Brief announcement: passive and active attacks on audience response systems using software defined radios

Audience response systems, also known as clickers, are used at many academic institutions to offer active learning environments. Since these systems are used to administer graded assignments, and sometimes even exams, it is crucial to assess their security. Our work seeks to exploit and document potential vulnerabilities of clickers. For this purpose, we use software defined radios to perform jamming, sniffing and spoofing attacks on an audience response system in production, which provide different possible methods of cheating. The results of our study demonstrate that clickers are easily exploitable. We build a prototype and show that it is practically possible to covertly steal or forge answers of a peer or even an entire classroom, with high levels of confidence. Additionally, we find that the receivers software of the system lacks protection against unexpected answers, which allows our spoofer to submit any ASCII character and opens the receiver up to possible fuzzing attacks. As a result of this study, we discourage using clickers for high-stake assessments, unless they provide proper security protection..http://people.bu.edu/staro/SSS2017_Brief_v0.pdfhttp://people.bu.edu/staro/SSS2017_Brief_v0.pdfhttp://people.bu.edu/staro/SSS2017_Brief_v0.pdfAccepted manuscrip

Magnetic and Magnetotransport Properties of La0.7ca0.3mn1-x(zn,cu)xo3

Magnetic and magnetotransport properties of two perovskite manganite samples of La0.7Ca0.3Mn0.9Zn0.1O3 and La0.7Ca0.3Mn0.95Cu0.05O3 prepared by conventional solid-state reaction have been studied in detail. Experimental results revealed that the temperature dependences of magnetization and resistance varied strongly around the phase-transition temperature. Maximum magnetoresistance (MR) values of La0.7Ca0.3Mn0.9Zn0.1O3 and La0.7Ca0.3Mn0.95Cu0.05O3 under an applied field of 400 Oe were about 21.4 % and 11.0 %, respectively. The maximum magnetic-entropy change (ΔSM) was 2.73 J/kg.K for La0.7Ca0.3Mn0.9Zn0.1O3, and 3.34 J/kg.K for La0.7Ca0.3Mn0.95Cu0.05O3 when the applied field was 45 kOe. Both the MR and ΔSM values obtained from two samples were smaller than those of the parent compound La0.7Ca0.3MnO3. This was due to the change in the Mn3+/Mn4+ ratio caused by Zn and Cu dopants, which led to a change in the type of the ferromagneticparamagnetic phase transition

Determinants of Risk Factors for Renal Impairment among HIV-Infected Patients Treated with Tenofovir Disoproxil Fumarate-Based Antiretroviral Regimen in Southern Vietnam

Background. The situation of renal impairment among HIV-infected patients treated with TDF-based antiretroviral (ARV) regimen greater than 3 years is little known when TDF use has been promptly increasing in Vietnam. Methods. We analyse demographic and clinical data from a cross-sectional survey of 400 HIV-infected patients aged ≥18 years, who were treatment-naive or switched TDF regimen within over 3 years between November 2018 and March 2019. Serological tests for serum creatinine, ALT, and AST were performed. Renal impairment was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Multivariate regression analyses were used to explore the risk factors associated with renal impairment. Results. At the baseline, 7.8% of respondents had estimated glomerular filtration rate (eGFR) of 30–59 mL/min/1.73 m2 and 0.8% had eGFR of 15–29 mL/min/1.73 m2, out of 34 (8.5%) of participants who had renal impairment. Multivariate analysis showed that participants who had preexposure to isoniazid (adjusted PR [aPR] = 0.35 Cl: 0.14–0.91) compared with nonexposure to isoniazid who had a BMI from 18.5 up to 25 kg/m2 (aPR = 0.31 Cl: 0.15–0.62) compared with BMI below 18.5 kg/m2 were less likely to suffer from renal impairment. Patients aged greater than 60 years (aPR = 26.75, 95% Cl: 3.38–211.62) compared with those aged 20–29 years were more likely to have increased risk of renal impairment. Conclusion. Our findings underscore the need for longitudinal studies to assess the influence of TDF on maintaining the low prevalence of renal impairment among HIV-infected patients in Vietnam

Fluorescent ligands for the A3 adenosine receptor.

Fluorescent probes are useful tools to investigate specific subcellular components in cells, tissues and organisms. A classic application of fluorescent ligands of a specific GPCR (G-protein coupled receptors) is the investigation of the receptor location, and, if their binding is reversible, it could provide pharmacological information such as affinity and proximity between interacting molecules. In cultured cell systems, methods based on fluorescence have permitted to observe the receptor cycling and the formation of oligomeric receptor complexes. In high throughput screening, fluorescent ligands represents a safer, more powerful and more versatile alternative to radioligands. [1] The introduction of the bulky fluorophore into a small molecule ligand could lead to deep modifications not only from a physicochemical point of view but also in its pharmacological properties. [2] In order to allow a correct interaction of the pharmacophore with its receptor, it is usually separated from the fluorophore by a linker or a spacer, which should be attached at a specific position that doesn't interfere with the ligand activity. Length and chemical nature of this spacer are optimised in order to obtain the desired biological activity. Also, the choice of the fluorescent molecule to link to the ligand is very important. [1,3] We decided to develop a fluorescent-ligand for the A3AR (A3 adenosine receptor) subtype using the pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine (PTP) as active scaffold at the hA3AR. [4] PTP bears a alkyldiamino spacer at the 5 position which possess a terminal amino group that could be functionalized with the fluorescein isothiocyanate (FITC). FITC represent a useful fluorescent tool because shows a significant extinction coefficent, high quantum yields, and water solubility. [3] The homology model of the hA3AR based on the crystal structure of the hA2AAR was used to perform the docking studies of conjugated derivatives (Prof. Stefano Moro, University of Padua) in order to evaluate what interactions occurs inside the binding pocket. References [1] R.J. Middleton, B. Kellam. Fluorophore-tagged GPCR ligands. Curr. Opin. Chem. Biol. 2005, 9, 517-525. [2] R.P. Haughland. Introduction to fluorescence techniques. Handbook of Fluorescent Probes and Research Products. Chapter 1. 2002 Eugene, Oregon: Molecular Probes. [3] N. Baindur, D.J. Triggle. Concepts and progress in the development and utilization of receptor-specific fluorescent ligands. Med. Res. Rev. 1994, 14, 591-664. [4] S.L. Cheong, S. Federico, G. Venkatesan, et al. The A3 adenosine receptor as multifaceted therapeutic target: pharmacology, medicinal chemistry and in silico approaches. Med. Res. Rev. In press: DOI 10.1002/med.2025

Novel fluorescent antagonist as a molecular probe in A3 adenosine receptor binding assays using flow cytometry.

The physiological role of the A3 adenosine receptor (AR) was explored in cardiac ischaemia, inflammatory diseases and cancer. We report a new fluorophore-conjugated human (h) A3AR antagonist for application to cell-based assays in ligand discovery and for receptor imaging. Fluorescent pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-ylamine (pyrazolo-triazolo-pyrimidine, PTP) and triazolo[1,5-c]quinazolin-5-yl)amine (triazolo-quinazoline, TQ) AR antagonists were compared. A chain-extended and click-conjugated Alexa Fluor-488 TQ derivative (MRS5449) displayed a radioligand binding Ki value of 6.4 2.5 nM in hA3AR-expressing CHO cell membranes. MRS5449 antagonized hA3AR agonist-induced inhibition of cyclic AMP accumulation in a concentration-dependent manner (KB = 4.8 nM). Using flow cytometry (FCM), MRS5449 saturated hA3ARs with very high specific-to-nonspecific binding ratio with an equilibrium binding constant 5.15 nM, comparable to the Kd value of 6.65 nM calculated from kinetic experiments. Ki values of known AR antagonists in inhibition of MRS5449 binding in whole cell FCM were consistent with radioligand binding in membranes, but agonist binding was 5-20 fold weaker than obtained with agonist radioligand [125I]I-AB-MECA. Further binding analysis of MRS5549 suggested multiple agonist binding states of the A3AR. Molecular docking predicted binding modes of these fluorescent antagonists. Thus, MRS5449 is a useful tool for hA3AR characterization

Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A_2A Adenosine Receptor

Molecular modeling of agonist binding to the human A_2A adenosine receptor (AR) was assessed and extended in light of crystallographic structures. Heterocyclic adenine nitrogens of cocrystallized agonist overlaid corresponding positions of the heterocyclic base of a bound triazolotriazine antagonist, and ribose moiety was coordinated in a hydrophilic region, as previously predicted based on modeling using the inactive receptor. Automatic agonist docking of 20 known potent nucleoside agonists to agonist-bound A_2AAR crystallographic structures predicted new stabilizing protein interactions to provide a structural basis for previous empirical structure activity relationships consistent with previous mutagenesis results. We predicted binding of novel C2 terminal amino acid conjugates of A_2AAR agonist CGS21680 and used these models to interpret effects on binding affinity of newly synthesized agonists. d-Amino acid conjugates were generally more potent than l-stereoisomers and free terminal carboxylates more potent than corresponding methyl esters. Amino acid moieties were coordinated close to extracellular loops 2 and 3. Thus, molecular modeling is useful in probing ligand recognition and rational design of GPCR-targeting compounds with specific pharmacological profiles

Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A_2A Adenosine Receptor

Molecular modeling of agonist binding to the human A_2A adenosine receptor (AR) was assessed and extended in light of crystallographic structures. Heterocyclic adenine nitrogens of cocrystallized agonist overlaid corresponding positions of the heterocyclic base of a bound triazolotriazine antagonist, and ribose moiety was coordinated in a hydrophilic region, as previously predicted based on modeling using the inactive receptor. Automatic agonist docking of 20 known potent nucleoside agonists to agonist-bound A_2AAR crystallographic structures predicted new stabilizing protein interactions to provide a structural basis for previous empirical structure activity relationships consistent with previous mutagenesis results. We predicted binding of novel C2 terminal amino acid conjugates of A_2AAR agonist CGS21680 and used these models to interpret effects on binding affinity of newly synthesized agonists. d-Amino acid conjugates were generally more potent than l-stereoisomers and free terminal carboxylates more potent than corresponding methyl esters. Amino acid moieties were coordinated close to extracellular loops 2 and 3. Thus, molecular modeling is useful in probing ligand recognition and rational design of GPCR-targeting compounds with specific pharmacological profiles

Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A_2A Adenosine Receptor

Molecular modeling of agonist binding to the human A_2A adenosine receptor (AR) was assessed and extended in light of crystallographic structures. Heterocyclic adenine nitrogens of cocrystallized agonist overlaid corresponding positions of the heterocyclic base of a bound triazolotriazine antagonist, and ribose moiety was coordinated in a hydrophilic region, as previously predicted based on modeling using the inactive receptor. Automatic agonist docking of 20 known potent nucleoside agonists to agonist-bound A_2AAR crystallographic structures predicted new stabilizing protein interactions to provide a structural basis for previous empirical structure activity relationships consistent with previous mutagenesis results. We predicted binding of novel C2 terminal amino acid conjugates of A_2AAR agonist CGS21680 and used these models to interpret effects on binding affinity of newly synthesized agonists. d-Amino acid conjugates were generally more potent than l-stereoisomers and free terminal carboxylates more potent than corresponding methyl esters. Amino acid moieties were coordinated close to extracellular loops 2 and 3. Thus, molecular modeling is useful in probing ligand recognition and rational design of GPCR-targeting compounds with specific pharmacological profiles