Preparation of stealthy etoposide proliposomes and the pharmacokinetics in rabbits

The objectives of the present study were to prepare stealthy etoposide proliposomes and study the pharmacokinetics in rabbits. Blank stealthy liposomes were prepared by film dispersion method. Stealthy etoposide liposomes were prepared by using the ammonium sulfate gradient loading procedure. Vacuum freeze-drying technique was used to dry stealthy etoposide liposomes. Encapsulation efficiency of stealthy etoposide proliposomes was determined by Sephadex chromatography. The morphology was observed by transmission electronic microscope. The particle size and zeta potential were measured by using electrophoretic light scattering technology. The pharmacokinetics in rabbits was evaluated by comparison with etoposide injection and conventional liposomes, respectively. Mean encapsulation efficiency of stealthy etoposide proliposomes was 83.92% ± 3.65% （n = 3）. The liposomes were round or oval. Mean particle size was （124.5 ±26.9） nm, and zeta potential was （-39.50 ±1.04） mV. Following intravenous injection administration at a dose of 1.5 mg/kg etoposide, the three kinds of etoposide preparations were fitted with the two-compartment model. T1/2 β and A UC values of stealthy etoposide proliposomes were （19.26 ± 3.16） h and （26.04 ±3.53） μg/h/mL, respectively. T1/2 β and AUC values of etoposide injection were （0.94 ± 0.21） h and （0.98 ± 0.26） μg/h/mL, respectively. T1/2β and AUC values of conventional liposomes were （7.99 ± 1.36） h and （11.65 ± 1.70） μg/h/mL, respectively. Results indicated that the stealthy etoposide proliposomes could significantly extend the duration of etoposide in blood circulation.

Preparation of anti-resistant stealthy liposomes by incorporating vincristine with quinacrine and the pharmacokinetics in Sprague-Dawley rats

Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups： each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.

Detection of Stealthy False Data Injection Attacks Against Cyber-Physical Systems:A Stochastic Coding Scheme

This paper,from the view of a defender,addresses the security problem of cyber-physical systems(CPSs)subject to stealthy false data injection(FDI)attacks that cannot be detected by a residual-based anomaly detector without other defensive measures.To detect such a class of FDI attacks,a stochastic coding scheme,which codes the sensor measurement with a Gaussian stochastic signal at the sensor side,is proposed to assist an anomaly detector to expose the FDI attack.In order to ensure the system performance in the normal operational context,a decoder is adopted to decode the coded sensor measurement when received at the controller side.With this detection scheme,the residual under the attack can be significantly different from that in the normal situation,and thus trigger an alarm.The design condition of the coding signal covariance is derived to meet the constraints of false alarm rate and attack detection rate.To minimize the trace of the coding signal covariance,the design problem of the coding signal is converted into a constraint non-convex optimization problem,and an estimation-optimization iteration algorithm is presented to obtain a numerical solution of the coding signal covariance.A numerical example is given to verify the effectiveness of the proposed scheme.

Analysis of Stealthy False Data Injection Attacks Against Networked Control Systems:Three Case Studies

This paper mainly investigates the security problem of a networked control system based on a Kalman filter.A false data injection attack scheme is proposed to only tamper the measurement output,and its stealthiness and effects on system performance are analyzed under three cases of system knowledge held by an attacker and a defender.Firstly,it is derived that the proposed attack scheme is stealthy for a residual-based detector when the attacker and the defender hold the same accurate system knowledge.Secondly,it is proven that the proposed attack scheme is still stealthy even if the defender actively modifies the Kalman filter gain so as to make it different from that of the attacker.Thirdly,the stealthiness condition of the proposed attack scheme based on an inaccurate model is given.Furthermore,for each case,the instability conditions of the closed-loop system under attack are derived.Finally,simulation results are provided to test the proposed attack scheme.

A Dual-polarized Frequency Selective Rasorber with a Tunable Transparent Band

A tunable dual polarization absorption-transmission-absorption(A-T-A)frequency selective absorbers(FSR)to address the issue of high insertion loss in current tunable FSRs is proposed.The lumped resistors are loaded onto the lossy layer to absorb electromagnetic waves within the absorption band.The varactor diodes are loaded onto another lossless layer to control the transmission frequency band of the FSR.Its equivalent circuit model is provided.The proposed tunable FSR can change the passband within the range of 14.5~15.5 GHz by changing the bias voltage applied to the lossless transmission layer,while maintaining insertion loss above-1.67 dB.The series resonant structure of the lossy layer generates bilateral absorption bands between 10.2~13.5 GHz and 17.2~22 GHz,with broadband reflection suppression ranging from 10.3 GHz to 22 GHz(70.7%).The prototype is manufactured,and the measured results have verified the simulation results.

Calcium-Doped Boron Nitride Aerogel Enables Infrared Stealth at High Temperature Up to 1300℃

Boron nitride(BN)aerogels,composed of nanoscale BN building units together with plenty of air in between these nanoscale building units,are ultralight ceramic materials with excellent thermal/electrical insulation,great chemical stability and high-temperature oxidation resistance,which offer considerable advantages for various applications under extreme conditions.However,previous BN aerogels cannot resist high temperature above 900℃ in air atmosphere,and hightemperature oxidation resistance enhancement for BN aerogels is still a great challenge.Herein,a calcium-doped BN(Ca-BN)aerogel with enhanced high-temperature stability(up to~1300℃ in air)was synthesized by introducing Ca atoms into crystal structure of BN building blocks via high-temperature reaction between calcium phosphate and melamine diborate architecture.Such Ca-BN aerogels could resist the burning of butane flame(~1300℃)and keep their megashape and microstructure very well.Furthermore,Ca-BN aerogel serves as thermal insulation layer,together with Al foil serving as both low-infrared-emission layer and high-infrared-reflection layer,forming a combination structure that can effectively hide high-temperature target(heated by butane flame).Such successful chemical doping of metal element into crystal structure of BN may be helpful in the future design and fabrication of advanced BN aerogel materials,and further extending their possible applications to extremely high-temperature environments.

Residual-Based False Data Injection Attacks Against Multi-Sensor Estimation Systems

This paper investigates the security issue of multisensor remote estimation systems.An optimal stealthy false data injection(FDI)attack scheme based on historical and current residuals,which only tampers with the measurement residuals of partial sensors due to limited attack resources,is proposed to maximally degrade system estimation performance.The attack stealthiness condition is given,and then the estimation error covariance in compromised state is derived to quantify the system performance under attack.The optimal attack strategy is obtained by solving several convex optimization problems which maximize the trace of the compromised estimation error covariance subject to the stealthiness condition.Moreover,due to the constraint of attack resources,the selection principle of the attacked sensor is provided to determine which sensor is attacked so as to hold the most impact on system performance.Finally,simulation results are presented to verify the theoretical analysis.

Research on Route Planning Method Based on Active-Attack Strategy

Aimed at modern high-density,high overlapped and powerful antipersonnel stealthy penetration environment,route planning techniques on active-attack strategy were thoroughly and further studied,in order to get good probability of survival and perfect efficiency of task accomplishment.It provides a new thought for and a new solution to the application of route planning in new era.

On Zero Dynamics and Controllable Cyber-Attacks in Cyber-Physical Systems and Dynamic Coding Schemes as Their Countermeasures

In this paper, we study stealthy cyber-attacks on actuators of cyber-physical systems(CPS), namely zero dynamics and controllable attacks. In particular, under certain assumptions, we investigate and propose conditions under which one can execute zero dynamics and controllable attacks in the CPS. The above conditions are derived based on the Markov parameters of the CPS and elements of the system observability matrix. Consequently, in addition to outlining the number of required actuators to be attacked, these conditions provide one with the minimum system knowledge needed to perform zero dynamics and controllable cyber-attacks. As a countermeasure against the above stealthy cyber-attacks, we develop a dynamic coding scheme that increases the minimum number of the CPS required actuators to carry out zero dynamics and controllable cyber-attacks to its maximum possible value. It is shown that if at least one secure input channel exists, the proposed dynamic coding scheme can prevent adversaries from executing the zero dynamics and controllable attacks even if they have complete knowledge of the coding system. Finally, two illustrative numerical case studies are provided to demonstrate the effectiveness and capabilities of our derived conditions and proposed methodologies.

NIR-activated nanosystems with self-modulated bacteria targeting for enhanced biofilm eradication and caries prevention

The efficacious delivery of antimicrobial drugs to intractable oral biofilms remains a challenge due to inadequate biofilm penetration and lack of pathogen targeting.Herein,we have developed a microenvironment-activated poly(ethylene glycol)(PEG)-sheddable nanoplatform to mediate targeted delivery of drugs into oral biofilms for the efficient prevention of dental caries.The PEGylated nanoplatform with enhanced biofilm penetration is capable of deshielding the PEG layer under slightly acidic conditions in a PEG chain length-dependent manner to re-expose the bacteria-targeting ligands,thereby facilitating targeted codelivery of ciprofloxacin(CIP)and IR780 to the bacteria after accumulation within biofilms.The nanoplatform tends to induce bacterial agglomeration and suffers from degradation in the acidic oral biofilm microenvironment,triggering rapid drug release on demand around bacterial cells.The self-modulating nanoplatform under near-infrared(NIR)irradiation accordingly displays greatly augmented potency in oral biofilm penetration and disruption compared with drugs alone.Topical oral treatment with nanoplatforms involving synergetic pharmacological and photothermal/photodynamic trinary therapy results in robust biofilm dispersion and efficacious suppression of severe tooth decay in rats.This versatile nanoplatform can promote local accumulation and specific drug transport into biofilms and represents a new paradigm for targeted drug delivery for the management of oral biofilm-associated infections.

PathMarker:protecting web contents against inside crawlers

Web crawlers have been misused for several malicious purposes such as downloading server data without permission from the website administrator.Moreover,armoured crawlers are evolving against new anti-crawler mechanisms in the arm races between crawler developers and crawler defenders.In this paper,based on one observation that normal users and malicious crawlers have different short-term and long-term download behaviours,we develop a new anti-crawler mechanism called PathMarker to detect and constrain persistent distributed crawlers.By adding a marker to each Uniform Resource Locator(URL),we can trace the page that leads to the access of this URL and the user identity who accesses this URL.With this supporting information,we can not only perform more accurate heuristic detection using the path related features,but also develop a Support Vector Machine based machine learning detection model to distinguish malicious crawlers from normal users via inspecting their different patterns of URL visiting paths and URL visiting timings.In addition to effectively detecting crawlers at the earliest stage,PathMarker can dramatically suppress the scraping efficiency of crawlers before they are detected.We deploy our approach on an online forum website,and the evaluation results show that PathMarker can quickly capture all 6 open-source and in-house crawlers,plus two external crawlers(i.e.,Googlebots and Yahoo Slurp).

PathMarker:protecting web contents against inside crawlers

Web crawlers have been misused for several malicious purposes such as downloading server data without permission from the website administrator.Moreover,armoured crawlers are evolving against new anti-crawler mechanisms in the arm races between crawler developers and crawler defenders.In this paper,based on one observation that normal users and malicious crawlers have different short-term and long-term download behaviours,we develop a new anti-crawler mechanism called PathMarker to detect and constrain persistent distributed crawlers.By adding a marker to each Uniform Resource Locator(URL),we can trace the page that leads to the access of this URL and the user identity who accesses this URL.With this supporting information,we can not only perform more accurate heuristic detection using the path related features,but also develop a Support Vector Machine based machine learning detection model to distinguish malicious crawlers from normal users via inspecting their different patterns of URL visiting paths and URL visiting timings.In addition to effectively detecting crawlers at the earliest stage,PathMarker can dramatically suppress the scraping efficiency of crawlers before they are detected.We deploy our approach on an online forum website,and the evaluation results show that PathMarker can quickly capture all 6 open-source and in-house crawlers,plus two external crawlers(i.e.,Googlebots and Yahoo Slurp).

Base communication model of IP covert timing channels

IP covert timing channel （IPCTC） is an unconventional communication channel which attaches time information to the packets of an overt channel as messages carders, e.g., using different inter-packet delays to transmit messages in a packet-switched network. Although the IPCTCs have many different communication methods, based on the concept of time, we categorized the base communication model of the IPCTCs into three types and then utilized the signal processing theory to build their mathematical models. As a result, the basic characteristics of the IPCTCs＇ base model were formally derived. Hence, the characteristics of any IPCTC can be derived from the base models that consist of the IPCTC. Furthermore, a set of approaches was devised to implement the base model of the IPCTCs in a TCP/IP network. Experimental results show the correctness of the pro- posed base model of the IPCTCs in this paper.