Fatigue assessment of notched parts plays imperative performance in structural integrity and reliability of major equipment. The theory of critical distance (TCD) involves determining the fatigue ...strength of notched parts from the linear elastic stress field surrounding the notch apex. In addition, the fatigue strength of engineering part is also size dependent. Accordingly, by coupling a plasticity reformulated TCD with the weakest link theory, this study elaborates a novel scheme for probabilistic low cycle fatigue (LCF) analysis under notch and size effects. Results of fatigue tests and complementary FE analysis with the proposed model is utilized to compute highly stressed volume (HSV). Furthermore, test data of titanium alloys TC4 (Ti-6Al-4V) and TC11 (Ti-6.5Al-3.5Mo-1.5Zr-0.3Si) as well as aluminum alloy 7075-T6 are utilized for model verification. Results specify that the model predicted P–S–N curves are in good agreement with experimental data.
In engineering practice, due to various functional requirements, structures with geometric discontinuities occur widely; in addition, most structures undergo complex multiaxial loads, which drives ...the development of relevant theories. As a result, to provide reference for structural anti-fatigue design and ensuring their operation safety, the establishment of fatigue lifing methods for notched components under multiaxial loads is critical and indispensable. In this paper, by combining the popular Fatemi-Socie critical plane model with the critical distance theory, a fatigue lifing model for notched structures under multiaxial loads was established, and its effectiveness was verified with the fatigue test data of TC4 stepped shaft specimens. Results show that the proposed model can overcome the conservative estimation problem when performing fatigue lifing based on the stress-strain data of critical points, with all predicted fatigue lives within two-time error bands. Finally, the method was applied to the fat
Purpose. To investigate the efficacy of idiopathic macular pucker (epimacular membrane) surgery and to identify the possible prognostic factor. Methods. This was a retrospective study which enrolled ...38 patients with idiopathic macular pucker who underwent 23-gauge pars plana vitrectomy (PPV) with indocyanine green-assisted peeling of epiretinal membrane (ERM) and internal limiting membrane (ILM). Visual outcomes were assessed at the baseline and during the follow-up including best-corrected visual acuity (BCVA) and metamorphopsia score, as well as outer plexiform layer (OPL) angle and central retinal thickness (CRT) using spectral-domain optical coherence tomography (SD-OCT). A comparison was made between patients with the prepeeling CRTs ≥500 μm and those <500 μm. A comparison was also made between patients with the prepeeling OPL angles ≥130° and those <130°. Based on the prepeeling parameters, the correlations between various prepeeling and postpeeling visual functions were analyzed. Results. Mean follow-up was 36.07 ± 4.62 months (range 1.30–96.70 months). BCVA was significantly improved from 0.26 ± 0.03 to 0.67 ± 0.04 p<0.001; metamorphopsia score was significantly reduced from 1.42 ± 0.16 to 0.61 ± 0.08 p<0.001; CRT was significantly decreased from 519.62 ± 13.41 μm to 385.37 ± 8.97 μm p<0.001. Greater prepeeling OPL angle (≥130°) was associated with significantly greater BCVA improvement (Snellen E/LogMAR: p=0.01/0.03) and greater metamorphopsia reduction p=0.03, as compared to smaller OPL angle (<130°) with less BCVA improvement and less metamorphopsia reduction. However, the final BCVA improvement and metamorphopsia reduction relevant to the prepeeling smaller CRT (<500 μm) did not significantly differ from that relevant to the prepeeling greater CRT (≥500 μm; p>0.05). Endophthalmitis, retinal tear, or retinal detachment was not observed after peeling. Conclusion. Indocyanine green-assisted ERM/ILM peeling combined with small gauge vitrectomy is associated with significant visual acuity improvement and metamorphopsia reduction in patients with idiopathic macular pucker. Greater prepeeling OPL angle rather than CRT might act as a useful prognostic factor in predicting better final visual functional outcomes.
Long-term cataract risks associated with first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), and their associations with metabolism-related diseases are not yet ...elucidated.
Using Taiwan National Health Insurance data, we conducted a propensity score matched population-based cohort study consisting of 10,014 patients with newly diagnosed schizophrenia from 2005 to 2009 and followed them until the end of 2013. A Cox hazard model with metabolism-related diseases as time-dependent covariates was adapted to estimate the hazard ratio (HR) of cataracts between SGAs and FGAs groups.
During the 8-year follow-up, patients receiving SGAs were associated with a higher risk of cataract than those receiving FGAs with an adjusted HR of 1.59 (95% confidence interval CI = 1.06–2.36). Patients receiving high-metabolic-risk SGAs (clozapine and olanzapine) showed the highest risk of cataracts among SGAs when compared with those receiving FGAs (aHR = 2.57, 95% CI: 1.35–4.88). SGAs demonstrated a stronger contribution in the risk of cataract in patients without diabetes mellitus (DM) and hyperlipidemia than in those developed these diseases. Patients who developed DM or hyperlipidemia after receiving antipsychotics had an approximately 2.5-fold increased cataract risk over those who did not develop these diseases.
Regardless of the condition of metabolic-related diseases, SGAs were independently associated with an increased risk of cataract. DM and hyperlipidemia developed after antipsychotics contributed to the risk of cataract risk.
GABRB3 encoding the β3 subunit of GABAA receptor has been implicated in multiple neuropsychiatric disorders, including substance abuse. Previous studies reported that SNPs at the 5' regulatory region ...of GABRB3 could regulate GABRB3 gene expression and associated with childhood absence epilepsy (CAE). The study aimed to investigate whether SNPs at the 5' regulatory region of GABRB3 were associated with heroin dependence in our population. We first re-sequenced 1.5 kb of the 5'regulatory region of GABRB3 gene to examine the SNP profile in the genomic DNA of 365 control subjects. Then, we conducted a case-control association analysis between 576 subjects with heroin dependence (549 males, 27 females) and 886 controls (472 males, 414 females) by genotyping the rs4906902 as a tag SNP. We also conducted a reporter gene assay to assess the promoter activity of two major haplotypes derived from SNPs at this region. We detected 3 common SNPs (rs4906902, rs8179184 and rs20317) at this region that had strong pair-wise linkage disequilibrium. The C allele of rs4906902 was found to be associated with increased risk of heroin dependence (odds ratio:1.27, p = 0.002). Two major haplotypes (C-A-G and T-G-C) derived from these 3 SNPs accounted for 99% of this sample, and reporter gene activity assay showed that haplotype C-A-G that contained the C allele of the tag SNP rs4906902 had higher activity than haplotype T-G-C. Our data suggest that GABRB3 might be associated with heroin dependence, and increased expression of GABRB3 might contribute to the pathogenesis of heroin dependence.
To investigate whether anti-placental growth factor (PGF) can inhibit subretinal fibrosis and whether this effect is mediated by the inhibitory effect of PGF on epithelial-mesenchymal transition ...(EMT) of retinal pigment epithelial (RPE) cells.
Subretinal fibrosis model was established in laser induced choroidal neovascularization (CNV) mice on day 21 after laser photocoagulation. Immunofluorescence staining (IFS) of cryosections and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of PGF. IFS of whole choroidal flat-mounts was used to detect the degree of subretinal fibrosis. IFS of cryosections and ELISA were used to detect the expression of EMT related indicators in subretinal fibrosis lesions.
The expression of PGF protein in subretinal fibrosis lesions was significantly up-regulated (
<0.05), and mainly co-stained with pan-cytokeratin labeled RPE cells. Intravitreal injection of anti-PGF neutralizing antibody reduced the area of subretinal fibrosis and the ratio of fibrotic/angiogenic area significantly at the concentrations of 0.25, 0.5, 1.0, and 2.0 µg/µL (all
<0.05). The expression of E-cadherin in the local RPE cells decreased, while α-SMA increased significantly in subretinal fibrosis lesions, and the application of anti-PGF neutralizing antibody could reverse these changes (
<0.05).
The expression of PGF is up-regulated in the lesion site of subretinal fibrosis and mainly expressed in RPE cells. Intravitreal injection of anti-PGF neutralizing antibody can significantly inhibit the degree of subretinal fibrosis in CNV mice, and this effect may be mediated by the inhibition of PGF on EMT of RPE cells.
Abstract Background Both alcoholism and heroin dependence are common substance use disorders with a high genetic basis. A recent genetic study reported that the autism susceptibility candidate 2 gene ...( AUTS2 ) was involved in regulating the alcohol drinking behavior. In our previous total gene expression profiling study, we found that the AUTS2 transcript was significantly down-regulated in lymphoblastoid cell lines (LCL) in heroin dependent individuals compared with control subjects, which prompted us to investigate whether AUTS2 is associated with heroin dependence. Methods We compared the AUTS2 transcript level of LCL between 124 heroin dependent males and 116 control males using real-time quantitative PCR, and conducted a genetic association study of the rs6943555 of AUTS2 with heroin dependence using a sample of 546 heroin dependent males and 373 control males. Results We first verified that the average transcript level of AUTS2 in the heroin dependent group was significantly lower than that in the control group ( p = 0.017). In the genetic association analysis, we found that AA homozygotes of rs6943555 were significantly over-represented in the heroin dependent subjects compared with the control subjects (odds ratio = 1.7, 95% confidence interval: 1.08–2.74, p = 0.017). Analyzing the sample from the AUTS2 transcript experiment, we found that AA carriers ( n = 19) had significantly lower AUTS2 mRNA levels in their LCL compared to TT carriers ( n = 97, p = 0.002) and AT carriers ( n = 91, p = 0.005). Conclusions Our data indicate that the AUTS2 gene might be associated with heroin dependence, and reduced AUTS2 gene expression might confer increased susceptibility to heroin dependence.
Schizophrenia and bipolar disorder are severe mental disorders with a major component of genetic factors in their etiology. Rare mutations play a significant role in these two disorders, and they are ...highly heterogeneous and personalized. Identification of personalized mutations is essential for the establishment of molecular diagnosis, providing insight into pathogenesis and guiding the personalized treatment for each affected patient. We conducted whole-genome sequencing analysis of families with schizophrenia and bipolar disorder to search for their genetic underpinnings. This report identified a rare missense mutation Arg1087Gln of BSN (bassoon presynaptic cytomatrix protein) co-segregating with schizophrenia in a family with multiple affected members. Furthermore, we identified the rare missense mutation Ser1535Leu of PCLO (piccolo presynaptic cytomatrix protein) in two sisters with bipolar disorder and another rare missense mutation, His5142Arg in PCLO, in a patient with schizophrenia. These three missense mutations were very rare and were predicted to be pathogenic. The BSN and PCLO genes encode two structurally related proteins of the presynaptic cytomatrix at the active zone that regulates neurotransmission at the presynaptic neuronal terminal. Our findings suggest the involvement of the presynaptic matrix in the pathogenesis of schizophrenia and bipolar disorder, and BSN and PCLO are the risk genes for schizophrenia and bipolar disorder.
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