Analysis of Outdoor Lighting Control Systems Applied to the New Smart City Models

Lighting accounts for more than 19% of the world’s electricity consumption. Simply replacing existing lighting systems with other LED technology would reduce energy consumption by up to 40%, and if we also use lighting controls, the figure can reach 80%. The transition to efficient lighting technologies (LEDs) is economically one of the most realistic and simple energy efficiency initiatives. Control systems play an important role in the world of lighting. Wherever you have exterior lighting, there will be a need for control. The systems that have been used so far have precedents that date back more than 35 years and allow control and monitoring functions of groups of light points, i.e. not individually. One of the major drawbacks of these systems is that they do not have flexibility, since they do not allow the individualization of the point of light, and in addition the orders that can emit are of generic character and affect the group, obtaining a rather inaccurate information of the installation. Complete telemanagement systems are currently being developed to meet the needs of different application segments. Experience shows that it is necessary to work with open systems so that the lighting management system works and communicates with other systems such as air treatment, safety systems, etc. Intelligent lighting, in addition to its control and energy management functions, also contributes to reducing the excess of artificial light to which our cities are subject, making them more livable

Ancestral Resurrection and Directed Evolution of Fungal Mesozoic Laccases

ABSTRACT Ancestral sequence reconstruction and resurrection provides useful information for protein engineering, yet its alliance with directed evolution has been little explored. In this study, we have resurrected several ancestral nodes of fungal laccases dating back 500 to 250 million years. Unlike modern laccases, the resurrected Mesozoic laccases were readily secreted by yeast, with similar kinetic parameters, a broader stability, and distinct pH activity profiles. The resurrected Agaricomycetes laccase carried 136 ancestral mutations, a molecular testimony to its origin, and it was subjected to directed evolution in order to improve the rate of 1,3- cyclopentanedione oxidation, a –diketone initiator commonly used in vinyl polymerization reactions. IMPORTANCE The broad variety of biotechnological uses of fungal laccases is beyond doubt (food, textiles, pulp and paper, pharma, biofuels, cosmetics, and bioremediation), and protein engineering (in particular, directed evolution) has become the key driver for adaptation of these enzymes to harsh industrial conditions. Usually, the first requirement for directed laccase evolution is heterologous expression, which presents an important hurdle and often a time-consuming process. In this work, we resurrected a fungal Mesozoic laccase node which showed strikingly high heterologous expression and pH stability. As a proof of concept that the ancestral laccase is a suitable blueprint for engineering, we performed a quick directed evolution campaign geared to the oxidation of the -diketone 1,3-cyclopentanedione, a poor laccase substrate that is used in the polymerization of vinyl monomers

Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study

[EN] Objective To examine the capability of MRI texture analysis to differentiate the primary site of origin of brain metastases following a radiomics approach. Methods Sixty-seven untreated brain metastases (BM) were found in 3D T1-weighted MRI of 38 patients with cancer: 27 from lung cancer, 23 from melanoma and 17 from breast cancer. These lesions were segmented in 2D and 3D to compare the discriminative power of 2D and 3D texture features. The images were quantized using different number of gray-levels to test the influence of quantization. Forty-three rotation-invariant texture features were examined. Feature selection and random forest classification were implemented within a nested cross-validation structure. Classification was evaluated with the area under receiver operating characteristic curve (AUC) considering two strategies: multiclass and one-versus-one. Results In the multiclass approach, 3D texture features were more discriminative than 2D features. The best results were achieved for images quantized with 32 gray-levels (AUC = 0.873 +/- 0.064) using the top four features provided by the feature selection method based on the p-value. In the one-versus-one approach, high accuracy was obtained when differentiating lung cancer BM from breast cancer BM (four features, AUC = 0.963 +/- 0.054) and melanoma BM (eight features, AUC = 0.936 +/- 0.070) using the optimal dataset (3D features, 32 gray-levels). Classification of breast cancer and melanoma BM was unsatisfactory (AUC = 0.607 +/- 0.180). Conclusion Volumetric MRI texture features can be useful to differentiate brain metastases from different primary cancers after quantizing the images with the proper number of gray-levels.This work has been partially funded by the Spanish Ministerio de Economia y Competitividad (MINECO) and FEDER funds under Grant BFU2015-64380-C2-2-R. Rafael Ortiz-Ramon was supported by grant ACIF/2015/078 from the Conselleria d'Educacio, Investigacio, Cultura i Esport of the Valencian Community (Spain). Andres Larroza was supported by grant FPU12/01140 from the Spanish Ministerio de Educacion, Cultura y Deporte (MECD).Ortiz-Ramón, R.; Larroza-Santacruz, A.; Ruiz-España, S.; Arana Fernandez De Moya, E.; Moratal, D. (2018). Classifying brain metastases by their primary site of origin using a radiomics approach based on texture analysis: a feasibility study. European Radiology. 28(11):4514-4523. https://doi.org/10.1007/s00330-018-5463-6S451445232811Gavrilovic IT, Posner JB (2005) Brain metastases: epidemiology and pathophysiology. J Neurooncol 75:5–14Stelzer KJ (2013) Epidemiology and prognosis of brain metastases. Surg Neurol Int 4:S192–S202Soffietti R, Cornu P, Delattre JY et al (2006) EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force. 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Magn Reson Imaging 21:983–987Fetit AE, Novak J, Peet AC, Arvanitis TN (2015) Three-dimensional textural features of conventional MRI improve diagnostic classification of childhood brain tumors. NMR Biomed 28:1174–1184Zacharaki EI, Wang S, Chawla S et al (2009) Classification of brain tumor type and grade using MRI texture and shape in a machine learning scheme. Magn Reson Med 62:1609–1618Georgiadis P, Cavouras D, Kalatzis I et al (2009) Enhancing the discrimination accuracy between metastases, gliomas and meningiomas on brain MRI by volumetric textural features and ensemble pattern recognition methods. Magn Reson Imaging 27:120–130Larroza A, Moratal D, Paredes-Sánchez A et al (2015) Support vector machine classification of brain metastasis and radiation necrosis based on texture analysis in MRI. J Magn Reson Imaging 42:1362–1368Li Z, Mao Y, Li H et al (2016) Differentiating brain metastases from different pathological types of lung cancers using texture analysis of T1 postcontrast MR. Magn Reson Med 76:1410–1419Fink KR, Fink JR (2013) Imaging of brain metastases. Surg Neurol Int 4:S209–S219Larroza A, Bodí V, Moratal D (2016) Texture analysis in magnetic resonance imaging: review and considerations for future applications. In: Assessment of cellular and organ function and dysfunction using direct and derived MRI methodologies. InTech, Rijeka, Croatia, pp 75–106Leite M, Rittner L, Appenzeller S et al (2015) Etiology-based classification of brain white matter hyperintensity on magnetic resonance imaging. J Med Imaging 2:14002Mahmoud-Ghoneim D, Alkaabi MK, De Certaines JD, Goettsche F-M (2008) The impact of image dynamic range on texture classification of brain white matter. BMC Med Imaging 8:1–8Depeursinge A, Foncubierta-Rodriguez A, Van De Ville D, Müller H (2014) Three-dimensional solid texture analysis in biomedical imaging: review and opportunities. Med Image Anal 18:176–196Ellingson BM, Bendszus M, Boxerman J et al (2015) Consensus recommendations for a standardized Brain Tumor Imaging Protocol in clinical trials. Neuro Oncol 17:1188–1198Mayerhoefer ME, Breitenseher MJ, Kramer J et al (2005) Texture analysis for tissue discrimination on T1-weighted MR images of the knee joint in a multicenter study: Transferability of texture features and comparison of feature selection methods and classifiers. J Magn Reson Imaging 22:674–680Waugh SA, Lerski RA, Bidaut L, Thompson AM (2011) The influence of field strength and different clinical breast MRI protocols on the outcome of texture analysis using foam phantoms. Med Phys 38:5058–5066Chan TF, Vese LA (2001) Active contours without edges. IEEE Trans Image Process 10:266–277Collewet G, Strzelecki M, Mariette F (2004) Influence of MRI acquisition protocols and image intensity normalization methods on texture classification. Magn Reson Imaging 22:81–91Gibbs P, Turnbull LW (2003) Textural analysis of contrast-enhanced MR images of the breast. Magn Reson Med 50:92–98Vallières M, Freeman CR, Skamene SR, El Naqa I (2015) A radiomics model from joint FDG-PET and MRI texture features for the prediction of lung metastases in soft-tissue sarcomas of the extremities. Phys Med Biol 60:5471–5496Kuhn M, Johnson K (2013) Data pre-processing. In: Applied predictive modeling, 1st ed. Springer, New York, NY, pp 27–59Fernández-Delgado M, Cernadas E, Barro S et al (2014) Do we need hundreds of classifiers to solve real world classification problems? J Mach Learn Res 15:3133–3181Caruana R, Karampatziakis N, Yessenalina A (2008) An empirical evaluation of supervised learning in high dimensions. In: Proceedings of the 25th international conference on Machine learning - ICML ’08. ACM Press, Helsinki, Finland, pp 96–103Kuhn M, Johnson K (2013) Over-fitting and model tuning. In: Applied predictive modeling, 1st ed. 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Iberian cured-ham consumption improves endothelial function in healthy subjects

Objectives: Previous studies have shown that dietary components such as oleic acid or polyphenols exert beneficial effects on endothelium. We aimed to assess the impact of regular consumption of Iberian cured-ham (ICH) on endothelial function. Design: An open-label, randomized controlled parallel study. Setting: Volunteers recruited through advertisements at a hospital in Madrid, Spain. Participants: 102 Caucasian adults (76.8% females) aged 25-55 years, and free from cardiometabolic disease. Intervention: Participants were randomized to an ICH-enriched ad libitum diet or an ad libitum diet without ICH for 6 weeks. Subjects in ICH group were randomly provided with either acorn- or mixed-fed ICH, and followed up for an additional 6-week period under their usual diet. Measurements: Clinical parameters, biomarkers of endothelial function and oxidative stress, microvascular vasodilatory response to hyperemia and arterial stiffness were measured before and after the intervention. Results: After 6 weeks, a larger decrease in PAI-1 was observed in subjects consuming ICH compared to the Control group (-6.2±17.7 vs. 0.3±1.4 ng/ml; p=0.020). Similarly, microvascular vasodilatory response to hyperemia showed a significant increase (112.4±391.7 vs. -56.0±327.9%; p=0.007). However, neither oxidative stress, hemodynamic nor clinical parameters differed significantly over the study. Additionally, after stopping ICH consumption, improvements in PAI-1 remained for 6 additional weeks with respect to baseline (p=0.006). Conclusion: The present study demonstrates, for the first time, that regular consumption of ICH improves endothelial function in healthy adults. Strategies aimed to preserve or improve the endothelial function may have implications in vascular aging beyond the prevention of the atherothrombotic disease

The RNA Polymerase II Factor RPAP1 Is Critical for Mediator-Driven Transcription and Cell Identity

The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa and required for stem cell differentiation in plants; however, very little is known about its mechanism of action or its role in mammalian cells. Here, we report that RPAP1 is essential for the expression of cell identity genes and for cell viability. Depletion of RPAP1 triggers cell de-differentiation, facilitates reprogramming toward pluripotency, and impairs differentiation. Mechanistically, we show that RPAP1 is essential for the interaction between RNA polymerase II (RNA Pol II) and Mediator, as well as for the recruitment of important regulators, such as the Mediator-specific RNA Pol II factor Gdown1 and the C-terminal domain (CTD) phosphatase RPAP2. In agreement, depletion of RPAP1 diminishes the loading of total and Ser5-phosphorylated RNA Pol II on many genes, with super-enhancer-driven genes among the most significantly downregulated. We conclude that Mediator/RPAP1/RNA Pol II is an ancient module, conserved from plants to mammals, critical for establishing and maintaining cell identity.We are grateful to Elisa Varela for assistance with morula and blastocyst fixa- tion. Work in the laboratory of M.S. is funded by the CNIO and the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) (SAF2013-48256-R), the European Research Co uncil (ERC-2014-AdG/66 9622), the Region al Government of Ma- drid co-funded by the Euro pean Social Fund (ReCaRe project), the Euro pean Union (RISK-IR project), the Botin Foundation and Banco Santander (Santander Universities Glo bal Division), the Ramon Areces Found ation, and the AXA Foundation. S.R. was funded by a contract from the Ramon y Cajal Program(RYC-2011-09242) and by the Spanish Ministry of Economy co- funded by the ERDF (SAF2013-49147- P and SAF2016-80874-PS

Neutrophil infiltration regulates clock-gene expression to organize daily hepatic metabolism.

Liver metabolism follows diurnal fluctuations through the modulation of molecular clock genes. Disruption of this molecular clock can result in metabolic disease but its potential regulation by immune cells remains unexplored. Here, we demonstrated that in steady state, neutrophils infiltrated the mouse liver following a circadian pattern and regulated hepatocyte clock-genes by neutrophil elastase (NE) secretion. NE signals through c-Jun NH2-terminal kinase (JNK) inhibiting fibroblast growth factor 21 (FGF21) and activating Bmal1 expression in the hepatocyte. Interestingly, mice with neutropenia, defective neutrophil infiltration or lacking elastase were protected against steatosis correlating with lower JNK activation, reduced Bmal1 and increased FGF21 expression, together with decreased lipogenesis in the liver. Lastly, using a cohort of human samples we found a direct correlation between JNK activation, NE levels and Bmal1 expression in the liver. This study demonstrates that neutrophils contribute to the maintenance of daily hepatic homeostasis through the regulation of the NE/JNK/Bmal1 axis.BGT and MC were fellows of the FPI: Severo Ochoa CNIC program (SVP-2013–067639) and (BES-2017–079711) respectively. IN was funded by EFSD/Lilly grants (2017 and 2019), the CNIC IPP FP7 Marie Curie Programme (PCOFUND-2012–600396), EFSD Rising Star award (2019), JDC-2018-Incorporación (MIN/JDC1802). T-L was a Juan de la Cierva fellow (JCI2011–11623). C.F has a Sara Borrell contract (CD19/00078). RJD is an Investigator of the Howard Hughes Medical Institute. This work was funded by the following grants to GS: funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n˚ ERC 260464, EFSD/Lilly European Diabetes Research Programme Dr Sabio, 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (Investigadores-BBVA-2017) IN[17] _BBM_BAS_0066, MINECO-FEDER SAF2016-79126-R and PID2019-104399RB-I00 , EUIN201785875, Comunidad de Madrid IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-3733 and Fundación AECC AECC PROYE19047SABI and AECC: INVES20026LEIV to ML. MM was funded by ISCIII and FEDER PI16/01548 and Junta de Castilla y León GRS 1362/A/16 and INT/M/17/17 and JL-T by Junta de Castilla y León GRS 1356/A/16 and GRS 1587/A/17. The study was additionally funded by MEIC grants to ML (MINECO-FEDER-SAF2015-74112-JIN) AT-L (MINECO-FEDERSAF2014-61233-JIN), RJD: Grant DK R01 DK107220 from the National Institutes of Health. AH: (SAF2015-65607-R). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia, Innovación y Universidades (MCNU) and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015–0505).S

Frequency of breast cancer with hereditary risk features in Spain: Analysis from GEICAM “El Álamo III” retrospective study

Purpose: To determine the frequency of breast cancer (BC) patients with hereditary risk features in a wide retrospective cohort of patients in Spain. Methods: a retrospective analysis was conducted from 10, 638 BC patients diagnosed between 1998 and 2001 in the GEICAM registry “El Álamo III”, dividing them into four groups according to modified ESMO and SEOM hereditary cancer risk criteria: Sporadic breast cancer group (R0); Individual risk group (IR); Familial risk group (FR); Individual and familial risk group (IFR) with both individual and familial risk criteria. Results: 7, 641 patients were evaluable. Of them, 2, 252 patients (29.5%) had at least one hereditary risk criteria, being subclassified in: FR 1.105 (14.5%), IR 970 (12.7%), IFR 177 (2.3%). There was a higher frequency of newly diagnosed metastatic patients in the IR group (5.1% vs 3.2%, p = 0.02). In contrast, in RO were lower proportion of big tumors (> T2) (43.8% vs 47.4%, p = 0.023), nodal involvement (43.4% vs 48.1%, p = 0.004) and lower histological grades (20.9% G3 for the R0 vs 29.8%) when compared to patients with any risk criteria. Conclusions: Almost three out of ten BC patients have at least one hereditary risk cancer feature that would warrant further genetic counseling. Patients with hereditary cancer risk seems to be diagnosed with worse prognosis factors

The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial.

Background Ivermectin inhibits the replication of SARS-CoV-2 in vitro at concentrations not readily achievable with currently approved doses. There is limited evidence to support its clinical use in COVID-19 patients. We conducted a Pilot, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of a single dose of ivermectin reduce the transmission of SARS-CoV-2 when administered early after disease onset. Methods Consecutive patients with non-severe COVID-19 and no risk factors for complicated disease attending the emergency room of the Clínica Universidad de Navarra between July 31, 2020 and September 11, 2020 were enrolled. All enrollments occurred within 72 h of onset of fever or cough. Patients were randomized 1:1 to receive ivermectin, 400 mcg/kg, single dose (n = 12) or placebo (n = 12). The primary outcome measure was the proportion of patients with detectable SARS-CoV-2 RNA by PCR from nasopharyngeal swab at day 7 post-treatment. The primary outcome was supported by determination of the viral load and infectivity of each sample. The differences between ivermectin and placebo were calculated using Fisher's exact test and presented as a relative risk ratio. This study is registered at ClinicalTrials.gov: NCT04390022. Findings All patients recruited completed the trial (median age, 26 [IQR 19-36 in the ivermectin and 21-44 in the controls] years; 12 [50%] women; 100% had symptoms at recruitment, 70% reported headache, 62% reported fever, 50% reported general malaise and 25% reported cough). At day 7, there was no difference in the proportion of PCR positive patients (RR 0·92, 95% CI: 0·77-1·09, p = 1·0). The ivermectin group had non-statistically significant lower viral loads at day 4 (p = 0·24 for gene E; p = 0·18 for gene N) and day 7 (p = 0·16 for gene E; p = 0·18 for gene N) post treatment as well as lower IgG titers at day 21 post treatment (p = 0·24). Patients in the ivermectin group recovered earlier from hyposmia/anosmia (76 vs 158 patient-days; p < 0.001). Interpretation Among patients with non-severe COVID-19 and no risk factors for severe disease receiving a single 400 mcg/kg dose of ivermectin within 72 h of fever or cough onset there was no difference in the proportion of PCR positives. There was however a marked reduction of self-reported anosmia/hyposmia, a reduction of cough and a tendency to lower viral loads and lower IgG titers which warrants assessment in larger trials. Funding ISGlobal, Barcelona Institute for Global Health and Clínica Universidad de Navarra