ResearchPad - eigenvectors https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Mesh smoothing algorithm based on exterior angles split]]> https://www.researchpad.co/article/elastic_article_13823 Since meshes of poor quality give rise to low accuracy in finite element analysis and kinds of inconveniences in many other applications, mesh smoothing is widely used as an essential technique for the improvement of mesh quality. With respect to this issue, the main contribution of this paper is that a novel mesh smoothing method based on an exterior-angle-split process is proposed. The proposed method contains three main stages: the first stage is independent element geometric transformation performed by exterior-angle-split operations, treating elements unconnected; the second stage is to offset scaling and displacement induced by element transformation; the third stage is to determine the final positions of nodes with a weighted strategy. Theoretical proof describes the regularity of this method and many numerical experiments illustrate its convergence. Not only is this method applicable for triangular mesh, but also can be naturally extended to arbitrary polygonal surface mesh. Quality improvements of demonstrations on triangular and quadrilateral meshes show the effectiveness of this method.

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<![CDATA[Controlling seizure propagation in large-scale brain networks]]> https://www.researchpad.co/article/5c7d95e6d5eed0c484734f24

Information transmission in the human brain is a fundamentally dynamic network process. In partial epilepsy, this process is perturbed and highly synchronous seizures originate in a local network, the so-called epileptogenic zone (EZ), before recruiting other close or distant brain regions. We studied patient-specific brain network models of 15 drug-resistant epilepsy patients with implanted stereotactic electroencephalography (SEEG) electrodes. Each personalized brain model was derived from structural data of magnetic resonance imaging (MRI) and diffusion tensor weighted imaging (DTI), comprising 88 nodes equipped with region specific neural mass models capable of demonstrating a range of epileptiform discharges. Each patient’s virtual brain was further personalized through the integration of the clinically hypothesized EZ. Subsequent simulations and connectivity modulations were performed and uncovered a finite repertoire of seizure propagation patterns. Across patients, we found that (i) patient-specific network connectivity is predictive for the subsequent seizure propagation pattern; (ii) seizure propagation is characterized by a systematic sequence of brain states; (iii) propagation can be controlled by an optimal intervention on the connectivity matrix; (iv) the degree of invasiveness can be significantly reduced via the proposed seizure control as compared to traditional resective surgery. To stop seizures, neurosurgeons typically resect the EZ completely. We showed that stability analysis of the network dynamics, employing structural and dynamical information, estimates reliably the spatiotemporal properties of seizure propagation. This suggests novel less invasive paradigms of surgical interventions to treat and manage partial epilepsy.

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<![CDATA[An algorithm of image mosaic based on binary tree and eliminating distortion error]]> https://www.researchpad.co/article/5c3d010fd5eed0c484037edc

The traditional image mosaic result based on SIFT feature points extraction, to some extent, has distortion errors: the larger the input image set, the greater the spliced panoramic distortion. To achieve the goal of creating a high-quality panorama, a new and improved algorithm based on the A-KAZE feature is proposed in this paper. This includes changing the way reference image are selected and putting forward a method for selecting a reference image based on the binary tree model, which takes the input image set as the leaf node set of a binary tree and uses the bottom-up approach to construct a complete binary tree. The root node image of the binary tree is the ultimate panorama obtained by stitching. Compared with the traditional way, the novel method improves the accuracy of feature points detection and enhances the stitching quality of the panorama. Additionally, the improved method proposes an automatic image straightening model to rectify the panorama, which further improves the panoramic distortion. The experimental results show that the proposed method cannot only enhance the efficiency of image stitching processing, but also reduce the panoramic distortion errors and obtain a better quality panoramic result.

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<![CDATA[Validation of modified radio-frequency identification tag firmware, using an equine population case study]]> https://www.researchpad.co/article/5c3fa5fcd5eed0c484caad7f

Background

Contact networks can be used to assess disease spread potential within a population. However, the data required to generate the networks can be challenging to collect. One method of collecting this type of data is by using radio-frequency identification (RFID) tags. The OpenBeacon RFID system generally consists of tags and readers. Communicating tags should be within 10m of the readers, which are powered by an external power source. The readers are challenging to implement in agricultural settings due to the lack of a power source and the large area needed to be covered.

Methods

OpenBeacon firmware was modified to use the tag’s onboard flash memory for data storage. The tags were deployed within an equine facility for a 7-day period. Tags were attached to the horses’ halters, worn by facility staff, and placed in strategic locations around the facility to monitor which participants had contact with the specified locations during the study period. When the tags came within 2m of each other, they recorded the contact event participant IDs, and start and end times. At the end of the study period, the data were downloaded to a computer and analyzed using network analysis methods.

Results

The resulting networks were plausible given the facility schedule as described in a survey completed by the facility manager. Furthermore, changes in the daily facility operations as described in the survey were reflected in the tag-collected data. In terms of the battery life, 88% of batteries maintained a charge for at least 6 days. Lastly, no consistent trends were evident in the horses’ centrality metrics.

Discussion

This study demonstrates the utility of RFID tags for the collection of equine contact data. Future work should include the collection of contact data from multiple equine facilities to better characterize equine disease spread potential in Ontario.

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<![CDATA[The empirical characteristics of human pattern vision defy theoretically-driven expectations]]> https://www.researchpad.co/article/5c102883d5eed0c4842475f9

Contrast is the most fundamental property of images. Consequently, any comprehensive model of biological vision must incorporate this attribute and provide a veritable description of its impact on visual perception. Current theoretical and computational models predict that vision should modify its characteristics at low contrast: for example, it should become broader (more lowpass) to protect from noise, as often demonstrated by individual neurons. We find that the opposite is true for human discrimination of elementary image elements: vision becomes sharper, not broader, as contrast approaches threshold levels. Furthermore, it suffers from increased internal variability at low contrast and it transitions from a surprisingly linear regime at high contrast to a markedly nonlinear processing mode in the low-contrast range. These characteristics are hard-wired in that they happen on a single trial without memory or expectation. Overall, the empirical results urge caution when attempting to interpret human vision from the standpoint of optimality and related theoretical constructs. Direct measurements of this phenomenon indicate that the actual constraints derive from intrinsic architectural features, such as the co-existence of complex-cell-like and simple-cell-like components. Small circuits built around these elements can indeed account for the empirical results, but do not appear to operate in a manner that conforms to optimality even approximately. More generally, our results provide a compelling demonstration of how far we still are from securing an adequate computational account of the most basic operations carried out by human vision.

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<![CDATA[Derivatives and inverse of cascaded linear+nonlinear neural models]]> https://www.researchpad.co/article/5bce3d5540307c69b197f50e

In vision science, cascades of Linear+Nonlinear transforms are very successful in modeling a number of perceptual experiences. However, the conventional literature is usually too focused on only describing the forward input-output transform. Instead, in this work we present the mathematics of such cascades beyond the forward transform, namely the Jacobian matrices and the inverse. The fundamental reason for this analytical treatment is that it offers useful analytical insight into the psychophysics, the physiology, and the function of the visual system. For instance, we show how the trends of the sensitivity (volume of the discrimination regions) and the adaptation of the receptive fields can be identified in the expression of the Jacobian w.r.t. the stimulus. This matrix also tells us which regions of the stimulus space are encoded more efficiently in multi-information terms. The Jacobian w.r.t. the parameters shows which aspects of the model have bigger impact in the response, and hence their relative relevance. The analytic inverse implies conditions for the response and model parameters to ensure appropriate decoding. From the experimental and applied perspective, (a) the Jacobian w.r.t. the stimulus is necessary in new experimental methods based on the synthesis of visual stimuli with interesting geometrical properties, (b) the Jacobian matrices w.r.t. the parameters are convenient to learn the model from classical experiments or alternative goal optimization, and (c) the inverse is a promising model-based alternative to blind machine-learning methods for neural decoding that do not include meaningful biological information. The theory is checked by building and testing a vision model that actually follows a modular Linear+Nonlinear program. Our illustrative derivable and invertible model consists of a cascade of modules that account for brightness, contrast, energy masking, and wavelet masking. To stress the generality of this modular setting we show examples where some of the canonical Divisive Normalization modules are substituted by equivalent modules such as the Wilson-Cowan interaction model (at the V1 cortex) or a tone-mapping model (at the retina).

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<![CDATA[Geometric feature descriptor and dissimilarity-based registration of remotely sensed imagery]]> https://www.researchpad.co/article/5b60219d463d7e3d6d2261cd

Image registration of remotely sensed imagery is challenging, as complex deformations are common. Different deformations, such as affine and homogenous transformation, combined with multimodal data capturing can emerge in the data acquisition process. These effects, when combined, tend to compromise the performance of the currently available registration methods. A new image transform, known as geometric mean projection transform, is introduced in this work. As it is deformation invariant, it can be employed as a feature descriptor, whereby it analyzes the functions of all vertical and horizontal signals in local areas of the image. Moreover, an invariant feature correspondence method is proposed as a point matching algorithm, which incorporates new descriptor’s dissimilarity metric. Considering the image as a signal, the proposed approach utilizes a square Eigenvector correlation (SEC) based on the Eigenvector properties. In our experiments on standard test images sourced from “Featurespace” and “IKONOS” datasets, the proposed method achieved higher average accuracy relative to that obtained from other state of the art image registration techniques. The accuracy of the proposed method was assessed using six standard evaluation metrics. Furthermore, statistical analyses, including t-test and Friedman test, demonstrate that the method developed as a part of this study is superior to the existing methods.

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<![CDATA[Coevolutionary dynamics of phenotypic diversity and contingent cooperation]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdce04

Phenotypic diversity is considered beneficial to the evolution of contingent cooperation, in which cooperators channel their help preferentially towards others of similar phenotypes. However, it remains largely unclear how phenotypic variation arises in the first place and thus leads to the construction of phenotypic complexity. Here we propose a mathematical model to study the coevolutionary dynamics of phenotypic diversity and contingent cooperation. Unlike previous models, our model does not assume any prescribed level of phenotypic diversity, but rather lets it be an evolvable trait. Each individual expresses one phenotype at a time and only the phenotypes expressed are visible to others. Moreover, individuals can differ in their potential of phenotypic variation, which is characterized by the number of distinct phenotypes they can randomly switch to. Each individual incurs a cost proportional to the number of potentially expressible phenotypes so as to retain phenotypic variation and expression. Our results show that phenotypic diversity coevolves with contingent cooperation under a wide range of conditions and that there exists an optimal level of phenotypic diversity best promoting contingent cooperation. It pays for contingent cooperators to elevate their potential of phenotypic variation, thereby increasing their opportunities of establishing cooperation via novel phenotypes, as these new phenotypes serve as secret tags that are difficult for defector to discover and chase after. We also find that evolved high levels of phenotypic diversity can occasionally collapse due to the invasion of defector mutants, suggesting that cooperation and phenotypic diversity can mutually reinforce each other. Thus, our results provide new insights into better understanding the coevolution of cooperation and phenotypic diversity.

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<![CDATA[Reliable Dual Tensor Model Estimation in Single and Crossing Fibers Based on Jeffreys Prior]]> https://www.researchpad.co/article/5989dab8ab0ee8fa60badad2

Purpose

This paper presents and studies a framework for reliable modeling of diffusion MRI using a data-acquisition adaptive prior.

Methods

Automated relevance determination estimates the mean of the posterior distribution of a rank-2 dual tensor model exploiting Jeffreys prior (JARD). This data-acquisition prior is based on the Fisher information matrix and enables the assessment whether two tensors are mandatory to describe the data. The method is compared to Maximum Likelihood Estimation (MLE) of the dual tensor model and to FSL’s ball-and-stick approach.

Results

Monte Carlo experiments demonstrated that JARD’s volume fractions correlated well with the ground truth for single and crossing fiber configurations. In single fiber configurations JARD automatically reduced the volume fraction of one compartment to (almost) zero. The variance in fractional anisotropy (FA) of the main tensor component was thereby reduced compared to MLE. JARD and MLE gave a comparable outcome in data simulating crossing fibers. On brain data, JARD yielded a smaller spread in FA along the corpus callosum compared to MLE. Tract-based spatial statistics demonstrated a higher sensitivity in detecting age-related white matter atrophy using JARD compared to both MLE and the ball-and-stick approach.

Conclusions

The proposed framework offers accurate and precise estimation of diffusion properties in single and dual fiber regions.

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<![CDATA[A rough set approach for determining weights of decision makers in group decision making]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdbd78

This study aims to present a novel approach for determining the weights of decision makers (DMs) based on rough group decision in multiple attribute group decision-making (MAGDM) problems. First, we construct a rough group decision matrix from all DMs’ decision matrixes on the basis of rough set theory. After that, we derive a positive ideal solution (PIS) founded on the average matrix of rough group decision, and negative ideal solutions (NISs) founded on the lower and upper limit matrixes of rough group decision. Then, we obtain the weight of each group member and priority order of alternatives by using relative closeness method, which depends on the distances from each individual group member’ decision to the PIS and NISs. Through comparisons with existing methods and an on-line business manager selection example, the proposed method show that it can provide more insights into the subjectivity and vagueness of DMs’ evaluations and selections.

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<![CDATA[Heuristic Strategies for Persuader Selection in Contagions on Complex Networks]]> https://www.researchpad.co/article/5989da76ab0ee8fa60b96d2e

Individual decision to accept a new idea or product is often driven by both self-adoption and others’ persuasion, which has been simulated using a double threshold model [Huang et al., Scientific Reports 6, 23766 (2016)]. We extend the study to consider the case with limited persuasion. That is, a set of individuals is chosen from the population to be equipped with persuasion capabilities, who may succeed in persuading their friends to take the new entity when certain conditions are satisfied. Network node centrality is adopted to characterize each node’s influence, based on which three heuristic strategies are applied to pick out persuaders. We compare these strategies for persuader selection on both homogeneous and heterogeneous networks. Two regimes of the underline networks are identified in which the system exhibits distinct behaviors: when networks are sufficiently sparse, selecting persuader nodes in descending order of node centrality achieves the best performance; when networks are sufficiently dense, however, selecting nodes with medium centralities to serve as the persuaders performs the best. Under respective optimal strategies for different types of networks, we further probe which centrality measure is most suitable for persuader selection. It turns out that for the first regime, degree centrality offers the best measure for picking out persuaders from homogeneous networks; while in heterogeneous networks, betweenness centrality takes its place. In the second regime, there is no significant difference caused by centrality measures in persuader selection for homogeneous network; while for heterogeneous networks, closeness centrality offers the best measure.

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<![CDATA[The Role of Temporal Trends in Growing Networks]]> https://www.researchpad.co/article/5989da59ab0ee8fa60b8f739

The rich get richer principle, manifested by the Preferential attachment (PA) mechanism, is widely considered one of the major factors in the growth of real-world networks. PA stipulates that popular nodes are bound to be more attractive than less popular nodes; for example, highly cited papers are more likely to garner further citations. However, it overlooks the transient nature of popularity, which is often governed by trends. Here, we show that in a wide range of real-world networks the recent popularity of a node, i.e., the extent by which it accumulated links recently, significantly influences its attractiveness and ability to accumulate further links. We proceed to model this observation with a natural extension to PA, named Trending Preferential Attachment (TPA), in which edges become less influential as they age. TPA quantitatively parametrizes a fundamental network property, namely the network’s tendency to trends. Through TPA, we find that real-world networks tend to be moderately to highly trendy. Networks are characterized by different susceptibilities to trends, which determine their structure to a large extent. Trendy networks display complex structural traits, such as modular community structure and degree-assortativity, occurring regularly in real-world networks. In summary, this work addresses an inherent trait of complex networks, which greatly affects their growth and structure, and develops a unified model to address its interaction with preferential attachment.

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<![CDATA[Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdca42

Mild traumatic brain injury (mTBI) is one of the most common neurological disorders worldwide. Posttraumatic complaints are frequently reported, interfering with outcome. However, a consistent neural substrate has not yet been found. We used graph analysis to further unravel the complex interactions between functional brain networks, complaints, anxiety and depression in the sub-acute stage after mTBI. This study included 54 patients with uncomplicated mTBI and 20 matched healthy controls. Posttraumatic complaints, anxiety and depression were measured at two weeks post-injury. Patients were selected based on presence (n = 34) or absence (n = 20) of complaints. Resting-state fMRI scans were made approximately four weeks post-injury. High order independent component analysis resulted in 89 neural components that were included in subsequent graph analyses. No differences in graph measures were found between patients with mTBI and healthy controls. Regarding the two patient subgroups, degree, strength, local efficiency and eigenvector centrality of the bilateral posterior cingulate/precuneus and bilateral parahippocampal gyrus were higher, and eigenvector centrality of the frontal pole/ bilateral middle & superior frontal gyrus was lower in patients with complaints compared to patients without complaints. In patients with mTBI, higher degree, strength and eigenvector centrality of default mode network components were related to higher depression scores, and higher degree and eigenvector centrality of executive network components were related to lower depression scores. In patients without complaints, one extra module was found compared to patients with complaints and healthy controls, consisting of the cingulate areas. In conclusion, this research extends the knowledge of functional network connectivity after mTBI. Specifically, our results suggest that an imbalance in the function of the default mode- and executive network plays a central role in the interaction between emotion regulation and the persistence of posttraumatic complaints.

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<![CDATA[Improvement of Source Number Estimation Method for Single Channel Signal]]> https://www.researchpad.co/article/5989daffab0ee8fa60bc61e5

Source number estimation methods for single channel signal have been investigated and the improvements for each method are suggested in this work. Firstly, the single channel data is converted to multi-channel form by delay process. Then, algorithms used in the array signal processing, such as Gerschgorin’s disk estimation (GDE) and minimum description length (MDL), are introduced to estimate the source number of the received signal. The previous results have shown that the MDL based on information theoretic criteria (ITC) obtains a superior performance than GDE at low SNR. However it has no ability to handle the signals containing colored noise. On the contrary, the GDE method can eliminate the influence of colored noise. Nevertheless, its performance at low SNR is not satisfactory. In order to solve these problems and contradictions, the work makes remarkable improvements on these two methods on account of the above consideration. A diagonal loading technique is employed to ameliorate the MDL method and a jackknife technique is referenced to optimize the data covariance matrix in order to improve the performance of the GDE method. The results of simulation have illustrated that the performance of original methods have been promoted largely.

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<![CDATA[Feedback between motion and sensation provides nonlinear boost in run-and-tumble navigation]]> https://www.researchpad.co/article/5989db53ab0ee8fa60bdce74

Many organisms navigate gradients by alternating straight motions (runs) with random reorientations (tumbles), transiently suppressing tumbles whenever attractant signal increases. This induces a functional coupling between movement and sensation, since tumbling probability is controlled by the internal state of the organism which, in turn, depends on previous signal levels. Although a negative feedback tends to maintain this internal state close to adapted levels, positive feedback can arise when motion up the gradient reduces tumbling probability, further boosting drift up the gradient. Importantly, such positive feedback can drive large fluctuations in the internal state, complicating analytical approaches. Previous studies focused on what happens when the negative feedback dominates the dynamics. By contrast, we show here that there is a large portion of physiologically-relevant parameter space where the positive feedback can dominate, even when gradients are relatively shallow. We demonstrate how large transients emerge because of non-normal dynamics (non-orthogonal eigenvectors near a stable fixed point) inherent in the positive feedback, and further identify a fundamental nonlinearity that strongly amplifies their effect. Most importantly, this amplification is asymmetric, elongating runs in favorable directions and abbreviating others. The result is a “ratchet-like” gradient climbing behavior with drift speeds that can approach half the maximum run speed of the organism. Our results thus show that the classical drawback of run-and-tumble navigation—wasteful runs in the wrong direction—can be mitigated by exploiting the non-normal dynamics implicit in the run-and-tumble strategy.

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<![CDATA[Friendship Concept and Community Network Structure among Elementary School and University Students]]> https://www.researchpad.co/article/5989da0fab0ee8fa60b792f8

We use complex network theory to study the differences between the friendship concepts in elementary school and university students. Four friendship networks were identified from surveys. Three of these networks are from elementary schools; two are located in the rural area of Yucatán and the other is in the urban area of Mérida, Yucatán. We analyzed the structure and the communities of these friendship networks and found significant differences among those at the elementary schools compared with those at the university. In elementary schools, the students make friends mainly in the same classroom, but there are also links among different classrooms because of the presence of siblings and relatives in the schools. These kinds of links (sibling-friend or relative-friend) are called, in this work, “mixed links”. The classification of the communities is based on their similarity with the classroom composition. If the community is composed principally of students in different classrooms, the community is classified as heterogeneous. These kinds of communities appear in the elementary school friendship networks mainly because of the presence of relatives and siblings. Once the links between siblings and relatives are removed, the communities resembled the classroom composition. On the other hand, the university students are more selective in choosing friends and therefore, even when they have friends in the same classroom, those communities are quite different to the classroom composition. Also, in the university network, we found heterogeneous communities even when the presence of sibling and relatives is negligible. These differences made up a topological structure quite different at different academic levels. We also found differences in the network characteristics. Once these differences are understood, the topological structure of the friendship network and the communities shaped in an elementary school could be predicted if we know the total number of students and the ties between siblings and relatives. However, at the university, we cannot do the same. This discovery implies that friendship is a dynamic concept that produces several changes in the friendship network structure and the way that people make groups of friends; it provides the opportunity to give analytic support to observational studies. Communities were also studied by gender and we found that when the links among relatives and siblings were removed, the number of communities formed by one gender alone increased. At the university, many communities formed by students of the same gender were also found.

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<![CDATA[The Efficiency of Split Panel Designs in an Analysis of Variance Model]]> https://www.researchpad.co/article/5989d9e2ab0ee8fa60b69efd

We consider split panel design efficiency in analysis of variance models, that is, the determination of the cross-sections series optimal proportion in all samples, to minimize parametric best linear unbiased estimators of linear combination variances. An orthogonal matrix is constructed to obtain manageable expression of variances. On this basis, we derive a theorem for analyzing split panel design efficiency irrespective of interest and budget parameters. Additionally, relative estimator efficiency based on the split panel to an estimator based on a pure panel or a pure cross-section is present. The analysis shows that the gains from split panel can be quite substantial. We further consider the efficiency of split panel design, given a budget, and transform it to a constrained nonlinear integer programming. Specifically, an efficient algorithm is designed to solve the constrained nonlinear integer programming. Moreover, we combine one at time designs and factorial designs to illustrate the algorithm’s efficiency with an empirical example concerning monthly consumer expenditure on food in 1985, in the Netherlands, and the efficient ranges of the algorithm parameters are given to ensure a good solution.

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<![CDATA[The Anatomy of the Global Football Player Transfer Network: Club Functionalities versus Network Properties]]> https://www.researchpad.co/article/5989da25ab0ee8fa60b8043f

Professional association football is a game of talent. The success of a professional club hinges largely on its ability of assembling the best team. Building on a dataset of player transfer records among more than 400 clubs in 24 world-wide top class leagues from 2011 to 2015, this study aims to relate a club’s success to its activities in the player transfer market from a network perspective. We confirm that modern professional football is indeed a money game, in which larger investment spent on the acquisition of talented players generally yields better team performance. However, further investigation shows that professional football clubs can actually play different strategies in surviving or even excelling this game, and the success of strategies is strongly associated to their network properties in the football player transfer network.

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<![CDATA[Diffusion Tensor Imaging in Patients with Glioblastoma Multiforme Using the Supertoroidal Model]]> https://www.researchpad.co/article/5989d9f5ab0ee8fa60b7002d

Purpose

Diffusion Tensor Imaging (DTI) is a powerful imaging technique that has led to improvements in the diagnosis and prognosis of cerebral lesions and neurosurgical guidance for tumor resection. Traditional tensor modeling, however, has difficulties in differentiating tumor-infiltrated regions and peritumoral edema. Here, we describe the supertoroidal model, which incorporates an increase in surface genus and a continuum of toroidal shapes to improve upon the characterization of Glioblastoma multiforme (GBM).

Materials and Methods

DTI brain datasets of 18 individuals with GBM and 18 normal subjects were acquired using a 3T scanner. A supertoroidal model of the diffusion tensor and two new diffusion tensor invariants, one to evaluate diffusivity, the toroidal volume (TV), and one to evaluate anisotropy, the toroidal curvature (TC), were applied and evaluated in the characterization of GBM brain tumors. TV and TC were compared with the mean diffusivity (MD) and fractional anisotropy (FA) indices inside the tumor, surrounding edema, as well as contralateral to the lesions, in the white matter (WM) and gray matter (GM).

Results

The supertoroidal model enhanced the borders between tumors and surrounding structures, refined the boundaries between WM and GM, and revealed the heterogeneity inherent to tumor-infiltrated tissue. Both MD and TV demonstrated high intensities in the tumor, with lower values in the surrounding edema, which in turn were higher than those of unaffected brain parenchyma. Both TC and FA were effective in revealing the structural degradation of WM tracts.

Conclusions

Our findings indicate that the supertoroidal model enables effective tensor visualization as well as quantitative scalar maps that improve the understanding of the underlying tissue structure properties. Hence, this approach has the potential to enhance diagnosis, preoperative planning, and intraoperative image guidance during surgical management of brain lesions.

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<![CDATA[Unveiling a novel transient druggable pocket in BACE-1 through molecular simulations: Conformational analysis and binding mode of multisite inhibitors]]> https://www.researchpad.co/article/5989db5aab0ee8fa60bdf7ce

The critical role of BACE-1 in the formation of neurotoxic ß-amyloid peptides in the brain makes it an attractive target for an efficacious treatment of Alzheimer’s disease. However, the development of clinically useful BACE-1 inhibitors has proven to be extremely challenging. In this study we examine the binding mode of a novel potent inhibitor (compound 1, with IC50 80 nM) designed by synergistic combination of two fragments—huprine and rhein—that individually are endowed with very low activity against BACE-1. Examination of crystal structures reveals no appropriate binding site large enough to accommodate 1. Therefore we have examined the conformational flexibility of BACE-1 through extended molecular dynamics simulations, paying attention to the highly flexible region shaped by loops 8–14, 154–169 and 307–318. The analysis of the protein dynamics, together with studies of pocket druggability, has allowed us to detect the transient formation of a secondary binding site, which contains Arg307 as a key residue for the interaction with small molecules, at the edge of the catalytic cleft. The formation of this druggable “floppy” pocket would enable the binding of multisite inhibitors targeting both catalytic and secondary sites. Molecular dynamics simulations of BACE-1 bound to huprine-rhein hybrid compounds support the feasibility of this hypothesis. The results provide a basis to explain the high inhibitory potency of the two enantiomeric forms of 1, together with the large dependence on the length of the oligomethylenic linker. Furthermore, the multisite hypothesis has allowed us to rationalize the inhibitory potency of a series of tacrine-chromene hybrid compounds, specifically regarding the apparent lack of sensitivity of the inhibition constant to the chemical modifications introduced in the chromene unit. Overall, these findings pave the way for the exploration of novel functionalities in the design of optimized BACE-1 multisite inhibitors.

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