1,280 research outputs found

    Towards Intelligent Databases

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    This article is a presentation of the objectives and techniques of deductive databases. The deductive approach to databases aims at extending with intensional definitions other database paradigms that describe applications extensionaUy. We first show how constructive specifications can be expressed with deduction rules, and how normative conditions can be defined using integrity constraints. We outline the principles of bottom-up and top-down query answering procedures and present the techniques used for integrity checking. We then argue that it is often desirable to manage with a database system not only database applications, but also specifications of system components. We present such meta-level specifications and discuss their advantages over conventional approaches

    Artemisinin-induced parasite dormancy: a plausible mechanism for treatment failure

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    <p>Abstract</p> <p>Background</p> <p>Artemisinin-combination therapy is a highly effective treatment for uncomplicated falciparum malaria but parasite recrudescence has been commonly reported following artemisinin (ART) monotherapy. The dormancy recovery hypothesis has been proposed to explain this phenomenon, which is different from the slower parasite clearance times reported as the first evidence of the development of ART resistance.</p> <p>Methods</p> <p>In this study, an existing <it>P. falciparum </it>infection model is modified to incorporate the hypothesis of dormancy. Published <it>in vitro </it>data describing the characteristics of dormant parasites is used to explore whether dormancy alone could be responsible for the high recrudescence rates observed in field studies using monotherapy. Several treatment regimens and dormancy rates were simulated to investigate the rate of clinical and parasitological failure following treatment.</p> <p>Results</p> <p>The model output indicates that following a single treatment with ART parasitological and clinical failures occur in up to 77% and 67% of simulations, respectively. These rates rapidly decline with repeated treatment and are sensitive to the assumed dormancy rate. The simulated parasitological and clinical treatment failure rates after 3 and 7 days of treatment are comparable to those reported from several field trials.</p> <p>Conclusions</p> <p>Although further studies are required to confirm dormancy <it>in vivo</it>, this theoretical study adds support for the hypothesis, highlighting the potential role of this parasite sub-population in treatment failure following monotherapy and reinforcing the importance of using ART in combination with other anti-malarials.</p

    Shift-Symmetric Configurations in Two-Dimensional Cellular Automata: Irreversibility, Insolvability, and Enumeration

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    The search for symmetry as an unusual yet profoundly appealing phenomenon, and the origin of regular, repeating configuration patterns have long been a central focus of complexity science and physics. To better grasp and understand symmetry of configurations in decentralized toroidal architectures, we employ group-theoretic methods, which allow us to identify and enumerate these inputs, and argue about irreversible system behaviors with undesired effects on many computational problems. The concept of so-called configuration shift-symmetry is applied to two-dimensional cellular automata as an ideal model of computation. Regardless of the transition function, the results show the universal insolvability of crucial distributed tasks, such as leader election, pattern recognition, hashing, and encryption. By using compact enumeration formulas and bounding the number of shift-symmetric configurations for a given lattice size, we efficiently calculate the probability of a configuration being shift-symmetric for a uniform or density-uniform distribution. Further, we devise an algorithm detecting the presence of shift-symmetry in a configuration. Given the resource constraints, the enumeration and probability formulas can directly help to lower the minimal expected error and provide recommendations for system's size and initialization. Besides cellular automata, the shift-symmetry analysis can be used to study the non-linear behavior in various synchronous rule-based systems that include inference engines, Boolean networks, neural networks, and systolic arrays.Comment: 22 pages, 9 figures, 2 appendice

    Automaton Meets Query Algebra: Towards a Unified Model for XQuery Evaluation over XML Data Streams

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    Abstract. In this work, we address the efficient evaluation of XQuery expressions over continuous XML data streams, which is essential for a broad range of applications including monitoring systems and infor-mation dissemination systems. While previous work has shown that au-tomata theory is suited for on-the-fly pattern retrieval over XML data streams, we find that automata-based approaches suffer from being not as flexibly optimizable as algebraic query systems. In fact, they enforce a rigid data-driven paradigm of execution. We thus now propose a unified query model to augment automata-style processing with algebra-based query optimization techniques. The proposed model has been success-fully applied in the Raindrop stream processing system. Our experimen-tal study confirms considerable performance gains with both established optimization techniques and our novel query rewrite rules.

    A complementary view on the growth of directory trees

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    Trees are a special sub-class of networks with unique properties, such as the level distribution which has often been overlooked. We analyse a general tree growth model proposed by Klemm {\em et. al.} (2005) to explain the growth of user-generated directory structures in computers. The model has a single parameter qq which interpolates between preferential attachment and random growth. Our analysis results in three contributions: First, we propose a more efficient estimation method for qq based on the degree distribution, which is one specific representation of the model. Next, we introduce the concept of a level distribution and analytically solve the model for this representation. This allows for an alternative and independent measure of qq. We argue that, to capture real growth processes, the qq estimations from the degree and the level distributions should coincide. Thus, we finally apply both representations to validate the model with synthetically generated tree structures, as well as with collected data of user directories. In the case of real directory structures, we show that qq measured from the level distribution are incompatible with qq measured from the degree distribution. In contrast to this, we find perfect agreement in the case of simulated data. Thus, we conclude that the model is an incomplete description of the growth of real directory structures as it fails to reproduce the level distribution. This insight can be generalised to point out the importance of the level distribution for modeling tree growth.Comment: 16 pages, 7 figure

    PNAS plus: plasmodium falciparum responds to amino acid starvation by entering into a hibernatory state

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    The human malaria parasite Plasmodium falciparum is auxotrophic for most amino acids. Its amino acid needs are met largely through the degradation of host erythrocyte hemoglobin; however the parasite must acquire isoleucine exogenously, because this amino acid is not present in adult human hemoglobin. We report that when isoleucine is withdrawn from the culture medium of intraerythrocytic P. falciparum, the parasite slows its metabolism and progresses through its developmental cycle at a reduced rate. Isoleucine-starved parasites remain viable for 72 h and resume rapid growth upon resupplementation. Protein degradation during starvation is important for maintenance of this hibernatory state. Microarray analysis of starved parasites revealed a 60% decrease in the rate of progression through the normal transcriptional program but no other apparent stress response. Plasmodium parasites do not possess a TOR nutrient-sensing pathway and have only a rudimentary amino acid starvation-sensing eukaryotic initiation factor 2α (eIF2α) stress response. Isoleucine deprivation results in GCN2-mediated phosphorylation of eIF2α, but kinase-knockout clones still are able to hibernate and recover, indicating that this pathway does not directly promote survival during isoleucine starvation. We conclude that P. falciparum, in the absence of canonical eukaryotic nutrient stress-response pathways, can cope with an inconsistent bloodstream amino acid supply by hibernating and waiting for more nutrient to be provided

    Reduction-cleavable desferrioxamine B pulldown system enriches Ni( ii )-superoxide dismutase from a Streptomyces proteome

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    Two resins with the hydroxamic acid siderophore desferrioxamine B (DFOB) immobilised as a free ligand or its Fe(iii) complex were prepared to screen the Streptomyces pilosus proteome for proteins involved in siderophore-mediated Fe(iii) uptake. The resin design included a disulfide bond to enable the release of bound proteins under mild reducing conditions. Proteomics analysis of the bound fractions did not identify proteins associated with siderophore-mediated Fe(iii) uptake, but identified nickel superoxide dismutase (NiSOD), which was enriched on the apo-DFOB-resin but not the Fe(iii)-DFOB-resin or the control resin. While DFOB is unable to sequester Fe(iii) from sites deeply buried in metalloproteins, the coordinatively unsaturated Ni(ii) ion in NiSOD is present in a surface-exposed loop region at the N-terminus, which might enable partial chelation. The results were consistent with the notion that the apo-DFOB-resin formed a ternary complex with NiSOD, which was not possible for either the coordinatively saturated Fe(iii)-DFOB-resin or the non-coordinating control resin systems. In support, ESI-TOF-MS measurements from a solution of a model Ni(ii)-SOD peptide and DFOB showed signals that correlated with a ternary Ni(ii)-SOD peptide–DFOB complex. Although any biological implications of a DFOB–NiSOD complex are unclear, the work shows that the metal coordination properties of siderophores might influence an array of metal-dependent biological processes beyond those established in iron uptake

    Case study on the efficacy of a lanthanum-enriched clay (Phoslock®) in controlling eutrophication in Lake Het Groene Eiland (The Netherlands)

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    Lake Het Groene Eiland was created in the beginning of 2008 by construction of dikes for isolating it from the surrounding 220-ha water body. This so-called claustrum of 5 ha was treated using lanthanum-modified clay (Phoslock®) to control eutrophication and mitigate cyanobacterial nuisance. Cyanobacteria chlorophyll-a were significantly lower in the claustrum than those in the reference water body, where a massive bloom developed in summer, 2008. However, PO4-P and TP did not statistically differ in these two waters. TN and NO3-N were significantly lower in the claustrum, where dense submerged macrophytes beds developed. Lanthanum concentrations were elevated after the applications of the modified clay in the claustrum, but filterable lanthanum dropped rapidly below the Dutch standard of 10.1 μg l−1. During winter, dozens of Canada geese resided at the claustrum. Geese droppings contained an average of 2 mg PO4-P g−1 dry weight and 12 mg NH3-N g−1 dry weight and might present a growing source of nutrients to the water. Constructing the claustrum enabled unrestricted bathing in subsequent three summers, as no swimming bans had to be issued due to cyanobacteria blooms. However, the role of the modified clay in this positive outcome remains unclear, and longevity of the measures questionable.
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