121,700 research outputs found

    Novel 5-oxo-hexahydroquinoline derivatives: design, synthesis, in vitro P-glycoprotein-mediated multidrug resistance reversal profile and molecular dynamics simulation study

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    Overexpression of the efflux pump P-glycoprotein (P-gp) is one of the important mechanisms of multidrug resistance (MDR) in many tumor cells. In this study, 26 novel 5-oxo-hexahydroquinoline derivatives containing different nitrophenyl moieties at C-4 and various carboxamide substituents at C-3 were designed, synthesized and evaluated for their ability to inhibit P-gp by measuring the amount of rhodamine 123 (Rh123) accumulation in uterine sarcoma cells that overexpress P-gp (MES-SA/Dx5) using flow cytometry. The effect of compounds with highest MDR reversal activities was further evaluated by measuring the alterations of MES-SA/Dx5 cells' sensitivity to doxorubicin (DXR) using MTT assay. The results of both biological assays indicated that compounds bearing 2-nitrophenyl at C-4 position and compounds with 4-chlorophenyl carboxamide at C-3 demonstrated the highest activities in resistant cells, while they were devoid of any effect in parental nonresistant MES-SA cells. One of the active derivatives, 5c, significantly increased intracellular Rh123 at 100 mu M, and it also significantly reduced the IC50 of DXR by 70.1% and 88.7% at 10 and 25 mu M, respectively, in MES-SA/Dx5 cells. The toxicity of synthesized compounds against HEK293 as a noncancer cell line was also investigated. All tested derivatives except for 2c compound showed no cytotoxicity. A molecular dynamics simulation study was also performed to investigate the possible binding site of 5c in complex with human P-gp, which showed that this compound formed 11 average H-bonds with Ser909, Thr911, Arg547, Arg543 and Ser474 residues of P-gp. A good agreement was found between the results of the computational and experimental studies. The findings of this study show that some 5-oxo-hexahydroquinoline derivatives could serve as promising candidates for the discovery of new agents for P-gp-mediated MDR reversal

    Systemization of Pluggable Transports for Censorship Resistance

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    An increasing number of countries implement Internet censorship at different scales and for a variety of reasons. In particular, the link between the censored client and entry point to the uncensored network is a frequent target of censorship due to the ease with which a nation-state censor can control it. A number of censorship resistance systems have been developed thus far to help circumvent blocking on this link, which we refer to as link circumvention systems (LCs). The variety and profusion of attack vectors available to a censor has led to an arms race, leading to a dramatic speed of evolution of LCs. Despite their inherent complexity and the breadth of work in this area, there is no systematic way to evaluate link circumvention systems and compare them against each other. In this paper, we (i) sketch an attack model to comprehensively explore a censor's capabilities, (ii) present an abstract model of a LC, a system that helps a censored client communicate with a server over the Internet while resisting censorship, (iii) describe an evaluation stack that underscores a layered approach to evaluate LCs, and (iv) systemize and evaluate existing censorship resistance systems that provide link circumvention. We highlight open challenges in the evaluation and development of LCs and discuss possible mitigations.Comment: Content from this paper was published in Proceedings on Privacy Enhancing Technologies (PoPETS), Volume 2016, Issue 4 (July 2016) as "SoK: Making Sense of Censorship Resistance Systems" by Sheharbano Khattak, Tariq Elahi, Laurent Simon, Colleen M. Swanson, Steven J. Murdoch and Ian Goldberg (DOI 10.1515/popets-2016-0028

    Secure and Efficient RNS Approach for Elliptic Curve Cryptography

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    Scalar multiplication, the main operation in elliptic curve cryptographic protocols, is vulnerable to side-channel (SCA) and fault injection (FA) attacks. An efficient countermeasure for scalar multiplication can be provided by using alternative number systems like the Residue Number System (RNS). In RNS, a number is represented as a set of smaller numbers, where each one is the result of the modular reduction with a given moduli basis. Under certain requirements, a number can be uniquely transformed from the integers to the RNS domain (and vice versa) and all arithmetic operations can be performed in RNS. This representation provides an inherent SCA and FA resistance to many attacks and can be further enhanced by RNS arithmetic manipulation or more traditional algorithmic countermeasures. In this paper, extending our previous work, we explore the potentials of RNS as an SCA and FA countermeasure and provide an description of RNS based SCA and FA resistance means. We propose a secure and efficient Montgomery Power Ladder based scalar multiplication algorithm on RNS and discuss its SCAFA resistance. The proposed algorithm is implemented on an ARM Cortex A7 processor and its SCA-FA resistance is evaluated by collecting preliminary leakage trace results that validate our initial assumptions

    Parametrical modeling and design optimization of blood plasma separation device with microchannel mechanism

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    This paper presents an analysis of biofluid behavior in a T-shaped microchannel device and a design optimization for improved biofluid performance in terms of particle liquid separation. The biofluid is modeled with single phase shear rate non-Newtonian flow with blood property. The separation of red blood cell from plasma is evident based on biofluid distribution in the microchannels against various relevant effects and findings, including Zweifach-Fung bifurcation law, Fahraeus effect, Fahraeus-Lindqvist effect and cell free phenomenon. The modeling with the initial device shows that this T-microchannel device can separate red blood cell from plasma but the separation efficiency among different bifurcations varies largely. In accordance with the imbalanced performance, a design optimization is conducted. This includes implementing a series of simulations to investigate the effect of the lengths of the main and branch channels to biofluid behavior and searching an improved design with optimal separation performance. It is found that changing relative lengths of branch channels is effective to both uniformity of flow rate ratio among bifurcations and reduction of difference of the flow velocities between the branch channels, whereas extending the length of the main channel from bifurcation region is only effective for uniformity of flow rate ratio

    Silicon micromachined hollow microneedles for transdermal liquid transfer

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    This paper presents an improved design and fabrication process [ 13 for hollow micro needles with the proper mechanical strength and sharpness to be applied for painless transdermal transfer of liquids. Tests have shown that liquids like blood are drawn into the needle by capillary forces, reducing the need for active pumping. The fabrication method allows different needle shapes like blades and pencils, is robust enough to be applied for largerscale production, and enables the development of a complete micro-TAS for e.g. blood analysis
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