Information Leakage Games

We consider a game-theoretic setting to model the interplay between attacker and defender in the context of information flow, and to reason about their optimal strategies. In contrast with standard game theory, in our games the utility of a mixed strategy is a convex function of the distribution on the defender's pure actions, rather than the expected value of their utilities. Nevertheless, the important properties of game theory, notably the existence of a Nash equilibrium, still hold for our (zero-sum) leakage games, and we provide algorithms to compute the corresponding optimal strategies. As typical in (simultaneous) game theory, the optimal strategy is usually mixed, i.e., probabilistic, for both the attacker and the defender. From the point of view of information flow, this was to be expected in the case of the defender, since it is well known that randomization at the level of the system design may help to reduce information leaks. Regarding the attacker, however, this seems the first work (w.r.t. the literature in information flow) proving formally that in certain cases the optimal attack strategy is necessarily probabilistic

Stretching the Rules: Monocentric Chromosomes with Multiple Centromere Domains

The centromere is a functional chromosome domain that is essential for faithful chromosome segregation during cell division and that can be reliably identified by the presence of the centromere-specific histone H3 variant CenH3. In monocentric chromosomes, the centromere is characterized by a single CenH3-containing region within a morphologically distinct primary constriction. This region usually spans up to a few Mbp composed mainly of centromere-specific satellite DNA common to all chromosomes of a given species. In holocentric chromosomes, there is no primary constriction; the centromere is composed of many CenH3 loci distributed along the entire length of a chromosome. Using correlative fluorescence light microscopy and high-resolution electron microscopy, we show that pea (Pisum sativum) chromosomes exhibit remarkably long primary constrictions that contain 3-5 explicit CenH3-containing regions, a novelty in centromere organization. In addition, we estimate that the size of the chromosome segment delimited by two outermost domains varies between 69 Mbp and 107 Mbp, several factors larger than any known centromere length. These domains are almost entirely composed of repetitive DNA sequences belonging to 13 distinct families of satellite DNA and one family of centromeric retrotransposons, all of which are unevenly distributed among pea chromosomes. We present the centromeres of Pisum as novel ``meta-polycentric'' functional domains. Our results demonstrate that the organization and DNA composition of functional centromere domains can be far more complex than previously thought, do not require single repetitive elements, and do not require single centromere domains in order to segregate properly. Based on these findings, we propose Pisum as a useful model for investigation of centromere architecture and the still poorly understood role of repetitive DNA in centromere evolution, determination, and function

Effect of condensed tannins in the methanogenic potential and in vitro digestion efficiency of ryegrass

Los rumiantes son capaces de degradar y fermentar los componentes de la pared celular de forrajeras. En el retículo-rumen, la fermentación microbiana particiona la energía bruta del sustrato en ácidos grasos volátiles, biomasa microbiana (BM) y gases de desecho (e.g. metano, CH4). Estos últimos son eliminados y representan, no solo contaminación ambiental por su efecto invernadero; sino también una pérdida de la energía disponible en el alimento. Numerosas especies vegetales poseen metabolitos secundarios, tales como los taninos condensados (TC), que, aunque tienen propiedades antimicrobianas y astringentes, su uso racional podría generar un mejor aprovechamiento de los forrajes con potenciales efectos mitigadores del CH4 entérico. En este contexto, se evaluó el efecto de cuatro dosis de TC de Quebracho (Schinopsis balansae, 0, 1,5, 3,0 y 4,5 mg TC cada 100 mg de sustrato; correspondientes a los tratamientos Ctrl, TC1, TC2 y TC3) mediante la técnica de producción de gas in vitro (PGiv), en presencia o ausencia de polietilenglicol (inhibidor específico de los TC), para determinar el impacto en la fermentación ruminal del raigrás (Lolium perenne). La digestibilidad disminuyó en TC3, mientras que la PGiv aumentó asociada a las mayores tasas iniciales. No hubo efecto de los TC sobre la producción de CH4, tampoco en la síntesis de BM. Por otro lado, el agregado de TC disminuyó la concentración de ácido propiónico, aumentado la relación acético: propiónico. Se concluye que los TC de Quebracho a las dosis estudiadas, no produjeron un efecto mitigador del CH4, además de modificar los parámetros de fermentación, sobre todo con una inclusión de 4,5 mg de TC/100 mg de sustrato incubado.Ruminants are capable of degrading and fermenting the forage cell wall components. In reticulo-rumen, the microbial fermentation partition gross energy of the substrate into volatile fatty acids, microbial biomass (MB) and waste gases (e.g. methane, CH4). These gases are eliminated and they represent, not only environmental pollution due to its greenhouse effect, but they also represent loss of the energy available in the forage. Numerous plant species have secondary compounds, such as condensed tannins (CT), although they have antimicrobial and astringent properties, their rational use could generate a better use of forages with potential mitigating effects of enteric CH4. In this context, it was evaluated the effect of four doses of Quebracho (Schinopsis balansae, 0, 1.5, 3.0 and 4.5 mg of CT per 100 mg of substrate, correspond to treatments Ctrl, TC1, TC2 and TC3) using the in vitro gas production technique (ivGP), in the presence or absence of polyethylene glycol (specific inhibitor of CT), to determine the impact on ruminal fermentation of ryegrass (Lolium perenne). The digestibility decreased in TC3, while the ivGP increased asociated with the higher initial rates. There was no effect of the CT on the CH4 production, neither in the synthesis of MB. On the other hand, the addition of CT decreased propionic acid concentration, increasing the acetic: propionic ratio. It is concluded that the CT of Quebracho, at the doses studied, did not produce a CH4 mitigating effect, in addition to modifying the fermentation parameters, especially with an inclusion of 4.5 mg of CT/ 100 mg of incubated substrate.Fil: Cantet, Juan Manuel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Neumann Reiter, A. M.. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal; ArgentinaFil: Colombatto, Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Unidad Ejecutora de Investigaciones en Producción Animal. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Unidad Ejecutora de Investigaciones en Producción Animal; ArgentinaFil: Wawrzkiewicz, Marisa. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal; ArgentinaFil: Jaurena, Gustavo. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal; Argentin

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes

Hansen’s disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease’s complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas

INTRODUCTION: ScFv(FRP5)-ETA is a recombinant antibody toxin with binding specificity for ErbB2 (HER2). It consists of an N-terminal single-chain antibody fragment (scFv), genetically linked to truncated Pseudomonas exotoxin A (ETA). Potent antitumoral activity of scFv(FRP5)-ETA against ErbB2-overexpressing tumor cells was previously demonstrated in vitro and in animal models. Here we report the first systemic application of scFv(FRP5)-ETA in human cancer patients. METHODS: We have performed a phase I dose-finding study, with the objective to assess the maximum tolerated dose and the dose-limiting toxicity of intravenously injected scFv(FRP5)-ETA. Eighteen patients suffering from ErbB2-expressing metastatic breast cancers, prostate cancers, head and neck cancer, non small cell lung cancer, or transitional cell carcinoma were treated. Dose levels of 2, 4, 10, 12.5, and 20 μg/kg scFv(FRP5)-ETA were administered as five daily infusions each for two consecutive weeks. RESULTS: No hematologic, renal, and/or cardiovascular toxicities were noted in any of the patients treated. However, transient elevation of liver enzymes was observed, and considered dose limiting, in one of six patients at the maximum tolerated dose of 12.5 μg/kg, and in two of three patients at 20 μg/kg. Fifteen minutes after injection, peak concentrations of more than 100 ng/ml scFv(FRP5)-ETA were obtained at a dose of 10 μg/kg, indicating that predicted therapeutic levels of the recombinant protein can be applied without inducing toxic side effects. Induction of antibodies against scFv(FRP5)-ETA was observed 8 days after initiation of therapy in 13 patients investigated, but only in five of these patients could neutralizing activity be detected. Two patients showed stable disease and in three patients clinical signs of activity in terms of signs and symptoms were observed (all treated at doses ≥ 10 μg/kg). Disease progression occurred in 11 of the patients. CONCLUSION: Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 μg/kg in patients with ErbB2-expressing tumors, justifying further clinical development

Mycobacterium leprae diversity and population dynamics in medieval Europe from novel ancient genomes.

Funder: Max-Planck SocietyFunder: St John’s College, CambridgeFunder: Fondation Raoul FollereauFunder: University of Zurich’s University Research Priority Program “Evolution in Action: From Genomes to Ecosystems”Funder: the Senckenberg Centre for Human Evolution and Palaeoenvironment (S-HEP) at the University of TübingenBackgroundHansen's disease (leprosy), widespread in medieval Europe, is today mainly prevalent in tropical and subtropical regions with around 200,000 new cases reported annually. Despite its long history and appearance in historical records, its origins and past dissemination patterns are still widely unknown. Applying ancient DNA approaches to its major causative agent, Mycobacterium leprae, can significantly improve our understanding of the disease's complex history. Previous studies have identified a high genetic continuity of the pathogen over the last 1500 years and the existence of at least four M. leprae lineages in some parts of Europe since the Early Medieval period.ResultsHere, we reconstructed 19 ancient M. leprae genomes to further investigate M. leprae's genetic variation in Europe, with a dedicated focus on bacterial genomes from previously unstudied regions (Belarus, Iberia, Russia, Scotland), from multiple sites in a single region (Cambridgeshire, England), and from two Iberian leprosaria. Overall, our data confirm the existence of similar phylogeographic patterns across Europe, including high diversity in leprosaria. Further, we identified a new genotype in Belarus. By doubling the number of complete ancient M. leprae genomes, our results improve our knowledge of the past phylogeography of M. leprae and reveal a particularly high M. leprae diversity in European medieval leprosaria.ConclusionsOur findings allow us to detect similar patterns of strain diversity across Europe with branch 3 as the most common branch and the leprosaria as centers for high diversity. The higher resolution of our phylogeny tree also refined our understanding of the interspecies transfer between red squirrels and humans pointing to a late antique/early medieval transmission. Furthermore, with our new estimates on the past population diversity of M. leprae, we gained first insights into the disease's global history in relation to major historic events such as the Roman expansion or the beginning of the regular transatlantic long distance trade. In summary, our findings highlight how studying ancient M. leprae genomes worldwide improves our understanding of leprosy's global history and can contribute to current models of M. leprae's worldwide dissemination, including interspecies transmissions

Determination of nutrient salts by automatic methods both in seawater and brackish water: the phosphate blank

9 páginas, 2 tablas, 2 figurasThe main inconvenience in determining nutrients in seawater by automatic methods is simply solved: the preparation of a suitable blank which corrects the effect of the refractive index change on the recorded signal. Two procedures are proposed, one physical (a simple equation to estimate the effect) and the other chemical (removal of the dissolved phosphorus with ferric hydroxide).Support for this work came from CICYT (MAR88-0245 project) and Conselleria de Pesca de la Xunta de GaliciaPeer reviewe