A Multi-step Virtual Screening Protocol for the Identification of Novel Non-acidic Microsomal Prostaglandin E2 Synthase-1 (mPGES-1) Inhibitors

Microsomal prostaglandin E₂ synthase-1 (mPGES-1) is a potential therapeutic target for the treatment of inflammatory diseases and certain types of cancer. To identify novel scaffolds for mPGES-1 inhibition, we applied a virtual screening (VS) protocol that comprises molecular docking, fingerprints-based clustering with diversity-based selection, protein–ligand interactions fingerprints, and molecular dynamics (MD) simulations with molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The hits identified were carefully analyzed to ensure the selection of novel scaffolds that establish stable interactions with key residues in the mPGES-1 binding pocket and inhibit the catalytic activity of the enzyme. As a result, we discovered two promising chemotypes, 4-(2-chlorophenyl)-N-[(2-{[(propan-2-yl)sulfamoyl]methyl}phenyl)methyl]piperazine-1-carboxamide ( 6 ) and N-(4-methoxy-3-{[4-(6-methyl-1,3-benzothiazol-2-yl)phenyl]sulfamoyl}phenyl)acetamide ( 8 ), as non-acidic mPGES-1 inhibitors with IC₅₀ values of 1.2 and 1.3 μm , respectively. Minimal structural optimization of 8 resulted in three more compounds with promising improvements in inhibitory activity (IC₅₀: 0.3–0.6 μm ). The unprecedented chemical structures of 6 and 8 , which are amenable to further derivatization, reveal a new and attractive approach for the development of mPGES-1 inhibitors with potential anti-inflammatory and anticancer properties.     

Colloid retention in porous media: mechanistic confirmation of wedging and retention in zones of flow stagnation

A three-dimensional particle tracking model for colloid transport in porous media was developed that predicts colloid retention in porous media in the presence of an energy barrier via two mechanisms: (1) wedging of colloids within grain to grain contacts; (2) retention of colloids (without attachment) in flow stagnation zones. The model integrates forces experienced by colloids during transport in porous media, i.e., fluid drag, gravity, diffusion, and colloid-surface Derjaguin-Landau-Verwey-Overbeek interactions. The model was implemented for a fluid flow field that explicitly represented grain to grain contacts. The model utilized a variable time stepping routine to allow finer time steps in zones of rapid change in fluid velocity and colloid-surface interaction forces. Wedging was favored by colloid: collector ratios greater than about 0.005, with this threshold ratio increasing with decreasing fluid velocity. Retention in flow stagnation zones was demonstrated for colloid: collector ratios less than about 0.005, with this threshold decreasing with increasing fluid velocity. Both wedging and retention in flow stagnation zones were sensitive to colloid-surface interaction forces (energy barrier height and secondary energy minimum depth). The model provides a mechanistic basis for colloid retention in the presence of an energy barrier via processes that were recently hypothesized to explain experimental observations.     

Microencapsulation of Extra Virgin Olive Oil by Spray Drying: Effect of Wall Materials Composition,Process Conditions,and Emulsification Method

Food and Bioprocess Technology - The objective of the study was to investigate the microencapsulation of extra virgin olive oil by spray drying to increase its stability and application area. The...     

Analysis of diffracted fields with the extended theory of the boundary diffraction wave for impedance surfaces

Uniform diffracted fields from impedance surfaces are investigated by the extended theory of boundary diffraction wave (ETBDW). The new vector potential of the ETBDW is constructed by considering the pseudoimpedance boundary condition. The method is applied to the diffraction problem from an impedance half-plane. It is shown that the total fields from an impedance half-plane reduce to the case of a perfectly electric or magnetic conducting and opaque half-plane for special values of surface impedance. The total and diffracted fields are compared numerically with the exact solution for the impedance half-plane and modified theory of physical optics (MTPO) solution for an impedance wedge. The numerical results show that the field expressions are in very good agreement with the exact and MTPO solutions.     

Selective IgA deficiency and ankylosing spondylitis

A man with an ankylosing spondylitis (AS) and selective IgA deficiency is described. There have been several reports in the literature indicating coexistence of AS with selective IgA deficiency. As it is suggested in the literature, we believe that selective IgA deficiency is a poor prognostic factor in AS.     

Comparative clinical and angiographic analysis of the initial efficacy and long-term follow-up of Wiktor stent implantation with conventional balloon angioplasty

This study was retrospectively designed to examine if the Wiktor stent, a balloon-expandable tantalum coil stent, provides a more favorable procedural and long-term clinical and angiographic outcome than does conventional coronary balloon angioplasty (POBA). From April 1995 to April 1996, we implanted 56 Wiktor stents in 46 lesions (LAD: 23, RCA: 16, CX: 7) in 42 patients (average age 53 +/- 10 years). Coronary lesions from the stent group were matched with similar lesions of another 42 POBA patients whose characteristics were identical to the Wiktor group. Revascularization indications in the Wiktor and POBA groups, respectively, were recent myocardial infarction (RMI) (45%, 40%), unstable (31%, 39%) and stable (24%, 21%) angina pectoris. 7% of the stents and 17% of the POBA balloons were less than 3 mm in diameter (p > 0.05). Procedural success was significantly greater in the Wiktor group than in the POBA group (100% vs. 92%, p < 0.05). Neither major cardiac event (death, CABG, acute myocardial infarction) nor (sub)acute occlusion was encountered in the Wiktor group during the hospitalization period and 1 month follow-up. There was 1 urgent CABG and 4 subacute occlusions in the POBA group. Control angiography at 8 months was performed in patients of both groups, of whom some were symptomatic at long-term follow-up or completely event free for 8 months. Angiographic restenosis (> 50% diameter stenosis) occurred in 25% of the Wiktor patients and in 43% of those in the POBA group (p < 0.05). For an 18 month clinical follow-up, 91% of the patients in the Wiktor group were asymptomatic and without ischemia in radionuclide imaging (RI), whereas 79% of the POBA patients were angina-free and 74% were without ischemia in the RI study. In conclusion, Wiktor stent implantation, with no major cardiac event or subacute occlusion, provides a more favorable procedural and long-term clinical and angiographic outcome than does conventional POBA.     

Multiple bilateral chondromatous hamartomas of the lung. A rare entity mimicking metastatic carcinoma

Multiple chondromatous hamartomas are extremely rare and we have not found any bilateral presentation in the literature. We report the case of a 47-year-old woman presenting with a cough, chest pain and dyspnea. Chest x-ray and computed tomography revealed multiple and bilateral pulmonary nodules. A metastatic carcinoma was considered, but the open lung biopsy revealed a chondromatous hamartoma of the lung. The pathogenesis of hamartomas is discussed and the recent literature is reviewed.     

Modeling of ferrofluid magnetic actuation with dynamic magnetic fields in small channels

One of the most important and promising research areas in biomedical and micropumping applications is magnetic actuation of ferrofluids with dynamic magnetic fields. For ensuring the use of ferrofluids in various applications in engineering fields, their flows generated by magnetic fields should be extensively investigated and simulated. In this study, simulations of ferrofluid actuation with dynamic magnetic fields were performed by modeling it using the COMSOL Multiphysics software, and iron oxide nanoparticle-based ferrofluids at different angles of rotating magnets were considered to provide insight into ferrofluid flow in small channels. Ferrofluid flows were modeled at different magnetic flux densities provided by rotating magnets, and velocity profiles inside the channel were analyzed. It was shown that ferrofluid actuation can be considered as a futuristic micropumping alternative, simulation results matched well with the experimental results of previous work, and the established model could serve as a tool to analyze ferrofluid flows generated by dynamic magnetic fields. The results of the model show that flow rates up to 100 µl/s can be reached at a rotation angle of 30° by using dynamic magnetic fields. Various applications including biomedical applications might be envisaged.     

Performance of Masonry Stone Buildings during the March 25 and 28, 2004 A?kale (Erzurum) Earthquakes in Turkey

This paper reviews the performance of stone masonry buildings during the March 25 and 28, 2004, A?kale (Erzurum) earthquakes. A?kale is a township located 35?km from Erzurum city in Turkey. A majority of the buildings in the affected region are built in masonry. Most of the masonry buildings were formed with random or coursed stone walls without any reinforcement supporting heavy clay tile roofing over wooden logs. A large number of such buildings were heavily damaged or collapsed. The cracking and failure patterns of the buildings are examined and interpreted relative to current provisions for earthquake resistance of masonry structures. The damages are due to several reasons such as site effect, location, and length of the fault, and the poor construction quality of the buildings. In addition to these reasons, the two earthquakes hit the buildings within three days, causing progressive damage. Low strength stone masonry buildings with mud mortar are weak against earthquakes, and should be avoided in high seismic zones.     

Utilization of Refractory Metals and Alloys in Fusion Reactor Structures

In design of fusion reactors, structural material selection is very crucial to improve reactor’s performance. Different types of materials have been proposed for use in fusion reactor structures. Among these materials, refractory metals and alloys having capability to withstand high temperatures and high neutron wall loads have been considered to get high power density in fusion reactors. However, these materials have insufficient technological database and are very expensive compared to steels. In addition to that, except chromium and some chromium alloys they show no low activation property. This study gives an overview of potential of refractory metals and alloys for possible use in fusion reactors.