Supporting authorize-then-authenticate for wi-fi access based on an electronic identity infrastructure

Federated electronic identity systems are increasingly used in commercial and public services to let users share their electronic identities (eIDs) across countries and providers. In Europe, the eIDAS Regulation and its implementation-the eIDAS Network-allowing mutual recognition of citizen’s eIDs in various countries, is now in action. We discuss authorization (before authentication), named also authorize-then-authenticate (AtA), in services exploiting the eIDAS Network. In the eIDAS Network, each European country runs a national eIDAS Node, which transfers in other Member State countries, via the eIDAS protocol, some personal attributes, upon successful authentication of a person in his home country. Service Providers in foreign countries typically use these attributes to implement authorization decisions for the requested service. We present a scenario where AtA is required, namely Wi-Fi access, in which the service provider has to implement access control decisions before the person is authenticated through the eIDAS Network with his/her national eID. The Wi-Fi access service is highly required in public and private places (e.g. shops, hotels, a.s.o.), but its use typically involves users’ registration at service providers and is still subject to security attacks. The eIDAS Network supports different authentication assurance levels, thus it might be exploited for a more secure and widely available Wi-Fi access service to the citizens with no prior registration, by exploiting their national eIDs. We propose first a model that discusses AtA in eIDAS-based services, and we consider different possible implementation choices. We describe next the implementation of AtA in an eIDAS-based Wi-Fi access service leveraging the eIDAS Network and a Zeroshell captive portal supporting the eIDAS protocol. We discuss the problems encountered and the deploy-ment issues that may impact on the service acceptance by the users and its exploitation on large scale

Electronic identification for universities: Building cross-border services based on the eIDAS infrastructure

The European Union (EU) Regulation 910/2014 on electronic IDentification, Authentication, and trust Services (eIDAS) for electronic transactions in the internal market went into effect on 29 September 2018, meaning that EU Member States are required to recognize the electronic identities issued in the countries that have notified their eID schemes. Technically speaking, a unified interoperability platform—named eIDAS infrastructure—has been set up to connect the EU countries’ national eID schemes to allow a person to authenticate in their home EU country when getting access to services provided by an eIDAS-enabled Service Provider (SP) in another EU country. The eIDAS infrastructure allows the transfer of authentication requests and responses back and forth between its nodes, transporting basic attributes about a person, e.g., name, surname, date of birth, and a so-called eIDAS identifier. However, to build new eIDAS-enabled services in specific domains, additional attributes are needed. We describe our approach to retrieve and transport new attributes through the eIDAS infrastructure, and we detail their exploitation in a selected set of academic services. First, we describe the definition and the support for the additional attributes in the eIDAS nodes. We then present a solution for their retrieval from our university. Finally, we detail the design, implementation, and installation of two eIDAS-enabled academic services at our university: the eRegistration in the Erasmus student exchange program and the Login facility with national eIDs on the university portal

Therapeutic administration of broadly neutralizing FI6 antibody reveals lack of interaction between human IgG1 and pig Fc receptors

Influenza virus infection is a significant global health threat. Because of the lack of cross-protective universal vaccines, short time window during which antivirals are effective and drug resistance, new therapeutic anti-influenza strategies are required. Broadly, cross-protective antibodies that target conserved sites in the hemagglutinin (HA) stem region have been proposed as therapeutic agents. FI6 is the first proven such monoclonal antibody to bind to H1–H16 and is protective in mice and ferrets. Multiple studies have shown that Fc-dependent mechanisms are essential for FI6 in vivo efficacy. Here, we show that therapeutic administration of FI6 either intravenously or by aerosol to pigs did not reduce viral load in nasal swabs or broncho-alveolar lavage, but aerosol delivery of FI6 reduced gross pathology significantly. We demonstrate that pig Fc receptors do not bind human IgG1 and that FI6 did not mediate antibody-dependent cytotoxicity (ADCC) with pig PBMC, confirming that ADCC is an important mechanism of protection by anti-stem antibodies in vivo. Enhanced respiratory disease, which has been associated with pigs with cross-reactive non-neutralizing anti-HA antibodies, did not occur after FI6 administration. Our results also show that in vitro neutralizing antibody responses are not a robust correlate of protection for the control of influenza infection and pathology in a natural host model

Nuevo prototipo de máquina frigorífica de absorción de LiBr-H₂O de simple y doble efecto con absorbedor adiabático refrigerado por aire de alta eficiencia : descripción, simulación y resultados experimentales

Due to unsustainable growth of air conditioning market, a great interest in solar cooling technologies has emerged. The coincidence between availability of solar irradiation and peaks of cooling demand makes solar cooling a very attractive option to replace conventional refrigeration machines based on electricity. What is more, solar cooling systems normally use natural refrigerants that are not harmful to the environment. However, an improvement of the current technology is needed for solar cooling systems to compete with electricity‐powered air conditioning systems. In this work, a novel air‐cooled single–double‐effect LiBr/H₂O absorption prototype is proposed as a solution to improve the viability of solar cooling systems. This prototype presents the following distinguishing features: firstly, it is directly air‐cooled, which means that no cooling tower is needed; secondly, it is made up by compact heat exchangers, which allows for a reduced size of about 1 m₃; thirdly, it incorporates an adiabatic absorber operating with flat‐fan solution sheets, which permits the working solution not to crystallize at high ambient temperatures; lastly, it can be powered by solar heat in its single‐effect mode (4.5 kW), or by an alternative source such as fuel or waste heat in its double‐effect stage (7 kW). In this way, 100% of the cooling demand may be supplied by a single absorption machine using solar energy as far as possible or, when it is not available, efficiently utilizing a fuel or even waste heat, for instance in a trigeneration system. This thesis includes a detailed description of that single–double‐effect absorption prototype as well as the fundamentals for its numerical simulation. Likewise, experimental results from a testing campaign carried out in Madrid during 2010 are presented and discussed. A solar facility with evacuated flat‐plate collectors was used to test the single-effect operation mode of the prototype. In turn, the double‐effect stage was fired by a thermal oil facility with electrical resistances. As relevant results of the whole experimental campaign it is worth mentioning that the single‐effect stage was able to work with COP values around 0.6, whereas the double‐effect mode permitted to achieve values of about 1.0. The chilled water temperatures mostly ranged between 14°C and 16°C in single‐effect operation mode, while they were around 12°C for the double‐effect stage. Besides, it is highly noteworthy that after some 125 hours of operation under a wide range of conditions (outdoor temperatures up to 39.5°C), no solution crystallization was noticed. On the other hand, this work includes an in‐depth description of the absorber assembled in the single–double‐effect prototype. Furthermore, a mathematical model is developed for simulation of air‐cooled flat‐fan sheets adiabatic absorbers. As far as we know, there is not any numerical modeling for this kind of absorbers in the literature. Based on that model, which was as well experimentally validated in this study, the capacity of the prototype absorber is optimized as a function of the energy consumption of its ancillary equipment (solution pump and fan). Finally, the positive results derived from this work may be regarded as an important contribution to the development of air‐cooled LiBr/H₂O absorption technology. Even though a few improvements in the prototype are still required, it seems that the proposed system represents a feasible alternative to overcome some of the major obstacles concerning solar air conditioning. -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------La actual situación de insostenibilidad en el mercado de la climatización ha motivado un gran interés por la refrigeración solar como alternativa al uso de máquinas eléctricas. El hecho de que las horas de máxima radiación solar coincidan con los momentos de mayor demanda de frío en los edificios, hace que estos sistemas sean especialmente indicados para sustituir a los equipos convencionales de aire acondicionado. Además, hay que añadir que esta tecnología normalmente utiliza refrigerantes naturales que no son dañinos para el medio ambiente. Sin embargo, los sistemas actuales de refrigeración solar necesitan una mejora sustancial para poder competir directamente con los aparatos tradicionales de climatización. Como una posible solución para mejorar la viabilidad de los sistemas de refrigeración solar, en este trabajo se presenta un nuevo prototipo de máquina de absorción de LiBr/H₂O que integra los ciclos de simple y doble efecto en una misma unidad. Las principales características que hacen de este prototipo una novedad tecnológica son las siguientes: en primer lugar, se trata de una máquina directamente condensada por aire, eliminando así la necesidad de instalar torres de refrigeración; en segundo lugar, el prototipo está básicamente formado por intercambiadores de calor compactos, con lo que se alcanza un tamaño final de máquina muy reducido, aproximadamente 1 m3; en tercer lugar, el prototipo incorpora un absorbedor adiabático con láminas planas que evita que la disolución cristalice a altas temperaturas ; por último, la máquina puede funcionar como una unidad de simple efecto (4.5 kW), alimentada en este caso por energía solar, o como una unidad de doble efecto (7 kW), quemando combustibles o utilizando calor residual. De este modo, se podría llegar cubrir el 100% de la demanda de refrigeración con una sola unidad que saca el máximo partido a la energía solar y, cuando ésta no es suficiente, utiliza eficientemente combustibles o incluso el calor residual procedente de otros procesos, por ejemplo en una planta de trigeneración. En esta tesis doctoral se incluye una descripción detallada del prototipo de simple y doble efecto así como los fundamentos teóricos para su simulación numérica. Asimismo, se presentan y discuten los resultados experimentales obtenidos durante una campaña de ensayos llevada a cabo en Madrid durante el año 2010. Para probar el funcionamiento del prototipo como máquina de absorción de simple efecto se ha utilizado una instalación solar con colectores planos de vacío. En cambio, para ensayar el prototipo como máquina de doble efecto se ha utilizado un aceite térmico como fuente de energía. Como resultados destacados de la campaña de experimentación cabe mencionar que los valores del COP se movieron entorno a 0.6 en simple efecto y alrededor de 1.0 en doble efecto. A su vez, se alcanzaron temperaturas de agua fría entre 14°C y 16°C para el simple efecto y de aproximadamente 12°C para el doble efecto. Además, es de gran relevancia el hecho de que, después de unas 125 horas de funcionamiento bajo condiciones de trabajo muy diferentes (hasta 39.5°C de temperatura exterior), la disolución de LiBr/H₂O no se haya cristalizado en ningún momento. Por otra parte, este trabajo incluye una descripción detallada del absorbedor instalado en el prototipo. Asimismo, se ha desarrollado un modelo matemático para simular absorbedores adiabáticos de láminas directamente refrigerados por aire. Por lo que sabemos, hasta el momento no se ha publicado ninguna modelización numérica para este tipo de absorbedores. Tomando como referencia el modelo propuesto, que también ha sido validado experimentalmente en este estudio, se ha realizado una optimización de la capacidad del absorbedor del prototipo en función del consumo energético de sus equipos auxiliares (bomba de disolución y ventilador). Por último, los buenos resultados obtenidos con este prototipo nos hacen pensar que este trabajo representa una contribución importante al desarrollo de las máquinas de absorción de LiBr/H₂O refrigeradas por aire. A pesar de que el prototipo todavía no está totalmente optimizado, con él se ha demostrado que la tecnología propuesta en esta tesis doctoral constituye una alternativa viable para superar algunos de los principales problemas relacionados con la refrigeración solar

Electrocardiographic changes in a rare case of flecainide poisoning: a case report

Flecainide is a class Ic anti - arrhythmic drug with sodium channel blocking activities. We report a case of a 57 year - old woman who attempted a suicide by ingesting approximately 1,8 gr of flecainide. On the surface electrocardiogram this results in a large QRS complex and in prolongation of the QTc interval. Overdose with a class Ic drug is very uncommon, its management is difficult and the mortality high

Maturation of SARS-CoV-2 Spike-specific memory B cells drives resilience to viral escape

SUMMARYMemory B cells (MBCs) generate rapid antibody responses upon secondary encounter with a pathogen. Here, we investigated the kinetics, avidity and cross-reactivity of serum antibodies and MBCs in 155 SARS-CoV-2 infected and vaccinated individuals over a 16-month timeframe. SARS-CoV-2-specific MBCs and serum antibodies reached steady-state titers with comparable kinetics in infected and vaccinated individuals. Whereas MBCs of infected individuals targeted both pre- and postfusion Spike (S), most vaccine-elicited MBCs were specific for prefusion S, consistent with the use of prefusion-stabilized S in mRNA vaccines. Furthermore, a large fraction of MBCs recognizing postfusion S cross-reacted with human betacoronaviruses. The avidity of MBC-derived and serum antibodies increased over time resulting in enhanced resilience to viral escape by SARS-CoV-2 variants, including Omicron BA.1 and BA.2 sub-lineages, albeit only partially for BA.4 and BA.5 sublineages. Overall, the maturation of high-affinity and broadly-reactive MBCs provides the basis for effective recall responses to future SARS-CoV-2 variants

CCR2 Acts as Scavenger for CCL2 during Monocyte Chemotaxis

<div><h3>Background</h3><p>Leukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces or on matrices along the attracting gradient towards increasing concentrations of agonist. On the other hand agonist-induced desensitization and internalization is a general paradigm for chemokine receptors which is inconsistent with the prolonged migratory capacity.</p> <h3>Methodology/Principal Findings</h3><p>Chemotaxis of monocytes was monitored in response to fluorescent CCL2-mCherry by time-lapse video microscopy. Uptake of the fluorescent agonist was used as indirect measure to follow the endogenous receptor CCR2 expressed on primary human monocytes. During chemotaxis CCL2-mCherry becomes endocytosed as cargo of CCR2, however, the internalization of CCR2 is not accompanied by reduced responsiveness of the cells due to desensitization.</p> <h3>Conclusions/Significance</h3><p>During chemotaxis CCR2 expressed on monocytes internalizes with the bound chemoattractant, but cycles rapidly back to the plasma membrane to maintain high responsiveness. Moreover, following relocation of the source of attractant, monocytes can rapidly reverse their polarization axis organizing a new leading edge along the newly formed gradient, suggesting a uniform distribution of highly receptive CCR2 on the plasma membrane. The present observations further indicate that during chemotaxis CCR2 acts as scavenger consuming the chemokine forming the attracting cue.</p> </div

Transcriptional responses to glucose in Saccharomyces cerevisiae strains lacking a functional protein kinase A

Background The pattern of gene transcripts in the yeast Saccharomyces cerevisiae is strongly affected by the presence of glucose. An increased activity of protein kinase A (PKA), triggered by a rise in the intracellular concentration of cAMP, can account for many of the effects of glucose on transcription. In S. cerevisiae three genes, TPK1, TPK2, and TPK3, encode catalytic subunits of PKA. The lack of viability of tpk1 tpk2 tpk3 triple mutants may be suppressed by mutations such as yak1 or msn2/msn4. To investigate the requirement for PKA in glucose control of gene expression, we have compared the effects of glucose on global transcription in a wild-type strain and in two strains devoid of PKA activity, tpk1 tpk2 tpk3 yak1 and tpk1 tpk2 tpk3 msn2 msn4. Results We have identified different classes of genes that can be induced -or repressed- by glucose in the absence of PKA. Representative examples are genes required for glucose utilization and genes involved in the metabolism of other carbon sources, respectively. Among the genes responding to glucose in strains devoid of PKA some are also controlled by a redundant signalling pathway involving PKA activation, while others are not affected when PKA is activated through an increase in cAMP concentration. On the other hand, among genes that do not respond to glucose in the absence of PKA, some give a full response to increased cAMP levels, even in the absence of glucose, while others appear to require the cooperation of different signalling pathways. We show also that, for a number of genes controlled by glucose through a PKA-dependent pathway, the changes in mRNA levels are transient. We found that, in cells grown in gluconeogenic conditions, expression of a small number of genes, mainly connected with the response to stress, is reduced in the strains lacking PKA. Conclusions In S. cerevisiae, the transcriptional responses to glucose are triggered by a variety of pathways, alone or in combination, in which PKA is often involved. Redundant signalling pathways confer a greater robustness to the response to glucose, while cooperative pathways provide a greater flexibility.BT/BiotechnologyApplied Science

Environmental and Genetic Determinants of Colony Morphology in Yeast

Nutrient stresses trigger a variety of developmental switches in the budding yeast Saccharomyces cerevisiae. One of the least understood of such responses is the development of complex colony morphology, characterized by intricate, organized, and strain-specific patterns of colony growth and architecture. The genetic bases of this phenotype and the key environmental signals involved in its induction have heretofore remained poorly understood. By surveying multiple strain backgrounds and a large number of growth conditions, we show that limitation for fermentable carbon sources coupled with a rich nitrogen source is the primary trigger for the colony morphology response in budding yeast. Using knockout mutants and transposon-mediated mutagenesis, we demonstrate that two key signaling networks regulating this response are the filamentous growth MAP kinase cascade and the Ras-cAMP-PKA pathway. We further show synergistic epistasis between Rim15, a kinase involved in integration of nutrient signals, and other genes in these pathways. Ploidy, mating-type, and genotype-by-environment interactions also appear to play a role in the controlling colony morphology. Our study highlights the high degree of network reuse in this model eukaryote; yeast use the same core signaling pathways in multiple contexts to integrate information about environmental and physiological states and generate diverse developmental outputs