Interdependence of piezoelectric coefficient and film thickness in LiTaO3 cantilevers

Electromechanical energy demands on homogenous thick films of piezoceramics with sufficiently large piezoelectric constant and reproducible performance. Single-phase LiTaO₃ films deposited by sol-gel processing have been fabricated as cantilevers to investigate the interdependence of dielectric and piezoelectric properties as a function of film thickness. Phase pure LiTaO₃ films with varying thickness in the range of 2.07-4.37 µm on stainless steel substrates were obtained after calcination of samples at 650°C. The relative permittivity of optimized spin-coated films peaked at 479.73 (1 kHz), whereas the piezoelectric coefficient (d₃₃ mode) determined by piezoresponse force microscopy was in the range of 21-24 pm/V. The effect of poling was studied through the butterfly and phase curves. A figure of merit (FOM) up to 3.29 (10⁻¹⁸ m²/V²) was determined for cantilever devices, which were able to generate a peak-to-peak voltage of 0.046-0.15 V using a 1 MΩ resistor as an impedance load at a fixed acceleration of 1.5 m/s². While the power density was in the range of ~4-20 × 10⁻⁹ W/m³, which increased with the increasing film thickness. The leakage current density decreased in the range of 4 × 10⁻⁵-6 × 10⁻⁷ A/m² in the same direction. As both ferroelectric and piezoelectric properties of LiTaO₃ films are dependent on film thickness, an optimal energy conversion efficiency was obtained for a thickness of ~3 µm. Furthermore, these devices were tested up to a temperature of 150°C for voltage generation. Given the need for lead-free piezoelectric materials for environmental applications, these LiTaO₃ cantilevers are very promising for vibrational energy harvester (VEH) applications especially due to their cost effectiveness, small size, stability at higher temperatures, and repeatable properties, which makes them suitable for MEMS devices for industrial applications.     

The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes

Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. Bone is an adipocyte-rich organ since 50 to 70% of the adult bone marrow (BM) volume comprise bone marrow adipocytes (BM-Ads), which are likely to produce chemokines within the bone microenvironment. Using in vitro migration assays, we demonstrated that soluble factors released by human primary BM-Ads are able to support the directed migration of PCa cells in a CCR3-dependent manner. In addition, we showed that CCL7, a chemokine previously involved in the CCR3-dependent migration of PCa cells outside of the prostate gland, is released by human BM-Ads. These effects are amplified by obesity and ageing, two clinical conditions known to promote aggressive and metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone metastasis vs. primary tumors at mRNA levels using Oncomine microarray database. In addition, immunohistochemistry experiments demonstrated overexpression of CCR3 in bone versus visceral metastases. These results underline the potential importance of BM-Ads in the bone metastatic process and imply a CCR3/CCL7 axis whose pharmacological interest needs to be evaluated.     

Development of a Robust High-Throughput Screening Platform for Inhibitors of the Striatal-Enriched Tyrosine Phosphatase (STEP)

Many human diseases are the result of abnormal expression or activation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Not surprisingly, more than 30 tyrosine kinase inhibitors (TKIs) are currently in clinical use and provide unique treatment options for many patients. PTPs on the other hand have long been regarded as “undruggable” and only recently have gained increased attention in drug discovery. Striatal-enriched tyrosine phosphatase (STEP) is a neuron-specific PTP that is overactive in Alzheimer’s disease (AD) and other neurodegenerative and neuropsychiatric disorders, including Parkinson’s disease, schizophrenia, and fragile X syndrome. An emergent model suggests that the increase in STEP activity interferes with synaptic function and contributes to the characteristic cognitive and behavioral deficits present in these diseases. Prior efforts to generate STEP inhibitors with properties that warrant clinical development have largely failed. To identify novel STEP inhibitor scaffolds, we developed a biophysical, label-free high-throughput screening (HTS) platform based on the protein thermal shift (PTS) technology. In contrast to conventional HTS using STEP enzymatic assays, we found the PTS platform highly robust and capable of identifying true hits with confirmed STEP inhibitory activity and selectivity. This new platform promises to greatly advance STEP drug discovery and should be applicable to other PTP targets.     

Tumor Suppressive Role of miR-342-5p in Human Chondrosarcoma Cells and 3D Organoids

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.     

On the representation, measurement, and discovery of fuzzy associations

The use of fuzzy sets to describe associations between data extends the types of relationships that may be represented, facilitates the interpretation of rules in linguistic terms, and avoids unnatural boundaries in the partitioning of the attribute domains. In addition, the partial membership values provide a method for incorporating the distribution of the data into the assessment of a rule. This paper investigates techniques to identify and evaluate associations in a relational database that are expressible by fuzzy if-then rules. Extensions of the classical confidence measure based on the /spl alpha/-cut decompositions of the fuzzy sets are proposed to incorporate the distribution of the data into the assessment of a relationship and identify robustness in an association. A rule learning strategy that discovers both the presence and the type of an association is presented.     

Designing emotional, metaphoric, natural and intuitive interfaces for interactive art, edutainment and mobile communications

We are artists working since 1991 on the creation of interactive computer installations for which we design metaphoric, emotional, natural, intuitive and multi-modal interfaces. The interactive experiences we create are situated between art, design, entertainment and edutainment. When creating our interactive systems we often develop novel interface technologies that match conceptual and metaphoric content with technically novel interface solutions. While our main focus is to design interactive systems for the art context, our interactive or immersive systems also often find use in edutainment and in mobile communications areas. The following article summarizes some of our key concepts for our interface designs and presents some of our interactive technologies in more detail.     

The impact of deforestation on cloud cover over the Amazon arc of deforestation

Atmospheric general circulation model (AGCM) simulations predict that a complete deforestation of the Amazon basin would lead to a significant climate change; however, it is more difficult to determine the amount of deforestation that would lead to a detectable climate change. This paper examines whether cloudiness has already changed locally in the Brazilian arc of deforestation, one of the most deforested regions of the Amazon basin, where over 15% of the primary forest has been converted to pasture and agriculture. Three pairs of deforested/forested areas have been selected at a scale compatible with that of climate model grids to compare changes in land cover with changes in cloudiness observed in satellite data over a 10-year period from 1984 to 1993. Analysis of cloud cover trends suggests that a regional climate change may already be underway in the most deforested part of the arc of deforestation. Although changes in cloud cover over deforested areas are not significant for interannual variations, they are for the seasonal and diurnal distributions. During the dry season, observations show more low-level clouds in early afternoon and less convection at night and in early morning over deforested areas. During the wet season, convective cloudiness is enhanced in the early night over deforested areas. Generally speaking, the results suggest that deforestation may lead to increased seasonality; however, some of the differences observed between deforested and forested areas may be related to their different geographical locations.     

Set Computation for Nonlinear Control

This paper proposes a new approach to solve the problem of finding a control sequence for a nonlinear discrete-time system that should satisfy given set-membership specifications on the state and the output vectors. This approach is based on set computation and constraint propagation. Two illustrative examples are provided. The approach is then extended to deal with the robust control problem of nonlinear discrete-time systems. This revised version was published online in June 2006 with corrections to the Cover Date.     

Influence of frequency, electrode material and superimposed dc onac electroluminescence in polymer films

Summarizes new results on the influence of some experimental parameters on ac electroluminescence (EL) of polymers used as insulating materials in electrical engineering. Electroluminescence under a uniform ac field is investigated in low density polyethylene (PE) and polyethylene naphthalate (PEN) films with semi-transparent electrodes on both sides. Particular emphasis is given to polyethylene. The dependence of EL on the voltage frequency is investigated in the range of 10^-2 Hz to 10⁺² Hz with the help of phase-resolved measurements. The influence of the electrode/polymer contact is investigated by changing the electrode material (gold, silver, and calcium). The effect of a superimposed dc bias on the ac voltage is also reported     

A Compared Study of Two Correctness Proofs for the Standardized Algorithm of ABR Conformance

The ABR conformance protocol is a real-time program that controls dataflow rates on ATM networks. A crucial part of this protocol is the dynamical computation of the expected rate of data cells. We present here a modelling of the corresponding program with its environment, using the notion of (parametric) timed automata. A fundamental property of the service provided by the protocol to the user is expressed in this framework and proved by two different methods. The first proof relies on inductive invariants, and was originally verified using theorem-proving assistant COQ. The second proof is based on reachability analysis, and was obtained using model-checker HYTECH. We explain and compare these two proofs in the unified framework of timed automata.