Search results for: competitive inhibitors

Authors: Mir Mohammad Reza Hosseini

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In new years immune checkpoint inhibitors have gathered care as being one of the greatest talented kinds of immunotherapy on the prospect. There has been a specific emphasis on the immune checkpoint molecules, cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). In 2011, ipilimumab, the primary antibody obstructive an immune checkpoint (CTLA4) was authorized. It is now documented that recognized tumors have many devices of overpowering the antitumor immune response, counting manufacture of repressive cytokines, staffing of immunosuppressive immune cells, and upregulation of coinhibitory receptors recognized as immune checkpoints. This was fast followed by the growth of monoclonal antibodies directing PD1 (pembrolizumab and nivolumab) and PDL1 (atezolizumab and durvalumab). Anti-PD1/PDL1 antibodies have developed some of the greatest extensively set anticancer therapies. We also compare and difference their present place in cancer therapy and designs of immune-related toxicities and deliberate the role of dual immune checkpoint inhibition and plans for the organization of immune-related opposing proceedings. In this review, the employed code and present growth of numerous immune checkpoint inhibitors are abridged, while the communicating device and new development of Immune checkpoint inhibitors in cancer therapy-based synergistic therapies with additional immunotherapy, chemotherapy, phototherapy, and radiotherapy in important and clinical educations in the historical 5 years are portrayed and tinted. Lastly, we disapprovingly measure these methods and effort to find their fortes and faintness based on pre-clinical and clinical information.

Keywords: checkpoint, cancer therapy, PD-1, PDL-1, CTLA4, immunosuppressive

Procedia PDF Downloads 137

Authors: Shimaa A. Higazy, Olfat E. El-Azabawy, Ahmed M. Al-Sabagh, Notaila M. Nasser, Eman A. Khamis

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In this work, two novel Schiff base polymers (PSB1 and PSB₂) with extra-high protective barrier features were facilely prepared via Polycondensation reactions. They were applied for the first time as effective corrosion inhibitors in the sour corrosive media of petroleum environments containing hydrogen sulfide (H₂S) gas. For studying the polymers' inhibitive action on the carbon steel, numerous corrosion testing methods including potentiodynamic polarization (PDP), open circuit potential, and electrochemical impedance spectroscopy (EIS) have been employed at various temperatures (298-328 K) in the oil wells formation water with H₂S concentrations of 100, 400, and 700 ppm as aggressive media. The activation energy (Ea) and other thermodynamic parameters were computed to describe the mechanism of adsorption. The corrosion morphological traits and steel samples' surfaces composition were analyzed by field emission scanning electron microscope and energy dispersive X-ray analysis. The PSB2 inhibited sour corrosion more effectively than PSB1 when subjected to electrochemical testing. The 100 ppm concentration of PSB2 exhibited 82.18 % and 81.14 % inhibition efficiencies at 298 K in PDP and EIS measurements, respectively. While at 328 K, the inhibition efficiencies were 61.85 % and 67.4 % at the same dosage and measurements. These poly Schiff bases exhibited fascinating performance as corrosion inhibitors in sour environment. They provide a great corrosion inhibition platform for the sustainable future environment.

Keywords: schiff base polymers, corrosion inhibitors, sour corrosive media, potentiodynamic polarization, H₂S concentrations

Procedia PDF Downloads 63

Authors: Rajesh Kumar, Anil Kamboj

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Inhibition of α- amylase play a vital role in the clinical management of postprandial hyperglycemia. Although, powerful synthetic inhibitors are available, natural inhibitors are potentially safer. The present study was carried out to evaluate α- amylase inhibition activity from hydroalcoholic extracts from aerial parts of Cestrum nocturnum. Hydroalcoholic extract was prepared by Soxhletation Method. The extract showed strong inhibition towards α- amylase activity and IC50 value were 45.9 µg. This In vitro studies indicate the potential of C. nocturnum in the development of effective anti-diabetic agents.

Keywords: α- amylase, cestrum nocturnum, hyperglycemia, hydroalcoholic extracts, diabetes

Procedia PDF Downloads 289

Authors: T. Niracharapa, W. Angkana

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Since information and communication technology (ICT) plays a critical role in enhancing national competitiveness, it is a driving force for social and economic growth and prosperity. The ASEAN Economic Community (AEC) will integrate this into ASEAN countries as a new mechanism and a measure that will improve economic performance as a global economy. Government policies may support or impede such harmonization. This study was to investigate, analyze the status of Thai IT entrepreneurs and define key strategies to enhance their competitive advantage. Data were collected based on in-depth interviews, questionnaires, focus groups, seminars and fieldwork on information technology excluding communication. SWOT was used as a tool to analyze the study. The results of this study can be used to enable the government to guide policy, measures and strategies for creating a competitive advantage for Thailand’s IT entrepreneurs in the global market.

Keywords: AEC, ASEAN, competitive advantage, IT entrepreneurs

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Authors: Benarous Khedidja, Yousfi Mohamed

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Infections caused by Candida species manifest in a number of diseases, including candidemia, vulvovaginal candidiasis, endocarditis, and peritonitis. These Candida species have been reported to have lipolytic activity by secretion of lipolytic enzymes such as esterases, lipases and phospholipases. These Extracellular hydrolytic enzymes seem to play an important role in Candida overgrowth. Candidiasis is commonly treated with antimycotics such as clotrimazole and nystatin, which bind to a major component of the fungal cell membrane (ergosterol). This binding forms pores in the membrane that lead to death of the fungus. Due to their secondary effects, scientists have thought of another treatment basing on lipase inhibition but we haven’t found any lipase inhibitors used as candidiasis treatment. In this work, we are interested to lipases inhibitors such as alkaloids as another candidiasis treatment. In the first part, we have proceeded to optimize the alkaloid structures and protein 3D structure using Hyperchem software. Secondly, we have docked inhibitors using Genetic algorithm with GOLD software. The results have shown ten possibilities of binding inhibitor to Candida rugosa lipase (CRL) but only one possibility has been accepted depending on the weakest binding energy.

Keywords: marrubiin, candida rugosa lipase, docking, gold

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Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

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Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

Procedia PDF Downloads 62

Authors: K. Żak, S. Przetocka, R. Kitel, K. Guzik, B. Musielak, S. Malicki, G. Dubin, T. A. Holak

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Studies on tumor genesis revealed a number of factors that may potentially serve as molecular targets for immunotherapies. One of such promising targets are PD1 and PDL1 proteins. PD1 (Programmed cell death protein 1) is expressed by activated T cells and plays a critical role in modulation of the host's immune response. One of the PD1 ligands -PDL1- is expressed by macrophages, monocytes and cancer cells which exploit it to avoid immune attack. The notion of the mechanisms used by cancer cells to block the immune system response was utilized in the development of therapies blocking PD1-PDL1 interaction. Up to date, human PD1-PDL1 complex has not been crystallized and structure of the mouse-human complex does not provide a complete view of the molecular basis of PD1-PDL1 interactions. The purpose of this study is to obtain crystal structure of the human PD1-PDL1 complex which shall allow rational design of small molecule inhibitors of the interaction. In addition, the study presents results of binding small-molecules to PD1 and fragment docking towards PD1 protein which will facilitate the design and development of small–molecule inhibitors of PD1-PDL1 interaction.

Keywords: PD1, PDL1, cancer, small molecule, drug discovery

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Authors: Rania Sherif Abd El-Azim

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The role of corporate social responsibility (CSR) in business has evolved and led to an era where industry leaders can no longer overlook the importance of being participative corporate citizens. This is not only because of the media’s skeptical attitude toward whether or not companies’ CSR efforts are sincere but also due to key stakeholders’ ability to hold companies to a higher standard than ever before as companies can gain competitive advantage through CSR. These programs result in addressing global challenges, such as climate, and poverty, or simply improving employee retention, so it has become increasingly clear that CSR is not just the new trend for companies but a necessary tool that organizations must integrate into their overall business strategies to build a stronger reputation as well as to also increase credibility among their key audience and enhance customers’ willingness to repurchase, pay premium price and enhancing positive word of mouth. According to the literature review, the link between CSR and competitive advantage at the firm level has long been an important topic for both CSR researchers and practitioners. Thus CSR can play an important role in enhancing the firm's competitive advantage, which seems an attractive area to investigate specially in Egypt. So, this paper will investigate the role of corporate social responsibility in enhancing the firm competitive advantage.

Keywords: corporate social responsibility, competitive advantage, corporate reputation, customers' willingness to repurchase, willingness to pay premium price, positive word of mouth

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Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

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The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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Authors: Abdolrasoul Ghasemi, Ali Arabmazar Yazdi, Yasaman Boroumand, Aliasghar Banouei

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In regional studies, choosing an appropriate approach to analyze regional success or failure has always been a challenge. Hence, this study introduces an innovative approach to establish a link between regional success and failure in the past as well as the potential success of a region in the future. The former can be sought in the historical evaluation of comparative advantages, while the latter is portrayed as competitive advantage analysis with a forward-looking approach. Based on the interaction of comparative and competitive advantages, activities are classified into four groups, including activities with no advantage, hidden advantage, fragile advantage and synergistic advantage. In analyzing the comparative advantage of activities, the location quotient method is applied, and in analyzing their competitive advantage, Porter`s diamond model using the survey method is applied. According to the results, the share of no advantage, fragile advantage, hidden advantage and synergic advantage activities are respectively 10%, 42%, 16%, and 32%. Also, to achieve economic development in regional activities, our model provides various levels of priority. First, the activities with synergistic advantage should be prioritized, then the ones with hidden advantage, and finally the activities with fragile advantage.

Keywords: regional advantage, comparative advantage, competitive advantage, Porter's diamond model

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Authors: Alireza Rahimi, Abdolreza Farhadian, Arash Tajik, Elaheh Sadeh, Avni Berisha, Esmaeil Akbari Nezhad

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Although natural polymers have been shown to have some inhibitory properties on sour corrosion, they are not considered very effective green corrosion inhibitors. Accordingly, effective corrosion inhibitors should be developed based on natural resources to mitigate sour corrosion in the oil and gas industry. Here, Arabic gum was employed as an eco-friendly precursor for the synthesis of innovative polyurethanes designed as highly efficient corrosion inhibitors for sour oilfield solutions. A comprehensive assessment, combining experimental and computational analyses, was conducted to evaluate the inhibitory performance of the inhibitor. Electrochemical measurements demonstrated that a concentration of 200 mM of the inhibitor offered substantial protection to mild steel against sour corrosion, yielding inhibition efficiencies of 98% and 95% at 25 ºC and 60 ºC, respectively. Additionally, the presence of the inhibitor led to a smoother steel surface, indicating the adsorption of polyurethane molecules onto the metal surface. X-ray photoelectron spectroscopy results further validated the chemical adsorption of the inhibitor on mild steel surfaces. Scanning Kelvin probe microscopy revealed a shift in the potential distribution of the steel surface towards negative values, indicating inhibitor adsorption and corrosion process inhibition. Molecular dynamic simulation indicated high adsorption energy values for the inhibitor, suggesting its spontaneous adsorption onto the Fe (110) surface. These findings underscore the potential of Arabic gum as a viable resource for the development of polyurethanes under mild conditions, serving as effective corrosion inhibitors for sour solutions.

Keywords: environmental effect, Arabic gum, corrosion inhibitor, sour corrosion, molecular dynamics simulation

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Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

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Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

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Authors: Michio Kurosu

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

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

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Authors: Nattapong Techarattanased

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The objectives of this research were to study the influence of market orientation and supply chain management on competitive capability in case of the automotive parts industry in Thailand. This study employed by survey research and questionnaire was used to collect the data from 400 entrepreneurs in the automotive parts industry in Thailand. The descriptive statistics and multiple regression analysis were used to analyze data. The results revealed that the overall dimensions of marketing orientation, namely, responsiveness, intelligence generation, and intelligence dissemination were rated at the high level. As well, the overall dimensions of supply chain management, namely, collaboration, communication, trust, and commitment were also rated at the high level. Furthermore, the hypothesis testing results showed that supply chain management and market orientation affected competitive capability of the automotive parts industry in Thailand which these two variables could be combined to predict competitive capability of the automotive parts industry in Thailand by 31.5 percent.

Keywords: automotive parts industry, competitive capability, market orientation, supply chain management

Procedia PDF Downloads 286

Authors: Mona Rashidirad, Hamid Salimian

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Dynamic capabilities, as the most considerable capabilities of firms in the current fast-moving economy may not be sufficient for performance improvement, but their contribution to performance is undeniable. While much of the extant literature investigates the impact of dynamic capabilities on organisational performance, little attention has been devoted to understand whether and how dynamic capabilities create value. Dynamic capabilities as the mirror of competitive strategies should enable firms to search and seize new ideas, integrate and coordinate the firm’s resources and capabilities in order to create value. A careful investigation to the existing knowledge base remains us puzzled regarding the relationship among competitive strategies, dynamic capabilities and value creation. This study thus attempts to fill in this gap by empirically investigating the impact of dynamic capabilities on value creation and the mediating impact of competitive strategy on this relationship. We aim to contribute to dynamic capability view (DCV), in both theoretical and empirical senses, by exploring the impact of dynamic capabilities on firms’ value creation and whether competitive strategy can play any role in strengthening/weakening this relationship. Using a sample of 491 firms in the UK telecommunications market, the results demonstrate that dynamic sensing, learning, integrating and coordinating capabilities play a significant role in firm’s value creation, and competitive strategy mediates the impact of dynamic capabilities on value creation. Adopting DCV, this study investigates whether the value generating from dynamic capabilities depends on firms’ competitive strategy. This study argues a firm’s competitive strategy can mediate its ability to derive value from its dynamic capabilities and it explains the extent a firm’s competitive strategy may influence its value generation. The results of the dynamic capabilities-value relationships support our expectations and justify the non-financial value added of the four dynamic capability processes in a highly turbulent market, such as UK telecommunications. Our analytical findings of the relationship among dynamic capabilities, competitive strategy and value creation provide further evidence of the undeniable role of competitive strategy in deriving value from dynamic capabilities. The results reinforce the argument for the need to consider the mediating impact of organisational contextual factors, such as firm’s competitive strategy to examine how they interact with dynamic capabilities to deliver value. The findings of this study provide significant contributions to theory. Unlike some previous studies which conceptualise dynamic capabilities as a unidimensional construct, this study demonstrates the benefits of understanding the details of the link among the four types of dynamic capabilities, competitive strategy and value creation. In terms of contributions to managerial practices, this research draws attention to the importance of competitive strategy in conjunction with development and deployment of dynamic capabilities to create value. Managers are now equipped with solid empirical evidence which explains why DCV has become essential to firms in today’s business world.

Keywords: dynamic capabilities, resource based theory, value creation, competitive strategy

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Authors: Samira Ghizellaoui, Manel Boumagoura

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Calcium carbonate precipitation is a widespread problem, especially in hard water systems. The main water supply that supplies the city of Constantine with drinking water is underground water called Hamma water. This water has a very high hardness of around 590 mg/L CaCO₃. This leads to the formation of scale, consisting mainly of calcium carbonate, which can be responsible for the clogging of valves and the deterioration of equipment (water heaters, washing machines and encrustations in the pipes). Plant extracts used as scale inhibitors have attracted the attention of several researchers. In recent years, green inhibitors have attracted great interest because they are biodegradable, non-toxic and do not affect the environment. The aim of our work is to evaluate the effectiveness of a chemical antiscale treatment in the presence of three green inhibitors: gallicacid; quercetin; alginate, and three mixtures: (gallic acid-quercetin); (quercetin-alginate); (gallic acid-alginate). The results show that the inhibitory effect is manifested from an addition of 1mg/L of gallic acid, 10 mg/L of quercetin, 0.2 mg/L of alginate, 0.4mg/L of (gallic acid-quercetin), 2mg/L of (quercetin-alginate) and 0.4 mg/L of (gallic acid-alginate). On the other hand, 100 mg/L (Drinking water standard) of Ca2+is reached for partial softening at 4 mg/L of gallic acid, 40 mg/L of quercetin, 0.6mg/L of alginate, 4mg/L of (gallic acid-quercetin), 10mg/L of (quercetin-alginate) and 1.6 mg/L of (gallic acid-alginate).

Keywords: water, scaling, calcium carbonate, green inhibitor

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Authors: Shieh Shiow-Fang

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Superstitious thoughts or actions often occur during athletic competitions. Often "superstitious rituals" have a positive impact on the performance of competitive athletes. Athletes affirm the many psychological benefits of religious beliefs mostly in a positive way. Method: By snowball sampling, we recruited 10 experienced competitive athletes as participants. We used in-person and online one-to-one in-depth interviews to collect their experiences about sports superstition. The total interview time was 795 minutes. We analyzed the raw data with the grounded theory processes suggested by Strauss and Corbin (1990). Results: The factors affecting athlete performance are ritual beliefs, taboo awareness, learning norms, and spontaneous attribution behaviors. Conclusion: We concluded that sports superstition reflects several psychological implications. The analysis results of this paper can provide another research perspective for the future study of sports superstition behavior.

Keywords: superstition, taboo awarences, competitive athlete, learning norms

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Authors: Meng-Hui Chen, Chiao-Wei Yu, Pei-Chann Chang

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Imperial competitive algorithm (ICA) simulates a multi-agent algorithm. Each agent is like a kingdom has its country, and the strongest country in each agent is called imperialist, others are colony. Countries are competitive with imperialist which in the same kingdom by evolving. So this country will move in the search space to find better solutions with higher fitness to be a new imperialist. The main idea in this paper is using the peculiarity of ICA to explore the search space to solve the kinds of combinational problems. Otherwise, we also study to use the greed search to increase the local search ability. To verify the proposed algorithm in this paper, the experimental results of traveling salesman problem (TSP) is according to the traveling salesman problem library (TSPLIB). The results show that the proposed algorithm has higher performance than the other known methods.

Keywords: traveling salesman problem, artificial chromosomes, greedy search, imperial competitive algorithm

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Authors: Yomna Ibrahim El-Gazzar, Hussien Ibrahim El-Subbagh, Hanan Hanaa Georgey, Ghada S. Hassan Hassan

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Dihydrofolate reductase (DHFR) is an enzyme that has pivotal importance in biochemistry and medicinal chemistry. It catalyzes the reduction of dihydrofolate to tetrahydrofolate and intimately couples with thymidylate synthase. Thymidylate synthase is a crucial enzyme that catalyzes the reductive methylation of (dUMP) to (dTMP) utilizing N5, N10-methylenetetrahydrofolate as a cofactor. A new series of 2-substituted thio-quinazolin-4-one analogs was designed that possessed electron withdrawing or donating functional groups (Cl or OCH3) at position 6- or 7-, 4-methoxyphenyl function at position 3-.The thiol function is used to connect to either 1,2,4-triazole, or 1,3,4-thiadiazole via a methylene bridge. Most of the functional groups designed to be accommodated on the quinazoline ring such as thioether, alkyl to increase lipid solubility of polar compounds, a character very much needed in the nonclassical DHFR inhibitors. The target compounds were verified with spectral data and elemental analysis. DHFR inhibitions, as well as antitumor activity, were applied on three cell lines (MCF-7, CACO-2, HEPG-2).

Keywords: nonclassical antifolates, DHFR Inhibitors, antitumor activity, quinazoline ring

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Authors: Chengli Liu, C. K. M. Lee

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The tradition competitive newsvendor game assumes decision makers are rational. However, there are behavioral biases when people make decisions, such as loss aversion, mental accounting and overconfidence. Overestimation of a subject’s own performance is one type of overconfidence. The objective of this research is to analyze the impact of the overestimated demand in the newsvendor competitive game with two players. This study builds a competitive newsvendor game model where newsvendors have private information of their demands, which is overestimated. At the same time, demands of each newsvendor forecasted by a third party institution are available. This research shows that the overestimation leads to demand steal effect, which reduces the competitor’s order quantity. However, the overall supply of the product increases due to overestimation. This study illustrates the boundary condition for the overestimated newsvendor to have the equilibrium order drop due to the demand steal effect from the other newsvendor. A newsvendor who has higher critical fractile will see its equilibrium order decrease with the drop of estimation level from the other newsvendor.

Keywords: bias, competing newsvendor, Nash equilibrium, overestimation

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Authors: Shieh Shiow-fang

Abstract:

Superstitious thoughts or actions often occur during athletic competitions. Often "superstitious rituals" have a positive impact on the performance of competitive athletes. Athletes affirm the many psychological benefits of religious beliefs mostly in a positive way. Method: By snowball sampling, we recruited 10 experienced competitive athletes as participants. We used in-person and online one-to-one in-depth interview to collect their experiences about sport superstition. The total interview time was 795 minutes. We analyzed the raw data with the grounded theory processes suggested by Strauss and Corbin (1990). Results: The factors affecting athlete performance are ritual beliefs, taboo awareness, learning norms, and spontaneous attribution behaviors. Conclusion: We concluded that sports superstition reflects several psychological implications. The analysis results of this paper can provide another research perspective for the future study of sports superstition behavior.

Keywords: superstition, taboo awareness, learning norms, competitive athlete

Procedia PDF Downloads 48

Authors: A. Acidi, A. Abbaci

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We present the viability of using thermally stable, practically non-volatile ionic liquids as corrosion inhibitors in aqueous monoethanolamine system. Carbon steel 1020, which widely used as construction material in CO2 capture plants, has been taken as a test material. Corrosion inhibition capacities of typical room-temperature ionic liquids constituting imidazolium cation in concentration range ≤ 3% by weight in CO2 capture applications were investigated. Electrochemical corrosion experiments using the potentiodynamic polarization technique for measuring corrosion current were carried out. The results show that ionic liquids possess ability to suppressing severe operational problems of corrosion in typical CO2 capture plants.

Keywords: carbon dioxide, carbon steel, monoethanolamine, corrosion rate, ionic liquids, tafel fit

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Authors: Mehdi Seifbarghy, Zahra Nasiri

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Competitive location problem deals with locating new facilities to provide a service (or goods) to the customers of a given geographical area where other facilities (competitors) offering the same service are already present. The new facilities will have to compete with the existing facilities for capturing the market share. This paper proposes a new model to maximize the market share in which customers choose the facilities based on traveling time, waiting time and attractiveness. The attractiveness of a facility is considered as a parameter in the model. A heuristic is proposed to solve the problem.

Keywords: competitive location, market share, facility attractiveness, heuristic

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Authors: Wilhelmus Hary Susilo

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The marketplace would have at least some resources that are unique (e.g., well communication, knowledgeable employees, consumer value, effective transaction, efficient production processes and institutional branding). The institutions should have an advantage in resources and then could lead to positions of competitive advantage. These major challenges focus on increasing unique consumer value on reliable purchases that influence of loyalty and pursuit of a sustainable competitive advantage from the Institutions in Jakarta. Furthermore, a research was conducted with a quantitative method and a confirmatory strategic research design. The research resulted in entire confirmatory factors analysis (1st CFA and 2nd CFA) among variables pertains to; χ2//Df (9.30, 4.38, 6.95, 2.76, 2.97, 2.91, 2.32 and 6.90), GFI (0.72, 0.82, 0.82, 0.81, 0.78, 0.84, 0.89 and 0.70) and CFI (0.90, 0.95, 0.93, 0.92, 0.95, 0.91, 0.96 and 0.89), which indicates a good model. Furthermore, the hybrid model is well fit with, χ2//Df=1.84, P value = 0.00, RMSEA = 0.076, GFI = 0.76, NNFI= 0.95, PNFI= 0.82, IFI= 0.96, RFI= 0.91, AGFI= 0.71 and CFI= 0.96. The result was significant hypothesis, i.e. variables of communitization marketing 3.0 and price perception influenced to unique value of consumer with tvalue =4.46 and 5.89. Furthermore, the consumers value influenced the purchasing with t value = 5.94. Additionally, the loyalty, the ‘communitization’, and the character building marketing 3.0 are affecting the pursuit of a sustainable competitive advantage from institutions with t value = 7.57, -2.12, and 2.04. Finally, the test between the most superior variable dimensions is significantly correlated between INOV and WDES, RESPON and ATT covariance matrix value= 0.72 and 0.71. Thus, ‘communitization’ and character building marketing 3.0 with dimensions of responsibility and technologies would increase a competitive advantage with the dimensions of the innovation and the job design from the institutions.

Keywords: consumer loyalty, marketing 3.0, unique consumer value, purchase, sustainable competitive advantage

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Authors: C. Iitake, K. Iitake

Abstract:

Background and Aims: The number of diabetic patients based on obesity is increasing drastically in Asia. Since most patients have multiple complications, if one medicine can treat those at the same time, it would contribute to financial savings and patients’ compliance. A Japanese-made DPP-4 inhibitor, Anagliptin is only sold in Japan and South Korea. It is said to have its unique aspect of lowering LDL-cholesterol (LDL-C) levels together with lowering blood glucose. We have assessed 63 patients in our faculty to investigate this fact clinically and statistically. Method: Patients with type 2 diabetes who has been treated with Anagliptin for the first time was investigated changes in HbA1c, fasting and random blood glucose and LDL-C levels from the baseline at 1 month, 6 months and 1 year. Results: 29 patients (46.1%) were given DPP-4 inhibitors for the first time (original group), and 34 patients (53.9%) were using other DPP-4 inhibitors before Anagliptin (exchanged group). The change in HbA1c and fasting glucose from the baseline were -2.0% (P < 0.001) and -38.3mg/dl (P < 0.01) respectively with original group, -0.5% (P < 0.01) and -29.4mg/dl (P < 0.01) respectively with exchanged group. 23 patients (36.5%) were using statins or fibrates and 28 patients (44.4%) were using none, and its LDL-C change were -8.1mg/dl (P = 0.2582) and -10.1mg/dl(P < 0.05) respectively. 16 patients(25%) with LDL-C level ≥ 140mg/dl, change were -21.7mg/dl(P < 0.05). LDL-C change did not have a correlation coefficient (=-0.03238) with change in HbA1c and was not affected by other diabetic drugs. Conclusion: These findings indicate that Anagliptin is a potential treatment option for type 2 diabetes complicated by hyperlipidemia.

Keywords: DPP-4 inhibitors, anagliptin, LDL-cholesterol, type 2 diabetes

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Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

Abstract:

Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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Authors: Ragy Raafat Gaber Attaalla

Abstract:

For cardiovascular illness, oral P2Y12 inhibitors including clopidogrel, prasugrel, and ticagrelor are frequently recommended. Each of these medications has advantages and disadvantages. In the absence of genotyping, it has been demonstrated that the stronger platelet aggregation inhibitors prasugrel and ticagrelor are superior than clopidogrel at preventing significant adverse cardiovascular events following an acute coronary syndrome and percutaneous coronary intervention (PCI). Both, nevertheless, come with a higher risk of bleeding unrelated to a coronary artery bypass. As a prodrug, clopidogrel needs to be bioactivated, principally by the CYP2C19 enzyme. A CYP2C19 no function allele and diminished or absent CYP2C19 enzyme activity are present in about 30% of people. The reduced exposure to the active metabolite of clopidogrel and reduced inhibition of platelet aggregation among clopidogrel-treated carriers of a CYP2C19 no function allele likely contributed to the reduced efficacy of clopidogrel in clinical trials. Clopidogrel's pharmacogenetic results are strongest when used in conjunction with PCI, but evidence for other indications is growing. One of the most typical examples of clinical pharmacogenetic application is CYP2C19 genotype-guided antiplatelet medication following PCI. Guidance is available from expert consensus groups and regulatory bodies to assist with incorporating genetic information into P2Y12 inhibitor prescribing decisions. Here, we examine the data supporting genotype-guided P2Y12 inhibitor selection's effects on clopidogrel response and outcomes and discuss tips for pharmacogenetic implementation. We also discuss procedures for using genotype data to choose P2Y12 inhibitor therapies as well as any unmet research needs. Finally, choosing a P2Y12 inhibitor medication that optimally balances the atherothrombotic and bleeding risks may be influenced by both clinical and genetic factors.

Keywords: inhibitors, cardiovascular events, coronary intervention, pharmacogenetic implementation

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Authors: Driouiche Ali, Karmal Ilham

Abstract:

The Agadir region is characterized by a dry climate, ranging from arid attenuated by oceanic influences to hyper-arid. The water mobilized in the agricultural sector of greater Agadir is 95% of underground origin and comes from the water table of Chtouka. The rest represents the surface waters of the Youssef Ben Tachfine dam. These waters are intended for the irrigation of 26880 hectares of modern agriculture. More than 120 boreholes and wells are currently exploited. Their depth varies between 10 m and 200 m and the unit flow rates of the boreholes are 5 to 50 l/s. A drop in the level of the water table of about 1.5 m/year, on average, has been observed during the last five years. Farmers are thus called upon to improve irrigation methods. Thus, localized or drip irrigation is adopted to allow rational use of water. The importance of this irrigation system is due to the fact that water is applied directly to the root zone and its compatibility with fertilization. However, this irrigation system faces a thorny problem which is the clogging of pipes and drippers. This leads to a lack of uniformity of irrigation over time. This so-called scaling phenomenon, the consequences of which are harmful (cleaning or replacement of pipes), leads to considerable unproductive expenditure. The objective set by this work is the search for green inhibitors likely to prevent this phenomenon of scaling. This study requires a better knowledge of these waters, their physico-chemical characteristics and their scaling power. Thus, using the "LCGE" controlled degassing technique, we initially evaluated, on pure calco-carbonic water at 30°F, the scaling-inhibiting power of some available plant extracts in our region of Souss-Massa. We then carried out a comparative study of the efficacy of these green inhibitors. The action of the most effective green inhibitor on real agricultural waters was then studied.

Keywords: green inhibitors, localized irrigation, plant extracts, scaling inhibition

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Authors: Gokhan Zengin, Abdurrahman Aktumsek

Abstract:

The key enzyme inhibitory theory is one of the most accepted strategies in the treatment of global health problems including Alzheimer’s Disease and Diabetes mellitus. For this reason, the enzyme inhibitory potentials of different solvent extracts from Linaria genistifolia subsp. genistifolia were investigated against cholinesterase, and tyrosinase. The in vitro enzyme inhibitory potentials were measured with a microplate reader. The acetone and methanol extracts exhibited the strongest enzyme inhibitory effects on cholinesterase. However, the water extract was only active on tyrosinase. The results suggested that Linaria genistifolia subsp. genistifolia could be considered as a source of natural enzyme inhibitors for the treatment of major health problems.

Keywords: enzyme inhibitors, cholinesterase, tyrosinase, linaria, Turkey

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Authors: Adèle Oliva, Samuel Fosso Wamba

Abstract:

This study looks at how firms can create competitive advantages through effective reserve logistics strategies. Upon using data collected from reverse supply chain managers of electronic commerce companies, the study found that improved reverse logistics management can have a positive impact on companies’ business benefits. These include playing a role in the implementation of many factors that highly influence the decision to purchase, customers’ loyalty, as well as increasing companies’ turnover. As a result, through an efficient design and management of their reverse flow, companies can decrease the costs associated to returned products.

Keywords: reverse logistics, competitive advantage, case study, business value

Procedia PDF Downloads 428