Non-monotonic changes in clonogenic cell survival induced by disulphonated aluminum phthalocyanine photodynamic treatment in a human glioma cell line

<p>Abstract</p> <p>Background</p> <p>Photodynamic therapy (PDT) involves excitation of sensitizer molecules by visible light in the presence of molecular oxygen, thereby generating reactive oxygen species (ROS) through electron/energy transfer processes. The ROS, thus produced can cause damage to both the structure and the function of the cellular constituents resulting in cell death. Our preliminary investigations of dose-response relationships in a human glioma cell line (BMG-1) showed that disulphonated aluminum phthalocyanine (AlPcS₂) photodynamically induced loss of cell survival in a concentration dependent manner up to 1 μM, further increases in AlPcS₂concentration (>1 μM) were, however, observed to decrease the photodynamic toxicity. Considering the fact that for most photosensitizers only monotonic dose-response (survival) relationships have been reported, this result was unexpected. The present studies were, therefore, undertaken to further investigate the concentration dependent photodynamic effects of AlPcS₂.</p> <p>Methods</p> <p>Concentration-dependent cellular uptake, sub-cellular localization, proliferation and photodynamic effects of AlPcS₂were investigated in BMG-1 cells by absorbance and fluorescence measurements, image analysis, cell counting and colony forming assays, flow cytometry and micronuclei formation respectively.</p> <p>Results</p> <p>The cellular uptake as a function of extra-cellular AlPcS₂concentrations was observed to be biphasic. AlPcS₂was distributed throughout the cytoplasm with intense fluorescence in the perinuclear regions at a concentration of 1 μM, while a weak diffuse fluorescence was observed at higher concentrations. A concentration-dependent decrease in cell proliferation with accumulation of cells in G₂+M phase was observed after PDT. The response of clonogenic survival after AlPcS₂-PDT was non-monotonic with respect to AlPcS₂concentration.</p> <p>Conclusions</p> <p>Based on the results we conclude that concentration-dependent changes in physico-chemical properties of sensitizer such as aggregation may influence intracellular transport and localization of photosensitizer. Consequent modifications in the photodynamic induction of lesions and their repair leading to different modes of cell death may contribute to the observed non-linear effects.</p

Antimicrobial activity against oral pathogens and immunomodulatory effects and toxicity of geopropolis produced by the stingless bee Melipona fasciculata Smith

<p>Abstract</p> <p>Background</p> <p>Native bees of the tribe Meliponini produce a distinct kind of propolis called geopropolis. Although many pharmacological activities of propolis have already been demonstrated, little is known about geopropolis, particularly regarding its antimicrobial activity against oral pathogens. The present study aimed at investigating the antimicrobial activity of <it>M. fasciculata </it>geopropolis against oral pathogens, its effects on <it>S. mutans </it>biofilms, and the chemical contents of the extracts. A gel prepared with a geopropolis extract was also analyzed for its activity on <it>S. mutans </it>and its immunotoxicological potential.</p> <p>Methods</p> <p>Antimicrobial activities of three hydroalcoholic extracts (HAEs) of geopropolis, and hexane and chloroform fractions of one extract, were evaluated using the agar diffusion method and the broth dilution technique. Ethanol (70%, v/v) and chlorhexidine (0.12%, w/w) were used as negative and positive controls, respectively. Total phenol and flavonoid concentrations were assayed by spectrophotometry. Immunotoxicity was evaluated in mice by topical application in the oral cavity followed by quantification of biochemical and immunological parameters, and macro-microscopic analysis of animal organs.</p> <p>Results</p> <p>Two extracts, HAE-2 and HAE-3, showed inhibition zones ranging from 9 to 13 mm in diameter for <it>S. mutans </it>and <it>C. albicans</it>, but presented no activity against <it>L</it>. <it>acidophilus</it>. The MBCs for HAE-2 and HAE-3 against <it>S. mutans </it>were 6.25 mg/mL and 12.5 mg/mL, respectively. HAE-2 was fractionated, and its chloroform fraction had an MBC of 14.57 mg/mL. HAE-2 also exhibited bactericidal effects on <it>S. mutans </it>biofilms after 3 h of treatment. Significant differences (p < 0.05) in total phenol and flavonoid concentrations were observed among the samples. Signs toxic effects were not observed after application of the geopropolis-based gel, but an increase in the production of IL-4 and IL-10, anti-inflammatory cytokines, was detected.</p> <p>Conclusions</p> <p>In summary, geopropolis produced by <it>M. fasciculata </it>can exert antimicrobial action against <it>S. mutans </it>and <it>C. albicans</it>, with significant inhibitory activity against <it>S. mutans </it>biofilms. The extract with the highest flavonoid concentration, HAE-2, presented the highest antimicrobial activity. In addition, a geopropolis-based gel is not toxic in an animal model and displays anti-inflammatory effect.</p

Experimental and numerical determination of casting-mold interfacial heat transfer coefficient in the high pressure die casting of A-360 aluminum alloy

Although die casting is a near net shape manufacturing process, it mainly involves a thermal process. Therefore, in order to produce high quality parts, it is important to determine casting-mold interfacial heat transfer coefficient and heat flux. In this paper the effects of different injection parameters (second phase velocity, injection pressure, pouring and die temperature) on heat flux and interfacial heat transfer coefficient were investigated experimentally and numerically. Experiments were performed in cylindrical geometry using a cast aluminum alloy A360 against H13 steel mold. Selected injection parameters were 1.7-2.5 m/s for second phase velocity, 100-200 bar for third phase pressure, 983-1053 K for pouring temperature and 373, 433, 493, 553 K for the die temperature. These parameters were used for both non-vacuum and vacuum conditions in the cavity of the mold. The effects of the application under vacuum conditions were also studied. Temperatures were measured as functions of time, using 18 thermocouples, which were mounted at different depths of casting and mold material. Measured and calculated temperature values are found compatible. Interfacial heat transfer coefficient h and heat flux q depending on the experimentally measured temperature values were calculated with finite difference method using explicit technique in C# programming language. In addition to experiments, Flow-3D software simulations were performed using the same parameters. Interfacial heat transfer coefficient and heat flux results obtained from Flow-3D are also presented in the study. Interfacial heat transfer coefficient has decreased as a result of increasing of temperature of mold and pouring. In addition, interfacial heat transfer coefficient values have increased slightly with the increase of injection speed and pressure. It was observed that the values of interfacial heat transfer coefficient and heat flux have also increased when vacuum was applied inside the cavity of the mold. When all injection parameters are considered, it is seen that the interfacial heat transfer coefficient varies between 92-117 kW/m² K

Decentralized process modeling notations for horizontal change approach

Horizontal Change Approach (HOC-A) is a software process improvement approach that enables individuals to define and improve their own processes. It is assumed that peer-wise conflict resolution efforts among individuals are crucial and supply continuous process improvement for the total processes. In order to support individual process modeling and improvement, HOC-A requires a notation that supports decentralized process modeling. In this paper, we give a brief description of HOC-A in the light of previous research on decentralized process modeling. Then, we analyze notations that can be used for decentralized process modeling and discuss their applicability to HOC-A

Process-product unification in a decentralized environment: A status report

Process-product unification and decentralization when considered together reflect the actual behavior of software development organizations These two concepts enable team members to switch between process and product activities easily, and empower them to take process definition, enactment and monitoring responsibility. In this paper, we investigate the requirements of software development techniques and tools that support unification and decentralization. Our focus is on defining a modeling notation that enables developers to encode both product and process related information, using a single representation that captures all the knowledge related to a specific software project

Scalar leptoquark production at TESLA and CLIC based e−γe-\gamma colliders

We study scalar leptoquark production at TESLA and CLIC based e-gamma colliders. Both direct and resolved contributions to the cross section are examined. We find that the masses of scalar leptoquarks can be probed up to the mass values about 70% of the collider energies