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Astrocytes are intimately linked with brain vessels, a relationship that is critical for neuronal health and function. However, astroglial factors driving these physical and functional associations during postnatal brain development have yet to be identified. We characterized structural and transcriptional changes in mouse cortical astrocytes and microvessels during the first two postnatal weeks and found that high-mobility group box 1 (Hmgb1), normally upregulated with injury and involved in adult cerebrovascular repair, was highly expressed in astrocytes at birth and then decreased rapidly. Astrocyte-selective ablation ofHmgb1at birth affected astrocyte morphology and endfoot placement, altered distribution of endfoot proteins connexin43 and aquaporin-4, induced transcriptional changes in astrocytes related to cytoskeleton remodeling, and profoundly disrupted endothelial ultrastructure. While lack of astroglialHmgb1did not affect the blood-brain barrier or angiogenesis postnatally, it impaired neurovascular coupling and behavior in adult mice. These findings identify astroglialHmgb1as a key player in postnatal gliovascular maturation.

Principal component analysis (PCA) is often used for analyzing data in the most diverse areas. In this work, we report an integrated approach to several theoretical and practical aspects of PCA. We start by providing, in an intuitive and accessible manner, the basic principles underlying PCA and its applications. Next, we present a systematic, though no exclusive, survey of some representative works illustrating the potential of PCA applications to a wide range of areas. An experimental investigation of the ability of PCA for variance explanation and dimensionality reduction is also developed, which confirms the efficacy of PCA and also shows that standardizing or not the original data can have important effects on the obtained results. Overall, we believe the several covered issues can assist researchers from the most diverse areas in using and interpreting PCA.

Evidence supports early rehabilitation after stroke to limit disability. However, stroke survivors are typically sedentary and experience significant cardiovascular and muscular deconditioning. Despite growing consensus that preclinical and clinical stroke recovery research should be aligned, there have been few attempts to incorporate cardiovascular and skeletal muscle deconditioning into animal models of stroke. Here, we demonstrate in rats that a hindlimb sensorimotor cortex stroke results in both cardiovascular and skeletal muscle deconditioning and impairments in gait akin to those observed in humans. To reduce poststroke behavioral, cardiovascular, and skeletal muscle perturbations, we then used a combinatorial intervention consisting of aerobic and resistance exercise in conjunction with administration of resveratrol (RESV), a drug with exercise mimetic properties. A combination of aerobic and resistance exercise mitigated decreases in cardiovascular fitness and attenuated skeletal muscle abnormalities. RESV, beginning 24 hours poststroke, reduced acute hindlimb impairments, improved recovery in hindlimb function, increased vascular density in the perilesional cortex, and attenuated skeletal muscle fiber changes. Early RESV treatment and aerobic and resistance exercise independently provided poststroke benefits, at a time when individuals are rapidly becoming deconditioned as a result of inactivity. Although no additive effects were observed in these experiments, this approach represents a promising strategy to reduce poststroke behavioral impairments and minimize deconditioning. As such, this treatment regime has potential for enabling patients to engage in more intensive rehabilitation at an earlier time following stroke when mechanisms of neuroplasticity are most prevalent.

The increasing interest in complex networks research has been motivated by intrinsic features of this area, such as the generality of the approach to represent and model virtually any discrete system, and the incorporation of concepts and methods deriving from many areas, from statistical physics to sociology, which are often used in an independent way. Yet, for this same reason, it would be desirable to integrate these various aspects into a more coherent and organic framework, which would imply in several benefits normally allowed by the systematization in science, including the identification of new types of problems and the cross-fertilization between fields. More specifically, the identification of the main areas to which the concepts frequently used in complex networks can be applied paves the way to adopting and applying a larger set of concepts and methods deriving from those respective areas. Among the several areas that have been used in complex networks research, pattern recognition, optimization, linear algebra, and time series analysis seem to play a particularly basic and recurrent role. In the present manuscript, we propose a systematic way to integrate the concepts from these diverse areas regarding complex networks research. In order to do so, we start by grouping the multidisciplinary concepts into three main groups of representations, namely features, similarity, and network connectivity. Then we show that several of the analysis and modeling approaches to complex networks can be thought as a composition of maps between these three groups, with emphasis on nine main types of mappings, which are presented and illustrated. For instance, we argue that many models used to generate networks can be understood as a mapping from features to similarity, and then to network connectivity concepts. Such a systematization of principles and approaches also provides an opportunity to review some of the most closely related works in the literature, which is also developed in this article.

Several natural and artificial structures and systems are somehow optimized for performing specific functionalities. The structure and topology of cities are no exception, as it is critically important to ensure effective access to the several resources as well as overall mobility. The present work addresses the important subject of improving the plan of a given city through the incorporation of avenues and other expressways such as bridges and tunnels. More specifically, we start with the topology of a real city and consider the incorporation of an expressway between any two locations in the city, keeping one location fixed and varying the angle of the other. The whole city area is covered in this manner, which allows us to derive a respective energy surface indicating the gain obtained regarding the average shortest path length for each of the possible situations. These surfaces therefore provide a complete picture of how much each city can be improved regarding minimal distances. Quite distinct surfaces have been obtained for 18 considered European cities. These surfaces are then characterized in terms of the number of local extrema and respective spatial complexity, expressed in terms of a raggedness measurement. Measurements are also obtained respectively to the geometry and topology of the considered cities. It is shown that the shortest path gain depends strongly on some of the considered measurements, especially lacunarity and transitivity. Interestingly, the intricacy of the energy surfaces resulted in relatively little correlation with the topological and geometrical measurements.

The interaction between cities and their respective green regions corresponds to an interesting issue that has received growing attention over the last decades. These relationships have multiple natures, ranging from providing habitat for animal life to temperature and humidity dynamics. Several methods based on area, size, shape, and distance have been considered in the literature. Given that several important contributions of green regions to urban areas involve temperature, humidity, and gases exchanges, which are intrinsically related to physical diffusion, it becomes particularly interesting to simulate the diffusion of green effects over urban areas as a means of better understanding the respective influences. The present work reports a related approach. Once the green regions of a given city are automatically identified by semantic segmentation and have eventual artifacts eliminated, successive convolutions are applied as a means to obtain the unfolding of the diffusion of the green effects along time. As illustrated, the diffusion dynamics is intrinsically interesting because it can be strongly affected by the spatial distribution of the green mass. In particular, we observed that smaller green regions could substantially contribute to the diffusion. The reported approach has been illustrated with respect to the Brazilian city of Ribeirão Preto, whose small- and medium-sized green regions were found to complement in an effective manner the diffusion of the green effects as inferred from the performed simulations under specific parameter settings.

With the expansion of electronic publishing, a new dynamics of scientific articles dissemination was initiated. Still substantially important, citations became a longer term effect. Nowadays, many works are widely disseminated even before publication, in the form of preprints. Another important new element concerns the views of published articles. Thanks to the availability of respective data by some journals, such as PLoS ONE, it became possible to develop investigations on how scientific works are viewed along time, often before the first citations appear. This provides the main theme of the present work. More specifically, our research was motivated by preliminary observations that the view profiles along time tend to present a piecewise linear nature. A methodology was then delineated in order to identify the main segments in the view profiles, which allowed several related measurements to be derived. In particular, we focused on the inclination and length of each subsequent segment. Basic statistics indicated that the inclination can vary substantially along subsequent segments, while the segment lengths resulted more stable. Complementary joint statistics analysis, considering pairwise correlations, provided further information about the properties of the views. In order to better understand the view profiles, we performed respective multivariate statistical analysis, including principal component analysis and hierarchical clustering. The results suggest that a portion of the polygonal views are organized into clusters or groups. These groups were characterized in terms of prototypes indicating the relative increase or decrease along subsequent segments. Four respective distinct models were then developed for representing the observed segments. It was found that models incorporating joint dependencies between the properties of the segments provided the most accurate results among the considered alternatives.

Prostate cancer (PCa) is a pervasive condition that is manifested in a wide range of histologic patterns in biopsy samples. Given the importance of identifying abnormal prostate tissue to improve prognosis, many computerized methodologies aimed at assisting pathologists in diagnosis have been developed. It is often argued that improved diagnosis of a tissue region can be obtained by considering measurements that can take into account several properties of its surroundings, therefore providing a more robust context for the analysis. Here we propose a novel methodology that can be used for systematically defining contextual features regarding prostate glands. This is done by defining a Gland Context Network (GCN), a representation of the prostate sample containing information about the spatial relationship between glands as well as the similarity between their appearance. We show that such a network can be used for establishing contextual features at any spatial scale, therefore providing information that is not easily obtained from traditional shape and textural features. Furthermore, it is shown that even basic features derived from a GCN can lead to state-of-the-art classification performance regarding PCa. All in all, GCNs can assist in defining more effective approaches for PCa grading.

Despite the great differences among cities, they face similar challenges regarding social inequality, politics and criminality. Urban art express these feelings from the citizen point-of-view. In particular, the drawing and painting of public surfaces may carry rich information about the time and region it was made. Existing studies have explored the spatial distribution of graffiti, but most of them considered graffiti as a whole, with no separation among the types. Also, the analyses rarely take into account the city topology. In this work, we propose to categorize the graffiti into three types: simple scribbles, complex scribbles, canvases. We analyze the spatial distribution and identify the spatial bias of each type. To further analyze the spatial distribution of the types, we apply concepts from complex networks. First, regions (communities) defined by the connectivity profiles of the city network are obtained and the prevalence of each type of graffiti over these regions are analyzed. Next, a measure based on the dynamics of the network (accessibility) is calculated and compared to the distribution of the graffiti types. A case study is performed in the analysis of three different categories of graffiti in the city of Sao Paulo, Brazil. The results showed that the categories present characteristic spatial distributions. The ratio of each type per community of the network, though, does not pose significant deviations. Finally, a small positive correlation was observed between the locations of each graffiti type and the accessibility., To be submitted to EPL

While the neuronal underpinnings of autism spectrum disorder (ASD) are being unraveled, vascular contributions to ASD remain elusive. Here, we investigated postnatal cerebrovascular development in the 16p11.2df/+ mouse model of 16p11.2 deletion ASD syndrome. We discover that 16p11.2 hemizygosity leads to male-specific, endothelium-dependent structural and functional neurovascular abnormalities. In 16p11.2df/+ mice, endothelial dysfunction results in impaired cerebral angiogenesis at postnatal day 14, and in altered neurovascular coupling and cerebrovascular reactivity at postnatal day 50. Moreover, we show that there is defective angiogenesis in primary 16p11.2df/+ mouse brain endothelial cells and in induced-pluripotent-stem-cell-derived endothelial cells from human carriers of the 16p11.2 deletion. Finally, we find that mice with an endothelium-specific 16p11.2 deletion (16p11.2ΔEC) partially recapitulate some of the behavioral changes seen in 16p11.2 syndrome, specifically hyperactivity and impaired motor learning. By showing that developmental 16p11.2 haploinsufficiency from endothelial cells results in neurovascular and behavioral changes in adults, our results point to a potential role for endothelial impairment in ASD.

Hierarchical agglomerative methods stand out as particularly effective and popular approaches for clustering data. Yet, these methods have not been systematically compared regarding the important issue of false positives while searching for clusters. A model of clusters involving a higher density nucleus surrounded by a transition, followed by outliers is adopted as a means to quantify the relevance of the obtained clusters and address the problem of false positives. Six traditional methodologies, namely the single, average, median, complete, centroid and Ward’s linkage criteria are compared with respect to the adopted model. Unimodal and bimodal datasets obeying uniform, gaussian, exponential and power-law distributions are considered for this comparison. The obtained results include the verification that many methods detect two clusters in unimodal data. The single-linkage method was found to be more resilient to false positives. Also, several methods detected clusters not corresponding directly to the nucleus.