Antioxidant activity of cyclolinopeptides

Cyclolinopeptides (CLs) are hydrophobic cyclic peptides found in flaxseed. They show immunosuppressive activity, but the biological function of these compounds is largely unknown. This thesis presents the results of studies that were conducted to determine whether CLs could act as antioxidants. In the first study, flaxseed oil was passed over a silica adsorbent column to remove polar compounds. The polar compounds were then eluted from the silica absorbant using a series of increasingly polar solvents. Individual polar fractions were then added back to the silica-treated flaxseed oil and the oxidative stability index of these samples was determined at 100 °C. A polar fraction containing mainly CLA, β/γ- and δ-tocopherol increased the induction time of silica-treated flaxseed oil from 2.3 ± 0.28 h to 3.2 ± 0.41 h. A positive effect of the polar fraction containing a mixture of CLA and CLD-CLG on the oxidative stability of oil was also observed. The antioxidant mechanism of CLs was investigated in several model systems using electron spin resonance spectroscopy. The concentration of radicals in a DMPO (5,5-dimethyl-1-pyrroline-N-oxide) radical-CLs reaction mixture was monitored. All CLs exhibited dose dependent scavenging activities. CLA–CLC reactions with DMPO-OH at a concentration of 5 mM resulted in a 24–30% decrease in electron paramagnetic resonance (EPR) signal intensity. The reaction of CLs and the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•) revealed a more complex interaction than simple radical scavenging. Peptides (CLG and CLG") that contained both tryptophan and methionine showed stronger radical scavenging activity than did CLs containing methionine or methionine sulfoxide but not tryptophan (CLB and CLC). Irradiation of the reaction mixture of DPPH• and peptide with UV light also affected the radical scavenging behaviour. Scavenging activities of DPPH• by CLB, CLC and CLA were enhanced by light, whereas scavenging of DPPH• by the tryptophan containing peptides CLG and CLG″ was not affected. High-performance liquid chromatography with mass spectrometry (HPLC-MS) analysis of the reaction mixtures after a radical scavenging reaction was used to determine the impact of radical scavenging on the peptides. These reactions revealed new masses that were identified and characterized. It was established that DPPH• reacted with the methionine of CLB and with tryptophan in CLG and CLG, by formation of a new covalently-bonded species. Covalent linkages between these amino acids (alone or in peptides) and DPPH• have not been reported previously

COMPUTER SIMULATION: TRAFFIC-RELATED AIR POLLUTION AND THE TRAFFIC SIGNAL CYCLE TIME OPTIMIZATION

Emissions from motor vehicles, one of the most important air pollution sources in the city, is emerging as a growing problem in large-scale cities. The amounts of emissions are affected by the number of vehicles in traffic, vehicle technology, geometric and traffic conditions of highways and intersections, and environmental factors. Traffic flow is mostly interrupted at Intersections in local traffic, especially in city centers. Emissions of these points, where traffic behavior is changed and vehicles stop and go, are higher as compared to uninterrupted flows. In this study, current state emissions at 120 Intersection were determined by SIDRA INTERSECTION software. Then, new emissions are determined by the same software after improvement in signalization. As a result of the study, fuel consumption and pollutant emissions were calculated before and after improvement. As a result of observations at the intersection, current state fuel consumption was calculated as 1718.2, l/hour, and CO2, CO, HC, and NOX emissions were 40464.7, 3.821, 0.482, and 5.060 kg/hour respectively for the morning. After that current state fuel consumption was calculated as 1492.1, l/hour, and CO2, CO, HC, and NOX emissions were 3522, 3.116, 0.406, and 3.246 kg/hour respectively for the evening. It has been determined that there were significant differences between the current state and after improvement. Improvements in geometric conditions or signalization at intersections may result in a decrease in vehicle emissions and improve the air quality in cities

Formulation and Evaluation of Fusidic Acid Emulgel

Emulgel have emerged as one of the most interesting topical delivery system as it has dual control release system i.e gel and emulsion. Topical applications of drug offers many advantages for delivering drug directly to the site of action and deliver the drug for extended period of time at effected site. The major objective behind this formulation is to enhance topical delivery of hydrophobic drug (Fusidic acid) by formulating Fusidic acid emulgel by using carbopol 934 as gelling agent. In addition light liquid paraffin as oil, span 20 as emulsifier and propylene glycol as co-surfactant were selected for the preparation of emulgel. Fusidic acid is steroidal bacteriostatic agent produced from Fusidium coccineum fungus belongs to class of steroids but has no corticosteroids effect and which is useful for the treatment of number of infections. Fusidic acid binds to protein and ribosomes and inhibits bacterial protein synthesis. The prepared emulgel were evaluated for their physical appearance, pH determination, viscosity, spreadability, in-vitro drug release, antimicrobial activity, skin irritation study and stability. All the prepared emulgel showed acceptable physical properties. The best formulation E9 shows better drug release when compared to all formulation. Keywords: Emulgel, Carbopol 934, Topical formulation, Antimicrobial activity, optimization, Fusidic aci

Formulation and evaluation of in situ ophthalmic gel of loteprednol etabonate

The aim of present study was to prepared ocular in-situ gel to increase the residence time of drug in cornea for improvement of ocular bioavailability of drug. In situ gel of Loteprednol etabonate was prepared by using carobopol 940 and different grades of HPMC in different ratios by pH triggered method. The prepared in situ gels were evaluated for pH, drug content, viscosity, gelling time, gelling strength spreadability and sterility testing. In vitro drug release study was carried by using diffusion cell with dialysis membrane. The drug content and pH of the formulation were found to be satisfactory. The gelling strength was found to be in the range of 34 seconds to 91 seconds. The viscosity and spredability of the formulations were found to be satisfactory. Formulation F5 containing 0.3 % carobopol 940 and 0.6 % HPMC K4M showed highest drug release of 80.30 %. The developed formulations showed sustained release of drug up to 8 hrs. From in-vitro drug release studies, it could be concluded that the developed in-situ gelling systems were thus a better alternative to conventional eye drops

Network Analysis of the Tel Aviv Mass Transit Plan

This paper analyzes the strategic transit network plan for the Tel Aviv metropolitan area, using graph theory and other recently developed transit network measures. The different transit modes included in the strategic plan are emphasized by adding weights to distinguish metro lines from light rail lines (LRT). This approach can help compare the combined metro or LRT alternatives of the new Tel Aviv plan to the metro-only alternatives  as well as measure the performance relative to the metro systems in other cities around the world. The analysis of the alternative plans in Tel Aviv showed that when metro and LRT lines were treated as homogeneous modes, in which all were considered as metro, the alternatives resembled medium developed metro systems, such as in Barcelona and Washington DC. In contrast, when the distinguished weights were included, the combined metro/LRT alternatives resembled less developed systems, such as in Lyon and Lisbon, and only the metro-only alterative score remained high. The results also showed that the alternatives have regional coverage, and the alternatives with more LRT lines score lower in coverage. The network structure analysis showed that the metro-oriented networks score higher in both directness and connectivity. When using the weighted measures, the existing plan (LRT-only) scores low on both directness and connectivity. The analysis of the results emphasizes the need for more metro lines in the Tel Aviv metropolitan area. The results also suggest that the analysis of the complex mass transit networks based on graph theory should consider differences in line technology reflected in the line speed and coverage. Document type: Articl

Geochemistry and geochronology of the Paleozoic sedimentary rocks in the Shar Khutul area, Central Mongolia

The study area is located in the central part of Tsetserleg terrane in the southwestern margin of the Khangai-Khentey orogenic system. The paper presents new data on geochemistry and geochronology of sedimentary rocks from the Shar Khutul area, where the Tsetserleg terrane consists of Silurian-Devonian oceanic plate stratigraphic unit and Carboniferous shallow water sediment. The Upper Silurian to Middle Devonian Erdenetsogt Formation (S3-D2er), which is an oceanic plate stratigraphic unit, is mainly composed of siliceous siltstone, volcanites, tuffs, quartzite, and cherts. The shallow water sediments are divided into Upper Devonian to Lower Carboniferous Tsetserleg Formation (D3-C1cc) and Lower–Middle Carboniferous Dzargalant Formation (C1-2dz). The Tsetserleg Formation (D3-C1cc) consists of only sedimentary rocks such as bluish-grey sandstones and siltstones, and Lower–Middle Carboniferous Dzargalant Formation (C1-2dz) is principally composed of medium- to coarse-grained, brown-greenish grey sandstones with thin-layers of dark siltstones and gravelites. The SiO2 content of the Shar Khutul area sandstones ranges from 63.85 to 67.95 wt.% and the average content of TiO2 is 0.72 wt.% and Al2O3 content is 14.38 wt.%. The Chemical Index of Alteration (CIA) value ranges from 48.71 to 56.94 and the range of Index of compositional variations (ICV) is from 0.98 to 1.24. Moreover, the samples studied show that most of the sandstones are generally immature and were derived from weakly weathered source rocks. The ratios of Eu/Eu* (0.83), La/Sc (3.81), La/Co (5.30), and Cr/Th (13.81) indicate that the derivation of the Shar Khutul area sandstones from felsic rock sources and confirm the signatures of a felsic igneous provenance and suggest an active continental margin tectonic setting of the source area. The clastic zircons from the medium grained sandstone (Erdenetsogt formation) yield ages between 2.5 Ga and 236 Ma and the detrital zircons exhibit four peak ages at 1.7-2.5 Ga (n = 13), 455-499 Ma (n = 6), 337-382 Ma (n = 13) and 236–250 Ma (n = 5)

Molecular basis of allergen cross-reactivity: Non-specific lipid transfer proteins from wheat flour and peach fruit as models

Peach non-specific lipid transfer protein (Pru p 3; nsLTP) has been characterized as the major food allergen in the adult Mediterranean population. Its wheat homologous protein, Tri a 14 has a relevant inhalant allergen in occupational baker's asthma. Different sensitization patterns to these allergens have been found in patients with this latter disorder. The objective of the present study was to characterize IgE epitopes of Tri a 14 and to compare them with those of Pru p 3 using three complementary strategies: the analysis of IgE-binding capacity of decapeptides bound to membrane, the identification of mimotopes using a phage display random peptide library, and the analysis of the surface electrostatic potential of both allergens. Thus, synthetic overlapping decapeptides, covering the Pru p 3 and Tri a 14 amino acid sequences, were used to identify sequential regions involved in recognition of IgE from baker's asthma patients sensitized to both nsLTPs. A phage display library was screened with total IgE from the same patients, and positive clones sequentially selected using the purified allergens, allowed to identify mimotopes (conformational epitopes) of Tri a 14 and Pru p 3. Both sequential regions and mimotopes were localized in the corresponding 3D molecular surface and their electrostatic properties were analyzed. Common sequential regions with strong IgE-binding capacity (residues 31–40 and 71–80) were identified in Tri a 14 and Pru p 3, whereas regions Tri a 1451–60 and Pru p 311–20 were found specific of each allergen. A major conformational epitope (mimotope), L34H35N36R39S40S42D43G74V75L77P78Y79T80, which comprised the two common sequential epitopes, was located in Tri a 14, and a very similar one in Pru p 3. However, differences were detected on the surface electrostatic potential of both mimotopes: a first part (around residues 31–45) showed similar positive features in both allergens, whereas a second part (around residues 74–80) was markedly negative in Tri a 14 but neutral-positive in Pru p 3. Tri a 14 and Pru p 3 have a similar conformational region involved in IgE-binding, although their electrostatic features are different. Additionally, common and specific sequential IgE-binding regions were mapped in both allergens. These findings could be instrumental in understanding the cross-reactivity and specificity of sensitization to both homologous allergens

Leishmania spp. proteome data sets: a comprehensive resource for vaccine development to target visceral leishmaniasis

Visceral leishmaniasis is a neglected infectious disease caused primarily by Leishmania donovani and Leishmania infantum protozoan parasites. A significant number of infections take a fatal course. Drug therapy is available but still costly and parasites resistant to first line drugs are observed. Despite many years of trial no commercial vaccine is available to date. However, development of a cost effective, needle-independent vaccine remains a high priority. Reverse vaccinology has attracted much attention since the term has been coined and the approach tested by Rappuoli and colleagues. This in silico selection of antigens from genomic and proteomic data sets was also adapted to aim at developing an anti-Leishmania vaccine. Here, an analysis of the efforts is attempted and the challenges to be overcome by these endeavors are discussed. Strategies that led to successful identification of antigens will be illustrated. Furthermore, these efforts are viewed in the context of anticipated modes of action of effective anti-Leishmania immune responses to highlight possible advantages and shortcomings