Search results for: causal discovery

Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Gabriella Jorge, Carlos A. Pérez, Hanna Friberg, Sara Söderlund, Jan Lagerlöf

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Fusarium Head Blight (FHB) is one of the most important Fusarium-caused diseases, which affects cereals with serious detrimental effects on yield and grain quality worldwide. Earthworms have been suggested as an alternative to control this disease, which requires a combination of preventive methods to reduce level of damage, although it has been proven that their effect is species dependent. Our objective was to evaluate the effect of the earthworms Aporrectodea longa and Lumbricus rubellus, on the inoculum of Fusarium graminearum on wheat straw. To test this we kept earthworms in vessels with soil, and F. graminearum-inoculated straw covering the surface, under controlled conditions for 6 weeks. Two factors were evaluated with a complete factorial design: earthworms (three levels: without earthworms, A. longa, and L. rubellus), and straw (two levels: inoculated with the pathogen, and sterile). The presence of L. rubellus significantly (P<0.05) reduced the amount of inoculated straw at the soil surface 31% after 6 weeks, while the presence of A. longa, most found in quiescence, did not have any significant effect on the amount of straw when compared to the control. After incubation, F. graminearum was detected by qPCR, only in the surface straw in those treatments inoculated with the pathogen but without earthworms. None of the treatments showed presence of Fusarium in the buried straw, soil or earthworm casts. Both earthworm species decreased in body weight during incubation, most likely due to the decrease in soil water content during the experiment, from 25% to 20%, and/or inadequate food supply, since no other source of food was added. However, this reduction in weight occurred indistinctly of the presence or not of Fusarium (P<0.05). This indicates that both species, of different ecological groups, anecic and epigeic, can reduce F. graminearum inoculum present in wheat straw, while their growth is not negatively affected by this pathogen. These promising results place A. longa, and L. rubellus as potential biocontrol agents of this fungal plant pathogen responsible for Fusarium Head Blight disease in wheat, although further ongoing experiments are needed to confirm the repeatability of these results.

Keywords: Aporrectodea longa, biological control, fungal plant pathogen, Lumbricus rubellus, qPCR, wheat straw

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Authors: G. A. Khalid, R. Prabhu, W. Whittington, M. D. Jones

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To establish a causal relationship of infant head injury consequences, this present study addresses the necessary challenges of cranial geometry and the physical response complexities of the paediatric head tissues. Herein, we describe a new approach to characterising and understanding infant head impact mechanics by developing printed head models, using high resolution clinical postmortem imaging, to provide the most complete anatomical representation currently available, and biological material response data-matched polypropylene polymers, to replicate the relative mechanical response properties of immature cranial bone, sutures and fontanelles. Additive manufacturing technology was applied to creating a physical polymeric model of a newborn infant skull, using PolyJet printed materials. Infant skull materials responses, were matched by a response characterisation study, utilising uniaxial tensile testing (1 mm min-1 loading rate), to determine: the stiffness, ultimate tensile strength and maximum strain of rigid and rubber additively manufactured acrylates. The results from the mechanical experiments confirm that the polymeric materials RGD835 Vero White Plus (White), representing the frontal and parietal bones; RGD8510- DM Rigid Light Grey25 (Grey), representing the occipital bone; and FLX9870-DM (Black) representing the suture and fontanelles, were found to show a close stiffness -correlation (E) at ambient temperatures. A 3D physical model of infant head was subsequently printed from the matched materials and subsequently validated against results obtained from a series of Post Mortem Human Surrogate (PMHS) tests. A close correlation was demonstrated between the model impact tests and the PMHS. This study, therefore, represents a key step towards applying printed physical models to understanding head injury biomechanics and is useful in the efforts to predict and mitigate head injury consequences in infants, whether accidental or by abuse.

Keywords: infant head trauma, infant skull, material response, post mortem human subjects, polyJet printing

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Authors: Djebbar Atmani, Dina Kilani, Tristan Richard

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Medicinal plants are an important source for the discovery of potential new substances for use in medicine and food. Pistacia lentiscus, Fraxinus angustifolia and Clematis flammula, plants growing in the Mediterranean basin, are widely used in traditional medicine. Therefore, the present study was designed to investigate their antioxidant, anti-inflammatory, antidiabetic, anti-mutagenic/genotoxic and neuroprotective potential and identification of active compounds using appropriate methodology. Plant extracts and fractions exhibited high scavenging capacity against known radicals, enhanced superoxide dismutase and catalase activitiesand restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro enzymatic inhibition data, through inhibition of amylase and glucosidase activities. Administration of Pistacia lentiscus extracts significantly decreased carrageenan-induced mice paw oedema and reduced effectively IL-1β levels in cell culture, whereas Fraxinus angustifolia extracts showed good healing capacity against wounds when applied topically on rabbits. Pistacia lentiscus and Fraxinus angustifolia extracts showed good neuro-protection and restored cognitive functions in mice, while Clematis flammula extracts showed potent anti-ulcerogenic activity associated to a promising anti-mutagenic/genotoxic activity. HPLC-MS and NMR analyses allowed the identification and structural elucidation of several known and new anthocyanins, flavonols and flavanols. Therefore, Pistacia lentiscus, Fraxinus angustifolia and Clematis flammulacould be used in palliative treatments against inflammatory conditions and diabetes complications, as well as against deterioration of cognitive functions.

Keywords: pistacia lentiscus, clematis flammula, fraxinus angustifolia, phenolic compounds, biological activity

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Authors: Mahsa Hadipour Jahromy, Sara Rezaii

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Parkinson’s disease (PD) results primarily from the death of dopaminergic neurons in the substantia nigra. Soon after the discovery of levodopa and its beneficial effects in chronic administration, debilitating involuntary movements observed, termed levodopa-induced dyskinesia (LID) with poorly understood pathogenesis. Polyphenol-rich compounds, like pomegranate, provided neuroprotection in several animal models of brain diseases. In the present work, we investigated whether pomegranate has preventive effects following 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degenerations and the potential to diminish LID in mice. Mice model of PD was induced by MPTP (30 mg/kg daily for five consecutive days). To induce a mice model of LID, valid PD mice were treated with levodopa (50 mg/kg, i.p) for 15 days. Then the effects of chronic co-administration of pomegranate juice (20 ml/kg) with levodopa and continuing for 10 days, evaluated. Behavioural tests were performed in all groups, every other day including: Abnormal involuntary movements (AIMS), forelimb adjusting steps, cylinder, and catatonia tests. Finally, brain tissue sections were prepared to study substantia nigra changes and dopamine neuron density after treatments. With this MPTP regimen, significant movement disorders revealed in AIMS tests and there was a reduction in dopamine striatal density. Levodopa attenuates their loss caused by MPTP, however, in chronic administration, dyskinesia observed in forelimb adjusting step and cylinder tests. Besides, catatonia observed in some cases. Chronic pomegranate co-administration significantly improved LID in both tests and reduced dopaminergic loss in substantia nigra. These data indicate that pomegranate might be a good adjunct for preserving dopaminergic neurons in the substantia nigra and reducing LID in mice.

Keywords: levodopa-induced dyskinesia, MPTP, Parkinson’s disease, pomegranate

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Authors: Bindu I. Somarajan, Viney Gupta, Gagandeep Kaur Walia, Jasbir Kaur, Sunil Kumar, Shikha Gupta, Abadh K. Chaurasia, Dinesh Gupa, Abhinav Kaushik, Aditi Mehta, Vipin Gupta, Arundhati Sharma

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Background: Juvenile onset primary open angle glaucoma (JOAG), affects individuals under the age of 40 years. Studies on a few families of JOAG, that led to the discovery of the Myocilin gene, reported the disease to have an autosomal dominant pattern of inheritance. However, sporadic forms of JOAG been seen to be more common in some populations. Most pathological homozygous mutations in the CYP1B1 gene associated with JOAG have been seen among sporadic cases. Given the higher prevalence of sporadic JOAG cases in our population, we aimed to look for common mutations E229K and R368H, the two most common variants in the CYP1B1 gene associated with glaucoma. Objective: To determine the frequency and evaluate genotype phenotype correlation of CYP1B1 E229K and R368H mutations in a cohort of 120 sporadic Juvenile open angle glaucoma patients.Methods: Unrelated JOAG patients whose first degree relatives had been examined and found to be unaffected were included in the study. The patients and their parents were screened for E229K and R368H mutations. The phenotypic characteristics were compared between probands with and with out these mutations by SPSS v16. Results: Out of 120 JOAG patients included in the study, the E229K mutation was seen in 9 probands (7.5%) and R368H in 7 (5.8%). The average age of onset of the disease (p=0.3) and the highest untreated IOP (p=0.4) among those carrying mutations was not significantly different from those who did not have these mutations. The proportion of probands with angle dysgenesis among those with E229K and R368H mutations was 70% (11 out of 16) in comparison to 65% (67 out of 104) of those who did not harbour these mutations (p=0.56). Similarly the probands with moderate to high myopia among those with E229K and R368H mutations was 20% (3 out of 16) in comparison to 18% (18 out of 104) of those who did not harbour these mutations(p=0.59). Conclusion: The frequency of E229K and R368H mutations of the CYP1B1 gene is low even among sporadic JOAG patients. Moreover there is no clinical correlation between the presence of these mutations and disease severity

Keywords: CYP1B1, gene, IOP, JOAG, mutation

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Authors: Zachary Bolo Awino

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The need to gain and sustain a competitive advantage is overwhelming for businesses, especially now with cut throat competition. Innovation has been suggested as one way of gaining the advantage sustainably. But innovation can only happen within certain enabling environment and cultures. This study had one hypothesis: that there is no relationship between innovation and performance. This research was a cross sectional survey in which variables of interest are not controlled or manipulated. The cross sectional survey design is also appropriate for this study as it improves accuracy in generalizing findings, since it involves detailed study of a unit. Also known as one shot study, this design enhances uniform data collection and comparison across respondents. The population of the study was the 55 publicly quoted corporations in the Nairobi Securities Exchange (NSE) as at October 2013.The number was initially envisaged to be 60 but 5 firms were delisted or suspended during the year, hence leaving 55 firms as the population of study. The rationale for the choice for these firms is because they cut across the key economic sectors in Kenyan economy which include agriculture, commercial and services, manufacturing, finance and investment. This was a census survey and targeted all the firms listed at the Nairobi Securities Exchange as of October 2013. The primary data for the study was collected through the use of a structured questionnaire. A five point type Likert scale ranging from 1 - denoting to a less event to 5 - denoting to a greater extent was used. Respondents were from senior management of NSE. From the analyses, the study established that there was a strong positive relationship between innovation and performance, and organization innovation significantly contributes to employee engagement. Also there was a moderate positive relationship between innovation and performance. The study drew expressions of interrelations between various variables, offered generalization of understanding and meaning of these relationships, thus expanding the frontiers of knowledge both theoretical and practical with respect to innovation and firm performance. Major conclusion in this study was that there is a positive strong relationship between innovation and major measures of firm performance.

Keywords: emperical, innovation, NSE, organizations, performance

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Authors: Bibin Sagaram, Ronith Stanly, S. S. Suneesh

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Due to the dwindling supply of fuel reserves, engineers and designers now focus on fuel efficient designs for the solution of any problem; the transportation industry is not new to this kind of approach. Though the aerodynamic benefits of the dimples on a Golf-ball are known, it has never been scientifically tested on how such a design philosophy can improve the fuel efficiency of a real-life vehicle by imparting better aerodynamic performance. The main purpose of the paper is to establish the aerodynamic benefits of the Golf-ball-Inspired Dimpled Design in improving the fuel efficiency of a Super-mileage vehicle, constructed by Team Go Viridis for ‘Shell Eco Marathon Asia 2015’, and to predict the extent to which the results can be held valid for a road car. The body design was modeled in Autodesk Inventor and the Computational Fluid Dynamics (CFD) simulations were carried out using Ansys Fluent software. The aerodynamic parameters of designs (with and without the Golf-ball-Inspired Dimples) have been studied and the results are experimentally validated against those obtained from wind tunnel tests carried out on a 1:10 scaled-down 3D printed model. Test drives of the Super-mileage vehicle were carried out, under various conditions, to compare the variation in fuel efficiency with and without the Golf-ball-Inspired design. Primary investigations reveal an aerodynamic advantage of 25% for the vehicle with the Golf Ball Inspired Dimpled Design as opposed to the normal design. Initial tests conducted by ‘Mythbusters’ on Discovery Network using a modified road car has shown positive results which has motivated us to conduct such a research work using a custom-built experimental Super-Mileage vehicle. The content of the paper becomes relevant to the present Automotive and Energy industry where improving the fuel efficiency is of the top most priority.

Keywords: aerodynamics, CFD, fuel efficiency, golf ball

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Authors: Sadaf H. Khan, Jyoti Kumar

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Sick Building Syndrome (SBS) is a situation in which inhabitants of a building develop illness symptoms or get infected with a chronic disease as a result of the building in which they reside or work. Certain symptoms tend to get more severe as an individual spends more time in the building; however, they generally improve with time or even disappear when they leave that space. Though ‘Design of Built-Spaces’ is a crucial factor in regulating these symptoms but it still needs to be identified further as to what specific design features of a ‘Built-Space’ trigger sick building syndrome (SBS). Much of the research work present to date is focused on the physiological or physical sickness caused due to inappropriate built-space design. In this paper, the psychological aspects of sick building syndrome (SBS) will be investigated across the adult population, more specifically graduate students in India trying to settle in back to their previous physical work environments, i.e., campus, classrooms, hostels, after a very long hold which lasted more than a year due to lockdowns during Covid-19 crisis all over the world. The study will follow an analytical approach and the data will be collected through self-reported online surveys. The purpose of this study is to enquire causal agents, diagnosable symptoms and remedial design of built spaces which can enhance the productive level of built environments and better facilitate the inhabitants by improving their psychological wellbeing, which is the most uprising concern. The fact that SBS symptoms can be studied only within the initial few weeks as an occupant starts interacting with a built-environment and leaves as the occupant leaves that space or zone, the post-lockdown incoming of students back to their respective campuses provides an opportunity to clearly draw multiple conclusions of the relationship that exist between the Design of Built-Spaces and Psychological Sickness Syndrome associated with it. The study will be one of a kind approach for understanding and formulating methods to improve psychological wellbeing within a built-setting by better identifying factors associated with these psychological symptoms, including anxiety, mental fatigue, reduced attention span and reduced memory span as refined symptoms of SBS discussed in 1987 by Molhave within his study.

Keywords: built-environment psychology, built-space design, healthcare architecture, psychological wellbeing

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Authors: Anika Chebrolu

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Mono-targeted drugs can be of limited efficacy against complex diseases. Recently, multi-target drug design has been approached as a promising tool to fight against these challenging diseases. However, the scope of current computational approaches for multi-target drug design is limited. DeepLig presents a de-novo drug discovery platform that uses reinforcement learning to generate and optimize novel, potent, and multitargeted drug candidates against protein targets. DeepLig’s model consists of two networks in interplay: a generative network and a predictive network. The generative network, a Stack- Augmented Recurrent Neural Network, utilizes a stack memory unit to remember and recognize molecular patterns when generating novel ligands from scratch. The generative network passes each newly created ligand to the predictive network, which then uses multiple Graph Attention Networks simultaneously to forecast the average binding affinity of the generated ligand towards multiple target proteins. With each iteration, given feedback from the predictive network, the generative network learns to optimize itself to create molecules with a higher average binding affinity towards multiple proteins. DeepLig was evaluated based on its ability to generate multi-target ligands against two distinct proteins, multi-target ligands against three distinct proteins, and multi-target ligands against two distinct binding pockets on the same protein. With each test case, DeepLig was able to create a library of valid, synthetically accessible, and novel molecules with optimal and equipotent binding energies. We propose that DeepLig provides an effective approach to design multi-targeted drug therapies that can potentially show higher success rates during in-vitro trials.

Keywords: drug design, multitargeticity, de-novo, reinforcement learning

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Authors: Mathias Twizeyimana, Urmila Adhikari, Julius P. Sserumaga, David Ingham

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The management of aflatoxins (naturally occurring toxins produced by certain fungi, most importantly Aspergillus flavus and A. parasiticus) relies mostly on the use of best cultural practices and, in some cases, the use of the biological control consisting of atoxigenic strains inhibiting the toxigenic strains through competition resulting in considerable toxin reduction. At AgBiome, we have built a core collection of over 100,000 fully sequenced microbes from diverse environments and employ both the microbes and their sequences in the discovery of new biological products for disease and pest control. The most common approach to finding beneficial microbes consists of isolating microorganisms from samples collected from diverse environments, selecting antagonistic strains through empirical screening, studying modes of action, and stabilization through the formulation of selected microbial isolates. A total of 608 diverse bacterial strains were screened using a high-throughput assay (48-well assay) to identify strains that inhibit toxigenic A. flavus growth on maize kernels. Active strains in 48-well assay had their pathogen inhibiting activity confirmed using the Flask Assay and were concurrently tested for their ability to reduce the aflatoxin content in maize grains. Strains with best growth inhibition and reduction of aflatoxin were tested in the greenhouse and field trials. From the field trials, three bacterial strains, AFS000009 (Pseudomonas chlororaphis), AFS032321 (Bacillus subtilis), AFS024683 (Bacillus velezensis), had aflatoxin concentrations (ppb) values that were significantly lower than those of inoculated control. The identification of biological products with high efficacy in inhibiting pathogen growth and eventually reducing the aflatoxin content will provide a valuable alternative to control strategies used in aflatoxin contamination management.

Keywords: aflatoxin, microorganism bacteria, biocontrol, beneficial microbes

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Authors: Ann Ying-An Chen, Yi-Lun Tsai, Hso-Chi Chaung

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An understanding of pathogens and the immune system has played an utmost important role in agricultural research for the development of vaccinations. The immunological synapse, cell to cell interaction play a crucial role in triggering the body's immune system, such as activation between antigen-presenting cells (APCs) and different subsets of T-cell. If these interactions are regulated appropriately, the host has the ability to defend itself against a wide spectrum of infectious pathogens. The aim of this study is to establish and to characterize a porcine immune synapse system by co-culturing T cell/APC. In this study, blood samples were collected from specific-pathogen-free piglets, and peripheral blood mononuclear cells (PBMC) were separated by using Ficoll-Pague. The PBMC were then stained with CD4 (FITC) and CD25 (PE) antibodies. Different subsets of T cells sorted by fluorescence-activated cell sorting flow cytometer were co-cultured for 24 hrs with alveolar macrophages, and the profiles of cytokine secretion and mRNA transcription levels of Toll-like receptors were examined after. Results showed that the three stages of immune synapse were clearly visible and identified under both transmission and scanning electron microscope (TEM and SEM). The significant interaction differences in toll-like receptor expressions within the co-cultured cell system were observed. The TLR7 mRNA expressions in CD4+CD25- cells were lower than those in CD4+CD25+ and CD4 -CD25+. Interestingly, the IL-10 production levels in CD4+CD25- cells (7.732 pg/mL) were significantly higher than those of CD4+CD25+ (2.636 pg/mL) and CD4 -CD25+ (2.48 pg/mL). These findings demonstrated that a clear understanding of the porcine immune synapse system can contribute greatly for further investigations on the mechanism of T-cell activation, which can benefit in the discovery of potential adjuvant candidate or effective antigen epitopes in the development of vaccinations with high efficacy.

Keywords: antigen-presenting cells, immune synapse, pig, T subsets, toll-like receptor

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Authors: Abdulaziz Alsadhan, Naveed Khan

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In recent years intrusions on computer network are the major security threat. Hence, it is important to impede such intrusions. The hindrance of such intrusions entirely relies on its detection, which is primary concern of any security tool like Intrusion Detection System (IDS). Therefore, it is imperative to accurately detect network attack. Numerous intrusion detection techniques are available but the main issue is their performance. The performance of IDS can be improved by increasing the accurate detection rate and reducing false positive. The existing intrusion detection techniques have the limitation of usage of raw data set for classification. The classifier may get jumble due to redundancy, which results incorrect classification. To minimize this problem, Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA), and Local Binary Pattern (LBP) can be applied to transform raw features into principle features space and select the features based on their sensitivity. Eigen values can be used to determine the sensitivity. To further classify, the selected features greedy search, back elimination, and Particle Swarm Optimization (PSO) can be used to obtain a subset of features with optimal sensitivity and highest discriminatory power. These optimal feature subset used to perform classification. For classification purpose, Support Vector Machine (SVM) and Multilayer Perceptron (MLP) used due to its proven ability in classification. The Knowledge Discovery and Data mining (KDD’99) cup dataset was considered as a benchmark for evaluating security detection mechanisms. The proposed approach can provide an optimal intrusion detection mechanism that outperforms the existing approaches and has the capability to minimize the number of features and maximize the detection rates.

Keywords: Particle Swarm Optimization (PSO), Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA), Local Binary Pattern (LBP), Support Vector Machine (SVM), Multilayer Perceptron (MLP)

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Authors: Ahmed Khalil, Elhamy Tarabees, Svetlana Kovacikova

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The Red Sea Mountains have been famous for their ore deposits since ancient times. Also, petrographic analysis and previous potential field surveys indicated large unexplored accumulations of ore minerals in the area. Therefore, the main goal of the presented study is to contribute to the discovery of hitherto unknown ore mineral deposits in the Red Sea region. To achieve this goal, we used two geophysical techniques: land magnetic survey and magnetotelluric data. A high-resolution land magnetic survey has been acquired using two proton magnetometers, one instrument used as a base station for the diurnal correction and the other used to measure the magnetic field along the study area. Two hundred eighty land magnetic stations were measured over a mesh-like area with a 500m spacing interval. The necessary reductions concerning daily variation, regional gradient and time observation were applied. Then, the total intensity anomaly map was constructed and transformed into the reduced magnetic pole (RTP). The magnetic interpretation was carried out using the analytical signal as well as regional–residual separation is carried out using the power spectrum. Also, the tilt derivative method (TDR) technique is applied to delineate the structure and hidden anomalies. Data analysis has been performed using trend analysis and Euler deconvolution. The results indicate that magnetic contacts are not the dominant geological feature of the study area. The magnetotleruric survey consisted of two profiles with a total of 8 broadband measurement points with a duration of about 24 hours crossing a wadi um Gheig approximately 50 km south of El Quseir. Collected data have been inverted to the electrical resistivity model using the 3D modular 3D inversion technique ModEM. The model revealed a non-conductive body in its central part, probably corresponding to a dolerite dyke, with which possible ore mineralization could be related.

Keywords: magnetic survey, magnetotelluric, mineralization, 3d modeling

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Authors: Felermino D. M. A. Ali, S. C. Ng

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E-learning is an evolutionary form of distance learning and has become better over time as new technologies emerged. Today, efforts are still being made to embrace E-learning systems with emerging technologies in order to make them better. Among these advancements, Educational Data Mining (EDM) is one that is gaining a huge and increasing popularity due to its wide application for improving the teaching-learning process in online practices. However, even though EDM promises to bring many benefits to educational industry in general and E-learning environments in particular, its principal drawback is the lack of easy to use tools. The current EDM tools usually require users to have some additional technical expertise to effectively perform EDM tasks. Thus, in response to these limitations, this study intends to design and implement an EDM application framework which aims at automating and simplify the development of EDM in E-learning environment. The application framework introduces a Service-Oriented Architecture (SOA) that hides the complexity of technical details and enables users to perform EDM in an automated fashion. The framework was designed based on abstraction, extensibility, and interoperability principles. The framework implementation was made up of three major modules. The first module provides an abstraction for data gathering, which was done by extending Moodle LMS (Learning Management System) source code. The second module provides data mining methods and techniques as services; it was done by converting Weka API into a set of Web services. The third module acts as an intermediary between the first two modules, it contains a user-friendly interface that allows dynamically locating data provider services, and running knowledge discovery tasks on data mining services. An experiment was conducted to evaluate the overhead of the proposed framework through a combination of simulation and implementation. The experiments have shown that the overhead introduced by the SOA mechanism is relatively small, therefore, it has been concluded that a service-oriented architecture can be effectively used to facilitate educational data mining in E-learning environments.

Keywords: educational data mining, e-learning, distributed data mining, moodle, service-oriented architecture, Weka

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Authors: Ozgu Hafizoglu

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An analogy is an essential tool of human cognition that enables connecting diffuse and diverse systems with physical, behavioral, principal relations that are essential to learning, discovery, and innovation. The Cognitive Model of Analogy (CMA) leads and creates patterns of pathways to transfer information within and between domains in science, just as happens in the brain. The connectome of the brain shows how the brain operates with mental leaps between domains and mental hops within domains and the way how analogical reasoning mechanism operates. This paper demonstrates the CMA as an evolutionary approach to science, technology, and life. The model puts forward the challenges of deep uncertainty about the future, emphasizing the need for flexibility of the system in order to enable reasoning methodology to adapt to changing conditions in the new era, especially post-pandemic. In this paper, we will reveal how to draw an analogy to scientific research to discover new systems that reveal the fractal schema of analogical reasoning within and between the systems like within and between the brain regions. Distinct phases of the problem-solving processes are divided thusly: stimulus, encoding, mapping, inference, and response. Based on the brain research so far, the system is revealed to be relevant to brain activation considering each of these phases with an emphasis on achieving a better visualization of the brain’s mechanism in macro context; brain and spinal cord, and micro context: glia and neurons, relative to matching conditions of analogical reasoning and relational information, encoding, mapping, inference and response processes, and verification of perceptual responses in four-term analogical reasoning. Finally, we will relate all these terminologies with these mental leaps, mental maps, mental hops, and mental loops to make the mental model of CMA clear.

Keywords: analogy, analogical reasoning, brain connectome, cognitive model, neurons and glia, mental leaps, mental hops, mental loops

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Authors: Kiran Nawaz, Ahmad Ali Shahid, Sehrish Iftikhar, Waheed Anwar, Muhammad Nasir Subhani

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Chili (Solanum annum L.) attacks by many fungal pathogens, including members of Oomycetes which are responsible for root rot in different chili growing areas of the world. Oomycetes pathogens cause economic losses in different regions of the Pakistan. Most of the plant tissues, including roots, crowns, fruit, and leaves, are vulnerable to Phytophthora capsici. It is very difficult to manage the Phytophthora root rot of chili as many commercial varieties are tremendously vulnerable to P. capsici. The causal agent of the disease was isolated on corn meal agar (CMA) and identified on a morphological basis by using available taxonomic keys. The pathogen was also confirmed on the molecular basis through internal transcribed spacer region and with other molecular markers.The Blastn results showed 100% homology with already reported sequences of P. capsici in NCBI database. Most of the farmers have conventionally relied on foliar fungicide applications to control Phytophthora root rot in spite of their incomplete effectiveness. In this study, in vitro plate assay, seed soaking and foliar applications of 6 fungicides were evaluated against root rot of chili. In vitro assay revealed that significant inhibition of linear growth was obtained with Triflumizole at 7.0%, followed by Thiophanate methyl (8.9%), Etridiazole (6.0%), Propamocarb (5.9%) and 7.5% with Mefenoxam and Iprodione for P. capsici. The promising treatments of in vitro plate bioassay were evaluated in pot experiments under controlled conditions in the greenhouse. All fungicides were applied after at 6-day intervals. Results of pot experiment showed that all treatments considerably inhibited the percentage of P. capsici root rot incidence. In addition, application of seed soaking with all six fungicides combined with the foliar spray of the same components showed the significant reduction in root rot incidence. The combine treatments of all fungicides as in vitro bioassay, seed soaking followed by foliar spray is considered non-harmful control methods which have advantages and limitation. Hence, these applications proved effective and harmless for the management of soil-borne plant pathogens.

Keywords: blastn, bioassay, corn meal agar(CMA), oomycetes

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Authors: S. Jeyarajan

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Concept of knowledge is discovered from conducted study for successive Competition in Sri Lankan Non-State Higher Educational Institutes. The Concept discovered out of collected Knowledge Management Practices from Emerald inside likewise reputed literatures and of Non-State Higher Educational sector. A test is conducted to reveal existences and its reason behind of these collected practices in Sri Lankan Non-State Higher Education Institutes. Further, unavailability of such study and uncertain on number of participants for data collection in the Sri Lankan context contributed selection of research method as qualitative method, which used attributes of Delphi Method to manage those likewise uncertainty. Data are collected under Dramaturgical Method, which contributes efficient usage of the Delphi method. Grounded theory is selected as data analysis techniques, which is conducted in intermixed discourse to manage different perspectives of data that are collected systematically through perspective and modified snowball sampling techniques. Data are then analysed using Grounded Theory Development Techniques in Intermix discourses to manage differences in Data. Consequently, Agreement in the results of Grounded theories and of finding in the Foreign Study is discovered in the analysis whereas present study conducted as Qualitative Research and The Foreign Study conducted as Quantitative Research. As such, the Present study widens the discovery in the Foreign Study. Further, having discovered reason behind of the existences, the Present result shows Concept for Knowledge from Sri Lankan Non-State sector to manage higher educational Institutes in successful manner.

Keywords: adherence of snowball sampling into perspective sampling, Delphi method in qualitative method, grounded theory development in intermix discourses of analysis, knowledge management for success of higher educational institutes

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Authors: Rafael Bezerra de Souza, José Ribas Vieira

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The judicial litigation on socio-economic rights (SERs), in a context of increasing centrality of the judiciary as an area of political debate for civil society actors, has assumed greater importance in the last two decades. This tendency to seek social change through the courts generated a long tradition of research on the role of legal institutions and of legal mobilization in the US and some European countries. However, little is known about these processes in Latin America, Asia and Africa. A significant portion of the Brazilian constitutional doctrine did not bother to investigate the phenomenon of constitutional judicial litigation of socio-economic rights, in a practical and empirical look, from the functioning of democratic institutions. The central issue of this study draws attention to the theoretical and analytic deficit of Brazilian constitutional doctrine: the lack of a holistic understanding of the effects and impact of judicial decisions. Consequently, for a proper understanding was analyzed if the trend of judicial litigation in Brazil - to ensure the fulfillment of its institutional mission to protect and ensure the effectiveness of socio-economic rights - has been accompanied by the establishment of institutional mechanisms that enable decision making and the implementation of SERs in complex cases involving structural and public policy. The lack of empirical studies in Law in order to verify this hypothesis justified the adoption of the case study method as an interdisciplinary methodological strategy between Law and Political Science, aiming to construct an explanation of the Raposa Serra do Sol Case and, in a complementary way, the process-tracing technique. Drawings of small-n type or case studies, when guided by theory, are more suitable to problems it is supposed to increase the potential of intensive analysis of causal processes. As a preliminary result, the Brazilian Supreme Court was not a sufficient agent to implement a relevant social change and to assure the protection of the social rights, because there were few measures that directly impacted the behavior of other institutional political actors and should, therefore, be considered another actor within a complex institutional arrangement.

Keywords: courts, case study, judicial litigation, social change

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Authors: Sandra Cecilia Bautista-Rodríguez, Vladimir Melgarejo

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Climate change, loss of ecosystems, increasing poverty, increasing marginalization of rural communities and declining food security are global issues that require urgent attention. In this regard, a great deal of research has focused on how agroecosystems respond to these challenges as they provide ecosystem services (ES) that lead to higher levels of resilience, adaptation, productivity and self-sufficiency. Hence, the valuing of ecosystem services plays an important role in the decision-making process for the design and management of agroecosystems. This paper aims to define the link between ecosystem service valuation methods and ES value dimensions in agroecosystems from ecological economics and agroecology. The method used to identify valuation methodologies was a literature review in the fields of Agroecology and Ecological Economics, based on a strategy of information search and classification. The conceptual framework of the work is based on the multidimensionality of value, considering the social, ecological, political, technological and economic dimensions. Likewise, the valuation process requires consideration of the ecosystem function associated with ES, such as regulation, habitat, production and information functions. In this way, valuation methods for ES in agroecosystems can integrate more than one value dimension and at least one ecosystem function. The results allow correlating the ecosystem functions with the ecosystem services valued, and the specific tools or models used, the dimensions and valuation methods. The main methodologies identified are multi-criteria valuation (1), deliberative - consultative valuation (2), valuation based on system dynamics modeling (3), valuation through energy or biophysical balances (4), valuation through fuzzy logic modeling (5), valuation based on agent-based modeling (6). Amongst the main conclusions, it is highlighted that the system dynamics modeling approach has a high potential for development in valuation processes, due to its ability to integrate other methods, especially multi-criteria valuation and energy and biophysical balances, to describe through causal cycles the interrelationships between ecosystem services, the dimensions of value in agroecosystems, thus showing the relationships between the value of ecosystem services and the welfare of communities. As for methodological challenges, it is relevant to achieve the integration of tools and models provided by different methods, to incorporate the characteristics of a complex system such as the agroecosystem, which allows reducing the limitations in the processes of valuation of ES.

Keywords: ecological economics, agroecosystems, ecosystem services, valuation of ecosystem services

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Authors: King Kumire, Amos Kubeka

Abstract:

The synergy of machine learning and astronomical technology advancement is giving rise to the new space age, which is pronounced by better habitability assessments. To initiate this discussion, it should be recorded for definition purposes that the symbiotic relationship between astronomy and improved computing has been code-named the Cis-Astro gateway concept. The cosmological fate of this phrase has been unashamedly plagiarized from the cis-lunar gateway template and its associated LaGrange points which act as an orbital bridge to the moon from our planet Earth. However, for this study, the scientific audience is invited to bridge toward the discovery of new habitable planets. It is imperative to state that cosmic probes of this magnitude can be utilized as the starting nodes of the astrobiological search for galactic life. This research can also assist by acting as the navigation system for future space telescope launches through the delimitation of target exoplanets. The findings and the associated platforms can be harnessed as building blocks for the modeling of climate change on planet earth. The notion that if the human genus exhausts the resources of the planet earth or there is a bug of some sort that makes the earth inhabitable for humans explains the need to find an alternative planet to inhabit. The scientific community, through interdisciplinary discussions of the International Astronautical Federation so far has the common position that engineers can reduce space mission costs by constructing a stable cis-lunar orbit infrastructure for refilling and carrying out other associated in-orbit servicing activities. Similarly, the Cis-Astro gateway can be envisaged as a budget optimization technique that models extra-solar bodies and can facilitate the scoping of future mission rendezvous. It should be registered as well that this broad and voluminous catalog of exoplanets shall be narrowed along the way using machine learning filters. The gist of this topic revolves around the indirect economic rationale of establishing a habitability scoping platform.

Keywords: machine-learning, habitability, exoplanets, supercomputing

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Authors: King Kumire, Amos Kubeka

Abstract:

The synergy of machine learning and astronomical technology advancement is giving rise to the new space age, which is pronounced by better habitability assessments. To initiate this discussion, it should be recorded for definition purposes that the symbiotic relationship between astronomy and improved computing has been code-named the Cis-Astro gateway concept. The cosmological fate of this phrase has been unashamedly plagiarized from the cis-lunar gateway template and its associated LaGrange points which act as an orbital bridge to the moon from our planet Earth. However, for this study, the scientific audience is invited to bridge toward the discovery of new habitable planets. It is imperative to state that cosmic probes of this magnitude can be utilized as the starting nodes of the astrobiological search for galactic life. This research can also assist by acting as the navigation system for future space telescope launches through the delimitation of target exoplanets. The findings and the associated platforms can be harnessed as building blocks for the modeling of climate change on planet earth. The notion that if the human genus exhausts the resources of the planet earth or there is a bug of some sort that makes the earth inhabitable for humans explains the need to find an alternative planet to inhabit. The scientific community, through interdisciplinary discussions of the International Astronautical Federation so far, has the common position that engineers can reduce space mission costs by constructing a stable cis-lunar orbit infrastructure for refilling and carrying out other associated in-orbit servicing activities. Similarly, the Cis-Astro gateway can be envisaged as a budget optimization technique that models extra-solar bodies and can facilitate the scoping of future mission rendezvous. It should be registered as well that this broad and voluminous catalog of exoplanets shall be narrowed along the way using machine learning filters. The gist of this topic revolves around the indirect economic rationale of establishing a habitability scoping platform.

Keywords: exoplanets, habitability, machine-learning, supercomputing

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Authors: Rowland Brucken

Abstract:

This paper argues that nation-building theories that prioritize democratic governance best explain the successful post-independence development of Botswana. Three main competing schools of thought exist regarding the sequencing of policies that should occur to re-build weakened or failed states. The first posits that economic development should receive foremost attention, while democratization and a binding sense of nationalism can wait. A second group of experts identified constructing a sense of nationalism among a populace is necessary first, so that the state receives popular legitimacy and obedience that are prerequisites for development. Botswana, though, transitioned into a multi-party democracy and prosperous open economy due to the utilization of traditional democratic structures, enlightened and accountable leadership, and an educated technocratic civil service. With these political foundations already in place when the discovery of diamonds occurred, the resulting revenues were spent wisely on projects that grew the economy, improved basic living standards, and attracted foreign investment. Thus democratization preceded, and therefore provided an accountable basis for, economic development that might otherwise have been squandered by greedy and isolated elites to the detriment of the greater population. Botswana was one of the poorest nations in the world at the time of its independence in 1966, with little infrastructure, a dependence on apartheid South Africa for trade, and a largely subsistence economy. Over the next thirty years, though, its economy grew the fastest of any nation in the world. The transparent and judicious use of diamond returns is only a partial explanation, as the government also pursued economic diversification, mass education, and rural development in response to public needs. As nation-building has become a project undertaken by nations and multilateral agencies such as the United Nations and the North Atlantic Treaty Organization, Botswana may provide best practices that others should follow in attempting to reconstruct economically and politically unstable states.

Keywords: Botswana, democratization, economic development, nation-building

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Authors: Marco Sewald

Abstract:

Comparing present to past the numbers of Americans expatriating U. S. citizenship have risen. Even though these numbers are small compared to the immigrants, U. S. citizens expatriations have historically been much lower, making the uptick worrisome. In addition, the published lists and numbers from the U.S. government seems incomplete, with many not counted. Different branches of the U. S. government report different numbers and no one seems to know exactly how big the real number is, even though the IRS and the FBI both track and/or publish numbers of Americans who renounce. Since there is no single explanation, anecdotal evidence suggests this uptick is caused by global tax law and increased compliance burdens imposed by the U.S. lawmakers on U.S. citizens abroad. Within a research project the question arose about the reasons why a constant growing number of U.S. citizens are expatriating – the answers are believed helping to explain the underlying governmental policy rational, leading to such activities. While it is impossible to locate former U.S. citizens to conduct a survey on the reasons and the U.S. government is not commenting on the reasons given within the process of expatriation, the chosen methodology is Structural Equation Modeling (SEM), in the first step by re-using current surveys conducted by different researchers within the population of U. S. citizens residing abroad during the last years. Surveys questioning the personal situation in the context of tax, compliance, citizenship and likelihood to repatriate to the U. S. In general SEM allows: (1) Representing, estimating and validating a theoretical model with linear (unidirectional or not) relationships. (2) Modeling causal relationships between multiple predictors (exogenous) and multiple dependent variables (endogenous). (3) Including unobservable latent variables. (4) Modeling measurement error: the degree to which observable variables describe latent variables. Moreover SEM seems very appealing since the results can be represented either by matrix equations or graphically. Results: the observed variables (items) of the construct are caused by various latent variables. The given surveys delivered a high correlation and it is therefore impossible to identify the distinct effect of each indicator on the latent variable – which was one desired result. Since every SEM comprises two parts: (1) measurement model (outer model) and (2) structural model (inner model), it seems necessary to extend the given data by conducting additional research and surveys to validate the outer model to gain the desired results.

Keywords: expatriation of U. S. citizens, SEM, structural equation modeling, validating

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Authors: Ahmad Ali Shahid, Mukhtar Ahmed

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The demand for long staple fiber having better strength and length is increasing with the introduction of modern spinning and weaving industry in Pakistan. Work on gene discovery from developing cotton fibers has helped to identify dozens of genes that take part in cotton fiber development and several genes have been characterized for their role in fiber development. Sucrose synthase (SuS) is a key enzyme in the metabolism of sucrose in a plant cell, in cotton fiber it catalyzes a reversible reaction, but preferentially converts sucrose and UDP into fructose and UDP-glucose. UDP-glucose (UDPG) is a nucleotide sugar act as a donor for glucose residue in many glycosylation reactions and is essential for the cytosolic formation of sucrose and involved in the synthesis of cell wall cellulose. The study was focused on successful Agrobacterium-mediated stable transformation of SuS gene in pCAMBIA 1301 into cotton under a CaMV35S promoter. Integration and expression of the gene were confirmed by PCR, GUS assay, and real-time PCR. Young leaves of SuS overexpressing lines showed increased total soluble sugars and plant biomass as compared to non-transgenic control plants. Cellulose contents from fiber were significantly increased. SEM analysis revealed that fibers from transgenic cotton were highly spiral and fiber twist number increased per unit length when compared with control. Morphological data from field plants showed that transgenic plants performed better in field conditions. Incorporation of genes related to cotton fiber length and quality can provide new avenues for fiber improvement. The utilization of this technology would provide an efficient import substitution and sustained production of long-staple fiber in Pakistan to fulfill the industrial requirements.

Keywords: agrobacterium-mediated transformation, cotton fiber, sucrose synthase gene, staple length

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Authors: Mingke Ma

Abstract:

The recent discovery of the High-Income Trap phenomena and the established Middle-Income Trap literature have identified the similarity of the structural challenges that both Mainland China and Taiwan have been facing since the simultaneous growth slowdown from the 2000s. Mainland China and Taiwan’s ineffectiveness in productivity growth weakened their overall competitiveness in Global Value Chains. With the subsequent decline of industrial profitability, social compression from late development persists and jeopardises the social cohesion. From Ma Ying-jeou’s ‘633’ promise and Tsai Ing-wen’s ‘5+2’ industrial framework to Mainland China’s 11th to 14th Five-Year Plans, leaderships across the Strait have been striving to constitute new models for inclusive and sustainable development through policy responses. This study argues that social consensuses that have been constructed by the domestic political processes define the feasibility of the reform strategies, which further construct the conditions for Cross-Strait interactions. Based on the existing literature of New Institutional Economics, Middle/High Income Trap, and Compressed Development, this study adopts a Historical Institutionalist analytical framework to identify how the historical path-dependency contributes to the contemporary growth constraints in both economies and the political difficulty on navigating the institutional and Organisational change. It continues by tracing the political process of economic reform to examine the sustainability and resilience of the manifested social consensus that had empowered the proposed policy frameworks. Afterwards, it examines how the political outcomes in such a simultaneous process shared by both Mainland China and Taiwan construct the social, economic, institutional, and political foundations of contemporary Cross-Strait engagement.

Keywords: historical institutionalism, political economy, cross-strait relations, high/middle income trap

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Authors: Daniel F. Sava, Anton Ficai, Bogdan S. Vasile, Georgeta Voicu, Ecaterina Andronescu

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The energy crisis and environmental contamination are very serious problems, therefore searching for better and sustainable renewable energy is a must. It is predicted that the global energy demand will double until 2050. Solar water splitting and photocatalysis are considered as one of the solutions to these issues. The use of oxide semiconductors for solar water splitting and photocatalysis started in 1972 with the experiments of Fujishima and Honda on TiO2 electrodes. Since then, the evolution of nanoscience and characterization methods leads to a better control of size, shape and properties of materials. Although the past decade advancements are astonishing, for these applications the properties have to be controlled at a much finer level, allowing the control of charge-carrier lives, energy level positions, charge trapping centers, etc. Graphene has attracted a lot of attention, since its discovery in 2004, due to the excellent electrical, optical, mechanical and thermal properties that it possesses. These properties make it an ideal support for photocatalysts, thus graphene composites with oxide semiconductors are of great interest. We present in this work the synthesis and characterization of graphene-related materials and oxide semiconductors and their different composites. These materials can be used in constructing devices for different applications (batteries, water splitting devices, solar cells, etc), thus showing their application flexibility. The synthesized materials are different morphologies and sizes of TiO2, ZnO and Fe2O3 that are obtained through hydrothermal, sol-gel methods and graphene oxide which is synthesized through a modified Hummer method and reduced with different agents. Graphene oxide and the reduced form could also be used as a single material for transparent conductive films. The obtained single materials and composites were characterized through several methods: XRD, SEM, TEM, IR spectroscopy, RAMAN, XPS and BET adsorption/desorption isotherms. From the results, we see the variation of the properties with the variation of synthesis parameters, size and morphology of the particles.

Keywords: composites, graphene, hydrothermal, renewable energy

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Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

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Authors: Soultana Konstantinidou, Tiziana Schmidt, Elena Landi, Alessandro De Carli, Giovanni Maltinti, Darius Witt, Alicja Dziadosz, Agnieszka Lindstaedt, Michele Lai, Mauro Pistello, Valentina Cappello, Luciana Dente, Chiara Gabellini, Piotr Barski, Vittoria Raffa

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CRISPR/Cas9 technology has gained the interest of researchers in the field of biotechnology for genome editing. Since its discovery as a microbial adaptive immune defense, this system has been widely adopted and is acknowledged for having a variety of applications. However, critical barriers related to safety and delivery are persisting. Here, we propose a new concept of genome engineering, which is based on a nano-formulation of Cas9. The Cas9 enzyme was conjugated to a gold nanoparticle (AuNP-Cas9). The AuNP-Cas9 maintained its cleavage efficiency in vitro, to the same extent as the ribonucleoprotein, including non-conjugated Cas9 enzyme, and showed high gene editing efficiency in vivo in zebrafish embryos. Since CRISPR/Cas9 technology is extensively used in cancer research, melanoma was selected as a validation target. Cell studies were performed in A375 human melanoma cells. Particles per se had no impact on cell metabolism and proliferation. Intriguingly, the AuNP-Cas9 internalized spontaneously in cells and localized as a single particle in the cytoplasm and organelles. More importantly, the AuNP-Cas9 showed a high nuclear localization signal. The AuNP-Cas9, overcoming the delivery difficulties of Cas9, could be used in cellular biology and localization studies. Taking advantage of the plasmonic properties of gold nanoparticles, this technology could potentially be a bio-tool for combining gene editing and photothermal therapy in cancer cells. Further work will be focused on intracellular interactions of the nano-formulation and characterization of the optical properties.

Keywords: CRISPR/Cas9, gene editing, gold nanoparticles, nanotechnology

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Authors: Pooja Kumari, Anandkumar Tengli

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Aurora kinase enzyme, a protein on overexpression, leads to metastasis and is extremely important for women’s health in terms of prevention or treatment. While creating a targeted technique, the aim of the work is to design purine molecules that inhibit in aurora kinase enzyme and helps to suppress breast cancer. Purine molecules attached to an amino acid in DNA block protein synthesis or halt the replication and metastasis caused by the aurora kinase enzyme. Various protein related to the overexpression of aurora protein was docked with purine molecule using Biovia Drug Discovery, the perpetual software. Various parameters like X-ray crystallographic structure, presence of ligand, Ramachandran plot, resolution, etc., were taken into consideration for selecting the target protein. A higher negative binding scored molecule has been taken for simulation studies. According to the available research and computational analyses, purine compounds may be powerful enough to demonstrate a greater affinity for the aurora target. Despite being clinically effective now, purines were originally meant to fight breast cancer by inhibiting the aurora kinase enzyme. In in-silico studies, it is observed that purine compounds have a moderate to high potency compared to other molecules, and our research into the literature revealed that purine molecules have a lower risk of side effects. The research involves the design, synthesis, and identification of active purine molecules against breast cancer. Purines are structurally similar to the normal metabolites of adenine and guanine; hence interfere/compete with protein synthesis and suppress the abnormal proliferation of cells/tissues. As a result, purine target metastasis cells and stop the growth of kinase; purine derivatives bind with DNA and aurora protein which may stop the growth of protein or inhibits replication and stop metastasis of overexpressed aurora kinase enzyme.

Keywords: aurora kinases, in silico studies, medicinal chemistry, combination therapies, chronic cancer, clinical translation

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