Infantile familial cardiomyopathy due to mitochondrial complex I and IV associated deficiency

Two brothers, aged 27 and 20 months, born from consanguineous healthy parents, presented with cardiomyopathy, lactic acidosis and carnitine abnormalities in serum and muscle, without clinical evidence of muscle involvement. The histochemical reaction for cytochrome c oxidase (COX) activity was negative in all muscle fibres, although the holoenzyme and subunits were present at a normal level, as shown by immunocytochemistry. The COX activity was, respectively, 5 and 25% of control values, in muscle biopsies. Partial deficiency of complex IV was confirmed in fresh isolated muscle mitochondria from patient 2 and was associated with a defect of complex I. Patient 1 died at age 3 yr 6 months. Partial improvement of cardiomyopathy in patient 2 was obtained under carnitine therapy, but seizures occurred and CT scan and magnetic resonance imaging (MRI) revealed thalamic hypodensity. Thus, the disorder appears to be progressive despite the clinical stabilization of the cardiomyopathy. This further demonstrates the complexity and clinical heterogeneity of combined respiratory chain complex deficiencies.     

Transfection ability and intracellular DNA pathway of nanostructured gene-delivery systems

Considerable efforts have been devoted to the design of structured materials with functional properties. Polyelectrolyte multilayer films are now a well-established nanostructured concept with numerous potential applications, in particular as biomaterial coatings. This technique allows the preparation of nanostructured architectures exhibiting specific properties for cell-activation control and local drug delivery. In this study, we used a multilayered system made of poly-(l-lysine)/hyaluronic acid (PLL/HA) as a reservoir for active DNA complexes with nonviral gene-delivery vectors, PLL, beta-cyclodextrin (CD), and PLL-CD. When embedded into the multilayered films, the transfection efficiencies of the DNA complexes and the cell viability were improved. The highest transfection efficiency was obtained with the PLL-CD/plasmid DNA (pDNA) complexes. We found that this high transfection efficiency was related to an efficient internalization of the complexes in the cell cytoplasm and selected nuclei domains through a nonendocytotic pathway. For the first time, we report the intracellular pathway of the pDNA in complexes incorporated into the multilayered system.     

Towards historical document indexing: extraction of drop cap letters

This paper deals with the difficult problem of indexing ancient graphic images. It tackles the particular case of indexing drop caps (also called Lettrines) and specifically, considers the problem of letter extraction from this complex graphic images. Based on an analysis of the features of the images to be indexed, an original strategy is proposed. This approach relies on filtering the relevant information, on the basis of Meyer decomposition. Then, in order to accommodate the variability of representation of the information, a Zipf’s law modeling enables detection of the regions belonging to the letter, what allows it to be segmented. The overall process is evaluated using a relevant set of images, which shows the relevance of the approach.     

High Performance Organic Transistors Using Small Molecule Semiconductors and High Permittivity Semiconducting Polymers

High mobility organic semiconductor formulations with excellent uniformity across large area substrates are prepared via the use of formulations containing small molecule and high permittivity semiconducting oligomers. The use of these high‐k (k > 3.3) oligomers allows control of the wetting via the manipulation of the surface energy of the substrate being coated. Organic thin film transistors results with mobilities of up to 5 cm² V^‐1 s^‐1, standard deviation <10 %, on/off ratios of 10⁹ are presented.     

New insights in the relation between electron trap generation andthe statistical properties of oxide breakdown

In this paper it is demonstrated in a wide stress field range that breakdown in thin oxide layers occurs as soon as a critical density of neutral electron traps in the oxide is reached. It is proven that this corresponds to a critical hole fluence, since a unique relationship between electron trap generation and hole fluence is found independent of stress field and oxide thickness. In this way literature models relating breakdown to hole fluence or to trap generation are linked. A new model for intrinsic breakdown, based on a percolation concept, is proposed. It is shown that this model can explain the experimentally observed statistical features of the breakdown distribution, such as the increasing spread of the Q_BD-distribution for ultrathin oxides. An important consequence of this large spread is the strong area dependence of the Q_BD for ultrathin oxides     

An experimental comparison of clustering methods for content-based indexing of large image databases

In recent years, the expansion of acquisition devices such as digital cameras, the development of storage and transmission techniques of multimedia documents and the development of tablet computers facilitate the development of many large image databases as well as the interactions with the users. This increases the need for efficient and robust methods for finding information in these huge masses of data, including feature extraction methods and feature space structuring methods. The feature extraction methods aim to extract, for each image, one or more visual signatures representing the content of this image. The feature space structuring methods organize indexed images in order to facilitate, accelerate and improve the results of further retrieval. Clustering is one kind of feature space structuring methods. There are different types of clustering such as hierarchical clustering, density-based clustering, grid-based clustering, etc. In an interactive context where the user may modify the automatic clustering results, incrementality and hierarchical structuring are properties growing in interest for the clustering algorithms. In this article, we propose an experimental comparison of different clustering methods for structuring large image databases, using a rigorous experimental protocol. We use different image databases of increasing sizes (Wang, PascalVoc2006, Caltech101, Corel30k) to study the scalability of the different approaches.     

Assessment of temperature and voltage accelerating factors for 2.3–3.2 nm SiO2 thin oxides stressed to hard breakdown

The temperature and voltage acceleration for a large database of time dependent dielectric breakdown in 2.3 and 3.2 nm SiO₂ oxides is investigated. All results deal with the time to hard breakdown which is defined when a typical high current limit (1 mA) at operating voltage is reached rather than detecting the first current change as is conventionally done. Using an accurate experimental error evaluation, long range data are compared for consistency to the predictions of various state-of-the-art extrapolation models used to qualify these oxides, to point out which one describes the data best. The activation energies corresponding to the dominant degradation mechanisms are extracted over a temperature range from 50 °C to 125 °C for N type substrate stressed in accumulation regime. The voltage extrapolation models are compared for P and N type substrate with positive stress polarity on the gate. It is verified that a TDDB power voltage law is well predictive for both P substrate in inversion regime and N substrate in accumulation regime.     

Tumor-targeted polydiacetylene micelles for in vivo imaging and drug delivery

In vivo tumor targeting and drug delivery properties of small polymerized polydiacetylene (PDA) micelles (～10 nm) is investigated in a murine MDA-MB-231 xenograft model of breast cancer. Three micelles with different surface coatings are synthesized and tested for their ability to passively target tumor through the enhanced permeability and retention effect. After injection (24 h), fluorescence diffuse optical tomographic imaging indicates a tumor uptake of nearly 3% of the injected dose for the micelles with a 2 kDa poly(ethylene glycol) (PEG)-coating (PDA-PEG2000). The uptake of PDA micelles in tumors is confirmed by co-localization with [(18) F]-fluorodeoxyglucose (FDG) positron emission tomography. Although FDG has a higher diffusion rate in tumors, 40 ± 19% of the retained micelles is co-registered with the tumor volume visualized by FDG. Finally, PDA-PEG2000 micelles are loaded with the hydrophobic anticancer drug paclitaxel and used in vivo to inhibit tumor growth. These findings demonstrate the potential of PDA-PEG2000 micelles for both in vivo tumor imaging and drug delivery applications.     

Pyridylamino‐β‐cyclodextrin as a Molecular Chaperone for Lipopolysaccharide Embedded in a Multilayered Polyelectrolyte Architecture

Layer‐by‐layer self‐assembled polyelectrolyte films containing a charged cyclodextrin and lipopolysaccharide (LPS) are developed for the first time as a potential model for local endotoxin antagonist delivery. We have examined the biological activity of a lipopolysaccharide from E. coli incorporated into multilayered architectures made of poly‐(L ‐lysine) and poly‐(L ‐glutamic acid). Used in such build‐ups, a polycationic cyclodextrin, heptakis(6‐deoxy‐6‐pyridylamino)‐β‐cyclodextrin showed molecular chaperone properties by enabling restoration of the LPS biological activity whenever lost upon interaction with poly‐(L ‐lysine).     

The A and the extended V N-terminal regions of streptococcal protein I/IIf mediate the production of tumour necrosis factor alpha in the monocyte cell line THP-1

Signal transduction is ubiquitously involved in the initiation of physiological signals that lead to growth and proliferation of cells. The signaling cascade mediated by the mitogen-activated protein kinase (MAPK) is considered essential for T cell growth and function. Therefore, it was of interest to determine the influence of age on the induction of MAPK in mitogen-activated T cells. T cells from young (4-6 months) and old (24-26 months) rats responded to concanavalin A (Con A) stimulation by increasing MAPK, c-jun amino terminal kinase (JNK), and p21ras activities. The time course of induction of MAPK/JNK and p21ras activities was similar in T cells isolated from young and old rats. The induction of JNK activity did not change significantly with age; however, the induction of MAPK and p21ras activities was significantly less (50 to 65%) in T cells from old rats than in T cells from young rats. Although the relative protein levels of p42 and p44 MAPK did not change with age, the proportion of the phosphorylated p44 MAPK decreased with age. In addition, it was found that the in vitro kinase activities of the T cell receptor-associated protein tyrosine kinase Lck (p56Lck) and ZAP-70 but not Fyn (p59Fyn) were lower in T cells from old rats than in T cells from young rats. The decline in activities of these signaling molecules with age was not associated with changes in their corresponding protein levels. Thus, our results demonstrate that aging alters the activation of the signal transduction cascade that leads to T cell activation.