Search results for: Biomarker Discovery
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 823

Search results for: Biomarker Discovery

283 Female Athlete Triad: How Much Is Known

Authors: Nadine Abuqtaish

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Females’ participation in athletic sports events has increased in the last decades, and the discovery of eating disorders and menstrual dysfunction has been evident since the early 1980s. The term “Female athlete triad” was initially defined by the Task Force on Women’s Issues of the American College of Sports Medicine (ACSM) in 1992. Menstrual irregularities have been prevalent in competitive female athletes, especially in their adolescence and early adulthood age. Nutritional restrictions to maintain a certain physique and lean look are sought to be advantageous in female athletes such as gymnastics, cheerleading, or weight-sensitive sports such as endurance sports (cycling and marathoners). This stress places the female at risk of irregularities in their menstrual cycle which can lead them to lose their circadian estrogen levels. Estrogen is an important female reproductive hormone that plays a role in maintaining bone mass. Bone mineral density peaks by the age 25. Inadequate estrogen due to missed menstrual cycle or amenorrhea has been estimated to cause a yearly loss of 2% of bone mass, increasing the risk of osteoporosis in the postmenopausal phase. This paper is intended to have a better depth understanding of whether female athletes are being monitored by their official entities or coaches. A qualitative research method through online search engines and keywords “females, athletes, triad, amenorrhea, anorexia, osteoporosis” were used to collect the available primary sources from official public library databases. The latest consensus was published in 2014 by the Female Athlete Triad Coalition and the need for further research and emphasis on this issue is still lacking.

Keywords: female, athlete, triad, amenorrhea, anorexia, bone loss

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282 High Performance Concrete Using “BAUT” (Metal Aggregates) the Gateway to New Concrete Technology for Mega Structures

Authors: Arjun, Gautam, Sanjeev Naval

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Concrete technology has been changing rapidly and constantly since its discovery. Concrete is the most widely used man-made construction material, versatility of making concrete is the 2nd largest consumed material on earth. In this paper an effort has been made to use metal aggregates in concrete has been discussed, the metal aggregates has been named as “BAUT” which had outstandingly qualities to resist shear, tension and compression forces. In this paper, COARSE BAUT AGGREGATES (C.B.A.) 10mm & 20mm and FINE BAUT AGGREGATES (F.B.A.) 3mm were divided and used for making high performance concrete (H.P.C). This “BAUT” had cutting edge technology through draft and design by the use of Auto CAD, ANSYS software can be used effectively In this research paper we study high performance concrete (H.P.C) with “BAUT” and consider the grade of M65 and finally we achieved the result of 90-95 Mpa (high compressive strength) for mega structures and irregular structures where center of gravity (CG) is not balanced. High Performance BAUT Concrete is the extraordinary qualities like long-term performance, no sorptivity by BAUT AGGREGATES, better rheological, mechanical and durability proportion that conventional concrete. This high strength BAUT concrete using “BAUT” is applied in the construction of mega structure like skyscrapers, dam, marine/offshore structures, nuclear power plants, bridges, blats and impact resistance structures. High Performance BAUT Concrete which is a controlled concrete possesses invariable high strength, reasonable workability and negligibly permeability as compare to conventional concrete by the mix of Super Plasticizers (SMF), silica fume and fly ash.

Keywords: BAUT, High Strength Concrete, High Performance Concrete, Fine BAUT Aggregate, Coarse BAUT Aggregate, metal aggregates, cutting edge technology

Procedia PDF Downloads 478
281 Lost Maritime Culture in the Netherlands: Linking Material and Immaterial Datasets for a Modern Day Perception of the Late Medieval Maritime Cultural Landscape of the Zuiderzee Region

Authors: Y. T. van Popta

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This paper focuses on the never thoroughly examined yet in native relevant late medieval maritime cultural landscape of the former Zuiderzee (A.D. 1170-1932) in the center part of the Netherlands. Especially the northeastern part of the region, nowadays known as the Noordoostpolder, testifies of the dynamic battle of the Dutch against the water. This highly dynamic maritime region developed from a lake district into a sea and eventually into a polder. By linking physical and cognitive datasets from the Noordoostpol-der region in a spatial environment, new information on a late medieval maritime culture is brought to light, giving the opportunity to: (i) create a modern day perception on the late medieval maritime cultural landscape of the region and (ii) to underline the value of interdisciplinary and spatial research in maritime archaeology in general. Since the large scale reclamations of the region (A.D. 1932-1968), many remains have been discovered of a drowned and eroded late medieval maritime culture, represented by lost islands, drowned settlements, cultivated lands, shipwrecks and socio-economic networks. Recent archaeological research has proved the existence of this late medieval maritime culture by the discovery of the remains of the drowned settlement Fenehuysen (Veenhuizen) and its surroundings. The fact that this settlement and its cultivated surroundings remained hidden for so long proves that a large part of the maritime cultural landscape is ‘invisible’ and can only be found by extensive interdisciplinary research.

Keywords: drowned settlements, late middle ages, lost islands, maritime cultural landscape, the Netherlands

Procedia PDF Downloads 177
280 Tumor Cell Detection, Isolation and Monitoring Using Bi-Layer Magnetic Microfluidic Chip

Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari

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The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.

Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation

Procedia PDF Downloads 117
279 Rediscovery of Important Elements Contributing to Cultural Interchange Values Made during Restoration of Khanpur Gate

Authors: Poonam A. Trambadia, Ashish V. Trambadia

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The architecture of sultanate period of Ahmedabad had evolved just before the establishment of Mughal rule in North India. After shifting the capital of the kingdom from Patan to Ahmedabad, when the buildings and structures were being built, an interesting cultural blend happened in architecture. Many sultanate buildings in Ahmedabad historic city have resemblance with Patan including the names. Outer fortification walls and Gates were built during the rule of the third ruler in the late 15th century. All the gates had sandstone slabs supported by three arched entrance in sandstone with wooden shutter. A restoration project of Khanpur Gate was initiated in 2016. The paper identifies some evidences and some hidden layers of structures as important elements of cultural interchange while some were just forgotten in the process. The recycling of pre-existing elements of structures are examined and compared. There were layers uncovered that were hidden behind later repairs using traditional brick arch, which was taken out in the process. As the gate had partially collapsed, the restoration included piece by piece dismantling and restoring in the same sequence wherever required. The recycled materials found in the process were recorded and provided the basis for this study. The gate after this discovery sets a new example of fortification Gate built in Sultanate era. The comparison excludes Maratha and British Period Gates to avoid further confusion and focuses on 15th – 16th century sultanate architecture of Ahmedabad.

Keywords: Ahmedabad World Heritage, fortification, Indo-Islamic style, Sultanate architecture, cultural interchange

Procedia PDF Downloads 96
278 Knowledge, Attitudes, and Practices regarding Anthrax among Community Members, Health and Veterinary Workers in Maragua, Kenya

Authors: Isaiah Chacha, Samuel Arimi, Andrew Thaiya

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Background: This study was conducted to assess knowledge, attitudes and practices regarding anthrax in Maragua, Kenya to provide baseline information to design interventions. Methods: A cross sectional survey was conducted among head of households, health and veterinary workers in Maragua Sub-county in August and September 2014. Administered questionnaires were used to collect data from household members and a key informant interview held with health and veterinary workers. Multi stage sampling was used to obtain participants’ knowledge, attitudes and practices. Questions were scored and descriptively analyzed using Excel spreadsheet then exported to GenStat Discovery Edition 4. Results: A total of 293 community members were recruited in this study. The overall level of knowledge was 77.9% of all community members regarding cause, transmission, symptoms and prevention of the disease in both humans and animals. Majority of the participants (96.3%) had heard about anthrax. A total of 99 (33.8%) correspondents had seen a person with anthrax and 75.1% think that anthrax is a very serious disease in the area. Of the interviewed correspondents, 14.3% of them have had their animals (mostly cattle) suffer from anthrax while 15.7% had either suffered from anthrax or have had their family member who suffered from anthrax. Conclusion: The study findings indicate above average knowledge on cause, symptoms, transmission and prevention of anthrax among community members in humans and animals. Practices in this study were still risk among community members. Veterinary and Medical health planners should design anthrax awareness interventions as a team targeting to reach these communities and the public through barazas, radio, CHW and other communication channel on a regular basis.

Keywords: anthrax, attitudes, Kenya, knowledge, Maragua, practices

Procedia PDF Downloads 285
277 Integrating Explicit Instruction and Problem-Solving Approaches for Efficient Learning

Authors: Slava Kalyuga

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There are two opposing major points of view on the optimal degree of initial instructional guidance that is usually discussed in the literature by the advocates of the corresponding learning approaches. Using unguided or minimally guided problem-solving tasks prior to explicit instruction has been suggested by productive failure and several other instructional theories, whereas an alternative approach - using fully guided worked examples followed by problem solving - has been demonstrated as the most effective strategy within the framework of cognitive load theory. An integrated approach discussed in this paper could combine the above frameworks within a broader theoretical perspective which would allow bringing together their best features and advantages in the design of learning tasks for STEM education. This paper represents a systematic review of the available empirical studies comparing the above alternative sequences of instructional methods to explore effects of several possible moderating factors. The paper concludes that different approaches and instructional sequences should coexist within complex learning environments. Selecting optimal sequences depends on such factors as specific goals of learner activities, types of knowledge to learn, levels of element interactivity (task complexity), and levels of learner prior knowledge. This paper offers an outline of a theoretical framework for the design of complex learning tasks in STEM education that would integrate explicit instruction and inquiry (exploratory, discovery) learning approaches in ways that depend on a set of defined specific factors.

Keywords: cognitive load, explicit instruction, exploratory learning, worked examples

Procedia PDF Downloads 100
276 Hybrid-Nanoengineering™: A New Platform for Nanomedicine

Authors: Mewa Singh

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Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

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275 Histological Changes of Mice Lungs After Daily Exposure to Different Concentration of Incense Smoke

Authors: Samar Omar A. Rabah, Sahar Ragab El Hadad, Fatmah Albani

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Since the discovery of Agarwood (Incense tree), many studies reported its characteristic effects and variable benefits, as either to produce Arabian Incense or as a traditional medicine against many diseases. Laboratory experiments were carried out on the effect of different concentrations of Incense smoke inhalation on the lung weight and tissue in female mice. This research derives its importance from the fact that Incense is heavily used in Saudi Arabia in the absence of thorough studies of its effects on health. Eighty animals are used in this study, and they are divided into four groups, each is 20 animals. Three groups are exposed to different concentrations (2, 4 and 6 gm) of Incense smoke daily for three months, and the fourth group is the control. At the end of each month, five animals from each group were dissected. Obtained data showed an increase but not significant in animal body and lung weight, this results return to natural increase as a result of normal growth of animals. Light microscope reveals some changes in the lung tissue, such as focal emphysema, rupture in the alveolar walls, hemorrhage, congestion, edema and few peri-bronchial lymphoid cells. After continuous exposure to Incense smoke focal necrosis and degradation are observed in some cells of epithelial bronchioles. Also, fibrosis of peri-bronchial, thickening in alveolar walls and aggregation of lymphoid cells are demonstrated in some lungs sections. according to the above manifestations it could be concluded that exposure to Incense smoke causes pulmonary harmful effects. Therefore, we can recommend that Incense smoke will be used only in open places to reduce its harms.

Keywords: incense smoke, lungs, histological changes of lungs, agarwood

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274 [Keynote Talk]: Applying p-Balanced Energy Technique to Solve Liouville-Type Problems in Calculus

Authors: Lina Wu, Ye Li, Jia Liu

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We are interested in solving Liouville-type problems to explore constancy properties for maps or differential forms on Riemannian manifolds. Geometric structures on manifolds, the existence of constancy properties for maps or differential forms, and energy growth for maps or differential forms are intertwined. In this article, we concentrate on discovery of solutions to Liouville-type problems where manifolds are Euclidean spaces (i.e. flat Riemannian manifolds) and maps become real-valued functions. Liouville-type results of vanishing properties for functions are obtained. The original work in our research findings is to extend the q-energy for a function from finite in Lq space to infinite in non-Lq space by applying p-balanced technique where q = p = 2. Calculation skills such as Hölder's Inequality and Tests for Series have been used to evaluate limits and integrations for function energy. Calculation ideas and computational techniques for solving Liouville-type problems shown in this article, which are utilized in Euclidean spaces, can be universalized as a successful algorithm, which works for both maps and differential forms on Riemannian manifolds. This innovative algorithm has a far-reaching impact on research work of solving Liouville-type problems in the general settings involved with infinite energy. The p-balanced technique in this algorithm provides a clue to success on the road of q-energy extension from finite to infinite.

Keywords: differential forms, holder inequality, Liouville-type problems, p-balanced growth, p-harmonic maps, q-energy growth, tests for series

Procedia PDF Downloads 211
273 Conversion from Catholicism to Islam in and out of Prison: A Comparative Study

Authors: Nerissa Gloria Balboa, Aire Yukdawan, Venice Gordula, Rhea Jannagen Curva

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This research examined the lived experiences and compared their similarities and differences of former Catholics turned Muslim converts in and out of prison. Qualitative comparative study with an Interpretative Phenomenological Analysis approach was used to explore the lives of Muslim converts. Interviews were conducted at Islamic Studies, Call and Guidance of the Philippines (ISCAG) and Tarbiyyah Islamic Female Institute for Muslim converts out of prison, New Bilibid Prison (NBP) and Correctional Institution for Women (CIW) for Muslim converts in prison. Results of the study show that first, for Muslim converts out of prison, exploration begins through (1) experiences of Catholicism as a norm in the family and eventual realization of its emptiness in practice, (2) experiences of Islam as a norm in the environment and discovery of meaningfulness of Islam (3) experiences of gradual holistic transformation of being a Muslim; and (4) experiences of extension of oneself towards family and society. Secondly, for Muslim converts in prison, exploration begins through (1) experiences of Apathy towards Catholicism and eventual deviation from moral standards, (2) experiences of prison condition as an environment of reflection on spirituality; and (3) experiences of positive effects of being a Muslim inside Prison. Comparisons show that there exists similarities and differences across the two settings in terms of (1) experiences of Catholicism and the degree of its internalization and actualization, (2) experiences of Islamic encounters and the process of conversion; and (3) experience of Islamic devotion and Islamic construct for the self. Theoretical bases of religious conversion found in unique contexts are discussed, initiating a paradigm shift of thinking that is needed to address the deeply rooted prejudices within Catholic and Islamic circles.

Keywords: Catholicism, Islamic conversion, social psychology, religion

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272 An Open Trial of Mobile-Assisted Cognitive Behavioral Therapy for Negative Symptoms in Schizophrenia: Pupillometry Predictors of Outcome

Authors: Eric Granholm, Christophe Delay, Jason Holden, Peter Link

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Negative symptoms are an important unmet treatment needed for schizophrenia. We conducted an open trial of a novel blended intervention called mobile-assisted cognitive behavior therapy for negative symptoms (mCBTn). mCBTn is a weekly group therapy intervention combining in-person and smartphone-based CBT (CBT2go app) to improve experiential negative symptoms in people with schizophrenia. Both the therapy group and CBT2go app included recovery goal setting, thought challenging, scheduling of pleasurable activities and social interactions, and pleasure savoring interventions to modify defeatist attitudes, a target mechanism associated with negative symptoms, and improve experiential negative symptoms. We tested whether participants with schizophrenia or schizoaffective disorder (N=31) who met prospective criteria for persistent negative symptoms showed improvement in experiential negative symptoms. Retention was excellent (87% at 18 weeks) and severity of defeatist attitudes and motivation and pleasure negative symptoms declined significantly in mCBTn with large effect sizes. We also tested whether pupillary responses, a measure of cognitive effort, predicted improvement in negative symptoms mCBTn. Pupillary responses were recorded at baseline using a Tobii pupillometer during the digit span task with 3-, 6- and 9-digit spans. Mixed models showed that greater dilation during the task at baseline significantly predicted a greater reduction in experiential negative symptoms. Pupillary responses may provide a much-needed prognostic biomarker of which patients are most likely to benefit from CBT. Greater pupil dilation during a cognitive task predicted greater improvement in experiential negative symptoms. Pupil dilation has been linked to motivation and engagement of executive control, so these factors may contribute to benefits in interventions that train cognitive skills to manage negative thoughts and emotions. The findings suggest mCBTn is a feasible and effective treatment for experiential negative symptoms and justify a larger randomized controlled clinical trial. The findings also provide support for the defeatist attitude model of experiential negative symptoms and suggest that mobile-assisted interventions like mCBTn can strengthen and shorten intensive psychosocial interventions for schizophrenia.

Keywords: cognitive-behavioral therapy, mobile interventions, negative symptoms, pupillometry schizophrenia

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271 Network Pharmacological Evaluation of Holy Basil Bioactive Phytochemicals for Identifying Novel Potential Inhibitors Against Neurodegenerative Disorder

Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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270 Geochemical Study of Natural Bitumen, Condensate and Gas Seeps from Sousse Area, Central Tunisia

Authors: Belhaj Mohamed, M. Saidi, N. Boucherab, N. Ouertani, I. Bouazizi, M. Ben Jrad

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Natural hydrocarbon seepage has helped petroleum exploration as a direct indicator of gas and/or oil subsurface accumulations. Surface macro-seeps are generally an indication of a fault in an active Petroleum Seepage System belonging to a Total Petroleum System. This paper describes a case study in which multiple analytical techniques were used to identify and characterize trace petroleum-related hydrocarbons and other volatile organic compounds in groundwater samples collected from Sousse aquifer (Central Tunisia). The analytical techniques used for analyses of water samples included gas chromatography-mass spectrometry (GC-MS), capillary GC with flame-ionization detection, Compund Specific Isotope Analysis, Rock Eval Pyrolysis. The objective of the study was to confirm the presence of gasoline and other petroleum products or other volatile organic pollutants in those samples in order to assess the respective implication of each of the potentially responsible parties to the contamination of the aquifer. In addition, the degree of contamination at different depths in the aquifer was also of interest. The oil and gas seeps have been investigated using biomarker and stable carbon isotope analyses to perform oil-oil and oil-source rock correlations. The seepage gases are characterized by high CH4 content, very low δ13CCH4 values (-71,9 ‰) and high C1/C1–5 ratios (0.95–1.0), light deuterium–hydrogen isotope ratios (-198 ‰) and light δ13CC2 and δ13CCO2 values (-23,8‰ and-23,8‰ respectively) indicating a thermogenic origin with the contribution of the biogenic gas. An organic geochemistry study was carried out on the more ten oil seep samples. This study includes light hydrocarbon and biomarkers analyses (hopanes, steranes, n-alkanes, acyclic isoprenoids, and aromatic steroids) using GC and GC-MS. The studied samples show at least two distinct families, suggesting two different types of crude oil origins: the first oil seeps appears to be highly mature, showing evidence of chemical and/or biological degradation and was derived from a clay-rich source rock deposited in suboxic conditions. It has been sourced mainly by the lower Fahdene (Albian) source rocks. The second oil seeps was derived from a carbonate-rich source rock deposited in anoxic conditions, well correlated with the Bahloul (Cenomanian-Turonian) source rock.

Keywords: biomarkers, oil and gas seeps, organic geochemistry, source rock

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269 Screening and Isolation of Lead Molecules from South Indian Plant Extracts against NDM-1 Producing Escherichia coli

Authors: B. Chandar, M. K. Ramasamy, P. Madasamy

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The discovery and development of newer antibiotics are limited with the increase in resistance of such multi-drug resistant bacteria creating the need for alternative new therapeutic agents. The recently discovered New Delhi Metallo-betalactamase-1 (NDM-1), which confers antibiotic resistance to most of the currently available β-lactams, except colistin and tigecycline, is a global concern. Several antibacterial drugs approved are natural products or their semisynthetic derivatives, but plant extracts remain to be explored to find molecules that are effective against NDM-1 bacteria. Therefore, it is necessary to explore the possibility of finding new and effective antibacterial compounds against NDM-1 bacteria. In the present study, we have screened a diverse set South Indian plant species, and report most plant species as a potential source for antimicrobial compounds against NDM-1 bacteria. Ethanol extracts from the leaves of taxonomically diverse South Indian medicinal plants were screened for antibacterial activity against NDM-1 E. coli using streak plate method. Among the plant screened against NDM-1 E. coli, the ethanol extracts from many plant extracts showed minimum bactericidal concentration between 5 and 15 mg /ml and MIC between 2.54 and 5.12 mg/ml. These extracts also showed a potent synergistic effect when combined with antibiotics colistin and tetracycline. Combretum albidum that was effective was taken for further analysis. At 5mg/L concentration, these extracts inhibited the NDM-1 enzyme in vitro, and residual activity for Combretum albidum was 33.09%. Treatment of NDM-1 E. coli with the extracts disrupted the cell wall integrity and caused 89.7% cell death. The plant extract of Combretum albidum that was effective was subjected to fractionation and the fraction was further subjected to HPLC, LC-MS for identification of antibacterial compound.

Keywords: antibacterial activity, combretum albidum, Escherichia coli, NDM-1

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268 Configuring Systems to Be Viable in a Crisis: The Role of Intuitive Decision-Making

Authors: Ayham Fattoum, Simos Chari, Duncan Shaw

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Volatile, uncertain, complex, and ambiguous (VUCA) conditions threaten systems viability with emerging and novel events requiring immediate and localized responses. Such responsiveness is only possible through devolved freedom and emancipated decision-making. The Viable System Model (VSM) recognizes the need and suggests maximizing autonomy to localize decision-making and minimize residual complexity. However, exercising delegated autonomy in VUCA requires confidence and knowledge to use intuition and guidance to maintain systemic coherence. This paper explores the role of intuition as an enabler of emancipated decision-making and autonomy under VUCA. Intuition allows decision-makers to use their knowledge and experience to respond rapidly to novel events. This paper offers three contributions to VSM. First, it designs a system model that illustrates the role of intuitive decision-making in managing complexity and maintaining viability. Second, it takes a black-box approach to theory development in VSM to model the role of autonomy and intuition. Third, the study uses a multi-stage discovery-oriented approach (DOA) to develop theory, with each stage combining literature, data analysis, and model/theory development and identifying further questions for the subsequent stage. We synthesize literature (e.g., VSM, complexity management) with seven months of field-based insights (interviews, workshops, and observation of a live disaster exercise) to develop a framework of intuitive complexity management framework and VSM models. The results have practical implications for enhancing the resilience of organizations and communities.

Keywords: Intuition, complexity management, decision-making, viable system model

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267 Genome Editing in Sorghum: Advancements and Future Possibilities: A Review

Authors: Micheale Yifter Weldemichael, Hailay Mehari Gebremedhn, Teklehaimanot Hailesslasie

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The advancement of target-specific genome editing tools, including clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein9 (Cas9), mega-nucleases, base editing (BE), prime editing (PE), transcription activator-like endonucleases (TALENs), and zinc-finger nucleases (ZFNs), have paved the way for a modern era of gene editing. CRISPR/Cas9, as a versatile, simple, cost-effective and robust system for genome editing, has dominated the genome manipulation field over the last few years. The application of CRISPR/Cas9 in sorghum improvement is particularly vital in the context of ecological, environmental and agricultural challenges, as well as global climate change. In this context, gene editing using CRISPR/Cas9 can improve nutritional value, yield, resistance to pests and disease and tolerance to different abiotic stress. Moreover, CRISPR/Cas9 can potentially perform complex editing to reshape already available elite varieties and new genetic variations. However, existing research is targeted at improving even further the effectiveness of the CRISPR/Cas9 genome editing techniques to fruitfully edit endogenous sorghum genes. These findings suggest that genome editing is a feasible and successful venture in sorghum. Newer improvements and developments of CRISPR/Cas9 techniques have further qualified researchers to modify extra genes in sorghum with improved efficiency. The fruitful application and development of CRISPR techniques for genome editing in sorghum will not only help in gene discovery, creating new, improved traits in sorghum regulating gene expression sorghum functional genomics, but also in making site-specific integration events.

Keywords: CRISPR/Cas9, genome editing, quality, sorghum, stress, yield

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266 Culture, Consumption, and Markets of Aesthetics: A10-Year Literature Review

Authors: Chin-Hsiang Chu

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This article review the literature in the field among the marketing and aesthetics, the current market and customer-oriented product sales, and gradually from the practical functionality, transformed into the visual appearance of the concept note and the importance of marketing experience substance 'economic Aesthetics' trend. How to introduce the concept of aesthetic and differentiate products have become an important content of marketing management in for an organization in marketing.In previous studies,marketing aesthetic related researches are rare.Therefore, the purpose of this study to explore the connection between aesthetics and marketing of the market economy, and aggregated content through literature review, trying to find related research implications for the management of marketing aesthetics, market-oriented and customer value and development of the product. In this study, the problem statement and background, the development of the theory of evolution, as well as methods and results of discovery stage, literature review was conducted to explore. The results found: (1) Study of Aesthetics will help deepen the shopping environment and service environment commonly understood. (2) the perceived value of products imported aesthetic, consumer willingness to buy, and even premium products will be more attractive. (3) marketing personnel for general marketing management with a high degree of aesthetic identity. (4) management in marketing aesthetics connotation, aesthetic characteristics of five elements is greatly valued by the real-time, complex, specificity, attract sexual and richness. (5) allows consumers to experience through the process due to stimulate the senses, the mind and thinking with the corporate brand or have a deeper link. Results of this study can be used as business in a competitive market, new product development and design of the guide.

Keywords: marketing aesthetics, aesthetics economic, aesthetic, experiential marketing

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265 A Preparatory Method for Building Construction Implemented in a Case Study in Brazil

Authors: Aline Valverde Arroteia, Tatiana Gondim do Amaral, Silvio Burrattino Melhado

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During the last twenty years, the construction field in Brazil has evolved significantly in response to its market growing and competitiveness. However, this evolving path has faced many obstacles such as cultural barriers and the lack of efforts to achieve quality at the construction site. At the same time, the greatest amount of information generated on the designing or construction phases is lost due to the lack of an effective coordination of these activities. Face this problem, the aim of this research was to implement a French method named PEO which means preparation for building construction (in Portuguese) seeking to understand the design management process and its interface with the building construction phase. The research method applied was qualitative, and it was carried out through two case studies in the city of Goiania, in Goias, Brazil. The research was divided into two stages called pilot study at Company A and implementation of PEO at Company B. After the implementation; the results demonstrated the PEO method's effectiveness and feasibility while a booster on the quality improvement of design management. The analysis showed that the method has a purpose to improve the design and allow the reduction of failures, errors and rework commonly found in the production of buildings. Therefore, it can be concluded that the PEO is feasible to be applied to real estate and building companies. But, companies need to believe in the contribution they can make to the discovery of design failures in conjunction with other stakeholders forming a construction team. The result of PEO can be maximized when adopting the principles of simultaneous engineering and insertion of new computer technologies, which use a three-dimensional model of the building with BIM process.

Keywords: communication, design and construction interface management, preparation for building construction (PEO), proactive coordination (CPA)

Procedia PDF Downloads 135
264 Screening of Potential Cytotoxic Activities of Some Medicinal Plants of Saudi Arabia

Authors: Syed Farooq Adil, Merajuddinkhan, Mujeeb Khan, Hamad Z. Alkhathlan

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Phytochemicals from plant extracts belong to an important source of natural products which have demonstrated excellent cytotoxic activities. However, plants of different origins exhibit diverse chemical compositions and bioactivities. Therefore, the discovery of plants based new anticancer agents from different parts of the world is always challenging. In this study, methanolic extracts of different parts of 11 plants from Saudi Arabia have been tested in vitro for their anticancer potential on human liver cancer cell line (HepG2). Particularly, for this study, plants from Asteraceae, Resedaceae, and Polygonaceae families were chosen on the basis of locally available ethnobotanical data and their medicinal properties. Among 12 tested extract samples, three samples obtained from Artemisia monosperma stem, Ochradenus baccatus aerial parts, and Pulicaria glutinosa stem have demonstrated interesting cytotoxic activities with a cell viability of 29.3%, 28.4% and 24.2%, respectively. Whereas, four plant extracts including Calendula arvensis aerial parts, Scorzonera musilii whole plant, A. monosperma leaves show moderate anticancer properties bearing a cell viability ranging from 11.9 to 16.7%. The remaining extracts have shown poor cytotoxic activities. Subsequently, GC-MS analysis of methanolic extracts of the four most active plants extracts such as C. comosum, O. baccatus, P. glutinosa and A. monosperma detected the presence of 41 phytomolecules. Among which 3-(4-hydroxyphenyl) propionitrile (1), 8,11-octadecadiynoic acid methyl ester (2), 6,7-dimethoxycoumarin (3), and 1-(2-hydroxyphenyl) ethenone (4) were found to be the lead compounds of C. comosum, O. baccatus P. glutinosa and A. monosperma, respectively.

Keywords: medicinal plants, asteraceae, polygonaceae, hepg2

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263 Enhancing Vehicle Efficiency Through Vapor Absorption Refrigeration Systems

Authors: Yoftahe Nigussie Worku

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This paper explores the utilization of vapor absorption refrigeration systems (VARS) as an alternative to the conventional vapor compression refrigerant systems (VCRS) in vehicle air conditioning (AC) systems. Currently, most vehicles employ VCRS, which relies on engine power to drive the compressor, leading to additional fuel consumption. In contrast, VARS harnesses low-grade heat, specifically from the exhaust of high-power internal combustion engines, reducing the burden on the vehicle's engine. The historical development of vapor absorption technology is outlined, dating back to Michael Faraday's discovery in 1824 and the subsequent creation of the first vapor absorption refrigeration machine by Ferdinand Carre in 1860. The paper delves into the fundamental principles of VARS, emphasizing the replacement of mechanical processes with physicochemical interactions, utilizing heat rather than mechanical work. The study compares the basic concepts of the current vapor compression systems with the proposed vapor absorption systems, highlighting the efficiency gains achieved by eliminating the need for engine-driven compressors. The vapor absorption refrigeration cycle (VARC) is detailed, focusing on the generator's role in separating and vaporizing ammonia, chosen for its low-temperature evaporation characteristics. The project's statement underscores the need for increased efficiency in vehicle AC systems beyond the limitations of VCRS. By introducing VARS, driven by low-grade heat, the paper advocates for a reduction in engine power consumption and, consequently, a decrease in fuel usage. This research contributes to the ongoing efforts to enhance sustainability and efficiency in automotive climate control systems.

Keywords: VCRS, VARS, efficiency, sustainability

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262 TiO₂ Nanoparticles Induce DNA Damage and Expression of Biomarker of Oxidative Stress on Human Spermatozoa

Authors: Elena Maria Scalisi

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The increasing production and the use of TiO₂ nanoparticles (NPs) have inevitably led to their release into the environment, thereby posing a threat to organisms and also for human. Human exposure to TiO₂-NPs may occur during both manufacturing and use. TiO₂-NPs are common in consumer products for dermal application, toothpaste, food colorants, and nutritional supplements, then oral exposure may occur during use of such products. Into the body, TiO₂-NPs thanks to their small size (<100 nm), can, through testicular blood barrier inducing effect on testis and then on male reproductive health. The nanoscale size of TiO₂ increase the surface-to-volume ratio making them more reactive in a cell, then TiO₂ NPs increase their ability to produce reactive oxygen species (ROS). In male germ cells, ROS may have important implications in maintaining the normal functions of mature spermatozoa at physiological levels, moreover, in spermatozoa they are important signaling molecules for their hyperactivation and acrosome reaction. Nevertheless, an excess of ROS by external inputs such as NPs can increased the oxidative stress (OS), which results in damage DNA and apoptosis. The aim of our study has been investigate the impact of TiO₂ NPs on human spermatozoa, evaluating DNA damage and the expression of proteins involved in cell stress. According WHO guidelines 2021, we have exposed human spermatozoa in vitro to TiO₂ NP at concentrations 50 ppm, 100 ppm, 250 ppm, and 500 ppm for 1 hour (at 37°C and CO₂ at 5%). DNA damage was evaluated by Sperm Chromatin Dispersion Test (SCD) and TUNEL assay; moreover, we have evaluated the expression of biomarkers of oxidative stress like Heat Shock Protein 70 (HSP70) and Metallothioneins (MTs). Also, sperm parameters as motility viability have been evaluated. Our results not report a significant reduction in motility of spermatozoa at the end of the exposure. On the contrary, the progressive motility was increased at the highest concentration (500 ppm) and was statistically significant compared to control (p <0.05). Also, viability was not changed by exposure to TiO₂-NPs (p <0.05). However, increased DNA damage was observed at all concentrations, and the TUNEL assay highlighted the presence of single strand breaks in the DNA. The spermatozoa responded to the presence of TiO₂-NPs with the expression of Hsp70, which have a protective function because they allow the maintenance of cellular homeostasis in stressful/ lethal conditions. A positivity for MTs was observed mainly for the concentration of 4 mg/L. Although the biological and physiological function of the metallothionein (MTs) in the male genital organs is unclear, our results highlighted that the MTs expressed by spermatozoa maintain their biological role of detoxification from metals. Our results can give additional information to the data in the literature on the toxicity of TiO₂-NPs and reproduction.

Keywords: human spermatozoa, DNA damage, TiO₂-NPs, biomarkers

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261 Calpain-Mediated, Cisplain-Induced Apoptosis in Breast Cancer Cells

Authors: Shadia Al-Bahlani, Khadija Al-Bulushi, Zuweina Al-Hadidi, Buthaina Al-Dhahl, Nadia Al-Abri

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Breast cancer is the most common cancer in women worldwide. Triple-Negative Breast Cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. However, the role of calpain in cisplatin (CDDP)-induced apoptosis in TNBC cells is not fully understood. Here, TNBC (MDA-MB231) cells were treated with different concentration of CDDP (0, 20 & 40 µM) and calpain activation and apoptosis were measured by western blot and Hoechst Stain respectively. In addition, calpain modulation by either activation and/or inhibition and its effect on CDDP-induced apoptosis were assessed by the same above approaches. Our findings showed that CDDP induced endoplasmic reticulum stress and thus Calcium release and subsequently activate calpain α-fodrin cleavage indicated by the increase in GRP78 and Calmodulin protein expression and respectively in MDA-MB231 cells. It also induced apoptosis as measured by Hoechst stain and caspase-12 cleavage. Calpain activation by both Cyclopiazonic acid and Thapsigargin showed similar effect and enhanced the sensitivity of these cells to CDDP treatment. On the other hand, calpain inhibition by either specific siRNA and/or exogenous inhibitor (Calpeptin) had an adverse effect where it attenuated calpain activation and thus CDDP- induced apoptosis in these cells. Altogether, these findings suggested that calpain activation play an essential role in sensitizing the TNBC cells to CDDP-induced apoptosis. This might lead to the discovery of novel treatment to over this aggressive type of breast cancer.

Keywords: calpain, cisplatin, apoptosis, breast cancer

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260 Current Methods for Drug Property Prediction in the Real World

Authors: Jacob Green, Cecilia Cabrera, Maximilian Jakobs, Andrea Dimitracopoulos, Mark van der Wilk, Ryan Greenhalgh

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Predicting drug properties is key in drug discovery to enable de-risking of assets before expensive clinical trials and to find highly active compounds faster. Interest from the machine learning community has led to the release of a variety of benchmark datasets and proposed methods. However, it remains unclear for practitioners which method or approach is most suitable, as different papers benchmark on different datasets and methods, leading to varying conclusions that are not easily compared. Our large-scale empirical study links together numerous earlier works on different datasets and methods, thus offering a comprehensive overview of the existing property classes, datasets, and their interactions with different methods. We emphasise the importance of uncertainty quantification and the time and, therefore, cost of applying these methods in the drug development decision-making cycle. To the best of the author's knowledge, it has been observed that the optimal approach varies depending on the dataset and that engineered features with classical machine learning methods often outperform deep learning. Specifically, QSAR datasets are typically best analysed with classical methods such as Gaussian Processes, while ADMET datasets are sometimes better described by Trees or deep learning methods such as Graph Neural Networks or language models. Our work highlights that practitioners do not yet have a straightforward, black-box procedure to rely on and sets a precedent for creating practitioner-relevant benchmarks. Deep learning approaches must be proven on these benchmarks to become the practical method of choice in drug property prediction.

Keywords: activity (QSAR), ADMET, classical methods, drug property prediction, empirical study, machine learning

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259 People Living with HIV/AIDS: In the Face of Social Stigma and the Role of Therapeutic Communication

Authors: Semiu Bello

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Since the discovery of HIV/AIDS in 1981, it has been a major global challenge and its ravaging consequences have had negative imprints on both the affected and infected people. The challenge of HIV/AIDS does not only affect the developing countries of the world, the developed nations have had their share of the experiences. The disease has, therefore, attracted the attentions of national governments and international donor agencies with huge financial investments toward the eradication of the virus and its global menace. Socially, however, people living with HIV/AIDS have had to battle with an array of social challenges in regards to the infection; the social stigmas, which seem to be more prevalent in underdeveloped and developing societies. The social stigmas with which people living with HIV/AIDS have suffered from include, but not limited, to social isolation, group avoidance, loss of jobs, public ridicule and non-appointment to official and government positions. Given this background, this study examines the roles of therapeutic communication otherwise called patient-provider communication within a clinical environment, focusing on Olabisi Onabanjo University Teaching Hospital (OOUTH) Sagamu, Nigeria as a case study. In other words, this study will investigate the level of interpersonal communication, interactions, and relationships that often take place between people living with HIV/AIDS and health care providers including doctors, nurses and social workers. This study will methodologically adopt the in-depth interview to interview six members of people living with HIV/AIDS at OOUTH. The dimensions of the data will determine the policy prescriptions of this study, which as envisage, may contribute to the improved use of therapeutic communication by health care providers and may thereof improve the psychology of people living with HIV/AIDS in the face of any social stigma.

Keywords: health care providers, people living with HIV/AIDS, social stigma, therapeutic communication

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258 Fake News Detection Based on Fusion of Domain Knowledge and Expert Knowledge

Authors: Yulan Wu

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The spread of fake news on social media has posed significant societal harm to the public and the nation, with its threats spanning various domains, including politics, economics, health, and more. News on social media often covers multiple domains, and existing models studied by researchers and relevant organizations often perform well on datasets from a single domain. However, when these methods are applied to social platforms with news spanning multiple domains, their performance significantly deteriorates. Existing research has attempted to enhance the detection performance of multi-domain datasets by adding single-domain labels to the data. However, these methods overlook the fact that a news article typically belongs to multiple domains, leading to the loss of domain knowledge information contained within the news text. To address this issue, research has found that news records in different domains often use different vocabularies to describe their content. In this paper, we propose a fake news detection framework that combines domain knowledge and expert knowledge. Firstly, it utilizes an unsupervised domain discovery module to generate a low-dimensional vector for each news article, representing domain embeddings, which can retain multi-domain knowledge of the news content. Then, a feature extraction module uses the domain embeddings discovered through unsupervised domain knowledge to guide multiple experts in extracting news knowledge for the total feature representation. Finally, a classifier is used to determine whether the news is fake or not. Experiments show that this approach can improve multi-domain fake news detection performance while reducing the cost of manually labeling domain labels.

Keywords: fake news, deep learning, natural language processing, multiple domains

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257 Utilizing Mahogany (Swietenia Macrophylla) Fruits, Leaves, and Branches as Biochar for Soil Amendment in Okra (Abelmoschus Esculentus) Plant

Authors: Ayaka A. Matsuo, Gweyneth Victoria I. Maranan, Shawn Mikel Hobayan

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In this study, we delve into the application of mahogany fruits as biochar for soil amendment, aiming to evaluate their effectiveness in improving soil quality and influencing the growth parameters of okra plants through a comprehensive analysis employing various multivariate tests. In a more straightforward approach, our results show that biochar derived from isn't just a minor player but emerges as a key contributor to our study. This finding holds profound implications, as it highlights the material significance of biochar derived from Mahogany (Swietenia macrophylla) fruits, leaves, and branches in shaping the outcomes. The importance of this discovery lies in its contribution to an enhanced comprehension of the overall effects of biochar on the variables explored in our investigation. Notably, the positive changes observed in height, number of leaves, and width of leaves in okra plants further support the premise that the incorporation of biochar improves soil quality. These findings provide valuable insights for agricultural practices, suggesting that biochar derived from Mahogany (Swietenia macrophylla) fruits, leaves, and branches holds promise as a sustainable soil amendment with positive implications for plant growth. The statistical results from multivariate tests serve to solidify the conclusion that biochar plays a pivotal role in driving the observed outcomes in our study. In essence, this research not only sheds light on the potential of mahogany fruit-derived biochar but also emphasizes its significance in fostering healthier soil conditions and, consequently, enhanced plant growth.

Keywords: soil amendment, biochar, mahogany, soil health

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256 The Use of Mobile Phone as Enhancement to Mark Multiple Choice Objectives English Grammar and Literature Examination: An Exploratory Case Study of Preliminary National Diploma Students, Abdu Gusau Polytechnic, Talata Mafara, Zamfara State, Nigeria

Authors: T. Abdulkadir

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Most often, marking and assessment of multiple choice kinds of examinations have been opined by many as a cumbersome and herculean task to accomplished manually in Nigeria. Usually this may be in obvious nexus to the fact that mass numbers of candidates were known to take the same examination simultaneously. Eventually, marking such a mammoth number of booklets dared and dread even the fastest paid examiners who often undertake the job with the resulting consequences of stress and boredom. This paper explores the evolution, as well as the set aim to envision and transcend marking the Multiple Choice Objectives- type examination into a thing of creative recreation, or perhaps a more relaxing activity via the use of the mobile phone. A more “pragmatic” dimension method was employed to achieve this work, rather than the formal “in-depth research” based approach due to the “novelty” of the mobile-smartphone e-Marking Scheme discovery. Moreover, being an evolutionary scheme, no recent academic work shares a direct same topic concept with the ‘use of cell phone as an e-marking technique’ was found online; thus, the dearth of even miscellaneous citations in this work. Additional future advancements are what steered the anticipatory motive of this paper which laid the fundamental proposition. However, the paper introduces for the first time the concept of mobile-smart phone e-marking, the steps to achieve it, as well as the merits and demerits of the technique all spelt out in the subsequent pages.

Keywords: cell phone, e-marking scheme (eMS), mobile phone, mobile-smart phone, multiple choice objectives (MCO), smartphone

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255 Biological Studies of N-O Donor 4-Acypyrazolone Heterocycle and Its Pd/Pt Complexes of Therapeutic Importance

Authors: Omoruyi Gold Idemudia, Alexander P. Sadimenko

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The synthesis of N-heterocycles with novel properties, having broad spectrum biological activities that may become alternative medicinal drugs, have been attracting a lot of research attention due to the emergence of medicinal drug’s limitations such as disease resistance and their toxicity effects among others. Acylpyrazolones have been employed as pharmaceuticals as well as analytical reagent and their application as coordination complexes with transition metal ions have been well established. By way of a condensation reaction with amines acylpyrazolone ketones form a more chelating and superior group of compounds known as azomethines. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one was reacted with phenylhydrazine to get a new phenylhydrazone which was further reacted with aqueous solutions of palladium and platinum salts, in an effort towards the discovery of transition metal based synthetic drugs. The compounds were characterized by means of analytical, spectroscopic, thermogravimetric analysis TGA, as well as x-ray crystallography. 4-propyl-3-methyl-1-phenyl-2-pyrazolin-5-one phenylhydrazone crystallizes in a triclinic crystal system with a P-1 (No. 2) space group based on x-ray crystallography. The bidentate ON ligand formed a square planar geometry on coordinating with metal ions based on FTIR, electronic and NMR spectra as well as magnetic moments. Reported compounds showed antibacterial activities against the nominated bacterial isolates using the disc diffusion technique at 20 mg/ml in triplicates. The metal complexes exhibited a better antibacterial activity with platinum complex having an MIC value of 0.63 mg/ml. Similarly, ligand and complexes also showed antioxidant scavenging properties against 2, 2-diphenyl-1-picrylhydrazyl DPPH radical at 0.5mg/ml relative to ascorbic acid (standard drug).

Keywords: acylpyrazolone, antibacterial studies, metal complexes, phenylhydrazone, spectroscopy

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254 Library Screening and Evaluation of Mycobacterium tuberculosis Ketol-Acid Reductoisomerase Inhibitors

Authors: Vagolu S. Krishna, Shan Zheng, Estharla M. Rekha, Luke W. Guddat, Dharmarajan Sriram

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Tuberculosis (TB) remains a major threat to human health. This due to the fact that current drug treatments are less than optimal as well as the rising occurrence of multi drug-resistant and extensively drug-resistant strains of the etiological agent, Mycobacterium tuberculosis (Mt). Given the wide-spread significance of this disease, we have undertaken a design and evaluation program to discover new anti-TB drug leads. Here, our attention is focused on ketol-acid reductoisomerase (KARI), the second enzyme in the branched-chain amino acid biosynthesis pathway. Importantly, this enzyme is present in bacteria but not in humans, making it an attractive proposition for drug discovery. In the present work, we used high-throughput virtual screening to identify seventeen potential inhibitors of KARI using the Birla Institute of Technology and Science in-house database. Compounds were selected based on high docking scores, which were assigned as the result of favourable interactions between the compound and the active site of KARI. The Ki values for two leads, compounds 14 and 16 are 3.71 and 3.06 µM, respectively for Mt KARI. To assess the mode of binding, 100 ns molecular dynamics simulations for these two compounds in association with Mt KARI were performed and showed that the complex was stable with an average RMSD of less than 2.5 Å for all atoms. Compound 16 showed an MIC of 2.06 ± 0.91 µM and a 1.9 fold logarithmic reduction in the growth of Mt in an infected macrophage model. The two compounds exhibited low toxicity against murine macrophage RAW 264.7 cell lines. Thus, both compounds are promising candidates for development as an anti-TB drug leads.

Keywords: ketol-acid reductoisomerase, macrophage, molecular docking and dynamics, tuberculosis

Procedia PDF Downloads 98