80 research outputs found

    AnĂĄlisis del ciberataque para la seguridad de los estados y su incidencia en la transformaciĂłn del status quo: Stuxnet el virus informĂĄtico

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    La presente investigación realiza un anålisis del caso Stuxnet, las implicaciones en seguridad que trae consigo el uso del ciberataque como un medio para alterar o cambiar las relaciones de poder entre los Estados. Se examina bajo la teoría del realismo estructuralista de Kenneth Waltz, el cual expone acerca de las dinåmicas al interior de la estructura del sistema internacional y los constreñimientos que estån sujetos a ella. Los Estados estån interesados principalmente en su seguridad con el objetivo de sobrevivir y ello puede dirigir sus intereses para generar acciones que lo sostengan y aminore el riesgo o amenaza. El ciberataque Stuxnet responde a esta teoría como un medio por parte de Israel para deteriorar las capacidades nucleares de Irån, y reducir su rol en las relaciones de poder tanto en la región como en el åmbito internacional, ademås de contribuir a su propia supervivencia dependiente en el åmbito de la seguridad.The following investigation performs an insight of the Virus Stuxnet and its implications on security that follow with its use, as a means to alter or change the power relations between states. This is done using the theory of Structural Realism from Kenneth Waltz, which talks about the dynamics inside the international system and its constraints that are subject to it. States are interested primarily in their safety with the porpoise of survival and that may direct the rest of its interests upon actions to sustain it and lower the risk or threat. The Ciberattack of Stuxnet responds to this theory as a means by Israel to impair the nuclear capabilities of Iran, and reduce its role on the power relations both in the region and in the international atmosphere, as well contribute to its own survival dependent in the field of securityVICENTRE TORRIJOS, FACULTAD DE RELACIONES INTERNACIONALES UNIVERSIDAD DEL ROSARI

    The role of high-performance people management practices in Industry 4.0: the case of medium-sized Spanish firms

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    Purpose: This paper wants to build the case for the key role of high-performance people management practices in the development of I4.0 in SMEs. The research upon which this paper is based wants to prove that the consolidation of those practices should be a priority for any company willing to embark in this journey. The paper deals specifically with medium-sized Spanish firms which, on top, are already having significant issues with digitization. Design/methodology/approach: The paper starts by digging into the literature to see how past technologies have impacted productivity, followed by a review of the material available on digitization and Industry 4.0. It moves on to explore the relationship between people management practices, productivity and innovation. Finally, the focus is placed on Spanish medium-sized companies, understanding their current levels of consolidation of high-performance people management practices as well as digitization. With all this information, several propositions are posited for validation using the Delphi methodology. Findings: I4.0 is, at its core, about productivity improvements through business process and business model innovation. People management practices are found to be strongly correlated with both productivity and innovation. It has also been found that Spanish medium-sized firms already have a significant initial gap compared to those of other OECD countries not only in productivity, but also people management practices and digitization. The experts seem to agree on the key role of people management practices and that they should be a high priority for any firm seriously thinking about industry 4.0. This is not to say that strategy or leadership will not play a paramount role in any digital transformation, but to emphasize the fact that the normally-forgotten people management practices will be important enablers in this process. Originality/value: It is believed that this is a topic that has been mostly neglected in the I4.0 literature. In that sense, the findings of this paper could be relevant for small and medium-sized businesses embarking on the industry 4.0 journey. This will entail a significant investment of time and money and, if the key role of people management practices is not on the radar screen, it may have significant implications for the success of those ventures.Peer Reviewe

    Large-Scale Metasurfaces Made by an Exposed Resist

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    Phase-gradient metasurfaces have the potential to revolutionize photonics by offering ultrathin alternatives to a wide range of common optical elements, including bulky refractive optics, waveplates, and axicons. However, the fabrication of state-of-the-art metasurfaces typically involves several expensive, time-consuming, and potentially hazardous processing steps. To address this limitation, a facile methodology to construct phase-gradient metasurfaces from an exposed standard electron beam resist is developed. The method dramatically cuts the required processing time and cost as well as reduces safety hazards. The advantages of the method are demonstrated by constructing high-performance flat optics based on the Pancharatnam-Berry phase gradient concept for the entire visible wavelength range. Manufactured devices include macroscopic (1 cm diameter) positive lenses, gratings exhibiting anomalous reflection, and cylindrical metalenses on flexible plastic substrates

    Upwelling on the continental slope of the Alaskan Beaufort Sea : storms, ice, and oceanographic response

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    Author Posting. © American Geophysical Union, 2009. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 114 (2009): C00A13, doi:10.1029/2008JC005009.The characteristics of Pacific-born storms that cause upwelling along the Beaufort Sea continental slope, the oceanographic response, and the modulation of the response due to sea ice are investigated. In fall 2002 a mooring array located near 152°W measured 11 significant upwelling events that brought warm and salty Atlantic water to shallow depths. When comparing the storms that caused these events to other Aleutian lows that did not induce upwelling, interesting trends emerged. Upwelling occurred most frequently when storms were located in a region near the eastern end of the Aleutian Island Arc and Alaskan Peninsula. Not only were these storms deep but they generally had northward-tending trajectories. While the steering flow aloft aided this northward progression, the occurrence of lee cyclogenesis due to the orography of Alaska seems to play a role as well in expanding the meridional influence of the storms. In late fall and early winter both the intensity and frequency of the upwelling diminished significantly at the array site. It is argued that the reduction in amplitude was due to the onset of heavy pack ice, while the decreased frequency was due to two different upper-level atmospheric blocking patterns inhibiting the far field influence of the storms.The following grants provided support for this study: National Science Foundation grants OPP-0731928 (R.S.P.) and OPP-0713250 (R.S.P. and P.S.F.), Office of Naval Research grant N00014-07-1-1040 (D.J.T. and R.A.G.), Natural Sciences and Engineering Research Council of Canada (G.W.K.M.), Woods Hole Oceanographic Institution Arctic Initiative (J.Y.)

    Identification of Plasmodium vivax Proteins with Potential Role in Invasion Using Sequence Redundancy Reduction and Profile Hidden Markov Models

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    BACKGROUND: This study describes a bioinformatics approach designed to identify Plasmodium vivax proteins potentially involved in reticulocyte invasion. Specifically, different protein training sets were built and tuned based on different biological parameters, such as experimental evidence of secretion and/or involvement in invasion-related processes. A profile-based sequence method supported by hidden Markov models (HMMs) was then used to build classifiers to search for biologically-related proteins. The transcriptional profile of the P. vivax intra-erythrocyte developmental cycle was then screened using these classifiers. RESULTS: A bioinformatics methodology for identifying potentially secreted P. vivax proteins was designed using sequence redundancy reduction and probabilistic profiles. This methodology led to identifying a set of 45 proteins that are potentially secreted during the P. vivax intra-erythrocyte development cycle and could be involved in cell invasion. Thirteen of the 45 proteins have already been described as vaccine candidates; there is experimental evidence of protein expression for 7 of the 32 remaining ones, while no previous studies of expression, function or immunology have been carried out for the additional 25. CONCLUSIONS: The results support the idea that probabilistic techniques like profile HMMs improve similarity searches. Also, different adjustments such as sequence redundancy reduction using Pisces or Cd-Hit allowed data clustering based on rational reproducible measurements. This kind of approach for selecting proteins with specific functions is highly important for supporting large-scale analyses that could aid in the identification of genes encoding potential new target antigens for vaccine development and drug design. The present study has led to targeting 32 proteins for further testing regarding their ability to induce protective immune responses against P. vivax malaria

    Presynaptic External Calcium Signaling Involves the Calcium-Sensing Receptor in Neocortical Nerve Terminals

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    Nerve terminal invasion by an axonal spike activates voltage-gated channels, triggering calcium entry, vesicle fusion, and release of neurotransmitter. Ion channels activated at the terminal shape the presynaptic spike and so regulate the magnitude and duration of calcium entry. Consequently characterization of the functional properties of ion channels at nerve terminals is crucial to understand the regulation of transmitter release. Direct recordings from small neocortical nerve terminals have revealed that external [Ca(2+)] ([Ca(2+)](o)) indirectly regulates a non-selective cation channel (NSCC) in neocortical nerve terminals via an unknown [Ca(2+)](o) sensor. Here, we identify the first component in a presynaptic calcium signaling pathway.By combining genetic and pharmacological approaches with direct patch-clamp recordings from small acutely isolated neocortical nerve terminals we identify the extracellular calcium sensor. Our results show that the calcium-sensing receptor (CaSR), a previously identified G-protein coupled receptor that is the mainstay in serum calcium homeostasis, is the extracellular calcium sensor in these acutely dissociated nerve terminals. The NSCC currents from reduced function mutant CaSR mice were less sensitive to changes in [Ca(2+)](o) than wild-type. Calindol, an allosteric CaSR agonist, reduced NSCC currents in direct terminal recordings in a dose-dependent and reversible manner. In contrast, glutamate and GABA did not affect the NSCC currents.Our experiments identify CaSR as the first component in the [Ca(2+)](o) sensor-NSCC signaling pathway in neocortical terminals. Decreases in [Ca(2+)](o) will depress synaptic transmission because of the exquisite sensitivity of transmitter release to [Ca(2+)](o) following its entry via voltage-activated Ca(2+) channels. CaSR may detects such falls in [Ca(2+)](o) and increase action potential duration by increasing NSCC activity, thereby attenuating the impact of decreases in [Ca(2+)](o) on release probability. CaSR is positioned to detect the dynamic changes of [Ca(2+)](o) and provide presynaptic feedback that will alter brain excitability

    Determinants of synaptic integration and heterogeneity in rebound firing explored with data-driven models of deep cerebellar nucleus cells

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    Significant inroads have been made to understand cerebellar cortical processing but neural coding at the output stage of the cerebellum in the deep cerebellar nuclei (DCN) remains poorly understood. The DCN are unlikely to just present a relay nucleus because Purkinje cell inhibition has to be turned into an excitatory output signal, and DCN neurons exhibit complex intrinsic properties. In particular, DCN neurons exhibit a range of rebound spiking properties following hyperpolarizing current injection, raising the question how this could contribute to signal processing in behaving animals. Computer modeling presents an ideal tool to investigate how intrinsic voltage-gated conductances in DCN neurons could generate the heterogeneous firing behavior observed, and what input conditions could result in rebound responses. To enable such an investigation we built a compartmental DCN neuron model with a full dendritic morphology and appropriate active conductances. We generated a good match of our simulations with DCN current clamp data we recorded in acute slices, including the heterogeneity in the rebound responses. We then examined how inhibitory and excitatory synaptic input interacted with these intrinsic conductances to control DCN firing. We found that the output spiking of the model reflected the ongoing balance of excitatory and inhibitory input rates and that changing the level of inhibition performed an additive operation. Rebound firing following strong Purkinje cell input bursts was also possible, but only if the chloride reversal potential was more negative than −70 mV to allow de-inactivation of rebound currents. Fast rebound bursts due to T-type calcium current and slow rebounds due to persistent sodium current could be differentially regulated by synaptic input, and the pattern of these rebounds was further influenced by HCN current. Our findings suggest that active properties of DCN neurons could play a crucial role for signal processing in the cerebellum

    Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box

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    Chemical matter is needed to target the divergent biology associated with the different life cycle stages of Plasmodium. Here, we report the parallel de novo screening of the Medicines for Malaria Venture (MMV) Pandemic Response Box against Plasmodium asexual and liver stage parasites, stage IV/V gametocytes, gametes, oocysts and as endectocides. Unique chemotypes were identified with both multistage activity or stage-specific activity, including structurally diverse gametocyte-targeted compounds with potent transmission-blocking activity, such as the JmjC inhibitor ML324 and the antitubercular clinical candidate SQ109. Mechanistic investigations prove that ML324 prevents histone demethylation, resulting in aberrant gene expression and death in gametocytes. Moreover, the selection of parasites resistant to SQ109 implicates the druggable V-type H+-ATPase for the reduced sensitivity. Our data therefore provides an expansive dataset of compounds that could be redirected for antimalarial development and also point towards proteins that can be targeted in multiple parasite life cycle stages.Supplementary Data 1: Data of the supra-hexagonal plot in Figure 2ASupplementary Data 2: Complete dataset of all MMV PRB compounds’ activity on Plasmodium life cycle stagesSupplementary Data 3: Full SMFA dataset to support Figure 5CSupplementary Data 4: Transcriptome analysis of MMV1580488 (ML324) treated parasites to support Figure 6C.The Medicines for Malaria Venture and South African Technology Innovation Agency (TIA). This project was in part supported by the South African Medical Research Council with funds received from the South African Department of Science and Innovation, in partnership with the Medicines for Malaria Venture; and the DST/NRF South African Research Chairs Initiative Grant; and CSIR Parliamentary Grant funding as well as the Bill and Melinda Gates Foundation and the Australian NHMRC (APP1072217).http://www.nature.com/ncommshj2021BiochemistryGeneticsMicrobiology and Plant PathologyUP Centre for Sustainable Malaria Control (UP CSMC
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