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This paper proposes a novel knowledge-based approach to proactive recommendation. It exploits \(\mathcal{E}\mathcal{L}\) concept learning to automatically model user preferences and is different from traditional knowledge-based approaches that require users to input explicit needs. Given an item being browsed, a set of marked items and an integer threshold k which is used to determine user preferences (where individuals are treated as items), the approach learns recommendatory restricted \(\mathcal{E}\mathcal{L}\) concepts and returns unmarked instances of these concepts as recommendations. A recommendatory restricted \(\mathcal{E}\mathcal{L}\) concept is a most specific restricted \(\mathcal{E}\mathcal{L}\) concept that has at least k marked items, the item being browsed and at least one other unmarked item as instances. Intuitively, a recommendatory restricted \(\mathcal{E}\mathcal{L}\) concept models a maximal set of user preferences. To guarantee that a learned concept has a finite size and the learning process is efficient, the proposed approach does not handle general \(\mathcal{E}\mathcal{L}\) concepts but only restricted \(\mathcal{E}\mathcal{L}\) concepts which have restrictions on the number of nested quantifiers and the inner occurrence of existential restrictions. This paper treats the problem of learning recommendatory restricted \(\mathcal{E}\mathcal{L}\) concepts as the problem of maximal frequent itemset mining (MFI-mining) and presents an efficient MFI-mining algorithm to learn these concepts. Experimental results demonstrate the feasibility of the proposed approach in terms of efficiency and scalability.

Understanding and simulating multiphase flow through porous media have long been key and challenging issues to industry directed to the extraction of fluids from petroleum reservoirs as well as to the characterization and remediation of aquifers. The new application of nuclear magnetic resonance imaging (MRI) techniques for characterizing fractures and flow in fractured media is investigated. Specifically, a relaxation-weighted imaging technique is used for selectively highlighting either fracture or porous matrix regions. Many advantages over conventional spin-density MRI techniques for characterizing fractured media are demonstrated. Its use to speed image acquisition is also demonstrated. In addition, a multislice profile imaging technique is used to investigate imbibition and drainage displacement experiments in fractured porous media. These images demonstrate that the fractures can have profound effects on the fluid distributions in multiphase flow.

The inversion time (TI) weighted inversion-recovery spin-echo (IRSE) imaging technique was used for laboratory characterization of fractures and porous matrix in permeable media. The method is based on the fact that relaxation rates in fractures and those in surrounding porous matrix are substantially different. Thus, by selectively suppressing imaging signals from either fractures or porous matrix, one can highlight fluid distributions in either of these regions so that fractures can be unambiguously identified and surrounding porous structures can be characterized. The advantages over conventional NMR spin-echo imaging are demonstrated with various fractured porous rock types. A technique to speed acquisitions of images of fluid distributions in porous matrix is also demonstrated.

Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity. However, there is no effective pharmacotherapy for ischemic injury. Currently, combined treatment is highly recommended for this devastating injury. In the present study, we investigated neuroprotective effects of the combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and Lyciumbarbarum polysaccharide (LBP) on cortical neurons using an in vitro ischemic model. Our study demonstrated that treatment with docosahexaenoic acid (DHA), a major component of the ω-3 PUFAs family, significantly inhibited the increase of intracellular Ca(2+) in cultured wild type (WT) cortical neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R) injury and promoted their survival compared with the vehicle-treated control. The protective effects were further confirmed in cultured neurons with high endogenous ω-3 PUFAs that were isolated from fat-1 mice, in that a higher survival rate was found in fat-1 neurons compared with wild-type neurons after OGD/R injury. Our study also found that treatment with LBP (50 mg/L) activated Trk-B signaling in cortical neurons and significantly attenuated OGD/R-induced cell apoptosis compared with the control. Notably, both combining LBP treatment with ω-3 PUFAs administration to WT neurons and adding LBP to fat-1 neurons showed enhanced effects on protecting cortical neurons against OGD/R injury via concurrently regulating the intracellular calcium overload and neurotrophic pathway. The results of the study suggest that ω-3 PUFAs and LBP are promising candidates for combined pharmacotherapy for ischemic stroke.

Induced pluripotent stem (iPS) cells have been generated from somatic cells by ectopic expression of defined transcription factors. The important issues for clinical applications of iPS cells are the defined methods for somatic cell differentiation and how to effectively enrich desired cell population. Here we used humanized renilla green fluorescent protein under the control of Tα1 α-tubulin promoter as lineage selection marker for neuronal differentiation of iPS cells. Using fluorescence-activated cell sorting, green fluorescent protein positive cells were isolated and enriched to near-purity. These results indicated that the neuronal differentiation potential of iPS cells derived from adult somatic cells is similar to that of embryonic stem cells and the high-purity neurons may have important implications for neurodevelopmental studies, safety pharmacological studies, and transplantation studies.

This study was undertaken to observe the effects and possible mechanism of CC chemokine ligand 5 (CCL5) on invasion, proliferation and percentage of CD44+/CD24- subpopulation of human breast cancer line MCF-7 and to investigate the correlation of expression levels of CCL5 and its receptors with the progression of breast cancer. We used real-time RT-PCR to detect the expression levels of CCL5 and its receptors CCR5, CCR1 and CCR3 in 36 breast cancer specimens of different TNM stage and their corresponding normal breast tissue. CCL5 expression and invasive ability of four human breast cancer cell lines MCF-7, SK-BR-3, T-47D and MDA-MB-231 were analyzed by real-time RT-PCR and cell invasion assay, respectively. Effects of recombinant human CCL5 (rhCCL5) on cell proliferation and percentage of the CD44+/CD24- subpopulation in MCF-7 cells were analyzed respectively by MTT assay and flow cytometry. We also used cell invasion assay to detect the invasive ability of both CD44+/CD24- and CD44+/CD24+ subpopulations of MCF-7 cells treated with rhCCL5 and/or CCR5 monoclonal antibody. Our results revealed that CCL5 and CCR5 expression were higher in breast cancer tissue than those in their corresponding normal tissue and breast cancer tissue with higher TNM stage contained more CCL5 mRNA. In addition, CCR5 expression and invasive ability of CD44+/CD24- subpopulation were higher than those of CD44+/CD24+ subpopulation of MCF-7 cells. Moreover, treatment of rhCCL5 increased the proportion of CD44+/CD24- cells and the proliferation of MCF-7 cells. Induction of rhCCL5 increased the cell invasive ability of both CD44+/CD24- and CD44+/CD24+ cells, which could be partially antagonized by CCR5 monoclonal antibody. Collectively, our data show that CCL5 increased the proportion of CD44+/CD24- subpopulation and induced invasion and proliferation of MCF-7 cells, and expression of CCL5 and CCR5 in breast cancer tissue was positively correlated with breast cancer progression.

MG29 is a muscle-specific member of the synaptophysin family protein that participates in controlling the maturation and development of transverse tubule (TT) structure and the maintenance of intracellular Ca2+ signaling in skeletal muscle. Genetic ablation of MG29 leads to defective formation of the TT network in skeletal muscle, which resembles the abnormal TT structure observed in dystrophic muscles. We found that MG29 protein is drastically reduced in mouse models with muscular dystrophy (e.g. mdx and dysferlin-/-), and such reduced MG29 expression and disrupted TT structure were also observed in human patient biopsies with muscular dystrophy. The mg29 gene contains a unique 3’ untranslated region (UTR) with potential binding sites for microRNA (miRNA) or RNA-stabilizing factors. Mutagenesis studies revealed that miR-181a could target a region in the 3′UTR that is highly conserved between mouse and human mg29 genes to exhibit posttranscriptional control of MG29 expression in skeletal muscle. Overexpression of anti-sense miR-181a by microinjection into mouse flexor digitorum brevis fibers significantly increased the expression of endogenous MG29. Studies from other investigators have shown that miR-181a was elevated in human patients with muscular dystrophy. These data suggest an intriguing possibility that elevated miR-181a may be a contributing factor for the reduced MG29 expression under dystrophic conditions. Further understanding of the post-transcriptional regulation by microRNA of MG29 expression can provide more insights into the therapeutic targets of muscular dystrophy.

To study the genes change of hMSC before and after differentiation into neuron-like cells.hMSC were separated from marrow, cultured and expanded in culture medium. After hMSC being induced to differentiate with Shenqiye, Neuron-specific enolase (MSE), neurofilament (NF), and glial fibrillary acidic protein (GFAP) were detected by immunocytochemistry respectively. Using semi-quantitiative RT-PCR to detect ten genes change in hMSC before and after differentiation. Two genes were used to detect the gene sequence.When treated with the inducer--Shenqiye, hMSC exhibited neuronal phenotype. The expressions of NSE and NF in the neuron-like cells were positive, but the glial astrocyte marker GFAP was not found. hMSC expressed germline, ectodermal, endodermal and mesodermal genes prior to neurogenasis. After differentiation, germline genes did not express, while the expressions of endodermal and mesodermal genes were weakened. Ectodermal and neuronal genes expressed stronger.hMSC express multipotentiality, and the neural differentiation comprises quantitative modulation of gene expression rather than simple on-off switching of neural specific genes.

Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) share several clinical and neuropathologic features, and studies suggest that several gene mutations and polymorphisms are involved in both conditions. Matrix metalloproteinase-9 (MMP-9) is implicated in the pathogenesis of PD and ALS, and the C(−1562)T polymorphism in the MMP-9 gene leads to higher promoter activity. We therefore investigated whether this polymorphism predisposes to both PD and sporadic ALS (sALS). Samples from 351 subjects with PD and 351 healthy controls from two major cities in China were compared, while samples from 226 subjects with sALS were compared to the same number of controls from three centers in China. A possible association between the C(−1562)T polymorphism in the MMP-9 gene and PD or sALS was assessed by restriction fragment length polymorphism (RFLP) analysis. Our results show a significant association between the C(−1562)T polymorphism in the MMP-9 gene and risk of PD (odds ratio = 2.268, 95% CI 1.506–3.416, p

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder mainly affecting motor neurons. Mutations in superoxide dismutase-1 (SOD-1) account for about 20% of familial ALS patients. A robust supply of motoneurons carrying the mutated gene would help understand the causes of motoneuron death and develop new therapeutics for the disease. Here, we established induced pluripotent stem (iPS) cell lines from SOD1G93A mice and compared their potency in motoneuron generation with normal iPS cells and mouse embryonic stem cells (E14). Our results showed that iPS cells derived from SOD1G93A mice possessed the similar potency in neuronal differentiation to normal iPS cells and E14 cells and can be efficiently driven to motoneuron-like phenotype. These cells exhibited typical neuronal morphology, expressed key motoneuron markers, including ChAT and HB9, and generated repetitive trains of action potentials. Furthermore, these neurons highly expressed human SOD-1 and exhibited shorter neurites compared to controls. The present study provides evidence that ALS-iPS cells can be used as disease models in high-throughput screening and mechanistic studies due to their ability to efficiently differentiate into specific neuronal subtypes.

Induced pluripotent stem cells (iPSCs) hold promise for the treatment of motoneuron diseases because of their distinct features including pluripotency, self-derivation and potential ability to differentiate into motoneurons. However, it is still unknown whether human iPSC-derived motoneurons can functionally innervate target muscles in vivo, which is the definitive sign of successful cell therapy for motoneuron diseases. In the present study, we demonstrated that human iPSCs derived from mesenchymal cells of the umbilical cord possessed a high yield in neural differentiation. Using a chemically-defined in vitro system, human iPSCs efficiently differentiated into motoneurons which displayed typical morphology, expressed specific molecules, and generated repetitive trains of action potentials. When transplanted into the injured musculocutaneous nerve of rats, they survived robustly, extended axons along the nerve, and formed functional connections with the target muscle (biceps brachii), thereby protecting the muscle from atrophy. Our study provides evidence for the first time that human iPSC-derived motoneurons are truly functional not only in vitro but also in vivo, and they have potential for stem cell-based therapies for motoneuron diseases.

Background Parkinson’s disease (PD) is the second most common neurodegenerative disease, affecting 2% of the population aged over 65 years old. Mitochondrial defects and oxidative stress actively participate in degeneration of dopaminergic (DA) neurons in PD. Paeonolum, a main component isolated from Moutan cortex, has potent antioxidant ability. Here, we have examined the effects of paeonolum against MPP+-induced neurotoxicity in zebrafish and PC12 cells. Methods The overall viability and neurodegeneration of DA neurons was assessed in ETvmat2:green fluorescent protein (GFP) transgenic zebrafish, in which most monoaminergic neurons are labeled by GFP. Damage to PC12 cells was measured using a cell viability assay and assessment of nuclear morphology. Intracellular reactive oxygen species (ROS) and the level of total GSH were assessed. The mitochondrial cell death pathway including mitochondrial membrane potential, cytochrome C release and caspase-3 activity were also examined in PC12 cells. Results Paeonolum protected against MPP+-induced DA neurodegeneration and locomotor dysfunction in zebrafish in a concentration-dependent manner. Similar neuroprotection was replicated in the PC12 cellular model of MPP+ toxicity. Paeonolum attenuated MPP+-induced intracellular ROS accumulation and restored the level of total GSH in PC12 cells. Furthermore, paeonolum significantly inhibited the mitochondrial cell death pathway induced by MPP+. Conclusions Collectively, the present study demonstrates that paeonolum protects zebrafish and PC12 cells against MPP+-induced neurotoxicity.

Purpose High glucose level in diabetic patients may lead to advanced glycation end product (AGE) modified proteins. This study investigated AGE modified proteins in tears and compared their levels in diabetic patients (DM) with non-diabetic controls (CTL). Methods Basal tears were collected from DM with (DR) or without (DNR) retinopathy and CTL. Total AGE modified proteins were detected quantitatively by a dot immunobinding assay. The AGE modified proteins were separated in 1D- and 2D-SDS gels and detected by western-blotting. The individual AGE modified proteins were also compared between groups using densitometry. Results Compared with the CTL group, tear concentrations of AGE modified proteins were significantly elevated in DR and DNR groups. The concentration of AGE modified proteins in diabetic tears were positively correlated with AGE modified hemoglobin (HbA1c) and postprandial blood glucose level (PBG). Western blotting of AGE modified proteins from 1D-SDS gels showed several bands, the major one at around 60 kDa. The intensities of AGE modified protein bands were higher in DM tears than in CTL tears. Western blotting from 2D-SDS gels showed a strongly stained horizontal strip, which corresponded to the major band in 1D-SDS gels. Most of the other AGE modified protein species were within molecular weight of 30–60 kDa, PI 5.2–7.0. Densitometry analysis demonstrated several AGE modified proteins were elevated in DR or DNR tears. Conclusions Total and some individual AGE modified proteins were elevated in DM tears. AGE modified proteins in tears may be used as biomarkers to diagnose diabetes and/or diabetic retinopathy.