Pattern dependence in synergistic effects of total dose on single-event upset hardness

The pattern dependence in synergistic effects was studied in a 0.18 μm static random access memory（SRAM） circuit.Experiments were performed under two SEU test environments：3 Me V protons and heavy ions.Measured results show different trends.In heavy ion SEU test,the degradation in the peripheral circuitry also existed because the measured SEU cross section decreased regardless of the patterns written to the SRAM array.TCAD simulation was performed.TIDinduced degradation in n MOSFETs mainly induced the imprint effect in the SRAM cell,which is consistent with the measured results under the proton environment,but cannot explain the phenomena observed under heavy ion environment.A possible explanation could be the contribution from the radiation-induced GIDL in pMOSFETs.

Evaluation of Single Field Uniform Dose (SFUD) Proton Pencil Beam Scanning (PBS) Planning Strategy for Lung Mobile Tumor Using a Digital Phantom

Purpose: To quantitatively evaluate four different Proton SFUD PBS initial planning strategies for lung mobile tumor. Methods and Materials: A virtual lung patient’s four-dimensional computed tomography (4DCT) was generated in this study. To avoid the uncertainties from target delineation and imaging artifacts, a sphere with diameter of 3 cm representing a rigid mobile target (GTV) was inserted into the right side of the lung. The target motion is set in superior-inferior (SI) direction from ?5 mm to 5 mm. Four SFUD planning strategies were used based on: 1) Maximum-In-tensity-Projection Image (MIP-CT);2) CT_average with ITV overridden to muscle density (CTavg_muscle);3) CT_average with ITV overridden to tumor density (CTavg_tumor);4) CT_average without any override density (CTavg_only). Dose distributions were recalculated on each individual phase and accumulated together to assess the “actual” treatment. To estimate the impact of proton range uncertainties, +/?3.5% CT calibration curve was applied to the 4DCT phase images. Results: Comparing initial plan to the dose accumulation: MIP-CT based GTV D98 degraded 2.42 Gy (60.10 Gy vs 57.68 Gy). Heart D1 increased 6.19 Gy (1.88 Gy vs 8.07 Gy);CTavg_tumor based GTV D98 degraded 0.34 Gy (60.07 Gy vs 59.73 Gy). Heart D1 increased 2.24 Gy (3.74 Gy vs 5.98 Gy);CTavg_muscle based initial GTV D98 degraded 0.31 Gy (60.4 Gy vs 60.19 Gy). Heart D1 increased 3.44 Gy (4.38 Gy vs 7.82 Gy);CTavg_only based Initial GTV D98 degraded 6.63 Gy (60.11 Gy vs 53.48 Gy). Heart D1 increased 0.30 Gy (2.69 Gy vs 2.96 Gy);in the presence of ±3.5% range uncertainties, CTavg_tumor based plan’s accumulated GTV D98 degraded to 57.99 Gy (+3.5%) 59.38 Gy (?3.5%), and CTavg_muscle based plan’s accumulated GTV D98 degraded to 59.37 Gy (+3.5%) 59.37 Gy (?3.5%). Conclusion: This study shows that CTavg_Tumor and CTavg_Muscle based planning strategies provide the most robust GTV coverage. However, clinicians need to be aware that the actual dose to OARs at distal end of target may increase. The study also indicates that the current SFUD PBS planning strategy might not be sufficient to compensate the CT calibration uncertainty.

Pharmacokinetic study of single and multiple oral dose administration of antofloxacin hydrochloride in healthy male volunteers

Background A new fluroquinolone antibacterial agent,antofloxacin hydrochloride,developed in China,is an 8-NH2 derivant of levofloxacin.The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.Methods An open-label,non-randomized,single and multiple dose clinical trial was conducted.In single dose study,12 subjects took 200 mg antofloxacin hydrochloride.In multiple dose study,12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7.HPLC was used to assay the serum and urinary concentrations of antofloxacin.Results In single dose study,the maximum concentration of drug in serum （Cmax）,the time to reach Cmax （Tmax）,and the area under the serum concentration-time curve （AUC （O-∞）） of antofloxacin were （1.89±0.65） mg/L,（1.29±0.26） hours,39.1%.In multiple dose study,blood concentration of antofloxiacin achieved stable state on day 2 after dosing.The minimum concentration drug in serum （Cmin）,AUCss,mean concentration of drug in serum （Cav）,and degree offluctuation （DF） were （0.73±0.18） mg/L, （47.59±7.85） mg·h^-1·L^-1, （1.98±0.33） mg/L, and 1.74±0.60, respectively. On day 7 after dosing, Tmax ,Cmax and AUC （0-∞） was （1.14±0.50） hours, （2.52±0.38） mg/L, and （48.77±8.44） mg·h^-1·L^-1, respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.Conclusions The regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.

Boosting of the enhanced permeability and retention effect with nanocapsules improves the therapeutic effects of cetuximab

Objective:The introduction of therapeutic antibodies(tAbs)into clinical practice has revolutionized tumor treatment strategies,but their tumor therapy efficiency is still far below expectations because of the rapid degradation and limited tumor accumulation of tAbs.Methods:We developed a nanocapsule-based delivery system to induce the self-augmentation of the enhanced permeability and retention(EPR)effect.This system constantly penetrated across the blood-tumor barrier into the tumor while avoiding the attack of tAbs by the immune system.The biodistribution and therapeutic effect were tested with single dose administration of nanocapsule-tAbs in vivo.Results:The accumulation of Nano(cetuximab)within subcutaneous PC9 tumors was gradually enhanced over 6 days after single dose administration,which was contrary to the biodistribution of native cetuximab.Nano(cetuximab)accumulated in tumor tissues via the EPR effect and released cetuximab.The released cetuximab acted on vascular endothelial cells to destroy the blood-tumor barrier and induce self-augmentation of the EPR effect,which in turn contributed to further tumor accumulation of long-circulating Nano(cetuximab).Compared with single dose administration of native cetuximab,Nano(cetuximab)showed an effective tumor suppressive effect for 3 weeks.Conclusions:The nanocapsule-based delivery system efficiently delivered tAbs to tum or tissues and released them to boost the EPR effect,which facilitated further tumor accumulation of the tAbs.This novel self-augmentation of the EPR effect facilitated by the biological characteristics of tAbs and nanotechnology contributed to the improvement of the therapeutic effect of tAbs,and stimulated new ideas for antibody-based tumor therapy.

Dual antibiotic loaded bone cement in patients at high infection risks in arthroplasty: Rationale of use for prophylaxis and scientific evidence

In view of the demographic changes and projected increase of arthroplasty procedures worldwide,the number of prosthetic joint infection cases will naturally grow.Therefore,in order to counteract this trend more rigid rules and a stricter implementation of effective preventive strategies is of highest importance.In the absence of a"miracle weapon"priorities should lie in evidence-based measures including preoperative optimization of patients at higher infection risks,the fulfilment of strict hygiene rules in the operating theatre and an effective antibiotic prophylaxis regimen.Instead of a"one size fits all"philosophy,it has been proposed to adjust the antibiotic prophylaxis protocol to major infection risks taking into account important patient-and procedure-related risk factors.A stronger focus on the local application mode via use of high dose dual antibioticloaded bone cement in such risk situations may have its advantages and is easy to apply in the theatre.The more potent antimicrobial growth inhibition in vitro and the strong reduction of the prosthetic joint infection rate in risk for infection patients with aid of dual antibiotic-loaded bone cement in clinical studies align with this hypothesis.

The implication from six years of field experiment:the aging process induced lower rice production even with a high amount of biochar application

The single high-dose application of biochar to increase rice yield has been well reported.However,limited information is available about the long-term effects of increasing rice yield and soil fertility.This study was designed to perform a 6-year field experiment to unveil the rice yield with time due to various biochar application strategies.Moreover,an alternative strategy of the Annual Low dose biochar application(AL,8×35%=2.8 t ha^(−1))was also conducted to make a comparison with the High Single dose(HS,22.5 t ha^(−1)),and annual Rice Straw(RS,8 t ha^(−1))amendment to investigate the effects on annual rice yield attributes and soil nutrient concentrations.Results showed that the rice yield in AL with a lower biochar application exceeded that of HS significantly(p<0.05)in the 6th experimental year.The rice yield increased by 14.3%in RS,10.9%in AL,and 4.2%in HS.The unexpectedly higher rice yield in AL than HS resulted from enhanced soil total carbon(TC),pH,and available Ca.However,compared to AL,liable carbon fraction increased by 33.7%in HS,while refractory carbon fraction dropped by 22.3%.Likewise,biochar characterization showed that more oxygen functional groups existed in HS than in AL.Decreasing inert organic carbon pools due to the constant degradation of the aromatic part of biochar in HS led to a lower soil TC than AL,even with a higher amount of biochar application.Likewise,the annual depletion lowered the soil pH and available Ca declination in HS.Based on the obtained results,this study suggested AL as a promising strategy to enhance rice productivity,soil nutrient enrichment,and carbon sequestration in the paddy ecosystem.