A Bio-Conjugated Fullerene as a Subcellular-Targeted and Multifaceted Phototheranostic Agent

Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C₇₀@lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C₇₀@lysozyme are confirmed using UV-visible and 2D ¹H, ¹⁵N NMR spectroscopy. The excellent imaging contrast of C₇₀@lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C₇₀@lysozyme and its ability to initiate cell death by means of singlet oxygen (¹O₂) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C₇₀@lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.     

A simple model for deep dynamic stall conditions

The present study is focused on modeling of dynamic stall behavior of a pitching airfoil. The deep stall regime is in particular considered. A model is proposed, which has a low implementation and computational complexity but yet is able to deal with different types of dynamic stall conditions, including those characterized by multiple vortex shedding at the airfoil leading edge. The proposed model is appraised against an extensive data set of experimental (α,C_L) curves for NACA0012. The results of an existing widely used model, having comparable complexity, are also shown for comparison. The proposed model is able to well reproduce not only the classic curves of deep dynamic stall but also the curves characterized by lift oscillations at high angles of attack due to the shedding of multiple vortices. Furthermore, the model appears to be robust to variations of its parameters from the optimal values and of the airfoil geometry. Finally, the model is successfully implemented in a commercial CFD software and applied to the simulation of a vertical axis wind turbine within the actuator cylinder approach. The accuracy of the prediction of the turbine power coefficient in the whole rotation cycle is very good for the optimal working condition of the turbine, for which the model parameters were calibrated. Fairly good accuracy is also obtained in significantly different working conditions without any further calibration.     

Modeling and sensitivity analysis of fire emissions in southern Africa during SAFARI 2000

This paper uses three recently generated southern African satellite burned area products for the month of September 2000 in a sensitivity study of regional biomass burning emissions for a number of trace gases and particulates. Differences in the extent and location of areas burned among products generated from Moderate Resolution Imaging Spectroradiometer (MODIS), Systeme Pour l'Observation de la Terre (SPOT-VEGETATION), and Along Track Scanning Radiometer (ATSR-2) data are significant and result in different emissions estimates for woodland and grassland land cover types. Due to the different emission profiles in woodlands and grasslands, favoring relatively more products of incomplete combustion in woodlands compared with products of complete combustion in grasslands in the late dry season, these changes are not proportional to the differences in the burned area amounts. The importance of accurate burned area information not just in terms of the total area but also in terms of its spatial distribution becomes apparent from our modeling results. This paper highlights the urgent need for satellite data producers to provide accuracy assessments associated with satellite-derived products. Preferably, these accuracy data will be spatially explicit, or defined in a way that can be applied in a spatially explicit modeling context, to enable emissions uncertainties to be defined with respect to different landscape units in support of greenhouse gas emissions reporting.     

In vivo formation of 8-Epi-prostaglandin F2 alpha is increased in hypercholesterolemia

F2-isoprostanes are bioactive prostaglandin (PG)-like compounds that are produced from arachidonic acid through a nonenzymatic process of lipid peroxidation catalyzed by oxygen free-radicals. 8-Epi-PGF2 alpha may amplify the platelet response to agonists, circulates in plasma, and is excreted in urine. We examined the hypothesis that the formation of 8-epi-PGF2 alpha is altered in patients with hypercholesterolemia and contributes to platelet activation in this setting. Urine samples were obtained from 40 hypercholesterolemic patients and 40 age- and sex-matched control subjects for measurement of immunoreactive 8-epi-PGF2 alpha. Urinary excretion of 11-dehydro-thromboxane (TX) B2, a major metabolite of TXA2, was measured as an in vivo index of platelet activation. Low-dose aspirin, indobufen, and vitamin E were used to investigate the mechanism of formation and effects of 8-epi-PGF2 alpha on platelet activation. Urinary 8-epi-PGF2 alpha was significantly (P = .0001) higher in hypercholesterolemic patients than in control subjects: 473 +/- 305 versus 205 +/- 95 pg/mg creatinine. Its rate of excretion was inversely related to the vitamin E content of LDL and showed a positive correlation with urinary 11-dehydro-TXB2. Urinary 8-epi-PGF2 alpha was unchanged after 2-week dosing with aspirin and indobufen despite complete suppression of TX metabolite excretion. Vitamin E supplementation was associated with dose-dependent reductions in both urinary 8-epi-PGF2 alpha and 11-dehydro-TXB2 by 34% to 36% and 47% to 58% at 100 and 600 mg daily, respectively. We conclude that the in vivo formation of the F2-isoprostane 8-epi-PGF2 alpha is enhanced in the vast majority of patients with hypercholesterolemia. This provides an aspirin-insensitive mechanism possibly linking lipid peroxidation to amplification of platelet activation in the setting of hypercholesterolemia. Dose-dependent suppression of enhanced 8-epi-PGF2 alpha formation by vitamin E supplementation may contribute to the beneficial effects of antioxidant treatment.     

Comparison of a modified Sugiura procedure with portal systemic shunt for prevention of recurrent variceal bleeding in cirrhosis

BACKGROUND: There is no agreement on the management of patients with cirrhosis and recurrent variceal bleeding after failure of medical or endoscopic treatments or both. Portal systemic shunts are highly effective in preventing rebleeding but are associated with a high incidence of chronic encephalopathy. This study compared the results of a slightly modified Sugiura procedure (esophageal transection plus esophagogastric devascularization plus splenectomy) with those of nonselective portal systemic shunts in patients with previous variceal bleeding. METHODS: Fifty-four patients were included in this randomized controlled study between January 1984 and April 1989. The major end point was chronic encephalopathy. Secondary end points were recurrent variceal bleeding, survival, ascites, and hepatocellular carcinoma. RESULTS: Twenty-seven patients were assigned to each group. The rate of chronic encephalopathy was significantly (p = 0.002) lower after modified Sugiura procedure than after portal systemic shunt. Recurrent variceal bleeding was more frequent after modified Sugiura procedure than after portal systemic shunt, but the difference is not significant. One-, two-, and three-year survival rates were 93%, 81%, and 67%, respectively, in the modified Sugiura group and 78%, 66%, and 39%, respectively, in the portal systemic shunt group (p = 0.044). CONCLUSIONS: These results suggest that the modified Sugiura procedure is better overall than the nonselective portal systemic shunt in the management of patients with cirrhosis and recurrent variceal bleeding. Although the rebleeding rate is higher after the modified Sugiura procedure, this does not seem to affect mortality in these patients.     

Gamma-Ray-Induced Multi-Effect on Properties of Chalcogenide Glasses

Gamma-ray irradiations induced various alterations in sulfur- and selenium-based chalcogenide glasses. The absorbed dose was in the range of 0.01–3.6 MGy. The glasses exhibit prominent sensitivity to γ-ray irradiation, characterized by changes in some of the physical properties of the glasses, e.g., optical transmission, optical band gap, density, and thermal expansion coefficient. The effects on glass structure and microscopic morphology were also studied by Raman spectra and scanning electron microscopic observations.     

Sequential intraluminal endoscopic and laparoscopic treatment for bile duct stones associated with gallstones

BACKGROUND: On the basis of a flowchart including prior or current jaundice or pancreatitis, abnormal liver function, ultrasound or IV cholangiography, bile duct (BD) stones were suspected in 71/593 patients referred for gallstones. METHODS: When endoscopic retrograde cholangiography detected BD stones, endoscopic sphincterotomy (ES) and endoscopic BD clearance were attempted, followed by laparoscopic cholecystectomy (LC). BD stones were found in 44/71 patients. The sensitivity values of preoperative conditions were: 92% for IV cholangiography, 88% for abnormal liver function, 50% for ultrasound, and 37% for jaundice at admission. RESULTS: Endoscopic clearance succeeded in 37 patients and LC was completed in 33 patients. Conversion to open surgery (9%) was comparable with the rate in patients without BD stones. The median hospital stay for the sequential endoscopic and laparoscopic treatments was 13 days (range 4-54) or 22 days if open surgery was used. CONCLUSIONS: In conclusion, BD stones can be endoscopically cleared preoperatively in most patients without interfering with LC.     

Nonenzymatic browning induced by gamma-irradiation in model system Part IV. Three components system consisting of fructose, alanine and phenylalanine

Summary The effect of irradiation on the nonenzymatic browning reaction in the model system consisting of 0,03M-fructose, 0.01M-alanine and 0.01M-phenylalanine in aqueous solution was investigated. The loss of phenylalanine and fructose after irradiation, due to their high reactivity towards radical species of water radiolysis was greater compared with alanine. The heating of preirradiated solution caused only a slight decrease in the concentration of substrates. The characteristic absorption spectra for only irradiated and for irradiated and heated solutions were recorded. The heating produced a chromophore with a broadened absorption maximum about 285 nm. Two unidentified Amadori type compounds which gave positive response to ninhydrin were found by amino-acid analysis.

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Durch -Strahlung induzierte nichtenzymatische Bräunung im Modell-System Teil IV. Dreikomponentenmodellsystem aus Fructose, Alanin und Phenylalanin

Zusammenfassung Es wurde der Einfluß von -Strahlen auf die nichtenzymatische Bräunung im Dreikomponenten-Modellsystem, bestehend aus 0,03m-Fructose, 0,01m-Alanin und 0,01m-Phenylalanin in wäßriger Lösung untersucht. Der Verlust an Phenylalanin und Fructose nach der Bestrahlung war größer als bei Alanin wegen dessen größerer Reaktivität zu den Radikalen der Wasserradiolyse. Beim Erhitzen von bestrahlten Losungen wurde eine Abnahme in der Konzentration von Substraten beobachtet. Es wurden die charakteristischen Absorptionsspektren von lediglich bestrahlten und von bestrahlten und gleichzeitig erhitzten Lösungen aufgenommen. Beim Erhitzen wird ein Chromophor mit breitem Absorptionsmaximum bei ungefähr 285 nm, gebildet. Es wurden zwei nichtidentifizierte Amadoriprodukte mit positiver Ninhydrin-Reaktion bei den Aminosäureanalysen gefunden.

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For part 3 see [8]     

Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.