Design of parts and manufacturing systems for reliability and maintainability

The design of parts and manufacturing systems can be viewed from different perspectives. This paper discusses the design of parts and manufacturing systems from reliability and maintainability perspectives. A convenient method of considering reliability and maintainability is through the use of design rules which are based on empirical and theoretical knowledge. Four design rules for improvement of reliability and maintainability of systems are presented. The design rules are proven and substantiated with numerical results. The relationship between the design for reliability and maintainability rules and design for manufacturing process rules is discussed.     

MicroRNA Expression in Clear Cell Renal Cell Carcinoma Cell Lines and Tumor Biopsies: Potential Therapeutic Targets

This study was carried out to quantitate the expression levels of microRNA-17, -19a, -34a, -155, and -210 (miRs) expressed in nine clear cell renal cell carcinoma (ccRCC) and one chromophobe renal cell carcinoma cell line with and without sarcomatoid differentiation, and in six primary kidney tumors with matching normal kidney tissues. The data in the five non-sarcomatoid ccRCC cell lines—RC2, CAKI-1, 786-0, RCC4, and RCC4/VHL—and in the four ccRCC with sarcomatoid differentiation—RCJ41T1, RCJ41T2, RCJ41M, and UOK-127—indicated that miR-17 and -19a were expressed at lower levels relative to miR-34a, -155, and -210. Compared with RPTEC normal epithelial cells, miR-34a, miR-155, and miR-210 were expressed at higher levels, independent of the sarcomatoid differentiation status and hypoxia-inducible factors 1α and 2α (HIFs) isoform expression. In the one chromophobe renal cell carcinoma cell line, namely, UOK-276 with sarcomatoid differentiation, and expressing tumor suppressor gene TP53, miR-34a, which is a tumor suppressor gene, was expressed at higher levels than miR-210, -155, -17, and -19a. The pilot results generated in six tumor biopsies with matching normal kidney tissues indicated that while the expression of miR-17 and -19a were similar to the normal tissue expression profile, miR-210, -155, -and 34a were expressed at a higher level. To confirm that differences in the expression levels of the five miRs in the six tumor biopsies were statistically significant, the acquisition of a larger sample size is required. Data previously generated in ccRCC cell lines demonstrating that miR-210, miR-155, and HIFs are druggable targets using a defined dose and schedule of selenium-containing molecules support the concept that simultaneous and concurrent downregulation of miR-210, miR-155, and HIFs, which regulate target genes associated with increased tumor angiogenesis and drug resistance, may offer the potential for the development of a novel mechanism-based strategy for the treatment of patients with advanced ccRCC.     

NIR-Triggered Generation of Reactive Oxygen Species and Photodynamic Therapy Based on Mesoporous Silica-Coated LiYF4 Upconverting Nanoparticles

To date, the increase in reactive oxygen species (ROS) production for effectual photodynamic therapy (PDT) treatment still remains challenging. In this study, a facile and effective approach is utilized to coat mesoporous silica (mSiO₂) shell on the ligand-free upconversion nanoparticles (UCNPs) based on the LiYF₄ host material. Two kinds of mesoporous silica-coated UCNPs (UCNP@mSiO₂) that display green emission (doped with Ho³⁺) and red emission (doped with Er³⁺), respectively, were successfully synthesized and well characterized. Three photosensitizers (PSs), merocyanine 540 (MC 540), rose bengal (RB), and chlorin e6 (Ce6), with the function of absorption of green or red emission, were selected and loaded into the mSiO₂ shell of both UCNP@mSiO₂ nanomaterials. A comprehensive study for the three UCNP@mSiO₂/PS donor/acceptor pairs was performed to investigate the efficacy of fluorescence resonance energy transfer (FRET), ROS generation, and in vitro PDT using a MCF-7 cell line. ROS generation detection showed that as compared to the oleate-capped and ligand-free UCNP/PS pairs, the UCNP@mSiO₂/PS nanocarrier system demonstrated more pronounced ROS generation due to the UCNP@mSiO₂ nanoparticles in close vicinity to PS molecules and a higher loading capacity of the photosensitizer. As a result, the three LiYF₄ UCNP@mSiO₂/PS nanoplatforms displayed more prominent therapeutic efficacies in PDT by using in vitro cytotoxicity tests.     

Dried Blood Spots as Matrix for Evaluation of Valproate Levels and the Immediate and Delayed Metabolomic Changes Induced by Single Valproate Dose Treatment

The immediate and delayed metabolic changes in rats treated with valproate (VPA), a drug used for the treatment of epilepsy, were profiled. An established approach using dried blood spots (DBS) as sample matrices for gas chromatography/mass spectrometry-based metabolomics profiling was modified using double solvents in the extraction of analytes. With the modified method, some of the previously undetectable metabolites were recovered and subtle differences in the metabolic changes upon exposure to a single dose of VPA between males and female rats were identified. In male rats, changes in 2-hydroxybutyric acid, pipecolic acid, tetratriacontane and stearic acid were found between the control and treatment groups at various time points from 2.5 h up to 24 h. In contrast, such differences were not observed in female rats, which could be caused by the vast inter-individual variations in metabolite levels within the female group. Based on the measured DBS drug concentrations, clearance and apparent volume of distribution of VPA were estimated and the values were found to be comparable to those estimated previously from full blood drug concentrations. The current study indicated that DBS is a powerful tool to monitor drug levels and metabolic changes in response to drug treatment.     

MicroRNA-Based Diagnosis and Therapy

MicroRNAs (miRNAs) are a group of endogenous non-coding RNAs that regulate gene expression. Alteration in miRNA expression results in changes in the profile of genes involving a range of biological processes, contributing to numerous human disorders. With high stability in human fluids, miRNAs in the circulation are considered as promising biomarkers for diagnosis, as well as prognosis of disease. In addition, the translation of miRNA-based therapy from a research setting to clinical application has huge potential. The aim of the current review is to: (i) discuss how miRNAs traffic intracellularly and extracellularly; (ii) emphasize the role of circulating miRNAs as attractive potential biomarkers for diagnosis and prognosis; (iii) describe how circulating microRNA can be measured, emphasizing technical problems that may influence their relative levels; (iv) highlight some of the circulating miRNA panels available for clinical use; (v) discuss how miRNAs could be utilized as novel therapeutics, and finally (v) update those miRNA-based therapeutics clinical trials that could potentially lead to a breakthrough in the treatment of different human pathologies.     

Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/βcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.     

Molecular dynamics study on nanotube-resonators with mass migration applicable to both frequency-tuner and data-storage-media

We investigated the cantilevered carbon-nanotube-resonator including electromigratively movable nanoparticle via classical molecular dynamics simulations and continuum model. The change of the effective mass value, which was closely correlated with the position change of the encapsulated nanoparticle, could be regressed by a power function, the resonance frequency of the carbon-nanotube-resonator could be tuned by controlling the nanoparticle’s position, and the possible frequency-shift-ranges then reached 18–85%. The suggested device could be served as a data-storage-media for electromechanical nonvolatile-memory as well as a frequency-tuner.     

A conservative method of wavelet neural network based meta-modeling in constrained approximate optimization

The paper aims at the development of the wavelet neural network (WNN) based conservative meta-model that satisfies the constraint feasibility of approximate optimal solution. The WNN based constraint-feasible meta-model is formulated via exterior penalty method to optimally determine interconnection weights and dilation and translation coefficients in the network. Using Ackley’s path function, the approximation performance of WNN is first tested in comparison with BPN. The proposed approach of constraint feasibility is then verified through a ten-bar planar truss problem. For constrained approximate optimization, the structural design of a composite rotor blade is explored to support the proposed strategies.