A Call to Arms: Revisiting Database Design

Good database design is crucial to obtain a sound, consistent database, and - in turn - good database design methodologies are the best way to achieve the right design. These methodologies are taught to most Computer Science undergraduates, as part of any Introduction to Database class. They can be considered part of the "canon", and indeed, the overall approach to database design has been unchanged for years. Moreover, none of the major database research assessments identify database design as a strategic research direction. Should we conclude that database design is a solved problem? Our thesis is that database design remains a critical unsolved problem. Hence, it should be the subject of more research. Our starting point is the observation that traditional database design is not used in practice - and if it were used it would result in designs that are not well adapted to current environments. In short, database design has failed to keep up with the times. In this paper, we put forth arguments to support our viewpoint, analyze the root causes of this situation and suggest some avenues of research.Comment: Removed spurious column break. Nothing else was change

Publication of RDF streams with Ztreamy

Proceedings of ESWC 2014 Satellite Events, Anissaras, Crete, Greece, May 25–29, 2014There is currently an interest in the Semantic Web community for the development of tools and techniques to process RDF streams. Implementing an effective RDF stream processing system requires to address several aspects including stream generation, querying, reasoning, etc. In this work we focus on one of them: the distribution of RDF streams through the Web. In order to address this issue, we have developed Ztreamy, a scalable middleware which allows to publish and consume RDF streams through HTTP. The goal of this demo is to show the functionality of Ztreamy in two different scenarios with actual, heterogeneous streaming data.This work has been partially funded by the Spanish Government through the project HERMES-SMARTDRIVER (TIN2013-46801-C4-2-R)

A combined geochemical and μCT study on the CO2 reactivity of Surat Basin reservoir and cap-rock cores: porosity changes, mineral dissolution and fines migration

Geological storage of CO generally involves injection of a CO stream into a high porosity and permeability reservoir, contained by one or more overlying low permeability formations. Sandstone reservoirs and associated cap-rocks of targeted CO storage sites therefore have distinct properties such as porosity and mineral contents. Their geochemical response or reactivity to injected supercritical CO and associated changes in porosity, and permeability affecting scaling, mineral trapping, injectivity, or migration can therefore be very different. Six drill core samples including quartz-rich sandstones, calcite cemented sandstones, and feldspar or clay-rich cap-rocks from a proposed demonstration site in the Surat Basin, Australia, were characterized before and after reaction with pure supercritical CO and low salinity formation water. The quartz-rich sandstones have low reactivity, and maintain high porosities with visible pore connectivity after reaction, they are unlikely to be affected by scaling. Kaolin and fine grain movement observed via μCT and SEM could have the potential to open or plug pores, potentially increasing or decreasing permeability and CO injectivity. Calcite cemented sandstones had the greatest measured change in porosity after reaction via calcite dissolution. Narrow angular channels were formed in the calcite cement around framework grains, extending through to the center of the sub-plug in the courser grained rock, and surface roughness increased. Solution pH was however quickly passivated. The highest concentrations of Ca, Mn, Sr, and Mg were released to solution from calcite dissolution. Clay (and feldspar) rich cap-rock core had mainly microporosity and the smallest initial pore throat diameters associated with clays. Small changes to μCT calculated porosities after reaction were related to a decrease in chlorite X-ray density, and dissolution of patchy carbonate minerals. Pores were disconnected in μCT images, except for some created horizontal connection along a sandy lamination in a cap-rock. Dissolved concentrations of Ca, Fe, Si, Sr, Mn, Li and Mg increased via dissolution of both carbonate and silicate minerals. Dissolved Ca, Fe, Mn and Mg from silicate minerals in the cap-rock were available for longer term mineral trapping of CO. Potential increases in porosity and migration will be highest in the calcite cemented zones, while clay-rich cap-rocks could be expected to maintain integrity. There is a low likelihood of mineral trapping or scaling in the quartz rich lower Precipice Sandstone. Overlying rocks can provide Fe, Mg, Ca for mineral trapping of CO as ferroan carbonates such as siderite, ankerite and dolomite over longer time scales when pH is buffered. Changes to porosity, mineral content, and water chemistry after pure CO reaction observed here and in other published studies were dependent on mineral content and fluid accessibility. These results could be generalized to other sandstone reservoirs where it is expected to inject CO. The results can also be used to validate geochemical models to build longer term predictions

Mouse models for preeclampsia: disruption of redox-regulated signaling

The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

A Framework for Online Conformance Checking

Conformance checking – a branch of process mining – focuses on establishing to what extent actual executions of a process are in line with the expected behavior of a reference model. Current conformance checking techniques only allow for a-posteriori analysis: the amount of (non-)conformant behavior is quantified after the completion of the process instance. In this paper we propose a framework for online conformance checking: not only do we quantify (non-)conformant behavior as the execution is running, we also restrict the computation to constant time complexity per event analyzed, thus enabling the online analysis of a stream of events. The framework is instantiated with ideas coming from the theory of regions, and state similarity. An implementation is available in ProM and promising results have been obtained.Peer ReviewedPostprint (author's final draft

Multi-Modality Therapeutics with Potent Anti-Tumor Effects: Photochemical Internalization Enhances Delivery of the Fusion Toxin scFvMEL/rGel

BACKGROUND: There is a need for drug delivery systems (DDS) that can enhance cytosolic delivery of anti-cancer drugs trapped in the endo-lysosomal compartments. Exposure of cells to specific photosensitizers followed by light exposure (photochemical internalization, PCI) results in transfer of agents from the endocytic compartment into the cytosol. METHODOLOGY AND PRINCIPAL FINDINGS: The recombinant single-chain fusion construct scFvMEL/rGel is composed of an antibody targeting the progenitor marker HMW-MAA/NG2/MGP/gp240 and the highly effective toxin gelonin (rGel). Here we demonstrate enhanced tumor cell selectivity, cytosolic delivery and anti-tumor activity by applying PCI of scFvMEL/rGel. PCI performed by light activation of cells co-incubated with scFvMEL/rGel and the endo-lysosomal targeting photosensitizers AlPcS(2a) or TPPS(2a) resulted in enhanced cytotoxic effects against antigen-positive cell lines, while no differences in cytotoxicity between the scFvMEL/rGel and rGel were observed in antigen-negative cells. Mice bearing well-developed melanoma (A-375) xenografts (50-100 mm(3)) were treated with PCI of scFvMEL/rGel. By 30 days after injection, approximately 100% of mice in the control groups had tumors>800 mm(3). In contrast, by day 40, 50% of mice in the PCI of scFvMEL/rGel combination group had tumors<800 mm(3) with no increase in tumor size up to 110 days. PCI of scFvMEL/rGel resulted in a synergistic effect (p<0.05) and complete regression (CR) in 33% of tumor-bearing mice (n = 12). CONCLUSIONS/SIGNIFICANCE: This is a unique demonstration that a non-invasive multi-modality approach combining a recombinant, targeted therapeutic such as scFvMEL/rGel and PCI act in concert to provide potent in vivo efficacy without sacrificing selectivity or enhancing toxicity. The present DDS warrants further evaluation of its clinical potential