Peritrophic matrix of Phlebotomus duboscqi and its kinetics during Leishmania major development

Light microscopy of native preparations, histology, and electron microscopy have revealed that Phlebotomus duboscqi belongs to a class of sand fly species with prompt development of the peritrophic matrix (PM). Secretion of electron-lucent fibrils, presumably chitin, starts immediately after the ingestion of a blood meal and, about 6 h later, is followed by secretion of amorphous electron-dense components, presumably proteins and glycoproteins. The PM matures in less than 12 h and consists of a thin laminar outer layer and a thick amorphous inner layer. No differences have been found in the timing of the disintegration of the PM in females infected with Leishmania major. In both groups of females (infected and uninfected), the disintegration of the PM is initiated at the posterior end. Although parasites are present at high densities in the anterior part of the blood meal bolus, they escape from the PM at the posterior end only. These results suggest that L. major chitinase does not have an important role in parasite escape from the PM. Promastigotes remain in the intraperitrophic space until the PM is broken down by sand-fly-derived chitinases and only then migrate anteriorly. Disintegration of the PM occurs simultaneously with the morphological transformation of parasites from procyclic forms to long nectomonads. A novel role is ascribed to the anterior plug, a component of the PM secreted by the thoracic midgut; this plug functions as a temporary barrier to stop the forward migration of nectomonads to the thoracic midgut

Leishmania major Survival in Selective Phlebotomus papatasi Sand Fly Vector Requires a Specific SCG-Encoded Lipophosphoglycan Galactosylation Pattern

Phlebotomine sand flies that transmit the protozoan parasite Leishmania differ greatly in their ability to support different parasite species or strains in the laboratory: while some show considerable selectivity, others are more permissive. In “selective” sand flies, Leishmania binding and survival in the fly midgut typically depends upon the abundant promastigote surface adhesin lipophosphoglycan (LPG), which exhibits species- and strain-specific modifications of the dominant phosphoglycan (PG) repeat units. For the “selective” fly Phlebotomus papatasi PpapJ, side chain galactosyl-modifications (scGal) of PG repeats play key roles in parasite binding. We probed the specificity and properties of this scGal-LPG PAMP (Pathogen Associated Molecular Pattern) through studies of natural isolates exhibiting a wide range of galactosylation patterns, and of a panel of isogenic L. major engineered to express similar scGal-LPG diversity by transfection of SCG-encoded β1,3-galactosyltransferases with different activities. Surprisingly, both ‘poly-scGal’ and ‘null-scGal’ lines survived poorly relative to PpapJ-sympatric L. major FV1 and other ‘mono-scGal’ lines. However, survival of all lines was equivalent in P. duboscqi, which naturally transmit L. major strains bearing ‘null-scGal’-LPG PAMPs. We then asked whether scGal-LPG-mediated interactions were sufficient for PpapJ midgut survival by engineering Leishmania donovani, which normally express unsubstituted LPG, to express a ‘PpapJ-optimal’ scGal-LPG PAMP. Unexpectedly, these “L. major FV1-cloaked” L. donovani-SCG lines remained unable to survive within PpapJ flies. These studies establish that midgut survival of L. major in PpapJ flies is exquisitely sensitive to the scGal-LPG PAMP, requiring a specific ‘mono-scGal’ pattern. However, failure of ‘mono-scGal’ L. donovani-SCG lines to survive in selective PpapJ flies suggests a requirement for an additional, as yet unidentified L. major-specific parasite factor(s). The interplay of the LPG PAMP and additional factor(s) with sand fly midgut receptors may determine whether a given sand fly host is “selective” or “permissive”, with important consequences to both disease transmission and the natural co-evolution of sand flies and Leishmania

Approximating Fixation Probabilities in the Generalized Moran Process

We consider the Moran process, as generalized by Lieberman, Hauert and Nowak (Nature, 433:312--316, 2005). A population resides on the vertices of a finite, connected, undirected graph and, at each time step, an individual is chosen at random with probability proportional to its assigned 'fitness' value. It reproduces, placing a copy of itself on a neighbouring vertex chosen uniformly at random, replacing the individual that was there. The initial population consists of a single mutant of fitness $r>0$ placed uniformly at random, with every other vertex occupied by an individual of fitness 1. The main quantities of interest are the probabilities that the descendants of the initial mutant come to occupy the whole graph (fixation) and that they die out (extinction); almost surely, these are the only possibilities. In general, exact computation of these quantities by standard Markov chain techniques requires solving a system of linear equations of size exponential in the order of the graph so is not feasible. We show that, with high probability, the number of steps needed to reach fixation or extinction is bounded by a polynomial in the number of vertices in the graph. This bound allows us to construct fully polynomial randomized approximation schemes (FPRAS) for the probability of fixation (when $r\geq 1$) and of extinction (for all $r>0$).Comment: updated to the final version, which appeared in Algorithmic

Cyber attribution: An argumentation-based approach

Abstract Attributing a cyber-operation through the use of multiple pieces of tech-nical evidence (i.e., malware reverse-engineering and source tracking) and conven-tional intelligence sources (i.e., human or signals intelligence) is a difficult problem not only due to the effort required to obtain evidence, but the ease with which an adversary can plant false evidence. In this paper, we introduce a formal reasoning system called the InCA (Intelligent Cyber Attribution) framework that is designed to aid an analyst in the attribution of a cyber-operation even when the available information is conflicting and/or uncertain. Our approach combines argumentation-based reasoning, logic programming, and probabilistic models to not only attribute an operation but also explain to the analyst why the system reaches its conclusions.

A probabilistic framework for localization of attackers in MANETs

Typescript (photocopy).The wide diversity of farm ponds makes categorizing and making regional comparisons of these aquatic systems a difficult task. Before meaningful regional classifications can be identified, a large and diverse data set must be analyzed. To facilitate this task, a method of measuring basic productivity which requires a minimal amount of field and laboratory effort is needed. The Algal Assay Procedure-Bottle Test, which is designed to measure algal growth potential (AGP), was developed to be such a method. However, variability in the AGP, resulting from incomplete and inconsistent release of organically bound nutrients to bioavailable forms by the currently accepted pretreatment method (autoclaving), makes it difficult to compare assay results from samples taken at different stages of growth of the algal populations. Several alternative approaches to assay pretreatment were investigated in this study. The experimental treatments included exposure to short-wave ultraviolet radiation, and the addition of oxidizers (sulfuric acid or hydrogen peroxide) in conjunction with autoclaving and/or ultraviolet light exposure. Most of the treatments either did not significantly improve nutrient release or algal growth compared to autoclaving alone, or were toxic or inhibitory to algal growth. Of all the pretreatment methods investigated, the addition of hydrogen peroxide followed by UV light exposure and autoclaving showed the most promise as a means of obtaining the algal growth potential based on all nutrients present.

Computational Analysis of Terrorist Groups: Lashkar-e-TaibaLashkar-e-Taiba /

XIV, 234 p.online resource

Challenges of civilian distinction in cyberwarfare

Avoiding attacks on civilian targets during cyberwarfare is more difficult than it seems. We discuss ways in which an ostensibly military cyberattack could accidentally hit a civilian target. Civilian targets are easier to attack than military targets, and an adversary may be tempted to be careless in targeting. Dual-use targets are common in cyberspace since militaries frequently exploit civilian cyber infrastructure such as networks and common software, and hitting that infrastructure necessarily hurts civilians. Civilians can be necessary intermediate objectives to get to an adversary’s military, since direct Internet connections between militaries can be easily blocked. Cyberwarfare methods are unreliable, so cyberattacks tend to use many different methods simultaneously, increasing the risk of civilian spillover. Military cyberattacks are often seen by civilian authorities, then quickly analyzed and reported to the public; this enables criminals to quickly exploit the attack methods to harm civilians. Many attacks use automatic propagation methods which have difficulty distinguishing civilians. Finally, many cyberattacks spoof civilians, encouraging counterattacks on civilians; that is close to perfidy, which is outlawed by the laws of armed conflict. We discuss several additional problems, including the public’s underestimated dependence on digital technology, their unpreparedness for cyberwarfare, and the indirect lethal effects of cyberattacks. We conclude with proposed principles for ethical conduct of cyberwarfare to minimize unnecessary harm to civilians, and suggest designating cyberspace “safe havens”, enforcing reparations, and emphasizing cyber coercion rather than cyberwarfare