Sensitivity analysis of complex embedded real-time systems

The robustness of an architecture to changes is a major concern in the design of efficient and reliable state-of-the-art embedded real-time systems. Robustness is important during design process to identify if and in how far a system can accommodate later changes or updates, or whether it can be reused in a next generation product. In the product life-cycle, robustness helps the designer to perform changes as a result of product updates, integration of new components and subsystems, or modifications of the environment. In this paper we determine robustness as a performance reserve, the slack in performance before a system fails to meet timing requirements. This is measured as design sensitivity. Due to complex component interactions, resource sharing and functional dependencies, one-dimensional sensitivity analysis might not cover all effects that modifications of one system property may have on system performance. One reason is that the variation of one property can also affect the values of other system properties requiring new approaches to keep track of simultaneous parameter changes. In this paper we present a framework for one-dimensional and multi-dimensional sensitivity analysis of real-time systems. The framework is based on compositional analysis that is scalable to large systems. The one-dimensional sensitivity analysis combines a binary search technique with a set of formal equations derived from the real-time scheduling theory. The multi-dimensional sensitivity analysis engine consists of an exact algorithm that extends the one-dimensional approach, and a stochastic algorithm based on evolutionary search techniques.     

SI-ATRP Decoration of Magnetic Nanoparticles with PHEMA and Post-Polymerization Modification with Folic Acid for Tumor Cells’ Specific Targeting

Targeted nanocarriers could reach new levels of drug delivery, bringing new tools for personalized medicine. It is known that cancer cells overexpress folate receptors on the cell surface compared to healthy cells, which could be used to create new nanocarriers with specific targeting moiety. In addition, magnetic nanoparticles can be guided under the influence of an external magnetic field in different areas of the body, allowing their precise localization. The main purpose of this paper was to decorate the surface of magnetic nanoparticles with poly(2-hydroxyethyl methacrylate) (PHEMA) by surface-initiated atomic transfer radical polymerization (SI-ATRP) followed by covalent bonding of folic acid to side groups of the polymer to create a high specificity magnetic nanocarrier with increased internalization capacity in tumor cells. The biocompatibility of the nanocarriers was demonstrated by testing them on the NHDF cell line and folate-dependent internalization capacity was tested on three tumor cell lines: MCF-7, HeLa and HepG2. It has also been shown that a higher concentration of folic acid covalently bound to the polymer leads to a higher internalization in tumor cells compared to healthy cells. Last but not least, magnetic resonance imaging was used to highlight the magnetic properties of the functionalized nanoparticles obtained.     

Small Cells in Cellular Networks: Challenges of Future HetNets

Due to their low cost and easy deployment, small cells provide a viable and cost-effective way of improving the cellular coverage and capacity both for homes and enterprises, both in metropolitan and rural areas. Stimulated by their attractive features and advantages, the ongoing development and deployment of small cells by manufacturers and mobile network operators have seen a surge in recent years. Together with macro-cells, they form, what are called Heterogeneous Networks or HetNets. However, the successful rollout and operation of small cells are still facing significan issues. In this paper the need for, challenges and solutions of small cell deployments are analyzed. This analysis is conducted with respect to self-organizing features, interference coordination, energy efficiency and spectrum efficiency. The analysis is complemented with numerical results based on system simulations in Macro-only and HetNet scenarios and also on real measurements performed on an mobile operator network. Results show the clear improvement that a HetNet brings in term of user throughput and also the amunt of spectrum waste that is present in nowadays’ operator networks.     

Robust Index Assignment Using Hadamard Transform for Vector Quantization Transmission over Finite-Memory Contagion Channels

This paper presents a new index assignment (IA) method when vector quantization indices are transmitted over a particular class of Markov binary channels, namely the finite-memory contagion channels. (See F. Alajaji and T. Fuja, IEEE Trans. Inform. Theory, 40:2035-2041, 1994.) For this class of binary channels, the Hadamard transform of the vector formed with noise pattern probabilities obeys well-structured recursions, allowing an efficient evaluation of the channel distortion and also revealing a useful approximation based on the dominant terms in the channel distortion expression. The proposed IA method minimizes the distortion approximation and is very robust to changes in the parameters of the channel model. The same technique applies for both maximum likelihood and mean-squared error decoding methods. The IA algorithm is applied to the transmission of line spectral frequency parameters quantized as in the G.729 standard to show the usefulness of the proposed method.     

Entrapment of fluorescent signaling DNA aptamers in sol-gel-derived silica

We report on the first successful immobilization of a DNA aptamer, in particular, a fluorescence-signaling DNA aptamer, within a sol-gel-derived matrix. The specific aptamer examined in this study undergoes a structural switch in the presence of adenosine triphosphate (ATP) to release a dabcyl-labeled nucleotide strand (QDNA), which in turn relieves the quenching of a fluorescein label that is also present in the aptamer structure. It was demonstrated that aptamers containing a complementary QDNA strand along with either a short complimentary strand bearing fluorescein (tripartite structure) or a directly bound fluorescein moiety (bipartite structure) remained intact upon entrapment within biocompatible sol-gel derived materials and retained binding activity, structure-switching capabilities, and fluorescence signal generation that was selective and sensitive to ATP concentration. Studies were undertaken to evaluate the properties of the immobilized aptamers that were either in their native state or bound to streptavidin using a terminal biotin group on the aptamer, including response time, accessibility, and leaching. Furthermore, signaling abilities were optimized through evaluation of different QDNA constructs. These studies indicated that the aptamers remained in a state that was similar to solution, with moderate leaching, only minor decreases in accessibility to ATP, and an expected reduction in response time due to diffusional barriers to mass transport of the analyte through the silica matrix. Entrapment of the aptamer also resulted in protection of the DNA against degradation from nucleases, improving the potential for use of the aptamer for in vivo sensing. This work demonstrates that sol-gel-derived materials can be used to successfully immobilize and protect DNA-based biorecognition elements and, in particular, DNA aptamers, opening new possibilities for the development of DNA aptamer-based devices, such as affinity columns, microarrays, and fiber-optic sensors.     

Biosynthesis of silver nanoparticles in collagen gel improves their medical use in periodontitis treatment

Silver nanoparticles (AgNP) suspensions were biosynthesized by silver ions reduction in the presence of collagen, a nontoxic, organic polymer, intending to improve their medical use in periodontitis treatment. Spectrophotometric measurements showed a time- and concentration-dependent increase of AgNP formation in each suspension variant. Transmission electron microscopy revealed spherical morphology of AgNP in collagen and their mean diameter size was around 30?nm. The particle size distribution and zeta potential values of AgNP in collagen were determined by dynamic light scattering measurements. The surface charge of AgNP in collagen was positive, while commercial AgNP stabilized in citrate had negative surface charge. In vitro cytotoxicity testing of AgNP in collagen showed that they were biocompatible with human gingival fibroblasts in a wider range of concentrations than commercial nanoparticles. The antibacterial activity of AgNP in collagen against two pathogenic strains present in the periodontal pocket was dose-dependent and higher than that of AgNP in citrate. All these results demonstrated that AgNP prepared in collagen gel had improved properties, like small diameter, positive surface charge, high biocompatibility in human gingival fibroblasts, efficiency against bacterial growth and, thus, better therapeutic potential in periodontal disease treatment.     

DNA interaction of the CcrM DNA methyltransferase: a mutational and modeling study

Caulobacter crescentus CcrM is a DNA-(adenine N6)-methyltransferase that methylates adenine in the sequence GANTC with high specificity. To investigate its mechanism of DNA recognition, we used the crystal structure of a related methyltransferase (M1.MboII, which modifies GAAGA) as a starting point, and docked into it a DNA substrate to identify the protein regions that approach the DNA. After alignment of CcrM and M1.MboII, we identified four candidate regions in CcrM to contain residues involved in DNA recognition. We mutated 20 amino acid residues within these regions, purified the CcrM variants, and determined their DNA-binding and catalytic activity on a cognate GANTC substrate and on nine near-cognate substrates, each of which contained a single base-pair substitution in the recognition sequence. Altogether, we identified four residues in two of the regions, mutations of which resulted in a strong (>100-fold) reduction of methylation activity. Our data show that DNA recognition by CcrM is a cooperative process, because disruption of critical contacts led to loss of catalytic activity but not to a relaxation in specificity. In addition, we identified a change in the readout of the fifth base pair in the GANTC sequence with two other CcrM variants that showed smaller reductions in overall activity. Based on this and the sequence alignment of CcrM with other DNA methyltransferases of same or related recognition sequence, we propose roles for these two regions in DNA recognition by CcrM.