Spinal muscular atrophy (SMA) is caused by mutation of the Survival Motor Neurons 1 (SMN1) gene and is characterized by degeneration of spinal motor neurons. The severity of SMA is primarily influenced by the copy number of the SMN2 gene. Additional modifier genes that lie outside the SMA locus exist and one gene that could modify SMA is the Zinc Finger Protein (ZPR1) gene. To test the significance of ZPR1 downregulation in SMA, we examined the effect of reduced ZPR1 expression in mice with mild and severe SMA. We report that the reduced ZPR1 expression causes increase in the loss of motor neurons, hypermyelination in phrenic nerves, increase in respiratory distress and disease severity and reduces the lifespan of SMA mice. The deficiency of SMN-containing sub-nuclear bodies correlates with the severity of SMA. ZPR1 is required for the accumulation of SMN in sub-nuclear bodies. Further, we report that ZPR1 overexpression increases levels of SMN and promotes accumulation of SMN in sub-nuclear bodies in SMA patient fibroblasts. ZPR1 stimulates neurite growth and rescues axonal growth defects in SMN-deficient spinal cord neurons from SMA mice. These data suggest that the severity of disease correlates negatively with ZPR1 levels and ZPR1 may be a protective modifier of SMA.
Current music recommender systems typically act in a greedy manner by recommending songs with the highest user ratings. Greedy recommendation, however, is suboptimal over the long term: it does not actively gather information on user preferences and fails to recommend novel songs that are potentially interesting. A successful recommender system must balance the needs to explore user preferences and to exploit this information for recommendation. This article presents a new approach to music recommendation by formulating this exploration-exploitation trade-off as a reinforcement learning task. To learn user preferences, it uses a Bayesian model that accounts for both audio content and the novelty of recommendations. A piecewise-linear approximation to the model and a variational inference algorithm help to speed up Bayesian inference. One additional benefit of our approach is a single unified model for both music recommendation and playlist generation. We demonstrate the strong potential of the proposed approach with simulation results and a user study.
Objective: To determine the timing of treatment for the labial inversely impacted maxillary central incisors. Methods: Twenty-eight patients (mean age, 8.2 years) with labial inversely impacted maxillary central incisors were divided into early-treated and later-treated groups according to their dental age. All of the patients were treated with a combination of surgery and orthodontic traction using the Guide rod appliance. Cone-beam computed tomography images were taken immediately after treatment for assessing the root morphology, root length, and alveolar bone loss. Sagittal slices were evaluated at the widest labial-lingual width of the tooth in the axial view. All variables were evaluated by Simplant 13.0 software (Materialise Dental NV, Leuven, Belgium). Results: The rank sum test indicated that the root length of two groups showed a statistically significant difference between the impacted and homonym tooth, with a shorter length in the impacted tooth (P , .05). The D-value (difference of root length between the impacted and homonym tooth) and alveolar bone loss on the labial side of the impacted incisor are significantly less in the early-treated groups when compared with the later-treated groups (P , .05). Spearman rank correlation analysis showed a statistically positive association between the treatment timing and D-value (r 5 .623, P , .05). The chi-square test for morphology of root apex indicated that the incidence of the root-apex-directed labial side is significantly higher in the later-treated groups when compared with the early-treated groups. Conclusion: The labial inversely impacted maxillary central incisors should be treated early to promote root development by achieving a better morphology of root apex, thus reducing the risk of alveolar bone loss on the labial side. (Angle Orthod. 2016;86:768-774.)
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