Mitochondria-targeted disruptors and inhibitors of cytochrome c/cardiolipin peroxidase complexes: a new strategy in anti-apoptotic drug discovery

The critical role of mitochondria in programmed cell death leads to the design of mitochondriotropic agents as a strategy in regulating apoptosis. For anticancer therapy, stimulation of proapoptotic mitochondrial events in tumor cells and their suppression in surrounding normal cells represents a promising paradigm for new therapies. Different approaches targeting regulation of components of mitochondrial antioxidant system such as Mn-SOD demonstrated significant antitumor efficiency, particularly in combination therapy. This review is focused on a newly discovered early stage of mitochondria-dependent apoptosis - oxidative lipid signaling involving a mitochondria-specific phospholipid cardiolipin (CL). Cytochrome c (cyt c) acts as a CL-specific peroxidase very early in apoptosis. At this stage, the hostile events are still secluded within the mitochondria and do not reach the cytosolic targets. CL oxidation process is required for the release of pro-apoptotic factors into the cytosol. Manipulation of cyt c interactions with CL, inhibition of peroxidase activity, and prevention of CL peroxidation are prime targets for the discovery of anti-apoptotic drugs acting before the "point-of-no-return" in the fulfillment of the cell death program. Therefore, mitochondria-targeted disruptors and inhibitors of cyt c/CL peroxidase complexes and suppression of CL peroxidation represent new strategies in anti-apoptotic drug discovery.     

Assessment of Dewatering Requirements and Dewatering Well Design for an Open Pit Coal Mine in Central Anatolia

The Çeltikçi Coal Basin is a newly discovered coal basin in Central Anatolia where 11 years of open-cut mining has been planned. The bulk of the mining will be conducted below the regional water table; hence, determination of the dewatering requirements and proper design of the dewatering wells plays a critical role. This study (i) defined the dewatering requirements of the open-pit mine, (ii) established a dewatering well design for the area, and (iii) assessed the anticipated impacts of the dewatering activities. For this purpose, a 3-D numerical groundwater flow model was developed using the FEFLOW software. Yearly dewatering requirements were determined under transient conditions. For the dewatering well simulations, two types of dewatering wells were considered: permanent wells located at the open pit boundary that would increase in number as the excavation proceeds and wells located at the periphery of the yearly excavated area that would be operational for about two years. The simulation results indicated that 894 wells were required to satisfy dry working conditions; the average pumping rate throughout the mine life was calculated as 322 L/s. The impacts of open-pit dewatering on groundwater resources were assessed in terms of spring discharge and base flow rates in the nearby Kirmir stream. As a result of dewatering, most of the village water supply springs and fountains will dry up in the area. In addition, the base flow rates to the Kirmir stream will be decreased by 15%.

     

Mechanical and rheological behavior of highly filled polystyrene with lignin

The mechanical, rheological, and morphological properties of polystyrene (PS)/lignin blends over a wide range of lignin content (0–80 wt%) have been studied in this work. PS/lignin blends were compounded in an internal batch mixer with and without the addition of a linear triblock copolymer based on styrene, ethylene, and butylene (SEBS). A morphological analysis was carried out by scanning electron microscopy to determine the state of dispersion and the interfacial adhesion between the lignin particles and the PS matrix. It was found that the flexural and torsion moduli both increased, while the tensile properties decreased with increasing lignin content. Nevertheless, compatibilizer addition was found to improve the tensile properties of the lignin/PS blend. The shear rheological behavior of the lignin/PS blends was also studied in this work where viscosity, dynamic moduli, and activation energy were found to be very sensitive to both lignin and compatibilizer contents. POLYM. COMPOS., 2012. © 2012 Society of Plastics Engineers     

Design,development and modelling of single actuated,compliant and symmetrical multi link hopping mechanism

Journal of Mechanical Science and Technology - In this study, we present the design and development of a compliant multi-link hopping mechanism actuated by a single DC motor. Mechanism consists of...     

Using of Photoluminescent Tile for Evacuation of the Buildings During Electrical Failure

Photoluminescent pigments could be successfully applied on the wall tiles, floor tiles and porcelain tiles as well as glass substrates （glass mosaics, borders, and cutted glass with various designs）. For this applications, these products can be used for different purposes. In this study, these pigments are applied on the ceramic tiles and glass mosaics/tiles with traditional ceramic production line. These products are intentended to provide guidance in the event of a power failure. With this study also aimed to prevent potential accidents and injury during evacuation of building.     

Atmospheric concentrations, dry deposition and air-soil exchange of polycyclic aromatic hydrocarbons (PAHs) in an industrial region in Turkey

Concurrent ambient air and dry deposition samples were collected during two sampling periods at the Aliaga industrial region in Izmir, Turkey. Sigma 15-PAH (particulate+gas) concentrations ranged between 7.3 and 44.8 ng m(-3) (average+/-S.D., 25.2+/-8.8 ng m(-3)) and 10.2-71.9 ng m(-3) (44.1+/-16.6 ng m(-3)) in summer and winter, respectively. Winter/summer individual ambient PAH concentration ratios ranged between 0.8 (acenaphthene) and 6.6 (benz[a]anthracene) indicating that wintertime concentrations were affected by residential heating emissions. In contrast to the ambient concentrations, summation operator(15)-PAH particle dry deposition fluxes were higher in summer (5792+/-3516 ng m(-2)day(-1), average+/-S.D.) than in winter (2650+/-1829 ng m(-2)day(-1)), probably due to large particles from enhanced re-suspension of polluted soil particles and road dust. Average overall dry deposition velocity of PAHs calculated using the dry deposition fluxes and particle-phase concentrations was 2.9+/-3.5 cm s(-1). summation operator(15)-PAH concentrations in soils taken from 50 points in the area ranged between 11 and 4628 microg kg(-1) in dry weight. The spatial distribution of these concentrations indicated that the urban Aliaga, steel plants, the petroleum refinery, and the petrochemical plant are the major Sigma 15-PAH sources in the area. Fugacity calculations in air and soil showed that the soil acts as a secondary source to the atmosphere for low molecular weight PAHs in summer and as a sink for the higher molecular weight ones in summer and winter.     

Nigella sativa oil entrapped polycaprolactone nanoparticles for leishmaniasis treatment

This study is the first to investigate the antileishmanial activities of Nigella sativa oil (NSO) entrapped poly‐ɛ ‐caprolactone (PCL) nanoparticles on Leishmania infantum promastigotes and amastigotes in vitro. NSO molecules with variable initial doses of 50, 100, 150, and 200 mg were successfully encapsulated into PCL nanoparticles identified as formulations NSO1, NSO2, NSO3, and NSO4, respectively. This process was characterised by scanning electron microscope, dynamic light scattering, Fourier transform infrared, encapsulation efficiency measurements, and release profile evaluations. The resulting synthetised nanoparticles had sizes ranging between 200 and 390 nm. PCL nanoparticles encapsulated 98% to 80% of initial doses of NSO and after incubation released approximately 85% of entrapped oil molecules after 288 h. All investigated formulations demonstrated strong antileishmanial effects on L. infantum promastigotes by inhibiting up to 90% of parasites after 192 h. The tested formulations decreased infection indexes of macrophages in a range between 2.4‐ and 4.1‐fold in contrast to control, thus indicating the strong anti‐amastigote activities of NSO encapsulated PCL nanoparticles. Furthermore, NSO‐loaded PCL nanoparticles showed immunomodulatory effects by increasing produced nitric oxide amounts within macrophages by 2–3.5‐fold in contrast to use of free oil. The obtained data showed significant antileishmanial effects of NSO encapsulated PCL nanoparticles on L. infantum promastigotes and amastigotes.Inspec keywords: antibacterial activity, drug delivery systems, nanofabrication, nitrogen compounds, nanomedicine, microorganisms, cellular biophysics, diseases, scanning electron microscopy, oils, polymers, biomedical materials, nanoparticles, encapsulation, Fourier transform infrared spectraOther keywords: encapsulation efficiency measurements, entrapped oil molecules, investigated formulations, NSO‐loaded PCL nanoparticles, Nigella sativa oil entrapped polycaprolactone nanoparticles, antileishmanial activities, poly‐ε‐caprolactone nanoparticles, scanning electron microscope, DLS, Fourier transform infrared, release profile evaluations, Leishmania infantum promastigotes, Leishmania infantum amastigotes, parasites, infection, infection indexes, macrophages, immunomodulatory effects, time 288.0 hour, time 192.0 hour, mass 50.0 mg, mass 100.0 mg, mass 150.0 mg, mass 200.0 mg, size 200.0 nm to 390.0 nm