Search results for: drug delivery
1838 Identifying Physiological Markers That Are Sensitive to Cognitive Load in Preschoolers
Authors: Priyashri Kamlesh Sridhar, Suranga Nanayakkara
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Current frameworks in assessment follow lesson delivery and rely heavily on test performance or teacher’s observations. This, however, neglects the underlying cognitive load during the learning process. Identifying the pivotal points when the load occurs helps design effective pedagogies and tools that respond to learners’ cognitive state. There has been limited research on quantifying cognitive load in preschoolers, real-time. In this study, we recorded electrodermal activity and heart rate variability (HRV) from 10 kindergarteners performing executive function tasks and Johnson Woodcock test of cognitive abilities. Preliminary findings suggest that there are indeed sensitive task-dependent markers in skin conductance (number of SCRs and average amplitude of SCRs) and HRV (mean heart rate and low frequency component) captured during the learning process.Keywords: early childhood, learning, methodologies, pedagogies
Procedia PDF Downloads 3201837 Electronic Government Services Adoption from Multi-Nationalities Perspectives
Authors: Isaac Kofi Mensah, Jianing Mi, Cheng Feng
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Electronic government is the application of Information and Communication Technologies (ICTs) by the government to improve public service delivery to citizens and businesses. The purpose of this study is to investigate factors influencing the adoption and use of e-government services from different nationalities perspectives. The Technology Acceptance Model (TAM) will be used as the theoretical framework for the study. A questionnaire would be developed and administered to 500 potential respondents who are students from different nationalities in China. Predictors such as perceived usefulness, perceived ease of use, computer self-efficacy, trust in both the internet and government, social influence and perceived service quality would be examined with regard to their impact on the intention to use e-government services. This research is currently at the design and implementation stage. The completion of this study will provide useful insights into understanding factors impacting the decision to use e-government services from a cross and multi nationalities perspectives.Keywords: different nationalities, e-government, e-government services, technology acceptance model (TAM)
Procedia PDF Downloads 4291836 Influence of Natural Gum on Curcumin Supersaturationin Gastrointestinal Fluids
Authors: Patcharawalai Jaisamut, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee
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Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms.In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8)was investigated. The results indicated that all natural gums significantly increased the curcum insolubility (about 1.2-6-fold)when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.Keywords: curcumin, solubility, supersaturation, precipitation inhibitor
Procedia PDF Downloads 3491835 A Unified Model for Orotidine Monophosphate Synthesis: Target for Inhibition of Growth of Mycobacterium tuberculosis
Authors: N. Naga Subrahmanyeswara Rao, Parag Arvind Deshpande
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Understanding nucleotide synthesis reaction of any organism is beneficial to know the growth of it as in Mycobacterium tuberculosis to design anti TB drug. One of the reactions of de novo pathway which takes place in all organisms was considered. The reaction takes places between phosphoribosyl pyrophosphate and orotate catalyzed by orotate phosphoribosyl transferase and divalent metal ion gives orotdine monophosphate, a nucleotide. All the reaction steps of three experimentally proposed mechanisms for this reaction were considered to develop kinetic rate expression. The model was validated using the data for four organisms. This model could successfully describe the kinetics for the reported data. The developed model can serve as a reliable model to describe the kinetics in new organisms without the need of mechanistic determination. So an organism-independent model was developed.Keywords: mechanism, nucleotide, organism, tuberculosis
Procedia PDF Downloads 3341834 Strategic Model of Implementing E-Learning Using Funnel Model
Authors: Mohamed Jama Madar, Oso Wilis
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E-learning is the application of information technology in the teaching and learning process. This paper presents the Funnel model as a solution for the problems of implementation of e-learning in tertiary education institutions. While existing models such as TAM, theory-based e-learning and pedagogical model have been used over time, they have generally been found to be inadequate because of their tendencies to treat materials development, instructional design, technology, delivery and governance as separate and isolated entities. Yet it is matching components that bring framework of e-learning strategic implementation. The Funnel model enhances all these into one and applies synchronously and asynchronously to e-learning implementation where the only difference is modalities. Such a model for e-learning implementation has been lacking. The proposed Funnel model avoids ad-ad-hoc approach which has made other systems unused or inefficient, and compromised educational quality. Therefore, the proposed Funnel model should help tertiary education institutions adopt and develop effective and efficient e-learning system which meets users’ requirements.Keywords: e-learning, pedagogical, technology, strategy
Procedia PDF Downloads 4521833 Standardization of the Roots of Gnidia stenophylla Gilg: A Potential Medicinal Plant of South Eastern Ethiopia Traditionally Used as an Antimalarial
Authors: Mebruka Mohammed, Daniel Bisrat, Asfaw Debella, Tarekegn Birhanu
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Lack of quality control standards for medicinal plants and their preparations is considered major barrier to their integration in to effective primary health care in Ethiopia. Poor quality herbal preparations led to countless adverse reactions extending to death. Denial of penetration for the Ethiopian medicinal plants in to the world’s booming herbal market is also another significant loss resulting from absence of herbal quality control system. Thus, in the present study, Gnidia stenophylla Gilg (popular antimalarial plant of south eastern Ethiopia), is standardized and a full monograph is produced that can serve as a guideline in quality control of the crude drug. Morphologically, the roots are found to be cylindrical and tapering towards the end. It has a hard, corky and friable touch with saddle brown color externally and it is relatively smooth and pale brown internally. It has got characteristic pungent odor and very bitter taste. Microscopically it has showed lignified xylem vessels, wider medullary rays with some calcium oxalate crystals, reddish brown secondary metabolite contents and slender shaped long fibres. Physicochemical standards quantified and resulted: foreign matter (5.25%), moisture content (6.69%), total ash (40.80%), acid insoluble ash (8.00%), water soluble ash (2.30%), alcohol soluble extractive (15.27%), water soluble extractive (10.98%), foaming index (100.01 ml/g), swelling index (7.60 ml/g). Phytochemically: Phenols, flavonoids, steroids, tannins and saponins were detected in the root extract; TLC and HPLC fingerprints were produced and an analytical marker was also tentatively characterized as 3-(3,4-dihydro-3,5-dihydroxy-2-(4-hydroxy-5-methylhex-1-en-2-yl)-7-methoxy-4-oxo-2H-chromen-8-yl)-5-hydroxy-2-(4-hydroxyphenyl)-7-methoxy-4H-chromen-4-one. Residue wise pesticides (i.e. DDT, DDE, g-BHC) and radiochemical levels fall below the WHO limit while Heavy metals (i.e. Co, Ni, Cr, Pb, and Cu), total aerobic count and fungal load lie way above the WHO limit. In conclusion, the result can be taken as signal that employing non standardized medicinal plants could cause many health risks of the Ethiopian people and Africans’ at large (as 80% of inhabitants in the continent depends on it for primary health care). Therefore, following a more universal approach to herbal quality by adopting the WHO guidelines and developing monographs using the various quality parameters is inevitable to minimize quality breach and promote effective herbal drug usage.Keywords: Gnidia stenophylla Gilg, standardization/monograph, pharmacognostic, residue/impurity, quality
Procedia PDF Downloads 2891832 Synergistic Effect between Titanium Oxide and Silver Nanoparticles in Polymeric Binary Systems
Authors: Raquel C. A. G. Mota, Livia R. Menezes, Emerson O. da Silva
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Both silver nanoparticles and titanium dioxide have been extensively used in tissue engineering since they’ve been approved by the Food and Drug Administration (FDA), and present a bactericide effect when added to a polymeric matrix. In this work, the focus is on fabricating binary systems with both nanoparticles so that the synergistic effect can be investigated. The systems were tested by Nuclear Magnetic Resonance (NMR), Thermogravimetric Analysis (TGA), Fourier-Transformed Infrared (FTIR), and Differential Scanning Calorimetry (DSC), and X-ray Diffraction (XRD), and had both their bioactivity and bactericide effect tested. The binary systems presented different properties than the individual systems, enhancing both the thermal and biological properties as was to be expected. The crystallinity was also affected, as indicated by the finding of the DSC and XDR techniques, and the NMR showed a good dispersion of both nanoparticles in the polymer matrix. These findings indicate the potential of combining TiO₂ and silver nanoparticles in biomedicine.Keywords: metallic nanoparticles, nanotechnology, polymer nanocomposites, polymer science
Procedia PDF Downloads 1341831 Separation of Fexofenadine Enantiomers Using Beta Cyclodextrin as Chiral Counter Ion in Mobile Phase
Authors: R. Fegas, S. Zerkout, S. Taberkokt, M. Righezza
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The present work demonstrate the potential of Betacyclodextrine (BCD) for the chiral analysis of a drug .Various separation mechanisms were applied and several parameters affecting the separation were studied, including the type and concentration of chiral selector, and pH of buffer. A simple and sensitive high-performance liquid chromatography (HPLC) method was developed as an assay for fexofenadine enantiomers in pharmaceutical preparation. Fexofenadine enantiomers were separated using a mobile phase of 0.25mM NaH2PO4–acetonitrile (65:35, v/v) – Betacyclodextrine on achiral phenyl-urea column at a flow rate of 1ml/min and measurement at 220nm. The chiral mechanism of separation was mainly based on specific interaction between the solute and the stationary phase. The retention was directly controlled by mobile phase composition but not the selectivity which results of the two mechanisms, electrostatic interactions and partition mechanism.Keywords: fexofenadine enantiomer, HPLC, achiral phenyl-urea column
Procedia PDF Downloads 4581830 Logistics Hub Location and Scheduling Model for Urban Last-Mile Deliveries
Authors: Anastasios Charisis, Evangelos Kaisar, Steven Spana, Lili Du
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Logistics play a vital role in the prosperity of today’s cities, but current urban logistics practices are proving problematic, causing negative effects such as traffic congestion and environmental impacts. This paper proposes an alternative urban logistics system, leasing hubs inside cities for designated time intervals, and using handcarts for last-mile deliveries. A mathematical model for selecting the locations of hubs and allocating customers, while also scheduling the optimal times during the day for leasing hubs is developed. The proposed model is compared to current delivery methods requiring door-to-door truck deliveries. It is shown that truck traveled distances decrease by more than 60%. In addition, analysis shows that in certain conditions the approach can be economically competitive and successfully applied to address real problems.Keywords: hub location, last-mile, logistics, optimization
Procedia PDF Downloads 1941829 Technology Blending as an Innovative Construction Mechanism in the Global South
Authors: Janet Kaningen, Richard N. Kaningen, Jonas Kaningen
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This paper aims to discover the best ways to improve production efficiency, cost efficiency, community cohesion, and long-term sustainability in Ghana's housing delivery. Advanced Construction Technologies (ACTs) are set to become the sustainable mainstay of the construction industry due to the demand for innovative housing solutions. Advances in material science, building component production, and assembly technologies are leading to the development of next-generation materials such as polymeric-fiber-based products, light-metal alloys, and eco-materials. Modular housing construction has become more efficient and cost-effective than traditional building methods and is becoming increasingly popular for commercial, industrial, and residential projects. Effective project management and logistics will be imperative in the future speed and cost of modular construction housing.Keywords: technology blending, sustainability, housing, Ghana
Procedia PDF Downloads 871828 Gamma-Hydroxybutyrate (GHB): A Review for the Prehospital Clinician
Authors: Theo Welch
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Background: Gamma-hydroxybutyrate (GHB) is a depressant of the central nervous system with euphoric effects. It is being increasingly used recreationally in the United Kingdom (UK) despite associated morbidity and mortality. Due to the lack of evidence, healthcare professionals remain unsure as to the optimum management of GHB acute toxicity. Methods: A literature review was undertaken of its pharmacology and the emergency management of its acute toxicity.Findings: GHB is inexpensive and readily available over the Internet. Treatment of GHB acute toxicity is supportive. Clinicians should pay particular attention to the airway as emesis is common. Intubation is required in a minority of cases. Polydrug use is common and worsens prognosis. Conclusion: An inexpensive and readily available drug, GHB acute toxicity can be difficult to identify and treat. GHB acute toxicity is generally treated conservatively. Further research is needed to ascertain the indications, benefits, and risks of intubating patients with GHB acute toxicity. instructions give you guidelines for preparing papers for the conference.Keywords: GHB, gamma-hydroxybutyrate, prehospital, emergency, toxicity, management
Procedia PDF Downloads 2011827 Artificial Intelligence in Global Healthcare: Need for Robust Governance Frameworks
Authors: Sandeep Reddy, Sonia Allan, Simon Coghlan, Paul Cooper
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Artificial Intelligence (AI) and its application in medicine has generated ample interest amongst policymakers and clinicians. Successes with AI in medical imaging interpretation and clinical decision support are paving the way for its incorporation into routine healthcare delivery. While there has been a focus on the development of ethical principles to guide its application in healthcare, challenges of this application go beyond what ethics principles can address thus requiring robust governance frameworks. Also, while ethical challenges of medical artificial intelligence are being discussed, the ethics of deploying AI in lower-income countries receive less attention than in other developed economies. This creates an imperative not only for sound ethical guidelines but also for robust governance frameworks to regulate AI in medicine around the world. In this article, we discuss what components need to be considered in developing these governance frameworks and who should lead this worldwide effort.Keywords: artificial intelligence, global health, governance, ethics
Procedia PDF Downloads 1521826 Omni: Data Science Platform for Evaluate Performance of a LoRaWAN Network
Authors: Emanuele A. Solagna, Ricardo S, Tozetto, Roberto dos S. Rabello
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Nowadays, physical processes are becoming digitized by the evolution of communication, sensing and storage technologies which promote the development of smart cities. The evolution of this technology has generated multiple challenges related to the generation of big data and the active participation of electronic devices in society. Thus, devices can send information that is captured and processed over large areas, but there is no guarantee that all the obtained data amount will be effectively stored and correctly persisted. Because, depending on the technology which is used, there are parameters that has huge influence on the full delivery of information. This article aims to characterize the project, currently under development, of a platform that based on data science will perform a performance and effectiveness evaluation of an industrial network that implements LoRaWAN technology considering its main parameters configuration relating these parameters to the information loss.Keywords: Internet of Things, LoRa, LoRaWAN, smart cities
Procedia PDF Downloads 1481825 Mapping Protein Selectivity Landscapes
Authors: Niv Papo
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Characterizing the binding selectivity landscape of interacting proteins is crucial both for elucidating the underlying mechanisms of their interaction and for developing selective inhibitors. However, current mapping methods are laborious and cannot provide a sufficiently comprehensive description of the landscape. Here, we introduce a distinct and efficient strategy for comprehensively mapping the binding landscape of proteins using a combination of experimental multi-target selective library screening and in silico next-generation sequencing analysis. We map the binding landscape of a non-selective trypsin inhibitor, the amyloid protein precursor inhibitor (APPI), to each of four human serine proteases (kallikrein-6, mesotrypsin, and anionic and cationic trypsins). We then use this map to dissect and improve the affinity and selectivity of APPI variants toward each of the four proteases. Our strategy can be used as a platform for the development of a new generation of target-selective probes and therapeutic agents based on selective protein–protein interactions.Keywords: drug design, directed evolution, protein engineering, protease inhibition.
Procedia PDF Downloads 241824 Implant Guided Surgery and Immediate Loading
Authors: Omid Tavakol, Mahnaz Gholami
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Introduction : In this oral presentation the main goal is discussing immediate loading in dental implants , from treatment planning and surgical guide designing to delivery , follow up and occlusal consideration . Methods and materials : first of all systematic reviews about immediate loading will be considered . besides , a comparison will be made between immediate loading and conventional loading in terms of success rate and complications . After that different methods , prosthetic options and materials best used in immediate loading will be explained. Particularly multi unit abutments and their mechanism of function will be explained .Digital impressions and designing the temporaries is the next topic we are to explicate .Next issue is the differences between single unit , multiple unit and full arch implantation in immediate loading .Following we are going to describe methods for tissue engineering and papilla formation after extraction . Last slides are about a full mouth rehabilitation via immediate loading technique from surgical designing to follow up .At the end we would talk about potential complications , how to prevent from occurrence and what to do if we face up with .Keywords: guided surgery, digital implantology, immediate loading, digital dentistry
Procedia PDF Downloads 441823 Hepatoprotective Effect of Mycophenolate Mofetil against Tacrolimus Exposure in Rat
Authors: Ferjani Hanen, El Arem Amira, Boussema Ayed Imen, Bacha Hassen
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Tacrolimus (TAC), a calcineurin inhibitor, is clinically used as an immunosuppressive agent in the transplant recipient, but its use associated-hepatotoxicity. Mycophenolate mofetil (MMF), an anti-metabolite, is a potent immunosuppressive drug. MMF is not hepatotoxic and is the most common adjunctive immunosuppressant for TAC. The effects of TAC and MMF combination in the liver is still not well understood. This work aimed to investigate their combined effect against in liver in rats Wistar after 24 h. The oral median lethal doses (LD50) of TAC and MMF alone were evaluated in rats are 240 mg/kg and 500 mg/kg respectively. Oral administration of the MMF at 50 mg/kg to male Wistar intoxicated with TAC at 60 mg/kg, demonstrated a significant protective effect by lowering the levels of hepatic markers enzymes (AST, ALT) in the serum rat. MMF attenuated oxidative stress by restoring the activities of SOD, CAT and by reducing the malondialdehyde (MDA) and protein carbonyl levels liver. This study provided evidence that MMF protects rat liver from TAC-induced injury and suggests a most combination use for organ transplantation.Keywords: tacrolimus, mycophenolate mofetil, combination, liver, rat
Procedia PDF Downloads 3361822 In vitro and invivo Antioxidant Studies of Grewia crenata Leaves Extract in Albino Rats
Authors: A. N.Ukwuani, A. K. Abdulfatah
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G. crenata is used locally for the treatment of fractured bones, wound healing and inflammatory conditions. In vitro and in vivo antioxidant activity of hydromethanolic extracts of the leaves of G. crenata were assessed. The phytochemical analysis shows the presence of phenols, flavonoids, saponins, cardiac glycosides and tannins. An in vitro quantitative analysis of phenols, flavonoids and tannins respectively were (164±1.20, 199±0.88 and 88.67±0.88 mg/100g FW). In vivo studies of hydromethanolic extract demonstrated a dose dependent increase in hepatic superoxide dismutase (1.14±0.14, 2.13±0.11, 2.55±0.11 U/mg Protein) with improvement in hepatic glutathione (6.98±0.42, 8.91±0.37, 11.07±0.46 µM/mg Protein) and Catalase (4.47±0.05, 6.24±0.02, 7.17±0.04 U/mg Protein) and Total protein (6.18±0.08, 6.69±0.18, 7.27±0.16 mg/ml) respectively at 100-300mg/kg body weight Grewia crenata leaves when compared to the control and standard drug. It can be concluded from the present findings of that G. crenata leaves possess antioxidant potential.Keywords: Grewia crenata, antioxidant, hydromethanolic extract, in vivo, in vitro
Procedia PDF Downloads 5531821 Prominence of Biopsychosocial Formulation in Health Care Delivery for Aging Population: Empowering Caregiving through Natural Socio-Environmental Approaches
Authors: Kristine Demilou D. Santiago
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An access to a high-quality health care system is what sets apart industrialized nations, such as the United States from other developing countries, which in this case is specifically pertaining to their older population. But what was the underrated factor in the sphere of quality healthcare rendered to elderly people in the Western context? Will this salient factor could push conviction to prorogue the existing gaps between self-denial patient-client and cheek by jowl medications? Are the natural socio-environmental approaches of caregiving the protracted remedy to healthcare disparities for aging population considering their day to day living? The conceptual framework of this model is primarily associated with addressing health and illness of human beings considering the biological, psychological and socio-environmental factors around them. The relevance of biopsychosocial formulation advancing each of the characteristics in the Biopsychosocial (BPS) model in a balance contemplation is the tumult of this study in an attempt to respond to prevailing disparities in caregiving services for old-aged patients on a day to day living. Caregiving services have been the medium path connecting between the patient and its prescribed medications. Moreover, caregivers serve as positive reinforcers in a patient’s environment. Therefore, caregivers play an important role in healthcare delivery to patients. They are considered significant people whom their acts will give an impact to a patient’s view in life. This research study intends to present the supreme importance of biopsychosocial assessment to old-aged patients with mental health illness and conditions. Biopsychosocial assessment will secure the quality of full medication to an old-aged adult suffering from a mental illness. This is because it offers a recognizably wholesome approach to medical healing of old-aged adult patients. The principle of biopsychosocial supersedes the biomedicine being offered to old-aged adults having mental illness, but it does not take away the high relevance of scientific biomedicine in healing patients. The framework presented an overlapping participation of each of its factors in its BPS model that affects in general a person’s health. The correlation between the biological (physiological), psychological (mental) and social (environment) in a person’s health condition requires equal attention according to BPS, and it always coexist with each other. Indisputably said, bio-medicine has been and is being in its unceasing endeavor to provide scientifically proven health care medications for every individual seeking medical treatments. As we grow older and eventually reach the other side of the median population, not only our physiological aspects change, our psychological and socio-environmental changes happen too. Caregiving is a salient responsibility taking place on these inevitable changes.Keywords: biopsychosocial formulation, caregiving through natural approaches, US health care, BPS in caregiving, caregiving for aging population
Procedia PDF Downloads 981820 Framework for Government ICT Projects
Authors: Manal Rayes
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In its efforts to utilize the information and communication technology to enhance the quality of public service delivery, national and local governments around the world are competing to introduce more ICT applications as tools to automate processes related to law enforcement or policy execution, increase citizen orientation, trust, and satisfaction, and create one-stop-shops for public services. In its implementation, e-Government ICTs need to maintain transparency, participation, and collaboration. Due to this diverse of mixed goals and requirements, e-Government systems need to be designed based on special design considerations in order to eliminate the risks of failure to compliance to government regulations, citizen dissatisfaction, or market repulsion. In this article we suggest a framework with guidelines for designing government information systems that takes into consideration the special requirements of the public sector. Then we introduce two case studies and show how applying those guidelines would result in a more solid system design.Keywords: e-government, framework, guidelines, system design
Procedia PDF Downloads 3661819 Multifunctional Bending and Straightening Machines for Shipbuilding
Authors: V. Yu. Shungin, A. V. Popov
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At present, one of the main tasks of Russian shipbuilding yards is implementation of new technologies and replacement of main process equipment. In particular, conventional bending technologies with dies are being replaced with resource-saving methods of rotation (roller) banding. Such rolling bending is performed by multiple rolling of a plat in special bending rollers. Studies, conducted in JSC SSTC, allowed developing a theory of rotation bending, methods for calculation of process parameters, requirements to roller presses and bending accessories. This technology allows replacing old and expensive presses with new cheaper roller ones, having less power consumption and bending force. At first, roller presses were implemented in ship repair, however now they are widely employed at major shipbuilding yards. JSC SSTC develops bending technology and carries out design, manufacturing and delivery of roller presses.Keywords: bending/straightening machines, rotational bending, ship hull structures, multifunctional bending
Procedia PDF Downloads 5761818 In silico Analysis of Isoniazid Resistance in Mycobacterium tuberculosis
Authors: A. Nusrath Unissa, Sameer Hassan, Luke Elizabeth Hanna
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Altered drug binding may be an important factor in isoniazid (INH) resistance, rather than major changes in the enzyme’s activity as a catalase or peroxidase (KatG). The identification of structural or functional defects in the mutant KatGs responsible for INH resistance remains as an area to be explored. In this connection, the differences in the binding affinity between wild-type (WT) and mutants of KatG were investigated, through the generation of three mutants of KatG, Ser315Thr [S315T], Ser315Asn [S315N], Ser315Arg [S315R] and a WT [S315]) with the help of software-MODELLER. The mutants were docked with INH using the software-GOLD. The affinity is lower for WT than mutant, suggesting the tight binding of INH with the mutant protein compared to WT type. These models provide the in silico evidence for the binding interaction of KatG with INH and implicate the basis for rationalization of INH resistance in naturally occurring KatG mutant strains of Mycobacterium tuberculosis.Keywords: Mycobacterium tuberculosis, KatG, INH resistance, mutants, modelling, docking
Procedia PDF Downloads 3171817 Constitutive Androstane Receptor (CAR) Inhibitor CINPA1 as a Tool to Understand CAR Structure and Function
Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen
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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance
Procedia PDF Downloads 2871816 Identification and Quantification of Lisinopril from Pure, Formulated and Urine Samples by Micellar Thin Layer Chromatography
Authors: Sudhanshu Sharma
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Lisinopril, 1-[N-{(s)-I-carboxy-3 phenyl propyl}-L-proline dehydrate is a lysine analog of enalaprilat, the active metabolite of enalapril. It is long-acting, non-sulhydryl angiotensin-converting enzyme (ACE) inhibitor that is used for the treatment of hypertension and congestive heart failure in daily dosage 10-80 mg. Pharmacological activity of lisinopril has been proved in various experimental and clinical studies. Owing to its importance and widespread use, efforts have been made towards the development of simple and reliable analytical methods. As per our literature survey, lisinopril in pharmaceutical formulations has been determined by various analytical methodologies like polaragraphy, potentiometry, and spectrophotometry, but most of these analytical methods are not too suitable for the Identification of lisinopril from clinical samples because of the interferences caused by the amino acids and amino groups containing metabolites present in biological samples. This report is an attempt in the direction of developing a simple and reliable method for on plate identification and quantification of lisinopril in pharmaceutical formulations as well as from human urine samples using silica gel H layers developed with a new mobile phase comprising of micellar solutions of N-cetyl-N, N, N-trimethylammonium bromide (CTAB). Micellar solutions have found numerous practical applications in many areas of separation science. Micellar liquid chromatography (MLC) has gained immense popularity and wider applicability due to operational simplicity, cost effectiveness, relatively non-toxicity and enhanced separation efficiency, low aggressiveness. Incorporation of aqueous micellar solutions as mobile phase was pioneered by Armstrong and Terrill as they accentuated the importance of TLC where simultaneous separation of ionic or non-ionic species in a variety of matrices is required. A peculiarity of the micellar mobile phases (MMPs) is that they have no macroscopic analogues, as a result the typical separations can be easily achieved by using MMPs than aqueous organic mobile phases. Previously MMPs were successfully employed in TLC based critical separations of aromatic hydrocarbons, nucleotides, vitamin K1 and K5, o-, m- and p- aminophenol, amino acids, separation of penicillins. The human urine analysis for identification of selected drugs and their metabolites has emerged as an important investigation tool in forensic drug analysis. Among all chromatographic methods available only thin layer chromatography (TLC) enables a simple fast and effective separation of the complex mixtures present in various biological samples and is recommended as an approved testing for forensic drug analysis by federal Law. TLC proved its applicability during successful separation of bio-active amines, carbohydrates, enzymes, porphyrins, and their precursors, alkaloid and drugs from urine samples.Keywords: lisnopril, surfactant, chromatography, micellar solutions
Procedia PDF Downloads 3671815 The Impact of Inconclusive Results of Thin Layer Chromatography for Marijuana Analysis and It’s Implication on Forensic Laboratory Backlog
Authors: Ana Flavia Belchior De Andrade
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Forensic laboratories all over the world face a great challenge to overcame waiting time and backlog in many different areas. Many aspects contribute to this situation, such as an increase in drug complexity, increment in the number of exams requested and cuts in funding limiting laboratories hiring capacity. Altogether, those facts pose an essential challenge for forensic chemistry laboratories to keep both quality and time of response within an acceptable period. In this paper we will analyze how the backlog affects test results and, in the end, the whole judicial system. In this study data from marijuana samples seized by the Federal District Civil Police in Brazil between the years 2013 and 2017 were tabulated and the results analyzed and discussed. In the last five years, the number of petitioned exams increased from 822 in February 2013 to 1358 in March 2018, representing an increase of 32% in 5 years, a rise of more than 6% per year. Meanwhile, our data shows that the number of performed exams did not grow at the same rate. Product numbers are stationed as using the actual technology scenario and analyses routine the laboratory is running in full capacity. Marijuana detection is the most prevalence exam required, representing almost 70% of all exams. In this study, data from 7,110 (seven thousand one hundred and ten) marijuana samples were analyzed. Regarding waiting time, most of the exams were performed not later than 60 days after receipt (77%). Although some samples waited up to 30 months before being examined (0,65%). When marijuana´s exam is delayed we notice the enlargement of inconclusive results using thin-layer chromatography (TLC). Our data shows that if a marijuana sample is stored for more than 18 months, inconclusive results rise from 2% to 7% and when if storage exceeds 30 months, inconclusive rates increase to 13%. This is probably because Cannabis plants and preparations undergo oxidation under storage resulting in a decrease in the content of Δ9-tetrahydrocannabinol ( Δ9-THC). An inconclusive result triggers other procedures that require at least two more working hours of our analysts (e.g., GC/MS analysis) and the report would be delayed at least one day. Those new procedures increase considerably the running cost of a forensic drug laboratory especially when the backlog is significant as inconclusive results tend to increase with waiting time. Financial aspects are not the only ones to be observed regarding backlog cases; there are also social issues as legal procedures can be delayed and prosecution of serious crimes can be unsuccessful. Delays may slow investigations and endanger public safety by giving criminals more time on the street to re-offend. This situation also implies a considerable cost to society as at some point, if the exam takes a long time to be performed, an inconclusive can turn into a negative result and a criminal can be absolved by flawed expert evidence.Keywords: backlog, forensic laboratory, quality management, accreditation
Procedia PDF Downloads 1221814 Photochemical Degradation of Ibuprofren in Aqueous Solutions
Authors: Stavros Poulopoulos, Aphrodite Tetorou, Constantine Philippopoulos
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Day after day more pharmaceutical compounds that are not efficiently removed by conventional treatment methods are found in treated wastewaters and drinking waters. Due to their refractory nature, they escape conventional wastewater treatment facilities, and thus advanced oxidation processes have to be utilized to effectively eliminate them. In the present study, the removal of Ibuprofen from aqueous solutions containing the commercial drug Algofren (non-steroidal, anti-inflammatory) using UV irradiation, hydrogen peroxide, titanium dioxide and ferric ions was examined. All experiments were conducted in a batch photoreactor operated for 120 min. The main target was to select the most effective operating conditions for the mineralization of the solutions treated. The combination of Fe(III)/ H₂O₂/UV proved to be very efficient in terms of total organic carbon removal and ibuprofen conversion. For solutions containing 5 mg/L ibuprofen and initial total carbon 51.1 mg/L, complete mineralization was achieved by means of 2.2 ppm Fe(III) and 333 mg/L H₂O₂.Keywords: pharmaceuticals, photocatalytic, photo-Fenton, TiO₂
Procedia PDF Downloads 1491813 A Study of Lean Principles Implementation in the Libyan Healthcare and Industry Sectors
Authors: Nasser M. Amaitik, Ngwan F. Elsagzli
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The Lean technique is very important in the service and industrial fields. It is defined as an effective tool to eliminate the wastes. In lean the wastes are defined as anything which does not add value to the end product. There are wastes that can be avoided, but some are unavoidable to many reasons. The present study aims to apply the principles of lean in two different sectors, healthcare, and industry. Two case studies have been selected to apply the experimental work. The first case was Al-Jalaa Hospital while the second case study was the Technical Company of Aluminum Sections in Benghazi, Libya. In both case studies the Value Stream Map (VSM) of the current state has been constructed. The proposed plans have been implemented by merging or eliminating procedures or processes. The results obtained from both case studies showed improvement in capacity, idle time and utilized time.Keywords: healthcare service delivery, idle time, lean principles, utilized time, value stream mapping, wastes
Procedia PDF Downloads 2871812 Computing Customer Lifetime Value in E-Commerce Websites with Regard to Returned Orders and Payment Method
Authors: Morteza Giti
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As online shopping is becoming increasingly popular, computing customer lifetime value for better knowing the customers is also gaining more importance. Two distinct factors that can affect the value of a customer in the context of online shopping is the number of returned orders and payment method. Returned orders are those which have been shipped but not collected by the customer and are returned to the store. Payment method refers to the way that customers choose to pay for the price of the order which are usually two: Pre-pay and Cash-on-delivery. In this paper, a novel model called RFMSP is presented to calculated the customer lifetime value, taking these two parameters into account. The RFMSP model is based on the common RFM model while adding two extra parameter. The S represents the order status and the P indicates the payment method. As a case study for this model, the purchase history of customers in an online shop is used to compute the customer lifetime value over a period of twenty months.Keywords: RFMSP model, AHP, customer lifetime value, k-means clustering, e-commerce
Procedia PDF Downloads 3201811 In Silico Modeling of Drugs Milk/Plasma Ratio in Human Breast Milk Using Structures Descriptors
Authors: Navid Kaboudi, Ali Shayanfar
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Introduction: Feeding infants with safe milk from the beginning of their life is an important issue. Drugs which are used by mothers can affect the composition of milk in a way that is not only unsuitable, but also toxic for infants. Consuming permeable drugs during that sensitive period by mother could lead to serious side effects to the infant. Due to the ethical restrictions of drug testing on humans, especially women, during their lactation period, computational approaches based on structural parameters could be useful. The aim of this study is to develop mechanistic models to predict the M/P ratio of drugs during breastfeeding period based on their structural descriptors. Methods: Two hundred and nine different chemicals with their M/P ratio were used in this study. All drugs were categorized into two groups based on their M/P value as Malone classification: 1: Drugs with M/P>1, which are considered as high risk 2: Drugs with M/P>1, which are considered as low risk Thirty eight chemical descriptors were calculated by ACD/labs 6.00 and Data warrior software in order to assess the penetration during breastfeeding period. Later on, four specific models based on the number of hydrogen bond acceptors, polar surface area, total surface area, and number of acidic oxygen were established for the prediction. The mentioned descriptors can predict the penetration with an acceptable accuracy. For the remaining compounds (N= 147, 158, 160, and 174 for models 1 to 4, respectively) of each model binary regression with SPSS 21 was done in order to give us a model to predict the penetration ratio of compounds. Only structural descriptors with p-value<0.1 remained in the final model. Results and discussion: Four different models based on the number of hydrogen bond acceptors, polar surface area, and total surface area were obtained in order to predict the penetration of drugs into human milk during breastfeeding period About 3-4% of milk consists of lipids, and the amount of lipid after parturition increases. Lipid soluble drugs diffuse alongside with fats from plasma to mammary glands. lipophilicity plays a vital role in predicting the penetration class of drugs during lactation period. It was shown in the logistic regression models that compounds with number of hydrogen bond acceptors, PSA and TSA above 5, 90 and 25 respectively, are less permeable to milk because they are less soluble in the amount of fats in milk. The pH of milk is acidic and due to that, basic compounds tend to be concentrated in milk than plasma while acidic compounds may consist lower concentrations in milk than plasma. Conclusion: In this study, we developed four regression-based models to predict the penetration class of drugs during the lactation period. The obtained models can lead to a higher speed in drug development process, saving energy, and costs. Milk/plasma ratio assessment of drugs requires multiple steps of animal testing, which has its own ethical issues. QSAR modeling could help scientist to reduce the amount of animal testing, and our models are also eligible to do that.Keywords: logistic regression, breastfeeding, descriptors, penetration
Procedia PDF Downloads 721810 The Influence of Carbamazepine on the Activity of CYP3A4 in Patients with Alcoholism
Authors: Mikhail S. Zastrozhin, Valery V. Smirnov, Dmitry A. Sychev, Ludmila M. Savchenko, Evgeny A. Bryun, Mark O. Nechaev
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Cytochrome P-450 isoenzyme 3A4 takes part in the biotransformation of medical drugs. The activity of CYP isoenzymes depends on genetic (polymorphisms of genes which encoded it) and phenotypic factors (a kind of food, a concomitant drug therapy). The aim of the study was to evaluate a carbamazepine effect on the CYP3A4 activity in patients with alcohol addiction. The study included 25 men with alcohol dependence, who received haloperidol during the exacerbation of the addiction. CYP3A4 activity was assessed by urinary 6-beta-hydroxycortisol/cortisol ratios measured by high performance liquid chromatography with mass spectrometry. The study modeled a graph and an equation of the logarithmic regression, that reflects the dependence of CYP3A4 activity on a dose of carbamazepine: y = 5,5 * 9,1 * 10-5 * x2. The study statistically significant demonstrates the effect of carbamazepine on CYP2D6 isozyme activity in patients with alcohol addiction.Keywords: CYP3A4, biotransformation, carbamazepine, alcohol abuse
Procedia PDF Downloads 2781809 Evaluating Electronic Service Quality in Banking Iran
Authors: Vahid Bairami Rad
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With the rapid growth of the Internet and the globalization of the market, most enterprises are trying to attract and win customers in the highly competitive electronic market. Better e-service quality will enhance the relationship with customers and their satisfaction. So the measurement of eservice quality is very important but it is a complex process due to the complex nature of services. Literature predicts that there is a lack of universal definition of e-service quality. The e-service quality measures in banking have great importance in achieving high customer base. This paper proposes a conceptual model for measuring e-service quality in Iranian Banking Iran. Nine dimensions reliability, ease of use, personalization, security and trust, website aesthetic, responsiveness, contact and speed of delivery had been identified. The results of this paper may help to develop a proper scale to measure the e-service quality in Iranian Banking Industry, which may assist to maintain and improve the performance and effectiveness of e-service quality to retain customers.Keywords: electronic banking, Dimensions, customer service quality, electronic, communication
Procedia PDF Downloads 499