114 research outputs found

    Arya: Nearly linear-time zero-knowledge proofs for correct program execution

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    There have been tremendous advances in reducing interaction, communication and verification time in zero-knowledge proofs but it remains an important challenge to make the prover efficient. We construct the first zero-knowledge proof of knowledge for the correct execution of a program on public and private inputs where the prover computation is nearly linear time. This saves a polylogarithmic factor in asymptotic performance compared to current state of the art proof systems. We use the TinyRAM model to capture general purpose processor computation. An instance consists of a TinyRAM program and public inputs. The witness consists of additional private inputs to the program. The prover can use our proof system to convince the verifier that the program terminates with the intended answer within given time and memory bounds. Our proof system has perfect completeness, statistical special honest verifier zero-knowledge, and computational knowledge soundness assuming linear-time computable collision-resistant hash functions exist. The main advantage of our new proof system is asymptotically efficient prover computation. The prover’s running time is only a superconstant factor larger than the program’s running time in an apples-to-apples comparison where the prover uses the same TinyRAM model. Our proof system is also efficient on the other performance parameters; the verifier’s running time and the communication are sublinear in the execution time of the program and we only use a log-logarithmic number of rounds

    Checking and bootstrapping lexical norms by means of word similarity indexes

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    In psychology, lexical norms related to the se- mantic properties of words, such as concreteness and va- lence, are important research resources. Collecting such norms by asking judges to rate the words is very time consuming, which strongly limits the number of words that compose them. In the present article, we present a technique for estimating lexical norms based on the latent semantic analysis of a corpus. The analyses conducted emphasize the technique’s effectiveness for several semantic dimensions. In addition to the extension of norms, this technique can be used to check human ratings to identify words for which the rating is very different from the corpus-based estimate

    The T7-Related Pseudomonas putida Phage ϕ15 Displays Virion-Associated Biofilm Degradation Properties

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    Formation of a protected biofilm environment is recognized as one of the major causes of the increasing antibiotic resistance development and emphasizes the need to develop alternative antibacterial strategies, like phage therapy. This study investigates the in vitro degradation of single-species Pseudomonas putida biofilms, PpG1 and RD5PR2, by the novel phage ϕ15, a ‘T7-like virus’ with a virion-associated exopolysaccharide (EPS) depolymerase. Phage ϕ15 forms plaques surrounded by growing opaque halo zones, indicative for EPS degradation, on seven out of 53 P. putida strains. The absence of haloes on infection resistant strains suggests that the EPS probably act as a primary bacterial receptor for phage infection. Independent of bacterial strain or biofilm age, a time and dose dependent response of ϕ15-mediated biofilm degradation was observed with generally a maximum biofilm degradation 8 h after addition of the higher phage doses (104 and 106 pfu) and resistance development after 24 h. Biofilm age, an in vivo very variable parameter, reduced markedly phage-mediated degradation of PpG1 biofilms, while degradation of RD5PR2 biofilms and ϕ15 amplification were unaffected. Killing of the planktonic culture occurred in parallel with but was always more pronounced than biofilm degradation, accentuating the need for evaluating phages for therapeutic purposes in biofilm conditions. EPS degrading activity of recombinantly expressed viral tail spike was confirmed by capsule staining. These data suggests that the addition of high initial titers of specifically selected phages with a proper EPS depolymerase are crucial criteria in the development of phage therapy

    A Novel Manganese Efflux System, YebN, Is Required for Virulence by Xanthomonas oryzae pv. oryzae

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    Manganese ions (Mn2+) play a crucial role in virulence and protection against oxidative stress in bacterial pathogens. Such pathogens appear to have evolved complex mechanisms for regulating Mn2+ uptake and efflux. Despite numerous studies on Mn2+ uptake, however, only one efflux system has been identified to date. Here, we report on a novel Mn2+ export system, YebN, in Xanthomonas oryzae pv. oryzae (Xoo), the causative agent of bacterial leaf blight. Compared with wild-type PXO99, the yebN mutant was highly sensitive to Mn2+ and accumulated high concentrations of intracellular manganese. In addition, we found that expression of yebN was positively regulated by Mn2+ and the Mn2+-dependent transcription regulator, MntR. Interestingly, the yebN mutant was more tolerant to methyl viologen and H2O2 in low Mn2+ medium than PXO99, but more sensitive in high Mn2+ medium, implying that YebN plays an important role in Mn2+ homoeostasis and detoxification of reactive oxygen species (ROS). Notably, deletion of yebN rendered Xoo sensitive to hypo-osmotic shock, suggesting that YebN may protect against such stress. That mutation of yebN substantially reduced the Xoo growth rate and lesion formation in rice implies that YebN could be involved in Xoo fitness in host. Although YebN has two DUF204 domains, it lacks homology to any known metal transporter. Hence, this is the first report of a novel metal export system that plays essential roles in hypo-osmotic and oxidative stress, and virulence. Our results lay the foundations for elucidating the complex and fascinating relationship between metal homeostasis and host-pathogen interactions

    Bacteriophage-encoded depolymerases: their diversity and biotechnological applications

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    Bacteriophages (phages), natural enemies of bacteria, can encode enzymes able to degrade polymeric substances. These substances can be found in the bacterial cell surface, such as polysaccharides, or are produced by bacteria when they are living in biofilm communities, the most common bacterial lifestyle. Consequently, phages with depolymerase activity have a facilitated access to the host receptors, by degrading the capsular polysaccharides, and are believed to have a better performance against bacterial biofilms, since the degradation of extracellular polymeric substances by depolymerases might facilitate the access of phages to the cells within different biofilm layers. Since the diversity of phage depolymerases is not yet fully explored, this is the first review gathering information about all the depolymerases encoded by fully sequenced phages. Overall, in this study, 160 putative depolymerases, including sialidases, levanases, xylosidases, dextranases, hyaluronidases, peptidases as well as pectate/pectin lyases, were found in 143 phages (43 Myoviridae, 47 Siphoviridae, 37 Podoviridae, and 16 unclassified) infecting 24 genera of bacteria. We further provide information about the main applications of phage depolymerases, which can comprise areas as diverse as medical, chemical, or food-processing industry.DPP acknowledges the financial support from the Portuguese Foundation for Science and Technology (FCT) through the grant SFRH/BD/76440/2011. SS is an FCT investigator (IF/01413/2013). The authors also thank FCT for the Strategic Project of the UID/BIO/04469/2013 unit, FCT and European Union funds (FEDER/COMPETE) for the project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER027462)

    Mapping the Environmental Fitness Landscape of a Synthetic Gene Circuit

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    Gene expression actualizes the organismal phenotypes encoded within the genome in an environment-dependent manner. Among all encoded phenotypes, cell population growth rate (fitness) is perhaps the most important, since it determines how well-adapted a genotype is in various environments. Traditional biological measurement techniques have revealed the connection between the environment and fitness based on the gene expression mean. Yet, recently it became clear that cells with identical genomes exposed to the same environment can differ dramatically from the population average in their gene expression and division rate (individual fitness). For cell populations with bimodal gene expression, this difference is particularly pronounced, and may involve stochastic transitions between two cellular states that form distinct sub-populations. Currently it remains unclear how a cell population's growth rate and its subpopulation fractions emerge from the molecular-level kinetics of gene networks and the division rates of single cells. To address this question we developed and quantitatively characterized an inducible, bistable synthetic gene circuit controlling the expression of a bifunctional antibiotic resistance gene in Saccharomyces cerevisiae. Following fitness and fluorescence measurements in two distinct environments (inducer alone and antibiotic alone), we applied a computational approach to predict cell population fitness and subpopulation fractions in the combination of these environments based on stochastic cellular movement in gene expression space and fitness space. We found that knowing the fitness and nongenetic (cellular) memory associated with specific gene expression states were necessary for predicting the overall fitness of cell populations in combined environments. We validated these predictions experimentally and identified environmental conditions that defined a “sweet spot” of drug resistance. These findings may provide a roadmap for connecting the molecular-level kinetics of gene networks to cell population fitness in well-defined environments, and may have important implications for phenotypic variability of drug resistance in natural settings

    Undefined cellulase formulations hinder scientific reproducibility

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    In the shadow of a burgeoning biomass-to-fuels industry, biological conversion of lignocellulose to fermentable sugars in a cost-effective manner is key to the success of second-generation and advanced biofuel production. For the effective comparison of one cellulase preparation to another, cellulase assays are typically carried out with one or more engineered cellulase formulations or natural exoproteomes of known performance serving as positive controls. When these formulations have unknown composition, as is the case with several widely used commercial products, it becomes impossible to compare or reproduce work done today to work done in the future, where, for example, such preparations may not be available. Therefore, being a critical tenet of science publishing, experimental reproducibility is endangered by the continued use of these undisclosed products. We propose the introduction of standard procedures and materials to produce specific and reproducible cellulase formulations. These formulations are to serve as yardsticks to measure improvements and performance of new cellulase formulations

    Scalable Multi-Party Private Set-Intersection

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    In this work we study the problem of private set-intersection in the multi-party setting and design two protocols with the following improvements compared to prior work. First, our protocols are designed in the so-called star network topology, where a designated party communicates with everyone else, and take a new approach of leveraging the 2PC protocol of [FreedmanNP04]. This approach minimizes the usage of a broadcast channel, where our semi-honest protocol does not make any use of such a channel and all communication is via point-to-point channels. In addition, the communication complexity of our protocols scales with the number of parties. More concretely, (1) our first semi-honest secure protocol implies communication complexity that is linear in the input sizes, namely O((i=1nmi)κ)O((\sum_{i=1}^n m_i)\cdot\kappa) bits of communication where κ\kappa is the security parameter and mim_i is the size of PiP_i\u27s input set, whereas overall computational overhead is quadratic in the input sizes only for a designated party, and linear for the rest. We further reduce this overhead by employing two types of hashing schemes. (2) Our second protocol is proven secure in the malicious setting. This protocol induces communication complexity O((n^2 + nm_\maxx + nm_\minn\log m_\maxx)\kappa) bits of communication where m_\minn (resp. m_\maxx) is the minimum (resp. maximum) over all input sets sizes and nn is the number of parties
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