Bidimensional lifetime control for high-speed low-loss p-i-nrectifiers

In the paper a lifetime control technique able to control device carrier lifetime not only in the axial direction, but also in the longitudinal direction (two-dimensional (2-D) lifetime control), is analyzed. Static and dynamic losses of p-i-n diode using 2-D lifetime control are studied through mixed mode circuit-device simulations. It is shown that the 2-D technique gives a better tradeoff between static and dynamic behavior with respect to electron irradiation technique. The comparison with axial lifetime control shows that, notwithstanding similar performances achieved using the two techniques, 2-D lifetime control provides greater design flexibility     

Fusion between retinal rod outer segment membranes and model membranes: a role for photoreceptor peripherin/rds

Peripherin/rds plays an essential role in the maintenance of photoreceptor rod cell disk membrane structure. The purification of this protein to homogeneity [Boesze-Battaglia, K., et al. (1997) Biochemistry 36, 6835-6846] has allowed us to characterize the functional role of peripherin/rds in the maintenance of rod outer segment (ROS) membrane fusion processes. Utilizing a cell-free fusion assay system, we report that the fusion of R18-labeled ROS plasma membrane (R18-PM) with disk membranes or peripherin/rds-enriched large unilammellar vesicles (LUVs) is inhibited upon trypsinolysis of peripherin/rds. To understand this phenomenon, we tested the ability of a series of overlapping synthetic C-terminal peripherin/rds peptides to mediate model membrane fusion. Within the 63 amino acid long region of the C-terminus, we identified a minimal 15 residue long amino acid sequence (PP-5), which is necessary to promote membrane fusion. PP-5 was able to inhibit R18-PM disk membrane fusion and promoted ANTS/DPX contents mixing in a pure vesicle system. This peptide (PP-5) promoted calcium-induced vesicle aggregation of phosphatidylethanolamine:phosphatidylserine LUVs. FTIR analysis confirmed the structural prediction of this peptide as alpha-helical. When modeled as an alpha-helix, this peptide is amphiphilic with a hydrophobicity index of 0.75 and a hydrophobic moment of 0.59. PP-5 has substantial biochemical and functional homology with other well-characterized membrane fusion proteins. These results demonstrate the necessity for peripherin/rds in ROS membrane fusion, specifically the requirement for an intact C-terminal region of this protein.     

Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions

To determine whether oxidized LDL enhances atherogenesis by promoting monocyte recruitment into the vascular intima, we investigated whether LDL accumulation and oxidation precede intimal accumulation of monocytes in human fetal aortas (from spontaneous abortions and premature newborns who died within 12 h; fetal age 6.2+/-1.3 mo). For this purpose, a systematic assessment of fatty streak formation was carried out in fetal aortas from normocholesterolemic mothers (n = 22), hypercholesterolemic mothers (n = 33), and mothers who were hypercholesterolemic only during pregnancy (n = 27). Fetal plasma cholesterol levels showed a strong inverse correlation with fetal age (R = -0.88, P < 0.0001). In fetuses younger than 6 mo, fetal plasma cholesterol levels correlated with maternal ones (R = 0.86, P = 0.001), whereas in older fetuses no such correlation existed. Fetal aortas from hypercholesterolemic mothers and mothers with temporary hypercholesterolemia contained significantly more and larger lesions (758,651+/-87,449 and 451,255+/-37,448 micron2 per section, respectively; mean+/-SD) than aortas from normocholesterolemic mothers (61,862+/-9,555 micron2; P < 0.00005). Serial sections of the arch, thoracic, and abdominal aortas were immunostained for recognized markers of atherosclerosis: macrophages, apo B, and two different oxidation-specific epitopes (malondialdehyde- and 4-hydroxynonenal-lysine). Of the atherogenic sites that showed positive immunostaining for at least one of these markers, 58.6% were established lesions containing both macrophage/foam cells and oxidized LDL (OxLDL). 17.3% of all sites contained only native LDL, and 13.3% contained only OxLDL without monocyte/ macrophages. In contrast, only 4.3% of sites contained isolated monocytes in the absence of native or oxidized LDL. In addition, 6.3% of sites contained LDL and macrophages but few oxidation-specific epitopes. These results demonstrate that LDL oxidation and formation of fatty streaks occurs already during fetal development, and that both phenomena are greatly enhanced by maternal hypercholesterolemia. The fact that in very early lesions LDL and OxLDL are frequently found in the absence of monocyte/macrophages, whereas the opposite is rare, suggests that intimal LDL accumulation and oxidation contributes to monocyte recruitment in vivo.     

Endothelium-protective effects of epinine (N-methyldopamine) in myocardial ischemia-reperfusion in the isolated working rat heart

The effect of cardiac dopaminergic receptors stimulation with epinine (N-methyldopamine) on reperfusion injury was investigated in isolated working rat heart submitted to 15 min of global ischemia. Isolated Wistar rat hearts (n = 75) were used and subdivided into five groups: Group A control hearts, Group B epinine 10 ng/ml, Group C epinine 20 ng/ml, Group D epinine 40 ng/ml, Group E epinine 80 ng/ml. The drug was added to the perfusion buffer at the beginning of experimental procedures. Hemodynamic parameters, heart rhythm (epicardial ECG), heart weight changes, coronary microvascular permeability (FITC-albumin diffusion) and myocytes damage (necrosis enzymes release, immunoperoxidase labeling anti-LDH antibody) were evaluated. After ischemia in groups B and C a significant reduction of functional alterations and myocytes damage was observed with respect to Group A associated with a significant reduction of reperfusion edema (heart weight: Group A +29 +/- 3.5%, Group B +15 +/- 3.8%, Group C 16 +/- 5%, Group D 27 +/- 5%, Group E 33 +/- 4%). At reperfusion time, a significant proarrhythmic effect occurred only in groups D and E. A significant reduction of postischemic endothelial FITC-albumin diffusion was also observed in groups B and C (FITC-albumin diffusion, Group A 32.8 +/- 6% area, Group B 16.33 +/- 5% area, Group C 21.7 +/- 4.5% area, Group D 30 +/- 5% area, Group E 35 +/- 7% area). Our data show that, in isolated working rat heart, the dopaminergic stimulation with low-doses epinine may exert a cardioprotective effect against ischemia-reperfusion damage by modulating endothelial permeability changes and improving coronary microcirculation. The importance of dopaminergic receptors is also suggested by the evidence that at higher doses, when alpha and beta-adrenoceptors stimulation occurs, this cardioprotective effect is significantly reduced or lost.     

On mining complex sequential data by means of FCA and pattern structures

Nowadays data-sets are available in very complex and heterogeneous ways. Mining of such data collections is essential to support many real-world applications ranging from healthcare to marketing. In this work, we focus on the analysis of “complex” sequential data by means of interesting sequential patterns. We approach the problem using the elegant mathematical framework of formal concept analysis and its extension based on “pattern structures”. Pattern structures are used for mining complex data (such as sequences or graphs) and are based on a subsumption operation, which in our case is defined with respect to the partial order on sequences. We show how pattern structures along with projections (i.e. a data reduction of sequential structures) are able to enumerate more meaningful patterns and increase the computing efficiency of the approach. Finally, we show the applicability of the presented method for discovering and analysing interesting patient patterns from a French healthcare data-set on cancer. The quantitative and qualitative results (with annotations and analysis from a physician) are reported in this use-case which is the main motivation for this work.     

Behaviour of natural organic mater during ultrasonic irradiation

Ultrasonic irradiation has been one of the advanced oxidation methods for natural organic matter (NOM) removal. Its application simplicity and no production of toxic by-products make the system attractive. It has been shown that high power ultrasound produces strong cavitation in aqueous solution causing shock wave and reactive free radicals by the violent collapse of the cavitation bubble. These effects should contribute to the physical disruption and inactivation of microbial structures as well as to the decomposition of toxic chemicals in the water. The objective of this research was to investigate the effectiveness of low frequency – high power sonication for NOM removal (measured by both means of UV₂₅₄ absorbance and TOC) as well as controlling DBPs formation by varying irradiation time, light intensity, NOM concentration. Temperature, pH, conductivity, redox potential, and turbidity were monitored to evaluate the experimental study. The results indicate a strong capacity of sonication for NOM removal. The preliminary experiments showed that NOM removal is influenced by the intensity and time of sonication. Ultrasound, applied under such conditions, may be a realistic possibility for large-scale treatment; however, further studies should be performed to evaluate its effectiveness on different water sources.     

Retinal Pigment Epithelium Remodeling in Mouse Models of Retinitis Pigmentosa

In retinitis pigmentosa (RP), one of many possible genetic mutations causes rod degeneration, followed by cone secondary death leading to blindness. Accumulating evidence indicates that rod death triggers multiple, non-cell-autonomous processes, which include oxidative stress and inflammation/immune responses, all contributing to cone demise. Inflammation relies on local microglia and recruitment of immune cells, reaching the retina through breakdowns of the inner blood retinal barrier (iBRB). Leakage in the inner retina vasculature suggests similarly altered outer BRB, formed by junctions between retinal pigment epithelium (RPE) cells, which are crucial for retinal homeostasis, immune response, and privilege. We investigated the RPE structural integrity in three models of RP (rd9, rd10, and Tvrm4 mice) by immunostaining for zonula occludens-1 (ZO-1), an essential regulatory component of tight junctions. Quantitative image analysis demonstrated discontinuities in ZO-1 profiles in all mutants, despite different degrees of photoreceptor loss. ZO-1 interruption zones corresponded to leakage of in vivo administered, fluorescent dextran through the choroid-RPE interface, demonstrating barrier dysfunction. Dexamethasone, administered to rd10 mice for rescuing cones, also rescued RPE structure. Thus, previously undetected, stereotyped abnormalities occur in the RPE of RP mice; pharmacological targeting of inflammation supports a feedback loop leading to simultaneous protection of cones and the RPE.