Search results for: small molecule inhibitor

Authors: Axel Mancebo, Ana M. Bada, Angel Casacó, Bárbara González, Avelina León, María E. Arteaga, Consuelo González, Belinda Sánchez, Adriana Carr, Nuris Ledón, Arianna Iglesias

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Despite the many preventive and therapeutic modalities aimed at curing cancer, it remains as a serious world health problem. Promising recent developments suggest that cancer immunotherapy may be the next great hope for cancer treatment. EGFRs are receptor tyrosine kinases and it is considered an important therapeutic target related with tumor progression, and several types of molecular therapies, including monoclonal antibodies, small molecules, and vaccines, have been developed to target the HER family of receptors. On the other hand, gangliosides are membrane glycosphingolipids that contain two variants of sialic acid, the N-acetylated (NeuAc) and the N-glycolylated (NeuGc) variant. The high expression of this antigen-specific molecule has been associated with malignant tumor progression and immunosuppressive mechanisms, so ganglioside could be considered as the target for cancer immunotherapy. We have been working for several years in the safety evaluation of cancer vaccines targeting these two systems, the EGF receptor and ganglioside. We presented in this work results of repeated dose toxicity studies performed in Sprague Dawley rats and Cynomolgus monkeys, including clinical observations, body weight and rectal temperature measuring, clinical pathology analysis, gross necropsy and histological examination in rodent studies, and immunological evaluation. Immunizations were capable of inducing mainly inflammatory effects at the injection site, with findings largely attributable to the adjuvants used and probably enhanced by the immunological properties of the antigens. In general, these vaccines were shown to be well tolerated, and these studies in relevant species allow treating cancer patients with tumors during long periods with relative weight safety margin.

Keywords: cancer vaccines, safety, toxicology, rats, non human primates

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Authors: J. Constanzo, B. Paquette, G. Charest, L. Masson-Côté, M. Guillot

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Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The first step is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Eleven euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomographic (CT), to estimate positioning variations regarding to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates assessed from CT images, various regions of the brain were delimited and a treatment plan was generated. A dose of 37 Gy at 30% isodose which corresponds to 100 Gy in 100% of the target volume (X = 98.1; Y = 109.1; Z = 100.0) was set by Leksell Gamma Plan using sectors number 4, 5, 7, and 8 of the Gamma Knife unit with the 4-mm diameter collimators. Effects of positioning accuracy of the rat brain on the dose deposition were simulated by Gamma Plan and validated with dosimetric measurements. Our results showed that 90% of the target volume received 110 ± 4.7 Gy and the maximum of deposited dose was 124 ± 0.6 Gy, which corresponds to an excellent relative standard deviation of 0.5%. This dose deposition calculated with the Gamma Plan was validated with the dosimetric films resulting in a dose-profile agreement within 2%, both in X- and Z-axis,. Our results demonstrate the feasibility to standardize the irradiation procedure of a small volume in the rat brain using a Gamma Knife.

Keywords: brain irradiation, dosimetry, gamma knife, small-animal irradiation, stereotactic radiosurgery (SRS)

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Authors: J.Zambrano Nájera, M.Gómez Valentín

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Increases in urbanization during XX century, have brought as one major problem the increased of sediment production. Hydraulic erosion is one of the major causes of increasing of sediments in small urban catchments. Such increments in sediment yielding in header urban catchments can caused obstruction of drainage systems, making impossible to capture urban runoff, increasing runoff volumes and thus exacerbating problems of urban flooding. For these reasons, it is more and more important to study of sediment production in urban watershed for properly analyze and solve problems associated to sediments. The study of sediments production has improved with the use of mathematical modeling. For that reason, it is proposed a new physically based model applicable to small header urban watersheds that includes the advantages of distributed physically base models, but with more realistic data requirements. Additionally, in this paper the model proposed is compared with a lumped model, reviewing the results, the advantages and disadvantages between the both of them.

Keywords: erosion, hydrologic modeling, urban runoff, sediment modeling, sediment yielding, urban planning

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Authors: Cristian Sirbu-Dragomir, Stefan-Mihai Sofian, Adrian Predescu

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This paper aims to study Tesla pumps for circulating biofluids. It is desired to make a small pump for the circulation of biofluids. This type of pump will be studied because it has the following characteristics: It doesn’t have blades which results in very small frictions; Reduced friction forces; Low production cost; Increased adaptability to different types of fluids; Low cavitation (towards 0); Low shocks due to lack of blades; Rare maintenance due to low cavity; Very small turbulences in the fluid; It has a low number of changes in the direction of the fluid (compared to rotors with blades); Increased efficiency at low powers.; Fast acceleration; The need for a low torque; Lack of shocks in blades at sudden starts and stops. All these elements are necessary to be able to make a small pump that could be inserted into the thoracic cavity. The pump will be designed to combat myocardial infarction. Because the pump must be inserted in the thoracic cavity, elements such as Low friction forces, shocks as low as possible, low cavitation and as little maintenance as possible are very important. The operation should be performed once, without having to change the rotor after a certain time. Given the very small size of the pump, the blades of a classic rotor would be very thin and sudden starts and stops could cause considerable damage or require a very expensive material. At the same time, being a medical procedure, the low cost is important in order to be easily accessible to the population. The lack of turbulence or vortices caused by a classic rotor is again a key element because when it comes to blood circulation, the flow must be laminar and not turbulent. The turbulent flow can even cause a heart attack. Due to these aspects, Tesla's model could be ideal for this work. Usually, the pump is considered to reach an efficiency of 40% being used for very high powers. However, the author of this type of pump claimed that the maximum efficiency that the pump can achieve is 98%. The key element that could help to achieve this efficiency or one as close as possible is the fact that the pump will be used for low volumes and pressures. The key elements to obtain the best efficiency for this model are the number of rotors placed in parallel and the distance between them. The distance between them must be small, which helps to obtain a pump as small as possible. The principle of operation of such a rotor is to place in several parallel discs cut inside. Thus the space between the discs creates the vacuum effect by pulling the liquid through the holes in the rotor and throwing it outwards. Also, a very important element is the viscosity of the liquid. It dictates the distance between the disks to achieve a lossless power flow.

Keywords: lubrication, temperature, tesla-pump, viscosity

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Authors: Vedanki Khandenwal, Pawan Srivastava, Kartick Tarafder, Subhasis Ghosh

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We present here the experimental realization of controlled doping of graphene monolayers through charge transfer by trapping selected organic molecules between the graphene layer and underlying substrates. This charge transfer between graphene and trapped molecule leads to controlled n-type or p-type doping in monolayer graphene (MLG), depending on whether the trapped molecule acts as an electron donor or an electron acceptor. Doping controllability has been validated by a shift in corresponding Raman peak positions and a shift in Dirac points. In the transfer characteristics of field effect transistors, a significant shift of Dirac point towards positive or negative gate voltage region provides the signature of p-type or n-type doping of graphene, respectively, as a result of the charge transfer between graphene and the organic molecules trapped within it. In order to facilitate the charge transfer interaction, it is crucial for the trapped molecules to be situated in close proximity to the graphene surface, as demonstrated by findings in Raman and infrared spectroscopies. However, the mechanism responsible for this charge transfer interaction has remained unclear at the microscopic level. Generally, it is accepted that the dipole moment of adsorbed molecules plays a crucial role in determining the charge-transfer interaction between molecules and graphene. However, our findings clearly illustrate that the doping effect primarily depends on the reactivity of the constituent atoms in the adsorbed molecules rather than just their dipole moment. This has been illustrated by trapping various molecules at the graphene−substrate interface. Dopant molecules such as acetone (containing highly reactive oxygen atoms) promote adsorption across the entire graphene surface. In contrast, molecules with less reactive atoms, such as acetonitrile, tend to adsorb at the edges due to the presence of reactive dangling bonds. In the case of low-dipole moment molecules like toluene, there is a lack of substantial adsorption anywhere on the graphene surface. Observation of (i) the emergence of the Raman D peak exclusively at the edges for trapped molecules without reactive atoms and throughout the entire basal plane for those with reactive atoms, and (ii) variations in the density of attached molecules (with and without reactive atoms) to graphene with their respective dipole moments provides compelling evidence to support our claim. Additionally, these observations were supported by first principle density functional calculations.

Keywords: graphene, doping, charge transfer, liquid phase exfoliation

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Authors: Elaf Ahmed, Shahid Rasul, Ohoud Alharbi, Peng Wang

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Ultra-Small Nanoparticles of metals (USNPs) have attracted the attention from the perspective of both basic and developmental science in a wide range of fields. These NPs exhibit electrical, optical, magnetic, and catalytic phenomena. In addition, they are considered effective catalysts because of their enormously large surface area. Many chemical methods of synthesising USNPs are reported. However, the drawback of these methods is the use of different capping agents and ligands in the process of the production such as Polyvinylpyrrolidone, Thiol and Ethylene Glycol. In this research ultra-small nanoparticles of gold, palladium and platinum metal have been successfully produced using electrochemically active biofilm (EAB) after optimising the pH of the media. The production of ultra-small nanoparticles has been conducted in a reactor using a simple two steps method. Initially biofilm was grown on the surface of a carbon paper for 7 days using Shewanella Loihica bacteria. Then, biofilm was employed to synthesise platinum, palladium and gold nanoparticles in water using sodium lactate as electron donor without using any toxic chemicals at mild operating conditions. Electrochemically active biofilm oxidise the electron donor and produces electrons in the solution. Since these electrons are a strong reducing agent, they can reduce metal precursors quite effectively and quickly. The As-synthesized ultra-small nanoparticles have a size range between (2-7nm) and showed excellent catalytic activity on the degradation of methyl orange. The growth of metal USNPs is strongly related to the condition of the EAB. Where using low pH for the synthesis was not successful due to the fact that it might affect and destroy the bacterial cells. However, increasing the pH to 7 and 9, led to the successful formation of USNPs. By changing the pH value, we noticed a change in the size range of the produced NPs. The EAB seems to act as a Nano factory for the synthesis of metal nanoparticles by offering a green, sustainable and toxic free synthetic route without the use of any capping agents or ligands and depending only on their respiration pathway.

Keywords: electrochemically active biofilm, electron donor, shewanella loihica, ultra-small nanoparticles

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Authors: Rihab Hentati, Younes Boujelbene

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Nowadays we realize more and more than the value of a company is not only a function of its means of production but depends essentially on the managerial aptitude and orientation to implement the material and human means for generating profitability. Indeed, a productive R&D activity, a good strategy, and innovation are originally supplementary benefits that increase the value of the business. Is this ‘value-added’ closely linked to innovation? The purpose of our research is to Meta-analyze the results of 56 empirical studies in order to explain the overall effect of innovation on performance of small and medium-sized enterprises. In order to justify the differences in the results, we look for the moderating factors that may affect the innovation-performance relationship. We find a positive and significant relationship between innovation and performance in small and medium-sized enterprises. The results also note a positive relationship between entrepreneurial orientation, research and development (R&D), and performance in SMEs. In addition, innovation has a strong impact on performance measured both with accounting and market index. The originality of the article is based on a rigorous synthesis, based on several statistical tools, of an important subject of research in finance.

Keywords: innovation, performance, entrepreneurial orientation, meta-analysis, moderator variables

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Authors: Michal Spilacek, Marian Brazdil, Otakar Stelcl, Jiri Pospisil

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This paper shows an experimental testing of a small unit for combustion of solid fuels, such as charcoal and wood logs, that can provide electricity. One of the concepts is that the unit does not require a qualified personnel for its operation. The unit itself is composed of two main parts. The design requires a heat producing stove and an electricity producing thermoelectric generator. After the construction the unit was tested and the results shows that the emission release is within the legislative requirements for emission production and environmental protection. That qualifies such unit for indoor application.

Keywords: micro-cogeneration, thermoelectric generator, biomass combustion, wood stove

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Authors: Ubon Asuquo Essien, Okwudili Bismark Ibeagwa, Daberechi Peace Ubabuko

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The Broiler Poultry subsector is dominated by small scale production with low aggregate output. The high cost of inputs currently experienced in Nigeria tends to aggravate the situation; hence many broiler farmers struggle to break-even. This study was designed to examine income and input factors in small scale deep liter broiler production in Imo state, Nigeria. Specifically, the study examined; socio-economic characteristics of small scale deep liter broiler producing Poultry farmers; estimate cost and returns of broiler production in the area; analyze input factors in broiler production in the area and examined marketability, age and profitability of the enterprise. A multi-stage sampling technique was adopted in selecting 60 small scale broiler farmers who use deep liter system from 6 communities through the use of structured questionnaire. The socioeconomic characteristics of the broiler farmers and the profitability/ marketability age of the birds were described using descriptive statistical tools such as frequencies, means and percentages. Gross margin analysis was used to analyze the cost and returns to broiler production, while Cobb Douglas production function was employed to analyze input factors in broiler production. The result of the study revealed that the cost of feed (P<0.1), deep liter material (P<0.05) and medication (P<0.05) had a significant positive relationship with the gross return of broiler farmers in the study area, while cost of labour, fuel and day old chicks were not significant. Furthermore, Gross profit margin of the farmers who market their broiler at the 8th week of rearing was 80.7%; and 78.7% and 60.8% for farmers who market at the 10th week and 12th week of rearing, respectively. The business is, therefore, profitable but at varying degree. Government and Development partners should make deliberate efforts to curb the current rise in the prices of poultry feeds, drugs and timber materials used as bedding so as to widen the profit margin and encourage more farmers to go into the business. The farmers equally need more technical assistance from extension agents with regards to timely and profitable marketing.

Keywords: broilers, factor analysis, income, small scale

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Authors: Y. A. Prada, Fanny Guzman, Rafael Cabanzo, John J. Castillo, Enrique Mejia-Ospino

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In this work, we show the important results about of synthesis of photoluminiscents gold nanoclusters using a small peptide as template for biosensing applications. Interestingly, we design one peptide (NBC2854) homologue to conservative domain from 215 250 residue of a galactolectin protein which can recognize the proteophosphoglycans (PPG) from Leishmania. Peptide was synthetized by multiple solid phase synthesis using FMoc group methodology in acid medium. Finally, the peptide was purified by High-Performance Liquid Chromatography using a Vydac C-18 preparative column and the detection was at 215 nm using a Photo Diode Array detector. Molecular mass of this peptide was confirmed by MALDI-TOF and to verify the α-helix structure we use Circular Dichroism. By means of the methodology used we obtained a novel fluorescents gold nanoclusters (AuNC) using NBC2854 as a template. In this work, we described an easy and fast microsonic method for the synthesis of AuNC with ≈ 3.0 nm of hydrodynamic size and photoemission at 630 nm. The presence of cysteine residue in the C-terminal of the peptide allows the formation of Au-S bond which confers stability to Peptide-based gold nanoclusters. Interactions between the peptide and gold nanoclusters were confirmed by X-ray Photoemission and Raman Spectroscopy. Notably, from the ultrafine spectra shown in the MALDI-TOF analysis which containing only 3-7 KDa species was assigned to Au₈-₁₈[NBC2854]₂ clusters. Finally, we evaluated the Peptide-gold nanocluster as an optical biosensor based on fluorescence spectroscopy and the fluorescence signal of PPG (0.1 µg-mL⁻¹ to 1000 µg-mL⁻¹) was amplified at the same wavelength emission (≈ 630 nm). This can suggest that there is a strong interaction between PPG and Pep@AuNC, therefore, the increase of the fluorescence intensity can be related to the association mechanism that take place when the target molecule is sensing by the Pep@AuNC conjugate. Further spectroscopic studies are necessary to evaluate the fluorescence mechanism involve in the sensing of the PPG by the Pep@AuNC. To our best knowledge the fabrication of an optical biosensor based on Pep@AuNC for sensing biomolecules such as Proteophosphoglycans which are secreted in abundance by parasites Leishmania.

Keywords: biosensing, fluorescence, Leishmania, peptide-gold nanoclusters, proteophosphoglycans

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Authors: W. K. Zahra, M. A. El-Beltagy, R. R. Elkhadrawy

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So many practical problems in science and technology developed over the past decays. For instance, the mathematical boundary layer theory or the approximation of solution for different problems described by differential equations. When such problems consider large or small parameters, they become increasingly complex and therefore require the use of asymptotic methods. In this work, we consider the singularly perturbed boundary value problems which contain very small parameters. Moreover, we will consider these perturbation parameters as random variables. We propose a numerical method to solve this kind of problems. The proposed method is based on an exponential spline, Shishkin mesh discretization, and polynomial chaos expansion. The polynomial chaos expansion is used to handle the randomness exist in the perturbation parameter. Furthermore, the Monte Carlo Simulations (MCS) are used to validate the solution and the accuracy of the proposed method. Numerical results are provided to show the applicability and efficiency of the proposed method, which maintains a very remarkable high accuracy and it is ε-uniform convergence of almost second order.

Keywords: singular perturbation problem, polynomial chaos expansion, Shishkin mesh, two small parameters, exponential spline

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Authors: Mohammed Sabbah, Prospero Di Pierro, Raffaele Porta

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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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Authors: Tia Kristian Tajnšek, Matjaž Mazaj, Nataša Zabukovec Logar

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Metal-organic frameworks (MOFs) with their specific properties and the possibility of tuning the structure represent excellent candidates for use in the biomedical field. Their advantage lies in large pore surfaces and volumes, as well as the possibility of using bio-friendly or bioactive constituents. So-called bioMOFs are representatives of MOFs, which are constructed from at least one biomolecule (metal, a small bioactive molecule in metal clusters and/or linker) and are intended for bio-application (usually in the field of medicine; most commonly drug delivery). When designing a bioMOF for biomedical applications, we should adhere to some guidelines for an improved toxicological profile of the material. Such as (i) choosing an endogenous/nontoxic metal, (ii) GRAS (generally recognized as safe) linker, and (iii) nontoxic solvents. Design and synthesis of bioNICS-1 (bioMOF of National Institute of Chemistry Slovenia – 1) consider all these guidelines. Zinc (Zn) was chosen as an endogenous metal with an agreeable recommended daily intake (RDI) and LD50 value, and ascorbic acid (Vitamin C) was chosen as a GRAS and active linker. With these building blocks, we have synthesized a bioNICS-1 material. The synthesis was done in ethanol using a solvothermal method. The synthesis protocol was further optimized in three separate ways. Optimization of (i) synthesis parameters to improve the yield of the synthesis, (ii) input reactant ratio and addition of specific modulators for production of larger crystals, and (iii) differing of the heating source (conventional, microwave and ultrasound) to produce nano-crystals. With optimization strategies, the synthesis yield was increased. Larger crystals were prepared for structural analysis with the use of a proper species and amount of modulator. Synthesis protocol was adjusted to different heating sources, resulting in the production of nano-crystals of bioNICS-1 material. BioNICS-1 was further activated in ethanol and structurally characterized, resolving the crystal structure of new material.

Keywords: ascorbic acid, bioMOF, MOF, optimization, synthesis, zinc ascorbate

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Authors: Jiraporn Rojtinnakorn

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ICAM-2 (intercellular adhesion molecule 2) or CD102 (Cluster of Differentiation 102) is type I trans-membrane glycoproteins, composing 2-9 immunoglobulin-like C2-type domains. ICAM-2 plays the particular role in immune response and cell surveillance. It is concerned in innate and specific immunity, cell survival signal, apoptosis, and anticancer. EST clone of ICAM-2, from P. gigas blood cell EST libraries, showed high identity to human ICAM-2 (92%) with conserve region of ICAM N-terminal domain and part of Ig superfamily. Gene and protein of ICAM-2 has been founded in mammals. This is the first report of ICAM-2 in fish.

Keywords: ICAM-2, CD102, Pangasianodon gigas, antitumor

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Authors: Sibani Bisoyi, Ute Zschieschang, Alexander Hoyer, Hagen Klauk

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Abstract— Organic thin-film transistors (TFTs) have great potential to be used for various applications such as flexible displays or sensors. For some of these applications, the TFTs must be able to withstand temperatures in excess of 100 °C, for example to permit the integration with devices or components that require high process temperatures, or to make it possible that the devices can be subjected to the standard sterilization protocols required for biomedical applications. In this work, we have investigated how the thermal stability of low-voltage small-molecule semiconductor dinaphtho[2,3-b:2’,3’-f]thieno[3,2-b]thiophene (DNTT) TFTs is affected by the encapsulation of the TFTs and by the ambient in which the thermal stress is performed. We also studied to which extent the thermal stability of the TFTs depends on the channel length. Some of the TFTs were encapsulated with a layer of vacuum-deposited Teflon, while others were left without encapsulation, and the thermal stress was performed either in nitrogen or in air. We found that the encapsulation with Teflon has virtually no effect on the thermal stability of our TFTs. In contrast, the ambient in which the thermal stress is conducted was found to have a measurable effect, but in a surprising way: When the thermal stress is carried out in nitrogen, the mobility drops to 70% of its initial value at a temperature of 160 °C and to close to zero at 170 °C, whereas when the stress is performed in air, the mobility remains at 75% of its initial value up to a temperature of 160 °C and at 60% up to 180 °C. To understand this behavior, we studied the effect of the thermal stress on the semiconductor thin-film morphology by scanning electron microscopy. While the DNTT films remain continuous and conducting when the heating is carried out in air, the semiconductor morphology undergoes a dramatic change, including the formation of large, thick crystals of DNTT and a complete loss of percolation, when the heating is conducted in nitrogen. We also found that when the TFTs are heated to a temperature of 200 °C in air, all TFTs with a channel length greater than 50 µm are destroyed, while TFTs with a channel length of less than 50 µm survive, whereas when the TFTs are heated to the same temperature (200 °C) in nitrogen, only the TFTs with a channel smaller than 8 µm survive. This result is also linked to the thermally induced changes in the semiconductor morphology.

Keywords: organic thin-film transistors, encapsulation, thermal stability, thin-film morphology

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Authors: Heide Imai

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The paper will introduce and discuss specific examples of urban practices which take place within the dynamic urban landscape of contemporary Tokyo. The rising interest and importance of derelict places as resilient and creative clusters will be analysed, before relating this to the rediscovery of small urban niches and the emergence of different forms of social entrepreneurs. Secondly, two different case study areas will be introduced before discussing different forms of hybrid lifestyles, social micro scale enterprises and social innovations, understanding the concept of ‘small places of resilience’ as zones of human interaction, desire and care in which spontaneous practices take place.

Keywords: entrepreneurship, social innovation, Tokyo, urban regeneration

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Authors: Agnieszka E. Laudy, Karolina Stępien, Sergiusz Lulinski, Krzysztof Durka, Stefan Tyski

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1,3-dihydro-1-hydroxy-2,1-benzoxaborole and its derivatives are a particularly interesting group of synthetic agents and were successfully employed in supramolecular chemistry medicine. The first important compounds, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole and 5-chloro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole were identified as potent antifungal agents. In contrast, (S)-3-(aminomethyl)-7-(3-hydroxypropoxy)-1-hydroxy-1,3-dihydro-2,1-benzoxaborole hydrochloride is in the second phase of clinical trials as a drug for the treatment of Gram-negative bacterial infections of the Enterobacteriaceae family and Pseudomonas aeruginosa. Equally important and difficult task is to search for compounds active against Gram-negative bacilli, which have multi-drug-resistance efflux pumps actively removing many of the antibiotics from bacterial cells. We have examined whether halogen-substituted benzoxaborole-based derivatives and their analogues possess antibacterial activity and are substrates for multi-drug-resistance efflux pumps. The antibacterial activity of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole and 10 halogen-substituted its derivatives, as well as 1,2-phenylenediboronic acid and 3 synthesised fluoro-substituted its analogs, were evaluated. The activity against the reference strains of Gram-positive (n=5) and Gram-negative bacteria (n=10) was screened by the disc-diffusion test (0.4 mg of tested compounds was applied onto paper disc). The minimal inhibitory concentration values and the minimal bactericidal concentration values were estimated according to The Clinical and Laboratory Standards Institute and The European Committee on Antimicrobial Susceptibility Testing recommendations. During the minimal inhibitory concentration values determination with or without phenylalanine-arginine beta-naphthylamide (50 mg/L) efflux pump inhibitor, the concentrations of tested compounds ranged 0.39-400 mg/L in the broth medium supplemented with 1 mM magnesium sulfate. Generally, the studied benzosiloxaboroles and benzoxadiboroles showed a higher activity against Gram-positive cocci than against Gram-negative rods. Moreover, benzosiloxaboroles have the higher activity than benzoxadiboroles compounds. In this study, we demonstrated that substitution (mono-, di- or tetra-) of 1,3-dihydro-3-hydroxy-1,1-dimethyl-1,2,3-benzosiloxaborole with halogen groups resulted in an increase in antimicrobial activity as compared to the parent substance. Interestingly, the 6,7-dichloro-substituted parent substance was found to be the most potent against Gram-positive cocci: Staphylococcus sp. (minimal inhibitory concentration 6.25 mg/L) and Enterococcus sp. (minimal inhibitory concentration 25 mg/L). On the other hand, mono- and dichloro-substituted compounds were the most actively removed by efflux pumps present in Gram-negative bacteria mainly from Enterobacteriaceae family. In the presence of efflux pump inhibitor the minimal inhibitory concentration values of chloro-substituted benzosiloxaboroles decreased from 400 mg/L to 3.12 mg/L. Of note, the highest increase in bacterial susceptibility to tested compounds in the presence of phenylalanine-arginine beta-naphthylamide was observed for 6-chloro-, 6,7-dichloro- and 6,7-difluoro-substituted benzosiloxaboroles. In the case of Escherichia coli, Enterobacter cloacae and P. aeruginosa strains at least a 32-fold decrease in the minimal inhibitory concentration values of these agents were observed. These data demonstrate structure-activity relationships of the tested derivatives and highlight the need for further search for benzoxaboroles and related compounds with significant antimicrobial properties. Moreover, the influence of phenylalanine-arginine beta-naphthylamide on the susceptibility of Gram-negative rods to studied benzosiloxaboroles indicate that some tested agents are substrates for efflux pumps in Gram-negative rods.

Keywords: antibacterial activity, benzosiloxaboroles, efflux pumps, phenylalanine-arginine beta-naphthylamide

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Authors: Sanoj Sahu, Ramakar Jha

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Odisha (India) is in need of reliable, cost-effective power generation. A prolonged electricity crisis and increasing power demand have left over thousands of citizens without access to electricity, and much of the population suffers from sporadic outages. The purpose of this project is to build a methodology to evaluate small hydropower potential, which can be used to alleviate the Odisha’s energy problem among rural communities. This project has three major tasks: the design of a simple SHEP for a single location along a river in the Odisha; the development of water flow prediction equations through a linear regression analysis; and the design of an ArcGIS toolset to estimate the flow duration curves (FDCs) at locations where data do not exist. An explanation of the inputs to the tool, as well has how it produces a suitable output for SHEP evaluation will be presented. The paper also gives an explanation of hydroelectric power generation in the Odisha, SHEPs, and the technical and practical aspects of hydroelectric power. Till now, based on topographical and rainfall analysis we have located hundreds of sites. Further work on more number of site location and accuracy of location is to be done.

Keywords: small hydropower, ArcGIS, rainfall analysis, Odisha’s energy problem

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Authors: Vivian W. L. Tsang, Karen Lockhart, Samuel Spiegel, Annalee Yassi

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Background: Workers in the informal economy often incur exposure to well-documented occupational health hazards. Insufficient attention has been afforded to rigorously evaluating intervention programs to reduce the risks, especially in artisanal and small-scale gold mining (ASGM). Objectives: This systematic review, conducted as part of the World Health Organization’s Global Plan of Action for Workers’ Health, sought to assess the state of knowledge on occupational health programs and interventions for the informal artisanal and small-scale gold mining (ASGM) sector, an occupation which directly employs at least 50 million people. Methods: We used a comprehensive search strategy for four well-known databases relevant to health outcomes: PubMed, Engineering Village, OVID Medline, and Web of Science, and employed the PRISMA framework for our analysis. Findings: Ten studies met the inclusion criteria of a primary study focused on assessing the impact of interventions addressing occupational health concerns in ASGM. There were no studies evaluating or even identifying comprehensive occupational health and safety programs for this sector, although target interventions addressing specific hazards exist. Major areas of intervention –education and introduction of mercury-reducing/eliminating technology were identified, and the challenges and limitations of each intervention taken into the assessment. Even for these, however, there was a lack of standardization for measuring outcome or impact, let alone long-term health outcomes for miners and mining communities. Conclusion: There is an urgent need for research on comprehensive occupational health programs addressing the array of hazards faced by artisanal and small-scale miners.

Keywords: informal economy, artisanal and small-scale gold mining, occupational health, health and safety, workplace safety

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Authors: Z. Ansari, M. R. M. Rejab, D. Bachtiar, J. P. Siregar

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This study focus on the compression and tensile properties of new and recycle square honeycombs structure from sugar palm fibre (SPF) and polylactic acid (PLA) composite. The end data will determine the failure strength and energy absorption for both new and recycle composite. The control SPF specimens were fabricated from short fibre co-mingled with PLA by using a bra-blender set at 180°C and 50 rpm consecutively. The mixture of 30% fibre and 70% PLA were later on the hot press at 180°C into sheets with thickness 3mm consecutively before being assembled into a sandwich honeycomb structure. An INSTRON tensile machine and Abaqus 6.13 software were used for mechanical test and finite element simulation. The percentage of error from the simulation and experiment data was 9.20% and 9.17% for both new and recycled product. The small error of percentages was acceptable due to the nature of the simulation model to be assumed as a perfect model with no imperfect geometries. The energy absorption value from new to recycled product decrease from 312.86kJ to 282.10kJ. With this small decrements, it is still possible to implement a recycle SPF/PLA composite into everyday usages such as a car's interior or a small size furniture.

Keywords: failure modes, numerical modelling, polylactic acid, sugar palm fibres

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Authors: Shinta Holdsworth, Jan Axmacher, Darren J. Mann

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Beetles represent the most diverse insect taxon, and they contribute significantly to a wide range of vital ecological functions. Examples include decomposition by bark beetles, nitrogen recycling and dung processing by dung beetles or pest control by predatory ground beetles. Nonetheless, research into the distribution patterns, species richness and functional diversity of beetles particularly from tropical regions remains extremely limited. In our research, we aim to investigate the distribution and diversity patterns of beetles and the roles they play in small tropical island ecosystems in the Kepulauan Seribu Marine National Park and on Java. Our research furthermore provides insights into the effects anthropogenic activities have on the assemblage composition and diversity of beetles on the small islands. We recorded a substantial number of highly abundant small island species, including a substantial number of unique small island species across the study area, highlighting these islands’ potential importance for the regional conservation of genetic resources. The highly varied patterns observed in relation to the use of different trapping types - pitfall traps and flight interception traps (FITs) - underscores the need for complementary trapping strategies that combine multiple methods for beetle community surveys in tropical islands. The significant impacts of human activities have on the small island beetle faunas were also highlighted in our research. More island beetle species encountered in settlement than forest areas shows clear trend of positive links between anthropogenic activities and the overall beetle species richness. However, undisturbed forests harboured a high number of unique species, also in comparison to disturbed forests. Finally, our study suggests that, with regards to different feeding guilds, the diversity of herbivorous beetles on islands is strongly affected by the different levels of forest cover encountered.

Keywords: beetle diversity, forest disturbance, island biogeography, island settlement

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Authors: Eliane Abdo

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Small and medium sized firms “SMEs” play essential role in the countries’ economic development mainly in terms of production, employment and equitable distribution of income. For innovative SMEs, the investment in the human capital and in research and development are crucial to survive in a competitive environment. In this paper we perform a literature review to underline the financing difficulties and constraints which innovative SMEs face while investing in intangible assets: not only when defining amount of the investments but also while choosing its financing methods. Literature review revealed that in order to finance their intangible assets, SMEs rely in first on their internal financing: the availability of internal cash flows can then determine their investment’s decision. Moreover SMEs face difficulties to finance their intangibles by financial debts due to the uncertainty of future cash flow and the absence of physical guarantees; they will therefore go for the issuance of new shares as a second choice, since innovative companies have high opportunity of growth that attract new shareholders.

Keywords: small and medium sized firms, capital structure, intangible investment, financial constraints

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Authors: Ebrahim H. Kapeel, Ehab Safwat, Hossam Hendy, Ahmed M. Kamel, Yehia Z. Elhalwagy

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Motivated by the problem of the availability of high-fidelity flight simulation models for small unmanned aerial vehicles (UAVs). This paper focuses on the geometric-mass inertia modeling and the actuation system modeling for the small fixed-wing UAVs. The UAV geometric parameters for the body, wing, horizontal and vertical tail are physically measured. Pendulum experiment with high-grade sensors and data analysis using MATLAB is used to estimate the airplane moment of inertia (MOI) model. Finally, UAV’s actuation system is modeled by estimating each servo transfer function by using the system identification, which uses experimental measurement for input and output angles through using field-programmable gate array (FPGA). Experimental results for the designed models are given to illustrate the effectiveness of the methodology. It also gives a very promising result to finalize the open-loop flight simulation model through modeling the propulsion system and the aerodynamic system.

Keywords: unmanned aerial vehicle, geometric-mass inertia model, system identification, Simulink

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Khadse Saurabh, Talele Gokul, Surana Sanjay

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In an endeavor to find a new class of anti-inflammatory agents, a series of novel benzamides (ab1-ab16) were synthesized by utilizing some arylideneoxazolones (az1-az4) having 2-acetyloxyphenyl substitution on their second position. Structures of these synthesized compounds were confirmed by IR, 1H-NMR, 13C NMR, and HRMS. Among the tested benzamide compounds 3ab1, 3ab2, 3ab11, and 3ab16 showed promising anti-inflammatory activity with lessened propensity to cause gastro-intestinal hypermotility and ulceration when compared with standard Indomethacin. Virtual screening was performed by docking the designed compounds into the ATP binding site of COX-2 receptor to predict if these compounds have analogous binding mode to the COX-2 inhibitor.

Keywords: benzamides, anti-inflammatory, gastro-intestinal hypermotility, ulcerogenic activity, docking

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Authors: Isaiah Oluranti Olurinola, Michael Kayode Bolarinwa, Ebenezer Bowale, Ifeoluwa Ogunrinola

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Abstract - While much literature exists on microfinancing and its impact on the development of micro, small and medium-scale enterprises (MSME), yet little is known in respect of the impact of different types of education of owner-managers on the performances as well as innovative possibilities of such enterprises. This paper aims at contributing to the understanding of the impact of different types of education (academic, technical, apprenticeship, etc) that influence the performance of micro, small and medium-sized enterprise (MSME). This study utilises a recent and larger data-set collected in six states and FCT Abuja, Nigeria in the year 2014. Furthermore, the study carries out a comparative analysis of business performance among the different geo-political zones in Nigeria, given the educational attainment of the owner-managers. The data set were enterprise-based and were collected by the Nigerian Institute for Social and Economic Research (NISER) in the year 2014. Six hundred and eighty eight enterprises were covered in the survey. The method of data analysis for this study is the use of basic descriptive statistics in addition to the Logistic Regression model used in the prediction of the log of odds of business performance in relation to any of the identified educational attainment of the owner-managers in the sampled enterprises. An OLS econometric technique is also used to determine the effects of owner-managers' different educational types on the performance of the sampled MSME. Policy measures that will further enhance the contributions of education to MSME performance will be put forward.

Keywords: Business Performance, Education, Microfinancing, Micro, Small and Medium Scale Enterprises

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Authors: A. Khosravi, S. Ghadirian, J. S. McCartney

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Evaluation of the seismic-induced settlement of an unsaturated soil layer depends on several variables, among which the small strain shear modulus, Gmax, and soil’s state of stress have been demonstrated to be of particular significance. Recent interpretation of trends in Gmax revealed considerable effects of the degree of saturation and hydraulic hysteresis on the shear stiffness of soils in unsaturated states. Accordingly, the soil layer is expected to experience different settlement behaviors depending on the soil saturation and seasonal weathering conditions. In this study, a semi-empirical formulation was adapted to extend an existing Gmax model to infer hysteretic effects along different paths of the SWRC including scanning curves. The suitability of the proposed approach is validated against experimental results from a suction-controlled resonant column test and from data reported in literature. The model was observed to follow the experimental data along different paths of the SWRC, and showed a slight hysteresis in shear modulus along the scanning curves.

Keywords: hydraulic hysteresis, scanning path, small strain shear modulus, unsaturated soil

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Authors: Yadollah Hezarjaribi, Mahdie Yari Esboi

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In this paper, a novel MEMS capacitive pressure sensor with small size and high sensitivity is presented. This sensor has the separated clamped square diaphragm and the movable plate. The diaphragm material is polysilicon. The movable and fixed plates and mechanical coupling are gold. The substrate and diaphragm are pyrex glass and polysilicon, respectively. In capacitive sensor the sensitivity is proportional to deflection and capacitance changes with pressure for this reason with this design is improved the capacitance and sensitivity with small size. This sensor is designed for low pressure between 0-60 mmHg that is used for medical application such as treatment of an incurable disease called glaucoma. The size of this sensor is 350×350 µm2 and the thickness of the diaphragm is 2µm with 1μ air gap. This structure is designed by intellisuite software. In this MEMS capacitive pressure sensor the sensor sensitivity, diaphragm mechanical sensitivity for polysilicon diaphragm are 0.0469Pf/mmHg, 0.011 μm/mmHg, respectively. According to the simulating results for low pressure, the structure with polysilicon diaphragm has more change of the displacement and capacitance, this leads to high sensitivity than other diaphragms.

Keywords: glaucoma, MEMS capacitive pressure sensor, square clamped diaphragm, polysilicon

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Authors: Radostina Popova

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The paper presents an analysis of the innovation performance of small and medium-sized furniture enterprises in Bulgaria, accounting for over 97% of the companies in the sector. It contains advanced features of innovation in enterprises, specific features of the furniture industry in Bulgaria and analysis of the results of studies on the topic. The results from studies of three successive periods - 2006-2008; 2008-2010; 2010-2012, during which were studied 594 small and medium-sized furniture enterprises. There are commonly used in the EU definitions and indicators (European Commission, OECD, Oslo Manual), which allows for the comparability of results.

Keywords: innovation activity, competitiveness of innovation, furniture enterprises in Bulgaria

Procedia PDF Downloads 255

Authors: Malik Abid Hussain Khokhar, Muhammad Naveed Tahir, Muhammad Amin

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Energy demand has been increased manifold due to increasing population, urban sprawl and rapid socio-economic improvements. Low water capacity in dams for continuation of hydrological power, land cover and land use are the key parameters which are creating problems for more energy production. Overall installed hydropower capacity of Pakistan is more than 35000 MW whereas Pakistan is producing up to 17000 MW and the requirement is more than 22000 that is resulting shortfall of 5000 - 7000 MW. Therefore, there is a dire need to develop small hydropower to fulfill the up-coming requirements. In this regards, excessive rainfall, snow nurtured fast flowing perennial tributaries and streams in northern mountain regions of Pakistan offer a gigantic scope of hydropower potential throughout the year. Rivers flowing in KP (Khyber Pakhtunkhwa) province, GB (Gilgit Baltistan) and AJK (Azad Jammu & Kashmir) possess sufficient water availability for rapid energy growth. In the backdrop of such scenario, small hydropower plants are believed very suitable measures for more green environment and power sustainable option for the development of such regions. Aim of this study is to estimate hydropower potential sites for small hydropower plants and stream distribution as per steam network available in the available basins in the study area. The proposed methodology will focus on features to meet the objectives i.e. site selection of maximum hydropower potential for hydroelectric generation using well emerging GIS tool SWAT as hydrological run-off model on the Neelum, Kunhar and the Dor Rivers’ basins. For validation of the results, NDWI will be computed to show water concentration in the study area while overlaying on geospatial enhanced DEM. This study will represent analysis of basins, watershed, stream links, and flow directions with slope elevation for hydropower potential to produce increasing demand of electricity by installing small hydropower stations. Later on, this study will be benefitted for other adjacent regions for further estimation of site selection for installation of such small power plants as well.

Keywords: energy, stream network, basins, SWAT, evapotranspiration

Procedia PDF Downloads 209