Miracle-dz/UniFAR-FTUs huggingface dataset:
Potential natural mTOR inhibitors screened by in silico approach and suppress hepatic stellate cells activation

The mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase, plays a central role in the regulation of cell proliferation, growth, differentiation, migration, and survival. In this study, the 3-D structure of the mTOR (PDB ID: 2FAP) was used for the docking of 47 natural compounds and compared with pharmacophore model of 14 known mTOR inhibitors to identify the novel and specific natural inhibitor. The top four compounds, rutin, curcumin, antroquinonol, and benzyl cinnamate, have been selected based on their PLP score and further validated with hepatic stellate cells NHSC and THSC. Curcumin and antroquinonol significantly inhibited NHSC and THSC cells proliferation in a dose-dependent manner, whereas rutin and benzyl cinnamate showed less alteration of cell viability. Rutin inhibited the phosphorylation of mTOR (p-mTOR) and p-p70 S6 K in NHSC and THSC cells by Western blotting. Additionally, p-p70 S6 K protein was significantly decreased by incubation with benzyl cinnamate and curcumin in THSC cells. Taken together, this result suggests that rutin is a potential mTOR inhibitor in screen hits of molecular docking to hamper the activation of HSC and further applications in the treatment of liver fibrosis.
Exploiting segmentation for robust 3D object matching

While Iterative Closest Point (ICP) algorithms have been successful at aligning 3D point clouds, they do not take into account constraints arising from sensor viewpoints. More recent beam-based models take into account sensor noise and viewpoint, but problems still remain. In particular, good optimization strategies are still lacking for the beam-based model. In situations of occlusion and clutter, both beam-based and ICP approaches can fail to find good solutions. In this paper, we present both an optimization method for beambased models and a novel framework for modeling observation dependencies in beam-based models using over-segmentations. This technique enables reasoning about object extents and works well in heavy clutter. We also make available a ground-truth 3D dataset for testing algorithms in this area.
Ex Vivo Alloanergization with Belatacept: A Strategy to Selectively Modulate Alloresponses after Transplantation

Ex vivo alloanergization of human immune cells, via allostimulation in the presence of costimulatory blockade with either a combination of anti-B7.1 and anti-B7.2 antibodies or first-generation cytotoxic T-lymphocyte antigen 4-immunoglobulin (CTLA4-Ig), induces alloantigen-specific hyporesponsiveness and expands alloantigen-specific regulatory T cells (Treg). We have successfully used this approach in the clinical setting of haploidentical hematopoietic stem cell transplantation. Recently, the in vivo use of a new second-generation CTLA4-Ig, belatacept, has shown promise in controlling alloresponses after transplantation of both human kidneys and islet cells. We therefore compared the efficiency of first- and second-generation CTLA4-Ig in alloanergizing human peripheral blood mononuclear cells (PBMCs) and investigated whether ex vivo alloanergization with belatacept could be used to engineer an alloantigen-specific immunoregulatory population of autologous cells suitable for administration to recipients of cellular or solid organ transplant recipients. Alloanergization of HLA-mismatched human PBMCs with belatacept resulted in a greater reduction in subsequent alloresponses than alloanergization with first generation CTLA4-Ig. Moreover, subsequent ex vivo re-exposure of alloanergized cells to alloantigen in the absence of belatacept resulted in a significant expansion of Tregs with enhanced alloantigen-specific suppressive function. Alloanergized PBMCs retained functional Epstein-Barr virus (EBV)-specific T-cell responses, and expanded Tregs did not suppress EBV-specific proliferation of autologous cells. These results suggest that ex vivo alloanergization with belatacept provides a platform to engineer populations of recipient Treg with specificity for donor alloantigens but without nonspecific suppressive capacity. The potential advantages of such cells for solid organ transplantation include (1) reduction of the need for nonspecific immunosuppression, (2) retention of pathogen-specific immunity, and (3) control of graft rejection, if used as an intervention.
Compact microstrip diplexers based on a dual-passband filter

Novel microstrip diplexer structures composed of a dual-passband filter together with two matching circuits are proposed. By using only a single dual-passband filter, the proposed diplexer may be made compact when compared with the conventional diplexer configuration which has two single- passband filters. In this study, the dual-passband filter is realized using the parallel-coupled microstrip structures, and the matching circuits are developed based on the stepped- impedance transmission-line sections along with suitable open stubs. By suitably incorporating the open stubs into the matching circuits, a 3 rd-order Chebyshev microstrip diplexer with dual center frequencies at 2.36 GHz and 5.17 GHz and an acceptable isolation is implemented.
A Semantic Vector Space for Query by Image Example

image retrieval enables the user to search a database for visually similar images. In these scenarios, the user submits an example that is compared to the images in the database by their low-level characteristics such as colour, texture and shape. While visual similarity is essential for a vast number of applications, there are cases where a user needs to search for semantically similar images. For example, the user might want to find all images depicting bears on a river. This might be quite difficult using only low-level features, but using concept detectors for "bear" and "river" will produce results that are semantically closer to what the user requested. Following this idea, this paper studies a novel paradigm: query by semantic multimedia example. In this setting the user's query is processed at a semantic level: a vector of concept probabilities is inferred for each image and a similarity metric computes the distance between the concept vector of the query and of the concept vectors of the images in database. The system is evaluated with a COREL Stock Photo collection.
TLR4 Activation Promotes Bone Marrow MSC Proliferation and Osteogenic Differentiation via Wnt3a and Wnt5a Signaling

Mesenchymal stem cells (MSCs) from adult bone marrow maintain their self-renewal ability and the ability to differentiate into osteoblast. Thus, adult bone marrow MSCs play a key role in the regeneration of bone tissue. Previous studies indicated that TLR4 is expressed in MSCs and is critical in regulating the fate decision of MSCs. However, the exact functional role and underlying mechanisms of how TLR4 regulate bone marrow MSC proliferation and differentiation are unclear. Here, we found that activated TLR4 by its ligand LPS promoted the proliferation and osteogenic differentiation of MSCs in vitro. TLR4 activation by LPS also increased cytokine IL-6 and IL-1β production in MSCs. In addition, LPS treatment has no effect on inducing cell death of MSCs. Deletion of TLR4 expression in MSCs completely eliminated the effects of LPS on MSC proliferation, osteogenic differentiation and cytokine production. We also found that the mRNA and protein expression of Wnt3a and Wnt5a, two important factors in regulating MSC fate decision, was upregulated in a TLR4-dependent manner. Silencing Wnt3a with specific siRNA remarkably inhibited TLR4-induced MSC proliferation, while Wnt5a specific siRNA treatment significantly antagonized TLR4-induced MSC osteogenic differentiation. These results together suggested that TLR4 regulates bone marrow MSC proliferation and osteogenic differentiation through Wnt3a and Wnt5a signaling. These finding provide new data to understand the role and the molecular mechanisms of TLR4 in regulating bone marrow MSC functions. These data also provide new insight in developing new therapy in bone regeneration using MSCs by modulating TLR4 and Wnt signaling activity.
Acute and clinical effects of cryoballoon pulmonary vein isolation in patients with symptomatic paroxysmal and persistent atrial fibrillation.

AIMS To assess the acute effects, safety, and clinical outcome of atrial fibrillation (AF) ablation using a cryoballoon catheter. METHODS AND RESULTS Forty patients with paroxysmal or persistent AF underwent pulmonary vein (PV) isolation with a cryoballoon catheter (Arctic Front, CryoCath). Electrocardiograms were recorded in case of symptomatic AF recurrences, and a 24 h Holter recording was performed at last follow-up. Complete PV isolation was achieved in 39 (91%) of the 43 procedures (56% with the cryoballoon catheter alone, 44% with an additional conventional ryocatheter). The number of balloon applications per procedure was 9.6 +/- 1.6. The PV isolation rate was significantly higher (83.9%) if total vessel occlusions were obtained than if intermediate (63.6%, P = 0.01) or poor occlusions were achieved (38.1%, P = 0.0002). The mean procedure time was 239 +/- 48 min. At follow-up (mean 8.9 +/- 4.6 months), 52.5% of patients were free from arrhythmia-related symptoms and another 17.5% had reduction of arrhythmia-related symptoms. Two cases each of phrenic nerve paralysis and dysphagia occurred. CONCLUSIONS Cryoballoon PV isolation is a feasible technique with a high acute success rate and comparable clinical outcome to radiofrequency ablation. Although complications were rare, the need for an additional conventional cryocatheter warrants further development of the technique.
Robust Object Recognition via Visual Pathway Feedback

Object recognition, which consists of classification and detection, has two important attributes for robustness: (1) Closeness: detection windows should be close to object locations, and (2) Adaptiveness: object matching should be adaptive to object variations in classification. It is difficult to satisfy both attributes by considering classification and detection separately, thus recent studies combine them based on confidence contextualization and foreground modeling. However, these combinations neglect feature saliency and object structure, which are important for recognition. In fact, object recognition originates in the mechanism of "what" and "where" pathways in human visual systems, and more importantly, these pathways have feedback to each other, which provides a probable way to improve closeness and adaptiveness. Inspired by the feedback, we propose a robust object recognition framework by designing a computational model of the feedback mechanism. In the "what" feedback, the feature saliency from classification is exploited to rectify detection windows for better closeness, while in the "where" feedback, object parts from detection are used to model object matching of object structure for better adaptiveness. Experiments show that the "what" and "where" feedback can be effective to improve closeness and adaptiveness for robust object recognition, and encouraging results are obtained on the challenging PASCAL VOC 2007 dataset.
Generation of Tyrosine Hydroxylase Positive Neurons from Human Embryonic Stem Cells after Coculture with Cellular Substrates and Exposure to GDNF

Tyrosine hydroxylase (TH)–positive neurons were generated from human embryonic stem (hES) cells by coculturing on astrocytes or PA6 stromal cells. After 3 to 4 weeks in culture, TH‐positive cells with neuronal morphology developed. Coculture with astrocytes from the embryonic striatum produced a larger number of TH‐positive cells than did coculture with astrocytes from embryonic mesencephalon (329 ± 149 versus 33 ± 16 TH‐positive cells per well, p < .05). In other experiments using PA6 cells as a substrate, glial‐derived neurotrophic factor (GDNF) was added to the media of differentiating hES cells, and this led to a doubling of the number of TH‐positive cells (PA6: 443 ± 105 TH‐positive cells per well versus PA6 + GDNF: 934 ± 136, p < .05). We conclude that substrates of striatal astrocytes and PA6 cells can promote differentiation of human embryonic stem cells to a TH‐positive phenotype and that GDNF can increase the number of cells expressing that phenotype.
Solving the Traveling Salesman Problem Using New Operators in Genetic Algorithms

Problem statement: Genetic Algorithms (GAs) have been used as search algorithms to find near-optimal solutions for many NP problems. GAs require effective chromosome representations as well as carefully designed crossover and mutation operators to achieve an efficient search. The Traveling Salesman Problem (TSP), as an NP search problem, involves finding the shortest Hamiltonian Path or Cycle in a graph of N cities. The main objective of this study was to propose a new representation method of chromosomes using upper triangle binary matrices and a new crossover operator to be used as a heuristic method to find near-optimum solutions for the TSP. Approach: A proposed genetic algorithm, that employed these new methods of representation and crossover operator, had been implemented using DELPHI programming language on a personal computer. Also, for the purpose of comparisons, the genetic algorithm of Sneiw had been implemented using the same programming language on the same computer. Results: The outcomes obtained from running the proposed genetic algorithm on several TSP instances taken from the TSPLIB had showed that proposed methods found optimum solution of many TSP benchmark problems and near optimum of the others. Conclusion: Proposed chromosome representation minimized the memory space requirements and proposed genetic crossover operator improved the quality of the solutions in significantly less time in comparison with Sneiw's genetic algorithm.
SAPK2/p38-dependent F-Actin Reorganization Regulates Early Membrane Blebbing during Stress-induced Apoptosis

In endothelial cells, H2O2 induces the rapid formation of focal adhesion complexes at the ventral face of the cells and a major reorganization of the actin cytoskeleton into dense transcytoplasmic stress fibers. This change in actin dynamics results from the activation of the mitogen-activated protein (MAP) kinase stress-activated protein kinase-2/p38 (SAPK2/p38), which, via MAP kinase-activated protein (MAPKAP) kinase-2/3, leads to the phosphorylation of the actin polymerization modulator heat shock protein of 27 kD (HSP27). Here we show that the concomitant activation of the extracellular signal-regulated kinase (ERK) MAP kinase pathway by H2O2 accomplishes an essential survival function during this process. When the activation of ERK was blocked with PD098059, the focal adhesion complexes formed under the plasma membrane, and the actin polymerization activity led to a rapid and intense membrane blebbing. The blebs were delimited by a thin F-actin ring and contained enhanced levels of HSP27. Later, the cells displayed hallmarks of apoptosis, such as DEVD protease activities and internucleosomal DNA fragmentation. Bleb formation but not apoptosis was blocked by extremely low concentrations of the actin polymerization inhibitor cytochalasin D or by the SAPK2 inhibitor SB203580, indicating that the two processes are not in the same linear cascade. The role of HSP27 in mediating membrane blebbing was assessed in fibroblastic cells. In control fibroblasts expressing a low level of endogenous HSP27 or in fibroblasts expressing a high level of a nonphosphorylatable HSP27, H2O2 did not induce F-actin accumulation, nor did it generate membrane blebbing activity in the presence or absence of PD098059. In contrast, in fibroblasts that expressed wild-type HSP27 to a level similar to that found in endothelial cells, H2O2 induced accumulation of F-actin and caused bleb formation when the ERK pathway was inhibited. Cis-platinum, which activated SAPK2 but induced little ERK activity, also induced membrane blebbing that was dependent on the expression of HSP27. In these cells, membrane blebbing was not followed by caspase activation or DNA fragmentation. We conclude that the HSP27-dependent actin polymerization–generating activity of SAPK2 associated with a misassembly of the focal adhesions is responsible for induction of membrane blebbing by stressing agents.
Everyday occupational problems perceived by participants in a pain rehabilitation programme

Abstract Background: Knowledge of the diversity of occupational problems perceived by people with chronic pain is insufficient. Aims: To describe everyday occupational problems among patients with musculoskeletal pain enrolled in a pain rehabilitation programme, and to compare subgroups based on participant characteristics. Methods: The sample consisted of 152 men and women. Occupational performance was assessed with the Canadian Occupational Performance Measure (COPM). Other data were obtained from forms including sociodemographic variables and pain diagnoses. Major findings: The participants reported 706 prioritized everyday occupational problems categorized as self-care (37%), productivity (32%), and leisure (31%). Household management was the largest sub-category. Working, sitting, and cleaning the house were the specific occupational problems reported most frequently. Women reported significantly more occupations related to productivity and men reported more self-care occupations. Principal conclusion: Patients with pain have a wide range of occupational problems that need to be addressed, along with gender-specific needs.
Molecular dynamics study on compact heat storage materials

Storing heat in salt hydrates by the reversible sorption process of water vapor is one of the most promising forms of compact heat storage. The large storage capacity, low loss and low cost make it especially suitable for seasonal heat storage systems. However, the hydration and dehydration mechanisms of salt hydrates are not fully clear. In this study, a molecular dynamics approach towards deep understanding of hydration and dehydration is proposed. The studied material is MgSO 4 . In the molecular dynamics simulations, pieces of nanometer thick crystals are modeled from perfect crystalline structures and interact with water vapor. The dehydration simulation is performed at 450K, and a constant vapor pressure 20 mbar. The hydration simulation is performed at 300K. The properties including equilibrium pressure, dehydration rate, density, diffusion coefficient and radial distribution functions are studied. In this study, it is discovered that the slowdown in dehydration rate is caused by surface anhydrous MgSO 4 aggregates and surface adsorption of water molecules. free water molecules at temperatures of 300K 360K, 420K and 450K. The vacuum space attached is 600nm (b) Number of free water molecules at temperatures from 350 to 420K, 10K apart. The vacuum space attached is this case 100nm. In both simulations, the free water number increases and then equilibrates at certain value. A larger vacuum space requires more time to reach equilibrium.
Postthymic Expansion in Human CD4 Naive T Cells Defined by Expression of Functional High-Affinity IL-2 Receptors

As the thymus involutes with age, the maintenance of peripheral naive T cells in humans becomes strongly dependent on peripheral cell division. However, mechanisms that orchestrate homeostatic division remain unclear. In this study we present evidence that the frequency of naive CD4 T cells that express CD25 (IL-2 receptor α-chain) increases with age on subsets of both CD31+ and CD31− naive CD4 T cells. Analyses of TCR excision circles from sorted subsets indicate that CD25+ naive CD4 T cells have undergone more rounds of homeostatic proliferation than their CD25− counterparts in both the CD31+ and CD31− subsets, indicating that CD25 is a marker of naive CD4 T cells that have preferentially responded to survival signals from self-Ags or cytokines. CD25 expression on CD25− naive CD4 T cells can be induced by IL-7 in vitro in the absence of TCR activation. Although CD25+ naive T cells respond to lower concentrations of IL-2 as compared with their CD25− counterparts, IL-2 responsiveness is further increased in CD31− naive T cells by their expression of the signaling IL-2 receptor β-chain CD122, forming with common γ-chain functional high-affinity IL-2 receptors. CD25 plays a role during activation: CD25+ naive T cells stimulated in an APC-dependent manner were shown to produce increased levels of IL-2 as compared with their CD25− counterparts. This study establishes CD25+ naive CD4 T cells, which are further delineated by CD31 expression, as a major functionally distinct immune cell subset in humans that warrants further characterization in health and disease.
Bayesian Modeling of Biomolecular Assemblies with Cryo-EM Maps

A growing array of experimental techniques allows us to characterize the three-dimensional structure of large biological assemblies at increasingly higher resolution. In addition to X-ray crystallography and nuclear magnetic resonance in solution, new structure determination methods such cryo-electron microscopy (cryo-EM), crosslinking/mass spectrometry and solid-state NMR have emerged. Often it is not sufficient to use a single experimental method, but complementary data need to be collected by using multiple techniques. The integration of all datasets can only be achieved by computational means. This article describes Inferential structure determination, a Bayesian approach to integrative modeling of biomolecular complexes with hybrid structural data. I will introduce probabilistic models for cryo-EM maps and outline Markov chain Monte Carlo algorithms for sampling model structures from the posterior distribution. I will focus on rigid and flexible modeling with cryo-EM data and discuss some of the computational challenges of Bayesian inference in the context of biomolecular modeling.
Newly Identified NO‐Sensor Guanylyl Cyclase/Connexin 43 Association Is Involved in Cardiac Electrical Function

Background Guanylyl cyclase, a heme‐containing α1β1 heterodimer (GC1), produces cGMP in response to Nitric oxide (NO) stimulation. The NO‐GC1‐cGMP pathway negatively regulates cardiomyocyte contractility and protects against cardiac hypertrophy–related remodeling. We recently reported that the β1 subunit of GC1 is detected at the intercalated disc with connexin 43 (Cx43). Cx43 forms gap junctions (GJs) at the intercalated disc that are responsible for electrical propagation. We sought to determine whether there is a functional association between GC1 and Cx43 and its role in cardiac homeostasis. Methods and Results GC1 and Cx43 immunostaining at the intercalated disc and coimmunoprecipitation from membrane fraction indicate that GC1 and Cx43 are associated. Mice lacking the α subunit of GC1 (GCα1 knockout mice) displayed a significant decrease in GJ function (dye‐spread assay) and Cx43 membrane lateralization. In a cardiac‐hypertrophic model, angiotensin II treatment disrupted the GC1‐Cx43 association and induced significant Cx43 membrane lateralization, which was exacerbated in GCα1 knockout mice. Cx43 lateralization correlated with decreased Cx43‐containing GJs at the intercalated disc, predictors of electrical dysfunction. Accordingly, an ECG revealed that angiotensin II–treated GCα1 knockout mice had impaired ventricular electrical propagation. The phosphorylation level of Cx43 at serine 365, a protein‐kinase A upregulated site involved in trafficking/assembly of GJs, was decreased in these models. Conclusions GC1 modulates ventricular Cx43 location, hence GJ function, and partially protects from electrical dysfunction in an angiotensin II hypertrophy model. Disruption of the NO‐cGMP pathway is associated with cardiac electrical disturbance and abnormal Cx43 phosphorylation. This previously unknown NO/Cx43 signaling could be a protective mechanism against stress‐induced arrhythmia.