Electrostatic effects on nanofiber formation of self-assembling peptide amphiphiles

Cataloged from PDF version of article.Self-assembling peptide amphiphile molecules have been of interest to various tissue engineering studies. These molecules self-assemble into nanofibers which organize into three-dimensional networks to form hydrocolloid systems mimicking the extracellular matrix. The formation of nanofibers is affected by the electrostatic interactions among the peptides. In this work, we studied the effect of charged groups on the peptides on nanofiber formation. The self-assembly process was studied by pH and zeta potential measurements, FT-IR, circular dichroism, rheology, atomic force microscopy, scanning electron microscopy and transmission electron microscopy. The aggregation of the peptides was triggered upon neutralization of the charged residues by pH change or addition of electrolyte or biomacromolecules. Understanding the controlled formation of the hydrocolloid gels composed of peptide amphiphile nanofibers can lead us to develop in situ gel forming bioactive collagen mimetic nanofibers for various tissue engineering studies including bioactive surface coatings. (C) 2010 Elsevier Inc. All rights reserved

Slow release and delivery of antisense oligonucleotide drug by self-assembled peptide amphiphile nanofibers

Cataloged from PDF version of article.Antisense oligonucleotides provide a promising therapeutic approach for several disorders including cancer. Chemical stability, controlled release, and intracellular delivery are crucial factors determining their efficacy. Gels composed of nanofibrous peptide network have been previously suggested as carriers for controlled delivery of drugs to improve stability and to provide controlled release, but have not been used for oligonucleotide delivery. In this work, a self-assembled peptide nanofibrous system is formed by mixing a cationic peptide amphiphile (PA) with Bcl-2 antisense oligodeoxynucleotide (ODN), G3139, through electrostatic interactions. The self-assembly of PA-ODN gel was characterized by circular dichroism, rheology, atomic force microscopy (AFM) and scanning electron microscopy (SEM). AFM and SEM images revealed establishment of the nanofibrous PA-ODN network. Due to the electrostatic interactions between PA and ODN, ODN release can be controlled by changing PA and ODN concentrations in the PA-ODN gel. Cellular delivery of the ODN by PA-ODN nanofiber complex was observed by using fluorescently labeled ODN molecule. Cells incubated with PA-ODN complex had enhanced cellular uptake compared to cells incubated with naked ODN. Furthermore, Bcl-2 mRNA amounts were lower in MCF-7 human breast cancer cells in the presence of PA-ODN complex compared to naked ODN and mismatch ODN evidenced by quantitative RT-PCR studies. These results suggest that PA molecules can control ODN release, enhance cellular uptake and present a novel efficient approach for gene therapy studies and oligonucleotide based drug deliver

The Effect Of Image Resolution On Fluid Flow Simulations In Porous Media

Realistic simulations of flow in porous media are dependent upon having a three-dimensional, high resolution image of pore structure which is difficult to obtain. So, we ask the question, "How fine a resolution is necessary to adequately model flow in porous media?" To find the answer, we take a 7.5 p,m resolution image and coarsen it to five different resolutions. Lattice gas simulations are performed on each image. From the simulation results, we observe changes in permeability and velocity fields as the resolution is altered. The results show permeability varies by a factor of 5 over the resolution range. Flow paths change as the resolution is changed. We also find that the image processing has a large impact on the outcome of the simulations.Massachusetts Institute of Technology. Borehole Acoustics and Logging ConsortiumMassachusetts Institute of Technology. Earth Resources Laboratory. Reservoir Delineation Consortiu

Fluid Flow In Porous Media: NMR Imaging And Numerical Simulation

We use nuclear magnetic resonance (NMR) imaging to obtain a three-dimensional image of the pore structure in a limestone core, 4.5 mm in diameter and 10 mm in length, with a resolution of 40 μm. This image is converted into boundary conditions for simulation of fluid flow through the rock using the lattice gas method. The computed permeability is several orders of magnitude lower than the laboratory measured permeability, most likely a result of the image resolution being too coarse to resolve the smaller pore throats, which are believed to be significant for flow in this sample.Saudi AramcoMassachusetts Institute of Technology. Borehole Acoustics and Logging ConsortiumMassachusetts Institute of Technology. Earth Resources Laboratory. Reservoir Delineation Consortiu

Self-assembled one-dimensional soft nanostructures

The self-assembly process is a bottom-up approach and is the spontaneous aggregation of many different subunits into well-defined functional structures with varying properties. Self-assembly is an attractive method to develop one-dimensional nanostructures and is controlled by many factors including temperature, pH and electrolyte addition. Novel self-assembled one-dimensional nanostructures are finding applications in regenerative medicine and electronics as well as in fabrication of nanoscale electronic, mechanic, magnetic, optical, and combinatorial devices. Their utility comes from their high ratio of surface area to volume, and their quantum-confinement effects. This paper reviews one-dimensional self-assembled organic nanostructures classified according to the non-covalent forces acting on their formation. © 2010 The Royal Society of Chemistry

Heparin Mimetic Peptide Nanofibers Promote Angiogenesis

Cataloged from PDF version of article.New blood vessel formation (angiogenesis) is one of the most important processes required for functional tissue formation. Induction of angiogenesis is usually triggered by growth factors released by cells. Glycosaminoglycans (e.g., heparan sulphates) in the extracellular matrix aid in proper functioning of these growth factors. Therefore, exogeneous heparin or growth factors were required for promoting angiogenesis in previous regenerative medicine studies. Here we report for the first time induction of angiogenesis by a synthetic nanofibrous peptide scaffold without the addition of any exogenous growth factors or heparin. We designed and synthesized a self-assembling peptide amphiphile molecule that is functionalized with biologically active groups to mimic heparin. Like heparin, this molecule has the ability to interact with growth factors and effectively enhance their bioactivity. The nanofibers formed by these molecules were shown to form a 3D network mimicking the structural proteins in the extracellular matrix. Because of heparin mimicking capabilities of the peptide nanofibers, angiogenesis was induced without the addition of exogenous growth factors in vitro. Bioactive interactions between the nanofibers and the growth factors enabled robust vascularization in vivo as well. Heparin mimetic peptide nanofibers presented here provide new opportunities for angiogenesis and tissue regeneration by avoiding the use of heparin and exogenous growth factors. The synthetic peptide nanofiber scaffolds enriched with proper chemical functional groups shown in this study can be used to induce various desired physiological responses for tissue regeneration. © 2011 American Chemical Society

Deterministic seismic hazard assessment for Sultanate of Oman

The Sultanate of Oman forms the southeastern part of the Arabian plate, which is surrounded by relatively high active tectonic zones. Studies of seismic risk assessment in Oman have been an important on-going socioeconomic concern. Using the results of the seismic hazard assessment to improve building design and construction is an effective way to reduce the seismic risk. In the current study, seismic hazard assessment for the Sultanate of Oman is performed through the deterministic approach with particular attention on the uncertainty analysis applying a recently developed method. The input data set contains a defined seismotectonic model consisting of 26 seismic zones, maximum magnitudes, and 6 alternative ground motion prediction equations that were used in four different tectonic environments: obduction zone earthquake (Zagros fold thrust belt), subduction zone earthquakes (Makran subduction zones), normal and strike-slip transform earthquakes (Owen and Gulf of Aden zones), and stable craton seismicity (Arabian stable craton). This input data set yielded a total of 76 scenarios at each point of interest. A 10 % probability that any of the 76 scenarios may exceed the largest median ground acceleration is selected. The deterministic seismic hazards in terms of PGA, 5 % damped spectral acceleration at 0.1, 0.2, 1.0 and 2.0 s are performed at 254 selected points. The ground motion was calculated at the 50th and 84th percentile levels for selected probability of exceeding the median value. The largest ground motion in the Sultanate of Oman is observed in the northeastern part of the country.Oman Ministerial Cabinet (Project 22409017

Probabilistic seismic hazard maps for the sultanate of Oman

This study presents the results of the first probabilistic seismic hazard assessment (PSHA) in the framework of logic tree for Oman. The earthquake catalogue was homogenized, declustered, and used to define seismotectonic source model that characterizes the seismicity of Oman. Two seismic source models were used in the current study; the first consists of 26 seismic source zones, while the second is expressing the alternative view that seismicity is uniform along the entire Makran and Zagros zones. The recurrence parameters for all the seismogenic zones were determined using the doubly bounded exponential distribution except the zones of Makran, which were modelled using the characteristic distribution. Maximum earthquakes were determined and the horizontal ground accelerations in terms of geometric mean were calculated using ground-motion prediction relationships developed based upon seismic data obtained from active tectonic environments similar to those surrounding Oman. The alternative seismotectonic source models, maximum magnitude, and ground-motion prediction relationships were weighted and used to account for the epistemic uncertainty. Hazard maps at rock sites were produced for 5 % damped spectral acceleration (SA) values at 0.1, 0.2, 0.3, 1.0 and 2.0 s spectral periods as well as peak ground acceleration (PGA) for return periods of 475 and 2,475 years. The highest hazard is found in Khasab City with maximum SA at 0.2 s spectral period reaching 243 and 397 cm/s[superscript 2] for return periods 475 and 2,475 years, respectively. The sensitivity analysis reveals that the choice of seismic source model and the ground-motion prediction equation influences the results most.Oman Ministerial Cabinet (project number 22409017

Seismic microzonation for Muscat region, Sultanate of Oman

Site characterization was carried out for Muscat region using the ambient noise measurements applying the horizontal-to-vertical spectral ratio (HVSR) technique and using active seismic survey utilizing the multichannel analysis of surface waves (MASW) of survey data. Microtremors measurements were carried out at 459 sites using short-period sensors. This extensive survey allowed the fundamental resonance frequency of the soft soil to be mapped and areas prone to site amplification to be identified. The results indicate a progressive decrease in the fundamental resonance frequencies from the southern and eastern parts, where the bedrock outcrops, toward the northern coast where a thickness of sedimentary cover is present. Shear wave velocity (Vs) was evaluated using the 2-D MASW at carefully selected 99 representative sites in Muscat. These 99 sites were investigated with survey lines of 52 m length. 1-D and interpolated 2-D profiles were generated up to a depth range 20–40 m. The vertical Vs soundings were used in the SHAKE91 software in combination with suitable seismic input strong motion records to obtain the soil effect. Most of the study area has amplification values less than 2.0 for all the considered spectral periods. The estimated fundamental frequencies obtained using the H/V spectral ratio method and using SHAKE91 are found to be in a relatively good agreement. Maps of spectral amplification, earthquake characteristics on the ground surface for peak ground and spectral accelerations at 0.1, 0.2, 0.3, 1.0, and 2.0 s, for 475 years return period are produced. The surface ground motion maps show that the hazard level is moderate with expected PGA in the range 0.059–0.145 g for 475 years return period.Oman Ministerial Cabinet (project # 22409017

Quantification of Epstein-Barr virus DNA load, interleukin-6, interleukin-10, transforming growth factor-β1 and stem cell factor in plasma of patients with nasopharyngeal carcinoma

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common epithelial neoplasm among the Chinese populations in Southern China and South East Asia. Epstein-Barr virus (EBV) is known to be an important etiologic agent of NPC and the viral gene products are frequently detected in NPC tissues along with elevated antibody titres to the viral proteins (VCA and EA) in a majority of patients. Elevated plasma EBV DNA load is regarded as an important marker for the presence of the disease and for the monitoring of disease progression. However, other serum/plasma parameters such as the levels of certain interleukins and growth factors have also been implicated in NPC. The objectives of the present study are, 1) to investigate the correlations between plasma EBV DNA load and the levels of interleukin (IL)-6, IL-10, TGF-β1 and SCF (steel factor) and 2) to relate these parameters to the stages of NPC and the effect of treatment. METHODS: A total of 78 untreated NPC patients were enrolled in this study. Of these, 51 were followed-up after treatment. The remaining patients had irregular or were lost to follow-up. Plasma EBV DNA was quantified using real-time quantitative PCR. The levels of plasma interleukins and growth factors were quantified using ELISA. RESULTS: A significant decrease in EBV DNA load was detected in plasma of untreated NPC patients (1669 ± 637 copies/mL; n = 51) following treatment (57 ± 37 copies/mL, p < 0.05); n = 51). Plasma EBV DNA load was shown to be a good prognosticator for disease progression and clinical outcome in five of the follow-up patients. A significant difference in IL-6 levels was noted between the untreated patients (164 ± 37 pg/mL; n = 51) and following treatment (58 ± 16 pg/mL, p < 0.05; n = 51). Positive correlations between EBV DNA load and IL-10 (r(49) = 0.535, p < 0.01), between IL6 and IL-10 (r(49) = 0.474, p < 0.01) and between TGF and SCF (r(49) = 0.464, p < 0.01) were observed in patients following treatment. None of the parameters tested including IgA-VCA were associated with tumour stages. CONCLUSION: We conclude that among the parameters investigated, EBV DNA load and IL-6 levels were promising markers for the presence of NPC and for the assessment of treatment outcome