Delayed and time-variant patrolling strategies against attackers with local observation capabilities

Surveillance of graph-represented environments is an application of autonomous patrolling robots that received remarkable attention during the last years. In this problem setting, computing a patrolling strategy is a central task to guarantee an effective protection level. Literature provides a vast set of methods where the patrolling strategies explicitly consider the presence of a rational adversary and fully informed attacker, which is characterized by worst-case (for the patroller) observation capabilities. In this work, we consider an attacker that does not have any prior knowledge on the environment and the patrolling strategy. Instead, we assume that the attacker can only access local observations on the vertex potentially under attack. We study the definition of patrolling strategies under the assumption that the attacker, when planning an attack on a particular location, tries to forecast the arrivals of the patroller on that particular location. We model our patrolling strategies with Markov chains where we seek the generation of arrivals that are difficult to forecast. To this end we introduce time-variance in the transition matrix used to determine the patrollers movements on the graph-represented environment

Security Games for Node Localization through Verifiable Multilateration

Most applications of wireless sensor networks (WSNs) rely on data about the positions of sensor nodes, which are not necessarily known beforehand. Several localization approaches have been proposed but most of them omit to consider that WSNs could be deployed in adversarial settings, where hostile nodes under the control of an attacker coexist with faithful ones. Verifiable multilateration (VM) was proposed to cope with this problem by leveraging on a set of trusted landmark nodes that act as verifiers. Although VM is able to recognize reliable localization measures, it allows for regions of undecided positions that can amount to the 40 percent of the monitored area. We studied the properties of VM as a noncooperative two-player game where the first player employs a number of verifiers to do VM computations and the second player controls a malicious node. The verifiers aim at securely localizing malicious nodes, while malicious nodes strive to masquerade as unknown and to pretend false positions. Thanks to game theory, the potentialities of VM are analyzed with the aim of improving the defender's strategy. We found that the best placement for verifiers is an equilateral triangle with edge equal to the power range R, and maximum deception in the undecided region is approximately 0.27R. Moreover, we characterized-in terms of the probability of choosing an unknown node to examine further-the strategies of the players

Stability of the antimalarial drug dihydroartemisinin in under physiologically-relevant conditions : implications for clinical treatment, pharmacokinetic and in vitro assays

Artemisinins are peroxidic antimalarial drugs known to be very potent but chemically highly unstable; they degrade in the presence of ferrous iron, Fe(II)-heme or biological reductants. Less documented is how this translates into chemical stability and antimalarial activity across a range of conditions applying to in vitro testing and clinical situations. Dihydroartemisinin (DHA) is studied here because it is both an antimalarial drug on its own and the main metabolite of other artemisinins. The behavior of DHA in PBS, plasma or erythrocytes lysate at different temperatures and pH ranges was examined. The antimalarial activity of the residual drug was evaluated using the chemosensitivity assay on P. falciparum, and the extent of decomposition of DHA was established through use of HPLC-ECD analysis. The role of the Fe(II)-heme was investigated by blocking its reactivity using carbon monoxide. A significant reduction in the antimalarial activity of DHA was seen after incubation in plasma and to a lesser extent in erythrocytes lysate: activity was reduced by half after 3 hours and almost completely abolished after 24 hours. Serum-enriched media also affected DHA activity. Effects were temperature and pH-dependent and paralleled the increased rate of decomposition of DHA from pH 7 upwards and in plasma. These results suggest that particular care should be taken in conducting and interpreting in vitro studies, prone as they are to experimental and drug storage conditions. Disorders such as fever, hemolysis or acidosis associated with malaria severity may contribute to artemisinins instability and reduce their clinical efficacy

Genome-scale definition of the transcriptional programme associated with compromised PU.1 activity in acute myeloid leukaemia.

Transcriptional dysregulation is associated with haematological malignancy. Although mutations of the key haematopoietic transcription factor PU.1 are rare in human acute myeloid leukaemia (AML), they are common in murine models of radiation-induced AML, and PU.1 downregulation and/or dysfunction has been described in human AML patients carrying the fusion oncogenes RUNX1-ETO and PML-RARA. To study the transcriptional programmes associated with compromised PU.1 activity, we adapted a Pu.1-mutated murine AML cell line with an inducible wild-type PU.1. PU.1 induction caused transition from leukaemia phenotype to monocytic differentiation. Global binding maps for PU.1, CEBPA and the histone mark H3K27Ac with and without PU.1 induction showed that mutant PU.1 retains DNA-binding ability, but the induction of wild-type protein dramatically increases both the number and the height of PU.1-binding peaks. Correlating chromatin immunoprecipitation (ChIP) Seq with gene expression data, we found that PU.1 recruitment coupled with increased histone acetylation induces gene expression and activates a monocyte/macrophage transcriptional programme. PU.1 induction also caused the reorganisation of a subgroup of CEBPA binding peaks. Finally, we show that the PU.1 target gene set defined in our model allows the stratification of primary human AML samples, shedding light on both known and novel AML subtypes that may be driven by PU.1 dysfunction.X18.1.1 cells were kindly donated by Dr Wendy Cook (LaTrobe University, Melbourne). MSCV-puro-PuER plasmid was kindly donated by Dr Peter Laslo (University of Leeds). ChIP sequencing was performed at the Genomics Core Facility, CRUK Cambridge Institute. Research in the Göttgens laboratory is supported by Leukaemia and Lymphoma Research, the MRC, BBSRC, CRUK, Leukemia and Lymphoma Society, NIHR Cambridge Biomedical Research Centre and core infrastructure support by the Wellcome Trust to the Wellcome Trust and MRC Cambridge Stem Cell Institute and CIMR. JIS is supported by CRUK and the Raymond and Beverly Sackler Foundation.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/leu.2015.17

Oxidative inactivation of SARS-CoV-2 on photoactive AgNPs@Tio2 ceramic tiles

The current SARS-CoV-2 pandemic causes serious public health, social, and economic issues all over the globe. Surface transmission has been claimed as a possible SARS-CoV-2 infection route, especially in heavy contaminated environmental surfaces, including hospitals and crowded public places. Herein, we studied the deactivation of SARS-CoV-2 on photoactive AgNPs@TiO2 coated on industrial ceramic tiles under dark, UVA, and LED light irradiations. SARS-CoV-2 inactivation is effective under any light/dark conditions. The presence of AgNPs has an important key to limit the survival of SARS-CoV-2 in the dark; moreover, there is a synergistic action when TiO2 is decorated with Ag to enhance the virus photocatalytic inactivation even under LED. The radical oxidation was confirmed as the the central mechanism behind SARS-CoV-2 damage/inactivation by ESR analysis under LED light. Therefore, photoactive AgNPs@TiO2 ceramic tiles could be exploited to fight surface infections, especially during viral severe pandemics

Bilevel programming methods for computing single-leader-multi-follower equilibria in normal-form and polymatrix games

The concept of leader-follower (or Stackelberg) equilibrium plays a central role in a number of real-world applications bordering on mathematical optimization and game theory. While the single-follower case has been investigated since the inception of bilevel programming with the seminal work of von Stackelberg, results for the case with multiple followers are only sporadic and not many computationally affordable methods are available. In this work, we consider Stackelberg games with two or more followers who play a (pure or mixed) Nash equilibrium once the leader has committed to a (pure or mixed) strategy, focusing on normal-form and polymatrix games. As customary in bilevel programming, we address the two extreme cases where, if the leader\u2019s commitment originates more Nash equilibria in the followers\u2019 game, one which either maximizes (optimistic case) or minimizes (pessimistic case) the leader\u2019s utility is selected. First, we show that, in both cases and when assuming mixed strategies, the optimization problem associated with the search problem of finding a Stackelberg equilibrium is NP-hard and not in Poly-APX unless P= NP. We then consider different situations based on whether the leader or the followers can play mixed strategies or are restricted to pure strategies only, proposing exact nonconvex mathematical programming formulations for the optimistic case for normal-form and polymatrix games. For the pessimistic problem, which cannot be tackled with a (single-level) mathematical programming formulation, we propose a heuristic black-box algorithm. All the methods and formulations that we propose are thoroughly evaluated computationally

New hydrophilic riminophenazines as potent antiprotozoal agents

Malaria and leishmaniasis are life-threatening human parasitosis caused by protozoa-infected insect vectors. In most of affected countries, the expansive and hazardous therapies available to fight protozoan infections are generally harmed by the spread of drug resistance phenomena upon prolonged treatments. This scenario highlights the need of novel antiprotozoal agents hopefully able to act trough new mechanism(s) of action. Interestingly, the fat-soluble antimycobacterial drug Clofazimine was reported to exhibit a moderate antiprotozoal action and some interesting antileishmanial in vitro and in vivo effects were reported in few preliminary, yet promising, studies.1,4 Intrigued by these results, we have previously prepared a series of basic Clofazimine analogues which demonstrated the beneficial effects of the introduction of a basic head on the antiprotozoal activity.5 Here, to further investigate the role of balancing between the lipo- and hydrophilicity on the antiparasitic activity of these riminophenazines, we report the synthesis and the in vitro evaluation as leishmanicidal (L. tropica and L. infantum promastigotes) and antiplasmodial (chloroquine sensitive and resistant P. falciparum strains) agents of a family of hydrophilic C-2 aminopyridinyl substituted riminophenazines, bearing in C-3 differently decorated basic side chains. Results showed that most of the new compounds potently inhibited the growth of protozoa with IC50 in the high nanomolar range and underlined the key role of the hydrophilic C-2 aminopyridinyl moiety to improve the leishmanicidal activity. In addition, the length and the nature of the basic side chain differently influenced the antiprotozoal activity and the selectivity index versus mammalian cells, providing useful information for further structural optimizations