499 research outputs found

    Looking for Hypergiants in PeeringDB

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    Improving Lifelong Learning by Fostering Students' Learning Strategies at University

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    The foundation of how students usually learn is laid early in their academic lives. However, many or even most students do not primarily rely on those learning strategies that are most favorable from a scientific point of view. To change students' learning behavior when they start their university education, we developed a computer-based adaptive learning environment to train favorable learning strategies and change students' habits using them. This learning environment pursues three main goals: acquiring declarative and conditional knowledge about learning strategies, consolidating that knowledge, and applying these learning strategies in practice. In this report, we describe four experimental studies conducted to optimize this learning environment (n = 336). With those studies, we improved the learning environment with respect to how motivating it is, investigated an efficient way to consolidate knowledge, and explored how to facilitate the formation of effective implementation intentions for applying learning strategies and changing learning habits. Our strategy-training module is implemented in the curriculum for freshman students at the Department of Psychology, University of Freiburg (Germany). Around 120 students take part in our program every year. An open version of this training intervention is freely available to everyone

    Open Connect Everywhere: A Glimpse at the Internet Ecosystem through the Lens of the Netflix CDN

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    The importance of IXPs to interconnect different networks and exchange traffic locally has been well studied over the last few years. However, far less is known about the role IXPs play as a platform to enable large-scale content delivery and to reach a world-wide customer base. In this paper, we study the infrastructure deployment of a content hypergiant, Netflix, and show that the combined worldwide IXP substrate is the major corner stone of its Content Delivery Network. To meet its worldwide demand for high-quality video delivery, Netflix has built a dedicated CDN. Its scale allows us to study a major part of the Internet ecosystem, by observing how Netflix takes advantage of the combined capabilities of IXPs and ISPs present in different regions. We find wide disparities in the regional Netflix deployment and traffic levels at IXPs and ISPs across various local ecosystems. This highlights the complexity of large-scale content delivery as well as differences in the capabilities of IXPs in specific regions. On a global scale we find that the footprint provided by IXPs allows Netflix to deliver most of its traffic directly from them. This highlights the additional role that IXPs play in the Internet ecosystem, not just in terms of interconnection, but also allowing players such as Netflix to deliver significant amounts of traffic

    Percolation Systems away from the Critical Point

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    This article reviews some effects of disorder in percolation systems even away from the critical density p_c. For densities below p_c, the statistics of large clusters defines the animals problem. Its relation to the directed animals problem and the Lee-Yang edge singularity problem is described. Rare compact clusters give rise to Griffiths singuraties in the free energy of diluted ferromagnets, and lead to a very slow relaxation of magnetization. In biassed diffusion on percolation clusters, trapping in dead-end branches leads to asymptotic drift velocity becoming zero for strong bias, and very slow relaxation of velocity near the critical bias field.Comment: Minor typos fixed. Submitted to Praman

    An Empirical Study of the Cost of DNS-over-HTTPS

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    DNS is a vital component for almost every networked application. Originally it was designed as an unencrypted protocol, making user security a concern. DNS-over-HTTPS (DoH) is the latest proposal to make name resolution more secure. In this paper we study the current DNS-over-HTTPS ecosystem, especially the cost of the additional security. We start by surveying the current DoH landscape by assessing standard compliance and supported features of public DoH servers. We then compare different transports for secure DNS, to highlight the improvements DoH makes over its predecessor, DNS-over-TLS (DoT). These improvements explain in part the significantly larger take-up of DoH in comparison to DoT. Finally, we quantify the overhead incurred by the additional layers of the DoH transport and their impact on web page load times. We find that these overheads only have limited impact on page load times, suggesting that it is possible to obtain the improved security of DoH with only marginal performance impact

    mRNA Display Selection of an Optimized MDM2-Binding Peptide That Potently Inhibits MDM2-p53 Interaction

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    p53 is a tumor suppressor protein that prevents tumorigenesis through cell cycle arrest or apoptosis of cells in response to cellular stress such as DNA damage. Because the oncoprotein MDM2 interacts with p53 and inhibits its activity, MDM2-p53 interaction has been a major target for the development of anticancer drugs. While previous studies have used phage display to identify peptides (such as DI) that inhibit the MDM2-p53 interaction, these peptides were not sufficiently optimized because the size of the phage-displayed random peptide libraries did not cover all of the possible sequences. In this study, we performed selection of MDM2-binding peptides from large random peptide libraries in two stages using mRNA display. We identified an optimal peptide named MIP that inhibited the MDM2-p53 and MDMX-p53 interactions 29- and 13-fold more effectively than DI, respectively. Expression of MIP fused to the thioredoxin scaffold protein in living cells by adenovirus caused stabilization of p53 through its interaction with MDM2, resulting in activation of the p53 pathway. Furthermore, expression of MIP also inhibited tumor cell proliferation in a p53-dependent manner more potently than DI. These results show that two-stage, mRNA-displayed peptide selection is useful for the rapid identification of potent peptides that target oncoproteins

    Rapid intraoperative insulin assay: a novel method to differentiate insulinoma from nesidioblastosis in the pediatric patient

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    Introduction: Hyperinsulinism is the most common cause of recurrent and persistent hypoglycemia in infancy and childhood. Causes can include nesidioblastosis, pancreatic islet cell tumors such as insulinoma, and associations with multiple endocrine neoplasia syndromes. Although new, improved imaging techniques have allowed for more precise preoperative localization of insulinomas, the differentiation of nesidioblastosis and insulinoma, particularly in children, can be challenging. To improve intraoperative localization and confirmation of successful resection of insulinoma, a novel hormonal assay, the rapid intraoperative insulin assay, is reported for the first time in a pediatric patient. This intraoperative radioimmunoassay for insulin yields results within several minutes and confirms complete resection of insulinoma. Case description: We present a case of pancreatic insulinoma in a child with symptoms of severe hypoglycemia, causing seizures. The insulinoma was enucleated laparoscopically, and rapid intra-operative insulin assay used to determine the success of the procedure. Discussion and evaluation: This rapid intra-operative test provides a valuable adjunct for determining complete excision in complicated cases of recurrent or questionable insulinoma. Although not a common problem, for pediatric patients in whom the diagnosis is not clear, this test may provide a novel approach to confirming disease. Conclusion: We propose the use of this assay in facilitating intra-operative resection and confirmation of complete excision in pediatric patients. This population may especially benefit from this novel assay to confirm complete resection and to differentiate multiple etiologies of hyperinsulinism

    Interventional radiology virtual simulator for liver biopsy

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    Purpose Training in Interventional Radiology currently uses the apprenticeship model, where clinical and technical skills of invasive procedures are learnt during practice in patients. This apprenticeship training method is increasingly limited by regulatory restrictions on working hours, concerns over patient risk through trainees’ inexperience and the variable exposure to case mix and emergencies during training. To address this, we have developed a computer-based simulation of visceral needle puncture procedures. Methods A real-time framework has been built that includes: segmentation, physically based modelling, haptics rendering, pseudo-ultrasound generation and the concept of a physical mannequin. It is the result of a close collaboration between different universities, involving computer scientists, clinicians, clinical engineers and occupational psychologists. Results The technical implementation of the framework is a robust and real-time simulation environment combining a physical platform and an immersive computerized virtual environment. The face, content and construct validation have been previously assessed, showing the reliability and effectiveness of this framework, as well as its potential for teaching visceral needle puncture. Conclusion A simulator for ultrasound-guided liver biopsy has been developed. It includes functionalities and metrics extracted from cognitive task analysis. This framework can be useful during training, particularly given the known difficulties in gaining significant practice of core skills in patients

    Effective Rheology of Bubbles Moving in a Capillary Tube

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    We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

    C-Terminal Substitution of MDM2 Interacting Peptides Modulates Binding Affinity by Distinctive Mechanisms

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    The complex between the proteins MDM2 and p53 is a promising drug target for cancer therapy. The residues 19–26 of p53 have been biochemically and structurally demonstrated to be a most critical region to maintain the association of MDM2 and p53. Variation of the amino acid sequence in this range obviously alters the binding affinity. Surprisingly, suitable substitutions contiguous to this region of the p53 peptides can yield tightly binding peptides. The peptide variants may differ by a single residue that vary little in their structural conformations and yet are characterized by large differences in their binding affinities. In this study a systematic analysis into the role of single C-terminal mutations of a 12 residue fragment of the p53 transactivation domain (TD) and an equivalent phage optimized peptide (12/1) were undertaken to elucidate their mechanistic and thermodynamic differences in interacting with the N-terminal of MDM2. The experimental results together with atomistically detailed dynamics simulations provide insight into the principles that govern peptide design protocols with regard to protein-protein interactions and peptidomimetic design
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