Targeted Disruption of Core 1 β1,3-galactosyltransferase (C1galt1) Induces Apical Endocytic Trafficking in Human Corneal Keratinocytes

Exposed mucosal surfaces limit constitutive endocytosis under physiological conditions to prevent uptake of macromolecules and pathogens and, therefore, cellular damage. It is now accepted that cell surface mucins, a group of high molecular weight glycoproteins on the epithelial glycocalyx, defined by their extensive O-glycosylation, play a major role in maintaining barrier function in these surfaces, but the precise mechanisms are unclear.In this work, we utilized a stable tetracycline-inducible RNA interfering system targeting the core 1 ß1,3-galactosyltransferase (C1galt1 or T-synthase), a critical galactosyltransferase required for the synthesis of core 1 O-glycans, to explore the role of mucin-type carbohydrates in apical endocytic trafficking in human corneal keratinocytes. Using cell surface biotinylation and subcellular fractionation, we found increased accumulation of plasma membrane protein in endosomes after C1galt1 depletion. Confocal laser scanning microscopy and fluorometry revealed increased translocation of negatively charged fluorescent nanospheres after C1galt1 knockdown sustained by an active transport process and largely independent of apical intercellular junctions. Internalization of nanospheres could be blocked by dynasore, nocodazole, chlorpromazine, and hyperosmotic sucrose, suggesting a mechanism for clathrin-coated pit budding and vesicular trafficking. This possibility was supported by experiments showing nanosphere colocalization with clathrin heavy chain in the cytoplasm.Together, the data suggest that core 1 O-glycans contribute to maintenance of apical barrier function on exposed mucosal surfaces by preventing clathrin-mediated endocytosis

A phenomenological explanation of the autoignition propagation under HCCI conditions

[EN] A phenomenological explanation about the autoignition propagation under HCCI conditions is developed in this paper. To do so, diffusive effects from the burned zones to the fresh mixture, pressure waves based effects and expansion effects caused by combustion are taken into account. Additionally, different Damkohler numbers have been defined and evaluated in order to characterize the phenomenon and quantify the relevance of each effect. The theoretical explanation has been evaluated by means of chemiluminescence measurements performed in a Rapid Compression Expansion Machine (RCEM), which allow to estimate the velocity of propagation of the autoignition front. The results showed that under HCCI conditions the autoignition propagation is controlled, in general, by the pressure waves established in the combustion chamber, since the characteristic time of the autoignition propagation is too short to assume the absence of pressure gradients in the chamber. Thus, the thermodynamic conditions reached behind the pressure wave promote the autoignition and explain the high propagation velocities associated to the reaction front. Besides, the results also showed that the contribution of diffusive phenomena on the propagation is negligible, since the characteristic time of diffusion is too long compared to the characteristic time of the autoignition propagation. Finally, the experimental measurements showed that the autoignition propagation is affected by a really relevant cycle-to-cycle variation. The turbulence generated by the combustion has, by definition, an aleatory behavior, leading to random heterogeneity distribution and, therefore, to somewhat random autoignition propagation.The authors would like to thank different members of the CMT-Motores TTrmicos team of the Universitat Politecnica de Valencia for their contribution to this work. The authors would also like to thank the Spanish Ministry of Education for financing the PhD. Studies of Dario Lopez-Pintor (grant FPU13/02329). This research has been partially funded by FEDER and the Spanish Government through project TRA2015-67136-R.Desantes, J.; López, JJ.; García-Oliver, JM.; López-Pintor, D. (2017). A phenomenological explanation of the autoignition propagation under HCCI conditions. Fuel. 206:43-57. https://doi.org/10.1016/j.fuel.2017.05.075S435720

Experimental validation and analysis of seven different chemical kinetic mechanisms for n-dodecane using a Rapid Compression-Expansion Machine

[EN] Seven different chemical kinetic mechanisms for n-dodecane, two detailed and five reduced, have been evaluated under Engine Combustion Network (ECN) thermodynamic conditions by comparison to experimental measurements in a Rapid Compression-Expansion Machine (RCEM). The target ECN conditions are imposed at Top Dead Center (TDC), which cover a wide range of temperatures (from 850 K to 1000 K), oxygen molar fractions (0.21 and 0.15) and equivalence ratios (0.8, 0.9 and 1), while the pressure is fixed to keep a constant density at TDC equal to 22.8 kg/m(3). The results obtained have been used to validate the chemical kinetic simulations, which have been performed with CHEMKIN, by comparing both cool flames and high temperature ignition delays, as well as the heat released in each stage of the combustion process in case of having a two-stage ignition pattern. The experimental results show good agreement with the chemical kinetic simulations. In fact, the mean relative deviation in ignition delay between experiments and simulations among all the chemical mechanisms is equal to 18.0% (3 CAD) for both cool flames and high temperature ignition. In general, closer correspondence has been obtained for the ignition delay referred to the high-temperature stage of the process, being the cool flames phenomenon more difficult to reproduce. Moreover, the differences between the reduced mechanisms and the most detailed one have been analyzed, concluding that the enhanced specific reaction rates of the most reduced mechanisms cause differences not only on the ignition delays, but also on the Negative Temperature Coefficient (NTC) behavior and on the heat released during cool flames. (C) 2017 The Combustion Institute. Published by Elsevier Inc. All rights reserved.The authors would also like to thank the Spanish Ministry of Education for financing the PhD. Studies of Dario Lopez-Pintor (grant FPU13/02329). This study was partially funded by the Spanish Ministry of Economy and Competitiveness in the frame of the COMEFF (TRA2014-59483-R) project.Desantes, J.; López, JJ.; García-Oliver, JM.; López-Pintor, D. (2017). Experimental validation and analysis of seven different chemical kinetic mechanisms for n-dodecane using a Rapid Compression-Expansion Machine. Combustion and Flame. 182:76-89. https://doi.org/10.1016/j.combustflame.2017.04.004S768918

ImageNet-Patch: A dataset for benchmarking machine learning robustness against adversarial patches

Adversarial patches are optimized contiguous pixel blocks in an input image that cause a machine-learning model to misclassify it. However, their optimization is computationally demanding, and requires careful hyperparameter tuning, potentially leading to suboptimal robustness evaluations. To overcome these issues, we propose ImageNet-Patch, a dataset to benchmark machine-learning models against adversarial patches. The dataset is built by first optimizing a set of adversarial patches against an ensemble of models, using a state-of-the-art attack that creates transferable patches. The corresponding patches are then randomly rotated and translated, and finally applied to the ImageNet data. We use ImageNet-Patch to benchmark the robustness of 127 models against patch attacks, and also validate the effectiveness of the given patches in the physical domain (i.e., by printing and applying them to real-world objects). We conclude by discussing how our dataset could be used as a benchmark for robustness, and how our methodology can be generalized to other domains. We open source our dataset and evaluation code at https://github.com/pralab/ImageNet-Patch

A system for profiling the IXPs in a region and monitoring their growth: spotlight at the internet frontier

This work aims at designing and implementing a system able to profile and help manage the set of Internet eXchange Points (IXPs) in an Internet region. As part of the Internet Society's strategy to help monitor and understand the evolution of IXPs in a particular region, a route-collector data analyzer tool was developed before being deployed and tested in AfriNIC. In fact, traffic localization efforts in the African peering ecosystem would be more sustained, and their efficacy assessed if they were supported by a platform, which evaluates and reports in real time about their impact on the Internet. We, thus, built the “African” Route-collectors Data Analyzer (ARDA), an open source web platform for analyzing publicly available routing information collected since 2005, by local route-collectors. ARDA evaluates predefined metrics that picture the status of the interconnection at local, national, and regional levels. It shows that a small proportion of AfriNIC ASes (roughly 17%) are peering in the region. Through them, 58% of all African networks are visible at one IXP or more. These have been static from April to September 2017, and even February 2018, underlining the need for increased efforts to improve local interconnectivity. We show how ARDA can help detect the impact of policies on the growth of local IXPs or continually provide the community with up-to-date empirical data on the evolution of the IXP substrate. Given its features, this tool will be a helpful compass for stakeholders in the quest for better traffic localization and new interconnection opportunities in the targeted region.This work was partially funded by the Internet Society (ISOC). Support to this work was also provided by IMDEA Networks Institute, the National Science Foundation (NSF) CNS-1414177, and NSF OAC-1724853.We are grateful to Nishal Goburdhan and Dibya Khatiwada for their technical support as well as to The African IXP Association (Af-IX), Packet Clearing House (PCH), and Hisham Ibrahim for their cooperation.Publicad

Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae in Fresh Produce

15 p.Fresh vegetables are an essential part of a healthy diet, but microbial contamination of fruits and vegetables is a serious concern to human health, not only for the presence of foodborne pathogens but because they can be a vehicle for the transmission of antibiotic-resistant bacteria. This work aimed to investigate the importance of fresh produce in the transmission of extended-spectrum β-lactamases (ESBL)-producing Enterobacteriaceae. A total of 174 samples of vegetables (117) and farm environment (57) were analysed to determine enterobacterial contamination and presence of ESBL-producing Enterobacteriaceae. Enterobacterial counts above the detection limit were found in 82.9% vegetable samples and 36.8% environmental samples. The average count was 4.2 log cfu/g or mL, with a maximum value of 6.2 log cfu/g in a parsley sample. Leafy vegetables showed statistically significant higher mean counts than other vegetables. A total of 15 ESBL-producing isolates were obtained from vegetables (14) and water (1) samples and were identified as Serratia fonticola (11) and Rahnella aquatilis (4). Five isolates of S. fonticola were considered multi-drug resistant. Even though their implication in human infections is rare, they can become an environmental reservoir of antibiotic-resistance genes that can be further disseminated along the food chainS

FOXO Transcription Factors & Gene Expression

This paper attempts to highlight ForkHead box transcription factors (FOXO -1, -3, and -4) importance of subcellular localization in U87MG and myoblasts

Structure–activity relationships of dinucleotides: Potent and selective agonists of P2Y receptors

Dinucleoside polyphosphates act as agonists on purinergic P2Y receptors to mediate a variety of cellular processes. Symmetrical, naturally occurring purine dinucleotides are found in most living cells and their actions are generally known. Unsymmetrical purine dinucleotides and all pyrimidine containing dinucleotides, however, are not as common and therefore their actions are not well understood. To carry out a thorough examination of the activities and specificities of these dinucleotides, a robust method of synthesis was developed to allow manipulation of either nucleoside of the dinucleotide as well as the phosphate chain lengths. Adenosine containing dinucleotides exhibit some level of activity on P2Y1 while uridine containing dinucleotides have some level of agonist response on P2Y2 and P2Y6. The length of the linking phosphate chain determines a different specificity; diphosphates are most accurately mimicked by dinucleoside triphosphates and triphosphates most resemble dinucleoside tetraphosphates. The pharmacological activities and relative metabolic stabilities of these dinucleotides are reported with their potential therapeutic applications being discussed

Four years tracking unrevealed topological changes in the african interdomain

Despite extensive studies on the Internet topology, little is still known about the AS level topology of the African Internet, especially when it comes to its IXP substrate. The main reason for this is the lack of vantage points that are needed to obtain the proper information. From 2013 to 2016, we enhanced the RIPE Atlas measurement infrastructure in the region to shed light on both IPv4 and IPv6 topologies interconnecting local ISPs. We increased the number of vantage points in Africa by 278.3% and carried out measurements between them at random periods. To infer results that depict the behavior of ISPs in the region, we propose reproducible traceroute data analysis techniques suitable for the treatment of any set of similar measurements. We first reveal a large variety of ISP transit habits and their dependence on socio-economic factors. We then compare QoS within African countries, European countries, and the US to find that West African networks in particular need to promote investments in fiber networks and to implement traffic engineering techniques. Our results indicate the remaining dominance of ISPs based outside Africa for the provision of intra-continental paths, but also shed light on traffic localization efforts. We map, in our traceroute data, 62.2% of the IXPs in Africa and infer their respective peers. Finally, we highlight the launch of new IXPs and quantify their impacts on end-to-end connectivity. The study clearly demonstrates that to better assess interdomain routing in a continent, it is necessary to perform measurements from a diversified range of vantage points.The work done by Rodérick Fanou was funded by IMDEA Networks Institute as part of the project “Mapping and Measuring the African Internet”. Francisco Valera has been partially funded by the European Commission under FP7 project LEONE (FP7-317647).Publicad

Los incendios forestales en Galicia y su investigación

El trabajo se centra en la investigación policial de los incendios forestales en Galicia, examinándose sus características generales, las cuestiones relativas a la investigación de las causas y, ya en el ámbito de las pruebas personales, la prueba testimonial, el uso de inteligencia criminal y la actividad operativa. A título introductorio, se realizan una serie de precisiones sobre las características de los incendios en Galicia y sobre los perfiles policial y socio-psicológico de sus autores. A modo de conclusión se incide en la necesidad de redirigir la investigación de las causas del incendio, de tal manera que pueda poner de manifiesto, también, la existencia de comportamientos sectoriales antisociales, de desórdenes relativos a conductas imprudentes o de factores estructurales que coadyuven a la virulencia del incendio