Modeling of gold microbeams as strain and pressure sensors for characterizing MEMS packages

This work presents the modeling of gold microbeams for characterizing Micro-electro-mechanical systems (MEMS) packages in terms of both strains induced to the MEMS devices and hermetic sealing capability. The proposed test structures are based on arrays of rectangular-shaped clamped-free and clamped–clamped beams, to be realized with a film of electroplated gold by surface micromachining technology. The resonant frequency of the microbeams is modeled by FEM simulations as a function of substrate deformations, which could be induced by the package. Clamped–clamped bridges show a linear change of the square of the resonant frequency in case of in-plane deformations, in fairly good agreement with an approximate analytical model. Cantilever beams are modeled as variable capacitors to detect out-of-plane deformations. Finally, an analytical model to study cantilever beams as resonators for detecting pressure changes is discussed and compared with preliminary experimental results, showing an impact on the quality factor in a range from 10^?2 mbar to 1?bar.     

PI3K and AKT: Unfaithful Partners in Cancer

The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway regulates multiple cellular processes. An overactivation of the pathway is frequently present in human malignancies and plays a key role in cancer progression. Hence, its inhibition has become a promising approach in cancer therapy. However, the development of resistances, such as the abrogation of negative feedback mechanisms or the activation of other proliferative signaling pathways, has considerably limited the anticancer efficacy of PI3K/AKT inhibitors. In addition, emerging evidence points out that although AKT is acknowledged as the major downstream effector of PI3K, both PI3K and AKT can operate independently of each other in cancer, revealing another level of complexity in this pathway. Here, we highlight the complex relationship between PI3K and AKT in cancer and further discuss the consequences of this relationship for cancer therapy.     

TEM investigation on zirconate formation and chromium poisoning in LSM/YSZ cathode

Cell durability is a crucial technological issue for SOFC commercialization, and considerable progress has been made in recent years. A number of degradation pathways have been established, amongst which microstructural changes, poisoning effects and formation of less conductive phases. In this study, transmission electron microscopy was used to observe submicron-scale effects on selected cathode zones of an anode supported cell tested in SOFC stack repeat element configuration. The test has been performed with a dedicated segmented test bench, at 800 °C for 1900 h, which allowed to spatially resolve degradation processes, and therefore to improve their correlation with localized post-test analysis. Evidence is presented of reaction products (mainly SrZrO₃) at the LSM/YSZ interfaces as well as of contaminants, in particular Cr, but also Si. A polarized cell segment is compared to an unpolarized one, to assess any influence of cathode polarization.     

A hierarchical modeling approach for risk assessment in developmental toxicity studies

Within the past decade, there has been an increasing interest in the problem of joint analysis of clustered multiple outcome data, motivated by developmental toxicity applications. Typically, a toxic insult early in gestation may result in a resorbed fetus or a fetal death. If however the fetus survives the entire gestation period, growth reduction such as low birth weight may occur, or can exhibit a malformation. Ideally, a model should take the complete hierarchical structure of the data into account. So far, however, one has tackled the challenges in this setting only partly each time making different restricting assumptions (e.g., restriction to viable fetuses only). In addition, because of genetic similarity and the same treatment conditions, offsprings of the same mother behave more alike than those of another mother. Thus, responses on different fetuses within a cluster are likely to be correlated. The ultimate scientific question requires assessing the full effect of dose administration, not only in the malformation and weight outcome, but also in the death outcome. A hierarchical Bayesian method is proposed to this effect. Such a model can serve as a basis for quantitative risk assessment.     

Extra-cellular volume estimation by electrical impedance--phase measurement or curve fitting: a comparative study

The intestinal polyamine transporters have not yet been identified. Our aim was to characterize specific polyamine binding sites in rabbit intestinal brush-border membranes (IBBM) as a starting step for identification of polyamine transporters. This was investigated at 4 degrees and at low membrane concentration. Saturation isotherms for [3H]putrescine (PUT) binding indicated a single population of sites (puT) with a dissociation equilibrium constant Kd of 3.8 microM and a density of sites Bmax of 58 pmol/mg of protein. [3H]spermidine (SPD) binding also involved only one class of sites (spD), albeit with a lower affinity (Kd = 106 microM) and higher abundance (Bmax = 1240 pmol/mg of protein) than puT. On the contrary, [14C]spermine (SPM) bound two classes of sites (spM1 and spM2) differing in their affinity (Kd = 2.5 and 31.4 microM) and abundance (Bmax = 467 and 1617 pmol/mg of protein, respectively). Membrane association of SPM at 4 degrees was much faster than that of SPD and PUT, both of which proceeded at a similar rate. In contrast to PUT and SPD dissociation, SPM dissociation at 23 degrees did not follow a first-order reaction. Specifically bound [3H]PUT, unlike [3H]SPD and [14C]SPM, dissociated at 23 degrees independently of the addition of nonradioactive polyamine. Methylglyoxal-bis-(guanylhydrazone) was an extremely potent inhibitor of PUT binding (Ki = 3.2 +/- 1.5 nM), but as with PUT and cadaverine (CAD), it did not alter [3H]SPD and [14C]SPM binding substantially. The intestinal brush-border membrane may contain at least three sites specific for polyamine binding and exhibiting different ligand selectivity. Site puT might be associated with the transport system already described for intestinal uptake of PUT.     

Experimental and Theoretical Investigation of Degradation Mechanisms by Particle Coarsening in SOFC Electrodes

Performance degradation data obtained from single solid oxide fuel cells, tested at 850 °C with air and humidified H₂ and using Ni‐YSZ anode supported cells, are presented here. Microscopic investigation is carried out on both anode and cathode to quantify variations in the morphology at different operation times. The comparison between the measurements on the cells and the SEM image analysis allows to conclude that there is no relationship between the initial cell activation and microstructural modifications of the electrodes. On the other hand, it was found that cell degradation is strictly related to the coarsening of Ni particles occurring in the anode. A theoretical analysis based on an electrode micromodel has been performed in order to compare the variation in performance, expected from particle size change, with the observed data. The model confirmed the conclusions of the experimental results.     

On auto- and cross-interdependence in interval field finite element analysis

This paper discusses the concepts of auto- and cross-interdependence in interval field finite element analysis. In classic interval analysis, independent intervals are used to construct hyper-rectangular input spaces that correspond to the bounded uncertainty that is present on some model parameters. This is a direct result from the inability of modeling interdependence. Such assumption of complete independence might prove in some cases to be highly over-conservative. A first example is the modeling of spatial uncertainty, where the interdependence is governed by allowable spatial gradients of field realizations. Secondly, interdependence can also occur in case uncertainty in several structural quantities has the same root cause (eg, the manufacturing process). Recent work by the authors introduced concepts for modeling dependence between intervals in a spatial and multivariate context. However, it is unclear how an analyst has to deal with multiple quantities that have a spatial uncertainty component and are furthermore interdependent. This paper presents an approach to link multiple interval fields using recently introduced convex hull pair constructions and inverse distance weighting interpolation. Two case studies to illustrate the new methodology are included, proving the flexibility of the methodology in the modeling of auto- and cross-interdependence between multiple interval scalars and/or interval fields.     

Analysis of the effect of structural defects on the fatigue strength of RFSSW joints using C‐scan scanning acoustic microscopy and SEM

Solid‐state refill friction stir spot welding (RFSSW) technology offers significant benefits in the fabrication of aluminium structures in the transport and aerospace industries. In this paper, the joining of 1.6‐mm‐thick Alclad 7075‐T6 aluminium alloy sheets is investigated. High‐cycle fatigue strength tests of single‐lap welded joints were carried out on an Instron E10000 testing machine with a limited number of cycles equal to 2 × 10⁶. The welding of overlap fatigue specimens was conducted using an RPS100 spot welder by Harms & Wende GmbH & Co KG. C‐mode scanning acoustic microscopy (C‐SAM) and scanning electron microscopy (SEM) were utilised to evaluate the joint quality and characterise the microstructure. The paper discusses the effect of the maximum load force and defects (voids, hook, kissing bond, bonding ligament, etc) associated with the material flow in the weld on the failure mechanism. Insufficient plasticisation of sheet material and mixing of the material in the weld area are crucial defects that influence the number of destructive cycles. The weld defects in the joint structure are a source of a decrease in the fatigue life compared with the fatigue life of defect‐free welds. It was also found that RFSSW joint defects can be effectively detected by the nondestructive C‐SAM method.     

Variability,heterogeneity, and anisotropy in the quasi‐static response of laser sintered PA12 components

Additive manufacturing (AM) receives an increasing industrial interest thanks to its advantages in the economic production of highly complex and small‐series components. Especially laser sintering (LS) is in this context of particular interest for the production of plastic components, as it is generally deemed the most robust AM technology for polymer parts and therefore is expected to enable AM for functional components in the near future. However, to date, designers are often confronted with a severe lack of knowledge on the possible mechanical behavior of AM components. More specifically, the unit‐to‐unit variability, heterogeneity (within‐part variation), and anisotropy of the mechanical properties very often prove to be substantial and therefore require more elaborated studies in order to take these effects into account in the engineering of reliable components. Moreover, typical experimental results that are used for the determination of the elastic stiffness tensor are subject to variability, caused by the influence of the difference in thermal history between produced parts. This work therefore focuses first on the identification and quantification of the variability and heterogeneity in the quasi‐static response of laser sintering‐polyamide 12 (LS‐PA12) components. Second, also the anisotropy in this quasi‐static response is studied. For the first part, uniaxial tensile tests are performed and the variability on the quasi‐static properties is quantified by means of statistical analysis. Also, the elastic stiffness tensor is identified based on these tests. Next, the heterogeneity in the tested specimens is investigated by means of digital image correlation. Finally, in order to study the anisotropy in the quasi‐static properties, the Virtual Fields Method is applied to determine the variability in the elastic stiffness tensor of the LS‐PA12 material. A variability with a coefficient of variance of up to 6.5% on Young's modulus was measured. It was also found that the production planning has an important influence on the homogeneity of the mechanical properties of the produced parts. Finally, the Virtual Fields Method showed that, contrary to most literature on the topic, the elastic properties of LS‐PA12 material is best described using an isotropic material model.     

Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca²⁺ release from the sarcoplasmic reticulum (0 mM Ca²⁺), but it reduced the subsequent tonic phase characterised by Ca²⁺ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca²⁺ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K⁺ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.