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.     

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.     

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.     

Engineering of Janus-Like Dendrimers with Peptides Derived from Glycoproteins of Herpes Simplex Virus Type 1: Toward a Versatile and Novel Antiviral Platform

Novel antiviral nanotherapeutics, which may inactivate the virus and block it from entering host cells, represent an important challenge to face viral global health emergencies around the world. Using a combination of bioorthogonal copper-catalyzed 1,3-dipolar alkyne/azide cycloaddition (CuAAC) and photoinitiated thiol–ene coupling, monofunctional and bifunctional peptidodendrimer conjugates were obtained. The conjugates are biocompatible and demonstrate no toxicity to cells at biologically relevant concentrations. Furthermore, the orthogonal addition of multiple copies of two different antiviral peptides on the surface of a single dendrimer allowed the resulting bioconjugates to inhibit Herpes simplex virus type 1 at both the early and the late stages of the infection process. The presented work builds on further improving this attractive design to obtain a new class of therapeutics.     

A new short-path distillation system applied to the reduction of cholesterol in butter and lard

A molecular distillation plant, built particularly to increase the separation efficiency and to obtain safer working conditions, was tested to remove cholesterol from anhydrous butter and lard. A preliminary experiment was carried out with butter to evaluate the fractionation obtained at temperatures between 190 and 250°C and residual pressures between 10⁻³ and 10⁻⁴ torr. A second experiment was carried out at 185°C and at the maximum operational vacuum, evaluating the fractionation achieved within a time scale between 30 and 180 min. Cholesterol was almost completely removed during the second hour with minimal loss of low-molecular weight triglycerides. An experiment was carried out with lard at 250°C and maximum achievable operational vacuum (10⁻⁴ Torr), lasting approximately 6 h, and cholesterol was removed almost completely during the second hour without significant modifications in the triglyceride composition. This situation remained constant throughout the duration of the test.     

The effect of protein binding on ibuprofen adsorption to activated carbons

The potential of a range of polymer-based activated carbons to remove a non-steroidal anti-inflammatory drug ibuprofen from protein containing and protein-free solutions was studied. The adsorption capacity of five activated carbons produced from phenol-formaldehyde resin precursors (MAST Carbon Ltd) was compared to a cellulose coated activated carbon Norit RBX used in a commercial Adsorba^®300C haemoperfusion column (Gambro).Ibuprofen adsorption was studied in batch experiments over 24 h at pH=7.6 and 25 °C and adsorption equilibrium data were correlated with the Langmuir and Freundlich equations.Results showed that uncoated mesoporous MAST carbons can remove ibuprofen from model solutions both in the presence and absence of serum albumin. Ibuprofen is a highly protein-bound drug and the presence of serum albumin significantly affects the adsorption of ibuprofen by cellulose-coated microporous carbon used in Adsorba^®300C column.