Cybersecurity Games: Mathematical Approaches for Cyber Attack and Defense Modeling

Cyber-attacks targeting individuals and enterprises have become a predominant part of the computer/information age. Such attacks are becoming more sophisticated and prevalent on a day-to-day basis. The exponential growth of cyber plays and cyber players necessitate the inauguration of new methods and research for better understanding the cyber kill chain, particularly with the rise of advanced and novel malware and the extraordinary growth in the population of Internet residents, especially connected Internet of Things (IoT) devices. Mathematical modeling could be used to represent real-world cyber-attack situations. Such models play a beneficial role when it comes to the secure design and evaluation of systems/infrastructures by providing a better understanding of the threat itself and the attacker\u27s conduct during the lifetime of a cyber attack. Therefore, the main goal of this dissertation is to construct a proper theoretical framework to be able to model and thus evaluate the defensive strategies/technologies\u27 effectiveness from a security standpoint. To this end, we first present a Markov-based general framework to model the interactions between the two famous players of (network) security games, i.e., a system defender and an attacker taking actions to reach its attack objective(s) in the game. We mainly focus on the most significant and tangible aspects of sophisticated cyber attacks: (1) the amount of time it takes for the adversary to accomplish its mission and (2) the success probabilities of fulfilling the attack objective(s) by translating attacker-defender interactions into well-defined games and providing rigorous cryptographic security guarantees for a system given both players\u27 tactics and strategies. We study various attack-defense scenarios, including Moving Target Defense (MTD) strategies, multi-stage attacks, and Advanced Persistent Threats (APT). We provide general theorems about how the probability of a successful adversary defeating a defender’s strategy is related to the amount of time (or any measure of cost) spent by the adversary in such scenarios. We also introduce the notion of learning in cybersecurity games and describe a general game of consequences meaning that each player\u27s chances of making a progressive move in the game depend on its previous actions. Finally, we walk through a malware propagation and botnet construction game in which we investigate the importance of defense systems\u27 learning rates to fight against the self-propagating class of malware such as worms and bots. We introduce a new propagation modeling and containment strategy called the learning-based model and study the containment criterion for the propagation of the malware based on theoretical and simulation analysis

Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle size 205.93-352.76 μm.The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model. © 2011 by Tabriz University of Medical Sciences

Preparation, Physicochemical Characterization and Performance Evaluation of Gold Nanoparticles in Radiotherapy

Purpose: The aim of the present study was preparation, physicochemical characterization and performance evaluation of gold nanoparticles (GNPs) in radiotherapy. Another objective was the investigation of anti-bacterial efficacy of gold nanoparticle against E. coli clinical strains. Methods: Gold nanoparticles prepared by controlled reduction of an aqueous HAuCl4 solution using Tri sodium citrate. Particle size analysis and Transmission electron microscopy were used for physicochemical characterization. Polymer gel dosimetry was used for evaluation of the enhancement of absorbed dose. Diffusion method in agar media was used for investigation of anti-bacterial effect. Results: Gold nanoparticles synthesized in size range from 57 nm to 346 nm by planning different formulation. Gold nanoparticle in 57 nm size increased radiation dose effectiveness with the magnitude of about 21 %. At the concentration of 400 ppm, Nano gold exhibited significant anti-bacterial effect against E. coli clinical strains. Conclusion: It is concluded that gold nanoparticles can be applied as dose enhancer in radiotherapy. The Investigation of anti-bacterial efficacy showed that gold nanoparticle had significant effect against E. coli clinical strains

The Effects of Lyophilization on the Physico-Chemical Stability of Sirolimus Liposomes

Purpose: The major limitation in the widespread use of liposome drug delivery system is its instability. Lyophilization is a promising approach to ensure the long-term stability of liposomes. The aim of this study was to prepare sirolimus-loaded liposomes, study their stability and investigate the effect of lyophilization either in the presence or in the absence of lyoprotectant on liposome properties. Methods: Two types of multi-lamellar liposomes, conventional and fusogenic, containing sirolimus were prepared by modified thin film hydration method with different ratio of dipalmitoylphosphatidylcholine (DPPC), cholesterol and dioleoylphosphoethanolamine (DOPE), and were lyophilized with or without dextrose as lyoprotectant. Chemical stability investigation was performed at 4°C and 25°C until 6 months using a validated HPLC method. Physical stability was studied with determination of particle size (PS) and encapsulation efficiency (EE %) of formulations through 6 months. Results: Chemical stability test at 4°C and 25°C until 6 months showed that drug content of liposomes decreased 8.4% and 20.2% respectively. Initial mean EE % and PS were 72.8 % and 582 nm respectively. After 6 months mean EE % for suspended form, lyophilized without lyoprotectant and lyophilized with lyoprotectant were 54.8 %, 62.3% and 67.1 % at 4°C and 48.2%, 60.4 % and 66.8 % at 25°C respectively. Corresponding data for mean PS were 8229 nm, 2397 nm and 688nm at 4°C and 9362 nm, 1944 nm and 737 nm at 25°C respectively. Conclusion: It is concluded that lyophilization with and without dextrose could increase shelf life of liposome and dextrose has lyoprotectant effect that stabilized liposomes in the lyophilization process

Healing the Hill Cipher, Improved Approach to Secure Modified Hill against Zero-plaintext Attack

Hill Cipher is a symmetric cryptosystem that was claimed to suffer from known-plaintext attack for many years. Different methods have been proposed to make this cipher more secure against known attacks. The introduced classic Hill cipher by Tourani and Falahati in 2011 that was devised in two variants and based upon affine transformation, was considered to be more secure against known attacks. Recently, this well modified Hill cipher is claimed to be vulnerable to zero-plaintext attack. In this paper, by using a chaotic map and scrambling methods, a novel cryptosystem based on Tourani and Falahati Hill cipher is presented which overcomes the zero-plaintext attack. The proposed Hill cipher is more reliable and faster

A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption

Purpose. Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. Methods. A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. Results. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. Conclusion. The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption

Effects of polyethylene glycols on intestinal efflux pump expression and activity in Caco-2 cells

The present study was planned to investigate the influence of polyethylene glycols (PEGs) on the activity and expression of P-glycoprotein (P-gp). Sub-toxic concentrations of PEGs in Caco-2 cells were determined using the MTT test assay. Then the measurement of Rhodamine-123 (Rho-123) uptake, a P-gp fluorescence substrate, in Caco-2 cells confronting PEG 400 (1% and 2% w/v), PEG 4000 (2% and 4% w/v), PEG 6000 (2% and 4% w/v), PEG 10000 (2% and 4% w/v), PEG 15000 (1% and 2% w/v), and PEG 35000 (2% and 4% w/v) overnight was taken to elucidate whether non-toxic concentrations of PEGs are able to impact P-gp activity. Furthermore, western blotting was carried out to investigate P-gp protein expression. The results showed that PEG 400 at concentrations of 1% (w/v) and 2% (w/v) and PEG 6000 at the concentration of 4% (w/v) are notably capable of blocking P-gp. Based on the obtained results it is concluded that the mentioned excipients could be used to obstruct P-gp efflux transporter in order to increase the bioavailability of co-administered substrate drug.O presente estudo foi planejado para investigar a influência de polietileno glicóis sobre a atividade e expressão da P- glicoproteína (P-gp) . Concentrações sub-tóxicas de PGPs e em células Caco-2 foram determinadas por meio do ensaio de MTT. Em seguida, efetuou-se a a medida de captura de Rodamina-123 (Rho-123), um substrato fluorescente de P-gp, em células Caco-2, confrontando com PEG 400 (1% e 2% m/v), PEG 4000 (2% e 4% m/v) e PEG 6000 (2% e 4% m /v), PEG 10000 (2% e 4% w/v), PEG 15000 (1% e 2% m/v), e PEG 35000 (2% e 4% m/v). Essa medida foi efetuada durante a noite, para saber se as concentrações não tóxicas de excipientes são capazes de influenciar a actividade da P-gp. Além disso, realizou-se o western blotting para investigar a expressão da proteína P-gp. Os resultados mostraram que o PEG 400, nas concentrações de 1% (m/v) e 2% (m/v), e PEG 6000, na concentração de 4% (m/v) são capazes de bloquear P-gp. Com base nos resultados conclui-se que os excipientes mencionados poderiam ser utilizados para obstruir o efluxo por P-gp, a fim de aumentar a biodisponibilidade de do fármaco co-administrado

A study on Inhibitory Effects of Titanium Dioxide Nanoparticles and its Photocatalytic Type on Staphylococcus aureus, Escherichia coli and Aspergillus flavus

Backgrounds and Objectives: Photocatalyst titanium dioxide nanoparticles can oxidize organic and inorganic compounds of microorganisms in aqueous solutions after exposure to UV light. In the present study, the inhibitory effect of titanium dioxide and its photocatalyst type on Aspergillus flavus, Escherichia coli and Staphylococcus aureus is investigated. Materials and Methods: Toxicogenic strains of Staphylococcus aureus, Escherichia coli and Aspergillus flavus were cultured in their selective media and two groups of samples both included three different concentrations of nanoparticles (0.1, 0.5 and 1 g l-1) and two control samples without any nanoparticles were considered. The first category of samples was placed on the shaker for 20 min, and the second category was irradiated by a UV lamp while shaking for 20, 40 and 60 min on a rotary shaker. Thereafter, they were cultured by using pour plate method in agar and after incubation the colonies were counted. Results and Conclusion: Based on obtained results the photocatalyst titanium dioxide had an inhibitory effect at concentration of 1 g l-1 at the highest timeframe (60 min). In addition, the test variables i.e. the type of bacteria, concentration of nanoparticles and time had a significant effect on the growth inhibition of microorganisms. Regarding the economic aspects of contamination control and its importance in dairy products, application of photocatalystic nanoparticles of titanium dioxide is recommended.

Kinetics study of hydrochlorothiazide lactose liquid state interaction using conventional isothermal arrhenius method under basic and neutral conditions

The Maillard reaction of hydrochlorothiazide (HCTZ) and lactose has been previously demonstrated in pharmaceutical formulations. In this study, the activation energy of - hydrohlorothiazide and lactose interaction in the liquid state was ascertained under basic and neutral conditions. Conventional isothermal High Performance Liquid Chromatography (HPLC) technique was employed to ascertain the kinetic parameters using Arrhenius method. Results: The activation energy obtained was 82.43 and 100.28 kJ/mol under basic and neutral conditions, respectively. Consequently, it can be inferred that Maillard reaction is significantly affected by pH, which can be used as a control factor whenever the reaction potentially occurs