Review and analysis of advances in functionalized, smart, and multifunctional asphalt mixtures

Road pavements are designed to withstand road traffic and weathering actions while ensuring comfortable and safe riding conditions as well as low costs and damage to the environment. When a road pavement has additional abilities or reacts to an external stimulus, it is considered to be smart and multifunctional. Examples of such abilities that have been investigated in asphalt mixtures are photocatalytic, superhydrophobic, self-cleaning, de-icing/anti-icing, self-healing, thermochromic, and latent heat thermal energy storage abilities. These abilities are developed using different materials such as nano/microparticles (including semiconductor materials and microcapsules), fibers, phase change materials (PCMs), and dyes, often using dissimilar techniques such as spray coating, volume incorporation, spreading, and asphalt binder modification. Owing to their large surface areas, road pavements are true recipients for large amounts of nano/micromaterials, and consequently, act as important “tools” to stimulate an emerging sector related to the scale of production of materials in the form of nanoparticles. Moreover, smart and multifunctional road pavements can be included in the domain of clean technology (e.g., photocatalytic pavements that promote the environmental depollution of NOx-type gases emitted as vehicle exhaust gases). In this context, they can contribute to materializing the transition to a novel socio-economic model known as “Green Recovery” that is environmentally friendly, sustainable, and inclusive. This model is a very important path toward economic and employment recovery, a vision to which many countries are strongly committed. Therefore, this work reviews new capabilities imparted to asphalt mixtures and provides recommendations.This work was supported by FCT (Fundação para a Ciência e a Tecnologia) under the framework of the Strategic Funding UIDB/04029/2020, UIDB/04650/2020, and UID/FIS/04650/2019, and the PTDC/FIS-MAC/6606/2020, PTDC/FIS/120412/2010, and PEst-OE/ECI/UI4047/2019. The first author would like to acknowledge the FCT for the Ph.D. scholarship (SFRH/BD/137421/2018) and the third author would like to thank CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico - for the PQ 1-D scholarship (308,360/2017–6)

Effects of serine proteases inhibitors in bovine sperm cryopreservation.

Proceedings of the 30th Annual Meeting of the Brazilian Embryo Technology Society (SBTE); Foz do Iguaçu, PR, Brazil, August 25th to 27th, 2016, and 32nd Meeting of the European Embryo Transfer Association (AETE); Barcelona, Spain, September 9th and 10th, 2016

Caracterização físico-química e de compostos funcionais em frutos de pitaya.

A pitaya é uma fruta rústica, pertencente à família Cactaceae, sendo conhecida mundialmente como "Fruta-do-Dragão?. De acordo com a espécie, seus frutos podem apresentar características diversificadas, como formato, presença de espinhos, cor da casca e da polpa, refletindo em alta variabilidade genética (JUNQUEIRA et al., 2007). No Brasil é comum serem encontradas, em estágio nativo no Cerrado e Caatinga, espécies do gênero Selenicereus e Hylocereus, dentre elas a Selenicereus setaceus, popularmente conhecida como pitaya-do-cerrado (JUNQUEIRA et al., 2002). Atualmente, as espécies de pitaya mais cultivadas no mundo são a pitaya de casca vermelha (Hylocereus undatus (Haw.) Britton e Rose) e a de casca amarela (Selenicereus megalanthus (K. Schum ex Vaupel) (MIZRAHI et al., 1997; NERD et al., 2002). Devido ao seu sabor doce e suave, de polpa firme e repleta de sementes e aliado às suas propriedades nutricionais e funcionais, faz da pitaya um produto de grande aceitação nos mercados consumidores, o que têm despertado o interesse nos produtores. O alto valor pago pelo quilo da fruta, que pode variar de dez a sessenta reais, dependendo da época do ano e da demanda, também constitui um grande atrativo para o plantio dessa frutífera (JUNQUEIRA et al., 2002; SOUZA, 2010). Devido à escassez de estudos sobre a pitaya, torna-se fundamental a ampliação do conhecimento acerca dessa espécie, viabilizando a produção de mudas e fornecendo subsídios para a seleção de materiais promissores. Neste trabalho, objetivou-se realizar a caracterização físico-química e de compostos funcionais nas espécies de pitaya Hylocereus costaricencis e Hylocereus undatus

Artificial intelligence for predictive biomarker discovery in immuno-oncology: a systematic review

Background: The widespread use of immune checkpoint inhibitors (ICIs) has revolutionised treatment of multiple cancer types. However, selecting patients who may benefit from ICI remains challenging. Artificial intelligence (AI) approaches allow exploitation of high-dimension oncological data in research and development of precision immuno-oncology. Materials and methods: We conducted a systematic literature review of peer-reviewed original articles studying the ICI efficacy prediction in cancer patients across five data modalities: genomics (including genomics, transcriptomics, and epigenomics), radiomics, digital pathology (pathomics), and real-world and multimodality data. Results: A total of 90 studies were included in this systematic review, with 80% published in 2021-2022. Among them, 37 studies included genomic, 20 radiomic, 8 pathomic, 20 real-world, and 5 multimodal data. Standard machine learning (ML) methods were used in 72% of studies, deep learning (DL) methods in 22%, and both in 6%. The most frequently studied cancer type was non-small-cell lung cancer (36%), followed by melanoma (16%), while 25% included pan-cancer studies. No prospective study design incorporated AI-based methodologies from the outset; rather, all implemented AI as a post hoc analysis. Novel biomarkers for ICI in radiomics and pathomics were identified using AI approaches, and molecular biomarkers have expanded past genomics into transcriptomics and epigenomics. Finally, complex algorithms and new types of AI-based markers, such as meta-biomarkers, are emerging by integrating multimodal/multi-omics data. Conclusion: AI-based methods have expanded the horizon for biomarker discovery, demonstrating the power of integrating multimodal data from existing datasets to discover new meta-biomarkers. While most of the included studies showed promise for AI-based prediction of benefit from immunotherapy, none provided high-level evidence for immediate practice change. A priori planned prospective trial designs are needed to cover all lifecycle steps of these software biomarkers, from development and validation to integration into clinical practice

Investigating human audio-visual object perception with a combination of hypothesis-generating and hypothesis-testing fMRI analysis tools

Primate multisensory object perception involves distributed brain regions. To investigate the network character of these regions of the human brain, we applied data-driven group spatial independent component analysis (ICA) to a functional magnetic resonance imaging (fMRI) data set acquired during a passive audio-visual (AV) experiment with common object stimuli. We labeled three group-level independent component (IC) maps as auditory (A), visual (V), and AV, based on their spatial layouts and activation time courses. The overlap between these IC maps served as definition of a distributed network of multisensory candidate regions including superior temporal, ventral occipito-temporal, posterior parietal and prefrontal regions. During an independent second fMRI experiment, we explicitly tested their involvement in AV integration. Activations in nine out of these twelve regions met the max-criterion (A < AV > V) for multisensory integration. Comparison of this approach with a general linear model-based region-of-interest definition revealed its complementary value for multisensory neuroimaging. In conclusion, we estimated functional networks of uni- and multisensory functional connectivity from one dataset and validated their functional roles in an independent dataset. These findings demonstrate the particular value of ICA for multisensory neuroimaging research and using independent datasets to test hypotheses generated from a data-driven analysis

Wnt5a Regulates Ventral Midbrain Morphogenesis and the Development of A9–A10 Dopaminergic Cells In Vivo

Wnt5a is a morphogen that activates the Wnt/planar cell polarity (PCP) pathway and serves multiple functions during development. PCP signaling controls the orientation of cells within an epithelial plane as well as convergent extension (CE) movements. Wnt5a was previously reported to promote differentiation of A9–10 dopaminergic (DA) precursors in vitro. However, the signaling mechanism in DA cells and the function of Wnt5a during midbrain development in vivo remains unclear. We hereby report that Wnt5a activated the GTPase Rac1 in DA cells and that Rac1 inhibitors blocked the Wnt5a-induced DA neuron differentiation of ventral midbrain (VM) precursor cultures, linking Wnt5a-induced differentiation with a known effector of Wnt/PCP signaling. In vivo, Wnt5a was expressed throughout the VM at embryonic day (E)9.5, and was restricted to the VM floor and basal plate by E11.5–E13.5. Analysis of Wnt5a−/− mice revealed a transient increase in progenitor proliferation at E11.5, and a precociously induced NR4A2+ (Nurr1) precursor pool at E12.5. The excess NR4A2+ precursors remained undifferentiated until E14.5, when a transient 25% increase in DA neurons was detected. Wnt5a−/− mice also displayed a defect in (mid)brain morphogenesis, including an impairment in midbrain elongation and a rounded ventricular cavity. Interestingly, these alterations affected mostly cells in the DA lineage. The ventral Sonic hedgehog-expressing domain was broadened and flattened, a typical CE phenotype, and the domains occupied by Ngn2+ DA progenitors, NR4A2+ DA precursors and TH+ DA neurons were rostrocaudally reduced and laterally expanded. In summary, we hereby describe a Wnt5a regulation of Wnt/PCP signaling in the DA lineage and provide evidence for multiple functions of Wnt5a in the VM in vivo, including the regulation of VM morphogenesis, DA progenitor cell division, and differentiation of NR4A2+ DA precursors

Altered Perceptual Sensitivity to Kinematic Invariants in Parkinson's Disease

Ample evidence exists for coupling between action and perception in neurologically healthy individuals, yet the precise nature of the internal representations shared between these domains remains unclear. One experimentally derived view is that the invariant properties and constraints characterizing movement generation are also manifested during motion perception. One prominent motor invariant is the “two-third power law,” describing the strong relation between the kinematics of motion and the geometrical features of the path followed by the hand during planar drawing movements. The two-thirds power law not only characterizes various movement generation tasks but also seems to constrain visual perception of motion. The present study aimed to assess whether motor invariants, such as the two thirds power law also constrain motion perception in patients with Parkinson's disease (PD). Patients with PD and age-matched controls were asked to observe the movement of a light spot rotating on an elliptical path and to modify its velocity until it appeared to move most uniformly. As in previous reports controls tended to choose those movements close to obeying the two-thirds power law as most uniform. Patients with PD displayed a more variable behavior, choosing on average, movements closer but not equal to a constant velocity. Our results thus demonstrate impairments in how the two-thirds power law constrains motion perception in patients with PD, where this relationship between velocity and curvature appears to be preserved but scaled down. Recent hypotheses on the role of the basal ganglia in motor timing may explain these irregularities. Alternatively, these impairments in perception of movement may reflect similar deficits in motor production

Comparison of clinical rating scales in genetic frontotemporal dementia within the GENFI cohort

BACKGROUND: Therapeutic trials are now underway in genetic forms of frontotemporal dementia (FTD) but clinical outcome measures are limited. The two most commonly used measures, the Clinical Dementia Rating (CDR)+National Alzheimer’s Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) and the FTD Rating Scale (FRS), have yet to be compared in detail in the genetic forms of FTD. METHODS: The CDR+NACC FTLD and FRS were assessed cross-sectionally in 725 consecutively recruited participants from the Genetic FTD Initiative: 457 mutation carriers (77 microtubule-associated protein tau (MAPT), 187 GRN, 193 C9orf72) and 268 family members without mutations (non-carrier control group). 231 mutation carriers (51 MAPT, 92 GRN, 88 C9orf72) and 145 non-carriers had available longitudinal data at a follow-up time point. RESULTS: Cross-sectionally, the mean FRS score was lower in all genetic groups compared with controls: GRN mutation carriers mean 83.4 (SD 27.0), MAPT mutation carriers 78.2 (28.8), C9orf72 mutation carriers 71.0 (34.0), controls 96.2 (7.7), p<0.001 for all comparisons, while the mean CDR+NACC FTLD Sum of Boxes was significantly higher in all genetic groups: GRN mutation carriers mean 2.6 (5.2), MAPT mutation carriers 3.2 (5.6), C9orf72 mutation carriers 4.2 (6.2), controls 0.2 (0.6), p<0.001 for all comparisons. Mean FRS score decreased and CDR+NACC FTLD Sum of Boxes increased with increasing disease severity within each individual genetic group. FRS and CDR+NACC FTLD Sum of Boxes scores were strongly negatively correlated across all mutation carriers (r_{s} =−0.77, p<0.001) and within each genetic group (r_{s} =−0.67 to −0.81, p<0.001 in each group). Nonetheless, discrepancies in disease staging were seen between the scales, and with each scale and clinician-judged symptomatic status. Longitudinally, annualised change in both FRS and CDR+NACC FTLD Sum of Boxes scores initially increased with disease severity level before decreasing in those with the most severe disease: controls −0.1 (6.0) for FRS, −0.1 (0.4) for CDR+NACC FTLD Sum of Boxes, asymptomatic mutation carriers −0.5 (8.2), 0.2 (0.9), prodromal disease −2.3 (9.9), 0.6 (2.7), mild disease −10.2 (18.6), 3.0 (4.1), moderate disease −9.6 (16.6), 4.4 (4.0), severe disease −2.7 (8.3), 1.7 (3.3). Sample sizes were calculated for a trial of prodromal mutation carriers: over 180 participants per arm would be needed to detect a moderate sized effect (30%) for both outcome measures, with sample sizes lower for the FRS. CONCLUSIONS: Both the FRS and CDR+NACC FTLD measure disease severity in genetic FTD mutation carriers throughout the timeline of their disease, although the FRS may be preferable as an outcome measure. However, neither address a number of key symptoms in the FTD spectrum, for example, motor and neuropsychiatric deficits, which future scales will need to incorporate