The extent and nature of symbolic behavior among Neandertals are obscure. Although evidence for Neandertal body ornamentation has been proposed, all cave painting has been attributed to modern ...humans. Here we present dating results for three sites in Spain that show that cave art emerged in Iberia substantially earlier than previously thought. Uranium-thorium (U-Th) dates on carbonate crusts overlying paintings provide minimum ages for a red linear motif in La Pasiega (Cantabria), a hand stencil in Maltravieso (Extremadura), and red-painted speleothems in Ardales (Andalucía). Collectively, these results show that cave art in Iberia is older than 64.8 thousand years (ka). This cave art is the earliest dated so far and predates, by at least 20 ka, the arrival of modern humans in Europe, which implies Neandertal authorship.
The exponential growth of data traffic and connected devices, and the reduction of latency and costs, are considered major challenges for future mobile communication networks. The satisfaction of ...these challenges motivates revisiting the architecture of these networks. We propose an SDN-based design of a hierarchical architecture for the 5G packet core. In this article we focus on the design of its access cloud with the goal of providing low latency and scalable Ethernet-like support to terminals and MTC devices including mobility management. We examine and address its challenges in terms of network scalability and support for link-level mobility. We propose a link-level architecture that forwards frames from and to edge network elements (AP and routers) with a label that identifies the APs through which the terminal is reachable. An SDN local controller tracks and updates the users' location information at the edge network elements. Additionally, we propose to delegate in SDN local controllers the handling of non-scalable operations, such as broadcast and multicast messages, and network management procedures.
•NOx emissions from NEDC and Real Driving Emissions have been compared.•Statistical analysis was performed to study the influence of engine parameters.•NOx emissions increased under real driving due ...to the different behavior of the engine.•Real driving emissions achieve more homogeneous distribution of the engine operating modes.•NOx emissions under NEDC are bounded on a narrow window at low levels.
The interest of NOx engine emissions from diesel engines has been increasing during the last years. Particularly, the comparison of the real driving NOx emissions with the results obtained during homologation procedures has received a great attention. The main goal of this paper is to provide a statistical methodology, able to compare two different types of driving pattern conditions and the corresponding NOx engine emissions. In the present work, the two types of driving pattern analysed are the real-world driving and the chassis dyno following the New European Driving Cycle (NEDC). For the sake of generality, two types of circuits (Urban and Extra-urban) have been selected. A light-duty diesel vehicle, equipped with the same after-treatment system as Euro 5 engines, was used as a test vehicle. Although in this certifications only new vehicles have to fulfil Euro 6d temp, Real Driving Emissions test (RDE) is mandatory, it is necessary to quantify the real-world driving emissions for the previous certifications (Euro 5 and Euro 4 vehicles). The statistical study demonstrates the existence of significant differences among the fundamental variables of the engine (desired injection quantity, engine speed, vehicle velocity, exhaust gas recirculation (EGR) valve opening and NOx measured emissions) when real driving and NEDC procedures are compared. Although these results have been obtained by a deductive way, they led us to state that real driving NOx emissions strongly differs from NEDC driving ones. Therefore, this manuscript constitutes a further more proof of the non-representativeness of NEDC procedure as vehicle certification procedure.
Fatigue is one of the most prevalent symptoms among cancer patients. Specifically, in metastatic castration-resistant prostate cancer (mCRPC) patients, fatigue is the most common adverse event ...associated with current treatments. The purpose of this study is to describe the prevalence of fatigue and its impact on quality of life (QoL) in patients with CRPC in routine clinical practice.
This was a cross-sectional, multicentre study. Male chemo-naïve adults with high-risk non-metastatic (M0) CRPC and metastatic (M1) CRPC (mCRPC) were eligible. Fatigue was measured using the Brief Fatigue Inventory (BFI) and QoL was assessed using the Functional Assessment of Cancer Therapy questionnaire for patients with prostate cancer (FACT-P) and the FACT-General (FACT-G) questionnaire. Data were analysed using Mann-Whitney or Kruskal-Wallis tests (non-parametric distribution), a T-test or an ANOVA (parametric distribution) and the Fisher or chi-squared tests (categorical variables).
A total of 235 eligible patients were included in the study (74 31.5% with M0; and 161 68.5% with M1). Fatigue was present in 74%, with 38.5% of patients reporting moderate-to-severe fatigue. Mean FACT-G and FACT-P overall scores were 77.6 ± 16.3 and 108.7 ± 21.4, respectively, with no differences between the CRPC M0 and CRPC M1 subgroups. Fatigue intensity was associated with decreased FACT-G/P scores, with no differences between groups. Among 151 mCRPC patients with available treatment data, those treated with abiraterone-prednisone ≥3 months showed a significant reduction in fatigue intensity (p = 0.043) and interference (p = 0.04) compared to those on traditional hormone therapy (HT). Patients on abiraterone-prednisone ≥3 months showed significantly better FACT-G/P scores than patients on HT (p = 0.046 and 0.018, respectively).
Our data show a high prevalence and intensity of fatigue and its impact on QoL in chemo-naïve CRPC patients. There is an association between greater fatigue and less QoL, irrespective of the presence or absence of metastasis. Chemo-naïve mCRPC patients receiving more than 3 months of abiraterone acetate plus prednisone showed an improvement of fatigue and QoL when compared to those on traditional HT.
Not applicable since it is not an interventional study.
Context. The derivation of the effective temperature of a star is a critical first step in a detailed spectroscopic analysis. Spectroscopic methods suffer from systematic errors related to model ...simplifications. Photometric methods may be more robust, but are exposed to the distortions caused by interstellar reddening. Direct methods are difficult to apply, since fundamental data of high accuracy are hard to obtain. Aims. We explore a new approach in which the spectrum is used to characterize a star’s effective temperature based on a calibration established by a small set of standard stars. Methods. We perform principal component analysis on homogeneous libraries of stellar spectra, then calibrate a relationship between the principal components and the effective temperature using a set of stars with reliable effective temperatures. Results. We find that our procedure gives excellent consistency when spectra from a homogenous set of observations are used. Systematic offsets may appear when combining observations from different sources. Using as reference the spectra of stars with high-quality spectroscopic temperatures in the Elodie library, we define a temperature scale for FG-type disk dwarfs with an internal consistency of about 50 K, in excellent agreement with temperatures from direct determinations and widely used scales based on the infrared flux method.
Network function virtualization is considered one of the key technologies for developing future mobile networks. In this paper, we propose a theoretical framework to evaluate the performance of a ...Long-Term Evolution (LTE) virtualized mobility management entity (vMME) hosted in a data center. This theoretical framework consists of 1) a queuing network to model the vMME in a data center and 2) analytic expressions to estimate the overall mean system delay and the signaling workload to be processed by the vMME. We validate our mathematical model by simulation. One direct use of the proposed model is vMME dimensioning, i.e., to compute the number of vMME processing instances to provide a target system delay given the number of users in the system. Additionally, the paper includes a scalability analysis of the system. In our study, we consider the billing model and a data center setup of Amazon Elastic Compute Cloud service and estimate the processing time of MME processing instances for different LTE control procedures experimentally. For the considered setup, our results show that the vMME is scalable for signaling workloads up to 37 000 LTE control procedures per second for a target mean system delay of 1 ms. The system design and database performance assumed imposes this limit in the system scalability.
The Internet of Things is one of the hottest topics in communications today, with current revenues of $151B, around 7 billion connected devices, and an unprecedented growth expected for next years. A ...massive number of sensors and actuators are expected to emerge, requiring new wireless technologies that can extend their battery life and can cover large areas. LoRaWAN is one of the most outstanding technologies which fulfill these demands, attracting the attention of both academia and industry. In this paper, the design of a LoRaWAN testbed to support critical situations, such as emergency scenarios or natural disasters, is proposed. This self-healing LoRaWAN network architecture will provide resilience when part of the equipment in the core network may become faulty. This resilience is achieved by virtualizing and properly orchestrating the different network entities. Different options have been designed and implemented as real prototypes. Based on our performance evaluation, we claim that the usage of microservice orchestration with several replicas of the LoRaWAN network entities and a load balancer produces an almost seamless recovery which makes it a proper solution to recover after a system crash caused by any catastrophic event.
Oxidative stress causes biochemical changes in lipids and proteins; these changes can induce damage to the vascular endothelium and create maternal complications that are characteristic of ...preeclampsia. In this study, we evaluated the oxidative profile of lipoproteins isolated from women with preeclampsia.
Thirty women diagnosed with preeclampsia and thirty women without preeclampsia were included in the study. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, the formation of dityrosines, and the carbonylation of proteins were assessed as indicators of protein damage. The protective activity of HDL-c was evaluated by the paraoxonase-I activity present on the HDL-c particles. Serum lipid profiles were also quantified in both groups. Data were analysed using Student's t test and the Pearson correlation coefficient.
Our results demonstrated in PE women evident oxidative changes in the lipids and proteins in HDL-c and LDL-c particles and the activity of the antioxidant enzyme PON-I decreased 59.9%. HDL-c exhibited self-defence, as demonstrated by the negative correlation between paraoxonase-I activity and the formation of lipohydroperoxides in HDL-c (r = -0.3755, p < 0.005).
LDL-c and HDL-c isolated from women with preeclampsia show oxidative damage to lipids and proteins. We propose an oxidative profile based on the oxidation levels indicated by each of the markers used. We also found that paraoxonase-I is inactivated in the presence of lipohydroperoxides. Antioxidant support might be helpful to reduce oxidative stress in patients with preeclampsia. Further investigations are necessary to define the association between antioxidant activities and preeclampsia.
Abstract
The blood-brain barrier (BBB) is constituted by a specialized vascular endothelium that interacts directly with astrocytes, neurons and pericytes. It protects the brain from the molecules of ...the systemic circulation but it has to be overcome for the proper treatment of brain cancer, psychiatric disorders or neurodegenerative diseases, which are dramatically increasing as the population ages. In the present work we have revised the current knowledge on the cellular structure of the BBB and the different procedures utilized currently and those proposed to cross it. Chemical modifications of the drugs, such as increasing their lipophilicity, turn them more prone to be internalized in the brain. Other mechanisms are the use of molecular tools to bind the drugs such as small immunoglobulins, liposomes or nanoparticles that will act as Trojan Horses favoring the drug delivery in brain. This fusion of the classical pharmacology with nanotechnology has opened a wide field to many different approaches with promising results to hypothesize that BBB will not be a major problem for the new generation of neuroactive drugs. The present review provides an overview of all state-of-the-art of the BBB structure and function, as well as of the classic strategies and these appeared in recent years to deliver drugs into the brain for the treatment of Central Nervous System (CNS) diseases.
Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of Aβ42 versus Aβ40 peptide which is thought to drive the amyloid plaque formation in the brain of these ...patients. Little is known however whether ageing, the major risk factor for sporadic AD, affects amyloid beta‐peptide (Aβ) generation as well. Here we demonstrate that the secretion of Aβ is enhanced in an in vitro model of neuronal ageing, correlating with an increase in γ‐secretase complex formation. Moreover we found that peroxynitrite (ONOO−), produced by the reaction of superoxide anion with nitric oxide, promoted the nitrotyrosination of presenilin 1 (PS1), the catalytic subunit of γ‐secretase. This was associated with an increased association of the two PS1 fragments, PS1‐CTF and PS1‐NTF, which constitute the active catalytic centre. Furthermore, we found that peroxynitrite shifted the production of Aβ towards Aβ42 and increased the Aβ42/Aβ40 ratio. Our work identifies nitrosative stress as a potential mechanistic link between ageing and AD.
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