NALP1 is a transcriptional target for cAMP-response-element-binding protein (CREB) in myeloid leukaemia cells

NALP1 (also called DEFCAP, NAC, CARD7) has been shown to play a central role in the activation of inflammatory caspases and processing of pro-IL1β (pro-interleukin-1β). Previous studies showed that NALP1 is highly expressed in peripheral blood mononuclear cells. In the present study, we report that expression of NALP1 is absent from CD34+ haematopoietic blast cells, and its levels are upregulated upon differentiation of CD34+ cells into granulocytes and to a lesser extent into monocytes. In peripheral blood cells, the highest levels of NALP1 were observed in CD3+ (T-lymphocytes), CD15+ (granulocytes) and CD14+ (monocytes) cell populations. Notably, the expression of NALP1 was significantly increased in the bone marrow blast cell population of some patients with acute leukaemia, but not among tissue samples from thyroid and renal cancer. A search for consensus sites within the NALP1 promoter revealed a sequence for CREB (cAMP-response-element-binding protein) that was required for transcriptional activity. Moreover, treatment of TF1 myeloid leukaemia cells with protein kinase C and protein kinase A activators induced CREB phosphorylation and upregulated the mRNA and protein levels of NALP1. Conversely, ectopic expression of a dominant negative form of CREB in TF1 cells blocked the transcriptional activity of the NALP1 promoter and significantly reduced the expression of NALP1. Thus NALP1 is transcriptionally regulated by CREB in myeloid cells, a mechanism that may contribute to modulate the response of these cells to pro-inflammatory stimuli

LES CORDILLERES BETIQUES DANS LE CADRE GEODYNAMIQUE NEOALPIN DE LA MEDITERRANEE OCCIDENTALE

L'origine et la construction des Cordillères Bétiques, en tant que partie des chaines alpines qui bordent la Méditerranée, garde un étroit rapport avec l'évolution géodynamique de toute la région méditerrané­enne occidentale. Pendant l'étape néoalpine eut lieu la subduction de l'Afrique vers le Nord et l'ouverture du bassin Algéro-Provençal, avec la création d'une croute océanique. L'effet combiné des deux facteurs origina un manque d'espace entre l'Ibérie et l'Afrique et en conséquence l'expulsion des Zones lnternes vers l'Ouest, ju­squ'à collision avec les marges passives d'Ibérie et d'Afrique (Zones Externes bétiques et rifaines, respective­ment). Cela se produisit essentiellement pendant l'Aquitanien? - Burdigalien et, bien qu'avec moins d'intensité, continua pendant le Miocène moyen jusqu'à suture du contact Zones Internes/Zones Externes. Immédiatement après cela d'importantes failles N60-90E et NO-SE s'originèrent. Pendant ce processus les directions de compression ont été ONO-ESE à NO-SE dans les Cordillères Bé­tiques tandis que, à partir du Miocène supérieur, la direction changea graduellement à NNO-SSE, donnant lieu alors aux bassins néogènes intramontagneux les plus importants. Le bassin d'Alboran, avec une croute continentale amincie, se forma camme le prolongement occidental de l'ouverture du bassin Algéro-Provençal et ses caractéristiques essentielles furent déjà établies au Burdigalien

Evaluation of dimensionality reduction methods applied to numerical weather models for solar radiation forecasting

The interest in solar radiation prediction has increased greatly in recent times among the scientific community. In this context, Machine Learning techniques have shown their ability to learn accurate prediction models. The aim of this paper is to go one step further and automatically achieve interpretability during the learning process by performing dimensionality reduction on the input variables. To this end, three non standard multivariate feature selection approaches are applied, based on the adaptation of strong learning algorithms to the feature selection task, as well as a battery of classic dimensionality reduction models. The goal is to obtain robust sets of features that not only improve prediction accuracy but also provide more interpretable and consistent results. Real data from the Weather Research and Forecasting model, which produces a very large number of variables, is used as the input. As is to be expected, the results prove that dimensionality reduction in general is a useful tool for improving performance, as well as easing the interpretability of the results. In fact, the proposed non standard methods offer important accuracy improvements and one of them provides with an intuitive and reduced selection of features and mesoscale nodes (around 10% of the initial variables centered on three specific nodes).This work has been partially supported by the projects TIN2014-54583-C2-2-R, TEC2014-52289-R and TEC2016-81900-REDT of the Spanish Interministerial Commission of Science and Technology (MICYT), and by Comunidad Autónoma de Madrid, under project PRICAM P2013ICE-2933

Tuning shape, composition and magnetization of three-dimensional cobalt nanowires grown by Focused Electron Beam Induced Deposition (FEBID)

Electron beam induced deposition of 3D cobalt nanowires with simultaneous high metallic content (≈80% at.) and small diameter (<100 nm) has been achieved by optimization of the growth parameters. Two different growth modes have been identified, denoted as radial and linear. In the radial mode, the wire diameter is at least  ≈120 nm and the Co content is greater than  ≈85% at. In the linear mode, the diameter is smaller than 80 nm and the Co content is at best  ≈80% at. A sharp transition between both growth modes can occur inside a single nanowire for certain experimental conditions. Electron holography measurements indicate that in optimized Co nanowires the magnetic induction is high enough for applications in spintronics, magnetic sensing and actuation at the nanoscale.This work was supported by the Spanish Ministry of Economy and Competitivity through projects No. MAT2014-51982C2-1-R, MAT2014-51982C2-2-R and MAT2015-69725-REDT, including FEDER funds and by the Aragon Regional Government (Construyendo Europa desde Aragón) through project E26, with FEDER funding. This work was conducted within the framework of the COST Action CM1301 (CELINA). AFP acknowledges funding from a EPSRC Early Career Fellowship EP/M008517/1 and from a Winton Fellowship. In order to comply with EPSRC policy on research data, all metadata associated to this publication can be accessed via https://doi.org/10.17863/CAM.8106. JP-N grant is funded by the Ayuda para Contratos Predoctorales para la Formación de Doctores, Convocatoria Res. 05/06/15 (BOE 12/06/15) of the Secretaría de Estado de Investigación, Desarrollo e Innovación in the Subprograma Estatal de Formación of the Spanish Ministry of Economy and Competitiveness (MINECO) with the participation of the European Social Fund

Tenofovir Nephrotoxicity: 2011 Update

Tenofovir is an acyclic nucleotide analogue reverse-transcriptase inhibitor structurally similar to the nephrotoxic drugs adefovir and cidofovir. Tenofovir is widely used to treat HIV infection and approved for treatment of hepatitis B virus. Despite initial cell culture and clinical trials results supporting the renal safety of tenofovir, its clinical use is associated with a low, albeit significant, risk of kidney injury. Proximal tubular cell secretion of tenofovir explains the accumulation of the drug in these mitochondria-rich cells. Tenofovir nephrotoxicity is characterized by proximal tubular cell dysfunction that may be associated with acute kidney injury or chronic kidney disease. Withdrawal of the drug leads to improvement of analytical parameters that may be partial. Understanding the risk factors for nephrotoxicity and regular monitoring of proximal tubular dysfunction and serum creatinine in high-risk patients is required to minimize nephrotoxicity. Newer, structurally similar molecular derivatives that do not accumulate in proximal tubules are under study

The Emerging Threat of Ai-driven Cyber Attacks: A Review

Cyberattacks are becoming more sophisticated and ubiquitous. Cybercriminals are inevitably adopting Artificial Intelligence (AI) techniques to evade the cyberspace and cause greater damages without being noticed. Researchers in cybersecurity domain have not researched the concept behind AI-powered cyberattacks enough to understand the level of sophistication this type of attack possesses. This paper aims to investigate the emerging threat of AI-powered cyberattacks and provide insights into malicious used of AI in cyberattacks. The study was performed through a three-step process by selecting only articles based on quality, exclusion, and inclusion criteria that focus on AI-driven cyberattacks. Searches in ACM, arXiv Blackhat, Scopus, Springer, MDPI, IEEE Xplore and other sources were executed to retrieve relevant articles. Out of the 936 papers that met our search criteria, a total of 46 articles were finally selected for this study. The result shows that 56% of the AI-Driven cyberattack technique identified was demonstrated in the access and penetration phase, 12% was demonstrated in exploitation, and command and control phase, respectively; 11% was demonstrated in the reconnaissance phase; 9% was demonstrated in the delivery phase of the cybersecurity kill chain. The findings in this study shows that existing cyber defence infrastructures will become inadequate to address the increasing speed, and complex decision logic of AI-driven attacks. Hence, organizations need to invest in AI cybersecurity infrastructures to combat these emerging threats

Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI

BACKGROUND: Atherosclerosis is a chronic inflammatory disease, but data on arterial inflammation at early stages is limited. OBJECTIVES: The purpose of this study was to characterize vascular inflammation by hybrid 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS: Carotid, aortic, and ilio-femoral 18F-FDG PET/MRI was performed in 755 individuals (age 40 to 54 years; 83.7% men) with known plaques detected by 2-/3-dimensional vascular ultrasound and/or coronary calcification in the PESA (Progression of Early Subclinical Atherosclerosis) study. The authors evaluated the presence, distribution, and number of arterial inflammatory foci (increased 18F-FDG uptake) and plaques with or without inflammation (coincident 18F-FDG uptake). RESULTS: Arterial inflammation was present in 48.2% of individuals (24.4% femorals, 19.3% aorta, 15.8% carotids, and 9.3% iliacs) and plaques in 90.1% (73.9% femorals, 55.8% iliacs, and 53.1% carotids). 18F-FDG arterial uptakes and plaques significantly increased with cardiovascular risk factors (p < 0.01). Coincident 18F-FDG uptakes were present in 287 of 2,605 (11%) plaques, and most uptakes were detected in plaque-free arterial segments (459 of 746; 61.5%). Plaque burden, defined by plaque presence, number, and volume, was significantly higher in individuals with arterial inflammation than in those without (p < 0.01). The number of plaques and 18F-FDG uptakes showed a positive albeit weak correlation (r = 0.25; p < 0.001). CONCLUSIONS: Arterial inflammation is highly prevalent in middle-aged individuals with known subclinical atherosclerosis. Large-scale multiterritorial PET/MRI allows characterization of atherosclerosis-related arterial inflammation and demonstrates 18F-FDG uptake in plaque-free arterial segments and, less frequently, within plaques. These findings suggest an arterial inflammatory state at early stages of atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).The PESA study is cofunded equally by the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and Banco Santander. The study also receives funding from the Instituto de Salud Carlos III (PI15/02019) and the European Regional Development Fund (ERDF) “A way to make Europe.” The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades, and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Dr. Sanchez-González is an employee of Philips Healthcare. Dr. Bueno has received research funding from the Instituto de Salud Carlos III, Spain (PIE16/00021 & PI17/01799), AstraZeneca, Bristol-Myers Squibb, Janssen, and Novartis; has received consulting fees from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, and Novartis; and has received speaking fees or support for attending scientific meetings from AstraZeneca, Bayer, Bristol-Myers Squibb-Pfizer, Novartis, and MEDSCAPE-the heart.org.S