Search results for: natural product based drug designs

Authors: Sourabh Harihar, Henk Jan Verhagen

Abstract:

The nurturing of a mangrove ecosystem requires a protected coastal environment with adequate drainage of the soil substratum. In a conceptual design undertaken for a mangrove rejuvenation project along the eastern coast of Mumbai (India), various engineering alternatives have been thought of as a protective coastal structure and drainage system. One such design uses bamboo-pile walls in creating shielded compartments in the form of various layouts, coupled with bamboo drains. The bamboo-based design is found to be environmentally and economically advantageous over other designs like sand-dikes which are multiple times more expensive. Moreover, employing a natural material such as bamboo helps the structure naturally blend with the developing mangrove habitat, allaying concerns about dismantling the structure post mangrove growth. A cost-minimising and eco-friendly bamboo structure, therefore, promises to pave the way for large rehabilitation projects in future. As mangrove ecosystems in many parts of the world increasingly face the threat of destruction due to urban development and climate change, protective nature-based designs that can be built in a short duration are the need of the hour.

Keywords: bamboo, environment, mangrove, rehabilitation

Procedia PDF Downloads 282

Authors: Temesgen Geremew

Abstract:

Functionalized nanoparticles have emerged as a revolutionary platform for drug delivery, offering significant advantages over traditional methods. By strategically modifying their surface properties, these nanoparticles can be designed to target specific tissues and cells, significantly reducing off-target effects and enhancing therapeutic efficacy. This targeted approach allows for lower drug doses, minimizing systemic exposure and potential side effects. Additionally, functionalization enables controlled release of the encapsulated drug, improving drug stability and reducing the frequency of administration, leading to improved patient compliance. This work explores the immense potential of functionalized nanoparticles in revolutionizing drug delivery, addressing limitations associated with conventional therapies and paving the way for personalized medicine with precise and targeted treatment strategies.

Keywords: nanoparticles, drug, nanomaterials, applications

Procedia PDF Downloads 67

Authors: Khushbu Priyadarshi, Chandramani Pathak

Abstract:

Cancer cells can develop resistance to conventional therapies especially chemotherapeutic drugs. Resistance to chemotherapy is another challenge in cancer therapeutics. Therefore, it is important to address this issue. Gallic acid (GA) is a natural plant compound that exhibits various biological properties including anti-proliferative, anti-inflammatory, anti-oxidant and anti-bacterial. Despite of the wide spectrum biological properties GA has cytotoxic response and low bioavailability. To overcome this problem, GA was conjugated with the Polyamidoamine(PAMAM) dendrimer for improving the bioavailability and efficient delivery in drug-resistant HCT-116 Colon Cancer cells. Gallic acid was covalently linked to 4.0 G PAMAM dendrimer. PAMAM dendrimer is well established nanocarrier but has cytotoxicity due to presence of amphiphilic nature of amino group. In our study we have modified surface of PAMAM dendrimer with Gallic acid and examine their anti-proliferative effects in drug-resistant HCT-116 cells. Further, drug-resistant colon cancer cells were established and thereafter treated with different concentration of PAMAM-GA to examine their anti-proliferative potential. Our results show that PAMAM-GA conjugate induces apoptotic cell death in HCT-116 and drug-resistant cells observed by Annexin-PI staining. In addition, it also shows that multidrug-resistant drug transporter P-gp protein expression was downregulated with increasing the concentration of GA conjugate. After that we also observed the significant difference in Rh123 efflux and accumulation in drug sensitive and drug-resistant cancer cells. Thus, our study suggests that conjugation of anti-cancer agents with PAMAM could improve drug resistant property and cytotoxic response to treatment of cancer.

Keywords: drug resistance, gallic acid, PAMAM dendrimer, P-glycoprotein

Procedia PDF Downloads 149

Authors: Yani Shi, Jiaqi Yan

Abstract:

A new product is important for companies to extend consumers and manifest competitiveness. New product often involves new features that consumers might not be familiar with while it may also have a competitive advantage to attract consumers compared to established products. However, although most online retailers employ recommendation agents (RA) to influence consumers’ product choice decision, recommended new products are not accepted and chosen as expected. We argue that it might also be caused by providing a new product recommendation in the wrong way at the wrong time. This study seeks to discuss how new product evaluations sourced from third parties could be employed in RAs as evidence of the superiority for the new product and how the new product recommendation could be provided to a consumer at the right time so that it can be accepted and finally chosen during the consumer’s decision-making process. A 2*2 controlled laboratory experiment was conducted to understand the selection of new product recommendation sources and recommendation timing. Human subjects were randomly assigned to one of the four treatments to minimize the effects of individual differences on the results. Participants were told to make purchase choices from our product categories. We find that a new product recommended right after a similar existing product and with the source of the expert review will be more likely to be accepted. Based on this study, both theoretical and practical contributions are provided regarding new product recommendation.

Keywords: new product recommendation, recommendation timing, recommendation source, recommendation agents

Procedia PDF Downloads 154

Authors: Joseph E. Hummer

Abstract:

An efficient freeway system will be essential to the development of Africa, and interchanges are a key to that efficiency. Around the world, many interchanges between freeways and surface streets, called service interchanges, are of the diamond configuration, and interchanges using roundabouts or loop ramps are also popular. However, many diamond interchanges have serious operational problems, interchanges with roundabouts fail at high demand levels, and loops use lots of expensive land. Newer service interchange designs provide other options. The most popular new interchange design in the US at the moment is the double crossover diamond (DCD), also known as the diverging diamond. The DCD has enormous potential, but also has several significant limitations. The objectives of this paper are to review new service interchange options and to highlight some of the main features of those alternatives. The paper tests four conventional and seven unconventional designs using seven measures related to efficiency, cost, and safety. The results show that there is no superior design in all measures investigated. The DCD is better than most designs tested on most measures examined. However, the DCD was only superior to all other designs for bridge width. The DCD performed relatively poorly for capacity and for serving pedestrians. Based on the results, African freeway designers are encouraged to investigate the full range of alternatives that could work at the spot of interest. Diamonds and DCDs have their niches, but some of the other designs investigated could be optimum at some spots.

Keywords: interchange, diamond, diverging diamond, capacity, safety, cost

Procedia PDF Downloads 252

Authors: S. Dey, T. Mukhopadhyay, S. Adhikari

Abstract:

This paper presents an exhaustive comparative investigation on sampling techniques of polynomial regression model based stochastic natural frequency of composite plates. Both individual and combined variations of input parameters are considered to map the computational time and accuracy of each modelling techniques. The finite element formulation of composites is capable to deal with both correlated and uncorrelated random input variables such as fibre parameters and material properties. The results obtained by Polynomial regression (PR) using different sampling techniques are compared. Depending on the suitability of sampling techniques such as 2k Factorial designs, Central composite design, A-Optimal design, I-Optimal, D-Optimal, Taguchi’s orthogonal array design, Box-Behnken design, Latin hypercube sampling, sobol sequence are illustrated. Statistical analysis of the first three natural frequencies is presented to compare the results and its performance.

Keywords: composite plate, natural frequency, polynomial regression model, sampling technique, uncertainty quantification

Procedia PDF Downloads 513

Authors: Dwarakanadha Reddy Peram, D. Swarnalatha, C. Gopinath

Abstract:

The main aim of this research work was to design and development characterization of Pioglitazone transdermal drug delivery system by using various polymers such as Olibanum with different concentration by solvent evaporation technique. The prepared formulations were evaluated for different physicochemical characteristics like thickness, folding endurance, drug content, percentage moisture absorption, percentage moisture loss, percentage elongation break test and weight uniformity. The diffusion studies were performed by using modified Franz diffusion cells. The result of dissolution studies shows that formulation, F3 (Olibanum with 50 mg) showed maximum release of 99.95 % in 12hrs, whereas F1 (Olibanum and EC backing membrane) showed minimum release of 93.65% in 12 hr. Based on the drug release and physicochemical values obtained the formulation F3 is considered as an optimized formulation which shows higher percentage of drug release of 99.95 % in 12 hr. The developed transdermal patches increase the therapeutic efficacy and reduced toxic effect of pioglitazone.

Keywords: pioglitazone, olibanum, transdermal drug delivery system, drug release percantage

Procedia PDF Downloads 209

Authors: Shasline Gedeon, Tiffany W. Ardley, Ying Wang, Nathan J. Gesmundo, Katarina A. Sarris, Ana L. Aguirre

Abstract:

Drug discovery and delivery involve drug targeting, an approach that helps find a drug against a chosen target through high throughput screening and other methods by way of identifying the physical properties of the potential lead compound. Physical properties of potential drug candidates have been an imperative focus since the unveiling of Lipinski's Rule of 5 for oral drugs. Throughout a compound's journey from discovery, clinical phase trials, then becoming a classified drug on the market, the desirable properties are optimized while minimizing/eliminating toxicity and undesirable properties. In the pharmaceutical industry, the ability to generate molecules in parallel with maximum efficiency is a substantial factor achieved through sp²-sp² carbon coupling reactions, e.g., Suzuki Coupling reactions. These reaction types allow for the increase of aromatic fragments onto a compound. More recent literature has found benefits to decreasing aromaticity, calling for more sp³-sp² carbon coupling reactions instead. The objective of this project is to provide a comparison between various sp³-sp² carbon coupling methods and reaction conditions, collecting data on production of the desired product. There were four different coupling methods being tested amongst three cores and 4-5 installation groups per method; each method ran under three distinct reaction conditions. The tested methods include the Photoredox Decarboxylative Coupling, the Photoredox Potassium Alkyl Trifluoroborate (BF3K) Coupling, the Photoredox Cross-Electrophile (PCE) Coupling, and the Weix Cross-Electrophile (WCE) Coupling. The results concluded that the Decarboxylative method was very difficult in yielding product despite the several literature conditions chosen. The BF3K and PCE methods produced competitive results. Amongst the two Cross-Electrophile coupling methods, the Photoredox method surpassed the Weix method on numerous accounts. The results will be used to build future libraries.

Keywords: drug discovery, high throughput chemistry, photoredox chemistry, sp³-sp² carbon coupling methods

Procedia PDF Downloads 144

Authors: Ehsan B. Haghighi, Pavel Makhnatch, Jörgen Rogstam

Abstract:

The ice rink floor is the largest heat exchanger in an ice rink. The important part of the floor consists of concrete, and the thermophysical properties of this concrete have strong influence on the energy usage of the ice rink. The thermal conductivity of concrete can be increased by using iron ore as ballast. In this study the Transient Plane Source (TPS) method showed an increase up to 58.2% of thermal conductivity comparing the improved concrete to standard concrete. Moreover, two alternative ice rink floor designs are suggested to incorporate the improved concrete. A 2D simulation was developed to investigate the temperature distribution in the conventional and the suggested designs. The results show that the suggested designs reduce the temperature difference between the ice surface and the brine by 1-4 ˚C, when comparing with convectional designs at equal heat flux. This primarily leads to an increased coefficient of performance (COP) in the primary refrigeration cycle and secondly to a decrease in the secondary refrigerant pumping power. The suggested designs have great potential to reduce the energy usage of ice rinks. Depending on the load scenario in the ice rink, the saving potential lies in the range of 3-10% of the refrigeration system energy usage. This calculation is based on steady state conditions and the potential with improved dynamic behavior is expected to increase the potential saving.

Keywords: Concrete, iron ore, ice rink, energy saving

Procedia PDF Downloads 342

Authors: Kiyohiro Yamazaki

Abstract:

The purpose of this paper is to examine the hypothesis explaining the mechanism in the case, where the product is deleted or reduced the fundamental function of the product through the product concept changes in the digital camera industry. This paper points out not owning the fundamental technology might cause the change of the product concept. Casio could create new competitive factor so that this paper discusses a possibility of the mechanism of changing the product concept.

Keywords: firm without fundamental technology, product development, product concept, digital camera industry, Casio

Procedia PDF Downloads 562

Authors: Yaxian Chen, Yeonhee Park

Abstract:

Driven by evolving FDA recommendations, modern clinical trials demand innovative designs that strike a balance between statistical rigor and ethical considerations. Covariate-adjusted response-adaptive (CARA) designs bridge this gap by utilizing patient attributes and responses to skew treatment allocation in favor of the treatment that is best for an individual patient’s profile. However, existing CARA designs for survival outcomes often hinge on specific parametric models, constraining their applicability in clinical practice. In this article, we address this limitation by introducing a CARA design for survival outcomes (CARAS) based on the Cox model and a variance estimator. This method addresses issues of model misspecification and enhances the flexibility of the design. We also propose a group sequential overlapweighted log-rank test to preserve type I error rate in the context of group sequential trials using extensive simulation studies to demonstrate the clinical benefit, statistical efficiency, and robustness to model misspecification of the proposed method compared to traditional randomized controlled trial designs and response-adaptive randomization designs.

Keywords: cox model, log-rank test, optimal allocation ratio, overlap weight, survival outcome

Procedia PDF Downloads 64

Authors: Harald Lang, Michael Bader, A. Buchroithner

Abstract:

Holistic methods covering the development process as a whole – e.g. systems engineering – have established themselves in product design. However, technical product optimization, representing improvements in efficiency and/or minimization of loss, usually applies to single components of a system. A holistic approach is being defined based on a hierarchical point of view of systems engineering. This is subsequently presented using the example of an electromechanical flywheel energy storage system for automotive applications.

Keywords: design, product development, product optimization, systems engineering

Procedia PDF Downloads 624

Authors: Ayon Mukherjee

Abstract:

Covariate-adjusted response-adaptive (CARA) designs use the available responses to skew the treatment allocation in a clinical trial in towards treatment found at an interim stage to be best for a given patient's covariate profile. Extensive research has been done on various aspects of CARA designs with the patient responses assumed to follow a parametric model. However, ranges of application for such designs are limited in real-life clinical trials where the responses infrequently fit a certain parametric form. On the other hand, robust estimates for the covariate-adjusted treatment effects are obtained from the parametric assumption. To balance these two requirements, designs are developed which are free from distributional assumptions about the survival responses, relying only on the assumption of proportional hazards for the two treatment arms. The proposed designs are developed by deriving two types of optimum allocation designs, and also by using a distribution function to link the past allocation, covariate and response histories to the present allocation. The optimal designs are based on biased coin procedures, with a bias towards the better treatment arm. These are the doubly-adaptive biased coin design (DBCD) and the efficient randomized adaptive design (ERADE). The treatment allocation proportions for these designs converge to the expected target values, which are functions of the Cox regression coefficients that are estimated sequentially. These expected target values are derived based on constrained optimization problems and are updated as information accrues with sequential arrival of patients. The design based on the link function is derived using the distribution function of a probit model whose parameters are adjusted based on the covariate profile of the incoming patient. To apply such designs, the treatment allocation probabilities are sequentially modified based on the treatment allocation history, response history, previous patients’ covariates and also the covariates of the incoming patient. Given these information, an expression is obtained for the conditional probability of a patient allocation to a treatment arm. Based on simulation studies, it is found that the ERADE is preferable to the DBCD when the main aim is to minimize the variance of the observed allocation proportion and to maximize the power of the Wald test for a treatment difference. However, the former procedure being discrete tends to be slower in converging towards the expected target allocation proportion. The link function based design achieves the highest skewness of patient allocation to the best treatment arm and thus ethically is the best design. Other comparative merits of the proposed designs have been highlighted and their preferred areas of application are discussed. It is concluded that the proposed CARA designs can be considered as suitable alternatives to the traditional balanced randomization designs in survival trials in terms of the power of the Wald test, provided that response data are available during the recruitment phase of the trial to enable adaptations to the designs. Moreover, the proposed designs enable more patients to get treated with the better treatment during the trial thus making the designs more ethically attractive to the patients. An existing clinical trial has been redesigned using these methods.

Keywords: censored response, Cox regression, efficiency, ethics, optimal allocation, power, variability

Procedia PDF Downloads 165

Authors: Jackson Ishara, Ariel Buzera, Gustave N. Mushagalusa, Ahmed R. A. Hammam, Judith Munga, Paul Karanja, John Kinyuru

Abstract:

Numerous mushroom bioactive metabolites, including polysaccharides, eritadenine, lignin, chitosan, mevinolin, and astrakurkurone have been studied in life-threatening conditions and diseases such as diabetes, cardiovascular, hypertension, cancer, DNA damage, hypercholesterolemia, and obesity attempting to identify natural therapies. These bioactive metabolites have shown potential as antiviral and immune system strengthener natural agents through diverse cellular and physiological pathways modulation with no toxicity evidence, widely available, and affordable. In light of the emerging literature, this paper compiles the most recent information describing the molecular mechanisms that underlie the nutraceutical potentials of these mushroom metabolites suggesting their effectiveness if combined with existing drug therapies. The findings raise hope that these mushroom bioactive metabolites may be utilized as natural therapies considering their therapeutic potential while anticipating further research designing clinical trials and developing new drug therapies while encouraging their consumption as a natural adjuvant in preventing and controlling life-threatening conditions and diseases.

Keywords: bioactive metabolites, food functionality, health-threatening conditions, mushrooms, nutraceutical

Procedia PDF Downloads 103

Authors: Papon Thamvasupong, Kwanchanok Viravaidya-Pasuwat

Abstract:

Osteoarthritis affects a lot of people worldwide. Local injection of glucosamine is one of the alternative treatment methods to replenish the natural lubrication of cartilage. However, multiple injections can potentially lead to possible bacterial infection. Therefore, a drug delivery system is desired to reduce the frequencies of injections. A hydrogel is one of the delivery systems that can control the release of drugs. Thermo-reversible hydrogels can be beneficial to the drug delivery system especially in the local injection route because this formulation can change from liquid to gel after getting into human body. Once the gel is in the body, it will slowly release the drug in a controlled manner. In this study, various formulations of Pluronic-based hydrogels were synthesized for the controlled release of glucosamine. One of the challenges of the Pluronic controlled release system is its fast dissolution rate. To overcome this problem, alginate and calcium sulfate (CaSO₄) were added to the polymer solution. The characteristics of the hydrogels were investigated including the gelation temperature, gelation time, hydrogel dissolution and glucosamine release mechanism. Finally, a mathematical model of glucosamine release from Pluronic-alginate-hyaluronic acid hydrogel was developed. Our results have shown that crosslinking Pluronic gel with alginate did not significantly extend the dissolution rate of the gel. Moreover, the gel dissolution profiles and the glucosamine release mechanisms were best described using the zeroth-order kinetic model, indicating that the release of glucosamine was primarily governed by the gel dissolution.

Keywords: controlled release, drug delivery system, glucosamine, pluronic, thermoreversible hydrogel

Procedia PDF Downloads 270

Authors: Afsaneh Ghorbanzadeh, Afshin Farahbakhsh, Zakieh Bayat

Abstract:

The drug capsulation was used for release and targeted delivery in determined time, place and temperature or pH. The DOX nanocapsules were used to reduce and to minimize the unwanted side effects of drug. In this paper, the encapsulation methods of doxorubicin (DOX) and the labeling it by the magnetic core of iron (Fe3O4) has been studied. The Fe3O4 was conjugated with DOX via hydrazine bond. The solution was capsuled by the sensitive polymer of heat or pH such as chitosan-g-poly (N-isopropylacrylamide-co-N,N-dimethylacrylamide), dextran-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide) and mPEG-G2.5 PAMAM by hydrazine bond. The drug release was very slow at temperatures lower than 380°C. There was a rapid and controlled drug release at temperatures higher than 380°C. According to experiments, the use mPEG-G2.5PAMAM is the best method of DOX nanocapsules synthesis, because in this method, the drug delivery time to certain place is lower than other methods and the percentage of released drug is higher. The synthesized magnetic carrier system has potential applications in magnetic drug-targeting delivery and magnetic resonance imaging.

Keywords: drug carrier, drug release, doxorubicin, iron oxide NPs

Procedia PDF Downloads 417

Authors: Surajj Sarode, G. P. Vadnere, G. Vidya Sagar

Abstract:

Compression coating is one of the strategies for delivering drug to the colon based on Gastrointestinal PH and transit time concept. The main aim of these formulations to develop rapidly disintegrating Zaltoprofen core tablets compression-coated with a mixture of time-dependent hydrophilic swellable polymer HPMC K 15 and PH responsive soluble polymer Chitosan and Guar gum in different ratios. The effect of the proportion of HPMC, Chitosan and Guar gum in the coat on premature drug release in upper part (Stomach and small intestine) of GIT and the amount of drug release in colon target area was studied. The formulations are carried out by using Direct Compression method. Sodium starch Glycolate used for rapid disintegration. FTIR used for Drug-Polymer Interaction studies. The prepared tablets were evaluated for hardness, thickness, friability, in-vitro disintegration, in-Vitro dissolution and in-vitro kinetic study.

Keywords: zaltoprofen, chitosan, formulation, drug delivery

Procedia PDF Downloads 452

Authors: N. AlShaya, R. Alhomidan, S. Alromizan, W. Labib

Abstract:

Plant-based natural fibers are used more increasingly in construction materials. It is done to reduce the pressure on the built environment, which has been increased dramatically due to the increases world population and their needs. Plant-based natural fibers are abundant in many countries. Despite the low-cost of such environmental friendly renewable material, it has the ability to enhance the mechanical properties of construction materials. This paper presents an extensive discussion on the use of plant-based natural fibers as reinforcement for cement-based composites, with a particular emphasis upon fiber types; fiber characteristics, and fiber-cement composites performance. It also covers a thorough overview on the main factors, affecting the properties of plant-based natural fiber cement composite in it fresh and hardened state. The feasibility of using plant-based natural fibers in producing various construction materials; such as, mud bricks and blocks is investigated. In addition, other applications of using such fibers as internal curing agents as well as durability enhancer are also discussed. Finally, recommendation for possible future work in this area is presented.

Keywords: natural fibres, cement composites, construction materia, sustainability, stregth, durability

Procedia PDF Downloads 221

Authors: Fateme Nokhodchi Bonab

Abstract:

Studies related to magnetic resonance imaging (MRI) and drug delivery are reviewed in this study to demonstrate the role of transport theory in porous media in facilitating advances in biomedical applications. Diffusion processes are believed to be important in many therapeutic modalities such as: B. Delivery of drugs to the brain. We analyse the progress in the development of diffusion equations using the local volume average method and the evaluation of applications related to diffusion equations. Torsion and porosity have significant effects on diffusive transport. In this study, various relevant models of torsion are presented and mathematical modeling of drug release from biodegradable delivery systems is analysed. In this study, a new model of drug release kinetics from porous biodegradable polymeric microspheres under bulk and surface erosion of the polymer matrix is presented. Solute drug diffusion, drug dissolution from the solid phase, and polymer matrix erosion have been found to play a central role in controlling the overall drug release process. This work paves the way for MRI and drug delivery researchers to develop comprehensive models based on porous media theory that use fewer assumptions compared to other approaches.

Keywords: MRI, porous media, drug delivery, biomedical applications

Procedia PDF Downloads 89

Authors: Farzad Jalilian, Mehdi Mirzaei Alavijeh

Abstract:

Background: Substance addiction is one of the major worldwide problems that destroys economy, familial relationships, and the abuser’s career and has several side effects; in the meantime drug injection due to the possibility of shared use of syringes among drug users could have multiple complications to be followed. The purpose of this study was to determine the prevalence of drug injection among male prisoners in Kermanshah city, the west of Iran. Methods: In this cross-sectional study 615 male prisoners were randomly selected to participate voluntarily in the study. Participants filled out a writing self-report questionnaire. Data were analyzed by the SPSS software (ver. 21.0) at 95% significant level. Results: The mean age of respondents was 31.13 years [SD: 7.76]. Mean initiation age for drug use was 14.36 years (range, 9-34 years). Almost, 39.4 % reported a history of drug use before prison. Opium (33.2%) and crystal (27.1%) was the most used drug among prisoners. Furthermore, 9.3 % had a history of injection addiction. There was a significant correlation between age, crime type, marital status, economic status, unprotected sex and drug injection (P < 0.05). Conclusion: The low age of drug abuse and the prevalence of drug injection among offenders can be as a warning for responsible; in this regard, implementation of prevention programs to risky behavior and harm reduction among high-risk groups can follow useful results.

Keywords: substance abuse, drug injection, prison, Iran

Procedia PDF Downloads 485

Authors: Peng Hou

Abstract:

Natural products produced from marine bacteria serve as an immense reservoir for anti-infective drugs and therapeutic agents. Nowadays, heterologous expression of gene clusters of interests has been widely adopted as an effective strategy for natural product discovery. Briefly, the heterologous expression flowchart would be: biosynthetic gene cluster identification, pathway construction and expression, and product detection. However, gene cluster capture using traditional Transformation-associated recombination (TAR) protocol is low-efficient (0.5% positive colony rate). To make things worse, most of these putative new natural products are only predicted by bioinformatics analysis such as antiSMASH, and their corresponding natural products biosynthetic pathways are either not expressed or expressed at very low levels under laboratory conditions. Those setbacks have inspired us to focus on seeking new technologies to efficiently edit and refractor of biosynthetic gene clusters. Recently, two cutting-edge techniques have attracted our attention - the CRISPR-Cas9 and Gibson Assembly. By now, we have tried to pretreat Brevibacillus laterosporus strain genomic DNA with CRISPR-Cas9 nucleases that specifically generated breaks near the gene cluster of interest. This trial resulted in an increase in the efficiency of gene cluster capture (9%). Moreover, using Gibson Assembly by adding/deleting certain operon and tailoring enzymes regardless of end compatibility, the silent construct (~80kb) has been successfully refactored into an active one, yielded a series of analogs expected. With the appearances of the novel molecular tools, we are confident to believe that development of a high throughput mature pipeline for DNA assembly, transformation, product isolation and identification would no longer be a daydream for marine natural product discovery.

Keywords: biosynthesis, CRISPR-Cas9, DNA assembly, refactor, TAR cloning

Procedia PDF Downloads 282

Authors: Babak Bahri, Fatemeh Yassaee Meybodi, Changiz Eslahchi

Abstract:

In the pursuit of effective cancer therapies, the exploration of combinatorial drug regimens is crucial to leverage synergistic interactions between drugs, thereby improving treatment efficacy and overcoming drug resistance. However, identifying synergistic drug pairs poses challenges due to the vast combinatorial space and limitations of experimental approaches. This study introduces ClusterSyn, a machine learning (ML)-powered framework for classifying anti-cancer drug synergy scores. ClusterSyn employs a two-step approach involving drug clustering and synergy score prediction using a fully connected deep neural network. For each cell line in the training dataset, a drug graph is constructed, with nodes representing drugs and edge weights denoting synergy scores between drug pairs. Drugs are clustered using the Markov clustering (MCL) algorithm, and vectors representing the similarity of drug pairs to each cluster are input into the deep neural network for synergy score prediction (synergy or antagonism). Clustering results demonstrate effective grouping of drugs based on synergy scores, aligning similar synergy profiles. Subsequently, neural network predictions and synergy scores of the two drugs on others within their clusters are used to predict the synergy score of the considered drug pair. This approach facilitates comparative analysis with clustering and regression-based methods, revealing the superior performance of ClusterSyn over state-of-the-art methods like DeepSynergy and DeepDDS on diverse datasets such as Oniel and Almanac. The results highlight the remarkable potential of ClusterSyn as a versatile tool for predicting anti-cancer drug synergy scores.

Keywords: drug synergy, clustering, prediction, machine learning., deep learning

Procedia PDF Downloads 79

Authors: Myoung-Jin Lee, Sung-Jin Lee, Young-Kon Park, Jin-Wook Kim, Bo-Kyoung Kim, Song-Hun Chong, Sun-Ii Kim

Abstract:

The ability to resist the shear strength arises mainly from the web panel of steel girders and as such, the shear buckling strength of these girders has been extensively investigated. For example, Blaser’s reported that when buckling occurs, the tension field has an effect after the buckling strength of the steel is reached. The findings of these studies have been applied by AASHTO, AISC, and to the European Code that provides guidelines for designs aimed at preventing shear buckling. Steel girders are susceptible to corrosion resulting from exposure to natural elements such as rainfall, humidity, and temperature. This corrosion leads to a reduction in the size of the web panel section, thereby resulting in a decrease in the shear strength. The decrease in the panel section has a significant effect on the maintenance section of the bridge. However, in most conventional designs, the influence of corrosion is overlooked during the calculation of the shear buckling strength and hence over-design is common. Therefore, in this study, a steel girder with an A/D of 1:1, as well as a 6-mm-, 16-mm-, and 12-mm-thick web panel, flange, and intermediate reinforcing material, respectively, were used. The total length was set to that (3200 mm) of the default model. The effect of corrosion shear buckling was investigated by determining the volume amount of corrosion, shape of the erosion patterns, and the angular change in the tensile field of the shear buckling strength. This study provides the basic data that will enable designs that incorporate values closer (than those used in most conventional designs) to the actual shear buckling strength.

Keywords: corrosion, shear buckling strength, steel girder, shear strength

Procedia PDF Downloads 375

Authors: Ashraf Fayz Bekhet Abaskron

Abstract:

This research is done to create new compositions for designs, finding inspiration from watercolor artworks displayed in SuanSunandha Palace. The researcher made a study in the history of the landmark, its importance, the paintings in the Palace, the types and characteristics of the flowers painted, as well as the artistic elements and principles of designs that went into the paintings. The information obtained led to the creation of six totally new designs. The designs incorporated standard international designs and artistic principles and still kept to the original style of the watercolor paintings in SuanSunandha Palace. Following the paintings, the designs are divided into three categories: Orchids, Roses, and Flowers from literature. The researcher used the components of the flowers including rounded-petal flowers, wavy-edged petals, flowers with pointed petals, leaves, vines, and branches. All of them are represented in the original paintings. Upon the original, the researcher switched these elements and their proportions around to create a more modern design. The original forms are used as references since they contain the characteristics of each flower species. The work created achieved an updated trait and simultaneously reflects the charms and timeless beauty of the watercolor paintings displayed in SuanSunandha Palace, which still exists in today’s world.

Keywords: art, craft, design, Oman, weaving watercolor, painting, flower, Suan Sunandhagolden ratio, Fibonacci numbers, textile design, designs

Procedia PDF Downloads 34

Authors: Abidin Tortum, Kubra Kocabey

Abstract:

One of the sectors where the competition is experienced at the highest level in the world is the transformer sector, and sales can be made with a limited profit margin. For this reason, manufacturers must develop cost-cutting designs to achieve higher profits. The use of rectangular cores and coils in transformer design is one of the methods that can be used to reduce costs. According to the best knowledge we have obtained, we think that we are the first company producing rectangular core power transformers in our country. BETA, to reduce the cost of this project, more compact products to reveal, as we know it to increase the alleviate and competitiveness of the product, will perform cored coil design and production rectangle for the first-time power transformers in Turkey. The transformer to be designed shall be 16 MVA, 33/11 kV voltage level. With the rectangular design of the transformer core and windings, no-load losses can be reduced. Also, the least costly transformer type is rectangular. However, short-circuit forces on rectangular windings do not affect every point of the windings in the same way. Whereas more force is applied inwards to the mid-points of the low-voltage winding, the opposite occurs in the high-voltage winding. Therefore, the windings tend to deteriorate in the event of a short circuit. While trying to reach the project objectives, the difficulties in the design should be overcome. Rectangular core transformers to be produced in our country offer a more compact structure than conventional transformers. In other words, both height and width were smaller. Thus, the reducer takes up less space in the center. Because the transformer boiler is smaller, less oil is used, and its weight is lower. Biotemp natural ester fluid is used in rectangular transformer and the cooling performance of this oil is analyzed. The cost was also reduced with the reduction of dimensions. The decrease in the amount of oil used has also increased the environmental friendliness of the developed product. Transportation costs have been reduced by reducing the total weight. The amount of carbon emissions generated during the transportation process is reduced. Since the low-voltage winding is wound with a foil winding technique, a more resistant structure is obtained against short circuit forces. No-load losses were lower due to the use of a rectangular core. The project was handled in three phases. In the first stage, preliminary research and designs were carried out. In the second stage, the prototype manufacturing of the transformer whose designs have been completed has been started. The prototype developed in the last stage has been subjected to routine, type and special tests.

Keywords: rectangular core, power transformer, transformer, productivity

Procedia PDF Downloads 121

Authors: Surendra Agrawal, Pravina Gurjar, Supriya Bhide, Ram Gaud

Abstract:

Levamisole hydrochloride is a prominent anticancer drug in the treatment of colon cancer but resulted in toxic effects due poor bioavailability and poor cellular uptake by tumor cells. Levamisole is an unstable drug. Incorporation of this molecule in solid lipids may minimize their exposure to the aqueous environment and partly immobilize the drug molecules within the lipid matrix-both of which may protect the encapsulated drugs against degradation. The objectives of the study were to enhance bioavailability by sustaining drug release and to reduce the toxicities associated with the therapy. Solubility of the drug was determined in different lipids to select the components of Solid Lipid Nanoparticles (SLN). Pseudoternary phase diagrams were created using aqueous titration method. Formulations were subjected to particle size and stability evaluation to select the final test formulations which were characterized for average particle size, zeta potential, and in-vitro drug release and percentage transmittance to optimize the final formulation. SLN of Levamisole hydrochloride was prepared by Nanoprecipitation method. Glyceryl behenate (Compritol 888 ATO) was used as core comprising of Tween 80 as surfactant and Lecithin as co-surfactant in (1:1) ratio. Entrapment efficiency (EE) was found to be 45.89%. Particle size was found in the range of 100-600 nm. Zeta potential of the formulation was -17.0 mV revealing the stability of the product. In-vitro release study showed that 66 % drug released in 24 hours in pH 7.2 which represent that formulation can give controlled action at the intestinal environment. In pH 5.0 it showed 64% release indicating that it can even release drug in acidic environment of tumor cells. In conclusion, results revealed SLN to be a promising approach to sustain the drug release so as to increase bioavailability and cellular uptake of the drug with reduction in toxic effects as dose has been reduced with controlled delivery.

Keywords: SLN, nanoparticulate delivery of levamisole, pharmacy, pharmaceutical sciences

Procedia PDF Downloads 431

Authors: Jay Ananth

Abstract:

The drug discovery process currently requires numerous years of clinical testing as well as money just for a single drug to earn FDA approval. For drugs that even make it this far in the process, there is a very slim chance of receiving FDA approval, resulting in detrimental hurdles to drug accessibility. To minimize these inefficiencies, numerous studies have implemented computational methods, although few computational investigations have focused on a crucial feature of drugs: lipophilicity. Lipophilicity is a physical attribute of a compound that measures its solubility in lipids and is a determinant of drug efficacy. This project leverages Artificial Intelligence to predict the impact of a drug’s lipophilicity on its performance by accounting for factors such as binding affinity and toxicity. The model predicted lipophilicity and binding affinity in the validation set with very high R² scores of 0.921 and 0.788, respectively, while also being applicable to a variety of target receptors. The results expressed a strong positive correlation between lipophilicity and both binding affinity and toxicity. The model helps in both drug development and discovery, providing every pharmaceutical company with recommended lipophilicity levels for drug candidates as well as a rapid assessment of early-stage drugs prior to any testing, eliminating significant amounts of time and resources currently restricting drug accessibility.

Keywords: drug discovery, lipophilicity, ligand-receptor interactions, machine learning, drug development

Procedia PDF Downloads 111

Authors: Ahmed Almurshedi, Mark Atherton, Mares Cristinel, Tadeusz Stolarski, Masaaki Miyatake

Abstract:

Transportation and handling of delicate and lightweight objects is a significant issue in some industries. Two levitation prototype designs, a horn transducer design and surface-mounted piezoelectric actuator vibrating plate design, are compared. Both designs are based on the method of squeeze-film levitation (SFL) and the aim of this study is to evaluate the characteristics and performance of each. To this end, physical experiments are conducted and are demonstrated that the horn-type transducer prototype design produces better levitation performance but it design complexity and operating characteristics make it less suitable than the vibrating plate design for practical applications.

Keywords: floating, levitation, piezoelectric, squeeze-film, transducer

Procedia PDF Downloads 279

Authors: Sara D. Garduno-Diaz, Ramona Milcheva, Chanyu Xu

Abstract:

Women’s reproductive stages (pre-pregnancy, pregnancy, and lactation) represent a time of higher micronutrient needs. With a healthy food selection as the first path of choice to cover these increased needs, tandem micronutrient supplementation is often required. Because pregnancy and lactation should be treated with care, all supplements consumed should be of quality ingredients and manufactured through controlled processes. This work describes the process followed for the development of plant-based multiple micronutrient supplements aimed at addressing the growing demand for natural ingredients of non-animal origin. A list of key nutrients for inclusion was prioritized, followed by the identification and selection of qualified raw ingredient providers. Nutrient absorption into the food matrix was carried out through natural processes. The outcome is a new line of products meeting the set criteria of being gluten and lactose-free, suitable for vegans/vegetarians, and without artificial conservatives. In addition, each product provides the consumer with 10 vitamins, 6 inorganic nutrients, 1 source of essential fatty acids, and 1 source of phytonutrients each (maca, moringa, and chlorella). Each raw material, as well as the final product, was submitted to microbiological control three-fold (in-house and external). The final micronutrient mix was then tested for human factor contamination, pesticides, total aerobic microbial count, total yeast count, and total mold count. The product was created with the aim of meeting product standards for the European Union, as well as specific requirements for the German market in the food and pharma fields. The results presented here reach the point of introduction of the newly developed product to the market, with acceptability and effectiveness results to be published at a later date.

Keywords: fertility, lactation, organic, pregnancy, vegetarian

Procedia PDF Downloads 146

Authors: Asho Ali

Abstract:

Tuberculosis is a disease of grave concern which infects one-third of the global population. The high incidence of tuberculosis is further compounded by the increasing emergence of drug resistant strains including multi drug resistant (MDR). Global incidence MDR-TB is ~4%. Molecular epidemiological studies, based on the assumption that patients infected with clustered strains are epidemiologically linked, have helped understand the transmission dynamics of disease. It has also helped to investigate the basis of variation in Mycobacterium tuberculosis (MTB) strains, differences in transmission, and severity of disease or drug resistance mechanisms from across the globe. This has helped in developing strategies for the treatment and prevention of the disease including MDR.

Keywords: Mycobcaterium tuberculosis, molecular epidemiology, drug resistance, disease

Procedia PDF Downloads 403