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The automatic identification of epileptic EEG signals is significant in both relieving heavy workload of visual inspection of EEG recordings and treatment of epilepsy. This paper presents a novel method based on the theory of sparse representation to identify epileptic EEGs. At first, the raw EEG epochs are preprocessed via Gaussian low pass filtering and differential operation. Then, in the scheme of sparse representation based classification (SRC), a test EEG sample is sparsely represented on the training set by solving l₁-minimization problem, and the represented residuals associated with ictal and interictal training samples are computed. The test EEG sample is categorized as the class that yields the minimum represented residual. So unlike the conventional EEG classification methods, the choice and calculation of EEG features are avoided in the proposed framework. Moreover, the kernel trick is employed to generate a kernel version of the SRC method for improving the separability between ictal and interictal classes. The satisfactory recognition accuracy of 98.63% for ictal and interictal EEG classification and for ictal and normal EEG classification has been achieved by the kernel SRC. In addition, the fast speed makes the kernel SRC suit for the real-time seizure monitoring application in the near future.

The clinical efficacy and safety of acupuncture in the treatment of Seasonal Allergic Rhinitis (SAR) was evaluated by employing a two-phase crossover single-blind clinical trial. Thirty subjects were randomly assigned to two groups with 17 and 13 subjects respectively and treated with real or sham acupuncture (three times per week) for four consecutive weeks and then a crossover for treatments for a further four weeks without a washout period. The administration of real acupuncture treatment was guided by a syndrome differentiation according to Chinese Medicine Theory. Subjects were assessed by various criteria before, during and after the treatments. Outcome measures included subjective symptom scores using a five-point scale (FPS), relief medication scores (RMS) and adverse effect records. Twenty-six (26) subjects completed the study. There was a significant improvement in FPS (nasal and non-nasal symptoms) between the two types of acupuncture treatments. No significant differences were shown in RMS between the real acupuncture treatment group and the sham acupuncture treatment group. No side effects were observed for both groups. The results indicate that acupuncture is an effective and safe alternative treatment for the management of SAR.

Baicalein is an active flavonoid extracted from the root of Scutellaria baicalensis that has anticancer and anti-inflammatory properties; its effects on osteoblastic and angiogenic potential are controversial. The aim of this study was to investigate the effects of baicalein on odontoblastic differentiation and angiogenesis and the underlying mechanism in human dental pulp cells (HDPCs). Baicalein (1–10$\mu$M) had no cytotoxic effects and promoted alkaline phosphatase (ALP) activity, mineralization assayed by Alizarin Red-S staining, and the mRNA expression of marker genes, in a concentration-dependent manner. In addition, baicalein upregulated angiogenic factors and increased in vitro capillary-like tube formation. Moreover, baicalein upregulated bone morphogenetic protein (BMP)-2 mRNA and phosphorylation of Smad 1/5/8 and Wnt ligand mRNA, glycogen synthase kinase-3, and nuclear $\beta$-catenin. The odontogenic and angiogenic effects of baicalein were abolished by the BMP antagonist noggin and the Wnt/$\beta$-catenin receptor antagonist DKK-1. These results demonstrate that baicalein promoted odontoblastic differentiation and angiogenesis of HDPCs by activating the BMP and Wnt/$\beta$-catenin signal pathways. Our findings suggest that baicalein may contribute to dental pulp repair and regenerative endodontics.

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by CD4${}^{+}$ T cell-mediated immune cell infiltration and demyelination in the central nervous system (CNS). The subtypes of CD4${}^{+}$ T cells are T helper cells 1 (Th1), Th2, Th17, and regulatory T cells (Treg), while three other types of cells besides Th2 play a key role in MS and its classic animal model, experimental autoimmune encephalomyelitis (EAE). Tregs are responsible for immunosuppression, while pathogenic Th1 and Th17 cells cause autoimmune-associated demyelination. Therefore, suppressing Th1 and Th17 cell differentiation and increasing the percentage of Treg cells may contribute to the treatment of EAE/MS. Astragali Radix (AR) is a representative medicine with immunoregulatory, anti-inflammatory, antitumor, and neuroprotective effects.The active ingredients in AR include astragalus flavones, polysaccharides, and saponins. In this study, it was found that the total flavonoids of Astragus (TFA) could effectively treat EAE in mice by ameliorating EAE motor disorders, reducing inflammatory damage and demyelination, inhibiting the proportion of Th17 and Th1 cells, and promoting Tregs differentiation by regulating the JAK/STAT and NF$\kappa$B signaling pathways. This novel finding may increase the possibility of using AR or TFA as a drug with immunomodulatory effects for the treatment of autoimmune diseases.

Induced pluripotent stem cells (iPSCs) provide a great model to study the process of stem cell reprogramming and differentiation. Single-cell RNA sequencing (scRNA-seq) enables us to investigate the reprogramming process at single-cell level. Here, we introduce single-cell entropy (scEntropy) as a macroscopic variable to quantify the cellular transcriptome from scRNA-seq data during reprogramming and differentiation of iPSCs. scEntropy measures the relative order parameter of genomic transcriptions at single cell level during the process of cell fate changes, which show increase tendency during differentiation, and decrease upon reprogramming. Hence, scEntropy provides an intrinsic measurement of the cell state, and can be served as a pseudo-time of the stem cell differentiation process. Moreover, based on the evolutionary dynamics of scEntropy, we construct a phenomenological Fokker-Planck equation model and the corresponding stochastic differential equation for the process of cell state transitions during pluripotent stem cell differentiation. These equations provide further insights to infer the processes of cell fates changes and stem cell differentiation. This study is the first to introduce the novel concept of scEntropy to quantify the biological process of iPSC, and suggests that the scEntropy can provide a suitable macroscopic variable for single cells to describe cell fate transition during differentiation and reprogramming of stem cells.

This paper focuses on the relation between the presence of positive feedback loops and the occurrence of multiple states of gene expression. After a short recall on single feedback loops and their properties, we discuss more extensively the properties of positive loops. This discussion includes a theorem (demonstrated elsewhere) which states that the presence of positive loop(s) is a necessary condition for multistationarity. We also discuss some general principles for pattern formation, in terms of involvement of different types of positive feedback loops. Finally, we briefly mention recent experimental results involving positive loops in crucial differentiative processes.

By probabilistic optimization of partial safety factors for a class of structures a more uniform reliability of practical design of individual cases within the class is aimed at. The paper deals with an ultimate limit state design of a class of low rise industrial buildings subject to climatic loads and permanent loads. The optimization is carried out on selected representative structures, the reliability of which is calculated by the level II reliability method FORM. Probabilistic models of cross section resistance and of climatic loads pertinent to a continental climate are based on measurements. Peculiarities of the optimization procedure, particularly optimization stages in conjunction with the choice and possible differentiation of partial factors are discussed.

Background: The future in flexor tendon surgery involves tissue engineering approaches directed toward increasing early repair strength to accelerate tendon healing and to allow for earlier onset of rehabilitation. Previous work has shown that pluripotential mesenchymal stem cells may be successfully delivered to a tendon repair site using a suture carrier. The current work describes the use of Myostatin (GDF-8) to help guide these delivered pluripotential stem cells to differentiate down a tenocyte lineage to potentially maximize the reparative effects of these cells at the tendon repair site.

Methods: Primary rat bone marrow mesenchymal stem cells isolated from the long bones of male Sprague-Dawley rats were treated with 500 ng/ml myostatin for 24 h, 48 h, and 72 h. Collagen 1 A, scleraxis (Scx), and tenomodulin (Tnmd) expression, indicative of tenogenesis, was analyzed using real time PCR and immunohistochemistry staining. A migration assay was performed to assess the functional activity of BMSCs after they were treated with myostatin.

Results: Compared to the control cells (without treatment), the cells treated with 500 ng/ml myostatin for 72 h exhibited higher expression of Col 1A, Scx, and Tnmd. The mRNA expression of Col1A, Scx, Tnmd increased 15.3, 13 and 7 times respectively. Immunohistochemistry staining showed Scx and Tnmd were expressed in the cellular cytoplasm. In response to myostatin, the cells also showed a tendency to proliferate and migrate more than the control cells.

Conclusions: Myostatin (GDF-8) has the ability to increase rat bone marrow mesenchymal stem cell growth and differentiation toward a tenocyte lineage. This information could be useful for future studies regarding tendon repair.

Development of Uniform Embryoid Bodies for Differentiation, Using Mouse Embryonic Stem Cells.

Long-term use of thiazolidinedione (TZD) antidiabetic agents in patients with type 2 diabetes mellitus has been shown to increase the incidence of osteoporosis. Mechanical loading can enhance bone mass by promoting bone formation and suppressing bone resorption, which may be beneficial to patients with TZD-induced osteoporosis. In this study, we examined the cooperative effect of fluid shear stress (FSS) and ciglitazone (CIG), a type of TZD, on osteoblasts. The proliferation, osteoblast differentiation-related mRNA expression and translocation of nuclear factor κB (NFκB) of osteoblasts were assessed. The results show that CIG significantly decreased the proliferation of osteoblasts, inhibited the translocation of NFκB to the nucleus and reduced the mRNA expression of COX-2, IGF, Runx2 and OCN. At the same time, CIG also increased the mRNA expression of PPARγ. Conversely, FSS significantly increased the proliferation of osteoblasts, promoted the translocation of NFκB to the nucleus and increased the mRNA expression of COX-2, IGF, Runx2 and OCN but decreased the mRNA expression of PPARγ. When FSS and CIG were combined, FSS counteracted the effects of CIG on osteoblasts. Taken together, the current results suggest that FSS is able to arrest the effects of CIG on the proliferation and differentiation of osteoblasts.

We report a novel engineered microwells to spatially control differentiation of mouse embryoid bodies. With integrating multiple functionally distinct biomaterials by soft-photolithography technology, this method enables simple and reliable manufacture of biochemically heterogeneous microwells that are capable of regulating differentiation of stem cell in a spatial-specific manner. This simple technology offers a new dimension of spatial control over embryoid bodies development and has great potential in tissue engineering and biomedical applications.

Differentiation of endothelial progenitor cells (EPCs) plays important roles in endothelial repair after vessel injury. Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), and mechanical forces, including cyclic strain and shear stress, synergistically form the microenvironment of EPCs. However, the synergistic effect of cyclic strain, ECs, and VSMCs on the differentiation of EPCs remains unclear. In the present study, EPCs were indirectly co-cultured with stretched ECs or VSMCs that were subjected to 5%, 1.25-Hz cyclic strain by using FX-4000T Strain Unit. Then, Western blot and real-time PCR were used to examine expressions of EC marker, i.e., vascular cell adhesion molecule (VCAM), CD31, von Willebrand factor (vWF); VSMC markers, i.e., α-actin, Calponin, and SM22α; and signaling molecules, i.e., p-Akt and p-ERK. In static, co-cultured ECs increased expression of VCAM and phosphorylation of Akt and ERK in EPCs compared to that in EPCs cultured alone. In EPCs, co-cultured VSMCs decreased expressions of CD31 and vWF, but increased expressions of Calponin and SM22α. Stretched ECs reduced expressions of CD31 and vWF, enhanced Calponin and SM22α, and repressed phosphorylations of Akt and ERK in EPCs. Stretched VSMCs decreased CD31, increased Calponin and SM22α expressions, and repressed phosphorylation of Akt and ERK in EPCs. Our results suggest that ECs promoted EPC differentiation into ECs in static. VSMCs in static, as well as stretched ECs and stretched VSMCs, promoted EPC differentiation into VSMCs. Phosphorylation of Akt and ERK might be involved in EPC differentiation, mediated by the stretched ECs and VSMCs.

There have been no previous reports of tendon tissue engineering using mesenchymal stem cells (MSCs) with regard to quantitative evaluation of protein expression levels and observation of derived extracellular matrix (ECM) state. Therefore, we approached tendon tissue engineering from both perspectives. Human bone marrow MSCs (hBMSCs) were subjected to 8% or 10% cyclic stretching at 1 Hz to promote differentiation into tenocytes and ECM production. The type I collagen (Col I) and Tenascin-C (Tnc) protein expression levels were evaluated quantitatively by enzyme-linked immunosorbent assay (ELISA). Confocal fluorescence microscopy was employed to observe the derived ECM state. Col I state derived from 10%-stretched cells as ECM was elongated like actual tendon ECM, although the quantitative protein expression levels were slightly higher in 8%-stretched cells. The results suggested that the optimal uniaxial stretching ratio was different between protein expression levels and derived ECM state. Therefore, it is important to pay attention to both protein expression levels and ECM state in tendon tissue engineering.

Human neuroblastoma (SH-SY5Y) cells, with its ability to differentiate into neurons, have been widely used as the in vitro cell culture model for neuroscience research, especially in studying the pathogenesis of Parkinson's disease (PD) and developing therapeutic strategies. Cellular elasticity could potentially serve as a biomarker to quantitatively distinguish undifferentiated and differentiated SH-SY5Y cells. The goal of this work is to characterize the retinoic acid (RA) induced alternations of elastic properties of SH-SY5Y cells using atomic force microscopy (AFM). The elasticity was measured at multiple points of a single cell. Results have shown that the differentiation of SH-SY5Y cell led to a larger elastic modulus, which is three times more than that of undifferentiated cells. A higher indentation rate applied during AFM measurements led to a larger elastic modulus of the cell. This work provides new insights into the differentiation process identified by the elasticity marker, which could be extended to investigate the function, health and ageing of cells.

Oxygen concentration plays a key role in cell survival and viability. Besides, it has important effects on essential cellular biological processes such as cell migration, differentiation, proliferation and apoptosis. Therefore, the prediction of the cellular response to the alterations of the oxygen concentration can help significantly in the advances of cell culture research. Here, we present a 3D computational mechanotactic model to simulate all the previously mentioned cell processes under different oxygen concentrations. With this model, three cases have been studied. Starting with mesenchymal stem cells within an extracellular matrix with mechanical properties suitable for its differentiation into osteoblasts, and under different oxygen conditions to evaluate their behavior under normoxia, hypoxia and anoxia. The obtained results, which are consistent with the experimental observations, indicate that cells tend to migrate toward zones with higher oxygen concentration where they accelerate their differentiation and proliferation. This technique can be employed to control cell migration toward fracture zones to accelerate the healing process. Besides, as expected, to avoid cell apoptosis under conditions of anoxia and to avoid the inhibition of the differentiation and proliferation processes under conditions of hypoxia, the state of normoxia should be maintained throughout the entire cell-culture process.

Spinal cord injury (SCI) is a severe neurological disease. Although surgery within 8h after SCI can substantially reduce paraplegia, most patients still suffer from hypomusculariasis after neuron recovery, which results in insufficient lower limb muscles to support bodyweight. Currently, there is no effective method to prevent muscle atrophy. Previous studies have shown that low-frequency electromagnetics (LFE) can stimulate the differentiation, proliferation and fusion of muscle satellite cells, however, the optimal electromagnetic strength and effects on the immune system have not been established. Here, we investigated the influence of LFE at different electromagnetic strengths on muscle cell recovery and assessed the impact of chronic LFE on the immune system of SCI rats. The rat immune system was rapidly activated after SCI. High-energy LFE provoked intensive immune responses, while low-energy LFE did not affect immune responses. Simultaneously, LFE effectively prevented myotube reduction and atrophy in SCI rats. The mRNA and protein levels of Pax7 and MyoD were increased after LFE at both high and low electromagnetic strengths, with the latter leading to more robust increases. Indeed, LFE remarkably induced muscle cell fusion. Together, our results demonstrated that LFE activates muscle satellite cells via stimulating myogenic factors. Chronic low-energy LFE is a safe therapy with no adverse impact on the immune system of SCI rats. LFE with 1.5 mT energy should be considered as an optimal therapeutic strategy.

The reliability optimization has achieved great concern in recent years. Nowadays, many researchers obtain allocation results which can maximize the system reliability subject to the system budget. In these researches, the effect of system’s functions is always neglected or only considering the single main function of system. In addition, there are also no obvious evidences in results to distinguish the importance level of different units. However, complex systems tend to perform multiple functions. What’s more, the use frequency of each function and the combinations of units to realize different functions are not the same. In addition, the use demand of different functions is decided by different task environments, the demand differentiation of functions has led to the usage of frequency of various functions having different levels about reliability. Therefore, the reliability optimization allocation only considering cost constraint conditions is not accurate and will results in disaccord between the obtained results with actual situation.

Focusing on the problem mentioned above, a reliability optimization allocation method that considers cost constraint and importance factor is proposed. In this paper, we consider systems consisting of units characterized by different reliability and importance factors. Such systems are multi-function because they must perform different tasks depending on the combination of units. Different functions may work simultaneously. Firstly, the concept of importance factor is defined to describe the importance of a unit and the required importance factor level of system functions in the task is also given. To deal with the differentiation of system functions, the corresponding bound about importance factor are executed when looking for the optimal solution. Similarly, the cost constraint is also forced. Finally, in order to reduce the randomness of intelligent algorithm, a number of optimization are conducted and a rule is proposed to select the most optimal solution from all the optimal solutions which are obtained in every iterative loop.

Example of an integrated transmission device is presented. To begin with, we establish the reliability function of system as the objective optimization function. Then, the restraint of budget and different demands of importance factor of system functions are posed. Furthermore, using a genetic algorithm as the optimization tool, the optimization result can be obtained. Finally, the most optimal solution is selected. The results show that, the method, we proposed is more correct and more approximate than the reality. To verify the advantages and engineering applicability of the new method, the results obtained by the new method are compared with the results obtained under different conditions using basic genetic algorithm, without considering functions and the differentiation of functions, to solve the allocation problem of integrated transmission device, respectively.

The reliability optimization allocation method presented in this paper can not only consider the constraint of cost but also can consider the diversities of functions, and thus the optimization results will be more approximate in actual situation. At the same time, this paper can also provide guidance for the similar reliability optimization problem.

This article addresses the religious and entrepreneurial differentiation within Spanish Lookout, a Mennonite community in the Cayo district in Belize, Central America. In spite of the fact that most Mennonites live more or less on the edge of society, they have been able to establish a strong and stable economic position within Belize, although the different communities show a clear variation when it comes to social as well as in economic activities. Since their migration from Mexico to Belize in 1958, the Mennonites of Spanish Lookout, one of the modern communities, have developed a more differentiated economical system with commercial agriculture and agribusiness. The Mennonites maintain a remarkable transnational network, which consists of Mennonite communities and organizations in countries like Canada, the United States of America, and Mexico. These networks introduce innovations on different levels: from modern or better machines, to religious and social changes. The influences from Mennonites outside Belize on the social-economic system of the Spanish Lookout Mennonites, along with the developments within the community, will be the main focus of this article.

The ability of neural stem cells (NSCs) to home to diseased areas of the brain and their capacity to differentiate into all neural phenotypes provides a powerful tool for the treatment of both diffuse and localized neurologic/oncogenic disorders. NSCs are the most immature neural precursor cells in the nervous system and are defined by their ability to self-renew by symmetric division as well as to give rise to more mature progenitors of all neural lineages by asymmetric division. A full understanding of the molecular mechanisms regulating their migratory properties and their choice between various differentiation programs is essential if these cells are to be used for therapeutic applications. This review focuses on summarizing the factors and signaling molecules that are involved in migration and differentiation of neural stem cells and also gives an insight into therapeutic potential of these cells with an emphasis on glioma therapy.

We examine the notion of a vague ring. We develop a method of constructing vague rings which can be used in the construction of other algebraic structures. We make a connection between vague rings and M-adic topologies on rings and also to the solution of nonlinear systems of equations and to the convergence of Cauchy sequences in power series rings. We introduce the notion of Ω-vagueness which we apply to the integration and differentiation of fuzzy functions.