Search results for: protein stability
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5595

Search results for: protein stability

4545 Green Materials for Hot Mixed Asphalt Production

Authors: Salisu Dahiru, Jibrin M. Kaura, Abubakar I. Jumare, Sulaiman M. Mahmood

Abstract:

Reclaimed asphalt, used automobile tires and rice husk, were regarded as waste. These materials could be used in construction of new roads and for roads rehabilitation. Investigation into the production of a Green Hot Mixed Asphalt (GHMA) pavement using Reclaimed Asphalt Pavement (RAP) as partial replacement for coarse aggregate, Crumb Rubber (CR) from waste automobile tires as modifier for bitumen binder and Rice Husk Ash (RHA) as partial replacement of ordinary portland cement (OPC) filler, for roads construction and rehabilitation was presented. 30% Reclaimed asphalt of total aggregate, 15% Crumb Rubber of total binder content, 5% Rice Husk Ash of total mix, and 5.2% Crumb Rubber Modified Bitumen content were recommended for optimum performance. Loss of marshal stability was investigated on mix with the recommended optimum CRMB. The mix revealed good performance with only about 13% loss of stability after 24 hours of immersion in hot water bath, as against about 24% marshal stability lost reported in previous studies for conventional Hot Mixed Asphalt (HMA).

Keywords: rice husk, reclaimed asphalt, filler, crumb rubber, bitumen content green hot mix asphalt

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4544 Study the Difference Between the Mohr-Coulomb and the Barton-Bandis Joint Constitutive Models: A Case Study from the Iron Open Pit Mine, Canada

Authors: Abbas Kamalibandpey, Alain Beland, Joseph Mukendi Kabuya

Abstract:

Since a rock mass is a discontinuum medium, its behaviour is governed by discontinuities such as faults, joint sets, lithologic contact, and bedding planes. Thus, rock slope stability analysis in jointed rock masses is largely dependent upon discontinuities constitutive equations. This paper studies the difference between the Mohr-Coulomb (MC) and the Barton-Bandis (BB) joint constitutive numerical models for lithological contacts and joint sets. For the rock in these models, generalized Hoek-Brown criteria have been considered. The joint roughness coefficient (JRC) and the joint wall compressive strength (JCS) are vital parameters in the BB model. The numerical models are applied to the rock slope stability analysis in the Mont-Wright (MW) mine. The Mont-Wright mine is owned and operated by ArcelorMittal Mining Canada (AMMC), one of the largest iron-ore open pit operations in Canada. In this regard, one of the high walls of the mine has been selected to undergo slope stability analysis with RS2D software, finite element method. Three piezometers have been installed in this zone to record pore water pressure and it is monitored by radar. In this zone, the AMP-IF and QRMS-IF contacts and very persistent and altered joint sets in IF control the rock slope behaviour. The height of the slope is more than 250 m and consists of different lithologies such as AMP, IF, GN, QRMS, and QR. To apply the B-B model, the joint sets and geological contacts have been scanned by Maptek, and their JRC has been calculated by different methods. The numerical studies reveal that the JRC of geological contacts, AMP-IF and QRMS-IF, and joint sets in IF had a significant influence on the safety factor. After evaluating the results of rock slope stability analysis and the radar data, the B-B constitutive equation for discontinuities has shown acceptable results to the real condition in the mine. It should be noted that the difference in safety factors in MC and BB joint constitutive models in some cases is more than 30%.

Keywords: barton-Bandis criterion, Hoek-brown and Mohr-Coulomb criteria, open pit, slope stability

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4543 Preparation of Protective Coating Film on Metal Alloy

Authors: Rana Th. A. Al-rubaye

Abstract:

A novel chromium-free protective coating films based on a zeolite coating was growing onto a FeCrAlloy metal using in –situ hydrothermal method. The zeolite film was obtained using in-situ crystallization process that is capable of coating large surfaces with complex shape and in confined spaces has been developed. The zeolite coating offers an advantage of a high mechanical stability and thermal stability. The physico-chemical properties were investigated using X-ray diffraction (XRD), Electron microscopy (SEM), Energy Dispersive X–ray analysis (EDX) and Thermogravimetric Analysis (TGA). The transition from oxide-on-alloy wires to hydrothermally synthesised uniformly zeolite coated surfaces was followed using SEM and XRD. In addition, the robustness of the prepared coating was confirmed by subjecting these to thermal cycling (ambient to 550°C).

Keywords: fecralloy, zsm-5 zeolite, zeolite coatings, hydrothermal method

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4542 Analysis of Slope in an Excavated Gneiss Rock Using Geological Strength Index (GSI) in Ilorin, Kwara State, Nigeria

Authors: S. A. Agbalajobi, W. A. Bello

Abstract:

The study carried out analysis on slope stability in an excavated gneiss rock using geological strength index (GSI) in Ilorin, Kwara State, Nigeria. A kinematic analysis of planar discontinuity sets in a gneiss deposit was carried out to ascertain the degree of slope stability. Discontinuity orientations in the rock mass were mapped using compass clinometers. The average result of physical and mechanical properties such as specific gravity, unit weight, uniaxial compressive strength, point load index, and Schmidt rebound value are 2.64 g/m3, 25.95 kN/m3, 156 MPa, 6.5 MPa, and 53.12 respectively. Also, a statistical model equation relating the rock strength was developed. The analyses states that the rock face is susceptible to wedge failures having all the geometrical conditions associated with the occurrence of such failures were noticeable. It can be concluded that analyses of discontinuity orientation in relation to cut face direction in rock excavation is essential for mine planning to forestall mine accidents. Assessment of excavated slope methods was evident that one excavation method (blasting and/or use of hydraulic hammer) is applicable for the given rock strength, the ease of excavation decreases as the rock mass quality increases, thus blasting most suitable for such operation.

Keywords: slope stability, wedge failure, geological strength index (GSI), discontinuities and excavated slope

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4541 The Quantitative Optical Modulation of Dopamine Receptor-Mediated Endocytosis Using an Optogenetic System

Authors: Qiaoyue Kuang, Yang Li, Mizuki Endo, Takeaki Ozawa

Abstract:

G protein-coupled receptors (GPCR) are the largest family of receptor proteins that detect molecules outside the cell and activate cellular responses. Of the GPCRs, dopamine receptors, which recognize extracellular dopamine, are essential to mammals due to their roles in numerous physiological events, including autonomic movement, hormonal regulation, emotions, and the reward system in the brain. To precisely understand the physiological roles of dopamine receptors, it is important to spatiotemporally control the signaling mediated by dopamine receptors, which is strongly dependent on their surface expression. Conventionally, chemical-induced interactions were applied to trigger the endocytosis of cell surface receptors. However, these methods were subjected to diffusion and therefore lacked temporal and special precision. To further understand the receptor-mediated signaling and to control the plasma membrane expression of receptors, an optogenetic tool called E-fragment was developed. The C-terminus of a light-sensitive photosensory protein cyptochrome2 (CRY2) was attached to β-Arrestin, and the E-fragment was generated by fusing the C-terminal peptide of vasopressin receptor (V2R) to CRY2’s binding partner protein CIB. The CRY2-CIB heterodimerization triggered by blue light stimulation brings β-Arrestin to the vicinity of membrane receptors and results in receptor endocytosis. In this study, the E-fragment system was applied to dopamine receptors 1 and 2 (DRD1 and DRD2) to control dopamine signaling. First, confocal fluorescence microscope observation qualitatively confirmed the light-induced endocytosis of E-fragment fused receptors. Second, NanoBiT bioluminescence assay verified quantitatively that the surface amount of E-fragment labeled receptors decreased after light treatment. Finally, GloSensor bioluminescence assay results suggested that the E-fragment-dependent receptor light-induced endocytosis decreased cAMP production in DRD1 signaling and attenuated the inhibition effect of DRD2 on cAMP production. The developed optogenetic tool was able to induce receptor endocytosis by external light, providing opportunities to further understand numerous physiological activities by controlling receptor-mediated signaling spatiotemporally.

Keywords: dopamine receptors, endocytosis, G protein-coupled receptors, optogenetics

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4540 Synthesis and Characterization of Some New Diamines and Their Thermally Stable Polyimides

Authors: Zill-E-Huma, Humaira Siddiqi

Abstract:

This paper comprises of synthesis of thermally stable, mechanically strong polyimides. The polyimides were considered as most diverse class of polymers having unlimited applications. They were widely used as optical wave guides, in aerospace, for gas separation, as biomaterials and in electronics. Here the focus was to increase thermal stability and mechanical strength of polyimides. For this purpose two monomers were synthesized and were further polymerized via anhydrides to polyimides. The monomer diamines were synthesized by nucleophilic attack of aniline/2-fluoro aniline on hydroxy benzaldehydes. The two diamines synthesized were 3-(bis(4-aminophenyl) methyl) phenol (3OHDA) and 4-(bis(4-amino-3-fluorophenyl) methyl) phenol (2F4OHDA). These diamines were then reacted with dianhydrides to get polyimides. Two neat polyimides of both diamines with pyromellitic dianhydride (PMDA) and one neat polyimide of 4'-(Hexafluoroisopropylidene) diphthalic dianhydride (6FDA) with 3OHDA were synthesized. To compare the properties of synthesized polyimides like thermal stability, rigidity, flexibility, toughness etc. a commercial diamine oxydianiline (ODA) was used. Polyimides from oxydianiline were basically rigid. Nine different polyimide blends were synthesized from 3OHDA and commercial diamines ODA to have a better comparison of properties. TGA and mechanical testing results showed that with the increase in the percentage of 3OHDA in comparison to ODA the flexibility, toughness, strength of polyimide, thermal stability goes on increasing. So, synthesized diamines were responsible for improvement of properties of polyimides.

Keywords: diamines, dianhydrides, oxydianiline, polyimides

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4539 Stability Analysis of Stagnation-Point Flow past a Shrinking Sheet in a Nanofluid

Authors: Amin Noor, Roslinda Nazar, Norihan Md. Arifin

Abstract:

In this paper, a numerical and theoretical study has been performed for the stagnation-point boundary layer flow and heat transfer towards a shrinking sheet in a nanofluid. The mathematical nanofluid model in which the effect of the nanoparticle volume fraction is taken into account is considered. The governing nonlinear partial differential equations are transformed into a system of nonlinear ordinary differential equations using a similarity transformation which is then solved numerically using the function bvp4c from Matlab. Numerical results are obtained for the skin friction coefficient, the local Nusselt number as well as the velocity and temperature profiles for some values of the governing parameters, namely the nanoparticle volume fraction Φ, the shrinking parameter λ and the Prandtl number Pr. Three different types of nanoparticles are considered, namely Cu, Al2O3 and TiO2. It is found that solutions do not exist for larger shrinking rates and dual (upper and lower branch) solutions exist when λ < -1.0. A stability analysis has been performed to show which branch solutions are stable and physically realizable. It is also found that the upper branch solutions are stable while the lower branch solutions are unstable.

Keywords: heat transfer, nanofluid, shrinking sheet, stability analysis, stagnation-point flow

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4538 An Evolutionary Perspective on the Role of Extrinsic Noise in Filtering Transcript Variability in Small RNA Regulation in Bacteria

Authors: Rinat Arbel-Goren, Joel Stavans

Abstract:

Cell-to-cell variations in transcript or protein abundance, called noise, may give rise to phenotypic variability between isogenic cells, enhancing the probability of survival under stress conditions. These variations may be introduced by post-transcriptional regulatory processes such as non-coding, small RNAs stoichiometric degradation of target transcripts in bacteria. We study the iron homeostasis network in Escherichia coli, in which the RyhB small RNA regulates the expression of various targets as a model system. Using fluorescence reporter genes to detect protein levels and single-molecule fluorescence in situ hybridization to monitor transcripts levels in individual cells, allows us to compare noise at both transcript and protein levels. The experimental results and computer simulations show that extrinsic noise buffers through a feed-forward loop configuration the increase in variability introduced at the transcript level by iron deprivation, illuminating the important role that extrinsic noise plays during stress. Surprisingly, extrinsic noise also decouples of fluctuations of two different targets, in spite of RyhB being a common upstream factor degrading both. Thus, phenotypic variability increases under stress conditions by the decoupling of target fluctuations in the same cell rather than by increasing the noise of each. We also present preliminary results on the adaptation of cells to prolonged iron deprivation in order to shed light on the evolutionary role of post-transcriptional downregulation by small RNAs.

Keywords: cell-to-cell variability, Escherichia coli, noise, single-molecule fluorescence in situ hybridization (smFISH), transcript

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4537 Predicting COVID-19 Severity Using a Simple Parameters in Resource-Limited Settings

Authors: Sireethorn Nimitvilai, Ussanee Poolvivatchaikarn, Nuchanart Tomeun

Abstract:

Objective: To determine the simple laboratory parameters to predict disease severity among COVID-19 patients in resource-limited settings. Material and methods: A retrospective cohort study was conducted at Nakhonpathom Hospital, a 722-bed tertiary care hospital, with an average of 50,000 admissions per year, during April 15 and May 15, 2021. Eligible patients were adults aged ≥ 15 years who were hospitalized with COVID-19. Baseline characteristics, comorbid conditions ad laboratory findings at admission were collected. Predictive factors for severe COVID-19 infection were analyzed. Result: There were 207 patients (79 male and 128 female) and the mean age was 46.7 (16.8) years. Of these, 39 cases (18.8%) were severe and 168 (81.2%) cases were non-severe. Factors associated with severe COVID-19 were neutrophil to lymphocyte ratio ≥ 4 (OR 8.1, 95%CI 2.3-20.3, P < 0.001) and C-reactive protein to albumin ratio ≥ 10 (OR 3.49, 95%CI 1.3-9.1, p 0.01). Conclusions: Complete blood counts, C-reactive protein and albumin are simple, inexpensive, widely available tests and can be used to predict severe COVID-19 in resource-limited settings.

Keywords: COVID-19, predictor of severity, resource-limiting settings, simple laboratory parameters

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4536 Effect of Spermidine on Physicochemical Properties of Protein Based Films

Authors: Mohammed Sabbah, Prospero Di Pierro, Raffaele Porta

Abstract:

Protein-based edible films and coatings have attracted an increasing interest in recent years since they might be used to protect pharmaceuticals or improve the shelf life of different food products. Among them, several plant proteins represent an abundant, inexpensive and renewable raw source. These natural biopolymers are used as film forming agents, being able to form intermolecular linkages by various interactions. However, without the addition of a plasticizing agent, many biomaterials are brittle and, consequently, very difficult to be manipulated. Plasticizers are generally small and non-volatile organic additives used to increase film extensibility and reduce its crystallinity, brittleness and water vapor permeability. Plasticizers normally act by decreasing the intermolecular forces along the polymer chains, thus reducing the relative number of polymer-polymer contacts, producing a decrease in cohesion and tensile strength and thereby increasing film flexibility allowing its deformation without rupture. The most commonly studied plasticizers are polyols, like glycerol (GLY) and some mono or oligosaccharides. In particular, GLY not only increases film extensibility but also migrates inside the film network often causing the loss of desirable mechanical properties of the material. Therefore, replacing GLY with a different plasticizer might help to improve film characteristics allowing potential industrial applications. To improve film properties, it seemed of interest to test as plasticizers some cationic small molecules like polyamines (PAs). Putrescine, spermidine (SPD), and spermine are PAs widely distributed in nature and of particular interest for their biological activities that may have some beneficial health effects. Since PAs contains amino instead of hydroxyl functional groups, they are able to trigger ionic interactions with negatively charged proteins. Bitter vetch (Vicia ervilia; BV) is an ancient grain legume crop, originated in the Mediterranean region, which can be found today in many countries around the world. This annual Vicia genus shows several favorable features, being their seeds a cheap and abundant protein source. The main objectives of this study were to investigate the effect of different concentrations of SPD on the mechanical and permeability properties of films prepared with native or heat denatured BV proteins in the presence of different concentrations of SPD and/or GLY. Therefore, a BV seed protein concentrate (BVPC), containing about 77% proteins, was used to prepare film forming solutions (FFSs), whereas GLY and SPD were added as film plasticizers, either singly or in combination, at various concentrations. Since a primary plasticizer is generally defined as a molecule that when added to a material makes it softer, more flexible and easier to be processed, our findings lead to consider SPD as a possible primary plasticizer of protein-based films. In fact, the addition of millimolar concentrations of SPD to BVPC FFS allowed obtaining handleable biomaterials with improved properties. Moreover, SPD can be also considered as a secondary plasticizer, namely an 'extender', because of its ability even to enhance the plasticizing performance of GLY. In conclusion, our studies indicate that innovative edible protein-based films and coatings can be obtained by using PAs as new plasticizers.

Keywords: edible films, glycerol, plasticizers, polyamines, spermidine

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4535 NS5ABP37 Inhibits Liver Cancer by Impeding Lipogenesis and Cholesterogenesis

Authors: Shenghu Feng, Jun Cheng

Abstract:

The molecular mechanism underlying nonalcoholic fatty liver disease (NAFLD) progression to hepatocellular carcinoma (HCC) remains unknown. In this study, immunohistochemistry staining result showed that NS5ABP37 protein expression decreased as with increasing degree of HCC malignancy. In agreement, NS5ABP37 protein overexpression significantly suppressed cell proliferation, caused G1/S cell cycle arrest, and induced apoptosis by increasing caspase-3/7 activity and cleaved caspase-3 levels. In addition, NS5ABP37 overexpression resulted in decreased intracellular TG and TC contents, with level reduction in SREBPs and downstream effectors. Furthermore, NS5ABP37 overexpression decreased SREBP1c and SREBP2 levels by inducing their respective promoters. Finally, ROS levels and ER-stress were both induced by NS5ABP37 overexpression. These findings together demonstrate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 cells and inducing oxidative stress and ER stress.

Keywords: NS5ABP37, liver cancer, lipid metabolism, oxidative stress, ER stress

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4534 Analytical Slope Stability Analysis Based on the Statistical Characterization of Soil Shear Strength

Authors: Bernardo C. P. Albuquerque, Darym J. F. Campos

Abstract:

Increasing our ability to solve complex engineering problems is directly related to the processing capacity of computers. By means of such equipments, one is able to fast and accurately run numerical algorithms. Besides the increasing interest in numerical simulations, probabilistic approaches are also of great importance. This way, statistical tools have shown their relevance to the modelling of practical engineering problems. In general, statistical approaches to such problems consider that the random variables involved follow a normal distribution. This assumption tends to provide incorrect results when skew data is present since normal distributions are symmetric about their means. Thus, in order to visualize and quantify this aspect, 9 statistical distributions (symmetric and skew) have been considered to model a hypothetical slope stability problem. The data modeled is the friction angle of a superficial soil in Brasilia, Brazil. Despite the apparent universality, the normal distribution did not qualify as the best fit. In the present effort, data obtained in consolidated-drained triaxial tests and saturated direct shear tests have been modeled and used to analytically derive the probability density function (PDF) of the safety factor of a hypothetical slope based on Mohr-Coulomb rupture criterion. Therefore, based on this analysis, it is possible to explicitly derive the failure probability considering the friction angle as a random variable. Furthermore, it is possible to compare the stability analysis when the friction angle is modelled as a Dagum distribution (distribution that presented the best fit to the histogram) and as a Normal distribution. This comparison leads to relevant differences when analyzed in light of the risk management.

Keywords: statistical slope stability analysis, skew distributions, probability of failure, functions of random variables

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4533 Development of an Electrochemical Aptasensor for the Detection of Human Osteopontin Protein

Authors: Sofia G. Meirinho, Luis G. Dias, António M. Peres, Lígia R. Rodrigues

Abstract:

The emerging development of electrochemical aptasen sors has enabled the easy and fast detection of protein biomarkers in standard and real samples. Biomarkers are produced by body organs or tumours and provide a measure of antigens on cell surfaces. When detected in high amounts in blood, they can be suggestive of tumour activity. These biomarkers are more often used to evaluate treatment effects or to assess the potential for metastatic disease in patients with established disease. Osteopontin (OPN) is a protein found in all body fluids and constitutes a possible biomarker because its overexpression has been related with breast cancer evolution and metastasis. Currently, biomarkers are commonly used for the development of diagnostic methods, allowing the detection of the disease in its initial stages. A previously described RNA aptamer was used in the current work to develop a simple and sensitive electrochemical aptasensor with high affinity for human OPN. The RNA aptamer was biotinylated and immobilized on a gold electrode by avidin-biotin interaction. The electrochemical signal generated from the aptamer–target molecule interaction was monitored electrochemically using cyclic voltammetry in the presence of [Fe (CN) 6]−3/− as a redox probe. The signal observed showed a current decrease due to the binding of OPN. The preliminary results showed that this aptasensor enables the detection of OPN in standard solutions, showing good selectivity towards the target in the presence of others interfering proteins such as bovine OPN and bovine serum albumin. The results gathered in the current work suggest that the proposed electrochemical aptasensor is a simple and sensitive detection tool for human OPN and so, may have future applications in cancer disease monitoring.

Keywords: osteopontin, aptamer, aptasensor, screen-printed electrode, cyclic voltammetry

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4532 Geological and Geotechnical Approach for Stabilization of Cut-Slopes in Power House Area of Luhri HEP Stage-I (210 MW), India

Authors: S. P. Bansal, Mukesh Kumar Sharma, Ankit Prabhakar

Abstract:

Luhri Hydroelectric Project Stage-I (210 MW) is a run of the river type development with a dam toe surface powerhouse (122m long, 50.50m wide, and 65.50m high) on the right bank of river Satluj in Himachal Pradesh, India. The project is located in the inner lesser Himalaya between Dhauladhar Range in the south and higher Himalaya in the north in the seismically active region. At the project, the location river is confined within narrow V-shaped valleys with little or no flat areas close to the river bed. Nearly 120m high cut slopes behind the powerhouse are proposed from the powerhouse foundation level of 795m to ± 915m to accommodate the surface powerhouse. The stability of 120m high cut slopes is a prime concern for the reason of risk involved. The slopes behind the powerhouse will be excavated in mainly in augen gneiss, fresh to weathered in nature, and biotite rich at places. The foliation joints are favorable and dipping inside the hill. Two valleys dipping steeper joints will be encountered on the slopes, which can cause instability during excavation. Geological exploration plays a vital role in designing and optimization of cut slopes. SWEDGE software has been used to analyze the geometry and stability of surface wedges in cut slopes. The slopes behind powerhouse have been analyzed in three zones for stability analysis by providing a break in the continuity of cut slopes, which shall provide quite substantial relief for slope stabilization measure. Pseudo static analysis has been carried out for the stabilization of wedges. The results indicate that many large wedges are forming, which have a factor of safety less than 1. The stability measures (support system, bench width, slopes) have been planned so that no wedge failure may occur in the future.

Keywords: cut slopes, geotechnical investigations, Himalayan geology, surface powerhouse, wedge failure

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4531 IgA/λ Plasma Cell Myeloma with λ Light Chain Amyloidosis: A Case Report

Authors: Kai Pei Huang, Ting Chung Hung, Li Ching Wu

Abstract:

Amyloidosis refers to a variety of conditions wherein amyloid proteins are abnormally deposited in organ or tissues and cause harm. Among the several forms of amyloidosis, the principal types of that in inpatient medical services are the AL amyloidosis (primary) and AA amyloidois (secondary). AL Amyloidois is due to deposition of protein derived from overproduction of immunoglobulin light chain in plasma cell myeloma. Furthermore, it is a systemic disorder that can present with a variety of symptoms, including heavy proteinemia and edema, heptosplenomegaly, otherwise unexplained heart failure. We reported a 78-year-old female presenting dysuria, oliguria and leg edema for several months. Laboratory data showed proteinuria (UPCR:1679.8), leukocytosis (WBC:16.2 x 10^3/uL), results of serum urea nitrogen (39mg/dL), creatinine (0.76 mg/dL), IgG (748 mg/dL.), IgA (635 mg/dL), IgM (63 mg/dL), kappa light chain(18.8 mg/dL), lambda light chain (110.0 mg/dL) and kappa/lambda ratio (0.17). Renal biopsy found amyloid fibrils in glomerular mesangial area, and Congo red stain highlights amyloid deposition in glomeruli. Additional lab studies included serum protein electrophoresis, which shows a major monoclonal peak in β region and minor small peak in gamma region, and the immunotyping studies for serum showed two IgA/λ type. We treated sample with beta-mercaptoethanol which reducing the polymerized immunoglobulin to clarify two IgA/λ are secreted from the same plasma cell clone in bone marrow. Later examination confirmed it existed plasma cell infiltration in bone marrow, and the immunohistochemical staining showed monotypic for λ light chain and are positive for IgA. All findings mentioned above reveal it is a case of plasma cell myeloma with λ Light Chain Amyloidosis.

Keywords: amyloidosis, immunoglobulin light chain, plasma cell myeloma, serum protein electrophoresis

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4530 Optimisation Model for Maximising Social Sustainability in Construction Scheduling

Authors: Laura Florez

Abstract:

The construction industry is labour intensive, and the behaviour and management of workers have a direct impact on the performance of construction projects. One of the issues it currently faces is how to recruit and maintain its workers. Construction is known as an industry where workers face the problem of short employment durations, frequent layoffs, and periods of unemployment between jobs. These challenges not only creates pressures on the workers but also project managers have to constantly train new workers, face skills shortage, and uncertainty on the quality of the workers it will attract. To consider worker’s needs and project managers expectations, one practice that can be implemented is to schedule construction projects to maintain a stable workforce. This paper proposes a mixed integer programming (MIP) model to schedule projects with the objective of maximising social sustainability of construction projects, that is, maximise labour stability. Aside from the social objective, the model accounts for equipment and financial resources required by the projects during the construction phase. To illustrate how the solution strategy works, a construction programme comprised of ten projects is considered. The projects are scheduled to maximise labour stability while simultaneously minimising time and minimising cost. The tradeoff between the values in terms of time, cost, and labour stability allows project managers to consider their preferences and identify which solution best suits their needs. Additionally, the model determines the optimal starting times for each of the projects, working patterns for the workers, and labour costs. This model shows that construction projects can be scheduled to not only benefit the project manager, but also benefit current workers and help attract new workers to the industry. Due to its practicality, it can be a valuable tool to support decision making and assist construction stakeholders when developing schedules that include social sustainability factors.

Keywords: labour stability, mixed-integer programming (MIP), scheduling, workforce management

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4529 Effects of Certain Natural Food Additives (Pectin, Gelatin and Whey Proteins) on the Qualities of Fermented Milk

Authors: Abderrahim Cheriguene, Fatiha Arioui

Abstract:

The experimental study focuses on the extraction of pectin, whey protein and gelatin, and the study of their functional properties. Microbiological, physicochemical and sensory approach integrated has been implanted to study the effect of the incorporation of these natural food additives in the matrix of a fermented milk type set yogurt, to study the stability of the product during the periods of fermentation and post-acidification over a period of 21 days at 4°C. Pectin was extracted in hot HCl solution. Thermo-precipitation was carried out to obtain the whey proteins while the gelatin was extracted by hydrolysis of the collagen from bovine ossein. The fermented milk was prepared by varying the concentration of the incorporated additives. The measures and controls carried performed periodically on fermented milk experimental tests were carried out: pH, acidity, viscosity, the enumeration of Streptococcus thermophilus, cohesiveness, adhesiveness, taste, aftertaste, whey exudation, and odor. It appears that the acidity, viscosity, and number of Streptococcus thermophilus increased with increasing concentration of additive added in the experimental tests. Indeed, it seems clear that the quality of fermented milk and storability is more improved than the incorporation rate is high. The products showed a better test and a firmer texture limiting the whey exudation.

Keywords: fermented milk, pectin, gelatin, whey proteins, functional properties, quality, conservation, valorization

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4528 Design of Rigid L-Shaped Retaining Walls

Authors: Ahmed Rouili

Abstract:

Cantilever L-shaped walls are known to be relatively economical as retaining solution. The design starts by proportioning the wall dimensions for which the stability is checked for. A ratio between the lengths of the base and the stem, falling between 0,5 to 0,7, ensure the stability requirements in most cases. However, the displacement pattern of the wall in terms of rotations and translations, and the lateral pressure profile, do not have the same figure for all wall’s proportioning, as it is usually assumed. In the present work, the results of a numerical analysis are presented, different wall geometries were considered. The results show that the proportioning governs the equilibrium between the instantaneous rotation and the translation of the wall-toe, also, the lateral pressure estimation based on the average value between the at-rest and the active pressure, recommended by most design standards, is found to be not applicable for all walls.

Keywords: cantilever wall, proportioning, numerical analysis, lateral pressure estimation

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4527 Nutritional Status in Ramadan Influences Body Compositions Differently in Men and Women

Authors: Meskure Pak, Nihal Buyukuslu

Abstract:

During Ramadan Muslims refrain from eating and drinking from dawn to sunset. Transformation of the eating habits cause profound changes in body composition. This study was performed during Ramadan of June-July 2015 with the regular fasting healthy adults (15 women and 15 men). The participants who were not fasting the whole month, have chronic diseases, pregnant and lactated were excluded. All attendances were informed about study. Written informed consent was taken from the voluntary participants. The work was approved by the Ethics and Research Committee of Istanbul Medipol University, Turkey. A questionnaire was conducted to determine the nutritional status, demographic and anthropometric data at the beginning, in the middle and at the end of Ramadan. Statistical Package for Social Sciences version 18.0 (SPSS, Chicago, IL, USA) was used for analyses. The mean ages of women and men were 34.4±9.45 and 28.9±10.55 years respectively. The BMI values (kg/m2) were slightly increased in men (26.5±3.9 to 26.2±3.7) and decreased in women (22.5±3.5 to 23.3±4.5). However the differences in BMI values between genders were not significant. Waist circumferences (WC) (cm) decreased in both women (80.2±14.6 to 79.4±17.7) and men (98.9±8.4 to 95.2±11.0) through the Ramadan. Fat percentages of women (27.0±71) increased in the middle of Ramadan (28.4±7.8) and decreased at the end of Ramadan (27.8±8.3). The fat percentages of men (21.5±6.3) were not affected in the middle of Ramadan (21.5±6.4) however decreased at the end of Ramadan (20.8±6.2). The total change in fat mass from beginning to end of Ramadan was higher in women than in men. The daily energy intake was higher in men than in women during Ramadan. In the middle of Ramadan energy intake (kcal) was reached to the highest level (2057.8±693.1) and at the end of Ramadan it decreased to the beginning level (1656.7±553.2) for men. However, daily energy intake of women slightly decreased from the beginning (1410.0±359.7) to the end (1409.2±366.7) of Ramadan. The comparison of energy intake between men and women was significant in the middle of Ramadan (p < 0.05). Water consumptions for both groups were increased in Ramadan fasting period. In comparison with the beginning of Ramadan, daily carbohydrate and fat consumptions increased and the consumption of protein decreased for men and for women at the end of Ramadan. The gender comparison resulted in a significant increase for protein and carbohydrate consumption of men in the middle of Ramadan (p < 0.05). In the first two weeks, the daily energy intake, the consumption of carbohydrates and fats seemed to increase for both men and women. However the later days of Ramadan daily fat consumption decreased to the level of beginning consumption levels which may indicate the nutritional adaptation period. In spite of the consumption of protein sources such as meat, poultry and egg increased, the decrease in the total amount of protein consumed in Ramadan may be due to a decrease in the consumption of milk and dairy products. In conclusion, the nutritional habits and preferred foods changed during Ramadan as a result affected the body composition.

Keywords: body composition, fasting, nutritional status, Ramadan

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4526 Assessing the Mechanical Safety, Durability, Strength, and Stability of Wooden Furniture Produced in Ghana

Authors: Haruna Seidu, Francis Wilson Owusu, Michael Mensah, Felix Boakye, James Korang, Safia Ibrahim

Abstract:

Over the years, wooden furniture produced in Ghana had no means of testing their products against standards. It was therefore difficult for such furniture producers to know whether their products conform to international standards. The setting up of the ISO 17025 compliant laboratory has become a reference and accessing point for determining the quality of the furniture they produce. The objective of the study includes the determination of mechanical safety, durability, strength, and stability of wooden furniture produced in Ghana. Twelve wooden furniture manufacturers were randomly selected to design furniture (chairs and tables) for testing. 9 out of the 12 produced chairs, and three provided tables. Standard testing methods were used in this experiment, including GS EN 581-1, GS EN 581-2, and GS EN 581-3. The test results analysis indicates 55.6% of the chairs tested passed all applicable tests. 66.7% of tables tested passed all the applicable tests. The percentage pass and failure of the 12 furniture were 58.3% and 41.7% respectively. In conclusion, chair manufacturers had good designs that withstand the standard testing of strength and durability; most failures occurred largely as a result of poor stability designs adopted for the construction of the chairs and tables. It was observed that the manufacturers did not use the software in designing their furniture.

Keywords: durability, international standards, mechanical safety, wooden furniture design

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4525 Geotechnical Engineering Solutions for Adaptation

Authors: Johnstone Walubengo Wangusi

Abstract:

Geotechnical engineering is a multidisciplinary field that encompasses the study of soil, rock, and groundwater properties and their interactions with civil engineering structures. This research paper provides an in-depth overview of geotechnical engineering, covering its fundamental principles, applications in civil infrastructure projects, and the challenges faced by practitioners in the field. Through a comprehensive examination of soil mechanics, foundation design, slope stability analysis, and geotechnical site investigation techniques, this paper aims to highlight the importance of geotechnical engineering in ensuring the safety, stability, and sustainability of infrastructure development. Additionally, it discusses emerging trends, innovative technologies, and future directions in geotechnical engineering research and practice.

Keywords: sustainable geotechnical engineering solutions, education and training for future generations geotechnical engineers, integration of geotechnical engineering and structural engineering, use of AI in geotechnical engineering modelling

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4524 Influence of Intermediate Principal Stress on Solution of Planar Stability Problems

Authors: M. Jahanandish, M. B. Zeydabadinejad

Abstract:

In this paper, von Mises and Drucker-Prager yield criteria, as typical ones that consider the effect of intermediate principal stress σ2, have been selected and employed for investigating the influence of σ2 on the solution of a typical stability problem. The bearing capacity factors have been calculated under plane strain condition (strip footing) and axisymmetric condition (circular footing) using the method of stress characteristics together with the criteria mentioned. Different levels of σ2 relative to the other two principal stresses have been considered. While a higher σ2 entry in yield criterion gives a higher bearing capacity; its entry in equilibrium equations (axisymmetric) causes substantial reduction.

Keywords: intermediate principal stress, plane strain, axisymmetric, yield criteria

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4523 Famotidine Loaded Solid Lipid Nanoparticles (SLN) for Oral Delivery System

Authors: Rachmat Mauludin, Novita R. Kusuma, Diky Mudhakir

Abstract:

Famotidine (FMT) is one of used substances in the treatment of hiperacidity and peptic ulcer, administered orally and parenterally via intravenous injection. Oral administration, which is more favorable, has been reported to have many obstacles in the process of the treatment, includes decreasing the bioavailability of FMT. This research was aimed to prepare FMT in form of solid lipid nanoparticles (SLN) with size ranging between 100-200 nm. The research was carried out also by optimizing factors that may affect physical stability of SLN. Formulation of Famotidine SLN was carried out by optimizing factors, such as duration of homogenization and sonication, lipid concentration, stabilizer composition and stabilizer concentration. SLN physical stability was evaluated (particle size distribution) for 42 days in 3 diferent temperatures. Entrapment efficiency and drug loading was determined indirectly and directly. The morphology of SLN was visualized by transmission electron microscope (TEM). In vitro release study of FMT was conducted in 2 mediums, at pH of 1.2 and 7.4. Chemical stability of FMT was determined by quantifying the concentration of FMT within 42 days. Famotidin SLN consisted of GMS as lipid and poloxamer 188, lecithin, and polysorbate 80 as stabilizers. Homogenization and sonication was performed for 5 minutes and 10 minutes. Physyical stability of nanoparticles at 3 different temperatures was no significant difference. The best formula was physically stable until 42 days with mean particle size below 200 nm. Nanoparticles produced was able to entrap FMT until 86.6%. Evaluation by TEM showed that nanoparticles was spherical and solid. In medium pH of 1.2, FMT was released only 30% during 4 hour. On the other hand, within 4 hours SLN could release FMT completely in medium pH of 7.4. The FMT concentration in nanoparticles dispersion was maintained until 95% in 42 days (40oC, RH 75%). Famotidine SLN was able to be produced with mean particle size ranging between 100-200 nm and physically stable for 42 days. SLN could be loaded by 86,6% of FMT. Morphologically, obtained SLN was spheric and solid. During 4 hours in medium pH of 1.2 and 7.4, FMT was released until 30% and 100%, respectively.

Keywords: solid lipid nanoparticle (SLN), famotidine (FMT), physicochemical properties, release study

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4522 Variation in Carboxylesterase Activity in Spodoptera litura Fabricious (Noctuidae: Lepidoptera) Populations from India

Authors: V. Karuppaiah, J. C. Padaria, C. Srivastava

Abstract:

The tobacco caterpillar, Spodoptera litura Fab (Lepidoptera: Noctuidae) is a polyphagous pest various field and horticulture crops in India. Pest had virtually developed resistance to all commonly used insecticides. Enhanced detoxification is the prime mechanism that is dictated by detoxification different enzymes and carboxylesterase is one of the major enzyme responsible development of resistance. In India, insecticide resistance studies on S. litura are mainly deployed on detoxification enzymes activity and investigation at gene level alteration i.e. at nucleotide level is very merger. In the present study, we collected the S. litura larvae from three different cauliflower growing belt viz., IARI, New Delhi (Delhi), Palari, Sonepat (Haryana) and Varanasi (Uttar Pradesh) to study the role of carboxylesterase activity and its gene level variation The CarE activity was measured using UV-VIS spectrophotometer with 3rd instar larvae of S. litura. The elevated activity of CarE was observed in Sonepat strain (28.09 ± 0.09 µmol/min/mg of protein) followed by Delhi (26.72 ± 0.04 µmol/min/mg of protein) and Varanasi strain (10.00 ± 0.44 µmol/min/mg of protein) of S. litura. The genomic DNA was isolated from 3rd instar larvae and CarE gene was amplified using a primer sequence, F:5’tccagagttccttgtcaggcac3’; R:5’ctgcatcaagcatgtctc3. CarE gene, about 500bp was partially amplified, sequenced and submitted to NCBI (Accession No. KF835886, KF835887 and KF835888). The sequence data revealed polymorphism at nucleotide level in all the three strains and gene found to have 88 to 97% similarity with previous available nucleotide sequences of S. litura, S. littoralis and S. exiqua. The polymorphism at the nucleotide level could be a reason for differential activity of carboxylesterase enzymes among the strains. However, investigation at gene expression level would be useful to analyze the overproduction of carboxylesterase enzyme.

Keywords: carboxylesterase, CarE gene, nucleotide polymorphism, insecticide resistance, spodoptera litura

Procedia PDF Downloads 922
4521 Effect of Formulated Insect Enriched Sprouted Soybean /Millet Based Food on Gut Health Markers in Albino Wistar Rats

Authors: Gadanya, A.M., Ponfa, S., Jibril, M.M., Abubakar, S. M.

Abstract:

Background: Edible insects such as grasshopper are important sources of food for humans, and have been consumed as traditional foods by many indigenous communities especially in Africa, Asia, and Latin America. These communities have developed their skills and techniques in harvesting, preparing, consuming, and preserving edible insects, widely contributing to the role played by the use of insects in human nutrition. Aim/ objective: This study was aimed at determining the effect of insect enriched sprouted soyabean /millet based food on some gut health markers in albino rats. Methods. Four different formulations of Complementary foods (i.e Complementary Food B (CFB): sprouted millet (SM), Complementary Food C (CFC): sprouted soyabean (SSB), Complementary Food D (CFD): sprouted soybean and millet (SSBM) in a ratio of (50:50) and Complementary Food E (CFE): insect (grasshopper) enriched sprouted soybean and millet (SSBMI) in a ratio of (50:25:25)) were prepared. Proximate composition and short chain fatty acid contents were determined. Thirty albino rats were divided into5 groups of six rats each. Group 1(CDA) were fed with basal diet and served as a control group, while groups 2,3,4 and 5 were fed with the corresponding complimentary foods CFB, CFC, CFD and CFE respectively daily for four weeks. Concentrations of fecal protein, serum total carotenoids and nitric oxide were determined. DNA extraction for molecular isolation and characterization were carried out followed by PCR, the use of mega 11 software and NCBI blast for construction of the phylogenetic tree and organism identification respectively. Results: Significant increase (P<0.05) in percentage ash, fat, protein and moisture contents, as well as short chain fatty acid (acetate, butyrate and propionate) concentrations were recorded in the insect enriched sprouted composite food (CFE) when compared with the CFA, CFB, CFC and CFD composite food. Faecal protein, carotenoid and nitric oxide concentrations were significantly lower (P>0.05) in group 5 in comparison to groups 1to 4. Ruminococcus bromii and Bacteroidetes were molecularly isolated and characterized by 16s rRNA from the sprouted millet/sprouted soybean and the insect enriched sprouted soybean/sprouted millet based food respectively. The presence of these bacterial strains in the feaces of the treated rats is an indication that the gut of the treated rats is colonized by good gut bacteria, hence, an improved gut health. Conclusion: Insect enriched sprouted soya bean/sprouted millet based complementary diet showed a high composition of ash, fat, protein and fiber. Thus, could increase the availability of short chain fatty acids whose role to the host organism cannot be overemphasized. It was also found to have decrease the level of faecal protein, carotenoid and nitric oxide in the serum which is an indication of an improvement in the immune system function.

Keywords: gut-health, insect, millet, soybean, sprouted

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4520 Airborne Pollutants and Lung Surfactant: Biophysical Impacts of Surface Oxidation Reactions

Authors: Sahana Selladurai, Christine DeWolf

Abstract:

Lung surfactant comprises a lipid-protein film that coats the alveolar surface and serves to prevent alveolar collapse upon repeated breathing cycles. Exposure of lung surfactant to high concentrations of airborne pollutants, for example tropospheric ozone in smog, can chemically modify the lipid and protein components. These chemical changes can impact the film functionality by decreasing the film’s collapse pressure (minimum surface tension attainable), altering it is mechanical and flow properties and modifying lipid reservoir formation essential for re-spreading of the film during the inhalation process. In this study, we use Langmuir monolayers spread at the air-water interface as model membranes where the compression and expansion of the film mimics the breathing cycle. The impact of ozone exposure on model lung surfactant films is measured using a Langmuir film balance, Brewster angle microscopy and a pendant drop tensiometer as a function of film and sub-phase composition. The oxidized films are analyzed using mass spectrometry where lipid and protein oxidation products are observed. Oxidation is shown to reduce surface activity, alter line tension (and film morphology) and in some cases visibly reduce the viscoelastic properties of the film when compared to controls. These reductions in functionality of the films are highly dependent on film and sub-phase composition, where for example, the effect of oxidation is more pronounced when using a physiologically relevant buffer as opposed to water as the sub-phase. These findings can lead to a better understanding on the impact of continuous exposure to high levels of ozone on the mechanical process of breathing, as well as understanding the roles of certain lung surfactant components in this process.

Keywords: lung surfactant, oxidation, ozone, viscoelasticity

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4519 Recovery of Food Waste: Production of Dog Food

Authors: K. Nazan Turhan, Tuğçe Ersan

Abstract:

The population of the world is approximately 8 billion, and it increases uncontrollably and irrepressibly, leading to an increase in consumption. This situation causes crucial problems, and food waste is one of these. The Food and Agriculture Organization of the United Nations (FAO) defines food waste as the discarding or alternative utilization of food that is safe and nutritious for the consumption of humans along the entire food supply chain, from primary production to end household consumer level. In addition, according to the estimation of FAO, one-third of all food produced for human consumption is lost or wasted worldwide every year. Wasting food endangers natural resources and causes hunger. For instance, excessive amounts of food waste cause greenhouse gas emissions, contributing to global warming. Therefore, waste management has been gaining significance in the last few decades at both local and global levels due to the expected scarcity of resources for the increasing population of the world. There are several ways to recover food waste. According to the United States Environmental Protection Agency’s Food Recovery Hierarchy, food waste recovery ways are source reduction, feeding hungry people, feeding animals, industrial uses, composting, and landfill/incineration from the most preferred to the least preferred, respectively. Bioethanol, biodiesel, biogas, agricultural fertilizer and animal feed can be obtained from food waste that is generated by different food industries. In this project, feeding animals was selected as a food waste recovery method and food waste of a plant was used to provide ingredient uniformity. Grasshoppers were used as a protein source. In other words, the project was performed to develop a dog food product by recovery of the plant’s food waste after following some steps. The collected food waste and purchased grasshoppers were sterilized, dried and pulverized. Then, they were all mixed with 60 g agar-agar solution (4%w/v). 3 different aromas were added, separately to the samples to enhance flavour quality. Since there are differences in the required amounts of different species of dogs, fulfilling all nutritional needs is one of the problems. In other words, there is a wide range of nutritional needs in terms of carbohydrates, protein, fat, sodium, calcium, and so on. Furthermore, the requirements differ depending on age, gender, weight, height, and species. Therefore, the product that was developed contains average amounts of each substance so as not to cause any deficiency or surplus. On the other hand, it contains more protein than similar products in the market. The product was evaluated in terms of contamination and nutritional content. For contamination risk, detection of E. coli and Salmonella experiments were performed, and the results were negative. For the nutritional value test, protein content analysis was done. The protein contents of different samples vary between 33.68% and 26.07%. In addition, water activity analysis was performed, and the water activity (aw) values of different samples ranged between 0.2456 and 0.4145.

Keywords: food waste, dog food, animal nutrition, food waste recovery

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4518 Analytical and Numerical Investigation of Friction-Restricted Growth and Buckling of Elastic Fibers

Authors: Peter L. Varkonyi, Andras A. Sipos

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The quasi-static growth of elastic fibers is studied in the presence of distributed contact with an immobile surface, subject to isotropic dry or viscous friction. Unlike classical problems of elastic stability modelled by autonomous dynamical systems with multiple time scales (slowly varying bifurcation parameter, and fast system dynamics), this problem can only be formulated as a non-autonomous system without time scale separation. It is found that the fibers initially converge to a trivial, straight configuration, which is later replaced by divergence reminiscent of buckling phenomena. In order to capture the loss of stability, a new definition of exponential stability against infinitesimal perturbations for systems defined over finite time intervals is developed. A semi-analytical method for the determination of the critical length based on eigenvalue analysis is proposed. The post-critical behavior of the fibers is studied numerically by using variational methods. The emerging post-critical shapes and the asymptotic behavior as length goes to infinity are identified for simple spatial distributions of growth. Comparison with physical experiments indicates reasonable accuracy of the theoretical model. Some applications from modeling plant root growth to the design of soft manipulators in robotics are briefly discussed.

Keywords: buckling, elastica, friction, growth

Procedia PDF Downloads 190
4517 Tailorability of Poly(Aspartic Acid)/BSA Complex by Self-Assembling in Aqueous Solutions

Authors: Loredana E. Nita, Aurica P. Chiriac, Elena Stoleru, Alina Diaconu, Tudorachi Nita

Abstract:

Self-assembly processes are an attractive method to form new and complex structures between macromolecular compounds to be used for specific applications. In this context, intramolecular and intermolecular bonds play a key role during self-assembling processes in preparation of carrier systems of bioactive substances. Polyelectrolyte complexes (PECs) are formed through electrostatic interactions, and though they are significantly below of the covalent linkages in their strength, these complexes are sufficiently stable owing to the association processes. The relative ease way of PECs formation makes from them a versatile tool for preparation of various materials, with properties that can be tuned by adjusting several parameters, such as the chemical composition and structure of polyelectrolytes, pH and ionic strength of solutions, temperature and post-treatment procedures. For example, protein-polyelectrolyte complexes (PPCs) are playing an important role in various chemical and biological processes, such as protein separation, enzyme stabilization and polymer drug delivery systems. The present investigation is focused on evaluation of the PPC formation between a synthetic polypeptide (poly(aspartic acid) – PAS) and a natural protein (bovine serum albumin - BSA). The PPC obtained from PAS and BSA in different ratio was investigated by corroboration of various techniques of characterization as: spectroscopy, microscopy, thermo-gravimetric analysis, DLS and zeta potential determination, measurements which were performed in static and/or dynamic conditions. The static contact angle of the sample films was also determined in order to evaluate the changes brought upon surface free energy of the prepared PPCs in interdependence with the complexes composition. The evolution of hydrodynamic diameter and zeta potential of the PPC, recorded in situ, confirm changes of both co-partners conformation, a 1/1 ratio between protein and polyelectrolyte being benefit for the preparation of a stable PPC. Also, the study evidenced the dependence of PPC formation on the temperature of preparation. Thus, at low temperatures the PPC is formed with compact structure, small dimension and hydrodynamic diameter, close to those of BSA. The behavior at thermal treatment of the prepared PPCs is in agreement with the composition of the complexes. From the contact angle determination results the increase of the PPC films cohesion, which is higher than that of BSA films. Also, a higher hydrophobicity corresponds to the new PPC films denoting a good adhesion of the red blood cells onto the surface of PSA/BSA interpenetrated systems. The SEM investigation evidenced as well the specific internal structure of PPC concretized in phases with different size and shape in interdependence with the interpolymer mixture composition.

Keywords: polyelectrolyte – protein complex, bovine serum albumin, poly(aspartic acid), self-assembly

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4516 Computational Approach to Identify Novel Chemotherapeutic Agents against Multiple Sclerosis

Authors: Syed Asif Hassan, Tabrej Khan

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Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder, of the central nervous system (CNS). In the present scenario, the current therapies either do not halt the progression of the disease or have side effects which limit the usage of current Disease Modifying Therapies (DMTs) for a longer period of time. Therefore, keeping the current treatment failure schema, we are focusing on screening novel analogues of the available DMTs that specifically bind and inhibit the Sphingosine1-phosphate receptor1 (S1PR1) thereby hindering the lymphocyte propagation toward CNS. The novel drug-like analogs molecule will decrease the frequency of relapses (recurrence of the symptoms associated with MS) with higher efficacy and lower toxicity to human system. In this study, an integrated approach involving ligand-based virtual screening protocol (Ultrafast Shape Recognition with CREDO Atom Types (USRCAT)) to identify the non-toxic drug like analogs of the approved DMTs were employed. The potency of the drug-like analog molecules to cross the Blood Brain Barrier (BBB) was estimated. Besides, molecular docking and simulation using Auto Dock Vina 1.1.2 and GOLD 3.01 were performed using the X-ray crystal structure of Mtb LprG protein to calculate the affinity and specificity of the analogs with the given LprG protein. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has a higher hypothetical affinity, also has greater negative value. Further, the non-specific ligands were screened out using the structural filter proposed by Baell and Holloway. Based on the USRCAT, Lipinski’s values, toxicity and BBB analysis, the drug-like analogs of fingolimod and BG-12 showed that RTL and CHEMBL1771640, respectively are non-toxic and permeable to BBB. The successful docking and DSX analysis showed that RTL and CHEMBL1771640 could bind to the binding pocket of S1PR1 receptor protein of human with greater affinity than as compared to their parent compound (Fingolimod). In this study, we also found that all the drug-like analogs of the standard MS drugs passed the Bell and Holloway filter.

Keywords: antagonist, binding affinity, chemotherapeutics, drug-like, multiple sclerosis, S1PR1 receptor protein

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