Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of the binding and activating sites of the sphingolipid activator protein, saposin C, with glucocerebrosidase

Saposin C is a sphingolipid activator protein of 8.5 kDa that activates lysosomal glucocerebrosidase. Previously, we synthesized and characterized a synthetic full‐length human saposin C protein that displays 85% of the activity of the native saposin C. In this study we use shorter synthetic peptides derived from the saposin C sequence to map binding and activation sites. By determining the activity and kinetic constant (Kact) values of these peptides, we have identified two functional domains, each comprising a binding site adjacent to or partially overlapping with an activation site. Domains 1 and 2 are located within amino acid positions 6–34 and 41–60, respectively. The activation sites span residues 27–34 and 41–49, whereas binding sites encompass residues 6–27 and 45–60. Peptides containing the sequences of either domain displayed 90% of the activity of the full‐length synthetic saposin C. Domain 2, however, bound to glucocerebrosidase by at least an order of magnitude more strongly than domain 1. Binding sites within these domains contain sequences that are excellent candidates for forming amphipathic helical structures. Competition assays demonstrated that the binding of one domain to glucocerebrosidase prevents binding of the other domain, and that saposin A and saposin C bind to the same sites on glucocerebrosidase. A model predicting a saposin C:glucocerebrosidase complex with a stoichiometry of 4:2, respectively, is presented.
Murine Salmonellosis Studied by Confocal Microscopy: Salmonella typhimurium Resides Intracellularly Inside Macrophages and Exerts a Cytotoxic Effect on Phagocytes In Vivo

Salmonella typhimurium is considered a facultative intracellular pathogen, but its intracellular location in vivo has not been demonstrated conclusively. Here we describe the development of a new method to study the course of the histopathological processes associated with murine salmonellosis using confocal laser scanning microscopy of immunostained sections of mouse liver. Confocal microscopy of 30-μm-thick sections was used to detect bacteria after injection of ∼100 CFU of S. typhimurium SL1344 intravenously into BALB/c mice, allowing salmonellosis to be studied in the murine model using more realistic small infectious doses. The appearance of bacteria in the mouse liver coincided in time and location with the infiltration of neutrophils in inflammatory foci. At later stages of disease the bacteria colocalized with macrophages and resided intracellularly inside these macrophages. Bacteria were cytotoxic for phagocytic cells, and apoptotic nuclei were detected immunofluorescently, whether phagocytes harbored intracellular bacteria or not. These data argue that Salmonella resides intracellularly inside macrophages in the liver and triggers cell death of phagocytes, processes which are involved in disease. This method is also applicable to other virulence models to examine infections at a cellular and subcellular level in vivo.
Performance Bounds and Differential Cost Approximations for Queueing Networks

A new bound is proposed relating the average cost sub-optimality of a myopic policy to its differential cost error. The bound is an expectation over the stationary distribution for this policy. For small queueing networks, we compute or approximate the distribution using the matrix analytic method and numerically test the bound. Product form approximations to the stationary distribution are also considered. Applications to approximate dynamic programming are also discussed.
Mining crucial features for automatic rehabilitation coaching systems

Our goal is to develop a system for coaching human motions (e.g. rehabilitation). Such a coaching system should have several function such as motion measurement, evaluation, and feedback. Among all, this paper focuses on how to modify a user's motion so that it gets closer to the good template of a target motion. To this end, it is important to efficiently advise the user to emulate the crucial features that define the good template. The proposed method automatically mines the crucial features of any kind of motions from a set of all motion features. The crucial features are mined based on feature sparsification through binary classification between the samples of good and other motions.
Analysis and Exploitation of Musician Social Networks for Recommendation and Discovery

This paper presents an extensive analysis of a sample of a social network of musicians. The network sample is first analyzed using standard complex network techniques to verify that it has similar properties to other web-derived complex networks. Content-based pairwise dissimilarity values between the musical data associated with the network sample are computed, and the relationship between those content-based distances and distances from network theory explored. Following this exploration, hybrid graphs and distance measures are constructed, and used to examine the community structure of the artist network. Finally, results of these investigations are shown to be mostly orthogonal between these distance spaces. These results are considered with a focus recommendation and discovery applications employing these hybrid measures as their basis.
Automating transfer function design for comprehensible volume rendering based on 3D field topology analysis

This paper describes initial results of a 3D field topology analysis for automating transfer function design aiming at comprehensible volume rendering. The conventional Reeb graph-based approach to describing topological features of 3D surfaces is extended to capture the topological skeleton of a volumetric field. Based on the analysis result, which is represented in the form of a hyper Reeb graph, a procedure is proposed for designing appropriate color/opacity transfer functions. Two analytic volume datasets are used to preliminarily prove the feasibility of the present design methodology.
A Design for Verification Approach Using an Embedding of PSL in aSML

In this paper, we propose to integrate an embedding of Property Specification Language (PSL) in Abstract State Machines Language (AsmL) with a top–down design for verification approach in order to enable the model checking of large systems at the early stages of the design process. We provide a complete embedding of PSL in the ASM language AsmL, which allows us to integrate PSL properties as a part of the design. For verification, we propose a technique based on the AsmL tool that translates the code containing both the design and the properties into a finite state machine (FSM) representation. We use the generated FSM to run model checking on an external tool, here SMV. Our approach takes advantage of the AsmL language capabilities to model designs at the system level as well as from the power of the AsmL tool in generating both C# code and FSMs from AsmL models. We applied our approach on the PCI-X bus standard, which AsmL model was constructed from the informal standard specifications and a subsequent UML model. Experimental results on the PCI-X bus case study showed a superiority of our approach to conventional verification.
Query Processing Using Distance Oracles for Spatial Networks

The popularity of location-based services and the need to do real-time processing on them has led to an interest in performing queries on transportation networks, such as finding shortest paths and finding nearest neighbors. The challenge here is that the efficient execution of spatial operations usually involves the computation of distance along a spatial network instead of "as the crow flies," which is not simple. Techniques are described that enable the determination of the network distance between any pair of points (i.e., vertices) with as little as O(n) space rather than having to store the n2 distances between all pairs. This is done by being willing to expend a bit more time to achieve this goal such as O(log n) instead of O(1), as well as by accepting an error ε in the accuracy of the distance that is provided. The strategy that is adopted reduces the space requirements and is based on the ability to identify groups of source and destination vertices for which the distance is approximately the same within some ε. The reductions are achieved by introducing a construct termed a distance oracle that yields an estimate of the network distance (termed the ε-approximate distance) between any two vertices in the spatial network. The distance oracle is obtained by showing how to adapt the well-separated pair technique from computational geometry to spatial networks. Initially, an e-approximate distance oracle of size O(n/(ε2)) is used that is capable of retrieving the approximate network distance in O(log n) time using a B-tree. The retrieval time can be theoretically reduced further to O(1) time by proposing another e-approximate distance oracle of size O((n log n)/(ε2)) that uses a hash table. Experimental results indicate that the proposed technique is scalable and can be applied to sufficiently large road networks. For example, a 10-percentapproximate oracle (ε = 0.1) on a large network yielded an average error of 0.9 percent with 90 percent of the answers having an error of 2 percent or less and an average retrieval time of 68 μ seconds. The fact that the network distance can be approximated by one value is used to show how a number of spatial queries can be formulated using appropriate SQL constructs and a few built-in primitives. The result is that these operations can be executed on almost any modern database with no modifications, while taking advantage of the existing query optimizers and query processing strategies.
General Retinal Vessel Segmentation Using Regularization-Based Multiconcavity Modeling

Detecting blood vessels in retinal images with the presence of bright and dark lesions is a challenging unsolved problem. In this paper, a novel multiconcavity modeling approach is proposed to handle both healthy and unhealthy retinas simultaneously. The differentiable concavity measure is proposed to handle bright lesions in a perceptive space. The line-shape concavity measure is proposed to remove dark lesions which have an intensity structure different from the line-shaped vessels in a retina. The locally normalized concavity measure is designed to deal with unevenly distributed noise due to the spherical intensity variation in a retinal image. These concavity measures are combined together according to their statistical distributions to detect vessels in general retinal images. Very encouraging experimental results demonstrate that the proposed method consistently yields the best performance over existing state-of-the-art methods on the abnormal retinas and its accuracy outperforms the human observer, which has not been achieved by any of the state-of-the-art benchmark methods. Most importantly, unlike existing methods, the proposed method shows very attractive performances not only on healthy retinas but also on a mixture of healthy and pathological retinas.
Massively parallel volume rendering using 2–3 swap image compositing

The ever-increasing amounts of simulation data produced by scientists demand high-end parallel visualization capability. However, image compositing, which requires interprocessor communication, is often the bottleneck stage for parallel rendering of large volume data sets. Existing image compositing solutions either incur a large number of messages exchanged among processors (such as the direct send method), or limit the number of processors that can be effectively utilized (such as the binary swap method). We introduce a new image compositing algorithm, called 2-3 swap, which combines the flexibility of the direct send method and the optimality of the binary swap method. The 2-3 swap algorithm allows an arbitrary number of processors to be used for compositing, and fully utilizes all participating processors throughout the course of the compositing. We experiment with this image compositing solution on a supercomputer with thousands of processors, and demonstrate its great flexibility as well as scalability.
Fast multidirectional vehicle detection on aerial images using region based convolutional neural networks

This paper proposes a coupled region based convolutional neural networks (R-CNN) to automatically detect vehicles in aerial images. Traditional methods are mostly based on sliding-window search, and use handcrafted or shallow-learning based features. They have limited description ability and heavy computational costs. Recently, a series of R-CNN based methods have achieved great success in general object detection. Inspired by the previous work, we propose a coupled R-CNN to detect small size vehicles in large-scale aerial images. First, a vehicle proposal network (VPN) is proposed to generate candidate vehicle-like regions, using a hyper feature map combined by feature maps of different layers. Then, a vehicle classification network (VCN) is developed to further verify the candidate regions and classify vehicles in eight directions. In this study, our method is tested on a challenge Munich vehicle dataset and the collected vehicle dataset, with improvements in accuracy and speed compared to existing methods.
Electric circuit coupling of a slotted semi-analytical model for induction motors based on harmonic modeling

The use of empirically determined coefficients to include the effects of leakage and fringing flux is a large drawback of traditional induction motor (IM) models, such as lumped parameter, magnetic equivalent circuit and anisotropic layer models. As an alternative, Finite Element Analysis (FEA) is often used to determine the magnetic field distribution accurately, although at the cost of a much longer computation time. A good alternative to FEA, both in terms of computation time and accuracy, is harmonic modeling. Therefore, in this work, a previously presented magnetic model for slotted IMs based on harmonic modeling, is extended. The main contribution is the implementation of a direct coupling between the magnetic model and the stator and rotor electric circuit models, both for steady-state and time-stepping approximation of the time dependence. Except for end winding leakage flux, no additional empirical coefficients are required to include leakage and fringing flux effects. The results of the models are validated against FEA results and measurements on a prototype. It is shown that good agreement is obtained for torque prediction, whereas the predicted stator current shows some discrepancy. This discrepancy is caused by saturation of the main magnetic flux path and can be accounted for by hybrid coupling to a model that includes the effect of non-linear soft-magnetic material on the main magnetic flux.
Users Are Known by the Company They Keep: Topic Models for Viewpoint Discovery in Social Networks

Social media platforms such as weblogs and social networking sites provide Internet users with an unprecedented means to express their opinions and debate on a wide range of issues. Concurrently with their growing importance in public communication, social media platforms may foster echo chambers and filter bubbles: homophily and content personalization lead users to be increasingly exposed to conforming opinions. There is therefore a need for unbiased systems able to identify and provide access to varied viewpoints. To address this task, we propose in this paper a novel unsupervised topic model, the Social Network Viewpoint Discovery Model (SNVDM). Given a specific issue (e.g., U.S. policy) as well as the text and social interactions from the users discussing this issue on a social networking site, SNVDM jointly identifies the issue's topics, the users' viewpoints, and the discourse pertaining to the different topics and viewpoints. In order to overcome the potential sparsity of the social network (i.e., some users interact with only a few other users), we propose an extension to SNVDM based on the Generalized Pólya Urn sampling scheme (SNVDM-GPU) to leverage "acquaintances of acquaintances" relationships. We benchmark the different proposed models against three baselines, namely TAM, SN-LDA, and VODUM, on a viewpoint clustering task using two real-world datasets. We thereby provide evidence that our model SNVDM and its extension SNVDM-GPU significantly outperform state-of-the-art baselines, and we show that utilizing social interactions greatly improves viewpoint clustering performance.
Increased pigmentation of iridial melanocytes in primates induced by a prostaglandin analogue.

The melanocytes in the mammalian eye have been thought to produce melanin only during fetal development and in the very young individual. The recent discovery that latanoprost, a prostaglandin analogue used in the treatment of glaucoma, causes increased pigmentation of the iris in monkeys and in humans indicates that the iridial melanocytes can produce melanin in adult individuals. Using microautoradiography of HG-(3)H-methimazole, a false melanin precursor, we observed in an earlier study that there seems to be an ongoing melanogenesis in adult mice in the iridial melanocytes and in the iridial pigment epithelium. In the present study latanoprost (13,14-dihydro-17-phenyl-18,19,20-trinor-PGF(2alpha)-isoprop yl ester) was applied once daily to the right eye of seven cynomolgus monkeys; the left eye served as an untreated control. Two animals developed clear-cut increased pigmentation of the iris in the treated eye during the first three months of treatment. These animals were injected intravenously with G-(3)H-methimazole and were killed 24 hr after the injection. The eyes were removed, fixed in 4% formalin supplemented with 10% acetic acid and embedded in paraffin or Polybed 812. Sections from the eyes were used for microautoradiography and light microscopic examination. A high uptake of radioactivity was observed in a few melanocytes in the iris of the untreated eye. There were also a low uptake in the melanocytes in the stroma of the ciliary body and the choroid. No accumulation was observed in the iridial or retinal pigment epithelium. In the iris of the treated eye the only observed difference from the untreated eye was an increased amount of melanin in the iridial melanocytes and an increased uptake of radioactivity in a great number of these cells. Thus it seems likely that treatment with latanoprost in some individuals causes an increase of the low normal melanin synthesis in iridal melanocytes.
Swarm-based motion features for anomaly detection in crowds

In this work we propose a novel approach to the detection of anomalous events occurring in crowded scenes. Swarm theory is applied for the creation of a motion feature first introduced in this work, the Histograms of Oriented Swarm Accelerations (HOSA), which are shown to effectively capture a scene's motion dynamics. The HOSA, together with the well known Histograms of Oriented Gradients (HOGs) describing appearance, are combined to provide a final descriptor based on both motion and appearance, to effectively characterize a crowded scene. Appearance and motion features are only extracted within spatiotemporal volumes of moving pixels (regions of interest) to ensure robustness to local noise and allow the detection of anomalies occurring only in a small region of the frame. Experiments and comparisons with the State of the Art (SoA) on a variety of benchmark datasets demonstrate the effectiveness of the proposed method, its flexibility and applicability to different crowd environments, and its superiority over currently existing approaches.
TrkB expression at the neuromuscular junction is reduced during aging

Introduction: Full‐length tyrosine kinase B (TrkB.FL) and truncated TrkB (TrkB.t1) receptors are colocalized with acetylcholine receptors (AChRs) at the neuromuscular junction. We have recently shown that reduced TrkB expression leads to age‐related alterations in AChR structure, neurotransmission failure, and muscle weakness. Methods: We investigated whether TrkB expression is reduced in the soleus muscle during aging. Results: TrkB protein expression was decreased in senescent (24‐month‐old) compared with 3–12‐month‐old mice. Loss of TrkB expression was concurrent with age‐related changes in AChR morphology. Changes in mRNA levels did not correlate with protein expression, because TrkB.FL copy number was increased in the senescent soleus. No change was seen in TrkB.t1 levels. Conclusions: The results suggest that reduced TrkB expression during aging may result from reduced TrkB.FL mRNA translation or increased TrkB protein turnover. Thus, maintaining adequate TrkB signaling is a potential therapeutic tool to improve muscle function during senescence. Muscle Nerve 47: 532–538, 2013
Combined Na+/Ca2+ Exchanger and L-Type Calcium Channel Block as a Potential Strategy to Suppress Arrhythmias and Maintain Ventricular Function

Background—L-type calcium channel (LTCC) and Na+/Ca2+ exchanger (NCX) have been implicated in repolarization-dependent arrhythmias, but also modulate calcium and contractility. Although LTCC inhibition is negative inotropic, NCX inhibition has the opposite effect. Combined block may, therefore, offer an advantage for hemodynamics and antiarrhythmic efficiency, particularly in diseased hearts. In a model of proarrhythmia, the dog with chronic atrioventricular block, we investigated whether combined inhibition of NCX and LTCC with SEA-0400 is effective against dofetilide-induced torsade de pointes arrhythmias (TdP), while maintaining calcium homeostasis and hemodynamics. Methods and Results—Left ventricular pressure (LVP) and ECG were monitored during infusion of SEA-0400 and verapamil in anesthetized dogs. Different doses were tested against dofetilide-induced TdP in chronic atrioventricular block dogs. In ventricular myocytes, effects of SEA-0400 were tested on action potentials, calcium transients, and early afterdepolarizations. In cardiomyocytes, SEA-0400 (1 &mgr;mol/L) blocked 66±3% of outward NCX, 50±2% of inward NCX, and 33±9% of LTCC current. SEA-0400 had no effect on systolic calcium, but slowed relaxation, despite action potential shortening, and increased diastolic calcium. SEA-0400 stabilized dofetilide-induced lability of repolarization and suppressed early afterdepolarizations. In vivo, SEA-0400 (0.4 and 0.8 mg/kg) had no effect on left ventricular pressure and suppressed dofetilide-induced TdPs dose dependently. Verapamil (0.3 mg/kg) also inhibited TdP, but caused a 15±8% drop of left ventricular pressure. A lower dose of verapamil without effects on left ventricular pressure (0.06 mg/kg) was not antiarrhythmic. Conclusions—In chronic atrioventricular block dogs, SEA-0400 treatment is effective against TdP. Unlike specific inhibition of LTCC, combined NCX and LTCC inhibition has no negative effects on cardiac hemodynamics.