181 research outputs found
Multitask Learning on Graph Neural Networks: Learning Multiple Graph Centrality Measures with a Unified Network
The application of deep learning to symbolic domains remains an active
research endeavour. Graph neural networks (GNN), consisting of trained neural
modules which can be arranged in different topologies at run time, are sound
alternatives to tackle relational problems which lend themselves to graph
representations. In this paper, we show that GNNs are capable of multitask
learning, which can be naturally enforced by training the model to refine a
single set of multidimensional embeddings and decode them
into multiple outputs by connecting MLPs at the end of the pipeline. We
demonstrate the multitask learning capability of the model in the relevant
relational problem of estimating network centrality measures, focusing
primarily on producing rankings based on these measures, i.e. is vertex
more central than vertex given centrality ?. We then show that a GNN
can be trained to develop a \emph{lingua franca} of vertex embeddings from
which all relevant information about any of the trained centrality measures can
be decoded. The proposed model achieves accuracy on a test dataset of
random instances with up to 128 vertices and is shown to generalise to larger
problem sizes. The model is also shown to obtain reasonable accuracy on a
dataset of real world instances with up to 4k vertices, vastly surpassing the
sizes of the largest instances with which the model was trained ().
Finally, we believe that our contributions attest to the potential of GNNs in
symbolic domains in general and in relational learning in particular.Comment: Published at ICANN2019. 10 pages, 3 Figure
Occupation time of exclusion processes with conductances
Em publicação em "Journal of statistical physics". ISSN 0022-4715.We obtain the fluctuations for the occupation time of one-dimensional symmetric exclusion processes with speed change, where the transition rates ({\em conductances}) are driven by a general function . The approach does not require sharp bounds on the spectral gap of the system nor the jump rates to be bounded from above or below. We present some examples and for one of them, we observe that the fluctuations of the current are trivial, but the fluctuations of the occupation time are given by a fractional Brownian Motion. This shows that, in general, the fluctuations of the current and of the occupation time are not of same order.CAPESFundação para a CiĂȘncia e a Tecnologia (FCT)CNP
Kinetics and fracture resistance of lithiated silicon nanostructure pairs controlled by their mechanical interaction
Following an explosion of studies of silicon as a negative electrode for Li-ion batteries, the anomalous volumetric changes and fracture of lithiated single Si particles have attracted significant attention in various fields, including mechanics. However, in real batteries, lithiation occurs simultaneously in clusters of Si in a confined medium. Hence, understanding how the individual Si structures interact during lithiation in a closed space is necessary. Here, we demonstrate physical and mechanical interactions of swelling Si structures during lithiation using well-defined Si nanopillar pairs. Ex situ SEM and in situ TEM studies reveal that compressive stresses change the reaction kinetics so that preferential lithiation occurs at free surfaces when the pillars are mechanically clamped. Such mechanical interactions enhance the fracture resistance of lithiated Si by lessening the tensile stress concentrations in Si structures. This study will contribute to improved design of Si structures at the electrode level for high-performance Li-ion batteries.open1
Analysis of the piggyBac transposase reveals a functional nuclear targeting signal in the 94 c-terminal residues
<p>Abstract</p> <p>Background</p> <p>The <it>piggyBac</it> transposable element is a popular tool for germ-line transgenesis of eukaryotes. Despite this, little is known about the mechanism of transposition or the transposase (TPase) itself. A thorough understanding of just how <it>piggyBac</it> works may lead to more effective use of this important mobile element. A PSORTII analysis of the TPase amino acid sequence predicts a bipartite nuclear localization signal (NLS) near the c-terminus, just upstream of a putative ZnF (ZnF).</p> <p>Results</p> <p>We fused the <it>piggyBac</it> TPase upstream of and in-frame with the enhanced yellow fluorescent protein (EYFP) in the <it>Drosophila melanogaster</it> inducible metallothionein protein. Using Drosophila Schneider 2 (S2) cells and the deep red fluorescent nuclear stain Draq5, we were able to track the pattern of <it>piggyBac</it> localization with a scanning confocal microscope 48 hours after induction with copper sulphate.</p> <p>Conclusion</p> <p>Through n and c-terminal truncations, targeted internal deletions, and specific amino acid mutations of the <it>piggyBac</it> TPase open reading frame, we found that not only is the PSORTII-predicted NLS required for the TPase to enter the nucleus of S2 cells, but there are additional requirements for negatively charged amino acids a short length upstream of this region for nuclear localization.</p
Development of the piggyBac transposable system for Plasmodium berghei and its application for random mutagenesis in malaria parasites
Background: The genome of a number of species of malaria parasites ( Plasmodium spp.) has been sequenced in the hope of identifying new drug and vaccine targets. However, almost one-half of predicted Plasmodium genes are annotated as hypothetical and are difficult to analyse in bulk due to the inefficiency of current reverse genetic methodologies for Plasmodium. Recently, it has been shown that the transposase piggyBac integrates at random into the genome of the human malaria parasite P. falciparum offering the possibility to develop forward genetic screens to analyse Plasmodium gene function. This study reports the development and application of the piggyBac transposition system for the rodent malaria parasite P. berghei and the evaluation of its potential as a tool in forward genetic studies. P. berghei is the most frequently used malaria parasite model in gene function analysis since phenotype screens throughout the complete Plasmodium life cycle are possible both in vitro and in vivo. Results: We demonstrate that piggyBac based gene inactivation and promoter-trapping is both easier and more efficient in P. berghei than in the human malaria parasite, P. falciparum. Random piggyBac-mediated insertion into genes was achieved after parasites were transfected with the piggyBac donor plasmid either when transposase was expressed either from a helper plasmid or a stably integrated gene in the genome. Characterization of more than 120 insertion sites demonstrated that more than 70 most likely affect gene expression classifying their protein products as non-essential for asexual blood stage development. The non-essential nature of two of these genes was confirmed by targeted gene deletion one of which encodes P41, an ortholog of a human malaria vaccine candidate. Importantly for future development of whole genome phenotypic screens the remobilization of the piggyBac element in parasites that stably express transposase was demonstrated. Conclusion: These data demonstrate that piggyBac behaved as an efficient and random transposon in P. berghei. Remobilization of piggyBac element shows that with further development the piggyBac system can be an effective tool to generate random genome-wide mutation parasite libraries, for use in large-scale phenotype screens in vitro and in viv
Properties, production, and applications of camelid single-domain antibody fragments
Camelids produce functional antibodies devoid of light chains of which the single N-terminal domain is fully capable of antigen binding. These single-domain antibody fragments (VHHs or NanobodiesÂź) have several advantages for biotechnological applications. They are well expressed in microorganisms and have a high stability and solubility. Furthermore, they are well suited for construction of larger molecules and selection systems such as phage, yeast, or ribosome display. This minireview offers an overview of (1) their properties as compared to conventional antibodies, (2) their production in microorganisms, with a focus on yeasts, and (3) their therapeutic applications
On Maximum Weight Clique Algorithms, and How They Are Evaluated
Maximum weight clique and maximum weight independent set solvers are often benchmarked using maximum clique problem instances, with weights allocated to vertices by taking the vertex number mod 200 plus 1. For constraint programming approaches, this rule has clear implications, favouring weight-based rather than degree-based heuristics. We show that similar implications hold for dedicated algorithms, and that additionally, weight distributions affect whether certain inference rules are cost-effective. We look at other families of benchmark instances for the maximum weight clique problem, coming from winner determination problems, graph colouring, and error-correcting codes, and introduce two new families of instances, based upon kidney exchange and the Research Excellence Framework. In each case the weights carry much more interesting structure, and do not in any way resemble the 200 rule. We make these instances available in the hopes of improving the quality of future experiments
Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release
Micelles are colloidal particles with a size around 5â100Â nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a âmagic bulletâ a major step forward
Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications
Superparamagnetic iron oxide nanoparticles
can providemultiple benefits for biomedical applications
in aqueous environments such asmagnetic separation or
magnetic resonance imaging. To increase the colloidal
stability and allow subsequent reactions, the introduction
of hydrophilic functional groups onto the particlesâ
surface is essential. During this process, the original
coating is exchanged by preferably covalently bonded
ligands such as trialkoxysilanes. The duration of the
silane exchange reaction, which commonly takes more
than 24 h, is an important drawback for this approach. In
this paper, we present a novel method, which introduces
ultrasonication as an energy source to dramatically
accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove
the generic character, different functional groups were
introduced on the surface including polyethylene glycol
chains, carboxylic acid, amine, and thiol groups. Their
colloidal stability in various aqueous buffer solutions as
well as human plasma and serum was investigated to
allow implementation in biomedical and sensing
applications.status: publishe
Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)
Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved
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