Mathematical Model of Helical Gear Topography Measurements and Tooth Flank Errors Separation

During large-size gear topological modification by form grinding, the helical gear tooth surface geometrical shape will be complex and it is difficult for the traditional scanning measurement to characterize the whole tooth surface. Therefore, in order to characterize the actual tooth surfaces, an on-machine topography measurement approach is proposed for topological modification helical gears on the five-axis CNC gear form grinding machine that can measure the modified gear tooth deviations on the machine immediately after grinding. Combined with gear form grinding kinematics principles, the mathematical model of topography measurements is established based on the polar coordinate method. The mathematical models include calculating trajectory of the centre of measuring probe, defining gear flanks by grid of points, and solving coordinate values of topology measurement. Finally, a numerical example of on-machine topography measurement is presented. By establishing the topography diagram and the contour map of tooth error, the tooth surface modification amount and the tooth flank errors are separated, respectively. Research results can serve as foundation for topological modification and tooth surface errors closed-loop feedback correction

Closed-Loop Feedback Flank Errors Correction of Topographic Modification of Helical Gears Based on Form Grinding

To increase quality, reduce heavy-duty gear noise, and avoid edge contact in manufacturing helical gears, a closed-loop feedback correction method in topographic modification tooth flank is proposed based on the gear form grinding. Equations of grinding wheel profile and grinding wheel additional radial motion are derived according to tooth segmented profile modification and longitudinal modification. Combined with gear form grinding kinematics principles, the equations of motion for each axis of five-axis computer numerical control forming grinding machine are established. Such topographical modification is achieved in gear form grinding with on-machine measurement. Based on a sensitivity analysis of polynomial coefficients of axis motion and the topographic flank errors by on-machine measuring, the corrections are determined through an optimization process that targets minimization of the tooth flank errors. A numerical example of gear grinding, including on-machine measurement and closed-loop feedback correction completing process, is presented. The validity of this flank correction method is demonstrated for tooth flank errors that are reduced. The approach is useful to precision manufacturing of spiral bevel and hypoid gears, too

LncRNAs: the bridge linking RNA and colorectal cancer.

Long noncoding RNAs (lncRNAs) are transcribed by genomic regions (exceeding 200 nucleotides in length) that do not encode proteins. While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, lncRNAs control pleiotropic cancer phenotypes through interactions with other cellular molecules including DNA, protein, and RNA. Recent studies have demonstrated that dysregulation of lncRNAs is influential in proliferation, angiogenesis, metastasis, invasion, apoptosis, stemness, and genome instability in colorectal cancer (CRC), with consequent clinical implications. In this review, we explicate the roles of different lncRNAs in CRC, and the potential implications for their clinical application

Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.

Ovarian cancer constitutes one of the most lethal gynaecological malignancies worldwide and currently no satisfactory therapeutic approaches have been established. Therefore, elucidation of molecular mechanisms to develop targeted therapy of ovarian cancer is crucial. PDLIM2 is critical to promote ubiquitination of nuclear p65 and thus its role in inflammation has been highlighted recently. We demonstrate that PDLIM2 is decreased in both ovarian high-grade serous carcinoma and in various human ovarian cancer cell lines compared with normal ovary tissues and human ovarian surface epithelial cells (HOSE). Further functional analysis revealed that PDLIM2 is epigenetically repressed in ovarian cancer development and inhibition of PDLIM2 promoted ovarian cancer growth both in vivo and in vitro via NOS2-derived nitric oxide signaling, leading to recruitment of M2 type macrophages. These results suggest that PDLIM2 might be involved in ovarian cancer pathogenesis, which could serve as a promising therapeutic target for ovarian cancer patients

Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development

The effects of cardiac structure, valvular regurgitation, and left ventricular diastolic dysfunction on the diagnostic accuracy of Murray law–based quantitative flow ratio

ObjectiveThe study aimed to investigate the diagnostic accuracy of Murray law–based quantitative flow ratio (μQFR) from a single angiographic view in patients with abnormal cardiac structure, left ventricular diastolic dysfunction, and valvular regurgitation.BackgroundμQFR is a novel fluid dynamics method for deriving fractional flow reserve (FFR). In addition, current studies of μQFR mainly analyzed patients with normal cardiac structure and function. The accuracy of μQFR when patients had abnormal cardiac structure, left ventricular diastolic dysfunction, and valvular regurgitation has not been clear.MethodsThis study retrospectively analyzed 261 patients with 286 vessels that underwent both FFR and μQFR prior to intervention. The cardiac structure and function were measured using echocardiography. Pressure wire–derived FFR ≤0.80 was defined as hemodynamically significant coronary stenosis.ResultsμQFR had a moderate correlation with FFR (r = 0.73, p < 0.001), and the Bland–Altman plot presented no difference between the μQFR and FFR (0.006 ± 0.075, p = 0.192). With FFR as the standard, the diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of μQFR were 94.06% (90.65–96.50), 82.56% (72.87–89.90), 99.00% (96.44–99.88), 97.26 (89.91–99.30), and 92.96% (89.29–95.44), respectively. The concordance of μQFR/FFR was not associated with abnormal cardiac structure, valvular regurgitation (aortic valve, mitral valve, and tricuspid valve), and left ventricular diastolic function. Coronary hemodynamics showed no difference between normality and abnormality of cardiac structure and left ventricular diastolic function. Coronary hemodynamics demonstrated no difference among valvular regurgitation (none, mild, moderate, or severe).ConclusionμQFR showed an excellent agreement with FFR. The effect of abnormal cardiac structure, valvular regurgitation, and left ventricular diastolic function did not correlate with the diagnostic accuracy of μQFR. Coronary hemodynamics showed no difference in patients with abnormal cardiac structure, valvular regurgitation, and left ventricular diastolic function

Chronic salmon calcitonin exerts an antidepressant effect via modulating the p38 MAPK signaling pathway

Depression is a common recurrent psychiatric disorder with a high lifetime prevalence and suicide rate. At present, although several traditional clinical drugs such as fluoxetine and ketamine, are widely used, medications with a high efficiency and reduced side effects are of urgent need. Our group has recently reported that a single administration of salmon calcitonin (sCT) could ameliorate a depressive-like phenotype via the amylin signaling pathway in a mouse model established by chronic restraint stress (CRS). However, the molecular mechanism underlying the antidepressant effect needs to be addressed. In this study, we investigated the antidepressant potential of sCT applied chronically and its underlying mechanism. In addition, using transcriptomics, we found the MAPK signaling pathway was upregulated in the hippocampus of CRS-treated mice. Further phosphorylation levels of ERK/p38/JNK kinases were also enhanced, and sCT treatment was able only to downregulate the phosphorylation level of p38/JNK, with phosphorylated ERK level unaffected. Finally, we found that the antidepressant effect of sCT was blocked by p38 agonists rather than JNK agonists. These results provide a mechanistic explanation of the antidepressant effect of sCT, suggesting its potential for treating the depressive disorder in the clinic

Salmon Calcitonin Exerts an Antidepressant Effect by Activating Amylin Receptors

Depressive disorder is defined as a psychiatric disease characterized by the core symptoms of anhedonia and learned helplessness. Currently, the treatment of depression still calls for medications with high effectiveness, rapid action, and few side effects, although many drugs, including fluoxetine and ketamine, have been approved for clinical usage by the Food and Drug Administration (FDA). In this study, we focused on calcitonin as an amylin receptor polypeptide, of which the antidepressant effect has not been reported, even if calcitonin gene-related peptides have been previously demonstrated to improve depressive-like behaviors in rodents. Here, the antidepressant potential of salmon calcitonin (sCT) was first evaluated in a chronic restraint stress (CRS) mouse model of depression. We observed that the immobility duration in CRS mice was significantly increased during the tail suspension test and forced swimming test. Furthermore, a single administration of sCT was found to successfully rescue depressive-like behaviors in CRS mice. Lastly, AC187 as a potent amylin receptor antagonist was applied to investigate the roles of amylin receptors in depression. We found that AC187 significantly eliminated the antidepressant effects of sCT. Taken together, our data revealed that sCT could ameliorate a depressive-like phenotype probably via the amylin signaling pathway. sCT should be considered as a potential therapeutic candidate for depressive disorder in the future