Among brain tumors, gliomas are the most common and aggressive, leading to a very short life expectancy in their highest grade. Thus, treatment planning is a key stage to improve the quality of life ...of oncological patients. Magnetic resonance imaging (MRI) is a widely used imaging technique to assess these tumors, but the large amount of data produced by MRI prevents manual segmentation in a reasonable time, limiting the use of precise quantitative measurements in the clinical practice. So, automatic and reliable segmentation methods are required; however, the large spatial and structural variability among brain tumors make automatic segmentation a challenging problem. In this paper, we propose an automatic segmentation method based on Convolutional Neural Networks (CNN), exploring small 3 ×3 kernels. The use of small kernels allows designing a deeper architecture, besides having a positive effect against overfitting, given the fewer number of weights in the network. We also investigated the use of intensity normalization as a pre-processing step, which though not common in CNN-based segmentation methods, proved together with data augmentation to be very effective for brain tumor segmentation in MRI images. Our proposal was validated in the Brain Tumor Segmentation Challenge 2013 database (BRATS 2013), obtaining simultaneously the first position for the complete, core, and enhancing regions in Dice Similarity Coefficient metric (0.88, 0.83, 0.77) for the Challenge data set. Also, it obtained the overall first position by the online evaluation platform. We also participated in the on-site BRATS 2015 Challenge using the same model, obtaining the second place, with Dice Similarity Coefficient metric of 0.78, 0.65, and 0.75 for the complete, core, and enhancing regions, respectively.
Many see the periaqueductal gray (PAG) as a region responsible for the downstream control of defensive reactions. Here we provide a detailed review of anatomical and functional data on the different ...parts of the PAG together with the dorsal raphe, which completes the circle of periaqueductal nuclei. Based on anatomical features, we propose a new subdivision of the periaqueductal gray that accounts for the distinct characteristics of the area. We provide a comprehensive functional view of the periaqueductal gray, going beyond simple panic and escape to integrate data on fear, anxiety, and depression. Importantly, we conclude that this periaqueductal cluster of nuclei is broadly involved in motivated behavior controlling not only aversive but also appetitive behavior and with some involvement in more complex motivational processes such as approach-avoidance conflict resolution. In sum, these highly conserved nuclei surrounding the aqueduct appear to be the simplest, foundational, elements of integrated motivated goal-directed control of all types.
•A multi-scale Fully Convolutional Neural Network for retinal vessel segmentation.•Rotations as the basis of a joint strategy for data augmentation and prediction.•The Stationary Wavelet Transform as ...a way to stack new channels into the input.
The retinal vascular condition is a reliable biomarker of several ophthalmologic and cardiovascular diseases, so automatic vessel segmentation may be crucial to diagnose and monitor them. In this paper, we propose a novel method that combines the multiscale analysis provided by the Stationary Wavelet Transform with a multiscale Fully Convolutional Neural Network to cope with the varying width and direction of the vessel structure in the retina. Our proposal uses rotation operations as the basis of a joint strategy for both data augmentation and prediction, which allows us to explore the information learned during training to refine the segmentation. The method was evaluated on three publicly available databases, achieving an average accuracy of 0.9576, 0.9694, and 0.9653, and average area under the ROC curve of 0.9821, 0.9905, and 0.9855 on the DRIVE, STARE, and CHASE_DB1 databases, respectively. It also appears to be robust to the training set and to the inter-rater variability, which shows its potential for real-world applications.
Microplastics (MPs) are emerging contaminants of freshwater ecosystems. Once in aquatic systems, most of these plastic particles undergo processes of fragmentation, biofouling, and sedimentation, ...resulting in increased concentrations of smaller sized and irregularly-shaped particles in the sediment. High levels of MPs in freshwater sediments can denote a potential threat to benthic and sediment-dwelling organisms such as dipteran larvae. This study evaluates the ecotoxicological effect of three pools of irregularly-shaped polyethylene (PE) microplastics (pools containing 90% of the particles within 32–63 μm (size-class A), 63–250 μm (size-class B) and 125–500 μm (size-class C)), with concentrations ranging from 1.25 to 20 g Kg−1 sediment, on the dipteran Chironomus riparius life-history traits. After ten days of exposure, larvae ingested PE particles typically in the 32–63 μm range, even when 90% of the particles possessed higher size (i.e., in size-classes B and C) and the larvae mandible allowed the ingestion of such bigger-sized particles. Thus, the number of ingested particles was higher in size-class A, followed by B and C, and led to a significant reduction with similar magnitude on larval growth (Lowest Observed Effect Concentrations (LOEC) = 2.5 g Kg−1 sediment DW) and a significant delay on imagoes emergence (e.g., LOEC = 1.5 g Kg−1 sediment DW for females).
The results from this study show that the ingestion and persistence of small-sized polyethylene microplastics caused significant impairments on life-history traits of C. riparius. Considering their role on freshwater food-webs and the potential persistence of small-sized PE particles in their larval gut, these results also point for the potential adverse effects of small-sized microplastics at the community and ecosystem level.
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•Chironomus riparius larvae ingested polyethylene (PE) particles.•Polyethylene particles in the larval gut were mainly in the range of 32–63 μm.•Effects of PE particles on C. riparius growth and emergence were dose-dependent.•Emergence was the most sensitive endpoint for female imagoes.
Dementia is characterized by the impairment of cognition and behavior of people over 65 years. Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the world, as approximately ...47 million people are affected by this disease and the tendency is that this number will increase to 62% by 2030. Two microscopic features assist in the characterization of the disease, the amyloid plaques and neurofibrillary agglomerates. All these factors are responsible for the slow and gradual deterioration of memory that affect language, personality or cognitive control. For the AD diagnosis, neuropsychological tests are performed in different spheres of cognitive functions but since not all cognitive functions may be affected, cerebrospinal fluid biomarkers are used along with these tests. To date, cholinesterase inhibitors are used as treatment, they are the only drugs that have shown significant improvements in the cognitive functions of AD patients. Despite the proven effectiveness of cholinesterase inhibitors, an AD carrier, even while being treated, is continually subjected to progressive degeneration of the neuronal tissue. For this reason, other biochemical pathways associated with the pathophysiology of AD have been explored as alternatives to the treatment of this condition such as inhibition of β-secretase and glycogen synthase kinase-3β. The present study aims to conduct a review of the epidemiology, pathophysiology, symptoms, diagnosis and treatment of Alzheimer's disease, emphasizing the research and development of new therapeutic approaches.
The quest for safer anti‐inflammatory drugs is still the focus of several medicinal chemistry programs. Chromones (4H‐chromen‐4‐ones) are a group of naturally occurring compounds ubiquitous in ...plants, and the chromone core has proven to be a privileged scaffold in medicinal chemistry. Herein we provide an overview of the relevance of chromones as anti‐inflammatory agents, specifically as inhibitors of cyclooxygenase (COX), 5‐lipoxygenase (5‐LOX), interleukin‐5 (IL‐5), and nitric oxide (.NO) production. Numerous structure–activity relationships and mechanisms of action are discussed. This review is therefore intended to provide a foundation for the design and synthesis of novel chromone‐based compound libraries for further development into safer and more efficient anti‐inflammatory agents.
Fact! The chromone nucleus is an important scaffold for the development of anti‐inflammatory agents. Their interactions with important enzymes involved in inflammatory processes and their privileged features are not very well documented. In this minireview we discuss the structure–activity relationships of chromones as well as their mechanisms of action.
Despite intensive effort and resulting gains in understanding the mechanisms underlying neuropathic pain, limited success in therapeutic approaches have been attained. A recently identified, ...nonchannel, nonneurotransmitter therapeutic target for pain is the enzyme soluble epoxide hydrolase (sEH). The sEH degrades natural analgesic lipid mediators, epoxy fatty acids (EpFAs), therefore its inhibition stabilizes these bioactive mediators. Here we demonstrate the effects of EpFAs on diabetes induced neuropathic pain and define a previously unknown mechanism of pain, regulated by endoplasmic reticulum (ER) stress. The activation of ER stress is first quantified in the peripheral nervous system of type I diabetic rats. We demonstrate that both pain and markers of ER stress are reversed by a chemical chaperone. Next, we identify the EpFAs as upstream modulators of ER stress pathways. Chemical inducers of ER stress invariably lead to pain behavior that is reversed by a chemical chaperone and an inhibitor of sEH. The rapid occurrence of pain behavior with inducers, equally rapid reversal by blockers and natural incidence of ER stress in diabetic peripheral nervous system (PNS) argue for a major role of the ER stress pathways in regulating the excitability of the nociceptive system. Understanding the role of ER stress in generation and maintenance of pain opens routes to exploit this system for therapeutic purposes.
Here we define the causative role of endoplasmic reticulum (ER) stress on selective modulation of pain signaling. High levels of ER stress and neuropathic pain in diabetic animals are reduced using ER stress blockers. In healthy animals, turning on the ER stress signal transduction cascade generates an immediate but lasting and site restricted painful phenotype, which is reversible by ER stress blockers. This previously unnoticed mechanism explains the broad lack of efficacy of available analgesics and should ignite the discovery of a new generation of therapeutics that do not directly quell ion channel or neurotransmitter activity.
The increasing number of distributed renewable energy systems and smart-grid technologies, are transforming electricity grids and markets, allowing the growth of peer-to-peer (P2P) energy markets, ...where consumers and prosumers trade directly with each other. Policymakers are then faced with the task of assessing alternative ways to manage and organize the electricity grid and market.
This work explores the potential of P2P energy trading under different available technologies and market paradigms, by analysing the economic benefits for residential consumers and prosumers, given different solar generation contexts and load flexibility levels. The model is applied to the Portuguese residential sector.
Results show that with best techno-economic sizing solution for solar photovoltaic (PV), the greater economic gains come from flexibility, reaching a maximum of 28% for consumers and 55% for prosumers, in a P2P trading scenario. However, if we consider flexibility and a high-solar fraction PV sizing, the savings would reach 29% for consumers and 113% for prosumers. P2P economic benefits are found to depend on the type of participating agents involved, demand profile, PV surplus and monetization schemes, level of flexible equipment, which will greatly influence which trading strategies work best, meaning that each case study needs a tailored P2P trading scheme.
•The potential economic benefits of different energy trading paradigms are analysed.•Solar PV and load flexibility are considered as energy trading technologies.•Typical consumers and prosumers from the Portuguese residential sector are assessed.•P2P shows savings for consumers and prosumers up to 28% and 55%, respectively.•If we consider flexibility, respective savings increase to 29% and 113%.
Aggregates of conjugated polymers exhibit two classes of fundamental electronic interactions: those occurring within a given chain and those occurring between chains. The impact of such excitonic ...interactions on the photophysics of polymer films can be understood using concepts of J- and H-aggregation originally developed by Kasha and coworkers to treat aggregates of small molecules. In polymer assemblies, intrachain through-bond interactions lead to J-aggregate behavior, whereas interchain Coulombic interactions lead to H-aggregate behavior. The photophysics of common emissive conjugated polymer films are determined by a competition between intrachain, J-favoring interactions and interchain, H-favoring interactions. We review formalisms describing absorption and photoluminescence lineshapes, based on intra- and intermolecular excitonic coupling, electron-vibrational coupling, and correlated energetic disorder. Examples include regioregular polythiophenes, pheneylene-vinylenes, and polydiacetylene.
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