Search results for: pedestrian target selection

Authors: S. Zolghadri, M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani

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In this study, the absorbed dose of human organs after injection of ¹⁷⁷Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, ¹⁷⁷Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.

Keywords: ¹⁷⁷Lu, breast cancer, compartmental modeling, dosimetry

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Authors: Ahlem Dhahri, Audrey Becuwe

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This study examines the adoption of sustainable purchasing practices among Tunisian SMEs, with a focus on assessing how environmental and social sustainability maturity affects the implementation of sustainable supplier selection (SSS) criteria. Using institutional theory to classify coercive, normative, and mimetic pressures, as well as emerging drivers and barriers, this study explores the institutional factors influencing sustainable purchasing practices and the specific barriers faced by Tunisian SMEs in this area. An exploratory, abductive qualitative research design was adopted for this multiple case study, which involved 19 semi-structured interviews with owners and managers of 17 Tunisian manufacturing SMEs. The Gioia method was used to analyze the data, thus enabling the identification of key themes and relationships directly from the raw data. This approach facilitated a structured interpretation of the institutional factors influencing sustainable purchasing practices, with insights drawn from the participants' perspectives. The study reveals that Tunisian SMEs are at different levels of sustainability maturity, with a significant impact on their procurement practices. SMEs with advanced sustainability maturity integrate both environmental and social criteria into their supplier selection processes, while those with lower maturity levels rely on mostly traditional criteria such as cost, quality, and delivery. Key institutional drivers identified include regulatory pressure, market expectations, and stakeholder influence. Additional emerging drivers—such as certifications and standards, economic incentives, environmental commitment as a core value, and group-wide strategic alignment—also play a critical role in driving sustainable procurement. Conversely, the study reveals significant barriers, including economic constraints, limited awareness, and resource limitations. It also identifies three main categories of emerging barriers: (1) logistical and supply chain constraints, including retailer/intermediary dependency, tariff regulations, and a perceived lack of direct responsibility in B2B supply chains; (2) economic and financial constraints; and (3) operational barriers, such as unilateral environmental responsibility, a product-centric focus and the influence of personal relationships. Providing valuable insights into the role of sustainability maturity in supplier selection, this study is the first to explore sustainable procurement practices in the Tunisian SME context. Integrating an analysis of institutional drivers, including emerging incentives and barriers, provides practical implications for SMEs seeking to improve sustainability in procurement. The results highlight the need for stronger regulatory frameworks and support mechanisms to facilitate the adoption of sustainable practices among SMEs in Tunisia.

Keywords: Tunisian SME, sustainable supplier selection, institutional theory, determinant, qualitative study

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Authors: Souvik Phadikar, Nidul Sinha, Rajdeep Ghosh

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In brainwaves research using electroencephalogram (EEG) signals, finding the most relevant and effective feature set for identification of activities in the human brain is a big challenge till today because of the random nature of the signals. The feature extraction method is a key issue to solve this problem. Finding those features that prove to give distinctive pictures for different activities and similar for the same activities is very difficult, especially for the number of activities. The performance of a classifier accuracy depends on this quality of feature set. Further, more number of features result in high computational complexity and less number of features compromise with the lower performance. In this paper, a novel idea of the selection of optimal feature set using a heuristically optimized deep autoencoder is presented. Using various feature extraction methods, a vast number of features are extracted from the EEG signals and fed to the autoencoder deep neural network. The autoencoder encodes the input features into a small set of codes. To avoid the gradient vanish problem and normalization of the dataset, a meta-heuristic search algorithm is used to minimize the mean square error (MSE) between encoder input and decoder output. To reduce the feature set into a smaller one, 4 hidden layers are considered in the autoencoder network; hence it is called Heuristically Optimized Deep Autoencoder (HO-DAE). In this method, no features are rejected; all the features are combined into the response of responses of the hidden layer. The results reveal that higher accuracy can be achieved using optimal reduced features. The proposed HO-DAE is also compared with the regular autoencoder to test the performance of both. The performance of the proposed method is validated and compared with the other two methods recently reported in the literature, which reveals that the proposed method is far better than the other two methods in terms of classification accuracy.

Keywords: autoencoder, brainwave signal analysis, electroencephalogram, feature extraction, feature selection, optimization

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Authors: Irina Khutsishvili

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In the present research, a decision support methodology for the multi-attribute group decision-making (MAGDM) problem is developed, namely for the selection of investment projects. The objective of the investment project selection problem is to choose the best project among the set of projects, seeking investment, or to rank all projects in descending order. The project selection is made considering a set of weighted attributes. To evaluate the attributes in our approach, expert assessments are used. In the proposed methodology, lingual expressions (linguistic terms) given by all experts are used as initial attribute evaluations, since they are the most natural and convenient representation of experts' evaluations. Then lingual evaluations are converted into trapezoidal fuzzy numbers, and the aggregate trapezoidal hesitant fuzzy decision matrix will be built. The case is considered when information on the attribute weights is completely unknown. The attribute weights are identified based on the De Luca and Termini information entropy concept, determined in the context of hesitant fuzzy sets. The decisions are made using the extended Technique for Order Performance by Similarity to Ideal Solution (TOPSIS) method under a hesitant fuzzy environment. Hence, a methodology is based on a trapezoidal valued hesitant fuzzy TOPSIS decision-making model with entropy weights. The ranking of alternatives is performed by the proximity of their distances to both the fuzzy positive-ideal solution (FPIS) and the fuzzy negative-ideal solution (FNIS). For this purpose, the weighted hesitant Hamming distance is used. An example of investment decision-making is shown that clearly explains the procedure of the proposed methodology.

Keywords: In the present research, a decision support methodology for the multi-attribute group decision-making (MAGDM) problem is developed, namely for the selection of investment projects. The objective of the investment project selection problem is to choose the best project among the set of projects, seeking investment, or to rank all projects in descending order. The project selection is made considering a set of weighted attributes. To evaluate the attributes in our approach, expert assessments are used. In the proposed methodology, lingual expressions (linguistic terms) given by all experts are used as initial attribute evaluations since they are the most natural and convenient representation of experts' evaluations. Then lingual evaluations are converted into trapezoidal fuzzy numbers, and the aggregate trapezoidal hesitant fuzzy decision matrix will be built. The case is considered when information on the attribute weights is completely unknown. The attribute weights are identified based on the De Luca and Termini information entropy concept, determined in the context of hesitant fuzzy sets. The decisions are made using the extended Technique for Order Performance by Similarity to Ideal Solution (TOPSIS) method under a hesitant fuzzy environment. Hence, a methodology is based on a trapezoidal valued hesitant fuzzy TOPSIS decision-making model with entropy weights. The ranking of alternatives is performed by the proximity of their distances to both the fuzzy positive-ideal solution (FPIS) and the fuzzy negative-ideal solution (FNIS). For this purpose, the weighted hesitant Hamming distance is used. An example of investment decision-making is shown that clearly explains the procedure of the proposed methodology.

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Authors: Elif Tugce Aksun Tumerkan

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Fluorescent proteins (FPs) have become very popular since green fluorescent protein discovered from crystal jellyfish. It is known that Anthozoa species have a wide range of chromophore organisms, and the initial crystal structure for non-fluorescent chromophores obtained from the reef-building coral has been determined. There are also differently coloured pigments in non-bioluminescent Anthozoa zooxanthellate and azooxanthellate which are frequently members of the GFP-like protein family. The development of fluorescent proteins (FPs) and their applications is an outstanding example of basic science leading to practical biotechnological and medical applications. Fluorescent proteins have several applications in science and are used as important indicators in molecular biology and cell-based research. With rising interest in cell biology, FPs have used as biosensor indicators and probes in pharmacology and cell biology. Using fluorescent proteins in genetically encoded metabolite sensors has many advantages than chemical probes for metabolites such as easily introduced into any cell or organism in any sub-cellular localization and giving chance to fixing to fluoresce of different colours or characteristics. There are different factors effects to signalling mechanism when they used as a biosensor. While there are wide ranges of research have been done on the significance and applications of fluorescent proteins, the cell signalling response of FPs and target cell are less well understood. In this study, it was aimed to clarify the response of adaptive mechanisms of coral species such as pH, temperature and symbiotic relationship and target cells properties on the signalling capacity. Corals are a rich natural source of fluorescent proteins that change with environmental conditions such as light, heat stress and injury. Adaptation mechanism of coral species to these types of environmental variations is important factor due to FPs properties have affected by this mechanism. Since fluorescent proteins obtained from nature, their own ecological property like the symbiotic relationship is observed very commonly in coral species and living conditions have the impact on FPs efficiency. Target cell properties also have an effect on signalling and visualization. The dynamicity of detector that used for reading fluorescence and the level of background fluorescence are key parameters for the quality of the fluorescent signal. Among the factors, it can be concluded that coral species adaptive characteristics have the strongest effect on FPs signalling capacity.

Keywords: biosensor, cell biology, environmental conditions, fluorescent protein, sea anemone

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Authors: Kristine Kalnica-Dorosenko, Aiga Svede

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Amblyopia or 'lazy eye' is impaired or dim vision without obvious defect or change in the eye. It is often associated with abnormal visual experience, most commonly strabismus, anisometropia or both, and form deprivation. The main task of amblyopia treatment is to ameliorate etiological factors to create a clear retinal image and, to ensure the participation of the amblyopic eye in the visual process. The treatment of amblyopia and eccentric fixation is usually associated with problems in the therapy. Eccentric fixation is present in around 44% of all patients with amblyopia and in 30% of patients with strabismic amblyopia. In Latvia, amblyopia is carefully treated in various clinics, but eccentricity diagnosis is relatively rare. Conflict which has developed relating to the relationship between the visual disorder and the degree of eccentric fixation in amblyopia should to be rethoughted, because it has an important bearing on the cause and treatment of amblyopia, and the role of the eccentric fixation in this case. Visuoscopy is the most frequently used method for determination of eccentric fixation. With traditional visuoscopy, a fixation target is projected onto the patient retina, and the examiner asks to look straight directly at the center of the target. An optometrist then observes the point on the macula used for fixation. This objective test provides clinicians with direct observation of the fixation point of the eye. It requires patients to voluntarily fixate the target and assumes the foveal reflex accurately demarcates the center of the foveal pit. In the end, by having a very simple method to evaluate fixation, it is possible to indirectly evaluate treatment improvement, as eccentric fixation is always associated with reduced visual acuity. So, one may expect that if eccentric fixation in amlyopic eye is found with visuoscopy, then visual acuity should be less than 1.0 (in decimal units). With occlusion or another amblyopia therapy, one would expect both visual acuity and fixation to improve simultaneously, that is fixation would become more central. Consequently, improvement in fixation pattern by treatment is an indirect measurement of improvement of visual acuity. Evaluation of eccentric fixation in the child may be helpful in identifying amblyopia in children prior to measurement of visual acuity. This is very important because the earlier amblyopia is diagnosed – the better the chance of improving visual acuity.

Keywords: amblyopia, eccentric fixation, visual acuity, visuoscopy

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Authors: Eng. M. Ahmed, A. Ibrahim, M. Ashour

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One of the major concerns facing dam is the repair of their structures to prevent the seepage under them. In previous years, many existing dams have been treated by grouting, but with varying degrees of success. One of the major reasons for this erratic performance is the unsuitable selection of the grouting materials to reduce the seepage. Grouting is an effective way to improve the engineering properties of the soil and strengthen of the permeability of the soil to reduce the seepage. The purpose of this paper is to focus on the efficiency of current available grouting materials and techniques from construction, environmental and economical point of view. The seepage reduction usually accomplished by either chemical grouting or cementious grouting using ultrafine cement. In addition, the study shows a comparison between grouting materials according to their degree of permeability reduction and cost. The application of seepage reduction is based on the permeation grouting using grout curtain installation. The computer program (SEEP/W) is employed to model a dam rested on sandy soil, using grout curtain to reduce seepage quantity and hydraulic gradient by different grouting materials. This study presents a relationship that takes into account the permeability of the soil, grout curtain spacing and a new performance parameter that can be used to predict the best selection of grouting materials for seepage reduction.

Keywords: seepage, sandy soil, grouting, permeability

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Authors: Scott A. Ochsner, Christopher M. Watkins, Apollo McOwiti, David L. Steffen Lauren B. Becnel, Neil J. McKenna

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Understanding signaling by nuclear receptors (NRs) requires an appreciation of their cognate ligand- and tissue-specific transcriptomes. While target gene regulation data are abundant in this field, they reside in hundreds of discrete publications in formats refractory to routine query and analysis and, accordingly, their full value to the NR signaling community has not been realized. One of the mandates of the Nuclear Receptor Signaling Atlas (NURSA) is to facilitate access of the community to existing public datasets. Pursuant to this mandate we are developing a freely-accessible community web resource, Transcriptomine, to bring together the sum total of available expression array and RNA-Seq data points generated by the field in a single location. Transcriptomine currently contains over 25,000,000 gene fold change datapoints from over 1200 contrasts relevant to over 100 NRs, ligands and coregulators in over 200 tissues and cell lines. Transcriptomine is designed to accommodate a spectrum of end users ranging from the bench researcher to those with advanced bioinformatic training. Visualization tools allow users to build custom charts to compare and contrast patterns of gene regulation across different tissues and in response to different ligands. Our resource affords an entirely new paradigm for leveraging gene expression data in the NR signaling field, empowering users to query gene fold changes across diverse regulatory molecules, tissues and cell lines, target genes, biological functions and disease associations, and that would otherwise be prohibitive in terms of time and effort. Transcriptomine will be regularly updated with gene lists from future genome-wide expression array and expression-sequencing datasets in the NR signaling field.

Keywords: target gene database, informatics, gene expression, transcriptomics

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Authors: Tamirat Solomon, Aberash Yohannis, Efrem Gulfo

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The plantation of trees, which harmonizes the agroecology of the environment, has been implemented in Ethiopia with great concern for a noticeably degraded environment. This study was designed to evaluate the effectiveness of green legacy, species selection and, the rate of survival, and the management status in the study areas. A systematic sampling method was employed to collect the required data from 144 quadrants measuring a 15m radius with an interval of 40m apart. Additionally, 244 sample households were selected for the socioeconomic study in addition to secondary data collected from office recordings. The data collected was analyzed using multivariate analysis, considering exposure and outcome variables. The findings of this study indicated that four exotic tree species, namely; A. salgina, C. fistula, A. indica, and G. robusta, were commonly selected tree species for degraded land restoration in the study areas. Among the seedlings planted at the four study sites, a total of 79.9% survived, and A. salgina was the dominant and best performed species, A. indica was the least survived species in the entire study area. The age of the seedling before planting significantly (p = 0.05) affected the survival potential of most seedlings of species, and the majority (82%) of local communities expressed their positive attitudes and willingness to manage the restoration works in the study areas. It was recommended to consider the inclusion of native species in the restoration effort and evaluate the co-existence of native flora with exotic and its competition for nutrients, water, and light in addition to the invading potentials in the ecosystem. In general, before embarking on degraded land restoration, species selection, adequate preparation of seedlings, and species diversity composition that exactly fit the socioeconomic and ecological demands of the areas must get the attention for the success of the restoration.

Keywords: plantation forest, degraded land, forest restoration, plantation survival, species selection

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Authors: Nichole Haag, Kimberly Velk, Tyler McCune, Chun Wu

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Methicillin/multiple-resistant Staphylococcus aureus (MRSA) are infectious bacteria that are resistant to common antibiotics. A previous in silico study in our group has identified a hypothetical protein SAV1226 as one of the potential drug targets. In this study, we reported the bioinformatics characterization, as well as cloning, expression, purification and kinetic assays of hypothetical protein SAV1226 from methicillin/vancomycin-resistant Staphylococcus aureus Mu50 strain. MALDI-TOF/MS analysis revealed a low degree of structural similarity with known proteins. Kinetic assays demonstrated that hypothetical protein SAV1226 is neither a domain of an ATP dependent dihydroxyacetone kinase nor of a phosphotransferase system (PTS) dihydroxyacetone kinase, suggesting that the function of hypothetical protein SAV1226 might be misannotated on public databases such as UniProt and InterProScan 5.

Keywords: Methicillin-resistant Staphylococcus aureus, dihydroxyacetone kinase, essential genes, drug target, phosphoryl group donor

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Authors: Sayyed Benyamin Alavi, Giovanni Cerri, Leila Chennaoui, Ambra Giovannelli, Stefano Mazzoni

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Primary energy consumption and emissions of pollutants (including CO2) sustainability call to search methodologies to lower power absorption for unit of a given product. Cool production plants based on vapour compression are widely used for many applications: air conditioning, food conservation, domestic refrigerators and freezers, special industrial processes, etc. In the field of cool production, the amount of Yearly Consumed Primary Energy is enormous, thus, saving some percentage of it, leads to big worldwide impact in the energy consumption and related energy sustainability. Among various techniques to reduce power required by a Vapour Compression Cool Production Plant (VCCPP), the technique based on Power Regeneration by means of Internal Direct Cycle (IDC) will be considered in this paper. Power produced by IDC reduces power need for unit of produced Cool Power by the VCCPP. The paper contains basic concepts that lead to develop IDCs and the proposed options to use the IDC Power. Among various selections for using turbo machines, Best Economically Available Technologies (BEATs) have been explored. Based on vehicle engine turbochargers, they have been taken into consideration for this application. According to BEAT Database and similarity rules, the best turbo machine selection leads to the minimum nominal power required by VCCPP Main Compressor. Results obtained installing the prototype in “ad hoc” designed test bench will be discussed and compared with the expected performance. Forecasts for the upgrading VCCPP, various applications will be given and discussed. 4-6% saving is expected for air conditioning cooling plants and 15-22% is expected for cryogenic plants.

Keywords: Refrigeration Plant, Vapour Pressure Amplifier, Compressor, Expander, Turbine, Turbomachinery Selection, Power Saving

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Authors: Imed Feki, Faouzi Msahli

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Selection of relevant parameters from a high dimensional process operation setting space is a problem frequently encountered in industrial process modelling. This paper presents a method for selecting the most relevant fabric physical parameters for each sensory quality feature. The proposed relevancy criterion has been developed using two approaches. The first utilizes a fuzzy sensitivity criterion by exploiting from experimental data the relationship between physical parameters and all the sensory quality features for each evaluator. Next an OWA aggregation procedure is applied to aggregate the ranking lists provided by different evaluators. In the second approach, another panel of experts provides their ranking lists of physical features according to their professional knowledge. Also by applying OWA and a fuzzy aggregation model, the data sensitivity-based ranking list and the knowledge-based ranking list are combined using our proposed percolation technique, to determine the final ranking list. The key issue of the proposed percolation technique is to filter automatically and objectively the relevant features by creating a gap between scores of relevant and irrelevant parameters. It permits to automatically generate threshold that can effectively reduce human subjectivity and arbitrariness when manually choosing thresholds. For a specific sensory descriptor, the threshold is defined systematically by iteratively aggregating (n times) the ranking lists generated by OWA and fuzzy models, according to a specific algorithm. Having applied the percolation technique on a real example, of a well known finished textile product especially the stonewashed denims, usually considered as the most important quality criteria in jeans’ evaluation, we separate the relevant physical features from irrelevant ones for each sensory descriptor. The originality and performance of the proposed relevant feature selection method can be shown by the variability in the number of physical features in the set of selected relevant parameters. Instead of selecting identical numbers of features with a predefined threshold, the proposed method can be adapted to the specific natures of the complex relations between sensory descriptors and physical features, in order to propose lists of relevant features of different sizes for different descriptors. In order to obtain more reliable results for selection of relevant physical features, the percolation technique has been applied for combining the fuzzy global relevancy and OWA global relevancy criteria in order to clearly distinguish scores of the relevant physical features from those of irrelevant ones.

Keywords: data sensitivity, feature selection, fuzzy logic, OWA operators, percolation technique

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Authors: Piotr Ciuman, Barbara Lipska

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The aim of presented research was to improve numerical predictions of air parameters distribution in the actual natatorium by the selection of calculation formula of mass flux of moisture emitted from the pool. Selected correlation should ensure the best compliance of numerical results with the measurements' results of these parameters in the facility. The numerical model of the natatorium was developed, for which boundary conditions were prepared on the basis of measurements' results carried out in the actual facility. Numerical calculations were carried out with the use of ANSYS CFX software, with six formulas being implemented, which in various ways made the moisture emission dependent on water surface temperature and air parameters in the natatorium. The results of calculations with the use of these formulas were compared for air parameters' distributions: Specific humidity, velocity and temperature in the facility. For the selection of the best formula, numerical results of these parameters in occupied zone were validated by comparison with the measurements' results carried out at selected points of this zone.

Keywords: experimental validation, indoor swimming pool, moisture emission, natatorium, numerical calculations CFD, thermal and humidity conditions, ventilation

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Bachir Bentouati, Lakhdar Chaib, Saliha Chettih, Gai-Ge Wang

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The problem of economic dispatch (ED) is the basic problem of power framework, its main goal is to find the most favorable generation dispatch to generate each unit, reduce the whole power generation cost, and meet all system limitations. A heuristic algorithm, recently developed called Stud Krill Herd (SKH), has been employed in this paper to treat non-convex ED problems. The proposed KH has been modified using Stud selection and crossover (SSC) operator, to enhance the solution quality and avoid local optima. We are demonstrated SKH effects in two case study systems composed of 13-unit and 40-unit test systems to verify its performance and applicability in solving the ED problems. In the above systems, SKH can successfully obtain the best fuel generator and distribute the load requirements for the online generators. The results showed that the use of the proposed SKH method could reduce the total cost of generation and optimize the fulfillment of the load requirements.

Keywords: stud krill herd, economic dispatch, crossover, stud selection, valve-point effect

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Authors: Karthikeyan Kalirajan, Ashok Joshi

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An optimization problem is to setup to maximize the terminal kinetic energy of a maneuverable reentry vehicle (MaRV). The target location, the impact angle is given as constraints. The MaRV uses an explicit guidance law called Vector guidance. This law has two gains which are taken as decision variables. The problem is to find the optimal value of these gains which will result in minimum miss distance and impact angle error. Using a simple 3DOF non-rotating flat earth model and Lockheed martin HP-MARV as the reentry vehicle, the nature of solutions of the optimization problem is studied. This is achieved by carrying out a parametric study for a range of closed loop gain values and the corresponding impact angle error and the miss distance values are generated. The results show that there are well defined lower and upper bounds on the gains that result in near optimal terminal guidance solution. It is found from this study, that there exist common permissible regions (values of gains) where all constraints are met. Moreover, the permissible region lies between flat regions and hence the optimization algorithm has to be chosen carefully. It is also found that, only one of the gain values is independent and that the other dependent gain value is related through a simple straight-line expression. Moreover, to reduce the computational burden of finding the optimal value of two gains, a guidance law called Diveline guidance is discussed, which uses single gain. The derivation of the Diveline guidance law from Vector guidance law is discussed in this paper.

Keywords: Marv guidance, reentry trajectory, trajectory optimization, guidance gain selection

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Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto

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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.

Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking

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Authors: Temesgen Sidamo, Prakruti S. Rao, Eleni Akllilu, Workineh Shibeshi, Yumi Park, Yong-Soon Cho, Jae-Gook Shin, Scott K. Heysell, Stellah G. Mpagama, Ephrem Engidawork

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The fluoroquinolones (FQs) are used off-label for the treatment of multidrug-resistant tuberculosis (MDR-TB), and for evaluation in shortening the duration of drug-susceptible TB in recently prioritized regimens. Within the class, levofloxacin (LFX) and moxifloxacin (MXF) play a substantial role in ensuring success in treatment outcomes. However, sub-therapeutic plasma concentrations of either LFX or MXF may drive unfavorable treatment outcomes. To the best of our knowledge, the pharmacokinetics of LFX and MXF in Ethiopian patients with MDR-TB have not yet been investigated. Therefore, the aim of this study was to develop a population pharmacokinetic (PopPK) model of levofloxacin (LFX) and moxifloxacin (MXF) and assess the percent probability of target attainment (PTA) as defined by the ratio of the area under the plasma concentration-time curve over 24-h (AUC0-24) and the in vitro minimum inhibitory concentration (MIC) (AUC0-24/MIC) in Ethiopian MDR-TB patients. Steady-state plasma was collected from 39 MDR-TB patients enrolled in the programmatic treatment course and the drug concentrations were determined using optimized liquid chromatography-tandem mass spectrometry. In addition, the in vitro MIC of the patients' pretreatment clinical isolates was determined. PopPK and simulations were run at various doses, and PK parameters were estimated. The effect of covariates on the PK parameters and the PTA for maximum mycobacterial kill and resistance prevention was also investigated. LFX and MXF both fit in a one-compartment model with adjustments. The apparent volume of distribution (V) and clearance (CL) of LFX were influenced by serum creatinine (Scr), whereas the absorption constant (Ka) and V of MXF were influenced by Scr and BMI, respectively. The PTA for LFX maximal mycobacterial kill at the critical MIC of 0.5 mg/L was 29%, 62%, and 95% with the simulated 750 mg, 1000 mg, and 1500 mg doses, respectively, whereas the PTA for resistance prevention at 1500 mg was only 4.8%, with none of the lower doses achieving this target. At the critical MIC of 0.25 mg/L, there was no difference in the PTA (94.4%) for maximum bacterial kill among the simulated doses of MXF (600 mg, 800 mg, and 1000 mg), but the PTA for resistance prevention improved proportionately with dose. Standard LFX and MXF doses may not provide adequate drug exposure. LFX PopPK is more predictable for maximum mycobacterial kill, whereas MXF's resistance prevention target increases with dose. Scr and BMI are likely to be important covariates in dose optimization or therapeutic drug monitoring (TDM) studies in Ethiopian patients.

Keywords: population PK, PTA, moxifloxacin, levofloxacin, MDR-TB patients, ethiopia

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Authors: Norbert Csizmadia

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The 21st Century's main power centers are the cities. More than 52% of the world’s population lives in cities, in particular in the megacities which have a population over 10 million people and is still growing. According to various research and forecasts, the main economic concentration will be in 40 megacities and global centers. Based on various competitiveness analyzes and indices, global city centers, and city networks are outlined, but if we look at other aspects of urban development like complexity, connectivity, creativity, technological development, viability, green cities, pedestrian and child friendly cities, creative and cultural centers, cultural spaces and knowledge centers, we get a city competitiveness index with quite new complex indicators. The research shows this result. In addition to the megacities and the global centers, with the investigation of functionality, we got 64 so-called ‘fusiononopolis’ (i.e., fusion-polis) which stand for the most decisive economic power centers of the 21st century. In this city competition Asian centers considerably rise, as the world's functional city competitiveness index is being formed.

Keywords: economic geography, human geography, technological development, urbanism

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Authors: A. Ishag, E. Witruk, C. Altmayer

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Motivation and attitudes are considered as hypothetical psychological constructs in explaining the process of second language learning. Gardner (1985) – who first systematically investigated the motivational factors in second language acquisition – found that L2 achievement is related not only to the individual learner’s linguistic aptitude or general intelligence but also to the learner’s motivation and interest in learning the target language. Traditionally language learning motivation can be divided into two types: integrative motivation – the desire to integrate oneself with the target culture; and instrumental motivation – the desire to learn a language in order to meet a specific language requirement such as for employment. One of the Gardner’s main ideas is that the integrative motivation plays an important role in second language acquisition. It is directly and positively related to second language achievement more than instrumental motivation. However, the significance of integrative motivation reflects a rather controversial set of findings. On the other hand, Students’ attitudes towards the target language, its speakers and the learning context may all play some part in explaining their success in learning a language. Accordingly, the present study aims at exploring the significance of motivational and attitudinal factors in learning foreign languages, namely English and German among Sudanese undergraduate students from a psycholinguistic and interdisciplinary perspective. The sample composed of 221 students from the English and German language departments respectively at the University of Khartoum in Sudan. The results indicate that English language’s learners are instrumentally motivated and that German language’s learners have positive attitudes towards the German language community and culture. Furthermore, there are statistical significant differences in the attitudes toward the two languages due to gender; where female students have more positive attitudes than their male counterparts. However, there are no differences along the variables of academic grade and study level. Finally, the reasons of studying the English or German language have also been indicated.

Keywords: motivation and attitudes, foreign language learning, english language, german language

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Authors: Giorgio Bertolazzi, Panayiotis Benos, Michele Tumminello, Claudia Coronnello

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MicroRNAs are small non-coding RNAs that post-transcriptionally regulate the expression levels of messenger RNAs. MicroRNA regulation activity depends on the recognition of binding sites located on mRNA molecules. ComiR (Combinatorial miRNA targeting) is a user friendly web tool realized to predict the targets of a set of microRNAs, starting from their expression profile. ComiR incorporates miRNA expression in a thermodynamic binding model, and it associates each gene with the probability of being a target of a set of miRNAs. ComiR algorithms were trained with the information regarding binding sites in the 3’UTR region, by using a reliable dataset containing the targets of endogenously expressed microRNA in D. melanogaster S2 cells. This dataset was obtained by comparing the results from two different experimental approaches, i.e., inhibition, and immunoprecipitation of the AGO1 protein; this protein is a component of the microRNA induced silencing complex. In this work, we tested whether including coding region binding sites in the ComiR algorithm improves the performance of the tool in predicting microRNA targets. We focused the analysis on the D. melanogaster species and updated the ComiR underlying database with the currently available releases of mRNA and microRNA sequences. As a result, we find that the ComiR algorithm trained with the information related to the coding regions is more efficient in predicting the microRNA targets, with respect to the algorithm trained with 3’utr information. On the other hand, we show that 3’utr based predictions can be seen as complementary to the coding region based predictions, which suggests that both predictions, from 3'UTR and coding regions, should be considered in a comprehensive analysis. Furthermore, we observed that the lists of targets obtained by analyzing data from one experimental approach only, that is, inhibition or immunoprecipitation of AGO1, are not reliable enough to test the performance of our microRNA target prediction algorithm. Further analysis will be conducted to investigate the effectiveness of the tool with data from other species, provided that validated datasets, as obtained from the comparison of RISC proteins inhibition and immunoprecipitation experiments, will be available for the same samples. Finally, we propose to upgrade the existing ComiR web-tool by including the coding region based trained model, available together with the 3’UTR based one.

Keywords: AGO1, coding region, Drosophila melanogaster, microRNA target prediction

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Authors: Mahdieh Khalilinezhad, Silvana Dellepiane, Gianni Vernazza

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The aim of the present work is to build a model based on tissue characterization that is able to discriminate pathological and non-pathological regions from three-phasic CT images. Based on feature selection in different phases, in this research, we design a neural network system that has optimal neuron number in a hidden layer. Our approach consists of three steps: feature selection, feature reduction, and classification. For each ROI, 6 distinct set of texture features are extracted such as first order histogram parameters, absolute gradient, run-length matrix, co-occurrence matrix, autoregressive model, and wavelet, for a total of 270 texture features. We show that with the injection of liquid and the analysis of more phases the high relevant features in each region changed. Our results show that for detecting HCC tumor phase3 is the best one in most of the features that we apply to the classification algorithm. The percentage of detection between these two classes according to our method, relates to first order histogram parameters with the accuracy of 85% in phase 1, 95% phase 2, and 95% in phase 3.

Keywords: multi-phasic liver images, texture analysis, neural network, hidden layer

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Authors: Sara Saboonian, Pierre Filion

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The dispersed-suburban model has been the dominant one across North America for the past seventy years, characterized by automobile reliance, low density, and land-use specialization. Two planning models have emerged as possible alternatives to address the ills inflicted by this development pattern. First, there is intensification, which promotes efficient infrastructure by connecting high-density, multi-functional, and walkable nodes with public transit services within the suburban landscape. Second is green infrastructure, which provides environmental health and human well-being by preserving and restoring ecosystem services. This research studies incompatibilities and the possibility of amalgamating the two alternatives in an attempt to develop a comprehensive alternative to suburban model that advocates density, multi-functionality and transit- and pedestrian-conduciveness, with measures capable of mitigating the adverse environmental impacts of compactness. The research investigates three Canadian urban growth centers, where intensification is the current planning practice, and the awareness of green infrastructure benefits is on the rise. However, these three centers are contrasted by their development stage, the presence or absence of protected natural land, their environmental approach, and their adverse environmental consequences according to the planning cannons of different periods. The methods include reviewing the literature on green infrastructure planning, criticizing the Ontario provincial plans for intensification, surveying residents’ preferences for alternative models, and interviewing officials who deal with the local planning for the centers. Moreover, the research draws on recalling debates between New Urbanism and Landscape/Ecological Urbanism. The case studies expose the difficulties in creating urban growth centres that accommodate green infrastructure while adhering to intensification principles. First, the dominant status of intensification and the obstacles confronting intensification have monopolized the planners’ concerns. Second, the tension between green infrastructure and intensification explains the absence of the green infrastructure typologies that correspond to intensification-compatible forms and dynamics. Finally, the lack of highlighted social-economic benefits of green infrastructure reduces residents’ participation. Moreover, the results from the research provide insight into predominating urbanization theories, New Urbanism and Landscape/Ecological Urbanism. In order to understand political, planning, and ecological dynamics of such blending, dexterous context-specific planning is required. Findings suggest the influence of the following factors on amalgamating intensification and green infrastructure. Initially, producing ecosystem services-based justifications for green infrastructure development in the intensification context provides an expert-driven backbone for the implementation programs. This knowledge-base should be translated to effectively imbue different urban stakeholders. Moreover, due to the limited greenfields in intensified areas, spatial distribution and development of multi-level corridors such as pedestrian-hospitable settings and transportation networks along green infrastructure measures are required. Finally, to ensure the long-term integrity of implemented green infrastructure measures, significant investment in public engagement and education, as well as clarification of management responsibilities is essential.

Keywords: ecosystem services, green infrastructure, intensification, planning

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Authors: Sareh Rajabi, Taha Anjamrooz, Salwa Bheiry

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The continuous increase in the world population, resource shortage and the warning of climate change cause various environmental and social issues to the world. Thus, sustainability concept is much needed nowadays. Organizations are progressively falling under strong worldwide pressure to integrate sustainability practices into their project decision-making development. Construction projects in the industry are amongst the most significant, since it is one of the biggest divisions and of main significance for the national economy and hence has a massive effect on the environment and society. So, it is important to discover approaches to incorporate sustainability into the management of those projects. This study presents a combined sustainability index of projects with sustainable transportation which has been formed as per a comprehensive literature review and survey study. Transportation systems enable the movement of goods and services worldwide, and it is leading to economic growth and creating jobs while creating negative impacts on the environment and society. This research is study to quantify the sustainability indicators, through 1) identifying the importance of sustainable transportation indicators that are based on the sustainable practices used for the construction projects and 2) measure the effectiveness of practices through these indicators on the three sustainable pillars. A total 26 sustainability indicators have been selected and grouped under each related sustainability pillars. A survey was used to collect the opinion about the sustainability indicators by a scoring system. A combined sustainability index considering three sustainable pillars can be helpful in evaluating the transportation sustainable practices of a project and making decisions regarding project selection. In addition to focus on the issue of financial resource allocation in a project selection, the decision-maker could take into account the sustainability as an important key in addition to the project’s return and risk. The purpose of this study is to measure the performance of transportation sustainability which allow companies to assess multiple projects selection. This is useful to decision makers to rank and focus more on future sustainable projects.

Keywords: sustainable transportation, transportation performances, sustainable indicators, sustainable construction practice, sustainability

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Authors: Philip Speranza

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As everyday transit options are shifting from autocentric to pedestrian and bicycle oriented modes for healthy living, downtown streets are becoming more attractive places to live. However, tools and methods to measure the natural environment at the small scale of streets do not exist. Fortunately, a combination of mobile data collection technology and parametric urban design software now allows an interface to relate urban ecological conditions. This paper describes creation of an interactive tool to measure urban phenomena of air, water, and heat/light at the scale of new three-by-three block pedestrianized areas in Barcelona called Superilles. Each Superilla limits transit to the exterior of the blocks and to create more walkable and bikeable interior streets for healthy living. The research will describe the integration of data collection, analysis, and design output via a live interface using parametric software Rhino Grasshopper and the Human User Interface (UI) plugin.

Keywords: transit, urban design, GIS, parametric design, Superilles, Barcelona, urban ecology

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Authors: Reihaneh Rafiemanzelat

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One of the most recent fields of investigation in urban issues focuses on the walkability in urban spaces. The paper aims to establish the theoretical relationship between the people's link with definite urban public spaces and the social identity processes derived from the relation with these places. The theoretical aspects which are examined for this purpose are: the concept of walkability and its developments and the social identity theories derived from walkable spaces. In fact, the paper presents the main results obtained from an empirical investigation which concern to the genesis of urban social identity in particular street as one of the main elements of public spaces in cities. İsmet İnönü Blvd which known as Salamis Street in Famagusta, North Cyprus is one of the main street in city whit high level of physical and social activities all the time. The urban social identity of users was analyzed, focusing on three main factors: walkability of space, social identification, and image of the space. These three factors were analyzed in relation to a series of items in the initial questionnaire, evaluation of existing natural resources, and environmental attitudes.

Keywords: walkability, urban public space, pedestrian, social activity, social identity

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Authors: Sabin Aslam, Sultan Habibullah Khan, James G. Thomson, Abhaya M. Dandekar

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Losses due to viral diseases are posing a serious threat to crop production. A quick breakdown of resistance to viruses like Cotton Leaf Curl Virus (CLCuV) demands the application of a proficient technology to engineer durable resistance. Gene stacking has recently emerged as a potential approach for integrating multiple genes in crop plants. In the present study, recombinase technology has been used for site-specific gene stacking. A target vector (pG-Rec) was designed for engineering a predetermined specific site in the plant genome whereby genes can be stacked repeatedly. Using Agrobacterium-mediated transformation, the pG-Rec was transformed into Coker-312 along with Nicotiana tabacum L. cv. Xanthi and Nicotiana benthamiana. The transgene analysis of target lines was conducted through junction PCR. The transgene positive target lines were used for further transformations to site-specifically stack two genes of interest using Bxb1 and PhiC31 recombinases. In the first instance, Cas9 driven by multiplex gRNAs (for Rep gene of CLCuV) was site-specifically integrated into the target lines and determined by the junction PCR and real-time PCR. The resulting plants were subsequently used to stack the second gene of interest (AVP3 gene from Arabidopsis for enhancing cotton plant growth). The addition of the genes is simultaneously achieved with the removal of marker genes for recycling with the next round of gene stacking. Consequently, transgenic marker-free plants were produced with two genes stacked at the specific site. These transgenic plants can be potential germplasm to introduce resistance against various strains of cotton leaf curl virus (CLCuV) and abiotic stresses. The results of the research demonstrate gene stacking in crop plants, a technology that can be used to introduce multiple genes sequentially at predefined genomic sites. The current climate change scenario highlights the use of such technologies so that gigantic environmental issues can be tackled by several traits in a single step. After evaluating virus resistance in the resulting plants, the lines can be a primer to initiate stacking of further genes in Cotton for other traits as well as molecular breeding with elite cotton lines.

Keywords: cotton, CRISPR/Cas9, gene stacking, genome editing, recombinases

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Authors: Junie B. Billones, Maria Constancia O. Carrillo, Voltaire G. Organo, Stephani Joy Y. Macalino, Inno A. Emnacen, Jamie Bernadette A. Sy

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The drug discovery and development process is generally known to be a very lengthy and labor-intensive process. Therefore, in order to be able to deliver prompt and effective responses to cure certain diseases, there is an urgent need to reduce the time and resources needed to design, develop, and optimize potential drugs. Computer-aided drug design (CADD) is able to alleviate this issue by applying computational power in order to streamline the whole drug discovery process, starting from target identification to lead optimization. This drug design approach can be predominantly applied to diseases that cause major public health concerns, such as tuberculosis. Hitherto, there has been no concrete cure for this disease, especially with the continuing emergence of drug resistant strains. In this study, CADD is employed for tuberculosis by first identifying a key enzyme in the mycobacterium’s metabolic pathway that would make a good drug target. One such potential target is the lipoate protein ligase B enzyme (LipB), which is a key enzyme in the M. tuberculosis metabolic pathway involved in the biosynthesis of the lipoic acid cofactor. Its expression is considerably up-regulated in patients with multi-drug resistant tuberculosis (MDR-TB) and it has no known back-up mechanism that can take over its function when inhibited, making it an extremely attractive target. Using cutting-edge computational methods, compounds from AnalytiCon Discovery Natural Derivatives database were screened and docked against the LipB enzyme in order to rank them based on their binding affinities. Compounds which have better binding affinities than LipB’s known inhibitor, decanoic acid, were subjected to in silico toxicity evaluation using the ADMET and TOPKAT protocols. Out of the 31,692 compounds in the database, 112 of these showed better binding energies than decanoic acid. Furthermore, 12 out of the 112 compounds showed highly promising ADMET and TOPKAT properties. Future studies involving in vitro or in vivo bioassays may be done to further confirm the therapeutic efficacy of these 12 compounds, which eventually may then lead to a novel class of anti-tuberculosis drugs.

Keywords: pharmacophore, molecular docking, lipoate protein ligase B (LipB), ADMET, TOPKAT

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Authors: Zuzana Sedláková, Magda Kárászová, Jiří Vejražka, Lenka Morávková, Pavel Izák

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Membrane separations are mentioned frequently as a possibility for CO2 capture. Selectivity of ionic liquid membranes is strongly determined by different solubility of separated gases in ionic liquids. The solubility of separated gases usually varies over an order of magnitude, differently from diffusivity of gases in ionic liquids, which is usually of the same order of magnitude for different gases. The present work evaluates the selection of an appropriate ionic liquid for the selective membrane preparation based on the gas solubility in an ionic liquid. The current state of the art of CO2 capture patents and technologies based on the membrane separations was considered. An overview is given of the discussed transport mechanisms. Ionic liquids seem to be promising candidates thanks to their tunable properties, wide liquid range, reasonable thermal stability, and negligible vapor pressure. However, the uses of supported liquid membranes are limited by their relatively short lifetime from the industrial point of view. On the other hand, ionic liquids could overcome these problems due to their negligible vapor pressure and their tunable properties by adequate selection of the cation and anion.

Keywords: biogas upgrading, carbon dioxide separation, ionic liquid membrane, transport properties

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Authors: Rahul Agarwal, Ashutosh Singh

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Colorectal cancer (CRC) also refers as bowel cancer or colon cancer. It involves the development of abnormal growth of cells in colon or rectum part of the body. This work leads to the development of a miRNA database in colorectal cancer. We named this database- miCoRe. This database comprises of all validated colon-rectal cancer miRNAs information from various published literature with an effectual knowledge based information retrieval system. miRNAs have been collected from various published literature reports. MySQL is used for main-framework of miCoRe while the front-end was developed in PHP script. The aim of developing miCoRe is to create a comprehensive central repository of colorectal carcinoma miRNAs with all germane information of miRNAs and their target genes. The current version of miCoRe consists of 238 miRNAs which are known to be implicated in malignancy of CRC. Alongside with miRNA information, miCoRe also contains the information related to the target genes of these miRNA. miCoRe furnishes the information about the mechanism of incidence and progression of the disease, which would further help the researchers to look for colorectal specific miRNAs therapies and CRC specific targeted drug designing. Moreover, it will also help in development of biomarkers for the better and early detection of CRC and will help in better clinical management of the disease.

Keywords: colorectal cancer, database, miCoRe, miRNAs

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