1,107 research outputs found

    Study of the mechanism of cell death caused by peptides targeting CD47 in leukemia cell lines.

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    CD47 activation through the C-terminus of thrombospondin-1 or its derived peptides (4N1K and PKHB1) induce regulated cell death (RCD) in several types of cancer. Recently, it was demonstrated that PKHB1, the first serum-stable CD47 agonist peptide, induce caspase-independent, calcium-dependent RCD in CLL cells, even in those resistant to conventional therapy. Therefore, the objective of the present work was to study the PKHB1-induced cell death mechanism in other types of leukemia. To that end, cell death induction was evaluated by flow cytometry, analyzing phosphatidilserine exposure (Ann-V) and plasma membrane permeability (PI), as well as caspase dependance (inhibitor Q-VD-OPH) or calcium dependance (BAPTA, calcium chelator). The results show that PKHB1 is a better inductor of cell death, compared to 4N1K, and it is selective to different types of leukemia (MEC-1, CEM, Junket, K562, HL-60, L5178Y-R), since it does not kill human peripheral mononuclear cells, nor cells derived from lymphoid organs of healthy mice. PKHB1-induced killing is caspase-independent in all cases. Additionally, in CEM (human T lymphoblasts of acute lymphocytic leukemia, the principal type of childhood cancer) and L5178Y-R (murine T lymphoblasts) cells, death is not modulated by co-culture with chemoprotective bone marrow stromal cells; calcium chelation, however, inhibits PKHB1-induced cell death. Together, the results indicate that PKHB1 is effective in different types of leukemia, and induce caspase-independent, microenvironment-independent calcium-dependent RCD, in leukemic T lymphocytes. These results suggest that PKHB1-induced RCD could be conserved in different types of leukemia, and set the basis for further studies on murine models

    Construcción metodológica de la aplicabilidad de la teoría de la justicia de John Rawls en el marco de la distribución de la riqueza en Colombia

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    La distribución de la riqueza es uno de presupuestos elementales que devienen de la estructura de la hacienda pública para la consecución de los fines esenciales de un Estado. En ese orden de ideas, la repartición de los recursos se materializa en la formulación de los presupuestos anuales ya sea nacionales, regionales o locales. Sin embargo, en la práctica se tiene que la distribución de los recursos no siempre implica que se vea reflejado en las necesidades de los ciudadanos, como quiera que la importancia y la prioridad está sujeta a la coyuntura política, económica y social que se encuentre atendiendo el Gobierno Nacional. El problema que suscita a partir de allí es, si la distribución de la riqueza no se aplica en una masa universal, sino en focos específicos, ¿cómo se puede lograr la justicia, que se supone se persigue como fin indispensable de un Estado? Por otro lado, Rawls propone un modelo de justicia como equidad en el que los bienes primarios redunden especialmente entre los menos aventajados, como solución a la regla de Pareto. Teniendo en cuenta estos postulados, la presente ponencia se construye con el fin de presentar un primer modelo de metodología en el que sea aplicable la teoría de la justicia de Rawls en la distribución de la riqueza, como mecanismo necesario para la consecución de los fines del Estado, sin desconocer el modelo económico o la estructura misma del Estado.Facultad de Humanidades y Ciencias de la Educació

    Multiple feature models for image matching

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    The common approach to image matching is to detect spatial features present in both images and create a mapping that relates both images. The main draw back of this method takes place when more than one matching is likely. A first simplification to this ambiguity is to represent with apara-metric model the point locus where the matching is highly likely,and then use a POCS(projection on to convex sets)procedure combined with Tikhonov regularization that results in the mapping vectors. However,if there is more than one model perpixel,the regularization and constrainforcing process faces a multiplechoice dilemma that has no easy solution. This work proposes a frame work to overcome this draw back: the combined projection over multiple models base don the norm of the projection–pointdis-tance. This approach is tested on a stereo-pair that presents multiple choices of similar likelihood.This work is partially supported by the Spanish Ministerio de Ciencia y Tecnología,under grant TIC2002-03033

    An Innovative Strategy Based on Secure Element for Cyber–Physical Authentication in Safety-Critical Manufacturing Supply Chain

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    This research has been founded by the European Union’s Horizon 2020 Research and Innovation program under grant agreement No. 871518, a project named, A COmprehensive cyber-intelligence framework for resilient coLLABorative manufacturing Systems, COLLABS [55].The accurate tracking of every production step and related outcome in a supply chain is a stringent requirement in safety-critical sectors such as civil aviation. In such a framework, trusted traceability and accountability can be reliably and securely managed by means of blockchain-based solutions. Unfortunately, blockchain cannot guarantee the provenance and accuracy of the stored information. To overcome such a limitation, this paper proposes a secure solution to strongly rely on the tracking information of the physical assets in the supply chain. The proposed solution exploits Hardware Security Modules (HSMs) to provide required cryptographic primitives through a Near-Field Communication (NFC) connection. In our approach, each transfer of the assets is authenticated, verified, and recorded in the blockchain through the HSM. Transaction entries are signed, thus providing a guarantee of ownership and authenticity. The proposed infrastructure has been subject of an exhaustive security analysis and proved resilient against counterfeiting attempts, stakeholder repudiations, and misleading information.Horizon 2020 Framework Programme 871518 H202

    Design of wide-beam leaky-wave antenna arrays based on the bilinear transformation of IIR digital filters and the Z transform

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    In the pioneering work, the radiation diagrams of leaky wave antenna arrays can achieve attenuation nulls and gains at specific angles by manually placing the zeros and the poles in the Z domain of the corresponding discrete linear time-invariant (LTI) system. This handcrafted design procedure does not allow radiation diagrams with wide beams since the interaction between poles involved in the wide beam and their corresponding leaky modes cannot be easily handled. To overcome this limitation, this paper describes a novel method for designing radiation diagrams of leaky-wave antenna arrays based on the theory of IIR discrete filters. The proposed method relies on the design of discrete filters with the prototypes of analog low-pass filters defined by Butterworth and Chebyshev type I polynomials, whose roots along with the bilinear transformation provide the location of the poles and the zeros of the discrete LTI system and, therefore, the parameters of the leaky-wave antenna array. Results with different designs and a comparison with other approaches show the utility and effectiveness of this novel method to design wide-beam leaky-wave antenna arrays.This work was supported by the Spanish National project PID2019-103982RB-C42/AEI/10.13039/501100011033

    Improving glaucoma diagnosis assembling deep networks and voting schemes

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    Glaucoma is a group of eye conditions that damage the optic nerve, the health of which is vital for good eyesight. This damage is often caused by higher-than-normal pressure in the eye. In the past few years, the applications of artificial intelligence and data science have increased rapidly in medicine especially in imaging applications. In particular, deep learning tools have been successfully applied obtaining, in some cases, results superior to those obtained by humans. In this article, we present a soft novel ensemble model based on the K-NN algorithm, that combines the probability of class membership obtained by several deep learning models. In this research, three models of different nature (CNN, CapsNets and Convolutional Autoencoders) have been selected searching for diversity. The latent space of these models are combined using the local information provided by the true sample labels and the K-NN algorithm is applied to determine the final decision. The results obtained on two different datasets of retinal images show that the proposed ensemble model improves the diagnosis capabilities for both the individual models and the state-of-the-art results.This research was funded by Instituto de Salud Carlos III grant number AES2017-PI17/007 and Fundación Séneca grant number 20901/PI/18. The APC was funded by Fundación Séneca grant number 20901/PI/18

    Improving hand gestures recognition capabilities by ensembling convolutional networks

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    Hand gestures provide humans a convenient way to interact with computers and many applications. However, factors such as the complexity of hand gesture models, differences in hand size and position, and other factors can affect the performance of the recognition and classification algorithms. Some developments of deep learning such as Convolutional Neural Networks (CNN) and Capsule Networks (CapsNets) have been proposed to improve the performance of image recognition systems in this particular field. While CNNs are undoubtedly the most widely used networks for object detection and image classification, CapsNets emerged to solve part of the limitations of the former. For this reason, in this work a particular ensemble of both networks is proposed to solve the American Sign Language recognition problem very effectively. The method is based on increasing diversity in both the model and the dataset. The results obtained show that the proposed ensemble model together with a simple data augmentation process produces a very competitive accuracy performance with the all considered datasets.This work has been partially supported by Instituto de Salud Carlos III (Project PI17/00771, Ministerio de Economía y de Competitividad, Government of Spain) and Fundación Séneca (Project 20901/PI/18, Agencia de Ciencia y Tecnología, Murcia)

    Integration Host Factor (IHF) binds to the promoter region of the phtD operon involved in phaseolotoxin synthesis in P. syringae pv. phaseolicola NPS3121

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    <p>Abstract</p> <p>Background</p> <p><it>Pseudomonas syringae </it>pv. phaseolicola, the causal agent of halo blight disease in beans, produces a toxin known as phaseolotoxin, in whose synthesis participate a group of genes organized within the genome in a region known as the "Pht cluster". This region, which is thought to have been acquired by horizontal gene transfer, includes 5 transcriptional units, two monocistronic (<it>argK, phtL</it>) and three polycistronic (<it>phtA, phtD, phtM</it>), whose expression is temperature dependent. So far, the regulatory mechanisms involved in phaseolotoxin synthesis have not been elucidated and the only well-established fact is the requirement of low temperatures for its synthesis. In this work, we searched for regulatory proteins that could be involved in phaseolotoxin synthesis, focusing on the regulation of the <it>phtD </it>operon.</p> <p>Results</p> <p>In this study we identified the global regulator IHF (Integration Host Factor), which binds to the promoter region of the <it>phtD </it>operon, exerting a negative effect on the expression of this operon. This is the first regulatory protein identified as part of the phaseolotoxin synthesis system. Our findings suggest that the Pht cluster was similarly regulated in the ancestral cluster by IHF or similar protein, and integrated into the global regulatory mechanism of <it>P. syringae </it>pv. phaseolicola, after the horizontal gene transfer event by using the host IHF protein.</p> <p>Conclusion</p> <p>This study identifies the IHF protein as one element involved in the regulation of phaseolotoxin synthesis in <it>P. syringae </it>pv. phaseolicola NPS3121 and provides new insights into the regulatory mechanisms involved in phaseolotoxin production.</p
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