Search results for: relative binding affinity

Authors: Maria Amaia Iza Padilla, Ibai Ostolozaga

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The objective of this paper is to analyze how transportation costs between regions within a country can affect not only domestic trade but also the allocation of resources in a given region, aggregate productivity, and relative domestic prices (tradable versus non-tradable). On the one hand, there is a vast literature that analyzes the transportation costs faced by countries when trading with the rest of the world. However, this paper focuses on the effect of transportation costs on domestic trade. Countries differ in their domestic road infrastructure and transport quality. There is also some literature that focuses on the effect of road infrastructure on the price difference between regions but not on relative prices at the aggregate level. On the other hand, this work is also related to the literature on resource misallocation. Finally, the paper is also related to the literature analyzing the effect of trade on the development of the manufacturing sector. Using the World Bank Enterprise Survey database, it is observed cross-country differences in the proportion of firms that consider transportation as an obstacle. From the International Comparison Program, we obtain a significant negative correlation between GDP per worker and relative prices (manufacturing sector prices relative to the service sector). Furthermore, there is a significant negative correlation between a country’s transportation quality and the relative price of manufactured goods with respect to the price of services in that country. This is consistent with the empirical evidence of a negative correlation between transportation quality and GDP per worker, on the one hand, and the negative correlation between GDP per worker and domestic relative prices, on the other. It is also shown that in a country, the share of manufacturing firms whose main market is at the local (regional) level is negatively related to the quality of the transportation infrastructure within the country. Similarly, this index is positively related to the share of manufacturing firms whose main market is national or international. The data also shows that those countries with a higher proportion of manufacturing firms operating locally have higher relative prices. With this information in hand, the paper attempts to quantify the effects of the allocation of resources between and within sectors. The higher the trade barriers caused by transportation costs, the less efficient allocation, which causes lower aggregate productivity. Second, it is built a two-sector model where regions within a country trade with each other. On the one hand, it is found that with respect to the manufacturing sector, those countries with less trade between their regions will be characterized by a smaller variety of goods, less productive manufacturing firms on average, and higher relative prices for manufactured goods relative to service sector prices. Thus, the decline in the relative price of manufactured goods in more advanced countries could also be explained by the degree of trade between regions. This trade allows for efficient intra-industry allocation (traders are more productive, and resources are allocated more efficiently)).

Keywords: misallocation, relative prices, TFP, transportation cost

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Authors: Mukunda Upreti, Jill Storry, Rafael Björk, Emilie Louvet, Johan Normark, Sven Bergström

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Borrelia duttonii and most other relapsing fever species are Gram-negative bacteria which cause a blood borne infection characterized by the binding of bacterium to erythrocytes. The bacteria associate with two or more erythrocytes to form clusters of cells into rosettes. Rosetting is a major virulence factor and the mechanism is believed to facilitate persistence of bacteria in the circulatory system and the avoidance of host immune cells through masking or steric hindrance effects. However, the molecular mechanisms of rosette formation are still poorly understood. This study aims at determining the molecules involved in the rosette formation phenomenon. Fractionated serum, using different affinity purification methods, was investigated as a rosetting agent and IgG and at least one other serum components were needed for rosettes to form. An IgG titration curve demonstrated that IgG alone is not enough to restore rosette formation level to the level whole serum gives. IgG hydrolysis by IdeS ( Immunoglobulin G-degrading enzyme of Streptococcus pyogenes) and deglycosylation using N-Glycanase proved that the whole IgG molecule regardless of saccharide moieties is critical for Borrelia induced rosetting. Complement components C3 and C4 were also important serum molecules necessary to maintain optimum rosetting rates. The deactivation of complement network and serum depletion with C3 and C4 significantly reduced the rosette formation rate. The dependency of IgG and complement components also implied involvement of the complement receptor (CR1). Rosette formation test with Knops null RBC and sCR1 confirmed that CR1 is also part of Borrelia induced rosette formation.

Keywords: complement components C3 and C4, complement receptor 1, Immunoglobulin G, Knops null, Rosetting

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Authors: Varun Goel

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Solar energy is a good option among renewable energy resources due to its easy availability and abundance. The simplest and most efficient way to utilize solar energy is to convert it into thermal energy and this can be done with the help of solar collectors. The thermal performance of such collectors is poor due to less heat transfer from the collector surface to air. In this work, experimental investigations of single pass solar air heater having triangular duct and provided with roughness element on the underside of the absorber plate. V-shaped ribs are used for investigation having three different values of relative roughness pitch (p/e) ranges from 4-16 for a fixed value of angle of attack (α), relative roughness height (e/Dh) and a relative gap distance (d/x) values are 60°, 0.044 and 0.60 respectively. Result shows that considerable augmentation in heat transfer has been obtained by providing roughness.

Keywords: artificial roughness, solar air heater, triangular duct, V-shaped ribs

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Authors: Christina Roman, Deepak Koirala, Joseph A. Piccirilli

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Phage displaying synthetic Fab libraries have been used to obtain Fabs that bind to specific RNA targets with high affinity and specificity. These Fabs have been demonstrated to facilitate RNA crystallization. However, the antibody framework used in the construction of these phage display libraries contains numerous bulky, flexible, and charged residues, which facilitate solubility and hinder aggregation. These residues can interfere with crystallization due to the entropic cost associated with burying them within crystal contacts. To systematically reduce the surface entropy of the Fabs and improve their crystallization properties, a protein engineering strategy termed surface entropy reduction (SER) is being applied to the Fab framework. In this approach, high entropy residues are mutated to smaller ones such as alanine or serine. Focusing initially on Fab BL3-6, which binds an RNA AAACA pentaloop with 20nM affinity, the SER P server (http://services.mbi.ucla.edu/SER/) was used and analysis was performed on existing RNA-Fab BL3-6 co-crystal structures. From this analysis twelve surface entropy reduced mutants were designed. These SER mutants were expressed and are now being measured for their crystallization and diffraction performance with various RNA targets. So far, one mutant has generated 3.02 angstrom diffraction with the yjdF riboswitch RNA. Ultimately, the most productive mutations will be combined into a new Fab framework to be used in a optimized phage displayed Fab library.

Keywords: antibody fragment, crystallography, RNA, surface entropy reduction

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Authors: Evgeny A. Ermakov, Lyudmila P. Smirnova, Valentina N. Buneva

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Schizophrenia associated with dysregulation of neurotransmitter processes in the central nervous system and disturbances in the humoral immune system resulting in the formation of antibodies (Abs) to the various components of the nervous tissue. Abs to different neuronal receptors and DNA were detected in the blood of patients with schizophrenia. Abs hydrolyzing DNA were detected in pool of polyclonal autoantibodies in autoimmune and infectious diseases, such catalytic Abs were named abzymes. It is believed that DNA-hydrolyzing abzymes are cytotoxic, cause nuclear DNA fragmentation and induce cell death by apoptosis. Abzymes with DNAase activity are interesting because of the mechanism of formation and the possibility of use as diagnostic markers. Therefore, in our work we have set following goals: to determine the level anti-DNA Abs in the serum of patients with schizophrenia and to study DNA-hydrolyzing activity of IgG of patients with schizophrenia. Materials and methods: In our study there were included 41 patients with a verified diagnosis of paranoid or simple schizophrenia and 24 healthy donors. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the serum proteins on protein G-Sepharose and gel filtration. The levels of anti-DNA Abs were determined using ELISA. DNA-hydrolyzing activity was detected as the level of supercoiled pBluescript DNA transition in circular and linear forms, the hydrolysis products were analyzed by agarose electrophoresis followed by ethidium bromide stain. To correspond the registered catalytic activity directly to the antibodies we carried out a number of strict criteria: electrophoretic homogeneity of the antibodies, gel filtration (acid shock analysis) and in situ activity. Statistical analysis was performed in ‘Statistica 9.0’ using the non-parametric Mann-Whitney test. Results: The sera of approximately 30% of schizophrenia patients displayed a higher level of Abs interacting with single-stranded (ssDNA) and double-stranded DNA (dsDNA) compared with healthy donors. The average level of Abs interacting with ssDNA was only 1.1-fold lower than that for interacting with dsDNA. IgG of patient with schizophrenia were shown to possess DNA hydrolyzing activity. Using affinity chromatography, electrophoretic analysis of isolated IgG homogeneity, gel filtration in acid shock conditions and in situ DNAse activity analysis we proved that the observed activity is intrinsic property of studied antibodies. We have shown that the relative DNAase activity of IgG in patients with schizophrenia averaged 55.4±32.5%, IgG of healthy donors showed much lower activity (average of 9.1±6.5%). It should be noted that DNAase activity of IgG in patients with schizophrenia with a negative symptoms was significantly higher (73.3±23.8%), than in patients with positive symptoms (43.3±33.1%). Conclusion: Anti-DNA Abs of patients with schizophrenia not only bind DNA, but quite efficiently hydrolyze the substrate. The data show a correlation with the level of DNase activity and leading symptoms of patients with schizophrenia.

Keywords: anti-DNA antibodies, abzymes, DNA hydrolysis, schizophrenia

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Authors: W. Nootcharin, S. Sujittra, K. Mayuso, K. Kornphimol, M. Rawiwan

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Silver has distinct antibacterial properties and has been used as a component of commercial products with many applications. An increasing number of commercial products cause risks of silver effects for human and environment such as the symptoms of Argyria and the release of silver to the environment. Therefore, the detection of silver in the aquatic environment is important. The colorimetric chemosensor is designed by the basic of ligand interactions with a metal ion, leading to the change of signals for the naked-eyes which are very useful method to this application. Dithizone ligand is considered as one of the effective chelating reagents for metal ions due to its high selectivity and sensitivity of a photochromic reaction for silver as well as the linear backbone of dithizone affords the rotation of various isomeric forms. The present study is focused on the conformation and interaction of silver ion and silver nanoparticles (AgNPs) with dithizone using density functional theory (DFT). The interaction parameters were determined in term of binding energy of complexes and the geometry optimization, frequency of the structures and calculation of binding energies using density functional approaches B3LYP and the 6-31G(d,p) basis set. Moreover, the interaction of silver–dithizone complexes was supported by UV–Vis spectroscopy, FT-IR spectrum that was simulated by using B3LYP/6-31G(d,p) and 1H NMR spectra calculation using B3LYP/6-311+G(2d,p) method compared with the experimental data. The results showed the ion exchange interaction between hydrogen of dithizone and silver atom, with minimized binding energies of silver–dithizone interaction. However, the result of AgNPs in the form of complexes with dithizone. Moreover, the AgNPs-dithizone complexes were confirmed by using transmission electron microscope (TEM). Therefore, the results can be the useful information for determination of complex interaction using the analysis of computer simulations.

Keywords: silver nanoparticles, dithizone, DFT, NMR

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Authors: Nusrat Masood, Vijaya Dubey, Suaib Luqman

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Caspase 3, a member of cysteine-aspartic acid protease family, is an imperative indicator for cell death particularly when substantiating apoptosis. Thus, caspase 3 is an interesting target for the discovery and development of anticancer agent. We adopted a four level assessment of both terpenoids and flavonoids and thus experimentally performed the enzymatic assay in cell free system as well as in cancer cell line which was validated through real time expression and molecular interaction studies. A significant difference was observed with both the class of natural products indicating terpenoids as better activators of caspase 3 compared to flavonoids both in the cell free system as well as in cell lines. The expression analysis, activation constant and binding energy also correlate well with the enzyme activity. Overall, terpenoids had an unswerving effect on caspase 3 in all the tested system while flavonoids indirectly affect enzyme activity.

Keywords: Caspase 3, terpenoids, flavonoids, activation constant, binding energy

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Authors: Bo-Gaun Chen, Chiung-Hui Huang, Mei-Ching Chiang, Kuo-Hsing Lee, Chia-Chen Ho, Chin-Ping Huang, Chin-Heng Tien

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It is known that the natural dyeing of cloth results moderate color, but with poor color fastness. This study points out the correlation between the macroscopic color fastness of natural dye to the cotton fiber and the microscopic binding energy of dye molecule to the cellulose. With the additive metallic mordant, the new-formed coordination bond bridges the dye to the fiber surface and thus affects the color fastness as well as the color appearance. The density functional theory (DFT) calculation is therefore used to explore the most possible mechanism during the dyeing process. Finally, the experimental results reflect the strong effect of three different metal ions on the natural dyeing clothes.

Keywords: binding energy, color fastness, density functional theory (DFT), natural dyeing, metallic mordant

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Authors: Joanna Gerszon, Aleksandra Rodacka

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In the pathogenesis of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, protein and peptide aggregation processes play a vital role in contributing to the formation of intracellular and extracellular protein deposits. One of the major components of these deposits is the oxidatively modified glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Therefore, the purpose of this research was to answer the question whether piceatannol, a stilbene derivative, counteracts and/or slows down oxidative stress-induced GAPDH aggregation. The study also aimed to determine if this natural occurring compound prevents unfavorable nuclear translocation of GAPDH in hippocampal cells. The isothermal titration calorimetry (ITC) analysis indicated that one molecule of GAPDH can bind up to 8 molecules of piceatannol (7.3 ± 0.9). As a consequence of piceatannol binding to the enzyme, the loss of activity was observed. Parallel with GAPDH inactivation the changes in zeta potential, and loss of free thiol groups were noted. Nevertheless, the ligand-protein binding does not influence the secondary structure of the GAPDH. Precise molecular docking analysis of the interactions inside the active center allowed to presume that these effects are due to piceatannol ability to assemble a covalent binding with nucleophilic cysteine residue (Cys149) which is directly involved in the catalytic reaction. Molecular docking also showed that simultaneously 11 molecules of ligand can be bound to dehydrogenase. Taking into consideration obtained data, the influence of piceatannol on level of GAPDH aggregation induced by excessive oxidative stress was examined. The applied methods (thioflavin-T binding-dependent fluorescence as well as microscopy methods - transmission electron microscopy, Congo Red staining) revealed that piceatannol significantly diminishes level of GAPDH aggregation. Finally, studies involving cellular model (Western blot analyses of nuclear and cytosolic fractions and confocal microscopy) indicated that piceatannol-GAPDH binding prevents GAPDH from nuclear translocation induced by excessive oxidative stress in hippocampal cells. In consequence, it counteracts cell apoptosis. These studies demonstrate that by binding with GAPDH, piceatannol blocks cysteine residue and counteracts its oxidative modifications, that induce oligomerization and GAPDH aggregation as well as it prevents hippocampal cells from apoptosis by retaining GAPDH in the cytoplasm. All these findings provide a new insight into the role of piceatannol interaction with GAPDH and present a potential therapeutic strategy for some neurological disorders related to GAPDH aggregation. This work was supported by the by National Science Centre, Poland (grant number 2017/25/N/NZ1/02849).

Keywords: glyceraldehyde-3-phosphate dehydrogenase, neurodegenerative disease, neuroprotection, piceatannol, protein aggregation

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Authors: Sujata Sharma, Avinash Singh, Lovely Gautam, Pradeep Sharma, Mau Sinha, Asha Bhushan, Punit Kaur, Tej P. Singh

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Peptidyl-tRNA hydrolase (Pth) Pth is an essential bacterial enzyme that catalyzes the release of free tRNA and peptide moeities from peptidyl tRNAs during stalling of protein synthesis. In order to design inhibitors of Pth from Pseudomonas aeruginosa (PaPth), we have determined the structures of PaPth in its native state and in the bound states with two compounds, amino acylate-tRNA analogue (AAtA) and 5-azacytidine (AZAC). The peptidyl-tRNA hydrolase gene from Pseudomonas aeruginosa was amplified by Phusion High-Fidelity DNA Polymerase using forward and reverse primers, respectively. The E. coliBL21 (λDE3) strain was used for expression of the recombinant peptidyl-tRNA hydrolase from Pseudomonas aeruginosa. The protein was purified using a Ni-NTA superflow column. The crystallization experiments were carried out using hanging drop vapour diffusion method. The crystals diffracted to 1.50 Å resolution. The data were processed using HKL-2000. The polypeptide chain of PaPth consists of 194 amino acid residues from Met1 to Ala194. The centrally located β-structure is surrounded by α-helices from all sides except the side that has entrance to the substrate binding site. The structures of the complexes of PaPth with AAtA and AZAC showed the ligands bound to PaPth in the substrate binding cleft and interacted with protein atoms extensively. The residues that formed intermolecular hydrogen bonds with the atoms of AAtA included Asn12, His22, Asn70, Gly113, Asn116, Ser148, and Glu161 of the symmetry related molecule. The amino acids that were involved in hydrogen bonded interactions in case of AZAC included, His22, Gly113, Asn116, and Ser148. As indicated by fittings of two ligands and the number of interactions made by them with protein atoms, AAtA appears to be a more compatible with the structure of the substrate binding cleft. However, there is a further scope to achieve a better stacking than that of O-tyrosyl moiety because it is not still ideally stacked. These observations about the interactions between the protein and ligands have provided the information about the mode of binding of ligands, nature and number of interactions. This information may be useful for the design of tight inhibitors of Pth enzymes.

Keywords: peptidyl tRNA hydrolase, Acinetobacter baumannii, Pth enzymes, O-tyrosyl

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Authors: John Mambambo

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Debates on the link between Bantu languages are often epitomized by animated theoretical critiques, including the language zoning and groupings. This evaluative, qualitative inquiry hovers above theoretical critiques to offer the sparsely studied ChiShona and isiXhosa code-switching nexus, a yawning gap in scholarship. Using interviews, questionnaires and observations, data germane to the study were collected from a purposively selected group of Shona speakers who had resided in Xhosa-speaking communities for not less than a year. Deploying Myers-Scotton’s Markedness theory, the paper gazes into the pragmatic linguistic affinity that is affirmed through the Shona-Xhosa code-switching in Cape Town. The assorted social variables motivating bilingual speakers to code-switch in Cape Town are also explored in this study. The study unveils that Shona speakers are motivated to code-switch by the linguistic affinity between ChiShona and isiXhosa. Other socio-political justifications also give an impetus to this phenomenon. The Matrix Language Frame Model affirms that ChiShona is the base while isiXhosa is the embedded language during code-switching. This paper is a momentous advancement of the extant literature on code-switching. It is a unique contribution to the nexus between ChiShona and isiXhosa languages, providing fresh insights into the discourse on African language comparison studies.

Keywords: code-switching, chishona, isiXhosa, bilingualism

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Authors: Junhang Luo

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With the transformation of spatial structure and the deepening of urban development, the demand for a better life and the concerns for social resources equities of residents are increasing. As an important social resource, park plays an essential role in building environmentally sustainable cities. Thus, it is important to examine park accessibility for low-income and how it works in relative deprivation, so as to provide all residents with equitable services. Using the network and buffer methods of GIS, this paper analyzes urban park accessibility for low-income residents in Chongqing, China. And then conduct a satisfaction evaluation of park resource accessibility with low-incomes through questionnaire surveys from deprivation dimensions. Results show that the level of park accessibility in Chongqing varies significantly and the degree of relative deprivation is relatively high. Public transportation convenience improves and the number of community park increases contribute positively to improving park accessibility and alleviating the relative deprivation of public resources. Combined with the innovation pattern of social governance in China, it suggests that urban park accessibility needs to be jointly governed and optimized by multiple social resources from the government to the public, and the service efficiency needs the index system and planning standards according to local conditions to improve quality and promote equity. At the same time, building a perfect park system and complete legislation assurance system will also play a positive role in ensuring that all residents can enjoy the urban public space more fairly, especially low-income groups.

Keywords: urban park, accessibility, relative deprivation, GIS network analysis, chongqing

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Authors: Esther Van Andel, Stefanie C. Lange, Maarten M. J. Smulders, Han Zuilhof

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False outcomes of diagnostic tests are a major concern in medical health care. To improve the reliability of surface-based diagnostic tests, it is of crucial importance to diminish background signals that arise from the non-specific binding of biomolecules, a process called fouling. The aim is to create surfaces that repel all biomolecules except the molecule of interest. This can be achieved by incorporating antifouling protein repellent coatings in between the sensor surface and it’s recognition elements (e.g. antibodies, sugars, aptamers). Zwitterionic polymer brushes are considered excellent antifouling materials, however, to be able to bind the molecule of interest, the polymer brushes have to be functionalized and so far this was only achieved at the expense of either antifouling or binding capacity. To overcome this limitation, we combined both features into one single monomer: a zwitterionic sulfobetaine, ensuring antifouling capabilities, equipped with a clickable azide moiety which allows for further functionalization. By copolymerizing this monomer together with a standard sulfobetaine, the number of azides (and with that the number of recognition elements) can be tuned depending on the application. First, the clickable azido-monomer was synthesized and characterized, followed by copolymerizing this monomer to yield functionalizable antifouling brushes. The brushes were fully characterized using surface characterization techniques like XPS, contact angle measurements, G-ATR-FTIR and XRR. As a proof of principle, the brushes were subsequently functionalized with biotin via strain-promoted alkyne azide click reactions, which yielded a fully zwitterionic biotin-containing 3D-functionalized coating. The sensing capacity was evaluated by reflectometry using avidin and fibrinogen containing protein solutions. The surfaces showed excellent antifouling properties as illustrated by the complete absence of non-specific fibrinogen binding, while at the same time clear responses were seen for the specific binding of avidin. A great increase in signal-to-noise ratio was observed, even when the amount of functional groups was lowered to 1%, compared to traditional modification of sulfobetaine brushes that rely on a 2D-approach in which only the top-layer can be functionalized. This study was performed on stoichiometric silicon nitride surfaces for future microring resonator based assays, however, this methodology can be transferred to other biosensor platforms which are currently being investigated. The approach presented herein enables a highly efficient strategy for selective binding with retained antifouling properties for improved signal-to-noise ratios in binding assays. The number of recognition units can be adjusted to a specific need, e.g. depending on the size of the analyte to be bound, widening the scope of these functionalizable surface coatings.

Keywords: antifouling, signal-to-noise ratio, surface functionalization, zwitterionic polymer brushes

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Authors: Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, Thomas Hughes, Paul Millner, David G. Jayne

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Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: colorectal cancer, silica nanoparticles, Affimers, antibodies, imaging

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Authors: Javad Shamsi Soosahab, Reza Ziaie Moayed

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The compressive and tensile bearing capacity of helical piles in sand is investigated by means of numerical modeling. The analyses are carried out using two-dimensional finite-element software, Optum G2. The load–displacement behavior under compression and tension is compared in different relative densities for constant and various elastic modulus. The criterion used to find the ultimate axial load is the load corresponding to 5% of the helical diameter. The results show that relative density of sand plays an essential role in the response of ultimate capacities towards various condition. Increase in elastic modulus with depth is found to play a relatively more significant role to the increase in ultimate compressive load capacities, however tension bearing capacity decreases.

Keywords: helical piles, Optum G2, relative density, constant and various elastic modulus

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Authors: Mahasen M. Abdel Mageed, H. S. Zaghloul

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Annihilations, phase shifts, scattering lengths, and elastic cross sections of low energy positrons scattering from magnesium atoms were studied using the least-squares variational method (LSVM). The possibility of positron binding to the magnesium atoms is investigated. A trial wavefunction is suggested to represent e+-Mg elastic scattering and scattering parameters were derived to estimate the binding energy and annihilation rates. The trial function is taken to depend on several adjustable parameters and is improved iteratively by increasing the number of terms. The present results have the same behavior as reported semi-empirical, theoretical, and experimental results. Especially, the estimated positive scattering length supports the possibility of positron-magnesium bound state system that was confirmed in previous experimental and theoretical work.

Keywords: bound wavefunction, positron annihilation, scattering phase shift, scattering length

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Authors: Mayank, Navneet Kaur, Narinder Singh

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The V599 mutations in the BRAF protein are extremely oncogenic, responsible for countless of malignant conditions. Along with wild type, V599E, V599D, and V599R are the important mutated variants of the BRAF proteins. The BRAF inhibitory anticancer agents are continuously developing, and sorafenib is a BRAF inhibitor that is under clinical use. The crystal structure of sorafenib bounded to wild type, and V599 is known, showing a similar interaction pattern in both the case. The mutated 599th residue, in both the case, is also found not interacting directly with the co-crystallized sorafenib molecule. However, the IC50 value of sorafenib was found extremely different in both the case, i.e., 22 nmol/L for wild and 38 nmol/L for V599E protein. Molecular docking study and MMGBSA binding energy results also revealed a significant difference in the binding pattern of sorafenib in both the case. Therefore, to explore the role of distinctively situated 599th residue, we have further conducted comprehensive computational studies. The molecular dynamics simulation, residue interaction network (RIN) analysis, and residue correlation study results revealed the importance of the 599th residue on the therapeutic outcome and overall dynamic of the BRAF protein. Therefore, although the position of 599th residue is very much distinctive from the ligand-binding cavity of BRAF, still it has exceptional control over the overall functional outcome of the protein. The insight obtained here may seem extremely important and guide us while designing ideal BRAF inhibitory anticancer molecules.

Keywords: BRAF, oncogenic, sorafenib, computational studies

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Authors: Austin Jiang, Richard M. Salmon, Nicholas W. Morrell, Wei Li

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BMP10 is highly expressed in the developing heart and plays essential roles in cardiogenesis. BMP10 deletion in mice results in embryonic lethality due to impaired cardiac development. In adults, BMP10 expression is restricted to the right atrium, though ventricular hypertrophy is accompanied by increased BMP10 expression in a rat hypertension model. However, reports of BMP10 activity in the circulation are inconclusive. In particular it is not known whether in vivo secreted BMP10 is active or whether additional factors are required to achieve its bioactivity. It has been shown that high-affinity binding of the BMP10 prodomain to the mature ligand inhibits BMP10 signaling activity in C2C12 cells, and it was proposed that prodomain-bound BMP10 (pBMP10) complex is latent. In this study, we demonstrated that the BMP10 prodomain did not inhibit BMP10 signaling activity in multiple endothelial cells, and that recombinant human pBMP10 complex, expressed in mammalian cells and purified under native conditions, was fully active. In addition, both BMP10 in human plasma and BMP10 secreted from the mouse right atrium were fully active. Finally, we confirmed that active BMP10 secreted from mouse right atrium was in the prodomain-bound form. Our data suggest that circulating BMP10 in adults is fully active and that the reported vascular quiescence function of BMP10 in vivo is due to the direct activity of pBMP10 and does not require an additional activation step. Moreover, being an active ligand, recombinant pBMP10 may have therapeutic potential as an endothelial-selective BMP ligand, in conditions characterized by loss of BMP9/10 signaling.

Keywords: bone morphogenetic protein 10 (BMP10), endothelial cell, signal transduction, transforming growth factor beta (TGF-B)

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Authors: Cindy Woods

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After years of implacable neoliberal globalization, multinational corporations have moved from the periphery to the center of the international legal agenda. Human rights advocates have long called for greater corporate accountability in the international arena. The creation of the Global Compact in 2000, while aimed at fostering greater corporate respect for human rights, did not silence these calls. After multiple unsuccessful attempts to adopt a set of norms relating to the human rights responsibilities of transnational corporations, the United Nations succeeded in 2008 with the Guiding Principles on Business and Human Rights (Guiding Principles). The Guiding Principles, praised by some within the international human rights community for their recognition of an individual corporate responsibility to respect human rights, have not escaped their share of criticism. Many view the Guiding Principles to be toothless, failing to directly impose obligations upon corporations, and call for binding international obligations on corporate entities. After decades of attempting to promulgate human rights obligations for multinational corporations, the existing legal frameworks in place fall short of protecting individuals from the human rights abuses of multinational corporations. The Global Compact and Guiding Principles are proof of the United Nations’ unwillingness to impose international legal obligations on corporate actors. In June 2014, the Human Rights Council adopted a resolution to draft international legally binding human rights norms for business entities; however, key players in the international arena have already announced they will not cooperate with such efforts. This Note, through an overview of the existing corporate accountability frameworks and a study of Newmont Mining’s Minas Conga project in Peru, argues that binding international human rights obligations on corporations are necessary to fully protect human rights. Where states refuse to or simply cannot uphold their duty to protect individuals from transnational businesses’ human rights transgressions, there must exist mechanisms to pursue justice directly against the multinational corporation.

Keywords: business and human rights, Latin America, international treaty on business and human rights, mining, human rights

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Authors: Dileep Kumar Verma, Sunil Kumar Lal

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Influenza still remains one of the most challenging diseases posing significant threat to public health causing seasonal epidemics and pandemics. Influenza A Virus (IAV) surface protein hemagglutinin is known to play an important role in viral attachment to the host sialic acid receptors and concentrate in lipid rafts for efficient viral fusion. Selective nature of Influenza A virus to utilize rafts micro-domain for efficient virus assembly and budding has been explored in depth. However, the detailed mechanism of IAV binding to host cell membrane and entry into the host remains elusive. In the present study we investigated the role of lipid rafts in early life cycle events of IAV. Role of host lipid rafts was studied using raft disruption method by extraction of cholesterol by Methyl-β-Cyclodextrin. Using GM1, a well-known lipid raft marker, we were able to observe co-localization of IAV on lipid rafts on the host cell membrane. This experiment suggests a direct involvement of lipid rafts in the initiation of the IAV life cycle. Upon disruption of lipid rafts by Methyl-b-cyclodextrin, we observed a significant reduction in IAV binding on the host cell surface indicating a significant decrease in virus attachment to coherent membrane rafts. Our results provide proof that host lipid rafts and their constituents play an important role in the adsorption of IAV. This study opens a new avenues in IAV virus-host interactions to combat infection at a very early steps of the viral lifecycle.

Keywords: lipid raft, adsorption, cholesterol, methyl-β-cyclodextrin, GM1

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Authors: Hasan Basri Jumin

Abstract:

Application of crude palm oil waste combined to suitable concentration of benzyl-adenine give the significant effect to mean relative growth rate of vegetable plants and the same pattern in net assimilation rate crude palm oil waste has also significantly increased during 28 days old plants. Combination of treatment of suitable concentration of crude palm oil and benzyl adenine increased the growth and production of vegetable plants. The relative growth rate of vegetable plants was rapid 3 weeks after planting and gradually decreased at the end of the harvest time period. Combination of 400 mg.l-1 CPO with 1.0 mgl-1 till 10mgl-1 BA increased the Mean Relative Growth Rate (MRGR), Net assimilation rate (NAR), Leaf area and dry weight of Brassica juncea, Brassica oleraceae and Lactuca sativa.

Keywords: benzyladenine, crude-palm-oil, nutrient, vegetable, waste

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Authors: Sulaiman Gafar Muhamad

Abstract:

A rapid spectrophotometric method for the micro-determination of phenylephrine-HCl (PHE) has been developed. The proposed method involves the coupling of phenylephrine-HCl with diazotized 2,4-dinitroaniline in alkaline medium at λmax 455 nm. Under the present optimum condition, Beer’s law was obeyed in the range of 1.0-20 μg/ml of PHE with molar absorptivity of 1.915 ×104 l. mol-1.cm-1, with a relative error of 0.015 and a relative standard deviation of 0.024%. The current method has been applied successfully to estimate phenylephrine-HCl in pharmaceutical preparations (nose drop and syrup).

Keywords: diazo-coupling, 2, 4-dinitroaniline, phenylephrine-HCl, spectrophotometry

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Authors: Keyur Raval, Steffen Krohn, Bruno Moerschbacher

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Chitin, the biopolymer of the N-acetylglucosamine, is the most abundant biopolymer on the planet after cellulose. Industrially, chitin is isolated and purified from the shell residues of shrimps. A deacetylated derivative of chitin i.e. chitosan has more market value and applications owing to it solubility and overall cationic charge compared to the parent polymer. This deacetylation on an industrial scale is performed chemically using alkalis like sodium hydroxide. This reaction not only is hazardous to the environment owing to negative impact on the marine ecosystem. A greener option to this process is the enzymatic process. In nature, the naïve chitin is converted to chitosan by chitin deacetylase (CDA). This enzymatic conversion on the industrial scale is however hampered by the crystallinity of chitin. Thus, this enzymatic action requires the substrate i.e. chitin to be soluble which is technically difficult and an energy consuming process. We in this project wanted to address this shortcoming of CDA. In lieu of this, we have modeled a fusion protein with CDA and an auxiliary protein. The main interest being to increase the accessibility of the enzyme towards crystalline chitin. A similar fusion work with chitinases had improved the catalytic ability towards insoluble chitin. In the first step, suitable partners were searched through the protein data bank (PDB) wherein the domain architecture were sought. The next step was to create the models of the fused product using various in silico techniques. The models were created by MODELLER and evaluated for properties such as the energy or the impairment of the binding sites. A fusion PCR has been designed based on the linker sequences generated by MODELLER and would be tested for its activity towards insoluble chitin.

Keywords: chitin deacetylase, modeling, chitin binding domain, chitinases

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Authors: Hasan Basri Jumin

Abstract:

Using the slaughterhouse waste combined to suitable dose of nitrogen fertilizer to Apium glaviolen gives the significant effect to mean relative growth rate. The same pattern also showed significantly in net assimilation rate. The net assimilation rate increased significantly during 42 days old plants. Combination of treatment of 100 ml/l animal slaughterhouse waste and 0.1 g/kg nitrogen fertilizer/kg soil increased the vegetative growth of Apium glaviolens. The biomass of plant and mean relative growth rate of Apium glaviolens were rapidly increased in 4 weeks after planting and gradually decreased after 35 days at the harvest time. Combination of 100 ml/l slaughterhouse waste and applied 0.1 g/kg nitrogen fertilizer has increased all parameters. The highest vegetative growth, biomass, mean relative growth rate and net assimilation rate were received from 0.56 mg-l.m-2.days-1.

Keywords: Apium glaviolent, nitrogen, pollutant, slaughterhouse, waste

Procedia PDF Downloads 338

Authors: Satoshi Furukawa, Satomu Morita, Lisa Wingenfeld, Katsuji Nishi, Masahito Hitosugi

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We studied the expression of hypoxia-related antigens (e.g., cold-inducible antigens and apoptotic antigens) in the myocardium and the cerebellumthat were obtained from individuals after death by carbon monoxide or hypothermia. The immunohistochemistry results revealed that expression of cold-inducible RNA binding protein (CIRBP) and RNA-binding protein 3 (RBM3) may be associated with hpyothermic and the hypoxic conditions. The expression of CIRBP and RBM3 in the myocardium was different from their expression in the cerebellum, especially in the Purkinje cells. The results indicate that agonal duration influences antigen expression. In the hypothermic condition, the myocardium uses more ATP since the force of the excitation-contraction coupling of the myocardium increases by more than 400% when the experimental temperature is reduced from 35°C to 25°C. The results obtained in this study indicate that physicians should pay attention to the myocardium when cooling the patient’s body to protect the brain.

Keywords: carbon monoxide death, cerebellum, CIRBP, hypothermic death, myocardium, RBM3

Procedia PDF Downloads 337

Authors: Mohamed M. Ibrahim, Gaber A. M. Mersal, Salih Al-Juaid, Samir A. El-Shazly

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A series of mixed ligand complexes, viz., [Cu(BPy)(Gly)X]Y {X = Cl (1), Y = 0; X = 0, Y = ClO4- (2); X = H2O, Y = NO3- (3); X = H2O, Y = CH3COO- (4); and [Cu(BPy)(Gly)-(H2O)]2(SO4) (5) have been synthesized. Their structures and properties were characterized by elemental analysis, thermal analaysis, IR, UV–vis, and ESR spectroscopy, as well as electrochemical measurements including cyclic voltammetry, electrical molar conductivity, and magnetic moment measurements. Complexes 1 and 2 formed slightly distorted square-pyramidal coordination geometries of CuN3OCl and CuN3O2, respectively in which the N,O-donor glycine and N,N-donor bipyridyl bind at the basal plane with chloride ion or water as the axial ligand. Complex 3 shows square planar CuN3O coordination geometry, which exhibits chemically significant hydrogen bonding interactions besides showing coordination polymer formation. The superoxide dismutase and catalase-like activities of all complexes were tested and were found to be promising candidates as durable electron-transfer catalyst being close to the efficiency of the mimicking enzymes displaying either catalase or tyrosinase activity to serve for complete reactive oxygen species (ROS) detoxification, both with respect to superoxide radicals and related peroxides. The DNA binding interaction with super coiled pGEM-T plasmid DNA was investigated by using spectral (absorption and emission) titration and electrochemical techniques. The results revealed that DNA intercalate with complexes 1 and 2 through the groove binding mode. The calculated intrinsic binding constant (Kb) of 1 and 2 were 4.71 and 2.429 × 105 M−1, respectively. Gel electrophoresis study reveals the fact that both complexes cleave super coiled pGEM-T plasmid DNA to nicked and linear forms in the absence of any additives. On the other hand, the interaction of both complexes with DNA, the quasi-reversible CuII/CuI redox couple slightly improves its reversibility with considerable decrease in current intensity. All the experimental results indicate that the bipyridyl mixed copper(II) complex (1) intercalate more effectively into the DNA base pairs.

Keywords: enzyme mimics, mixed ligand complexes, X-ray structures, antioxidant, DNA-binding, DNA cleavage

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Authors: Gulmira Kenenbay, Urishbay Chomanov, Aruzhan Shoman, Rabiga Kassimbek

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The main task of the meat-processing industry is the production of meat products as the main source of animal protein, ensuring the vital activity of the human body, in the required volumes, high quality, diverse assortment. Providing the population with high-quality food products what are biologically full, balanced in composition of basic nutrients and enriched by targeted physiologically active components, is one of the highest priority scientific and technical problems to be solved. In this regard, the formulation of a new brine from sprouted wheat for meat delicacies from horse meat, beef and pork has been developed. The new brine contains flavored aromatic ingredients, juice of the germinated wheat and vegetable juice. The viscosity of meat of horse meat, beef and pork were studied during massaging. Thermodynamic indices, water activity and binding energy of horse meat, beef and pork with application of new brine are investigated. A recipe for meat products with vegetable additives has been developed. Organoleptic evaluation of meat products was carried out. Physicochemical parameters of meat products with vegetable additives are carried out. Analysis of the obtained data shows that the values of the index aw (water activity) and the binding energy of moisture in the experimental samples of meat products are higher than in the control samples. It has been established by investigations that with increasing water activity and the binding energy of moisture, the tenderness of ready meat delicacies increases with the use of a new brine.

Keywords: compounding, functional products, delicatessen products, brine, vegetable additives

Procedia PDF Downloads 151

Authors: Henok Hailemariam, Frank Wuttke

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Collapsible soils are weak soils that appear to be stable in their natural state, normally dry condition, but rapidly deform under saturation (wetting), thus generating large and unexpected settlements which often yield disastrous consequences for structures unwittingly built on such deposits. In this study, a prediction model for the relative subsidence of stressed collapsible soils based on dielectric permittivity measurement is presented. Unlike most existing methods for soil subsidence prediction, this model does not require moisture content as an input parameter, thus providing the opportunity to obtain accurate estimation of the relative subsidence of collapsible soils using dielectric measurement only. The prediction model is developed based on an existing relative subsidence prediction model (which is dependent on soil moisture condition) and an advanced theoretical frequency and temperature-dependent electromagnetic mixing equation (which effectively removes the moisture content dependence of the original relative subsidence prediction model). For large scale sub-surface soil exploration purposes, the spatial sub-surface soil dielectric data over wide areas and high depths of weak (collapsible) soil deposits can be obtained using non-destructive high frequency electromagnetic (HF-EM) measurement techniques such as ground penetrating radar (GPR). For laboratory or small scale in-situ measurements, techniques such as an open-ended coaxial line with widely applicable time domain reflectometry (TDR) or vector network analysers (VNAs) are usually employed to obtain the soil dielectric data. By using soil dielectric data obtained from small or large scale non-destructive HF-EM investigations, the new model can effectively predict the relative subsidence of weak soils without the need to extract samples for moisture content measurement. Some of the resulting benefits are the preservation of the undisturbed nature of the soil as well as a reduction in the investigation costs and analysis time in the identification of weak (problematic) soils. The accuracy of prediction of the presented model is assessed by conducting relative subsidence tests on a collapsible soil at various initial soil conditions and a good match between the model prediction and experimental results is obtained.

Keywords: collapsible soil, dielectric permittivity, moisture content, relative subsidence

Procedia PDF Downloads 332

Authors: Tahir Majeed, Michael Handschuh, René Meier

Abstract:

Rheumatoid arthritis patients have swelling and pain at the joints of the hand. The regions where the patient feels pain also show increased body temperature. Thermal cameras can be used to detect the rise in temperature of the affected regions. To monitor the disease progression of rheumatoid arthritis patients, they must visit the clinic regularly for scanning and examination. After scanning and evaluation, the dosage of the medicine is regulated accordingly. To monitor the disease progression over time, the correlation between the images between different visits must be established. It has been observed that by using low-cost thermal cameras, the thermal measurements do not remain the same over time, even within a single scanning. In some situations, temperatures can vary as much as 2°C within the same scanning sequence. In this paper, it has been shown that although the absolute temperature varies over time, the relative difference between the different regions remains similar. Results have been computed over four scanning sequences and are presented.

Keywords: relative thermal difference, rheumatoid arthritis, thermal imaging, thermal sensors

Procedia PDF Downloads 174

Authors: Khwaja Naweed Seddiqi, Zabihullah Mahdi, Shigeo Honma

Abstract:

Recently increasing oil production from petroleum reservoirs is one of the most important issues in the global energy sector. So, in this paper, the recovery of oil by the waterflooding technique from petroleum reservoir are considered. To investigate the aforementioned phenomena, the relative permeability of two immiscible fluids in sand is measured in the laboratory based on the steady-state method. Two sorts of oils, kerosene and heavy oil, and water are pumped simultaneously into a vertical sand column with different pumping ratio. From the change in fractional discharge measured at the outlet, a method for determining the relative permeability is developed focusing on the displacement mechanism in sand. Then, displacement mechanism of two immiscible fluids in the sand is investigated under the Buckley-Leveret frontal displacement theory and laboratory experiment. Two sorts of experiments, one is the displacement of pore water by oil, the other is the displacement of pore oil by water, are carried out. It is revealed that the relative permeability curves display tolerably different shape owing to the properties of oils, and produce different amount of residual oils and irreducible water saturation.

Keywords: petroleum reservoir engineering, relative permeability, two-phase flow, immiscible displacement in porous media, steady-state method, waterflooding

Procedia PDF Downloads 215