STORING MESSAGE RECORDS IN A BLOCK CHAIN LEDGER FOR HIGH THROUGHPUT TRAFFIC

Techniques are provided herein for recording every message transaction of a network inside a block chain in a scalable manner. The authenticity of a message may be verified independently without transferring any data during the verification process

Operations and Performance of the PACS Instrument 3He Sorption Cooler on board of the Herschel Space Observatory

A 3He sorption cooler produced the operational temperature of 285mK for the bolometer arrays of the Photodetector Array Camera and Spectrometer (PACS) instrument of the Herschel Space Observatory. This cooler provided a stable hold time between 60 and 73h, depending on the operational conditions of the instrument. The respective hold time could be determined by a simple functional relation established early on in the mission and reliably applied by the scientific mission planning for the entire mission. After exhaustion of the liquid 3He due to the heat input by the detector arrays, the cooler was recycled for the next operational period following a well established automatic procedure. We give an overview of the cooler operations and performance over the entire mission and distinguishing in-between the start conditions for the cooler recycling and the two main modes of PACS photometer operations. As a spin-off, the cooler recycling temperature effects on the Herschel cryostat 4He bath were utilized as an alternative method to dedicated Direct Liquid Helium Content Measurements in determining the lifetime of the liquid Helium coolant.Comment: 34 pages, 13 figures, accepted in Experimental Astronom

Selective In Vivo and In Vitro Effects of a Small Molecule Inhibitor of Cyclin-Dependent Kinase 4

Background: Cyclin-dependent kinase 4 (Cdk4) represents a prime target for the treatment of cancer because most human cancers are characterized by overexpression of its activating partner cyclin D1, loss of the natural Cdk4-specific inhibitor p16, or mutation(s) in Cdk4's catalytic subunit. All of these can cause deregulated cell growth, resulting in tumor formation. We sought to identify a small molecule that could inhibit the kinase activity of Cdk4 in vitro and to then ascertain the effects of that inhibitor on cell growth and tumor volume in vivo. Methods: A triaminopyrimidine derivative, CINK4 (a chemical inhibitor of Cdk4), was identified by screening for compounds that could inhibit Cdk4 enzyme activity in vitro. Kinase assays were performed on diverse human Cdks and on other kinases that were expressed in and purified from insect cells to determine the specificity of CINK4. Cell cycle effects of CINK4 on tumor and normal cells were studied by flow cytometry, and changes in phosphorylation of the retinoblastoma protein (pRb), a substrate of Cdk4, were determined by western blotting. The effect of the inhibitor on tumor growth in vivo was studied by use of tumors established through xenografts of HCT116 colon carcinoma cells in mice. Statistical tests were two-sided. Results: CINK4 specifically inhibited Cdk4/cyclin D1 in vitro. It caused growth arrest in tumor cells and in normal cells and prevented pRb phosphorylation. CINK4 treatment resulted in statistically significantly (P = .031) smaller mean tumor volumes in a mouse xenograft model. Conclusions: Like p16, the natural inhibitor of Cdk4, CINK4 inhibits Cdk4 activity in vitro and slows tumor growth in vivo. The specificity of CINK4 for Cdk4 raises the possibility that this small molecule or one with a similar structure could have therapeutic valu

Improving Context-Awareness in Self-Adaptation Using the DYNAMICO Reference Model

International audienceSelf-adaptation mechanisms modify target systems dynamically to address adaptation goals, which may evolve continuously due to changes in system requirements. These changes affect values and thresholds of observed context variables and monitoring logic, or imply the addition and/or deletion of context variables, thus compromising self-adaptivity effectiveness under static monitoring infrastructures. Nevertheless, self-adaptation approaches often focus on adapting target systems only rather than monitoring infrastructures. Previously, we proposed DYNAMICO, a reference model for self-adaptive systems where adaptation goals and monitoring requirements change dynamically. This paper presents an implementation of DYNAMICO comprising our SMARTERCONTEXT monitoring infrastructure and QOS-CARE adaptation framework in a self-adaptation solution that maintains its context-awareness relevance. To evaluate our reference model we use self-adaptive system properties and the Znn.com exemplar to compare the Rainbow system with our DYNAMICO implementation. The results of the evaluation demonstrate the applicability, feasibility, and effectiveness of DYNAMICO, especially for self-adaptive systems with context-awareness requirements

A Framework for the Design Configuration of Accountable Selfish-Resilient Peer-to-Peer Systems

International audienceA challenge in designing a peer-to-peer (P2P) system is to ensure that the system is able to tolerate selfish nodes that strategically deviate from their specification whenever doing so is convenient. In this paper, we propose RACOON, a framework for the design of P2P systems that are resilient to selfish behaviours. While most existing solutions target specific systems or types of selfishness, RACOON proposes a generic and semi-automatic approach that achieves robust and reusable results. Also, RACOON supports the system designer in the performance-oriented tuning of the system, by proposing a novel approach that combines Game Theory and simulations. We illustrate the benefits of using RACOON by designing two P2P systems: a live streaming and an anonymous communication system. In simulations and a real deployment of the two applications on a testbed comprising 100 nodes, the systems designed using RACOON achieve both resilience to selfish nodes and high performance

Development of an LDL Receptor-Targeted Peptide Susceptible to Facilitate the Brain Access of Diagnostic or Therapeutic Agents

Blood-brain barrier (BBB) crossing and brain penetration are really challenging for the delivery of therapeutic agents and imaging probes. The development of new crossing strategies is needed, and a wide range of approaches (invasive or not) have been proposed so far. The receptor-mediated transcytosis is an attractive mechanism, allowing the non-invasive penetration of the BBB. Among available targets, the low-density lipoprotein (LDL) receptor (LDLR) shows favorable characteristics mainly because of the lysosome-bypassed pathway of LDL delivery to the brain, allowing an intact discharge of the carried ligand to the brain targets. The phage display technology was employed to identify a dodecapeptide targeted to the extracellular domain of LDLR (ED-LDLR). This peptide was able to bind the ED-LDLR in the presence of natural ligands and dissociated at acidic pH and in the absence of calcium, in a similar manner as the LDL. In vitro, our peptide was endocytosed by endothelial cells through the caveolae-dependent pathway, proper to the LDLR route in BBB, suggesting the prevention of its lysosomal degradation. The in vivo studies performed by magnetic resonance imaging and fluorescent lifetime imaging suggested the brain penetration of this ED-LDLR-targeted peptide

Can a Common Currency Foster a Shared Social Identity across Different Nations? The Case of the Euro

Fostering the emergence of a “European identity” was one of the declared goals of the euro adoption. Now, years after the physical introduction of the common currency, we investigate whether there has been an effect on a shared European identity. We use two different datasets in order to assess the impact of the euro adoption on the fostering of a self-declared “European Identity”. We find that the effect of the euro is statistically insignificant. We interpret this result as suggesting that the euro did not have the desired positive effect on feelings of European identity. This result holds important implications for European policy makers. It also sheds new light on the formation of social identities

Global response of Plasmodium falciparum to hyperoxia: a combined transcriptomic and proteomic approach

<p>Abstract</p> <p>Background</p> <p>Over its life cycle, the <it>Plasmodium falciparum </it>parasite is exposed to different environmental conditions, particularly to variations in O₂pressure. For example, the parasite circulates in human venous blood at 5% O₂pressure and in arterial blood, particularly in the lungs, at 13% O₂pressure. Moreover, the parasite is exposed to 21% O₂levels in the salivary glands of mosquitoes.</p> <p>Methods</p> <p>To study the metabolic adaptation of <it>P. falciparum </it>to different oxygen pressures during the intraerythrocytic cycle, a combined approach using transcriptomic and proteomic techniques was undertaken.</p> <p>Results</p> <p>Even though hyperoxia lengthens the parasitic cycle, significant transcriptional changes were detected in hyperoxic conditions in the late-ring stage. Using PS 6.0™ software (Ariadne Genomics) for microarray analysis, this study demonstrate up-expression of genes involved in antioxidant systems and down-expression of genes involved in the digestive vacuole metabolism and the glycolysis in favour of mitochondrial respiration. Proteomic analysis revealed increased levels of heat shock proteins, and decreased levels of glycolytic enzymes. Some of this regulation reflected post-transcriptional modifications during the hyperoxia response.</p> <p>Conclusions</p> <p>These results seem to indicate that hyperoxia activates antioxidant defence systems in parasites to preserve the integrity of its cellular structures. Moreover, environmental constraints seem to induce an energetic metabolism adaptation of <it>P. falciparum</it>. This study provides a better understanding of the adaptive capabilities of <it>P. falciparum </it>to environmental changes and may lead to the development of novel therapeutic targets.</p

Local Increase of Arginase Activity in Lesions of Patients with Cutaneous Leishmaniasis in Ethiopia

The leishmaniases are a complex of diseases caused by Leishmania parasites. Currently, the diseases affect an estimated 12 million people in 88 countries, and approximately 350 million more people are at risk. The leishmaniases belong to the most neglected tropical diseases, affecting the poorest populations, for whom access to diagnosis and effective treatment are often not available. Leishmania parasites infect cells of the immune system called macrophages, which have the capacity to eliminate the intracellular parasites when they receive the appropriate signals from other cells of the immune system. In nonhealing persistent leishmaniasis, lymphocytes are unable to transmit the signals to macrophages required to kill the intracellular parasites. The local upregulation of the enzyme arginase has been shown to impair lymphocyte effector functions at the site of pathology. In this study, we tested the activity of this enzyme in skin lesions of patients presenting with localized cutaneous leishmaniasis. Our results show that arginase is highly upregulated in these lesions. This increase in arginase activity coincides with lower expression of a signalling molecule in lymphocytes, which is essential for efficient activation of these cells. These results suggest that increased arginase expression in the localized cutaneous lesions might contribute to persistent disease in patients presenting with cutaneous leishmaniasis