A new approach to reliability prediction is needed

This paper starts from the main objections regarding MIL-HDBK-217 and the BELLCORE method for reliability prediction, objections asserting that these methods are approximate, complicated and unconvincing. To support these assertions, and by applying techniques specific to reliability theory, the author has developed a reliability model which is plausible for certain elements of technical systems. The existence of such a model, which in practice is useless because the failure rate expression is too complicated, proves clearly the inefficiency of classical methods.     

Energy and exergy performance of residential heating systems with separate mechanical ventilation

The paper brings new evidence on the impact of separate mechanical ventilation system on the annual energy and exergy performance of several design alternatives of residential heating systems, when they are designed for a house in Montreal. Mathematical models of residential heating, ventilation and domestic hot water (HVAC–DHW) systems, which are needed for this purpose, are developed and furthermore implemented in the Engineering Equation Solver (EES) environment. The Coefficient of Performance and the exergy efficiency are estimated as well as the entropy generation and exergy destruction of the overall system. The equivalent greenhouse gas emissions due to the on-site and off-site use of primary energy sources are also estimated. The addition of a mechanical ventilation system with heat recovery to any HVAC–DHW system discussed in the paper increases the energy efficiency; however, it decreases the exergy efficiency, which indicates a potential long-term damaging impact on the natural environment. Therefore, the use of a separate mechanical ventilation system in a house should be considered with caution, and recommended only when other means for controlling the indoor air quality cannot be applied.     

The importance of cellular internalization of antibody-targeted carbon nanotubes in the photothermal ablation of breast cancer cells

Single-walled carbon nanotubes (CNTs) convert absorbed near infrared (NIR) light into heat. The use of CNTs in the NIR-mediated photothermal ablation of tumor cells is attractive because the penetration of NIR light through normal tissues is optimal and the side effects are minimal. Targeted thermal ablation with minimal collateral damage can be achieved by using CNTs attached to tumor-specific monoclonal antibodies (MAbs). However, the role that the cellular internalization of CNTs plays in the subsequent sensitivity of the target cells to NIR-mediated photothermal ablation remains undefined. To address this issue, we used CNTs covalently coupled to an anti-Her2 or a control MAb and tested their ability to bind, internalize, and photothermally ablate Her2(+) but not Her2(-) breast cancer cell lines. Using flow cytometry, immunofluorescence, and confocal Raman microscopy, we observed the gradual time-dependent receptor-mediated endocytosis of anti-Her2-CNTs whereas a control MAb-CNT conjugate did not bind to the cells. Most importantly, the Her2(+) cells that internalized the MAb-CNTs were more sensitive to NIR-mediated photothermal damage than cells that could bind to, but not internalize the MAb-CNTs. These results suggest that both the targeting and internalization of MAb-CNTs might result in the most effective thermal ablation of tumor cells following their exposure to NIR light.     

Recent Advances on the Roles of PCSK-9 Inhibitors in the Management of Acute Ischemic Stroke Patients

Acute ischemic stroke (AIS) represents an important cause of disability and death. Since only a minor percentage of patients with AIS are eligible for acute therapy, the management of risk factors is mandatory. An important risk factor of AIS is hyperlipemia. The current guidelines recommend a strict correction of it. Statins are recommended as the first-line treatment, while proprotein convertase subtilin/kexin type 9 (PCSK-9) inhibitors are administered as a second or even third option when the goal for a low-density lipoprotein cholesterol (LDL-C) level is not achieved. PCSK-9 inhibitors effectively decrease the LDL-C levels through the inhibition of PCSK-9-LDL-receptor complex formation. The in-depth understanding of the PCSK-9 protein mechanism in the metabolism of LDL-C led to the development of effective targeted approaches. Furthermore, a better understanding of the LDL-C metabolic pathway led to the development of newer approaches, which increased the therapeutic options. This article aims to offer an overview of the PCSK-9 inhibitors and their mechanism in reducing the LDL-C levels. Moreover, we will present the main indications of the current guidelines for patients with hyperlipemia and for those who have suffered an acute ischemic stroke, as well as the importance of LDL-C reduction in decreasing the rate of a recurrence.     

The Implications of Noncoding RNAs in the Evolution and Progression of Nonalcoholic Fatty Liver Disease (NAFLD)-Related HCC

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver pathology worldwide. Meanwhile, liver cancer represents the sixth most common malignancy, with hepatocellular carcinoma (HCC) as the primary, most prevalent subtype. Due to the rising incidence of metabolic disorders, NAFLD has become one of the main contributing factors to HCC development. However, although NAFLD might account for about a fourth of HCC cases, there is currently a significant gap in HCC surveillance protocols regarding noncirrhotic NAFLD patients, so the majority of NAFLD-related HCC cases were diagnosed in late stages when survival chances are minimal. However, in the past decade, the focus in cancer genomics has shifted towards the noncoding part of the genome, especially on the microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), which have proved to be involved in the regulation of several malignant processes. This review aims to summarize the current knowledge regarding some of the main dysregulated, noncoding RNAs (ncRNAs) and their implications for NAFLD and HCC development. A central focus of the review is on miRNA and lncRNAs that can influence the progression of NAFLD towards HCC and how they can be used as potential screening tools and future therapeutic targets.     

Halo orbit mission correction maneuvers using optimal control

This paper addresses the computation of the required trajectory correction maneuvers for a halo orbit space mission to compensate for the launch velocity errors introduced by inaccuracies of the launch vehicle. By combining dynamical systems theory with optimal control techniques, we are able to provide a compelling portrait of the complex landscape of the trajectory design space. This approach enables automation of the analysis to perform parametric studies that simply were not available to mission designers a few years ago, such as how the magnitude of the errors and the timing of the first trajectory correction maneuver affects the correction ΔV. The impetus for combining dynamical systems theory and optimal control in this problem arises from design issues for the Genesis Discovery Mission being developed for NASA by the Jet Propulsion Laboratory.     

Chemiluminescence study on HALS antioxidant activity in LDPE

Summary The kinetic study on thermal degradation of stabilised low density polyethylene by chemiluminescence investigations was performed. Four hindered amine light stabilisers, additive compounds, were used as thermal protector on polymer substrate. The experiments were carried out on the samples consisting of polyetylene and 0.25% (w/w) of hindered amine. Three temperatures (180, 190 and 200 °C) were selected for this assay allowing the calculation of the activation energy required for thermal oxidation of polyethylene matrix. A discussion on mechanistic aspects concerning the antioxidant efficiency of studied compounds is also presented.     

Effects of random heterogeneity of soil properties on bearing capacity

This study examines the effect of random heterogeneity of soil properties on bearing capacity. The stochastic soil property considered is the undrained shear strength and two major sources of uncertainty are identified with it: inherent spatial variability (modeled as a non-Gaussian, homogeneous stochastic field) and uncertainty in the estimation of its expected value (modeled as a random variable). The two sources of uncertainty are treated separately, before being eventually combined. A Monte Carlo simulation approach is followed in combination with non-linear finite element analysis. It is demonstrated that the inherent spatial variability of soil shear strength can drastically modify the basic form of the failure mechanism in this bearing capacity problem. Consequently, there is no ‘average’ failure mechanism (surface) in this problem, leading to the conclusion that Monte Carlo simulation is the only methodology capable of providing a solution to this geomechanics problem. It is further demonstrated that this behavior of the failure mechanism translates into a substantial reduction in the ultimate bearing capacity (in an average sense), compared to the corresponding deterministic (homogeneous soil) case. In addition, differential settlements are computed in the stochastic analysis, something impossible in a deterministic analysis of a symmetric problem. A parametric study is performed using fragility curves to investigate the effects of various probabilistic parameters involved in the problem. It is found that the coefficient of variation and the marginal probability distribution of the soil's shear strength (both controlling the amount of loose pockets in the soil mass) are the two most important parameters in reducing the bearing capacity (in an average sense) and producing substantial differential settlements in heterogeneous soils (compared to homogeneous soils). A technique is finally introduced for determining ‘overall’ fragility curves that account for both inherent soil spatial variability and uncertainty in the expected value of soil strength. Based on such ‘overall’ fragility curves obtained at failure (ultimate bearing capacity), nominal values of the bearing capacity of a heterogeneous soil deposit corresponding to an exceedance probability of 5% are established for a range of probabilistic characteristics.