential application in the space irradiation environment.

Abnormal response to irradiation dose of E' center of quartz

In order to obtain accumlated dose for ESR dating, the additive dose method is usu-ally used. When samples are irradiated by an αradioactive source in different doses. theESR signals of some centers of the samples grow up with the increase of irradiation dosesuntil saturation. Models have been suggested and theoretical explanations have beengiven. They believe that the electrons in crystal are in the valence band under